ILLUSTRATIVE CASE

An otherwise healthy 56-year-old woman presents to the emergency department (ED) with a productive cough of 4 days’ duration. A review of her history is negative for recurrent upper respiratory infections, smoking, or environmental exposures. Her physical exam is unremarkable and, more specifically, her pulmonary exam and vital signs (temperature, respiratory rate, and heart rate) are within normal limits. The patient states that last year her friend had similar symptoms and was given a diagnosis of pneumonia. Is it necessary to order a chest x-ray in this patient to rule out community-acquired pneumonia (CAP)?

CAP is a common pulmonary condition seen in the outpatient setting in the United States, representing more than 4.5 million outpatient visits in the years 2009 to 2010.² Historically, a diagnosis of CAP has been based on clinical findings in conjunction with infiltrates seen on chest x-ray.

In 2017, more than 5 million visits to the ED were due to a cough.³ The use of radiographic imaging in EDs has been increasing. There were 49 million x-rays and 2.7 million noncardiac chest computed tomography (CT) scans performed in 2016, many of which were for patients with cough.^3,4 Although imaging is an extremely useful tool and indicated in many instances, the ability to rule out CAP in an adult who presents with a cough by using a set of simple, clinically based heuristics without requiring imaging would help to increase efficiency, limit cost, and decrease exposure of patients to unnecessary and potentially harmful diagnostic studies.

Clinical decision rules (CDRs) are simple heuristics that can stratify patients as either high risk or low risk for specific diseases. Two older large, prospective cross-­sectional studies developed CDRs to determine the probability of CAP based on symptoms (eg, night sweats, myalgias, and sputum production) and clinical findings (eg, temperature > 37.8 °C [100 °F], tachypnea, tachycardia, rales, and decreased breath sounds).^5,6 This meta-analysis includes these studies and more recent studies^7-9 used to develop a CDR that focuses solely on a few specific signs and symptoms that can reliably rule out CAP without imaging, and so prove highly useful for busy primary care clinicians.

STUDY SUMMARY

This simple approach rules out CAP in outpatients 99.6% of the time

This systematic review and meta-analysis included studies that used 2 or more signs, symptoms, or point-of-care tests to determine the patient’s risk for CAP.¹ Twelve studies (N = 10,254) met inclusion criteria by applying a CDR to adults or adolescents presenting with respiratory signs or symptoms potentially suggestive of CAP to either an outpatient setting or an ED. Prospective cohort, cross-sectional, and case-control studies were included when a chest x-ray or CT was utilized as the primary reference standard. Exclusion criteria included studies of military or nursing home populations and studies in which the majority of patients had hospital- or ventilator-associated pneumonia or were immunocompromised.

For adult outpatients who present with acute cough, this clinical decision rule can quickly and accurately rule out CAP without the need for diagnostic imaging.

A simple, highly useful CDR emerged from 3 of the studies (N = 1865).^7-9 Two of these studies were described as case-control studies with prospective enrollment of patients older than 17 years in both outpatient and ED settings.^7,8 One study was conducted in the United States (mean age, 65 years) and the other in Iran (mean age, 60 years). The third was a Chilean prospective cohort study of ED patients older than 15 years (mean age, 53 years).⁹ In each of these studies, the outpatient or ED physicians collected all clinical data and documented their physical exam prior to receiving the chest radiograph results. The radiologists were masked to the clinical findings at the time of their interpretation.

Results. From the meta-analysis, a simple CDR emerged for patients with normal vital signs (temperature, respiratory rate, and heart rate) and a normal pulmonary exam that virtually ruled out CAP (sensitivity = 96%; 95% CI, 92%–98%; and negative likelihood ratio = 0.10; 95% CI, 0.07–0.13). In patients presenting to an outpatient clinic with acute cough with a 4% baseline prevalence rate of pneumonia, this CDR ruled out CAP 99.6% of the time.

Continue to: WHAT'S NEW

A clinical decision rule validated for accuracy

This is the first validated CDR that accurately rules out CAP in the outpatient or ED setting using parameters easily obtainable during a clinical exam.

CAVEATS

Proceed with caution in the young and the very old

Two of the 3 studies in this CDR had an overall moderate risk of bias, whereas the third study was determined to be at low risk of bias, based on appraisal with the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) framework.¹⁰

The mean age range in these 3 studies was 53 to 66 years (without further data such as standard deviation), suggesting that application of the CDR to adults who fall at extremes of age should be done with a modicum of caution.

Additionally, although the symptom complex of COVID-19 pneumonia would suggest that this CDR would likely remain accurate today, it has not been validated in patients with COVID-19 infection.

CHALLENGES TO IMPLEMENTATION

Potential reluctance to forgo imaging

Beyond the caveats regarding COVID-19, the use of a simple CDR to reliably exclude pneumonia should have no barrier to implementation in an outpatient primary care setting or ED, although there could be reluctance on the part of both providers and patients to fully embrace this simple tool without a confirmatory chest x-ray.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

An otherwise healthy 56-year-old woman presents to the emergency department (ED) with a productive cough of 4 days’ duration. A review of her history is negative for recurrent upper respiratory infections, smoking, or environmental exposures. Her physical exam is unremarkable and, more specifically, her pulmonary exam and vital signs (temperature, respiratory rate, and heart rate) are within normal limits. The patient states that last year her friend had similar symptoms and was given a diagnosis of pneumonia. Is it necessary to order a chest x-ray in this patient to rule out community-acquired pneumonia (CAP)?

CAP is a common pulmonary condition seen in the outpatient setting in the United States, representing more than 4.5 million outpatient visits in the years 2009 to 2010.² Historically, a diagnosis of CAP has been based on clinical findings in conjunction with infiltrates seen on chest x-ray.

In 2017, more than 5 million visits to the ED were due to a cough.³ The use of radiographic imaging in EDs has been increasing. There were 49 million x-rays and 2.7 million noncardiac chest computed tomography (CT) scans performed in 2016, many of which were for patients with cough.^3,4 Although imaging is an extremely useful tool and indicated in many instances, the ability to rule out CAP in an adult who presents with a cough by using a set of simple, clinically based heuristics without requiring imaging would help to increase efficiency, limit cost, and decrease exposure of patients to unnecessary and potentially harmful diagnostic studies.

Clinical decision rules (CDRs) are simple heuristics that can stratify patients as either high risk or low risk for specific diseases. Two older large, prospective cross-­sectional studies developed CDRs to determine the probability of CAP based on symptoms (eg, night sweats, myalgias, and sputum production) and clinical findings (eg, temperature > 37.8 °C [100 °F], tachypnea, tachycardia, rales, and decreased breath sounds).^5,6 This meta-analysis includes these studies and more recent studies^7-9 used to develop a CDR that focuses solely on a few specific signs and symptoms that can reliably rule out CAP without imaging, and so prove highly useful for busy primary care clinicians.

STUDY SUMMARY

This simple approach rules out CAP in outpatients 99.6% of the time

This systematic review and meta-analysis included studies that used 2 or more signs, symptoms, or point-of-care tests to determine the patient’s risk for CAP.¹ Twelve studies (N = 10,254) met inclusion criteria by applying a CDR to adults or adolescents presenting with respiratory signs or symptoms potentially suggestive of CAP to either an outpatient setting or an ED. Prospective cohort, cross-sectional, and case-control studies were included when a chest x-ray or CT was utilized as the primary reference standard. Exclusion criteria included studies of military or nursing home populations and studies in which the majority of patients had hospital- or ventilator-associated pneumonia or were immunocompromised.

For adult outpatients who present with acute cough, this clinical decision rule can quickly and accurately rule out CAP without the need for diagnostic imaging.

A simple, highly useful CDR emerged from 3 of the studies (N = 1865).^7-9 Two of these studies were described as case-control studies with prospective enrollment of patients older than 17 years in both outpatient and ED settings.^7,8 One study was conducted in the United States (mean age, 65 years) and the other in Iran (mean age, 60 years). The third was a Chilean prospective cohort study of ED patients older than 15 years (mean age, 53 years).⁹ In each of these studies, the outpatient or ED physicians collected all clinical data and documented their physical exam prior to receiving the chest radiograph results. The radiologists were masked to the clinical findings at the time of their interpretation.

Results. From the meta-analysis, a simple CDR emerged for patients with normal vital signs (temperature, respiratory rate, and heart rate) and a normal pulmonary exam that virtually ruled out CAP (sensitivity = 96%; 95% CI, 92%–98%; and negative likelihood ratio = 0.10; 95% CI, 0.07–0.13). In patients presenting to an outpatient clinic with acute cough with a 4% baseline prevalence rate of pneumonia, this CDR ruled out CAP 99.6% of the time.

Continue to: WHAT'S NEW

A clinical decision rule validated for accuracy

This is the first validated CDR that accurately rules out CAP in the outpatient or ED setting using parameters easily obtainable during a clinical exam.

CAVEATS

Proceed with caution in the young and the very old

Two of the 3 studies in this CDR had an overall moderate risk of bias, whereas the third study was determined to be at low risk of bias, based on appraisal with the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) framework.¹⁰

The mean age range in these 3 studies was 53 to 66 years (without further data such as standard deviation), suggesting that application of the CDR to adults who fall at extremes of age should be done with a modicum of caution.

Additionally, although the symptom complex of COVID-19 pneumonia would suggest that this CDR would likely remain accurate today, it has not been validated in patients with COVID-19 infection.

CHALLENGES TO IMPLEMENTATION

Potential reluctance to forgo imaging

Beyond the caveats regarding COVID-19, the use of a simple CDR to reliably exclude pneumonia should have no barrier to implementation in an outpatient primary care setting or ED, although there could be reluctance on the part of both providers and patients to fully embrace this simple tool without a confirmatory chest x-ray.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

An otherwise healthy 56-year-old woman presents to the emergency department (ED) with a productive cough of 4 days’ duration. A review of her history is negative for recurrent upper respiratory infections, smoking, or environmental exposures. Her physical exam is unremarkable and, more specifically, her pulmonary exam and vital signs (temperature, respiratory rate, and heart rate) are within normal limits. The patient states that last year her friend had similar symptoms and was given a diagnosis of pneumonia. Is it necessary to order a chest x-ray in this patient to rule out community-acquired pneumonia (CAP)?

CAP is a common pulmonary condition seen in the outpatient setting in the United States, representing more than 4.5 million outpatient visits in the years 2009 to 2010.² Historically, a diagnosis of CAP has been based on clinical findings in conjunction with infiltrates seen on chest x-ray.

In 2017, more than 5 million visits to the ED were due to a cough.³ The use of radiographic imaging in EDs has been increasing. There were 49 million x-rays and 2.7 million noncardiac chest computed tomography (CT) scans performed in 2016, many of which were for patients with cough.^3,4 Although imaging is an extremely useful tool and indicated in many instances, the ability to rule out CAP in an adult who presents with a cough by using a set of simple, clinically based heuristics without requiring imaging would help to increase efficiency, limit cost, and decrease exposure of patients to unnecessary and potentially harmful diagnostic studies.

Clinical decision rules (CDRs) are simple heuristics that can stratify patients as either high risk or low risk for specific diseases. Two older large, prospective cross-­sectional studies developed CDRs to determine the probability of CAP based on symptoms (eg, night sweats, myalgias, and sputum production) and clinical findings (eg, temperature > 37.8 °C [100 °F], tachypnea, tachycardia, rales, and decreased breath sounds).^5,6 This meta-analysis includes these studies and more recent studies^7-9 used to develop a CDR that focuses solely on a few specific signs and symptoms that can reliably rule out CAP without imaging, and so prove highly useful for busy primary care clinicians.

STUDY SUMMARY

This simple approach rules out CAP in outpatients 99.6% of the time

This systematic review and meta-analysis included studies that used 2 or more signs, symptoms, or point-of-care tests to determine the patient’s risk for CAP.¹ Twelve studies (N = 10,254) met inclusion criteria by applying a CDR to adults or adolescents presenting with respiratory signs or symptoms potentially suggestive of CAP to either an outpatient setting or an ED. Prospective cohort, cross-sectional, and case-control studies were included when a chest x-ray or CT was utilized as the primary reference standard. Exclusion criteria included studies of military or nursing home populations and studies in which the majority of patients had hospital- or ventilator-associated pneumonia or were immunocompromised.

For adult outpatients who present with acute cough, this clinical decision rule can quickly and accurately rule out CAP without the need for diagnostic imaging.

A simple, highly useful CDR emerged from 3 of the studies (N = 1865).^7-9 Two of these studies were described as case-control studies with prospective enrollment of patients older than 17 years in both outpatient and ED settings.^7,8 One study was conducted in the United States (mean age, 65 years) and the other in Iran (mean age, 60 years). The third was a Chilean prospective cohort study of ED patients older than 15 years (mean age, 53 years).⁹ In each of these studies, the outpatient or ED physicians collected all clinical data and documented their physical exam prior to receiving the chest radiograph results. The radiologists were masked to the clinical findings at the time of their interpretation.

Results. From the meta-analysis, a simple CDR emerged for patients with normal vital signs (temperature, respiratory rate, and heart rate) and a normal pulmonary exam that virtually ruled out CAP (sensitivity = 96%; 95% CI, 92%–98%; and negative likelihood ratio = 0.10; 95% CI, 0.07–0.13). In patients presenting to an outpatient clinic with acute cough with a 4% baseline prevalence rate of pneumonia, this CDR ruled out CAP 99.6% of the time.

Continue to: WHAT'S NEW

A clinical decision rule validated for accuracy

This is the first validated CDR that accurately rules out CAP in the outpatient or ED setting using parameters easily obtainable during a clinical exam.

CAVEATS

Proceed with caution in the young and the very old

Two of the 3 studies in this CDR had an overall moderate risk of bias, whereas the third study was determined to be at low risk of bias, based on appraisal with the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) framework.¹⁰

The mean age range in these 3 studies was 53 to 66 years (without further data such as standard deviation), suggesting that application of the CDR to adults who fall at extremes of age should be done with a modicum of caution.

Additionally, although the symptom complex of COVID-19 pneumonia would suggest that this CDR would likely remain accurate today, it has not been validated in patients with COVID-19 infection.

CHALLENGES TO IMPLEMENTATION

Potential reluctance to forgo imaging

Beyond the caveats regarding COVID-19, the use of a simple CDR to reliably exclude pneumonia should have no barrier to implementation in an outpatient primary care setting or ED, although there could be reluctance on the part of both providers and patients to fully embrace this simple tool without a confirmatory chest x-ray.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

THE CASE

John C* is a 57-year-old man with hypertension, hyperlipidemia, and schizophrenia who followed up with a psychiatrist monthly at the community mental health center (CMHC). He had no primary care doctor. His psychiatrist referred him to our new Integrated Behavioral Health (IBH) clinic, also located in the CMHC, to see a family physician for complaints of urinary frequency, blurred vision, thirst, and weight loss. An on-site fingerstick revealed his blood glucose to be 357 mg/dL. Given the presumptive diagnosis of diabetes, we checked his bloodwork, prescribed metformin, and referred him for diabetes education. That evening, his lab results showed a hemoglobin A1C > 17%, a basic metabolic panel with an anion gap, ketones in the urine, and a low C-peptide level. We were unable to reach Mr. C by phone for further management.

● How would you proceed with this patient?

* The patient’s name has been changed to protect his identity.

Coordination of behavioral health and primary care can take many forms, from simple synchronized care via referral, to co-located services, to fully integrated care.¹ Reverse integration, the subject of this article, is the provision of primary care in mental health or substance use disorder treatment settings. Published evidence to date regarding this model is minimal. This article describes our experience in developing a model of reverse integration in which family physicians and nurse practitioners are embedded in a CMHC with psychiatric providers, counselors, and social workers to jointly address physical and behavioral health care issues and address social determinants of health.

The rationale for reverse integration

Many individuals with serious mental illness (SMI), including schizophrenia and bipolar disorder, have rates of comorbid chronic physical health conditions that are higher than in the general population. These conditions include obesity, diabetes, metabolic syndrome, cardiovascular disease, chronic obstructive pulmonary disease, HIV, viral hepatitis, and tuberculosis.² Outcomes in the SMI group are also considerably worse than in the general population. People with SMI have a demonstrated loss of up to 32 years of potential life per patient compared with the general-­population average, primarily due to poor physical health.² Maladaptive health behaviors such as poor diet, lack of physical activity, tobacco use, and substance use contribute to this increased mortality.^2,3 Social determinants of poor health are more prevalent among individuals with SMI, and a relative inability to collaborate in one’s own health care due to psychiatric symptoms further exacerbates the challenges.

Patients at a community mental health center may grow tired of conversation or feel overwhelmed in completing multiple tasks. Visits may need to be shorter and more frequent.

Many individuals with SMI receive psychiatric care, case management, counseling, and psychosocial services in CMHCs. Their psychiatric caregiver may be their only regular health care provider. Family physicians—who receive residency training in behavioral health and social determinants of health in community settings—are distinctively capable of improving overall health care outcomes of patients with SMI.

THE ADVANTAGES OF A REVERSE-INTEGRATION PRACTICE MODEL

Delivering primary care in a CMHC with a behavioral health team can benefit patients with SMI and be a satisfying practice for family physicians. Specifically, family physicians

• find that caring for complex patients can be less stressful because they benefit from the knowledge and resources of the CMHC team. The CMHC team offers case management, counseling, employment services, and housing assistance, so the primary care provider and patient are well supported.
• see fewer patients per hour due to higher visit complexity (and coding). In our experience, team-based care and additional time with patients make complex patient care more enjoyable and less frustrating.
• benefit from a situation in which patients feel safe because the CMHC support staff knows them well.

Continue to: Other benefits

Other benefits. When primary care is delivered in a CMHC, there are “huddles” and warm handoffs that allow for bidirectional collaboration and care coordination between the primary care and behavioral health teams in real time. In addition, family medicine residents, medical students, and other learners can be successfully included in an IBH clinic for patients with SMI. The behavioral health team provides the mentorship, education, and modelling of skills needed to work with this population, including limit-setting, empathy, patience, and motivational interviewing.

For their part, learners self-report increased comfort and interest in working with underserved populations and improved awareness of the social determinants of health after these experiences.^4,5 Many patients at CMHCs are comfortable working with learners if continuity is maintained with a primary care provider.

Challenges we’ve faced, tips we can offer

For primary care providers, the unique workplace culture, terminology, and patient population encountered in a CMHC can be challenging. Also challenging can be the combining of things such as electronic medical records (EMRs).

Culture. The CMHC model focuses on team-based care spearheaded by case managers, in contrast to the traditional family medicine model wherein the physician coordinates services. Case managers provide assessments of client stability and readiness to be seen. They also attend primary care visits to support patient interactions, provide important psychosocial information, and assess adherence to care.

Terminology. It’s not always easy to shift to different terminology in this culture. Thus, orientation needs to address things such as the use of the word “patient,” rather than “client,” when charting.

Continue to: The complexities of the patient population

The complexities of the patient population. Many patients treated at a CMHC have a history of trauma, anxiety, and paranoia, requiring adjustments to exam practices such as using smaller speculums, providing more physical space, and offering to leave examination room doors open while patients are waiting.

In addition, individuals with SMI often have multiple health conditions, but they may become uncomfortable with physical closeness, grow tired of conversation, or feel overwhelmed when asked to complete multiple tasks in 1 visit. As a result, visits may need to be shorter and more frequent.

It’s also worth noting that, in our experience, CMHC patients may have a higher no-show rate than typical primary care clinics, requiring flexibility in scheduling. To fill vacant primary care time slots, our front desk staff uses strategies such as waiting lists and offering walk-in visits to patients who are on site for other services.

Ideally, IBH clinics use a single, fully integrated EMR, but this is not always possible. If the primary care and CMHC EMR systems do not connect, then record review and repeat documentation is needed, while care is taken to adhere to the confidentiality standards of a particular state.

Standards of care and state policies. Written standards of care, procedures, and accreditation in CMHCs rarely include provisions for common primary care practice, such as vaccines, in-clinic medications, and implements for simple procedures. To provide these services in our clinic, we ordered/stocked the needed supplies and instituted protocols that mirrored our other outpatient family medicine clinical sites.

Continue to: Some states may have...

Some states may have policies that prevent reimbursement for mental health and primary care services billed on the same day. Seeing a family physician and a psychiatry provider on the same day is convenient for patients and allows for collaboration between providers. But reimbursement rules can vary by state, so starting an IBH clinic like this requires research into local billing regulations.

WANT TO START AN INTEGRATED BEHAVIORAL HEALTH CLINIC?

Detailed instruction on starting a primary care clinic in a CMHC is beyond the scope of this article. However, the Substance Abuse and Mental Health Services Administration provides guidance on integrating primary care services into a local CMHC.⁶ Start by performing a baseline needs assessment of the CMHC and its patients to help guide clinic design. Leadership buy-in is key.

The community mental health center model focuses on team-based care spearheaded by case managers. This contrasts with the family medicine model, in which the physician coordinates services.

Leadership must provide adequate time and financial and technological support. This includes identifying appropriate space for primary care, offering training on using the EMR, and obtaining support from Finance to develop a realistic and competent business plan with an appropriate budgetary runway for start-up. (This may include securing grants in the beginning.)

We recommend starting small and expanding slowly. Once the clinic is operational, formal pathways for good communication are necessary. This includes holding regular team meetings to develop and revise clinic workflows—eg, patient enrollment, protocols, and administrative procedures such as managing medications and vaccinations—as well as addressing space, staffing, and training issues that arise. The IBH transitional leadership structure must include clinicians from both primary care and behavioral health, support staff, and the administration. Finally, you need the right staff—people who are passionate, flexible, and interested in trying something new.

THE CASE

The next day, an outreach was made to the CMHC nurse, who had the case manager go to Mr. C’s house and bring him to the CMHC for education on insulin injection, glucometer use, and diabetes nutrition. Mr. C was prescribed long-acting insulin at bedtime; his metformin was stopped and he was monitored closely.

Continue to: Mr. C now calls...

Mr. C now calls the CMHC nurse every few weeks to report his blood sugar levels, have his insulin dose adjusted, or just say “hello.” He continues to see his psychiatrist every month and his family physician every 4 months. The team collaborates as issues arise. His diabetes has been well controlled for more than 3 years.

The IBH clinic has grown in number of patients and family medicine providers, is self-sustaining, and has expanded services to include hepatitis C treatment. 

THE CASE

John C* is a 57-year-old man with hypertension, hyperlipidemia, and schizophrenia who followed up with a psychiatrist monthly at the community mental health center (CMHC). He had no primary care doctor. His psychiatrist referred him to our new Integrated Behavioral Health (IBH) clinic, also located in the CMHC, to see a family physician for complaints of urinary frequency, blurred vision, thirst, and weight loss. An on-site fingerstick revealed his blood glucose to be 357 mg/dL. Given the presumptive diagnosis of diabetes, we checked his bloodwork, prescribed metformin, and referred him for diabetes education. That evening, his lab results showed a hemoglobin A1C > 17%, a basic metabolic panel with an anion gap, ketones in the urine, and a low C-peptide level. We were unable to reach Mr. C by phone for further management.

● How would you proceed with this patient?

* The patient’s name has been changed to protect his identity.

Coordination of behavioral health and primary care can take many forms, from simple synchronized care via referral, to co-located services, to fully integrated care.¹ Reverse integration, the subject of this article, is the provision of primary care in mental health or substance use disorder treatment settings. Published evidence to date regarding this model is minimal. This article describes our experience in developing a model of reverse integration in which family physicians and nurse practitioners are embedded in a CMHC with psychiatric providers, counselors, and social workers to jointly address physical and behavioral health care issues and address social determinants of health.

The rationale for reverse integration

Many individuals with serious mental illness (SMI), including schizophrenia and bipolar disorder, have rates of comorbid chronic physical health conditions that are higher than in the general population. These conditions include obesity, diabetes, metabolic syndrome, cardiovascular disease, chronic obstructive pulmonary disease, HIV, viral hepatitis, and tuberculosis.² Outcomes in the SMI group are also considerably worse than in the general population. People with SMI have a demonstrated loss of up to 32 years of potential life per patient compared with the general-­population average, primarily due to poor physical health.² Maladaptive health behaviors such as poor diet, lack of physical activity, tobacco use, and substance use contribute to this increased mortality.^2,3 Social determinants of poor health are more prevalent among individuals with SMI, and a relative inability to collaborate in one’s own health care due to psychiatric symptoms further exacerbates the challenges.

Patients at a community mental health center may grow tired of conversation or feel overwhelmed in completing multiple tasks. Visits may need to be shorter and more frequent.

Many individuals with SMI receive psychiatric care, case management, counseling, and psychosocial services in CMHCs. Their psychiatric caregiver may be their only regular health care provider. Family physicians—who receive residency training in behavioral health and social determinants of health in community settings—are distinctively capable of improving overall health care outcomes of patients with SMI.

THE ADVANTAGES OF A REVERSE-INTEGRATION PRACTICE MODEL

Delivering primary care in a CMHC with a behavioral health team can benefit patients with SMI and be a satisfying practice for family physicians. Specifically, family physicians

• find that caring for complex patients can be less stressful because they benefit from the knowledge and resources of the CMHC team. The CMHC team offers case management, counseling, employment services, and housing assistance, so the primary care provider and patient are well supported.
• see fewer patients per hour due to higher visit complexity (and coding). In our experience, team-based care and additional time with patients make complex patient care more enjoyable and less frustrating.
• benefit from a situation in which patients feel safe because the CMHC support staff knows them well.

Continue to: Other benefits

Other benefits. When primary care is delivered in a CMHC, there are “huddles” and warm handoffs that allow for bidirectional collaboration and care coordination between the primary care and behavioral health teams in real time. In addition, family medicine residents, medical students, and other learners can be successfully included in an IBH clinic for patients with SMI. The behavioral health team provides the mentorship, education, and modelling of skills needed to work with this population, including limit-setting, empathy, patience, and motivational interviewing.

For their part, learners self-report increased comfort and interest in working with underserved populations and improved awareness of the social determinants of health after these experiences.^4,5 Many patients at CMHCs are comfortable working with learners if continuity is maintained with a primary care provider.

Challenges we’ve faced, tips we can offer

For primary care providers, the unique workplace culture, terminology, and patient population encountered in a CMHC can be challenging. Also challenging can be the combining of things such as electronic medical records (EMRs).

Culture. The CMHC model focuses on team-based care spearheaded by case managers, in contrast to the traditional family medicine model wherein the physician coordinates services. Case managers provide assessments of client stability and readiness to be seen. They also attend primary care visits to support patient interactions, provide important psychosocial information, and assess adherence to care.

Terminology. It’s not always easy to shift to different terminology in this culture. Thus, orientation needs to address things such as the use of the word “patient,” rather than “client,” when charting.

Continue to: The complexities of the patient population

The complexities of the patient population. Many patients treated at a CMHC have a history of trauma, anxiety, and paranoia, requiring adjustments to exam practices such as using smaller speculums, providing more physical space, and offering to leave examination room doors open while patients are waiting.

In addition, individuals with SMI often have multiple health conditions, but they may become uncomfortable with physical closeness, grow tired of conversation, or feel overwhelmed when asked to complete multiple tasks in 1 visit. As a result, visits may need to be shorter and more frequent.

It’s also worth noting that, in our experience, CMHC patients may have a higher no-show rate than typical primary care clinics, requiring flexibility in scheduling. To fill vacant primary care time slots, our front desk staff uses strategies such as waiting lists and offering walk-in visits to patients who are on site for other services.

Ideally, IBH clinics use a single, fully integrated EMR, but this is not always possible. If the primary care and CMHC EMR systems do not connect, then record review and repeat documentation is needed, while care is taken to adhere to the confidentiality standards of a particular state.

Standards of care and state policies. Written standards of care, procedures, and accreditation in CMHCs rarely include provisions for common primary care practice, such as vaccines, in-clinic medications, and implements for simple procedures. To provide these services in our clinic, we ordered/stocked the needed supplies and instituted protocols that mirrored our other outpatient family medicine clinical sites.

Continue to: Some states may have...

Some states may have policies that prevent reimbursement for mental health and primary care services billed on the same day. Seeing a family physician and a psychiatry provider on the same day is convenient for patients and allows for collaboration between providers. But reimbursement rules can vary by state, so starting an IBH clinic like this requires research into local billing regulations.

WANT TO START AN INTEGRATED BEHAVIORAL HEALTH CLINIC?

Detailed instruction on starting a primary care clinic in a CMHC is beyond the scope of this article. However, the Substance Abuse and Mental Health Services Administration provides guidance on integrating primary care services into a local CMHC.⁶ Start by performing a baseline needs assessment of the CMHC and its patients to help guide clinic design. Leadership buy-in is key.

The community mental health center model focuses on team-based care spearheaded by case managers. This contrasts with the family medicine model, in which the physician coordinates services.

Leadership must provide adequate time and financial and technological support. This includes identifying appropriate space for primary care, offering training on using the EMR, and obtaining support from Finance to develop a realistic and competent business plan with an appropriate budgetary runway for start-up. (This may include securing grants in the beginning.)

We recommend starting small and expanding slowly. Once the clinic is operational, formal pathways for good communication are necessary. This includes holding regular team meetings to develop and revise clinic workflows—eg, patient enrollment, protocols, and administrative procedures such as managing medications and vaccinations—as well as addressing space, staffing, and training issues that arise. The IBH transitional leadership structure must include clinicians from both primary care and behavioral health, support staff, and the administration. Finally, you need the right staff—people who are passionate, flexible, and interested in trying something new.

THE CASE

The next day, an outreach was made to the CMHC nurse, who had the case manager go to Mr. C’s house and bring him to the CMHC for education on insulin injection, glucometer use, and diabetes nutrition. Mr. C was prescribed long-acting insulin at bedtime; his metformin was stopped and he was monitored closely.

Continue to: Mr. C now calls...

Mr. C now calls the CMHC nurse every few weeks to report his blood sugar levels, have his insulin dose adjusted, or just say “hello.” He continues to see his psychiatrist every month and his family physician every 4 months. The team collaborates as issues arise. His diabetes has been well controlled for more than 3 years.

The IBH clinic has grown in number of patients and family medicine providers, is self-sustaining, and has expanded services to include hepatitis C treatment. 

THE CASE

John C* is a 57-year-old man with hypertension, hyperlipidemia, and schizophrenia who followed up with a psychiatrist monthly at the community mental health center (CMHC). He had no primary care doctor. His psychiatrist referred him to our new Integrated Behavioral Health (IBH) clinic, also located in the CMHC, to see a family physician for complaints of urinary frequency, blurred vision, thirst, and weight loss. An on-site fingerstick revealed his blood glucose to be 357 mg/dL. Given the presumptive diagnosis of diabetes, we checked his bloodwork, prescribed metformin, and referred him for diabetes education. That evening, his lab results showed a hemoglobin A1C > 17%, a basic metabolic panel with an anion gap, ketones in the urine, and a low C-peptide level. We were unable to reach Mr. C by phone for further management.

● How would you proceed with this patient?

* The patient’s name has been changed to protect his identity.

Coordination of behavioral health and primary care can take many forms, from simple synchronized care via referral, to co-located services, to fully integrated care.¹ Reverse integration, the subject of this article, is the provision of primary care in mental health or substance use disorder treatment settings. Published evidence to date regarding this model is minimal. This article describes our experience in developing a model of reverse integration in which family physicians and nurse practitioners are embedded in a CMHC with psychiatric providers, counselors, and social workers to jointly address physical and behavioral health care issues and address social determinants of health.

The rationale for reverse integration

Many individuals with serious mental illness (SMI), including schizophrenia and bipolar disorder, have rates of comorbid chronic physical health conditions that are higher than in the general population. These conditions include obesity, diabetes, metabolic syndrome, cardiovascular disease, chronic obstructive pulmonary disease, HIV, viral hepatitis, and tuberculosis.² Outcomes in the SMI group are also considerably worse than in the general population. People with SMI have a demonstrated loss of up to 32 years of potential life per patient compared with the general-­population average, primarily due to poor physical health.² Maladaptive health behaviors such as poor diet, lack of physical activity, tobacco use, and substance use contribute to this increased mortality.^2,3 Social determinants of poor health are more prevalent among individuals with SMI, and a relative inability to collaborate in one’s own health care due to psychiatric symptoms further exacerbates the challenges.

Patients at a community mental health center may grow tired of conversation or feel overwhelmed in completing multiple tasks. Visits may need to be shorter and more frequent.

Many individuals with SMI receive psychiatric care, case management, counseling, and psychosocial services in CMHCs. Their psychiatric caregiver may be their only regular health care provider. Family physicians—who receive residency training in behavioral health and social determinants of health in community settings—are distinctively capable of improving overall health care outcomes of patients with SMI.

THE ADVANTAGES OF A REVERSE-INTEGRATION PRACTICE MODEL

Delivering primary care in a CMHC with a behavioral health team can benefit patients with SMI and be a satisfying practice for family physicians. Specifically, family physicians

• find that caring for complex patients can be less stressful because they benefit from the knowledge and resources of the CMHC team. The CMHC team offers case management, counseling, employment services, and housing assistance, so the primary care provider and patient are well supported.
• see fewer patients per hour due to higher visit complexity (and coding). In our experience, team-based care and additional time with patients make complex patient care more enjoyable and less frustrating.
• benefit from a situation in which patients feel safe because the CMHC support staff knows them well.

Continue to: Other benefits

Other benefits. When primary care is delivered in a CMHC, there are “huddles” and warm handoffs that allow for bidirectional collaboration and care coordination between the primary care and behavioral health teams in real time. In addition, family medicine residents, medical students, and other learners can be successfully included in an IBH clinic for patients with SMI. The behavioral health team provides the mentorship, education, and modelling of skills needed to work with this population, including limit-setting, empathy, patience, and motivational interviewing.

For their part, learners self-report increased comfort and interest in working with underserved populations and improved awareness of the social determinants of health after these experiences.^4,5 Many patients at CMHCs are comfortable working with learners if continuity is maintained with a primary care provider.

Challenges we’ve faced, tips we can offer

For primary care providers, the unique workplace culture, terminology, and patient population encountered in a CMHC can be challenging. Also challenging can be the combining of things such as electronic medical records (EMRs).

Culture. The CMHC model focuses on team-based care spearheaded by case managers, in contrast to the traditional family medicine model wherein the physician coordinates services. Case managers provide assessments of client stability and readiness to be seen. They also attend primary care visits to support patient interactions, provide important psychosocial information, and assess adherence to care.

Terminology. It’s not always easy to shift to different terminology in this culture. Thus, orientation needs to address things such as the use of the word “patient,” rather than “client,” when charting.

Continue to: The complexities of the patient population

The complexities of the patient population. Many patients treated at a CMHC have a history of trauma, anxiety, and paranoia, requiring adjustments to exam practices such as using smaller speculums, providing more physical space, and offering to leave examination room doors open while patients are waiting.

In addition, individuals with SMI often have multiple health conditions, but they may become uncomfortable with physical closeness, grow tired of conversation, or feel overwhelmed when asked to complete multiple tasks in 1 visit. As a result, visits may need to be shorter and more frequent.

It’s also worth noting that, in our experience, CMHC patients may have a higher no-show rate than typical primary care clinics, requiring flexibility in scheduling. To fill vacant primary care time slots, our front desk staff uses strategies such as waiting lists and offering walk-in visits to patients who are on site for other services.

Ideally, IBH clinics use a single, fully integrated EMR, but this is not always possible. If the primary care and CMHC EMR systems do not connect, then record review and repeat documentation is needed, while care is taken to adhere to the confidentiality standards of a particular state.

Standards of care and state policies. Written standards of care, procedures, and accreditation in CMHCs rarely include provisions for common primary care practice, such as vaccines, in-clinic medications, and implements for simple procedures. To provide these services in our clinic, we ordered/stocked the needed supplies and instituted protocols that mirrored our other outpatient family medicine clinical sites.

Continue to: Some states may have...

Some states may have policies that prevent reimbursement for mental health and primary care services billed on the same day. Seeing a family physician and a psychiatry provider on the same day is convenient for patients and allows for collaboration between providers. But reimbursement rules can vary by state, so starting an IBH clinic like this requires research into local billing regulations.

WANT TO START AN INTEGRATED BEHAVIORAL HEALTH CLINIC?

Detailed instruction on starting a primary care clinic in a CMHC is beyond the scope of this article. However, the Substance Abuse and Mental Health Services Administration provides guidance on integrating primary care services into a local CMHC.⁶ Start by performing a baseline needs assessment of the CMHC and its patients to help guide clinic design. Leadership buy-in is key.

The community mental health center model focuses on team-based care spearheaded by case managers. This contrasts with the family medicine model, in which the physician coordinates services.

Leadership must provide adequate time and financial and technological support. This includes identifying appropriate space for primary care, offering training on using the EMR, and obtaining support from Finance to develop a realistic and competent business plan with an appropriate budgetary runway for start-up. (This may include securing grants in the beginning.)

We recommend starting small and expanding slowly. Once the clinic is operational, formal pathways for good communication are necessary. This includes holding regular team meetings to develop and revise clinic workflows—eg, patient enrollment, protocols, and administrative procedures such as managing medications and vaccinations—as well as addressing space, staffing, and training issues that arise. The IBH transitional leadership structure must include clinicians from both primary care and behavioral health, support staff, and the administration. Finally, you need the right staff—people who are passionate, flexible, and interested in trying something new.

THE CASE

The next day, an outreach was made to the CMHC nurse, who had the case manager go to Mr. C’s house and bring him to the CMHC for education on insulin injection, glucometer use, and diabetes nutrition. Mr. C was prescribed long-acting insulin at bedtime; his metformin was stopped and he was monitored closely.

Continue to: Mr. C now calls...

Mr. C now calls the CMHC nurse every few weeks to report his blood sugar levels, have his insulin dose adjusted, or just say “hello.” He continues to see his psychiatrist every month and his family physician every 4 months. The team collaborates as issues arise. His diabetes has been well controlled for more than 3 years.

The IBH clinic has grown in number of patients and family medicine providers, is self-sustaining, and has expanded services to include hepatitis C treatment. 

In 2015-2016, almost 40% of adults and 18.5% of children ages 2 to 19 years in the United States met the definition for obesity—a chronic, relapsing, multifactorial, neurobehavioral disease that results in adverse metabolic, biomechanical, and psychosocial health consequences.^1,2

Tremendous resources have been invested in research, policy development, and public education to try to prevent obesity and its related complications. Despite this, the obesity epidemic has worsened. Here, we explore how to evaluate and treat obese patients in a primary care setting based on the evidence and our experience seeing patients specifically for weight management in a family medicine residency teaching clinic. Pharmacotherapy and surgery, while often helpful, are outside the scope of this article.

It begins withan obesity-friendly office

Patients may have reservations about health care interactions specific to obesity, so it is important to invite them into a setting that facilitates trust and encourages collaboration. Actively engage patients with unhealthy weight by creating an environment where they feel comfortable. Offer wide chairs without armrests, which will easily accommodate patients of all sizes, and ensure that scales have a weight capacity > 400 lb. Communicate a message to patients, via waiting room materials and videos, that focuses on health rather than on weight or body mass index (BMI).

Understand the patient’s goals and challenges

Most (although not all) family physicians will see obese patients in the context of a visit for diabetes, hypertension, or another condition. However, we feel that having visits specifically to address weight in the initial stages of weight management is helpful. The focus of an initial visit should be getting to know how obesity has affected the patient and what his or her motive is in attempting to lose weight. Explore previous attempts at weight loss and establish what the patient’s highest weight has been, as this will impact weight-loss goals. For example, if a patient has weighed > 300 lb all her adult life, it will be extremely difficult to maintain a weight loss of 150 lb.

What else to ask about. Discuss stressors that may be causing increased food intake or poor food choices, including hunger, anger, loneliness, and sleep difficulties. Multidisciplinary care including a psychologist can aid in addressing these issues. Ask patients if they keep a food diary (and if not, recommend that they start), as food diaries are often helpful in elucidating eating and drinking patterns. Determine a patient’s current and past levels of physical activity, as this will guide the fitness goals you develop for him or her.

Screen for psychosocial disorders

As noted earlier, the physical component of obesity is commonly associated with mood disorders such as anxiety and depression.² This requires a multidisciplinary team effort to facilitate healing in the patient struggling with obesity.

Screening for depression and anxiety using standardized tools such as the Patient Health Questionnaire-9 or the Generalized Anxiety Disorder-7 is encouraged in patients who are overweight or obese. Positive screens should be addressed as part of the patient’s treatment plan, as untreated depression and anxiety can inhibit success with weight loss. Be mindful that many medications commonly used to treat these conditions can impair weight loss and even promote weight gain.

Continue to: Don't overlook binge-eating disorders

Don’t overlook binge-eating disorders. Screening specifically for binge-eating disorders is important, given the implications on treatment. The US Department of Veterans Affairs developed a single-item tool for this purpose, the VA Binge Eating Screener. The validated questionnaire asks, “On average, how often have you eaten extremely large amounts of food at one time and felt that your eating was out of control at that time?” Response options are: “Never,” “< 1 time/week,” “1 time/week,” “2-4 times/week,” and “5+ times/week.” A response of ≥ 2 times/week had a sensitivity of 88.9% and specificity of 83.2% for binge-eating disorder.³

For patients who prefer a vegan or vegetarian whole food diet, it is important to note that these diets are generally deficient in vitamin B12 and omega 3 fatty acids, so supplementing these should be considered.

Patients with positive screens should undergo psychotherapy and consider pharmacotherapy with lisdexamfetamine as part of their treatment plan. Caution should be used if recommending intermittent fasting for someone with binge-eating disorder.

Evaluate for underlying causes and assess for comorbidities

Review the patient’s current medication list and history. Many medications can cause weight gain, and weight loss can often be achieved by deprescribing such medications. When feasible, prescribe an alternative medication with a more favorable weight profile. A previous article in The Journal of Family Practice addresses this in more depth.⁴

Laboratory and other testing

Laboratory analysis should primarily be focused on determining treatment alterations specific to underlying pathophysiology. Tests to consider ordering are outlined in the Table. Identification of underlying causes and/or comorbid conditions through such testing can guide medication changes, treatment choices, and diet recommendations.

Diabetes and insulin resistance. The American Diabetes Association recommends screening patients who are overweight or obese and have an additional risk factor for diabetes.⁵ This can be done by obtaining a fasting glucose level, hemoglobin A1C, or a 2-hour oral glucose tolerance test.

Continue to: Since it is known that...

Since it is known that insulin resistance increases the risk for coronary heart disease⁶ and can be treated effectively,⁷ we recommend testing for insulin resistance in patients who do not already have impaired fasting glucose, prediabetes, type 2 diabetes, or impaired glucose tolerance. The homeostatic model assessment for insulin resistance (HOMA-IR)⁸ is a measure of insulin resistance and can be calculated from the fasting insulin and fasting glucose levels. This measure should not be done in isolation, but it can be a useful adjunct in identifying patients with insulin resistance and directing treatment.

If there is evidence of diabetes or insulin resistance, consider treatment with metformin ± initiation of a low-carbohydrate diet.

Hypothyroidism. Consider screening for thyroid dysfunction with a thyroid-stimulating hormone level, if it has not been checked previously.

Renal abnormalities. When serum creatinine levels and glomerular filtration rate indicate chronic kidney disease, consider recommending a protein-restricted diet and adjust medications according to renal dosing protocols, as indicated.

Liver abnormalities, including nonalcoholic fatty liver disease (NAFLD). Monitor aspartate aminotransferase and alanine aminotransferase for resolution of elevations as weight loss is achieved. If abnormalities persist, consider ordering a liver ultrasound. Traditionally, low-calorie diets have been prescribed to treat NAFLD, but evidence shows that low-carbohydrate diets can also be effective.⁹

Continue to: Hypertriglyceridemia and low high-density lipoprotein (HDL) levels

Hypertriglyceridemia and low high-density lipoprotein (HDL) levels. Obtain a lipid panel if one has not been completed within the past several years, as hypertriglyceridemia and low HDL can improve dramatically with specific dietary changes.⁷ Observe trends to assess for resolution of lipid abnormalities as weight loss is achieved.

Gout. Consider checking a uric acid level if you are thinking about recommending a low-carbohydrate diet, particularly in patients with a history of gout, as this may temporarily increase the risk of gout flare.

Hypovitaminosis D. If the patient’s vitamin D level is low, consider appropriate supplementation to support the patient’s overall health. While vitamin D deficiency is common in obesity, the role of supplementation in this population is unclear.

Cardiovascular disease. Consider ordering an electrocardiogram, particularly if you are thinking of prescribing medication therapy. Use caution with initiation of certain medications, such as phentermine or diethylproprion, in the presence of arrhythmias or active cardiovascular disease.

Obstructive sleep apnea. Sleep health is important to address, since obesity is one of the most significant risk factors for obstructive sleep apnea.¹⁰ If your patient is given a diagnosis of OSA following a sleep study, consider treatment with continuous positive airway pressure (CPAP), although there are conflicting studies regarding the effects of CPAP therapy in OSA on weight.^11,12

Continue to: Provide guidance on lifestyle changes

Provide guidance on lifestyle changes

Addressing obesity with patients can be challenging in a busy primary care clinic, but it is imperative to helping patients achieve overall health. Counseling on nutrition and physical activity is an important part of this process.

There is no one-size-fits-all approach to nutrition counseling. Focus on creating individualized plans through which patients can achieve success. Some guidance follows, but also beware of common pitfalls that we have observed in clinical practice which, when addressed, can enable significant weight loss (see “Common pitfalls inhibiting weight loss”).

Choose an approach that works for the patient. Commonly prescribed diets to address obesity include, but are not limited to, Atkins, Dietary Approaches to Stop Hypertension (DASH), Glycemic Index, Mediterranean, Ornish, Paleolithic, Zone, whole food plant-based, and ketogenic. We attempt to engage patients in making the decision on what food choices are appropriate for them considering their food availability, culture, and belief systems. For patients who prefer a vegan or vegetarian whole food diet, it is important to note that these diets are generally deficient in vitamin B12 and omega 3 fatty acids, so supplementing these should be considered.

We recommend that patients focus on eliminating sweetened beverages, such as soft drinks, sports drinks, energy drinks, vitamin water, sweet tea, chocolate milk, and Frappuccinos.

Rather than focus on a specific diet, which may not be sustainable long term, encourage healthy eating habits. Low-­carbohydrate diets have been shown to promote greater weight loss compared to low-fat diets.^13,14 Low-calorie diets can also be quite effective in promoting short-term weight loss. In our clinic, when weight loss is the primary goal, patients are typically encouraged to focus on either calorie or carbohydrate restriction in the initial stages of weight loss.

Eliminate sugar and refined carbohydrates. While rigorous mortality data are not available, more recent trials have demonstrated significant improvements in atherosclerotic cardiovascular disease risk markers, including weight reduction and diabetes reversal, when following a diet that markedly decreases carbohydrate intake, especially sugar and refined carbohydrates.^7,14-17

Continue to: We recommend that patients focus...

We recommend that patients focus on eliminating sweetened beverages, such as soft drinks, sports drinks, energy drinks, vitamin water, sweet tea, chocolate milk, and Frappuccinos. We also recommend substantially limiting or eliminating fruit juices and fruit smoothies due to their high sugar content. For example, 8 oz of orange juice contains 26 g of carbohydrates, which is almost as much as 8 oz of soda.

Compared with eating whole fruit, consuming fruit juice has demonstrated a small amount of weight gain in young children and adults.^18,19 It also has shown a higher insulin response compared with eating the same amount of carbohydrates in whole fruit.²⁰ Better options to drink include water, unsweetened tea, and black coffee. Also, avoid ultra-processed carbohydrates from foods such as breads, cereals, and pastries, as they have similar effects on blood glucose when compared to sugar.²¹

Greatly restrict highly processed foods. The evidence suggests that the availability of processed food is associated with increasing obesity.²² Simple advice to offer your patients is to encourage them to shop the perimeter of the grocery store, where fresh produce, meat, and dairy products are primarily located, and avoid the inner aisles, which contain primarily processed foods. Choosing food items with 5 or fewer ingredients is a starting point when teaching patients to read labels.

Consider limiting saturated fats. In 1977, the Dietary Guidelines for Americans recommended that Americans eat no more than 30% of total energy intake from fat and less than 10% of total energy intake from saturated fat; however, no randomized controlled trials had been done that supported this recommendation and epidemiologic data supporting it were weak.²³

The 2015 Dietary Guidelines continue to recommend limiting total energy intake from saturated fats.²⁴ While there may be a small decrease in cardiovascular risk with a reduction of saturated fat intake and replacement with unsaturated fats, no overall mortality benefit has been demonstrated.^24,25 More research is needed in this area to guide patients in decisions regarding consumption of saturated fats and what types of unsaturated fats are best for their health.

Continue to: Eat only 3 meals per day

Eat only 3 meals per day, but aim for fewer than that. The prescription of fasting is a modality that can be used for weight loss and improved health. Fasting has been a prescribed healing practice for thousands of years.²⁶ It is a practice that virtually every major religion in the world embraces. Studies have demonstrated fasting to be safe and effective in the setting of obesity without significant comorbidities, and it may promote weight loss and metabolic health.^26-29

There are multiple types of intermittent fasting. A practical way for patients to start is by restricting the number of hours in which they eat or drink calorie-containing beverages to 8 hours per day. In our experience, this regimen is easier for most patients to follow than alternate-day or other longer fasts. While there has been caution in the prescription of intermittent fasting due to concerns about causing eating disorders, a recent small study did not demonstrate increased risk of eating disorders with daily intermittent fasting.³⁰

Participate in healthy exercise. Nonpharmacologic office-based strategies for treating obesity have generally focused on increasing exercise and decreasing caloric intake.³¹ While exercise has significant health benefits, including preventing weight regain, evidence does not support monotherapy with exercise as an effective long-term weight-loss strategy.³² There are no studies available that adequately support prescribing an exact dose of exercise.³³ Generally, less than 150 minutes of exercise per week is not effective and more than that does have a dose-related response.³³

Follow up to help patients stay on target

There is no ideal interval for follow-up visits. However, frequent visits—anywhere from weekly to monthly—in the initial stages of weight loss increase the patient’s sense of accountability and, in our experience, seem to be helpful.

Patients may also choose to track their progress by weighing themselves regularly. A small study published in the International Journal of Obesity found that patients who weighed themselves daily had greater and more sustained weight loss than those who didn’t.³⁴ But the decision of whether to weigh one’s self at home should be individualized for each patient.

CORRESPONDENCE
Wesley Eichorn, DO, 1000 Oakland Drive, Kalamazoo, MI 49008; [email protected]

In 2015-2016, almost 40% of adults and 18.5% of children ages 2 to 19 years in the United States met the definition for obesity—a chronic, relapsing, multifactorial, neurobehavioral disease that results in adverse metabolic, biomechanical, and psychosocial health consequences.^1,2

Tremendous resources have been invested in research, policy development, and public education to try to prevent obesity and its related complications. Despite this, the obesity epidemic has worsened. Here, we explore how to evaluate and treat obese patients in a primary care setting based on the evidence and our experience seeing patients specifically for weight management in a family medicine residency teaching clinic. Pharmacotherapy and surgery, while often helpful, are outside the scope of this article.

It begins withan obesity-friendly office

Patients may have reservations about health care interactions specific to obesity, so it is important to invite them into a setting that facilitates trust and encourages collaboration. Actively engage patients with unhealthy weight by creating an environment where they feel comfortable. Offer wide chairs without armrests, which will easily accommodate patients of all sizes, and ensure that scales have a weight capacity > 400 lb. Communicate a message to patients, via waiting room materials and videos, that focuses on health rather than on weight or body mass index (BMI).

Understand the patient’s goals and challenges

Most (although not all) family physicians will see obese patients in the context of a visit for diabetes, hypertension, or another condition. However, we feel that having visits specifically to address weight in the initial stages of weight management is helpful. The focus of an initial visit should be getting to know how obesity has affected the patient and what his or her motive is in attempting to lose weight. Explore previous attempts at weight loss and establish what the patient’s highest weight has been, as this will impact weight-loss goals. For example, if a patient has weighed > 300 lb all her adult life, it will be extremely difficult to maintain a weight loss of 150 lb.

What else to ask about. Discuss stressors that may be causing increased food intake or poor food choices, including hunger, anger, loneliness, and sleep difficulties. Multidisciplinary care including a psychologist can aid in addressing these issues. Ask patients if they keep a food diary (and if not, recommend that they start), as food diaries are often helpful in elucidating eating and drinking patterns. Determine a patient’s current and past levels of physical activity, as this will guide the fitness goals you develop for him or her.

Screen for psychosocial disorders

As noted earlier, the physical component of obesity is commonly associated with mood disorders such as anxiety and depression.² This requires a multidisciplinary team effort to facilitate healing in the patient struggling with obesity.

Screening for depression and anxiety using standardized tools such as the Patient Health Questionnaire-9 or the Generalized Anxiety Disorder-7 is encouraged in patients who are overweight or obese. Positive screens should be addressed as part of the patient’s treatment plan, as untreated depression and anxiety can inhibit success with weight loss. Be mindful that many medications commonly used to treat these conditions can impair weight loss and even promote weight gain.

Continue to: Don't overlook binge-eating disorders

Don’t overlook binge-eating disorders. Screening specifically for binge-eating disorders is important, given the implications on treatment. The US Department of Veterans Affairs developed a single-item tool for this purpose, the VA Binge Eating Screener. The validated questionnaire asks, “On average, how often have you eaten extremely large amounts of food at one time and felt that your eating was out of control at that time?” Response options are: “Never,” “< 1 time/week,” “1 time/week,” “2-4 times/week,” and “5+ times/week.” A response of ≥ 2 times/week had a sensitivity of 88.9% and specificity of 83.2% for binge-eating disorder.³

For patients who prefer a vegan or vegetarian whole food diet, it is important to note that these diets are generally deficient in vitamin B12 and omega 3 fatty acids, so supplementing these should be considered.

Patients with positive screens should undergo psychotherapy and consider pharmacotherapy with lisdexamfetamine as part of their treatment plan. Caution should be used if recommending intermittent fasting for someone with binge-eating disorder.

Evaluate for underlying causes and assess for comorbidities

Review the patient’s current medication list and history. Many medications can cause weight gain, and weight loss can often be achieved by deprescribing such medications. When feasible, prescribe an alternative medication with a more favorable weight profile. A previous article in The Journal of Family Practice addresses this in more depth.⁴

Laboratory and other testing

Laboratory analysis should primarily be focused on determining treatment alterations specific to underlying pathophysiology. Tests to consider ordering are outlined in the Table. Identification of underlying causes and/or comorbid conditions through such testing can guide medication changes, treatment choices, and diet recommendations.

Diabetes and insulin resistance. The American Diabetes Association recommends screening patients who are overweight or obese and have an additional risk factor for diabetes.⁵ This can be done by obtaining a fasting glucose level, hemoglobin A1C, or a 2-hour oral glucose tolerance test.

Continue to: Since it is known that...

Since it is known that insulin resistance increases the risk for coronary heart disease⁶ and can be treated effectively,⁷ we recommend testing for insulin resistance in patients who do not already have impaired fasting glucose, prediabetes, type 2 diabetes, or impaired glucose tolerance. The homeostatic model assessment for insulin resistance (HOMA-IR)⁸ is a measure of insulin resistance and can be calculated from the fasting insulin and fasting glucose levels. This measure should not be done in isolation, but it can be a useful adjunct in identifying patients with insulin resistance and directing treatment.

If there is evidence of diabetes or insulin resistance, consider treatment with metformin ± initiation of a low-carbohydrate diet.

Hypothyroidism. Consider screening for thyroid dysfunction with a thyroid-stimulating hormone level, if it has not been checked previously.

Renal abnormalities. When serum creatinine levels and glomerular filtration rate indicate chronic kidney disease, consider recommending a protein-restricted diet and adjust medications according to renal dosing protocols, as indicated.

Liver abnormalities, including nonalcoholic fatty liver disease (NAFLD). Monitor aspartate aminotransferase and alanine aminotransferase for resolution of elevations as weight loss is achieved. If abnormalities persist, consider ordering a liver ultrasound. Traditionally, low-calorie diets have been prescribed to treat NAFLD, but evidence shows that low-carbohydrate diets can also be effective.⁹

Continue to: Hypertriglyceridemia and low high-density lipoprotein (HDL) levels

Hypertriglyceridemia and low high-density lipoprotein (HDL) levels. Obtain a lipid panel if one has not been completed within the past several years, as hypertriglyceridemia and low HDL can improve dramatically with specific dietary changes.⁷ Observe trends to assess for resolution of lipid abnormalities as weight loss is achieved.

Gout. Consider checking a uric acid level if you are thinking about recommending a low-carbohydrate diet, particularly in patients with a history of gout, as this may temporarily increase the risk of gout flare.

Hypovitaminosis D. If the patient’s vitamin D level is low, consider appropriate supplementation to support the patient’s overall health. While vitamin D deficiency is common in obesity, the role of supplementation in this population is unclear.

Cardiovascular disease. Consider ordering an electrocardiogram, particularly if you are thinking of prescribing medication therapy. Use caution with initiation of certain medications, such as phentermine or diethylproprion, in the presence of arrhythmias or active cardiovascular disease.

Obstructive sleep apnea. Sleep health is important to address, since obesity is one of the most significant risk factors for obstructive sleep apnea.¹⁰ If your patient is given a diagnosis of OSA following a sleep study, consider treatment with continuous positive airway pressure (CPAP), although there are conflicting studies regarding the effects of CPAP therapy in OSA on weight.^11,12

Continue to: Provide guidance on lifestyle changes

Provide guidance on lifestyle changes

Addressing obesity with patients can be challenging in a busy primary care clinic, but it is imperative to helping patients achieve overall health. Counseling on nutrition and physical activity is an important part of this process.

There is no one-size-fits-all approach to nutrition counseling. Focus on creating individualized plans through which patients can achieve success. Some guidance follows, but also beware of common pitfalls that we have observed in clinical practice which, when addressed, can enable significant weight loss (see “Common pitfalls inhibiting weight loss”).

Choose an approach that works for the patient. Commonly prescribed diets to address obesity include, but are not limited to, Atkins, Dietary Approaches to Stop Hypertension (DASH), Glycemic Index, Mediterranean, Ornish, Paleolithic, Zone, whole food plant-based, and ketogenic. We attempt to engage patients in making the decision on what food choices are appropriate for them considering their food availability, culture, and belief systems. For patients who prefer a vegan or vegetarian whole food diet, it is important to note that these diets are generally deficient in vitamin B12 and omega 3 fatty acids, so supplementing these should be considered.

We recommend that patients focus on eliminating sweetened beverages, such as soft drinks, sports drinks, energy drinks, vitamin water, sweet tea, chocolate milk, and Frappuccinos.

Rather than focus on a specific diet, which may not be sustainable long term, encourage healthy eating habits. Low-­carbohydrate diets have been shown to promote greater weight loss compared to low-fat diets.^13,14 Low-calorie diets can also be quite effective in promoting short-term weight loss. In our clinic, when weight loss is the primary goal, patients are typically encouraged to focus on either calorie or carbohydrate restriction in the initial stages of weight loss.

Eliminate sugar and refined carbohydrates. While rigorous mortality data are not available, more recent trials have demonstrated significant improvements in atherosclerotic cardiovascular disease risk markers, including weight reduction and diabetes reversal, when following a diet that markedly decreases carbohydrate intake, especially sugar and refined carbohydrates.^7,14-17

Continue to: We recommend that patients focus...

We recommend that patients focus on eliminating sweetened beverages, such as soft drinks, sports drinks, energy drinks, vitamin water, sweet tea, chocolate milk, and Frappuccinos. We also recommend substantially limiting or eliminating fruit juices and fruit smoothies due to their high sugar content. For example, 8 oz of orange juice contains 26 g of carbohydrates, which is almost as much as 8 oz of soda.

Compared with eating whole fruit, consuming fruit juice has demonstrated a small amount of weight gain in young children and adults.^18,19 It also has shown a higher insulin response compared with eating the same amount of carbohydrates in whole fruit.²⁰ Better options to drink include water, unsweetened tea, and black coffee. Also, avoid ultra-processed carbohydrates from foods such as breads, cereals, and pastries, as they have similar effects on blood glucose when compared to sugar.²¹

Greatly restrict highly processed foods. The evidence suggests that the availability of processed food is associated with increasing obesity.²² Simple advice to offer your patients is to encourage them to shop the perimeter of the grocery store, where fresh produce, meat, and dairy products are primarily located, and avoid the inner aisles, which contain primarily processed foods. Choosing food items with 5 or fewer ingredients is a starting point when teaching patients to read labels.

Consider limiting saturated fats. In 1977, the Dietary Guidelines for Americans recommended that Americans eat no more than 30% of total energy intake from fat and less than 10% of total energy intake from saturated fat; however, no randomized controlled trials had been done that supported this recommendation and epidemiologic data supporting it were weak.²³

The 2015 Dietary Guidelines continue to recommend limiting total energy intake from saturated fats.²⁴ While there may be a small decrease in cardiovascular risk with a reduction of saturated fat intake and replacement with unsaturated fats, no overall mortality benefit has been demonstrated.^24,25 More research is needed in this area to guide patients in decisions regarding consumption of saturated fats and what types of unsaturated fats are best for their health.

Continue to: Eat only 3 meals per day

Eat only 3 meals per day, but aim for fewer than that. The prescription of fasting is a modality that can be used for weight loss and improved health. Fasting has been a prescribed healing practice for thousands of years.²⁶ It is a practice that virtually every major religion in the world embraces. Studies have demonstrated fasting to be safe and effective in the setting of obesity without significant comorbidities, and it may promote weight loss and metabolic health.^26-29

There are multiple types of intermittent fasting. A practical way for patients to start is by restricting the number of hours in which they eat or drink calorie-containing beverages to 8 hours per day. In our experience, this regimen is easier for most patients to follow than alternate-day or other longer fasts. While there has been caution in the prescription of intermittent fasting due to concerns about causing eating disorders, a recent small study did not demonstrate increased risk of eating disorders with daily intermittent fasting.³⁰

Participate in healthy exercise. Nonpharmacologic office-based strategies for treating obesity have generally focused on increasing exercise and decreasing caloric intake.³¹ While exercise has significant health benefits, including preventing weight regain, evidence does not support monotherapy with exercise as an effective long-term weight-loss strategy.³² There are no studies available that adequately support prescribing an exact dose of exercise.³³ Generally, less than 150 minutes of exercise per week is not effective and more than that does have a dose-related response.³³

Follow up to help patients stay on target

There is no ideal interval for follow-up visits. However, frequent visits—anywhere from weekly to monthly—in the initial stages of weight loss increase the patient’s sense of accountability and, in our experience, seem to be helpful.

Patients may also choose to track their progress by weighing themselves regularly. A small study published in the International Journal of Obesity found that patients who weighed themselves daily had greater and more sustained weight loss than those who didn’t.³⁴ But the decision of whether to weigh one’s self at home should be individualized for each patient.

CORRESPONDENCE
Wesley Eichorn, DO, 1000 Oakland Drive, Kalamazoo, MI 49008; [email protected]

In 2015-2016, almost 40% of adults and 18.5% of children ages 2 to 19 years in the United States met the definition for obesity—a chronic, relapsing, multifactorial, neurobehavioral disease that results in adverse metabolic, biomechanical, and psychosocial health consequences.^1,2

Tremendous resources have been invested in research, policy development, and public education to try to prevent obesity and its related complications. Despite this, the obesity epidemic has worsened. Here, we explore how to evaluate and treat obese patients in a primary care setting based on the evidence and our experience seeing patients specifically for weight management in a family medicine residency teaching clinic. Pharmacotherapy and surgery, while often helpful, are outside the scope of this article.

It begins withan obesity-friendly office

Patients may have reservations about health care interactions specific to obesity, so it is important to invite them into a setting that facilitates trust and encourages collaboration. Actively engage patients with unhealthy weight by creating an environment where they feel comfortable. Offer wide chairs without armrests, which will easily accommodate patients of all sizes, and ensure that scales have a weight capacity > 400 lb. Communicate a message to patients, via waiting room materials and videos, that focuses on health rather than on weight or body mass index (BMI).

Understand the patient’s goals and challenges

Most (although not all) family physicians will see obese patients in the context of a visit for diabetes, hypertension, or another condition. However, we feel that having visits specifically to address weight in the initial stages of weight management is helpful. The focus of an initial visit should be getting to know how obesity has affected the patient and what his or her motive is in attempting to lose weight. Explore previous attempts at weight loss and establish what the patient’s highest weight has been, as this will impact weight-loss goals. For example, if a patient has weighed > 300 lb all her adult life, it will be extremely difficult to maintain a weight loss of 150 lb.

What else to ask about. Discuss stressors that may be causing increased food intake or poor food choices, including hunger, anger, loneliness, and sleep difficulties. Multidisciplinary care including a psychologist can aid in addressing these issues. Ask patients if they keep a food diary (and if not, recommend that they start), as food diaries are often helpful in elucidating eating and drinking patterns. Determine a patient’s current and past levels of physical activity, as this will guide the fitness goals you develop for him or her.

Screen for psychosocial disorders

As noted earlier, the physical component of obesity is commonly associated with mood disorders such as anxiety and depression.² This requires a multidisciplinary team effort to facilitate healing in the patient struggling with obesity.

Screening for depression and anxiety using standardized tools such as the Patient Health Questionnaire-9 or the Generalized Anxiety Disorder-7 is encouraged in patients who are overweight or obese. Positive screens should be addressed as part of the patient’s treatment plan, as untreated depression and anxiety can inhibit success with weight loss. Be mindful that many medications commonly used to treat these conditions can impair weight loss and even promote weight gain.

Continue to: Don't overlook binge-eating disorders

Don’t overlook binge-eating disorders. Screening specifically for binge-eating disorders is important, given the implications on treatment. The US Department of Veterans Affairs developed a single-item tool for this purpose, the VA Binge Eating Screener. The validated questionnaire asks, “On average, how often have you eaten extremely large amounts of food at one time and felt that your eating was out of control at that time?” Response options are: “Never,” “< 1 time/week,” “1 time/week,” “2-4 times/week,” and “5+ times/week.” A response of ≥ 2 times/week had a sensitivity of 88.9% and specificity of 83.2% for binge-eating disorder.³

For patients who prefer a vegan or vegetarian whole food diet, it is important to note that these diets are generally deficient in vitamin B12 and omega 3 fatty acids, so supplementing these should be considered.

Patients with positive screens should undergo psychotherapy and consider pharmacotherapy with lisdexamfetamine as part of their treatment plan. Caution should be used if recommending intermittent fasting for someone with binge-eating disorder.

Evaluate for underlying causes and assess for comorbidities

Review the patient’s current medication list and history. Many medications can cause weight gain, and weight loss can often be achieved by deprescribing such medications. When feasible, prescribe an alternative medication with a more favorable weight profile. A previous article in The Journal of Family Practice addresses this in more depth.⁴

Laboratory and other testing

Laboratory analysis should primarily be focused on determining treatment alterations specific to underlying pathophysiology. Tests to consider ordering are outlined in the Table. Identification of underlying causes and/or comorbid conditions through such testing can guide medication changes, treatment choices, and diet recommendations.

Diabetes and insulin resistance. The American Diabetes Association recommends screening patients who are overweight or obese and have an additional risk factor for diabetes.⁵ This can be done by obtaining a fasting glucose level, hemoglobin A1C, or a 2-hour oral glucose tolerance test.

Continue to: Since it is known that...

Since it is known that insulin resistance increases the risk for coronary heart disease⁶ and can be treated effectively,⁷ we recommend testing for insulin resistance in patients who do not already have impaired fasting glucose, prediabetes, type 2 diabetes, or impaired glucose tolerance. The homeostatic model assessment for insulin resistance (HOMA-IR)⁸ is a measure of insulin resistance and can be calculated from the fasting insulin and fasting glucose levels. This measure should not be done in isolation, but it can be a useful adjunct in identifying patients with insulin resistance and directing treatment.

If there is evidence of diabetes or insulin resistance, consider treatment with metformin ± initiation of a low-carbohydrate diet.

Hypothyroidism. Consider screening for thyroid dysfunction with a thyroid-stimulating hormone level, if it has not been checked previously.

Renal abnormalities. When serum creatinine levels and glomerular filtration rate indicate chronic kidney disease, consider recommending a protein-restricted diet and adjust medications according to renal dosing protocols, as indicated.

Liver abnormalities, including nonalcoholic fatty liver disease (NAFLD). Monitor aspartate aminotransferase and alanine aminotransferase for resolution of elevations as weight loss is achieved. If abnormalities persist, consider ordering a liver ultrasound. Traditionally, low-calorie diets have been prescribed to treat NAFLD, but evidence shows that low-carbohydrate diets can also be effective.⁹

Continue to: Hypertriglyceridemia and low high-density lipoprotein (HDL) levels

Hypertriglyceridemia and low high-density lipoprotein (HDL) levels. Obtain a lipid panel if one has not been completed within the past several years, as hypertriglyceridemia and low HDL can improve dramatically with specific dietary changes.⁷ Observe trends to assess for resolution of lipid abnormalities as weight loss is achieved.

Gout. Consider checking a uric acid level if you are thinking about recommending a low-carbohydrate diet, particularly in patients with a history of gout, as this may temporarily increase the risk of gout flare.

Hypovitaminosis D. If the patient’s vitamin D level is low, consider appropriate supplementation to support the patient’s overall health. While vitamin D deficiency is common in obesity, the role of supplementation in this population is unclear.

Cardiovascular disease. Consider ordering an electrocardiogram, particularly if you are thinking of prescribing medication therapy. Use caution with initiation of certain medications, such as phentermine or diethylproprion, in the presence of arrhythmias or active cardiovascular disease.

Obstructive sleep apnea. Sleep health is important to address, since obesity is one of the most significant risk factors for obstructive sleep apnea.¹⁰ If your patient is given a diagnosis of OSA following a sleep study, consider treatment with continuous positive airway pressure (CPAP), although there are conflicting studies regarding the effects of CPAP therapy in OSA on weight.^11,12

Continue to: Provide guidance on lifestyle changes

Provide guidance on lifestyle changes

Addressing obesity with patients can be challenging in a busy primary care clinic, but it is imperative to helping patients achieve overall health. Counseling on nutrition and physical activity is an important part of this process.

There is no one-size-fits-all approach to nutrition counseling. Focus on creating individualized plans through which patients can achieve success. Some guidance follows, but also beware of common pitfalls that we have observed in clinical practice which, when addressed, can enable significant weight loss (see “Common pitfalls inhibiting weight loss”).

Choose an approach that works for the patient. Commonly prescribed diets to address obesity include, but are not limited to, Atkins, Dietary Approaches to Stop Hypertension (DASH), Glycemic Index, Mediterranean, Ornish, Paleolithic, Zone, whole food plant-based, and ketogenic. We attempt to engage patients in making the decision on what food choices are appropriate for them considering their food availability, culture, and belief systems. For patients who prefer a vegan or vegetarian whole food diet, it is important to note that these diets are generally deficient in vitamin B12 and omega 3 fatty acids, so supplementing these should be considered.

We recommend that patients focus on eliminating sweetened beverages, such as soft drinks, sports drinks, energy drinks, vitamin water, sweet tea, chocolate milk, and Frappuccinos.

Rather than focus on a specific diet, which may not be sustainable long term, encourage healthy eating habits. Low-­carbohydrate diets have been shown to promote greater weight loss compared to low-fat diets.^13,14 Low-calorie diets can also be quite effective in promoting short-term weight loss. In our clinic, when weight loss is the primary goal, patients are typically encouraged to focus on either calorie or carbohydrate restriction in the initial stages of weight loss.

Eliminate sugar and refined carbohydrates. While rigorous mortality data are not available, more recent trials have demonstrated significant improvements in atherosclerotic cardiovascular disease risk markers, including weight reduction and diabetes reversal, when following a diet that markedly decreases carbohydrate intake, especially sugar and refined carbohydrates.^7,14-17

Continue to: We recommend that patients focus...

We recommend that patients focus on eliminating sweetened beverages, such as soft drinks, sports drinks, energy drinks, vitamin water, sweet tea, chocolate milk, and Frappuccinos. We also recommend substantially limiting or eliminating fruit juices and fruit smoothies due to their high sugar content. For example, 8 oz of orange juice contains 26 g of carbohydrates, which is almost as much as 8 oz of soda.

Compared with eating whole fruit, consuming fruit juice has demonstrated a small amount of weight gain in young children and adults.^18,19 It also has shown a higher insulin response compared with eating the same amount of carbohydrates in whole fruit.²⁰ Better options to drink include water, unsweetened tea, and black coffee. Also, avoid ultra-processed carbohydrates from foods such as breads, cereals, and pastries, as they have similar effects on blood glucose when compared to sugar.²¹

Greatly restrict highly processed foods. The evidence suggests that the availability of processed food is associated with increasing obesity.²² Simple advice to offer your patients is to encourage them to shop the perimeter of the grocery store, where fresh produce, meat, and dairy products are primarily located, and avoid the inner aisles, which contain primarily processed foods. Choosing food items with 5 or fewer ingredients is a starting point when teaching patients to read labels.

Consider limiting saturated fats. In 1977, the Dietary Guidelines for Americans recommended that Americans eat no more than 30% of total energy intake from fat and less than 10% of total energy intake from saturated fat; however, no randomized controlled trials had been done that supported this recommendation and epidemiologic data supporting it were weak.²³

The 2015 Dietary Guidelines continue to recommend limiting total energy intake from saturated fats.²⁴ While there may be a small decrease in cardiovascular risk with a reduction of saturated fat intake and replacement with unsaturated fats, no overall mortality benefit has been demonstrated.^24,25 More research is needed in this area to guide patients in decisions regarding consumption of saturated fats and what types of unsaturated fats are best for their health.

Continue to: Eat only 3 meals per day

Eat only 3 meals per day, but aim for fewer than that. The prescription of fasting is a modality that can be used for weight loss and improved health. Fasting has been a prescribed healing practice for thousands of years.²⁶ It is a practice that virtually every major religion in the world embraces. Studies have demonstrated fasting to be safe and effective in the setting of obesity without significant comorbidities, and it may promote weight loss and metabolic health.^26-29

There are multiple types of intermittent fasting. A practical way for patients to start is by restricting the number of hours in which they eat or drink calorie-containing beverages to 8 hours per day. In our experience, this regimen is easier for most patients to follow than alternate-day or other longer fasts. While there has been caution in the prescription of intermittent fasting due to concerns about causing eating disorders, a recent small study did not demonstrate increased risk of eating disorders with daily intermittent fasting.³⁰

Participate in healthy exercise. Nonpharmacologic office-based strategies for treating obesity have generally focused on increasing exercise and decreasing caloric intake.³¹ While exercise has significant health benefits, including preventing weight regain, evidence does not support monotherapy with exercise as an effective long-term weight-loss strategy.³² There are no studies available that adequately support prescribing an exact dose of exercise.³³ Generally, less than 150 minutes of exercise per week is not effective and more than that does have a dose-related response.³³

Follow up to help patients stay on target

There is no ideal interval for follow-up visits. However, frequent visits—anywhere from weekly to monthly—in the initial stages of weight loss increase the patient’s sense of accountability and, in our experience, seem to be helpful.

Patients may also choose to track their progress by weighing themselves regularly. A small study published in the International Journal of Obesity found that patients who weighed themselves daily had greater and more sustained weight loss than those who didn’t.³⁴ But the decision of whether to weigh one’s self at home should be individualized for each patient.

CORRESPONDENCE
Wesley Eichorn, DO, 1000 Oakland Drive, Kalamazoo, MI 49008; [email protected]

For patients with Barrett’s esophagus, surveillance endoscopy detects high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) more often than previously reported, according to a retrospective analysis of more than 1,000 patients.

Neoplasia detection rate, defined as findings on initial surveillance endoscopy, was also lower than that observed in past studies, according to lead author Lovekirat Dhaliwal, MBBS, of Mayo Clinic, Rochester, Minn., and colleagues.

This study’s findings may help define quality control benchmarks for endoscopic surveillance of Barrett’s esophagus, the investigators wrote in Clinical Gastroenterology and Hepatology. Accurate metrics are needed, they noted, because almost 9 out of 10 patients with Barrett’s esophagus present with EAC outside of a surveillance program, which “may represent missed opportunities at screening.” At the same time, a previous study by the investigators and one from another group, have suggested that 25%-33% of HGD/EAC cases may go undetected by initial surveillance endoscopy.

“Dysplasia detection in [Barrett’s esophagus] is challenging because of its patchy distribution and often subtle appearance,” the investigators noted. “Lack of compliance with recommended biopsy guidelines is also well-documented.”

On the other hand, Dr. Dhaliwal and colleagues suggested that previous studies may not accurately portray community practice and, therefore, have limited value in determining quality control metrics. A 2019 review, for instance, reported a neoplasia detection rate of 7% among patients with Barrett’s esophagus, but this finding “is composed of data from largely referral center cohorts with endoscopy performed by experienced academic gastroenterologists,” they wrote, which may lead to overestimation of such detection.

To better characterize this landscape, the investigators conducted a retrospective analysis involving 1,066 patients with Barrett’s esophagus who underwent initial surveillance endoscopy between 1991 and 2019. Approximately three out of four surveillance endoscopies (77%) were performed by gastroenterologists, while the remaining were performed by nongastroenterologists, such as family practitioners or surgeons. About 60% of patients were adequately biopsied according to the Seattle protocol.

Analysis revealed that the neoplasia detection rate was 4.9% (95% confidence interval, 3.8%-6.4%), which is less than the previously reported rate of 7%. HGD was more common than EAC (33 cases vs. 20 cases). Out of 1,066 patients, 391 without neoplasia on initial endoscopy underwent repeat endoscopy within a year. Among these individuals, HGD or EAC was detected in eight patients, which suggests that 13% of diagnoses were missed on initial endoscopy, a rate well below the previously reported range of 25%-33%.
 

Technology challenged by technique

The neoplasia detection rate “appeared to increase significantly from 1991 to 2019 on univariate analysis (particularly after 2000), but this was not observed on multivariate analysis,” the investigators wrote. “This was despite the introduction of high definition monitors and high resolution endoscopes in subsequent years.

“This may suggest that in a low dysplasia prevalence setting, basic techniques such as careful white light inspection of the [Barrett’s esophagus] mucosa along with targeted and Seattle protocol biopsies may be more important,” they noted.

The importance of technique may be further supported by another finding: Gastroenterologists detected neoplasia almost four times as often as did nongastroenterologists (odds ratio, 3.6; P = .0154).

“This finding is novel and may be due to additional training in endoscopy, lesion recognition, and familiarity with surveillance guidelines in gastroenterologists,” the investigators wrote. “If this finding is replicated in other cohorts, it may support recommendations for the performance of surveillance by endoscopists trained in gastrointestinal endoscopy and well-versed in surveillance guidelines.

“[U]sing neoplasia detection as a quality metric coupled with outcome measures such as missed dysplasia rates could improve adherence to established biopsy protocols and improve the quality of care to patients,” they wrote. “Ultimately, this can be an opportunity to develop a high-value, evidence-based quality metric in [Barrett’s esophagus] surveillance.”

The authors acknowledged some limitations to their study. Its retrospective design meant no one biopsy protocol could be adopted across the entire study period; however, the results were “unchanged” when restricted to the period after introduction of the Seattle protocol in 2000. The study’s long period could have left results susceptible to changing guidelines, but the neoplasia detection rates remained relatively stable over time.

“Because prior reports consisted largely of tertiary care center cohorts, our findings may reflect the absence of referral bias and be more generalizable,” the investigators wrote.

The study was funded by the National Institute of Aging and the National Cancer Institute. The investigators disclosed relationships with Celgene, Nine Point Medical, Takeda, and others.

For patients with Barrett’s esophagus, surveillance endoscopy detects high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) more often than previously reported, according to a retrospective analysis of more than 1,000 patients.

Neoplasia detection rate, defined as findings on initial surveillance endoscopy, was also lower than that observed in past studies, according to lead author Lovekirat Dhaliwal, MBBS, of Mayo Clinic, Rochester, Minn., and colleagues.

This study’s findings may help define quality control benchmarks for endoscopic surveillance of Barrett’s esophagus, the investigators wrote in Clinical Gastroenterology and Hepatology. Accurate metrics are needed, they noted, because almost 9 out of 10 patients with Barrett’s esophagus present with EAC outside of a surveillance program, which “may represent missed opportunities at screening.” At the same time, a previous study by the investigators and one from another group, have suggested that 25%-33% of HGD/EAC cases may go undetected by initial surveillance endoscopy.

“Dysplasia detection in [Barrett’s esophagus] is challenging because of its patchy distribution and often subtle appearance,” the investigators noted. “Lack of compliance with recommended biopsy guidelines is also well-documented.”

On the other hand, Dr. Dhaliwal and colleagues suggested that previous studies may not accurately portray community practice and, therefore, have limited value in determining quality control metrics. A 2019 review, for instance, reported a neoplasia detection rate of 7% among patients with Barrett’s esophagus, but this finding “is composed of data from largely referral center cohorts with endoscopy performed by experienced academic gastroenterologists,” they wrote, which may lead to overestimation of such detection.

To better characterize this landscape, the investigators conducted a retrospective analysis involving 1,066 patients with Barrett’s esophagus who underwent initial surveillance endoscopy between 1991 and 2019. Approximately three out of four surveillance endoscopies (77%) were performed by gastroenterologists, while the remaining were performed by nongastroenterologists, such as family practitioners or surgeons. About 60% of patients were adequately biopsied according to the Seattle protocol.

Analysis revealed that the neoplasia detection rate was 4.9% (95% confidence interval, 3.8%-6.4%), which is less than the previously reported rate of 7%. HGD was more common than EAC (33 cases vs. 20 cases). Out of 1,066 patients, 391 without neoplasia on initial endoscopy underwent repeat endoscopy within a year. Among these individuals, HGD or EAC was detected in eight patients, which suggests that 13% of diagnoses were missed on initial endoscopy, a rate well below the previously reported range of 25%-33%.
 

Technology challenged by technique

The neoplasia detection rate “appeared to increase significantly from 1991 to 2019 on univariate analysis (particularly after 2000), but this was not observed on multivariate analysis,” the investigators wrote. “This was despite the introduction of high definition monitors and high resolution endoscopes in subsequent years.

“This may suggest that in a low dysplasia prevalence setting, basic techniques such as careful white light inspection of the [Barrett’s esophagus] mucosa along with targeted and Seattle protocol biopsies may be more important,” they noted.

The importance of technique may be further supported by another finding: Gastroenterologists detected neoplasia almost four times as often as did nongastroenterologists (odds ratio, 3.6; P = .0154).

“This finding is novel and may be due to additional training in endoscopy, lesion recognition, and familiarity with surveillance guidelines in gastroenterologists,” the investigators wrote. “If this finding is replicated in other cohorts, it may support recommendations for the performance of surveillance by endoscopists trained in gastrointestinal endoscopy and well-versed in surveillance guidelines.

“[U]sing neoplasia detection as a quality metric coupled with outcome measures such as missed dysplasia rates could improve adherence to established biopsy protocols and improve the quality of care to patients,” they wrote. “Ultimately, this can be an opportunity to develop a high-value, evidence-based quality metric in [Barrett’s esophagus] surveillance.”

The authors acknowledged some limitations to their study. Its retrospective design meant no one biopsy protocol could be adopted across the entire study period; however, the results were “unchanged” when restricted to the period after introduction of the Seattle protocol in 2000. The study’s long period could have left results susceptible to changing guidelines, but the neoplasia detection rates remained relatively stable over time.

“Because prior reports consisted largely of tertiary care center cohorts, our findings may reflect the absence of referral bias and be more generalizable,” the investigators wrote.

The study was funded by the National Institute of Aging and the National Cancer Institute. The investigators disclosed relationships with Celgene, Nine Point Medical, Takeda, and others.

For patients with Barrett’s esophagus, surveillance endoscopy detects high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) more often than previously reported, according to a retrospective analysis of more than 1,000 patients.

Neoplasia detection rate, defined as findings on initial surveillance endoscopy, was also lower than that observed in past studies, according to lead author Lovekirat Dhaliwal, MBBS, of Mayo Clinic, Rochester, Minn., and colleagues.

This study’s findings may help define quality control benchmarks for endoscopic surveillance of Barrett’s esophagus, the investigators wrote in Clinical Gastroenterology and Hepatology. Accurate metrics are needed, they noted, because almost 9 out of 10 patients with Barrett’s esophagus present with EAC outside of a surveillance program, which “may represent missed opportunities at screening.” At the same time, a previous study by the investigators and one from another group, have suggested that 25%-33% of HGD/EAC cases may go undetected by initial surveillance endoscopy.

“Dysplasia detection in [Barrett’s esophagus] is challenging because of its patchy distribution and often subtle appearance,” the investigators noted. “Lack of compliance with recommended biopsy guidelines is also well-documented.”

On the other hand, Dr. Dhaliwal and colleagues suggested that previous studies may not accurately portray community practice and, therefore, have limited value in determining quality control metrics. A 2019 review, for instance, reported a neoplasia detection rate of 7% among patients with Barrett’s esophagus, but this finding “is composed of data from largely referral center cohorts with endoscopy performed by experienced academic gastroenterologists,” they wrote, which may lead to overestimation of such detection.

To better characterize this landscape, the investigators conducted a retrospective analysis involving 1,066 patients with Barrett’s esophagus who underwent initial surveillance endoscopy between 1991 and 2019. Approximately three out of four surveillance endoscopies (77%) were performed by gastroenterologists, while the remaining were performed by nongastroenterologists, such as family practitioners or surgeons. About 60% of patients were adequately biopsied according to the Seattle protocol.

Analysis revealed that the neoplasia detection rate was 4.9% (95% confidence interval, 3.8%-6.4%), which is less than the previously reported rate of 7%. HGD was more common than EAC (33 cases vs. 20 cases). Out of 1,066 patients, 391 without neoplasia on initial endoscopy underwent repeat endoscopy within a year. Among these individuals, HGD or EAC was detected in eight patients, which suggests that 13% of diagnoses were missed on initial endoscopy, a rate well below the previously reported range of 25%-33%.
 

Technology challenged by technique

The neoplasia detection rate “appeared to increase significantly from 1991 to 2019 on univariate analysis (particularly after 2000), but this was not observed on multivariate analysis,” the investigators wrote. “This was despite the introduction of high definition monitors and high resolution endoscopes in subsequent years.

“This may suggest that in a low dysplasia prevalence setting, basic techniques such as careful white light inspection of the [Barrett’s esophagus] mucosa along with targeted and Seattle protocol biopsies may be more important,” they noted.

The importance of technique may be further supported by another finding: Gastroenterologists detected neoplasia almost four times as often as did nongastroenterologists (odds ratio, 3.6; P = .0154).

“This finding is novel and may be due to additional training in endoscopy, lesion recognition, and familiarity with surveillance guidelines in gastroenterologists,” the investigators wrote. “If this finding is replicated in other cohorts, it may support recommendations for the performance of surveillance by endoscopists trained in gastrointestinal endoscopy and well-versed in surveillance guidelines.

“[U]sing neoplasia detection as a quality metric coupled with outcome measures such as missed dysplasia rates could improve adherence to established biopsy protocols and improve the quality of care to patients,” they wrote. “Ultimately, this can be an opportunity to develop a high-value, evidence-based quality metric in [Barrett’s esophagus] surveillance.”

The authors acknowledged some limitations to their study. Its retrospective design meant no one biopsy protocol could be adopted across the entire study period; however, the results were “unchanged” when restricted to the period after introduction of the Seattle protocol in 2000. The study’s long period could have left results susceptible to changing guidelines, but the neoplasia detection rates remained relatively stable over time.

“Because prior reports consisted largely of tertiary care center cohorts, our findings may reflect the absence of referral bias and be more generalizable,” the investigators wrote.

The study was funded by the National Institute of Aging and the National Cancer Institute. The investigators disclosed relationships with Celgene, Nine Point Medical, Takeda, and others.

Working night shifts has been associated with an increased risk for certain cancers, as well as other health disorders. Indeed, the World Health Organization’s International Agency for Research on Cancer (IARC) has classified night shift work as “probably carcinogenic to humans.”

But why night shift should elevate the risk for cancer has been unclear.

A new study shows that a simulated night shift schedule significantly altered the normal circadian rhythmicity of genes that are involved in cancer hallmark pathways. It also found that this circadian misalignment caused circadian dysregulation of genes involved in key DNA repair pathways.

“Taken together, these findings suggest that night shift schedules throw off the timing of expression of cancer-related genes in a way that reduces the effectiveness of the body’s DNA repair processes when they are most needed,” said co-corresponding author Jason McDermott, a computational scientist with the Pacific Northwest National Laboratory’s biological sciences division in Richland, Wash.

The study was published online in the Journal of Pineal Research.
 

Study conducted among volunteers 

The study was carried out among healthy volunteers who were subjected to simulated night shift or day shift schedules.

The cohort comprised 14 adults between the ages of 22 and 34 years who had normal nighttime sleep schedules. They were randomly assigned (seven in each group) to a simulated day shift schedule that involved 3 days of daytime wakefulness (6 a.m.-10 p.m.), or a simulated night shift schedule involving 3 days of nighttime wakefulness (6 p.m.-10 a.m.).

After the 3 days of simulated shift work, all participants were then kept in a constant routine protocol (used to study humans’ internally generated biological rhythms independent of any external influences). As part of the protocol, they were kept awake for 24 hours in a semi-reclined posture under laboratory conditions with constant light exposure and room temperature and evenly distributed food intake (hourly isocaloric snacks).

Blood samples were collected at 3-hour intervals and used for leukocyte transcriptome analysis and DNA damage assessment.

The authors found that the circadian expression of canonical clock genes was substantially altered by the simulated night shift schedule vs. the day shift schedule. Four genes (CRY1, CRY2, PER2, and NR1D2) lost their normal day-shift rhythmicity following the night shift schedule, and NPAS2 gene expression was not rhythmic during the day shift but exhibited circadian rhythmicity in the simulated night shift condition. Three other genes (NR1D1, PER3, and DBP) were significantly rhythmic during both shifts.

The team also looked at the effect of night shift on circadian rhythmicity in cancer hallmark genes, using a panel of 726 genes. The analysis showed that:

• 257 (35.4%) were rhythmic after at least one of the two simulated shift work conditions.
• 113 (15.6%) were rhythmic in day shift only.
• 96 (13.2%) were rhythmic during night shift only.
• 48 (6.6%) were rhythmic during both shifts.

A subset of 10 (1.4%) genes exhibited a significant phase advance (3.7 to 8.3 hours) or phase delay (2.8 to 7.0 hours) during the night shift vs. the day shift.

Thus, the authors concluded, shift work caused significant disturbances in the rhythmicity of gene expression in cancer hallmark pathways.

Findings also showed that night shift work increases endogenous and exogenous DNA damage. Endogenous DNA damage was generally higher after the night shift compared to the day shift, and across the 24-hour constant routine the percentage of cells with BRCA1 and g H2AX foci was significantly higher for night shift.
 

Next steps

The team said that the next step is to conduct the same experiment with real-world shift workers who have been consistently on day or night shifts for many years to determine whether in night workers the unrepaired DNA damage builds up over time, which could ultimately increase the risk for cancer.

If what happens in real-world shift workers is consistent with the current findings, this work could eventually be used to develop prevention strategies and drugs that could address the mistiming of DNA repair processes, they suggested.  

“Night shift workers face considerable health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” co-senior author Hans Van Dongen, PhD, a professor at Washington State University in Pullman and director of the WSU Sleep and Performance Research Center, Spokane, said in a statement. “It is high time that we find diagnosis and treatment solutions for this underserved group of essential workers so that the medical community can address their unique health challenges.”

The study was supported by start-up funds from Washington State University and a Center for Human Health and the Environment grant from North Carolina State University, and in part by the United States Army Medical Research and Development Command, the National Institutes of Health, CDMRP (Congressionally Directed Medical Research Programs) Peer Reviewed Cancer Research Program award, and the BRAVE investment.

The authors have disclosed no relevant financial relationships.

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

Working night shifts has been associated with an increased risk for certain cancers, as well as other health disorders. Indeed, the World Health Organization’s International Agency for Research on Cancer (IARC) has classified night shift work as “probably carcinogenic to humans.”

But why night shift should elevate the risk for cancer has been unclear.

A new study shows that a simulated night shift schedule significantly altered the normal circadian rhythmicity of genes that are involved in cancer hallmark pathways. It also found that this circadian misalignment caused circadian dysregulation of genes involved in key DNA repair pathways.

“Taken together, these findings suggest that night shift schedules throw off the timing of expression of cancer-related genes in a way that reduces the effectiveness of the body’s DNA repair processes when they are most needed,” said co-corresponding author Jason McDermott, a computational scientist with the Pacific Northwest National Laboratory’s biological sciences division in Richland, Wash.

The study was published online in the Journal of Pineal Research.
 

Study conducted among volunteers 

The study was carried out among healthy volunteers who were subjected to simulated night shift or day shift schedules.

The cohort comprised 14 adults between the ages of 22 and 34 years who had normal nighttime sleep schedules. They were randomly assigned (seven in each group) to a simulated day shift schedule that involved 3 days of daytime wakefulness (6 a.m.-10 p.m.), or a simulated night shift schedule involving 3 days of nighttime wakefulness (6 p.m.-10 a.m.).

After the 3 days of simulated shift work, all participants were then kept in a constant routine protocol (used to study humans’ internally generated biological rhythms independent of any external influences). As part of the protocol, they were kept awake for 24 hours in a semi-reclined posture under laboratory conditions with constant light exposure and room temperature and evenly distributed food intake (hourly isocaloric snacks).

Blood samples were collected at 3-hour intervals and used for leukocyte transcriptome analysis and DNA damage assessment.

The authors found that the circadian expression of canonical clock genes was substantially altered by the simulated night shift schedule vs. the day shift schedule. Four genes (CRY1, CRY2, PER2, and NR1D2) lost their normal day-shift rhythmicity following the night shift schedule, and NPAS2 gene expression was not rhythmic during the day shift but exhibited circadian rhythmicity in the simulated night shift condition. Three other genes (NR1D1, PER3, and DBP) were significantly rhythmic during both shifts.

The team also looked at the effect of night shift on circadian rhythmicity in cancer hallmark genes, using a panel of 726 genes. The analysis showed that:

• 257 (35.4%) were rhythmic after at least one of the two simulated shift work conditions.
• 113 (15.6%) were rhythmic in day shift only.
• 96 (13.2%) were rhythmic during night shift only.
• 48 (6.6%) were rhythmic during both shifts.

A subset of 10 (1.4%) genes exhibited a significant phase advance (3.7 to 8.3 hours) or phase delay (2.8 to 7.0 hours) during the night shift vs. the day shift.

Thus, the authors concluded, shift work caused significant disturbances in the rhythmicity of gene expression in cancer hallmark pathways.

Findings also showed that night shift work increases endogenous and exogenous DNA damage. Endogenous DNA damage was generally higher after the night shift compared to the day shift, and across the 24-hour constant routine the percentage of cells with BRCA1 and g H2AX foci was significantly higher for night shift.
 

Next steps

The team said that the next step is to conduct the same experiment with real-world shift workers who have been consistently on day or night shifts for many years to determine whether in night workers the unrepaired DNA damage builds up over time, which could ultimately increase the risk for cancer.

If what happens in real-world shift workers is consistent with the current findings, this work could eventually be used to develop prevention strategies and drugs that could address the mistiming of DNA repair processes, they suggested.  

“Night shift workers face considerable health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” co-senior author Hans Van Dongen, PhD, a professor at Washington State University in Pullman and director of the WSU Sleep and Performance Research Center, Spokane, said in a statement. “It is high time that we find diagnosis and treatment solutions for this underserved group of essential workers so that the medical community can address their unique health challenges.”

The study was supported by start-up funds from Washington State University and a Center for Human Health and the Environment grant from North Carolina State University, and in part by the United States Army Medical Research and Development Command, the National Institutes of Health, CDMRP (Congressionally Directed Medical Research Programs) Peer Reviewed Cancer Research Program award, and the BRAVE investment.

The authors have disclosed no relevant financial relationships.

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

Working night shifts has been associated with an increased risk for certain cancers, as well as other health disorders. Indeed, the World Health Organization’s International Agency for Research on Cancer (IARC) has classified night shift work as “probably carcinogenic to humans.”

But why night shift should elevate the risk for cancer has been unclear.

A new study shows that a simulated night shift schedule significantly altered the normal circadian rhythmicity of genes that are involved in cancer hallmark pathways. It also found that this circadian misalignment caused circadian dysregulation of genes involved in key DNA repair pathways.

“Taken together, these findings suggest that night shift schedules throw off the timing of expression of cancer-related genes in a way that reduces the effectiveness of the body’s DNA repair processes when they are most needed,” said co-corresponding author Jason McDermott, a computational scientist with the Pacific Northwest National Laboratory’s biological sciences division in Richland, Wash.

The study was published online in the Journal of Pineal Research.
 

Study conducted among volunteers 

The study was carried out among healthy volunteers who were subjected to simulated night shift or day shift schedules.

The cohort comprised 14 adults between the ages of 22 and 34 years who had normal nighttime sleep schedules. They were randomly assigned (seven in each group) to a simulated day shift schedule that involved 3 days of daytime wakefulness (6 a.m.-10 p.m.), or a simulated night shift schedule involving 3 days of nighttime wakefulness (6 p.m.-10 a.m.).

After the 3 days of simulated shift work, all participants were then kept in a constant routine protocol (used to study humans’ internally generated biological rhythms independent of any external influences). As part of the protocol, they were kept awake for 24 hours in a semi-reclined posture under laboratory conditions with constant light exposure and room temperature and evenly distributed food intake (hourly isocaloric snacks).

Blood samples were collected at 3-hour intervals and used for leukocyte transcriptome analysis and DNA damage assessment.

The authors found that the circadian expression of canonical clock genes was substantially altered by the simulated night shift schedule vs. the day shift schedule. Four genes (CRY1, CRY2, PER2, and NR1D2) lost their normal day-shift rhythmicity following the night shift schedule, and NPAS2 gene expression was not rhythmic during the day shift but exhibited circadian rhythmicity in the simulated night shift condition. Three other genes (NR1D1, PER3, and DBP) were significantly rhythmic during both shifts.

The team also looked at the effect of night shift on circadian rhythmicity in cancer hallmark genes, using a panel of 726 genes. The analysis showed that:

• 257 (35.4%) were rhythmic after at least one of the two simulated shift work conditions.
• 113 (15.6%) were rhythmic in day shift only.
• 96 (13.2%) were rhythmic during night shift only.
• 48 (6.6%) were rhythmic during both shifts.

A subset of 10 (1.4%) genes exhibited a significant phase advance (3.7 to 8.3 hours) or phase delay (2.8 to 7.0 hours) during the night shift vs. the day shift.

Thus, the authors concluded, shift work caused significant disturbances in the rhythmicity of gene expression in cancer hallmark pathways.

Findings also showed that night shift work increases endogenous and exogenous DNA damage. Endogenous DNA damage was generally higher after the night shift compared to the day shift, and across the 24-hour constant routine the percentage of cells with BRCA1 and g H2AX foci was significantly higher for night shift.
 

Next steps

The team said that the next step is to conduct the same experiment with real-world shift workers who have been consistently on day or night shifts for many years to determine whether in night workers the unrepaired DNA damage builds up over time, which could ultimately increase the risk for cancer.

If what happens in real-world shift workers is consistent with the current findings, this work could eventually be used to develop prevention strategies and drugs that could address the mistiming of DNA repair processes, they suggested.  

“Night shift workers face considerable health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” co-senior author Hans Van Dongen, PhD, a professor at Washington State University in Pullman and director of the WSU Sleep and Performance Research Center, Spokane, said in a statement. “It is high time that we find diagnosis and treatment solutions for this underserved group of essential workers so that the medical community can address their unique health challenges.”

The study was supported by start-up funds from Washington State University and a Center for Human Health and the Environment grant from North Carolina State University, and in part by the United States Army Medical Research and Development Command, the National Institutes of Health, CDMRP (Congressionally Directed Medical Research Programs) Peer Reviewed Cancer Research Program award, and the BRAVE investment.

The authors have disclosed no relevant financial relationships.

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

Exercise may help prevent cognitive decline in high-risk patients with early Parkinson’s disease, new research suggests. Investigators found that patients with Parkinson’s disease who were APOE epsilon4 carriers had greater cognitive decline compared with non-APOE epsilon4 carriers, but the findings also revealed higher physical activity appeared to slow cognitive decline in this higher risk group.

“The main finding of the current study is that higher physical activity was related to slower APOE epsilon4-associated cognitive decline in patients with early Parkinson’s disease, which was shown to be robust in sensitivity analyses,” wrote the researchers, led by Ryul Kim, MD, Inha University Hospital, Incheon, Korea.

The study was published online March 31 in Neurology.
 

Unclear mechanism

The APOE epsilon4 allele is known to be a “major risk factor” for Alzheimer’s disease, but “accumulating evidence shows that this allele also has a potential role in cognitive impairment in Parkinson’s disease,” the authors noted.

Previous research shows physical activity has beneficial effects in patients with Parkinson’s disease, but the mechanisms underlying these effects are “not well understood.” Additional data suggest physical activity modifies the APOE epsilon4 effect on the development and progression of Alzheimer’s disease.

“These observations led us to hypothesize that physical activity also plays a role in modulating the association between APOE [epsilon4] and cognition in Parkinson’s disease,” but no studies have yet reported on this interaction in patients with Parkinson’s disease, the authors noted.

To investigate, they drew on data from the Parkinson’s Progression Markers Initiative (PPMI) – a cohort study conducted to identify Parkinson’s disease progression markers.

The current analysis included 173 patients recently diagnosed with Parkinson’s disease but not yet treated for the condition. The cohort’s mean age was 63.3 ± 10.0 years, age of Parkinson’s disease onset was 59.4 ± 10.0 years, and 68% were male. Of these participants, 46 were APOE epsilon4 carriers.

Dopamine transporter (DAT) activity was assessed using imaging at enrollment and again at years 2 and 4. Cognitive function was assessed at years 2, 3, and 4 using the Montreal Cognitive Assessment (MoCA) test.
 

Protective effect

Although APOE epsilon4 carriers tended to be younger than noncarriers, the age of Parkinson’s disease onset did not differ between the 2 groups, and there were also no significant differences between the groups in demographic and clinical variables.

There were larger declines in MoCA scores in the APOE epsilon4 carriers versus the noncarriers (0.21 ± 1.40 and 0.08 ± 1.15 respectively).

The APOE epsilon4 allele was associated with a “steeper” rate of cognitive decline, compared with the non-APOE epsilon4 allele (estimate −1.33 [95% confidence interval, −2.12 to −0.47, P = .002).

There was a significant interaction of physical activity, APOE epsilon4, and time: Higher physical activity was associated with slower APOE epsilon4-related cognitive decline (estimate 0.007 [0.003 to 0.011, P = .001).

However, the researchers found no significant main effects of the APOE epsilon4 allele or physical activity on the change in the MoCA score.

“Considering that dopaminergic treatment may affect cognitive function, particularly in the early stage of Parkinson’s disease, we additionally included the levodopa daily equivalent dose (LEDD) and its interaction with time as covariates in the model,” the investigators noted.

They found that the interactive association between physical activity and the APOE epsilon4 allele on cognitive decline remained significant, even when participants who had normal cognitive performance at year 2 were included in the study population or when LEDD variables were included as covariates in the model.

Both high- and low-intensity exercise were significantly associated with slower APOE epsilon4-related cognitive decline.

There was no significant interaction between physical activity and APOE epsilon4 with changes in striatal DAT activities.

“Increased physical activity attenuated APOE epsilon4-related vulnerability to early cognitive decline in patients with Parkinson’s disease,” the authors noted, adding that the effect “did not appear to be mediated by striatal dopamine activity.”

They hypothesized that physical activity may “offer a greater protective effect” on cerebral amyloid accumulation in APOE epsilon4 carriers. It is also possible that physical activity will counteract the negative impact of the APOE epsilon4 allele through improved brain mechanism and decreased neuroinflammation.
 

‘The next blockbuster drug’

Commenting on the study in an interview, Bastiaan R. Bloem, MD, PhD, director of the center of expertise for Parkinson & movement disorders, Radboud University Medical Center, Nijmegen, Netherlands, said exercise might be seen as “the next blockbuster drug.”

Dr. Bloem, who was not involved in the study, noted there is “quite robust evidence now that exercise acts as symptomatic therapy, like a drug, alleviating sleep [disturbances], depression, constipation, and motor symptoms.”

The study “sheds new light on the idea of exercise as not only alleviating symptoms but actually as a potential disease modifier,” said Dr. Bloem, whose research has focused on the beneficial effects of a rigorous exercise program, combined with tablet-based gamificaton and a reward system in stabilizing motor symptoms in patients with Parkinson’s disease over time.

“The reward system created additional motivation for the patients with Parkinson’s disease who often experience depression and apathy that interfere with motivation,” he said.

The current study has important take-home messages for practicing clinicians. “Physicians should encourage exercise in patients, and patients should also take the lead themselves,” Dr. Bloem said. “It doesn’t matter what type of exercise you do, but it should have an aerobic component, should be safe so the patient doesn’t fall down, should have enough intensity to cause the patient to pant, and should be individualized and enjoyable so the patients stick to it,” he emphasized.

Dr. Bloem noted that yoga and mindfulness are also helpful. “If we’ve learned anything from the COVID-19 crisis, it’s that chronic stress is deleterious to all of us and particularly bad for people with PD, because you need dopamine to be able to handle stress, and the lack of dopamine in people with PD makes them deteriorate faster.”

The study was supported by a research grant of National Research Foundation by the Ministry of Science and ICT (MSIT) in Korea. The authors and Dr. Bloem have disclosed no relevant financial relationships.

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

Exercise may help prevent cognitive decline in high-risk patients with early Parkinson’s disease, new research suggests. Investigators found that patients with Parkinson’s disease who were APOE epsilon4 carriers had greater cognitive decline compared with non-APOE epsilon4 carriers, but the findings also revealed higher physical activity appeared to slow cognitive decline in this higher risk group.

“The main finding of the current study is that higher physical activity was related to slower APOE epsilon4-associated cognitive decline in patients with early Parkinson’s disease, which was shown to be robust in sensitivity analyses,” wrote the researchers, led by Ryul Kim, MD, Inha University Hospital, Incheon, Korea.

The study was published online March 31 in Neurology.
 

Unclear mechanism

The APOE epsilon4 allele is known to be a “major risk factor” for Alzheimer’s disease, but “accumulating evidence shows that this allele also has a potential role in cognitive impairment in Parkinson’s disease,” the authors noted.

Previous research shows physical activity has beneficial effects in patients with Parkinson’s disease, but the mechanisms underlying these effects are “not well understood.” Additional data suggest physical activity modifies the APOE epsilon4 effect on the development and progression of Alzheimer’s disease.

“These observations led us to hypothesize that physical activity also plays a role in modulating the association between APOE [epsilon4] and cognition in Parkinson’s disease,” but no studies have yet reported on this interaction in patients with Parkinson’s disease, the authors noted.

To investigate, they drew on data from the Parkinson’s Progression Markers Initiative (PPMI) – a cohort study conducted to identify Parkinson’s disease progression markers.

The current analysis included 173 patients recently diagnosed with Parkinson’s disease but not yet treated for the condition. The cohort’s mean age was 63.3 ± 10.0 years, age of Parkinson’s disease onset was 59.4 ± 10.0 years, and 68% were male. Of these participants, 46 were APOE epsilon4 carriers.

Dopamine transporter (DAT) activity was assessed using imaging at enrollment and again at years 2 and 4. Cognitive function was assessed at years 2, 3, and 4 using the Montreal Cognitive Assessment (MoCA) test.
 

Protective effect

Although APOE epsilon4 carriers tended to be younger than noncarriers, the age of Parkinson’s disease onset did not differ between the 2 groups, and there were also no significant differences between the groups in demographic and clinical variables.

There were larger declines in MoCA scores in the APOE epsilon4 carriers versus the noncarriers (0.21 ± 1.40 and 0.08 ± 1.15 respectively).

The APOE epsilon4 allele was associated with a “steeper” rate of cognitive decline, compared with the non-APOE epsilon4 allele (estimate −1.33 [95% confidence interval, −2.12 to −0.47, P = .002).

There was a significant interaction of physical activity, APOE epsilon4, and time: Higher physical activity was associated with slower APOE epsilon4-related cognitive decline (estimate 0.007 [0.003 to 0.011, P = .001).

However, the researchers found no significant main effects of the APOE epsilon4 allele or physical activity on the change in the MoCA score.

“Considering that dopaminergic treatment may affect cognitive function, particularly in the early stage of Parkinson’s disease, we additionally included the levodopa daily equivalent dose (LEDD) and its interaction with time as covariates in the model,” the investigators noted.

They found that the interactive association between physical activity and the APOE epsilon4 allele on cognitive decline remained significant, even when participants who had normal cognitive performance at year 2 were included in the study population or when LEDD variables were included as covariates in the model.

Both high- and low-intensity exercise were significantly associated with slower APOE epsilon4-related cognitive decline.

There was no significant interaction between physical activity and APOE epsilon4 with changes in striatal DAT activities.

“Increased physical activity attenuated APOE epsilon4-related vulnerability to early cognitive decline in patients with Parkinson’s disease,” the authors noted, adding that the effect “did not appear to be mediated by striatal dopamine activity.”

They hypothesized that physical activity may “offer a greater protective effect” on cerebral amyloid accumulation in APOE epsilon4 carriers. It is also possible that physical activity will counteract the negative impact of the APOE epsilon4 allele through improved brain mechanism and decreased neuroinflammation.
 

‘The next blockbuster drug’

Commenting on the study in an interview, Bastiaan R. Bloem, MD, PhD, director of the center of expertise for Parkinson & movement disorders, Radboud University Medical Center, Nijmegen, Netherlands, said exercise might be seen as “the next blockbuster drug.”

Dr. Bloem, who was not involved in the study, noted there is “quite robust evidence now that exercise acts as symptomatic therapy, like a drug, alleviating sleep [disturbances], depression, constipation, and motor symptoms.”

The study “sheds new light on the idea of exercise as not only alleviating symptoms but actually as a potential disease modifier,” said Dr. Bloem, whose research has focused on the beneficial effects of a rigorous exercise program, combined with tablet-based gamificaton and a reward system in stabilizing motor symptoms in patients with Parkinson’s disease over time.

“The reward system created additional motivation for the patients with Parkinson’s disease who often experience depression and apathy that interfere with motivation,” he said.

The current study has important take-home messages for practicing clinicians. “Physicians should encourage exercise in patients, and patients should also take the lead themselves,” Dr. Bloem said. “It doesn’t matter what type of exercise you do, but it should have an aerobic component, should be safe so the patient doesn’t fall down, should have enough intensity to cause the patient to pant, and should be individualized and enjoyable so the patients stick to it,” he emphasized.

Dr. Bloem noted that yoga and mindfulness are also helpful. “If we’ve learned anything from the COVID-19 crisis, it’s that chronic stress is deleterious to all of us and particularly bad for people with PD, because you need dopamine to be able to handle stress, and the lack of dopamine in people with PD makes them deteriorate faster.”

The study was supported by a research grant of National Research Foundation by the Ministry of Science and ICT (MSIT) in Korea. The authors and Dr. Bloem have disclosed no relevant financial relationships.

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

Exercise may help prevent cognitive decline in high-risk patients with early Parkinson’s disease, new research suggests. Investigators found that patients with Parkinson’s disease who were APOE epsilon4 carriers had greater cognitive decline compared with non-APOE epsilon4 carriers, but the findings also revealed higher physical activity appeared to slow cognitive decline in this higher risk group.

“The main finding of the current study is that higher physical activity was related to slower APOE epsilon4-associated cognitive decline in patients with early Parkinson’s disease, which was shown to be robust in sensitivity analyses,” wrote the researchers, led by Ryul Kim, MD, Inha University Hospital, Incheon, Korea.

The study was published online March 31 in Neurology.
 

Unclear mechanism

The APOE epsilon4 allele is known to be a “major risk factor” for Alzheimer’s disease, but “accumulating evidence shows that this allele also has a potential role in cognitive impairment in Parkinson’s disease,” the authors noted.

Previous research shows physical activity has beneficial effects in patients with Parkinson’s disease, but the mechanisms underlying these effects are “not well understood.” Additional data suggest physical activity modifies the APOE epsilon4 effect on the development and progression of Alzheimer’s disease.

“These observations led us to hypothesize that physical activity also plays a role in modulating the association between APOE [epsilon4] and cognition in Parkinson’s disease,” but no studies have yet reported on this interaction in patients with Parkinson’s disease, the authors noted.

To investigate, they drew on data from the Parkinson’s Progression Markers Initiative (PPMI) – a cohort study conducted to identify Parkinson’s disease progression markers.

The current analysis included 173 patients recently diagnosed with Parkinson’s disease but not yet treated for the condition. The cohort’s mean age was 63.3 ± 10.0 years, age of Parkinson’s disease onset was 59.4 ± 10.0 years, and 68% were male. Of these participants, 46 were APOE epsilon4 carriers.

Dopamine transporter (DAT) activity was assessed using imaging at enrollment and again at years 2 and 4. Cognitive function was assessed at years 2, 3, and 4 using the Montreal Cognitive Assessment (MoCA) test.
 

Protective effect

Although APOE epsilon4 carriers tended to be younger than noncarriers, the age of Parkinson’s disease onset did not differ between the 2 groups, and there were also no significant differences between the groups in demographic and clinical variables.

There were larger declines in MoCA scores in the APOE epsilon4 carriers versus the noncarriers (0.21 ± 1.40 and 0.08 ± 1.15 respectively).

The APOE epsilon4 allele was associated with a “steeper” rate of cognitive decline, compared with the non-APOE epsilon4 allele (estimate −1.33 [95% confidence interval, −2.12 to −0.47, P = .002).

There was a significant interaction of physical activity, APOE epsilon4, and time: Higher physical activity was associated with slower APOE epsilon4-related cognitive decline (estimate 0.007 [0.003 to 0.011, P = .001).

However, the researchers found no significant main effects of the APOE epsilon4 allele or physical activity on the change in the MoCA score.

“Considering that dopaminergic treatment may affect cognitive function, particularly in the early stage of Parkinson’s disease, we additionally included the levodopa daily equivalent dose (LEDD) and its interaction with time as covariates in the model,” the investigators noted.

They found that the interactive association between physical activity and the APOE epsilon4 allele on cognitive decline remained significant, even when participants who had normal cognitive performance at year 2 were included in the study population or when LEDD variables were included as covariates in the model.

Both high- and low-intensity exercise were significantly associated with slower APOE epsilon4-related cognitive decline.

There was no significant interaction between physical activity and APOE epsilon4 with changes in striatal DAT activities.

“Increased physical activity attenuated APOE epsilon4-related vulnerability to early cognitive decline in patients with Parkinson’s disease,” the authors noted, adding that the effect “did not appear to be mediated by striatal dopamine activity.”

They hypothesized that physical activity may “offer a greater protective effect” on cerebral amyloid accumulation in APOE epsilon4 carriers. It is also possible that physical activity will counteract the negative impact of the APOE epsilon4 allele through improved brain mechanism and decreased neuroinflammation.
 

‘The next blockbuster drug’

Commenting on the study in an interview, Bastiaan R. Bloem, MD, PhD, director of the center of expertise for Parkinson & movement disorders, Radboud University Medical Center, Nijmegen, Netherlands, said exercise might be seen as “the next blockbuster drug.”

Dr. Bloem, who was not involved in the study, noted there is “quite robust evidence now that exercise acts as symptomatic therapy, like a drug, alleviating sleep [disturbances], depression, constipation, and motor symptoms.”

The study “sheds new light on the idea of exercise as not only alleviating symptoms but actually as a potential disease modifier,” said Dr. Bloem, whose research has focused on the beneficial effects of a rigorous exercise program, combined with tablet-based gamificaton and a reward system in stabilizing motor symptoms in patients with Parkinson’s disease over time.

“The reward system created additional motivation for the patients with Parkinson’s disease who often experience depression and apathy that interfere with motivation,” he said.

The current study has important take-home messages for practicing clinicians. “Physicians should encourage exercise in patients, and patients should also take the lead themselves,” Dr. Bloem said. “It doesn’t matter what type of exercise you do, but it should have an aerobic component, should be safe so the patient doesn’t fall down, should have enough intensity to cause the patient to pant, and should be individualized and enjoyable so the patients stick to it,” he emphasized.

Dr. Bloem noted that yoga and mindfulness are also helpful. “If we’ve learned anything from the COVID-19 crisis, it’s that chronic stress is deleterious to all of us and particularly bad for people with PD, because you need dopamine to be able to handle stress, and the lack of dopamine in people with PD makes them deteriorate faster.”

The study was supported by a research grant of National Research Foundation by the Ministry of Science and ICT (MSIT) in Korea. The authors and Dr. Bloem have disclosed no relevant financial relationships.

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

Specialty palliative care interventions improve outcomes in patients with hematologic malignancies but are underutilized, according to findings from a systematic literature review.

Outcomes that were improved, as demonstrated by 16 studies that met inclusion criteria for the review, included symptom management, inpatient mortality, health care utilization, health care costs, and caregiver-reported outcomes, Elizabeth Elliott, DO, a hematology and oncology fellow at the Cardinal Bernardin Cancer Center, Loyola University, Maywood, Ill., and colleagues reported.

The findings were published online in the Journal of Pain and Symptom Management.
 

Palliative care needs

Patients with hematologic malignancies, including leukemia, myeloma, and lymphoma, have a high need for supportive care, the authors noted, adding that, although its use has increased over time, palliative care (PC) is often provided late in the disease course – sometimes only in the final days of life.

“Compared with their solid tumor counterparts, patients with hematologic malignancies experience higher symptom burdens, have higher rates of cancer-directed care near death, and are more likely to die while hospitalized than at home or in hospice,” they wrote. “Despite this need, specialist palliative care is less commonly utilized in patients with hematologic malignancies than other cancer types.”

Given the high health care utilization among patients with hematologic malignancies, earlier and more widespread utilization of PC in this population may significantly reduce health care costs, they added.
 

Palliative care benefits

Of 5,345 studies published between 2005 and 2020 and screened for the current review, 16 met inclusion criteria, including 10 retrospective cohort studies; 4 prospective cohort studies; and 2 randomized, controlled studies.

Nine studies included only patients with hematologic malignancies and seven included both patients with solid tumors and patients with hematologic malignancies. Each study assessed as being of moderate quality.

Benefits of PC as demonstrated in the studies included:

Symptom management: One study, for example, showed that an integrated psychological and PC intervention improved traumatic stress levels, degree and number of physical symptoms, pain intensity, depressive symptoms, and quality of life, compared with no intervention. Another showed that the percentage of patients reporting moderate to severe pain improved from 57% to 18% with a PC intervention, and the number reporting depressive episodes improved from 13% to 5%.

Reduced in-patient death: Findings from eight studies showed that 21.9%-83% of those receiving PC died at home, compared with 6.0%-8.9% of controls. Two studies showed that PC provided at least 20 days prior to death decreased the likelihood of inpatient death and death in an ICU, compared with controls, and one showed that the rate of in-hospital deaths was 30% for those with home PC or hospice, compared with 80% of controls.

Health care utilization: The studies showed that hospitalization occurred in 45%-76.3% of hematologic malignancy patients who received PC, compared with 98% of controls. The odds ratio for hospitalization among acute leukemia patients receiving PC was 0.64, compared with 2.53 among those in a historical control group.

Caregiver-reported outcomes: One randomized, controlled study showed that PC was associated with smaller increases in depression scores, improved coping, and improved scores in multiple quality of life domains in caregivers versus controls.

Survival: One study showed that a larger percentage of hematologic malignancy patients who died 1-6 months after diagnosis had not received PC (28% vs. 23%), whereas more of those who died 6-12 months or 12 or more months after diagnosis had received PC (23.9 vs. 14.9% and 42.5% vs. 22.0%).

Health care costs: Two studies showed a decrease in inpatient costs after a palliative care consultation. Decreases in hospitalization costs were $2,321 and $1,506 for less medically complex patients and $3,515 and $5,617 for more medically complex patient.

Improving PC utilization

One potential strategy to promote earlier referrals to PC is improved education for hematologists, the authors said, citing a study showing that 98% of oncology fellows at one center reported improvement in their ability to assess and manage patient symptoms after completion of a 4-week mandatory PC rotation.

“Another strategy to improve referrals to PC of hematologic malignancies patients could be the creation of programs which facilitate collaboration between PC providers and hematologists, such as the palliative and supportive care special interest group within the American Society for Transplantation and Cellular Therapy,” they wrote.

A third strategy “could be to provide a concurrent care model, in which cancer directed therapy (such as transfusions) is provided at the same time as hospice care,” they added, explaining that such an approach was shown in a study of patients with advanced non–small cell lung cancer to be associated with less aggressive medical treatment and lower costs.

The authors also stressed that patient with solid tumors and those with hematologic malignancies have differing supportive care needs and health care utilization, but several studies included in the current review included both types of cancer.

“Further studies investigating PC use exclusively in patients with hematologic malignancies are needed. Our results demonstrate a strong argument for hematologists to refer their patients early and often for specialized PC,” they concluded.

Indeed, when PC is integrated within hematologic malignancies, impacts occur that are similar to those seen in a variety of other diseases and include improved symptom control, enhanced caregiver experience, and reduced burdens on the health care system, Toby C Campbell, MD, said in an interview.

“The benefits of providing palliative care concurrent with standard cancer care is felt by all the major stakeholders in this care: the patients, their caregivers, and the health care system around them,” said Dr. Campbell, a thoracic medical oncologist and professor in the division of hematology, medical oncology, and palliative care at the University of Wisconsin–Madison.
 

Overcoming challenges

However, this is “new territory” for most programs, added Dr. Campbell, who also is the University of Wisconsin health chief of palliative care and holds the Ellen and Peter O. Johnson Chair in Palliative Care .

“The palliative care clinicians have a lot of learning to do if they’re going to enter this space and provide expert care,” he said, adding that expert care is what is needed and what was studied in this review. “Providing palliative care to patients with hematologic malignancies has a unique pace and a number of subspecialized therapeutic options with which the palliative care clinician must become familiar.”

Examples include bone marrow transplantation with prolonged hospitalizations and transfusion support, he said.

“Palliative care programs, in order to provide high quality care, will need to familiarize themselves with these therapies and develop close partnership with hematologists to integrate seamlessly into the patient’s care,” he added. “At some centers, culture changes will be necessary concurrent with the clinical practice change of integrating palliative care and it is the responsibility of the palliative care clinicians to bring their very best to these new relationships and patient populations.”

The authors reported having no disclosures. Dr. Campbell also reported having no disclosures.

[email protected]

Specialty palliative care interventions improve outcomes in patients with hematologic malignancies but are underutilized, according to findings from a systematic literature review.

Outcomes that were improved, as demonstrated by 16 studies that met inclusion criteria for the review, included symptom management, inpatient mortality, health care utilization, health care costs, and caregiver-reported outcomes, Elizabeth Elliott, DO, a hematology and oncology fellow at the Cardinal Bernardin Cancer Center, Loyola University, Maywood, Ill., and colleagues reported.

The findings were published online in the Journal of Pain and Symptom Management.
 

Palliative care needs

Patients with hematologic malignancies, including leukemia, myeloma, and lymphoma, have a high need for supportive care, the authors noted, adding that, although its use has increased over time, palliative care (PC) is often provided late in the disease course – sometimes only in the final days of life.

“Compared with their solid tumor counterparts, patients with hematologic malignancies experience higher symptom burdens, have higher rates of cancer-directed care near death, and are more likely to die while hospitalized than at home or in hospice,” they wrote. “Despite this need, specialist palliative care is less commonly utilized in patients with hematologic malignancies than other cancer types.”

Given the high health care utilization among patients with hematologic malignancies, earlier and more widespread utilization of PC in this population may significantly reduce health care costs, they added.
 

Palliative care benefits

Of 5,345 studies published between 2005 and 2020 and screened for the current review, 16 met inclusion criteria, including 10 retrospective cohort studies; 4 prospective cohort studies; and 2 randomized, controlled studies.

Nine studies included only patients with hematologic malignancies and seven included both patients with solid tumors and patients with hematologic malignancies. Each study assessed as being of moderate quality.

Benefits of PC as demonstrated in the studies included:

Symptom management: One study, for example, showed that an integrated psychological and PC intervention improved traumatic stress levels, degree and number of physical symptoms, pain intensity, depressive symptoms, and quality of life, compared with no intervention. Another showed that the percentage of patients reporting moderate to severe pain improved from 57% to 18% with a PC intervention, and the number reporting depressive episodes improved from 13% to 5%.

Reduced in-patient death: Findings from eight studies showed that 21.9%-83% of those receiving PC died at home, compared with 6.0%-8.9% of controls. Two studies showed that PC provided at least 20 days prior to death decreased the likelihood of inpatient death and death in an ICU, compared with controls, and one showed that the rate of in-hospital deaths was 30% for those with home PC or hospice, compared with 80% of controls.

Health care utilization: The studies showed that hospitalization occurred in 45%-76.3% of hematologic malignancy patients who received PC, compared with 98% of controls. The odds ratio for hospitalization among acute leukemia patients receiving PC was 0.64, compared with 2.53 among those in a historical control group.

Caregiver-reported outcomes: One randomized, controlled study showed that PC was associated with smaller increases in depression scores, improved coping, and improved scores in multiple quality of life domains in caregivers versus controls.

Survival: One study showed that a larger percentage of hematologic malignancy patients who died 1-6 months after diagnosis had not received PC (28% vs. 23%), whereas more of those who died 6-12 months or 12 or more months after diagnosis had received PC (23.9 vs. 14.9% and 42.5% vs. 22.0%).

Health care costs: Two studies showed a decrease in inpatient costs after a palliative care consultation. Decreases in hospitalization costs were $2,321 and $1,506 for less medically complex patients and $3,515 and $5,617 for more medically complex patient.

Improving PC utilization

One potential strategy to promote earlier referrals to PC is improved education for hematologists, the authors said, citing a study showing that 98% of oncology fellows at one center reported improvement in their ability to assess and manage patient symptoms after completion of a 4-week mandatory PC rotation.

“Another strategy to improve referrals to PC of hematologic malignancies patients could be the creation of programs which facilitate collaboration between PC providers and hematologists, such as the palliative and supportive care special interest group within the American Society for Transplantation and Cellular Therapy,” they wrote.

A third strategy “could be to provide a concurrent care model, in which cancer directed therapy (such as transfusions) is provided at the same time as hospice care,” they added, explaining that such an approach was shown in a study of patients with advanced non–small cell lung cancer to be associated with less aggressive medical treatment and lower costs.

The authors also stressed that patient with solid tumors and those with hematologic malignancies have differing supportive care needs and health care utilization, but several studies included in the current review included both types of cancer.

“Further studies investigating PC use exclusively in patients with hematologic malignancies are needed. Our results demonstrate a strong argument for hematologists to refer their patients early and often for specialized PC,” they concluded.

Indeed, when PC is integrated within hematologic malignancies, impacts occur that are similar to those seen in a variety of other diseases and include improved symptom control, enhanced caregiver experience, and reduced burdens on the health care system, Toby C Campbell, MD, said in an interview.

“The benefits of providing palliative care concurrent with standard cancer care is felt by all the major stakeholders in this care: the patients, their caregivers, and the health care system around them,” said Dr. Campbell, a thoracic medical oncologist and professor in the division of hematology, medical oncology, and palliative care at the University of Wisconsin–Madison.
 

Overcoming challenges

However, this is “new territory” for most programs, added Dr. Campbell, who also is the University of Wisconsin health chief of palliative care and holds the Ellen and Peter O. Johnson Chair in Palliative Care .

“The palliative care clinicians have a lot of learning to do if they’re going to enter this space and provide expert care,” he said, adding that expert care is what is needed and what was studied in this review. “Providing palliative care to patients with hematologic malignancies has a unique pace and a number of subspecialized therapeutic options with which the palliative care clinician must become familiar.”

Examples include bone marrow transplantation with prolonged hospitalizations and transfusion support, he said.

“Palliative care programs, in order to provide high quality care, will need to familiarize themselves with these therapies and develop close partnership with hematologists to integrate seamlessly into the patient’s care,” he added. “At some centers, culture changes will be necessary concurrent with the clinical practice change of integrating palliative care and it is the responsibility of the palliative care clinicians to bring their very best to these new relationships and patient populations.”

The authors reported having no disclosures. Dr. Campbell also reported having no disclosures.

[email protected]

Specialty palliative care interventions improve outcomes in patients with hematologic malignancies but are underutilized, according to findings from a systematic literature review.

Outcomes that were improved, as demonstrated by 16 studies that met inclusion criteria for the review, included symptom management, inpatient mortality, health care utilization, health care costs, and caregiver-reported outcomes, Elizabeth Elliott, DO, a hematology and oncology fellow at the Cardinal Bernardin Cancer Center, Loyola University, Maywood, Ill., and colleagues reported.

The findings were published online in the Journal of Pain and Symptom Management.
 

Palliative care needs

Patients with hematologic malignancies, including leukemia, myeloma, and lymphoma, have a high need for supportive care, the authors noted, adding that, although its use has increased over time, palliative care (PC) is often provided late in the disease course – sometimes only in the final days of life.

“Compared with their solid tumor counterparts, patients with hematologic malignancies experience higher symptom burdens, have higher rates of cancer-directed care near death, and are more likely to die while hospitalized than at home or in hospice,” they wrote. “Despite this need, specialist palliative care is less commonly utilized in patients with hematologic malignancies than other cancer types.”

Given the high health care utilization among patients with hematologic malignancies, earlier and more widespread utilization of PC in this population may significantly reduce health care costs, they added.
 

Palliative care benefits

Of 5,345 studies published between 2005 and 2020 and screened for the current review, 16 met inclusion criteria, including 10 retrospective cohort studies; 4 prospective cohort studies; and 2 randomized, controlled studies.

Nine studies included only patients with hematologic malignancies and seven included both patients with solid tumors and patients with hematologic malignancies. Each study assessed as being of moderate quality.

Benefits of PC as demonstrated in the studies included:

Symptom management: One study, for example, showed that an integrated psychological and PC intervention improved traumatic stress levels, degree and number of physical symptoms, pain intensity, depressive symptoms, and quality of life, compared with no intervention. Another showed that the percentage of patients reporting moderate to severe pain improved from 57% to 18% with a PC intervention, and the number reporting depressive episodes improved from 13% to 5%.

Reduced in-patient death: Findings from eight studies showed that 21.9%-83% of those receiving PC died at home, compared with 6.0%-8.9% of controls. Two studies showed that PC provided at least 20 days prior to death decreased the likelihood of inpatient death and death in an ICU, compared with controls, and one showed that the rate of in-hospital deaths was 30% for those with home PC or hospice, compared with 80% of controls.

Health care utilization: The studies showed that hospitalization occurred in 45%-76.3% of hematologic malignancy patients who received PC, compared with 98% of controls. The odds ratio for hospitalization among acute leukemia patients receiving PC was 0.64, compared with 2.53 among those in a historical control group.

Caregiver-reported outcomes: One randomized, controlled study showed that PC was associated with smaller increases in depression scores, improved coping, and improved scores in multiple quality of life domains in caregivers versus controls.

Survival: One study showed that a larger percentage of hematologic malignancy patients who died 1-6 months after diagnosis had not received PC (28% vs. 23%), whereas more of those who died 6-12 months or 12 or more months after diagnosis had received PC (23.9 vs. 14.9% and 42.5% vs. 22.0%).

Health care costs: Two studies showed a decrease in inpatient costs after a palliative care consultation. Decreases in hospitalization costs were $2,321 and $1,506 for less medically complex patients and $3,515 and $5,617 for more medically complex patient.

Improving PC utilization

One potential strategy to promote earlier referrals to PC is improved education for hematologists, the authors said, citing a study showing that 98% of oncology fellows at one center reported improvement in their ability to assess and manage patient symptoms after completion of a 4-week mandatory PC rotation.

“Another strategy to improve referrals to PC of hematologic malignancies patients could be the creation of programs which facilitate collaboration between PC providers and hematologists, such as the palliative and supportive care special interest group within the American Society for Transplantation and Cellular Therapy,” they wrote.

A third strategy “could be to provide a concurrent care model, in which cancer directed therapy (such as transfusions) is provided at the same time as hospice care,” they added, explaining that such an approach was shown in a study of patients with advanced non–small cell lung cancer to be associated with less aggressive medical treatment and lower costs.

The authors also stressed that patient with solid tumors and those with hematologic malignancies have differing supportive care needs and health care utilization, but several studies included in the current review included both types of cancer.

“Further studies investigating PC use exclusively in patients with hematologic malignancies are needed. Our results demonstrate a strong argument for hematologists to refer their patients early and often for specialized PC,” they concluded.

Indeed, when PC is integrated within hematologic malignancies, impacts occur that are similar to those seen in a variety of other diseases and include improved symptom control, enhanced caregiver experience, and reduced burdens on the health care system, Toby C Campbell, MD, said in an interview.

“The benefits of providing palliative care concurrent with standard cancer care is felt by all the major stakeholders in this care: the patients, their caregivers, and the health care system around them,” said Dr. Campbell, a thoracic medical oncologist and professor in the division of hematology, medical oncology, and palliative care at the University of Wisconsin–Madison.
 

Overcoming challenges

However, this is “new territory” for most programs, added Dr. Campbell, who also is the University of Wisconsin health chief of palliative care and holds the Ellen and Peter O. Johnson Chair in Palliative Care .

“The palliative care clinicians have a lot of learning to do if they’re going to enter this space and provide expert care,” he said, adding that expert care is what is needed and what was studied in this review. “Providing palliative care to patients with hematologic malignancies has a unique pace and a number of subspecialized therapeutic options with which the palliative care clinician must become familiar.”

Examples include bone marrow transplantation with prolonged hospitalizations and transfusion support, he said.

“Palliative care programs, in order to provide high quality care, will need to familiarize themselves with these therapies and develop close partnership with hematologists to integrate seamlessly into the patient’s care,” he added. “At some centers, culture changes will be necessary concurrent with the clinical practice change of integrating palliative care and it is the responsibility of the palliative care clinicians to bring their very best to these new relationships and patient populations.”

The authors reported having no disclosures. Dr. Campbell also reported having no disclosures.

[email protected]

Protection against norovirus gastroenteritis is supported in part by norovirus-specific CD8+ T cells that reside in peripheral, intestinal, and lymphoid tissues, according to investigators.

These findings, and the molecular tools used to discover them, could guide development of a norovirus vaccine and novel cellular therapies, according to lead author Ajinkya Pattekar, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“Currently, there are no approved pharmacologic therapies against norovirus, and despite several promising clinical trials, an effective vaccine is not available,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, which may stem from an incomplete understanding of norovirus immunity, according to Dr. Pattekar and colleagues.

They noted that most previous research has focused on humoral immunity, which appears variable between individuals, with some people exhibiting a strong humoral response, while others mount only partial humoral protection. The investigators also noted that, depending on which studies were examined, this type of defense could last years or fade within weeks to months and that “immune mechanisms other than antibodies may be important for protection against noroviruses.”

Specifically, cellular immunity may be at work. A 2020 study involving volunteers showed that T cells were cross-reactive to a type of norovirus the participants had never been exposed to.

“These findings suggest that T cells may target conserved epitopes and could offer cross-protection against a broad range of noroviruses,” Dr. Pattekar and colleagues wrote.

To test this hypothesis, they first collected peripheral blood mononuclear cells (PBMCs) from three healthy volunteers with unknown norovirus exposure history. Then serum samples were screened for norovirus functional antibodies via the binding between virus-like particles (VLPs) and histo–blood group antigens (HBGAs). This revealed disparate profiles of blocking antibodies against various norovirus strains. While donor 1 and donor 2 had antibodies against multiple strains, donor 3 lacked norovirus antibodies. Further testing showed that this latter individual was a nonsecretor with limited exposure history.

Next, the investigators tested donor PBMCs for norovirus-specific T-cell responses with use of overlapping libraries of peptides for each of the three norovirus open reading frames (ORF1, ORF2, and ORF3). T-cell responses, predominantly involving CD8+ T cells, were observed in all donors. While donor 1 had the greatest response to ORF1, donors 2 and 3 had responses that focused on ORF2.

“Thus, norovirus-specific T cells targeting ORF1 and ORF2 epitopes are present in peripheral blood from healthy donors regardless of secretor status,” the investigators wrote.

To better characterize T-cell epitopes, the investigators subdivided the overlapping peptide libraries into groups of shorter peptides, then exposed serum to these smaller component pools. This revealed eight HLA class I restricted epitopes that were derived from a genogroup II.4 pandemic norovirus strain; this group of variants has been responsible for all six of the norovirus pandemics since 1996.

Closer examination of the epitopes showed that they were “broadly conserved beyond GII.4.” Only one epitope exhibited variation in the C-terminal aromatic anchor, and it was nondominant. The investigators therefore identified seven immunodominant CD8+ epitopes, which they considered “valuable targets for vaccine and cell-based therapies.

“These data further confirm that epitope-specific CD8+ T cells are a universal feature of the overall norovirus immune response and could be an attractive target for future vaccines,” the investigators wrote.

Additional testing involving samples of spleen, mesenteric lymph nodes, and duodenum from deceased individuals showed presence of norovirus-specific CD8+ T cells, with particular abundance in intestinal tissue, and distinct phenotypes and functional properties in different tissue types.

“Future studies using tetramers and intestinal samples should build on these observations and fully define the location and microenvironment of norovirus-specific T cells,” the investigators wrote. “If carried out in the context of a vaccine trial, such studies could be highly valuable in elucidating tissue-resident memory correlates of norovirus immunity.”

The study was funded by the National Institutes of Health, the Wellcome Trust, and Deutsche Forschungsgemeinschaft. The investigators reported no conflicts of interest.

Protection against norovirus gastroenteritis is supported in part by norovirus-specific CD8+ T cells that reside in peripheral, intestinal, and lymphoid tissues, according to investigators.

These findings, and the molecular tools used to discover them, could guide development of a norovirus vaccine and novel cellular therapies, according to lead author Ajinkya Pattekar, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“Currently, there are no approved pharmacologic therapies against norovirus, and despite several promising clinical trials, an effective vaccine is not available,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, which may stem from an incomplete understanding of norovirus immunity, according to Dr. Pattekar and colleagues.

They noted that most previous research has focused on humoral immunity, which appears variable between individuals, with some people exhibiting a strong humoral response, while others mount only partial humoral protection. The investigators also noted that, depending on which studies were examined, this type of defense could last years or fade within weeks to months and that “immune mechanisms other than antibodies may be important for protection against noroviruses.”

Specifically, cellular immunity may be at work. A 2020 study involving volunteers showed that T cells were cross-reactive to a type of norovirus the participants had never been exposed to.

“These findings suggest that T cells may target conserved epitopes and could offer cross-protection against a broad range of noroviruses,” Dr. Pattekar and colleagues wrote.

To test this hypothesis, they first collected peripheral blood mononuclear cells (PBMCs) from three healthy volunteers with unknown norovirus exposure history. Then serum samples were screened for norovirus functional antibodies via the binding between virus-like particles (VLPs) and histo–blood group antigens (HBGAs). This revealed disparate profiles of blocking antibodies against various norovirus strains. While donor 1 and donor 2 had antibodies against multiple strains, donor 3 lacked norovirus antibodies. Further testing showed that this latter individual was a nonsecretor with limited exposure history.

Next, the investigators tested donor PBMCs for norovirus-specific T-cell responses with use of overlapping libraries of peptides for each of the three norovirus open reading frames (ORF1, ORF2, and ORF3). T-cell responses, predominantly involving CD8+ T cells, were observed in all donors. While donor 1 had the greatest response to ORF1, donors 2 and 3 had responses that focused on ORF2.

“Thus, norovirus-specific T cells targeting ORF1 and ORF2 epitopes are present in peripheral blood from healthy donors regardless of secretor status,” the investigators wrote.

To better characterize T-cell epitopes, the investigators subdivided the overlapping peptide libraries into groups of shorter peptides, then exposed serum to these smaller component pools. This revealed eight HLA class I restricted epitopes that were derived from a genogroup II.4 pandemic norovirus strain; this group of variants has been responsible for all six of the norovirus pandemics since 1996.

Closer examination of the epitopes showed that they were “broadly conserved beyond GII.4.” Only one epitope exhibited variation in the C-terminal aromatic anchor, and it was nondominant. The investigators therefore identified seven immunodominant CD8+ epitopes, which they considered “valuable targets for vaccine and cell-based therapies.

“These data further confirm that epitope-specific CD8+ T cells are a universal feature of the overall norovirus immune response and could be an attractive target for future vaccines,” the investigators wrote.

Additional testing involving samples of spleen, mesenteric lymph nodes, and duodenum from deceased individuals showed presence of norovirus-specific CD8+ T cells, with particular abundance in intestinal tissue, and distinct phenotypes and functional properties in different tissue types.

“Future studies using tetramers and intestinal samples should build on these observations and fully define the location and microenvironment of norovirus-specific T cells,” the investigators wrote. “If carried out in the context of a vaccine trial, such studies could be highly valuable in elucidating tissue-resident memory correlates of norovirus immunity.”

The study was funded by the National Institutes of Health, the Wellcome Trust, and Deutsche Forschungsgemeinschaft. The investigators reported no conflicts of interest.

Protection against norovirus gastroenteritis is supported in part by norovirus-specific CD8+ T cells that reside in peripheral, intestinal, and lymphoid tissues, according to investigators.

These findings, and the molecular tools used to discover them, could guide development of a norovirus vaccine and novel cellular therapies, according to lead author Ajinkya Pattekar, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“Currently, there are no approved pharmacologic therapies against norovirus, and despite several promising clinical trials, an effective vaccine is not available,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, which may stem from an incomplete understanding of norovirus immunity, according to Dr. Pattekar and colleagues.

They noted that most previous research has focused on humoral immunity, which appears variable between individuals, with some people exhibiting a strong humoral response, while others mount only partial humoral protection. The investigators also noted that, depending on which studies were examined, this type of defense could last years or fade within weeks to months and that “immune mechanisms other than antibodies may be important for protection against noroviruses.”

Specifically, cellular immunity may be at work. A 2020 study involving volunteers showed that T cells were cross-reactive to a type of norovirus the participants had never been exposed to.

“These findings suggest that T cells may target conserved epitopes and could offer cross-protection against a broad range of noroviruses,” Dr. Pattekar and colleagues wrote.

To test this hypothesis, they first collected peripheral blood mononuclear cells (PBMCs) from three healthy volunteers with unknown norovirus exposure history. Then serum samples were screened for norovirus functional antibodies via the binding between virus-like particles (VLPs) and histo–blood group antigens (HBGAs). This revealed disparate profiles of blocking antibodies against various norovirus strains. While donor 1 and donor 2 had antibodies against multiple strains, donor 3 lacked norovirus antibodies. Further testing showed that this latter individual was a nonsecretor with limited exposure history.

Next, the investigators tested donor PBMCs for norovirus-specific T-cell responses with use of overlapping libraries of peptides for each of the three norovirus open reading frames (ORF1, ORF2, and ORF3). T-cell responses, predominantly involving CD8+ T cells, were observed in all donors. While donor 1 had the greatest response to ORF1, donors 2 and 3 had responses that focused on ORF2.

“Thus, norovirus-specific T cells targeting ORF1 and ORF2 epitopes are present in peripheral blood from healthy donors regardless of secretor status,” the investigators wrote.

To better characterize T-cell epitopes, the investigators subdivided the overlapping peptide libraries into groups of shorter peptides, then exposed serum to these smaller component pools. This revealed eight HLA class I restricted epitopes that were derived from a genogroup II.4 pandemic norovirus strain; this group of variants has been responsible for all six of the norovirus pandemics since 1996.

Closer examination of the epitopes showed that they were “broadly conserved beyond GII.4.” Only one epitope exhibited variation in the C-terminal aromatic anchor, and it was nondominant. The investigators therefore identified seven immunodominant CD8+ epitopes, which they considered “valuable targets for vaccine and cell-based therapies.

“These data further confirm that epitope-specific CD8+ T cells are a universal feature of the overall norovirus immune response and could be an attractive target for future vaccines,” the investigators wrote.

Additional testing involving samples of spleen, mesenteric lymph nodes, and duodenum from deceased individuals showed presence of norovirus-specific CD8+ T cells, with particular abundance in intestinal tissue, and distinct phenotypes and functional properties in different tissue types.

“Future studies using tetramers and intestinal samples should build on these observations and fully define the location and microenvironment of norovirus-specific T cells,” the investigators wrote. “If carried out in the context of a vaccine trial, such studies could be highly valuable in elucidating tissue-resident memory correlates of norovirus immunity.”

The study was funded by the National Institutes of Health, the Wellcome Trust, and Deutsche Forschungsgemeinschaft. The investigators reported no conflicts of interest.

Incorporation of a nonintensive fitness intervention for women with obesity into a standard fertility treatment program could be cost effective, a new analysis finds.

Financial data for the Canadian Fit-for-Fertility program were presented March 20 at the annual meeting of the Endocrine Society by Matea Belan, PhD, of the division of endocrinology at the University of Sherbrooke (Que.).

Women with obesity and infertility are typically advised to lose 5%-10% of their body weight as first-line fertility treatment, as doing so has been shown to increase rates of ovulation and pregnancy. But most established fertility treatment programs don’t incorporate organized lifestyle modification interventions, Dr. Belan explained during a press briefing.

“Mostly they’re just given general advice, not resources. It’s up to the woman to seek help for lifestyle. Our idea is to give them access to intervention that’s integrated into the setting of a fertility clinic,” she said.

Primary results from the Fit-for-Fertility program, including significant weight loss and a 40% increased live birth rate at 18 months, compared with standard fertility treatment, were presented at ENDO 2019 and reported at the time by this news organization.

In the new analysis, the cost in Canadian dollars per additional newborn achieved with the Fit-for-Fertility program was similar to the willingness-to-pay for in vitro fertilization from a health system perspective.

The final goal, lead investigator Jean-Patrice Baillargeon, MD, said in an interview, “would be to convince stakeholders, and mainly the provincial government, to cover the costs of our lifestyle program. This would not be more costly than funding IVF, but [would provide] more long-term benefits for the whole family and the offspring.”

Chloe A. Zera, MD, said in an interview that she supports the idea in principle, but is concerned that, in the U.S. health care system, women don’t always have access to fertility and obesity treatments to begin with.

“There’s a huge equity issue. People with Medicaid don’t necessarily get coverage for IVF. ... Even many commercially insured people are paying out of pocket, which can be $10,000 to $15,000 for a cycle just for the medications, so the cost to patients on the individual level is huge,” said Dr. Zera, who is associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston.

She added: “I’m prolifestyle modification. I’m also proequity in health care delivery so I would want to make sure that the way it’s delivered incorporates that as a consideration. ... Is that money better spent on primary prevention of obesity and access to basic services and basic reproductive health care for everybody?”
 

Primary results: Improvements in overall and spontaneous pregnancy rates

The study included 130 women with infertility and a body mass index of at least 30 kg/m2 (mean, 40), of whom 65 were randomized to the Fit-for-Fitness program and 65 to standard fertility treatment that did not include a lifestyle intervention, although those women could consult professionals on their own. The women in the lifestyle intervention group had to stop medical fertility treatments for the first 6 months but could use them thereafter while the controls continued to use them throughout.

Based on motivational interviewing, the program focused on womens’ individual likes and dislikes, experiences, and perceived capacities, aiming to improve healthful habits gradually and with “low intensity” so as to maintain them in the long run.

The program combined individual sessions with a nutritionist and kinesiologist every 6 weeks and 12 mandatory group sessions. The women were asked to reduce their total caloric intake by about 500 calories/day but weren’t asked to change their diets. They were also advised to increase physical activity by about 150 minutes/week.

“We want to keep it sustainable in time, so they don’t have a relapse when they become pregnant, and to help the newborn and spouse too. It’s about improving and maintaining habits,” Dr. Belan explained during the briefing.

At 6 months, mean weight changes were –3.4% versus –0.89% for the intervention versus control groups (P = .003).

“What is important for women with obesity and infertility is to improve their lifestyle, both physical activity and nutrition, even if the weight loss is minimal,” noted Dr. Baillargeon, professor of medicine, health sciences research and physiology, also at the University of Sherbrooke.

A total of 46 intervention and 52 control patients finished the 18-month study. Pregnancies occurred in 61% of the intervention group versus 39% of the controls, while spontaneous pregnancies – among those not using medical fertility treatments – occurred in 33.3% versus 12.3% (P = .009).

The primary outcome, live births at 18 months, occurred in 51.0% of the intervention group versus 36.8% of controls, which wasn’t a statistically significant difference, but was “highly clinically significant,” Dr. Belan said.
 

Cost per additional newborn similar to IVF

Costs (in Canadian dollars) considered in the analysis included those related to the management of infertility, obesity, pregnancy, and childbirth. The incremental cost-effectiveness ratios, a standard cost-effectiveness measure, per live birth were $24,393 from a societal perspective, $12,633 for the health system, and $5,980 for the patient.

Because the $12,633 health system cost per additional newborn with the Fit-for-Fertility program is similar to the health system’s willingness-to-pay for IVF of up to $15,000, a lifestyle intervention could be considered cost-efficient compared with the standard of care, Dr. Belan said.

“We think that the Fit-for-Fertility program could be deemed cost effective and could represent an interesting alternative to the usual standard of care for women with obesity seeking fertility treatments,” she commented.

The Canadian Institutes of Health Research is funding a larger randomized, controlled trial of the program at six Canadian centers to validate these results.

Dr. Belan, Dr. Baillargeon, and Dr. Zera reported no relevant financial relationships.

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

Incorporation of a nonintensive fitness intervention for women with obesity into a standard fertility treatment program could be cost effective, a new analysis finds.

Financial data for the Canadian Fit-for-Fertility program were presented March 20 at the annual meeting of the Endocrine Society by Matea Belan, PhD, of the division of endocrinology at the University of Sherbrooke (Que.).

Women with obesity and infertility are typically advised to lose 5%-10% of their body weight as first-line fertility treatment, as doing so has been shown to increase rates of ovulation and pregnancy. But most established fertility treatment programs don’t incorporate organized lifestyle modification interventions, Dr. Belan explained during a press briefing.

“Mostly they’re just given general advice, not resources. It’s up to the woman to seek help for lifestyle. Our idea is to give them access to intervention that’s integrated into the setting of a fertility clinic,” she said.

Primary results from the Fit-for-Fertility program, including significant weight loss and a 40% increased live birth rate at 18 months, compared with standard fertility treatment, were presented at ENDO 2019 and reported at the time by this news organization.

In the new analysis, the cost in Canadian dollars per additional newborn achieved with the Fit-for-Fertility program was similar to the willingness-to-pay for in vitro fertilization from a health system perspective.

The final goal, lead investigator Jean-Patrice Baillargeon, MD, said in an interview, “would be to convince stakeholders, and mainly the provincial government, to cover the costs of our lifestyle program. This would not be more costly than funding IVF, but [would provide] more long-term benefits for the whole family and the offspring.”

Chloe A. Zera, MD, said in an interview that she supports the idea in principle, but is concerned that, in the U.S. health care system, women don’t always have access to fertility and obesity treatments to begin with.

“There’s a huge equity issue. People with Medicaid don’t necessarily get coverage for IVF. ... Even many commercially insured people are paying out of pocket, which can be $10,000 to $15,000 for a cycle just for the medications, so the cost to patients on the individual level is huge,” said Dr. Zera, who is associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston.

She added: “I’m prolifestyle modification. I’m also proequity in health care delivery so I would want to make sure that the way it’s delivered incorporates that as a consideration. ... Is that money better spent on primary prevention of obesity and access to basic services and basic reproductive health care for everybody?”
 

Primary results: Improvements in overall and spontaneous pregnancy rates

The study included 130 women with infertility and a body mass index of at least 30 kg/m2 (mean, 40), of whom 65 were randomized to the Fit-for-Fitness program and 65 to standard fertility treatment that did not include a lifestyle intervention, although those women could consult professionals on their own. The women in the lifestyle intervention group had to stop medical fertility treatments for the first 6 months but could use them thereafter while the controls continued to use them throughout.

Based on motivational interviewing, the program focused on womens’ individual likes and dislikes, experiences, and perceived capacities, aiming to improve healthful habits gradually and with “low intensity” so as to maintain them in the long run.

The program combined individual sessions with a nutritionist and kinesiologist every 6 weeks and 12 mandatory group sessions. The women were asked to reduce their total caloric intake by about 500 calories/day but weren’t asked to change their diets. They were also advised to increase physical activity by about 150 minutes/week.

“We want to keep it sustainable in time, so they don’t have a relapse when they become pregnant, and to help the newborn and spouse too. It’s about improving and maintaining habits,” Dr. Belan explained during the briefing.

At 6 months, mean weight changes were –3.4% versus –0.89% for the intervention versus control groups (P = .003).

“What is important for women with obesity and infertility is to improve their lifestyle, both physical activity and nutrition, even if the weight loss is minimal,” noted Dr. Baillargeon, professor of medicine, health sciences research and physiology, also at the University of Sherbrooke.

A total of 46 intervention and 52 control patients finished the 18-month study. Pregnancies occurred in 61% of the intervention group versus 39% of the controls, while spontaneous pregnancies – among those not using medical fertility treatments – occurred in 33.3% versus 12.3% (P = .009).

The primary outcome, live births at 18 months, occurred in 51.0% of the intervention group versus 36.8% of controls, which wasn’t a statistically significant difference, but was “highly clinically significant,” Dr. Belan said.
 

Cost per additional newborn similar to IVF

Costs (in Canadian dollars) considered in the analysis included those related to the management of infertility, obesity, pregnancy, and childbirth. The incremental cost-effectiveness ratios, a standard cost-effectiveness measure, per live birth were $24,393 from a societal perspective, $12,633 for the health system, and $5,980 for the patient.

Because the $12,633 health system cost per additional newborn with the Fit-for-Fertility program is similar to the health system’s willingness-to-pay for IVF of up to $15,000, a lifestyle intervention could be considered cost-efficient compared with the standard of care, Dr. Belan said.

“We think that the Fit-for-Fertility program could be deemed cost effective and could represent an interesting alternative to the usual standard of care for women with obesity seeking fertility treatments,” she commented.

The Canadian Institutes of Health Research is funding a larger randomized, controlled trial of the program at six Canadian centers to validate these results.

Dr. Belan, Dr. Baillargeon, and Dr. Zera reported no relevant financial relationships.

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

Incorporation of a nonintensive fitness intervention for women with obesity into a standard fertility treatment program could be cost effective, a new analysis finds.

Financial data for the Canadian Fit-for-Fertility program were presented March 20 at the annual meeting of the Endocrine Society by Matea Belan, PhD, of the division of endocrinology at the University of Sherbrooke (Que.).

Women with obesity and infertility are typically advised to lose 5%-10% of their body weight as first-line fertility treatment, as doing so has been shown to increase rates of ovulation and pregnancy. But most established fertility treatment programs don’t incorporate organized lifestyle modification interventions, Dr. Belan explained during a press briefing.

“Mostly they’re just given general advice, not resources. It’s up to the woman to seek help for lifestyle. Our idea is to give them access to intervention that’s integrated into the setting of a fertility clinic,” she said.

Primary results from the Fit-for-Fertility program, including significant weight loss and a 40% increased live birth rate at 18 months, compared with standard fertility treatment, were presented at ENDO 2019 and reported at the time by this news organization.

In the new analysis, the cost in Canadian dollars per additional newborn achieved with the Fit-for-Fertility program was similar to the willingness-to-pay for in vitro fertilization from a health system perspective.

The final goal, lead investigator Jean-Patrice Baillargeon, MD, said in an interview, “would be to convince stakeholders, and mainly the provincial government, to cover the costs of our lifestyle program. This would not be more costly than funding IVF, but [would provide] more long-term benefits for the whole family and the offspring.”

Chloe A. Zera, MD, said in an interview that she supports the idea in principle, but is concerned that, in the U.S. health care system, women don’t always have access to fertility and obesity treatments to begin with.

“There’s a huge equity issue. People with Medicaid don’t necessarily get coverage for IVF. ... Even many commercially insured people are paying out of pocket, which can be $10,000 to $15,000 for a cycle just for the medications, so the cost to patients on the individual level is huge,” said Dr. Zera, who is associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston.

She added: “I’m prolifestyle modification. I’m also proequity in health care delivery so I would want to make sure that the way it’s delivered incorporates that as a consideration. ... Is that money better spent on primary prevention of obesity and access to basic services and basic reproductive health care for everybody?”
 

Primary results: Improvements in overall and spontaneous pregnancy rates

The study included 130 women with infertility and a body mass index of at least 30 kg/m2 (mean, 40), of whom 65 were randomized to the Fit-for-Fitness program and 65 to standard fertility treatment that did not include a lifestyle intervention, although those women could consult professionals on their own. The women in the lifestyle intervention group had to stop medical fertility treatments for the first 6 months but could use them thereafter while the controls continued to use them throughout.

Based on motivational interviewing, the program focused on womens’ individual likes and dislikes, experiences, and perceived capacities, aiming to improve healthful habits gradually and with “low intensity” so as to maintain them in the long run.

The program combined individual sessions with a nutritionist and kinesiologist every 6 weeks and 12 mandatory group sessions. The women were asked to reduce their total caloric intake by about 500 calories/day but weren’t asked to change their diets. They were also advised to increase physical activity by about 150 minutes/week.

“We want to keep it sustainable in time, so they don’t have a relapse when they become pregnant, and to help the newborn and spouse too. It’s about improving and maintaining habits,” Dr. Belan explained during the briefing.

At 6 months, mean weight changes were –3.4% versus –0.89% for the intervention versus control groups (P = .003).

“What is important for women with obesity and infertility is to improve their lifestyle, both physical activity and nutrition, even if the weight loss is minimal,” noted Dr. Baillargeon, professor of medicine, health sciences research and physiology, also at the University of Sherbrooke.

A total of 46 intervention and 52 control patients finished the 18-month study. Pregnancies occurred in 61% of the intervention group versus 39% of the controls, while spontaneous pregnancies – among those not using medical fertility treatments – occurred in 33.3% versus 12.3% (P = .009).

The primary outcome, live births at 18 months, occurred in 51.0% of the intervention group versus 36.8% of controls, which wasn’t a statistically significant difference, but was “highly clinically significant,” Dr. Belan said.
 

Cost per additional newborn similar to IVF

Costs (in Canadian dollars) considered in the analysis included those related to the management of infertility, obesity, pregnancy, and childbirth. The incremental cost-effectiveness ratios, a standard cost-effectiveness measure, per live birth were $24,393 from a societal perspective, $12,633 for the health system, and $5,980 for the patient.

Because the $12,633 health system cost per additional newborn with the Fit-for-Fertility program is similar to the health system’s willingness-to-pay for IVF of up to $15,000, a lifestyle intervention could be considered cost-efficient compared with the standard of care, Dr. Belan said.

“We think that the Fit-for-Fertility program could be deemed cost effective and could represent an interesting alternative to the usual standard of care for women with obesity seeking fertility treatments,” she commented.

The Canadian Institutes of Health Research is funding a larger randomized, controlled trial of the program at six Canadian centers to validate these results.

Dr. Belan, Dr. Baillargeon, and Dr. Zera reported no relevant financial relationships.

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

A new protocol designed to help patients in rheumatology clinics quit smoking proved both efficient and effective in referring willing participants to free tobacco quit lines.

seanika/ThinkStock

“Rheumatology visits provide a unique opportunity to address smoking as a chronic modifiable risk factor in populations at high risk for cardiovascular disease, pulmonary disease, and rheumatic disease progression,” wrote Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, and colleagues. The study was published in Arthritis Care & Research.

To assess the effectiveness of implementing a smoking cessation protocol for patients with rheumatic diseases, the researchers launched a quasi-experimental cohort study in which their Quit Connect protocol was tested at three rheumatology clinics. Adapting the Ask, Advise, Connect primary care protocol to a new setting, nurses and medical assistants were trained to use electronic health record (EHR) prompts that would check if patients who smoked were ready to quit within 30 days, advise them to do so, and then use electronic referrals to connect them to state-run tobacco quit lines. An extended baseline period – October 2012 to March 2016 – was compared to a 6-month intervention period from April to October 2016.

Across 54,090 pre- and postimplementation rheumatology clinic visits, 4,601 were with current smokers. Demographics were similar across both periods: The mean age of the patients was 51 years, about two-thirds were female, and 85% were White.

Clinicians’ assessment of tobacco use before and after implementation of the program stayed steady at 96% of patient visits, but the percentage of tobacco users’ visits that included checking for readiness to quit within the next 30 days rose from 3% (135 of 4,078) to 80% (421 of 523).

Before the implementation of the program, 0.6% of eligible visits with current smokers included a quit-line referral offer. After implementation, 93 (18%) of the 523 smokers who visited – 122 of whom said they were ready to quit – were offered referrals, a 26-fold increase. Of the 93 offered referrals, 66 (71%) accepted and 16 set a quit date or reported having quit; 11 accepted counseling services and nicotine replacement.

Although clinic staff reported encountering several obstacles, such as the need to craft nonthreatening language for challenging patients, they also contributed their own talking points that were included in the EHR tools and desktop brochures. On average, the protocol took less than 90 seconds to perform.

Rheumatologists can make headway on patients quitting smoking

“While smoking cessation programs require time and resources to implement, this study suggests a role for evidence-based protocols within rheumatology centers,” Medha Barbhaiya, MD, a rheumatologist at the Hospital for Special Surgery in New York, said in an interview. “Given that current smokers are at an increased risk of developing more severe rheumatic disease and cardiovascular disease, and patients often visit their rheumatologist multiple times yearly, rheumatologists may be well-positioned to address smoking cessation with patients.”

In regard to next steps, she noted that “while future large studies in diverse cohorts are needed to confirm these findings, implementing a formal smoking cessation protocol within rheumatology centers may provide a unique opportunity for rheumatologists to directly help patients modify their disease risk, leading to improved health outcomes.”

The authors acknowledged their study’s limitations, including the fact that it was a prepost design and not a randomized trial. They also recognized that many tobacco users require 8-10 attempts before permanently quitting, likely lessening the lasting impact of the short-term study. They did cite expert analysis, however, that says “connecting patients to evidence-based resources makes them more likely to permanently quit.”

The study was supported in part by Pfizer’s office of Independent Grants for Learning and Change and by a grant collaboration from the University of Wisconsin Clinical and Translational Science Award and the University of Wisconsin School of Medicine and Public Health’s Wisconsin Partnership Program, through the NIH National Center for Advancing Translational Sciences.

A new protocol designed to help patients in rheumatology clinics quit smoking proved both efficient and effective in referring willing participants to free tobacco quit lines.

seanika/ThinkStock

“Rheumatology visits provide a unique opportunity to address smoking as a chronic modifiable risk factor in populations at high risk for cardiovascular disease, pulmonary disease, and rheumatic disease progression,” wrote Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, and colleagues. The study was published in Arthritis Care & Research.

To assess the effectiveness of implementing a smoking cessation protocol for patients with rheumatic diseases, the researchers launched a quasi-experimental cohort study in which their Quit Connect protocol was tested at three rheumatology clinics. Adapting the Ask, Advise, Connect primary care protocol to a new setting, nurses and medical assistants were trained to use electronic health record (EHR) prompts that would check if patients who smoked were ready to quit within 30 days, advise them to do so, and then use electronic referrals to connect them to state-run tobacco quit lines. An extended baseline period – October 2012 to March 2016 – was compared to a 6-month intervention period from April to October 2016.

Across 54,090 pre- and postimplementation rheumatology clinic visits, 4,601 were with current smokers. Demographics were similar across both periods: The mean age of the patients was 51 years, about two-thirds were female, and 85% were White.

Clinicians’ assessment of tobacco use before and after implementation of the program stayed steady at 96% of patient visits, but the percentage of tobacco users’ visits that included checking for readiness to quit within the next 30 days rose from 3% (135 of 4,078) to 80% (421 of 523).

Before the implementation of the program, 0.6% of eligible visits with current smokers included a quit-line referral offer. After implementation, 93 (18%) of the 523 smokers who visited – 122 of whom said they were ready to quit – were offered referrals, a 26-fold increase. Of the 93 offered referrals, 66 (71%) accepted and 16 set a quit date or reported having quit; 11 accepted counseling services and nicotine replacement.

Although clinic staff reported encountering several obstacles, such as the need to craft nonthreatening language for challenging patients, they also contributed their own talking points that were included in the EHR tools and desktop brochures. On average, the protocol took less than 90 seconds to perform.

Rheumatologists can make headway on patients quitting smoking

“While smoking cessation programs require time and resources to implement, this study suggests a role for evidence-based protocols within rheumatology centers,” Medha Barbhaiya, MD, a rheumatologist at the Hospital for Special Surgery in New York, said in an interview. “Given that current smokers are at an increased risk of developing more severe rheumatic disease and cardiovascular disease, and patients often visit their rheumatologist multiple times yearly, rheumatologists may be well-positioned to address smoking cessation with patients.”

In regard to next steps, she noted that “while future large studies in diverse cohorts are needed to confirm these findings, implementing a formal smoking cessation protocol within rheumatology centers may provide a unique opportunity for rheumatologists to directly help patients modify their disease risk, leading to improved health outcomes.”

The authors acknowledged their study’s limitations, including the fact that it was a prepost design and not a randomized trial. They also recognized that many tobacco users require 8-10 attempts before permanently quitting, likely lessening the lasting impact of the short-term study. They did cite expert analysis, however, that says “connecting patients to evidence-based resources makes them more likely to permanently quit.”

The study was supported in part by Pfizer’s office of Independent Grants for Learning and Change and by a grant collaboration from the University of Wisconsin Clinical and Translational Science Award and the University of Wisconsin School of Medicine and Public Health’s Wisconsin Partnership Program, through the NIH National Center for Advancing Translational Sciences.

A new protocol designed to help patients in rheumatology clinics quit smoking proved both efficient and effective in referring willing participants to free tobacco quit lines.

seanika/ThinkStock

“Rheumatology visits provide a unique opportunity to address smoking as a chronic modifiable risk factor in populations at high risk for cardiovascular disease, pulmonary disease, and rheumatic disease progression,” wrote Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, and colleagues. The study was published in Arthritis Care & Research.

To assess the effectiveness of implementing a smoking cessation protocol for patients with rheumatic diseases, the researchers launched a quasi-experimental cohort study in which their Quit Connect protocol was tested at three rheumatology clinics. Adapting the Ask, Advise, Connect primary care protocol to a new setting, nurses and medical assistants were trained to use electronic health record (EHR) prompts that would check if patients who smoked were ready to quit within 30 days, advise them to do so, and then use electronic referrals to connect them to state-run tobacco quit lines. An extended baseline period – October 2012 to March 2016 – was compared to a 6-month intervention period from April to October 2016.

Across 54,090 pre- and postimplementation rheumatology clinic visits, 4,601 were with current smokers. Demographics were similar across both periods: The mean age of the patients was 51 years, about two-thirds were female, and 85% were White.

Clinicians’ assessment of tobacco use before and after implementation of the program stayed steady at 96% of patient visits, but the percentage of tobacco users’ visits that included checking for readiness to quit within the next 30 days rose from 3% (135 of 4,078) to 80% (421 of 523).

Before the implementation of the program, 0.6% of eligible visits with current smokers included a quit-line referral offer. After implementation, 93 (18%) of the 523 smokers who visited – 122 of whom said they were ready to quit – were offered referrals, a 26-fold increase. Of the 93 offered referrals, 66 (71%) accepted and 16 set a quit date or reported having quit; 11 accepted counseling services and nicotine replacement.

Although clinic staff reported encountering several obstacles, such as the need to craft nonthreatening language for challenging patients, they also contributed their own talking points that were included in the EHR tools and desktop brochures. On average, the protocol took less than 90 seconds to perform.

Rheumatologists can make headway on patients quitting smoking

“While smoking cessation programs require time and resources to implement, this study suggests a role for evidence-based protocols within rheumatology centers,” Medha Barbhaiya, MD, a rheumatologist at the Hospital for Special Surgery in New York, said in an interview. “Given that current smokers are at an increased risk of developing more severe rheumatic disease and cardiovascular disease, and patients often visit their rheumatologist multiple times yearly, rheumatologists may be well-positioned to address smoking cessation with patients.”

In regard to next steps, she noted that “while future large studies in diverse cohorts are needed to confirm these findings, implementing a formal smoking cessation protocol within rheumatology centers may provide a unique opportunity for rheumatologists to directly help patients modify their disease risk, leading to improved health outcomes.”

The authors acknowledged their study’s limitations, including the fact that it was a prepost design and not a randomized trial. They also recognized that many tobacco users require 8-10 attempts before permanently quitting, likely lessening the lasting impact of the short-term study. They did cite expert analysis, however, that says “connecting patients to evidence-based resources makes them more likely to permanently quit.”

The study was supported in part by Pfizer’s office of Independent Grants for Learning and Change and by a grant collaboration from the University of Wisconsin Clinical and Translational Science Award and the University of Wisconsin School of Medicine and Public Health’s Wisconsin Partnership Program, through the NIH National Center for Advancing Translational Sciences.