Home-Based Primary Care (HBPC) is a unique interdisciplinary program within the Veteran’s Health Administration (VHA) that specifically targets veterans with complex, chronic disabling diseases who have difficulty traveling to a VHA facility.¹ Veterans are provided comprehensive longitudinal primary care in their homes, with the goal of maximizing the veteran’s independence. Clinical pharmacists are known as medication experts and have an essential role within interdisciplinary teams, including HBPC, improving medication safety, and decreasing inappropriate prescribing practices.^2,3 Clinical pharmacy specialists (CPSs) within the VHA work collaboratively but autonomously as advanced practice providers assisting with the pharmacologic management of many diseases and chronic conditions. The remainder of this article will refer to the HBPC pharmacist as a CPS.

The CPS is actively involved in providing comprehensive medication management (CMM) services across VHA and has the expertise to effectively assist veterans in achieving targeted clinical outcomes. While the value and role of CPSs in the primary care setting are described extensively in the literature, data regarding the CPS in HBPC are limited.^4-6 Therefore, the purpose of the assessment was to evaluate the status of the HBPC pharmacy workforce, identify current pharmacist activities and strong practices, and clarify national variations among programs. Future use of this analysis may assist with standardization of the HBPC CPS role and development of business rules in combination with a workload-based staffing model tool.

Background

The role of the pharmacist in the HBPC setting has evolved from providing basic medication therapy reviews to an advanced role providing CMM services under a VHA scope of practice (SOP), which outlines 8 functions that may be authorized, including medication prescriptive authority.⁷ The SOP may be disease specific (limited) but is increasingly transitioning to have a practice-area scope (global), which is consistent with other VHA advanced practice providers.⁷ Effective use of a CPS in this role allows for optimization of CMM and increasing veteran access to VHA care.

The VHA employed 7,285 pharmacists in 2014.⁸ Many were considered CPSs with prescriptive authority. These pharmacists were responsible for ordering more than 1.7 million distinct prescriptions across the VHA in fiscal year 2014, which represented 2.6% of the total prescriptions that year.⁷ A 2007 VHA study also demonstrated both an increase in appropriate prescribing practices and improved medication use when CPSs worked in collaboration with the HBPC team.⁹ With this evolution of VHA pharmacists, there has been an increase in the use of CPSs in HBPC and changes in staffing ratios to allow for additional clinical activities and comprehensive patient care provision.¹

The HBPC model serves a complex population in which each veteran has about 8 chronic conditions.^1,10 An interdisciplinary team consisting of various health care professionals, such as physicians, nurse practitioners, nurses, social workers, registered dietitians, psychologists, rehabilitation therapists, pharmacists, etc, work collaboratively to care for these veterans in the patient’s home. This team is a type of patient-centered medical home (PCMH) that focuses on providing primary care services to an at-risk veteran population who have difficulty leaving the home.¹ Home-based primary care has been shown to be cost-effective, reducing average annual cost of health care by up to 24%.¹⁰ Another study showed that patients using HBPC had a 27% reduction in hospital admissions and 69% reduction in inpatient hospital days when compared with patients who were not using HBPC.¹¹

The interdisciplinary team meets at least once weekly to discuss and design individualized care plans for veterans enrolled in the program. It is desirable for pharmacists on these teams to have special expertise and certification in geriatric pharmacotherapy and chronic disease management (eg, board-certified geriatric pharmacist [BCGP], board-certified pharmacotherapy specialist [BCPS], or board-certified ambulatory care pharmacist [BCACP]) due to the complexity of comorbidities of these veterans.¹² Additional education such as postgraduate pharmacy residency training also is beneficial for CPSs in this setting.

The CPS proactively performs CMM that is often greater in scope than a targeted disease review due to multiple comorbid conditions that are often present within veteran patients.¹ These comprehensive medication reviews are considered a core function and must be performed on enrollment in HBPC, quarterly, and when clinically indicated or requested by the team.¹³ Sufficient time must be allocated to the CPS in order to provide these high-quality medication reviews. Additional core functions of the CPS are outlined in the functional statement and/or SOP, but responsibilities include CMM and disease management. This typically consists of prescribing and/or adjusting medications, as well as providing patient and caregiver education, which can be performed either face-to-face or via telehealth visits (eg, telephone and video). A CPS also may make home visits to assess the veteran, either independently or with other disciplines of the HBPC team.

The HBPC Subject Matter Expert (SME) workgroup was chartered by the Veterans Affairs Central Office (VACO) Pharmacy Benefits Management Service (PBM) Clinical Pharmacy Practice Office (CPPO) to explore pharmacy practice changes in the HBPC setting. This workgroup serves as clinical practice leadership within the HBPC setting to provide expertise and lead initiatives supporting the advanced practice role of the HBPC CPS.

As HBPC programs expanded throughout VHA, it was paramount to determine the current state of HBPC pharmacy practice by collecting necessary data points to assess uniformity and better understand opportunities for practice standardization. The SME workgroup developed a voluntary yet comprehensive survey assessment that served to proactively assess the future of HBPC pharmacy.

 

Methods

The HBPC SME workgroup, in conjunction with CPPO, developed the assessment. Questions were designed and tested within a small group of CPSs and then distributed electronically. In August 2014, the assessment was e-mailed to all 21 VHA service areas with an active HBPC program, and responses were collected through a Microsoft SharePoint (Redmond, WA) survey. A response was requested from chiefs of pharmacy, clinical pharmacy leadership, or a representative.

This voluntary assessment contained 24 multipart questions related to background information of HBPC programs and clinical pharmacy services. Duplicate responses were consolidated and clarified with individual sites post hoc.

Descriptive statistics were used to analyze responses. To standardize the comparison across sites with a variety of full-time equivalent employees (FTEEs), the average patient census was divided by the CPS FTEE allocated to the programs at that site. For example, if a site reported 316 patients with 0.25 CPS FTEE, a standardized ratio for this site was 1,264 patients per FTEE. If a patient census range was reported, the median number would be used.

Results

The team received responses from 130 of 141 VHA facilities (92%), encompassing 270 CPSs. A total of 168.75 FTEEs were officially designated as HBPC CPSs. All 21 VHA service areas at the time were represented. The majority of responding programs (67%) had < 1 CPS FTEE allocated to HBPC; many of these CPSs were working in other pharmacy areas but were only dedicated to HBPC part-time. 

The remaining programs (33%) used 1 FTEE per CPS. The average patient census for each program was 245, ranging from 35 to 850 patients. Sixty-eight percent of sites had an average patient census > 151 per FTEE (Figure).

Nearly 90% of CPSs completed postgraduate year 1 residency training. Fifty-seven percent of CPSs held advanced certifications, such as BCGP, BCACP, or BCPS. Sixty-two percent of CPSs with these specialized board certifications had residency training. Use of a SOP was reported by 76% of CPSs, and 66% of these had a global practice-area scope. Table 1 outlines the functions authorized by a global or limited SOP.⁶ 

A higher percentage of those with global SOPs were authorized to perform physical assessment (69% vs 39%), order vaccines (57% vs 20%), and enter consults (75% vs 46%) compared with those with limited SOPs, respectively.

Overall, 52% of sites reported CPS involvement in CMM of primarily anticoagulation, diabetes mellitus (DM), anemia, hyperlipidemia, and hypertension. The reported average time spent for each disease encounter is delineated in Table 2. 

Those sites with CPSs who were not participating in disease management averaged a larger patient load compared with those who managed 4 of the 5 diseases (42.6% with 100-199 patients per pharmacist and 51.4% with 1-99 patients per pharmacist, respectively). Whether global or limited, 60% of CPSs reported using SOPs at least 25% of the time.

Thirty-five percent of sites reported CPS participation in home visits, and the majority of those completed between 1 and 10 home visits per month. The types of interventions provided often included medication education, assessment of medication adherence, and CMM for DM, hyperlipidemia, hypertension, etc. Multiple interventions often were made during each home visit.

The workload of medication reviews was divided among multiple CPSs in 55% of the programs. The majority of programs completed fewer than 20 initial medication reviews per month and between 21 and 80 quarterly medication reviews per month (81% and 62%, respectively). The average time for a CPS to complete initial medication reviews was 78 minutes and 42 minutes for quarterly medication reviews.

Sites with CPSs that held a SOP (76%) took an average of 83 minutes to complete an initial medication review and 48 minutes to complete a quarterly review. Sites with CPSs without a SOP (24%) took an average of 72 minutes to complete an initial medication review and 36 minutes to complete a quarterly review. Many CPSs allocate ≤ 20 hours per month on routine pharmacy functions (eg, prescription verification, dispensing activities, nonformulary medication requests) and ≤ 20 hours per month on nonpatient care activities (eg, education, medication use evaluations, training, projects), 67% and 82%, respectively.

Ninety-seven percent of CPSs actively attended weekly HBPC program interdisciplinary team (IDT) meetings, with 67% attending 1 weekly IDT meeting and 30% attending 2 to 5 weekly IDT meetings. Time spent attending IDT and roundtable discussions averaged 3.5 hours per week. Multiple programs noted growth within the 12 months preceding the survey, as 37 sites were granted approval for a total of 29.75 additional CPS FTEEs, and an additional 10 sites had a total of 9.25 FTEEs pending approval.

 

Discussion

Analysis of this assessment allowed the HBPC CPS SME workgroup to identify strong practices and variations in individual HBPC pharmacy programs. The majority of CPSs (66%) are using global, practice area-based SOPs, which allows more autonomy via direct patient care to veterans through CMM and home visits. This trend suggests the focus of the HBPC CPS role has expanded beyond traditional pharmacist activities. These global SOPs result in a higher yield of CPS functions, such as developing, documenting, and executing therapeutic plans and prescribing medications (Table 1). A higher percentage of CPSs with a practice area-based SOP were authorized to perform all 8 functions. Therefore, increased use of practice area-based SOPs and the expansion of the HBPC CPS role can support the team and increase clinical services available to veterans.

Clinical pharmacy specialists using SOPs take longer to complete medication reviews compared with those not using SOPs. Although the assessment was not designed to evaluate the reasons for these time differences, post-hoc follow-up clarification with individual sites determined CPS use of a SOP can lend to a more time-intensive and comprehensive medication review. This may lead to more optimized and safe medication regimens and elimination of unnecessary and/or inappropriate medications for HBPC veterans.

While only 35% of pharmacists were participating in the home visits at the time of this assessment, this is another area to explore as an opportunity to expand CMM. Although the assessment showed the majority of these home visits addressed medication education and adherence, programs may find it advantageous to provide CPS home visits for veterans identified as high risk or requiring specialized CMM. Additional data are needed regarding the ideal population to target for CPS home visits, as well as the estimated benefits of conducting home visits, such as outcomes and efficiency.

With growth noted in multiple programs, HBPC leadership should continue to encourage expanded pharmacist roles at an advanced practice level with SOPs, to provide veteran-centered care. This practice allows the team to concentrate efforts on patient acuity while increasing veteran access to VHA care. Additional CPS FTEEs are necessary to allow for expansion of the HBPC CPS role. The data also demonstrate HBPC often uses a part-time workforce where pharmacists are assigned to HBPC < 40 hours per week, and multiple pharmacists may be used to fulfill 1 CPS FTEE position. Home-Based Primary Care programs are encouraged to consolidate the number of CPSs involved as core individuals to promote continuity and avoid fragmented care.

Limitations

One limitation of the assessment is that the questions were designed and tested by a small group of CPSs, which may have led to response bias and potential misinterpretation of some questions. Time spent on medication reviews may have been underestimated, as some sites reported the maximum allowable workload credit time rather than actual time spent. Recall bias also is a limitation because the assessment relied on the recollection of the CPS or chief of pharmacy. Additionally, while the assessment focused on quantity and time spent on medication reviews, it was not designed to evaluate quality. Examination of what constitutes a high-quality medication review would be helpful to provide guidance and standardize care across the VHA.

Conclusion

Clinical pharmacy specialists practicing in the VHA HBPC setting are highly trained clinicians. A significant percentage of CPSs practice with a SOP that includes prescriptive privileges. However, variations in practice and function exist in the system. This presents an excellent opportunity for future standardization and promotion of the highest and best use of the CPS to improve quality of care for HBPC. With the expansion of the CPS role, there is potential for pharmacists to increase clinical activities and improve care for home-based veterans. The CPPO HBPC SME workgroup will continue to examine and explore the CPS role in this practice setting, develop staffing and practice guidance documents, and assess the benefit of CPS home visits.

Home-Based Primary Care (HBPC) is a unique interdisciplinary program within the Veteran’s Health Administration (VHA) that specifically targets veterans with complex, chronic disabling diseases who have difficulty traveling to a VHA facility.¹ Veterans are provided comprehensive longitudinal primary care in their homes, with the goal of maximizing the veteran’s independence. Clinical pharmacists are known as medication experts and have an essential role within interdisciplinary teams, including HBPC, improving medication safety, and decreasing inappropriate prescribing practices.^2,3 Clinical pharmacy specialists (CPSs) within the VHA work collaboratively but autonomously as advanced practice providers assisting with the pharmacologic management of many diseases and chronic conditions. The remainder of this article will refer to the HBPC pharmacist as a CPS.

The CPS is actively involved in providing comprehensive medication management (CMM) services across VHA and has the expertise to effectively assist veterans in achieving targeted clinical outcomes. While the value and role of CPSs in the primary care setting are described extensively in the literature, data regarding the CPS in HBPC are limited.^4-6 Therefore, the purpose of the assessment was to evaluate the status of the HBPC pharmacy workforce, identify current pharmacist activities and strong practices, and clarify national variations among programs. Future use of this analysis may assist with standardization of the HBPC CPS role and development of business rules in combination with a workload-based staffing model tool.

Background

The role of the pharmacist in the HBPC setting has evolved from providing basic medication therapy reviews to an advanced role providing CMM services under a VHA scope of practice (SOP), which outlines 8 functions that may be authorized, including medication prescriptive authority.⁷ The SOP may be disease specific (limited) but is increasingly transitioning to have a practice-area scope (global), which is consistent with other VHA advanced practice providers.⁷ Effective use of a CPS in this role allows for optimization of CMM and increasing veteran access to VHA care.

The VHA employed 7,285 pharmacists in 2014.⁸ Many were considered CPSs with prescriptive authority. These pharmacists were responsible for ordering more than 1.7 million distinct prescriptions across the VHA in fiscal year 2014, which represented 2.6% of the total prescriptions that year.⁷ A 2007 VHA study also demonstrated both an increase in appropriate prescribing practices and improved medication use when CPSs worked in collaboration with the HBPC team.⁹ With this evolution of VHA pharmacists, there has been an increase in the use of CPSs in HBPC and changes in staffing ratios to allow for additional clinical activities and comprehensive patient care provision.¹

The HBPC model serves a complex population in which each veteran has about 8 chronic conditions.^1,10 An interdisciplinary team consisting of various health care professionals, such as physicians, nurse practitioners, nurses, social workers, registered dietitians, psychologists, rehabilitation therapists, pharmacists, etc, work collaboratively to care for these veterans in the patient’s home. This team is a type of patient-centered medical home (PCMH) that focuses on providing primary care services to an at-risk veteran population who have difficulty leaving the home.¹ Home-based primary care has been shown to be cost-effective, reducing average annual cost of health care by up to 24%.¹⁰ Another study showed that patients using HBPC had a 27% reduction in hospital admissions and 69% reduction in inpatient hospital days when compared with patients who were not using HBPC.¹¹

The interdisciplinary team meets at least once weekly to discuss and design individualized care plans for veterans enrolled in the program. It is desirable for pharmacists on these teams to have special expertise and certification in geriatric pharmacotherapy and chronic disease management (eg, board-certified geriatric pharmacist [BCGP], board-certified pharmacotherapy specialist [BCPS], or board-certified ambulatory care pharmacist [BCACP]) due to the complexity of comorbidities of these veterans.¹² Additional education such as postgraduate pharmacy residency training also is beneficial for CPSs in this setting.

The CPS proactively performs CMM that is often greater in scope than a targeted disease review due to multiple comorbid conditions that are often present within veteran patients.¹ These comprehensive medication reviews are considered a core function and must be performed on enrollment in HBPC, quarterly, and when clinically indicated or requested by the team.¹³ Sufficient time must be allocated to the CPS in order to provide these high-quality medication reviews. Additional core functions of the CPS are outlined in the functional statement and/or SOP, but responsibilities include CMM and disease management. This typically consists of prescribing and/or adjusting medications, as well as providing patient and caregiver education, which can be performed either face-to-face or via telehealth visits (eg, telephone and video). A CPS also may make home visits to assess the veteran, either independently or with other disciplines of the HBPC team.

The HBPC Subject Matter Expert (SME) workgroup was chartered by the Veterans Affairs Central Office (VACO) Pharmacy Benefits Management Service (PBM) Clinical Pharmacy Practice Office (CPPO) to explore pharmacy practice changes in the HBPC setting. This workgroup serves as clinical practice leadership within the HBPC setting to provide expertise and lead initiatives supporting the advanced practice role of the HBPC CPS.

As HBPC programs expanded throughout VHA, it was paramount to determine the current state of HBPC pharmacy practice by collecting necessary data points to assess uniformity and better understand opportunities for practice standardization. The SME workgroup developed a voluntary yet comprehensive survey assessment that served to proactively assess the future of HBPC pharmacy.

 

Methods

The HBPC SME workgroup, in conjunction with CPPO, developed the assessment. Questions were designed and tested within a small group of CPSs and then distributed electronically. In August 2014, the assessment was e-mailed to all 21 VHA service areas with an active HBPC program, and responses were collected through a Microsoft SharePoint (Redmond, WA) survey. A response was requested from chiefs of pharmacy, clinical pharmacy leadership, or a representative.

This voluntary assessment contained 24 multipart questions related to background information of HBPC programs and clinical pharmacy services. Duplicate responses were consolidated and clarified with individual sites post hoc.

Descriptive statistics were used to analyze responses. To standardize the comparison across sites with a variety of full-time equivalent employees (FTEEs), the average patient census was divided by the CPS FTEE allocated to the programs at that site. For example, if a site reported 316 patients with 0.25 CPS FTEE, a standardized ratio for this site was 1,264 patients per FTEE. If a patient census range was reported, the median number would be used.

Results

The team received responses from 130 of 141 VHA facilities (92%), encompassing 270 CPSs. A total of 168.75 FTEEs were officially designated as HBPC CPSs. All 21 VHA service areas at the time were represented. The majority of responding programs (67%) had < 1 CPS FTEE allocated to HBPC; many of these CPSs were working in other pharmacy areas but were only dedicated to HBPC part-time. 

The remaining programs (33%) used 1 FTEE per CPS. The average patient census for each program was 245, ranging from 35 to 850 patients. Sixty-eight percent of sites had an average patient census > 151 per FTEE (Figure).

Nearly 90% of CPSs completed postgraduate year 1 residency training. Fifty-seven percent of CPSs held advanced certifications, such as BCGP, BCACP, or BCPS. Sixty-two percent of CPSs with these specialized board certifications had residency training. Use of a SOP was reported by 76% of CPSs, and 66% of these had a global practice-area scope. Table 1 outlines the functions authorized by a global or limited SOP.⁶ 

A higher percentage of those with global SOPs were authorized to perform physical assessment (69% vs 39%), order vaccines (57% vs 20%), and enter consults (75% vs 46%) compared with those with limited SOPs, respectively.

Overall, 52% of sites reported CPS involvement in CMM of primarily anticoagulation, diabetes mellitus (DM), anemia, hyperlipidemia, and hypertension. The reported average time spent for each disease encounter is delineated in Table 2. 

Those sites with CPSs who were not participating in disease management averaged a larger patient load compared with those who managed 4 of the 5 diseases (42.6% with 100-199 patients per pharmacist and 51.4% with 1-99 patients per pharmacist, respectively). Whether global or limited, 60% of CPSs reported using SOPs at least 25% of the time.

Thirty-five percent of sites reported CPS participation in home visits, and the majority of those completed between 1 and 10 home visits per month. The types of interventions provided often included medication education, assessment of medication adherence, and CMM for DM, hyperlipidemia, hypertension, etc. Multiple interventions often were made during each home visit.

The workload of medication reviews was divided among multiple CPSs in 55% of the programs. The majority of programs completed fewer than 20 initial medication reviews per month and between 21 and 80 quarterly medication reviews per month (81% and 62%, respectively). The average time for a CPS to complete initial medication reviews was 78 minutes and 42 minutes for quarterly medication reviews.

Sites with CPSs that held a SOP (76%) took an average of 83 minutes to complete an initial medication review and 48 minutes to complete a quarterly review. Sites with CPSs without a SOP (24%) took an average of 72 minutes to complete an initial medication review and 36 minutes to complete a quarterly review. Many CPSs allocate ≤ 20 hours per month on routine pharmacy functions (eg, prescription verification, dispensing activities, nonformulary medication requests) and ≤ 20 hours per month on nonpatient care activities (eg, education, medication use evaluations, training, projects), 67% and 82%, respectively.

Ninety-seven percent of CPSs actively attended weekly HBPC program interdisciplinary team (IDT) meetings, with 67% attending 1 weekly IDT meeting and 30% attending 2 to 5 weekly IDT meetings. Time spent attending IDT and roundtable discussions averaged 3.5 hours per week. Multiple programs noted growth within the 12 months preceding the survey, as 37 sites were granted approval for a total of 29.75 additional CPS FTEEs, and an additional 10 sites had a total of 9.25 FTEEs pending approval.

 

Discussion

Analysis of this assessment allowed the HBPC CPS SME workgroup to identify strong practices and variations in individual HBPC pharmacy programs. The majority of CPSs (66%) are using global, practice area-based SOPs, which allows more autonomy via direct patient care to veterans through CMM and home visits. This trend suggests the focus of the HBPC CPS role has expanded beyond traditional pharmacist activities. These global SOPs result in a higher yield of CPS functions, such as developing, documenting, and executing therapeutic plans and prescribing medications (Table 1). A higher percentage of CPSs with a practice area-based SOP were authorized to perform all 8 functions. Therefore, increased use of practice area-based SOPs and the expansion of the HBPC CPS role can support the team and increase clinical services available to veterans.

Clinical pharmacy specialists using SOPs take longer to complete medication reviews compared with those not using SOPs. Although the assessment was not designed to evaluate the reasons for these time differences, post-hoc follow-up clarification with individual sites determined CPS use of a SOP can lend to a more time-intensive and comprehensive medication review. This may lead to more optimized and safe medication regimens and elimination of unnecessary and/or inappropriate medications for HBPC veterans.

While only 35% of pharmacists were participating in the home visits at the time of this assessment, this is another area to explore as an opportunity to expand CMM. Although the assessment showed the majority of these home visits addressed medication education and adherence, programs may find it advantageous to provide CPS home visits for veterans identified as high risk or requiring specialized CMM. Additional data are needed regarding the ideal population to target for CPS home visits, as well as the estimated benefits of conducting home visits, such as outcomes and efficiency.

With growth noted in multiple programs, HBPC leadership should continue to encourage expanded pharmacist roles at an advanced practice level with SOPs, to provide veteran-centered care. This practice allows the team to concentrate efforts on patient acuity while increasing veteran access to VHA care. Additional CPS FTEEs are necessary to allow for expansion of the HBPC CPS role. The data also demonstrate HBPC often uses a part-time workforce where pharmacists are assigned to HBPC < 40 hours per week, and multiple pharmacists may be used to fulfill 1 CPS FTEE position. Home-Based Primary Care programs are encouraged to consolidate the number of CPSs involved as core individuals to promote continuity and avoid fragmented care.

Limitations

One limitation of the assessment is that the questions were designed and tested by a small group of CPSs, which may have led to response bias and potential misinterpretation of some questions. Time spent on medication reviews may have been underestimated, as some sites reported the maximum allowable workload credit time rather than actual time spent. Recall bias also is a limitation because the assessment relied on the recollection of the CPS or chief of pharmacy. Additionally, while the assessment focused on quantity and time spent on medication reviews, it was not designed to evaluate quality. Examination of what constitutes a high-quality medication review would be helpful to provide guidance and standardize care across the VHA.

Conclusion

Clinical pharmacy specialists practicing in the VHA HBPC setting are highly trained clinicians. A significant percentage of CPSs practice with a SOP that includes prescriptive privileges. However, variations in practice and function exist in the system. This presents an excellent opportunity for future standardization and promotion of the highest and best use of the CPS to improve quality of care for HBPC. With the expansion of the CPS role, there is potential for pharmacists to increase clinical activities and improve care for home-based veterans. The CPPO HBPC SME workgroup will continue to examine and explore the CPS role in this practice setting, develop staffing and practice guidance documents, and assess the benefit of CPS home visits.

Home-Based Primary Care (HBPC) is a unique interdisciplinary program within the Veteran’s Health Administration (VHA) that specifically targets veterans with complex, chronic disabling diseases who have difficulty traveling to a VHA facility.¹ Veterans are provided comprehensive longitudinal primary care in their homes, with the goal of maximizing the veteran’s independence. Clinical pharmacists are known as medication experts and have an essential role within interdisciplinary teams, including HBPC, improving medication safety, and decreasing inappropriate prescribing practices.^2,3 Clinical pharmacy specialists (CPSs) within the VHA work collaboratively but autonomously as advanced practice providers assisting with the pharmacologic management of many diseases and chronic conditions. The remainder of this article will refer to the HBPC pharmacist as a CPS.

The CPS is actively involved in providing comprehensive medication management (CMM) services across VHA and has the expertise to effectively assist veterans in achieving targeted clinical outcomes. While the value and role of CPSs in the primary care setting are described extensively in the literature, data regarding the CPS in HBPC are limited.^4-6 Therefore, the purpose of the assessment was to evaluate the status of the HBPC pharmacy workforce, identify current pharmacist activities and strong practices, and clarify national variations among programs. Future use of this analysis may assist with standardization of the HBPC CPS role and development of business rules in combination with a workload-based staffing model tool.

Background

The role of the pharmacist in the HBPC setting has evolved from providing basic medication therapy reviews to an advanced role providing CMM services under a VHA scope of practice (SOP), which outlines 8 functions that may be authorized, including medication prescriptive authority.⁷ The SOP may be disease specific (limited) but is increasingly transitioning to have a practice-area scope (global), which is consistent with other VHA advanced practice providers.⁷ Effective use of a CPS in this role allows for optimization of CMM and increasing veteran access to VHA care.

The VHA employed 7,285 pharmacists in 2014.⁸ Many were considered CPSs with prescriptive authority. These pharmacists were responsible for ordering more than 1.7 million distinct prescriptions across the VHA in fiscal year 2014, which represented 2.6% of the total prescriptions that year.⁷ A 2007 VHA study also demonstrated both an increase in appropriate prescribing practices and improved medication use when CPSs worked in collaboration with the HBPC team.⁹ With this evolution of VHA pharmacists, there has been an increase in the use of CPSs in HBPC and changes in staffing ratios to allow for additional clinical activities and comprehensive patient care provision.¹

The HBPC model serves a complex population in which each veteran has about 8 chronic conditions.^1,10 An interdisciplinary team consisting of various health care professionals, such as physicians, nurse practitioners, nurses, social workers, registered dietitians, psychologists, rehabilitation therapists, pharmacists, etc, work collaboratively to care for these veterans in the patient’s home. This team is a type of patient-centered medical home (PCMH) that focuses on providing primary care services to an at-risk veteran population who have difficulty leaving the home.¹ Home-based primary care has been shown to be cost-effective, reducing average annual cost of health care by up to 24%.¹⁰ Another study showed that patients using HBPC had a 27% reduction in hospital admissions and 69% reduction in inpatient hospital days when compared with patients who were not using HBPC.¹¹

The interdisciplinary team meets at least once weekly to discuss and design individualized care plans for veterans enrolled in the program. It is desirable for pharmacists on these teams to have special expertise and certification in geriatric pharmacotherapy and chronic disease management (eg, board-certified geriatric pharmacist [BCGP], board-certified pharmacotherapy specialist [BCPS], or board-certified ambulatory care pharmacist [BCACP]) due to the complexity of comorbidities of these veterans.¹² Additional education such as postgraduate pharmacy residency training also is beneficial for CPSs in this setting.

The CPS proactively performs CMM that is often greater in scope than a targeted disease review due to multiple comorbid conditions that are often present within veteran patients.¹ These comprehensive medication reviews are considered a core function and must be performed on enrollment in HBPC, quarterly, and when clinically indicated or requested by the team.¹³ Sufficient time must be allocated to the CPS in order to provide these high-quality medication reviews. Additional core functions of the CPS are outlined in the functional statement and/or SOP, but responsibilities include CMM and disease management. This typically consists of prescribing and/or adjusting medications, as well as providing patient and caregiver education, which can be performed either face-to-face or via telehealth visits (eg, telephone and video). A CPS also may make home visits to assess the veteran, either independently or with other disciplines of the HBPC team.

The HBPC Subject Matter Expert (SME) workgroup was chartered by the Veterans Affairs Central Office (VACO) Pharmacy Benefits Management Service (PBM) Clinical Pharmacy Practice Office (CPPO) to explore pharmacy practice changes in the HBPC setting. This workgroup serves as clinical practice leadership within the HBPC setting to provide expertise and lead initiatives supporting the advanced practice role of the HBPC CPS.

As HBPC programs expanded throughout VHA, it was paramount to determine the current state of HBPC pharmacy practice by collecting necessary data points to assess uniformity and better understand opportunities for practice standardization. The SME workgroup developed a voluntary yet comprehensive survey assessment that served to proactively assess the future of HBPC pharmacy.

 

Methods

The HBPC SME workgroup, in conjunction with CPPO, developed the assessment. Questions were designed and tested within a small group of CPSs and then distributed electronically. In August 2014, the assessment was e-mailed to all 21 VHA service areas with an active HBPC program, and responses were collected through a Microsoft SharePoint (Redmond, WA) survey. A response was requested from chiefs of pharmacy, clinical pharmacy leadership, or a representative.

This voluntary assessment contained 24 multipart questions related to background information of HBPC programs and clinical pharmacy services. Duplicate responses were consolidated and clarified with individual sites post hoc.

Descriptive statistics were used to analyze responses. To standardize the comparison across sites with a variety of full-time equivalent employees (FTEEs), the average patient census was divided by the CPS FTEE allocated to the programs at that site. For example, if a site reported 316 patients with 0.25 CPS FTEE, a standardized ratio for this site was 1,264 patients per FTEE. If a patient census range was reported, the median number would be used.

Results

The team received responses from 130 of 141 VHA facilities (92%), encompassing 270 CPSs. A total of 168.75 FTEEs were officially designated as HBPC CPSs. All 21 VHA service areas at the time were represented. The majority of responding programs (67%) had < 1 CPS FTEE allocated to HBPC; many of these CPSs were working in other pharmacy areas but were only dedicated to HBPC part-time. 

The remaining programs (33%) used 1 FTEE per CPS. The average patient census for each program was 245, ranging from 35 to 850 patients. Sixty-eight percent of sites had an average patient census > 151 per FTEE (Figure).

Nearly 90% of CPSs completed postgraduate year 1 residency training. Fifty-seven percent of CPSs held advanced certifications, such as BCGP, BCACP, or BCPS. Sixty-two percent of CPSs with these specialized board certifications had residency training. Use of a SOP was reported by 76% of CPSs, and 66% of these had a global practice-area scope. Table 1 outlines the functions authorized by a global or limited SOP.⁶ 

A higher percentage of those with global SOPs were authorized to perform physical assessment (69% vs 39%), order vaccines (57% vs 20%), and enter consults (75% vs 46%) compared with those with limited SOPs, respectively.

Overall, 52% of sites reported CPS involvement in CMM of primarily anticoagulation, diabetes mellitus (DM), anemia, hyperlipidemia, and hypertension. The reported average time spent for each disease encounter is delineated in Table 2. 

Those sites with CPSs who were not participating in disease management averaged a larger patient load compared with those who managed 4 of the 5 diseases (42.6% with 100-199 patients per pharmacist and 51.4% with 1-99 patients per pharmacist, respectively). Whether global or limited, 60% of CPSs reported using SOPs at least 25% of the time.

Thirty-five percent of sites reported CPS participation in home visits, and the majority of those completed between 1 and 10 home visits per month. The types of interventions provided often included medication education, assessment of medication adherence, and CMM for DM, hyperlipidemia, hypertension, etc. Multiple interventions often were made during each home visit.

The workload of medication reviews was divided among multiple CPSs in 55% of the programs. The majority of programs completed fewer than 20 initial medication reviews per month and between 21 and 80 quarterly medication reviews per month (81% and 62%, respectively). The average time for a CPS to complete initial medication reviews was 78 minutes and 42 minutes for quarterly medication reviews.

Sites with CPSs that held a SOP (76%) took an average of 83 minutes to complete an initial medication review and 48 minutes to complete a quarterly review. Sites with CPSs without a SOP (24%) took an average of 72 minutes to complete an initial medication review and 36 minutes to complete a quarterly review. Many CPSs allocate ≤ 20 hours per month on routine pharmacy functions (eg, prescription verification, dispensing activities, nonformulary medication requests) and ≤ 20 hours per month on nonpatient care activities (eg, education, medication use evaluations, training, projects), 67% and 82%, respectively.

Ninety-seven percent of CPSs actively attended weekly HBPC program interdisciplinary team (IDT) meetings, with 67% attending 1 weekly IDT meeting and 30% attending 2 to 5 weekly IDT meetings. Time spent attending IDT and roundtable discussions averaged 3.5 hours per week. Multiple programs noted growth within the 12 months preceding the survey, as 37 sites were granted approval for a total of 29.75 additional CPS FTEEs, and an additional 10 sites had a total of 9.25 FTEEs pending approval.

 

Discussion

Analysis of this assessment allowed the HBPC CPS SME workgroup to identify strong practices and variations in individual HBPC pharmacy programs. The majority of CPSs (66%) are using global, practice area-based SOPs, which allows more autonomy via direct patient care to veterans through CMM and home visits. This trend suggests the focus of the HBPC CPS role has expanded beyond traditional pharmacist activities. These global SOPs result in a higher yield of CPS functions, such as developing, documenting, and executing therapeutic plans and prescribing medications (Table 1). A higher percentage of CPSs with a practice area-based SOP were authorized to perform all 8 functions. Therefore, increased use of practice area-based SOPs and the expansion of the HBPC CPS role can support the team and increase clinical services available to veterans.

Clinical pharmacy specialists using SOPs take longer to complete medication reviews compared with those not using SOPs. Although the assessment was not designed to evaluate the reasons for these time differences, post-hoc follow-up clarification with individual sites determined CPS use of a SOP can lend to a more time-intensive and comprehensive medication review. This may lead to more optimized and safe medication regimens and elimination of unnecessary and/or inappropriate medications for HBPC veterans.

While only 35% of pharmacists were participating in the home visits at the time of this assessment, this is another area to explore as an opportunity to expand CMM. Although the assessment showed the majority of these home visits addressed medication education and adherence, programs may find it advantageous to provide CPS home visits for veterans identified as high risk or requiring specialized CMM. Additional data are needed regarding the ideal population to target for CPS home visits, as well as the estimated benefits of conducting home visits, such as outcomes and efficiency.

With growth noted in multiple programs, HBPC leadership should continue to encourage expanded pharmacist roles at an advanced practice level with SOPs, to provide veteran-centered care. This practice allows the team to concentrate efforts on patient acuity while increasing veteran access to VHA care. Additional CPS FTEEs are necessary to allow for expansion of the HBPC CPS role. The data also demonstrate HBPC often uses a part-time workforce where pharmacists are assigned to HBPC < 40 hours per week, and multiple pharmacists may be used to fulfill 1 CPS FTEE position. Home-Based Primary Care programs are encouraged to consolidate the number of CPSs involved as core individuals to promote continuity and avoid fragmented care.

Limitations

One limitation of the assessment is that the questions were designed and tested by a small group of CPSs, which may have led to response bias and potential misinterpretation of some questions. Time spent on medication reviews may have been underestimated, as some sites reported the maximum allowable workload credit time rather than actual time spent. Recall bias also is a limitation because the assessment relied on the recollection of the CPS or chief of pharmacy. Additionally, while the assessment focused on quantity and time spent on medication reviews, it was not designed to evaluate quality. Examination of what constitutes a high-quality medication review would be helpful to provide guidance and standardize care across the VHA.

Conclusion

Clinical pharmacy specialists practicing in the VHA HBPC setting are highly trained clinicians. A significant percentage of CPSs practice with a SOP that includes prescriptive privileges. However, variations in practice and function exist in the system. This presents an excellent opportunity for future standardization and promotion of the highest and best use of the CPS to improve quality of care for HBPC. With the expansion of the CPS role, there is potential for pharmacists to increase clinical activities and improve care for home-based veterans. The CPPO HBPC SME workgroup will continue to examine and explore the CPS role in this practice setting, develop staffing and practice guidance documents, and assess the benefit of CPS home visits.

 

BALTIMORE – An 8-year cohort study has found that patients with obstructive sleep apnea who are prone to worsening of hypoxemia at night have a heightened risk of developing metabolic syndrome, an investigator reported at the annual meeting of the Associated Professional Sleep Societies

“Considering that we have a very high prevalence of moderate to severe obstructive sleep apnea (OSA) in the general population, this is a very important finding because it indicates that we need some clinical options of treating OSA in those that have metabolic syndrome to decrease the risk of morbidity and mortality and cardiac events in these patients,” said Camila Hirotsu, PhD, of the Federal University of São Paulo (Brazil).

Dr. Hirotsu presented 8-year follow-up results of the EPISONO cohort, an observational prospective study conducted in Brazil, the goal of which was to evaluate the how OSA can impact the risk of developing metabolic syndrome (MetS) the general population. MetS is defined as a cluster of three or more cardiovascular metabolic components: low HDL levels, high glucose and triglycerides, hypertension and abdominal obesity. Dr. Hirotsu said that 50%-60% of MetS patients have OSA (PLoS One 2010;5:e12065).

The study enrolled 1,074 patients at baseline, closing enrollment in 2008, and obtained follow-up on 712, evaluated from July 2015 to April 2016. After exclusions, the study evaluated 476 patients who were free of MetS at baseline. Of those 476, 44% went on to develop MetS.

Median age of patients who developed MetS was 40.8 years vs. 36.1 for those who did not. Patients who developed MetS also had a higher body mass index, but were not obese: 26.9 kg/m² vs. 23.8 kg/m². Patients were evaluated by completing questionnaires, undergoing full polysomnography, and having clinical assessments.

Patients with moderate to severe OSA were found to have an odds ratio of 2.47 (P = .016) of developing incident MetS, Dr. Hirotsu said. Rates of moderate to severe OSA were 21.3% for the group that developed MetS vs. 9% for the non-MetS group, said Dr. Hirotsu.

The study determined that the following sleep changes were associated with incident MetS: apnea-hypopnea index (AHI) (OR 1.16); 3% oxygen desaturation index (ODI) (OR 1.24); and time with oxygen saturation by pulse oximeter (SpO2) less than 90% (OR 1.42).

 

“Moderate to severe OSA at baseline and worsening of nocturnal hyperemia from baseline to follow-up are really independent risk factors to increase the incidence of MetS in the general population,” Dr. Hirotsu said.

A secondary aim of the study was to evaluate the impact of MetS on the risk of developing OSA in the general population. “It seems that MetS is not really an independent risk factor for OSA.”

Dr. Hirotsu reported having no conflicts of interest.

 

 

BALTIMORE – An 8-year cohort study has found that patients with obstructive sleep apnea who are prone to worsening of hypoxemia at night have a heightened risk of developing metabolic syndrome, an investigator reported at the annual meeting of the Associated Professional Sleep Societies

“Considering that we have a very high prevalence of moderate to severe obstructive sleep apnea (OSA) in the general population, this is a very important finding because it indicates that we need some clinical options of treating OSA in those that have metabolic syndrome to decrease the risk of morbidity and mortality and cardiac events in these patients,” said Camila Hirotsu, PhD, of the Federal University of São Paulo (Brazil).

Dr. Hirotsu presented 8-year follow-up results of the EPISONO cohort, an observational prospective study conducted in Brazil, the goal of which was to evaluate the how OSA can impact the risk of developing metabolic syndrome (MetS) the general population. MetS is defined as a cluster of three or more cardiovascular metabolic components: low HDL levels, high glucose and triglycerides, hypertension and abdominal obesity. Dr. Hirotsu said that 50%-60% of MetS patients have OSA (PLoS One 2010;5:e12065).

The study enrolled 1,074 patients at baseline, closing enrollment in 2008, and obtained follow-up on 712, evaluated from July 2015 to April 2016. After exclusions, the study evaluated 476 patients who were free of MetS at baseline. Of those 476, 44% went on to develop MetS.

Median age of patients who developed MetS was 40.8 years vs. 36.1 for those who did not. Patients who developed MetS also had a higher body mass index, but were not obese: 26.9 kg/m² vs. 23.8 kg/m². Patients were evaluated by completing questionnaires, undergoing full polysomnography, and having clinical assessments.

Patients with moderate to severe OSA were found to have an odds ratio of 2.47 (P = .016) of developing incident MetS, Dr. Hirotsu said. Rates of moderate to severe OSA were 21.3% for the group that developed MetS vs. 9% for the non-MetS group, said Dr. Hirotsu.

The study determined that the following sleep changes were associated with incident MetS: apnea-hypopnea index (AHI) (OR 1.16); 3% oxygen desaturation index (ODI) (OR 1.24); and time with oxygen saturation by pulse oximeter (SpO2) less than 90% (OR 1.42).

 

“Moderate to severe OSA at baseline and worsening of nocturnal hyperemia from baseline to follow-up are really independent risk factors to increase the incidence of MetS in the general population,” Dr. Hirotsu said.

A secondary aim of the study was to evaluate the impact of MetS on the risk of developing OSA in the general population. “It seems that MetS is not really an independent risk factor for OSA.”

Dr. Hirotsu reported having no conflicts of interest.

 

 

BALTIMORE – An 8-year cohort study has found that patients with obstructive sleep apnea who are prone to worsening of hypoxemia at night have a heightened risk of developing metabolic syndrome, an investigator reported at the annual meeting of the Associated Professional Sleep Societies

“Considering that we have a very high prevalence of moderate to severe obstructive sleep apnea (OSA) in the general population, this is a very important finding because it indicates that we need some clinical options of treating OSA in those that have metabolic syndrome to decrease the risk of morbidity and mortality and cardiac events in these patients,” said Camila Hirotsu, PhD, of the Federal University of São Paulo (Brazil).

Dr. Hirotsu presented 8-year follow-up results of the EPISONO cohort, an observational prospective study conducted in Brazil, the goal of which was to evaluate the how OSA can impact the risk of developing metabolic syndrome (MetS) the general population. MetS is defined as a cluster of three or more cardiovascular metabolic components: low HDL levels, high glucose and triglycerides, hypertension and abdominal obesity. Dr. Hirotsu said that 50%-60% of MetS patients have OSA (PLoS One 2010;5:e12065).

The study enrolled 1,074 patients at baseline, closing enrollment in 2008, and obtained follow-up on 712, evaluated from July 2015 to April 2016. After exclusions, the study evaluated 476 patients who were free of MetS at baseline. Of those 476, 44% went on to develop MetS.

Median age of patients who developed MetS was 40.8 years vs. 36.1 for those who did not. Patients who developed MetS also had a higher body mass index, but were not obese: 26.9 kg/m² vs. 23.8 kg/m². Patients were evaluated by completing questionnaires, undergoing full polysomnography, and having clinical assessments.

Patients with moderate to severe OSA were found to have an odds ratio of 2.47 (P = .016) of developing incident MetS, Dr. Hirotsu said. Rates of moderate to severe OSA were 21.3% for the group that developed MetS vs. 9% for the non-MetS group, said Dr. Hirotsu.

The study determined that the following sleep changes were associated with incident MetS: apnea-hypopnea index (AHI) (OR 1.16); 3% oxygen desaturation index (ODI) (OR 1.24); and time with oxygen saturation by pulse oximeter (SpO2) less than 90% (OR 1.42).

 

“Moderate to severe OSA at baseline and worsening of nocturnal hyperemia from baseline to follow-up are really independent risk factors to increase the incidence of MetS in the general population,” Dr. Hirotsu said.

A secondary aim of the study was to evaluate the impact of MetS on the risk of developing OSA in the general population. “It seems that MetS is not really an independent risk factor for OSA.”

Dr. Hirotsu reported having no conflicts of interest.

 

 

BALTIMORE – Analysis of data from a national multicenter study of women’s health has found that middle-aged black women were at higher risk for sleep problems than their white counterparts, according to a presentation at the annual meeting of the Associated Sleep Societies.

“Race is emerging as a significant moderator in the relationship between sleep and health outcomes,” said Marissa Bowman, a doctoral student at the University of Pittsburgh. The study was based on 10- to 15-year follow-up data from the SWAN (Study of Women’s Health Across the Nation) sleep research. The researchers evaluated sleep in 265 midlife women, 45% of whom were black.

She noted that black women in the study were more likely to have poor sleep quality as assessed by Pittsburgh Sleep Quality Index, shorter sleep duration as assessed by polysomnography, longer periods of wakefulness after sleep onset, shorter sleep efficiency, and apnea-hypopnea index greater than 15. The study evaluated six factors of sleep quality: regularity, satisfaction, alertness, timing, efficiency, and duration.

At baseline, the study assessed sleep health using both actigraphy and a daily diary, along with body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHpR), then collected data on the anthropometric factors 10-15 years later.

Cross-sectional and prospective analyses found that sleep health was correlated with lower BMI but was not significantly associated with WC or WHpR. A prospective analysis found no overall significant correlation between sleep health and any of the three factors. But in a separate the analysis of the study group by race, all three anthropometric factors had a stronger link to sleep health in black women than in those of European descent, respectively, with beta coefficients of –0.14 vs. 0.1 for BMI, –0.17 and 0.1 for WC and –0.17 and 0.07 for WHpR.

“We need to explain this association and conceptualize how sleep health might be more strongly related with weight in African Americans,” Ms. Bowman said. “One possibility might be that sleep health reflects a health disparity. We can see how race is related to other health disparities, and this might be one of them.”

During questions, Ms. Bowman acknowledged that SWAN did not have data on what kind of access to health care the black women in the study had. “That might be a possible reason they’re not getting their sleep treated; they’re not getting other health factors treated,” she said.

Ms. Bowman and her coauthors reported no financial relationships. The study was funded by the National Institute on Aging, National Institutes of Health, and the National Institutes of Health Office of Research on Women’s Health.

 

BALTIMORE – Analysis of data from a national multicenter study of women’s health has found that middle-aged black women were at higher risk for sleep problems than their white counterparts, according to a presentation at the annual meeting of the Associated Sleep Societies.

“Race is emerging as a significant moderator in the relationship between sleep and health outcomes,” said Marissa Bowman, a doctoral student at the University of Pittsburgh. The study was based on 10- to 15-year follow-up data from the SWAN (Study of Women’s Health Across the Nation) sleep research. The researchers evaluated sleep in 265 midlife women, 45% of whom were black.

She noted that black women in the study were more likely to have poor sleep quality as assessed by Pittsburgh Sleep Quality Index, shorter sleep duration as assessed by polysomnography, longer periods of wakefulness after sleep onset, shorter sleep efficiency, and apnea-hypopnea index greater than 15. The study evaluated six factors of sleep quality: regularity, satisfaction, alertness, timing, efficiency, and duration.

At baseline, the study assessed sleep health using both actigraphy and a daily diary, along with body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHpR), then collected data on the anthropometric factors 10-15 years later.

Cross-sectional and prospective analyses found that sleep health was correlated with lower BMI but was not significantly associated with WC or WHpR. A prospective analysis found no overall significant correlation between sleep health and any of the three factors. But in a separate the analysis of the study group by race, all three anthropometric factors had a stronger link to sleep health in black women than in those of European descent, respectively, with beta coefficients of –0.14 vs. 0.1 for BMI, –0.17 and 0.1 for WC and –0.17 and 0.07 for WHpR.

“We need to explain this association and conceptualize how sleep health might be more strongly related with weight in African Americans,” Ms. Bowman said. “One possibility might be that sleep health reflects a health disparity. We can see how race is related to other health disparities, and this might be one of them.”

During questions, Ms. Bowman acknowledged that SWAN did not have data on what kind of access to health care the black women in the study had. “That might be a possible reason they’re not getting their sleep treated; they’re not getting other health factors treated,” she said.

Ms. Bowman and her coauthors reported no financial relationships. The study was funded by the National Institute on Aging, National Institutes of Health, and the National Institutes of Health Office of Research on Women’s Health.

 

BALTIMORE – Analysis of data from a national multicenter study of women’s health has found that middle-aged black women were at higher risk for sleep problems than their white counterparts, according to a presentation at the annual meeting of the Associated Sleep Societies.

“Race is emerging as a significant moderator in the relationship between sleep and health outcomes,” said Marissa Bowman, a doctoral student at the University of Pittsburgh. The study was based on 10- to 15-year follow-up data from the SWAN (Study of Women’s Health Across the Nation) sleep research. The researchers evaluated sleep in 265 midlife women, 45% of whom were black.

She noted that black women in the study were more likely to have poor sleep quality as assessed by Pittsburgh Sleep Quality Index, shorter sleep duration as assessed by polysomnography, longer periods of wakefulness after sleep onset, shorter sleep efficiency, and apnea-hypopnea index greater than 15. The study evaluated six factors of sleep quality: regularity, satisfaction, alertness, timing, efficiency, and duration.

At baseline, the study assessed sleep health using both actigraphy and a daily diary, along with body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHpR), then collected data on the anthropometric factors 10-15 years later.

Cross-sectional and prospective analyses found that sleep health was correlated with lower BMI but was not significantly associated with WC or WHpR. A prospective analysis found no overall significant correlation between sleep health and any of the three factors. But in a separate the analysis of the study group by race, all three anthropometric factors had a stronger link to sleep health in black women than in those of European descent, respectively, with beta coefficients of –0.14 vs. 0.1 for BMI, –0.17 and 0.1 for WC and –0.17 and 0.07 for WHpR.

“We need to explain this association and conceptualize how sleep health might be more strongly related with weight in African Americans,” Ms. Bowman said. “One possibility might be that sleep health reflects a health disparity. We can see how race is related to other health disparities, and this might be one of them.”

During questions, Ms. Bowman acknowledged that SWAN did not have data on what kind of access to health care the black women in the study had. “That might be a possible reason they’re not getting their sleep treated; they’re not getting other health factors treated,” she said.

Ms. Bowman and her coauthors reported no financial relationships. The study was funded by the National Institute on Aging, National Institutes of Health, and the National Institutes of Health Office of Research on Women’s Health.

 

BALTIMORE – Although the national trend of legalization of marijuana for medical and recreational uses has accelerated, physicians should be cautious about prescribing medical marijuana to treat sleep disorders, a sleep specialist told attendees at the annual meeting of the Associated Professional Sleep Societies.

“Increased legalization of medical marijuana may cause reduction in perception of the risk of potential harm” said Ashima Sahni, MD, of Northwestern University, Chicago.

Doug Menuez/thinkstock

She noted the long-term implications of marijuana use have been documented, including decreased cognition, lack of motivation, and psychotic effects. Marijuana also appears to affect sleep, although most studies were done in the 1970s and showed mixed results, she said.

“Overall the consensus is that the short-term use of medical marijuana causes an increase in slow-wave sleep (SWS), a decrease in sleep onset latency, a decrease in wake after sleep onset (WASO) and a decrease in REM sleep,” Dr. Sahni said. But chronic use decreases SWS and results in inconsistencies in REM sleep patterns and sleep fragmentation. These changes lead to a self-perpetuating negative cycle that causes chronic users to progressively increase their intake, furthering sleep disruption, she noted.

Marijuana withdrawal also can cause significant disturbances in sleep patterns, including reduced total sleep time and SWS, increased WASO, increased REM sleep associated with strange dreams, and increased limb movements during sleep, Dr. Sahni said. “The effects can be seen as early as 24 hours after discontinuation and can last as long as 6 weeks,” she said. In addition, poor sleep quality prior to a withdrawal attempt has been linked to relapse (Am J Psychiatry. 2004;161:1967-77).

The use of medical marijuana in the management of sleep disorders is fraught with controversy, Dr. Sahni said. She reviewed studies investigating the use of dronabinol for obstructive sleep apnea (OSA). “This is not medical marijuana,” Dr. Sahni said. “It’s a synthetic tetrahydrocannabinol (THC) cannabinoid, which acts on the nonselective CB1 and CB2 agonists,” she said. THC is the euphoria-inducing compound in marijuana. While the mechanism of action of dronabinol is similar to marijuana, the pharmacokinetics may differ. Dronabinol has been approved by the Food and Drug Administration for cancer-related nausea and appetite stimulation in AIDS patients. She referred to a proof-of-concept study of 17 patients with OSA in which dronabinol reduced the apnea-hypopnea index (AHI) with no degradation of sleep architecture or serious adverse events (Front Psychiatry. 2013 Jan 22;4:1-5). Dr. Sahni also noted a randomized, placebo-controlled trial of 73 patients that reported an average reduction in AHI of 12.9 (Sleep. 2018 Jan 1;41[1]; doi: 10.1093/sleep/zsx184). But she pointed out that the American Academy of Sleep Medicine does not recommend medical cannabis or its synthetic extracts for treatment of OSA (J Clin Sleep Med. 2018 Apr 15;14:679-81).

Insomnia, on the other hand, represents the most common use of medical marijuana for sleep. “Studies have shown mixed results because of differences in the ratios of THC to CBD [corticobasal degeneration] in the forms of marijuana examined,” she said. “In the short term, subjective sleepiness is reported to be better, but then the self-perpetuating negative cycle initiates with chronic long-term use.”

 

In treatment of nightmares and posttraumatic stress syndrome, Dr. Sahni cited studies that found “good effects” of medical marijuana use (CNS Neurosci Ther. 2009;15:84-8; J Clin Psychopharmacol. 2014 Oct;34:559-64). For REM behavior disorder, medical marijuana was found to be beneficial in four patients with Parkinson disease (J Clin Pharm Ther. 2014 Oct;39:564-6). In poorly treated restless leg syndrome, medical marijuana was reported to be beneficial (Sleep Med. 2017 Aug;36:182-3).

“It should be noted that these were very small studies and therefore more research is needed before we change our medical practices toward various sleep disorders,” Dr. Sahni said.

Dr. Sahni and her coauthors reported having no financial relationships to disclose.

 

BALTIMORE – Although the national trend of legalization of marijuana for medical and recreational uses has accelerated, physicians should be cautious about prescribing medical marijuana to treat sleep disorders, a sleep specialist told attendees at the annual meeting of the Associated Professional Sleep Societies.

“Increased legalization of medical marijuana may cause reduction in perception of the risk of potential harm” said Ashima Sahni, MD, of Northwestern University, Chicago.

Doug Menuez/thinkstock

She noted the long-term implications of marijuana use have been documented, including decreased cognition, lack of motivation, and psychotic effects. Marijuana also appears to affect sleep, although most studies were done in the 1970s and showed mixed results, she said.

“Overall the consensus is that the short-term use of medical marijuana causes an increase in slow-wave sleep (SWS), a decrease in sleep onset latency, a decrease in wake after sleep onset (WASO) and a decrease in REM sleep,” Dr. Sahni said. But chronic use decreases SWS and results in inconsistencies in REM sleep patterns and sleep fragmentation. These changes lead to a self-perpetuating negative cycle that causes chronic users to progressively increase their intake, furthering sleep disruption, she noted.

Marijuana withdrawal also can cause significant disturbances in sleep patterns, including reduced total sleep time and SWS, increased WASO, increased REM sleep associated with strange dreams, and increased limb movements during sleep, Dr. Sahni said. “The effects can be seen as early as 24 hours after discontinuation and can last as long as 6 weeks,” she said. In addition, poor sleep quality prior to a withdrawal attempt has been linked to relapse (Am J Psychiatry. 2004;161:1967-77).

The use of medical marijuana in the management of sleep disorders is fraught with controversy, Dr. Sahni said. She reviewed studies investigating the use of dronabinol for obstructive sleep apnea (OSA). “This is not medical marijuana,” Dr. Sahni said. “It’s a synthetic tetrahydrocannabinol (THC) cannabinoid, which acts on the nonselective CB1 and CB2 agonists,” she said. THC is the euphoria-inducing compound in marijuana. While the mechanism of action of dronabinol is similar to marijuana, the pharmacokinetics may differ. Dronabinol has been approved by the Food and Drug Administration for cancer-related nausea and appetite stimulation in AIDS patients. She referred to a proof-of-concept study of 17 patients with OSA in which dronabinol reduced the apnea-hypopnea index (AHI) with no degradation of sleep architecture or serious adverse events (Front Psychiatry. 2013 Jan 22;4:1-5). Dr. Sahni also noted a randomized, placebo-controlled trial of 73 patients that reported an average reduction in AHI of 12.9 (Sleep. 2018 Jan 1;41[1]; doi: 10.1093/sleep/zsx184). But she pointed out that the American Academy of Sleep Medicine does not recommend medical cannabis or its synthetic extracts for treatment of OSA (J Clin Sleep Med. 2018 Apr 15;14:679-81).

Insomnia, on the other hand, represents the most common use of medical marijuana for sleep. “Studies have shown mixed results because of differences in the ratios of THC to CBD [corticobasal degeneration] in the forms of marijuana examined,” she said. “In the short term, subjective sleepiness is reported to be better, but then the self-perpetuating negative cycle initiates with chronic long-term use.”

 

In treatment of nightmares and posttraumatic stress syndrome, Dr. Sahni cited studies that found “good effects” of medical marijuana use (CNS Neurosci Ther. 2009;15:84-8; J Clin Psychopharmacol. 2014 Oct;34:559-64). For REM behavior disorder, medical marijuana was found to be beneficial in four patients with Parkinson disease (J Clin Pharm Ther. 2014 Oct;39:564-6). In poorly treated restless leg syndrome, medical marijuana was reported to be beneficial (Sleep Med. 2017 Aug;36:182-3).

“It should be noted that these were very small studies and therefore more research is needed before we change our medical practices toward various sleep disorders,” Dr. Sahni said.

Dr. Sahni and her coauthors reported having no financial relationships to disclose.

 

BALTIMORE – Although the national trend of legalization of marijuana for medical and recreational uses has accelerated, physicians should be cautious about prescribing medical marijuana to treat sleep disorders, a sleep specialist told attendees at the annual meeting of the Associated Professional Sleep Societies.

“Increased legalization of medical marijuana may cause reduction in perception of the risk of potential harm” said Ashima Sahni, MD, of Northwestern University, Chicago.

Doug Menuez/thinkstock

She noted the long-term implications of marijuana use have been documented, including decreased cognition, lack of motivation, and psychotic effects. Marijuana also appears to affect sleep, although most studies were done in the 1970s and showed mixed results, she said.

“Overall the consensus is that the short-term use of medical marijuana causes an increase in slow-wave sleep (SWS), a decrease in sleep onset latency, a decrease in wake after sleep onset (WASO) and a decrease in REM sleep,” Dr. Sahni said. But chronic use decreases SWS and results in inconsistencies in REM sleep patterns and sleep fragmentation. These changes lead to a self-perpetuating negative cycle that causes chronic users to progressively increase their intake, furthering sleep disruption, she noted.

Marijuana withdrawal also can cause significant disturbances in sleep patterns, including reduced total sleep time and SWS, increased WASO, increased REM sleep associated with strange dreams, and increased limb movements during sleep, Dr. Sahni said. “The effects can be seen as early as 24 hours after discontinuation and can last as long as 6 weeks,” she said. In addition, poor sleep quality prior to a withdrawal attempt has been linked to relapse (Am J Psychiatry. 2004;161:1967-77).

The use of medical marijuana in the management of sleep disorders is fraught with controversy, Dr. Sahni said. She reviewed studies investigating the use of dronabinol for obstructive sleep apnea (OSA). “This is not medical marijuana,” Dr. Sahni said. “It’s a synthetic tetrahydrocannabinol (THC) cannabinoid, which acts on the nonselective CB1 and CB2 agonists,” she said. THC is the euphoria-inducing compound in marijuana. While the mechanism of action of dronabinol is similar to marijuana, the pharmacokinetics may differ. Dronabinol has been approved by the Food and Drug Administration for cancer-related nausea and appetite stimulation in AIDS patients. She referred to a proof-of-concept study of 17 patients with OSA in which dronabinol reduced the apnea-hypopnea index (AHI) with no degradation of sleep architecture or serious adverse events (Front Psychiatry. 2013 Jan 22;4:1-5). Dr. Sahni also noted a randomized, placebo-controlled trial of 73 patients that reported an average reduction in AHI of 12.9 (Sleep. 2018 Jan 1;41[1]; doi: 10.1093/sleep/zsx184). But she pointed out that the American Academy of Sleep Medicine does not recommend medical cannabis or its synthetic extracts for treatment of OSA (J Clin Sleep Med. 2018 Apr 15;14:679-81).

Insomnia, on the other hand, represents the most common use of medical marijuana for sleep. “Studies have shown mixed results because of differences in the ratios of THC to CBD [corticobasal degeneration] in the forms of marijuana examined,” she said. “In the short term, subjective sleepiness is reported to be better, but then the self-perpetuating negative cycle initiates with chronic long-term use.”

 

In treatment of nightmares and posttraumatic stress syndrome, Dr. Sahni cited studies that found “good effects” of medical marijuana use (CNS Neurosci Ther. 2009;15:84-8; J Clin Psychopharmacol. 2014 Oct;34:559-64). For REM behavior disorder, medical marijuana was found to be beneficial in four patients with Parkinson disease (J Clin Pharm Ther. 2014 Oct;39:564-6). In poorly treated restless leg syndrome, medical marijuana was reported to be beneficial (Sleep Med. 2017 Aug;36:182-3).

“It should be noted that these were very small studies and therefore more research is needed before we change our medical practices toward various sleep disorders,” Dr. Sahni said.

Dr. Sahni and her coauthors reported having no financial relationships to disclose.

 

Venetoclax (Venclexta) has received regular approval from the Food and Drug Administration for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.

The approval was based results from the MURANO trial of 389 patients, which was a randomized, multicenter, open-label trial of venetoclax plus rituximab versus bendamustine plus rituximab.

Efficacy in this trial was based on progression-free survival. After a median follow-up of 23 months, the median progression-free survival had not been reached in the venetoclax arm, while it was 18.1 months in the bendamustine arm (hazard ratio, 0.19; 95% confidence interval, 0.13-0.28; P less than .0001). The venetoclax arm had an overall response rate of 92%, compared with 72% in the bendamustine arm.

Neutropenia, diarrhea, upper respiratory tract infection, fatigue, cough, and nausea were the most common adverse events seen in the venetoclax arm. Grade 3 or 4 neutropenia developed in 64% of those patients, and grade 4 in 31%. The most common infection in venetoclax patients was pneumonia, but overall, 21% of patients in that arm experienced some kind of infection.

Because of the rapid reduction in tumor size, tumor lysis syndrome is possible with venetoclax treatment, the FDA noted.

In 2016, the FDA granted accelerated approval to venetoclax for treatment of patients with CLL with 17d deletion who had received at least one prior line of therapy.

cpalmer@mdedge.com

 

Venetoclax (Venclexta) has received regular approval from the Food and Drug Administration for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.

The approval was based results from the MURANO trial of 389 patients, which was a randomized, multicenter, open-label trial of venetoclax plus rituximab versus bendamustine plus rituximab.

Efficacy in this trial was based on progression-free survival. After a median follow-up of 23 months, the median progression-free survival had not been reached in the venetoclax arm, while it was 18.1 months in the bendamustine arm (hazard ratio, 0.19; 95% confidence interval, 0.13-0.28; P less than .0001). The venetoclax arm had an overall response rate of 92%, compared with 72% in the bendamustine arm.

Neutropenia, diarrhea, upper respiratory tract infection, fatigue, cough, and nausea were the most common adverse events seen in the venetoclax arm. Grade 3 or 4 neutropenia developed in 64% of those patients, and grade 4 in 31%. The most common infection in venetoclax patients was pneumonia, but overall, 21% of patients in that arm experienced some kind of infection.

Because of the rapid reduction in tumor size, tumor lysis syndrome is possible with venetoclax treatment, the FDA noted.

In 2016, the FDA granted accelerated approval to venetoclax for treatment of patients with CLL with 17d deletion who had received at least one prior line of therapy.

cpalmer@mdedge.com

 

Venetoclax (Venclexta) has received regular approval from the Food and Drug Administration for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.

The approval was based results from the MURANO trial of 389 patients, which was a randomized, multicenter, open-label trial of venetoclax plus rituximab versus bendamustine plus rituximab.

Efficacy in this trial was based on progression-free survival. After a median follow-up of 23 months, the median progression-free survival had not been reached in the venetoclax arm, while it was 18.1 months in the bendamustine arm (hazard ratio, 0.19; 95% confidence interval, 0.13-0.28; P less than .0001). The venetoclax arm had an overall response rate of 92%, compared with 72% in the bendamustine arm.

Neutropenia, diarrhea, upper respiratory tract infection, fatigue, cough, and nausea were the most common adverse events seen in the venetoclax arm. Grade 3 or 4 neutropenia developed in 64% of those patients, and grade 4 in 31%. The most common infection in venetoclax patients was pneumonia, but overall, 21% of patients in that arm experienced some kind of infection.

Because of the rapid reduction in tumor size, tumor lysis syndrome is possible with venetoclax treatment, the FDA noted.

In 2016, the FDA granted accelerated approval to venetoclax for treatment of patients with CLL with 17d deletion who had received at least one prior line of therapy.

cpalmer@mdedge.com

Click Here to Read Content 

In this supplement to The Hospitalist, Dr. Hameed Ali discusses HE and the importance of identifying and properly managing this common complication of cirrhosis.

Topics include:

• The various stages of HE
• The burden of HE and hospital readmission rates
• A medication for overt HE management

 

About the Author:
Hameed Q. Ali, DO, FHM
Clinical Assistant Professor
Department of Internal Medicine
Texas A&M Health Science Center
Temple, TX

Click Here to Read Content

 

XIF.0097.USA.18

 

Click Here to Read Content 

In this supplement to The Hospitalist, Dr. Hameed Ali discusses HE and the importance of identifying and properly managing this common complication of cirrhosis.

Topics include:

• The various stages of HE
• The burden of HE and hospital readmission rates
• A medication for overt HE management

 

About the Author:
Hameed Q. Ali, DO, FHM
Clinical Assistant Professor
Department of Internal Medicine
Texas A&M Health Science Center
Temple, TX

Click Here to Read Content

 

XIF.0097.USA.18

 

Click Here to Read Content 

In this supplement to The Hospitalist, Dr. Hameed Ali discusses HE and the importance of identifying and properly managing this common complication of cirrhosis.

Topics include:

• The various stages of HE
• The burden of HE and hospital readmission rates
• A medication for overt HE management

 

About the Author:
Hameed Q. Ali, DO, FHM
Clinical Assistant Professor
Department of Internal Medicine
Texas A&M Health Science Center
Temple, TX

Click Here to Read Content

 

XIF.0097.USA.18

 

 

CHICAGO – The combination of ibrutinib plus venetoclax yielded a high rate of undetectable minimal residual disease (MRD) when used as first-line treatment for chronic lymphocytic leukemia (CLL), according to preliminary results of the CAPTIVATE trial.

Of the first 30 patients in the trial, 23 (77%) had undetectable blood MRD after just six cycles of combined treatment, said investigator William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston.

Also, of the 14 patients completing 12 cycles of the combination, 12 (86%) had undetectable bone marrow MRD, including all complete responders and most of the partial responders.

“These early results show a highly active and safe treatment with 12 cycles of combined treatment with ibrutinib and venetoclax,” Dr. Wierda said in a presentation of the CAPTIVATE results at the annual meeting of the American Society of Clinical Oncology.

Those MRD results are “at least as good as we can achieve with chemoimmunotherapy,” Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington, said during a discussion of the CAPTIVATE study results.

Dr. Cheson referenced MRD results from a 2016 analysis of the CLL8 and CLL10 trials, which included patients treated with fludarabine, cyclophosphamide, and rituximab (FCR) and bendamustine plus rituximab (BR). In that analysis, 33.6% of patients achieved MRD-negative complete response and 29.1% achieved MRD-negative partial response.

In CAPTIVATE, by contrast, all of the complete remissions were MRD negative, as were a majority of the partial responders, Dr. Cheson noted.

 

Venetoclax and ibrutinib have “clinically complimentary activity” that provided a rationale for combining the two, Dr. Wierda said at ASCO. Ibrutinib is a BTK inhibitor that has a high rate of response and durable disease control, though continuous treatment is indicated, he said, because most patients achieve partial remissions as best response and continue to have residual disease in blood or bone marrow. Venetoclax, he added, is a BCL-2 inhibitor that produces durable partial remissions, though “residual disease is typically present in the form of persistently enlarged lymph nodes,” he said. “Venetoclax is highly effective at clearing disease from blood and bone marrow.”

The phase 2 CAPTIVATE trial includes a total of 164 patients younger than 70 years of age who receive a 3-cycle ibrutinib lead-in, followed by ibrutinib plus venetoclax for 12 cycles. At that point, patients are randomized according to MRD status. Patients with confirmed undetectable MRD are randomized to further treatment with ibrutinib or placebo, and those with undetectable MRD not confirmed are randomized to ibrutinib versus ibrutinib plus venetoclax.

In addition to early efficacy data, Dr. Wierda also reported some safety data. Compared with the single-agent ibrutinib lead-in period, combined ibrutinib plus venetoclax treatment had more gastrointestinal-associated events and neutropenia. Almost half of patients (45%) have had a treatment-related grade 3-4 adverse event, though just 18 (11%) have had treatment-related adverse events classified as serious, and there have been no adverse event-related deaths on study.

The high activity of ibrutinib plus venetoclax in CAPTIVATE supports further study of the combination, Dr. Wierda said. A randomized, open-label phase 3 trial of ibrutinib plus venetoclax versus chlorambucil plus obinutuzumab as first-line treatment for CLL is currently recruiting.

The study was sponsored by Pharmacyclics, an AbbVie company. Dr. Wierda reported consulting and research funding from Pharmacyclics, AbbVie, and several other companies.

SOURCE: Wierda WG et al. ASCO 2018, Abstract 7502.

 

CHICAGO – The combination of ibrutinib plus venetoclax yielded a high rate of undetectable minimal residual disease (MRD) when used as first-line treatment for chronic lymphocytic leukemia (CLL), according to preliminary results of the CAPTIVATE trial.

Of the first 30 patients in the trial, 23 (77%) had undetectable blood MRD after just six cycles of combined treatment, said investigator William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston.

Also, of the 14 patients completing 12 cycles of the combination, 12 (86%) had undetectable bone marrow MRD, including all complete responders and most of the partial responders.

“These early results show a highly active and safe treatment with 12 cycles of combined treatment with ibrutinib and venetoclax,” Dr. Wierda said in a presentation of the CAPTIVATE results at the annual meeting of the American Society of Clinical Oncology.

Those MRD results are “at least as good as we can achieve with chemoimmunotherapy,” Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington, said during a discussion of the CAPTIVATE study results.

Dr. Cheson referenced MRD results from a 2016 analysis of the CLL8 and CLL10 trials, which included patients treated with fludarabine, cyclophosphamide, and rituximab (FCR) and bendamustine plus rituximab (BR). In that analysis, 33.6% of patients achieved MRD-negative complete response and 29.1% achieved MRD-negative partial response.

In CAPTIVATE, by contrast, all of the complete remissions were MRD negative, as were a majority of the partial responders, Dr. Cheson noted.

 

Venetoclax and ibrutinib have “clinically complimentary activity” that provided a rationale for combining the two, Dr. Wierda said at ASCO. Ibrutinib is a BTK inhibitor that has a high rate of response and durable disease control, though continuous treatment is indicated, he said, because most patients achieve partial remissions as best response and continue to have residual disease in blood or bone marrow. Venetoclax, he added, is a BCL-2 inhibitor that produces durable partial remissions, though “residual disease is typically present in the form of persistently enlarged lymph nodes,” he said. “Venetoclax is highly effective at clearing disease from blood and bone marrow.”

The phase 2 CAPTIVATE trial includes a total of 164 patients younger than 70 years of age who receive a 3-cycle ibrutinib lead-in, followed by ibrutinib plus venetoclax for 12 cycles. At that point, patients are randomized according to MRD status. Patients with confirmed undetectable MRD are randomized to further treatment with ibrutinib or placebo, and those with undetectable MRD not confirmed are randomized to ibrutinib versus ibrutinib plus venetoclax.

In addition to early efficacy data, Dr. Wierda also reported some safety data. Compared with the single-agent ibrutinib lead-in period, combined ibrutinib plus venetoclax treatment had more gastrointestinal-associated events and neutropenia. Almost half of patients (45%) have had a treatment-related grade 3-4 adverse event, though just 18 (11%) have had treatment-related adverse events classified as serious, and there have been no adverse event-related deaths on study.

The high activity of ibrutinib plus venetoclax in CAPTIVATE supports further study of the combination, Dr. Wierda said. A randomized, open-label phase 3 trial of ibrutinib plus venetoclax versus chlorambucil plus obinutuzumab as first-line treatment for CLL is currently recruiting.

The study was sponsored by Pharmacyclics, an AbbVie company. Dr. Wierda reported consulting and research funding from Pharmacyclics, AbbVie, and several other companies.

SOURCE: Wierda WG et al. ASCO 2018, Abstract 7502.

 

CHICAGO – The combination of ibrutinib plus venetoclax yielded a high rate of undetectable minimal residual disease (MRD) when used as first-line treatment for chronic lymphocytic leukemia (CLL), according to preliminary results of the CAPTIVATE trial.

Of the first 30 patients in the trial, 23 (77%) had undetectable blood MRD after just six cycles of combined treatment, said investigator William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston.

Also, of the 14 patients completing 12 cycles of the combination, 12 (86%) had undetectable bone marrow MRD, including all complete responders and most of the partial responders.

“These early results show a highly active and safe treatment with 12 cycles of combined treatment with ibrutinib and venetoclax,” Dr. Wierda said in a presentation of the CAPTIVATE results at the annual meeting of the American Society of Clinical Oncology.

Those MRD results are “at least as good as we can achieve with chemoimmunotherapy,” Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington, said during a discussion of the CAPTIVATE study results.

Dr. Cheson referenced MRD results from a 2016 analysis of the CLL8 and CLL10 trials, which included patients treated with fludarabine, cyclophosphamide, and rituximab (FCR) and bendamustine plus rituximab (BR). In that analysis, 33.6% of patients achieved MRD-negative complete response and 29.1% achieved MRD-negative partial response.

In CAPTIVATE, by contrast, all of the complete remissions were MRD negative, as were a majority of the partial responders, Dr. Cheson noted.

 

Venetoclax and ibrutinib have “clinically complimentary activity” that provided a rationale for combining the two, Dr. Wierda said at ASCO. Ibrutinib is a BTK inhibitor that has a high rate of response and durable disease control, though continuous treatment is indicated, he said, because most patients achieve partial remissions as best response and continue to have residual disease in blood or bone marrow. Venetoclax, he added, is a BCL-2 inhibitor that produces durable partial remissions, though “residual disease is typically present in the form of persistently enlarged lymph nodes,” he said. “Venetoclax is highly effective at clearing disease from blood and bone marrow.”

The phase 2 CAPTIVATE trial includes a total of 164 patients younger than 70 years of age who receive a 3-cycle ibrutinib lead-in, followed by ibrutinib plus venetoclax for 12 cycles. At that point, patients are randomized according to MRD status. Patients with confirmed undetectable MRD are randomized to further treatment with ibrutinib or placebo, and those with undetectable MRD not confirmed are randomized to ibrutinib versus ibrutinib plus venetoclax.

In addition to early efficacy data, Dr. Wierda also reported some safety data. Compared with the single-agent ibrutinib lead-in period, combined ibrutinib plus venetoclax treatment had more gastrointestinal-associated events and neutropenia. Almost half of patients (45%) have had a treatment-related grade 3-4 adverse event, though just 18 (11%) have had treatment-related adverse events classified as serious, and there have been no adverse event-related deaths on study.

The high activity of ibrutinib plus venetoclax in CAPTIVATE supports further study of the combination, Dr. Wierda said. A randomized, open-label phase 3 trial of ibrutinib plus venetoclax versus chlorambucil plus obinutuzumab as first-line treatment for CLL is currently recruiting.

The study was sponsored by Pharmacyclics, an AbbVie company. Dr. Wierda reported consulting and research funding from Pharmacyclics, AbbVie, and several other companies.

SOURCE: Wierda WG et al. ASCO 2018, Abstract 7502.

 

Physicians who treat obstructive sleep apnea reported that patients with OSA can experience excessive sleepiness despite being on optimized airway treatment, findings from an online surgery of clinicians show.

Jazz Pharmaceuticals and the social media network Sermo conducted an online questionnaire on topics in excessive sleepiness and obstructive sleep apnea. The study was conducted March 30-31, 2018.

Of the 476 neurologists, pulmonologists, and psychiatrists who responded, 81% said that patients could experience excessive sleepiness even when their airway treatment has been optimized. That 81% was then asked what percentage of their patients with OSA experienced such symptoms. Almost one-third of respondents said that 16%-30% of their patients experience excessive sleepiness on optimized airway treatment, which works out to about 30% of neurologists, 40% of pulmonologists, and 23% of psychiatrists, Jazz reported.

When asked how often they assess their OSA patients’ sleepiness, 46% of respondents said every 3 months, 28% said every 6 months, 19% said once a month, 6% said once a year, and 0.4% (one neurologist and one pulmonologist) said never. The method of evaluation varied by specialty: 82% of pulmonologists most often use the Epworth Sleepiness Scale and 76% of psychiatrists primarily use an informal set of questions, with neurologists in between but leaning toward informal questions, Jazz reported.

“As more scientific evidence emerges around the neuronal injury occurring due to OSA and the potential neurocognitive effects of excessive sleepiness, it’s imperative that pulmonologists, neurologists and psychiatrists understand the impact ES [excessive sleepiness] can have on patients’ lives,” Richard K. Bogan, MD, of the University of South Carolina, Columbia, a paid consultant to Jazz, said in a written statement.
 

rfranki@mdedge.com

 

Physicians who treat obstructive sleep apnea reported that patients with OSA can experience excessive sleepiness despite being on optimized airway treatment, findings from an online surgery of clinicians show.

Jazz Pharmaceuticals and the social media network Sermo conducted an online questionnaire on topics in excessive sleepiness and obstructive sleep apnea. The study was conducted March 30-31, 2018.

Of the 476 neurologists, pulmonologists, and psychiatrists who responded, 81% said that patients could experience excessive sleepiness even when their airway treatment has been optimized. That 81% was then asked what percentage of their patients with OSA experienced such symptoms. Almost one-third of respondents said that 16%-30% of their patients experience excessive sleepiness on optimized airway treatment, which works out to about 30% of neurologists, 40% of pulmonologists, and 23% of psychiatrists, Jazz reported.

When asked how often they assess their OSA patients’ sleepiness, 46% of respondents said every 3 months, 28% said every 6 months, 19% said once a month, 6% said once a year, and 0.4% (one neurologist and one pulmonologist) said never. The method of evaluation varied by specialty: 82% of pulmonologists most often use the Epworth Sleepiness Scale and 76% of psychiatrists primarily use an informal set of questions, with neurologists in between but leaning toward informal questions, Jazz reported.

“As more scientific evidence emerges around the neuronal injury occurring due to OSA and the potential neurocognitive effects of excessive sleepiness, it’s imperative that pulmonologists, neurologists and psychiatrists understand the impact ES [excessive sleepiness] can have on patients’ lives,” Richard K. Bogan, MD, of the University of South Carolina, Columbia, a paid consultant to Jazz, said in a written statement.
 

rfranki@mdedge.com

 

Physicians who treat obstructive sleep apnea reported that patients with OSA can experience excessive sleepiness despite being on optimized airway treatment, findings from an online surgery of clinicians show.

Jazz Pharmaceuticals and the social media network Sermo conducted an online questionnaire on topics in excessive sleepiness and obstructive sleep apnea. The study was conducted March 30-31, 2018.

Of the 476 neurologists, pulmonologists, and psychiatrists who responded, 81% said that patients could experience excessive sleepiness even when their airway treatment has been optimized. That 81% was then asked what percentage of their patients with OSA experienced such symptoms. Almost one-third of respondents said that 16%-30% of their patients experience excessive sleepiness on optimized airway treatment, which works out to about 30% of neurologists, 40% of pulmonologists, and 23% of psychiatrists, Jazz reported.

When asked how often they assess their OSA patients’ sleepiness, 46% of respondents said every 3 months, 28% said every 6 months, 19% said once a month, 6% said once a year, and 0.4% (one neurologist and one pulmonologist) said never. The method of evaluation varied by specialty: 82% of pulmonologists most often use the Epworth Sleepiness Scale and 76% of psychiatrists primarily use an informal set of questions, with neurologists in between but leaning toward informal questions, Jazz reported.

“As more scientific evidence emerges around the neuronal injury occurring due to OSA and the potential neurocognitive effects of excessive sleepiness, it’s imperative that pulmonologists, neurologists and psychiatrists understand the impact ES [excessive sleepiness] can have on patients’ lives,” Richard K. Bogan, MD, of the University of South Carolina, Columbia, a paid consultant to Jazz, said in a written statement.
 

rfranki@mdedge.com

 

SAN DIEGO – Customized airway stents made from 3-dimensional imaging software provided compelling outcomes in patients with nonmalignant, anatomically complex, and symptomatic stenosis for whom conventional stents were not suitable or failed, results from a small study demonstrated.

“Anatomically complex airway stenosis remains a challenging situation,” lead study author Nicolas Guibert, MD, said at an international conference of the American Thoracic Society. “Conventional devices are either not suited or may result in a significant complication rate, including poor clinical tolerance, migration, or granulation tissue reaction due to lack of congruence.”

Doug Brunk/MDedge News

Dr. Guibert, a pulmonologist at Toulouse (France) University Hospital, and his associates hypothesized that patient-specific, fully customized 3-D stents created by computer-assisted design has the potential for improving tolerance and decreasing the complication rate. In a feasibility study, they recruited 10 patients with nonmalignant, anatomically complex, and symptomatic stenosis for whom conventional stents were not suitable or failed. After computer-assisted segmentation of the airways from a CT-scan and virtual relief of the stenosis, a virtual 3-D stent and corresponding mold was designed for each patient, a process that takes 3-4 weeks, including sterilization. Numerical data were then entered into a 3-D computer numeric control machine to produce the Ertacetal mold, from which the silicon stent is made. The researchers placed the stents under general anesthesia through rigid bronchoscopy and collected data on complication rate, dyspnea as defined by the New York Heart Association classification, quality of life as defined by the VQ11 measure, and respiratory function at day 7 and at 3, 6, and 12 months. Congruence of the stent was assessed preoperatively via bronchoscopy and at 1 week via CT scan.

Dr. Guibert reported results from eight patients. Of these, three had posttransplant complex airway stenoses involving the bronchus intermedius. Each improved after placement of the customized stents. For example, one patient with vanishing bronchus intermedius syndrome experienced improvements in NYHA dyspnea score from 3 to 1, the VQ11 score from 22 to 11/55, and forced expiratory volume in 1 second (FEV₁₎ from 70% to 107%. The stent was removed after 3 months. Meanwhile, a patient with localized malacia and stenosis of the right main bronchus experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 score from 27 to 15/55, and FEV₁ from 70% to 102%. That person’s stent is still in place with no complications. Another patient with localized malacia and stenosis of the bronchus intermedius experienced improvements in FEV₁ from 84% to 100%. That person’s device was removed after 3 months, with no residual stenosis.

A fourth patient underwent stent placement for localized malacia (cartilage ring rupture). That person experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 from 23 to 15/55, and FEV₁ from 66% to 92%, and peak flow from 49% to 82%. The device is still in place with no complications. A fifth patient received stent placement for extensive tracheobronchomalacia, but it had imperfect congruence and was removed after 3 months because it caused intense cough.

One patient with post-tracheotomy stenosis experienced improvements in NYHA dyspnea score from 3 to 0, VQ11 from 29 to 12/55, and peak flow from 45% to 81%. That person’s device is still in place, Dr. Guibert said. Two other patients treated for post-tracheotomy experienced stent migration (conventional stents also migrated in these two cases), despite good bronchoscopic congruence after placement.

“Tracheal diseases result in suboptimal congruence, probably due to higher respiratory variation,” Dr. Guibert said. “These devices need to be studied in less selected populations and the technology has to be improved.” He reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Guibert N et al. ATS 2018, Abstract 4433.


 

 

SAN DIEGO – Customized airway stents made from 3-dimensional imaging software provided compelling outcomes in patients with nonmalignant, anatomically complex, and symptomatic stenosis for whom conventional stents were not suitable or failed, results from a small study demonstrated.

“Anatomically complex airway stenosis remains a challenging situation,” lead study author Nicolas Guibert, MD, said at an international conference of the American Thoracic Society. “Conventional devices are either not suited or may result in a significant complication rate, including poor clinical tolerance, migration, or granulation tissue reaction due to lack of congruence.”

Doug Brunk/MDedge News

Dr. Guibert, a pulmonologist at Toulouse (France) University Hospital, and his associates hypothesized that patient-specific, fully customized 3-D stents created by computer-assisted design has the potential for improving tolerance and decreasing the complication rate. In a feasibility study, they recruited 10 patients with nonmalignant, anatomically complex, and symptomatic stenosis for whom conventional stents were not suitable or failed. After computer-assisted segmentation of the airways from a CT-scan and virtual relief of the stenosis, a virtual 3-D stent and corresponding mold was designed for each patient, a process that takes 3-4 weeks, including sterilization. Numerical data were then entered into a 3-D computer numeric control machine to produce the Ertacetal mold, from which the silicon stent is made. The researchers placed the stents under general anesthesia through rigid bronchoscopy and collected data on complication rate, dyspnea as defined by the New York Heart Association classification, quality of life as defined by the VQ11 measure, and respiratory function at day 7 and at 3, 6, and 12 months. Congruence of the stent was assessed preoperatively via bronchoscopy and at 1 week via CT scan.

Dr. Guibert reported results from eight patients. Of these, three had posttransplant complex airway stenoses involving the bronchus intermedius. Each improved after placement of the customized stents. For example, one patient with vanishing bronchus intermedius syndrome experienced improvements in NYHA dyspnea score from 3 to 1, the VQ11 score from 22 to 11/55, and forced expiratory volume in 1 second (FEV₁₎ from 70% to 107%. The stent was removed after 3 months. Meanwhile, a patient with localized malacia and stenosis of the right main bronchus experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 score from 27 to 15/55, and FEV₁ from 70% to 102%. That person’s stent is still in place with no complications. Another patient with localized malacia and stenosis of the bronchus intermedius experienced improvements in FEV₁ from 84% to 100%. That person’s device was removed after 3 months, with no residual stenosis.

A fourth patient underwent stent placement for localized malacia (cartilage ring rupture). That person experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 from 23 to 15/55, and FEV₁ from 66% to 92%, and peak flow from 49% to 82%. The device is still in place with no complications. A fifth patient received stent placement for extensive tracheobronchomalacia, but it had imperfect congruence and was removed after 3 months because it caused intense cough.

One patient with post-tracheotomy stenosis experienced improvements in NYHA dyspnea score from 3 to 0, VQ11 from 29 to 12/55, and peak flow from 45% to 81%. That person’s device is still in place, Dr. Guibert said. Two other patients treated for post-tracheotomy experienced stent migration (conventional stents also migrated in these two cases), despite good bronchoscopic congruence after placement.

“Tracheal diseases result in suboptimal congruence, probably due to higher respiratory variation,” Dr. Guibert said. “These devices need to be studied in less selected populations and the technology has to be improved.” He reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Guibert N et al. ATS 2018, Abstract 4433.


 

 

SAN DIEGO – Customized airway stents made from 3-dimensional imaging software provided compelling outcomes in patients with nonmalignant, anatomically complex, and symptomatic stenosis for whom conventional stents were not suitable or failed, results from a small study demonstrated.

“Anatomically complex airway stenosis remains a challenging situation,” lead study author Nicolas Guibert, MD, said at an international conference of the American Thoracic Society. “Conventional devices are either not suited or may result in a significant complication rate, including poor clinical tolerance, migration, or granulation tissue reaction due to lack of congruence.”

Doug Brunk/MDedge News

Dr. Guibert, a pulmonologist at Toulouse (France) University Hospital, and his associates hypothesized that patient-specific, fully customized 3-D stents created by computer-assisted design has the potential for improving tolerance and decreasing the complication rate. In a feasibility study, they recruited 10 patients with nonmalignant, anatomically complex, and symptomatic stenosis for whom conventional stents were not suitable or failed. After computer-assisted segmentation of the airways from a CT-scan and virtual relief of the stenosis, a virtual 3-D stent and corresponding mold was designed for each patient, a process that takes 3-4 weeks, including sterilization. Numerical data were then entered into a 3-D computer numeric control machine to produce the Ertacetal mold, from which the silicon stent is made. The researchers placed the stents under general anesthesia through rigid bronchoscopy and collected data on complication rate, dyspnea as defined by the New York Heart Association classification, quality of life as defined by the VQ11 measure, and respiratory function at day 7 and at 3, 6, and 12 months. Congruence of the stent was assessed preoperatively via bronchoscopy and at 1 week via CT scan.

Dr. Guibert reported results from eight patients. Of these, three had posttransplant complex airway stenoses involving the bronchus intermedius. Each improved after placement of the customized stents. For example, one patient with vanishing bronchus intermedius syndrome experienced improvements in NYHA dyspnea score from 3 to 1, the VQ11 score from 22 to 11/55, and forced expiratory volume in 1 second (FEV₁₎ from 70% to 107%. The stent was removed after 3 months. Meanwhile, a patient with localized malacia and stenosis of the right main bronchus experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 score from 27 to 15/55, and FEV₁ from 70% to 102%. That person’s stent is still in place with no complications. Another patient with localized malacia and stenosis of the bronchus intermedius experienced improvements in FEV₁ from 84% to 100%. That person’s device was removed after 3 months, with no residual stenosis.

A fourth patient underwent stent placement for localized malacia (cartilage ring rupture). That person experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 from 23 to 15/55, and FEV₁ from 66% to 92%, and peak flow from 49% to 82%. The device is still in place with no complications. A fifth patient received stent placement for extensive tracheobronchomalacia, but it had imperfect congruence and was removed after 3 months because it caused intense cough.

One patient with post-tracheotomy stenosis experienced improvements in NYHA dyspnea score from 3 to 0, VQ11 from 29 to 12/55, and peak flow from 45% to 81%. That person’s device is still in place, Dr. Guibert said. Two other patients treated for post-tracheotomy experienced stent migration (conventional stents also migrated in these two cases), despite good bronchoscopic congruence after placement.

“Tracheal diseases result in suboptimal congruence, probably due to higher respiratory variation,” Dr. Guibert said. “These devices need to be studied in less selected populations and the technology has to be improved.” He reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Guibert N et al. ATS 2018, Abstract 4433.


 

 

CHICAGO – A set of blood-based assays that search for abnormalities in cell-free DNA show moderately good sensitivity for detecting lung cancer in its early stages, according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).

“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”

Susan London/MDedge News

Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.

“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.

“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”

The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.

The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”

 

Susan London/MDedge News

“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”

Study details

The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.

The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.

Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.

 

Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”

Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.

Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).

An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).

 

Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.

SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.

 

CHICAGO – A set of blood-based assays that search for abnormalities in cell-free DNA show moderately good sensitivity for detecting lung cancer in its early stages, according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).

“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”

Susan London/MDedge News

Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.

“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.

“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”

The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.

The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”

 

Susan London/MDedge News

“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”

Study details

The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.

The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.

Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.

 

Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”

Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.

Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).

An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).

 

Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.

SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.

 

CHICAGO – A set of blood-based assays that search for abnormalities in cell-free DNA show moderately good sensitivity for detecting lung cancer in its early stages, according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).

“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”

Susan London/MDedge News

Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.

“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.

“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”

The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.

The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”

 

Susan London/MDedge News

“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”

Study details

The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.

The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.

Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.

 

Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”

Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.

Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).

An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).

 

Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.

SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.