A 63-year-old woman presented with an acute exacerbation of chronic back pain after a fall. She was taking warfarin because of a history of factor V Leiden, deep vein thrombosis, and pulmonary embolism, for which a temporary inferior vena cava (IVC) filter had been placed 8 years ago. Her physicians had subsequently tried to remove the filter, without success. Some time after that, 1 of the filter struts had been removed after it migrated through her abdominal wall.

Laboratory testing revealed a supratherapeutic international normalized ratio of 8.5.

The patient underwent endovascular aneurysm repair with adequate placement of a vascular graft. She was discharged on therapeutic anticoagulation, and her back pain had notably improved.

COMPLICATIONS OF IVC FILTERS

In the United States, the use of IVC filters has increased significantly over the last decade, with placement rates ranging from 12% to 17% in patients with venous thromboembolism.¹

The American Heart Association recommends filter placement for patients with venous thromboembolism for whom anticoagulation has failed or is contraindicated, patients unable to withstand pulmonary embolism, and patients who are hemodynamically unstable.² While indications vary in the guidelines released by different societies, filters are most often placed in patients who have an acute bleed, significant surgery after admission for venous thromboembolism, metastatic cancer, and severe illness.³

Complications can occur during and after insertion and during removal. They are more frequent with temporary than with permanent filters, and include filter movement and fracture as well as occlusion and penetration.^4,5

In our patient, we believe that the 3 remaining filter struts likely penetrated the wall of the IVC to the extent that they encountered adjacent structures (aorta, duodenum, kidney).

Of cases of IVC filter penetration reported to a US Food and Drug Administration database, 13.1% involved small bowel perforation, 6.5% involved aortic perforation, and 4.2% involved retroperitoneal bleeding. Symptoms such as abdominal and back pain were present in 38.3% of cases involving IVC penetration.⁵

Therefore, the differential diagnosis for patients with a history of IVC filter placement presenting with these symptoms should address filter complications, including occlusion,  incorrect placement, fracture, migration, and penetration of the filter.⁴ If complications occur, treatment options include anticoagulation, endovascular repair, and surgical intervention.

A 63-year-old woman presented with an acute exacerbation of chronic back pain after a fall. She was taking warfarin because of a history of factor V Leiden, deep vein thrombosis, and pulmonary embolism, for which a temporary inferior vena cava (IVC) filter had been placed 8 years ago. Her physicians had subsequently tried to remove the filter, without success. Some time after that, 1 of the filter struts had been removed after it migrated through her abdominal wall.

Laboratory testing revealed a supratherapeutic international normalized ratio of 8.5.

The patient underwent endovascular aneurysm repair with adequate placement of a vascular graft. She was discharged on therapeutic anticoagulation, and her back pain had notably improved.

COMPLICATIONS OF IVC FILTERS

In the United States, the use of IVC filters has increased significantly over the last decade, with placement rates ranging from 12% to 17% in patients with venous thromboembolism.¹

The American Heart Association recommends filter placement for patients with venous thromboembolism for whom anticoagulation has failed or is contraindicated, patients unable to withstand pulmonary embolism, and patients who are hemodynamically unstable.² While indications vary in the guidelines released by different societies, filters are most often placed in patients who have an acute bleed, significant surgery after admission for venous thromboembolism, metastatic cancer, and severe illness.³

Complications can occur during and after insertion and during removal. They are more frequent with temporary than with permanent filters, and include filter movement and fracture as well as occlusion and penetration.^4,5

In our patient, we believe that the 3 remaining filter struts likely penetrated the wall of the IVC to the extent that they encountered adjacent structures (aorta, duodenum, kidney).

Of cases of IVC filter penetration reported to a US Food and Drug Administration database, 13.1% involved small bowel perforation, 6.5% involved aortic perforation, and 4.2% involved retroperitoneal bleeding. Symptoms such as abdominal and back pain were present in 38.3% of cases involving IVC penetration.⁵

Therefore, the differential diagnosis for patients with a history of IVC filter placement presenting with these symptoms should address filter complications, including occlusion,  incorrect placement, fracture, migration, and penetration of the filter.⁴ If complications occur, treatment options include anticoagulation, endovascular repair, and surgical intervention.

A 63-year-old woman presented with an acute exacerbation of chronic back pain after a fall. She was taking warfarin because of a history of factor V Leiden, deep vein thrombosis, and pulmonary embolism, for which a temporary inferior vena cava (IVC) filter had been placed 8 years ago. Her physicians had subsequently tried to remove the filter, without success. Some time after that, 1 of the filter struts had been removed after it migrated through her abdominal wall.

Laboratory testing revealed a supratherapeutic international normalized ratio of 8.5.

The patient underwent endovascular aneurysm repair with adequate placement of a vascular graft. She was discharged on therapeutic anticoagulation, and her back pain had notably improved.

COMPLICATIONS OF IVC FILTERS

In the United States, the use of IVC filters has increased significantly over the last decade, with placement rates ranging from 12% to 17% in patients with venous thromboembolism.¹

The American Heart Association recommends filter placement for patients with venous thromboembolism for whom anticoagulation has failed or is contraindicated, patients unable to withstand pulmonary embolism, and patients who are hemodynamically unstable.² While indications vary in the guidelines released by different societies, filters are most often placed in patients who have an acute bleed, significant surgery after admission for venous thromboembolism, metastatic cancer, and severe illness.³

Complications can occur during and after insertion and during removal. They are more frequent with temporary than with permanent filters, and include filter movement and fracture as well as occlusion and penetration.^4,5

In our patient, we believe that the 3 remaining filter struts likely penetrated the wall of the IVC to the extent that they encountered adjacent structures (aorta, duodenum, kidney).

Of cases of IVC filter penetration reported to a US Food and Drug Administration database, 13.1% involved small bowel perforation, 6.5% involved aortic perforation, and 4.2% involved retroperitoneal bleeding. Symptoms such as abdominal and back pain were present in 38.3% of cases involving IVC penetration.⁵

Therefore, the differential diagnosis for patients with a history of IVC filter placement presenting with these symptoms should address filter complications, including occlusion,  incorrect placement, fracture, migration, and penetration of the filter.⁴ If complications occur, treatment options include anticoagulation, endovascular repair, and surgical intervention.

Most patients admitted with pulmonary embolism (PE) do not need transthoracic echocardiography (TTE); it should be performed in hemodynamically unstable patients, as well as in hemodynamically stable patients with specific elevated cardiac biomarkers and imaging features.

The decision to perform TTE should be based on clinical presentation, PE burden, and imaging findings (eg, computed tomographic angiography). TTE helps to stratify risk, guide management, monitor response to therapy, and give prognostic information for a subset of patients at increased risk for PE-related adverse events.

RISK STRATIFICATION IN PULMONARY EMBOLISM

PE has a spectrum of presentations ranging from no symptoms to shock. Based on the clinical presentation, PE can be categorized as high, intermediate, or low risk.

High-risk PE, often referred to as “massive” PE, is defined in current American Heart Association guidelines as acute PE with sustained hypotension (systolic blood pressure < 90 mm Hg for at least 15 minutes or requiring inotropic support), persistent profound bradycardia (heart rate < 40 beats per minute with signs or symptoms of shock), syncope, or cardiac arrest.¹

Intermediate-risk or “submassive” PE is more challenging to identify because patients are more hemodynamically stable, yet have evidence on electrocardiography, TTE, computed tomography, or cardiac biomarker testing—ie, N-terminal pro-B-type natriuretic peptide (NT-proBNP) or troponin—that indicates myocardial injury or volume overload.¹

Low-risk PE is acute PE in the absence of clinical markers of adverse prognosis that define massive or submassive PE.¹

ECHOCARDIOGRAPHIC FEATURES OF HIGH-RISK PULMONARY EMBOLISM

Certain TTE findings suggest increased risk of a poor outcome and may warrant therapy that is more invasive and aggressive. High-risk features include the following:

• Impaired right ventricular function
• Interventricular septum bulging into the left ventricle (“D-shaped” septum)
• Dilated proximal pulmonary arteries
• Increased severity of tricuspid regurgitation
• Elevated right atrial pressure
• Elevated pulmonary artery pressure
• Free-floating right ventricular thrombi, which are associated with a mortality rate of up to 45% and can be detected in 7% to 18% of patients⁶
• Tricuspid annular plane systolic excursion, an echocardiographic measure of right ventricular function¹; a value less than 17 mm suggests impaired right ventricular systolic function⁷
• The McConnell sign, a feature of acute massive PE: akinesia of the mid-free wall of the right ventricle and hypercontractility of the apex.

These TTE findings often lead to treatment with thrombolysis, transfer to the intensive care unit, and activation of the interventional team for catheter-based therapies.^1,8 Free-floating right heart thrombi or thrombus straddling the interatrial septum (“thrombus in transit”) through a patent foramen ovale may require surgical embolectomy.⁸

PATIENT SELECTION AND INDICATIONS FOR ECHOCARDIOGRAPHY

Most patients admitted with pulmonary embolism (PE) do not need transthoracic echocardiography (TTE); it should be performed in hemodynamically unstable patients, as well as in hemodynamically stable patients with specific elevated cardiac biomarkers and imaging features.

The decision to perform TTE should be based on clinical presentation, PE burden, and imaging findings (eg, computed tomographic angiography). TTE helps to stratify risk, guide management, monitor response to therapy, and give prognostic information for a subset of patients at increased risk for PE-related adverse events.

RISK STRATIFICATION IN PULMONARY EMBOLISM

PE has a spectrum of presentations ranging from no symptoms to shock. Based on the clinical presentation, PE can be categorized as high, intermediate, or low risk.

High-risk PE, often referred to as “massive” PE, is defined in current American Heart Association guidelines as acute PE with sustained hypotension (systolic blood pressure < 90 mm Hg for at least 15 minutes or requiring inotropic support), persistent profound bradycardia (heart rate < 40 beats per minute with signs or symptoms of shock), syncope, or cardiac arrest.¹

Intermediate-risk or “submassive” PE is more challenging to identify because patients are more hemodynamically stable, yet have evidence on electrocardiography, TTE, computed tomography, or cardiac biomarker testing—ie, N-terminal pro-B-type natriuretic peptide (NT-proBNP) or troponin—that indicates myocardial injury or volume overload.¹

Low-risk PE is acute PE in the absence of clinical markers of adverse prognosis that define massive or submassive PE.¹

ECHOCARDIOGRAPHIC FEATURES OF HIGH-RISK PULMONARY EMBOLISM

Certain TTE findings suggest increased risk of a poor outcome and may warrant therapy that is more invasive and aggressive. High-risk features include the following:

• Impaired right ventricular function
• Interventricular septum bulging into the left ventricle (“D-shaped” septum)
• Dilated proximal pulmonary arteries
• Increased severity of tricuspid regurgitation
• Elevated right atrial pressure
• Elevated pulmonary artery pressure
• Free-floating right ventricular thrombi, which are associated with a mortality rate of up to 45% and can be detected in 7% to 18% of patients⁶
• Tricuspid annular plane systolic excursion, an echocardiographic measure of right ventricular function¹; a value less than 17 mm suggests impaired right ventricular systolic function⁷
• The McConnell sign, a feature of acute massive PE: akinesia of the mid-free wall of the right ventricle and hypercontractility of the apex.

These TTE findings often lead to treatment with thrombolysis, transfer to the intensive care unit, and activation of the interventional team for catheter-based therapies.^1,8 Free-floating right heart thrombi or thrombus straddling the interatrial septum (“thrombus in transit”) through a patent foramen ovale may require surgical embolectomy.⁸

PATIENT SELECTION AND INDICATIONS FOR ECHOCARDIOGRAPHY

Most patients admitted with pulmonary embolism (PE) do not need transthoracic echocardiography (TTE); it should be performed in hemodynamically unstable patients, as well as in hemodynamically stable patients with specific elevated cardiac biomarkers and imaging features.

The decision to perform TTE should be based on clinical presentation, PE burden, and imaging findings (eg, computed tomographic angiography). TTE helps to stratify risk, guide management, monitor response to therapy, and give prognostic information for a subset of patients at increased risk for PE-related adverse events.

RISK STRATIFICATION IN PULMONARY EMBOLISM

PE has a spectrum of presentations ranging from no symptoms to shock. Based on the clinical presentation, PE can be categorized as high, intermediate, or low risk.

High-risk PE, often referred to as “massive” PE, is defined in current American Heart Association guidelines as acute PE with sustained hypotension (systolic blood pressure < 90 mm Hg for at least 15 minutes or requiring inotropic support), persistent profound bradycardia (heart rate < 40 beats per minute with signs or symptoms of shock), syncope, or cardiac arrest.¹

Intermediate-risk or “submassive” PE is more challenging to identify because patients are more hemodynamically stable, yet have evidence on electrocardiography, TTE, computed tomography, or cardiac biomarker testing—ie, N-terminal pro-B-type natriuretic peptide (NT-proBNP) or troponin—that indicates myocardial injury or volume overload.¹

Low-risk PE is acute PE in the absence of clinical markers of adverse prognosis that define massive or submassive PE.¹

ECHOCARDIOGRAPHIC FEATURES OF HIGH-RISK PULMONARY EMBOLISM

Certain TTE findings suggest increased risk of a poor outcome and may warrant therapy that is more invasive and aggressive. High-risk features include the following:

• Impaired right ventricular function
• Interventricular septum bulging into the left ventricle (“D-shaped” septum)
• Dilated proximal pulmonary arteries
• Increased severity of tricuspid regurgitation
• Elevated right atrial pressure
• Elevated pulmonary artery pressure
• Free-floating right ventricular thrombi, which are associated with a mortality rate of up to 45% and can be detected in 7% to 18% of patients⁶
• Tricuspid annular plane systolic excursion, an echocardiographic measure of right ventricular function¹; a value less than 17 mm suggests impaired right ventricular systolic function⁷
• The McConnell sign, a feature of acute massive PE: akinesia of the mid-free wall of the right ventricle and hypercontractility of the apex.

These TTE findings often lead to treatment with thrombolysis, transfer to the intensive care unit, and activation of the interventional team for catheter-based therapies.^1,8 Free-floating right heart thrombi or thrombus straddling the interatrial septum (“thrombus in transit”) through a patent foramen ovale may require surgical embolectomy.⁸

PATIENT SELECTION AND INDICATIONS FOR ECHOCARDIOGRAPHY

A 76-year-old man whose history included abdominal aortic aneurysm repair, bilateral femoral artery bypass for popliteal artery aneurysm, hypertension, and peptic ulcer disease was admitted to a community hospital with pleuritic chest pain and shortness of breath. Two days earlier, he had undergone repair of a ventral hernia.

At the time of that admission, he reported no fever, chills, night sweats, cough, or history of heart or lung disease. His vital signs were normal, and physical examination had revealed no apparent respiratory distress, no jugular venous distention, normal heart sounds, and no pedal edema; however, decreased air entry was noted in the right lung base. Initial serum levels of troponin and N-terminal pro-B-type natriuretic peptide were normal.

At that time, computed tomographic angiography of the chest showed segmental pulmonary emboli in the left upper and right lower lobes of the lungs and right pleural effusion. Transthoracic echocardiography showed normal atrial and ventricular sizes with no right or left ventricular systolic dysfunction and a left ventricular ejection fraction of 59%.

Treatment with intravenous heparin was started, and the patient was transferred to our hospital.

PLEURAL EFFUSION AND PULMONARY EMBOLISM

1. Which of the following is true about pleural effusion?

• It is rarely, if ever, associated with pulmonary embolism
• Most patients with pleural effusion due to pulmonary embolism do not have pleuritic chest pain
• Pulmonary embolism should be excluded in all cases of pleural effusion without a clear cause

Pulmonary embolism should be excluded in all cases of pleural effusion that do not have a clear cause. As for the other answer choices:

• Pulmonary embolism is the fourth leading cause of pleural effusion in the United States, after heart failure, pneumonia, and malignancy.¹
• About 75% of patients who develop pleural effusion in the setting of pulmonary embolism complain of pleuritic chest pain on the side of the effusion.² Most effusions are unilateral, small, and usually exudative.³

EVALUATION BEGINS: RESULTS OF THORACENTESIS

Our patient continued to receive intravenous heparin.

He underwent thoracentesis on hospital day 3, and 1,000 mL of turbid sanguineous pleural fluid was removed. Analysis of the fluid showed pH 7.27, white blood cell count 3.797 × 10⁹/L with 80% neutrophils, and lactate dehydrogenase (LDH) concentration 736 U/L (a ratio of pleural fluid LDH to a concurrent serum LDH > 0.6 is suggestive of an exudate); the fluid was also sent for culture and cytology. Thoracentesis was terminated early due to cough, and follow-up chest radiography showed a moderate-sized pneumothorax.

Computed tomography (CT) of the chest at this time showed a small wedge-shaped area of lung consolidation in the right lower lobe (also seen on CT done 1 day before admission to our hospital), with an intrinsic air-fluid level suggesting a focal infarct or lung abscess, now obscured by adjacent consolidation and atelectasis. In the interval since the previous CT, the multiloculated right pleural effusion had increased in size (Figure 1).

THE NEXT STEP

2. What is the most appropriate next step for this patient?

• Consult an interventional radiologist for chest tube placement
• Start empiric antibiotic therapy and ask an interventional radiologist to place a chest tube
• Start empiric antibiotic therapy, withhold anticoagulation, and consult a thoracic surgeon
• Start empiric antibiotic therapy and consult a thoracic surgeon while continuing anticoagulation

The most appropriate next step is to start empiric antibiotic therapy and consult a thoracic surgeon while continuing anticoagulation.

In this patient, it is appropriate to initiate antibiotics empirically on the basis of his significant pleural loculations, a wedge-shaped consolidation, and 80% neutrophils in the pleural fluid, all of which suggest infection. The unmasking of a wedge-shaped consolidation after thoracentesis, with a previously noted air-fluid level and an interval increase in multiloculated pleural fluid, raises suspicion of a necrotic infection that may have ruptured into the pleural space, a possible lung infarct, or a malignancy. Hence, simply placing a chest tube may not be enough.

Blood in the pleural fluid does not necessitate withholding anticoagulation unless the bleeding is heavy. A pleural fluid hematocrit greater than 50% of the peripheral blood hematocrit suggests hemothorax and is an indication to withhold anticoagulation.¹ Our patient’s pleural fluid was qualitatively sanguineous but not frankly bloody, and therefore we judged that it was not necessary to stop his heparin.

HOW DOES PULMONARY INFARCTION PRESENT CLINICALLY?

3. Which of the following statements about pulmonary infarction is incorrect?

• Cavitation and infarction are more common with larger emboli
• Cavitation occurs in fewer than 10% of pulmonary infarctions
• Lung abscess develops in more than 50% of pulmonary infarctions
• Pulmonary thromboembolism is the most common cause of pulmonary infarction

Lung abscess develops in far fewer than 50% of cases of pulmonary infarction. The rest of the statements are correct.

Cavitation complicates about 4% to 7% of infarctions and is more common when the infarction is 4 cm or greater in diameter.⁴ These cavities are usually single and predominantly on the right side in the apical or posterior segment of the upper lobe or the apical segment of the right lower lobe, as in our patient.^5–8 CT demonstrating scalloped inner margins and cross-cavity band shadows suggests a cavitary pulmonary infarction.^9,10

Infection and abscess in pulmonary infarction are poorly understood but have been linked to larger infarctions, coexistent congestion or atelectasis, and dental or oropharyngeal infection. In an early series of 550 cases of pulmonary infarction, 23 patients (4.2%) developed lung abscess and 6 (1.1%) developed empyema.¹¹ The mean time to cavitation for an infected pulmonary infarction has been reported to be 18 days.¹²

A reversed halo sign, generally described as a focal, rounded area of ground-glass opacity surrounded by a nearly complete ring of consolidation, has been reported to be more frequent with pulmonary infarction than with other diseases, especially when in the lower lobes.¹³

CASE CONTINUED: THORACOSCOPY

A cardiothoracic surgeon was consulted, intravenous heparin was discontinued, an inferior vena cava filter was placed, and the patient underwent video-assisted thoracoscopy.

Purulent fluid was noted on the lateral aspect of right lower lobe; this appeared to be the ruptured cavitary lesion functioning like an uncontrolled bronchopleural fistula. Two chest tubes, sizes 32F and 28F, were placed after decortication, resection of the lung abscess, and closure of the bronchopleural fistula. No significant air leak was noted after resection of this segment of lung.

Pathologic study showed acute organizing pneumonia with abscess formation; no malignant cells or granulomas were seen (Figure 2). Pleural fluid cultures grew Streptococcus intermedius, while the tissue culture was negative for any growth, including acid-fast bacilli and fungi.

On 3 different occasions, both chest tubes were shortened, backed out 2 cm, and resecured with sutures and pins, and Heimlich valves were applied before the patient was discharged.

Intravenous piperacillin-tazobactam was started on the fifth hospital day. On discharge, the patient was advised to continue this treatment for 3 weeks at home.

The patient was receiving enoxaparin subcutaneously in prophylactic doses; 72 hours after the thorascopic procedure this was increased to therapeutic doses, continuing after discharge. Bridging to warfarin was not advised in view of his chest tubes.

Our patient appeared to have developed a right lower lobe infarction that cavitated and ruptured into the pleural space, causing a bronchopleural fistula with empyema after a recent pulmonary embolism. Other reported causes of pulmonary infarction in pulmonary embolism are malignancy and heavy clot burden,⁶ but these have not been confirmed in subsequent studies.⁵ Malignancy was ruled out by biopsy of the resected portion of the lung, and our patient did not have a history of heart failure. A clear cavity was not noted (because it ruptured into the pleura), but an air-fluid level was described in a wedge-shaped consolidation, suggesting infarction.

How common is pulmonary infarction after pulmonary embolism?

Pulmonary infarction occurs in few patients with pulmonary embolism.¹³ Since the lungs receive oxygen from the airways and have a dual blood supply from the pulmonary and bronchial arteries, they are not particularly vulnerable to ischemia. However, the reported incidence of pulmonary infarction in patients with pulmonary embolism has ranged from 10% to higher than 30%.^5,14,15

The reasons behind pulmonary infarction with complications after pulmonary embolism have varied in different case series in different eras. CT, biopsy, or autopsy studies reveal pulmonary infarction after pulmonary embolism to be more common than suspected by clinical symptoms.

In a Mayo Clinic series of 43 cases of pulmonary infarction diagnosed over a 6-year period by surgical lung biopsy, 18 (42%) of the patients had underlying pulmonary thromboembolism, which was the most common cause.¹⁶

 

 

RISK FACTORS FOR PULMONARY INFARCTION

4. Which statement about risk factors for pulmonary infarction in pulmonary embolism is incorrect?

• Heart failure may be a risk factor for pulmonary infarction
• Pulmonary hemorrhage is a risk factor for pulmonary infarction
• Pulmonary infarction is more common with more proximal sites of pulmonary embolism
• Collateral circulation may protect against pulmonary infarction

Infarction is more common with emboli that are distal rather than proximal.

Dalen et al¹⁵ suggested that after pulmonary embolism, pulmonary hemorrhage is an important contributor to the development of pulmonary infarction independent of the presence or absence of associated cardiac or pulmonary disease, but that the effect depends on the site of obstruction.

This idea was first proposed in 1913, when Karsner and Ghoreyeb¹⁷ showed that when pulmonary arteries are completely obstructed, the bronchial arteries take over, except when the embolism is present in a small branch of the pulmonary artery. This is because the physiologic anastomosis between the pulmonary artery and the bronchial arteries is located at the precapillary level of the pulmonary artery, and the bronchial circulation does not take over until the pulmonary arterial pressure in the area of the embolism drops to zero.

Using CT data, Kirchner et al⁵ confirmed that the risk of pulmonary infarction is higher if the obstruction is peripheral, ie, distal.

Using autopsy data, Tsao et al¹⁸ reported a higher risk of pulmonary infarction in embolic occlusion of pulmonary vessels less than 3 mm in diameter.

Collateral circulation has been shown to protect against pulmonary infarction. For example, Miniati et al¹⁴ showed that healthy young patients with pulmonary embolism were more prone to develop pulmonary infarction, probably because they had less efficient collateral systems in the peripheral lung fields. In lung transplant recipients, it has been shown that the risk of infarction decreased with development of collateral circulation.¹⁹

Dalen et al,¹⁵ however, attributed delayed resolution of pulmonary hemorrhage (as measured by resolution of infiltrate on chest radiography) to higher underlying pulmonary venous pressure in patients with heart failure and consequent pulmonary infarction. In comparison, healthy patients without cardiac or pulmonary disease have faster resolution of pulmonary hemorrhage when present, and less likelihood of pulmonary infarction (and death in submassive pulmonary embolism).

Data on the management of infected pulmonary infarction are limited. Mortality rates have been as high as 41% with noninfected and 73% with infected cavitary infarctions.⁴ Some authors have advocated early surgical resection in view of high rates of failure of medical treatment due to lack of blood supply within the cavity and continued risk of infection.

KEY POINTS

In patients with a recently diagnosed pulmonary embolism and concurrent symptoms of bacterial pneumonia, a diagnosis of cavitary pulmonary infarction should be considered.

Consolidations that are pleural-based with sharp, rounded margins and with focal areas of central hyperlucencies representing hemorrhage on the mediastinal windows on CT are more likely to represent a pulmonary infarct.²⁰

A 76-year-old man whose history included abdominal aortic aneurysm repair, bilateral femoral artery bypass for popliteal artery aneurysm, hypertension, and peptic ulcer disease was admitted to a community hospital with pleuritic chest pain and shortness of breath. Two days earlier, he had undergone repair of a ventral hernia.

At the time of that admission, he reported no fever, chills, night sweats, cough, or history of heart or lung disease. His vital signs were normal, and physical examination had revealed no apparent respiratory distress, no jugular venous distention, normal heart sounds, and no pedal edema; however, decreased air entry was noted in the right lung base. Initial serum levels of troponin and N-terminal pro-B-type natriuretic peptide were normal.

At that time, computed tomographic angiography of the chest showed segmental pulmonary emboli in the left upper and right lower lobes of the lungs and right pleural effusion. Transthoracic echocardiography showed normal atrial and ventricular sizes with no right or left ventricular systolic dysfunction and a left ventricular ejection fraction of 59%.

Treatment with intravenous heparin was started, and the patient was transferred to our hospital.

PLEURAL EFFUSION AND PULMONARY EMBOLISM

1. Which of the following is true about pleural effusion?

• It is rarely, if ever, associated with pulmonary embolism
• Most patients with pleural effusion due to pulmonary embolism do not have pleuritic chest pain
• Pulmonary embolism should be excluded in all cases of pleural effusion without a clear cause

Pulmonary embolism should be excluded in all cases of pleural effusion that do not have a clear cause. As for the other answer choices:

• Pulmonary embolism is the fourth leading cause of pleural effusion in the United States, after heart failure, pneumonia, and malignancy.¹
• About 75% of patients who develop pleural effusion in the setting of pulmonary embolism complain of pleuritic chest pain on the side of the effusion.² Most effusions are unilateral, small, and usually exudative.³

EVALUATION BEGINS: RESULTS OF THORACENTESIS

Our patient continued to receive intravenous heparin.

He underwent thoracentesis on hospital day 3, and 1,000 mL of turbid sanguineous pleural fluid was removed. Analysis of the fluid showed pH 7.27, white blood cell count 3.797 × 10⁹/L with 80% neutrophils, and lactate dehydrogenase (LDH) concentration 736 U/L (a ratio of pleural fluid LDH to a concurrent serum LDH > 0.6 is suggestive of an exudate); the fluid was also sent for culture and cytology. Thoracentesis was terminated early due to cough, and follow-up chest radiography showed a moderate-sized pneumothorax.

Computed tomography (CT) of the chest at this time showed a small wedge-shaped area of lung consolidation in the right lower lobe (also seen on CT done 1 day before admission to our hospital), with an intrinsic air-fluid level suggesting a focal infarct or lung abscess, now obscured by adjacent consolidation and atelectasis. In the interval since the previous CT, the multiloculated right pleural effusion had increased in size (Figure 1).

THE NEXT STEP

2. What is the most appropriate next step for this patient?

• Consult an interventional radiologist for chest tube placement
• Start empiric antibiotic therapy and ask an interventional radiologist to place a chest tube
• Start empiric antibiotic therapy, withhold anticoagulation, and consult a thoracic surgeon
• Start empiric antibiotic therapy and consult a thoracic surgeon while continuing anticoagulation

The most appropriate next step is to start empiric antibiotic therapy and consult a thoracic surgeon while continuing anticoagulation.

In this patient, it is appropriate to initiate antibiotics empirically on the basis of his significant pleural loculations, a wedge-shaped consolidation, and 80% neutrophils in the pleural fluid, all of which suggest infection. The unmasking of a wedge-shaped consolidation after thoracentesis, with a previously noted air-fluid level and an interval increase in multiloculated pleural fluid, raises suspicion of a necrotic infection that may have ruptured into the pleural space, a possible lung infarct, or a malignancy. Hence, simply placing a chest tube may not be enough.

Blood in the pleural fluid does not necessitate withholding anticoagulation unless the bleeding is heavy. A pleural fluid hematocrit greater than 50% of the peripheral blood hematocrit suggests hemothorax and is an indication to withhold anticoagulation.¹ Our patient’s pleural fluid was qualitatively sanguineous but not frankly bloody, and therefore we judged that it was not necessary to stop his heparin.

HOW DOES PULMONARY INFARCTION PRESENT CLINICALLY?

3. Which of the following statements about pulmonary infarction is incorrect?

• Cavitation and infarction are more common with larger emboli
• Cavitation occurs in fewer than 10% of pulmonary infarctions
• Lung abscess develops in more than 50% of pulmonary infarctions
• Pulmonary thromboembolism is the most common cause of pulmonary infarction

Lung abscess develops in far fewer than 50% of cases of pulmonary infarction. The rest of the statements are correct.

Cavitation complicates about 4% to 7% of infarctions and is more common when the infarction is 4 cm or greater in diameter.⁴ These cavities are usually single and predominantly on the right side in the apical or posterior segment of the upper lobe or the apical segment of the right lower lobe, as in our patient.^5–8 CT demonstrating scalloped inner margins and cross-cavity band shadows suggests a cavitary pulmonary infarction.^9,10

Infection and abscess in pulmonary infarction are poorly understood but have been linked to larger infarctions, coexistent congestion or atelectasis, and dental or oropharyngeal infection. In an early series of 550 cases of pulmonary infarction, 23 patients (4.2%) developed lung abscess and 6 (1.1%) developed empyema.¹¹ The mean time to cavitation for an infected pulmonary infarction has been reported to be 18 days.¹²

A reversed halo sign, generally described as a focal, rounded area of ground-glass opacity surrounded by a nearly complete ring of consolidation, has been reported to be more frequent with pulmonary infarction than with other diseases, especially when in the lower lobes.¹³

CASE CONTINUED: THORACOSCOPY

A cardiothoracic surgeon was consulted, intravenous heparin was discontinued, an inferior vena cava filter was placed, and the patient underwent video-assisted thoracoscopy.

Purulent fluid was noted on the lateral aspect of right lower lobe; this appeared to be the ruptured cavitary lesion functioning like an uncontrolled bronchopleural fistula. Two chest tubes, sizes 32F and 28F, were placed after decortication, resection of the lung abscess, and closure of the bronchopleural fistula. No significant air leak was noted after resection of this segment of lung.

Pathologic study showed acute organizing pneumonia with abscess formation; no malignant cells or granulomas were seen (Figure 2). Pleural fluid cultures grew Streptococcus intermedius, while the tissue culture was negative for any growth, including acid-fast bacilli and fungi.

On 3 different occasions, both chest tubes were shortened, backed out 2 cm, and resecured with sutures and pins, and Heimlich valves were applied before the patient was discharged.

Intravenous piperacillin-tazobactam was started on the fifth hospital day. On discharge, the patient was advised to continue this treatment for 3 weeks at home.

The patient was receiving enoxaparin subcutaneously in prophylactic doses; 72 hours after the thorascopic procedure this was increased to therapeutic doses, continuing after discharge. Bridging to warfarin was not advised in view of his chest tubes.

Our patient appeared to have developed a right lower lobe infarction that cavitated and ruptured into the pleural space, causing a bronchopleural fistula with empyema after a recent pulmonary embolism. Other reported causes of pulmonary infarction in pulmonary embolism are malignancy and heavy clot burden,⁶ but these have not been confirmed in subsequent studies.⁵ Malignancy was ruled out by biopsy of the resected portion of the lung, and our patient did not have a history of heart failure. A clear cavity was not noted (because it ruptured into the pleura), but an air-fluid level was described in a wedge-shaped consolidation, suggesting infarction.

How common is pulmonary infarction after pulmonary embolism?

Pulmonary infarction occurs in few patients with pulmonary embolism.¹³ Since the lungs receive oxygen from the airways and have a dual blood supply from the pulmonary and bronchial arteries, they are not particularly vulnerable to ischemia. However, the reported incidence of pulmonary infarction in patients with pulmonary embolism has ranged from 10% to higher than 30%.^5,14,15

The reasons behind pulmonary infarction with complications after pulmonary embolism have varied in different case series in different eras. CT, biopsy, or autopsy studies reveal pulmonary infarction after pulmonary embolism to be more common than suspected by clinical symptoms.

In a Mayo Clinic series of 43 cases of pulmonary infarction diagnosed over a 6-year period by surgical lung biopsy, 18 (42%) of the patients had underlying pulmonary thromboembolism, which was the most common cause.¹⁶

 

 

RISK FACTORS FOR PULMONARY INFARCTION

4. Which statement about risk factors for pulmonary infarction in pulmonary embolism is incorrect?

• Heart failure may be a risk factor for pulmonary infarction
• Pulmonary hemorrhage is a risk factor for pulmonary infarction
• Pulmonary infarction is more common with more proximal sites of pulmonary embolism
• Collateral circulation may protect against pulmonary infarction

Infarction is more common with emboli that are distal rather than proximal.

Dalen et al¹⁵ suggested that after pulmonary embolism, pulmonary hemorrhage is an important contributor to the development of pulmonary infarction independent of the presence or absence of associated cardiac or pulmonary disease, but that the effect depends on the site of obstruction.

This idea was first proposed in 1913, when Karsner and Ghoreyeb¹⁷ showed that when pulmonary arteries are completely obstructed, the bronchial arteries take over, except when the embolism is present in a small branch of the pulmonary artery. This is because the physiologic anastomosis between the pulmonary artery and the bronchial arteries is located at the precapillary level of the pulmonary artery, and the bronchial circulation does not take over until the pulmonary arterial pressure in the area of the embolism drops to zero.

Using CT data, Kirchner et al⁵ confirmed that the risk of pulmonary infarction is higher if the obstruction is peripheral, ie, distal.

Using autopsy data, Tsao et al¹⁸ reported a higher risk of pulmonary infarction in embolic occlusion of pulmonary vessels less than 3 mm in diameter.

Collateral circulation has been shown to protect against pulmonary infarction. For example, Miniati et al¹⁴ showed that healthy young patients with pulmonary embolism were more prone to develop pulmonary infarction, probably because they had less efficient collateral systems in the peripheral lung fields. In lung transplant recipients, it has been shown that the risk of infarction decreased with development of collateral circulation.¹⁹

Dalen et al,¹⁵ however, attributed delayed resolution of pulmonary hemorrhage (as measured by resolution of infiltrate on chest radiography) to higher underlying pulmonary venous pressure in patients with heart failure and consequent pulmonary infarction. In comparison, healthy patients without cardiac or pulmonary disease have faster resolution of pulmonary hemorrhage when present, and less likelihood of pulmonary infarction (and death in submassive pulmonary embolism).

Data on the management of infected pulmonary infarction are limited. Mortality rates have been as high as 41% with noninfected and 73% with infected cavitary infarctions.⁴ Some authors have advocated early surgical resection in view of high rates of failure of medical treatment due to lack of blood supply within the cavity and continued risk of infection.

KEY POINTS

In patients with a recently diagnosed pulmonary embolism and concurrent symptoms of bacterial pneumonia, a diagnosis of cavitary pulmonary infarction should be considered.

Consolidations that are pleural-based with sharp, rounded margins and with focal areas of central hyperlucencies representing hemorrhage on the mediastinal windows on CT are more likely to represent a pulmonary infarct.²⁰

A 76-year-old man whose history included abdominal aortic aneurysm repair, bilateral femoral artery bypass for popliteal artery aneurysm, hypertension, and peptic ulcer disease was admitted to a community hospital with pleuritic chest pain and shortness of breath. Two days earlier, he had undergone repair of a ventral hernia.

At the time of that admission, he reported no fever, chills, night sweats, cough, or history of heart or lung disease. His vital signs were normal, and physical examination had revealed no apparent respiratory distress, no jugular venous distention, normal heart sounds, and no pedal edema; however, decreased air entry was noted in the right lung base. Initial serum levels of troponin and N-terminal pro-B-type natriuretic peptide were normal.

At that time, computed tomographic angiography of the chest showed segmental pulmonary emboli in the left upper and right lower lobes of the lungs and right pleural effusion. Transthoracic echocardiography showed normal atrial and ventricular sizes with no right or left ventricular systolic dysfunction and a left ventricular ejection fraction of 59%.

Treatment with intravenous heparin was started, and the patient was transferred to our hospital.

PLEURAL EFFUSION AND PULMONARY EMBOLISM

1. Which of the following is true about pleural effusion?

• It is rarely, if ever, associated with pulmonary embolism
• Most patients with pleural effusion due to pulmonary embolism do not have pleuritic chest pain
• Pulmonary embolism should be excluded in all cases of pleural effusion without a clear cause

Pulmonary embolism should be excluded in all cases of pleural effusion that do not have a clear cause. As for the other answer choices:

• Pulmonary embolism is the fourth leading cause of pleural effusion in the United States, after heart failure, pneumonia, and malignancy.¹
• About 75% of patients who develop pleural effusion in the setting of pulmonary embolism complain of pleuritic chest pain on the side of the effusion.² Most effusions are unilateral, small, and usually exudative.³

EVALUATION BEGINS: RESULTS OF THORACENTESIS

Our patient continued to receive intravenous heparin.

He underwent thoracentesis on hospital day 3, and 1,000 mL of turbid sanguineous pleural fluid was removed. Analysis of the fluid showed pH 7.27, white blood cell count 3.797 × 10⁹/L with 80% neutrophils, and lactate dehydrogenase (LDH) concentration 736 U/L (a ratio of pleural fluid LDH to a concurrent serum LDH > 0.6 is suggestive of an exudate); the fluid was also sent for culture and cytology. Thoracentesis was terminated early due to cough, and follow-up chest radiography showed a moderate-sized pneumothorax.

Computed tomography (CT) of the chest at this time showed a small wedge-shaped area of lung consolidation in the right lower lobe (also seen on CT done 1 day before admission to our hospital), with an intrinsic air-fluid level suggesting a focal infarct or lung abscess, now obscured by adjacent consolidation and atelectasis. In the interval since the previous CT, the multiloculated right pleural effusion had increased in size (Figure 1).

THE NEXT STEP

2. What is the most appropriate next step for this patient?

• Consult an interventional radiologist for chest tube placement
• Start empiric antibiotic therapy and ask an interventional radiologist to place a chest tube
• Start empiric antibiotic therapy, withhold anticoagulation, and consult a thoracic surgeon
• Start empiric antibiotic therapy and consult a thoracic surgeon while continuing anticoagulation

The most appropriate next step is to start empiric antibiotic therapy and consult a thoracic surgeon while continuing anticoagulation.

In this patient, it is appropriate to initiate antibiotics empirically on the basis of his significant pleural loculations, a wedge-shaped consolidation, and 80% neutrophils in the pleural fluid, all of which suggest infection. The unmasking of a wedge-shaped consolidation after thoracentesis, with a previously noted air-fluid level and an interval increase in multiloculated pleural fluid, raises suspicion of a necrotic infection that may have ruptured into the pleural space, a possible lung infarct, or a malignancy. Hence, simply placing a chest tube may not be enough.

Blood in the pleural fluid does not necessitate withholding anticoagulation unless the bleeding is heavy. A pleural fluid hematocrit greater than 50% of the peripheral blood hematocrit suggests hemothorax and is an indication to withhold anticoagulation.¹ Our patient’s pleural fluid was qualitatively sanguineous but not frankly bloody, and therefore we judged that it was not necessary to stop his heparin.

HOW DOES PULMONARY INFARCTION PRESENT CLINICALLY?

3. Which of the following statements about pulmonary infarction is incorrect?

• Cavitation and infarction are more common with larger emboli
• Cavitation occurs in fewer than 10% of pulmonary infarctions
• Lung abscess develops in more than 50% of pulmonary infarctions
• Pulmonary thromboembolism is the most common cause of pulmonary infarction

Lung abscess develops in far fewer than 50% of cases of pulmonary infarction. The rest of the statements are correct.

Cavitation complicates about 4% to 7% of infarctions and is more common when the infarction is 4 cm or greater in diameter.⁴ These cavities are usually single and predominantly on the right side in the apical or posterior segment of the upper lobe or the apical segment of the right lower lobe, as in our patient.^5–8 CT demonstrating scalloped inner margins and cross-cavity band shadows suggests a cavitary pulmonary infarction.^9,10

Infection and abscess in pulmonary infarction are poorly understood but have been linked to larger infarctions, coexistent congestion or atelectasis, and dental or oropharyngeal infection. In an early series of 550 cases of pulmonary infarction, 23 patients (4.2%) developed lung abscess and 6 (1.1%) developed empyema.¹¹ The mean time to cavitation for an infected pulmonary infarction has been reported to be 18 days.¹²

A reversed halo sign, generally described as a focal, rounded area of ground-glass opacity surrounded by a nearly complete ring of consolidation, has been reported to be more frequent with pulmonary infarction than with other diseases, especially when in the lower lobes.¹³

CASE CONTINUED: THORACOSCOPY

A cardiothoracic surgeon was consulted, intravenous heparin was discontinued, an inferior vena cava filter was placed, and the patient underwent video-assisted thoracoscopy.

Purulent fluid was noted on the lateral aspect of right lower lobe; this appeared to be the ruptured cavitary lesion functioning like an uncontrolled bronchopleural fistula. Two chest tubes, sizes 32F and 28F, were placed after decortication, resection of the lung abscess, and closure of the bronchopleural fistula. No significant air leak was noted after resection of this segment of lung.

Pathologic study showed acute organizing pneumonia with abscess formation; no malignant cells or granulomas were seen (Figure 2). Pleural fluid cultures grew Streptococcus intermedius, while the tissue culture was negative for any growth, including acid-fast bacilli and fungi.

On 3 different occasions, both chest tubes were shortened, backed out 2 cm, and resecured with sutures and pins, and Heimlich valves were applied before the patient was discharged.

Intravenous piperacillin-tazobactam was started on the fifth hospital day. On discharge, the patient was advised to continue this treatment for 3 weeks at home.

The patient was receiving enoxaparin subcutaneously in prophylactic doses; 72 hours after the thorascopic procedure this was increased to therapeutic doses, continuing after discharge. Bridging to warfarin was not advised in view of his chest tubes.

Our patient appeared to have developed a right lower lobe infarction that cavitated and ruptured into the pleural space, causing a bronchopleural fistula with empyema after a recent pulmonary embolism. Other reported causes of pulmonary infarction in pulmonary embolism are malignancy and heavy clot burden,⁶ but these have not been confirmed in subsequent studies.⁵ Malignancy was ruled out by biopsy of the resected portion of the lung, and our patient did not have a history of heart failure. A clear cavity was not noted (because it ruptured into the pleura), but an air-fluid level was described in a wedge-shaped consolidation, suggesting infarction.

How common is pulmonary infarction after pulmonary embolism?

Pulmonary infarction occurs in few patients with pulmonary embolism.¹³ Since the lungs receive oxygen from the airways and have a dual blood supply from the pulmonary and bronchial arteries, they are not particularly vulnerable to ischemia. However, the reported incidence of pulmonary infarction in patients with pulmonary embolism has ranged from 10% to higher than 30%.^5,14,15

The reasons behind pulmonary infarction with complications after pulmonary embolism have varied in different case series in different eras. CT, biopsy, or autopsy studies reveal pulmonary infarction after pulmonary embolism to be more common than suspected by clinical symptoms.

In a Mayo Clinic series of 43 cases of pulmonary infarction diagnosed over a 6-year period by surgical lung biopsy, 18 (42%) of the patients had underlying pulmonary thromboembolism, which was the most common cause.¹⁶

 

 

RISK FACTORS FOR PULMONARY INFARCTION

4. Which statement about risk factors for pulmonary infarction in pulmonary embolism is incorrect?

• Heart failure may be a risk factor for pulmonary infarction
• Pulmonary hemorrhage is a risk factor for pulmonary infarction
• Pulmonary infarction is more common with more proximal sites of pulmonary embolism
• Collateral circulation may protect against pulmonary infarction

Infarction is more common with emboli that are distal rather than proximal.

Dalen et al¹⁵ suggested that after pulmonary embolism, pulmonary hemorrhage is an important contributor to the development of pulmonary infarction independent of the presence or absence of associated cardiac or pulmonary disease, but that the effect depends on the site of obstruction.

This idea was first proposed in 1913, when Karsner and Ghoreyeb¹⁷ showed that when pulmonary arteries are completely obstructed, the bronchial arteries take over, except when the embolism is present in a small branch of the pulmonary artery. This is because the physiologic anastomosis between the pulmonary artery and the bronchial arteries is located at the precapillary level of the pulmonary artery, and the bronchial circulation does not take over until the pulmonary arterial pressure in the area of the embolism drops to zero.

Using CT data, Kirchner et al⁵ confirmed that the risk of pulmonary infarction is higher if the obstruction is peripheral, ie, distal.

Using autopsy data, Tsao et al¹⁸ reported a higher risk of pulmonary infarction in embolic occlusion of pulmonary vessels less than 3 mm in diameter.

Collateral circulation has been shown to protect against pulmonary infarction. For example, Miniati et al¹⁴ showed that healthy young patients with pulmonary embolism were more prone to develop pulmonary infarction, probably because they had less efficient collateral systems in the peripheral lung fields. In lung transplant recipients, it has been shown that the risk of infarction decreased with development of collateral circulation.¹⁹

Dalen et al,¹⁵ however, attributed delayed resolution of pulmonary hemorrhage (as measured by resolution of infiltrate on chest radiography) to higher underlying pulmonary venous pressure in patients with heart failure and consequent pulmonary infarction. In comparison, healthy patients without cardiac or pulmonary disease have faster resolution of pulmonary hemorrhage when present, and less likelihood of pulmonary infarction (and death in submassive pulmonary embolism).

Data on the management of infected pulmonary infarction are limited. Mortality rates have been as high as 41% with noninfected and 73% with infected cavitary infarctions.⁴ Some authors have advocated early surgical resection in view of high rates of failure of medical treatment due to lack of blood supply within the cavity and continued risk of infection.

KEY POINTS

In patients with a recently diagnosed pulmonary embolism and concurrent symptoms of bacterial pneumonia, a diagnosis of cavitary pulmonary infarction should be considered.

Consolidations that are pleural-based with sharp, rounded margins and with focal areas of central hyperlucencies representing hemorrhage on the mediastinal windows on CT are more likely to represent a pulmonary infarct.²⁰

Mary, age 38, was hospitalized for acute cholecystitis requiring laparoscopic surgery. Her hospital course was uneventful. At the time of discharge, I, her inpatient doctor, prescribed 15 hydrocodone tablets for postoperative pain. I never saw her again. Did she struggle to stop taking the hydrocodone I prescribed?

Heather is a 50-year-old patient in my addiction medicine clinic who developed opioid use disorder while being treated for chronic pain. After much hardship and to her credit, she is now in long-term remission. Did her opioid use disorder start with an opioid prescription for an accepted indication?

The issues Mary and Heather face seem unrelated, but these 2 patients may be at different time points in the progression of the same disease. As a hospitalist, I want to optimize the chances that patients taking opioids for acute pain will be able to stop taking them.

CHRONIC USE VS OPIOID USE DISORDER

There is a distinction between chronic use of opioids and opioid use disorder. The latter is also known as addiction.

Patients who take opioids daily do not necessarily have opioid use disorder, even if they have physiologic dependence on them. Physiologic opioid dependence is commonly confused with opioid use disorder, but it is the expected result of regularly taking these drugs.

Opioid use disorder is a chronic disease of the brain characterized by loss of control over opioid use, resulting in harm. The Diagnostic and Statistical Manual, fifth edition, excludes physiologic dependence on opioids (tolerance and withdrawal) from its criteria for opioid use disorder if the patient is taking opioids solely under medical supervision.¹ To be diagnosed with opioid use disorder, patients need to do only 2 of the following within 12 months:

• Take more of the drug than intended
• Want or try to cut down without success
• Spend a lot of time in getting, using, or recovering from the drug
• Crave the drug
• Fail to meet commitments due to the drug
• Continue to use the drug, even though it causes social or relationship problems
• Give up or reduce other activities because of the drug
• Use the drug even when it isn’t safe
• Continue to use even when it causes physical or psychological problems
• Develop tolerance (but, as noted, not if taking the drug as directed under a doctor’s supervision)
• Experience withdrawal (again, but not if taking the drug under medical supervision).

WHY DO SOME PATIENTS STRUGGLE TO STOP TAKING OPIOIDS?

Studying opioid use disorder as an outcome in large groups of patients is complicated by imperfect medical documentation. However, using pharmacy claims data, researchers can accurately describe opioid prescription patterns in large groups of patients over time. This means we can count how many patients keep taking prescribed opioids but not how many become addicted.

In a country where nearly 40% of adults are prescribed an opioid annually, the question is not why people start taking opioids, but why some have to struggle to stop.² Several recent studies used pharmacy claims data to identify factors that may predict chronic opioid use in patients prescribed opioids for acute pain. The findings suggest that we can better treat acute pain to prevent chronic opioid use.

We don’t yet know how to protect patients like Mary from opioid use disorder, but the following 3 studies have already changed my practice.

HIGHER TOTAL DOSE MEANS HIGHER RISK

[Shah A, Hayes CJ, Martin BC. Characteristics of initial prescription episodes and likelihood of long-term opioid use—United States, 2006–2015. MMWR Morb Mortal Wkly Rep 2017; 66(10):265–269.]

Shah et al³ reported a study of nearly 1.3 million opioid-naive patients who received opioid prescriptions. Of those prescribed at least 1 day of opioids, 6% were still taking them 1 year later, and 2.9% were still taking them 3 years later.

Opioid exposure in acute pain was measured in total “morphine milligram equivalents” (MME), ie, the cumulative amount of opioids prescribed in the treatment episode, standardized across different types of opioids. We usually think of exposure in terms of how many milligrams a patient takes per day, which correlates with mortality in chronic opioid use.⁴ But this study showed a linear relationship between total MME prescribed for acute pain and ongoing opioid use in opioid-naive patients. By itself, the difference between daily and total MME made the article revelatory.

But the study went further, asking how much is too much: ie, What is the cutoff MME above which the patient is at risk of chronic opioid use? The relationship between acute opioid dose and chronic use is linear and starts early. Shah et al suggested that a total threshold of 700 MME predicts chronic opioid use—140 hydrocodone tablets, or 1 month of regular use.³

Many doctors worry that specific opioids such as oxycodone, hydromorphone, and fentanyl may be more habit-forming. Surprisingly, this study showed that these drugs were associated with rates of chronic use similar to those of other opioids when they controlled for potency.

Bottom line. Total opioid use in acute pain was the best predictor of chronic opioid use, and it showed that chronicity begins earlier than thought.

 

 

DON’T BE A ‘HIGH-INTENSITY’ PRESCRIBER

[Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017; 376(7):663–673.]

Barnett et al⁵ analyzed opioid prescribing for acute pain in the emergency department, using Medicare pharmacy data from 377,629 previously opioid-naive patients. They categorized the emergency providers into quartiles based on the frequency of opioid prescribing.

The relative risk of ongoing opioid use 1 year after being treated by a “high-intensity” prescriber (ie, one in the top quartile) was 30% greater than in similar patients seen by a low-intensity prescriber (ie, one in the bottom quartile). In addition, those who were treated by high-intensity prescribers were more likely to have a serious fall.

In designing the study, the authors assumed that patients visiting an emergency department had their doctor assigned randomly. They controlled for many patient variables that might have confounded the results, such as age, sex, race, depression, medical comorbidities, and geographic region. Were the higher rates of ongoing opioid use in the high-intensity-prescriber group due to the higher prescribing rates of their emergency providers, or did the providers counsel patients differently? This is not known.

Bottom line. Different doctors manage similar patients differently when it comes to pain, and those who prescribe more opioids for acute pain put their patients at risk of chronic opioid use and falls. I don’t want to be a high-intensity opioid prescriber.

SURGERY AND CHRONIC OPIOID USE

[Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg 2017; 152(6):e170504.]

Brummett et al⁶ examined ongoing opioid use after surgery in 36,177 opioid-naive patients and in a nonsurgical control group. After 3 months, 6% of the patients who underwent surgery remained on opioids, compared with only 0.4% of the nonsurgical controls. Whether the surgery was major or minor did not affect the rate of postoperative opioid use.

Risk factors for ongoing opioid use were preexisting addiction to anything (including tobacco), mood disorders, and preoperative pain disorders. These risk factors have previously been reported in nonsurgical patients.⁷

Brummett et al speculated that patients are counseled about postoperative opioids in a way that leads them to overestimate the safety and efficacy of these drugs for treating other common pain conditions.⁶ 

Bottom line. Patients with mental health comorbidities have a hard time stopping opioids. The remarkable finding in this study was the similarity between major and minor surgery in terms of chronic opioid use. If postoperative opioids treat only the pain caused by the surgery, major surgery should be associated with greater opioid use. The similarity suggests that a mechanism other than postoperative pain confers risk of chronic opioid use.

THINKING ABOUT OPIOIDS

Collectively, these articles describe elements of acute pain treatment that correlate with chronic ongoing opioid use: a higher cumulative dose,³ being seen by a physician who prescribes a lot of opioids,⁵ undergoing surgery,⁶ and psychiatric comorbidity.⁶ They made me wonder if opioid use for acute pain acts as an inoculation, analogous to inoculating a Petri dish with bacteria.  The likelihood of chronic opioid use arises from the inoculum dose, the host response, and the context of inoculation. 

These articles do not show how patients taking opioids chronically for pain become addicted. Stumbo et al⁸ interviewed 283 opioid-dependent patients and identified 5 pathways to opioid use disorder, 3 of which were related to pain control: inadequately controlled chronic pain, exposure to opioids during acute pain episodes, and chronic pain in patients who already had substance use disorders. Brat et al⁹ recently estimated the risk of opioid use disorder after receiving opioids postoperatively to be less than 1%, but it increased dramatically with duration of opioid treatment.

A patient who fills an opioid prescription does not necessarily have chronic pain. Nor do all patients with chronic pain require an opioid prescription. These studies did not establish whether the patients had a pain syndrome. In practice, we call our patients who chronically take opioids our “chronic pain patients.” But 40% of Americans have chronic pain, while only 5% take opioids daily for pain.^11,12

We assume that those taking opioids have the most severe pain. But Brummett et al suggested that continued opioid use is predicted less by pain and more by psychiatric comorbidity.⁶ More than half of the opioid prescriptions in the United States are written for patients with serious mental illness, who represent one-sixth of that population.¹¹ Maybe chronic opioid use for pain has more to do with vulnerability to opioids and less to do with a pain syndrome.

I now think about daily opioid use in much the same way as I think about daily prednisone use. Patients on daily prednisone have a characteristic set of medical risks from the prednisone itself, regardless of its indication. Yet we do not consider these patients addicted to prednisone. Opioid use may be similar.

Like most doctors, I am troubled by the continued rise in the opioid overdose rate.¹³ Yet addiction and death from overdose are not the only risks that patients on chronic opioids face; they also have higher rates of falls, cardiovascular death, pneumonia, death from chronic obstructive pulmonary disease, and motor vehicle crashes.^14–17 Patients on chronic opioids for pain have greater mental health comorbidity and worse function.¹⁸

Most concerning, chronic opioid treatment for pain lacks proof of benefit. In fact, a recent study disproved the benefit of opioids for chronic pain compared with nonopioid options.¹⁹ When I meet with patients who are taking chronic opioids for pain, I often can’t identify why the drugs were started or ought to be continued, and I anticipate a bad outcome. Yet the patient is afraid to stop the drug. For these reasons, chronic opioid use for pain strikes me as worth considering separately from opioid use disorder.

 

 

HOW THIS CHANGED MY PRACTICE

The studies described above have had a powerful effect on my clinical care as a hospitalist.

I now talk to all patients starting opioids about how hard it can be to stop. Some patients are defensive at first, believing this does not apply to them. But I politely continue.

People with depression and anxiety can have a harder time stopping opioids. Addiction is both a risk with ongoing opioid use and a possible outcome of acute opioid use.⁸ But one can struggle to stop opioids without being addicted or depressed. Even the healthiest person may wish to continue opioids past the point of benefit.

I am careful not to invalidate the patient’s experience of pain. It is challenging for patients to find the balance between current discomfort and a possible future adverse effect. In these conversations, I imagine how I would want a loved one counseled on their pain control. This centers me as I choose my words and my tone.

I now monitor the total amount of opioid I prescribe for acute pain in addition to the daily dose. I give my patients as few opioids as reasonable, and advise them to take the minimum dose required for tolerable comfort. I offer nonopioid options as the preferred choice, presenting them as effective and safe. I do this irrespective of the indication for opioids.

I limit opioids in all patients, not just those with comorbidities. I include in my shared decision-making process the risk of chronic opioid use when I prescribe opioids for acute pain, carefully distinguishing it from opioid use disorder. Instead of excess opioids, I give patients my office phone number to call in case they struggle. I rarely get calls. But I find patients would rather have access to a doctor than extra pills. And offering them my contact information lets me limit opioids while letting them know that I am committed to their comfort and health.

As an addiction medicine doctor, I consult on patients not taking their opioids as prescribed. Caring for these patients is intellectually and emotionally draining; they suffer daily, and the opioids they take provide a modicum of relief at a high cost. The publications I have discussed here provide insight into how a troubled relationship with opioids begins. I remind myself that these patients have an iatrogenic condition. Their behaviors that we label “aberrant” may reflect an adverse reaction to medications prescribed to them for acute pain.

Mary, my patient with postoperative pain after cholecystectomy, may over time develop opioid use disorder as Heather did. That progression may have begun with the hydrocodone I prescribed and the counseling I gave her, and it may proceed to chronic opioid use and then opioid use disorder.

I am looking closely at the care I give for acute pain in light of these innovative studies. But even more so, they have increased the compassion with which I care for patients like Heather, those harmed by prescribed opioids.

Mary, age 38, was hospitalized for acute cholecystitis requiring laparoscopic surgery. Her hospital course was uneventful. At the time of discharge, I, her inpatient doctor, prescribed 15 hydrocodone tablets for postoperative pain. I never saw her again. Did she struggle to stop taking the hydrocodone I prescribed?

Heather is a 50-year-old patient in my addiction medicine clinic who developed opioid use disorder while being treated for chronic pain. After much hardship and to her credit, she is now in long-term remission. Did her opioid use disorder start with an opioid prescription for an accepted indication?

The issues Mary and Heather face seem unrelated, but these 2 patients may be at different time points in the progression of the same disease. As a hospitalist, I want to optimize the chances that patients taking opioids for acute pain will be able to stop taking them.

CHRONIC USE VS OPIOID USE DISORDER

There is a distinction between chronic use of opioids and opioid use disorder. The latter is also known as addiction.

Patients who take opioids daily do not necessarily have opioid use disorder, even if they have physiologic dependence on them. Physiologic opioid dependence is commonly confused with opioid use disorder, but it is the expected result of regularly taking these drugs.

Opioid use disorder is a chronic disease of the brain characterized by loss of control over opioid use, resulting in harm. The Diagnostic and Statistical Manual, fifth edition, excludes physiologic dependence on opioids (tolerance and withdrawal) from its criteria for opioid use disorder if the patient is taking opioids solely under medical supervision.¹ To be diagnosed with opioid use disorder, patients need to do only 2 of the following within 12 months:

• Take more of the drug than intended
• Want or try to cut down without success
• Spend a lot of time in getting, using, or recovering from the drug
• Crave the drug
• Fail to meet commitments due to the drug
• Continue to use the drug, even though it causes social or relationship problems
• Give up or reduce other activities because of the drug
• Use the drug even when it isn’t safe
• Continue to use even when it causes physical or psychological problems
• Develop tolerance (but, as noted, not if taking the drug as directed under a doctor’s supervision)
• Experience withdrawal (again, but not if taking the drug under medical supervision).

WHY DO SOME PATIENTS STRUGGLE TO STOP TAKING OPIOIDS?

Studying opioid use disorder as an outcome in large groups of patients is complicated by imperfect medical documentation. However, using pharmacy claims data, researchers can accurately describe opioid prescription patterns in large groups of patients over time. This means we can count how many patients keep taking prescribed opioids but not how many become addicted.

In a country where nearly 40% of adults are prescribed an opioid annually, the question is not why people start taking opioids, but why some have to struggle to stop.² Several recent studies used pharmacy claims data to identify factors that may predict chronic opioid use in patients prescribed opioids for acute pain. The findings suggest that we can better treat acute pain to prevent chronic opioid use.

We don’t yet know how to protect patients like Mary from opioid use disorder, but the following 3 studies have already changed my practice.

HIGHER TOTAL DOSE MEANS HIGHER RISK

[Shah A, Hayes CJ, Martin BC. Characteristics of initial prescription episodes and likelihood of long-term opioid use—United States, 2006–2015. MMWR Morb Mortal Wkly Rep 2017; 66(10):265–269.]

Shah et al³ reported a study of nearly 1.3 million opioid-naive patients who received opioid prescriptions. Of those prescribed at least 1 day of opioids, 6% were still taking them 1 year later, and 2.9% were still taking them 3 years later.

Opioid exposure in acute pain was measured in total “morphine milligram equivalents” (MME), ie, the cumulative amount of opioids prescribed in the treatment episode, standardized across different types of opioids. We usually think of exposure in terms of how many milligrams a patient takes per day, which correlates with mortality in chronic opioid use.⁴ But this study showed a linear relationship between total MME prescribed for acute pain and ongoing opioid use in opioid-naive patients. By itself, the difference between daily and total MME made the article revelatory.

But the study went further, asking how much is too much: ie, What is the cutoff MME above which the patient is at risk of chronic opioid use? The relationship between acute opioid dose and chronic use is linear and starts early. Shah et al suggested that a total threshold of 700 MME predicts chronic opioid use—140 hydrocodone tablets, or 1 month of regular use.³

Many doctors worry that specific opioids such as oxycodone, hydromorphone, and fentanyl may be more habit-forming. Surprisingly, this study showed that these drugs were associated with rates of chronic use similar to those of other opioids when they controlled for potency.

Bottom line. Total opioid use in acute pain was the best predictor of chronic opioid use, and it showed that chronicity begins earlier than thought.

 

 

DON’T BE A ‘HIGH-INTENSITY’ PRESCRIBER

[Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017; 376(7):663–673.]

Barnett et al⁵ analyzed opioid prescribing for acute pain in the emergency department, using Medicare pharmacy data from 377,629 previously opioid-naive patients. They categorized the emergency providers into quartiles based on the frequency of opioid prescribing.

The relative risk of ongoing opioid use 1 year after being treated by a “high-intensity” prescriber (ie, one in the top quartile) was 30% greater than in similar patients seen by a low-intensity prescriber (ie, one in the bottom quartile). In addition, those who were treated by high-intensity prescribers were more likely to have a serious fall.

In designing the study, the authors assumed that patients visiting an emergency department had their doctor assigned randomly. They controlled for many patient variables that might have confounded the results, such as age, sex, race, depression, medical comorbidities, and geographic region. Were the higher rates of ongoing opioid use in the high-intensity-prescriber group due to the higher prescribing rates of their emergency providers, or did the providers counsel patients differently? This is not known.

Bottom line. Different doctors manage similar patients differently when it comes to pain, and those who prescribe more opioids for acute pain put their patients at risk of chronic opioid use and falls. I don’t want to be a high-intensity opioid prescriber.

SURGERY AND CHRONIC OPIOID USE

[Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg 2017; 152(6):e170504.]

Brummett et al⁶ examined ongoing opioid use after surgery in 36,177 opioid-naive patients and in a nonsurgical control group. After 3 months, 6% of the patients who underwent surgery remained on opioids, compared with only 0.4% of the nonsurgical controls. Whether the surgery was major or minor did not affect the rate of postoperative opioid use.

Risk factors for ongoing opioid use were preexisting addiction to anything (including tobacco), mood disorders, and preoperative pain disorders. These risk factors have previously been reported in nonsurgical patients.⁷

Brummett et al speculated that patients are counseled about postoperative opioids in a way that leads them to overestimate the safety and efficacy of these drugs for treating other common pain conditions.⁶ 

Bottom line. Patients with mental health comorbidities have a hard time stopping opioids. The remarkable finding in this study was the similarity between major and minor surgery in terms of chronic opioid use. If postoperative opioids treat only the pain caused by the surgery, major surgery should be associated with greater opioid use. The similarity suggests that a mechanism other than postoperative pain confers risk of chronic opioid use.

THINKING ABOUT OPIOIDS

Collectively, these articles describe elements of acute pain treatment that correlate with chronic ongoing opioid use: a higher cumulative dose,³ being seen by a physician who prescribes a lot of opioids,⁵ undergoing surgery,⁶ and psychiatric comorbidity.⁶ They made me wonder if opioid use for acute pain acts as an inoculation, analogous to inoculating a Petri dish with bacteria.  The likelihood of chronic opioid use arises from the inoculum dose, the host response, and the context of inoculation. 

These articles do not show how patients taking opioids chronically for pain become addicted. Stumbo et al⁸ interviewed 283 opioid-dependent patients and identified 5 pathways to opioid use disorder, 3 of which were related to pain control: inadequately controlled chronic pain, exposure to opioids during acute pain episodes, and chronic pain in patients who already had substance use disorders. Brat et al⁹ recently estimated the risk of opioid use disorder after receiving opioids postoperatively to be less than 1%, but it increased dramatically with duration of opioid treatment.

A patient who fills an opioid prescription does not necessarily have chronic pain. Nor do all patients with chronic pain require an opioid prescription. These studies did not establish whether the patients had a pain syndrome. In practice, we call our patients who chronically take opioids our “chronic pain patients.” But 40% of Americans have chronic pain, while only 5% take opioids daily for pain.^11,12

We assume that those taking opioids have the most severe pain. But Brummett et al suggested that continued opioid use is predicted less by pain and more by psychiatric comorbidity.⁶ More than half of the opioid prescriptions in the United States are written for patients with serious mental illness, who represent one-sixth of that population.¹¹ Maybe chronic opioid use for pain has more to do with vulnerability to opioids and less to do with a pain syndrome.

I now think about daily opioid use in much the same way as I think about daily prednisone use. Patients on daily prednisone have a characteristic set of medical risks from the prednisone itself, regardless of its indication. Yet we do not consider these patients addicted to prednisone. Opioid use may be similar.

Like most doctors, I am troubled by the continued rise in the opioid overdose rate.¹³ Yet addiction and death from overdose are not the only risks that patients on chronic opioids face; they also have higher rates of falls, cardiovascular death, pneumonia, death from chronic obstructive pulmonary disease, and motor vehicle crashes.^14–17 Patients on chronic opioids for pain have greater mental health comorbidity and worse function.¹⁸

Most concerning, chronic opioid treatment for pain lacks proof of benefit. In fact, a recent study disproved the benefit of opioids for chronic pain compared with nonopioid options.¹⁹ When I meet with patients who are taking chronic opioids for pain, I often can’t identify why the drugs were started or ought to be continued, and I anticipate a bad outcome. Yet the patient is afraid to stop the drug. For these reasons, chronic opioid use for pain strikes me as worth considering separately from opioid use disorder.

 

 

HOW THIS CHANGED MY PRACTICE

The studies described above have had a powerful effect on my clinical care as a hospitalist.

I now talk to all patients starting opioids about how hard it can be to stop. Some patients are defensive at first, believing this does not apply to them. But I politely continue.

People with depression and anxiety can have a harder time stopping opioids. Addiction is both a risk with ongoing opioid use and a possible outcome of acute opioid use.⁸ But one can struggle to stop opioids without being addicted or depressed. Even the healthiest person may wish to continue opioids past the point of benefit.

I am careful not to invalidate the patient’s experience of pain. It is challenging for patients to find the balance between current discomfort and a possible future adverse effect. In these conversations, I imagine how I would want a loved one counseled on their pain control. This centers me as I choose my words and my tone.

I now monitor the total amount of opioid I prescribe for acute pain in addition to the daily dose. I give my patients as few opioids as reasonable, and advise them to take the minimum dose required for tolerable comfort. I offer nonopioid options as the preferred choice, presenting them as effective and safe. I do this irrespective of the indication for opioids.

I limit opioids in all patients, not just those with comorbidities. I include in my shared decision-making process the risk of chronic opioid use when I prescribe opioids for acute pain, carefully distinguishing it from opioid use disorder. Instead of excess opioids, I give patients my office phone number to call in case they struggle. I rarely get calls. But I find patients would rather have access to a doctor than extra pills. And offering them my contact information lets me limit opioids while letting them know that I am committed to their comfort and health.

As an addiction medicine doctor, I consult on patients not taking their opioids as prescribed. Caring for these patients is intellectually and emotionally draining; they suffer daily, and the opioids they take provide a modicum of relief at a high cost. The publications I have discussed here provide insight into how a troubled relationship with opioids begins. I remind myself that these patients have an iatrogenic condition. Their behaviors that we label “aberrant” may reflect an adverse reaction to medications prescribed to them for acute pain.

Mary, my patient with postoperative pain after cholecystectomy, may over time develop opioid use disorder as Heather did. That progression may have begun with the hydrocodone I prescribed and the counseling I gave her, and it may proceed to chronic opioid use and then opioid use disorder.

I am looking closely at the care I give for acute pain in light of these innovative studies. But even more so, they have increased the compassion with which I care for patients like Heather, those harmed by prescribed opioids.

Mary, age 38, was hospitalized for acute cholecystitis requiring laparoscopic surgery. Her hospital course was uneventful. At the time of discharge, I, her inpatient doctor, prescribed 15 hydrocodone tablets for postoperative pain. I never saw her again. Did she struggle to stop taking the hydrocodone I prescribed?

Heather is a 50-year-old patient in my addiction medicine clinic who developed opioid use disorder while being treated for chronic pain. After much hardship and to her credit, she is now in long-term remission. Did her opioid use disorder start with an opioid prescription for an accepted indication?

The issues Mary and Heather face seem unrelated, but these 2 patients may be at different time points in the progression of the same disease. As a hospitalist, I want to optimize the chances that patients taking opioids for acute pain will be able to stop taking them.

CHRONIC USE VS OPIOID USE DISORDER

There is a distinction between chronic use of opioids and opioid use disorder. The latter is also known as addiction.

Patients who take opioids daily do not necessarily have opioid use disorder, even if they have physiologic dependence on them. Physiologic opioid dependence is commonly confused with opioid use disorder, but it is the expected result of regularly taking these drugs.

Opioid use disorder is a chronic disease of the brain characterized by loss of control over opioid use, resulting in harm. The Diagnostic and Statistical Manual, fifth edition, excludes physiologic dependence on opioids (tolerance and withdrawal) from its criteria for opioid use disorder if the patient is taking opioids solely under medical supervision.¹ To be diagnosed with opioid use disorder, patients need to do only 2 of the following within 12 months:

• Take more of the drug than intended
• Want or try to cut down without success
• Spend a lot of time in getting, using, or recovering from the drug
• Crave the drug
• Fail to meet commitments due to the drug
• Continue to use the drug, even though it causes social or relationship problems
• Give up or reduce other activities because of the drug
• Use the drug even when it isn’t safe
• Continue to use even when it causes physical or psychological problems
• Develop tolerance (but, as noted, not if taking the drug as directed under a doctor’s supervision)
• Experience withdrawal (again, but not if taking the drug under medical supervision).

WHY DO SOME PATIENTS STRUGGLE TO STOP TAKING OPIOIDS?

Studying opioid use disorder as an outcome in large groups of patients is complicated by imperfect medical documentation. However, using pharmacy claims data, researchers can accurately describe opioid prescription patterns in large groups of patients over time. This means we can count how many patients keep taking prescribed opioids but not how many become addicted.

In a country where nearly 40% of adults are prescribed an opioid annually, the question is not why people start taking opioids, but why some have to struggle to stop.² Several recent studies used pharmacy claims data to identify factors that may predict chronic opioid use in patients prescribed opioids for acute pain. The findings suggest that we can better treat acute pain to prevent chronic opioid use.

We don’t yet know how to protect patients like Mary from opioid use disorder, but the following 3 studies have already changed my practice.

HIGHER TOTAL DOSE MEANS HIGHER RISK

[Shah A, Hayes CJ, Martin BC. Characteristics of initial prescription episodes and likelihood of long-term opioid use—United States, 2006–2015. MMWR Morb Mortal Wkly Rep 2017; 66(10):265–269.]

Shah et al³ reported a study of nearly 1.3 million opioid-naive patients who received opioid prescriptions. Of those prescribed at least 1 day of opioids, 6% were still taking them 1 year later, and 2.9% were still taking them 3 years later.

Opioid exposure in acute pain was measured in total “morphine milligram equivalents” (MME), ie, the cumulative amount of opioids prescribed in the treatment episode, standardized across different types of opioids. We usually think of exposure in terms of how many milligrams a patient takes per day, which correlates with mortality in chronic opioid use.⁴ But this study showed a linear relationship between total MME prescribed for acute pain and ongoing opioid use in opioid-naive patients. By itself, the difference between daily and total MME made the article revelatory.

But the study went further, asking how much is too much: ie, What is the cutoff MME above which the patient is at risk of chronic opioid use? The relationship between acute opioid dose and chronic use is linear and starts early. Shah et al suggested that a total threshold of 700 MME predicts chronic opioid use—140 hydrocodone tablets, or 1 month of regular use.³

Many doctors worry that specific opioids such as oxycodone, hydromorphone, and fentanyl may be more habit-forming. Surprisingly, this study showed that these drugs were associated with rates of chronic use similar to those of other opioids when they controlled for potency.

Bottom line. Total opioid use in acute pain was the best predictor of chronic opioid use, and it showed that chronicity begins earlier than thought.

 

 

DON’T BE A ‘HIGH-INTENSITY’ PRESCRIBER

[Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017; 376(7):663–673.]

Barnett et al⁵ analyzed opioid prescribing for acute pain in the emergency department, using Medicare pharmacy data from 377,629 previously opioid-naive patients. They categorized the emergency providers into quartiles based on the frequency of opioid prescribing.

The relative risk of ongoing opioid use 1 year after being treated by a “high-intensity” prescriber (ie, one in the top quartile) was 30% greater than in similar patients seen by a low-intensity prescriber (ie, one in the bottom quartile). In addition, those who were treated by high-intensity prescribers were more likely to have a serious fall.

In designing the study, the authors assumed that patients visiting an emergency department had their doctor assigned randomly. They controlled for many patient variables that might have confounded the results, such as age, sex, race, depression, medical comorbidities, and geographic region. Were the higher rates of ongoing opioid use in the high-intensity-prescriber group due to the higher prescribing rates of their emergency providers, or did the providers counsel patients differently? This is not known.

Bottom line. Different doctors manage similar patients differently when it comes to pain, and those who prescribe more opioids for acute pain put their patients at risk of chronic opioid use and falls. I don’t want to be a high-intensity opioid prescriber.

SURGERY AND CHRONIC OPIOID USE

[Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg 2017; 152(6):e170504.]

Brummett et al⁶ examined ongoing opioid use after surgery in 36,177 opioid-naive patients and in a nonsurgical control group. After 3 months, 6% of the patients who underwent surgery remained on opioids, compared with only 0.4% of the nonsurgical controls. Whether the surgery was major or minor did not affect the rate of postoperative opioid use.

Risk factors for ongoing opioid use were preexisting addiction to anything (including tobacco), mood disorders, and preoperative pain disorders. These risk factors have previously been reported in nonsurgical patients.⁷

Brummett et al speculated that patients are counseled about postoperative opioids in a way that leads them to overestimate the safety and efficacy of these drugs for treating other common pain conditions.⁶ 

Bottom line. Patients with mental health comorbidities have a hard time stopping opioids. The remarkable finding in this study was the similarity between major and minor surgery in terms of chronic opioid use. If postoperative opioids treat only the pain caused by the surgery, major surgery should be associated with greater opioid use. The similarity suggests that a mechanism other than postoperative pain confers risk of chronic opioid use.

THINKING ABOUT OPIOIDS

Collectively, these articles describe elements of acute pain treatment that correlate with chronic ongoing opioid use: a higher cumulative dose,³ being seen by a physician who prescribes a lot of opioids,⁵ undergoing surgery,⁶ and psychiatric comorbidity.⁶ They made me wonder if opioid use for acute pain acts as an inoculation, analogous to inoculating a Petri dish with bacteria.  The likelihood of chronic opioid use arises from the inoculum dose, the host response, and the context of inoculation. 

These articles do not show how patients taking opioids chronically for pain become addicted. Stumbo et al⁸ interviewed 283 opioid-dependent patients and identified 5 pathways to opioid use disorder, 3 of which were related to pain control: inadequately controlled chronic pain, exposure to opioids during acute pain episodes, and chronic pain in patients who already had substance use disorders. Brat et al⁹ recently estimated the risk of opioid use disorder after receiving opioids postoperatively to be less than 1%, but it increased dramatically with duration of opioid treatment.

A patient who fills an opioid prescription does not necessarily have chronic pain. Nor do all patients with chronic pain require an opioid prescription. These studies did not establish whether the patients had a pain syndrome. In practice, we call our patients who chronically take opioids our “chronic pain patients.” But 40% of Americans have chronic pain, while only 5% take opioids daily for pain.^11,12

We assume that those taking opioids have the most severe pain. But Brummett et al suggested that continued opioid use is predicted less by pain and more by psychiatric comorbidity.⁶ More than half of the opioid prescriptions in the United States are written for patients with serious mental illness, who represent one-sixth of that population.¹¹ Maybe chronic opioid use for pain has more to do with vulnerability to opioids and less to do with a pain syndrome.

I now think about daily opioid use in much the same way as I think about daily prednisone use. Patients on daily prednisone have a characteristic set of medical risks from the prednisone itself, regardless of its indication. Yet we do not consider these patients addicted to prednisone. Opioid use may be similar.

Like most doctors, I am troubled by the continued rise in the opioid overdose rate.¹³ Yet addiction and death from overdose are not the only risks that patients on chronic opioids face; they also have higher rates of falls, cardiovascular death, pneumonia, death from chronic obstructive pulmonary disease, and motor vehicle crashes.^14–17 Patients on chronic opioids for pain have greater mental health comorbidity and worse function.¹⁸

Most concerning, chronic opioid treatment for pain lacks proof of benefit. In fact, a recent study disproved the benefit of opioids for chronic pain compared with nonopioid options.¹⁹ When I meet with patients who are taking chronic opioids for pain, I often can’t identify why the drugs were started or ought to be continued, and I anticipate a bad outcome. Yet the patient is afraid to stop the drug. For these reasons, chronic opioid use for pain strikes me as worth considering separately from opioid use disorder.

 

 

HOW THIS CHANGED MY PRACTICE

The studies described above have had a powerful effect on my clinical care as a hospitalist.

I now talk to all patients starting opioids about how hard it can be to stop. Some patients are defensive at first, believing this does not apply to them. But I politely continue.

People with depression and anxiety can have a harder time stopping opioids. Addiction is both a risk with ongoing opioid use and a possible outcome of acute opioid use.⁸ But one can struggle to stop opioids without being addicted or depressed. Even the healthiest person may wish to continue opioids past the point of benefit.

I am careful not to invalidate the patient’s experience of pain. It is challenging for patients to find the balance between current discomfort and a possible future adverse effect. In these conversations, I imagine how I would want a loved one counseled on their pain control. This centers me as I choose my words and my tone.

I now monitor the total amount of opioid I prescribe for acute pain in addition to the daily dose. I give my patients as few opioids as reasonable, and advise them to take the minimum dose required for tolerable comfort. I offer nonopioid options as the preferred choice, presenting them as effective and safe. I do this irrespective of the indication for opioids.

I limit opioids in all patients, not just those with comorbidities. I include in my shared decision-making process the risk of chronic opioid use when I prescribe opioids for acute pain, carefully distinguishing it from opioid use disorder. Instead of excess opioids, I give patients my office phone number to call in case they struggle. I rarely get calls. But I find patients would rather have access to a doctor than extra pills. And offering them my contact information lets me limit opioids while letting them know that I am committed to their comfort and health.

As an addiction medicine doctor, I consult on patients not taking their opioids as prescribed. Caring for these patients is intellectually and emotionally draining; they suffer daily, and the opioids they take provide a modicum of relief at a high cost. The publications I have discussed here provide insight into how a troubled relationship with opioids begins. I remind myself that these patients have an iatrogenic condition. Their behaviors that we label “aberrant” may reflect an adverse reaction to medications prescribed to them for acute pain.

Mary, my patient with postoperative pain after cholecystectomy, may over time develop opioid use disorder as Heather did. That progression may have begun with the hydrocodone I prescribed and the counseling I gave her, and it may proceed to chronic opioid use and then opioid use disorder.

I am looking closely at the care I give for acute pain in light of these innovative studies. But even more so, they have increased the compassion with which I care for patients like Heather, those harmed by prescribed opioids.

My urologic career began in the late 1980s, just before prostate-specific antigen (PSA) testing was introduced. Ever since, a busy prostate cancer practice has given me a frontline view of the benefits and possible harms of PSA screening.

See related article

In the pre-PSA era, about half of men with newly diagnosed prostate cancer presented with incurable disease, either locally advanced or metastatic. The most common treatment was bilateral orchiectomy, which was the only safe form of androgen deprivation available.

Fast-forward a few years to the mid-1990s. Within 5 years after the introduction of PSA testing, the rate of incurable disease at diagnosis fell to just 5%, and treatment for localized disease skyrocketed, including radical prostatectomy, external beam radiation, and brachytherapy. As a result of earlier diagnosis and improved treatments, the death rate from prostate cancer in US men has fallen more than 30% since 1990.

The first-hand experience of seeing this massive stage migration to curable disease has forever convinced me that PSA screening is beneficial. Robust statistical models lend credence to this belief, with estimates that screening is responsible for 45% to 70% of this decline in mortality.¹

Fast-forward again to 2012, when the US Preventive Services Task Force (USPSTF) published a strong recommendation against screening. The recommendation had so much force that as recently as 2014, only 11% of men at highest risk of prostate cancer in the Cleveland Clinic system were screened for it,² mirroring national trends.

What happened? Colored by the experience in the era before PSA, when men presented frequently with painful metastatic disease and had an average life expectancy of 18 to 24 months, it was widely believed that all detected prostate cancer required treatment. What was not appreciated was that while PSA detects lots of prostate cancer, the most common reason for PSA levels to reach a range worrisome enough to trigger biopsy was actually benign prostatic hypertrophy.

The resulting increase in the number of biopsies resulted in the detection of a substantial number of low-grade cancers that were never destined to cause clinical harm but that got treated anyway, based on the fear that all cancers had metastatic potential. The USPSTF based its recommendation against screening on the harms caused by this overdetection and overtreatment of nonlethal disease, focusing on risks of biopsy such as sepsis, and on treatment-related adverse effects such as changes in urinary, bowel, and sexual function.

RANDOMIZED TRIALS SHOW A BENEFIT FROM SCREENING

As a result of this controversy, several large randomized trials designed to test whether PSA screening was beneficial were organized and begun in the 1990s, with one in the United States and another in Europe.^3,4 Mature data from both trials have now established that there is indeed benefit to population-level screening.

The US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), was initially reported to show no difference in prostate cancer-specific mortality rates in those screened vs not screened, but because more than 90% of the men in the no-screening arm were screened anyway, that conclusion is erroneous.³

With 13-year follow-up and far less PSA contamination in the unscreened arm, the European Randomized Study of Screening for Prostate Cancer (ERSPC) in men ages 55 to 69 demonstrated a 27% reduction in the rate of death and a 35% reduction in the need for palliative treatments (androgen deprivation or radiation, or both) for metastatic disease in those screened vs not screened, clearly establishing substantial clinical benefit to PSA screening.⁴

A recent analysis of both trials that controlled for PSA drop-ins (comparing those actually screened with those actually not screened) concluded that the benefit of screening in terms of mortality reduction (estimated at about 30%) are equal in both trials.⁵ A large cohort study from Kaiser Permanente with 16-year follow-up has suggested that PSA screening has both a prostate cancer-specific benefit and an overall mortality benefit.⁶

 

 

ACTIVE SURVEILLANCE CAN REDUCE OVERTREATMENT

In parallel with the design and completion of these trials, there was a significant effort to better identify and manage patients initially overdiagnosed with nonlethal cancers by developing active surveillance regimens.

This management strategy recognizes that most low-grade cancers pose no short-term risk to the patient’s health or longevity, that definitive therapy can be deferred, and that with regular monitoring by digital rectal examination, PSA measurement, and repeat biopsy, cancers that progress can still be cured. The result of this strategy is a marked reduction in the harms caused by overtreatment (ie, the aforementioned adverse effects), as well as the avoidance of unnecessary treatment in many patients.

A randomized trial and 2 large prospective cohort studies have confirmed the long-term safety of this approach,^7–9 and the development of commercially available, biopsy-based gene expression profiling tools promises to further improve risk stratification at diagnosis and during follow-up for individual patients.¹⁰

NEW USPSTF RECOMMENDATIONS: AN INDIVIDUAL, INFORMED DECISION

Based on the results of the ERSPC and the widespread adoption and safety of active surveillance, which together show benefit to screening and fewer harms in overdetection and overtreatment, in 2018 the USPSTF recast its recommendations. In upgrading the recommendation from “D” to “C,” the recommendation now states that for men ages 55 to 69, PSA screening should be an individual decision after a discussion with an informed provider, although men over 70 are still advised not to undergo screening at all.¹¹

Some may think that this recommendation has arrived just in time, or that it should be  made even stronger to actually recommend screening, as recent data from 2 national registries—the Surveillance, Epidemiology, and End Results program and the National Cancer Database—show that the fall in screening after the 2012 USPSTF guidelines has resulted in an increase in men presenting with advanced stage disease.^12,13 (All of you Back to the Future fans, please return to the mid to late 1980s to see how that plays out.)

So the pendulum has now swung back in favor of screening, largely supported by solid data showing meaningful clinical benefit, better understanding of PSA and prostate cancer biology, and adoption of active surveillance.

AN IDEAL SCREENING PROGRAM

An ideal screening program would detect only biologically significant cancers, thus eliminating overdetection and overtreatment. There is reason for optimism on this front.

Second-generation PSA tests have better diagnostic accuracy for high-grade disease than earlier tests. Two such tests, the Prostate Health Index (Beckman Coulter) and the 4K-score (Opko Health), are commercially available though not usually covered by commercial insurers.¹⁴ A third test, IsoPSA (Cleveland Diagnostics), is under development. Most hospital laboratories will be able to be run this test with no need for a central laboratory.¹⁵ All 3 tests have been shown to reduce unnecessary biopsies (because of a low probability of finding a biologically significant cancer) by 30% to 45% and will help reduce overdetection.

Moreover, multiparametric magnetic resonance imaging of the prostate has been shown to improve detection of high-grade cancers,¹⁶ and a randomized trial has suggested that its incorporation into a screening strategy is cost-effective and could be better than PSA testing plus transrectal ultrasonography alone (the current standard of care).¹⁷

Several risk scores based on germline genomics also hold promise for better identifying those at risk and for helping to de-intensify screening for those unlikely to have high-grade cancer.¹⁸

Screening for prostate cancer reduces mortality rates and the burden of metastatic disease, and the paradigm continues to evolve. Men at risk by virtue of age (55 to 69, and healthy men > 70), family history, race, and newly identified factors (germline genetics) all deserve an informed discussion on the benefits and risks of screening

My urologic career began in the late 1980s, just before prostate-specific antigen (PSA) testing was introduced. Ever since, a busy prostate cancer practice has given me a frontline view of the benefits and possible harms of PSA screening.

See related article

In the pre-PSA era, about half of men with newly diagnosed prostate cancer presented with incurable disease, either locally advanced or metastatic. The most common treatment was bilateral orchiectomy, which was the only safe form of androgen deprivation available.

Fast-forward a few years to the mid-1990s. Within 5 years after the introduction of PSA testing, the rate of incurable disease at diagnosis fell to just 5%, and treatment for localized disease skyrocketed, including radical prostatectomy, external beam radiation, and brachytherapy. As a result of earlier diagnosis and improved treatments, the death rate from prostate cancer in US men has fallen more than 30% since 1990.

The first-hand experience of seeing this massive stage migration to curable disease has forever convinced me that PSA screening is beneficial. Robust statistical models lend credence to this belief, with estimates that screening is responsible for 45% to 70% of this decline in mortality.¹

Fast-forward again to 2012, when the US Preventive Services Task Force (USPSTF) published a strong recommendation against screening. The recommendation had so much force that as recently as 2014, only 11% of men at highest risk of prostate cancer in the Cleveland Clinic system were screened for it,² mirroring national trends.

What happened? Colored by the experience in the era before PSA, when men presented frequently with painful metastatic disease and had an average life expectancy of 18 to 24 months, it was widely believed that all detected prostate cancer required treatment. What was not appreciated was that while PSA detects lots of prostate cancer, the most common reason for PSA levels to reach a range worrisome enough to trigger biopsy was actually benign prostatic hypertrophy.

The resulting increase in the number of biopsies resulted in the detection of a substantial number of low-grade cancers that were never destined to cause clinical harm but that got treated anyway, based on the fear that all cancers had metastatic potential. The USPSTF based its recommendation against screening on the harms caused by this overdetection and overtreatment of nonlethal disease, focusing on risks of biopsy such as sepsis, and on treatment-related adverse effects such as changes in urinary, bowel, and sexual function.

RANDOMIZED TRIALS SHOW A BENEFIT FROM SCREENING

As a result of this controversy, several large randomized trials designed to test whether PSA screening was beneficial were organized and begun in the 1990s, with one in the United States and another in Europe.^3,4 Mature data from both trials have now established that there is indeed benefit to population-level screening.

The US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), was initially reported to show no difference in prostate cancer-specific mortality rates in those screened vs not screened, but because more than 90% of the men in the no-screening arm were screened anyway, that conclusion is erroneous.³

With 13-year follow-up and far less PSA contamination in the unscreened arm, the European Randomized Study of Screening for Prostate Cancer (ERSPC) in men ages 55 to 69 demonstrated a 27% reduction in the rate of death and a 35% reduction in the need for palliative treatments (androgen deprivation or radiation, or both) for metastatic disease in those screened vs not screened, clearly establishing substantial clinical benefit to PSA screening.⁴

A recent analysis of both trials that controlled for PSA drop-ins (comparing those actually screened with those actually not screened) concluded that the benefit of screening in terms of mortality reduction (estimated at about 30%) are equal in both trials.⁵ A large cohort study from Kaiser Permanente with 16-year follow-up has suggested that PSA screening has both a prostate cancer-specific benefit and an overall mortality benefit.⁶

 

 

ACTIVE SURVEILLANCE CAN REDUCE OVERTREATMENT

In parallel with the design and completion of these trials, there was a significant effort to better identify and manage patients initially overdiagnosed with nonlethal cancers by developing active surveillance regimens.

This management strategy recognizes that most low-grade cancers pose no short-term risk to the patient’s health or longevity, that definitive therapy can be deferred, and that with regular monitoring by digital rectal examination, PSA measurement, and repeat biopsy, cancers that progress can still be cured. The result of this strategy is a marked reduction in the harms caused by overtreatment (ie, the aforementioned adverse effects), as well as the avoidance of unnecessary treatment in many patients.

A randomized trial and 2 large prospective cohort studies have confirmed the long-term safety of this approach,^7–9 and the development of commercially available, biopsy-based gene expression profiling tools promises to further improve risk stratification at diagnosis and during follow-up for individual patients.¹⁰

NEW USPSTF RECOMMENDATIONS: AN INDIVIDUAL, INFORMED DECISION

Based on the results of the ERSPC and the widespread adoption and safety of active surveillance, which together show benefit to screening and fewer harms in overdetection and overtreatment, in 2018 the USPSTF recast its recommendations. In upgrading the recommendation from “D” to “C,” the recommendation now states that for men ages 55 to 69, PSA screening should be an individual decision after a discussion with an informed provider, although men over 70 are still advised not to undergo screening at all.¹¹

Some may think that this recommendation has arrived just in time, or that it should be  made even stronger to actually recommend screening, as recent data from 2 national registries—the Surveillance, Epidemiology, and End Results program and the National Cancer Database—show that the fall in screening after the 2012 USPSTF guidelines has resulted in an increase in men presenting with advanced stage disease.^12,13 (All of you Back to the Future fans, please return to the mid to late 1980s to see how that plays out.)

So the pendulum has now swung back in favor of screening, largely supported by solid data showing meaningful clinical benefit, better understanding of PSA and prostate cancer biology, and adoption of active surveillance.

AN IDEAL SCREENING PROGRAM

An ideal screening program would detect only biologically significant cancers, thus eliminating overdetection and overtreatment. There is reason for optimism on this front.

Second-generation PSA tests have better diagnostic accuracy for high-grade disease than earlier tests. Two such tests, the Prostate Health Index (Beckman Coulter) and the 4K-score (Opko Health), are commercially available though not usually covered by commercial insurers.¹⁴ A third test, IsoPSA (Cleveland Diagnostics), is under development. Most hospital laboratories will be able to be run this test with no need for a central laboratory.¹⁵ All 3 tests have been shown to reduce unnecessary biopsies (because of a low probability of finding a biologically significant cancer) by 30% to 45% and will help reduce overdetection.

Moreover, multiparametric magnetic resonance imaging of the prostate has been shown to improve detection of high-grade cancers,¹⁶ and a randomized trial has suggested that its incorporation into a screening strategy is cost-effective and could be better than PSA testing plus transrectal ultrasonography alone (the current standard of care).¹⁷

Several risk scores based on germline genomics also hold promise for better identifying those at risk and for helping to de-intensify screening for those unlikely to have high-grade cancer.¹⁸

Screening for prostate cancer reduces mortality rates and the burden of metastatic disease, and the paradigm continues to evolve. Men at risk by virtue of age (55 to 69, and healthy men > 70), family history, race, and newly identified factors (germline genetics) all deserve an informed discussion on the benefits and risks of screening

My urologic career began in the late 1980s, just before prostate-specific antigen (PSA) testing was introduced. Ever since, a busy prostate cancer practice has given me a frontline view of the benefits and possible harms of PSA screening.

See related article

In the pre-PSA era, about half of men with newly diagnosed prostate cancer presented with incurable disease, either locally advanced or metastatic. The most common treatment was bilateral orchiectomy, which was the only safe form of androgen deprivation available.

Fast-forward a few years to the mid-1990s. Within 5 years after the introduction of PSA testing, the rate of incurable disease at diagnosis fell to just 5%, and treatment for localized disease skyrocketed, including radical prostatectomy, external beam radiation, and brachytherapy. As a result of earlier diagnosis and improved treatments, the death rate from prostate cancer in US men has fallen more than 30% since 1990.

The first-hand experience of seeing this massive stage migration to curable disease has forever convinced me that PSA screening is beneficial. Robust statistical models lend credence to this belief, with estimates that screening is responsible for 45% to 70% of this decline in mortality.¹

Fast-forward again to 2012, when the US Preventive Services Task Force (USPSTF) published a strong recommendation against screening. The recommendation had so much force that as recently as 2014, only 11% of men at highest risk of prostate cancer in the Cleveland Clinic system were screened for it,² mirroring national trends.

What happened? Colored by the experience in the era before PSA, when men presented frequently with painful metastatic disease and had an average life expectancy of 18 to 24 months, it was widely believed that all detected prostate cancer required treatment. What was not appreciated was that while PSA detects lots of prostate cancer, the most common reason for PSA levels to reach a range worrisome enough to trigger biopsy was actually benign prostatic hypertrophy.

The resulting increase in the number of biopsies resulted in the detection of a substantial number of low-grade cancers that were never destined to cause clinical harm but that got treated anyway, based on the fear that all cancers had metastatic potential. The USPSTF based its recommendation against screening on the harms caused by this overdetection and overtreatment of nonlethal disease, focusing on risks of biopsy such as sepsis, and on treatment-related adverse effects such as changes in urinary, bowel, and sexual function.

RANDOMIZED TRIALS SHOW A BENEFIT FROM SCREENING

As a result of this controversy, several large randomized trials designed to test whether PSA screening was beneficial were organized and begun in the 1990s, with one in the United States and another in Europe.^3,4 Mature data from both trials have now established that there is indeed benefit to population-level screening.

The US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), was initially reported to show no difference in prostate cancer-specific mortality rates in those screened vs not screened, but because more than 90% of the men in the no-screening arm were screened anyway, that conclusion is erroneous.³

With 13-year follow-up and far less PSA contamination in the unscreened arm, the European Randomized Study of Screening for Prostate Cancer (ERSPC) in men ages 55 to 69 demonstrated a 27% reduction in the rate of death and a 35% reduction in the need for palliative treatments (androgen deprivation or radiation, or both) for metastatic disease in those screened vs not screened, clearly establishing substantial clinical benefit to PSA screening.⁴

A recent analysis of both trials that controlled for PSA drop-ins (comparing those actually screened with those actually not screened) concluded that the benefit of screening in terms of mortality reduction (estimated at about 30%) are equal in both trials.⁵ A large cohort study from Kaiser Permanente with 16-year follow-up has suggested that PSA screening has both a prostate cancer-specific benefit and an overall mortality benefit.⁶

 

 

ACTIVE SURVEILLANCE CAN REDUCE OVERTREATMENT

In parallel with the design and completion of these trials, there was a significant effort to better identify and manage patients initially overdiagnosed with nonlethal cancers by developing active surveillance regimens.

This management strategy recognizes that most low-grade cancers pose no short-term risk to the patient’s health or longevity, that definitive therapy can be deferred, and that with regular monitoring by digital rectal examination, PSA measurement, and repeat biopsy, cancers that progress can still be cured. The result of this strategy is a marked reduction in the harms caused by overtreatment (ie, the aforementioned adverse effects), as well as the avoidance of unnecessary treatment in many patients.

A randomized trial and 2 large prospective cohort studies have confirmed the long-term safety of this approach,^7–9 and the development of commercially available, biopsy-based gene expression profiling tools promises to further improve risk stratification at diagnosis and during follow-up for individual patients.¹⁰

NEW USPSTF RECOMMENDATIONS: AN INDIVIDUAL, INFORMED DECISION

Based on the results of the ERSPC and the widespread adoption and safety of active surveillance, which together show benefit to screening and fewer harms in overdetection and overtreatment, in 2018 the USPSTF recast its recommendations. In upgrading the recommendation from “D” to “C,” the recommendation now states that for men ages 55 to 69, PSA screening should be an individual decision after a discussion with an informed provider, although men over 70 are still advised not to undergo screening at all.¹¹

Some may think that this recommendation has arrived just in time, or that it should be  made even stronger to actually recommend screening, as recent data from 2 national registries—the Surveillance, Epidemiology, and End Results program and the National Cancer Database—show that the fall in screening after the 2012 USPSTF guidelines has resulted in an increase in men presenting with advanced stage disease.^12,13 (All of you Back to the Future fans, please return to the mid to late 1980s to see how that plays out.)

So the pendulum has now swung back in favor of screening, largely supported by solid data showing meaningful clinical benefit, better understanding of PSA and prostate cancer biology, and adoption of active surveillance.

AN IDEAL SCREENING PROGRAM

An ideal screening program would detect only biologically significant cancers, thus eliminating overdetection and overtreatment. There is reason for optimism on this front.

Second-generation PSA tests have better diagnostic accuracy for high-grade disease than earlier tests. Two such tests, the Prostate Health Index (Beckman Coulter) and the 4K-score (Opko Health), are commercially available though not usually covered by commercial insurers.¹⁴ A third test, IsoPSA (Cleveland Diagnostics), is under development. Most hospital laboratories will be able to be run this test with no need for a central laboratory.¹⁵ All 3 tests have been shown to reduce unnecessary biopsies (because of a low probability of finding a biologically significant cancer) by 30% to 45% and will help reduce overdetection.

Moreover, multiparametric magnetic resonance imaging of the prostate has been shown to improve detection of high-grade cancers,¹⁶ and a randomized trial has suggested that its incorporation into a screening strategy is cost-effective and could be better than PSA testing plus transrectal ultrasonography alone (the current standard of care).¹⁷

Several risk scores based on germline genomics also hold promise for better identifying those at risk and for helping to de-intensify screening for those unlikely to have high-grade cancer.¹⁸

Screening for prostate cancer reduces mortality rates and the burden of metastatic disease, and the paradigm continues to evolve. Men at risk by virtue of age (55 to 69, and healthy men > 70), family history, race, and newly identified factors (germline genetics) all deserve an informed discussion on the benefits and risks of screening

Taurine, also known as 2-aminoethanesulfonic acid, is a naturally occurring beta-amino acid (which has a sulphonic acid group instead of carboxylic acid, differentiating it from other amino acids) yielded by methionine and cysteine metabolism in the liver.^1,2 An important free beta-amino acid in mammals, it is often the free amino acid present in the greatest concentrations in several cell types in humans.^1,2 Dietary intake of taurine also plays an important role in maintaining the body’s taurine levels because of mammals’ limited ability to synthesize it.¹

olavs/Thinkstock

Notably in terms of dermatologic treatment options, the combination product taurine bromamine is known to impart antioxidant, anti-inflammatory, and antibacterial activities.³ And taurine itself is associated with antioxidant, anti-inflammatory, antifibrotic, and immunomodulatory characteristics,^1,4 and is noted for conferring antiaging benefits.⁵

Acne and other inflammatory conditions

The use of topical taurine bromamine, the physiological product of hypobromous acid and taurine, is one of the new emerging approaches to treating acne.^6,7

In response to the problem of evolving antibiotic resistance, Marcinkiewicz reported in 2009 on the then-new therapeutic option of topical taurine bromamine for the treatment of inflammatory skin disorders such as acne. The author pointed out that Propionibacterium acnes is particularly sensitive to taurine bromamine, with the substance now known to suppress H₂O₂ production by activated neutrophils, likely contributing to moderating the severity and lowering the number of inflammatory acne lesions. In a 6-week double-blind pilot clinical study, Marcinkiewicz and his team compared the efficacy of 0.5% taurine bromamine cream with 1% clindamycin gel in 40 patients with mild to moderate acne. Treatments, which were randomly assigned, occurred twice daily through the study. Amelioration of acne symptoms was comparable in the two groups, with more than 90% of patients improving clinically and experiencing similar decreases in acne lesions (65% in the taurine bromamine group and 68% in the clindamycin group). Marcinkiewicz concluded that these results indicate the viability of taurine bromamine as an option for inflammatory acne therapy, particularly for patients who have shown antibiotic resistance.³

Wide-ranging protection potential

In 2003, Janeke et al. conducted analyses that showed that taurine accumulation defended cultured human keratinocytes from osmotically- and UV-induced apoptosis, suggesting the importance of taurine as an epidermal osmolyte necessary for maintaining keratinocyte hydration in a dry environment.²

Three years later, Collin et al. demonstrated the dynamic protective effects of taurine on the human hair follicle in an in vitro study in which taurine promoted hair survival and protected against TGF-beta1-induced damage.¹

Taurine has also been found to stabilize and protect the catalytic activity of the hemoprotein cytochrome P450 3A4, which is a key enzyme responsible for metabolizing various endogenous as well as foreign substances, including drugs.⁸
 

Penetration enhancement

In 2016, Mueller et al. studied the effects of urea and taurine as hydrophilic penetration enhancers on stratum corneum lipid models as both substances are known to exert such effects. With inconclusive results as to the roots of such activity, they speculated that both entities enhance penetration through the introduction of copious water into the corneocytes, resulting from the robust water-binding capacity of urea and the consequent osmotic pressure related to taurine.⁹

Possible skin whitening and anti-aging roles and other promising lab results

Based on their previous work demonstrating that azelaic acid, a saturated dicarboxylic acid found naturally in wheat, rye, and barley, suppressed melanogenesis, Yu and Kim investigated the antimelanogenic activity of azelaic acid and taurine in B16F10 mouse melanoma cells in 2010. They found that the combination of the two substances exhibited a greater inhibitory effect in melanocytes than azelaic acid alone, with melanin production and tyrosinase activity suppressed without inducing cytotoxicity. The investigators concluded the combination of azelaic acid and taurine may be an effective approach for treating hyperpigmentation.¹⁰

In 2015, Ito et al. investigated the possible anti-aging role of taurine using a taurine transporter knockout mouse model. They noted that aging-related disorders affecting the skin, heart, skeletal muscle, and liver and resulting in a shorter lifespan have been correlated with tissue taurine depletion. The researchers proposed that proper protein folding allows endogenous taurine to perform as an antiaging molecule.⁵

Also in 2015, Kim et al. investigated potential mechanisms of the antiproliferative activity of taurine on murine B16F10 melanoma cells via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red assays and microscopic analysis. They found that taurine prevented cell proliferation and engendered apoptosis in B16F10 cells, concluding that taurine may have a role to play as a chemotherapeutic agent for skin cancer.¹¹

In 2014, Ashkani-Esfahani et al. studied the impact of taurine on cutaneous leishmaniasis wounds in a mouse model. Investigators induced 18 mice with wounds using L. major promastigotes, and divided them into a taurine injection group, taurine gel group, and no treatment group, performing treatments every 24 hours over 21 days. The taurine treatment groups exhibited significantly greater numerical fibroblast density, collagen bundle volume density, and vessel length densities compared with the nontreatment group. The taurine injection group displayed higher fibroblast numerical density than did the taurine gel group. The researchers concluded that taurine has the capacity to enhance wound healing and tissue regeneration but showed no direct anti-leishmaniasis effect.⁴

Conclusion

Taurine has been found over the last few decades to impart salutary effects for human health. This beta-amino acid that occurs naturally in humans and other mammals also appears to hold promising potential in the dermatologic realm, particularly for its anti-inflammatory and antioxidant effects. More research is needed to ascertain just how pivotal this compound can be for skin health.

Dr. Baumann is a private practice dermatologist, researcher, author and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].

References

1. Int J Cosmet Sci. 2006 Aug;28(4):289-98.

2. J Invest Dermatol. 2003 Aug;121(2):354-61.

3. Pol Arch Med Wewn. 2009 Oct;119(10):673-6.

4. Adv Biomed Res. 2014 Oct 7;3:204.

5. Adv Exp Med Biol. 2015;803:481-7.

6. Am J Clin Dermatol. 2012 Dec 1;13(6):357-64.

7. Eur J Dermatol. 2008 Jul-Aug;18(4):433-9.

8. Biochemistry (Mosc). 2015 Mar;80(3):366-73.

9. Biochim Biophys Acta. 2016 Sep;1858(9):2006-18.

10. J Biomed Sci. 2010 Aug 24;17 Suppl 1:S45.

11. Adv Exp Med Biol. 2015;803:167-77.

Taurine, also known as 2-aminoethanesulfonic acid, is a naturally occurring beta-amino acid (which has a sulphonic acid group instead of carboxylic acid, differentiating it from other amino acids) yielded by methionine and cysteine metabolism in the liver.^1,2 An important free beta-amino acid in mammals, it is often the free amino acid present in the greatest concentrations in several cell types in humans.^1,2 Dietary intake of taurine also plays an important role in maintaining the body’s taurine levels because of mammals’ limited ability to synthesize it.¹

olavs/Thinkstock

Notably in terms of dermatologic treatment options, the combination product taurine bromamine is known to impart antioxidant, anti-inflammatory, and antibacterial activities.³ And taurine itself is associated with antioxidant, anti-inflammatory, antifibrotic, and immunomodulatory characteristics,^1,4 and is noted for conferring antiaging benefits.⁵

Acne and other inflammatory conditions

The use of topical taurine bromamine, the physiological product of hypobromous acid and taurine, is one of the new emerging approaches to treating acne.^6,7

In response to the problem of evolving antibiotic resistance, Marcinkiewicz reported in 2009 on the then-new therapeutic option of topical taurine bromamine for the treatment of inflammatory skin disorders such as acne. The author pointed out that Propionibacterium acnes is particularly sensitive to taurine bromamine, with the substance now known to suppress H₂O₂ production by activated neutrophils, likely contributing to moderating the severity and lowering the number of inflammatory acne lesions. In a 6-week double-blind pilot clinical study, Marcinkiewicz and his team compared the efficacy of 0.5% taurine bromamine cream with 1% clindamycin gel in 40 patients with mild to moderate acne. Treatments, which were randomly assigned, occurred twice daily through the study. Amelioration of acne symptoms was comparable in the two groups, with more than 90% of patients improving clinically and experiencing similar decreases in acne lesions (65% in the taurine bromamine group and 68% in the clindamycin group). Marcinkiewicz concluded that these results indicate the viability of taurine bromamine as an option for inflammatory acne therapy, particularly for patients who have shown antibiotic resistance.³

Wide-ranging protection potential

In 2003, Janeke et al. conducted analyses that showed that taurine accumulation defended cultured human keratinocytes from osmotically- and UV-induced apoptosis, suggesting the importance of taurine as an epidermal osmolyte necessary for maintaining keratinocyte hydration in a dry environment.²

Three years later, Collin et al. demonstrated the dynamic protective effects of taurine on the human hair follicle in an in vitro study in which taurine promoted hair survival and protected against TGF-beta1-induced damage.¹

Taurine has also been found to stabilize and protect the catalytic activity of the hemoprotein cytochrome P450 3A4, which is a key enzyme responsible for metabolizing various endogenous as well as foreign substances, including drugs.⁸
 

Penetration enhancement

In 2016, Mueller et al. studied the effects of urea and taurine as hydrophilic penetration enhancers on stratum corneum lipid models as both substances are known to exert such effects. With inconclusive results as to the roots of such activity, they speculated that both entities enhance penetration through the introduction of copious water into the corneocytes, resulting from the robust water-binding capacity of urea and the consequent osmotic pressure related to taurine.⁹

Possible skin whitening and anti-aging roles and other promising lab results

Based on their previous work demonstrating that azelaic acid, a saturated dicarboxylic acid found naturally in wheat, rye, and barley, suppressed melanogenesis, Yu and Kim investigated the antimelanogenic activity of azelaic acid and taurine in B16F10 mouse melanoma cells in 2010. They found that the combination of the two substances exhibited a greater inhibitory effect in melanocytes than azelaic acid alone, with melanin production and tyrosinase activity suppressed without inducing cytotoxicity. The investigators concluded the combination of azelaic acid and taurine may be an effective approach for treating hyperpigmentation.¹⁰

In 2015, Ito et al. investigated the possible anti-aging role of taurine using a taurine transporter knockout mouse model. They noted that aging-related disorders affecting the skin, heart, skeletal muscle, and liver and resulting in a shorter lifespan have been correlated with tissue taurine depletion. The researchers proposed that proper protein folding allows endogenous taurine to perform as an antiaging molecule.⁵

Also in 2015, Kim et al. investigated potential mechanisms of the antiproliferative activity of taurine on murine B16F10 melanoma cells via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red assays and microscopic analysis. They found that taurine prevented cell proliferation and engendered apoptosis in B16F10 cells, concluding that taurine may have a role to play as a chemotherapeutic agent for skin cancer.¹¹

In 2014, Ashkani-Esfahani et al. studied the impact of taurine on cutaneous leishmaniasis wounds in a mouse model. Investigators induced 18 mice with wounds using L. major promastigotes, and divided them into a taurine injection group, taurine gel group, and no treatment group, performing treatments every 24 hours over 21 days. The taurine treatment groups exhibited significantly greater numerical fibroblast density, collagen bundle volume density, and vessel length densities compared with the nontreatment group. The taurine injection group displayed higher fibroblast numerical density than did the taurine gel group. The researchers concluded that taurine has the capacity to enhance wound healing and tissue regeneration but showed no direct anti-leishmaniasis effect.⁴

Conclusion

Taurine has been found over the last few decades to impart salutary effects for human health. This beta-amino acid that occurs naturally in humans and other mammals also appears to hold promising potential in the dermatologic realm, particularly for its anti-inflammatory and antioxidant effects. More research is needed to ascertain just how pivotal this compound can be for skin health.

Dr. Baumann is a private practice dermatologist, researcher, author and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].

References

1. Int J Cosmet Sci. 2006 Aug;28(4):289-98.

2. J Invest Dermatol. 2003 Aug;121(2):354-61.

3. Pol Arch Med Wewn. 2009 Oct;119(10):673-6.

4. Adv Biomed Res. 2014 Oct 7;3:204.

5. Adv Exp Med Biol. 2015;803:481-7.

6. Am J Clin Dermatol. 2012 Dec 1;13(6):357-64.

7. Eur J Dermatol. 2008 Jul-Aug;18(4):433-9.

8. Biochemistry (Mosc). 2015 Mar;80(3):366-73.

9. Biochim Biophys Acta. 2016 Sep;1858(9):2006-18.

10. J Biomed Sci. 2010 Aug 24;17 Suppl 1:S45.

11. Adv Exp Med Biol. 2015;803:167-77.

Taurine, also known as 2-aminoethanesulfonic acid, is a naturally occurring beta-amino acid (which has a sulphonic acid group instead of carboxylic acid, differentiating it from other amino acids) yielded by methionine and cysteine metabolism in the liver.^1,2 An important free beta-amino acid in mammals, it is often the free amino acid present in the greatest concentrations in several cell types in humans.^1,2 Dietary intake of taurine also plays an important role in maintaining the body’s taurine levels because of mammals’ limited ability to synthesize it.¹

olavs/Thinkstock

Notably in terms of dermatologic treatment options, the combination product taurine bromamine is known to impart antioxidant, anti-inflammatory, and antibacterial activities.³ And taurine itself is associated with antioxidant, anti-inflammatory, antifibrotic, and immunomodulatory characteristics,^1,4 and is noted for conferring antiaging benefits.⁵

Acne and other inflammatory conditions

The use of topical taurine bromamine, the physiological product of hypobromous acid and taurine, is one of the new emerging approaches to treating acne.^6,7

In response to the problem of evolving antibiotic resistance, Marcinkiewicz reported in 2009 on the then-new therapeutic option of topical taurine bromamine for the treatment of inflammatory skin disorders such as acne. The author pointed out that Propionibacterium acnes is particularly sensitive to taurine bromamine, with the substance now known to suppress H₂O₂ production by activated neutrophils, likely contributing to moderating the severity and lowering the number of inflammatory acne lesions. In a 6-week double-blind pilot clinical study, Marcinkiewicz and his team compared the efficacy of 0.5% taurine bromamine cream with 1% clindamycin gel in 40 patients with mild to moderate acne. Treatments, which were randomly assigned, occurred twice daily through the study. Amelioration of acne symptoms was comparable in the two groups, with more than 90% of patients improving clinically and experiencing similar decreases in acne lesions (65% in the taurine bromamine group and 68% in the clindamycin group). Marcinkiewicz concluded that these results indicate the viability of taurine bromamine as an option for inflammatory acne therapy, particularly for patients who have shown antibiotic resistance.³

Wide-ranging protection potential

In 2003, Janeke et al. conducted analyses that showed that taurine accumulation defended cultured human keratinocytes from osmotically- and UV-induced apoptosis, suggesting the importance of taurine as an epidermal osmolyte necessary for maintaining keratinocyte hydration in a dry environment.²

Three years later, Collin et al. demonstrated the dynamic protective effects of taurine on the human hair follicle in an in vitro study in which taurine promoted hair survival and protected against TGF-beta1-induced damage.¹

Taurine has also been found to stabilize and protect the catalytic activity of the hemoprotein cytochrome P450 3A4, which is a key enzyme responsible for metabolizing various endogenous as well as foreign substances, including drugs.⁸
 

Penetration enhancement

In 2016, Mueller et al. studied the effects of urea and taurine as hydrophilic penetration enhancers on stratum corneum lipid models as both substances are known to exert such effects. With inconclusive results as to the roots of such activity, they speculated that both entities enhance penetration through the introduction of copious water into the corneocytes, resulting from the robust water-binding capacity of urea and the consequent osmotic pressure related to taurine.⁹

Possible skin whitening and anti-aging roles and other promising lab results

Based on their previous work demonstrating that azelaic acid, a saturated dicarboxylic acid found naturally in wheat, rye, and barley, suppressed melanogenesis, Yu and Kim investigated the antimelanogenic activity of azelaic acid and taurine in B16F10 mouse melanoma cells in 2010. They found that the combination of the two substances exhibited a greater inhibitory effect in melanocytes than azelaic acid alone, with melanin production and tyrosinase activity suppressed without inducing cytotoxicity. The investigators concluded the combination of azelaic acid and taurine may be an effective approach for treating hyperpigmentation.¹⁰

In 2015, Ito et al. investigated the possible anti-aging role of taurine using a taurine transporter knockout mouse model. They noted that aging-related disorders affecting the skin, heart, skeletal muscle, and liver and resulting in a shorter lifespan have been correlated with tissue taurine depletion. The researchers proposed that proper protein folding allows endogenous taurine to perform as an antiaging molecule.⁵

Also in 2015, Kim et al. investigated potential mechanisms of the antiproliferative activity of taurine on murine B16F10 melanoma cells via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red assays and microscopic analysis. They found that taurine prevented cell proliferation and engendered apoptosis in B16F10 cells, concluding that taurine may have a role to play as a chemotherapeutic agent for skin cancer.¹¹

In 2014, Ashkani-Esfahani et al. studied the impact of taurine on cutaneous leishmaniasis wounds in a mouse model. Investigators induced 18 mice with wounds using L. major promastigotes, and divided them into a taurine injection group, taurine gel group, and no treatment group, performing treatments every 24 hours over 21 days. The taurine treatment groups exhibited significantly greater numerical fibroblast density, collagen bundle volume density, and vessel length densities compared with the nontreatment group. The taurine injection group displayed higher fibroblast numerical density than did the taurine gel group. The researchers concluded that taurine has the capacity to enhance wound healing and tissue regeneration but showed no direct anti-leishmaniasis effect.⁴

Conclusion

Taurine has been found over the last few decades to impart salutary effects for human health. This beta-amino acid that occurs naturally in humans and other mammals also appears to hold promising potential in the dermatologic realm, particularly for its anti-inflammatory and antioxidant effects. More research is needed to ascertain just how pivotal this compound can be for skin health.

Dr. Baumann is a private practice dermatologist, researcher, author and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].

References

1. Int J Cosmet Sci. 2006 Aug;28(4):289-98.

2. J Invest Dermatol. 2003 Aug;121(2):354-61.

3. Pol Arch Med Wewn. 2009 Oct;119(10):673-6.

4. Adv Biomed Res. 2014 Oct 7;3:204.

5. Adv Exp Med Biol. 2015;803:481-7.

6. Am J Clin Dermatol. 2012 Dec 1;13(6):357-64.

7. Eur J Dermatol. 2008 Jul-Aug;18(4):433-9.

8. Biochemistry (Mosc). 2015 Mar;80(3):366-73.

9. Biochim Biophys Acta. 2016 Sep;1858(9):2006-18.

10. J Biomed Sci. 2010 Aug 24;17 Suppl 1:S45.

11. Adv Exp Med Biol. 2015;803:167-77.

Click here to access the November 2018 Digital Edition.

Table of Contents

• Why Do We Need the VA?

• Providing Rural Veterans With Access to Exercise Through Gerofit

• Reducing COPD Readmission Rates: Using a COPD Care Service During Care Transitions

• Skin-Colored Papules on the Chest

• Initiative to Minimize Pharmaceutical Risk in Older Veterans (IMPROVE) Polypharmacy Clinic

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Click here to access the November 2018 Digital Edition.

Table of Contents

• Why Do We Need the VA?

• Providing Rural Veterans With Access to Exercise Through Gerofit

• Reducing COPD Readmission Rates: Using a COPD Care Service During Care Transitions

• Skin-Colored Papules on the Chest

• Initiative to Minimize Pharmaceutical Risk in Older Veterans (IMPROVE) Polypharmacy Clinic

Image

Click here to access the November 2018 Digital Edition.

Table of Contents

• Why Do We Need the VA?

• Providing Rural Veterans With Access to Exercise Through Gerofit

• Reducing COPD Readmission Rates: Using a COPD Care Service During Care Transitions

• Skin-Colored Papules on the Chest

• Initiative to Minimize Pharmaceutical Risk in Older Veterans (IMPROVE) Polypharmacy Clinic

Image

The finding by Kachman et al. that consultations have decreased at their institution is an interesting and important observation.¹ In contrast, our study found that more than a third of hospitalists reported an increase in consultation requests.² There may be several explanations for this discrepancy. First, as Kachman et al. suggest, there may be differences between hospitalist perception and actual consultation use. Second, a significant variability in consultation may exist between hospitals. Although our study examined four institutions, we were unable to examine the variability between them, which requires further study. Third, there may be considerable variability between individual hospitalist practices, which is consistent with the findings reported by Kachman et al. Finally, the fact that our study examined only nonteaching services may be another explanation as Kachman et al. found that hospitalists on nonteaching services ordered more consultations than those on teaching services. These findings are consistent with a recent study conducted by Perez et al., who found that hospitalists on teaching services utilized fewer consultations and had lower direct care costs and shorter lengths of stay compared with those on nonteaching services.³ This finding raises the question of whether consultations impact care costs and lengths of stay, a topic that should be explored in future studies.

Disclosures

The authors report no conflicts of interest.

The finding by Kachman et al. that consultations have decreased at their institution is an interesting and important observation.¹ In contrast, our study found that more than a third of hospitalists reported an increase in consultation requests.² There may be several explanations for this discrepancy. First, as Kachman et al. suggest, there may be differences between hospitalist perception and actual consultation use. Second, a significant variability in consultation may exist between hospitals. Although our study examined four institutions, we were unable to examine the variability between them, which requires further study. Third, there may be considerable variability between individual hospitalist practices, which is consistent with the findings reported by Kachman et al. Finally, the fact that our study examined only nonteaching services may be another explanation as Kachman et al. found that hospitalists on nonteaching services ordered more consultations than those on teaching services. These findings are consistent with a recent study conducted by Perez et al., who found that hospitalists on teaching services utilized fewer consultations and had lower direct care costs and shorter lengths of stay compared with those on nonteaching services.³ This finding raises the question of whether consultations impact care costs and lengths of stay, a topic that should be explored in future studies.

Disclosures

The authors report no conflicts of interest.

The finding by Kachman et al. that consultations have decreased at their institution is an interesting and important observation.¹ In contrast, our study found that more than a third of hospitalists reported an increase in consultation requests.² There may be several explanations for this discrepancy. First, as Kachman et al. suggest, there may be differences between hospitalist perception and actual consultation use. Second, a significant variability in consultation may exist between hospitals. Although our study examined four institutions, we were unable to examine the variability between them, which requires further study. Third, there may be considerable variability between individual hospitalist practices, which is consistent with the findings reported by Kachman et al. Finally, the fact that our study examined only nonteaching services may be another explanation as Kachman et al. found that hospitalists on nonteaching services ordered more consultations than those on teaching services. These findings are consistent with a recent study conducted by Perez et al., who found that hospitalists on teaching services utilized fewer consultations and had lower direct care costs and shorter lengths of stay compared with those on nonteaching services.³ This finding raises the question of whether consultations impact care costs and lengths of stay, a topic that should be explored in future studies.

Disclosures

The authors report no conflicts of interest.

We thank Dr. Santhosh and colleagues for their letter concerning our article.¹ We agree that the diagnostic journey includes interactions both between and across teams, not just those within the patient’s team. In an article currently in press in Diagnosis, we examine how systems and cognitive factors interact during the process of diagnosis. Specifically, we reported on how communication between consultants can be both a barrier and facilitator to the diagnostic process.² We found that the frequency, quality, and pace of communication between and across inpatient teams and specialists are essential to timely diagnoses. As diagnostic errors remain a costly and morbid issue in the hospital setting, efforts to improve communication are clearly needed.³

Santhosh et al. raise an interesting point regarding cognitive load in evaluating diagnosis. Cognitive load is a multidimensional construct that represents the load that performing a specific task poses on a learner’s cognitive system.⁴ Components often used for measuring load include (a) task characteristics such as format, complexity, and time pressure; (b) subject characteristics such as expertise level, age, and spatial abilities; and (c) mental load and effort that originate from the interaction between task and subject characteristics.⁵ While there is little doubt that measuring these constructs has face value in diagnosis, we know of no instruments that are nimble, straightforward, or suitable for such measurement in the clinical setting. Furthermore, unlike handoffs (which lend themselves to structured frameworks), diagnostic evolution occurs across multiple individuals (from attendings to house staff and students), specialties (from emergency physicians to medical and surgical specialists), and over time. A unifying framework and tool to measure cognitive load across these elements would not only be novel, but a welcomed and much-needed component to facilitate diagnostic efforts. We hope that our ethnographic work will spur the development of these types of instruments and highlight opportunities for implementation. A future that both measures cognitive load and targets interventions to reduce or balance these across members of the diagnostic team would be welcomed.

Disclosures

The authors have nothing to disclose.

Funding

This project was supported by grant number P30HS024385 from the Agency for Healthcare Research and Quality. The funding source played no role in study design, data acquisition, analysis or decision to report these data.

We thank Dr. Santhosh and colleagues for their letter concerning our article.¹ We agree that the diagnostic journey includes interactions both between and across teams, not just those within the patient’s team. In an article currently in press in Diagnosis, we examine how systems and cognitive factors interact during the process of diagnosis. Specifically, we reported on how communication between consultants can be both a barrier and facilitator to the diagnostic process.² We found that the frequency, quality, and pace of communication between and across inpatient teams and specialists are essential to timely diagnoses. As diagnostic errors remain a costly and morbid issue in the hospital setting, efforts to improve communication are clearly needed.³

Santhosh et al. raise an interesting point regarding cognitive load in evaluating diagnosis. Cognitive load is a multidimensional construct that represents the load that performing a specific task poses on a learner’s cognitive system.⁴ Components often used for measuring load include (a) task characteristics such as format, complexity, and time pressure; (b) subject characteristics such as expertise level, age, and spatial abilities; and (c) mental load and effort that originate from the interaction between task and subject characteristics.⁵ While there is little doubt that measuring these constructs has face value in diagnosis, we know of no instruments that are nimble, straightforward, or suitable for such measurement in the clinical setting. Furthermore, unlike handoffs (which lend themselves to structured frameworks), diagnostic evolution occurs across multiple individuals (from attendings to house staff and students), specialties (from emergency physicians to medical and surgical specialists), and over time. A unifying framework and tool to measure cognitive load across these elements would not only be novel, but a welcomed and much-needed component to facilitate diagnostic efforts. We hope that our ethnographic work will spur the development of these types of instruments and highlight opportunities for implementation. A future that both measures cognitive load and targets interventions to reduce or balance these across members of the diagnostic team would be welcomed.

Disclosures

The authors have nothing to disclose.

Funding

This project was supported by grant number P30HS024385 from the Agency for Healthcare Research and Quality. The funding source played no role in study design, data acquisition, analysis or decision to report these data.

We thank Dr. Santhosh and colleagues for their letter concerning our article.¹ We agree that the diagnostic journey includes interactions both between and across teams, not just those within the patient’s team. In an article currently in press in Diagnosis, we examine how systems and cognitive factors interact during the process of diagnosis. Specifically, we reported on how communication between consultants can be both a barrier and facilitator to the diagnostic process.² We found that the frequency, quality, and pace of communication between and across inpatient teams and specialists are essential to timely diagnoses. As diagnostic errors remain a costly and morbid issue in the hospital setting, efforts to improve communication are clearly needed.³

Santhosh et al. raise an interesting point regarding cognitive load in evaluating diagnosis. Cognitive load is a multidimensional construct that represents the load that performing a specific task poses on a learner’s cognitive system.⁴ Components often used for measuring load include (a) task characteristics such as format, complexity, and time pressure; (b) subject characteristics such as expertise level, age, and spatial abilities; and (c) mental load and effort that originate from the interaction between task and subject characteristics.⁵ While there is little doubt that measuring these constructs has face value in diagnosis, we know of no instruments that are nimble, straightforward, or suitable for such measurement in the clinical setting. Furthermore, unlike handoffs (which lend themselves to structured frameworks), diagnostic evolution occurs across multiple individuals (from attendings to house staff and students), specialties (from emergency physicians to medical and surgical specialists), and over time. A unifying framework and tool to measure cognitive load across these elements would not only be novel, but a welcomed and much-needed component to facilitate diagnostic efforts. We hope that our ethnographic work will spur the development of these types of instruments and highlight opportunities for implementation. A future that both measures cognitive load and targets interventions to reduce or balance these across members of the diagnostic team would be welcomed.

Disclosures

The authors have nothing to disclose.

Funding

This project was supported by grant number P30HS024385 from the Agency for Healthcare Research and Quality. The funding source played no role in study design, data acquisition, analysis or decision to report these data.