MUNICH – Women with cardiac disease who became pregnant had a nearly 100-fold higher mortality rate, compared with pregnant women without cardiac disease, according to the outcomes of more than 5,700 pregnancies in an international registry of women with cardiac disease.

Mitchel L. Zoler/MDedge News

In addition to increased mortality, women with cardiac disease who become pregnant also had a greater than 100-fold higher rate of developing heart failure, compared with pregnant women without cardiac disease.

Despite these highly elevated relative risks, the absolute rate of serious complications from pregnancy for most women with heart disease was relatively modest. The worst prognosis by far was for the 1% of women in the registry who had pulmonary arterial hypertension at the time their pregnancy began. For these women, mortality during pregnancy was about 9%, and new-onset heart failure occurred in about one third. Another subgroup showing particularly poor outcomes were women classified with WHO IV maternal cardiovascular risk by the modified World Health Organization criteria, which corresponds to having an “extremely high risk of maternal mortality or severe morbidity,” according to guidelines published in the European Heart Journal (2011 Dec 1;32[24]:3147-97).These women, constituting 7% of the registry cohort, had a 2.5% mortality rate during pregnancy and a 33% incidence of heart failure.

Across all women with cardiac disease enrolled in the registry, the incidence of death during pregnancy was 0.6% and the incidence of heart failure was 11%. Women without cardiac disease have rates of 0.007% and less than 0.1%, respectively, Jolien Roos-Hesselink, MD, said at the annual congress of the European Society of Cardiology.

“The most important message of my talk is that all patients should be counseled, not just the women at high risk, for whom pregnancy is contraindicated, but also the women at low risk,” who can have a child with relative safety, she said. “Many women [with cardiac disease] can go through pregnancy at low risk.” Counseling is the key so that women know their risk before becoming pregnant, stressed Dr. Roos-Hesselink, a cardiologist at Erasmus Medical Center in Rotterdam, the Netherlands.

Based on the observed rates of mortality and other complications, pulmonary arterial hypertension and the other cardiac conditions that define a WHO IV maternal risk classification remain contraindications for pregnancy, she said. According to the 2011 guidelines from the European Society of Cardiology for managing cardiovascular disease during pregnancy, the full list of conditions that define a WHO IV classification are the following:

• Pulmonary arterial hypertension of any cause.
• Severe systemic ventricular dysfunction (a left ventricular ejection fraction of less than 30%) or New York Heart Association functional class III or IV.
• Previous peripartum cardiomyopathy with any residual impairment of left ventricular function.
• Severe mitral stenosis or severe symptomatic aortic stenosis.
• Marfan syndrome with the aorta dilated to more than 45 mm.
• Aortic dilatation greater than 50 mm in aortic disease associated with a bicuspid aortic valve.
• Native severe coarctation.

The registry data, collected during 2007-2018, showed a clear increase in the percentage of women with WHO class IV cardiovascular disease who became pregnant and entered the registry despite the contraindication designation for that classification, rising from about 1% of enrolled women in 2008 and 2009 to more than 10% of women in 2013, 2016, and 2017. “Individualization is necessary, but all these women are at very high risk and should be counseled against pregnancy,” Dr. Roos-Hesselink said.

The Registry of Pregnancy and Cardiac Disease (ROPAC) enrolled 5,739 pregnant women at any of 138 participating centers in 53 countries including the United States. Clinicians submitted WHO classification of cardiovascular risk for 5,711 of these women. The most common risk was congenital heart disease in 57% of enrolled women, followed by valvular heart disease in 29% and cardiomyopathy in 7%. Nearly 1,200 women in the registry – about 21% of the total – had a WHO I classification, which meant that they would be expected to have no detectable increase in mortality rate during pregnancy, compared with women without cardiac disease, and either no rise in morbidity or a mild effect.

Delivery was by cesarean section in 44% of the pregnancies, roughly twice the rate in women without diagnosed cardiac disease, even though published guidelines don’t advise cesarean delivery because of cardiac disease, Dr. Roos-Hesselink said. “Cesarean sections are used too often, in my opinion,” she commented, but added that many of these women require delivery at a tertiary, specialized center.

Overall fetal mortality was 1%, nearly threefold higher than in pregnancies in women without cardiac disease, and the overall incidence of fetal and neonatal complications was especially high, at 53%, in women with pulmonary arterial hypertension. The incidence of obstetrical complications was roughly similar across the range of cardiac disease type, ranging from 16% to 24%. Premature delivery occurred in 28% of women in the high-risk WHO IV class, compared with a 13% rate among women in the WHO I class. The mortality rate was 0.2% among the WHO class I women, and their heart failure incidence was 5%.

The ROPAC registry is sponsored by the European Society of Cardiology. Dr. Roos-Hesselink had no disclosures.

[email protected]


 

MUNICH – Women with cardiac disease who became pregnant had a nearly 100-fold higher mortality rate, compared with pregnant women without cardiac disease, according to the outcomes of more than 5,700 pregnancies in an international registry of women with cardiac disease.

Mitchel L. Zoler/MDedge News

In addition to increased mortality, women with cardiac disease who become pregnant also had a greater than 100-fold higher rate of developing heart failure, compared with pregnant women without cardiac disease.

Despite these highly elevated relative risks, the absolute rate of serious complications from pregnancy for most women with heart disease was relatively modest. The worst prognosis by far was for the 1% of women in the registry who had pulmonary arterial hypertension at the time their pregnancy began. For these women, mortality during pregnancy was about 9%, and new-onset heart failure occurred in about one third. Another subgroup showing particularly poor outcomes were women classified with WHO IV maternal cardiovascular risk by the modified World Health Organization criteria, which corresponds to having an “extremely high risk of maternal mortality or severe morbidity,” according to guidelines published in the European Heart Journal (2011 Dec 1;32[24]:3147-97).These women, constituting 7% of the registry cohort, had a 2.5% mortality rate during pregnancy and a 33% incidence of heart failure.

Across all women with cardiac disease enrolled in the registry, the incidence of death during pregnancy was 0.6% and the incidence of heart failure was 11%. Women without cardiac disease have rates of 0.007% and less than 0.1%, respectively, Jolien Roos-Hesselink, MD, said at the annual congress of the European Society of Cardiology.

“The most important message of my talk is that all patients should be counseled, not just the women at high risk, for whom pregnancy is contraindicated, but also the women at low risk,” who can have a child with relative safety, she said. “Many women [with cardiac disease] can go through pregnancy at low risk.” Counseling is the key so that women know their risk before becoming pregnant, stressed Dr. Roos-Hesselink, a cardiologist at Erasmus Medical Center in Rotterdam, the Netherlands.

Based on the observed rates of mortality and other complications, pulmonary arterial hypertension and the other cardiac conditions that define a WHO IV maternal risk classification remain contraindications for pregnancy, she said. According to the 2011 guidelines from the European Society of Cardiology for managing cardiovascular disease during pregnancy, the full list of conditions that define a WHO IV classification are the following:

• Pulmonary arterial hypertension of any cause.
• Severe systemic ventricular dysfunction (a left ventricular ejection fraction of less than 30%) or New York Heart Association functional class III or IV.
• Previous peripartum cardiomyopathy with any residual impairment of left ventricular function.
• Severe mitral stenosis or severe symptomatic aortic stenosis.
• Marfan syndrome with the aorta dilated to more than 45 mm.
• Aortic dilatation greater than 50 mm in aortic disease associated with a bicuspid aortic valve.
• Native severe coarctation.

The registry data, collected during 2007-2018, showed a clear increase in the percentage of women with WHO class IV cardiovascular disease who became pregnant and entered the registry despite the contraindication designation for that classification, rising from about 1% of enrolled women in 2008 and 2009 to more than 10% of women in 2013, 2016, and 2017. “Individualization is necessary, but all these women are at very high risk and should be counseled against pregnancy,” Dr. Roos-Hesselink said.

The Registry of Pregnancy and Cardiac Disease (ROPAC) enrolled 5,739 pregnant women at any of 138 participating centers in 53 countries including the United States. Clinicians submitted WHO classification of cardiovascular risk for 5,711 of these women. The most common risk was congenital heart disease in 57% of enrolled women, followed by valvular heart disease in 29% and cardiomyopathy in 7%. Nearly 1,200 women in the registry – about 21% of the total – had a WHO I classification, which meant that they would be expected to have no detectable increase in mortality rate during pregnancy, compared with women without cardiac disease, and either no rise in morbidity or a mild effect.

Delivery was by cesarean section in 44% of the pregnancies, roughly twice the rate in women without diagnosed cardiac disease, even though published guidelines don’t advise cesarean delivery because of cardiac disease, Dr. Roos-Hesselink said. “Cesarean sections are used too often, in my opinion,” she commented, but added that many of these women require delivery at a tertiary, specialized center.

Overall fetal mortality was 1%, nearly threefold higher than in pregnancies in women without cardiac disease, and the overall incidence of fetal and neonatal complications was especially high, at 53%, in women with pulmonary arterial hypertension. The incidence of obstetrical complications was roughly similar across the range of cardiac disease type, ranging from 16% to 24%. Premature delivery occurred in 28% of women in the high-risk WHO IV class, compared with a 13% rate among women in the WHO I class. The mortality rate was 0.2% among the WHO class I women, and their heart failure incidence was 5%.

The ROPAC registry is sponsored by the European Society of Cardiology. Dr. Roos-Hesselink had no disclosures.

[email protected]


 

MUNICH – Women with cardiac disease who became pregnant had a nearly 100-fold higher mortality rate, compared with pregnant women without cardiac disease, according to the outcomes of more than 5,700 pregnancies in an international registry of women with cardiac disease.

Mitchel L. Zoler/MDedge News

In addition to increased mortality, women with cardiac disease who become pregnant also had a greater than 100-fold higher rate of developing heart failure, compared with pregnant women without cardiac disease.

Despite these highly elevated relative risks, the absolute rate of serious complications from pregnancy for most women with heart disease was relatively modest. The worst prognosis by far was for the 1% of women in the registry who had pulmonary arterial hypertension at the time their pregnancy began. For these women, mortality during pregnancy was about 9%, and new-onset heart failure occurred in about one third. Another subgroup showing particularly poor outcomes were women classified with WHO IV maternal cardiovascular risk by the modified World Health Organization criteria, which corresponds to having an “extremely high risk of maternal mortality or severe morbidity,” according to guidelines published in the European Heart Journal (2011 Dec 1;32[24]:3147-97).These women, constituting 7% of the registry cohort, had a 2.5% mortality rate during pregnancy and a 33% incidence of heart failure.

Across all women with cardiac disease enrolled in the registry, the incidence of death during pregnancy was 0.6% and the incidence of heart failure was 11%. Women without cardiac disease have rates of 0.007% and less than 0.1%, respectively, Jolien Roos-Hesselink, MD, said at the annual congress of the European Society of Cardiology.

“The most important message of my talk is that all patients should be counseled, not just the women at high risk, for whom pregnancy is contraindicated, but also the women at low risk,” who can have a child with relative safety, she said. “Many women [with cardiac disease] can go through pregnancy at low risk.” Counseling is the key so that women know their risk before becoming pregnant, stressed Dr. Roos-Hesselink, a cardiologist at Erasmus Medical Center in Rotterdam, the Netherlands.

Based on the observed rates of mortality and other complications, pulmonary arterial hypertension and the other cardiac conditions that define a WHO IV maternal risk classification remain contraindications for pregnancy, she said. According to the 2011 guidelines from the European Society of Cardiology for managing cardiovascular disease during pregnancy, the full list of conditions that define a WHO IV classification are the following:

• Pulmonary arterial hypertension of any cause.
• Severe systemic ventricular dysfunction (a left ventricular ejection fraction of less than 30%) or New York Heart Association functional class III or IV.
• Previous peripartum cardiomyopathy with any residual impairment of left ventricular function.
• Severe mitral stenosis or severe symptomatic aortic stenosis.
• Marfan syndrome with the aorta dilated to more than 45 mm.
• Aortic dilatation greater than 50 mm in aortic disease associated with a bicuspid aortic valve.
• Native severe coarctation.

The registry data, collected during 2007-2018, showed a clear increase in the percentage of women with WHO class IV cardiovascular disease who became pregnant and entered the registry despite the contraindication designation for that classification, rising from about 1% of enrolled women in 2008 and 2009 to more than 10% of women in 2013, 2016, and 2017. “Individualization is necessary, but all these women are at very high risk and should be counseled against pregnancy,” Dr. Roos-Hesselink said.

The Registry of Pregnancy and Cardiac Disease (ROPAC) enrolled 5,739 pregnant women at any of 138 participating centers in 53 countries including the United States. Clinicians submitted WHO classification of cardiovascular risk for 5,711 of these women. The most common risk was congenital heart disease in 57% of enrolled women, followed by valvular heart disease in 29% and cardiomyopathy in 7%. Nearly 1,200 women in the registry – about 21% of the total – had a WHO I classification, which meant that they would be expected to have no detectable increase in mortality rate during pregnancy, compared with women without cardiac disease, and either no rise in morbidity or a mild effect.

Delivery was by cesarean section in 44% of the pregnancies, roughly twice the rate in women without diagnosed cardiac disease, even though published guidelines don’t advise cesarean delivery because of cardiac disease, Dr. Roos-Hesselink said. “Cesarean sections are used too often, in my opinion,” she commented, but added that many of these women require delivery at a tertiary, specialized center.

Overall fetal mortality was 1%, nearly threefold higher than in pregnancies in women without cardiac disease, and the overall incidence of fetal and neonatal complications was especially high, at 53%, in women with pulmonary arterial hypertension. The incidence of obstetrical complications was roughly similar across the range of cardiac disease type, ranging from 16% to 24%. Premature delivery occurred in 28% of women in the high-risk WHO IV class, compared with a 13% rate among women in the WHO I class. The mortality rate was 0.2% among the WHO class I women, and their heart failure incidence was 5%.

The ROPAC registry is sponsored by the European Society of Cardiology. Dr. Roos-Hesselink had no disclosures.

[email protected]


 

Care transitions between hospitals and skilled nursing facilities (SNFs) are a vulnerable time for patients. The current health care climate of decreasing hospital length of stay, readmission penalties, and increasing patient complexity has made hospital care transitions an important safety concern. Suboptimal transitions across clinical settings can result in adverse events, inadequately controlled comorbidities, deficient patient and caregiver preparation for discharge, medication errors, relocation stress, and overall increased morbidity and mortality.^1,2 Such care transitions also may generate unnecessary spending, including avoidable readmissions, emergency department utilization, and duplicative laboratory and imaging studies. Approximately 23% of patients admitted to SNFs are readmitted to acute care hospitals within 30 days, and these patients have increased mortality rates in risk-adjusted analyses. ^3,4

Compounding the magnitude of this risk and vulnerability is the significant growth in the number of patients discharged to SNFs over the past 30 years. In 2013, more than 20% of Medicare patients discharged from acute care hospitals were destined for SNFs.^5,6 Paradoxically, despite the increasing need for SNF providers, there is a shortage of clinicians with training in geriatrics or nursing home care.⁷ The result is a growing need to identify organizational systems to optimize physician practice in these settings, enhance quality of care, especially around transitions, and increase educational training opportunities in SNFs for future practitioners.

Many SNFs today are staffed by physicians and other licensed clinicians whose exclusive practice location is the nursing facility or possibly several such facilities. This prevailing model of care can isolate the physicians, depriving them of interaction with clinicians in other specialties, and can contribute to burnout.⁸ This model does not lend itself to academic scholarship, quality improvement (QI), and student or resident training, as each of these endeavors depends on interprofessional collaboration as well as access to an academic medical center with additional resources.⁹

Few studies have described innovative hospitalist rotation models from acute to subacute care. The Cleveland Clinic implemented the Connected Care model where hospital-employed physicians and advanced practice professionals integrated into postacute care and reduced the 30-day hospital readmission rate from SNFs from 28% to 22%.¹⁰ Goth and colleagues performed a comparative effectiveness trial between a postacute care hospitalist (PACH) model and a community-based physician model of nursing home care. They found that the institution of a PACH model in a nursing home was associated with a significant increase in laboratory costs, nonsignificant reduction in medication errors and pharmacy costs, and no improvement in fall rates.¹¹ The conclusion was that the PACH model may lead to greater clinician involvement and that the potential decrease in pharmacy costs and medications errors may offset the costs associated with additional laboratory testing. Overall, there has been a lack of studies on the impact of these hospitalist rotation models from acute to subacute care on educational programs, QI activities, and the interprofessional environment.

To achieve a system in which physicians in a SNF can excel in these areas, Veterans Affairs Boston Healthcare System (VABHS) adopted a staffing model in which academic hospitalist physicians rotate between the inpatient hospital and subacute settings. This report describes the model structure, the varying roles of the physicians, and early indicators of its positive effects on educational programs, QI activities, and the interprofessional environment.

Methods

The VABHS consists of a 159-bed acute care hospital in West Roxbury, Massachusetts; and a 110-bed SNF in Brockton, Massachusetts, with 3 units: a 65-bed transitional care unit (TCU), a 30-bed long-term care unit, and a 15-bed palliative care/hospice unit. The majority of patients admitted to the SNF are transferred from the acute care hospital in West Roxbury and other regional hospitals. Prior to 2015, the TCU was staffed with full-time clinicians who exclusively practiced in the SNF.

In the new staffing model, 6 hospitalist physicians divide their clinical time between the acute care hospital’s inpatient medical service and the TCU. The hospitalists come from varied backgrounds in terms of years in practice and advanced training (Table 1). 

The amount of nonclinical (protected) time and clinical time on the acute inpatient service and the TCU varies for each physician. For example, a physician serves as principal investigator for several major research grants and has a hospital-wide administrative leadership role; as a result, the principal investigator has fewer months of clinical responsibility. Physicians are expected to use the protected time for scholarship, educational program development and teaching, QI, and administrative responsibilities. The VABHS leadership determines the amount of protected time based on individualized benchmarks for research, education, and administrative responsibilities that follow VA national and local institutional guidelines. These metrics and time allocations are negotiated at the time of recruitment and then are reviewed annually.

The TCU also is staffed with 4 full-time clinicians (2 physicians and 2 physician assistants) who provide additional continuity of care. The new hospitalist staffing model only required an approximate 10% increase in TCU clinical staffing full-time equivalents. Patients and admissions are divided equally among clinicians on service (census per clinician 12-15 patients), with redistribution of patients at times of transition from clinical to nonclinical time. Blocks of clinical time are scheduled for greater than 2 weeks at a time to preserve continuity. In addition, the new staffing model allocates assignment of clinical responsibilities that allows for clinicians to take leave without resultant shortages in clinical coverage.

To facilitate communication among physicians serving in the acute inpatient facility and the TCU, leaders of both of these programs meet monthly and ad hoc to review the transitions of care between the 2 settings. The description of this model and its assessment have been reviewed and deemed exempt from oversight by the VA Boston Healthcare System Research and Development Committee.

Results

Since the implementation of this staffing model in 2015, the system has grown considerably in the breadth and depth of educational programming, QI, and systems redesign in the TCU and, more broadly, in the SNF. The TCU, which previously had limited training opportunities, has experienced marked expansion of educational offerings. It is now a site for core general medicine rotations for first-year psychiatry residents and physician assistant students. The TCU also has expanded as a clinical site for transitions-in-care internal medicine resident curricula and electives, as well as a clinical site for a geriatrics fellowship.

A hospitalist developed and implemented a 4-week interprofessional curriculum for all clinical trainees and students, which occurs continuously. The curriculum includes a monthly academic conference and 12 didactic lectures and is taught by 16 interprofessional faculty from the TCU and the Palliative Care/Hospice Unit, including medicine, geriatric and palliative care physicians, physician assistants, social workers, physical and occupational therapists, pharmacists, and a geriatric psychologist. The goal of the curriculum is to provide learners the knowledge, attitudes, and skills necessary to perform effective, efficient, and safe transfers between clinical settings as well as education in transitional care. In addition, using a team of interprofessional faculty, the curriculum develops the interprofessional competencies of teamwork and communication. The curriculum also has provided a significant opportunity for interprofessional collaboration among faculty who have volunteered their teaching time in the development and teaching of the curriculum, with potential for improved clinical staff knowledge of other disciplines.

Quality improvement and system redesign projects in care transitions also have expanded (Table 2). 

Early assessment indicates that the new staffing model is having positive effects on the clinical environment of the TCU. A survey was conducted of a convenience sample of all physicians, nurse managers, social workers, and other members of the clinical team in the TCU (N=24)(Table 3), with response categories ranging on a Likert scale from 1 (very negative) to 5 (very positive). 

Although not rigorously analyzed using qualitative research methods, comments from respondents have consistently indicated that this staffing model increases the transfer of clinical and logistical knowledge among staff members working in the acute inpatient facility and the TCU. 

Discussion

With greater numbers of increasingly complex patients transitioning from the hospital to SNF, health care systems need to expand the capacity of their skilled nursing systems, not only to provide clinical care, but also to support QI and medical education. The VABHS developed a physician staffing model with the goal of enriching physician practice and enhancing QI and educational opportunities in its SNF. The model offers an opportunity to improve transitions in care as physicians gain a greater knowledge of both the hospital and subacute clinical settings. This hospitalist rotation model may improve the knowledge necessary for caring for patients moving across care settings, as well as improve communication between settings. It also has served as a foundation for systematic innovation in QI and education at this institution. Clinical staff in the transitional care setting have reported positive effects of this model on clinical skills and patient care, educational opportunities, as well as a desire for replication in other health care systems.

The potential generalizability of this model requires careful consideration. The VABHS is a tertiary care integrated health care system, enabling physicians to work in multiple clinical settings. Other settings may not have the staffing or clinical volume to sustain such a model. In addition, this model may increase discontinuity in patient care as hospitalists move between acute and subacute settings and nonclinical roles. This loss of continuity may be a greater concern in the SNF setting, as the inpatient hospitalist model generally involves high provider turnover as shift work. Our survey included nurse managers, and not floor nurses due to survey administration limitations, and feedback may not have captured a comprehensive view from CLC staff. Moreover, some of the perceived positive impacts also may be related to professional and personal attributes of the physicians rather than the actual model of care. In addition, the survey response rate was 86%. However, the nature of the improvement work (focused on care transitions) and educational opportunities (interprofessional care) would likely not occur had the physicians been based in one clinical setting.

Other new physician staffing models have been designed to improve the continuity between the hospital, subacute, and outpatient settings. For example, the University of Chicago Comprehensive Care model pairs patients with trained hospitalists who provide both inpatient and outpatient care, thereby optimizing continuity between these settings.¹⁴ At CareMore Health System, high-risk patients also are paired with hospitalists, referred to as “extensivists,” who lead care teams that follow patients between settings and provide acute, postacute, and outpatient care.¹⁵ In these models, a single physician takes responsibility for the patient throughout transitions of care and through various care settings. Both models have shown reduction in hospital readmissions. One concern with such models is that the treatment teams need to coexist in the various settings of care, and the ability to impact and create systematic change within each environment is limited. This may limit QI, educational opportunities, and system level impact within each environment of care.

In comparison, the “transitionalist” model proposed here features hospitalist physicians rotating between the acute inpatient hospital and subacute care with dedicated time in each environment. This innovative organizational structure may enhance physician practice and enrich QI and educational opportunities in SNFs. Further evaluation will include the impact on quality metrics of patient care and patient satisfaction, as this model has the potential to influence quality, cost, and overall health outcomes.

Acknowledgments
We would like to thank Shivani Jindal, Matthew Russell, Matthew Ronan, Juman Hijab, Wei Shen, Sandra Vilbrun-Bruno, and Jack Earnshaw for their significant contributions to this staffing model. We would also like to thank Paul Conlin, Jay Orlander, and the leadership team of Veterans Affairs Boston Healthcare System for supporting this staffing model.

Care transitions between hospitals and skilled nursing facilities (SNFs) are a vulnerable time for patients. The current health care climate of decreasing hospital length of stay, readmission penalties, and increasing patient complexity has made hospital care transitions an important safety concern. Suboptimal transitions across clinical settings can result in adverse events, inadequately controlled comorbidities, deficient patient and caregiver preparation for discharge, medication errors, relocation stress, and overall increased morbidity and mortality.^1,2 Such care transitions also may generate unnecessary spending, including avoidable readmissions, emergency department utilization, and duplicative laboratory and imaging studies. Approximately 23% of patients admitted to SNFs are readmitted to acute care hospitals within 30 days, and these patients have increased mortality rates in risk-adjusted analyses. ^3,4

Compounding the magnitude of this risk and vulnerability is the significant growth in the number of patients discharged to SNFs over the past 30 years. In 2013, more than 20% of Medicare patients discharged from acute care hospitals were destined for SNFs.^5,6 Paradoxically, despite the increasing need for SNF providers, there is a shortage of clinicians with training in geriatrics or nursing home care.⁷ The result is a growing need to identify organizational systems to optimize physician practice in these settings, enhance quality of care, especially around transitions, and increase educational training opportunities in SNFs for future practitioners.

Many SNFs today are staffed by physicians and other licensed clinicians whose exclusive practice location is the nursing facility or possibly several such facilities. This prevailing model of care can isolate the physicians, depriving them of interaction with clinicians in other specialties, and can contribute to burnout.⁸ This model does not lend itself to academic scholarship, quality improvement (QI), and student or resident training, as each of these endeavors depends on interprofessional collaboration as well as access to an academic medical center with additional resources.⁹

Few studies have described innovative hospitalist rotation models from acute to subacute care. The Cleveland Clinic implemented the Connected Care model where hospital-employed physicians and advanced practice professionals integrated into postacute care and reduced the 30-day hospital readmission rate from SNFs from 28% to 22%.¹⁰ Goth and colleagues performed a comparative effectiveness trial between a postacute care hospitalist (PACH) model and a community-based physician model of nursing home care. They found that the institution of a PACH model in a nursing home was associated with a significant increase in laboratory costs, nonsignificant reduction in medication errors and pharmacy costs, and no improvement in fall rates.¹¹ The conclusion was that the PACH model may lead to greater clinician involvement and that the potential decrease in pharmacy costs and medications errors may offset the costs associated with additional laboratory testing. Overall, there has been a lack of studies on the impact of these hospitalist rotation models from acute to subacute care on educational programs, QI activities, and the interprofessional environment.

To achieve a system in which physicians in a SNF can excel in these areas, Veterans Affairs Boston Healthcare System (VABHS) adopted a staffing model in which academic hospitalist physicians rotate between the inpatient hospital and subacute settings. This report describes the model structure, the varying roles of the physicians, and early indicators of its positive effects on educational programs, QI activities, and the interprofessional environment.

Methods

The VABHS consists of a 159-bed acute care hospital in West Roxbury, Massachusetts; and a 110-bed SNF in Brockton, Massachusetts, with 3 units: a 65-bed transitional care unit (TCU), a 30-bed long-term care unit, and a 15-bed palliative care/hospice unit. The majority of patients admitted to the SNF are transferred from the acute care hospital in West Roxbury and other regional hospitals. Prior to 2015, the TCU was staffed with full-time clinicians who exclusively practiced in the SNF.

In the new staffing model, 6 hospitalist physicians divide their clinical time between the acute care hospital’s inpatient medical service and the TCU. The hospitalists come from varied backgrounds in terms of years in practice and advanced training (Table 1). 

The amount of nonclinical (protected) time and clinical time on the acute inpatient service and the TCU varies for each physician. For example, a physician serves as principal investigator for several major research grants and has a hospital-wide administrative leadership role; as a result, the principal investigator has fewer months of clinical responsibility. Physicians are expected to use the protected time for scholarship, educational program development and teaching, QI, and administrative responsibilities. The VABHS leadership determines the amount of protected time based on individualized benchmarks for research, education, and administrative responsibilities that follow VA national and local institutional guidelines. These metrics and time allocations are negotiated at the time of recruitment and then are reviewed annually.

The TCU also is staffed with 4 full-time clinicians (2 physicians and 2 physician assistants) who provide additional continuity of care. The new hospitalist staffing model only required an approximate 10% increase in TCU clinical staffing full-time equivalents. Patients and admissions are divided equally among clinicians on service (census per clinician 12-15 patients), with redistribution of patients at times of transition from clinical to nonclinical time. Blocks of clinical time are scheduled for greater than 2 weeks at a time to preserve continuity. In addition, the new staffing model allocates assignment of clinical responsibilities that allows for clinicians to take leave without resultant shortages in clinical coverage.

To facilitate communication among physicians serving in the acute inpatient facility and the TCU, leaders of both of these programs meet monthly and ad hoc to review the transitions of care between the 2 settings. The description of this model and its assessment have been reviewed and deemed exempt from oversight by the VA Boston Healthcare System Research and Development Committee.

Results

Since the implementation of this staffing model in 2015, the system has grown considerably in the breadth and depth of educational programming, QI, and systems redesign in the TCU and, more broadly, in the SNF. The TCU, which previously had limited training opportunities, has experienced marked expansion of educational offerings. It is now a site for core general medicine rotations for first-year psychiatry residents and physician assistant students. The TCU also has expanded as a clinical site for transitions-in-care internal medicine resident curricula and electives, as well as a clinical site for a geriatrics fellowship.

A hospitalist developed and implemented a 4-week interprofessional curriculum for all clinical trainees and students, which occurs continuously. The curriculum includes a monthly academic conference and 12 didactic lectures and is taught by 16 interprofessional faculty from the TCU and the Palliative Care/Hospice Unit, including medicine, geriatric and palliative care physicians, physician assistants, social workers, physical and occupational therapists, pharmacists, and a geriatric psychologist. The goal of the curriculum is to provide learners the knowledge, attitudes, and skills necessary to perform effective, efficient, and safe transfers between clinical settings as well as education in transitional care. In addition, using a team of interprofessional faculty, the curriculum develops the interprofessional competencies of teamwork and communication. The curriculum also has provided a significant opportunity for interprofessional collaboration among faculty who have volunteered their teaching time in the development and teaching of the curriculum, with potential for improved clinical staff knowledge of other disciplines.

Quality improvement and system redesign projects in care transitions also have expanded (Table 2). 

Early assessment indicates that the new staffing model is having positive effects on the clinical environment of the TCU. A survey was conducted of a convenience sample of all physicians, nurse managers, social workers, and other members of the clinical team in the TCU (N=24)(Table 3), with response categories ranging on a Likert scale from 1 (very negative) to 5 (very positive). 

Although not rigorously analyzed using qualitative research methods, comments from respondents have consistently indicated that this staffing model increases the transfer of clinical and logistical knowledge among staff members working in the acute inpatient facility and the TCU. 

Discussion

With greater numbers of increasingly complex patients transitioning from the hospital to SNF, health care systems need to expand the capacity of their skilled nursing systems, not only to provide clinical care, but also to support QI and medical education. The VABHS developed a physician staffing model with the goal of enriching physician practice and enhancing QI and educational opportunities in its SNF. The model offers an opportunity to improve transitions in care as physicians gain a greater knowledge of both the hospital and subacute clinical settings. This hospitalist rotation model may improve the knowledge necessary for caring for patients moving across care settings, as well as improve communication between settings. It also has served as a foundation for systematic innovation in QI and education at this institution. Clinical staff in the transitional care setting have reported positive effects of this model on clinical skills and patient care, educational opportunities, as well as a desire for replication in other health care systems.

The potential generalizability of this model requires careful consideration. The VABHS is a tertiary care integrated health care system, enabling physicians to work in multiple clinical settings. Other settings may not have the staffing or clinical volume to sustain such a model. In addition, this model may increase discontinuity in patient care as hospitalists move between acute and subacute settings and nonclinical roles. This loss of continuity may be a greater concern in the SNF setting, as the inpatient hospitalist model generally involves high provider turnover as shift work. Our survey included nurse managers, and not floor nurses due to survey administration limitations, and feedback may not have captured a comprehensive view from CLC staff. Moreover, some of the perceived positive impacts also may be related to professional and personal attributes of the physicians rather than the actual model of care. In addition, the survey response rate was 86%. However, the nature of the improvement work (focused on care transitions) and educational opportunities (interprofessional care) would likely not occur had the physicians been based in one clinical setting.

Other new physician staffing models have been designed to improve the continuity between the hospital, subacute, and outpatient settings. For example, the University of Chicago Comprehensive Care model pairs patients with trained hospitalists who provide both inpatient and outpatient care, thereby optimizing continuity between these settings.¹⁴ At CareMore Health System, high-risk patients also are paired with hospitalists, referred to as “extensivists,” who lead care teams that follow patients between settings and provide acute, postacute, and outpatient care.¹⁵ In these models, a single physician takes responsibility for the patient throughout transitions of care and through various care settings. Both models have shown reduction in hospital readmissions. One concern with such models is that the treatment teams need to coexist in the various settings of care, and the ability to impact and create systematic change within each environment is limited. This may limit QI, educational opportunities, and system level impact within each environment of care.

In comparison, the “transitionalist” model proposed here features hospitalist physicians rotating between the acute inpatient hospital and subacute care with dedicated time in each environment. This innovative organizational structure may enhance physician practice and enrich QI and educational opportunities in SNFs. Further evaluation will include the impact on quality metrics of patient care and patient satisfaction, as this model has the potential to influence quality, cost, and overall health outcomes.

Acknowledgments
We would like to thank Shivani Jindal, Matthew Russell, Matthew Ronan, Juman Hijab, Wei Shen, Sandra Vilbrun-Bruno, and Jack Earnshaw for their significant contributions to this staffing model. We would also like to thank Paul Conlin, Jay Orlander, and the leadership team of Veterans Affairs Boston Healthcare System for supporting this staffing model.

Care transitions between hospitals and skilled nursing facilities (SNFs) are a vulnerable time for patients. The current health care climate of decreasing hospital length of stay, readmission penalties, and increasing patient complexity has made hospital care transitions an important safety concern. Suboptimal transitions across clinical settings can result in adverse events, inadequately controlled comorbidities, deficient patient and caregiver preparation for discharge, medication errors, relocation stress, and overall increased morbidity and mortality.^1,2 Such care transitions also may generate unnecessary spending, including avoidable readmissions, emergency department utilization, and duplicative laboratory and imaging studies. Approximately 23% of patients admitted to SNFs are readmitted to acute care hospitals within 30 days, and these patients have increased mortality rates in risk-adjusted analyses. ^3,4

Compounding the magnitude of this risk and vulnerability is the significant growth in the number of patients discharged to SNFs over the past 30 years. In 2013, more than 20% of Medicare patients discharged from acute care hospitals were destined for SNFs.^5,6 Paradoxically, despite the increasing need for SNF providers, there is a shortage of clinicians with training in geriatrics or nursing home care.⁷ The result is a growing need to identify organizational systems to optimize physician practice in these settings, enhance quality of care, especially around transitions, and increase educational training opportunities in SNFs for future practitioners.

Many SNFs today are staffed by physicians and other licensed clinicians whose exclusive practice location is the nursing facility or possibly several such facilities. This prevailing model of care can isolate the physicians, depriving them of interaction with clinicians in other specialties, and can contribute to burnout.⁸ This model does not lend itself to academic scholarship, quality improvement (QI), and student or resident training, as each of these endeavors depends on interprofessional collaboration as well as access to an academic medical center with additional resources.⁹

Few studies have described innovative hospitalist rotation models from acute to subacute care. The Cleveland Clinic implemented the Connected Care model where hospital-employed physicians and advanced practice professionals integrated into postacute care and reduced the 30-day hospital readmission rate from SNFs from 28% to 22%.¹⁰ Goth and colleagues performed a comparative effectiveness trial between a postacute care hospitalist (PACH) model and a community-based physician model of nursing home care. They found that the institution of a PACH model in a nursing home was associated with a significant increase in laboratory costs, nonsignificant reduction in medication errors and pharmacy costs, and no improvement in fall rates.¹¹ The conclusion was that the PACH model may lead to greater clinician involvement and that the potential decrease in pharmacy costs and medications errors may offset the costs associated with additional laboratory testing. Overall, there has been a lack of studies on the impact of these hospitalist rotation models from acute to subacute care on educational programs, QI activities, and the interprofessional environment.

To achieve a system in which physicians in a SNF can excel in these areas, Veterans Affairs Boston Healthcare System (VABHS) adopted a staffing model in which academic hospitalist physicians rotate between the inpatient hospital and subacute settings. This report describes the model structure, the varying roles of the physicians, and early indicators of its positive effects on educational programs, QI activities, and the interprofessional environment.

Methods

The VABHS consists of a 159-bed acute care hospital in West Roxbury, Massachusetts; and a 110-bed SNF in Brockton, Massachusetts, with 3 units: a 65-bed transitional care unit (TCU), a 30-bed long-term care unit, and a 15-bed palliative care/hospice unit. The majority of patients admitted to the SNF are transferred from the acute care hospital in West Roxbury and other regional hospitals. Prior to 2015, the TCU was staffed with full-time clinicians who exclusively practiced in the SNF.

In the new staffing model, 6 hospitalist physicians divide their clinical time between the acute care hospital’s inpatient medical service and the TCU. The hospitalists come from varied backgrounds in terms of years in practice and advanced training (Table 1). 

The amount of nonclinical (protected) time and clinical time on the acute inpatient service and the TCU varies for each physician. For example, a physician serves as principal investigator for several major research grants and has a hospital-wide administrative leadership role; as a result, the principal investigator has fewer months of clinical responsibility. Physicians are expected to use the protected time for scholarship, educational program development and teaching, QI, and administrative responsibilities. The VABHS leadership determines the amount of protected time based on individualized benchmarks for research, education, and administrative responsibilities that follow VA national and local institutional guidelines. These metrics and time allocations are negotiated at the time of recruitment and then are reviewed annually.

The TCU also is staffed with 4 full-time clinicians (2 physicians and 2 physician assistants) who provide additional continuity of care. The new hospitalist staffing model only required an approximate 10% increase in TCU clinical staffing full-time equivalents. Patients and admissions are divided equally among clinicians on service (census per clinician 12-15 patients), with redistribution of patients at times of transition from clinical to nonclinical time. Blocks of clinical time are scheduled for greater than 2 weeks at a time to preserve continuity. In addition, the new staffing model allocates assignment of clinical responsibilities that allows for clinicians to take leave without resultant shortages in clinical coverage.

To facilitate communication among physicians serving in the acute inpatient facility and the TCU, leaders of both of these programs meet monthly and ad hoc to review the transitions of care between the 2 settings. The description of this model and its assessment have been reviewed and deemed exempt from oversight by the VA Boston Healthcare System Research and Development Committee.

Results

Since the implementation of this staffing model in 2015, the system has grown considerably in the breadth and depth of educational programming, QI, and systems redesign in the TCU and, more broadly, in the SNF. The TCU, which previously had limited training opportunities, has experienced marked expansion of educational offerings. It is now a site for core general medicine rotations for first-year psychiatry residents and physician assistant students. The TCU also has expanded as a clinical site for transitions-in-care internal medicine resident curricula and electives, as well as a clinical site for a geriatrics fellowship.

A hospitalist developed and implemented a 4-week interprofessional curriculum for all clinical trainees and students, which occurs continuously. The curriculum includes a monthly academic conference and 12 didactic lectures and is taught by 16 interprofessional faculty from the TCU and the Palliative Care/Hospice Unit, including medicine, geriatric and palliative care physicians, physician assistants, social workers, physical and occupational therapists, pharmacists, and a geriatric psychologist. The goal of the curriculum is to provide learners the knowledge, attitudes, and skills necessary to perform effective, efficient, and safe transfers between clinical settings as well as education in transitional care. In addition, using a team of interprofessional faculty, the curriculum develops the interprofessional competencies of teamwork and communication. The curriculum also has provided a significant opportunity for interprofessional collaboration among faculty who have volunteered their teaching time in the development and teaching of the curriculum, with potential for improved clinical staff knowledge of other disciplines.

Quality improvement and system redesign projects in care transitions also have expanded (Table 2). 

Early assessment indicates that the new staffing model is having positive effects on the clinical environment of the TCU. A survey was conducted of a convenience sample of all physicians, nurse managers, social workers, and other members of the clinical team in the TCU (N=24)(Table 3), with response categories ranging on a Likert scale from 1 (very negative) to 5 (very positive). 

Although not rigorously analyzed using qualitative research methods, comments from respondents have consistently indicated that this staffing model increases the transfer of clinical and logistical knowledge among staff members working in the acute inpatient facility and the TCU. 

Discussion

With greater numbers of increasingly complex patients transitioning from the hospital to SNF, health care systems need to expand the capacity of their skilled nursing systems, not only to provide clinical care, but also to support QI and medical education. The VABHS developed a physician staffing model with the goal of enriching physician practice and enhancing QI and educational opportunities in its SNF. The model offers an opportunity to improve transitions in care as physicians gain a greater knowledge of both the hospital and subacute clinical settings. This hospitalist rotation model may improve the knowledge necessary for caring for patients moving across care settings, as well as improve communication between settings. It also has served as a foundation for systematic innovation in QI and education at this institution. Clinical staff in the transitional care setting have reported positive effects of this model on clinical skills and patient care, educational opportunities, as well as a desire for replication in other health care systems.

The potential generalizability of this model requires careful consideration. The VABHS is a tertiary care integrated health care system, enabling physicians to work in multiple clinical settings. Other settings may not have the staffing or clinical volume to sustain such a model. In addition, this model may increase discontinuity in patient care as hospitalists move between acute and subacute settings and nonclinical roles. This loss of continuity may be a greater concern in the SNF setting, as the inpatient hospitalist model generally involves high provider turnover as shift work. Our survey included nurse managers, and not floor nurses due to survey administration limitations, and feedback may not have captured a comprehensive view from CLC staff. Moreover, some of the perceived positive impacts also may be related to professional and personal attributes of the physicians rather than the actual model of care. In addition, the survey response rate was 86%. However, the nature of the improvement work (focused on care transitions) and educational opportunities (interprofessional care) would likely not occur had the physicians been based in one clinical setting.

Other new physician staffing models have been designed to improve the continuity between the hospital, subacute, and outpatient settings. For example, the University of Chicago Comprehensive Care model pairs patients with trained hospitalists who provide both inpatient and outpatient care, thereby optimizing continuity between these settings.¹⁴ At CareMore Health System, high-risk patients also are paired with hospitalists, referred to as “extensivists,” who lead care teams that follow patients between settings and provide acute, postacute, and outpatient care.¹⁵ In these models, a single physician takes responsibility for the patient throughout transitions of care and through various care settings. Both models have shown reduction in hospital readmissions. One concern with such models is that the treatment teams need to coexist in the various settings of care, and the ability to impact and create systematic change within each environment is limited. This may limit QI, educational opportunities, and system level impact within each environment of care.

In comparison, the “transitionalist” model proposed here features hospitalist physicians rotating between the acute inpatient hospital and subacute care with dedicated time in each environment. This innovative organizational structure may enhance physician practice and enrich QI and educational opportunities in SNFs. Further evaluation will include the impact on quality metrics of patient care and patient satisfaction, as this model has the potential to influence quality, cost, and overall health outcomes.

Acknowledgments
We would like to thank Shivani Jindal, Matthew Russell, Matthew Ronan, Juman Hijab, Wei Shen, Sandra Vilbrun-Bruno, and Jack Earnshaw for their significant contributions to this staffing model. We would also like to thank Paul Conlin, Jay Orlander, and the leadership team of Veterans Affairs Boston Healthcare System for supporting this staffing model.

The American Association for Cancer Research (AACR) has released its annual Cancer Progress Report spotlighting 22 new approvals for cancer treatment during the last 12 months.

Among the advances outlined in the AACR Cancer Progress Report 2018 are “revolutionary new immunotherapeutics called CAR T–cell therapies, exciting new targeted radiotherapeutics, and numerous new targeted therapeutics that are expanding the scope of precision medicine,” the AACR said in a written statement.

Despite this progress, however, cancer continues to pose immense public health challenges.

The number of new cancer cases in the United States is predicted to increase from more than 1.7 million in 2018 to almost 2.4 million in 2035, due in large part to the rising number of people age 65 and older, according to the report.

AACR calls on elected officials to:

• Maintain “robust, sustained, and predictable growth” of the National Institutes of Health budget, increasing it at least $2 billion in fiscal year (FY) 2019, for a total funding level of at least $39.1 billion.
• Make sure that the $711 million in funding provided through the 21st Century Cures Act for targeted initiatives – including the National Cancer Moonshot – “is fully appropriated in FY 2019 and is supplemental to the healthy increase for the NIH’s base budget.”
• Raise the Food and Drug Administration’s base budget in FY 2019 to $3.1 billion – a $308 million increase above its FY 2018 level – to secure support for regulatory science and speed the development of medical products, ones that are safe and effective. Particularly, in FY 2019, the AACR backs a funding level of $20 million for the FDA Oncology Center of Excellence.
• Provide the Centers for Disease Control and Prevention Cancer Prevention and Control Programs with total funding of at least $517 million. This would include funding for “comprehensive cancer control, cancer registries, and screening and awareness programs for specific cancers.”

Read the full report and watch video stories from patients here.


 

The American Association for Cancer Research (AACR) has released its annual Cancer Progress Report spotlighting 22 new approvals for cancer treatment during the last 12 months.

Among the advances outlined in the AACR Cancer Progress Report 2018 are “revolutionary new immunotherapeutics called CAR T–cell therapies, exciting new targeted radiotherapeutics, and numerous new targeted therapeutics that are expanding the scope of precision medicine,” the AACR said in a written statement.

Despite this progress, however, cancer continues to pose immense public health challenges.

The number of new cancer cases in the United States is predicted to increase from more than 1.7 million in 2018 to almost 2.4 million in 2035, due in large part to the rising number of people age 65 and older, according to the report.

AACR calls on elected officials to:

• Maintain “robust, sustained, and predictable growth” of the National Institutes of Health budget, increasing it at least $2 billion in fiscal year (FY) 2019, for a total funding level of at least $39.1 billion.
• Make sure that the $711 million in funding provided through the 21st Century Cures Act for targeted initiatives – including the National Cancer Moonshot – “is fully appropriated in FY 2019 and is supplemental to the healthy increase for the NIH’s base budget.”
• Raise the Food and Drug Administration’s base budget in FY 2019 to $3.1 billion – a $308 million increase above its FY 2018 level – to secure support for regulatory science and speed the development of medical products, ones that are safe and effective. Particularly, in FY 2019, the AACR backs a funding level of $20 million for the FDA Oncology Center of Excellence.
• Provide the Centers for Disease Control and Prevention Cancer Prevention and Control Programs with total funding of at least $517 million. This would include funding for “comprehensive cancer control, cancer registries, and screening and awareness programs for specific cancers.”

Read the full report and watch video stories from patients here.


 

The American Association for Cancer Research (AACR) has released its annual Cancer Progress Report spotlighting 22 new approvals for cancer treatment during the last 12 months.

Among the advances outlined in the AACR Cancer Progress Report 2018 are “revolutionary new immunotherapeutics called CAR T–cell therapies, exciting new targeted radiotherapeutics, and numerous new targeted therapeutics that are expanding the scope of precision medicine,” the AACR said in a written statement.

Despite this progress, however, cancer continues to pose immense public health challenges.

The number of new cancer cases in the United States is predicted to increase from more than 1.7 million in 2018 to almost 2.4 million in 2035, due in large part to the rising number of people age 65 and older, according to the report.

AACR calls on elected officials to:

• Maintain “robust, sustained, and predictable growth” of the National Institutes of Health budget, increasing it at least $2 billion in fiscal year (FY) 2019, for a total funding level of at least $39.1 billion.
• Make sure that the $711 million in funding provided through the 21st Century Cures Act for targeted initiatives – including the National Cancer Moonshot – “is fully appropriated in FY 2019 and is supplemental to the healthy increase for the NIH’s base budget.”
• Raise the Food and Drug Administration’s base budget in FY 2019 to $3.1 billion – a $308 million increase above its FY 2018 level – to secure support for regulatory science and speed the development of medical products, ones that are safe and effective. Particularly, in FY 2019, the AACR backs a funding level of $20 million for the FDA Oncology Center of Excellence.
• Provide the Centers for Disease Control and Prevention Cancer Prevention and Control Programs with total funding of at least $517 million. This would include funding for “comprehensive cancer control, cancer registries, and screening and awareness programs for specific cancers.”

Read the full report and watch video stories from patients here.


 

Photo by Nina Matthews

A nationwide cohort study suggests an association between a woman’s use of hormonal contraceptives and leukemia in her offspring.

Children of mothers who used hormonal contraception, either during pregnancy or in the 3 months beforehand, had a 1.5-fold greater risk of leukemia, when compared to children of mothers who had never used hormonal contraception.

This increased risk translated to one additional case of leukemia per about 50,000 children exposed to hormonal contraceptives.

The increased risk appeared limited to non-lymphoid leukemia.

Marie Hargreave, PhD, of the Danish Cancer Society Research Center in Copenhagen, Denmark, and her colleagues reported these findings in The Lancet Oncology.

The study included 1,185,157 children born between 1996 and 2014 and followed for a median of 9.3 years. Data on these children were collected from the Danish Medical Birth Registry and the Danish Cancer Registry.

The researchers looked at redeemed prescriptions from the Danish National Prescription Registry to determine the mothers’ contraceptive use and divided the women into three categories:

• Mothers who had never used hormonal contraceptives
• Those with previous hormonal contraceptive use, defined as greater than 3 months before the start of pregnancy
• Mothers with recent contraceptive use, defined as during or within 3 months of pregnancy.

Results

There were 606 children diagnosed with leukemia in the study cohort—465 with lymphoid leukemia and 141 with non-lymphoid leukemia.

Overall, children born to mothers with previous or recent use of hormonal contraceptives had a significantly increased risk of developing any leukemia. The hazard ratios (HRs) were as follows:

• Previous use of hormonal contraceptives—HR=1.25 (P=0.039)
• Recent use—HR=1.46 (P=0.011)
• Use within 3 months of pregnancy—HR=1.42 (P=0.025)
• Use during pregnancy—HR=1.78 (P=0.070).

The risk of lymphoid leukemia did not increase significantly with maternal use of hormonal contraceptives. The HRs were as follows:

• Previous use of hormonal contraceptives—HR=1.23 (P=0.089)
• Recent use—HR=1.27 (P=0.167)
• Use within 3 months of pregnancy—HR=1.28 (P=0.173)
• Use during pregnancy—HR=1.22 (P=0.635).

However, the risk of non-lymphoid leukemia was significantly increased in children born to mothers with recent hormonal contraceptive use. The HRs were as follows:

• Previous use of hormonal contraceptives—HR=1.33 (P=0.232)
• Recent use—HR=2.17 (P=0.008)
• Use within 3 months of pregnancy—HR=1.95 (P=0.033)
• Use during pregnancy—HR=3.87 (P=0.006).

The association between recent contraceptive use and any leukemia was strongest in children ages 6 to 10 years. The researchers said this was not surprising because the incidence of non-lymphoid leukemia increases after the age of 6.

The researchers estimated that a mother’s recent use of hormonal contraceptives would have resulted in about one additional case of leukemia per 47,170 children; in other words, 25 additional cases of leukemia over the study period.

This low risk of leukemia “is not a major concern with regard to the safety of hormonal contraceptives,” the researchers said.

However, the findings do suggest the intrauterine hormonal environment affects leukemia development in children, and this should be explored in future research.

This study was supported by the Danish Cancer Research Foundation and other foundations. One author reported grants from the sponsoring foundations, and another author reported speaking fees from Jazz Pharmaceuticals and Shire Pharmaceuticals.

Photo by Nina Matthews

A nationwide cohort study suggests an association between a woman’s use of hormonal contraceptives and leukemia in her offspring.

Children of mothers who used hormonal contraception, either during pregnancy or in the 3 months beforehand, had a 1.5-fold greater risk of leukemia, when compared to children of mothers who had never used hormonal contraception.

This increased risk translated to one additional case of leukemia per about 50,000 children exposed to hormonal contraceptives.

The increased risk appeared limited to non-lymphoid leukemia.

Marie Hargreave, PhD, of the Danish Cancer Society Research Center in Copenhagen, Denmark, and her colleagues reported these findings in The Lancet Oncology.

The study included 1,185,157 children born between 1996 and 2014 and followed for a median of 9.3 years. Data on these children were collected from the Danish Medical Birth Registry and the Danish Cancer Registry.

The researchers looked at redeemed prescriptions from the Danish National Prescription Registry to determine the mothers’ contraceptive use and divided the women into three categories:

• Mothers who had never used hormonal contraceptives
• Those with previous hormonal contraceptive use, defined as greater than 3 months before the start of pregnancy
• Mothers with recent contraceptive use, defined as during or within 3 months of pregnancy.

Results

There were 606 children diagnosed with leukemia in the study cohort—465 with lymphoid leukemia and 141 with non-lymphoid leukemia.

Overall, children born to mothers with previous or recent use of hormonal contraceptives had a significantly increased risk of developing any leukemia. The hazard ratios (HRs) were as follows:

• Previous use of hormonal contraceptives—HR=1.25 (P=0.039)
• Recent use—HR=1.46 (P=0.011)
• Use within 3 months of pregnancy—HR=1.42 (P=0.025)
• Use during pregnancy—HR=1.78 (P=0.070).

The risk of lymphoid leukemia did not increase significantly with maternal use of hormonal contraceptives. The HRs were as follows:

• Previous use of hormonal contraceptives—HR=1.23 (P=0.089)
• Recent use—HR=1.27 (P=0.167)
• Use within 3 months of pregnancy—HR=1.28 (P=0.173)
• Use during pregnancy—HR=1.22 (P=0.635).

However, the risk of non-lymphoid leukemia was significantly increased in children born to mothers with recent hormonal contraceptive use. The HRs were as follows:

• Previous use of hormonal contraceptives—HR=1.33 (P=0.232)
• Recent use—HR=2.17 (P=0.008)
• Use within 3 months of pregnancy—HR=1.95 (P=0.033)
• Use during pregnancy—HR=3.87 (P=0.006).

The association between recent contraceptive use and any leukemia was strongest in children ages 6 to 10 years. The researchers said this was not surprising because the incidence of non-lymphoid leukemia increases after the age of 6.

The researchers estimated that a mother’s recent use of hormonal contraceptives would have resulted in about one additional case of leukemia per 47,170 children; in other words, 25 additional cases of leukemia over the study period.

This low risk of leukemia “is not a major concern with regard to the safety of hormonal contraceptives,” the researchers said.

However, the findings do suggest the intrauterine hormonal environment affects leukemia development in children, and this should be explored in future research.

This study was supported by the Danish Cancer Research Foundation and other foundations. One author reported grants from the sponsoring foundations, and another author reported speaking fees from Jazz Pharmaceuticals and Shire Pharmaceuticals.

Photo by Nina Matthews

A nationwide cohort study suggests an association between a woman’s use of hormonal contraceptives and leukemia in her offspring.

Children of mothers who used hormonal contraception, either during pregnancy or in the 3 months beforehand, had a 1.5-fold greater risk of leukemia, when compared to children of mothers who had never used hormonal contraception.

This increased risk translated to one additional case of leukemia per about 50,000 children exposed to hormonal contraceptives.

The increased risk appeared limited to non-lymphoid leukemia.

Marie Hargreave, PhD, of the Danish Cancer Society Research Center in Copenhagen, Denmark, and her colleagues reported these findings in The Lancet Oncology.

The study included 1,185,157 children born between 1996 and 2014 and followed for a median of 9.3 years. Data on these children were collected from the Danish Medical Birth Registry and the Danish Cancer Registry.

The researchers looked at redeemed prescriptions from the Danish National Prescription Registry to determine the mothers’ contraceptive use and divided the women into three categories:

• Mothers who had never used hormonal contraceptives
• Those with previous hormonal contraceptive use, defined as greater than 3 months before the start of pregnancy
• Mothers with recent contraceptive use, defined as during or within 3 months of pregnancy.

Results

There were 606 children diagnosed with leukemia in the study cohort—465 with lymphoid leukemia and 141 with non-lymphoid leukemia.

Overall, children born to mothers with previous or recent use of hormonal contraceptives had a significantly increased risk of developing any leukemia. The hazard ratios (HRs) were as follows:

• Previous use of hormonal contraceptives—HR=1.25 (P=0.039)
• Recent use—HR=1.46 (P=0.011)
• Use within 3 months of pregnancy—HR=1.42 (P=0.025)
• Use during pregnancy—HR=1.78 (P=0.070).

The risk of lymphoid leukemia did not increase significantly with maternal use of hormonal contraceptives. The HRs were as follows:

• Previous use of hormonal contraceptives—HR=1.23 (P=0.089)
• Recent use—HR=1.27 (P=0.167)
• Use within 3 months of pregnancy—HR=1.28 (P=0.173)
• Use during pregnancy—HR=1.22 (P=0.635).

However, the risk of non-lymphoid leukemia was significantly increased in children born to mothers with recent hormonal contraceptive use. The HRs were as follows:

• Previous use of hormonal contraceptives—HR=1.33 (P=0.232)
• Recent use—HR=2.17 (P=0.008)
• Use within 3 months of pregnancy—HR=1.95 (P=0.033)
• Use during pregnancy—HR=3.87 (P=0.006).

The association between recent contraceptive use and any leukemia was strongest in children ages 6 to 10 years. The researchers said this was not surprising because the incidence of non-lymphoid leukemia increases after the age of 6.

The researchers estimated that a mother’s recent use of hormonal contraceptives would have resulted in about one additional case of leukemia per 47,170 children; in other words, 25 additional cases of leukemia over the study period.

This low risk of leukemia “is not a major concern with regard to the safety of hormonal contraceptives,” the researchers said.

However, the findings do suggest the intrauterine hormonal environment affects leukemia development in children, and this should be explored in future research.

This study was supported by the Danish Cancer Research Foundation and other foundations. One author reported grants from the sponsoring foundations, and another author reported speaking fees from Jazz Pharmaceuticals and Shire Pharmaceuticals.

©Raimond Spekking

In a prospective study, Hispanic pediatric patients with acute lymphoblastic leukemia (ALL) had a risk of methotrexate-induced neurotoxicity that was more than twice the risk observed in non-Hispanic white patients.

However, there was no significant difference in methotrexate neurotoxicity between non-Hispanic black patients and non-Hispanic white patients.

There were no cases of neurotoxicity among patients of other races/ethnicities.

Michael E. Scheurer, PhD, of Baylor College of Medicine in Houston, Texas, and his colleagues conducted this study and detailed the results in Clinical Cancer Research.

The study included 280 patients with newly diagnosed ALL. Most patients (85.7%) had B-ALL, 10.7% had T-ALL, and 3.6% had lymphoblastic lymphoma.

Nearly half of the patients (48.2%) were Hispanic, 36.2% were non-Hispanic white, 8.3% were non-Hispanic black, and 7.3% were non-Hispanic “other.”

The patients, who had a mean age of 8.4 years at diagnosis, were treated with modern ALL protocols and were followed from diagnosis to the start of maintenance/continuation therapy.

Methotrexate neurotoxicity was seen in 39 patients at the time of the analysis. Of those patients, 29 (74.4%) were Hispanic.

Compared with non-Hispanic whites, Hispanics had a high risk of methotrexate neurotoxicity, even after the researchers accounted for age, sex, ALL risk stratification, and other factors. The adjusted hazard ratio (HR) was 2.43 (P=0.036).

“We had observed that our Hispanic patients tended to experience neurotoxicity more often than other groups, but we were surprised to see the magnitude of the difference,” Dr. Scheurer said.

There was no significant difference in methotrexate neurotoxicity between non-Hispanic black patients and non-Hispanic white patients. The adjusted HR for non-Hispanic black patients was 1.23 (P=0.80).

Patients in the “other” racial/ethnic group did not experience any neurotoxic events.

All nine patients who experienced a second neurotoxic event were Hispanic.

Patients who had neurotoxicity received an average of 2.25 fewer doses of intrathecal methotrexate (P<0.01) and 1.81 fewer doses of intravenous methotrexate (P=0.084) than patients without neurotoxicity.

About three-quarters (74.4%) of patients experiencing methotrexate neurotoxicity received leucovorin rescue, according to the investigators, who noted that leucovorin may interact with methotrexate and reduce its efficacy.

Relapse occurred in 15.4% (6/39) of patients with neurotoxicity and 2.1% (13/241) of patients with no neurotoxicity (P=0.0038).

The investigators said these findings add to the growing body of evidence that Hispanics and other minority pediatric patients with ALL experience “significant disparities” in treatment outcomes.

It remains unclear why Hispanic patients would have a higher risk of methotrexate neurotoxicity, and that must be explored in future studies, the investigators said.

The team is currently investigating whether biomarkers could be used to identify patients at risk of methotrexate neurotoxicity.

“Biomarkers may someday allow us to identify patients upfront, before even beginning therapy, who might be at risk for such outcomes,” Dr. Scheurer said. “If we can identify these at-risk patients, we can potentially employ strategies to either fully prevent or mitigate these toxicities.”

This research was supported by the National Institutes of Health and Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, a St. Baldrick’s Foundation Consortium Research Grant. The researchers said they had no potential conflicts of interest.

©Raimond Spekking

In a prospective study, Hispanic pediatric patients with acute lymphoblastic leukemia (ALL) had a risk of methotrexate-induced neurotoxicity that was more than twice the risk observed in non-Hispanic white patients.

However, there was no significant difference in methotrexate neurotoxicity between non-Hispanic black patients and non-Hispanic white patients.

There were no cases of neurotoxicity among patients of other races/ethnicities.

Michael E. Scheurer, PhD, of Baylor College of Medicine in Houston, Texas, and his colleagues conducted this study and detailed the results in Clinical Cancer Research.

The study included 280 patients with newly diagnosed ALL. Most patients (85.7%) had B-ALL, 10.7% had T-ALL, and 3.6% had lymphoblastic lymphoma.

Nearly half of the patients (48.2%) were Hispanic, 36.2% were non-Hispanic white, 8.3% were non-Hispanic black, and 7.3% were non-Hispanic “other.”

The patients, who had a mean age of 8.4 years at diagnosis, were treated with modern ALL protocols and were followed from diagnosis to the start of maintenance/continuation therapy.

Methotrexate neurotoxicity was seen in 39 patients at the time of the analysis. Of those patients, 29 (74.4%) were Hispanic.

Compared with non-Hispanic whites, Hispanics had a high risk of methotrexate neurotoxicity, even after the researchers accounted for age, sex, ALL risk stratification, and other factors. The adjusted hazard ratio (HR) was 2.43 (P=0.036).

“We had observed that our Hispanic patients tended to experience neurotoxicity more often than other groups, but we were surprised to see the magnitude of the difference,” Dr. Scheurer said.

There was no significant difference in methotrexate neurotoxicity between non-Hispanic black patients and non-Hispanic white patients. The adjusted HR for non-Hispanic black patients was 1.23 (P=0.80).

Patients in the “other” racial/ethnic group did not experience any neurotoxic events.

All nine patients who experienced a second neurotoxic event were Hispanic.

Patients who had neurotoxicity received an average of 2.25 fewer doses of intrathecal methotrexate (P<0.01) and 1.81 fewer doses of intravenous methotrexate (P=0.084) than patients without neurotoxicity.

About three-quarters (74.4%) of patients experiencing methotrexate neurotoxicity received leucovorin rescue, according to the investigators, who noted that leucovorin may interact with methotrexate and reduce its efficacy.

Relapse occurred in 15.4% (6/39) of patients with neurotoxicity and 2.1% (13/241) of patients with no neurotoxicity (P=0.0038).

The investigators said these findings add to the growing body of evidence that Hispanics and other minority pediatric patients with ALL experience “significant disparities” in treatment outcomes.

It remains unclear why Hispanic patients would have a higher risk of methotrexate neurotoxicity, and that must be explored in future studies, the investigators said.

The team is currently investigating whether biomarkers could be used to identify patients at risk of methotrexate neurotoxicity.

“Biomarkers may someday allow us to identify patients upfront, before even beginning therapy, who might be at risk for such outcomes,” Dr. Scheurer said. “If we can identify these at-risk patients, we can potentially employ strategies to either fully prevent or mitigate these toxicities.”

This research was supported by the National Institutes of Health and Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, a St. Baldrick’s Foundation Consortium Research Grant. The researchers said they had no potential conflicts of interest.

©Raimond Spekking

In a prospective study, Hispanic pediatric patients with acute lymphoblastic leukemia (ALL) had a risk of methotrexate-induced neurotoxicity that was more than twice the risk observed in non-Hispanic white patients.

However, there was no significant difference in methotrexate neurotoxicity between non-Hispanic black patients and non-Hispanic white patients.

There were no cases of neurotoxicity among patients of other races/ethnicities.

Michael E. Scheurer, PhD, of Baylor College of Medicine in Houston, Texas, and his colleagues conducted this study and detailed the results in Clinical Cancer Research.

The study included 280 patients with newly diagnosed ALL. Most patients (85.7%) had B-ALL, 10.7% had T-ALL, and 3.6% had lymphoblastic lymphoma.

Nearly half of the patients (48.2%) were Hispanic, 36.2% were non-Hispanic white, 8.3% were non-Hispanic black, and 7.3% were non-Hispanic “other.”

The patients, who had a mean age of 8.4 years at diagnosis, were treated with modern ALL protocols and were followed from diagnosis to the start of maintenance/continuation therapy.

Methotrexate neurotoxicity was seen in 39 patients at the time of the analysis. Of those patients, 29 (74.4%) were Hispanic.

Compared with non-Hispanic whites, Hispanics had a high risk of methotrexate neurotoxicity, even after the researchers accounted for age, sex, ALL risk stratification, and other factors. The adjusted hazard ratio (HR) was 2.43 (P=0.036).

“We had observed that our Hispanic patients tended to experience neurotoxicity more often than other groups, but we were surprised to see the magnitude of the difference,” Dr. Scheurer said.

There was no significant difference in methotrexate neurotoxicity between non-Hispanic black patients and non-Hispanic white patients. The adjusted HR for non-Hispanic black patients was 1.23 (P=0.80).

Patients in the “other” racial/ethnic group did not experience any neurotoxic events.

All nine patients who experienced a second neurotoxic event were Hispanic.

Patients who had neurotoxicity received an average of 2.25 fewer doses of intrathecal methotrexate (P<0.01) and 1.81 fewer doses of intravenous methotrexate (P=0.084) than patients without neurotoxicity.

About three-quarters (74.4%) of patients experiencing methotrexate neurotoxicity received leucovorin rescue, according to the investigators, who noted that leucovorin may interact with methotrexate and reduce its efficacy.

Relapse occurred in 15.4% (6/39) of patients with neurotoxicity and 2.1% (13/241) of patients with no neurotoxicity (P=0.0038).

The investigators said these findings add to the growing body of evidence that Hispanics and other minority pediatric patients with ALL experience “significant disparities” in treatment outcomes.

It remains unclear why Hispanic patients would have a higher risk of methotrexate neurotoxicity, and that must be explored in future studies, the investigators said.

The team is currently investigating whether biomarkers could be used to identify patients at risk of methotrexate neurotoxicity.

“Biomarkers may someday allow us to identify patients upfront, before even beginning therapy, who might be at risk for such outcomes,” Dr. Scheurer said. “If we can identify these at-risk patients, we can potentially employ strategies to either fully prevent or mitigate these toxicities.”

This research was supported by the National Institutes of Health and Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, a St. Baldrick’s Foundation Consortium Research Grant. The researchers said they had no potential conflicts of interest.

Photo courtesy of Abbvie

The U.S. Food and Drug Administration (FDA) has expanded the label for venetoclax tablets (Venclexta^®) to include data on minimal residual disease (MRD).

The drug’s prescribing information now includes details on MRD negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was FDA approved in June for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL.

The patients were randomized to receive:

• Venetoclax at 400 mg daily for 24 months (after a 5-week ramp-up period) plus rituximab at 375 mg/m² on day 1 for the first cycle and at 500 mg/m²  on day 1 for cycles 2 to 6 (n=194)
• Bendamustine at 70 mg/m² on days 1 and 2 for 6 cycles plus rituximab at the same schedule as the venetoclax arm (n=195).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction, and the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood 3 months after the last dose of rituximab. At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response (CR) or CR with incomplete marrow recovery (CRi). MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Three percent (3/106) of patients in the venetoclax arm who achieved CR/CRi were MRD negative in both the peripheral blood and the bone marrow.

“The rates of MRD negativity seen with Venclexta plus rituximab are very encouraging,” said MURANO investigator John Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

Additional results from the MURANO trial were published in The New England Journal of Medicine in March and are included in the prescribing information for venetoclax.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside the U.S.

Photo courtesy of Abbvie

The U.S. Food and Drug Administration (FDA) has expanded the label for venetoclax tablets (Venclexta^®) to include data on minimal residual disease (MRD).

The drug’s prescribing information now includes details on MRD negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was FDA approved in June for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL.

The patients were randomized to receive:

• Venetoclax at 400 mg daily for 24 months (after a 5-week ramp-up period) plus rituximab at 375 mg/m² on day 1 for the first cycle and at 500 mg/m²  on day 1 for cycles 2 to 6 (n=194)
• Bendamustine at 70 mg/m² on days 1 and 2 for 6 cycles plus rituximab at the same schedule as the venetoclax arm (n=195).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction, and the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood 3 months after the last dose of rituximab. At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response (CR) or CR with incomplete marrow recovery (CRi). MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Three percent (3/106) of patients in the venetoclax arm who achieved CR/CRi were MRD negative in both the peripheral blood and the bone marrow.

“The rates of MRD negativity seen with Venclexta plus rituximab are very encouraging,” said MURANO investigator John Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

Additional results from the MURANO trial were published in The New England Journal of Medicine in March and are included in the prescribing information for venetoclax.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside the U.S.

Photo courtesy of Abbvie

The U.S. Food and Drug Administration (FDA) has expanded the label for venetoclax tablets (Venclexta^®) to include data on minimal residual disease (MRD).

The drug’s prescribing information now includes details on MRD negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was FDA approved in June for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL.

The patients were randomized to receive:

• Venetoclax at 400 mg daily for 24 months (after a 5-week ramp-up period) plus rituximab at 375 mg/m² on day 1 for the first cycle and at 500 mg/m²  on day 1 for cycles 2 to 6 (n=194)
• Bendamustine at 70 mg/m² on days 1 and 2 for 6 cycles plus rituximab at the same schedule as the venetoclax arm (n=195).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction, and the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood 3 months after the last dose of rituximab. At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response (CR) or CR with incomplete marrow recovery (CRi). MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Three percent (3/106) of patients in the venetoclax arm who achieved CR/CRi were MRD negative in both the peripheral blood and the bone marrow.

“The rates of MRD negativity seen with Venclexta plus rituximab are very encouraging,” said MURANO investigator John Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

Additional results from the MURANO trial were published in The New England Journal of Medicine in March and are included in the prescribing information for venetoclax.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside the U.S.

About 10 years ago, this 63-year-old man noticed a lesion on his eyelid. It didn’t bother him, so he ignored it—until recently, when it reached a size sufficient to interfere with his vision. This development, and subsequent commentary from friends concerned by its proximity to his eye and fears of cancer, disturbed him enough to seek evaluation.

He first consulted an ophthalmologist, who provided a diagnosis that the patient promptly forgot. However, he was also advised to see a dermatologist or plastic surgeon for further evaluation, since the lesion does not affect the eye itself. The patient wants the lesion removed but seeks a dermatology referral first.

He denies pain, discomfort, or trauma to the affected area.

EXAMINATION
A translucent, round, 7-mm cystic lesion is located on the left lateral lower eyelid just below the margin, resembling a bleb. No redness is seen in the area. Palpation confirms the soft, cystic nature of the lesion.

Examination of the other eye and the rest of the patient’s facial skin reveals no abnormalities.

What is the diagnosis?

DISCUSSION
This is a typical presentation of an apocrine hidrocystoma (AH), a benign lesion of uncertain etiology. The eyelid is rich in apocrine, eccrine, and sebaceous glands, all of which can transform into cysts via traumatic plugging.

AH is also known as cystadenoma, Moll gland cyst, or sudoriferous cyst. It is an entity distinct from chalazions (a granulomatous reaction to sebaceous glands in the eyelid) and lacrimal duct cysts. The differential includes basal cell carcinoma, intradermal nevus, and eccrine cyst.

In my experience, merely incising and draining the cyst is useless in the long run; while this does reduce swelling, it also invites recurrence. Therefore, removal by saucerization and cauterization of the base is the best treatment option.

TAKE-HOME LEARNING POINTS

• Apocrine hidrocystomas (AHs) are benign cysts derived from plugged apocrine sweat glands, which are found in numerous areas around the body, including the eyes.
• AHs are also known as cystadenomas, Moll gland cysts, or sudoriferous cysts.
• Though AHs are often found near the eye, they are not technically an eye problem—but they do have potential to obstruct the visual field.
• Removal is usually by saucerization, with cautery of the base for hemostasis and prevention of recurrence.

About 10 years ago, this 63-year-old man noticed a lesion on his eyelid. It didn’t bother him, so he ignored it—until recently, when it reached a size sufficient to interfere with his vision. This development, and subsequent commentary from friends concerned by its proximity to his eye and fears of cancer, disturbed him enough to seek evaluation.

He first consulted an ophthalmologist, who provided a diagnosis that the patient promptly forgot. However, he was also advised to see a dermatologist or plastic surgeon for further evaluation, since the lesion does not affect the eye itself. The patient wants the lesion removed but seeks a dermatology referral first.

He denies pain, discomfort, or trauma to the affected area.

EXAMINATION
A translucent, round, 7-mm cystic lesion is located on the left lateral lower eyelid just below the margin, resembling a bleb. No redness is seen in the area. Palpation confirms the soft, cystic nature of the lesion.

Examination of the other eye and the rest of the patient’s facial skin reveals no abnormalities.

What is the diagnosis?

DISCUSSION
This is a typical presentation of an apocrine hidrocystoma (AH), a benign lesion of uncertain etiology. The eyelid is rich in apocrine, eccrine, and sebaceous glands, all of which can transform into cysts via traumatic plugging.

AH is also known as cystadenoma, Moll gland cyst, or sudoriferous cyst. It is an entity distinct from chalazions (a granulomatous reaction to sebaceous glands in the eyelid) and lacrimal duct cysts. The differential includes basal cell carcinoma, intradermal nevus, and eccrine cyst.

In my experience, merely incising and draining the cyst is useless in the long run; while this does reduce swelling, it also invites recurrence. Therefore, removal by saucerization and cauterization of the base is the best treatment option.

TAKE-HOME LEARNING POINTS

• Apocrine hidrocystomas (AHs) are benign cysts derived from plugged apocrine sweat glands, which are found in numerous areas around the body, including the eyes.
• AHs are also known as cystadenomas, Moll gland cysts, or sudoriferous cysts.
• Though AHs are often found near the eye, they are not technically an eye problem—but they do have potential to obstruct the visual field.
• Removal is usually by saucerization, with cautery of the base for hemostasis and prevention of recurrence.

About 10 years ago, this 63-year-old man noticed a lesion on his eyelid. It didn’t bother him, so he ignored it—until recently, when it reached a size sufficient to interfere with his vision. This development, and subsequent commentary from friends concerned by its proximity to his eye and fears of cancer, disturbed him enough to seek evaluation.

He first consulted an ophthalmologist, who provided a diagnosis that the patient promptly forgot. However, he was also advised to see a dermatologist or plastic surgeon for further evaluation, since the lesion does not affect the eye itself. The patient wants the lesion removed but seeks a dermatology referral first.

He denies pain, discomfort, or trauma to the affected area.

EXAMINATION
A translucent, round, 7-mm cystic lesion is located on the left lateral lower eyelid just below the margin, resembling a bleb. No redness is seen in the area. Palpation confirms the soft, cystic nature of the lesion.

Examination of the other eye and the rest of the patient’s facial skin reveals no abnormalities.

What is the diagnosis?

DISCUSSION
This is a typical presentation of an apocrine hidrocystoma (AH), a benign lesion of uncertain etiology. The eyelid is rich in apocrine, eccrine, and sebaceous glands, all of which can transform into cysts via traumatic plugging.

AH is also known as cystadenoma, Moll gland cyst, or sudoriferous cyst. It is an entity distinct from chalazions (a granulomatous reaction to sebaceous glands in the eyelid) and lacrimal duct cysts. The differential includes basal cell carcinoma, intradermal nevus, and eccrine cyst.

In my experience, merely incising and draining the cyst is useless in the long run; while this does reduce swelling, it also invites recurrence. Therefore, removal by saucerization and cauterization of the base is the best treatment option.

TAKE-HOME LEARNING POINTS

• Apocrine hidrocystomas (AHs) are benign cysts derived from plugged apocrine sweat glands, which are found in numerous areas around the body, including the eyes.
• AHs are also known as cystadenomas, Moll gland cysts, or sudoriferous cysts.
• Though AHs are often found near the eye, they are not technically an eye problem—but they do have potential to obstruct the visual field.
• Removal is usually by saucerization, with cautery of the base for hemostasis and prevention of recurrence.

CASE Reckless driving, impulse buying

Mr. A, age 73, is admitted to the inpatient psychiatric unit at a community hospital for evaluation of a psychotic episode. His admission to the unit was initiated by his primary care physician, who noted that Mr. A was “not making sense” during a routine visit. Mr. A was speaking rapidly about how he had discovered that high-dose omega-3 fatty acid supplements were a “cure” for Alzheimer’s disease. He also believes that he was recently appointed as CEO of Microsoft and Apple for his discoveries.

Three months earlier, Mr. A had started taking high doses of omega-3 fatty acid supplements (10 to 15 g/d) because he believed they were the cure for memory problems, pain, and depression. At that time, he discontinued taking nortriptyline, 25 mg/d, and citalopram, 40 mg/d, which his outpatient psychiatrist had prescribed for major depressive disorder (MDD). Mr. A also had stopped taking buprenorphine, 2 mg, sublingual, 4 times a day, which he had been prescribed for chronic pain.

Mr. A’s wife reports that during the last 2 months, her husband had become irritable, impulsive, grandiose, and was sleeping very little. She added that although her husband’s ophthalmologist had advised him to not drive due to impaired vision, he had been driving recklessly across the metropolitan area. He had also spent nearly $15,000 buying furniture and other items for their home.

In addition to MDD, Mr. A has a history of chronic kidney disease, Leber’s hereditary optic neuropathy, and chronic pain. He has been taking vitamin D3, 2,000 U/d, as a nutritional supplement.

[polldaddy:10091672]

The authors’ observations

Mr. A met the DSM-5 criteria for a manic episode (Table 1¹). His manic and delusional symptoms are new. He has a long-standing diagnosis of MDD, which for many years had been successfully treated with antidepressants without a manic switch. The absence of a manic switch when treated with antidepressants without a mood stabilizer suggested that Mr. A did not have bipolarity in terms of a mood disorder diathesis.² In addition, it would be unusual for an individual to develop a new-onset or primary bipolar disorder after age 60. Individuals in this age group who present with manic symptoms for the first time are preponderantly found to have a general medical or iatrogenic cause for the emergence of these symptoms.³ Mr. A has a history of chronic kidney disease, Leber’s hereditary optic neuropathy, and chronic pain.

Typically a sedentary man, Mr. A had been exhibiting disinhibited behavior, grandiosity, insomnia, and psychosis. These symptoms began 3 months before he was admitted to the psychiatric unit, when he had started taking high doses of omega-3 fatty acid supplements.

Continue to: EVALUATION Persistent mania

EVALUATION Persistent mania

On initial examination, Mr. A is upset and irritable. He is casually dressed and well-groomed. He lacks insight and says he was brought to the hospital against his will, and it is his wife “who is the one who is crazy.” He is oriented to person, place, and time. At times he is found roaming the hallways, being intrusive, hyperverbal, and tangential with pressured speech. He is very difficult to redirect, and regularly interrupts the interview. His vital signs are stable. He walks well, with slow and steady gait, and displays no tremor or bradykinesia.

[polldaddy:10091674]

The authors’ observations

In order to rule out organic causes, a complete blood count, comprehensive metabolic panel, thyroid profile, urine drug screen, and brain MRI were ordered. No abnormalities were found. DHA and EPA levels were not measured because such testing was not available at the laboratory at the hospital.

Mania emerging after the sixth decade of life is a rare occurrence. Therefore, we made a substantial effort to try to find another cause that might explain Mr. A’s unusual presentation (Table 2).

Omega-3 fatty acid–induced mania. The major types of omega-3 polyunsaturated fatty acids are EPA and DHA and their precursor, alpha-linolenic acid (ALA). EPA and DHA are found primarily in fatty fish, such as salmon, and in fish oil supplements. Omega-3 fatty acids have beneficial anti-inflammatory, antioxidative, and neuro­plastic effects.⁴ Having properties similar to selective serotonin reuptake inhibitors, omega-3 fatty acids are thought to help prevent depression, have few interactions with other medications, and have a lower adverse-effect burden than antidepressants. They have been found to be beneficial as a maintenance treatment and for prevention of depressive episodes in bipolar depression, but no positive association has been found for bipolar mania.⁵

Continue to: However, very limited evidence suggests...

However, very limited evidence suggests that omega-3 fatty acid supplements, particularly those with flaxseed oil, can induce hypomania or mania. This association was first reported by Rudin⁶ in 1981, and later reported in other studies.⁷How omega-3 fatty acids might induce mania is unclear.

Mr. A was reportedly taking high doses of an omega-3 fatty acid supplement. We hypothesized that the antidepressant effect of this supplement may have precipitated a manic episode. Mr. A had no history of manic episodes in the past and was stable during the treatment with the outpatient psychiatrist. A first episode mania in the seventh decade of life would be highly unusual without an organic etiology. After laboratory tests found no abnormalities that would point to an organic etiology, iatrogenic causes were considered. After a review of the literature, there was anecdotal evidence for the induction of mania in clinical trials studying the effects of omega-3 supplements on affective disorders.

This led us to ask: How much omega-3 fatty acid supplements, if any, can a patient with a depressive or bipolar disorder safely take? Currently, omega-3 fatty acid supplements are not FDA-approved for the treatment of depression or bipolar disorder. However, patients may take 1.5 to 2 g/d for MDD. Further research is needed to determine the optimal dose. It is unclear at this time if omega-3 fatty acid supplementation has any benefit in the acute or maintenance treatment of bipolar disorder.

Alternative nutritional supplements for mood disorders. Traditionally, mood disorders, such as MDD and bipolar disorder, have been treated with psycho­tropic medications. However, through the years, sporadic studies have examined the efficacy of nutritional interventions as a cost-effective approach to preventing and treating these conditions.⁵ Proponents of this approach believe such supplements can increase efficacy, as well as decrease the required dose of psychotropic medications, thus potentially minimizing adverse effects. However, their overuse can pose a potential threat of toxicity or unexpected adverse effects, such as precipitation of mania. Table 3⁸ lists over-the-counter nutritional and/or herbal agents that may cause mania.

Continue to: TREATMENT Nonadherence leads to a court order

On admission, Mr. A receives a dose of hydrocodone/acetaminophen (10 mg/325 mg, by mouth every 4 hours as needed) and lorazepam. His intake of omega-3 fatty acid supplements is discontinued during treatment. He is alert but tangential with loosening of associations. His speech is rapid; he continues to be grandiose and oblivious to the reason for his hospitalization. He is able to spontaneously discuss recent life events. After a week-long period of nonadherence to treatment, Mr. A requires a court order for psychiatric treatment and undergoes inpatient treatment for a total of 30 days.

[polldaddy:10091676]

The authors’ observations

During an acute manic episode, the goal of treatment is urgent mood stabilization. Monotherapy can be used; however, in emergent settings, a combination is often used for a rapid response. The most commonly used agents are lithium, anticonvulsants such as valproic acid, and antipsychotics.⁹ In addition, benzodiazepines can be used for insomnia, agitation, or anxiety. The decision to use lithium, an anticonvulsant, or an antipsychotic depends upon the specific medication’s adverse effects, the patient’s medical history, previous medication trials, drug–drug interactions, patient preference, and cost.

Because Mr. A has a history of chronic kidney disease, lithium was contraindicated. Therefore, risperidone was initiated and titrated up to 6 mg/d. Mr. A showed some improvement, but his response was not optimal, as he experienced continued irritability, insomnia, and delusions. Valproic acid was started, and the dose was titrated to 1,000 mg/d, which equates to a serum blood level of 54.2 mg/dL.

[polldaddy:10091678]

Continue to: The authors' observations

After the acute episode of mania resolves, maintenance pharmacotherapy typically involves continuing the same regimen that achieved mood stabilization. Monotherapy is typically preferred to combination therapy, but it is not always possible after a manic episode.¹⁰ A reasonable approach is to slowly taper the antipsychotic after several months of dual therapy if symptoms continue to be well-controlled. Further adjustments may be necessary, depending on the medications’ adverse effects. Moreover, further acute episodes of mania or depression will also determine future treatment.

OUTCOME Resolution of delusions

Mr. A is discharged 30 days after admission. At this point, his acute manic episode has resolved with non-tangential, non-pressured speech, improved sleep, and decreased impulsivity. His grandiose delusions also have resolved. He is prescribed valproic acid, 1,000 mg/d, and risperidone, 6 mg/d at bedtime, under the care of his outpatient psychiatrist.

Bottom Line

Initial presentation of a manic episode in an older patient is rare. It is important to rule out organic causes. Weak evidence suggests omega-3 fatty acid supplements may have the potential to induce mania in certain patients.

Related Resource

• Ramaswamy S, Driscoll D, Rodriguez A, et al. Nutraceuticals for traumatic brain injury: Should you recommend their use? Current Psychiatry. 2017;16(7):34-38,40,41-45.

Drug Brand Names

Buprenorphine • Suboxone, Subutex
Citalopram • Celexa
Hydrocodone/acetaminophen • Vicodin
Lithium • Eskalith, Lithobid
Lorazepam• Ativan
Nortriptyline • Pamelor
Risperidone • Risperdal
Valproic acid • Depakote

CASE Reckless driving, impulse buying

Mr. A, age 73, is admitted to the inpatient psychiatric unit at a community hospital for evaluation of a psychotic episode. His admission to the unit was initiated by his primary care physician, who noted that Mr. A was “not making sense” during a routine visit. Mr. A was speaking rapidly about how he had discovered that high-dose omega-3 fatty acid supplements were a “cure” for Alzheimer’s disease. He also believes that he was recently appointed as CEO of Microsoft and Apple for his discoveries.

Three months earlier, Mr. A had started taking high doses of omega-3 fatty acid supplements (10 to 15 g/d) because he believed they were the cure for memory problems, pain, and depression. At that time, he discontinued taking nortriptyline, 25 mg/d, and citalopram, 40 mg/d, which his outpatient psychiatrist had prescribed for major depressive disorder (MDD). Mr. A also had stopped taking buprenorphine, 2 mg, sublingual, 4 times a day, which he had been prescribed for chronic pain.

Mr. A’s wife reports that during the last 2 months, her husband had become irritable, impulsive, grandiose, and was sleeping very little. She added that although her husband’s ophthalmologist had advised him to not drive due to impaired vision, he had been driving recklessly across the metropolitan area. He had also spent nearly $15,000 buying furniture and other items for their home.

In addition to MDD, Mr. A has a history of chronic kidney disease, Leber’s hereditary optic neuropathy, and chronic pain. He has been taking vitamin D3, 2,000 U/d, as a nutritional supplement.

[polldaddy:10091672]

The authors’ observations

Mr. A met the DSM-5 criteria for a manic episode (Table 1¹). His manic and delusional symptoms are new. He has a long-standing diagnosis of MDD, which for many years had been successfully treated with antidepressants without a manic switch. The absence of a manic switch when treated with antidepressants without a mood stabilizer suggested that Mr. A did not have bipolarity in terms of a mood disorder diathesis.² In addition, it would be unusual for an individual to develop a new-onset or primary bipolar disorder after age 60. Individuals in this age group who present with manic symptoms for the first time are preponderantly found to have a general medical or iatrogenic cause for the emergence of these symptoms.³ Mr. A has a history of chronic kidney disease, Leber’s hereditary optic neuropathy, and chronic pain.

Typically a sedentary man, Mr. A had been exhibiting disinhibited behavior, grandiosity, insomnia, and psychosis. These symptoms began 3 months before he was admitted to the psychiatric unit, when he had started taking high doses of omega-3 fatty acid supplements.

Continue to: EVALUATION Persistent mania

EVALUATION Persistent mania

On initial examination, Mr. A is upset and irritable. He is casually dressed and well-groomed. He lacks insight and says he was brought to the hospital against his will, and it is his wife “who is the one who is crazy.” He is oriented to person, place, and time. At times he is found roaming the hallways, being intrusive, hyperverbal, and tangential with pressured speech. He is very difficult to redirect, and regularly interrupts the interview. His vital signs are stable. He walks well, with slow and steady gait, and displays no tremor or bradykinesia.

[polldaddy:10091674]

The authors’ observations

In order to rule out organic causes, a complete blood count, comprehensive metabolic panel, thyroid profile, urine drug screen, and brain MRI were ordered. No abnormalities were found. DHA and EPA levels were not measured because such testing was not available at the laboratory at the hospital.

Mania emerging after the sixth decade of life is a rare occurrence. Therefore, we made a substantial effort to try to find another cause that might explain Mr. A’s unusual presentation (Table 2).

Omega-3 fatty acid–induced mania. The major types of omega-3 polyunsaturated fatty acids are EPA and DHA and their precursor, alpha-linolenic acid (ALA). EPA and DHA are found primarily in fatty fish, such as salmon, and in fish oil supplements. Omega-3 fatty acids have beneficial anti-inflammatory, antioxidative, and neuro­plastic effects.⁴ Having properties similar to selective serotonin reuptake inhibitors, omega-3 fatty acids are thought to help prevent depression, have few interactions with other medications, and have a lower adverse-effect burden than antidepressants. They have been found to be beneficial as a maintenance treatment and for prevention of depressive episodes in bipolar depression, but no positive association has been found for bipolar mania.⁵

Continue to: However, very limited evidence suggests...

However, very limited evidence suggests that omega-3 fatty acid supplements, particularly those with flaxseed oil, can induce hypomania or mania. This association was first reported by Rudin⁶ in 1981, and later reported in other studies.⁷How omega-3 fatty acids might induce mania is unclear.

Mr. A was reportedly taking high doses of an omega-3 fatty acid supplement. We hypothesized that the antidepressant effect of this supplement may have precipitated a manic episode. Mr. A had no history of manic episodes in the past and was stable during the treatment with the outpatient psychiatrist. A first episode mania in the seventh decade of life would be highly unusual without an organic etiology. After laboratory tests found no abnormalities that would point to an organic etiology, iatrogenic causes were considered. After a review of the literature, there was anecdotal evidence for the induction of mania in clinical trials studying the effects of omega-3 supplements on affective disorders.

This led us to ask: How much omega-3 fatty acid supplements, if any, can a patient with a depressive or bipolar disorder safely take? Currently, omega-3 fatty acid supplements are not FDA-approved for the treatment of depression or bipolar disorder. However, patients may take 1.5 to 2 g/d for MDD. Further research is needed to determine the optimal dose. It is unclear at this time if omega-3 fatty acid supplementation has any benefit in the acute or maintenance treatment of bipolar disorder.

Alternative nutritional supplements for mood disorders. Traditionally, mood disorders, such as MDD and bipolar disorder, have been treated with psycho­tropic medications. However, through the years, sporadic studies have examined the efficacy of nutritional interventions as a cost-effective approach to preventing and treating these conditions.⁵ Proponents of this approach believe such supplements can increase efficacy, as well as decrease the required dose of psychotropic medications, thus potentially minimizing adverse effects. However, their overuse can pose a potential threat of toxicity or unexpected adverse effects, such as precipitation of mania. Table 3⁸ lists over-the-counter nutritional and/or herbal agents that may cause mania.

Continue to: TREATMENT Nonadherence leads to a court order

On admission, Mr. A receives a dose of hydrocodone/acetaminophen (10 mg/325 mg, by mouth every 4 hours as needed) and lorazepam. His intake of omega-3 fatty acid supplements is discontinued during treatment. He is alert but tangential with loosening of associations. His speech is rapid; he continues to be grandiose and oblivious to the reason for his hospitalization. He is able to spontaneously discuss recent life events. After a week-long period of nonadherence to treatment, Mr. A requires a court order for psychiatric treatment and undergoes inpatient treatment for a total of 30 days.

[polldaddy:10091676]

The authors’ observations

During an acute manic episode, the goal of treatment is urgent mood stabilization. Monotherapy can be used; however, in emergent settings, a combination is often used for a rapid response. The most commonly used agents are lithium, anticonvulsants such as valproic acid, and antipsychotics.⁹ In addition, benzodiazepines can be used for insomnia, agitation, or anxiety. The decision to use lithium, an anticonvulsant, or an antipsychotic depends upon the specific medication’s adverse effects, the patient’s medical history, previous medication trials, drug–drug interactions, patient preference, and cost.

Because Mr. A has a history of chronic kidney disease, lithium was contraindicated. Therefore, risperidone was initiated and titrated up to 6 mg/d. Mr. A showed some improvement, but his response was not optimal, as he experienced continued irritability, insomnia, and delusions. Valproic acid was started, and the dose was titrated to 1,000 mg/d, which equates to a serum blood level of 54.2 mg/dL.

[polldaddy:10091678]

Continue to: The authors' observations

After the acute episode of mania resolves, maintenance pharmacotherapy typically involves continuing the same regimen that achieved mood stabilization. Monotherapy is typically preferred to combination therapy, but it is not always possible after a manic episode.¹⁰ A reasonable approach is to slowly taper the antipsychotic after several months of dual therapy if symptoms continue to be well-controlled. Further adjustments may be necessary, depending on the medications’ adverse effects. Moreover, further acute episodes of mania or depression will also determine future treatment.

OUTCOME Resolution of delusions

Mr. A is discharged 30 days after admission. At this point, his acute manic episode has resolved with non-tangential, non-pressured speech, improved sleep, and decreased impulsivity. His grandiose delusions also have resolved. He is prescribed valproic acid, 1,000 mg/d, and risperidone, 6 mg/d at bedtime, under the care of his outpatient psychiatrist.

Bottom Line

Initial presentation of a manic episode in an older patient is rare. It is important to rule out organic causes. Weak evidence suggests omega-3 fatty acid supplements may have the potential to induce mania in certain patients.

Related Resource

• Ramaswamy S, Driscoll D, Rodriguez A, et al. Nutraceuticals for traumatic brain injury: Should you recommend their use? Current Psychiatry. 2017;16(7):34-38,40,41-45.

Drug Brand Names

Buprenorphine • Suboxone, Subutex
Citalopram • Celexa
Hydrocodone/acetaminophen • Vicodin
Lithium • Eskalith, Lithobid
Lorazepam• Ativan
Nortriptyline • Pamelor
Risperidone • Risperdal
Valproic acid • Depakote

CASE Reckless driving, impulse buying

Mr. A, age 73, is admitted to the inpatient psychiatric unit at a community hospital for evaluation of a psychotic episode. His admission to the unit was initiated by his primary care physician, who noted that Mr. A was “not making sense” during a routine visit. Mr. A was speaking rapidly about how he had discovered that high-dose omega-3 fatty acid supplements were a “cure” for Alzheimer’s disease. He also believes that he was recently appointed as CEO of Microsoft and Apple for his discoveries.

Three months earlier, Mr. A had started taking high doses of omega-3 fatty acid supplements (10 to 15 g/d) because he believed they were the cure for memory problems, pain, and depression. At that time, he discontinued taking nortriptyline, 25 mg/d, and citalopram, 40 mg/d, which his outpatient psychiatrist had prescribed for major depressive disorder (MDD). Mr. A also had stopped taking buprenorphine, 2 mg, sublingual, 4 times a day, which he had been prescribed for chronic pain.

Mr. A’s wife reports that during the last 2 months, her husband had become irritable, impulsive, grandiose, and was sleeping very little. She added that although her husband’s ophthalmologist had advised him to not drive due to impaired vision, he had been driving recklessly across the metropolitan area. He had also spent nearly $15,000 buying furniture and other items for their home.

In addition to MDD, Mr. A has a history of chronic kidney disease, Leber’s hereditary optic neuropathy, and chronic pain. He has been taking vitamin D3, 2,000 U/d, as a nutritional supplement.

[polldaddy:10091672]

The authors’ observations

Mr. A met the DSM-5 criteria for a manic episode (Table 1¹). His manic and delusional symptoms are new. He has a long-standing diagnosis of MDD, which for many years had been successfully treated with antidepressants without a manic switch. The absence of a manic switch when treated with antidepressants without a mood stabilizer suggested that Mr. A did not have bipolarity in terms of a mood disorder diathesis.² In addition, it would be unusual for an individual to develop a new-onset or primary bipolar disorder after age 60. Individuals in this age group who present with manic symptoms for the first time are preponderantly found to have a general medical or iatrogenic cause for the emergence of these symptoms.³ Mr. A has a history of chronic kidney disease, Leber’s hereditary optic neuropathy, and chronic pain.

Typically a sedentary man, Mr. A had been exhibiting disinhibited behavior, grandiosity, insomnia, and psychosis. These symptoms began 3 months before he was admitted to the psychiatric unit, when he had started taking high doses of omega-3 fatty acid supplements.

Continue to: EVALUATION Persistent mania

EVALUATION Persistent mania

On initial examination, Mr. A is upset and irritable. He is casually dressed and well-groomed. He lacks insight and says he was brought to the hospital against his will, and it is his wife “who is the one who is crazy.” He is oriented to person, place, and time. At times he is found roaming the hallways, being intrusive, hyperverbal, and tangential with pressured speech. He is very difficult to redirect, and regularly interrupts the interview. His vital signs are stable. He walks well, with slow and steady gait, and displays no tremor or bradykinesia.

[polldaddy:10091674]

The authors’ observations

In order to rule out organic causes, a complete blood count, comprehensive metabolic panel, thyroid profile, urine drug screen, and brain MRI were ordered. No abnormalities were found. DHA and EPA levels were not measured because such testing was not available at the laboratory at the hospital.

Mania emerging after the sixth decade of life is a rare occurrence. Therefore, we made a substantial effort to try to find another cause that might explain Mr. A’s unusual presentation (Table 2).

Omega-3 fatty acid–induced mania. The major types of omega-3 polyunsaturated fatty acids are EPA and DHA and their precursor, alpha-linolenic acid (ALA). EPA and DHA are found primarily in fatty fish, such as salmon, and in fish oil supplements. Omega-3 fatty acids have beneficial anti-inflammatory, antioxidative, and neuro­plastic effects.⁴ Having properties similar to selective serotonin reuptake inhibitors, omega-3 fatty acids are thought to help prevent depression, have few interactions with other medications, and have a lower adverse-effect burden than antidepressants. They have been found to be beneficial as a maintenance treatment and for prevention of depressive episodes in bipolar depression, but no positive association has been found for bipolar mania.⁵

Continue to: However, very limited evidence suggests...

However, very limited evidence suggests that omega-3 fatty acid supplements, particularly those with flaxseed oil, can induce hypomania or mania. This association was first reported by Rudin⁶ in 1981, and later reported in other studies.⁷How omega-3 fatty acids might induce mania is unclear.

Mr. A was reportedly taking high doses of an omega-3 fatty acid supplement. We hypothesized that the antidepressant effect of this supplement may have precipitated a manic episode. Mr. A had no history of manic episodes in the past and was stable during the treatment with the outpatient psychiatrist. A first episode mania in the seventh decade of life would be highly unusual without an organic etiology. After laboratory tests found no abnormalities that would point to an organic etiology, iatrogenic causes were considered. After a review of the literature, there was anecdotal evidence for the induction of mania in clinical trials studying the effects of omega-3 supplements on affective disorders.

This led us to ask: How much omega-3 fatty acid supplements, if any, can a patient with a depressive or bipolar disorder safely take? Currently, omega-3 fatty acid supplements are not FDA-approved for the treatment of depression or bipolar disorder. However, patients may take 1.5 to 2 g/d for MDD. Further research is needed to determine the optimal dose. It is unclear at this time if omega-3 fatty acid supplementation has any benefit in the acute or maintenance treatment of bipolar disorder.

Alternative nutritional supplements for mood disorders. Traditionally, mood disorders, such as MDD and bipolar disorder, have been treated with psycho­tropic medications. However, through the years, sporadic studies have examined the efficacy of nutritional interventions as a cost-effective approach to preventing and treating these conditions.⁵ Proponents of this approach believe such supplements can increase efficacy, as well as decrease the required dose of psychotropic medications, thus potentially minimizing adverse effects. However, their overuse can pose a potential threat of toxicity or unexpected adverse effects, such as precipitation of mania. Table 3⁸ lists over-the-counter nutritional and/or herbal agents that may cause mania.

Continue to: TREATMENT Nonadherence leads to a court order

On admission, Mr. A receives a dose of hydrocodone/acetaminophen (10 mg/325 mg, by mouth every 4 hours as needed) and lorazepam. His intake of omega-3 fatty acid supplements is discontinued during treatment. He is alert but tangential with loosening of associations. His speech is rapid; he continues to be grandiose and oblivious to the reason for his hospitalization. He is able to spontaneously discuss recent life events. After a week-long period of nonadherence to treatment, Mr. A requires a court order for psychiatric treatment and undergoes inpatient treatment for a total of 30 days.

[polldaddy:10091676]

The authors’ observations

During an acute manic episode, the goal of treatment is urgent mood stabilization. Monotherapy can be used; however, in emergent settings, a combination is often used for a rapid response. The most commonly used agents are lithium, anticonvulsants such as valproic acid, and antipsychotics.⁹ In addition, benzodiazepines can be used for insomnia, agitation, or anxiety. The decision to use lithium, an anticonvulsant, or an antipsychotic depends upon the specific medication’s adverse effects, the patient’s medical history, previous medication trials, drug–drug interactions, patient preference, and cost.

Because Mr. A has a history of chronic kidney disease, lithium was contraindicated. Therefore, risperidone was initiated and titrated up to 6 mg/d. Mr. A showed some improvement, but his response was not optimal, as he experienced continued irritability, insomnia, and delusions. Valproic acid was started, and the dose was titrated to 1,000 mg/d, which equates to a serum blood level of 54.2 mg/dL.

[polldaddy:10091678]

Continue to: The authors' observations

After the acute episode of mania resolves, maintenance pharmacotherapy typically involves continuing the same regimen that achieved mood stabilization. Monotherapy is typically preferred to combination therapy, but it is not always possible after a manic episode.¹⁰ A reasonable approach is to slowly taper the antipsychotic after several months of dual therapy if symptoms continue to be well-controlled. Further adjustments may be necessary, depending on the medications’ adverse effects. Moreover, further acute episodes of mania or depression will also determine future treatment.

OUTCOME Resolution of delusions

Mr. A is discharged 30 days after admission. At this point, his acute manic episode has resolved with non-tangential, non-pressured speech, improved sleep, and decreased impulsivity. His grandiose delusions also have resolved. He is prescribed valproic acid, 1,000 mg/d, and risperidone, 6 mg/d at bedtime, under the care of his outpatient psychiatrist.

Bottom Line

Initial presentation of a manic episode in an older patient is rare. It is important to rule out organic causes. Weak evidence suggests omega-3 fatty acid supplements may have the potential to induce mania in certain patients.

Related Resource

• Ramaswamy S, Driscoll D, Rodriguez A, et al. Nutraceuticals for traumatic brain injury: Should you recommend their use? Current Psychiatry. 2017;16(7):34-38,40,41-45.

Drug Brand Names

Buprenorphine • Suboxone, Subutex
Citalopram • Celexa
Hydrocodone/acetaminophen • Vicodin
Lithium • Eskalith, Lithobid
Lorazepam• Ativan
Nortriptyline • Pamelor
Risperidone • Risperdal
Valproic acid • Depakote

The average cost of outpatient care for Medicare recipients with chronic hepatitis B (CH-B) rose by 400% from 2005 to 2014, according to investigators.

utah778/Thinkstock

Inpatient costs also increased, although less dramatically, reported lead author Min Kim, MD, of the Inova Fairfax Hospital Center for Liver Diseases in Falls Church, Virginia, and her colleagues. The causes of these spending hikes may range from policy changes and expanded screening to an aging immigrant population.

“According to the National Health and Nutrition Examination Survey, from 1988 to 2012 most people with CH-B in the United States were foreign born and accounted for up to 70% of all CH-B infections,” the authors wrote in the Journal of Clinical Gastroenterology. “The Centers for Disease Control [and Prevention] estimates that Asians, who comprise 5% of the U.S. population, account for 50% of all chronic CH-B infections.” Despite these statistics, the clinical and economic impacts of an aging immigrant population are unknown. The investigators therefore assessed patient characteristics associated with increased 1-year mortality and the impact of demographic changes on Medicare costs.

The retrospective study began with a random sample of Medicare beneficiaries from 2005 to 2014. From this group, 18,603 patients with CH-B were identified by ICD-9 codes V02.61, 070.2, 070.3, 070.42, and 070.52. Patients with ICD-9-CM codes of 197.7, 155.1, or 155.2 were excluded, as were records containing insufficient information about year, region, or race. Patients were analyzed collectively and as inpatients (n = 6,550) or outpatients (n = 13,648).

Cost of care (per patient, per year) and 1-year mortality were evaluated. Patient characteristics included age, sex, race/ethnicity, geographic region, type of Medicare eligibility, length of stay, Charlson comorbidity index, presence of decompensated cirrhosis, and/or hepatocellular carcinoma (HCC).

Most dramatically, outpatient charges rose more than 400% during the study period, from $9,257 in 2005 to $47,864 in 2014 (P less than .001). Inpatient charges increased by almost 50%, from $66,610 to $94,221 (P less than .001). (All values converted to 2016 dollars.)

Although the increase in outpatient costs appears seismic, the authors noted that costs held steady from 2005 to 2010 before spiking dramatically, reaching a peak of $58,450 in 2013 before settling down to $47,864 the following year. This spike may be caused by changes in screening measures and policies. In 2009, the American Association for the Study of Liver Diseases expanded screening guidelines to include previously ineligible patients with CH-B, and in 2010, the Centers for Medicare & Medicaid Services expanded ICD-9 and ICD-10 codes for CH-B from 9 to 25.

“It seems plausible that the increase in CH-B prevalence, and its associated costs, might actually be a reflection of [these factors],” the authors noted. Still, “additional studies are needed to clarify this observation.”

Turning to patient characteristics, the authors reported that 1-year mortality was independently associated most strongly with decompensated cirrhosis (odds ratio, 3.02) and hepatocellular carcinoma (OR, 2.64). In comparison with white patients, Asians were less likely to die (OR, 0.47).

“It is possible that this can be explained through differences in transmission mode and disease progression of CH-B between these two demographics,” the authors wrote. “A majority of Asian Medicare recipients with CH-B likely acquired it perinatally and did not develop significant liver disease. In contrast, whites with CH-B generally acquired it in adulthood, increasing the chance of developing liver disease.”

Over the 10-year study period, Medicare beneficiaries with CH-B became more frequently Asian and less frequently male. While the number of outpatient visits and average Charlson comorbidity index increased, decreases were reported for length of stay, rates of 1-year mortality, hospitalization, and HCC – the latter of which is most closely associated with higher costs of care.

The investigators suggested that the decreased incidence of HCC was caused by “better screening programs for HCC and/or more widespread use of antiviral treatment for CH-B.”

“Although advances in antiviral treatment have effectively reduced hospitalization and disease progression,” the authors wrote, “vulnerable groups – especially immigrants and individuals living in poverty – present an important challenge for better identification of infected individuals and their linkage to care. In this context, it is vital to target these cohorts to reduce further mortality and resource utilization, as well as optimize long-term public health and financial benefits.”

Study funding was provided by Seattle Genetics. One coauthor reported compensation from Gilead Sciences, AbbVie, Intercept Pharmaceuticals, GlaxoSmithKline, and Bristol-Myers Squibb.

SOURCE: Kim M et al. J Clin Gastro. 2018 Aug 13. doi: 10.1097/MCG.0000000000001110.

The average cost of outpatient care for Medicare recipients with chronic hepatitis B (CH-B) rose by 400% from 2005 to 2014, according to investigators.

utah778/Thinkstock

Inpatient costs also increased, although less dramatically, reported lead author Min Kim, MD, of the Inova Fairfax Hospital Center for Liver Diseases in Falls Church, Virginia, and her colleagues. The causes of these spending hikes may range from policy changes and expanded screening to an aging immigrant population.

“According to the National Health and Nutrition Examination Survey, from 1988 to 2012 most people with CH-B in the United States were foreign born and accounted for up to 70% of all CH-B infections,” the authors wrote in the Journal of Clinical Gastroenterology. “The Centers for Disease Control [and Prevention] estimates that Asians, who comprise 5% of the U.S. population, account for 50% of all chronic CH-B infections.” Despite these statistics, the clinical and economic impacts of an aging immigrant population are unknown. The investigators therefore assessed patient characteristics associated with increased 1-year mortality and the impact of demographic changes on Medicare costs.

The retrospective study began with a random sample of Medicare beneficiaries from 2005 to 2014. From this group, 18,603 patients with CH-B were identified by ICD-9 codes V02.61, 070.2, 070.3, 070.42, and 070.52. Patients with ICD-9-CM codes of 197.7, 155.1, or 155.2 were excluded, as were records containing insufficient information about year, region, or race. Patients were analyzed collectively and as inpatients (n = 6,550) or outpatients (n = 13,648).

Cost of care (per patient, per year) and 1-year mortality were evaluated. Patient characteristics included age, sex, race/ethnicity, geographic region, type of Medicare eligibility, length of stay, Charlson comorbidity index, presence of decompensated cirrhosis, and/or hepatocellular carcinoma (HCC).

Most dramatically, outpatient charges rose more than 400% during the study period, from $9,257 in 2005 to $47,864 in 2014 (P less than .001). Inpatient charges increased by almost 50%, from $66,610 to $94,221 (P less than .001). (All values converted to 2016 dollars.)

Although the increase in outpatient costs appears seismic, the authors noted that costs held steady from 2005 to 2010 before spiking dramatically, reaching a peak of $58,450 in 2013 before settling down to $47,864 the following year. This spike may be caused by changes in screening measures and policies. In 2009, the American Association for the Study of Liver Diseases expanded screening guidelines to include previously ineligible patients with CH-B, and in 2010, the Centers for Medicare & Medicaid Services expanded ICD-9 and ICD-10 codes for CH-B from 9 to 25.

“It seems plausible that the increase in CH-B prevalence, and its associated costs, might actually be a reflection of [these factors],” the authors noted. Still, “additional studies are needed to clarify this observation.”

Turning to patient characteristics, the authors reported that 1-year mortality was independently associated most strongly with decompensated cirrhosis (odds ratio, 3.02) and hepatocellular carcinoma (OR, 2.64). In comparison with white patients, Asians were less likely to die (OR, 0.47).

“It is possible that this can be explained through differences in transmission mode and disease progression of CH-B between these two demographics,” the authors wrote. “A majority of Asian Medicare recipients with CH-B likely acquired it perinatally and did not develop significant liver disease. In contrast, whites with CH-B generally acquired it in adulthood, increasing the chance of developing liver disease.”

Over the 10-year study period, Medicare beneficiaries with CH-B became more frequently Asian and less frequently male. While the number of outpatient visits and average Charlson comorbidity index increased, decreases were reported for length of stay, rates of 1-year mortality, hospitalization, and HCC – the latter of which is most closely associated with higher costs of care.

The investigators suggested that the decreased incidence of HCC was caused by “better screening programs for HCC and/or more widespread use of antiviral treatment for CH-B.”

“Although advances in antiviral treatment have effectively reduced hospitalization and disease progression,” the authors wrote, “vulnerable groups – especially immigrants and individuals living in poverty – present an important challenge for better identification of infected individuals and their linkage to care. In this context, it is vital to target these cohorts to reduce further mortality and resource utilization, as well as optimize long-term public health and financial benefits.”

Study funding was provided by Seattle Genetics. One coauthor reported compensation from Gilead Sciences, AbbVie, Intercept Pharmaceuticals, GlaxoSmithKline, and Bristol-Myers Squibb.

SOURCE: Kim M et al. J Clin Gastro. 2018 Aug 13. doi: 10.1097/MCG.0000000000001110.

The average cost of outpatient care for Medicare recipients with chronic hepatitis B (CH-B) rose by 400% from 2005 to 2014, according to investigators.

utah778/Thinkstock

Inpatient costs also increased, although less dramatically, reported lead author Min Kim, MD, of the Inova Fairfax Hospital Center for Liver Diseases in Falls Church, Virginia, and her colleagues. The causes of these spending hikes may range from policy changes and expanded screening to an aging immigrant population.

“According to the National Health and Nutrition Examination Survey, from 1988 to 2012 most people with CH-B in the United States were foreign born and accounted for up to 70% of all CH-B infections,” the authors wrote in the Journal of Clinical Gastroenterology. “The Centers for Disease Control [and Prevention] estimates that Asians, who comprise 5% of the U.S. population, account for 50% of all chronic CH-B infections.” Despite these statistics, the clinical and economic impacts of an aging immigrant population are unknown. The investigators therefore assessed patient characteristics associated with increased 1-year mortality and the impact of demographic changes on Medicare costs.

The retrospective study began with a random sample of Medicare beneficiaries from 2005 to 2014. From this group, 18,603 patients with CH-B were identified by ICD-9 codes V02.61, 070.2, 070.3, 070.42, and 070.52. Patients with ICD-9-CM codes of 197.7, 155.1, or 155.2 were excluded, as were records containing insufficient information about year, region, or race. Patients were analyzed collectively and as inpatients (n = 6,550) or outpatients (n = 13,648).

Cost of care (per patient, per year) and 1-year mortality were evaluated. Patient characteristics included age, sex, race/ethnicity, geographic region, type of Medicare eligibility, length of stay, Charlson comorbidity index, presence of decompensated cirrhosis, and/or hepatocellular carcinoma (HCC).

Most dramatically, outpatient charges rose more than 400% during the study period, from $9,257 in 2005 to $47,864 in 2014 (P less than .001). Inpatient charges increased by almost 50%, from $66,610 to $94,221 (P less than .001). (All values converted to 2016 dollars.)

Although the increase in outpatient costs appears seismic, the authors noted that costs held steady from 2005 to 2010 before spiking dramatically, reaching a peak of $58,450 in 2013 before settling down to $47,864 the following year. This spike may be caused by changes in screening measures and policies. In 2009, the American Association for the Study of Liver Diseases expanded screening guidelines to include previously ineligible patients with CH-B, and in 2010, the Centers for Medicare & Medicaid Services expanded ICD-9 and ICD-10 codes for CH-B from 9 to 25.

“It seems plausible that the increase in CH-B prevalence, and its associated costs, might actually be a reflection of [these factors],” the authors noted. Still, “additional studies are needed to clarify this observation.”

Turning to patient characteristics, the authors reported that 1-year mortality was independently associated most strongly with decompensated cirrhosis (odds ratio, 3.02) and hepatocellular carcinoma (OR, 2.64). In comparison with white patients, Asians were less likely to die (OR, 0.47).

“It is possible that this can be explained through differences in transmission mode and disease progression of CH-B between these two demographics,” the authors wrote. “A majority of Asian Medicare recipients with CH-B likely acquired it perinatally and did not develop significant liver disease. In contrast, whites with CH-B generally acquired it in adulthood, increasing the chance of developing liver disease.”

Over the 10-year study period, Medicare beneficiaries with CH-B became more frequently Asian and less frequently male. While the number of outpatient visits and average Charlson comorbidity index increased, decreases were reported for length of stay, rates of 1-year mortality, hospitalization, and HCC – the latter of which is most closely associated with higher costs of care.

The investigators suggested that the decreased incidence of HCC was caused by “better screening programs for HCC and/or more widespread use of antiviral treatment for CH-B.”

“Although advances in antiviral treatment have effectively reduced hospitalization and disease progression,” the authors wrote, “vulnerable groups – especially immigrants and individuals living in poverty – present an important challenge for better identification of infected individuals and their linkage to care. In this context, it is vital to target these cohorts to reduce further mortality and resource utilization, as well as optimize long-term public health and financial benefits.”

Study funding was provided by Seattle Genetics. One coauthor reported compensation from Gilead Sciences, AbbVie, Intercept Pharmaceuticals, GlaxoSmithKline, and Bristol-Myers Squibb.

SOURCE: Kim M et al. J Clin Gastro. 2018 Aug 13. doi: 10.1097/MCG.0000000000001110.

The two most common reasons for pediatric emergency department visits exhibit considerable and opposing seasonal variations, according to the Agency for Healthcare Research and Quality.

Of the 30 million ED visits by children aged 18 years and younger during fiscal year 2015, about 9.6 million, or just under 24%, were for respiratory disorders, making it the most common diagnosis by body system. The second-most common reason, injuries, was associated with approximately 7.9 million visits in 2015, the AHRQ reported recently in a statistical brief.

Over the 4-year period from 2011 to 2015, pediatric ED visits for respiratory disorders peaked during the months from October to March and dropped during April-September. In 2015, for example, there was a 43% difference between October-December, which was the highest-volume quarter, and July-September, which had the lowest volume of visits, the report showed.

The opposite pattern of seasonality was seen with visits for injury-related visits: The high point each year occurs in April-September, with the low in October-March. In 2015, there was a 30% difference between the lowest-volume quarter of January-March and the highest-volume quarter of July-September, based on the analysis of data from the Nationwide Emergency Department Sample.

[email protected]

The two most common reasons for pediatric emergency department visits exhibit considerable and opposing seasonal variations, according to the Agency for Healthcare Research and Quality.

Of the 30 million ED visits by children aged 18 years and younger during fiscal year 2015, about 9.6 million, or just under 24%, were for respiratory disorders, making it the most common diagnosis by body system. The second-most common reason, injuries, was associated with approximately 7.9 million visits in 2015, the AHRQ reported recently in a statistical brief.

Over the 4-year period from 2011 to 2015, pediatric ED visits for respiratory disorders peaked during the months from October to March and dropped during April-September. In 2015, for example, there was a 43% difference between October-December, which was the highest-volume quarter, and July-September, which had the lowest volume of visits, the report showed.

The opposite pattern of seasonality was seen with visits for injury-related visits: The high point each year occurs in April-September, with the low in October-March. In 2015, there was a 30% difference between the lowest-volume quarter of January-March and the highest-volume quarter of July-September, based on the analysis of data from the Nationwide Emergency Department Sample.

[email protected]

The two most common reasons for pediatric emergency department visits exhibit considerable and opposing seasonal variations, according to the Agency for Healthcare Research and Quality.

Of the 30 million ED visits by children aged 18 years and younger during fiscal year 2015, about 9.6 million, or just under 24%, were for respiratory disorders, making it the most common diagnosis by body system. The second-most common reason, injuries, was associated with approximately 7.9 million visits in 2015, the AHRQ reported recently in a statistical brief.

Over the 4-year period from 2011 to 2015, pediatric ED visits for respiratory disorders peaked during the months from October to March and dropped during April-September. In 2015, for example, there was a 43% difference between October-December, which was the highest-volume quarter, and July-September, which had the lowest volume of visits, the report showed.

The opposite pattern of seasonality was seen with visits for injury-related visits: The high point each year occurs in April-September, with the low in October-March. In 2015, there was a 30% difference between the lowest-volume quarter of January-March and the highest-volume quarter of July-September, based on the analysis of data from the Nationwide Emergency Department Sample.

[email protected]