The architecture of the glenohumeral joint makes it the most common large joint to become dislocated, accounting for approximately 45% of all dislocations. Anterior dislocation constitutes more than 95% of glenohumeral joint dislocations; posterior dislocation, only 2% to 5%.^1,2

For the family physician, determining appropriate follow-up after emergent reduction depends on several distinct variables, which we review here; subsequent treatment might involve, as we outline, physical therapy, immobilization, surgical intervention, or a combination of several modalities. Treatment decisions can make the difference between successful rehabilitation and potential disability, particularly in typically young and active patients.

Numerous mechanisms of injury

Anterior shoulder dislocations typically occur with the affected shoulder in a position of abduction and external rotation; 90% of patients are 21 to 30 years of age, and men are affected 3 times more often than women.² Unsurprisingly, athletes are affected most frequently, with the common sports-related mechanism of injury being either sudden pressure exerted on the abducted and externally rotated arm or a fall onto an outstretched hand with the arm elevated. Repetitive microtrauma from such sports as swimming, baseball, and volleyball can also lead to instability.

Bankart lesion. This tear of the anterior or inferior section of the labrum is the most characteristic lesion noted in anterior dislocations, found in 73% of first-time dislocations and 100% of recurrent dislocations.^3,4

Hills-Sachs lesion is often associated with a Bankart lesion. The Hills-Sachs lesion is an impaction fracture of the posterolateral aspect of the humeral head resulting from its displacement over the anterior lip of the glenoid. Hill-Sachs lesions are seen in 71% of first-time and recurrent dislocations.³

Less common concomitant injuries during anterior shoulder dislocation include rupture of the rotator-cuff tendons (particularly in patients older than 40 years), glenoid and proximal humerus fractures, a tear of the superior labrum (known as a “SLAP lesion”), cartilage injury, and neurovascular injury.

Posterior instability typically occurs as a result of a strong muscle contraction, as seen in electrocution or seizure; however, it can be caused by athletic trauma, particularly in football.⁵ Repetitive forces exerted on the forward-flexed and internally rotated shoulder position during blocking puts football players at increased risk of posterior instability.⁵

Continue to: Multidirectional instability

Multidirectional instability is more frequently attributable to congenital hyperlaxity of the glenohumeral joint capsule, rather than to acute injury. However, athletes can also develop capsular laxity from repetitive microtrauma to the shoulder.⁵

Emergent reduction: Prompt action needed

Acute dislocation of the shoulder should be reduced as soon as possible to minimize neurovascular injury and patient discomfort. (Typically, but not always, this is done in the emergency department.) It is crucial to have effective muscle relaxation before any attempt at reduction, to minimize the risk of iatrogenic injury to bone, cartilage, tendons, and neurovascular structures.

Muscle relaxation can be facilitated with intravenous midazolam or other agents, as specified by institutional protocol. Intra-articular lidocaine injection or intravenous fentanyl is often utilized in conjunction with the sedating agent to reduce pain and further accommodate relaxation.

Anterior reduction. Any one of several techniques can be used to perform emergent reduction of anterior shoulder dislocations, all of which have demonstrated success. The Milch technique is among the least traumatic for effective reduction.⁶ In this technique (FIGURE 1), the patient is supine; gentle but firm downward traction is applied to the humerus at the elbow of the affected arm while the arm is in abduction and external rotation. The provider can manipulate the humeral head at that point by placing a thumb in the patient’s axilla; the arm can also be further internally rotated and adducted until reduction is achieved.

Posterior reduction of a dislocation is performed while the patient is supine, with the body stabilized. Traction is applied on the adducted and internally rotated arm in conjunction with direct pressure on the posterior aspect of the humeral head (FIGURE 2).

Continue to: Follow-up actions

Follow-up actions. Before discharging the patient after reduction of a dislocation, it is essential to:

• perform post-reduction evaluation of shoulder stability at different levels of abduction
• perform a thorough neurovascular assessment
• obtain an anteroposterior (AP) radiograph to ensure proper positioning of the glenohumeral joint.

The reduced shoulder should be immobilized in a sling. The discharge plan should include pain management for several days and a follow-up appointment in 5 to 8 days with the primary care provider² (FIGURE 3).

Follow-up evaluation by the primary care provider

History. Prior to the initial examination at follow-up, obtain a comprehensive history that includes the nature of the injury and the direction of force that was placed on the shoulder. Determine whether the shoulder was reduced spontaneously or required manual reduction in the field or an emergency department. Note any associated injury sustained concurrently and the presence (or absence) of neck pain, numbness, tingling, or weakness in the affected arm.

Physical exam starts with thorough inspection of the affected shoulder, with comparison to the contralateral side, at rest and during shoulder motion. Palpation to reveal points of tenderness should include the anterior joint line, acromioclavicular joint, bicipital groove, subacromial space, acromion, and greater tuberosity.

Acute dislocation of the shoulder should be reduced as soon as possible to minimize neurovascular injury and patient discomfort.

Following inspection and palpation, assess active and passive range of motion in forward elevation, abduction, internal and external rotation at the side of the body, and internal and external rotation in shoulder abduction. Assessment might be limited by pain and apprehension, and should be performed within the patient’s comfortable range of motion.

Continue to: Once range of motion...

Once range of motion is determined, assess⁷:

• muscle power of the rotator cuff in abduction (for the supraspinatus muscle)
• resisted external rotation at the side of the body (the infraspinatus)
• resisted external rotation in abduction > 60° (the teres minor)
• resisted internal rotation (the subscapularis).

Specific tests for shoulder laxity and stability

It is important during the primary care follow-up examination to differentiate true instability and shoulder hyperlaxity, particularly in young, flexible patients (TABLE). Many of these patients present with painless hypermobility of the shoulder without true injury to the labrum or ligamentous structures. It might appear to the patient, or to family, that the shoulder is subluxating; however, the humeral head returns to a centered position on the glenoid in a hypermobile state—typically, without pain. Actual shoulder instability is defined as loss of the ability of the humeral head to re-center, accompanied by pain—pathology that is frequently associated with damage to the capsulolabral complex.

The load and shift test is used to assess anterior and posterior laxity. The patient is seated, and the forearm is allowed to rest on the thigh. Examination is performed using 1 hand to press anteriorly or posteriorly on the humeral head; the other hand is simultaneously positioned on the joint line to feel movement of the humeral head in relation to the glenoid (FIGURE 4).

The apprehension test is a common maneuver used to assess anterior shoulder instability. It is performed by positioning the affected arm to 90° external rotation and then elevating it to 90° abduction. Although this maneuver can be performed with the patient upright, it is beneficial to have them supine, to more easily control the arm (FIGURE 5). A positive test is noted when the patient reports a sensation of impending instability (apprehension), rather than pain alone.

Relocation test. When the apprehension test is positive, the supine position can be exploited to further perform the relocation test, in 2 stages (FIGURE 6):

• Apply a posteriorly directed force on the humeral head, which stabilizes the shoulder and typically alleviates symptoms.
• Release pressure quickly from the humeral head to assess recurrence of pain and apprehension as the humeral head snaps back against the anterior labrum.

Continue to: Combined, apprehension and relocation...

Combined, apprehension and relocation tests to identify anterior shoulder instability have been shown to significantly improve specificity while maintaining sensitivity.⁸

The posterior apprehension test is used to assess posterior instability. The patient is supine; the affected arm is placed in flexion, adduction, and internal rotation; and posterior pressure is applied (FIGURE 7). A positive test is noted when pain is reported at the posterior aspect of the shoulder. Clicking might be noted as the humeral head dislocates rearward.¹

Sulcus sign. Multidirectional instability is elicited using the sulcus sign. While the patient is seated upright, arms resting at their sides, a direct downward pull at elbow level will, when positive, reveal a depression (sulcus) at the lateral aspect of the affected shoulder as the humeral head translates inferiorly (FIGURE 8). A positive sulcus sign is documented in 3 grades, according to the amount of translation¹:

• Grade I: < 1 cm
• Grade II: 1-2 cm
• Grade III: > 2 cm.

Neurovascular status should be verified at every physical evaluation, with motor and sensory function tested in the axillary, musculocutaneous, median, radial, and ulnar nerve distributions. If nerve injury is suspected, electromyography and nerve-conduction testing is indicated.^9-13 Vascular compromise is much less common but equally important to assess.¹¹

Use of imaging

Post-reduction radiographs, including internal and external AP—and especially axillary—views are invaluable. Not only do they help to ensure reduction, but they also help to assess for fracture. A magnetic resonance imaging (MRI) arthrogram is the preferred imaging modality if a labral tear is suspected (FIGURE 9). Other concomitant shoulder injuries, such as subtle bone fracture, rotator cuff tear, and biceps pathology can also be reliably diagnosed with noncontrast MRI.

Continue to: Roadmap for treatment

The rate of recurrence after a first anterior shoulder dislocation is strongly associated with a person’s age and level of activity. Active patients younger than 20 years have a 92% to 96% recurrence rate¹⁴; patients 20 to 40 years, 25% to 48%; and patients older than 40 years, < 10%.¹⁵

Young, athletic patients who are treated nonoperatively are left at an unacceptably high risk of recurrence, leading to progressive damage to bony and soft-tissue structures.^16,17 Surgical labral repair after a first-time anterior dislocation produced improved outcomes in terms of recurrent dislocation (7.9%), compared to outcomes after nonsurgical treatment (52.9%),¹⁴ and has been associated with a lower incidence of future glenohumeral osteoarthritis.¹⁸ For those reasons, we recommend referral to an orthopedic surgeon for all patients younger than 20 years who sustain an anterior shoulder dislocation.

Patients older than 20 years who do not have concomitant shoulder injury, and who demonstrate full strength in abduction, external rotation, and internal rotation of the shoulder on clinical examination, have a low probability of associated rotator-cuff tear. They can be immobilized in a sling for 1 to 3 weeks, followed by a 6 to 12–week regimen of physical therapy.

Concomitant tear of the rotator cuff. Weakness on examination requires MRI or a magnetic resonance arthrogram for evaluation of associated rotator-cuff tear. A tear identified on MRI should be referred to an orthopedic surgeon because timely repair can be crucial to attaining best outcomes. Conservative treatment of traumatic full-­tendon rotator-cuff tear is associated with poor results, progression in the size of the tear, and advancement of muscle atrophy.^19,20 For patients younger than 40 years, arthroscopic rotator-cuff repair, with or without labral repair, produces excellent clinical outcomes, carries a low risk of complications, and results in a > 95% rate of return to a preoperative level of recreational and job activities.²¹

Patients who demonstrate weakness of the rotator-cuff muscles on examination, but who do not have a tear noted on MRI, should be evaluated by electromyography and nerve-conduction testing to assess nerve injury as an alternative cause of weakness.^10,11 If a neurologic deficit is found on nerve-conduction testing, the patient should be referred for neurologic evaluation.¹⁰

Continue to: Patients with negative findings...

Patients with negative findings on MRI and nerve-conduction studies should be offered physical therapy. Patients with recurrent anterior shoulder dislocation should be referred to an orthopedic surgeon for surgical repair. Frequently, improper or delayed treatment with chronic instability results in degenerative arthropathy of the joint²² (FIGURE 10).

Posterior and multidirectional instability can typically be treated conservatively; however, whereas posterior dislocation typically must be immobilized for 3 to 6 weeks post reduction, multidirectional instability does not require immobilization. Instead, physical therapy should start as soon as possible. In these cases, recurrent dislocation or subluxation that persists after conservative treatment should be referred for possible surgical intervention.⁵

Instability with associated fracture

Fracture concomitant with dislocation most commonly involves the humeral neck, humeral head, greater tuberosity, or the glenoid itself.² Clinical variables that predict a fracture associated with shoulder dislocation include²³:

• first episode of dislocation
• age ≥ 40 years
• fall from higher than 1 flight of stairs
• fight or assault
• motor vehicle crash.

A computed tomography scan with 3-dimensional reconstruction can help characterize associated fracture accurately—including location, size, and displacement—and can play an important role in treatment planning and prognosis in these complicated injuries. Displaced fracture should be referred to an orthopedic surgeon. Nondisplaced fracture of the humeral head or greater tuberosity (FIGURE 11) poses less risk of complications and can be treated conservatively with 6 weeks in an arm sling, followed by physical therapy.²⁴

Summing up

Management of shoulder dislocation must, first, be tailored to the individual and, second, account for several interactive factors—including age, direction of instability, functional demands, risk of recurrence, and associated injuries. In many patients, conservative treatment produces a favorable long-term outcome. Particularly in young, active patients with anterior shoulder instability, most surgeons consider open or arthroscopic reconstruction to be the treatment of choice.^2,18

Continue to: Pre-reduction and post-reduction...

Pre-reduction and post-reduction imaging should be carefully examined for the presence of concomitant injury, which might change the preferred treatment modality appreciably.

Last, communication among emergency department providers, the primary care provider, orthopedist, radiologist, and neurologist is crucial for determining an appropriate patient-centered approach to initial and long-term management.

CORRESPONDENCE
Nata Parnes, MD, Carthage Area Hospital, 3 Bridge Street, Carthage, NY; [email protected]

The architecture of the glenohumeral joint makes it the most common large joint to become dislocated, accounting for approximately 45% of all dislocations. Anterior dislocation constitutes more than 95% of glenohumeral joint dislocations; posterior dislocation, only 2% to 5%.^1,2

For the family physician, determining appropriate follow-up after emergent reduction depends on several distinct variables, which we review here; subsequent treatment might involve, as we outline, physical therapy, immobilization, surgical intervention, or a combination of several modalities. Treatment decisions can make the difference between successful rehabilitation and potential disability, particularly in typically young and active patients.

Numerous mechanisms of injury

Anterior shoulder dislocations typically occur with the affected shoulder in a position of abduction and external rotation; 90% of patients are 21 to 30 years of age, and men are affected 3 times more often than women.² Unsurprisingly, athletes are affected most frequently, with the common sports-related mechanism of injury being either sudden pressure exerted on the abducted and externally rotated arm or a fall onto an outstretched hand with the arm elevated. Repetitive microtrauma from such sports as swimming, baseball, and volleyball can also lead to instability.

Bankart lesion. This tear of the anterior or inferior section of the labrum is the most characteristic lesion noted in anterior dislocations, found in 73% of first-time dislocations and 100% of recurrent dislocations.^3,4

Hills-Sachs lesion is often associated with a Bankart lesion. The Hills-Sachs lesion is an impaction fracture of the posterolateral aspect of the humeral head resulting from its displacement over the anterior lip of the glenoid. Hill-Sachs lesions are seen in 71% of first-time and recurrent dislocations.³

Less common concomitant injuries during anterior shoulder dislocation include rupture of the rotator-cuff tendons (particularly in patients older than 40 years), glenoid and proximal humerus fractures, a tear of the superior labrum (known as a “SLAP lesion”), cartilage injury, and neurovascular injury.

Posterior instability typically occurs as a result of a strong muscle contraction, as seen in electrocution or seizure; however, it can be caused by athletic trauma, particularly in football.⁵ Repetitive forces exerted on the forward-flexed and internally rotated shoulder position during blocking puts football players at increased risk of posterior instability.⁵

Continue to: Multidirectional instability

Multidirectional instability is more frequently attributable to congenital hyperlaxity of the glenohumeral joint capsule, rather than to acute injury. However, athletes can also develop capsular laxity from repetitive microtrauma to the shoulder.⁵

Emergent reduction: Prompt action needed

Acute dislocation of the shoulder should be reduced as soon as possible to minimize neurovascular injury and patient discomfort. (Typically, but not always, this is done in the emergency department.) It is crucial to have effective muscle relaxation before any attempt at reduction, to minimize the risk of iatrogenic injury to bone, cartilage, tendons, and neurovascular structures.

Muscle relaxation can be facilitated with intravenous midazolam or other agents, as specified by institutional protocol. Intra-articular lidocaine injection or intravenous fentanyl is often utilized in conjunction with the sedating agent to reduce pain and further accommodate relaxation.

Anterior reduction. Any one of several techniques can be used to perform emergent reduction of anterior shoulder dislocations, all of which have demonstrated success. The Milch technique is among the least traumatic for effective reduction.⁶ In this technique (FIGURE 1), the patient is supine; gentle but firm downward traction is applied to the humerus at the elbow of the affected arm while the arm is in abduction and external rotation. The provider can manipulate the humeral head at that point by placing a thumb in the patient’s axilla; the arm can also be further internally rotated and adducted until reduction is achieved.

Posterior reduction of a dislocation is performed while the patient is supine, with the body stabilized. Traction is applied on the adducted and internally rotated arm in conjunction with direct pressure on the posterior aspect of the humeral head (FIGURE 2).

Continue to: Follow-up actions

Follow-up actions. Before discharging the patient after reduction of a dislocation, it is essential to:

• perform post-reduction evaluation of shoulder stability at different levels of abduction
• perform a thorough neurovascular assessment
• obtain an anteroposterior (AP) radiograph to ensure proper positioning of the glenohumeral joint.

The reduced shoulder should be immobilized in a sling. The discharge plan should include pain management for several days and a follow-up appointment in 5 to 8 days with the primary care provider² (FIGURE 3).

Follow-up evaluation by the primary care provider

History. Prior to the initial examination at follow-up, obtain a comprehensive history that includes the nature of the injury and the direction of force that was placed on the shoulder. Determine whether the shoulder was reduced spontaneously or required manual reduction in the field or an emergency department. Note any associated injury sustained concurrently and the presence (or absence) of neck pain, numbness, tingling, or weakness in the affected arm.

Physical exam starts with thorough inspection of the affected shoulder, with comparison to the contralateral side, at rest and during shoulder motion. Palpation to reveal points of tenderness should include the anterior joint line, acromioclavicular joint, bicipital groove, subacromial space, acromion, and greater tuberosity.

Acute dislocation of the shoulder should be reduced as soon as possible to minimize neurovascular injury and patient discomfort.

Following inspection and palpation, assess active and passive range of motion in forward elevation, abduction, internal and external rotation at the side of the body, and internal and external rotation in shoulder abduction. Assessment might be limited by pain and apprehension, and should be performed within the patient’s comfortable range of motion.

Continue to: Once range of motion...

Once range of motion is determined, assess⁷:

• muscle power of the rotator cuff in abduction (for the supraspinatus muscle)
• resisted external rotation at the side of the body (the infraspinatus)
• resisted external rotation in abduction > 60° (the teres minor)
• resisted internal rotation (the subscapularis).

Specific tests for shoulder laxity and stability

It is important during the primary care follow-up examination to differentiate true instability and shoulder hyperlaxity, particularly in young, flexible patients (TABLE). Many of these patients present with painless hypermobility of the shoulder without true injury to the labrum or ligamentous structures. It might appear to the patient, or to family, that the shoulder is subluxating; however, the humeral head returns to a centered position on the glenoid in a hypermobile state—typically, without pain. Actual shoulder instability is defined as loss of the ability of the humeral head to re-center, accompanied by pain—pathology that is frequently associated with damage to the capsulolabral complex.

The load and shift test is used to assess anterior and posterior laxity. The patient is seated, and the forearm is allowed to rest on the thigh. Examination is performed using 1 hand to press anteriorly or posteriorly on the humeral head; the other hand is simultaneously positioned on the joint line to feel movement of the humeral head in relation to the glenoid (FIGURE 4).

The apprehension test is a common maneuver used to assess anterior shoulder instability. It is performed by positioning the affected arm to 90° external rotation and then elevating it to 90° abduction. Although this maneuver can be performed with the patient upright, it is beneficial to have them supine, to more easily control the arm (FIGURE 5). A positive test is noted when the patient reports a sensation of impending instability (apprehension), rather than pain alone.

Relocation test. When the apprehension test is positive, the supine position can be exploited to further perform the relocation test, in 2 stages (FIGURE 6):

• Apply a posteriorly directed force on the humeral head, which stabilizes the shoulder and typically alleviates symptoms.
• Release pressure quickly from the humeral head to assess recurrence of pain and apprehension as the humeral head snaps back against the anterior labrum.

Continue to: Combined, apprehension and relocation...

Combined, apprehension and relocation tests to identify anterior shoulder instability have been shown to significantly improve specificity while maintaining sensitivity.⁸

The posterior apprehension test is used to assess posterior instability. The patient is supine; the affected arm is placed in flexion, adduction, and internal rotation; and posterior pressure is applied (FIGURE 7). A positive test is noted when pain is reported at the posterior aspect of the shoulder. Clicking might be noted as the humeral head dislocates rearward.¹

Sulcus sign. Multidirectional instability is elicited using the sulcus sign. While the patient is seated upright, arms resting at their sides, a direct downward pull at elbow level will, when positive, reveal a depression (sulcus) at the lateral aspect of the affected shoulder as the humeral head translates inferiorly (FIGURE 8). A positive sulcus sign is documented in 3 grades, according to the amount of translation¹:

• Grade I: < 1 cm
• Grade II: 1-2 cm
• Grade III: > 2 cm.

Neurovascular status should be verified at every physical evaluation, with motor and sensory function tested in the axillary, musculocutaneous, median, radial, and ulnar nerve distributions. If nerve injury is suspected, electromyography and nerve-conduction testing is indicated.^9-13 Vascular compromise is much less common but equally important to assess.¹¹

Use of imaging

Post-reduction radiographs, including internal and external AP—and especially axillary—views are invaluable. Not only do they help to ensure reduction, but they also help to assess for fracture. A magnetic resonance imaging (MRI) arthrogram is the preferred imaging modality if a labral tear is suspected (FIGURE 9). Other concomitant shoulder injuries, such as subtle bone fracture, rotator cuff tear, and biceps pathology can also be reliably diagnosed with noncontrast MRI.

Continue to: Roadmap for treatment

The rate of recurrence after a first anterior shoulder dislocation is strongly associated with a person’s age and level of activity. Active patients younger than 20 years have a 92% to 96% recurrence rate¹⁴; patients 20 to 40 years, 25% to 48%; and patients older than 40 years, < 10%.¹⁵

Young, athletic patients who are treated nonoperatively are left at an unacceptably high risk of recurrence, leading to progressive damage to bony and soft-tissue structures.^16,17 Surgical labral repair after a first-time anterior dislocation produced improved outcomes in terms of recurrent dislocation (7.9%), compared to outcomes after nonsurgical treatment (52.9%),¹⁴ and has been associated with a lower incidence of future glenohumeral osteoarthritis.¹⁸ For those reasons, we recommend referral to an orthopedic surgeon for all patients younger than 20 years who sustain an anterior shoulder dislocation.

Patients older than 20 years who do not have concomitant shoulder injury, and who demonstrate full strength in abduction, external rotation, and internal rotation of the shoulder on clinical examination, have a low probability of associated rotator-cuff tear. They can be immobilized in a sling for 1 to 3 weeks, followed by a 6 to 12–week regimen of physical therapy.

Concomitant tear of the rotator cuff. Weakness on examination requires MRI or a magnetic resonance arthrogram for evaluation of associated rotator-cuff tear. A tear identified on MRI should be referred to an orthopedic surgeon because timely repair can be crucial to attaining best outcomes. Conservative treatment of traumatic full-­tendon rotator-cuff tear is associated with poor results, progression in the size of the tear, and advancement of muscle atrophy.^19,20 For patients younger than 40 years, arthroscopic rotator-cuff repair, with or without labral repair, produces excellent clinical outcomes, carries a low risk of complications, and results in a > 95% rate of return to a preoperative level of recreational and job activities.²¹

Patients who demonstrate weakness of the rotator-cuff muscles on examination, but who do not have a tear noted on MRI, should be evaluated by electromyography and nerve-conduction testing to assess nerve injury as an alternative cause of weakness.^10,11 If a neurologic deficit is found on nerve-conduction testing, the patient should be referred for neurologic evaluation.¹⁰

Continue to: Patients with negative findings...

Patients with negative findings on MRI and nerve-conduction studies should be offered physical therapy. Patients with recurrent anterior shoulder dislocation should be referred to an orthopedic surgeon for surgical repair. Frequently, improper or delayed treatment with chronic instability results in degenerative arthropathy of the joint²² (FIGURE 10).

Posterior and multidirectional instability can typically be treated conservatively; however, whereas posterior dislocation typically must be immobilized for 3 to 6 weeks post reduction, multidirectional instability does not require immobilization. Instead, physical therapy should start as soon as possible. In these cases, recurrent dislocation or subluxation that persists after conservative treatment should be referred for possible surgical intervention.⁵

Instability with associated fracture

Fracture concomitant with dislocation most commonly involves the humeral neck, humeral head, greater tuberosity, or the glenoid itself.² Clinical variables that predict a fracture associated with shoulder dislocation include²³:

• first episode of dislocation
• age ≥ 40 years
• fall from higher than 1 flight of stairs
• fight or assault
• motor vehicle crash.

A computed tomography scan with 3-dimensional reconstruction can help characterize associated fracture accurately—including location, size, and displacement—and can play an important role in treatment planning and prognosis in these complicated injuries. Displaced fracture should be referred to an orthopedic surgeon. Nondisplaced fracture of the humeral head or greater tuberosity (FIGURE 11) poses less risk of complications and can be treated conservatively with 6 weeks in an arm sling, followed by physical therapy.²⁴

Summing up

Management of shoulder dislocation must, first, be tailored to the individual and, second, account for several interactive factors—including age, direction of instability, functional demands, risk of recurrence, and associated injuries. In many patients, conservative treatment produces a favorable long-term outcome. Particularly in young, active patients with anterior shoulder instability, most surgeons consider open or arthroscopic reconstruction to be the treatment of choice.^2,18

Continue to: Pre-reduction and post-reduction...

Pre-reduction and post-reduction imaging should be carefully examined for the presence of concomitant injury, which might change the preferred treatment modality appreciably.

Last, communication among emergency department providers, the primary care provider, orthopedist, radiologist, and neurologist is crucial for determining an appropriate patient-centered approach to initial and long-term management.

CORRESPONDENCE
Nata Parnes, MD, Carthage Area Hospital, 3 Bridge Street, Carthage, NY; [email protected]

The architecture of the glenohumeral joint makes it the most common large joint to become dislocated, accounting for approximately 45% of all dislocations. Anterior dislocation constitutes more than 95% of glenohumeral joint dislocations; posterior dislocation, only 2% to 5%.^1,2

For the family physician, determining appropriate follow-up after emergent reduction depends on several distinct variables, which we review here; subsequent treatment might involve, as we outline, physical therapy, immobilization, surgical intervention, or a combination of several modalities. Treatment decisions can make the difference between successful rehabilitation and potential disability, particularly in typically young and active patients.

Numerous mechanisms of injury

Anterior shoulder dislocations typically occur with the affected shoulder in a position of abduction and external rotation; 90% of patients are 21 to 30 years of age, and men are affected 3 times more often than women.² Unsurprisingly, athletes are affected most frequently, with the common sports-related mechanism of injury being either sudden pressure exerted on the abducted and externally rotated arm or a fall onto an outstretched hand with the arm elevated. Repetitive microtrauma from such sports as swimming, baseball, and volleyball can also lead to instability.

Bankart lesion. This tear of the anterior or inferior section of the labrum is the most characteristic lesion noted in anterior dislocations, found in 73% of first-time dislocations and 100% of recurrent dislocations.^3,4

Hills-Sachs lesion is often associated with a Bankart lesion. The Hills-Sachs lesion is an impaction fracture of the posterolateral aspect of the humeral head resulting from its displacement over the anterior lip of the glenoid. Hill-Sachs lesions are seen in 71% of first-time and recurrent dislocations.³

Less common concomitant injuries during anterior shoulder dislocation include rupture of the rotator-cuff tendons (particularly in patients older than 40 years), glenoid and proximal humerus fractures, a tear of the superior labrum (known as a “SLAP lesion”), cartilage injury, and neurovascular injury.

Posterior instability typically occurs as a result of a strong muscle contraction, as seen in electrocution or seizure; however, it can be caused by athletic trauma, particularly in football.⁵ Repetitive forces exerted on the forward-flexed and internally rotated shoulder position during blocking puts football players at increased risk of posterior instability.⁵

Continue to: Multidirectional instability

Multidirectional instability is more frequently attributable to congenital hyperlaxity of the glenohumeral joint capsule, rather than to acute injury. However, athletes can also develop capsular laxity from repetitive microtrauma to the shoulder.⁵

Emergent reduction: Prompt action needed

Acute dislocation of the shoulder should be reduced as soon as possible to minimize neurovascular injury and patient discomfort. (Typically, but not always, this is done in the emergency department.) It is crucial to have effective muscle relaxation before any attempt at reduction, to minimize the risk of iatrogenic injury to bone, cartilage, tendons, and neurovascular structures.

Muscle relaxation can be facilitated with intravenous midazolam or other agents, as specified by institutional protocol. Intra-articular lidocaine injection or intravenous fentanyl is often utilized in conjunction with the sedating agent to reduce pain and further accommodate relaxation.

Anterior reduction. Any one of several techniques can be used to perform emergent reduction of anterior shoulder dislocations, all of which have demonstrated success. The Milch technique is among the least traumatic for effective reduction.⁶ In this technique (FIGURE 1), the patient is supine; gentle but firm downward traction is applied to the humerus at the elbow of the affected arm while the arm is in abduction and external rotation. The provider can manipulate the humeral head at that point by placing a thumb in the patient’s axilla; the arm can also be further internally rotated and adducted until reduction is achieved.

Posterior reduction of a dislocation is performed while the patient is supine, with the body stabilized. Traction is applied on the adducted and internally rotated arm in conjunction with direct pressure on the posterior aspect of the humeral head (FIGURE 2).

Continue to: Follow-up actions

Follow-up actions. Before discharging the patient after reduction of a dislocation, it is essential to:

• perform post-reduction evaluation of shoulder stability at different levels of abduction
• perform a thorough neurovascular assessment
• obtain an anteroposterior (AP) radiograph to ensure proper positioning of the glenohumeral joint.

The reduced shoulder should be immobilized in a sling. The discharge plan should include pain management for several days and a follow-up appointment in 5 to 8 days with the primary care provider² (FIGURE 3).

Follow-up evaluation by the primary care provider

History. Prior to the initial examination at follow-up, obtain a comprehensive history that includes the nature of the injury and the direction of force that was placed on the shoulder. Determine whether the shoulder was reduced spontaneously or required manual reduction in the field or an emergency department. Note any associated injury sustained concurrently and the presence (or absence) of neck pain, numbness, tingling, or weakness in the affected arm.

Physical exam starts with thorough inspection of the affected shoulder, with comparison to the contralateral side, at rest and during shoulder motion. Palpation to reveal points of tenderness should include the anterior joint line, acromioclavicular joint, bicipital groove, subacromial space, acromion, and greater tuberosity.

Acute dislocation of the shoulder should be reduced as soon as possible to minimize neurovascular injury and patient discomfort.

Following inspection and palpation, assess active and passive range of motion in forward elevation, abduction, internal and external rotation at the side of the body, and internal and external rotation in shoulder abduction. Assessment might be limited by pain and apprehension, and should be performed within the patient’s comfortable range of motion.

Continue to: Once range of motion...

Once range of motion is determined, assess⁷:

• muscle power of the rotator cuff in abduction (for the supraspinatus muscle)
• resisted external rotation at the side of the body (the infraspinatus)
• resisted external rotation in abduction > 60° (the teres minor)
• resisted internal rotation (the subscapularis).

Specific tests for shoulder laxity and stability

It is important during the primary care follow-up examination to differentiate true instability and shoulder hyperlaxity, particularly in young, flexible patients (TABLE). Many of these patients present with painless hypermobility of the shoulder without true injury to the labrum or ligamentous structures. It might appear to the patient, or to family, that the shoulder is subluxating; however, the humeral head returns to a centered position on the glenoid in a hypermobile state—typically, without pain. Actual shoulder instability is defined as loss of the ability of the humeral head to re-center, accompanied by pain—pathology that is frequently associated with damage to the capsulolabral complex.

The load and shift test is used to assess anterior and posterior laxity. The patient is seated, and the forearm is allowed to rest on the thigh. Examination is performed using 1 hand to press anteriorly or posteriorly on the humeral head; the other hand is simultaneously positioned on the joint line to feel movement of the humeral head in relation to the glenoid (FIGURE 4).

The apprehension test is a common maneuver used to assess anterior shoulder instability. It is performed by positioning the affected arm to 90° external rotation and then elevating it to 90° abduction. Although this maneuver can be performed with the patient upright, it is beneficial to have them supine, to more easily control the arm (FIGURE 5). A positive test is noted when the patient reports a sensation of impending instability (apprehension), rather than pain alone.

Relocation test. When the apprehension test is positive, the supine position can be exploited to further perform the relocation test, in 2 stages (FIGURE 6):

• Apply a posteriorly directed force on the humeral head, which stabilizes the shoulder and typically alleviates symptoms.
• Release pressure quickly from the humeral head to assess recurrence of pain and apprehension as the humeral head snaps back against the anterior labrum.

Continue to: Combined, apprehension and relocation...

Combined, apprehension and relocation tests to identify anterior shoulder instability have been shown to significantly improve specificity while maintaining sensitivity.⁸

The posterior apprehension test is used to assess posterior instability. The patient is supine; the affected arm is placed in flexion, adduction, and internal rotation; and posterior pressure is applied (FIGURE 7). A positive test is noted when pain is reported at the posterior aspect of the shoulder. Clicking might be noted as the humeral head dislocates rearward.¹

Sulcus sign. Multidirectional instability is elicited using the sulcus sign. While the patient is seated upright, arms resting at their sides, a direct downward pull at elbow level will, when positive, reveal a depression (sulcus) at the lateral aspect of the affected shoulder as the humeral head translates inferiorly (FIGURE 8). A positive sulcus sign is documented in 3 grades, according to the amount of translation¹:

• Grade I: < 1 cm
• Grade II: 1-2 cm
• Grade III: > 2 cm.

Neurovascular status should be verified at every physical evaluation, with motor and sensory function tested in the axillary, musculocutaneous, median, radial, and ulnar nerve distributions. If nerve injury is suspected, electromyography and nerve-conduction testing is indicated.^9-13 Vascular compromise is much less common but equally important to assess.¹¹

Use of imaging

Post-reduction radiographs, including internal and external AP—and especially axillary—views are invaluable. Not only do they help to ensure reduction, but they also help to assess for fracture. A magnetic resonance imaging (MRI) arthrogram is the preferred imaging modality if a labral tear is suspected (FIGURE 9). Other concomitant shoulder injuries, such as subtle bone fracture, rotator cuff tear, and biceps pathology can also be reliably diagnosed with noncontrast MRI.

Continue to: Roadmap for treatment

The rate of recurrence after a first anterior shoulder dislocation is strongly associated with a person’s age and level of activity. Active patients younger than 20 years have a 92% to 96% recurrence rate¹⁴; patients 20 to 40 years, 25% to 48%; and patients older than 40 years, < 10%.¹⁵

Young, athletic patients who are treated nonoperatively are left at an unacceptably high risk of recurrence, leading to progressive damage to bony and soft-tissue structures.^16,17 Surgical labral repair after a first-time anterior dislocation produced improved outcomes in terms of recurrent dislocation (7.9%), compared to outcomes after nonsurgical treatment (52.9%),¹⁴ and has been associated with a lower incidence of future glenohumeral osteoarthritis.¹⁸ For those reasons, we recommend referral to an orthopedic surgeon for all patients younger than 20 years who sustain an anterior shoulder dislocation.

Patients older than 20 years who do not have concomitant shoulder injury, and who demonstrate full strength in abduction, external rotation, and internal rotation of the shoulder on clinical examination, have a low probability of associated rotator-cuff tear. They can be immobilized in a sling for 1 to 3 weeks, followed by a 6 to 12–week regimen of physical therapy.

Concomitant tear of the rotator cuff. Weakness on examination requires MRI or a magnetic resonance arthrogram for evaluation of associated rotator-cuff tear. A tear identified on MRI should be referred to an orthopedic surgeon because timely repair can be crucial to attaining best outcomes. Conservative treatment of traumatic full-­tendon rotator-cuff tear is associated with poor results, progression in the size of the tear, and advancement of muscle atrophy.^19,20 For patients younger than 40 years, arthroscopic rotator-cuff repair, with or without labral repair, produces excellent clinical outcomes, carries a low risk of complications, and results in a > 95% rate of return to a preoperative level of recreational and job activities.²¹

Patients who demonstrate weakness of the rotator-cuff muscles on examination, but who do not have a tear noted on MRI, should be evaluated by electromyography and nerve-conduction testing to assess nerve injury as an alternative cause of weakness.^10,11 If a neurologic deficit is found on nerve-conduction testing, the patient should be referred for neurologic evaluation.¹⁰

Continue to: Patients with negative findings...

Patients with negative findings on MRI and nerve-conduction studies should be offered physical therapy. Patients with recurrent anterior shoulder dislocation should be referred to an orthopedic surgeon for surgical repair. Frequently, improper or delayed treatment with chronic instability results in degenerative arthropathy of the joint²² (FIGURE 10).

Posterior and multidirectional instability can typically be treated conservatively; however, whereas posterior dislocation typically must be immobilized for 3 to 6 weeks post reduction, multidirectional instability does not require immobilization. Instead, physical therapy should start as soon as possible. In these cases, recurrent dislocation or subluxation that persists after conservative treatment should be referred for possible surgical intervention.⁵

Instability with associated fracture

Fracture concomitant with dislocation most commonly involves the humeral neck, humeral head, greater tuberosity, or the glenoid itself.² Clinical variables that predict a fracture associated with shoulder dislocation include²³:

• first episode of dislocation
• age ≥ 40 years
• fall from higher than 1 flight of stairs
• fight or assault
• motor vehicle crash.

A computed tomography scan with 3-dimensional reconstruction can help characterize associated fracture accurately—including location, size, and displacement—and can play an important role in treatment planning and prognosis in these complicated injuries. Displaced fracture should be referred to an orthopedic surgeon. Nondisplaced fracture of the humeral head or greater tuberosity (FIGURE 11) poses less risk of complications and can be treated conservatively with 6 weeks in an arm sling, followed by physical therapy.²⁴

Summing up

Management of shoulder dislocation must, first, be tailored to the individual and, second, account for several interactive factors—including age, direction of instability, functional demands, risk of recurrence, and associated injuries. In many patients, conservative treatment produces a favorable long-term outcome. Particularly in young, active patients with anterior shoulder instability, most surgeons consider open or arthroscopic reconstruction to be the treatment of choice.^2,18

Continue to: Pre-reduction and post-reduction...

Pre-reduction and post-reduction imaging should be carefully examined for the presence of concomitant injury, which might change the preferred treatment modality appreciably.

Last, communication among emergency department providers, the primary care provider, orthopedist, radiologist, and neurologist is crucial for determining an appropriate patient-centered approach to initial and long-term management.

CORRESPONDENCE
Nata Parnes, MD, Carthage Area Hospital, 3 Bridge Street, Carthage, NY; [email protected]

During the 2020-2021 influenza season, fewer cases of influenza were reported than in any previous year since 1997, when data were first recorded.¹FIGURE 1² shows the dramatic decline in the number of influenza-positive clinical samples reported to the Centers for Disease Control and Prevention (CDC) during the 2020-2021 influenza season compared with the 2019-2020 season. There was only one pediatric death attributed to influenza in 2020-2021, compared with a mean of 177 per year in the previous 3 seasons.

Deaths attributed to pneumonia and influenza were recorded over a recent 5-year period, with COVID-19 added in early mid-2020 (FIGURE 2).¹ Total cumulative deaths for 2020-2021 were extremely high, mostly due to COVID-19. Of the relatively few influenza cases last season, 37.5% were caused by influenza A and 62.5% by influenza B. The extremely low incidence of influenza precludes determining influenza vaccine effectiveness for last season.¹

In addition, other common respiratory pathogens—parainfluenza, adenoviruses, rhinoviruses, enteroviruses, and common coronaviruses—circulated last winter at historic lows.³ All of these historic lows can be attributed to the measures taken to mitigate the effect of the COVID-19 pandemic, including masks, social distancing, closure of certain venues that normally attract large crowds, and the closure of schools with a resulting increase in schooling at home. With the anticipated relaxation of these measures in 2021-2022, we can expect more influenza and other respiratory ailments due to common pathogens.

Updates to influenza vaccine recommendations

At its June 2021 meeting, the Advisory Committee on Immunization Practices (ACIP) approved the influenza vaccine recommendations for the 2021-2022 season.⁴ The central recommendation is unchanged: Everyone ≥ 6 months of age should receive a vaccine unless they have a contraindication. Updates to the previous recommendations include the content of the 2021 vaccines, the specific vaccines that will be available for different age groups, the timing of vaccine administration, advice on co-administration with COVID-19 vaccines, and the list of contraindications and precautions based on vaccine type.⁴

Viral composition of US vaccines for the 2021-22 season

The antigens that will be included in the 2021-2022 influenza vaccines are listed in TABLE 1.⁴ The B strains are the same as last year; the A strains have been updated. The H3N2 strain is the same in all vaccines, but the H1N1 strain differs based on whether the vaccine is egg based or non-egg based. The advantage of non-egg-based vaccines is that the production process does not take as long and can be delayed in an attempt to better reflect the influenza stains in worldwide circulation.

The influenza vaccines expected to be available for the 2021-22 season

TABLE 2⁴ lists the influenza vaccines approved for use in the United States and the ages for which they are approved.⁴ All products for 2021-2022 will be quadrivalent, containing 2 type-A and 2 type-B antigens. The only change in age indications is that cell culture–based inactivated influenza vaccine (ccIIV4) (Flucelvax Quadrivalent) is now approved for use starting at age 2 years; previously it was approved starting at age 4 years.⁴

Timing of vaccination

The onsets and peaks of influenza disease occur at different times each year and can also vary by geographic location. An analysis of 36 influenza seasons starting in 1982 showed that peak activity occurred most frequently in February (15 seasons), followed by December (7 seasons), and January and March (6 seasons each).⁵ Only once did peak activity occur in October and once in November. This information, along with observational studies showing the waning of influenza vaccine effectiveness after 5 to 6 months, especially in the elderly, informed the ACIP decision to modify their recommendation on the timing of vaccination. The recommendation now states that vaccine should be administered by the end of October and that July and August would have been too early, especially for older adults.

Continue to: Children ages 6 months...

Children ages 6 months through 8 years who have not been vaccinated previously require 2 doses separated by at least 4 weeks, and the first dose should be administered early enough to allow for the second by the end of October.⁴ Children who require only 1 dose can also receive the vaccine as soon as it is available, as there is less evidence that vaccine effectiveness wanes in children.

Earlier administration is also recommended for pregnant women in their third trimester. Delaying vaccination in this group could result in postpartum administration of the vaccine, thereby depriving infants of protection against influenza illness during their first 6 months after birth.⁴

Co-administration of influenza and COVID-19 vaccines

Current guidance from the CDC states that COVID-19 vaccines can be co-administered with other vaccines including influenza vaccines.⁶ However, there are no data by which to judge the efficacy of each vaccine in coadministration or the potential for increased adverse reactions. ACIP advises caution on 2 points: (1) physicians should watch for updated guidance as more information becomes available, and (2) there is the potential for increased reactogenicity after co-administration, especially with the more reactogenic influenza vaccines: adjuvanted inactivated influenza vaccine (aIIV4) and high-dose inactivated influenza vaccine (HD-IIV4). Moreover, these vaccines and the co-administered COVID-19 vaccine should be injected into different limbs.

Contraindications and precautions

Serious allergic reactions to influenza vaccines are rare—about 1.3 incidents per million doses administered.⁷ However, a previous severe allergic reaction to a particular vaccine or to any component of the vaccine is a contraindication for use of that vaccine. In addition, a history of severe allergic reaction to any influenza vaccine is a contraindication for all egg-based vaccines.

There are 2 precautions for all influenza vaccines: a concurrent moderate or severe acute illness (with or without fever), and a history of Guillain-Barré syndrome within 6 weeks of receiving any influenza vaccine. An additional precaution for ccIIV4 and recombinant influenza vaccine (RIV4) is a history of severe allergic reaction after administration of any other influenza vaccine. Administration of RIV4 or ccIIV4 to someone with such a history should occur in a medical setting and be supervised by someone who can recognize and treat a severe reaction.

Continue to: Live attenuated influenza vaccine...

Live attenuated influenza vaccine (LAIV) continues to have a considerably longer list of contraindications, which can be found in the published recommendations for 2021-2022.⁸

Final advice

The upcoming influenza season has the potential to be clinically challenging with the possibility of co-existing high rates of both COVID-19 and influenza. Recommend both influenza and COVID-19 vaccination to patients. Also, be sure to encourage and practice other preventive measures such as masking in crowds, frequent hand washing, isolation when sick, respiratory hygiene, and (for physicians) selected prescribing of influenza antiviral medications and meticulous office-based infection control practices.⁹

During the 2020-2021 influenza season, fewer cases of influenza were reported than in any previous year since 1997, when data were first recorded.¹FIGURE 1² shows the dramatic decline in the number of influenza-positive clinical samples reported to the Centers for Disease Control and Prevention (CDC) during the 2020-2021 influenza season compared with the 2019-2020 season. There was only one pediatric death attributed to influenza in 2020-2021, compared with a mean of 177 per year in the previous 3 seasons.

Deaths attributed to pneumonia and influenza were recorded over a recent 5-year period, with COVID-19 added in early mid-2020 (FIGURE 2).¹ Total cumulative deaths for 2020-2021 were extremely high, mostly due to COVID-19. Of the relatively few influenza cases last season, 37.5% were caused by influenza A and 62.5% by influenza B. The extremely low incidence of influenza precludes determining influenza vaccine effectiveness for last season.¹

In addition, other common respiratory pathogens—parainfluenza, adenoviruses, rhinoviruses, enteroviruses, and common coronaviruses—circulated last winter at historic lows.³ All of these historic lows can be attributed to the measures taken to mitigate the effect of the COVID-19 pandemic, including masks, social distancing, closure of certain venues that normally attract large crowds, and the closure of schools with a resulting increase in schooling at home. With the anticipated relaxation of these measures in 2021-2022, we can expect more influenza and other respiratory ailments due to common pathogens.

Updates to influenza vaccine recommendations

At its June 2021 meeting, the Advisory Committee on Immunization Practices (ACIP) approved the influenza vaccine recommendations for the 2021-2022 season.⁴ The central recommendation is unchanged: Everyone ≥ 6 months of age should receive a vaccine unless they have a contraindication. Updates to the previous recommendations include the content of the 2021 vaccines, the specific vaccines that will be available for different age groups, the timing of vaccine administration, advice on co-administration with COVID-19 vaccines, and the list of contraindications and precautions based on vaccine type.⁴

Viral composition of US vaccines for the 2021-22 season

The antigens that will be included in the 2021-2022 influenza vaccines are listed in TABLE 1.⁴ The B strains are the same as last year; the A strains have been updated. The H3N2 strain is the same in all vaccines, but the H1N1 strain differs based on whether the vaccine is egg based or non-egg based. The advantage of non-egg-based vaccines is that the production process does not take as long and can be delayed in an attempt to better reflect the influenza stains in worldwide circulation.

The influenza vaccines expected to be available for the 2021-22 season

TABLE 2⁴ lists the influenza vaccines approved for use in the United States and the ages for which they are approved.⁴ All products for 2021-2022 will be quadrivalent, containing 2 type-A and 2 type-B antigens. The only change in age indications is that cell culture–based inactivated influenza vaccine (ccIIV4) (Flucelvax Quadrivalent) is now approved for use starting at age 2 years; previously it was approved starting at age 4 years.⁴

Timing of vaccination

The onsets and peaks of influenza disease occur at different times each year and can also vary by geographic location. An analysis of 36 influenza seasons starting in 1982 showed that peak activity occurred most frequently in February (15 seasons), followed by December (7 seasons), and January and March (6 seasons each).⁵ Only once did peak activity occur in October and once in November. This information, along with observational studies showing the waning of influenza vaccine effectiveness after 5 to 6 months, especially in the elderly, informed the ACIP decision to modify their recommendation on the timing of vaccination. The recommendation now states that vaccine should be administered by the end of October and that July and August would have been too early, especially for older adults.

Continue to: Children ages 6 months...

Children ages 6 months through 8 years who have not been vaccinated previously require 2 doses separated by at least 4 weeks, and the first dose should be administered early enough to allow for the second by the end of October.⁴ Children who require only 1 dose can also receive the vaccine as soon as it is available, as there is less evidence that vaccine effectiveness wanes in children.

Earlier administration is also recommended for pregnant women in their third trimester. Delaying vaccination in this group could result in postpartum administration of the vaccine, thereby depriving infants of protection against influenza illness during their first 6 months after birth.⁴

Co-administration of influenza and COVID-19 vaccines

Current guidance from the CDC states that COVID-19 vaccines can be co-administered with other vaccines including influenza vaccines.⁶ However, there are no data by which to judge the efficacy of each vaccine in coadministration or the potential for increased adverse reactions. ACIP advises caution on 2 points: (1) physicians should watch for updated guidance as more information becomes available, and (2) there is the potential for increased reactogenicity after co-administration, especially with the more reactogenic influenza vaccines: adjuvanted inactivated influenza vaccine (aIIV4) and high-dose inactivated influenza vaccine (HD-IIV4). Moreover, these vaccines and the co-administered COVID-19 vaccine should be injected into different limbs.

Contraindications and precautions

Serious allergic reactions to influenza vaccines are rare—about 1.3 incidents per million doses administered.⁷ However, a previous severe allergic reaction to a particular vaccine or to any component of the vaccine is a contraindication for use of that vaccine. In addition, a history of severe allergic reaction to any influenza vaccine is a contraindication for all egg-based vaccines.

There are 2 precautions for all influenza vaccines: a concurrent moderate or severe acute illness (with or without fever), and a history of Guillain-Barré syndrome within 6 weeks of receiving any influenza vaccine. An additional precaution for ccIIV4 and recombinant influenza vaccine (RIV4) is a history of severe allergic reaction after administration of any other influenza vaccine. Administration of RIV4 or ccIIV4 to someone with such a history should occur in a medical setting and be supervised by someone who can recognize and treat a severe reaction.

Continue to: Live attenuated influenza vaccine...

Live attenuated influenza vaccine (LAIV) continues to have a considerably longer list of contraindications, which can be found in the published recommendations for 2021-2022.⁸

Final advice

The upcoming influenza season has the potential to be clinically challenging with the possibility of co-existing high rates of both COVID-19 and influenza. Recommend both influenza and COVID-19 vaccination to patients. Also, be sure to encourage and practice other preventive measures such as masking in crowds, frequent hand washing, isolation when sick, respiratory hygiene, and (for physicians) selected prescribing of influenza antiviral medications and meticulous office-based infection control practices.⁹

During the 2020-2021 influenza season, fewer cases of influenza were reported than in any previous year since 1997, when data were first recorded.¹FIGURE 1² shows the dramatic decline in the number of influenza-positive clinical samples reported to the Centers for Disease Control and Prevention (CDC) during the 2020-2021 influenza season compared with the 2019-2020 season. There was only one pediatric death attributed to influenza in 2020-2021, compared with a mean of 177 per year in the previous 3 seasons.

Deaths attributed to pneumonia and influenza were recorded over a recent 5-year period, with COVID-19 added in early mid-2020 (FIGURE 2).¹ Total cumulative deaths for 2020-2021 were extremely high, mostly due to COVID-19. Of the relatively few influenza cases last season, 37.5% were caused by influenza A and 62.5% by influenza B. The extremely low incidence of influenza precludes determining influenza vaccine effectiveness for last season.¹

In addition, other common respiratory pathogens—parainfluenza, adenoviruses, rhinoviruses, enteroviruses, and common coronaviruses—circulated last winter at historic lows.³ All of these historic lows can be attributed to the measures taken to mitigate the effect of the COVID-19 pandemic, including masks, social distancing, closure of certain venues that normally attract large crowds, and the closure of schools with a resulting increase in schooling at home. With the anticipated relaxation of these measures in 2021-2022, we can expect more influenza and other respiratory ailments due to common pathogens.

Updates to influenza vaccine recommendations

At its June 2021 meeting, the Advisory Committee on Immunization Practices (ACIP) approved the influenza vaccine recommendations for the 2021-2022 season.⁴ The central recommendation is unchanged: Everyone ≥ 6 months of age should receive a vaccine unless they have a contraindication. Updates to the previous recommendations include the content of the 2021 vaccines, the specific vaccines that will be available for different age groups, the timing of vaccine administration, advice on co-administration with COVID-19 vaccines, and the list of contraindications and precautions based on vaccine type.⁴

Viral composition of US vaccines for the 2021-22 season

The antigens that will be included in the 2021-2022 influenza vaccines are listed in TABLE 1.⁴ The B strains are the same as last year; the A strains have been updated. The H3N2 strain is the same in all vaccines, but the H1N1 strain differs based on whether the vaccine is egg based or non-egg based. The advantage of non-egg-based vaccines is that the production process does not take as long and can be delayed in an attempt to better reflect the influenza stains in worldwide circulation.

The influenza vaccines expected to be available for the 2021-22 season

TABLE 2⁴ lists the influenza vaccines approved for use in the United States and the ages for which they are approved.⁴ All products for 2021-2022 will be quadrivalent, containing 2 type-A and 2 type-B antigens. The only change in age indications is that cell culture–based inactivated influenza vaccine (ccIIV4) (Flucelvax Quadrivalent) is now approved for use starting at age 2 years; previously it was approved starting at age 4 years.⁴

Timing of vaccination

The onsets and peaks of influenza disease occur at different times each year and can also vary by geographic location. An analysis of 36 influenza seasons starting in 1982 showed that peak activity occurred most frequently in February (15 seasons), followed by December (7 seasons), and January and March (6 seasons each).⁵ Only once did peak activity occur in October and once in November. This information, along with observational studies showing the waning of influenza vaccine effectiveness after 5 to 6 months, especially in the elderly, informed the ACIP decision to modify their recommendation on the timing of vaccination. The recommendation now states that vaccine should be administered by the end of October and that July and August would have been too early, especially for older adults.

Continue to: Children ages 6 months...

Children ages 6 months through 8 years who have not been vaccinated previously require 2 doses separated by at least 4 weeks, and the first dose should be administered early enough to allow for the second by the end of October.⁴ Children who require only 1 dose can also receive the vaccine as soon as it is available, as there is less evidence that vaccine effectiveness wanes in children.

Earlier administration is also recommended for pregnant women in their third trimester. Delaying vaccination in this group could result in postpartum administration of the vaccine, thereby depriving infants of protection against influenza illness during their first 6 months after birth.⁴

Co-administration of influenza and COVID-19 vaccines

Current guidance from the CDC states that COVID-19 vaccines can be co-administered with other vaccines including influenza vaccines.⁶ However, there are no data by which to judge the efficacy of each vaccine in coadministration or the potential for increased adverse reactions. ACIP advises caution on 2 points: (1) physicians should watch for updated guidance as more information becomes available, and (2) there is the potential for increased reactogenicity after co-administration, especially with the more reactogenic influenza vaccines: adjuvanted inactivated influenza vaccine (aIIV4) and high-dose inactivated influenza vaccine (HD-IIV4). Moreover, these vaccines and the co-administered COVID-19 vaccine should be injected into different limbs.

Contraindications and precautions

Serious allergic reactions to influenza vaccines are rare—about 1.3 incidents per million doses administered.⁷ However, a previous severe allergic reaction to a particular vaccine or to any component of the vaccine is a contraindication for use of that vaccine. In addition, a history of severe allergic reaction to any influenza vaccine is a contraindication for all egg-based vaccines.

There are 2 precautions for all influenza vaccines: a concurrent moderate or severe acute illness (with or without fever), and a history of Guillain-Barré syndrome within 6 weeks of receiving any influenza vaccine. An additional precaution for ccIIV4 and recombinant influenza vaccine (RIV4) is a history of severe allergic reaction after administration of any other influenza vaccine. Administration of RIV4 or ccIIV4 to someone with such a history should occur in a medical setting and be supervised by someone who can recognize and treat a severe reaction.

Continue to: Live attenuated influenza vaccine...

Live attenuated influenza vaccine (LAIV) continues to have a considerably longer list of contraindications, which can be found in the published recommendations for 2021-2022.⁸

Final advice

The upcoming influenza season has the potential to be clinically challenging with the possibility of co-existing high rates of both COVID-19 and influenza. Recommend both influenza and COVID-19 vaccination to patients. Also, be sure to encourage and practice other preventive measures such as masking in crowds, frequent hand washing, isolation when sick, respiratory hygiene, and (for physicians) selected prescribing of influenza antiviral medications and meticulous office-based infection control practices.⁹

Our approach to caring for the growing number of community-dwelling US adults ages ≥ 65 years has shifted. Although we continue to manage disease and disability, there is an increasing emphasis on the promotion of healthy aging by optimizing health care needs and quality of life (QOL).

The American Geriatric Society (AGS) uses the term “healthy aging” to reflect a dedication to improving the health, independence, and QOL of older people.¹ The World Health Organization (WHO) defines healthy aging as “the process of developing and maintaining the functional ability that enables well-being in older age.”² Functional ability encompasses capabilities that align with a person’s values, including meeting basic needs; learning, growing, and making independent decisions; being mobile; building and maintaining healthy relationships; and contributing to society.² Similarly, the US Department of Health and Human Services has adopted a multidimensional approach to support people in creating “a productive and meaningful life” as they grow older.³

Numerous theoretical models have emerged from research on aging as a multidimensional construct, as evidenced by a 2016 citation analysis that identified 1755 articles written between 1902 and 2015 relating to “successful aging.”⁴ The analysis revealed 609 definitions operationalized by researchers’ measurement tools (mostly focused on physical function and other health metrics) and 1146 descriptions created by older adults, many emphasizing psychosocial strategies and cultural factors as key to successful aging.⁴

One approach that is likely to be useful for family physicians is the Age-Friendly Health System. This is an initiative of The John A. Hartford Foundation and the Institute for Healthcare Improvement that uses a multidisciplinary approach to create environments that foster inclusivity and address the needs of older people.⁵ Following this guidance, primary care providers use evidence-informed strategies that promote safety and address what matters most to older adults and their family caregivers.

Medicare annual wellness visits provide an opportunity to assess current health status as well as discuss behavior-change and risk-reduction strategies with patients.

The Age-Friendly Health System, as well as AGS and WHO, recognize that there are multiple aspects to well-being as one grows older. By using focused, evidence-based screening, assessments, and interventions, family physicians can best support aging patients in living their most fulfilling lives.

Here we present a review of evidence-based strategies that promote safety and address what matters most to older adults and their family caregivers using a 4-pronged framework, in the style of the Age-Friendly Health System model. However, the literature on healthy aging includes important messages about patient context and lifelong health behaviors, which we capture in an expanded set of thematic guidance. As such, we encourage family physicians to approach healthy aging as follows: (1) monitor health (screening and prevention), (2) promote mobility (physical function), (3) manage mentation (emotional health and cognitive function), and (4) encourage maintenance of social connections (social networks and QOL).

Monitoring health

Leverage Medicare annual wellness visits. A systematic approach is needed to prevent frailty and functional decline, and thus increase the QOL of older adults. To do this, it is important to focus on health promotion and disease prevention, while addressing existing ailments. One method is to leverage the Medicare annual wellness visit (AWV), which provides an opportunity to assess current health status as well as discuss behavior-change and risk-reduction strategies with patients.

Continue to: Although AWVs...

Although AWVs are an opportunity to improve patient outcomes, we are not taking full advantage of them.⁶ While AWVs have gained traction since their introduction in 2011, usage rates among ethnoracial minority groups has lagged behind.⁶ A 2018 cohort study examined reasons for disparate utilization rates among individuals ages ≥ 66 years (N = 14,687).⁷ Researchers found that differences in utilization between ethnoracial groups were explained by socioeconomic factors. Lower education and lower income, as well as rural living, were associated with lower rates of AWV completion.⁷ In addition, having a usual, nonemergent place to obtain medical care served as a powerful predictor of AWV utilization for all groups.⁷

Strategies to increase AWV completion rates among all eligible adults include increasing staff awareness of health literacy challenges and ensuring communication strategies are inclusive by providing printed materials in multiple languages, Braille, or larger typefaces; using accessible vocabulary that does not include medical jargon; and making medical interpreters accessible. In addition, training clinicians about unconscious bias and cultural humility can help foster empathy and awareness of differences in health beliefs and behaviors within diverse patient populations.

A 2019 scoping review of 11 studies (N > 60 million) focused on outcomes from Medicare AWVs for patients ages ≥ 65 years.⁸ This included uptake of preventive services, such as vaccinations or cancer screenings; advice, education, or referrals offered during the AWV; medication use; and hospitalization rates. Overall findings showed that older adults who received a Medicare AWV were more likely to receive referrals for preventive screenings and follow-through on these recommendations compared with those who did not undergo an AWV.⁸

The approach to caring for individuals later in life has shifted from management of disease and disability to promotion of healthy aging by optimizing health care needs and QOL.

Completion rates for vaccines, while remaining low overall, were higher among those who completed an AWV. Additionally, these studies showed improved completion of screenings for breast cancer, bone density, and colon cancer. Several studies in the scoping review supported the use of AWVs as an effective means by which to offer health education and advice related to health promotion and risk reduction, such as diet and lifestyle modifications.⁸ Little evidence exists on long-term outcomes related to AWV completion.⁸

Utilize shared decision-making to determine whether preventive screening makes sense for your patient. Although cancer remains the second leading cause of death among Americans ages ≥ 65 years,⁹ clear screening guidelines for this age group remain elusive.¹⁰ Physicians and patients often are reluctant to stop cancer screening despite lower life expectancy and fewer potential benefits of diagnosis in this population.⁹ Some recent studies reinforce the heterogeneity of the older adult population and further underscore the importance of individual-level decision-making.^11-14 It is important to let older adult patients and their caregivers know about the potential risks of screening tests, especially the possibility that incidental findings may lead to unwarranted additional care or monitoring.⁹

Continue to: Avoid these screening conversation missteps

Avoid these screening conversation missteps. A 2017 qualitative study asked 40 community-dwelling older adults (mean age = 76 years) about their preferences for discussing screening cessation with their physicians.¹³ Three themes emerged.First, they were open to stopping their screenings, especially when suggested by a trusted physician. Second, health status and physical function made sense as decision points, but life expectancy did not. Finally, lengthy discussions with expanded details about risks and benefits were not appreciated, especially if coupled with comments on the limited benefits for those nearing the end of life. When discussing life expectancy, patients preferred phrasing that focused on how the screening was unnecessary because it would not help them live longer.¹³

Ensure that your message is understood—and culturally relevant. Recent studies on lower health literacy among older adults^15,16 and ethnic and racial minorities^17-21—as revealed in the 2003 National Assessment of Adult Literacy²²—might offer clues to patient receptivity to discussions about preventive screening and other health decisions.

One study found a significant correlation between higher self-rated health literacy and higher engagement in health behaviors such as mammography screening, moderate physical activity, and tobacco avoidance.¹⁶ Perceptions of personal control over health status, as well as perceived social standing, also correlated with health literacy score levels.¹⁶ Another study concluded that lower health literacy combined with lower self-­efficacy, cultural beliefs about health topics (eg, diet and exercise), and distrust in the health care system contributed to lower rates of preventive care utilization among ethnocultural minority older adults in Canada, the United Kingdom, the United States, and Australia.¹⁸

Ensuring that easy-to-understand information is equitably shared with older adults of all races and ethnicities is critical. A 2018 study showed that distrust of the health system and cultural issues contributed to the lower incidence of colorectal cancer screenings in Hispanic and Asian American patients ages 50 to 75 years.²¹ Patients whose physicians engaged in “health literate practices” (eg, offering clear explanations of diagnostic plans and asking patients to describe what they understood) were more likely to obtain recommended breast and colorectal cancer screenings.²⁰ In particular, researchers found that non-Hispanic Blacks were nearly twice as likely to follow through on colorectal cancer screening if their physicians engaged in health literate practices.²⁰ In addition, receiving clear instructions from physicians increased the odds of completing breast cancer screening among Hispanic and non-­Hispanic White women.²⁰

Overall, screening information and recommendations should be standardized for all patients. This is particularly important in light of research that found that older non-Hispanic Black patients were less likely than their non-Hispanic White counterparts to receive information from their physicians about colorectal cancer screening.²⁰

Continue to: Mobility

Mobility

Encourage physical activity. Frequent exercise and other forms of physical activity are associated with healthy aging, as shown in a 2017 systematic review and meta-analysis of 23 studies (N = 174,114).²³ Despite considerable heterogeneity between studies in how researchers defined healthy aging and physical activity, they found that adults who incorporate regular movement and exercise into daily life are likely to continue to benefit from it into older age.²³ In addition, a 2016 secondary analysis of data from the InCHIANTI longitudinal aging study concluded that adults ages ≥ 65 years (N = 1149) who had maintained higher physical activity levels throughout adulthood had less physical function decline and reduced rates of mobility disability and premature death compared with those who reported being less active.²⁴

Preserve gait speed (and bolster health) with these activities. Walking speed, or gait, measured on a level surface has been used as a predictor for various aspects of well-being in older age, such as daily function, mobility, independence, falls, mortality, and hospitalization risk.²⁵ Reduced gait speed is also one of the key indicators of functional impairment in older adults.

A 2015 systematic review sought to determine which type of exercise intervention (resistance, coordination, or multimodal training) would be most effective in preserving gait speed in healthy older adults (N = 2495; mean age = 74.2 years).²⁵ While the 42 included studies were deemed to be fairly low quality, the review revealed (with large effect size [0.84]) that a number of exercise modalities might stave off loss of gait speed in older adults. Patients in the resistance training group had the greatest improvement in gait speed (0.11 m/s), followed by those in the coordination training group (0.09 m/s) and the multimodal training group (0.05 m/s).²⁵

Individuals who had maintained higher physical activity levels throughout adulthood had less physical functional decline and reduced rates of mobility disability and premature death.

Finally, muscle mass and strength offer a measure of physical performance and functionality. A 2020 systematic review of 83 studies (N = 108,428) showed that low muscle mass and strength, reduced handgrip strength, and lower physical performance were predictive of reduced capacities in activities of daily living and instrumental activities of daily living.²⁶ It is important to counsel adults to remain active throughout their lives and to include resistance training to maintain muscle mass and strength to preserve their motor function, mobility, independence, and QOL.

Use 1 of these scales to identify frailty. Frailty is a distinct clinical syndrome, in which an individual has low reserves and is highly vulnerable to internal and external stressors. It affects many community-­dwelling older adults. Within the literature, there has been ongoing discussion regarding the definition of frailty²⁷ (TABLE 1^28-31).

Continue to: The Fried Frailty Index...

The Fried Frailty Index defines frailty as a purely physical condition; patients need to exhibit 3 of 5 components (ie, weight loss, exhaustion, weakness, slowness, and low physical activity) to be deemed frail.³¹ The Edmonton Frail Scale is commonly used in geriatric assessments and counts impairments across several domains including physical activity, mood, cognition, and incontinence.^30,32,33 Physicians need to complete a training course prior to its use. Finally, the definition of frailty used by Rockwood et al^{28, 29} was used to develop the Clinical Frailty Scale, which relies on broader criteria that include social and psychological elements in addition to physical elements.The Clinical Frailty Scale uses clinician judgment to evaluate patient-specific domains (eg, comorbidities, functionality, and cognition) and to generate a score ranging from 1 (very fit) to 9 (terminally ill).²⁹ This scale is accessible and easy to implement. As a result, use of this scale has increased during the COVID-19 pandemic. All definitions include a pre-frail state, indicating the dynamic nature of frailty over time.

It is important to identify pre-frail and frail older adults using 1 of these screening tools. Interventions to reverse frailty that can be initiated in the primary care setting include identifying treatable medical conditions, assessing medication appropriateness, providing nutritional advice, and developing an exercise plan.³⁴

Conduct a nutritional assessment; consider this diet. Studies show that nutritional status can predict physical function and frailty risk in older adults. A 2017 systematic review of 19 studies (N = 22,270) of frail adults ages ≥ 65 years found associations related to specific dietary constructs (ie, micronutrients, macronutrients, antioxidants, overall diet quality, and timing of consumption).³⁵ Plant-based diets with higher levels of micronutrients, such as vitamins C and E and beta-carotene, or diets with more protein or macronutrients, regardless of source foods, all resulted in inverse associations with frailty syndrome.³⁵

A 2017 study showed that physical exercise and maintaining good nutritional status may be effective for preventing frailty in ­community-dwelling pre-frail older individuals.³⁶ A 2019 study showed that a combination of muscle strength training and protein supplementation was the most effective intervention to delay or reverse frailty and was easiest to implement in primary care.³⁷ A 2020 meta-analysis of 31 studies (N = 4794) addressing frailty among primary care patients > 60 years showed that interventions using predominantly resistance-based exercise and nutrition supplementation improved frailty status over the control.³⁸ Researchers also found that a comprehensive geriatric assessment or exercise—alone or in combination with nutrition education—reduced physical frailty.

Mentation

Screen and treat cognitive impairments. Cognitive function and autonomy in ­decision-making are important factors in healthy aging. Aspects of mental health (eg, depression and anxiety), sensory impairment (eg, visual and auditory impairment), and mentation issues (eg, delirium, dementia, and related conditions), as well as diet, physical exercise, and mobility, can all impede cognitive functionality. The long-term effects of depression, anxiety,³⁹ sensory deficits,⁴⁰ mobility,⁴¹ diet,⁴² and, ultimately, aging may impact Alzheimer disease (AD). The risk of an AD diagnosis increases with age.³⁹

Continue to: A 2018 prospective cohort study...

A 2018 prospective cohort study using data from the National Alzheimer’s Coordinating Center followed individuals (N = 12,053) who were cognitively asymptomatic at their initial visits to determine who developed clinical signs of AD.³⁹ Survival analysis showed several psychosocial factors—anxiety, sleep disturbances, and depressive episodes of any type (occurring within the past 2 years, clinician verified, lifetime report)—were significantly associated with an eventual AD diagnosis and increased the risk of AD.³⁹ More research is needed to verify the impact of early intervention for these conditions on neurodegenerative disease; however, screening and treating psychosocial factors such as anxiety and depression should be maintained.

For patients ages ≥ 65 years, it is recommended that eye examinations occur every 1 to 2 years.

Researchers evaluated the impact of a dual sensory impairment (DSI) on dementia risk using data from 2051 participants in the Ginkgo Evaluation of Memory Study.⁴⁰ Hearing and visual impairments (defined as DSI when these conditions coexist) or visual impairment alone were significantly associated with increased risk of dementia in older adults. The researchers reported that DSI was significantly associated with a higher risk of all-cause dementia (hazard ratio [HR] = 1.86; 95% CI, 1.25-2.76) and AD (HR = 2.12; 95% CI, 1.34-3.36).⁴⁰ Visual impairment alone was associated with an increased risk of all-cause dementia (HR = 1.32; 95% CI, 1.02-1.71).⁴⁰ These results suggest that screening of DSI or visual impairment earlier in the patient’s lifespan may identify those at high risk of dementia in older adulthood.

The American Academy of Ophthalmology recommends patients with healthy eyes be screened once during their 20s and twice in their 30s; a full examination is recommended by age 40. For patients ages ≥ 65 years, it is recommended that eye examinations occur every 1 to 2 years.⁴³

Diet and mobility play a big role in cognition. Diet⁴³ and exercise^41,42,44 are believed to have an impact on mentation, and recent studies show memory and global cognition could be malleable later in life. A 2015 meta-analysis of 490 treatment arms of 24 randomized controlled studies showed improvement in global cognition with consumption of a Mediterranean diet plus olive oil (effect size [ES] standardized mean difference [SMD] = 0.22; 95% CI, 0.16-0.27) and tai chi exercises (ES SMD = 0.18; 95% CI, 0.06-0.29).⁴² The analysis also found improved memory among participants who consumed the Mediterranean diet/olive oil combination (ES SMD = 0.22; 95% CI, 0.12-0.32) and soy isoflavone supplements (ES SMD = 0.11; 95% CI, 0.04-0.17). Although the ESs are small, they are significant and offer promising evidence that individual choices related to nutrition or exercise may influence cognition and memory.

A 2018 systematic review found that all domains of cognition showed improvement with 45 to 60 minutes of moderate-to-vigorous physical exercise.⁴⁴ Attention, executive function, memory, and working memory showed significant increases, whereas global cognition improvements were not statistically significant.⁴⁴ A 2016 meta-analysis of 26 studies (N = 26,355) found a positive association between an objective mobility measure (gait, lower-extremity function, and balance) and cognitive function (global, executive function, memory, and processing speed) in older adults.⁴¹ These results highlight that diet, mobility, and physical exercise impact cognitive functioning.

Continue to: Maintaining social connections

Maintaining social connections

Social isolation and loneliness—compounded by a pandemic. The US Department of Health and Human Services notes that “community connections” are among the key factors required for healthy aging.³ Similarly, the WHO definition of healthy aging considers whether individuals can build and sustain relationships with other people and find ways to engender their personal values through these connections.²

Prioritizing interventions that identify and connect isolated older adults to social support may increase survivability.

As people age, their social connections often decrease due to the death of friends and family, shifts in living arrangements, loss of mobility or eyesight (and thus self-­transport), and the onset or increased acuity of illness or chronic conditions.⁴⁵ This has been exacerbated by the COVID-19 pandemic, which has spurred shelter-in-place and stay-at-home orders along with recommendations for physical distancing (also known as social distancing), especially for older adults who are at higher risk.⁴⁶ Smith et al⁴⁷ calls this the COVID-19 Social Connectivity Paradox, in which older adults limit their interactions with others to protect their physical health and reduce their risk of contracting the virus, but as a result they may undermine their psychosocial health by placing themselves at risk of social isolation and loneliness.⁴⁷

The double threat. Social isolation and loneliness have been shown to negatively impact physical health and well-being, resulting in an increased risk of early death^48-50; higher likelihood of specific diagnoses, including dementia and cardiovascular conditions^48,50; and more frequent use of health care services.⁵⁰ These concepts, while related, represent different mechanisms for negative health outcomes. Social isolation is an objective condition when one has a lack of opportunities for interaction with other people; loneliness refers to the emotional disconnect one feels when separated from others. Few studies have compared outcomes between these concepts, but in those that have, social isolation appears to be more strongly associated with early death.^48-50

A 2013 observational study using data from the English Longitudinal Study on Aging found that both social isolation and loneliness were associated with increased mortality among men and women ages ≥ 52 years (N = 6500).⁴⁸ However, when studied independently, loneliness was not found to be a significant risk factor. In contrast, social isolation significantly impacted mortality risk, even after adjusting for demographic factors and baseline health status.⁴⁸ These findings are supported by a 2018 cohort study of individuals (N = 479,054) with a history of an acute cardiovascular event that concluded social isolation was a predictor of mortality, whereas loneliness was not.⁵⁰

A large 2015 meta-analysis (70 studies, N = 3,407,134) of mortality causes among community-dwelling older adults (average age, 66) confirmed that both objective measures of isolation, as well as subjective measures (such as feelings of loneliness or living alone), have a significant predictive effect in longer-term studies. Each measure shows an approximately 30% increase in the likelihood of death after an average of 7 years.⁴⁹

Continue to: Health care remains a connection point

The report offered information about potential avenues for intervention by primary care professionals beyond screening, such as participating in research studies that investigate screening tools and multisystem interventions; social prescribing (linking patients to embedded social work services or ­community-based organizations); referring patients to support groups; initiating ­cognitive-based therapy or other behavioral health interventions; or recommending mindfulness practices.⁵¹ However, most of the cited intervention studies were not specific to primary care settings and contained poor-quality evidence related to efficacy.

Isolation creates a greater reliance on health services due to a lack of a social support system, while a feeling of emotional disconnection (loneliness) seems to be a barrier to accessing care. A 2017 cohort study linking data from the Health and Retirement Study and Medicare claims revealed that social isolation predicts higher annual health expenditures (> $1600 per beneficiary) driven by hospitalization and skilled nursing facility usage, along with greater mortality, whereas individuals who are lonely result in reduced costs (a reduction of $770 annually) due to lower usage of inpatient and outpatient services.⁵² Prioritizing interventions that identify and connect isolated older adults to social support, therefore, may increase survivability by ensuring they have access to resources and health care interventions when needed.

Assessing and treating vision and hearing impairments and mental health issues may guard against losses in cognition.

In addition, these findings underscore the importance of looking at quality—not just quantity—of older adults’ social connections. A number of validated screening tools exist for social isolation and loneliness (TABLE 2^53-59); however, concerns exist about assessing risk using a unidimensional tool for a complex concern,⁴⁷ as well as identifying a problem without having evidence-based interventions to offer as solutions.^47,51 Until future studies resolve these concerns, leveraging the physician-patient relationship to broach these difficult subjects may help normalize the issues and create safe spaces to identify individuals who are at risk.

QOL is key to healthy aging. As Kusumastuti et al⁴ state, “successful ageing lies in the eyes of the beholder.” A 2019 systematic review of 48 qualitative studies revealed that community-dwelling older adults ages ≥ 50 years in 11 countries (N > 4175) perceive well-being by considering QOL within 9 domains: health perception, autonomy, role and activity, relationships, emotional comfort, attitude and adaptation, spirituality, financial security, and home and neighborhood.⁶⁰ Researchers found that as engagement in any one of these domains declines, older adults may shift their definition of health toward their remaining abilities.⁶⁰ This offers an explanation as to why patients might rate their health status much higher than their physicians do: older adults tend to have a more holistic concept of health.

Continue to: Take a multidimensional approach to healthy aging

Take a multidimensional approach to healthy aging

Although we have separately examined each of the 4 components of managing healthy aging in a community-dwelling adult, applying a multidimensional approach is most effective. Increasing use of the Medicare AWV provides an opportunity to assess patient health status, determine care preferences, and improve follow-through on preventive screening. It is also important to encourage older adults to engage in regular physical activity—especially muscle-strengthening exercises—and to discuss nutrition and caloric intake to prevent frailty and functional decline.

Assessing and treating vision and hearing impairments and mental health issues, including anxiety and depression, may guard against losses in cognition. When speaking with older adult patients about their social connections, consider asking not only about frequency of contact and access to resources such as food and transportation, but also about whether they are finding ways to bring their own values into those relationships to bolster their QOL. This guidance also may be useful for primary care practices and health care networks when planning future quality-improvement initiatives.

Additional research is needed to support the evidence base for aligning older adult preferences in health care interventions, such as preventive screenings. Also, clinical decision-making requires more clarity about the efficacy of specific diet and exercise interventions for older adults; the impact of early intervention for depression, anxiety, and sleep disorders on neurodegenerative disease; whether loneliness predicts mortality; and how health care delivery systems can be effective at building social connectivity.

Initiating health education, screening, and prevention throughout the patient’s lifespan can promote healthy aging outcomes later in life.

For now, it is essential to recognize that initiating health education, screening, and prevention throughout the patient’s lifespan can promote healthy aging outcomes. As family physicians, it is important to capitalize on longitudinal relationships with patients and begin educating younger patients using this multidimensional framework to promote living “a productive and meaningful life”at any age.³

CORRESPONDENCE

Lynn M. Wilson, DO, 707 Hamilton Street, 8th floor, Department of Family Medicine, Lehigh Valley Health Network, Allentown, PA 18101; [email protected]

Our approach to caring for the growing number of community-dwelling US adults ages ≥ 65 years has shifted. Although we continue to manage disease and disability, there is an increasing emphasis on the promotion of healthy aging by optimizing health care needs and quality of life (QOL).

The American Geriatric Society (AGS) uses the term “healthy aging” to reflect a dedication to improving the health, independence, and QOL of older people.¹ The World Health Organization (WHO) defines healthy aging as “the process of developing and maintaining the functional ability that enables well-being in older age.”² Functional ability encompasses capabilities that align with a person’s values, including meeting basic needs; learning, growing, and making independent decisions; being mobile; building and maintaining healthy relationships; and contributing to society.² Similarly, the US Department of Health and Human Services has adopted a multidimensional approach to support people in creating “a productive and meaningful life” as they grow older.³

Numerous theoretical models have emerged from research on aging as a multidimensional construct, as evidenced by a 2016 citation analysis that identified 1755 articles written between 1902 and 2015 relating to “successful aging.”⁴ The analysis revealed 609 definitions operationalized by researchers’ measurement tools (mostly focused on physical function and other health metrics) and 1146 descriptions created by older adults, many emphasizing psychosocial strategies and cultural factors as key to successful aging.⁴

One approach that is likely to be useful for family physicians is the Age-Friendly Health System. This is an initiative of The John A. Hartford Foundation and the Institute for Healthcare Improvement that uses a multidisciplinary approach to create environments that foster inclusivity and address the needs of older people.⁵ Following this guidance, primary care providers use evidence-informed strategies that promote safety and address what matters most to older adults and their family caregivers.

Medicare annual wellness visits provide an opportunity to assess current health status as well as discuss behavior-change and risk-reduction strategies with patients.

The Age-Friendly Health System, as well as AGS and WHO, recognize that there are multiple aspects to well-being as one grows older. By using focused, evidence-based screening, assessments, and interventions, family physicians can best support aging patients in living their most fulfilling lives.

Here we present a review of evidence-based strategies that promote safety and address what matters most to older adults and their family caregivers using a 4-pronged framework, in the style of the Age-Friendly Health System model. However, the literature on healthy aging includes important messages about patient context and lifelong health behaviors, which we capture in an expanded set of thematic guidance. As such, we encourage family physicians to approach healthy aging as follows: (1) monitor health (screening and prevention), (2) promote mobility (physical function), (3) manage mentation (emotional health and cognitive function), and (4) encourage maintenance of social connections (social networks and QOL).

Monitoring health

Leverage Medicare annual wellness visits. A systematic approach is needed to prevent frailty and functional decline, and thus increase the QOL of older adults. To do this, it is important to focus on health promotion and disease prevention, while addressing existing ailments. One method is to leverage the Medicare annual wellness visit (AWV), which provides an opportunity to assess current health status as well as discuss behavior-change and risk-reduction strategies with patients.

Continue to: Although AWVs...

Although AWVs are an opportunity to improve patient outcomes, we are not taking full advantage of them.⁶ While AWVs have gained traction since their introduction in 2011, usage rates among ethnoracial minority groups has lagged behind.⁶ A 2018 cohort study examined reasons for disparate utilization rates among individuals ages ≥ 66 years (N = 14,687).⁷ Researchers found that differences in utilization between ethnoracial groups were explained by socioeconomic factors. Lower education and lower income, as well as rural living, were associated with lower rates of AWV completion.⁷ In addition, having a usual, nonemergent place to obtain medical care served as a powerful predictor of AWV utilization for all groups.⁷

Strategies to increase AWV completion rates among all eligible adults include increasing staff awareness of health literacy challenges and ensuring communication strategies are inclusive by providing printed materials in multiple languages, Braille, or larger typefaces; using accessible vocabulary that does not include medical jargon; and making medical interpreters accessible. In addition, training clinicians about unconscious bias and cultural humility can help foster empathy and awareness of differences in health beliefs and behaviors within diverse patient populations.

A 2019 scoping review of 11 studies (N > 60 million) focused on outcomes from Medicare AWVs for patients ages ≥ 65 years.⁸ This included uptake of preventive services, such as vaccinations or cancer screenings; advice, education, or referrals offered during the AWV; medication use; and hospitalization rates. Overall findings showed that older adults who received a Medicare AWV were more likely to receive referrals for preventive screenings and follow-through on these recommendations compared with those who did not undergo an AWV.⁸

The approach to caring for individuals later in life has shifted from management of disease and disability to promotion of healthy aging by optimizing health care needs and QOL.

Completion rates for vaccines, while remaining low overall, were higher among those who completed an AWV. Additionally, these studies showed improved completion of screenings for breast cancer, bone density, and colon cancer. Several studies in the scoping review supported the use of AWVs as an effective means by which to offer health education and advice related to health promotion and risk reduction, such as diet and lifestyle modifications.⁸ Little evidence exists on long-term outcomes related to AWV completion.⁸

Utilize shared decision-making to determine whether preventive screening makes sense for your patient. Although cancer remains the second leading cause of death among Americans ages ≥ 65 years,⁹ clear screening guidelines for this age group remain elusive.¹⁰ Physicians and patients often are reluctant to stop cancer screening despite lower life expectancy and fewer potential benefits of diagnosis in this population.⁹ Some recent studies reinforce the heterogeneity of the older adult population and further underscore the importance of individual-level decision-making.^11-14 It is important to let older adult patients and their caregivers know about the potential risks of screening tests, especially the possibility that incidental findings may lead to unwarranted additional care or monitoring.⁹

Continue to: Avoid these screening conversation missteps

Avoid these screening conversation missteps. A 2017 qualitative study asked 40 community-dwelling older adults (mean age = 76 years) about their preferences for discussing screening cessation with their physicians.¹³ Three themes emerged.First, they were open to stopping their screenings, especially when suggested by a trusted physician. Second, health status and physical function made sense as decision points, but life expectancy did not. Finally, lengthy discussions with expanded details about risks and benefits were not appreciated, especially if coupled with comments on the limited benefits for those nearing the end of life. When discussing life expectancy, patients preferred phrasing that focused on how the screening was unnecessary because it would not help them live longer.¹³

Ensure that your message is understood—and culturally relevant. Recent studies on lower health literacy among older adults^15,16 and ethnic and racial minorities^17-21—as revealed in the 2003 National Assessment of Adult Literacy²²—might offer clues to patient receptivity to discussions about preventive screening and other health decisions.

One study found a significant correlation between higher self-rated health literacy and higher engagement in health behaviors such as mammography screening, moderate physical activity, and tobacco avoidance.¹⁶ Perceptions of personal control over health status, as well as perceived social standing, also correlated with health literacy score levels.¹⁶ Another study concluded that lower health literacy combined with lower self-­efficacy, cultural beliefs about health topics (eg, diet and exercise), and distrust in the health care system contributed to lower rates of preventive care utilization among ethnocultural minority older adults in Canada, the United Kingdom, the United States, and Australia.¹⁸

Ensuring that easy-to-understand information is equitably shared with older adults of all races and ethnicities is critical. A 2018 study showed that distrust of the health system and cultural issues contributed to the lower incidence of colorectal cancer screenings in Hispanic and Asian American patients ages 50 to 75 years.²¹ Patients whose physicians engaged in “health literate practices” (eg, offering clear explanations of diagnostic plans and asking patients to describe what they understood) were more likely to obtain recommended breast and colorectal cancer screenings.²⁰ In particular, researchers found that non-Hispanic Blacks were nearly twice as likely to follow through on colorectal cancer screening if their physicians engaged in health literate practices.²⁰ In addition, receiving clear instructions from physicians increased the odds of completing breast cancer screening among Hispanic and non-­Hispanic White women.²⁰

Overall, screening information and recommendations should be standardized for all patients. This is particularly important in light of research that found that older non-Hispanic Black patients were less likely than their non-Hispanic White counterparts to receive information from their physicians about colorectal cancer screening.²⁰

Continue to: Mobility

Mobility

Encourage physical activity. Frequent exercise and other forms of physical activity are associated with healthy aging, as shown in a 2017 systematic review and meta-analysis of 23 studies (N = 174,114).²³ Despite considerable heterogeneity between studies in how researchers defined healthy aging and physical activity, they found that adults who incorporate regular movement and exercise into daily life are likely to continue to benefit from it into older age.²³ In addition, a 2016 secondary analysis of data from the InCHIANTI longitudinal aging study concluded that adults ages ≥ 65 years (N = 1149) who had maintained higher physical activity levels throughout adulthood had less physical function decline and reduced rates of mobility disability and premature death compared with those who reported being less active.²⁴

Preserve gait speed (and bolster health) with these activities. Walking speed, or gait, measured on a level surface has been used as a predictor for various aspects of well-being in older age, such as daily function, mobility, independence, falls, mortality, and hospitalization risk.²⁵ Reduced gait speed is also one of the key indicators of functional impairment in older adults.

A 2015 systematic review sought to determine which type of exercise intervention (resistance, coordination, or multimodal training) would be most effective in preserving gait speed in healthy older adults (N = 2495; mean age = 74.2 years).²⁵ While the 42 included studies were deemed to be fairly low quality, the review revealed (with large effect size [0.84]) that a number of exercise modalities might stave off loss of gait speed in older adults. Patients in the resistance training group had the greatest improvement in gait speed (0.11 m/s), followed by those in the coordination training group (0.09 m/s) and the multimodal training group (0.05 m/s).²⁵

Individuals who had maintained higher physical activity levels throughout adulthood had less physical functional decline and reduced rates of mobility disability and premature death.

Finally, muscle mass and strength offer a measure of physical performance and functionality. A 2020 systematic review of 83 studies (N = 108,428) showed that low muscle mass and strength, reduced handgrip strength, and lower physical performance were predictive of reduced capacities in activities of daily living and instrumental activities of daily living.²⁶ It is important to counsel adults to remain active throughout their lives and to include resistance training to maintain muscle mass and strength to preserve their motor function, mobility, independence, and QOL.

Use 1 of these scales to identify frailty. Frailty is a distinct clinical syndrome, in which an individual has low reserves and is highly vulnerable to internal and external stressors. It affects many community-­dwelling older adults. Within the literature, there has been ongoing discussion regarding the definition of frailty²⁷ (TABLE 1^28-31).

Continue to: The Fried Frailty Index...

The Fried Frailty Index defines frailty as a purely physical condition; patients need to exhibit 3 of 5 components (ie, weight loss, exhaustion, weakness, slowness, and low physical activity) to be deemed frail.³¹ The Edmonton Frail Scale is commonly used in geriatric assessments and counts impairments across several domains including physical activity, mood, cognition, and incontinence.^30,32,33 Physicians need to complete a training course prior to its use. Finally, the definition of frailty used by Rockwood et al^{28, 29} was used to develop the Clinical Frailty Scale, which relies on broader criteria that include social and psychological elements in addition to physical elements.The Clinical Frailty Scale uses clinician judgment to evaluate patient-specific domains (eg, comorbidities, functionality, and cognition) and to generate a score ranging from 1 (very fit) to 9 (terminally ill).²⁹ This scale is accessible and easy to implement. As a result, use of this scale has increased during the COVID-19 pandemic. All definitions include a pre-frail state, indicating the dynamic nature of frailty over time.

It is important to identify pre-frail and frail older adults using 1 of these screening tools. Interventions to reverse frailty that can be initiated in the primary care setting include identifying treatable medical conditions, assessing medication appropriateness, providing nutritional advice, and developing an exercise plan.³⁴

Conduct a nutritional assessment; consider this diet. Studies show that nutritional status can predict physical function and frailty risk in older adults. A 2017 systematic review of 19 studies (N = 22,270) of frail adults ages ≥ 65 years found associations related to specific dietary constructs (ie, micronutrients, macronutrients, antioxidants, overall diet quality, and timing of consumption).³⁵ Plant-based diets with higher levels of micronutrients, such as vitamins C and E and beta-carotene, or diets with more protein or macronutrients, regardless of source foods, all resulted in inverse associations with frailty syndrome.³⁵

A 2017 study showed that physical exercise and maintaining good nutritional status may be effective for preventing frailty in ­community-dwelling pre-frail older individuals.³⁶ A 2019 study showed that a combination of muscle strength training and protein supplementation was the most effective intervention to delay or reverse frailty and was easiest to implement in primary care.³⁷ A 2020 meta-analysis of 31 studies (N = 4794) addressing frailty among primary care patients > 60 years showed that interventions using predominantly resistance-based exercise and nutrition supplementation improved frailty status over the control.³⁸ Researchers also found that a comprehensive geriatric assessment or exercise—alone or in combination with nutrition education—reduced physical frailty.

Mentation

Screen and treat cognitive impairments. Cognitive function and autonomy in ­decision-making are important factors in healthy aging. Aspects of mental health (eg, depression and anxiety), sensory impairment (eg, visual and auditory impairment), and mentation issues (eg, delirium, dementia, and related conditions), as well as diet, physical exercise, and mobility, can all impede cognitive functionality. The long-term effects of depression, anxiety,³⁹ sensory deficits,⁴⁰ mobility,⁴¹ diet,⁴² and, ultimately, aging may impact Alzheimer disease (AD). The risk of an AD diagnosis increases with age.³⁹

Continue to: A 2018 prospective cohort study...

A 2018 prospective cohort study using data from the National Alzheimer’s Coordinating Center followed individuals (N = 12,053) who were cognitively asymptomatic at their initial visits to determine who developed clinical signs of AD.³⁹ Survival analysis showed several psychosocial factors—anxiety, sleep disturbances, and depressive episodes of any type (occurring within the past 2 years, clinician verified, lifetime report)—were significantly associated with an eventual AD diagnosis and increased the risk of AD.³⁹ More research is needed to verify the impact of early intervention for these conditions on neurodegenerative disease; however, screening and treating psychosocial factors such as anxiety and depression should be maintained.

For patients ages ≥ 65 years, it is recommended that eye examinations occur every 1 to 2 years.

Researchers evaluated the impact of a dual sensory impairment (DSI) on dementia risk using data from 2051 participants in the Ginkgo Evaluation of Memory Study.⁴⁰ Hearing and visual impairments (defined as DSI when these conditions coexist) or visual impairment alone were significantly associated with increased risk of dementia in older adults. The researchers reported that DSI was significantly associated with a higher risk of all-cause dementia (hazard ratio [HR] = 1.86; 95% CI, 1.25-2.76) and AD (HR = 2.12; 95% CI, 1.34-3.36).⁴⁰ Visual impairment alone was associated with an increased risk of all-cause dementia (HR = 1.32; 95% CI, 1.02-1.71).⁴⁰ These results suggest that screening of DSI or visual impairment earlier in the patient’s lifespan may identify those at high risk of dementia in older adulthood.

The American Academy of Ophthalmology recommends patients with healthy eyes be screened once during their 20s and twice in their 30s; a full examination is recommended by age 40. For patients ages ≥ 65 years, it is recommended that eye examinations occur every 1 to 2 years.⁴³

Diet and mobility play a big role in cognition. Diet⁴³ and exercise^41,42,44 are believed to have an impact on mentation, and recent studies show memory and global cognition could be malleable later in life. A 2015 meta-analysis of 490 treatment arms of 24 randomized controlled studies showed improvement in global cognition with consumption of a Mediterranean diet plus olive oil (effect size [ES] standardized mean difference [SMD] = 0.22; 95% CI, 0.16-0.27) and tai chi exercises (ES SMD = 0.18; 95% CI, 0.06-0.29).⁴² The analysis also found improved memory among participants who consumed the Mediterranean diet/olive oil combination (ES SMD = 0.22; 95% CI, 0.12-0.32) and soy isoflavone supplements (ES SMD = 0.11; 95% CI, 0.04-0.17). Although the ESs are small, they are significant and offer promising evidence that individual choices related to nutrition or exercise may influence cognition and memory.

A 2018 systematic review found that all domains of cognition showed improvement with 45 to 60 minutes of moderate-to-vigorous physical exercise.⁴⁴ Attention, executive function, memory, and working memory showed significant increases, whereas global cognition improvements were not statistically significant.⁴⁴ A 2016 meta-analysis of 26 studies (N = 26,355) found a positive association between an objective mobility measure (gait, lower-extremity function, and balance) and cognitive function (global, executive function, memory, and processing speed) in older adults.⁴¹ These results highlight that diet, mobility, and physical exercise impact cognitive functioning.

Continue to: Maintaining social connections

Maintaining social connections

Social isolation and loneliness—compounded by a pandemic. The US Department of Health and Human Services notes that “community connections” are among the key factors required for healthy aging.³ Similarly, the WHO definition of healthy aging considers whether individuals can build and sustain relationships with other people and find ways to engender their personal values through these connections.²

Prioritizing interventions that identify and connect isolated older adults to social support may increase survivability.

As people age, their social connections often decrease due to the death of friends and family, shifts in living arrangements, loss of mobility or eyesight (and thus self-­transport), and the onset or increased acuity of illness or chronic conditions.⁴⁵ This has been exacerbated by the COVID-19 pandemic, which has spurred shelter-in-place and stay-at-home orders along with recommendations for physical distancing (also known as social distancing), especially for older adults who are at higher risk.⁴⁶ Smith et al⁴⁷ calls this the COVID-19 Social Connectivity Paradox, in which older adults limit their interactions with others to protect their physical health and reduce their risk of contracting the virus, but as a result they may undermine their psychosocial health by placing themselves at risk of social isolation and loneliness.⁴⁷

The double threat. Social isolation and loneliness have been shown to negatively impact physical health and well-being, resulting in an increased risk of early death^48-50; higher likelihood of specific diagnoses, including dementia and cardiovascular conditions^48,50; and more frequent use of health care services.⁵⁰ These concepts, while related, represent different mechanisms for negative health outcomes. Social isolation is an objective condition when one has a lack of opportunities for interaction with other people; loneliness refers to the emotional disconnect one feels when separated from others. Few studies have compared outcomes between these concepts, but in those that have, social isolation appears to be more strongly associated with early death.^48-50

A 2013 observational study using data from the English Longitudinal Study on Aging found that both social isolation and loneliness were associated with increased mortality among men and women ages ≥ 52 years (N = 6500).⁴⁸ However, when studied independently, loneliness was not found to be a significant risk factor. In contrast, social isolation significantly impacted mortality risk, even after adjusting for demographic factors and baseline health status.⁴⁸ These findings are supported by a 2018 cohort study of individuals (N = 479,054) with a history of an acute cardiovascular event that concluded social isolation was a predictor of mortality, whereas loneliness was not.⁵⁰

A large 2015 meta-analysis (70 studies, N = 3,407,134) of mortality causes among community-dwelling older adults (average age, 66) confirmed that both objective measures of isolation, as well as subjective measures (such as feelings of loneliness or living alone), have a significant predictive effect in longer-term studies. Each measure shows an approximately 30% increase in the likelihood of death after an average of 7 years.⁴⁹

Continue to: Health care remains a connection point

The report offered information about potential avenues for intervention by primary care professionals beyond screening, such as participating in research studies that investigate screening tools and multisystem interventions; social prescribing (linking patients to embedded social work services or ­community-based organizations); referring patients to support groups; initiating ­cognitive-based therapy or other behavioral health interventions; or recommending mindfulness practices.⁵¹ However, most of the cited intervention studies were not specific to primary care settings and contained poor-quality evidence related to efficacy.

Isolation creates a greater reliance on health services due to a lack of a social support system, while a feeling of emotional disconnection (loneliness) seems to be a barrier to accessing care. A 2017 cohort study linking data from the Health and Retirement Study and Medicare claims revealed that social isolation predicts higher annual health expenditures (> $1600 per beneficiary) driven by hospitalization and skilled nursing facility usage, along with greater mortality, whereas individuals who are lonely result in reduced costs (a reduction of $770 annually) due to lower usage of inpatient and outpatient services.⁵² Prioritizing interventions that identify and connect isolated older adults to social support, therefore, may increase survivability by ensuring they have access to resources and health care interventions when needed.

Assessing and treating vision and hearing impairments and mental health issues may guard against losses in cognition.

In addition, these findings underscore the importance of looking at quality—not just quantity—of older adults’ social connections. A number of validated screening tools exist for social isolation and loneliness (TABLE 2^53-59); however, concerns exist about assessing risk using a unidimensional tool for a complex concern,⁴⁷ as well as identifying a problem without having evidence-based interventions to offer as solutions.^47,51 Until future studies resolve these concerns, leveraging the physician-patient relationship to broach these difficult subjects may help normalize the issues and create safe spaces to identify individuals who are at risk.

QOL is key to healthy aging. As Kusumastuti et al⁴ state, “successful ageing lies in the eyes of the beholder.” A 2019 systematic review of 48 qualitative studies revealed that community-dwelling older adults ages ≥ 50 years in 11 countries (N > 4175) perceive well-being by considering QOL within 9 domains: health perception, autonomy, role and activity, relationships, emotional comfort, attitude and adaptation, spirituality, financial security, and home and neighborhood.⁶⁰ Researchers found that as engagement in any one of these domains declines, older adults may shift their definition of health toward their remaining abilities.⁶⁰ This offers an explanation as to why patients might rate their health status much higher than their physicians do: older adults tend to have a more holistic concept of health.

Continue to: Take a multidimensional approach to healthy aging

Take a multidimensional approach to healthy aging

Although we have separately examined each of the 4 components of managing healthy aging in a community-dwelling adult, applying a multidimensional approach is most effective. Increasing use of the Medicare AWV provides an opportunity to assess patient health status, determine care preferences, and improve follow-through on preventive screening. It is also important to encourage older adults to engage in regular physical activity—especially muscle-strengthening exercises—and to discuss nutrition and caloric intake to prevent frailty and functional decline.

Assessing and treating vision and hearing impairments and mental health issues, including anxiety and depression, may guard against losses in cognition. When speaking with older adult patients about their social connections, consider asking not only about frequency of contact and access to resources such as food and transportation, but also about whether they are finding ways to bring their own values into those relationships to bolster their QOL. This guidance also may be useful for primary care practices and health care networks when planning future quality-improvement initiatives.

Additional research is needed to support the evidence base for aligning older adult preferences in health care interventions, such as preventive screenings. Also, clinical decision-making requires more clarity about the efficacy of specific diet and exercise interventions for older adults; the impact of early intervention for depression, anxiety, and sleep disorders on neurodegenerative disease; whether loneliness predicts mortality; and how health care delivery systems can be effective at building social connectivity.

Initiating health education, screening, and prevention throughout the patient’s lifespan can promote healthy aging outcomes later in life.

For now, it is essential to recognize that initiating health education, screening, and prevention throughout the patient’s lifespan can promote healthy aging outcomes. As family physicians, it is important to capitalize on longitudinal relationships with patients and begin educating younger patients using this multidimensional framework to promote living “a productive and meaningful life”at any age.³

CORRESPONDENCE

Lynn M. Wilson, DO, 707 Hamilton Street, 8th floor, Department of Family Medicine, Lehigh Valley Health Network, Allentown, PA 18101; [email protected]

Our approach to caring for the growing number of community-dwelling US adults ages ≥ 65 years has shifted. Although we continue to manage disease and disability, there is an increasing emphasis on the promotion of healthy aging by optimizing health care needs and quality of life (QOL).

The American Geriatric Society (AGS) uses the term “healthy aging” to reflect a dedication to improving the health, independence, and QOL of older people.¹ The World Health Organization (WHO) defines healthy aging as “the process of developing and maintaining the functional ability that enables well-being in older age.”² Functional ability encompasses capabilities that align with a person’s values, including meeting basic needs; learning, growing, and making independent decisions; being mobile; building and maintaining healthy relationships; and contributing to society.² Similarly, the US Department of Health and Human Services has adopted a multidimensional approach to support people in creating “a productive and meaningful life” as they grow older.³

Numerous theoretical models have emerged from research on aging as a multidimensional construct, as evidenced by a 2016 citation analysis that identified 1755 articles written between 1902 and 2015 relating to “successful aging.”⁴ The analysis revealed 609 definitions operationalized by researchers’ measurement tools (mostly focused on physical function and other health metrics) and 1146 descriptions created by older adults, many emphasizing psychosocial strategies and cultural factors as key to successful aging.⁴

One approach that is likely to be useful for family physicians is the Age-Friendly Health System. This is an initiative of The John A. Hartford Foundation and the Institute for Healthcare Improvement that uses a multidisciplinary approach to create environments that foster inclusivity and address the needs of older people.⁵ Following this guidance, primary care providers use evidence-informed strategies that promote safety and address what matters most to older adults and their family caregivers.

Medicare annual wellness visits provide an opportunity to assess current health status as well as discuss behavior-change and risk-reduction strategies with patients.

The Age-Friendly Health System, as well as AGS and WHO, recognize that there are multiple aspects to well-being as one grows older. By using focused, evidence-based screening, assessments, and interventions, family physicians can best support aging patients in living their most fulfilling lives.

Here we present a review of evidence-based strategies that promote safety and address what matters most to older adults and their family caregivers using a 4-pronged framework, in the style of the Age-Friendly Health System model. However, the literature on healthy aging includes important messages about patient context and lifelong health behaviors, which we capture in an expanded set of thematic guidance. As such, we encourage family physicians to approach healthy aging as follows: (1) monitor health (screening and prevention), (2) promote mobility (physical function), (3) manage mentation (emotional health and cognitive function), and (4) encourage maintenance of social connections (social networks and QOL).

Monitoring health

Leverage Medicare annual wellness visits. A systematic approach is needed to prevent frailty and functional decline, and thus increase the QOL of older adults. To do this, it is important to focus on health promotion and disease prevention, while addressing existing ailments. One method is to leverage the Medicare annual wellness visit (AWV), which provides an opportunity to assess current health status as well as discuss behavior-change and risk-reduction strategies with patients.

Continue to: Although AWVs...

Although AWVs are an opportunity to improve patient outcomes, we are not taking full advantage of them.⁶ While AWVs have gained traction since their introduction in 2011, usage rates among ethnoracial minority groups has lagged behind.⁶ A 2018 cohort study examined reasons for disparate utilization rates among individuals ages ≥ 66 years (N = 14,687).⁷ Researchers found that differences in utilization between ethnoracial groups were explained by socioeconomic factors. Lower education and lower income, as well as rural living, were associated with lower rates of AWV completion.⁷ In addition, having a usual, nonemergent place to obtain medical care served as a powerful predictor of AWV utilization for all groups.⁷

Strategies to increase AWV completion rates among all eligible adults include increasing staff awareness of health literacy challenges and ensuring communication strategies are inclusive by providing printed materials in multiple languages, Braille, or larger typefaces; using accessible vocabulary that does not include medical jargon; and making medical interpreters accessible. In addition, training clinicians about unconscious bias and cultural humility can help foster empathy and awareness of differences in health beliefs and behaviors within diverse patient populations.

A 2019 scoping review of 11 studies (N > 60 million) focused on outcomes from Medicare AWVs for patients ages ≥ 65 years.⁸ This included uptake of preventive services, such as vaccinations or cancer screenings; advice, education, or referrals offered during the AWV; medication use; and hospitalization rates. Overall findings showed that older adults who received a Medicare AWV were more likely to receive referrals for preventive screenings and follow-through on these recommendations compared with those who did not undergo an AWV.⁸

The approach to caring for individuals later in life has shifted from management of disease and disability to promotion of healthy aging by optimizing health care needs and QOL.

Completion rates for vaccines, while remaining low overall, were higher among those who completed an AWV. Additionally, these studies showed improved completion of screenings for breast cancer, bone density, and colon cancer. Several studies in the scoping review supported the use of AWVs as an effective means by which to offer health education and advice related to health promotion and risk reduction, such as diet and lifestyle modifications.⁸ Little evidence exists on long-term outcomes related to AWV completion.⁸

Utilize shared decision-making to determine whether preventive screening makes sense for your patient. Although cancer remains the second leading cause of death among Americans ages ≥ 65 years,⁹ clear screening guidelines for this age group remain elusive.¹⁰ Physicians and patients often are reluctant to stop cancer screening despite lower life expectancy and fewer potential benefits of diagnosis in this population.⁹ Some recent studies reinforce the heterogeneity of the older adult population and further underscore the importance of individual-level decision-making.^11-14 It is important to let older adult patients and their caregivers know about the potential risks of screening tests, especially the possibility that incidental findings may lead to unwarranted additional care or monitoring.⁹

Continue to: Avoid these screening conversation missteps

Avoid these screening conversation missteps. A 2017 qualitative study asked 40 community-dwelling older adults (mean age = 76 years) about their preferences for discussing screening cessation with their physicians.¹³ Three themes emerged.First, they were open to stopping their screenings, especially when suggested by a trusted physician. Second, health status and physical function made sense as decision points, but life expectancy did not. Finally, lengthy discussions with expanded details about risks and benefits were not appreciated, especially if coupled with comments on the limited benefits for those nearing the end of life. When discussing life expectancy, patients preferred phrasing that focused on how the screening was unnecessary because it would not help them live longer.¹³

Ensure that your message is understood—and culturally relevant. Recent studies on lower health literacy among older adults^15,16 and ethnic and racial minorities^17-21—as revealed in the 2003 National Assessment of Adult Literacy²²—might offer clues to patient receptivity to discussions about preventive screening and other health decisions.

One study found a significant correlation between higher self-rated health literacy and higher engagement in health behaviors such as mammography screening, moderate physical activity, and tobacco avoidance.¹⁶ Perceptions of personal control over health status, as well as perceived social standing, also correlated with health literacy score levels.¹⁶ Another study concluded that lower health literacy combined with lower self-­efficacy, cultural beliefs about health topics (eg, diet and exercise), and distrust in the health care system contributed to lower rates of preventive care utilization among ethnocultural minority older adults in Canada, the United Kingdom, the United States, and Australia.¹⁸

Ensuring that easy-to-understand information is equitably shared with older adults of all races and ethnicities is critical. A 2018 study showed that distrust of the health system and cultural issues contributed to the lower incidence of colorectal cancer screenings in Hispanic and Asian American patients ages 50 to 75 years.²¹ Patients whose physicians engaged in “health literate practices” (eg, offering clear explanations of diagnostic plans and asking patients to describe what they understood) were more likely to obtain recommended breast and colorectal cancer screenings.²⁰ In particular, researchers found that non-Hispanic Blacks were nearly twice as likely to follow through on colorectal cancer screening if their physicians engaged in health literate practices.²⁰ In addition, receiving clear instructions from physicians increased the odds of completing breast cancer screening among Hispanic and non-­Hispanic White women.²⁰

Overall, screening information and recommendations should be standardized for all patients. This is particularly important in light of research that found that older non-Hispanic Black patients were less likely than their non-Hispanic White counterparts to receive information from their physicians about colorectal cancer screening.²⁰

Continue to: Mobility

Mobility

Encourage physical activity. Frequent exercise and other forms of physical activity are associated with healthy aging, as shown in a 2017 systematic review and meta-analysis of 23 studies (N = 174,114).²³ Despite considerable heterogeneity between studies in how researchers defined healthy aging and physical activity, they found that adults who incorporate regular movement and exercise into daily life are likely to continue to benefit from it into older age.²³ In addition, a 2016 secondary analysis of data from the InCHIANTI longitudinal aging study concluded that adults ages ≥ 65 years (N = 1149) who had maintained higher physical activity levels throughout adulthood had less physical function decline and reduced rates of mobility disability and premature death compared with those who reported being less active.²⁴

Preserve gait speed (and bolster health) with these activities. Walking speed, or gait, measured on a level surface has been used as a predictor for various aspects of well-being in older age, such as daily function, mobility, independence, falls, mortality, and hospitalization risk.²⁵ Reduced gait speed is also one of the key indicators of functional impairment in older adults.

A 2015 systematic review sought to determine which type of exercise intervention (resistance, coordination, or multimodal training) would be most effective in preserving gait speed in healthy older adults (N = 2495; mean age = 74.2 years).²⁵ While the 42 included studies were deemed to be fairly low quality, the review revealed (with large effect size [0.84]) that a number of exercise modalities might stave off loss of gait speed in older adults. Patients in the resistance training group had the greatest improvement in gait speed (0.11 m/s), followed by those in the coordination training group (0.09 m/s) and the multimodal training group (0.05 m/s).²⁵

Individuals who had maintained higher physical activity levels throughout adulthood had less physical functional decline and reduced rates of mobility disability and premature death.

Finally, muscle mass and strength offer a measure of physical performance and functionality. A 2020 systematic review of 83 studies (N = 108,428) showed that low muscle mass and strength, reduced handgrip strength, and lower physical performance were predictive of reduced capacities in activities of daily living and instrumental activities of daily living.²⁶ It is important to counsel adults to remain active throughout their lives and to include resistance training to maintain muscle mass and strength to preserve their motor function, mobility, independence, and QOL.

Use 1 of these scales to identify frailty. Frailty is a distinct clinical syndrome, in which an individual has low reserves and is highly vulnerable to internal and external stressors. It affects many community-­dwelling older adults. Within the literature, there has been ongoing discussion regarding the definition of frailty²⁷ (TABLE 1^28-31).

Continue to: The Fried Frailty Index...

The Fried Frailty Index defines frailty as a purely physical condition; patients need to exhibit 3 of 5 components (ie, weight loss, exhaustion, weakness, slowness, and low physical activity) to be deemed frail.³¹ The Edmonton Frail Scale is commonly used in geriatric assessments and counts impairments across several domains including physical activity, mood, cognition, and incontinence.^30,32,33 Physicians need to complete a training course prior to its use. Finally, the definition of frailty used by Rockwood et al^{28, 29} was used to develop the Clinical Frailty Scale, which relies on broader criteria that include social and psychological elements in addition to physical elements.The Clinical Frailty Scale uses clinician judgment to evaluate patient-specific domains (eg, comorbidities, functionality, and cognition) and to generate a score ranging from 1 (very fit) to 9 (terminally ill).²⁹ This scale is accessible and easy to implement. As a result, use of this scale has increased during the COVID-19 pandemic. All definitions include a pre-frail state, indicating the dynamic nature of frailty over time.

It is important to identify pre-frail and frail older adults using 1 of these screening tools. Interventions to reverse frailty that can be initiated in the primary care setting include identifying treatable medical conditions, assessing medication appropriateness, providing nutritional advice, and developing an exercise plan.³⁴

Conduct a nutritional assessment; consider this diet. Studies show that nutritional status can predict physical function and frailty risk in older adults. A 2017 systematic review of 19 studies (N = 22,270) of frail adults ages ≥ 65 years found associations related to specific dietary constructs (ie, micronutrients, macronutrients, antioxidants, overall diet quality, and timing of consumption).³⁵ Plant-based diets with higher levels of micronutrients, such as vitamins C and E and beta-carotene, or diets with more protein or macronutrients, regardless of source foods, all resulted in inverse associations with frailty syndrome.³⁵

A 2017 study showed that physical exercise and maintaining good nutritional status may be effective for preventing frailty in ­community-dwelling pre-frail older individuals.³⁶ A 2019 study showed that a combination of muscle strength training and protein supplementation was the most effective intervention to delay or reverse frailty and was easiest to implement in primary care.³⁷ A 2020 meta-analysis of 31 studies (N = 4794) addressing frailty among primary care patients > 60 years showed that interventions using predominantly resistance-based exercise and nutrition supplementation improved frailty status over the control.³⁸ Researchers also found that a comprehensive geriatric assessment or exercise—alone or in combination with nutrition education—reduced physical frailty.

Mentation

Screen and treat cognitive impairments. Cognitive function and autonomy in ­decision-making are important factors in healthy aging. Aspects of mental health (eg, depression and anxiety), sensory impairment (eg, visual and auditory impairment), and mentation issues (eg, delirium, dementia, and related conditions), as well as diet, physical exercise, and mobility, can all impede cognitive functionality. The long-term effects of depression, anxiety,³⁹ sensory deficits,⁴⁰ mobility,⁴¹ diet,⁴² and, ultimately, aging may impact Alzheimer disease (AD). The risk of an AD diagnosis increases with age.³⁹

Continue to: A 2018 prospective cohort study...

A 2018 prospective cohort study using data from the National Alzheimer’s Coordinating Center followed individuals (N = 12,053) who were cognitively asymptomatic at their initial visits to determine who developed clinical signs of AD.³⁹ Survival analysis showed several psychosocial factors—anxiety, sleep disturbances, and depressive episodes of any type (occurring within the past 2 years, clinician verified, lifetime report)—were significantly associated with an eventual AD diagnosis and increased the risk of AD.³⁹ More research is needed to verify the impact of early intervention for these conditions on neurodegenerative disease; however, screening and treating psychosocial factors such as anxiety and depression should be maintained.

For patients ages ≥ 65 years, it is recommended that eye examinations occur every 1 to 2 years.

Researchers evaluated the impact of a dual sensory impairment (DSI) on dementia risk using data from 2051 participants in the Ginkgo Evaluation of Memory Study.⁴⁰ Hearing and visual impairments (defined as DSI when these conditions coexist) or visual impairment alone were significantly associated with increased risk of dementia in older adults. The researchers reported that DSI was significantly associated with a higher risk of all-cause dementia (hazard ratio [HR] = 1.86; 95% CI, 1.25-2.76) and AD (HR = 2.12; 95% CI, 1.34-3.36).⁴⁰ Visual impairment alone was associated with an increased risk of all-cause dementia (HR = 1.32; 95% CI, 1.02-1.71).⁴⁰ These results suggest that screening of DSI or visual impairment earlier in the patient’s lifespan may identify those at high risk of dementia in older adulthood.

The American Academy of Ophthalmology recommends patients with healthy eyes be screened once during their 20s and twice in their 30s; a full examination is recommended by age 40. For patients ages ≥ 65 years, it is recommended that eye examinations occur every 1 to 2 years.⁴³

Diet and mobility play a big role in cognition. Diet⁴³ and exercise^41,42,44 are believed to have an impact on mentation, and recent studies show memory and global cognition could be malleable later in life. A 2015 meta-analysis of 490 treatment arms of 24 randomized controlled studies showed improvement in global cognition with consumption of a Mediterranean diet plus olive oil (effect size [ES] standardized mean difference [SMD] = 0.22; 95% CI, 0.16-0.27) and tai chi exercises (ES SMD = 0.18; 95% CI, 0.06-0.29).⁴² The analysis also found improved memory among participants who consumed the Mediterranean diet/olive oil combination (ES SMD = 0.22; 95% CI, 0.12-0.32) and soy isoflavone supplements (ES SMD = 0.11; 95% CI, 0.04-0.17). Although the ESs are small, they are significant and offer promising evidence that individual choices related to nutrition or exercise may influence cognition and memory.

A 2018 systematic review found that all domains of cognition showed improvement with 45 to 60 minutes of moderate-to-vigorous physical exercise.⁴⁴ Attention, executive function, memory, and working memory showed significant increases, whereas global cognition improvements were not statistically significant.⁴⁴ A 2016 meta-analysis of 26 studies (N = 26,355) found a positive association between an objective mobility measure (gait, lower-extremity function, and balance) and cognitive function (global, executive function, memory, and processing speed) in older adults.⁴¹ These results highlight that diet, mobility, and physical exercise impact cognitive functioning.

Continue to: Maintaining social connections

Maintaining social connections

Social isolation and loneliness—compounded by a pandemic. The US Department of Health and Human Services notes that “community connections” are among the key factors required for healthy aging.³ Similarly, the WHO definition of healthy aging considers whether individuals can build and sustain relationships with other people and find ways to engender their personal values through these connections.²

Prioritizing interventions that identify and connect isolated older adults to social support may increase survivability.

As people age, their social connections often decrease due to the death of friends and family, shifts in living arrangements, loss of mobility or eyesight (and thus self-­transport), and the onset or increased acuity of illness or chronic conditions.⁴⁵ This has been exacerbated by the COVID-19 pandemic, which has spurred shelter-in-place and stay-at-home orders along with recommendations for physical distancing (also known as social distancing), especially for older adults who are at higher risk.⁴⁶ Smith et al⁴⁷ calls this the COVID-19 Social Connectivity Paradox, in which older adults limit their interactions with others to protect their physical health and reduce their risk of contracting the virus, but as a result they may undermine their psychosocial health by placing themselves at risk of social isolation and loneliness.⁴⁷

The double threat. Social isolation and loneliness have been shown to negatively impact physical health and well-being, resulting in an increased risk of early death^48-50; higher likelihood of specific diagnoses, including dementia and cardiovascular conditions^48,50; and more frequent use of health care services.⁵⁰ These concepts, while related, represent different mechanisms for negative health outcomes. Social isolation is an objective condition when one has a lack of opportunities for interaction with other people; loneliness refers to the emotional disconnect one feels when separated from others. Few studies have compared outcomes between these concepts, but in those that have, social isolation appears to be more strongly associated with early death.^48-50

A 2013 observational study using data from the English Longitudinal Study on Aging found that both social isolation and loneliness were associated with increased mortality among men and women ages ≥ 52 years (N = 6500).⁴⁸ However, when studied independently, loneliness was not found to be a significant risk factor. In contrast, social isolation significantly impacted mortality risk, even after adjusting for demographic factors and baseline health status.⁴⁸ These findings are supported by a 2018 cohort study of individuals (N = 479,054) with a history of an acute cardiovascular event that concluded social isolation was a predictor of mortality, whereas loneliness was not.⁵⁰

A large 2015 meta-analysis (70 studies, N = 3,407,134) of mortality causes among community-dwelling older adults (average age, 66) confirmed that both objective measures of isolation, as well as subjective measures (such as feelings of loneliness or living alone), have a significant predictive effect in longer-term studies. Each measure shows an approximately 30% increase in the likelihood of death after an average of 7 years.⁴⁹

Continue to: Health care remains a connection point

The report offered information about potential avenues for intervention by primary care professionals beyond screening, such as participating in research studies that investigate screening tools and multisystem interventions; social prescribing (linking patients to embedded social work services or ­community-based organizations); referring patients to support groups; initiating ­cognitive-based therapy or other behavioral health interventions; or recommending mindfulness practices.⁵¹ However, most of the cited intervention studies were not specific to primary care settings and contained poor-quality evidence related to efficacy.

Isolation creates a greater reliance on health services due to a lack of a social support system, while a feeling of emotional disconnection (loneliness) seems to be a barrier to accessing care. A 2017 cohort study linking data from the Health and Retirement Study and Medicare claims revealed that social isolation predicts higher annual health expenditures (> $1600 per beneficiary) driven by hospitalization and skilled nursing facility usage, along with greater mortality, whereas individuals who are lonely result in reduced costs (a reduction of $770 annually) due to lower usage of inpatient and outpatient services.⁵² Prioritizing interventions that identify and connect isolated older adults to social support, therefore, may increase survivability by ensuring they have access to resources and health care interventions when needed.

Assessing and treating vision and hearing impairments and mental health issues may guard against losses in cognition.

In addition, these findings underscore the importance of looking at quality—not just quantity—of older adults’ social connections. A number of validated screening tools exist for social isolation and loneliness (TABLE 2^53-59); however, concerns exist about assessing risk using a unidimensional tool for a complex concern,⁴⁷ as well as identifying a problem without having evidence-based interventions to offer as solutions.^47,51 Until future studies resolve these concerns, leveraging the physician-patient relationship to broach these difficult subjects may help normalize the issues and create safe spaces to identify individuals who are at risk.

QOL is key to healthy aging. As Kusumastuti et al⁴ state, “successful ageing lies in the eyes of the beholder.” A 2019 systematic review of 48 qualitative studies revealed that community-dwelling older adults ages ≥ 50 years in 11 countries (N > 4175) perceive well-being by considering QOL within 9 domains: health perception, autonomy, role and activity, relationships, emotional comfort, attitude and adaptation, spirituality, financial security, and home and neighborhood.⁶⁰ Researchers found that as engagement in any one of these domains declines, older adults may shift their definition of health toward their remaining abilities.⁶⁰ This offers an explanation as to why patients might rate their health status much higher than their physicians do: older adults tend to have a more holistic concept of health.

Continue to: Take a multidimensional approach to healthy aging

Take a multidimensional approach to healthy aging

Although we have separately examined each of the 4 components of managing healthy aging in a community-dwelling adult, applying a multidimensional approach is most effective. Increasing use of the Medicare AWV provides an opportunity to assess patient health status, determine care preferences, and improve follow-through on preventive screening. It is also important to encourage older adults to engage in regular physical activity—especially muscle-strengthening exercises—and to discuss nutrition and caloric intake to prevent frailty and functional decline.

Assessing and treating vision and hearing impairments and mental health issues, including anxiety and depression, may guard against losses in cognition. When speaking with older adult patients about their social connections, consider asking not only about frequency of contact and access to resources such as food and transportation, but also about whether they are finding ways to bring their own values into those relationships to bolster their QOL. This guidance also may be useful for primary care practices and health care networks when planning future quality-improvement initiatives.

Additional research is needed to support the evidence base for aligning older adult preferences in health care interventions, such as preventive screenings. Also, clinical decision-making requires more clarity about the efficacy of specific diet and exercise interventions for older adults; the impact of early intervention for depression, anxiety, and sleep disorders on neurodegenerative disease; whether loneliness predicts mortality; and how health care delivery systems can be effective at building social connectivity.

Initiating health education, screening, and prevention throughout the patient’s lifespan can promote healthy aging outcomes later in life.

For now, it is essential to recognize that initiating health education, screening, and prevention throughout the patient’s lifespan can promote healthy aging outcomes. As family physicians, it is important to capitalize on longitudinal relationships with patients and begin educating younger patients using this multidimensional framework to promote living “a productive and meaningful life”at any age.³

CORRESPONDENCE

Lynn M. Wilson, DO, 707 Hamilton Street, 8th floor, Department of Family Medicine, Lehigh Valley Health Network, Allentown, PA 18101; [email protected]

For comatose survivors of out-of-hospital cardiac arrest (OHCA), moderate hypothermia to a target body temperature of 31°C did not improve outcomes, compared with guideline-recommended mild hypothermia (target temp 34°C) in the CAPITAL CHILL study.

The results “do not support the use of moderate therapeutic hypothermia to improve neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest,” write the investigators led by Michel Le May, MD, from the University of Ottawa Heart Institute, Ontario, Canada.

The CAPITAL CHILL results were first presented at the American College of Cardiology (ACC) 2021 Scientific Sessions in May.   

They have now been published online, October 19, in JAMA. 
 

High rates of brain injury and death

Comatose survivors of OHCA have high rates of severe brain injury and death. Current guidelines recommend targeted temperature management at 32°C to 36°C for 24 hours. However, small studies have suggested a potential benefit of targeting lower body temperatures.

In the CAPITAL CHILL study of 367 OHCA patients who were comatose on admission, there were no statistically significant differences in the primary composite outcome of all-cause mortality or poor neurologic outcome at 180 days with mild-versus-moderate hypothermia.

The primary composite outcome occurred in 89 of 184 (48.4%) patients in the moderate hypothermia group and 83 of 183 (45.4%) patients in the mild hypothermia group — a risk difference of 3.0% (95% confidence interval [CI], 7.2% - 13.2%) and relative risk of 1.07 (95% CI, 0.86 - 1.33; P = .56).

There was also no significant difference when looking at the individual components of mortality (43.5% vs 41.0%) and poor neurologic outcome (Disability Rating Scale score >5: 4.9% vs 4.4%).

The baseline characteristics of patients were similar in the moderate and mild hypothermia groups. The lack of a significant difference in the primary outcome was consistent after adjusting for baseline covariates as well as across all subgroups.

The rates of secondary outcomes were also similar between the two groups, except for a longer length of stay in the intensive care unit in the moderate hypothermia group compared with the mild hypothermia group, which would likely add to overall costs.

The researchers note that the Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial recently reported that targeted hypothermia at 33°C did not improve survival at 180 days compared with targeted normothermia at 37.5°C or less.

The CAPITAL CHILL study “adds to the spectrum of target temperature management, as it did not find any benefit of even further lowering temperatures to 31°C,” the study team says.

They caution that most patients in the trial had cardiac arrest secondary to a primary cardiac etiology and therefore the findings may not be applicable to cardiac arrest of all etiologies.

It’s also possible that the trial was underpowered to detect clinically important differences between moderate and mild hypothermia. Also, the number of patients presenting with a nonshockable rhythm was relatively small, and further study may be worthwhile in this subgroup, they say.

For now, however, the CAPITAL CHILL results provide no support for a lower target temperature of 31°C to improve outcomes in OHCA patients, Dr. Le May and colleagues conclude.

CAPITAL CHILL was an investigator-initiated study and funding was provided by the University of Ottawa Heart Institute Cardiac Arrest Program. Dr. Le May has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For comatose survivors of out-of-hospital cardiac arrest (OHCA), moderate hypothermia to a target body temperature of 31°C did not improve outcomes, compared with guideline-recommended mild hypothermia (target temp 34°C) in the CAPITAL CHILL study.

The results “do not support the use of moderate therapeutic hypothermia to improve neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest,” write the investigators led by Michel Le May, MD, from the University of Ottawa Heart Institute, Ontario, Canada.

The CAPITAL CHILL results were first presented at the American College of Cardiology (ACC) 2021 Scientific Sessions in May.   

They have now been published online, October 19, in JAMA. 
 

High rates of brain injury and death

Comatose survivors of OHCA have high rates of severe brain injury and death. Current guidelines recommend targeted temperature management at 32°C to 36°C for 24 hours. However, small studies have suggested a potential benefit of targeting lower body temperatures.

In the CAPITAL CHILL study of 367 OHCA patients who were comatose on admission, there were no statistically significant differences in the primary composite outcome of all-cause mortality or poor neurologic outcome at 180 days with mild-versus-moderate hypothermia.

The primary composite outcome occurred in 89 of 184 (48.4%) patients in the moderate hypothermia group and 83 of 183 (45.4%) patients in the mild hypothermia group — a risk difference of 3.0% (95% confidence interval [CI], 7.2% - 13.2%) and relative risk of 1.07 (95% CI, 0.86 - 1.33; P = .56).

There was also no significant difference when looking at the individual components of mortality (43.5% vs 41.0%) and poor neurologic outcome (Disability Rating Scale score >5: 4.9% vs 4.4%).

The baseline characteristics of patients were similar in the moderate and mild hypothermia groups. The lack of a significant difference in the primary outcome was consistent after adjusting for baseline covariates as well as across all subgroups.

The rates of secondary outcomes were also similar between the two groups, except for a longer length of stay in the intensive care unit in the moderate hypothermia group compared with the mild hypothermia group, which would likely add to overall costs.

The researchers note that the Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial recently reported that targeted hypothermia at 33°C did not improve survival at 180 days compared with targeted normothermia at 37.5°C or less.

The CAPITAL CHILL study “adds to the spectrum of target temperature management, as it did not find any benefit of even further lowering temperatures to 31°C,” the study team says.

They caution that most patients in the trial had cardiac arrest secondary to a primary cardiac etiology and therefore the findings may not be applicable to cardiac arrest of all etiologies.

It’s also possible that the trial was underpowered to detect clinically important differences between moderate and mild hypothermia. Also, the number of patients presenting with a nonshockable rhythm was relatively small, and further study may be worthwhile in this subgroup, they say.

For now, however, the CAPITAL CHILL results provide no support for a lower target temperature of 31°C to improve outcomes in OHCA patients, Dr. Le May and colleagues conclude.

CAPITAL CHILL was an investigator-initiated study and funding was provided by the University of Ottawa Heart Institute Cardiac Arrest Program. Dr. Le May has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For comatose survivors of out-of-hospital cardiac arrest (OHCA), moderate hypothermia to a target body temperature of 31°C did not improve outcomes, compared with guideline-recommended mild hypothermia (target temp 34°C) in the CAPITAL CHILL study.

The results “do not support the use of moderate therapeutic hypothermia to improve neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest,” write the investigators led by Michel Le May, MD, from the University of Ottawa Heart Institute, Ontario, Canada.

The CAPITAL CHILL results were first presented at the American College of Cardiology (ACC) 2021 Scientific Sessions in May.   

They have now been published online, October 19, in JAMA. 
 

High rates of brain injury and death

Comatose survivors of OHCA have high rates of severe brain injury and death. Current guidelines recommend targeted temperature management at 32°C to 36°C for 24 hours. However, small studies have suggested a potential benefit of targeting lower body temperatures.

In the CAPITAL CHILL study of 367 OHCA patients who were comatose on admission, there were no statistically significant differences in the primary composite outcome of all-cause mortality or poor neurologic outcome at 180 days with mild-versus-moderate hypothermia.

The primary composite outcome occurred in 89 of 184 (48.4%) patients in the moderate hypothermia group and 83 of 183 (45.4%) patients in the mild hypothermia group — a risk difference of 3.0% (95% confidence interval [CI], 7.2% - 13.2%) and relative risk of 1.07 (95% CI, 0.86 - 1.33; P = .56).

There was also no significant difference when looking at the individual components of mortality (43.5% vs 41.0%) and poor neurologic outcome (Disability Rating Scale score >5: 4.9% vs 4.4%).

The baseline characteristics of patients were similar in the moderate and mild hypothermia groups. The lack of a significant difference in the primary outcome was consistent after adjusting for baseline covariates as well as across all subgroups.

The rates of secondary outcomes were also similar between the two groups, except for a longer length of stay in the intensive care unit in the moderate hypothermia group compared with the mild hypothermia group, which would likely add to overall costs.

The researchers note that the Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial recently reported that targeted hypothermia at 33°C did not improve survival at 180 days compared with targeted normothermia at 37.5°C or less.

The CAPITAL CHILL study “adds to the spectrum of target temperature management, as it did not find any benefit of even further lowering temperatures to 31°C,” the study team says.

They caution that most patients in the trial had cardiac arrest secondary to a primary cardiac etiology and therefore the findings may not be applicable to cardiac arrest of all etiologies.

It’s also possible that the trial was underpowered to detect clinically important differences between moderate and mild hypothermia. Also, the number of patients presenting with a nonshockable rhythm was relatively small, and further study may be worthwhile in this subgroup, they say.

For now, however, the CAPITAL CHILL results provide no support for a lower target temperature of 31°C to improve outcomes in OHCA patients, Dr. Le May and colleagues conclude.

CAPITAL CHILL was an investigator-initiated study and funding was provided by the University of Ottawa Heart Institute Cardiac Arrest Program. Dr. Le May has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Diagnosis: Ecthyma Gangrenosum

Histopathology revealed basophilic bacterial rods around necrotic vessels with thrombosis and edema (Figure). Blood and tissue cultures grew Pseudomonas aeruginosa. Based on the histopathology and clinical presentation, a diagnosis of P aeruginosa–associated ecthyma gangrenosum (EG) was made. The patient’s symptoms resolved with intravenous cefepime, and he later was transitioned to oral levofloxacin for outpatient treatment.

Ecthyma gangrenosum is an uncommon cutaneous manifestation of bacteremia that most commonly occurs secondary to P aeruginosa in immunocompromised patients, particularly patients with severe neutropenia in the setting of recent chemotherapy.^1,2 Ecthyma gangrenosum can occur anywhere on the body, predominantly in moist areas such as the axillae and groin; the arms and legs, such as in our patient, as well as the trunk and face also may be involved.³ Other causes of EG skin lesions include methicillin-resistant Staphylococcus aureus, Citrobacter freundii, Escherichia coli, fungi such as Candida, and viruses such as herpes simplex virus.^2,4-6 Common predisposing conditions associated with EG include neutropenia, leukemia, HIV, diabetes mellitus, extensive burn wounds, and a history of immunosuppressive medications. It also has been known to occur in otherwise healthy, immunocompetent individuals with no difference in clinical manifestation.²

The diagnosis is clinicopathologic, with initial evaluation including blood and wound cultures as well as a complete blood cell count once EG is suspected. An excisional or punch biopsy is performed for confirmation, showing many gram-negative, rod-shaped bacteria in cases of pseudomonal EG.⁷ Histopathology is characterized by bacterial perivascular invasion that then leads to secondary arteriole thrombosis, tissue edema, and separation of the epidermis.^7,8 Resultant ischemic necrosis results in the classic macroscopic appearance of an erythematous macule that rapidly progresses into a central necrotic lesion surrounded by an erythematous or violaceous halo after undergoing a hemorrhagic bullous stage.1,9 A Wood lamp can be used to expedite the diagnosis, as Pseudomonas bacteria excretes a pigment (pyoverdine) that fluoresces yellowish green.¹⁰

Ecthyma gangrenosum can be classified as a primary skin lesion that may or may not be followed by bacteremia or as a lesion secondary to pseudomonal bacteremia.¹¹ Bacteremia has been reported in half of cases, with hematogenous metastasis of the infection, likely in manifestations with multiple bilateral lesions.² Our patient’s presentation of a single lesion revealed a positive blood culture result. Lesions also can develop by direct inoculation of the epidermis causing local destruction of the surrounding tissue. The nonbacteremic form of EG has been associated with a lower mortality rate of around 15% compared to patients with bacteremia ranging from 38% to 96%.¹² The presence of neutropenia is the most important prognostic factor for mortality at the time of diagnosis.¹³

Prompt empiric therapy should be initiated after obtaining wound and blood cultures in those with infection until the causative organism and its susceptibility are identified. Pseudomonal infections account for 4% of all cases of hospital-acquired bacteremia and are the third leading cause of gram-negative bloodstream infection.⁷ Initial broad-spectrum antibiotics include antipseudomonal β-lactams (piperacillin-tazobactam), cephalosporins (cefepime), fluoroquinolones (levofloxacin), and carbapenems (imipenem).^1,7 Medical therapy alone may be sufficient without requiring extensive surgical debridement to remove necrotic tissue in some patients. Surgical debridement usually is warranted for lesions larger than 10 cm in diameter.³ Our patient was treated with intravenous cefepime with resolution and was followed with outpatient oral levofloxacin as appropriate. A high index of suspicion should be maintained for relapsing pseudomonal EG infection among patients with AIDS, as the reported recurrence rate is 57%.¹⁴

Clinically, the differential diagnosis of EG presenting in immunocompromised patients or individuals with underlying malignancy includes pyoderma gangrenosum, papulonecrotic tuberculid, and leukemia cutis. An erythematous rash with central necrosis presenting in a patient with systemic symptoms is pathognomonic for erythema migrans and should be considered as a diagnostic possibility in areas endemic for Lyme disease in the United States, including the northeastern, mid-Atlantic, and north-central regions.¹⁵ A thorough history, physical examination, basic laboratory studies, and histopathology are critical to differentiate between these entities with similar macroscopic features. Pyoderma gangrenosum histologically manifests as a noninfectious, deep, suppurative folliculitis with leukocytoclastic vasculitis in 40% of cases.¹⁶ Although papulonecrotic tuberculid can present with dermal necrosis resulting from a hypersensitivity reaction to antigenic components of mycobacteria, there typically are granulomatous infiltrates present and a lack of observed organisms on histopathology.¹⁷ Although leukemia cutis infrequently occurs in patients diagnosed with leukemia, its salient features on pathology are nodular or diffuse infiltrates of leukemic cells in the dermis and subcutis with a high nuclear-to-cytoplasmic ratio, often with prominent nucleoli.¹⁸ Lyme disease can present in various ways; however, cutaneous involvement in the primary lesion is histologically characterized by a perivascular lymphohistiocytic infiltrate containing plasma cells at the periphery of the expanding annular lesion and eosinophils present at the center.¹⁹

The Diagnosis: Ecthyma Gangrenosum

Histopathology revealed basophilic bacterial rods around necrotic vessels with thrombosis and edema (Figure). Blood and tissue cultures grew Pseudomonas aeruginosa. Based on the histopathology and clinical presentation, a diagnosis of P aeruginosa–associated ecthyma gangrenosum (EG) was made. The patient’s symptoms resolved with intravenous cefepime, and he later was transitioned to oral levofloxacin for outpatient treatment.

Ecthyma gangrenosum is an uncommon cutaneous manifestation of bacteremia that most commonly occurs secondary to P aeruginosa in immunocompromised patients, particularly patients with severe neutropenia in the setting of recent chemotherapy.^1,2 Ecthyma gangrenosum can occur anywhere on the body, predominantly in moist areas such as the axillae and groin; the arms and legs, such as in our patient, as well as the trunk and face also may be involved.³ Other causes of EG skin lesions include methicillin-resistant Staphylococcus aureus, Citrobacter freundii, Escherichia coli, fungi such as Candida, and viruses such as herpes simplex virus.^2,4-6 Common predisposing conditions associated with EG include neutropenia, leukemia, HIV, diabetes mellitus, extensive burn wounds, and a history of immunosuppressive medications. It also has been known to occur in otherwise healthy, immunocompetent individuals with no difference in clinical manifestation.²

The diagnosis is clinicopathologic, with initial evaluation including blood and wound cultures as well as a complete blood cell count once EG is suspected. An excisional or punch biopsy is performed for confirmation, showing many gram-negative, rod-shaped bacteria in cases of pseudomonal EG.⁷ Histopathology is characterized by bacterial perivascular invasion that then leads to secondary arteriole thrombosis, tissue edema, and separation of the epidermis.^7,8 Resultant ischemic necrosis results in the classic macroscopic appearance of an erythematous macule that rapidly progresses into a central necrotic lesion surrounded by an erythematous or violaceous halo after undergoing a hemorrhagic bullous stage.1,9 A Wood lamp can be used to expedite the diagnosis, as Pseudomonas bacteria excretes a pigment (pyoverdine) that fluoresces yellowish green.¹⁰

Ecthyma gangrenosum can be classified as a primary skin lesion that may or may not be followed by bacteremia or as a lesion secondary to pseudomonal bacteremia.¹¹ Bacteremia has been reported in half of cases, with hematogenous metastasis of the infection, likely in manifestations with multiple bilateral lesions.² Our patient’s presentation of a single lesion revealed a positive blood culture result. Lesions also can develop by direct inoculation of the epidermis causing local destruction of the surrounding tissue. The nonbacteremic form of EG has been associated with a lower mortality rate of around 15% compared to patients with bacteremia ranging from 38% to 96%.¹² The presence of neutropenia is the most important prognostic factor for mortality at the time of diagnosis.¹³

Prompt empiric therapy should be initiated after obtaining wound and blood cultures in those with infection until the causative organism and its susceptibility are identified. Pseudomonal infections account for 4% of all cases of hospital-acquired bacteremia and are the third leading cause of gram-negative bloodstream infection.⁷ Initial broad-spectrum antibiotics include antipseudomonal β-lactams (piperacillin-tazobactam), cephalosporins (cefepime), fluoroquinolones (levofloxacin), and carbapenems (imipenem).^1,7 Medical therapy alone may be sufficient without requiring extensive surgical debridement to remove necrotic tissue in some patients. Surgical debridement usually is warranted for lesions larger than 10 cm in diameter.³ Our patient was treated with intravenous cefepime with resolution and was followed with outpatient oral levofloxacin as appropriate. A high index of suspicion should be maintained for relapsing pseudomonal EG infection among patients with AIDS, as the reported recurrence rate is 57%.¹⁴

Clinically, the differential diagnosis of EG presenting in immunocompromised patients or individuals with underlying malignancy includes pyoderma gangrenosum, papulonecrotic tuberculid, and leukemia cutis. An erythematous rash with central necrosis presenting in a patient with systemic symptoms is pathognomonic for erythema migrans and should be considered as a diagnostic possibility in areas endemic for Lyme disease in the United States, including the northeastern, mid-Atlantic, and north-central regions.¹⁵ A thorough history, physical examination, basic laboratory studies, and histopathology are critical to differentiate between these entities with similar macroscopic features. Pyoderma gangrenosum histologically manifests as a noninfectious, deep, suppurative folliculitis with leukocytoclastic vasculitis in 40% of cases.¹⁶ Although papulonecrotic tuberculid can present with dermal necrosis resulting from a hypersensitivity reaction to antigenic components of mycobacteria, there typically are granulomatous infiltrates present and a lack of observed organisms on histopathology.¹⁷ Although leukemia cutis infrequently occurs in patients diagnosed with leukemia, its salient features on pathology are nodular or diffuse infiltrates of leukemic cells in the dermis and subcutis with a high nuclear-to-cytoplasmic ratio, often with prominent nucleoli.¹⁸ Lyme disease can present in various ways; however, cutaneous involvement in the primary lesion is histologically characterized by a perivascular lymphohistiocytic infiltrate containing plasma cells at the periphery of the expanding annular lesion and eosinophils present at the center.¹⁹

The Diagnosis: Ecthyma Gangrenosum

Histopathology revealed basophilic bacterial rods around necrotic vessels with thrombosis and edema (Figure). Blood and tissue cultures grew Pseudomonas aeruginosa. Based on the histopathology and clinical presentation, a diagnosis of P aeruginosa–associated ecthyma gangrenosum (EG) was made. The patient’s symptoms resolved with intravenous cefepime, and he later was transitioned to oral levofloxacin for outpatient treatment.

Ecthyma gangrenosum is an uncommon cutaneous manifestation of bacteremia that most commonly occurs secondary to P aeruginosa in immunocompromised patients, particularly patients with severe neutropenia in the setting of recent chemotherapy.^1,2 Ecthyma gangrenosum can occur anywhere on the body, predominantly in moist areas such as the axillae and groin; the arms and legs, such as in our patient, as well as the trunk and face also may be involved.³ Other causes of EG skin lesions include methicillin-resistant Staphylococcus aureus, Citrobacter freundii, Escherichia coli, fungi such as Candida, and viruses such as herpes simplex virus.^2,4-6 Common predisposing conditions associated with EG include neutropenia, leukemia, HIV, diabetes mellitus, extensive burn wounds, and a history of immunosuppressive medications. It also has been known to occur in otherwise healthy, immunocompetent individuals with no difference in clinical manifestation.²

The diagnosis is clinicopathologic, with initial evaluation including blood and wound cultures as well as a complete blood cell count once EG is suspected. An excisional or punch biopsy is performed for confirmation, showing many gram-negative, rod-shaped bacteria in cases of pseudomonal EG.⁷ Histopathology is characterized by bacterial perivascular invasion that then leads to secondary arteriole thrombosis, tissue edema, and separation of the epidermis.^7,8 Resultant ischemic necrosis results in the classic macroscopic appearance of an erythematous macule that rapidly progresses into a central necrotic lesion surrounded by an erythematous or violaceous halo after undergoing a hemorrhagic bullous stage.1,9 A Wood lamp can be used to expedite the diagnosis, as Pseudomonas bacteria excretes a pigment (pyoverdine) that fluoresces yellowish green.¹⁰

Ecthyma gangrenosum can be classified as a primary skin lesion that may or may not be followed by bacteremia or as a lesion secondary to pseudomonal bacteremia.¹¹ Bacteremia has been reported in half of cases, with hematogenous metastasis of the infection, likely in manifestations with multiple bilateral lesions.² Our patient’s presentation of a single lesion revealed a positive blood culture result. Lesions also can develop by direct inoculation of the epidermis causing local destruction of the surrounding tissue. The nonbacteremic form of EG has been associated with a lower mortality rate of around 15% compared to patients with bacteremia ranging from 38% to 96%.¹² The presence of neutropenia is the most important prognostic factor for mortality at the time of diagnosis.¹³

Prompt empiric therapy should be initiated after obtaining wound and blood cultures in those with infection until the causative organism and its susceptibility are identified. Pseudomonal infections account for 4% of all cases of hospital-acquired bacteremia and are the third leading cause of gram-negative bloodstream infection.⁷ Initial broad-spectrum antibiotics include antipseudomonal β-lactams (piperacillin-tazobactam), cephalosporins (cefepime), fluoroquinolones (levofloxacin), and carbapenems (imipenem).^1,7 Medical therapy alone may be sufficient without requiring extensive surgical debridement to remove necrotic tissue in some patients. Surgical debridement usually is warranted for lesions larger than 10 cm in diameter.³ Our patient was treated with intravenous cefepime with resolution and was followed with outpatient oral levofloxacin as appropriate. A high index of suspicion should be maintained for relapsing pseudomonal EG infection among patients with AIDS, as the reported recurrence rate is 57%.¹⁴

Clinically, the differential diagnosis of EG presenting in immunocompromised patients or individuals with underlying malignancy includes pyoderma gangrenosum, papulonecrotic tuberculid, and leukemia cutis. An erythematous rash with central necrosis presenting in a patient with systemic symptoms is pathognomonic for erythema migrans and should be considered as a diagnostic possibility in areas endemic for Lyme disease in the United States, including the northeastern, mid-Atlantic, and north-central regions.¹⁵ A thorough history, physical examination, basic laboratory studies, and histopathology are critical to differentiate between these entities with similar macroscopic features. Pyoderma gangrenosum histologically manifests as a noninfectious, deep, suppurative folliculitis with leukocytoclastic vasculitis in 40% of cases.¹⁶ Although papulonecrotic tuberculid can present with dermal necrosis resulting from a hypersensitivity reaction to antigenic components of mycobacteria, there typically are granulomatous infiltrates present and a lack of observed organisms on histopathology.¹⁷ Although leukemia cutis infrequently occurs in patients diagnosed with leukemia, its salient features on pathology are nodular or diffuse infiltrates of leukemic cells in the dermis and subcutis with a high nuclear-to-cytoplasmic ratio, often with prominent nucleoli.¹⁸ Lyme disease can present in various ways; however, cutaneous involvement in the primary lesion is histologically characterized by a perivascular lymphohistiocytic infiltrate containing plasma cells at the periphery of the expanding annular lesion and eosinophils present at the center.¹⁹

The practice of internal medicine includes bedside procedures such as paracentesis, thoracentesis, and lumbar puncture (LP). The American Board of Internal Medicine requires graduates of internal medicine residency programs to be competent in the cognitive components of procedural training (eg, indications, contraindications, complications) and considers it essential that trainees have opportunities to perform procedures relevant to their intended career direction.¹ Whether or not the performance of procedures is part of a given hospitalist’s practice, it is necessary that hospitalists understand each procedure’s risks and mitigation strategies to prevent a range of periprocedural complications, including clinically significant bleeding. Numerous recommendations and guidelines exist describing bleeding risk for common procedures. In this Progress Note, we summarize and consolidate this literature, covering a range of scenarios common to the hospital setting, including thrombocytopenia, elevated international normalized ratio (INR), and the use of medications such as antiplatelet and anticoagulant agents (Table 1 and Table 2). We performed electronic searches in PubMed, focusing on literature published since 2016. Key search terms included paracentesis, thoracentesis, lumbar puncture, anticoagulant, antiplatelet, coagulopathy, INR, thrombocytopenia, and guideline. In addition, we used the following MeSH terms: spinal puncture AND blood coagulation disorders, spinal puncture AND platelet aggregation inhibitors, spinal puncture AND anticoagulants, paracentesis AND blood coagulation disorders, paracentesis AND platelet aggregation inhibitors, paracentesis AND anticoagulants, thoracentesis AND blood coagulation disorders, thoracentesis AND platelet aggregation inhibitors, and thoracentesis AND anticoagulants.

Weighing Risks and Benefits

Proceduralists should discuss risks and benefits with patients and the referring service before attempting to mitigate bleeding risk by holding antithrombotic agents or reversing coagulopathy, as these actions come with risks outside the anticipated procedure, in particular, an increased risk of thrombosis. There are many factors that influence an individual patient’s arterial thromboembolism and venous thromboembolism (VTE) risk, including surgical history, genetics, comorbidities, and the underlying indication for antithrombotic therapy. The American College of Chest Physicians updated their clinical practice guidelines describing perioperative thromboembolism risk stratification in 2012.¹² In general, higher-risk individuals include those with any mitral valve prosthesis, recent (within 6 months) stroke or transient ischemic attack (TIA), CHADS₂ score of 5 or 6, recent (within 3 months) VTE, or severe thrombophilia. Individuals at moderate risk include those with bileaflet aortic valve repair (AVR) with at least one major stroke risk factor, CHADS₂ score of 3 or 4, recent (within 3-12 months) or recurrent VTE, or active or recent (treatment within preceding 6 months) cancer. Finally, individuals at low risk include those with bileaflet AVR without major stroke risk factors, CHADS₂ score of 0 to 2, or VTE more than 12 months earlier. There are also patient-specific bleeding risk factors that should be considered, including hypertension, abnormal renal function, abnormal hepatic function, prior stroke, history of major bleeding (especially within the preceding 3 months), and bleeding history with a similar procedure.¹¹

Hepatic and Renal Dysfunction

In the setting of chronic liver disease, thrombocytopenia and elevated INR are generally not reliable indicators of bleeding risk.¹³ The included recommendations for INR and platelet count thresholds in the setting of chronic liver disease are derived from the referenced guidelines and supplemental personal communication with the guideline authors. Many antiplatelet and anticoagulant medications are partially cleared or metabolized by the liver, suggesting that hepatic dysfunction may impact drug clearance, but this has not been well studied. Impaired renal function should also be considered when determining appropriate hold times for antithrombotic drugs that are partially renally cleared. The periprocedural hold and restart times outlined in Table 2 are specific to patients without clinically significant hepatic or renal dysfunction. For patients with these conditions, further information on hold time adjustment can be found in the individual references.

Bridging Therapy

The decision to use bridging therapy prior to a bedside procedure must be individualized and take into account patient-specific factors. However, there is mounting evidence that bridging therapy is associated with higher risk of bleeding with no difference in the risk of thromboembolic events.^2,3,14 If the decision has been made to use bridging therapy with a heparin infusion prior to a bedside procedure, recommendations for hold and restart times can be found in Table 2.

Resuming Therapy

Another key consideration for procedures, especially those associated with a higher risk of bleeding, such as LP, is when to restart medications that have been held prior to the procedure. Table 2 provides a summary of the recommended postprocedural restart times for a variety of agents.

Other Considerations

Some guidelines referenced in this article are based on data collected on procedures performed by interventional radiologists, which may or may not accurately reflect the bleeding risks of bedside procedures performed by hospitalists. In the case of LP, we included some regional anesthesia and pain procedure guidelines based on the assumption that certain procedures are analogous to LP and associated with similar bleeding risks. Some of the guidelines referenced do not provide specific periprocedural INR and platelet thresholds (reported as “No threshold” in Table 1), instead offering statements that elevated INR and thrombocytopenia are not contraindications to bedside procedures and periprocedural transfusion of blood products is generally not recommended, based on the overall low risk of bleeding and lack of evidence for the efficacy of interventions intended to improve INR values and platelet counts in these situations. Patients undergoing paracentesis, thoracentesis, or LP may be on multiple antithrombotic agents, such as dual antiplatelet therapy. There are limited guidelines and studies on how to manage these agents in the periprocedural context; however, one guideline recommends continuing dual antiplatelet therapy for paracentesis, thoracentesis, and LP in patients who have cardiac stents.² There are also limited guidelines on how to handle patients on simultaneous antiplatelet and anticoagulant therapy.

Paracentesis is a common procedure that can be performed safely at the bedside. The overall rate of serious complications is low (1%-2%), with severe hemorrhage accounting for the majority of those complications (0.97%).¹⁵ Bleeding usually occurs from puncture of an abdominal wall vein, a mesenteric varix, or an inferior epigastric artery. Certain techniques may help to mitigate serious bleeding, including the use of ultrasound to avoid overlying vessels. Paracentesis is frequently performed in patients with cirrhosis, a population at increased risk for coagulopathy, although INR and platelet counts may not reflect aggregate bleeding risk in patients with cirrhosis. The American Association for the Study of Liver Diseases released new guidelines in 2021, stating that elevated prothrombin time or thrombocytopenia is not a contraindication to paracentesis.⁶ The most liberal guidelines for patients without chronic liver disease suggest correcting to an INR of 2.0 to 3.0, with multiple societies suggesting that a platelet count as low as 20,000/µL is safe.^2,3 As shown in Table 2, most guidelines recommend continuation of antiplatelet agents such as aspirin and thienopyridines (eg, clopidogrel, prasugrel), whereas recommendations vary regarding continuation of anticoagulant agents.

Akin to paracentesis, thoracentesis is generally considered to be a safe bedside procedure, with an incidence of thoracentesis-associated bleeding of less than 1%.¹⁵ Certain techniques may help to mitigate serious bleeding, including the insertion of the needle over the superior aspect of the rib in an effort to avoid the intercostal neurovascular bundle, which runs along the inferior aspect of each rib. Various clinical societies have proposed INR and platelet thresholds at which the risk of bleeding from thoracentesis is thought to be acceptable. The most liberal guidelines include a target INR of 2.0 to 3.0, although one group recommended an INR of <1.5.^2,5 Thoracentesis is commonly performed in patients with cirrhosis who develop hepatic hydrothorax. In this population, the Society of Interventional Radiology (SIR) guidelines state that there is no INR threshold that necessitates reversal strategies prior to the procedure.² For platelet count, there are multiple recommendations for greater than 20,000/µL and one for greater than 50,000/µL.^2,3,5 The recommendations for continuation or suspension of antiplatelet and anticoagulant medications prior to thoracentesis are similar to those for paracentesis. In general, continuing antiplatelet agents is felt to be safe, whereas there are mixed recommendations for anticoagulants, as described further in Table 2.

Compared to thoracentesis and paracentesis, LP is generally considered to be a higher-risk procedure owing to the rare possibility of spinal hematoma with associated neurologic compromise. In one retrospective review of more than 49,000 patients without coagulopathy who underwent LP, the risk for developing a spinal hematoma by 30 days post procedure was 0.20%.¹⁶ Certain techniques may help to mitigate serious bleeding, including the use of image guidance in patients with large body habitus or those with difficult anatomy. Compared with paracentesis and thoracentesis, guideline recommendations for safe INR and platelet thresholds in patients undergoing LP are based on a more limited body of evidence. Guidelines also suggest a target INR of anywhere from ≤1.5 to the most liberal suggestion of 2.0 to 3.0.^2-4 The SIR guidelines categorize LP as a low–bleeding risk procedure, with a platelet threshold of 20,000/µL but note that most other societies and guidelines regard LP as a high–bleeding risk procedure with more conservative platelet thresholds.² The Association of British Neurologists (ABN), however, allows platelets to be 40,000/µL or greater than 20,000/µL with an additional risk-benefit discussion.⁷ In contrast to paracentesis and thoracentesis, recommendations regarding hold times of antithrombotic medications prior to LP are more variable and sometimes more conservative. For example, some guidelines indicate that the thienopyridines can be continued, whereas others recommend holding them for up to 1 week prior to LP.^2,4,7

A theme throughout the recent literature and recommendations from clinical societies is that it is uncommon for there to be one unifying recommendation for every situation, especially regarding LP. Recent guidelines remain largely based on studies that are decades old. With bedside ultrasound becoming more accessible and established in daily practice, the risk of bleeding has been decreasing, potentially making periprocedural coagulopathies and antithrombotic agents less of a concern. For example, in a retrospective study of 69,859 paracenteses, ultrasound guidance reduced the risk of bleeding complications by 68%, an odds ratio of 0.32 (95% CI, 0.25-0.41).¹⁷ More research is needed to assess procedural bleeding risks in the context of current practice standards. This article focuses on a subset of bedside procedures most commonly performed by hospitalists. Similar references for other common bedside procedures, such as arthrocentesis, central venous catheter, and arterial line placement, would be helpful. Finally, this article does not capture such nuances as needle gauge, operator experience, availability of (and comfort with) ultrasound, and variations in patient anatomy, all of which are factors that can contribute to the complexities and risks of these bedside procedures.

Although not every internal medicine physician performs bedside procedures in their practice, it is vital that all understand the cognitive aspects of common bedside procedures. This necessitates the understanding of periprocedural risks and possible complications and applying that to individual patients. Correcting coagulopathy and stopping or reversing antithrombotic agents are mitigation strategies that are associated with risk. It is therefore important to understand when coagulopathy should be corrected and when antithrombotic agents should be held and for how long. With multiple existing and sometimes conflicting guidelines regarding periprocedural management of coagulopathy and antithrombotic agents, we hope that providing consolidated tables with this information will increase efficiency, aid in risk-benefit discussions between patients and care teams, and enhance patient safety.

The practice of internal medicine includes bedside procedures such as paracentesis, thoracentesis, and lumbar puncture (LP). The American Board of Internal Medicine requires graduates of internal medicine residency programs to be competent in the cognitive components of procedural training (eg, indications, contraindications, complications) and considers it essential that trainees have opportunities to perform procedures relevant to their intended career direction.¹ Whether or not the performance of procedures is part of a given hospitalist’s practice, it is necessary that hospitalists understand each procedure’s risks and mitigation strategies to prevent a range of periprocedural complications, including clinically significant bleeding. Numerous recommendations and guidelines exist describing bleeding risk for common procedures. In this Progress Note, we summarize and consolidate this literature, covering a range of scenarios common to the hospital setting, including thrombocytopenia, elevated international normalized ratio (INR), and the use of medications such as antiplatelet and anticoagulant agents (Table 1 and Table 2). We performed electronic searches in PubMed, focusing on literature published since 2016. Key search terms included paracentesis, thoracentesis, lumbar puncture, anticoagulant, antiplatelet, coagulopathy, INR, thrombocytopenia, and guideline. In addition, we used the following MeSH terms: spinal puncture AND blood coagulation disorders, spinal puncture AND platelet aggregation inhibitors, spinal puncture AND anticoagulants, paracentesis AND blood coagulation disorders, paracentesis AND platelet aggregation inhibitors, paracentesis AND anticoagulants, thoracentesis AND blood coagulation disorders, thoracentesis AND platelet aggregation inhibitors, and thoracentesis AND anticoagulants.

Weighing Risks and Benefits

Proceduralists should discuss risks and benefits with patients and the referring service before attempting to mitigate bleeding risk by holding antithrombotic agents or reversing coagulopathy, as these actions come with risks outside the anticipated procedure, in particular, an increased risk of thrombosis. There are many factors that influence an individual patient’s arterial thromboembolism and venous thromboembolism (VTE) risk, including surgical history, genetics, comorbidities, and the underlying indication for antithrombotic therapy. The American College of Chest Physicians updated their clinical practice guidelines describing perioperative thromboembolism risk stratification in 2012.¹² In general, higher-risk individuals include those with any mitral valve prosthesis, recent (within 6 months) stroke or transient ischemic attack (TIA), CHADS₂ score of 5 or 6, recent (within 3 months) VTE, or severe thrombophilia. Individuals at moderate risk include those with bileaflet aortic valve repair (AVR) with at least one major stroke risk factor, CHADS₂ score of 3 or 4, recent (within 3-12 months) or recurrent VTE, or active or recent (treatment within preceding 6 months) cancer. Finally, individuals at low risk include those with bileaflet AVR without major stroke risk factors, CHADS₂ score of 0 to 2, or VTE more than 12 months earlier. There are also patient-specific bleeding risk factors that should be considered, including hypertension, abnormal renal function, abnormal hepatic function, prior stroke, history of major bleeding (especially within the preceding 3 months), and bleeding history with a similar procedure.¹¹

Hepatic and Renal Dysfunction

In the setting of chronic liver disease, thrombocytopenia and elevated INR are generally not reliable indicators of bleeding risk.¹³ The included recommendations for INR and platelet count thresholds in the setting of chronic liver disease are derived from the referenced guidelines and supplemental personal communication with the guideline authors. Many antiplatelet and anticoagulant medications are partially cleared or metabolized by the liver, suggesting that hepatic dysfunction may impact drug clearance, but this has not been well studied. Impaired renal function should also be considered when determining appropriate hold times for antithrombotic drugs that are partially renally cleared. The periprocedural hold and restart times outlined in Table 2 are specific to patients without clinically significant hepatic or renal dysfunction. For patients with these conditions, further information on hold time adjustment can be found in the individual references.

Bridging Therapy

The decision to use bridging therapy prior to a bedside procedure must be individualized and take into account patient-specific factors. However, there is mounting evidence that bridging therapy is associated with higher risk of bleeding with no difference in the risk of thromboembolic events.^2,3,14 If the decision has been made to use bridging therapy with a heparin infusion prior to a bedside procedure, recommendations for hold and restart times can be found in Table 2.

Resuming Therapy

Another key consideration for procedures, especially those associated with a higher risk of bleeding, such as LP, is when to restart medications that have been held prior to the procedure. Table 2 provides a summary of the recommended postprocedural restart times for a variety of agents.

Other Considerations

Some guidelines referenced in this article are based on data collected on procedures performed by interventional radiologists, which may or may not accurately reflect the bleeding risks of bedside procedures performed by hospitalists. In the case of LP, we included some regional anesthesia and pain procedure guidelines based on the assumption that certain procedures are analogous to LP and associated with similar bleeding risks. Some of the guidelines referenced do not provide specific periprocedural INR and platelet thresholds (reported as “No threshold” in Table 1), instead offering statements that elevated INR and thrombocytopenia are not contraindications to bedside procedures and periprocedural transfusion of blood products is generally not recommended, based on the overall low risk of bleeding and lack of evidence for the efficacy of interventions intended to improve INR values and platelet counts in these situations. Patients undergoing paracentesis, thoracentesis, or LP may be on multiple antithrombotic agents, such as dual antiplatelet therapy. There are limited guidelines and studies on how to manage these agents in the periprocedural context; however, one guideline recommends continuing dual antiplatelet therapy for paracentesis, thoracentesis, and LP in patients who have cardiac stents.² There are also limited guidelines on how to handle patients on simultaneous antiplatelet and anticoagulant therapy.

Paracentesis is a common procedure that can be performed safely at the bedside. The overall rate of serious complications is low (1%-2%), with severe hemorrhage accounting for the majority of those complications (0.97%).¹⁵ Bleeding usually occurs from puncture of an abdominal wall vein, a mesenteric varix, or an inferior epigastric artery. Certain techniques may help to mitigate serious bleeding, including the use of ultrasound to avoid overlying vessels. Paracentesis is frequently performed in patients with cirrhosis, a population at increased risk for coagulopathy, although INR and platelet counts may not reflect aggregate bleeding risk in patients with cirrhosis. The American Association for the Study of Liver Diseases released new guidelines in 2021, stating that elevated prothrombin time or thrombocytopenia is not a contraindication to paracentesis.⁶ The most liberal guidelines for patients without chronic liver disease suggest correcting to an INR of 2.0 to 3.0, with multiple societies suggesting that a platelet count as low as 20,000/µL is safe.^2,3 As shown in Table 2, most guidelines recommend continuation of antiplatelet agents such as aspirin and thienopyridines (eg, clopidogrel, prasugrel), whereas recommendations vary regarding continuation of anticoagulant agents.

Akin to paracentesis, thoracentesis is generally considered to be a safe bedside procedure, with an incidence of thoracentesis-associated bleeding of less than 1%.¹⁵ Certain techniques may help to mitigate serious bleeding, including the insertion of the needle over the superior aspect of the rib in an effort to avoid the intercostal neurovascular bundle, which runs along the inferior aspect of each rib. Various clinical societies have proposed INR and platelet thresholds at which the risk of bleeding from thoracentesis is thought to be acceptable. The most liberal guidelines include a target INR of 2.0 to 3.0, although one group recommended an INR of <1.5.^2,5 Thoracentesis is commonly performed in patients with cirrhosis who develop hepatic hydrothorax. In this population, the Society of Interventional Radiology (SIR) guidelines state that there is no INR threshold that necessitates reversal strategies prior to the procedure.² For platelet count, there are multiple recommendations for greater than 20,000/µL and one for greater than 50,000/µL.^2,3,5 The recommendations for continuation or suspension of antiplatelet and anticoagulant medications prior to thoracentesis are similar to those for paracentesis. In general, continuing antiplatelet agents is felt to be safe, whereas there are mixed recommendations for anticoagulants, as described further in Table 2.

Compared to thoracentesis and paracentesis, LP is generally considered to be a higher-risk procedure owing to the rare possibility of spinal hematoma with associated neurologic compromise. In one retrospective review of more than 49,000 patients without coagulopathy who underwent LP, the risk for developing a spinal hematoma by 30 days post procedure was 0.20%.¹⁶ Certain techniques may help to mitigate serious bleeding, including the use of image guidance in patients with large body habitus or those with difficult anatomy. Compared with paracentesis and thoracentesis, guideline recommendations for safe INR and platelet thresholds in patients undergoing LP are based on a more limited body of evidence. Guidelines also suggest a target INR of anywhere from ≤1.5 to the most liberal suggestion of 2.0 to 3.0.^2-4 The SIR guidelines categorize LP as a low–bleeding risk procedure, with a platelet threshold of 20,000/µL but note that most other societies and guidelines regard LP as a high–bleeding risk procedure with more conservative platelet thresholds.² The Association of British Neurologists (ABN), however, allows platelets to be 40,000/µL or greater than 20,000/µL with an additional risk-benefit discussion.⁷ In contrast to paracentesis and thoracentesis, recommendations regarding hold times of antithrombotic medications prior to LP are more variable and sometimes more conservative. For example, some guidelines indicate that the thienopyridines can be continued, whereas others recommend holding them for up to 1 week prior to LP.^2,4,7

A theme throughout the recent literature and recommendations from clinical societies is that it is uncommon for there to be one unifying recommendation for every situation, especially regarding LP. Recent guidelines remain largely based on studies that are decades old. With bedside ultrasound becoming more accessible and established in daily practice, the risk of bleeding has been decreasing, potentially making periprocedural coagulopathies and antithrombotic agents less of a concern. For example, in a retrospective study of 69,859 paracenteses, ultrasound guidance reduced the risk of bleeding complications by 68%, an odds ratio of 0.32 (95% CI, 0.25-0.41).¹⁷ More research is needed to assess procedural bleeding risks in the context of current practice standards. This article focuses on a subset of bedside procedures most commonly performed by hospitalists. Similar references for other common bedside procedures, such as arthrocentesis, central venous catheter, and arterial line placement, would be helpful. Finally, this article does not capture such nuances as needle gauge, operator experience, availability of (and comfort with) ultrasound, and variations in patient anatomy, all of which are factors that can contribute to the complexities and risks of these bedside procedures.

Although not every internal medicine physician performs bedside procedures in their practice, it is vital that all understand the cognitive aspects of common bedside procedures. This necessitates the understanding of periprocedural risks and possible complications and applying that to individual patients. Correcting coagulopathy and stopping or reversing antithrombotic agents are mitigation strategies that are associated with risk. It is therefore important to understand when coagulopathy should be corrected and when antithrombotic agents should be held and for how long. With multiple existing and sometimes conflicting guidelines regarding periprocedural management of coagulopathy and antithrombotic agents, we hope that providing consolidated tables with this information will increase efficiency, aid in risk-benefit discussions between patients and care teams, and enhance patient safety.

The practice of internal medicine includes bedside procedures such as paracentesis, thoracentesis, and lumbar puncture (LP). The American Board of Internal Medicine requires graduates of internal medicine residency programs to be competent in the cognitive components of procedural training (eg, indications, contraindications, complications) and considers it essential that trainees have opportunities to perform procedures relevant to their intended career direction.¹ Whether or not the performance of procedures is part of a given hospitalist’s practice, it is necessary that hospitalists understand each procedure’s risks and mitigation strategies to prevent a range of periprocedural complications, including clinically significant bleeding. Numerous recommendations and guidelines exist describing bleeding risk for common procedures. In this Progress Note, we summarize and consolidate this literature, covering a range of scenarios common to the hospital setting, including thrombocytopenia, elevated international normalized ratio (INR), and the use of medications such as antiplatelet and anticoagulant agents (Table 1 and Table 2). We performed electronic searches in PubMed, focusing on literature published since 2016. Key search terms included paracentesis, thoracentesis, lumbar puncture, anticoagulant, antiplatelet, coagulopathy, INR, thrombocytopenia, and guideline. In addition, we used the following MeSH terms: spinal puncture AND blood coagulation disorders, spinal puncture AND platelet aggregation inhibitors, spinal puncture AND anticoagulants, paracentesis AND blood coagulation disorders, paracentesis AND platelet aggregation inhibitors, paracentesis AND anticoagulants, thoracentesis AND blood coagulation disorders, thoracentesis AND platelet aggregation inhibitors, and thoracentesis AND anticoagulants.

Weighing Risks and Benefits

Proceduralists should discuss risks and benefits with patients and the referring service before attempting to mitigate bleeding risk by holding antithrombotic agents or reversing coagulopathy, as these actions come with risks outside the anticipated procedure, in particular, an increased risk of thrombosis. There are many factors that influence an individual patient’s arterial thromboembolism and venous thromboembolism (VTE) risk, including surgical history, genetics, comorbidities, and the underlying indication for antithrombotic therapy. The American College of Chest Physicians updated their clinical practice guidelines describing perioperative thromboembolism risk stratification in 2012.¹² In general, higher-risk individuals include those with any mitral valve prosthesis, recent (within 6 months) stroke or transient ischemic attack (TIA), CHADS₂ score of 5 or 6, recent (within 3 months) VTE, or severe thrombophilia. Individuals at moderate risk include those with bileaflet aortic valve repair (AVR) with at least one major stroke risk factor, CHADS₂ score of 3 or 4, recent (within 3-12 months) or recurrent VTE, or active or recent (treatment within preceding 6 months) cancer. Finally, individuals at low risk include those with bileaflet AVR without major stroke risk factors, CHADS₂ score of 0 to 2, or VTE more than 12 months earlier. There are also patient-specific bleeding risk factors that should be considered, including hypertension, abnormal renal function, abnormal hepatic function, prior stroke, history of major bleeding (especially within the preceding 3 months), and bleeding history with a similar procedure.¹¹

Hepatic and Renal Dysfunction

In the setting of chronic liver disease, thrombocytopenia and elevated INR are generally not reliable indicators of bleeding risk.¹³ The included recommendations for INR and platelet count thresholds in the setting of chronic liver disease are derived from the referenced guidelines and supplemental personal communication with the guideline authors. Many antiplatelet and anticoagulant medications are partially cleared or metabolized by the liver, suggesting that hepatic dysfunction may impact drug clearance, but this has not been well studied. Impaired renal function should also be considered when determining appropriate hold times for antithrombotic drugs that are partially renally cleared. The periprocedural hold and restart times outlined in Table 2 are specific to patients without clinically significant hepatic or renal dysfunction. For patients with these conditions, further information on hold time adjustment can be found in the individual references.

Bridging Therapy

The decision to use bridging therapy prior to a bedside procedure must be individualized and take into account patient-specific factors. However, there is mounting evidence that bridging therapy is associated with higher risk of bleeding with no difference in the risk of thromboembolic events.^2,3,14 If the decision has been made to use bridging therapy with a heparin infusion prior to a bedside procedure, recommendations for hold and restart times can be found in Table 2.

Resuming Therapy

Another key consideration for procedures, especially those associated with a higher risk of bleeding, such as LP, is when to restart medications that have been held prior to the procedure. Table 2 provides a summary of the recommended postprocedural restart times for a variety of agents.

Other Considerations

Some guidelines referenced in this article are based on data collected on procedures performed by interventional radiologists, which may or may not accurately reflect the bleeding risks of bedside procedures performed by hospitalists. In the case of LP, we included some regional anesthesia and pain procedure guidelines based on the assumption that certain procedures are analogous to LP and associated with similar bleeding risks. Some of the guidelines referenced do not provide specific periprocedural INR and platelet thresholds (reported as “No threshold” in Table 1), instead offering statements that elevated INR and thrombocytopenia are not contraindications to bedside procedures and periprocedural transfusion of blood products is generally not recommended, based on the overall low risk of bleeding and lack of evidence for the efficacy of interventions intended to improve INR values and platelet counts in these situations. Patients undergoing paracentesis, thoracentesis, or LP may be on multiple antithrombotic agents, such as dual antiplatelet therapy. There are limited guidelines and studies on how to manage these agents in the periprocedural context; however, one guideline recommends continuing dual antiplatelet therapy for paracentesis, thoracentesis, and LP in patients who have cardiac stents.² There are also limited guidelines on how to handle patients on simultaneous antiplatelet and anticoagulant therapy.

Paracentesis is a common procedure that can be performed safely at the bedside. The overall rate of serious complications is low (1%-2%), with severe hemorrhage accounting for the majority of those complications (0.97%).¹⁵ Bleeding usually occurs from puncture of an abdominal wall vein, a mesenteric varix, or an inferior epigastric artery. Certain techniques may help to mitigate serious bleeding, including the use of ultrasound to avoid overlying vessels. Paracentesis is frequently performed in patients with cirrhosis, a population at increased risk for coagulopathy, although INR and platelet counts may not reflect aggregate bleeding risk in patients with cirrhosis. The American Association for the Study of Liver Diseases released new guidelines in 2021, stating that elevated prothrombin time or thrombocytopenia is not a contraindication to paracentesis.⁶ The most liberal guidelines for patients without chronic liver disease suggest correcting to an INR of 2.0 to 3.0, with multiple societies suggesting that a platelet count as low as 20,000/µL is safe.^2,3 As shown in Table 2, most guidelines recommend continuation of antiplatelet agents such as aspirin and thienopyridines (eg, clopidogrel, prasugrel), whereas recommendations vary regarding continuation of anticoagulant agents.

Akin to paracentesis, thoracentesis is generally considered to be a safe bedside procedure, with an incidence of thoracentesis-associated bleeding of less than 1%.¹⁵ Certain techniques may help to mitigate serious bleeding, including the insertion of the needle over the superior aspect of the rib in an effort to avoid the intercostal neurovascular bundle, which runs along the inferior aspect of each rib. Various clinical societies have proposed INR and platelet thresholds at which the risk of bleeding from thoracentesis is thought to be acceptable. The most liberal guidelines include a target INR of 2.0 to 3.0, although one group recommended an INR of <1.5.^2,5 Thoracentesis is commonly performed in patients with cirrhosis who develop hepatic hydrothorax. In this population, the Society of Interventional Radiology (SIR) guidelines state that there is no INR threshold that necessitates reversal strategies prior to the procedure.² For platelet count, there are multiple recommendations for greater than 20,000/µL and one for greater than 50,000/µL.^2,3,5 The recommendations for continuation or suspension of antiplatelet and anticoagulant medications prior to thoracentesis are similar to those for paracentesis. In general, continuing antiplatelet agents is felt to be safe, whereas there are mixed recommendations for anticoagulants, as described further in Table 2.

Compared to thoracentesis and paracentesis, LP is generally considered to be a higher-risk procedure owing to the rare possibility of spinal hematoma with associated neurologic compromise. In one retrospective review of more than 49,000 patients without coagulopathy who underwent LP, the risk for developing a spinal hematoma by 30 days post procedure was 0.20%.¹⁶ Certain techniques may help to mitigate serious bleeding, including the use of image guidance in patients with large body habitus or those with difficult anatomy. Compared with paracentesis and thoracentesis, guideline recommendations for safe INR and platelet thresholds in patients undergoing LP are based on a more limited body of evidence. Guidelines also suggest a target INR of anywhere from ≤1.5 to the most liberal suggestion of 2.0 to 3.0.^2-4 The SIR guidelines categorize LP as a low–bleeding risk procedure, with a platelet threshold of 20,000/µL but note that most other societies and guidelines regard LP as a high–bleeding risk procedure with more conservative platelet thresholds.² The Association of British Neurologists (ABN), however, allows platelets to be 40,000/µL or greater than 20,000/µL with an additional risk-benefit discussion.⁷ In contrast to paracentesis and thoracentesis, recommendations regarding hold times of antithrombotic medications prior to LP are more variable and sometimes more conservative. For example, some guidelines indicate that the thienopyridines can be continued, whereas others recommend holding them for up to 1 week prior to LP.^2,4,7

A theme throughout the recent literature and recommendations from clinical societies is that it is uncommon for there to be one unifying recommendation for every situation, especially regarding LP. Recent guidelines remain largely based on studies that are decades old. With bedside ultrasound becoming more accessible and established in daily practice, the risk of bleeding has been decreasing, potentially making periprocedural coagulopathies and antithrombotic agents less of a concern. For example, in a retrospective study of 69,859 paracenteses, ultrasound guidance reduced the risk of bleeding complications by 68%, an odds ratio of 0.32 (95% CI, 0.25-0.41).¹⁷ More research is needed to assess procedural bleeding risks in the context of current practice standards. This article focuses on a subset of bedside procedures most commonly performed by hospitalists. Similar references for other common bedside procedures, such as arthrocentesis, central venous catheter, and arterial line placement, would be helpful. Finally, this article does not capture such nuances as needle gauge, operator experience, availability of (and comfort with) ultrasound, and variations in patient anatomy, all of which are factors that can contribute to the complexities and risks of these bedside procedures.

Although not every internal medicine physician performs bedside procedures in their practice, it is vital that all understand the cognitive aspects of common bedside procedures. This necessitates the understanding of periprocedural risks and possible complications and applying that to individual patients. Correcting coagulopathy and stopping or reversing antithrombotic agents are mitigation strategies that are associated with risk. It is therefore important to understand when coagulopathy should be corrected and when antithrombotic agents should be held and for how long. With multiple existing and sometimes conflicting guidelines regarding periprocedural management of coagulopathy and antithrombotic agents, we hope that providing consolidated tables with this information will increase efficiency, aid in risk-benefit discussions between patients and care teams, and enhance patient safety.

Most hospital pediatricians can recall cases where an abnormal result in one unnecessary test led to a cascade of multiple further unnecessary treatments, procedures, and tests. These cases are well described in the literature and written off as a side effect of delivering high-quality, comprehensive pediatric care.¹ Unfortunately, however, these frequent events are not without consequence and can cause significant harm to patients, as well as stress and fear for parents and families, and indirectly waste valuable resources.

As we look forward to recovering from the COVID-19 pandemic, there are calls to prioritize high-value and more equitable care in the postpandemic world.² Choosing Wisely is a global movement comprised of clinician-led campaigns that partner with national specialty societies to develop lists of evidence-based recommendations of tests, treatments, and procedures that offer no added clinical value and may cause harm.³

In pediatrics, there is a growing recognition and published literature on the harms of overdiagnosis and unnecessary care in children.^4-6 Choosing Wisely recommendations are being used as a resource to drive healthcare prioritization and ensure low-value care is avoided so that greater focus can be placed on areas of need exacerbated by the pandemic. Using a Choosing Wisely perspective can drive quality and help inform a shift in practice, creating a roadmap for reducing testing or treatment cascades that harm patients and waste resources as we move toward the goal of high-value pediatric care. However, adoption of Choosing Wisely recommendations in pediatrics has been slow. For example, the pediatric working group of the Society of Hospital Medicine released a Choosing Wisely^® recommendation in 2013 against the use of continuous pulse oximetry monitoring in children with acute respiratory illness who are not on supplementary oxygen.⁷ Data from a cross-sectional study across 56 hospitals 6 years later found significant variation in this practice for infants hospitalized with bronchiolitis and not receiving supplemental oxygen; 46% were continuously monitored with pulse oximetry (range, 2%-92%).⁸

Traditionally, attention in children’s healthcare has focused on underuse (eg, immunizations or mental health) rather than overuse. Further, the weakness of the evidence base, with very few randomized controlled trials in children, limits our ability to provide sufficient confidence in the evidence supporting some of our recommendations.⁹

Second, there is also tremendous anxiety for both parents and frontline clinicians around diagnostic uncertainty of any kind when it comes to children. We endeavour to reassure ourselves and patients’ families by leaving no stone unturned. This approach can lead to unnecessary care, including false-positive test results, “incidentalomas,” and adverse effects from unnecessary medications. Despite the best intentions of assuaging caregivers’ anxiety, overuse of invasive and uncomfortable tests can have the opposite effect of increasing stress and trauma for both children and parents.

Third, there is compelling evidence that practice habits, once established, are difficult to break.¹⁰ Particularly in the high-stakes practice of hospital pediatric medicine, where we are conditioned to expect the worst and anticipate the unexpected. This “do everything to everyone” approach, however, can lead to significant harms for pediatric patients. For example, the exposure to ionizing radiation through unnecessary computed tomography (CT) scans can increase a child’s lifetime cancer risk.¹¹

The perpetuation of unnecessary care needs to change in pediatrics, especially for the most vulnerable young patients seeking hospital care. Implementation is a necessary next step to introduce recommendations into practice, and the Choosing Wisely efforts of the Hospital for Sick Children in Toronto, Canada, can offer insights into opportunities to embed this approach across similar quaternary care teaching hospitals, as well as general hospitals and the systems they support.

Creating Lists of Recommendations Aligned With Quality Metrics

The Hospital for Sick Children developed a hospital-specific Choosing Wisely list in 2016 to address a gap in existing Choosing Wisely Canada campaign recommendations related to pediatric hospitals.¹² Choosing Wisely Canada was initially focused on adult medicine, and a list of recommendations developed by the Canadian Paediatric Society relates mostly to overuse in pediatric outpatient settings and is not applicable to hospital-based practice.¹³ The Society of Hospital Medicine-Pediatric Hospital Medicine Choosing Wisely^® list predominantly pertained to unnecessary care of infants with bronchiolitis (eg, not to order chest radiographs in uncomplicated asthma and bronchiolitis). We had measured our compliance with this recommendation and found it was already well below the achievable benchmark of care in the United States,¹⁴ so we preferred to create a list that would resonate with our clinicians. Since the original list was created at the Hospital for Sick Children,¹² we have developed two subsequent lists of recommendations, which were released in 2018 and 2021 (Table).

The approach to list development used by staff pediatricians and trainees, with input from hospital staff and family advisors, has been described elsewhere.¹² The goal was to self-identify five local practices that we felt would help us reduce unnecessary care. This list served as the foundation of an organization-wide quality initiative driven by a steering committee that consisted of the clinician champions as well as representation from various groups at the hospital, including decision support, information services, the family advisory committee, and public affairs.

Each recommendation needed to be evidence-based and measurable, have a clinician champion to implement the recommendation, and have the potential to improve the quality and safety of the care we provided. “Balancing” measures needed to be carefully monitored to ensure that no diagnoses were being missed or negative effects resulted from decreasing these interventions. In order for a recommendation to be considered, a subgroup of the pediatric department’s clinical advisory committee reviewed the references provided to ensure that what was being suggested was based on published evidence and part of current national guidelines. The clinician champion needed to agree to lead the implementation project, and specific outcomes, including appropriate balancing measures, needed to be identified a priori, in addition to an appropriate mechanism to collect the data. Hospital executive leaders were supportive of the initiative and facilitated access to “in-kind” hospital resources as required, although no financial budget was provided. After some early success, the Department of Paediatrics provided part-time project management support to help coordinate the growth and administration of the initiative.

Measuring and Supporting Practice Change

The main implementation principles included targeted education/awareness, transparent measurement with audit/feedback, and, most importantly, embedding changes in the ordering process, essentially making it easy for frontline clinicians to do the right thing (and trickier to do the “wrong” thing). Audit and feedback have been used at both the individual provider level (eg, respiratory viral testing–ordering practices) and the divisional level (eg, ordering of postoperative antibiotics). These quality improvement initiatives have had a compelling impact. Scorecards have been developed and results shared internally using local divisional as well as hospital-wide tools, varying from staff meetings to screensavers across hospital computers and television screens and the hospital intranet. Evaluation is ongoing, but many of the initial results have been encouraging.^15-17

For example, the 2016 list includes recommendations related to emergency department (ED) test ordering. Implementation efforts to address unnecessary nasopharyngeal swabs for viral testing in bronchiolitis reduced this practice by 80%,¹⁵ and there has been a 50% reduction in ankle X-rays in children with acute ankle injuries who meet criteria for a low-risk examination.¹⁶ The 2016 list also included a recommendation related to inappropriate intravenous immunoglobulin (IVIG) use in children with typical acute immune thrombocytopenic purpura (ITP), and a targeted quality improvement initiative reduced inappropriate IVIG use by 50%, with no detectable increase in bleeding complications or readmission to hospital.¹⁷ These results have been sustained over a period of 3 or more years. Examples from the 2018 list include a 40% decrease in inappropriate urinary tract infection diagnosis and treatment in the ED and a four-fold decrease in the CT abdomen/pelvis imaging rate for low-risk trauma.¹⁸

The steering committee meets every 2 months and includes all of the clinician champions as well as representatives from strategic hospital resources and two family advisors (NGS). These meetings are chaired by the Associate Pediatrician-in-Chief (JNF) and the project manager. The progress of the active projects is discussed, and the experience of the group is used to problem-solve, plan ahead, and encourage academic presentation and publication of the various projects. Patient partnership and participation in committees has ensured that improvements to patient experience, satisfaction, and education are considered in the outcomes of implementation. Moreover, it has safeguarded that this effort is not misperceived as limiting care and remains focused on advancing quality, safety, and the patient experience.

While most projects have surpassed expectations, not all have proceeded as anticipated. The biggest challenge is finding a reliable and practical source for data collection. For example, at the time of initiation of the voiding cystourethrography (VCUG) recommendation, practice had presumably changed over the recent years, and compliance already exceeded the goal, illustrating the importance of current accurate data. The oxygen saturation–monitoring recommendation highlighted the challenge presented by data collection that requires manual audits; the inability to find staff to do this regularly significantly hampered this project. The critical role of the clinician champion was highlighted in a few projects when a lead was absent for a prolonged period of time (eg, due to a parental leave or change in job), with no willing replacement. There does seem to be a strong correlation between the commitment and passion of the clinician lead and the success of the project. We have incorporated the lessons learned into the development and rollout of the 2018 and 2021 lists.

The challenge is to scale up these successes to impact and change practice across the hospital pediatrics community. After 5 years, awareness of and engagement with this process are still not uniform across our hospital campus. Nevertheless, anecdotally, at the Hospital for Sick Children, there is a shift in culture where clinicians have processed the imperative to reduce overuse and unnecessary tests and treatments, with phrases such as “this is not very Choosing Wisely” entering the vernacular. It is becoming part of the culture. Second, the new generation of medical school trainees and residents has displayed a tremendous appetite and passion for stewardship and a sense that practice can change from the ground up. The SickKids Choosing Wisely efforts have been a hub for resident-led quality improvement projects and leadership for implementation of recommendations.¹⁹ As we continue to engage all providers at our hospital, we are also reaching out to the other community hospitals in our region, and all children’s hospitals in Canada, to share the principles and lessons learned from our program through a national community of practice.

Practicing pediatric medicine in a well-resourced hospital setting should not drive us to overuse in practice “just because we can.” The harms of this approach to our patients and health systems, coupled with the pressures of the pandemic, are compelling reasons to be responsible stewards. There are opportunities to reshape and rethink practice patterns and habits.²⁰ Overuse and overdiagnosis harm our patients and families physically and emotionally and indirectly waste resources urgently needed for investment upstream. Providing safe, quality, high-value care to our young patients requires constant critical thinking. The time is here to advance Choosing Wisely into pediatric hospital practice.

Most hospital pediatricians can recall cases where an abnormal result in one unnecessary test led to a cascade of multiple further unnecessary treatments, procedures, and tests. These cases are well described in the literature and written off as a side effect of delivering high-quality, comprehensive pediatric care.¹ Unfortunately, however, these frequent events are not without consequence and can cause significant harm to patients, as well as stress and fear for parents and families, and indirectly waste valuable resources.

As we look forward to recovering from the COVID-19 pandemic, there are calls to prioritize high-value and more equitable care in the postpandemic world.² Choosing Wisely is a global movement comprised of clinician-led campaigns that partner with national specialty societies to develop lists of evidence-based recommendations of tests, treatments, and procedures that offer no added clinical value and may cause harm.³

In pediatrics, there is a growing recognition and published literature on the harms of overdiagnosis and unnecessary care in children.^4-6 Choosing Wisely recommendations are being used as a resource to drive healthcare prioritization and ensure low-value care is avoided so that greater focus can be placed on areas of need exacerbated by the pandemic. Using a Choosing Wisely perspective can drive quality and help inform a shift in practice, creating a roadmap for reducing testing or treatment cascades that harm patients and waste resources as we move toward the goal of high-value pediatric care. However, adoption of Choosing Wisely recommendations in pediatrics has been slow. For example, the pediatric working group of the Society of Hospital Medicine released a Choosing Wisely^® recommendation in 2013 against the use of continuous pulse oximetry monitoring in children with acute respiratory illness who are not on supplementary oxygen.⁷ Data from a cross-sectional study across 56 hospitals 6 years later found significant variation in this practice for infants hospitalized with bronchiolitis and not receiving supplemental oxygen; 46% were continuously monitored with pulse oximetry (range, 2%-92%).⁸

Traditionally, attention in children’s healthcare has focused on underuse (eg, immunizations or mental health) rather than overuse. Further, the weakness of the evidence base, with very few randomized controlled trials in children, limits our ability to provide sufficient confidence in the evidence supporting some of our recommendations.⁹

Second, there is also tremendous anxiety for both parents and frontline clinicians around diagnostic uncertainty of any kind when it comes to children. We endeavour to reassure ourselves and patients’ families by leaving no stone unturned. This approach can lead to unnecessary care, including false-positive test results, “incidentalomas,” and adverse effects from unnecessary medications. Despite the best intentions of assuaging caregivers’ anxiety, overuse of invasive and uncomfortable tests can have the opposite effect of increasing stress and trauma for both children and parents.

Third, there is compelling evidence that practice habits, once established, are difficult to break.¹⁰ Particularly in the high-stakes practice of hospital pediatric medicine, where we are conditioned to expect the worst and anticipate the unexpected. This “do everything to everyone” approach, however, can lead to significant harms for pediatric patients. For example, the exposure to ionizing radiation through unnecessary computed tomography (CT) scans can increase a child’s lifetime cancer risk.¹¹

The perpetuation of unnecessary care needs to change in pediatrics, especially for the most vulnerable young patients seeking hospital care. Implementation is a necessary next step to introduce recommendations into practice, and the Choosing Wisely efforts of the Hospital for Sick Children in Toronto, Canada, can offer insights into opportunities to embed this approach across similar quaternary care teaching hospitals, as well as general hospitals and the systems they support.

Creating Lists of Recommendations Aligned With Quality Metrics

The Hospital for Sick Children developed a hospital-specific Choosing Wisely list in 2016 to address a gap in existing Choosing Wisely Canada campaign recommendations related to pediatric hospitals.¹² Choosing Wisely Canada was initially focused on adult medicine, and a list of recommendations developed by the Canadian Paediatric Society relates mostly to overuse in pediatric outpatient settings and is not applicable to hospital-based practice.¹³ The Society of Hospital Medicine-Pediatric Hospital Medicine Choosing Wisely^® list predominantly pertained to unnecessary care of infants with bronchiolitis (eg, not to order chest radiographs in uncomplicated asthma and bronchiolitis). We had measured our compliance with this recommendation and found it was already well below the achievable benchmark of care in the United States,¹⁴ so we preferred to create a list that would resonate with our clinicians. Since the original list was created at the Hospital for Sick Children,¹² we have developed two subsequent lists of recommendations, which were released in 2018 and 2021 (Table).

The approach to list development used by staff pediatricians and trainees, with input from hospital staff and family advisors, has been described elsewhere.¹² The goal was to self-identify five local practices that we felt would help us reduce unnecessary care. This list served as the foundation of an organization-wide quality initiative driven by a steering committee that consisted of the clinician champions as well as representation from various groups at the hospital, including decision support, information services, the family advisory committee, and public affairs.

Each recommendation needed to be evidence-based and measurable, have a clinician champion to implement the recommendation, and have the potential to improve the quality and safety of the care we provided. “Balancing” measures needed to be carefully monitored to ensure that no diagnoses were being missed or negative effects resulted from decreasing these interventions. In order for a recommendation to be considered, a subgroup of the pediatric department’s clinical advisory committee reviewed the references provided to ensure that what was being suggested was based on published evidence and part of current national guidelines. The clinician champion needed to agree to lead the implementation project, and specific outcomes, including appropriate balancing measures, needed to be identified a priori, in addition to an appropriate mechanism to collect the data. Hospital executive leaders were supportive of the initiative and facilitated access to “in-kind” hospital resources as required, although no financial budget was provided. After some early success, the Department of Paediatrics provided part-time project management support to help coordinate the growth and administration of the initiative.

Measuring and Supporting Practice Change

The main implementation principles included targeted education/awareness, transparent measurement with audit/feedback, and, most importantly, embedding changes in the ordering process, essentially making it easy for frontline clinicians to do the right thing (and trickier to do the “wrong” thing). Audit and feedback have been used at both the individual provider level (eg, respiratory viral testing–ordering practices) and the divisional level (eg, ordering of postoperative antibiotics). These quality improvement initiatives have had a compelling impact. Scorecards have been developed and results shared internally using local divisional as well as hospital-wide tools, varying from staff meetings to screensavers across hospital computers and television screens and the hospital intranet. Evaluation is ongoing, but many of the initial results have been encouraging.^15-17

For example, the 2016 list includes recommendations related to emergency department (ED) test ordering. Implementation efforts to address unnecessary nasopharyngeal swabs for viral testing in bronchiolitis reduced this practice by 80%,¹⁵ and there has been a 50% reduction in ankle X-rays in children with acute ankle injuries who meet criteria for a low-risk examination.¹⁶ The 2016 list also included a recommendation related to inappropriate intravenous immunoglobulin (IVIG) use in children with typical acute immune thrombocytopenic purpura (ITP), and a targeted quality improvement initiative reduced inappropriate IVIG use by 50%, with no detectable increase in bleeding complications or readmission to hospital.¹⁷ These results have been sustained over a period of 3 or more years. Examples from the 2018 list include a 40% decrease in inappropriate urinary tract infection diagnosis and treatment in the ED and a four-fold decrease in the CT abdomen/pelvis imaging rate for low-risk trauma.¹⁸

The steering committee meets every 2 months and includes all of the clinician champions as well as representatives from strategic hospital resources and two family advisors (NGS). These meetings are chaired by the Associate Pediatrician-in-Chief (JNF) and the project manager. The progress of the active projects is discussed, and the experience of the group is used to problem-solve, plan ahead, and encourage academic presentation and publication of the various projects. Patient partnership and participation in committees has ensured that improvements to patient experience, satisfaction, and education are considered in the outcomes of implementation. Moreover, it has safeguarded that this effort is not misperceived as limiting care and remains focused on advancing quality, safety, and the patient experience.

While most projects have surpassed expectations, not all have proceeded as anticipated. The biggest challenge is finding a reliable and practical source for data collection. For example, at the time of initiation of the voiding cystourethrography (VCUG) recommendation, practice had presumably changed over the recent years, and compliance already exceeded the goal, illustrating the importance of current accurate data. The oxygen saturation–monitoring recommendation highlighted the challenge presented by data collection that requires manual audits; the inability to find staff to do this regularly significantly hampered this project. The critical role of the clinician champion was highlighted in a few projects when a lead was absent for a prolonged period of time (eg, due to a parental leave or change in job), with no willing replacement. There does seem to be a strong correlation between the commitment and passion of the clinician lead and the success of the project. We have incorporated the lessons learned into the development and rollout of the 2018 and 2021 lists.

The challenge is to scale up these successes to impact and change practice across the hospital pediatrics community. After 5 years, awareness of and engagement with this process are still not uniform across our hospital campus. Nevertheless, anecdotally, at the Hospital for Sick Children, there is a shift in culture where clinicians have processed the imperative to reduce overuse and unnecessary tests and treatments, with phrases such as “this is not very Choosing Wisely” entering the vernacular. It is becoming part of the culture. Second, the new generation of medical school trainees and residents has displayed a tremendous appetite and passion for stewardship and a sense that practice can change from the ground up. The SickKids Choosing Wisely efforts have been a hub for resident-led quality improvement projects and leadership for implementation of recommendations.¹⁹ As we continue to engage all providers at our hospital, we are also reaching out to the other community hospitals in our region, and all children’s hospitals in Canada, to share the principles and lessons learned from our program through a national community of practice.

Practicing pediatric medicine in a well-resourced hospital setting should not drive us to overuse in practice “just because we can.” The harms of this approach to our patients and health systems, coupled with the pressures of the pandemic, are compelling reasons to be responsible stewards. There are opportunities to reshape and rethink practice patterns and habits.²⁰ Overuse and overdiagnosis harm our patients and families physically and emotionally and indirectly waste resources urgently needed for investment upstream. Providing safe, quality, high-value care to our young patients requires constant critical thinking. The time is here to advance Choosing Wisely into pediatric hospital practice.

Most hospital pediatricians can recall cases where an abnormal result in one unnecessary test led to a cascade of multiple further unnecessary treatments, procedures, and tests. These cases are well described in the literature and written off as a side effect of delivering high-quality, comprehensive pediatric care.¹ Unfortunately, however, these frequent events are not without consequence and can cause significant harm to patients, as well as stress and fear for parents and families, and indirectly waste valuable resources.

As we look forward to recovering from the COVID-19 pandemic, there are calls to prioritize high-value and more equitable care in the postpandemic world.² Choosing Wisely is a global movement comprised of clinician-led campaigns that partner with national specialty societies to develop lists of evidence-based recommendations of tests, treatments, and procedures that offer no added clinical value and may cause harm.³

In pediatrics, there is a growing recognition and published literature on the harms of overdiagnosis and unnecessary care in children.^4-6 Choosing Wisely recommendations are being used as a resource to drive healthcare prioritization and ensure low-value care is avoided so that greater focus can be placed on areas of need exacerbated by the pandemic. Using a Choosing Wisely perspective can drive quality and help inform a shift in practice, creating a roadmap for reducing testing or treatment cascades that harm patients and waste resources as we move toward the goal of high-value pediatric care. However, adoption of Choosing Wisely recommendations in pediatrics has been slow. For example, the pediatric working group of the Society of Hospital Medicine released a Choosing Wisely^® recommendation in 2013 against the use of continuous pulse oximetry monitoring in children with acute respiratory illness who are not on supplementary oxygen.⁷ Data from a cross-sectional study across 56 hospitals 6 years later found significant variation in this practice for infants hospitalized with bronchiolitis and not receiving supplemental oxygen; 46% were continuously monitored with pulse oximetry (range, 2%-92%).⁸

Traditionally, attention in children’s healthcare has focused on underuse (eg, immunizations or mental health) rather than overuse. Further, the weakness of the evidence base, with very few randomized controlled trials in children, limits our ability to provide sufficient confidence in the evidence supporting some of our recommendations.⁹

Second, there is also tremendous anxiety for both parents and frontline clinicians around diagnostic uncertainty of any kind when it comes to children. We endeavour to reassure ourselves and patients’ families by leaving no stone unturned. This approach can lead to unnecessary care, including false-positive test results, “incidentalomas,” and adverse effects from unnecessary medications. Despite the best intentions of assuaging caregivers’ anxiety, overuse of invasive and uncomfortable tests can have the opposite effect of increasing stress and trauma for both children and parents.

Third, there is compelling evidence that practice habits, once established, are difficult to break.¹⁰ Particularly in the high-stakes practice of hospital pediatric medicine, where we are conditioned to expect the worst and anticipate the unexpected. This “do everything to everyone” approach, however, can lead to significant harms for pediatric patients. For example, the exposure to ionizing radiation through unnecessary computed tomography (CT) scans can increase a child’s lifetime cancer risk.¹¹

The perpetuation of unnecessary care needs to change in pediatrics, especially for the most vulnerable young patients seeking hospital care. Implementation is a necessary next step to introduce recommendations into practice, and the Choosing Wisely efforts of the Hospital for Sick Children in Toronto, Canada, can offer insights into opportunities to embed this approach across similar quaternary care teaching hospitals, as well as general hospitals and the systems they support.

Creating Lists of Recommendations Aligned With Quality Metrics

The Hospital for Sick Children developed a hospital-specific Choosing Wisely list in 2016 to address a gap in existing Choosing Wisely Canada campaign recommendations related to pediatric hospitals.¹² Choosing Wisely Canada was initially focused on adult medicine, and a list of recommendations developed by the Canadian Paediatric Society relates mostly to overuse in pediatric outpatient settings and is not applicable to hospital-based practice.¹³ The Society of Hospital Medicine-Pediatric Hospital Medicine Choosing Wisely^® list predominantly pertained to unnecessary care of infants with bronchiolitis (eg, not to order chest radiographs in uncomplicated asthma and bronchiolitis). We had measured our compliance with this recommendation and found it was already well below the achievable benchmark of care in the United States,¹⁴ so we preferred to create a list that would resonate with our clinicians. Since the original list was created at the Hospital for Sick Children,¹² we have developed two subsequent lists of recommendations, which were released in 2018 and 2021 (Table).

The approach to list development used by staff pediatricians and trainees, with input from hospital staff and family advisors, has been described elsewhere.¹² The goal was to self-identify five local practices that we felt would help us reduce unnecessary care. This list served as the foundation of an organization-wide quality initiative driven by a steering committee that consisted of the clinician champions as well as representation from various groups at the hospital, including decision support, information services, the family advisory committee, and public affairs.

Each recommendation needed to be evidence-based and measurable, have a clinician champion to implement the recommendation, and have the potential to improve the quality and safety of the care we provided. “Balancing” measures needed to be carefully monitored to ensure that no diagnoses were being missed or negative effects resulted from decreasing these interventions. In order for a recommendation to be considered, a subgroup of the pediatric department’s clinical advisory committee reviewed the references provided to ensure that what was being suggested was based on published evidence and part of current national guidelines. The clinician champion needed to agree to lead the implementation project, and specific outcomes, including appropriate balancing measures, needed to be identified a priori, in addition to an appropriate mechanism to collect the data. Hospital executive leaders were supportive of the initiative and facilitated access to “in-kind” hospital resources as required, although no financial budget was provided. After some early success, the Department of Paediatrics provided part-time project management support to help coordinate the growth and administration of the initiative.

Measuring and Supporting Practice Change

The main implementation principles included targeted education/awareness, transparent measurement with audit/feedback, and, most importantly, embedding changes in the ordering process, essentially making it easy for frontline clinicians to do the right thing (and trickier to do the “wrong” thing). Audit and feedback have been used at both the individual provider level (eg, respiratory viral testing–ordering practices) and the divisional level (eg, ordering of postoperative antibiotics). These quality improvement initiatives have had a compelling impact. Scorecards have been developed and results shared internally using local divisional as well as hospital-wide tools, varying from staff meetings to screensavers across hospital computers and television screens and the hospital intranet. Evaluation is ongoing, but many of the initial results have been encouraging.^15-17

For example, the 2016 list includes recommendations related to emergency department (ED) test ordering. Implementation efforts to address unnecessary nasopharyngeal swabs for viral testing in bronchiolitis reduced this practice by 80%,¹⁵ and there has been a 50% reduction in ankle X-rays in children with acute ankle injuries who meet criteria for a low-risk examination.¹⁶ The 2016 list also included a recommendation related to inappropriate intravenous immunoglobulin (IVIG) use in children with typical acute immune thrombocytopenic purpura (ITP), and a targeted quality improvement initiative reduced inappropriate IVIG use by 50%, with no detectable increase in bleeding complications or readmission to hospital.¹⁷ These results have been sustained over a period of 3 or more years. Examples from the 2018 list include a 40% decrease in inappropriate urinary tract infection diagnosis and treatment in the ED and a four-fold decrease in the CT abdomen/pelvis imaging rate for low-risk trauma.¹⁸

The steering committee meets every 2 months and includes all of the clinician champions as well as representatives from strategic hospital resources and two family advisors (NGS). These meetings are chaired by the Associate Pediatrician-in-Chief (JNF) and the project manager. The progress of the active projects is discussed, and the experience of the group is used to problem-solve, plan ahead, and encourage academic presentation and publication of the various projects. Patient partnership and participation in committees has ensured that improvements to patient experience, satisfaction, and education are considered in the outcomes of implementation. Moreover, it has safeguarded that this effort is not misperceived as limiting care and remains focused on advancing quality, safety, and the patient experience.

While most projects have surpassed expectations, not all have proceeded as anticipated. The biggest challenge is finding a reliable and practical source for data collection. For example, at the time of initiation of the voiding cystourethrography (VCUG) recommendation, practice had presumably changed over the recent years, and compliance already exceeded the goal, illustrating the importance of current accurate data. The oxygen saturation–monitoring recommendation highlighted the challenge presented by data collection that requires manual audits; the inability to find staff to do this regularly significantly hampered this project. The critical role of the clinician champion was highlighted in a few projects when a lead was absent for a prolonged period of time (eg, due to a parental leave or change in job), with no willing replacement. There does seem to be a strong correlation between the commitment and passion of the clinician lead and the success of the project. We have incorporated the lessons learned into the development and rollout of the 2018 and 2021 lists.

The challenge is to scale up these successes to impact and change practice across the hospital pediatrics community. After 5 years, awareness of and engagement with this process are still not uniform across our hospital campus. Nevertheless, anecdotally, at the Hospital for Sick Children, there is a shift in culture where clinicians have processed the imperative to reduce overuse and unnecessary tests and treatments, with phrases such as “this is not very Choosing Wisely” entering the vernacular. It is becoming part of the culture. Second, the new generation of medical school trainees and residents has displayed a tremendous appetite and passion for stewardship and a sense that practice can change from the ground up. The SickKids Choosing Wisely efforts have been a hub for resident-led quality improvement projects and leadership for implementation of recommendations.¹⁹ As we continue to engage all providers at our hospital, we are also reaching out to the other community hospitals in our region, and all children’s hospitals in Canada, to share the principles and lessons learned from our program through a national community of practice.

Practicing pediatric medicine in a well-resourced hospital setting should not drive us to overuse in practice “just because we can.” The harms of this approach to our patients and health systems, coupled with the pressures of the pandemic, are compelling reasons to be responsible stewards. There are opportunities to reshape and rethink practice patterns and habits.²⁰ Overuse and overdiagnosis harm our patients and families physically and emotionally and indirectly waste resources urgently needed for investment upstream. Providing safe, quality, high-value care to our young patients requires constant critical thinking. The time is here to advance Choosing Wisely into pediatric hospital practice.

A 59-year-old man is observed in the hospital for substernal chest pain initially concerning for angina. Serial troponin testing is negative, and based on additional history of intermittent dysphagia, an elective upper endoscopy is recommended after discharge. The patient does not have health insurance and expresses anxiety about the cost of endoscopy. He asks how he could compare the costs at different hospitals. How do federal price transparency rules assist the hospitalist in addressing this patient’s question?

Healthcare costs continue to rise in the United States despite mounting concerns about wasteful spending and unaffordability.¹ One contributor is a lack of price transparency.² In theory, price transparency allows individuals to shop for services, spurring competition and lower prices. However, healthcare prices have historically been opaque to both physicians and patients; unlike other licensed professionals who provide clients estimates for their work (eg, lawyers, electricians), physicians are rarely able to offer patients real-time insight or guidance about costs, which most patients discover only when the bill arrives. The situation is particularly problematic for patients who bear higher out-of-pocket costs, such as the uninsured or those with high-deductible health plans.³

Decades of work to improve healthcare price transparency have unfortunately borne little fruit. Multiple states and organizations have attempted to disseminate price information on comparison websites.⁴ These efforts only modestly reduced some prices, with benefits confined to elective, single-episode, commodifiable services such as magnetic resonance imaging scans.⁵ The Affordable Care Act required hospitals to publish standard charges, also called a chargemaster (Table).⁶ However, chargemaster fees are notoriously inflated and inaccessible at the point of service, undercutting transparency.

Beginning January 2021, the Centers for Medicare & Medicaid Services (CMS) required all hospitals to publish negotiated prices—including payor-specific negotiated charges—for 300 “shoppable services” (Table).⁶ The list must include 70 common CMS-specified services, such as a basic metabolic panel, upper endoscopy, and prostate biopsy, as well as another 230 services that each hospital determines relevant to its patient population.

In circumstances where hospitals have negotiated different prices for a service, they must list each third-party payor and their payor-specific charge. The information must be prominently displayed, accessible without requiring the patient to enter personal information, and provided in a machine-readable file. CMS may impose a $300 daily penalty on hospitals failing to comply with the policy. Of note, the policy does not apply to clinics or ambulatory surgery centers.

As more hospitals share data, this policy will directly benefit both patients and physicians. It can benefit patients with the time, foresight, and ability to search for the lowest price for shoppable services. Other patients may also benefit indirectly, to the extent that insurers and other purchasers apply this information to negotiate lower and more uniform prices. Decreased price variation may also encourage hospitals to compete on quality to distinguish the value of their services. Hospitalists could benefit through the ability to directly help patients locate price information.

Despite these potential benefits, the policy has limitations. Price information about shoppable services is most useful for discharge planning, and other solutions are needed to address transparency before and during unplanned admissions. Patients who prioritize continuity with a hospital or physician may be less price sensitive, particularly for more complex services. Patients with commercial insurance may be shielded from cost considerations and personal incentives to comparison shop. Interpreting hospitals’ estimates remains difficult, as it can be unclear if professional fees are included or if certain prices are offered to outpatients.⁷ Price information is not accompanied by corresponding quality data. Additionally, price transparency may also fail to lower prices in heavily concentrated payor or provider markets, and it remains unknown whether some providers may actually raise prices after learning about higher rates negotiated by competitors.^8,9

Another issue is hospital participation. Early evidence suggests that most hospitals have not complied with the letter or spirit of the regulation.^7,10 A sample of the country’s 100 largest hospitals in February 2021 found 18 lacked downloadable files and 46 did not display payor-specific rates.¹¹ In addition, some hospitals posted prices on websites designed to block discovery by search engines, a tactic deemed illegal by CMS.¹² Thus far, enforcement efforts have consisted of warnings rather than financial penalties.

Despite its limitations, this policy represents a meaningful advance for healthcare competition and patient empowerment. Additionally, it signals federal willingness to address the lack of price transparency as a source of widespread patient and clinician frustration—a commitment that will be needed to sustain this policy and implement additional measures in the future.

CMS could consider five steps to augment the policy and maximize transparency and value for patients.

First, CMS could consider increasing daily nonparticipation penalties. Hospitals, particularly those in areas with less competition, have less incentive to participate given meager current penalties. Because the magnitude needed to compel action remains unknown, CMS could gradually escalate penalties over time until there is broader participation across hospitals.

Second, policymakers could aggregate price information centrally, organize the data around patients’ clinical scenarios, and advertise its availability. Currently, this information is scattered and time-consuming for hospitalists and patients to gather for decision-making. Additionally, CMS could encourage the development of third-party tools that aggregate and analyze machine-readable price data or require that prices be posted at the point of service.

Third, CMS could revise the policy to include quality as well as price information. Price alone does not offer a full enough picture of what consumers can expect from hospitals for shoppable services. Pairing price and quality information is better aligned to addressing costs in the context of value, rather than cost-cutting for its own purposes.

Fourth, over time, CMS could expand the list of services and sites required to report (eg, clinics and ambulatory surgical centers as well as hospitals).

Fifth, CMS rule-makers could set reporting standards and contextualize price information in common clinical scenarios. Patients may have difficulty shopping for complex healthcare services without understanding how they apply in different clinical situations. Decision-making would also be aided by reporting standards—for instance, for how prices are displayed and whether they include certain fees (eg, professional fees, pathology studies).

Hospitalists planning follow-up care should inform patients that price information is increasingly available and encourage them to search on the internet or contact hospital billing offices to request information (eg, discounted cash prices and minimum negotiated charges) before obtaining elective services after discharge. Hospitalists can also encourage patients to discuss shoppable services with their primary care physicians to understand the clinical context and make high-value decisions. Hospitalists who wish to build communication skills discussing costs with patients can increasingly find resources for these conversations and request that prices be displayed in the electronic health record for this purpose.^13,14 As conversations occur, hospitalists should seek to understand other factors, such as convenience and continuity relationships, that might influence choices.

Starting in 2021, CMS policy requires that hospitals report prices for services such as the endoscopy recommended for the patient in the scenario. Though the policy gives patients new hope for greater transparency and better prices, additional steps are needed to help patients and hospitalists achieve these benefits.

A 59-year-old man is observed in the hospital for substernal chest pain initially concerning for angina. Serial troponin testing is negative, and based on additional history of intermittent dysphagia, an elective upper endoscopy is recommended after discharge. The patient does not have health insurance and expresses anxiety about the cost of endoscopy. He asks how he could compare the costs at different hospitals. How do federal price transparency rules assist the hospitalist in addressing this patient’s question?

Healthcare costs continue to rise in the United States despite mounting concerns about wasteful spending and unaffordability.¹ One contributor is a lack of price transparency.² In theory, price transparency allows individuals to shop for services, spurring competition and lower prices. However, healthcare prices have historically been opaque to both physicians and patients; unlike other licensed professionals who provide clients estimates for their work (eg, lawyers, electricians), physicians are rarely able to offer patients real-time insight or guidance about costs, which most patients discover only when the bill arrives. The situation is particularly problematic for patients who bear higher out-of-pocket costs, such as the uninsured or those with high-deductible health plans.³

Decades of work to improve healthcare price transparency have unfortunately borne little fruit. Multiple states and organizations have attempted to disseminate price information on comparison websites.⁴ These efforts only modestly reduced some prices, with benefits confined to elective, single-episode, commodifiable services such as magnetic resonance imaging scans.⁵ The Affordable Care Act required hospitals to publish standard charges, also called a chargemaster (Table).⁶ However, chargemaster fees are notoriously inflated and inaccessible at the point of service, undercutting transparency.

Beginning January 2021, the Centers for Medicare & Medicaid Services (CMS) required all hospitals to publish negotiated prices—including payor-specific negotiated charges—for 300 “shoppable services” (Table).⁶ The list must include 70 common CMS-specified services, such as a basic metabolic panel, upper endoscopy, and prostate biopsy, as well as another 230 services that each hospital determines relevant to its patient population.

In circumstances where hospitals have negotiated different prices for a service, they must list each third-party payor and their payor-specific charge. The information must be prominently displayed, accessible without requiring the patient to enter personal information, and provided in a machine-readable file. CMS may impose a $300 daily penalty on hospitals failing to comply with the policy. Of note, the policy does not apply to clinics or ambulatory surgery centers.

As more hospitals share data, this policy will directly benefit both patients and physicians. It can benefit patients with the time, foresight, and ability to search for the lowest price for shoppable services. Other patients may also benefit indirectly, to the extent that insurers and other purchasers apply this information to negotiate lower and more uniform prices. Decreased price variation may also encourage hospitals to compete on quality to distinguish the value of their services. Hospitalists could benefit through the ability to directly help patients locate price information.

Despite these potential benefits, the policy has limitations. Price information about shoppable services is most useful for discharge planning, and other solutions are needed to address transparency before and during unplanned admissions. Patients who prioritize continuity with a hospital or physician may be less price sensitive, particularly for more complex services. Patients with commercial insurance may be shielded from cost considerations and personal incentives to comparison shop. Interpreting hospitals’ estimates remains difficult, as it can be unclear if professional fees are included or if certain prices are offered to outpatients.⁷ Price information is not accompanied by corresponding quality data. Additionally, price transparency may also fail to lower prices in heavily concentrated payor or provider markets, and it remains unknown whether some providers may actually raise prices after learning about higher rates negotiated by competitors.^8,9

Another issue is hospital participation. Early evidence suggests that most hospitals have not complied with the letter or spirit of the regulation.^7,10 A sample of the country’s 100 largest hospitals in February 2021 found 18 lacked downloadable files and 46 did not display payor-specific rates.¹¹ In addition, some hospitals posted prices on websites designed to block discovery by search engines, a tactic deemed illegal by CMS.¹² Thus far, enforcement efforts have consisted of warnings rather than financial penalties.

Despite its limitations, this policy represents a meaningful advance for healthcare competition and patient empowerment. Additionally, it signals federal willingness to address the lack of price transparency as a source of widespread patient and clinician frustration—a commitment that will be needed to sustain this policy and implement additional measures in the future.

CMS could consider five steps to augment the policy and maximize transparency and value for patients.

First, CMS could consider increasing daily nonparticipation penalties. Hospitals, particularly those in areas with less competition, have less incentive to participate given meager current penalties. Because the magnitude needed to compel action remains unknown, CMS could gradually escalate penalties over time until there is broader participation across hospitals.

Second, policymakers could aggregate price information centrally, organize the data around patients’ clinical scenarios, and advertise its availability. Currently, this information is scattered and time-consuming for hospitalists and patients to gather for decision-making. Additionally, CMS could encourage the development of third-party tools that aggregate and analyze machine-readable price data or require that prices be posted at the point of service.

Third, CMS could revise the policy to include quality as well as price information. Price alone does not offer a full enough picture of what consumers can expect from hospitals for shoppable services. Pairing price and quality information is better aligned to addressing costs in the context of value, rather than cost-cutting for its own purposes.

Fourth, over time, CMS could expand the list of services and sites required to report (eg, clinics and ambulatory surgical centers as well as hospitals).

Fifth, CMS rule-makers could set reporting standards and contextualize price information in common clinical scenarios. Patients may have difficulty shopping for complex healthcare services without understanding how they apply in different clinical situations. Decision-making would also be aided by reporting standards—for instance, for how prices are displayed and whether they include certain fees (eg, professional fees, pathology studies).

Hospitalists planning follow-up care should inform patients that price information is increasingly available and encourage them to search on the internet or contact hospital billing offices to request information (eg, discounted cash prices and minimum negotiated charges) before obtaining elective services after discharge. Hospitalists can also encourage patients to discuss shoppable services with their primary care physicians to understand the clinical context and make high-value decisions. Hospitalists who wish to build communication skills discussing costs with patients can increasingly find resources for these conversations and request that prices be displayed in the electronic health record for this purpose.^13,14 As conversations occur, hospitalists should seek to understand other factors, such as convenience and continuity relationships, that might influence choices.

Starting in 2021, CMS policy requires that hospitals report prices for services such as the endoscopy recommended for the patient in the scenario. Though the policy gives patients new hope for greater transparency and better prices, additional steps are needed to help patients and hospitalists achieve these benefits.

A 59-year-old man is observed in the hospital for substernal chest pain initially concerning for angina. Serial troponin testing is negative, and based on additional history of intermittent dysphagia, an elective upper endoscopy is recommended after discharge. The patient does not have health insurance and expresses anxiety about the cost of endoscopy. He asks how he could compare the costs at different hospitals. How do federal price transparency rules assist the hospitalist in addressing this patient’s question?

Healthcare costs continue to rise in the United States despite mounting concerns about wasteful spending and unaffordability.¹ One contributor is a lack of price transparency.² In theory, price transparency allows individuals to shop for services, spurring competition and lower prices. However, healthcare prices have historically been opaque to both physicians and patients; unlike other licensed professionals who provide clients estimates for their work (eg, lawyers, electricians), physicians are rarely able to offer patients real-time insight or guidance about costs, which most patients discover only when the bill arrives. The situation is particularly problematic for patients who bear higher out-of-pocket costs, such as the uninsured or those with high-deductible health plans.³

Decades of work to improve healthcare price transparency have unfortunately borne little fruit. Multiple states and organizations have attempted to disseminate price information on comparison websites.⁴ These efforts only modestly reduced some prices, with benefits confined to elective, single-episode, commodifiable services such as magnetic resonance imaging scans.⁵ The Affordable Care Act required hospitals to publish standard charges, also called a chargemaster (Table).⁶ However, chargemaster fees are notoriously inflated and inaccessible at the point of service, undercutting transparency.

Beginning January 2021, the Centers for Medicare & Medicaid Services (CMS) required all hospitals to publish negotiated prices—including payor-specific negotiated charges—for 300 “shoppable services” (Table).⁶ The list must include 70 common CMS-specified services, such as a basic metabolic panel, upper endoscopy, and prostate biopsy, as well as another 230 services that each hospital determines relevant to its patient population.

In circumstances where hospitals have negotiated different prices for a service, they must list each third-party payor and their payor-specific charge. The information must be prominently displayed, accessible without requiring the patient to enter personal information, and provided in a machine-readable file. CMS may impose a $300 daily penalty on hospitals failing to comply with the policy. Of note, the policy does not apply to clinics or ambulatory surgery centers.

As more hospitals share data, this policy will directly benefit both patients and physicians. It can benefit patients with the time, foresight, and ability to search for the lowest price for shoppable services. Other patients may also benefit indirectly, to the extent that insurers and other purchasers apply this information to negotiate lower and more uniform prices. Decreased price variation may also encourage hospitals to compete on quality to distinguish the value of their services. Hospitalists could benefit through the ability to directly help patients locate price information.

Despite these potential benefits, the policy has limitations. Price information about shoppable services is most useful for discharge planning, and other solutions are needed to address transparency before and during unplanned admissions. Patients who prioritize continuity with a hospital or physician may be less price sensitive, particularly for more complex services. Patients with commercial insurance may be shielded from cost considerations and personal incentives to comparison shop. Interpreting hospitals’ estimates remains difficult, as it can be unclear if professional fees are included or if certain prices are offered to outpatients.⁷ Price information is not accompanied by corresponding quality data. Additionally, price transparency may also fail to lower prices in heavily concentrated payor or provider markets, and it remains unknown whether some providers may actually raise prices after learning about higher rates negotiated by competitors.^8,9

Another issue is hospital participation. Early evidence suggests that most hospitals have not complied with the letter or spirit of the regulation.^7,10 A sample of the country’s 100 largest hospitals in February 2021 found 18 lacked downloadable files and 46 did not display payor-specific rates.¹¹ In addition, some hospitals posted prices on websites designed to block discovery by search engines, a tactic deemed illegal by CMS.¹² Thus far, enforcement efforts have consisted of warnings rather than financial penalties.

Despite its limitations, this policy represents a meaningful advance for healthcare competition and patient empowerment. Additionally, it signals federal willingness to address the lack of price transparency as a source of widespread patient and clinician frustration—a commitment that will be needed to sustain this policy and implement additional measures in the future.

CMS could consider five steps to augment the policy and maximize transparency and value for patients.

First, CMS could consider increasing daily nonparticipation penalties. Hospitals, particularly those in areas with less competition, have less incentive to participate given meager current penalties. Because the magnitude needed to compel action remains unknown, CMS could gradually escalate penalties over time until there is broader participation across hospitals.

Second, policymakers could aggregate price information centrally, organize the data around patients’ clinical scenarios, and advertise its availability. Currently, this information is scattered and time-consuming for hospitalists and patients to gather for decision-making. Additionally, CMS could encourage the development of third-party tools that aggregate and analyze machine-readable price data or require that prices be posted at the point of service.

Third, CMS could revise the policy to include quality as well as price information. Price alone does not offer a full enough picture of what consumers can expect from hospitals for shoppable services. Pairing price and quality information is better aligned to addressing costs in the context of value, rather than cost-cutting for its own purposes.

Fourth, over time, CMS could expand the list of services and sites required to report (eg, clinics and ambulatory surgical centers as well as hospitals).

Fifth, CMS rule-makers could set reporting standards and contextualize price information in common clinical scenarios. Patients may have difficulty shopping for complex healthcare services without understanding how they apply in different clinical situations. Decision-making would also be aided by reporting standards—for instance, for how prices are displayed and whether they include certain fees (eg, professional fees, pathology studies).

Hospitalists planning follow-up care should inform patients that price information is increasingly available and encourage them to search on the internet or contact hospital billing offices to request information (eg, discounted cash prices and minimum negotiated charges) before obtaining elective services after discharge. Hospitalists can also encourage patients to discuss shoppable services with their primary care physicians to understand the clinical context and make high-value decisions. Hospitalists who wish to build communication skills discussing costs with patients can increasingly find resources for these conversations and request that prices be displayed in the electronic health record for this purpose.^13,14 As conversations occur, hospitalists should seek to understand other factors, such as convenience and continuity relationships, that might influence choices.

Starting in 2021, CMS policy requires that hospitals report prices for services such as the endoscopy recommended for the patient in the scenario. Though the policy gives patients new hope for greater transparency and better prices, additional steps are needed to help patients and hospitalists achieve these benefits.

Orbital cellulitis/abscess (OCA) is a potential complication of sinusitis. If not treated promptly, it can result in vision loss, intracranial infection, or cavernous sinus thrombosis.^1,2 In 1970, Chandler et al³ classified orbital complications of acute sinusitis into five groups: inflammatory edema (group 1); orbital cellulitis (group 2); subperiosteal abscess (SPA) (group 3); orbital abscess (group 4); and cavernous sinus thrombosis (group 5). Group 1, or preseptal cellulitis, is significantly different from groups 2, 3, and 4, collectively referred to as OCA, which affect the actual orbital content.

Children with OCA are generally hospitalized so they can be treated with intravenous antibiotics. While orbital abscesses (group 4) are typically treated surgically, successful medical management has been reported for cases of orbital cellulitis and SPA (groups 2 and 3).^4,5 No widely accepted guidelines exist for the evaluation and medical management of OCA, resulting in significant variation in care.⁶ The purpose of this systematic review is to summarize existing evidence guiding the medical management of OCA regarding laboratory testing, imaging, and microbiology. This review does not address surgical considerations.

The review protocol has been registered in the PROSPERO International Prospective Register of Systematic Reviews (crd.york.ac.uk/prospero/index.asp; identifier: CRD42020158463), and the review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.⁷

Search Strategy

A systematic search of the literature was designed and conducted by a medical librarian (ES), with input from the research team (AB, SM). The search strategy included Medical Subject Headings (MeSH) terms and keywords related to orbital or subperiosteal cellulitis/abscess and children; see Appendix Table 1 for the complete search strategy. Searches were conducted in MEDLINE (Ovid), Web of Science Core Collection, Scopus, CINAHL (EBSCO), and Cochrane Central Register of Controlled Trials (CENTRAL) using advanced search techniques relative to each database. Searches were last conducted on February 9, 2021.

Eligibility Criteria

The study designs (retrospective and prospective) included in the search were limited to randomized clinical trials, cohort studies, case-control studies, and case series with participants <18 years of age. Case reports describing fewer than 5 patients and literature reviews were excluded. Studies including a combination of adult and pediatric patients were included if pediatric outcomes were reported separately. Only studies available in English were included.

Outcome Measures

The outcome measures were determined a priori based on three clinical questions:

• Q1. What is the role of inflammatory markers—white blood cell (WBC) count, C-reactive protein (CRP), and fever—in distinguishing between the following: preseptal cellulitis (group 1) and OCA (groups 2, 3, and 4); orbital cellulitis (group 2) and abscess (groups 3 and 4); and patients who do and do not require surgery?
• Q2. What is the role of imaging in the evaluation of OCA?
• Q3. What is the microbiology of OCA over the past 2 decades? What is the prevalence of methicillin-resistant Staphylococcus aureus (MRSA)?

Screening

Two review authors (AB, SM) performed both the title/abstract and full-text screen, independently applying the eligibility criteria. Disagreements were discussed, and conflicts were resolved with input from a third reviewer author (ES). Duplications were removed. When two studies had overlapping patient data, the study with fewer data points was excluded.

Data Extraction and Synthesis

All studies included after the full-text screen were divided based on the clinical question they answered (Q1, Q2, Q3 above). Some studies reported outcomes pertinent to more than one question. Two review authors were assigned to each clinical question. They independently reviewed each article and extracted the pertinent data into question-specific extraction sheets. Articles assigned to Q2 were reviewed by two pediatric neuroradiologists. For each study, the following details were extracted: authors, location, year, study type, study period, population, and number and ages of participants. Details that were question-specific included: (Q1) values and/or percentages for inflammatory markers; (Q2) reasons for imaging or type of imaging; and (Q3) participants managed surgically and culture results. The data were then synthesized in table and/or narrative format. For Q3, the organisms identified from intraoperative and blood cultures in each study were mathematically combined. When possible, prevalence was calculated using the number of patients with at least one pathogen recovered as the denominator. If this number was not available, the number of patients who underwent surgery was used as the denominator.

Quality Assessment

No randomized controlled trials were identified. More than 90% of the studies identified and included were retrospective descriptive studies. By the nature of the case series design, the study quality was felt to be poor, with high risk of bias. The Joanna Briggs Institute Critical Appraisal tools for systematic reviews were used to appraise each individual study included (Appendix Table 2).⁸ The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria were used in rating the quality of evidence for each question.⁹

A summary of the search strategy and study selection is provided in the Figure (PRISMA flow diagram). The initial search identified 3007 studies. After duplicates were removed and general eligibility criteria applied, 94 articles remained. Question-specific eligibility criteria, discussed in the following sections, were then applied, resulting in 63 articles included in the review.

Q1: Are Inflammatory Markers, Including Fever, WBC, and CRP, Useful in Distinguishing Preseptal Cellulitis (group 1) From OCA (Groups 2, 3, and 4); Orbital Cellulitis (group 2) From Abscess (Groups 3 and 4); or Identifying Patients Who Require Surgical Intervention?

Fever and elevation of the WBC count and CRP have been used to assess the severity of certain pediatric infections^10,11 and therefore may be helpful in distinguishing severity of illness in OCA. Studies included in this section provided numerical values for at least one of the following: WBC count, CRP, or percentage of patients with fever for at least one type of orbital infection. Included studies had at least five patients per group.

Thirty-three articles were screened for the inflammatory marker section. Thirteen were excluded for the following reasons: no numbers reported for inflammatory markers (n = 6); group 1 and groups 2, 3, and 4 results combined (n = 6); fewer than five patients with orbital cellulitis included (n = 1). Twenty studies were included: 18 case series and 2 retrospective cohorts. Appendix Table 3 summarizes the data from studies included. Based on GRADE criteria, the body of evidence included in this section is of low quality.⁹

Distinguishing Between Preseptal and OCA

Eleven studies were included in this section (Table 1). WBC count was significantly higher in patients with groups 2, 3, and 4 than group 1 in two studies (Devrim et al,¹²P < .01; Santos et al,¹³P = .025). CRP was significantly higher in patients with groups 2, 3, and 4 than group 1 in four studies (Öcal Demir et al,¹⁴P = .02; Devrim et al,¹²P < .01; Ohana-Sarna-Cahan et al,¹⁸P < .001; Santos et al,¹³P < .001). Patients with groups 2, 3, and 4 had a significantly higher fever rate in three studies (Botting et al,²¹P < .001; Ohana-Sarna-Cahan et al,¹⁸P = .0001; Santos et al,¹³ P = .029).

Distinguishing Between Orbital Cellulitis and Abscess

Seven studies were included in this section (Appendix Table 3). One study showed significantly higher WBC count in group 3 than group 2 (P = .004), although results were reported as percentage of patients above a cutoff number calculated to distinguish between cellulitis and abscess (Appendix Table 3).²² CRP was not significantly different between group 2 and groups 3 and 4. One study found a significantly higher fever rate in patients with group 3 compared to patients with group 2 (P < .001).²²

Identifying Patients Requiring Surgery

Six studies were included in this section (Appendix Table 3). One study found a significantly higher WBC count in patients treated surgically (Tabarino et al,²⁴P < .05). Patients treated surgically had a significantly higher CRP in two studies (Cohen et al,²⁵P = .02; Friling et al,²⁶ P = .04). Fever was inconsistently reported in the studies, with some using mean presenting temperatures and some using rates of fever. One study found a significantly higher mean presenting temperature in patients treated surgically (P = .027), but the difference between the two groups was 0.7 °C.²³

Summary

Most studies found no significant difference in WBC count, CRP, or fever between preseptal and OCA, cellulitis and abscess, or patients receiving medical and surgical interventions.

Q2: What Is the Role of Imaging in Evaluation of OCA?

Twenty-five articles were selected for the imaging section review. All the included studies were retrospective descriptive studies. Quantitative data extraction and analysis of these studies could not be performed because of their heterogeneous methodologies and lack of objective data. Therefore, the information gleaned from these studies is summarized in narrative format. Per GRADE criteria, the body of evidence included in this section is of low quality.

Who Needs Imaging?

Proptosis, ophthalmoplegia, decreased vision, and pain with eye movements are widely agreed-upon indications for imaging evaluation.^21,27,28 Because of concern for radiation exposure in pediatric patients, some authors suggested that computed tomography (CT) should only be obtained if patients fail to respond to medical therapy or if surgery is being considered.^17,29,30 However, Rudloe et al³¹ found that half of the patients with group 3 or higher disease on CT did not have proptosis, ophthalmoplegia, or pain with extraocular movement. In addition, evaluation of young children with acute periorbital swelling can be difficult, so a lower threshold for imaging is likely warranted in these younger patients.

What Type of Imaging Should Be Obtained?

The American College of Radiology 2018 Appropriateness Criteria (ACR criteria) for orbital imaging state that orbital CT is usually indicated for patients with suspected Chandler groups 2, 3, and 4 infections.³² CT with contrast is useful for evaluating the extent of orbital infection and size of the abscess and for delineating the adjacent osseous anatomy, which is essential for cases in which surgical intervention is planned.^{20,21,26,27,30,31,33,34} Distinguishing abscess from cellulitis on CT sometimes can be challenging; therefore, serial clinical examinations and, occasionally, surgical exploration may be required.^35,36

Magnetic resonance imaging (MRI) is helpful for evaluating intracranial complications (eg, epidural abscess),^27,37 but it is limited for evaluating the osseous components of the paranasal sinuses. Although one study suggested that rapid MRI is comparable to contrast CT for differentiating group 1 infections from groups 2, 3, and 4 infections, it provided limited assessment of other complications.³⁸ With no definitive studies comparing CT with MRI for orbital infections, adherence to the ACR criteria is recommended.

Orbital ultrasound is limited by its small field of view and artifact produced by the surrounding bony interface, both of which can obscure posterior intraorbital pathologies.^29,39,40 Plain radiographs are not helpful for evaluating OCA due to limited soft-tissue contrast.⁴¹

When Should Repeat Imaging Be Obtained?

Children with group 3 OCA have been successfully managed medically in a carefully monitored setting.⁴² Repeat CT imaging is sometimes useful in these patients, particularly if the clinical examination is difficult.^42-44 However, improvement in CT findings may lag behind clinical improvement.³⁹

Summary

Per ACR criteria, orbital CT with contrast is recommended to evaluate patients with suspected Chandler groups 2, 3, and 4 OCA. MRI is reserved for evaluating intracranial complications.

Q3: What Is the Microbiology of OCA? What Is the MRSA Prevalence?

Knowledge of the microbiology of OCA is essential for the appropriate selection of empiric antibiotics. Because fewer children with groups 2 and 3 OCA undergo surgery, intraoperative cultures often are not available to guide antibiotic selection.⁴⁵ As a result, significant variation exists in antibiotic prescribing.⁶

Studies discussing the microbiology of OCA were included only if they were published in the past 2 decades (2000-2020) and were excluded if the study period was before 1990, as microbiology changes over time and new vaccines are introduced. To be included, the majority of cultures reported had to be intraoperative (orbital or sinus) specimens. Studies reporting only nasal, conjunctival, or other surface cultures were excluded. When studies included patients with group 1 OCA, only microbiology data for groups 2, 3, and 4 OCA were extracted. The pattern of resistance for S aureus was not always explicitly reported; however, when non-MRSA active antibiotics were used, methicillin-susceptible S aureus was assumed. 

A total of 63 studies were screened for the microbiology section; 32 were excluded for the following reasons: published before 2000 or study period before 1990 (n = 18), reported surface cultures or culture site not clearly stated (n = 4), microbiology mixed between preseptal and orbital (n = 6), wrong study type (n = 2), and study group overlaps with a different article included (n = 2). Of the 32 studies included, 3 were prospective observational, 4 were retrospective cohort, and 25 were case series. Based on GRADE criteria, the body of evidence included in this section is of low quality.⁴²

Appendix Table 4 summarizes the microbiologic data from the studies included. In the group of children that had a positive culture (orbital, sinus, or blood), the most commonly recovered organisms reported were S aureus (median, 22%; range, 0%-100%), Streptococcus anginosus group (median, 16%; range, 0%-100%), group A Streptococcus (median, 12%; range, 0%-80%), and Streptococcus pneumoniae (median, 8%; range, 0%-100%). Streptococcus as a group had a median prevalence of 57%, ranging from 0% to 100%. MRSA prevalence had a median of 3% (interquartile range [IQR], 0%-13%). Median prevalence of polymicrobial cultures was 20%, and median prevalence of anaerobic organisms was 14% (Table 2). Orbital and sinus cultures had the highest yield, with an average return of an organism of 72% (median, 75%; IQR, 64%-84%). Blood culture results were reported in 14 studies and usually obtained in a subgroup of the study population. When obtained, blood cultures rarely yielded an organism (median, 10%; IQR, 5%-15%); the rate of identified bacteremia in the total population had a median of 5% (IQR, 5%-7%) across studies.

Microbiology was compared between studies completed in the United States and in other countries (Table 2). Based on median prevalence across studies, both S anginosus group and MRSA were more prevalent in the United States than internationally (28% vs 0% and 11% vs 0%, respectively). No clear trend in MRSA prevalence was evident over the 2 decades; however, the studies included were heterogeneous and did not have the power to detect such a trend.

Two reports suggest a difference of MRSA prevalence by patient age. Hsu et al⁴⁶ found that three of eight MRSA infections were in infants age <1 year, which accounted for 50% (3/6) of infants included in the study. Miller et al⁴⁷ reported MRSA in 4 of 9 (44%) infants with OCA. Age <1 year may be associated with increased frequency of MRSA infection in OCA.

Summary

Blood cultures have low yield. The most common organisms recovered from OCA are Streptococcus species (most commonly S anginosus group, group A Streptococcus, and pneumococcus) and S aureus. Polymicrobial infections including anaerobes are common. MRSA prevalence is low globally but varies significantly among geographic areas.

Our systematic review of the literature for the medical management of OCA revealed predominantly descriptive studies and only a limited number of comparison-based studies, likely reflecting the rarity of advanced forms of OCA. Given the lack of high-quality evidence and the level of heterogeneity among studies, the conclusions that can be drawn are limited.

Distinguishing between disease severity and OCA requiring surgical intervention remains challenging. Although studies in our review suggest a trend toward markers of inflammation (fever, elevated WBC count and CRP) being more common in more severe presentations, the results were mixed, and studies were low quality and underpowered to detect meaningful differences. For example, most studies do not define what constitutes a fever in their cohort. Our review suggests that markers of inflammation cannot be used to distinguish between Chandler groups or to identify patients requiring surgery. Of note, the presence of fever and elevated inflammatory markers may have influenced the decision to obtain imaging or to proceed to surgery, thereby also potentially biasing these clinical indicators toward predictors for more severe disease. Decisions regarding surgery should therefore be based on the entire clinical picture, including response to appropriate antibiotics.

We found a lack of high-quality evidence regarding the role of imaging in OCA, and the studies reviewed were heterogeneous. Recommendations for imaging therefore remain at the level of expert opinion (ACR criteria). CT imaging is the first-line modality for imaging in suspected OCA given the limitations of alternative imaging modalities, but the sensitivity and specificity of CT imaging remain unknown for diagnosis of orbital abscesses.

Our review of the published microbiology confirmed that Staphylococcus and Streptococcus species are the most common pathogens identified in OCA. Prevalence across the different studies varied greatly. Owing to the significant heterogeneity in studies, calculation of pooled prevalence was not possible. By using the number of positive cultures as our denominator (or total surgeries if number of positive cultures was unavailable), we likely overestimated the prevalence of S aureus. S aureus is generally recognized as a pyogenic pathogen, more likely to be associated with abscess formation.⁴⁸ Therefore, culture results obtained predominantly from abscesses likely result in an overestimate of S aureus in OCA (groups 2, 3, and 4). Regardless, MRSA prevalence was generally low, both nationally and internationally. The MRSA results from the study by McKinley at el⁴⁹ (Texas) was a notable outlier in the United States, with MRSA prevalence as high as 44% compared with the median prevalence of 3% (IQR, 0-13), highlighting the importance of local resistance patterns when choosing empiric antibiotics.

Limitations to the microbiology review included significant heterogeneity in both the types of cultures included and the reporting of results. Although we excluded studies that reported only surface culture results or did not specify culture type, we did include studies that had surface culture results combined with intraoperative culture results, making it impossible to separate the two. Since most of the cultures included in combined results reported organisms based on intraoperative cultures, we felt they provided valuable information that should be included. In most studies, blood cultures were not obtained in all participants, so the yield of blood cultures is likely an overestimate, as blood cultures are more likely to be obtained in higher-acuity patients.

Although the available evidence regarding the medical management of OCA remains low quality, certain limited conclusions can be drawn, as presented in this review. Further high-quality studies are needed to better inform the medical management of OCA.

The authors thank Dr Kyle Pronko for his help with data extraction for the imaging section.

Orbital cellulitis/abscess (OCA) is a potential complication of sinusitis. If not treated promptly, it can result in vision loss, intracranial infection, or cavernous sinus thrombosis.^1,2 In 1970, Chandler et al³ classified orbital complications of acute sinusitis into five groups: inflammatory edema (group 1); orbital cellulitis (group 2); subperiosteal abscess (SPA) (group 3); orbital abscess (group 4); and cavernous sinus thrombosis (group 5). Group 1, or preseptal cellulitis, is significantly different from groups 2, 3, and 4, collectively referred to as OCA, which affect the actual orbital content.

Children with OCA are generally hospitalized so they can be treated with intravenous antibiotics. While orbital abscesses (group 4) are typically treated surgically, successful medical management has been reported for cases of orbital cellulitis and SPA (groups 2 and 3).^4,5 No widely accepted guidelines exist for the evaluation and medical management of OCA, resulting in significant variation in care.⁶ The purpose of this systematic review is to summarize existing evidence guiding the medical management of OCA regarding laboratory testing, imaging, and microbiology. This review does not address surgical considerations.

The review protocol has been registered in the PROSPERO International Prospective Register of Systematic Reviews (crd.york.ac.uk/prospero/index.asp; identifier: CRD42020158463), and the review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.⁷

Search Strategy

A systematic search of the literature was designed and conducted by a medical librarian (ES), with input from the research team (AB, SM). The search strategy included Medical Subject Headings (MeSH) terms and keywords related to orbital or subperiosteal cellulitis/abscess and children; see Appendix Table 1 for the complete search strategy. Searches were conducted in MEDLINE (Ovid), Web of Science Core Collection, Scopus, CINAHL (EBSCO), and Cochrane Central Register of Controlled Trials (CENTRAL) using advanced search techniques relative to each database. Searches were last conducted on February 9, 2021.

Eligibility Criteria

The study designs (retrospective and prospective) included in the search were limited to randomized clinical trials, cohort studies, case-control studies, and case series with participants <18 years of age. Case reports describing fewer than 5 patients and literature reviews were excluded. Studies including a combination of adult and pediatric patients were included if pediatric outcomes were reported separately. Only studies available in English were included.

Outcome Measures

The outcome measures were determined a priori based on three clinical questions:

• Q1. What is the role of inflammatory markers—white blood cell (WBC) count, C-reactive protein (CRP), and fever—in distinguishing between the following: preseptal cellulitis (group 1) and OCA (groups 2, 3, and 4); orbital cellulitis (group 2) and abscess (groups 3 and 4); and patients who do and do not require surgery?
• Q2. What is the role of imaging in the evaluation of OCA?
• Q3. What is the microbiology of OCA over the past 2 decades? What is the prevalence of methicillin-resistant Staphylococcus aureus (MRSA)?

Screening

Two review authors (AB, SM) performed both the title/abstract and full-text screen, independently applying the eligibility criteria. Disagreements were discussed, and conflicts were resolved with input from a third reviewer author (ES). Duplications were removed. When two studies had overlapping patient data, the study with fewer data points was excluded.

Data Extraction and Synthesis

All studies included after the full-text screen were divided based on the clinical question they answered (Q1, Q2, Q3 above). Some studies reported outcomes pertinent to more than one question. Two review authors were assigned to each clinical question. They independently reviewed each article and extracted the pertinent data into question-specific extraction sheets. Articles assigned to Q2 were reviewed by two pediatric neuroradiologists. For each study, the following details were extracted: authors, location, year, study type, study period, population, and number and ages of participants. Details that were question-specific included: (Q1) values and/or percentages for inflammatory markers; (Q2) reasons for imaging or type of imaging; and (Q3) participants managed surgically and culture results. The data were then synthesized in table and/or narrative format. For Q3, the organisms identified from intraoperative and blood cultures in each study were mathematically combined. When possible, prevalence was calculated using the number of patients with at least one pathogen recovered as the denominator. If this number was not available, the number of patients who underwent surgery was used as the denominator.

Quality Assessment

No randomized controlled trials were identified. More than 90% of the studies identified and included were retrospective descriptive studies. By the nature of the case series design, the study quality was felt to be poor, with high risk of bias. The Joanna Briggs Institute Critical Appraisal tools for systematic reviews were used to appraise each individual study included (Appendix Table 2).⁸ The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria were used in rating the quality of evidence for each question.⁹

A summary of the search strategy and study selection is provided in the Figure (PRISMA flow diagram). The initial search identified 3007 studies. After duplicates were removed and general eligibility criteria applied, 94 articles remained. Question-specific eligibility criteria, discussed in the following sections, were then applied, resulting in 63 articles included in the review.

Q1: Are Inflammatory Markers, Including Fever, WBC, and CRP, Useful in Distinguishing Preseptal Cellulitis (group 1) From OCA (Groups 2, 3, and 4); Orbital Cellulitis (group 2) From Abscess (Groups 3 and 4); or Identifying Patients Who Require Surgical Intervention?

Fever and elevation of the WBC count and CRP have been used to assess the severity of certain pediatric infections^10,11 and therefore may be helpful in distinguishing severity of illness in OCA. Studies included in this section provided numerical values for at least one of the following: WBC count, CRP, or percentage of patients with fever for at least one type of orbital infection. Included studies had at least five patients per group.

Thirty-three articles were screened for the inflammatory marker section. Thirteen were excluded for the following reasons: no numbers reported for inflammatory markers (n = 6); group 1 and groups 2, 3, and 4 results combined (n = 6); fewer than five patients with orbital cellulitis included (n = 1). Twenty studies were included: 18 case series and 2 retrospective cohorts. Appendix Table 3 summarizes the data from studies included. Based on GRADE criteria, the body of evidence included in this section is of low quality.⁹

Distinguishing Between Preseptal and OCA

Eleven studies were included in this section (Table 1). WBC count was significantly higher in patients with groups 2, 3, and 4 than group 1 in two studies (Devrim et al,¹²P < .01; Santos et al,¹³P = .025). CRP was significantly higher in patients with groups 2, 3, and 4 than group 1 in four studies (Öcal Demir et al,¹⁴P = .02; Devrim et al,¹²P < .01; Ohana-Sarna-Cahan et al,¹⁸P < .001; Santos et al,¹³P < .001). Patients with groups 2, 3, and 4 had a significantly higher fever rate in three studies (Botting et al,²¹P < .001; Ohana-Sarna-Cahan et al,¹⁸P = .0001; Santos et al,¹³ P = .029).

Distinguishing Between Orbital Cellulitis and Abscess

Seven studies were included in this section (Appendix Table 3). One study showed significantly higher WBC count in group 3 than group 2 (P = .004), although results were reported as percentage of patients above a cutoff number calculated to distinguish between cellulitis and abscess (Appendix Table 3).²² CRP was not significantly different between group 2 and groups 3 and 4. One study found a significantly higher fever rate in patients with group 3 compared to patients with group 2 (P < .001).²²

Identifying Patients Requiring Surgery

Six studies were included in this section (Appendix Table 3). One study found a significantly higher WBC count in patients treated surgically (Tabarino et al,²⁴P < .05). Patients treated surgically had a significantly higher CRP in two studies (Cohen et al,²⁵P = .02; Friling et al,²⁶ P = .04). Fever was inconsistently reported in the studies, with some using mean presenting temperatures and some using rates of fever. One study found a significantly higher mean presenting temperature in patients treated surgically (P = .027), but the difference between the two groups was 0.7 °C.²³

Summary

Most studies found no significant difference in WBC count, CRP, or fever between preseptal and OCA, cellulitis and abscess, or patients receiving medical and surgical interventions.

Q2: What Is the Role of Imaging in Evaluation of OCA?

Twenty-five articles were selected for the imaging section review. All the included studies were retrospective descriptive studies. Quantitative data extraction and analysis of these studies could not be performed because of their heterogeneous methodologies and lack of objective data. Therefore, the information gleaned from these studies is summarized in narrative format. Per GRADE criteria, the body of evidence included in this section is of low quality.

Who Needs Imaging?

Proptosis, ophthalmoplegia, decreased vision, and pain with eye movements are widely agreed-upon indications for imaging evaluation.^21,27,28 Because of concern for radiation exposure in pediatric patients, some authors suggested that computed tomography (CT) should only be obtained if patients fail to respond to medical therapy or if surgery is being considered.^17,29,30 However, Rudloe et al³¹ found that half of the patients with group 3 or higher disease on CT did not have proptosis, ophthalmoplegia, or pain with extraocular movement. In addition, evaluation of young children with acute periorbital swelling can be difficult, so a lower threshold for imaging is likely warranted in these younger patients.

What Type of Imaging Should Be Obtained?

The American College of Radiology 2018 Appropriateness Criteria (ACR criteria) for orbital imaging state that orbital CT is usually indicated for patients with suspected Chandler groups 2, 3, and 4 infections.³² CT with contrast is useful for evaluating the extent of orbital infection and size of the abscess and for delineating the adjacent osseous anatomy, which is essential for cases in which surgical intervention is planned.^{20,21,26,27,30,31,33,34} Distinguishing abscess from cellulitis on CT sometimes can be challenging; therefore, serial clinical examinations and, occasionally, surgical exploration may be required.^35,36

Magnetic resonance imaging (MRI) is helpful for evaluating intracranial complications (eg, epidural abscess),^27,37 but it is limited for evaluating the osseous components of the paranasal sinuses. Although one study suggested that rapid MRI is comparable to contrast CT for differentiating group 1 infections from groups 2, 3, and 4 infections, it provided limited assessment of other complications.³⁸ With no definitive studies comparing CT with MRI for orbital infections, adherence to the ACR criteria is recommended.

Orbital ultrasound is limited by its small field of view and artifact produced by the surrounding bony interface, both of which can obscure posterior intraorbital pathologies.^29,39,40 Plain radiographs are not helpful for evaluating OCA due to limited soft-tissue contrast.⁴¹

When Should Repeat Imaging Be Obtained?

Children with group 3 OCA have been successfully managed medically in a carefully monitored setting.⁴² Repeat CT imaging is sometimes useful in these patients, particularly if the clinical examination is difficult.^42-44 However, improvement in CT findings may lag behind clinical improvement.³⁹

Summary

Per ACR criteria, orbital CT with contrast is recommended to evaluate patients with suspected Chandler groups 2, 3, and 4 OCA. MRI is reserved for evaluating intracranial complications.

Q3: What Is the Microbiology of OCA? What Is the MRSA Prevalence?

Knowledge of the microbiology of OCA is essential for the appropriate selection of empiric antibiotics. Because fewer children with groups 2 and 3 OCA undergo surgery, intraoperative cultures often are not available to guide antibiotic selection.⁴⁵ As a result, significant variation exists in antibiotic prescribing.⁶

Studies discussing the microbiology of OCA were included only if they were published in the past 2 decades (2000-2020) and were excluded if the study period was before 1990, as microbiology changes over time and new vaccines are introduced. To be included, the majority of cultures reported had to be intraoperative (orbital or sinus) specimens. Studies reporting only nasal, conjunctival, or other surface cultures were excluded. When studies included patients with group 1 OCA, only microbiology data for groups 2, 3, and 4 OCA were extracted. The pattern of resistance for S aureus was not always explicitly reported; however, when non-MRSA active antibiotics were used, methicillin-susceptible S aureus was assumed. 

A total of 63 studies were screened for the microbiology section; 32 were excluded for the following reasons: published before 2000 or study period before 1990 (n = 18), reported surface cultures or culture site not clearly stated (n = 4), microbiology mixed between preseptal and orbital (n = 6), wrong study type (n = 2), and study group overlaps with a different article included (n = 2). Of the 32 studies included, 3 were prospective observational, 4 were retrospective cohort, and 25 were case series. Based on GRADE criteria, the body of evidence included in this section is of low quality.⁴²

Appendix Table 4 summarizes the microbiologic data from the studies included. In the group of children that had a positive culture (orbital, sinus, or blood), the most commonly recovered organisms reported were S aureus (median, 22%; range, 0%-100%), Streptococcus anginosus group (median, 16%; range, 0%-100%), group A Streptococcus (median, 12%; range, 0%-80%), and Streptococcus pneumoniae (median, 8%; range, 0%-100%). Streptococcus as a group had a median prevalence of 57%, ranging from 0% to 100%. MRSA prevalence had a median of 3% (interquartile range [IQR], 0%-13%). Median prevalence of polymicrobial cultures was 20%, and median prevalence of anaerobic organisms was 14% (Table 2). Orbital and sinus cultures had the highest yield, with an average return of an organism of 72% (median, 75%; IQR, 64%-84%). Blood culture results were reported in 14 studies and usually obtained in a subgroup of the study population. When obtained, blood cultures rarely yielded an organism (median, 10%; IQR, 5%-15%); the rate of identified bacteremia in the total population had a median of 5% (IQR, 5%-7%) across studies.

Microbiology was compared between studies completed in the United States and in other countries (Table 2). Based on median prevalence across studies, both S anginosus group and MRSA were more prevalent in the United States than internationally (28% vs 0% and 11% vs 0%, respectively). No clear trend in MRSA prevalence was evident over the 2 decades; however, the studies included were heterogeneous and did not have the power to detect such a trend.

Two reports suggest a difference of MRSA prevalence by patient age. Hsu et al⁴⁶ found that three of eight MRSA infections were in infants age <1 year, which accounted for 50% (3/6) of infants included in the study. Miller et al⁴⁷ reported MRSA in 4 of 9 (44%) infants with OCA. Age <1 year may be associated with increased frequency of MRSA infection in OCA.

Summary

Blood cultures have low yield. The most common organisms recovered from OCA are Streptococcus species (most commonly S anginosus group, group A Streptococcus, and pneumococcus) and S aureus. Polymicrobial infections including anaerobes are common. MRSA prevalence is low globally but varies significantly among geographic areas.

Our systematic review of the literature for the medical management of OCA revealed predominantly descriptive studies and only a limited number of comparison-based studies, likely reflecting the rarity of advanced forms of OCA. Given the lack of high-quality evidence and the level of heterogeneity among studies, the conclusions that can be drawn are limited.

Distinguishing between disease severity and OCA requiring surgical intervention remains challenging. Although studies in our review suggest a trend toward markers of inflammation (fever, elevated WBC count and CRP) being more common in more severe presentations, the results were mixed, and studies were low quality and underpowered to detect meaningful differences. For example, most studies do not define what constitutes a fever in their cohort. Our review suggests that markers of inflammation cannot be used to distinguish between Chandler groups or to identify patients requiring surgery. Of note, the presence of fever and elevated inflammatory markers may have influenced the decision to obtain imaging or to proceed to surgery, thereby also potentially biasing these clinical indicators toward predictors for more severe disease. Decisions regarding surgery should therefore be based on the entire clinical picture, including response to appropriate antibiotics.

We found a lack of high-quality evidence regarding the role of imaging in OCA, and the studies reviewed were heterogeneous. Recommendations for imaging therefore remain at the level of expert opinion (ACR criteria). CT imaging is the first-line modality for imaging in suspected OCA given the limitations of alternative imaging modalities, but the sensitivity and specificity of CT imaging remain unknown for diagnosis of orbital abscesses.

Our review of the published microbiology confirmed that Staphylococcus and Streptococcus species are the most common pathogens identified in OCA. Prevalence across the different studies varied greatly. Owing to the significant heterogeneity in studies, calculation of pooled prevalence was not possible. By using the number of positive cultures as our denominator (or total surgeries if number of positive cultures was unavailable), we likely overestimated the prevalence of S aureus. S aureus is generally recognized as a pyogenic pathogen, more likely to be associated with abscess formation.⁴⁸ Therefore, culture results obtained predominantly from abscesses likely result in an overestimate of S aureus in OCA (groups 2, 3, and 4). Regardless, MRSA prevalence was generally low, both nationally and internationally. The MRSA results from the study by McKinley at el⁴⁹ (Texas) was a notable outlier in the United States, with MRSA prevalence as high as 44% compared with the median prevalence of 3% (IQR, 0-13), highlighting the importance of local resistance patterns when choosing empiric antibiotics.

Limitations to the microbiology review included significant heterogeneity in both the types of cultures included and the reporting of results. Although we excluded studies that reported only surface culture results or did not specify culture type, we did include studies that had surface culture results combined with intraoperative culture results, making it impossible to separate the two. Since most of the cultures included in combined results reported organisms based on intraoperative cultures, we felt they provided valuable information that should be included. In most studies, blood cultures were not obtained in all participants, so the yield of blood cultures is likely an overestimate, as blood cultures are more likely to be obtained in higher-acuity patients.

Although the available evidence regarding the medical management of OCA remains low quality, certain limited conclusions can be drawn, as presented in this review. Further high-quality studies are needed to better inform the medical management of OCA.

The authors thank Dr Kyle Pronko for his help with data extraction for the imaging section.

Orbital cellulitis/abscess (OCA) is a potential complication of sinusitis. If not treated promptly, it can result in vision loss, intracranial infection, or cavernous sinus thrombosis.^1,2 In 1970, Chandler et al³ classified orbital complications of acute sinusitis into five groups: inflammatory edema (group 1); orbital cellulitis (group 2); subperiosteal abscess (SPA) (group 3); orbital abscess (group 4); and cavernous sinus thrombosis (group 5). Group 1, or preseptal cellulitis, is significantly different from groups 2, 3, and 4, collectively referred to as OCA, which affect the actual orbital content.

Children with OCA are generally hospitalized so they can be treated with intravenous antibiotics. While orbital abscesses (group 4) are typically treated surgically, successful medical management has been reported for cases of orbital cellulitis and SPA (groups 2 and 3).^4,5 No widely accepted guidelines exist for the evaluation and medical management of OCA, resulting in significant variation in care.⁶ The purpose of this systematic review is to summarize existing evidence guiding the medical management of OCA regarding laboratory testing, imaging, and microbiology. This review does not address surgical considerations.

The review protocol has been registered in the PROSPERO International Prospective Register of Systematic Reviews (crd.york.ac.uk/prospero/index.asp; identifier: CRD42020158463), and the review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.⁷

Search Strategy

A systematic search of the literature was designed and conducted by a medical librarian (ES), with input from the research team (AB, SM). The search strategy included Medical Subject Headings (MeSH) terms and keywords related to orbital or subperiosteal cellulitis/abscess and children; see Appendix Table 1 for the complete search strategy. Searches were conducted in MEDLINE (Ovid), Web of Science Core Collection, Scopus, CINAHL (EBSCO), and Cochrane Central Register of Controlled Trials (CENTRAL) using advanced search techniques relative to each database. Searches were last conducted on February 9, 2021.

Eligibility Criteria

The study designs (retrospective and prospective) included in the search were limited to randomized clinical trials, cohort studies, case-control studies, and case series with participants <18 years of age. Case reports describing fewer than 5 patients and literature reviews were excluded. Studies including a combination of adult and pediatric patients were included if pediatric outcomes were reported separately. Only studies available in English were included.

Outcome Measures

The outcome measures were determined a priori based on three clinical questions:

• Q1. What is the role of inflammatory markers—white blood cell (WBC) count, C-reactive protein (CRP), and fever—in distinguishing between the following: preseptal cellulitis (group 1) and OCA (groups 2, 3, and 4); orbital cellulitis (group 2) and abscess (groups 3 and 4); and patients who do and do not require surgery?
• Q2. What is the role of imaging in the evaluation of OCA?
• Q3. What is the microbiology of OCA over the past 2 decades? What is the prevalence of methicillin-resistant Staphylococcus aureus (MRSA)?

Screening

Two review authors (AB, SM) performed both the title/abstract and full-text screen, independently applying the eligibility criteria. Disagreements were discussed, and conflicts were resolved with input from a third reviewer author (ES). Duplications were removed. When two studies had overlapping patient data, the study with fewer data points was excluded.

Data Extraction and Synthesis

All studies included after the full-text screen were divided based on the clinical question they answered (Q1, Q2, Q3 above). Some studies reported outcomes pertinent to more than one question. Two review authors were assigned to each clinical question. They independently reviewed each article and extracted the pertinent data into question-specific extraction sheets. Articles assigned to Q2 were reviewed by two pediatric neuroradiologists. For each study, the following details were extracted: authors, location, year, study type, study period, population, and number and ages of participants. Details that were question-specific included: (Q1) values and/or percentages for inflammatory markers; (Q2) reasons for imaging or type of imaging; and (Q3) participants managed surgically and culture results. The data were then synthesized in table and/or narrative format. For Q3, the organisms identified from intraoperative and blood cultures in each study were mathematically combined. When possible, prevalence was calculated using the number of patients with at least one pathogen recovered as the denominator. If this number was not available, the number of patients who underwent surgery was used as the denominator.

Quality Assessment

No randomized controlled trials were identified. More than 90% of the studies identified and included were retrospective descriptive studies. By the nature of the case series design, the study quality was felt to be poor, with high risk of bias. The Joanna Briggs Institute Critical Appraisal tools for systematic reviews were used to appraise each individual study included (Appendix Table 2).⁸ The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria were used in rating the quality of evidence for each question.⁹

A summary of the search strategy and study selection is provided in the Figure (PRISMA flow diagram). The initial search identified 3007 studies. After duplicates were removed and general eligibility criteria applied, 94 articles remained. Question-specific eligibility criteria, discussed in the following sections, were then applied, resulting in 63 articles included in the review.

Q1: Are Inflammatory Markers, Including Fever, WBC, and CRP, Useful in Distinguishing Preseptal Cellulitis (group 1) From OCA (Groups 2, 3, and 4); Orbital Cellulitis (group 2) From Abscess (Groups 3 and 4); or Identifying Patients Who Require Surgical Intervention?

Fever and elevation of the WBC count and CRP have been used to assess the severity of certain pediatric infections^10,11 and therefore may be helpful in distinguishing severity of illness in OCA. Studies included in this section provided numerical values for at least one of the following: WBC count, CRP, or percentage of patients with fever for at least one type of orbital infection. Included studies had at least five patients per group.

Thirty-three articles were screened for the inflammatory marker section. Thirteen were excluded for the following reasons: no numbers reported for inflammatory markers (n = 6); group 1 and groups 2, 3, and 4 results combined (n = 6); fewer than five patients with orbital cellulitis included (n = 1). Twenty studies were included: 18 case series and 2 retrospective cohorts. Appendix Table 3 summarizes the data from studies included. Based on GRADE criteria, the body of evidence included in this section is of low quality.⁹

Distinguishing Between Preseptal and OCA

Eleven studies were included in this section (Table 1). WBC count was significantly higher in patients with groups 2, 3, and 4 than group 1 in two studies (Devrim et al,¹²P < .01; Santos et al,¹³P = .025). CRP was significantly higher in patients with groups 2, 3, and 4 than group 1 in four studies (Öcal Demir et al,¹⁴P = .02; Devrim et al,¹²P < .01; Ohana-Sarna-Cahan et al,¹⁸P < .001; Santos et al,¹³P < .001). Patients with groups 2, 3, and 4 had a significantly higher fever rate in three studies (Botting et al,²¹P < .001; Ohana-Sarna-Cahan et al,¹⁸P = .0001; Santos et al,¹³ P = .029).

Distinguishing Between Orbital Cellulitis and Abscess

Seven studies were included in this section (Appendix Table 3). One study showed significantly higher WBC count in group 3 than group 2 (P = .004), although results were reported as percentage of patients above a cutoff number calculated to distinguish between cellulitis and abscess (Appendix Table 3).²² CRP was not significantly different between group 2 and groups 3 and 4. One study found a significantly higher fever rate in patients with group 3 compared to patients with group 2 (P < .001).²²

Identifying Patients Requiring Surgery

Six studies were included in this section (Appendix Table 3). One study found a significantly higher WBC count in patients treated surgically (Tabarino et al,²⁴P < .05). Patients treated surgically had a significantly higher CRP in two studies (Cohen et al,²⁵P = .02; Friling et al,²⁶ P = .04). Fever was inconsistently reported in the studies, with some using mean presenting temperatures and some using rates of fever. One study found a significantly higher mean presenting temperature in patients treated surgically (P = .027), but the difference between the two groups was 0.7 °C.²³

Summary

Most studies found no significant difference in WBC count, CRP, or fever between preseptal and OCA, cellulitis and abscess, or patients receiving medical and surgical interventions.

Q2: What Is the Role of Imaging in Evaluation of OCA?

Twenty-five articles were selected for the imaging section review. All the included studies were retrospective descriptive studies. Quantitative data extraction and analysis of these studies could not be performed because of their heterogeneous methodologies and lack of objective data. Therefore, the information gleaned from these studies is summarized in narrative format. Per GRADE criteria, the body of evidence included in this section is of low quality.

Who Needs Imaging?

Proptosis, ophthalmoplegia, decreased vision, and pain with eye movements are widely agreed-upon indications for imaging evaluation.^21,27,28 Because of concern for radiation exposure in pediatric patients, some authors suggested that computed tomography (CT) should only be obtained if patients fail to respond to medical therapy or if surgery is being considered.^17,29,30 However, Rudloe et al³¹ found that half of the patients with group 3 or higher disease on CT did not have proptosis, ophthalmoplegia, or pain with extraocular movement. In addition, evaluation of young children with acute periorbital swelling can be difficult, so a lower threshold for imaging is likely warranted in these younger patients.

What Type of Imaging Should Be Obtained?

The American College of Radiology 2018 Appropriateness Criteria (ACR criteria) for orbital imaging state that orbital CT is usually indicated for patients with suspected Chandler groups 2, 3, and 4 infections.³² CT with contrast is useful for evaluating the extent of orbital infection and size of the abscess and for delineating the adjacent osseous anatomy, which is essential for cases in which surgical intervention is planned.^{20,21,26,27,30,31,33,34} Distinguishing abscess from cellulitis on CT sometimes can be challenging; therefore, serial clinical examinations and, occasionally, surgical exploration may be required.^35,36

Magnetic resonance imaging (MRI) is helpful for evaluating intracranial complications (eg, epidural abscess),^27,37 but it is limited for evaluating the osseous components of the paranasal sinuses. Although one study suggested that rapid MRI is comparable to contrast CT for differentiating group 1 infections from groups 2, 3, and 4 infections, it provided limited assessment of other complications.³⁸ With no definitive studies comparing CT with MRI for orbital infections, adherence to the ACR criteria is recommended.

Orbital ultrasound is limited by its small field of view and artifact produced by the surrounding bony interface, both of which can obscure posterior intraorbital pathologies.^29,39,40 Plain radiographs are not helpful for evaluating OCA due to limited soft-tissue contrast.⁴¹

When Should Repeat Imaging Be Obtained?

Children with group 3 OCA have been successfully managed medically in a carefully monitored setting.⁴² Repeat CT imaging is sometimes useful in these patients, particularly if the clinical examination is difficult.^42-44 However, improvement in CT findings may lag behind clinical improvement.³⁹

Summary

Per ACR criteria, orbital CT with contrast is recommended to evaluate patients with suspected Chandler groups 2, 3, and 4 OCA. MRI is reserved for evaluating intracranial complications.

Q3: What Is the Microbiology of OCA? What Is the MRSA Prevalence?

Knowledge of the microbiology of OCA is essential for the appropriate selection of empiric antibiotics. Because fewer children with groups 2 and 3 OCA undergo surgery, intraoperative cultures often are not available to guide antibiotic selection.⁴⁵ As a result, significant variation exists in antibiotic prescribing.⁶

Studies discussing the microbiology of OCA were included only if they were published in the past 2 decades (2000-2020) and were excluded if the study period was before 1990, as microbiology changes over time and new vaccines are introduced. To be included, the majority of cultures reported had to be intraoperative (orbital or sinus) specimens. Studies reporting only nasal, conjunctival, or other surface cultures were excluded. When studies included patients with group 1 OCA, only microbiology data for groups 2, 3, and 4 OCA were extracted. The pattern of resistance for S aureus was not always explicitly reported; however, when non-MRSA active antibiotics were used, methicillin-susceptible S aureus was assumed. 

A total of 63 studies were screened for the microbiology section; 32 were excluded for the following reasons: published before 2000 or study period before 1990 (n = 18), reported surface cultures or culture site not clearly stated (n = 4), microbiology mixed between preseptal and orbital (n = 6), wrong study type (n = 2), and study group overlaps with a different article included (n = 2). Of the 32 studies included, 3 were prospective observational, 4 were retrospective cohort, and 25 were case series. Based on GRADE criteria, the body of evidence included in this section is of low quality.⁴²

Appendix Table 4 summarizes the microbiologic data from the studies included. In the group of children that had a positive culture (orbital, sinus, or blood), the most commonly recovered organisms reported were S aureus (median, 22%; range, 0%-100%), Streptococcus anginosus group (median, 16%; range, 0%-100%), group A Streptococcus (median, 12%; range, 0%-80%), and Streptococcus pneumoniae (median, 8%; range, 0%-100%). Streptococcus as a group had a median prevalence of 57%, ranging from 0% to 100%. MRSA prevalence had a median of 3% (interquartile range [IQR], 0%-13%). Median prevalence of polymicrobial cultures was 20%, and median prevalence of anaerobic organisms was 14% (Table 2). Orbital and sinus cultures had the highest yield, with an average return of an organism of 72% (median, 75%; IQR, 64%-84%). Blood culture results were reported in 14 studies and usually obtained in a subgroup of the study population. When obtained, blood cultures rarely yielded an organism (median, 10%; IQR, 5%-15%); the rate of identified bacteremia in the total population had a median of 5% (IQR, 5%-7%) across studies.

Microbiology was compared between studies completed in the United States and in other countries (Table 2). Based on median prevalence across studies, both S anginosus group and MRSA were more prevalent in the United States than internationally (28% vs 0% and 11% vs 0%, respectively). No clear trend in MRSA prevalence was evident over the 2 decades; however, the studies included were heterogeneous and did not have the power to detect such a trend.

Two reports suggest a difference of MRSA prevalence by patient age. Hsu et al⁴⁶ found that three of eight MRSA infections were in infants age <1 year, which accounted for 50% (3/6) of infants included in the study. Miller et al⁴⁷ reported MRSA in 4 of 9 (44%) infants with OCA. Age <1 year may be associated with increased frequency of MRSA infection in OCA.

Summary

Blood cultures have low yield. The most common organisms recovered from OCA are Streptococcus species (most commonly S anginosus group, group A Streptococcus, and pneumococcus) and S aureus. Polymicrobial infections including anaerobes are common. MRSA prevalence is low globally but varies significantly among geographic areas.

Our systematic review of the literature for the medical management of OCA revealed predominantly descriptive studies and only a limited number of comparison-based studies, likely reflecting the rarity of advanced forms of OCA. Given the lack of high-quality evidence and the level of heterogeneity among studies, the conclusions that can be drawn are limited.

Distinguishing between disease severity and OCA requiring surgical intervention remains challenging. Although studies in our review suggest a trend toward markers of inflammation (fever, elevated WBC count and CRP) being more common in more severe presentations, the results were mixed, and studies were low quality and underpowered to detect meaningful differences. For example, most studies do not define what constitutes a fever in their cohort. Our review suggests that markers of inflammation cannot be used to distinguish between Chandler groups or to identify patients requiring surgery. Of note, the presence of fever and elevated inflammatory markers may have influenced the decision to obtain imaging or to proceed to surgery, thereby also potentially biasing these clinical indicators toward predictors for more severe disease. Decisions regarding surgery should therefore be based on the entire clinical picture, including response to appropriate antibiotics.

We found a lack of high-quality evidence regarding the role of imaging in OCA, and the studies reviewed were heterogeneous. Recommendations for imaging therefore remain at the level of expert opinion (ACR criteria). CT imaging is the first-line modality for imaging in suspected OCA given the limitations of alternative imaging modalities, but the sensitivity and specificity of CT imaging remain unknown for diagnosis of orbital abscesses.

Our review of the published microbiology confirmed that Staphylococcus and Streptococcus species are the most common pathogens identified in OCA. Prevalence across the different studies varied greatly. Owing to the significant heterogeneity in studies, calculation of pooled prevalence was not possible. By using the number of positive cultures as our denominator (or total surgeries if number of positive cultures was unavailable), we likely overestimated the prevalence of S aureus. S aureus is generally recognized as a pyogenic pathogen, more likely to be associated with abscess formation.⁴⁸ Therefore, culture results obtained predominantly from abscesses likely result in an overestimate of S aureus in OCA (groups 2, 3, and 4). Regardless, MRSA prevalence was generally low, both nationally and internationally. The MRSA results from the study by McKinley at el⁴⁹ (Texas) was a notable outlier in the United States, with MRSA prevalence as high as 44% compared with the median prevalence of 3% (IQR, 0-13), highlighting the importance of local resistance patterns when choosing empiric antibiotics.

Limitations to the microbiology review included significant heterogeneity in both the types of cultures included and the reporting of results. Although we excluded studies that reported only surface culture results or did not specify culture type, we did include studies that had surface culture results combined with intraoperative culture results, making it impossible to separate the two. Since most of the cultures included in combined results reported organisms based on intraoperative cultures, we felt they provided valuable information that should be included. In most studies, blood cultures were not obtained in all participants, so the yield of blood cultures is likely an overestimate, as blood cultures are more likely to be obtained in higher-acuity patients.

Although the available evidence regarding the medical management of OCA remains low quality, certain limited conclusions can be drawn, as presented in this review. Further high-quality studies are needed to better inform the medical management of OCA.

The authors thank Dr Kyle Pronko for his help with data extraction for the imaging section.

The ability to read and correctly interpret research is an essential skill, but most hospitalists—and physicians in general—do not receive formal training in biostatistics during their medical education.^1-3 In addition to straightforward statistical tests that compare a single exposure and outcome, researchers commonly use statistical models to identify and quantify complex relationships among many exposures (eg, demographics, clinical characteristics, interventions, or other variables) and an outcome. Understanding statistical models can be challenging. Still, it is important to recognize the advantages and limitations of statistical models, how to interpret their results, and the potential implications of findings on current clinical practice.

In the article “Rates and Characteristics of Medical Malpractice Claims Against Hospitalists” published in the July 2021 issue of the Journal of Hospital Medicine, Schaffer et al⁴ used the Comparative Benchmarking System database, which is maintained by a malpractice insurer, to characterize malpractice claims against hospitalists. The authors used multiple logistic regression models to understand the relationship among clinical factors and indemnity payments. In this Progress Note, we describe situations in which logistic regression is the proper statistical method to analyze a data set, explain results from logistic regression analyses, and equip readers with skills to critically appraise conclusions drawn from these models.

Statistical models often are used to describe the relationship among one or more exposure variables (ie, independent variables) and an outcome (ie, dependent variable). These models allow researchers to evaluate the effects of multiple exposure variables simultaneously, which in turn allows them to “isolate” the effect of each variable; in other words, models facilitate an understanding of the relationship between each exposure variable and the outcome, adjusted for (ie, independent of) the other exposure variables in the model.

Several statistical models can be used to quantify relationships within the data, but each type of model has certain assumptions that must be satisfied. Two important assumptions include characteristics of the outcome (eg, the type and distribution) and the nature of the relationships among the outcome and independent variables (eg, linear vs nonlinear). Simple linear regression, one of the most basic statistical models used in research,⁵ assumes that (a) the outcome is continuous (ie, any numeric value is possible) and normally distributed (ie, its histogram is a bell-shaped curve) and (b) the relationship between the independent variable and the outcome is linear (ie, follows a straight line). If an investigator wanted to understand how weight is related to height, a simple linear regression could be used to develop a mathematical equation that tells us how the outcome (weight) generally increases as the independent variable (height) increases.

Often, the outcome in a study is not a continuous variable but a simple success/failure variable (ie, dichotomous variable that can be one of two possible values). Schaffer et al⁴ examined the binary outcome of whether a malpractice claim case would end in an indemnity payment or no payment. Linear regression models are not equipped to handle dichotomous outcomes. Instead, we need to use a different statistical model: logistic regression. In logistic regression, the probability (p) of a defined outcome event is estimated by creating a regression model.

A probability (p) is a measure of how likely an event (eg, a malpractice claim ends in an indemnity payment or not) is to occur. It is always between 0 (ie, the event will definitely not occur) and 1 (ie, the event will definitely occur). A p of 0.5 means there is a 50/50 chance that the event will occur (ie, equivalent to a coin flip). Because p is a probability, we need to make sure it is always between 0 and 1. If we were to try to model p with a linear regression, the model would assume that p could extend beyond 0 and 1. What can we do?

Applying a transformation is a commonly used tool in statistics to make data work better within statistical models.⁶ In this case, we will transform the variable p. In logistic regression, we model the probability of experiencing the outcome through a transformation called a logit. The logit represents the natural logarithm (ln) of the ratio of the probability of experiencing the outcome (p) vs the probability of not experiencing the outcome (1 – p), with the ratio being the odds of the event occurring.

This transformation works well for dichotomous outcomes because the logit transformation approximates a straight line as long as p is not too large or too small (between 0.05 and 0.95).

If we are performing a logistic regression with only one independent variable (x) and want to understand the relationship between this variable (x) and the probability of an outcome event (p), then our model is the equation of a line. The equation for the base model of logistic regression with one independent variable (x) is

where β₀ is the y-intercept and β₁ is the slope of the line. Equation (2) is identical to the algebraic equation y = mx + b for a line, just rearranged slightly. In this algebraic equation, m is the slope (the same as β₁) and b is the y-intercept (the same as β₀). We will see that β₀ and β₁ are estimated (ie, assigned numeric values) from the data collected to help us understand how x and

are related and are the basis for estimating odds ratios.

We can build more complex models using multivariable logistic regression by adding more independent variables to the right side of equation (2). Essentially, this is what Schaffer et al⁴ did when, for example, they described clinical factors associated with indemnity payments (Schaffer et al, Table 3).

There are two notable techniques used frequently with multivariable logistic regression models. The first involves choosing which independent variables to include in the model. One way to select variables for multivariable models is defining them a priori, that is deciding which variables are clinically or conceptually associated with the outcome before looking at the data. With this approach, we can test specific hypotheses about the relationships between the independent variables and the outcome. Another common approach is to look at the data and identify the variables that vary significantly between the two outcome groups. Schaffer et al⁴ used an a priori approach to define variables in their multivariable model (ie, “variables for inclusion into the multivariable model were determined a priori”).

A second technique is the evaluation of collinearity, which helps us understand whether the independent variables are related to each other. It is important to consider collinearity between independent variables because the inclusion of two (or more) variables that are highly correlated can cause interference between the two and create misleading results from the model. There are techniques to assess collinear relationships before modeling or as part of the model-building process to determine which variables should be excluded. If there are two (or more) independent variables that are similar, one (or more) must be removed from the model.

Fitting the model is the process by which statistical software (eg, SAS, Stata, R, SPSS) estimates the relationships among independent variables in the model and the outcome within a specific dataset. In equation (2), this essentially means that the software will evaluate the data and provide us with the best estimates for β₀ (the y-intercept) and β₁ (the slope) that describe the relationship between the variable x and

Modeling can be iterative, and part of the process may include removing variables from the model that are not significantly associated with the outcome to create a simpler solution, a process known as model reduction. The results from models describe the independent association between a specific characteristic and the outcome, meaning that the relationship has been adjusted for all the other characteristics in the model.

The relationships among the independent variables and outcome are most often represented as an odds ratio (OR), which quantifies the strength of the association between two variables and is directly calculated from the β values in the model. As the name suggests, an OR is a ratio of odds. But what are odds? Simply, the odds of an outcome (such as mortality) is the probability of experiencing the event divided by the probability of not experiencing that event; in other words, it is the ratio:

The concept of odds is often unfamiliar, so it can be helpful to consider the definition in the context of games of chance. For example, in horse race betting, the outcome of interest is that a horse will lose a race. Imagine that the probability of a horse losing a race is 0.8 and the probability of winning is 0.2. The odds of losing are

These odds usually are listed as 4-to-1, meaning that out of 5 races (ie, 4 + 1) the horse is expected to lose 4 times and win once. When odds are listed this way, we can easily calculate the associated probability by recognizing that the total number of expected races is the sum of two numbers (probability of losing: 4 races out of 5, or 0.80 vs probability of winning: 1 race out of 5, or 0.20).

In medical research, the OR typically represents the odds for one group of patients (A) compared with the odds for another group of patients (B) experiencing an outcome. If the odds of the outcome are the same for group A and group B, then OR = 1.0, meaning that the probability of the outcome is the same between the two groups. If the patients in group A have greater odds of experiencing the outcome compared with group B patients (and a greater probability of the outcome), then the OR will be >1. If the opposite is true, then the OR will be <1.

Schaffer et al⁴ estimated that the OR of an indemnity payment in malpractice cases involving errors in clinical judgment as a contributing factor was 5.01 (95% CI, 3.37-7.45). This means that malpractice cases involving errors in clinical judgement had a 5.01 times greater odds of indemnity payment compared with those without these errors after adjusting for all other variables in the model (eg, age, severity). Note that the 95% CI does not include 1.0. This indicates that the OR is statistically >1, and we can conclude that there is a significant relationship between errors in clinical judgment and payment that is unlikely to be attributed to chance alone.

In logistic regression for categorical independent variables, all categories are compared with a reference group within that variable, with the reference group serving as the denominator of the OR. The authors⁴ did not incorporate continuous independent variables in their multivariable logistic regression model. However, if the authors examined length of hospitalization as a contributing factor in indemnity payments, for example, the OR would represent a 1-unit increase in this variable (eg, 1-day increase in length of stay).

Logistic regression describes the relationships in data and is an important statistical model across many types of research. This Progress Note emphasizes the importance of weighing the advantages and limitations of logistic regression, provides a common approach to data transformation, and guides the correct interpretation of logistic regression model results.

The ability to read and correctly interpret research is an essential skill, but most hospitalists—and physicians in general—do not receive formal training in biostatistics during their medical education.^1-3 In addition to straightforward statistical tests that compare a single exposure and outcome, researchers commonly use statistical models to identify and quantify complex relationships among many exposures (eg, demographics, clinical characteristics, interventions, or other variables) and an outcome. Understanding statistical models can be challenging. Still, it is important to recognize the advantages and limitations of statistical models, how to interpret their results, and the potential implications of findings on current clinical practice.

In the article “Rates and Characteristics of Medical Malpractice Claims Against Hospitalists” published in the July 2021 issue of the Journal of Hospital Medicine, Schaffer et al⁴ used the Comparative Benchmarking System database, which is maintained by a malpractice insurer, to characterize malpractice claims against hospitalists. The authors used multiple logistic regression models to understand the relationship among clinical factors and indemnity payments. In this Progress Note, we describe situations in which logistic regression is the proper statistical method to analyze a data set, explain results from logistic regression analyses, and equip readers with skills to critically appraise conclusions drawn from these models.

Statistical models often are used to describe the relationship among one or more exposure variables (ie, independent variables) and an outcome (ie, dependent variable). These models allow researchers to evaluate the effects of multiple exposure variables simultaneously, which in turn allows them to “isolate” the effect of each variable; in other words, models facilitate an understanding of the relationship between each exposure variable and the outcome, adjusted for (ie, independent of) the other exposure variables in the model.

Several statistical models can be used to quantify relationships within the data, but each type of model has certain assumptions that must be satisfied. Two important assumptions include characteristics of the outcome (eg, the type and distribution) and the nature of the relationships among the outcome and independent variables (eg, linear vs nonlinear). Simple linear regression, one of the most basic statistical models used in research,⁵ assumes that (a) the outcome is continuous (ie, any numeric value is possible) and normally distributed (ie, its histogram is a bell-shaped curve) and (b) the relationship between the independent variable and the outcome is linear (ie, follows a straight line). If an investigator wanted to understand how weight is related to height, a simple linear regression could be used to develop a mathematical equation that tells us how the outcome (weight) generally increases as the independent variable (height) increases.

Often, the outcome in a study is not a continuous variable but a simple success/failure variable (ie, dichotomous variable that can be one of two possible values). Schaffer et al⁴ examined the binary outcome of whether a malpractice claim case would end in an indemnity payment or no payment. Linear regression models are not equipped to handle dichotomous outcomes. Instead, we need to use a different statistical model: logistic regression. In logistic regression, the probability (p) of a defined outcome event is estimated by creating a regression model.

A probability (p) is a measure of how likely an event (eg, a malpractice claim ends in an indemnity payment or not) is to occur. It is always between 0 (ie, the event will definitely not occur) and 1 (ie, the event will definitely occur). A p of 0.5 means there is a 50/50 chance that the event will occur (ie, equivalent to a coin flip). Because p is a probability, we need to make sure it is always between 0 and 1. If we were to try to model p with a linear regression, the model would assume that p could extend beyond 0 and 1. What can we do?

Applying a transformation is a commonly used tool in statistics to make data work better within statistical models.⁶ In this case, we will transform the variable p. In logistic regression, we model the probability of experiencing the outcome through a transformation called a logit. The logit represents the natural logarithm (ln) of the ratio of the probability of experiencing the outcome (p) vs the probability of not experiencing the outcome (1 – p), with the ratio being the odds of the event occurring.

This transformation works well for dichotomous outcomes because the logit transformation approximates a straight line as long as p is not too large or too small (between 0.05 and 0.95).

If we are performing a logistic regression with only one independent variable (x) and want to understand the relationship between this variable (x) and the probability of an outcome event (p), then our model is the equation of a line. The equation for the base model of logistic regression with one independent variable (x) is

where β₀ is the y-intercept and β₁ is the slope of the line. Equation (2) is identical to the algebraic equation y = mx + b for a line, just rearranged slightly. In this algebraic equation, m is the slope (the same as β₁) and b is the y-intercept (the same as β₀). We will see that β₀ and β₁ are estimated (ie, assigned numeric values) from the data collected to help us understand how x and

are related and are the basis for estimating odds ratios.

We can build more complex models using multivariable logistic regression by adding more independent variables to the right side of equation (2). Essentially, this is what Schaffer et al⁴ did when, for example, they described clinical factors associated with indemnity payments (Schaffer et al, Table 3).

There are two notable techniques used frequently with multivariable logistic regression models. The first involves choosing which independent variables to include in the model. One way to select variables for multivariable models is defining them a priori, that is deciding which variables are clinically or conceptually associated with the outcome before looking at the data. With this approach, we can test specific hypotheses about the relationships between the independent variables and the outcome. Another common approach is to look at the data and identify the variables that vary significantly between the two outcome groups. Schaffer et al⁴ used an a priori approach to define variables in their multivariable model (ie, “variables for inclusion into the multivariable model were determined a priori”).

A second technique is the evaluation of collinearity, which helps us understand whether the independent variables are related to each other. It is important to consider collinearity between independent variables because the inclusion of two (or more) variables that are highly correlated can cause interference between the two and create misleading results from the model. There are techniques to assess collinear relationships before modeling or as part of the model-building process to determine which variables should be excluded. If there are two (or more) independent variables that are similar, one (or more) must be removed from the model.

Fitting the model is the process by which statistical software (eg, SAS, Stata, R, SPSS) estimates the relationships among independent variables in the model and the outcome within a specific dataset. In equation (2), this essentially means that the software will evaluate the data and provide us with the best estimates for β₀ (the y-intercept) and β₁ (the slope) that describe the relationship between the variable x and

Modeling can be iterative, and part of the process may include removing variables from the model that are not significantly associated with the outcome to create a simpler solution, a process known as model reduction. The results from models describe the independent association between a specific characteristic and the outcome, meaning that the relationship has been adjusted for all the other characteristics in the model.

The relationships among the independent variables and outcome are most often represented as an odds ratio (OR), which quantifies the strength of the association between two variables and is directly calculated from the β values in the model. As the name suggests, an OR is a ratio of odds. But what are odds? Simply, the odds of an outcome (such as mortality) is the probability of experiencing the event divided by the probability of not experiencing that event; in other words, it is the ratio:

The concept of odds is often unfamiliar, so it can be helpful to consider the definition in the context of games of chance. For example, in horse race betting, the outcome of interest is that a horse will lose a race. Imagine that the probability of a horse losing a race is 0.8 and the probability of winning is 0.2. The odds of losing are

These odds usually are listed as 4-to-1, meaning that out of 5 races (ie, 4 + 1) the horse is expected to lose 4 times and win once. When odds are listed this way, we can easily calculate the associated probability by recognizing that the total number of expected races is the sum of two numbers (probability of losing: 4 races out of 5, or 0.80 vs probability of winning: 1 race out of 5, or 0.20).

In medical research, the OR typically represents the odds for one group of patients (A) compared with the odds for another group of patients (B) experiencing an outcome. If the odds of the outcome are the same for group A and group B, then OR = 1.0, meaning that the probability of the outcome is the same between the two groups. If the patients in group A have greater odds of experiencing the outcome compared with group B patients (and a greater probability of the outcome), then the OR will be >1. If the opposite is true, then the OR will be <1.

Schaffer et al⁴ estimated that the OR of an indemnity payment in malpractice cases involving errors in clinical judgment as a contributing factor was 5.01 (95% CI, 3.37-7.45). This means that malpractice cases involving errors in clinical judgement had a 5.01 times greater odds of indemnity payment compared with those without these errors after adjusting for all other variables in the model (eg, age, severity). Note that the 95% CI does not include 1.0. This indicates that the OR is statistically >1, and we can conclude that there is a significant relationship between errors in clinical judgment and payment that is unlikely to be attributed to chance alone.

In logistic regression for categorical independent variables, all categories are compared with a reference group within that variable, with the reference group serving as the denominator of the OR. The authors⁴ did not incorporate continuous independent variables in their multivariable logistic regression model. However, if the authors examined length of hospitalization as a contributing factor in indemnity payments, for example, the OR would represent a 1-unit increase in this variable (eg, 1-day increase in length of stay).

Logistic regression describes the relationships in data and is an important statistical model across many types of research. This Progress Note emphasizes the importance of weighing the advantages and limitations of logistic regression, provides a common approach to data transformation, and guides the correct interpretation of logistic regression model results.

The ability to read and correctly interpret research is an essential skill, but most hospitalists—and physicians in general—do not receive formal training in biostatistics during their medical education.^1-3 In addition to straightforward statistical tests that compare a single exposure and outcome, researchers commonly use statistical models to identify and quantify complex relationships among many exposures (eg, demographics, clinical characteristics, interventions, or other variables) and an outcome. Understanding statistical models can be challenging. Still, it is important to recognize the advantages and limitations of statistical models, how to interpret their results, and the potential implications of findings on current clinical practice.

In the article “Rates and Characteristics of Medical Malpractice Claims Against Hospitalists” published in the July 2021 issue of the Journal of Hospital Medicine, Schaffer et al⁴ used the Comparative Benchmarking System database, which is maintained by a malpractice insurer, to characterize malpractice claims against hospitalists. The authors used multiple logistic regression models to understand the relationship among clinical factors and indemnity payments. In this Progress Note, we describe situations in which logistic regression is the proper statistical method to analyze a data set, explain results from logistic regression analyses, and equip readers with skills to critically appraise conclusions drawn from these models.

Statistical models often are used to describe the relationship among one or more exposure variables (ie, independent variables) and an outcome (ie, dependent variable). These models allow researchers to evaluate the effects of multiple exposure variables simultaneously, which in turn allows them to “isolate” the effect of each variable; in other words, models facilitate an understanding of the relationship between each exposure variable and the outcome, adjusted for (ie, independent of) the other exposure variables in the model.

Several statistical models can be used to quantify relationships within the data, but each type of model has certain assumptions that must be satisfied. Two important assumptions include characteristics of the outcome (eg, the type and distribution) and the nature of the relationships among the outcome and independent variables (eg, linear vs nonlinear). Simple linear regression, one of the most basic statistical models used in research,⁵ assumes that (a) the outcome is continuous (ie, any numeric value is possible) and normally distributed (ie, its histogram is a bell-shaped curve) and (b) the relationship between the independent variable and the outcome is linear (ie, follows a straight line). If an investigator wanted to understand how weight is related to height, a simple linear regression could be used to develop a mathematical equation that tells us how the outcome (weight) generally increases as the independent variable (height) increases.

Often, the outcome in a study is not a continuous variable but a simple success/failure variable (ie, dichotomous variable that can be one of two possible values). Schaffer et al⁴ examined the binary outcome of whether a malpractice claim case would end in an indemnity payment or no payment. Linear regression models are not equipped to handle dichotomous outcomes. Instead, we need to use a different statistical model: logistic regression. In logistic regression, the probability (p) of a defined outcome event is estimated by creating a regression model.

A probability (p) is a measure of how likely an event (eg, a malpractice claim ends in an indemnity payment or not) is to occur. It is always between 0 (ie, the event will definitely not occur) and 1 (ie, the event will definitely occur). A p of 0.5 means there is a 50/50 chance that the event will occur (ie, equivalent to a coin flip). Because p is a probability, we need to make sure it is always between 0 and 1. If we were to try to model p with a linear regression, the model would assume that p could extend beyond 0 and 1. What can we do?

Applying a transformation is a commonly used tool in statistics to make data work better within statistical models.⁶ In this case, we will transform the variable p. In logistic regression, we model the probability of experiencing the outcome through a transformation called a logit. The logit represents the natural logarithm (ln) of the ratio of the probability of experiencing the outcome (p) vs the probability of not experiencing the outcome (1 – p), with the ratio being the odds of the event occurring.

This transformation works well for dichotomous outcomes because the logit transformation approximates a straight line as long as p is not too large or too small (between 0.05 and 0.95).

If we are performing a logistic regression with only one independent variable (x) and want to understand the relationship between this variable (x) and the probability of an outcome event (p), then our model is the equation of a line. The equation for the base model of logistic regression with one independent variable (x) is

where β₀ is the y-intercept and β₁ is the slope of the line. Equation (2) is identical to the algebraic equation y = mx + b for a line, just rearranged slightly. In this algebraic equation, m is the slope (the same as β₁) and b is the y-intercept (the same as β₀). We will see that β₀ and β₁ are estimated (ie, assigned numeric values) from the data collected to help us understand how x and

are related and are the basis for estimating odds ratios.

We can build more complex models using multivariable logistic regression by adding more independent variables to the right side of equation (2). Essentially, this is what Schaffer et al⁴ did when, for example, they described clinical factors associated with indemnity payments (Schaffer et al, Table 3).

There are two notable techniques used frequently with multivariable logistic regression models. The first involves choosing which independent variables to include in the model. One way to select variables for multivariable models is defining them a priori, that is deciding which variables are clinically or conceptually associated with the outcome before looking at the data. With this approach, we can test specific hypotheses about the relationships between the independent variables and the outcome. Another common approach is to look at the data and identify the variables that vary significantly between the two outcome groups. Schaffer et al⁴ used an a priori approach to define variables in their multivariable model (ie, “variables for inclusion into the multivariable model were determined a priori”).

A second technique is the evaluation of collinearity, which helps us understand whether the independent variables are related to each other. It is important to consider collinearity between independent variables because the inclusion of two (or more) variables that are highly correlated can cause interference between the two and create misleading results from the model. There are techniques to assess collinear relationships before modeling or as part of the model-building process to determine which variables should be excluded. If there are two (or more) independent variables that are similar, one (or more) must be removed from the model.

Fitting the model is the process by which statistical software (eg, SAS, Stata, R, SPSS) estimates the relationships among independent variables in the model and the outcome within a specific dataset. In equation (2), this essentially means that the software will evaluate the data and provide us with the best estimates for β₀ (the y-intercept) and β₁ (the slope) that describe the relationship between the variable x and

Modeling can be iterative, and part of the process may include removing variables from the model that are not significantly associated with the outcome to create a simpler solution, a process known as model reduction. The results from models describe the independent association between a specific characteristic and the outcome, meaning that the relationship has been adjusted for all the other characteristics in the model.

The relationships among the independent variables and outcome are most often represented as an odds ratio (OR), which quantifies the strength of the association between two variables and is directly calculated from the β values in the model. As the name suggests, an OR is a ratio of odds. But what are odds? Simply, the odds of an outcome (such as mortality) is the probability of experiencing the event divided by the probability of not experiencing that event; in other words, it is the ratio:

The concept of odds is often unfamiliar, so it can be helpful to consider the definition in the context of games of chance. For example, in horse race betting, the outcome of interest is that a horse will lose a race. Imagine that the probability of a horse losing a race is 0.8 and the probability of winning is 0.2. The odds of losing are

These odds usually are listed as 4-to-1, meaning that out of 5 races (ie, 4 + 1) the horse is expected to lose 4 times and win once. When odds are listed this way, we can easily calculate the associated probability by recognizing that the total number of expected races is the sum of two numbers (probability of losing: 4 races out of 5, or 0.80 vs probability of winning: 1 race out of 5, or 0.20).

In medical research, the OR typically represents the odds for one group of patients (A) compared with the odds for another group of patients (B) experiencing an outcome. If the odds of the outcome are the same for group A and group B, then OR = 1.0, meaning that the probability of the outcome is the same between the two groups. If the patients in group A have greater odds of experiencing the outcome compared with group B patients (and a greater probability of the outcome), then the OR will be >1. If the opposite is true, then the OR will be <1.

Schaffer et al⁴ estimated that the OR of an indemnity payment in malpractice cases involving errors in clinical judgment as a contributing factor was 5.01 (95% CI, 3.37-7.45). This means that malpractice cases involving errors in clinical judgement had a 5.01 times greater odds of indemnity payment compared with those without these errors after adjusting for all other variables in the model (eg, age, severity). Note that the 95% CI does not include 1.0. This indicates that the OR is statistically >1, and we can conclude that there is a significant relationship between errors in clinical judgment and payment that is unlikely to be attributed to chance alone.

In logistic regression for categorical independent variables, all categories are compared with a reference group within that variable, with the reference group serving as the denominator of the OR. The authors⁴ did not incorporate continuous independent variables in their multivariable logistic regression model. However, if the authors examined length of hospitalization as a contributing factor in indemnity payments, for example, the OR would represent a 1-unit increase in this variable (eg, 1-day increase in length of stay).

Logistic regression describes the relationships in data and is an important statistical model across many types of research. This Progress Note emphasizes the importance of weighing the advantages and limitations of logistic regression, provides a common approach to data transformation, and guides the correct interpretation of logistic regression model results.