Patients with highly active lupus nephritis who took the investigational oral calcineurin inhibitor voclosporin plus mycophenolate mofetil and tapered corticosteroids were twice as likely to achieve complete remission by 24 weeks, compared against placebo-treated patients who also received standard of care treatment in a phase IIb study trial reported by Aurinia Pharmaceuticals.

The 24-week complete remission primary endpoint of the AURA-LV(Aurinia Urinary Protein Reduction Active–Lupus With Voclosporin) study – defined as a urine protein/creatinine ratio of 0.5 mg/mg or less as well as normal stable renal function (estimated glomerular filtration rate of 60 mL/min per 1.73 m² or greater or no confirmed decrease from baseline in eGFR of 20% or greater) – occurred in 32.6% of patients who were randomized to take 23.7 mg of voclosporin twice daily, which was significantly higher than the 19.3% rate observed in the placebo-treated group. The rate was 27.3% in a higher-dose group that received 39.5 mg of voclosporin twice daily.

©London_England/Thinkstock

Serious adverse events occurred at higher rates in both voclosporin arms of the trial than in the placebo arm, but Aurinia said in its statement announcing the results that the nature of the events was consistent with highly active lupus nephritis. A total of 13 deaths occurred, including 2 in the high-dose arm, 10 in the low-dose arm, and 1 in the placebo arm, but the company said that the investigator deemed the deaths as unrelated to voclosporin. Eleven of the deaths occurred in Asia.

Both low- and high-dose voclosporin arms attained a partial response by 24 weeks (50% drop in urine protein per creatinine ratio) in a significantly higher percentage of patients than did the placebo arm (69.7% and 65.9%, respectively, vs. 49.4%).

The Lupus Research Alliance welcomed the results of the study but noted that more needs to be known about the risk-benefit profile of the drug, specifically in reference to the 12 deaths reported in those who took voclosporin. “The magnitude of benefit is quite striking and unprecedented in lupus nephritis, but the number of deaths is a concern that must be taken seriously. We are very hopeful that further analysis of the safety data will confirm that voclosporin can provide a safe and effective treatment,” Margaret G. Dowd, co–chief executive officer of the Lupus Research Alliance, said in a statement.

The trial enrolled and randomized 265 patients diagnosed with highly active lupus nephritis (according to clinical signs and renal biopsy features) across centers in more than 20 countries. Besides being randomized to either active treatment arm or placebo, all patients received mycophenolate mofetil (CellCept) and oral corticosteroids that started at 20-25 mg/daily and then tapered down to 5 mg daily by week 8 and 2.5 mg daily by week 16. All patients also had an initial 500-1,000 mg intravenous dose of steroids.

Aurinia said that the study will continue to 48 weeks, and these data will be available in early 2017.

[email protected]

Patients with highly active lupus nephritis who took the investigational oral calcineurin inhibitor voclosporin plus mycophenolate mofetil and tapered corticosteroids were twice as likely to achieve complete remission by 24 weeks, compared against placebo-treated patients who also received standard of care treatment in a phase IIb study trial reported by Aurinia Pharmaceuticals.

The 24-week complete remission primary endpoint of the AURA-LV(Aurinia Urinary Protein Reduction Active–Lupus With Voclosporin) study – defined as a urine protein/creatinine ratio of 0.5 mg/mg or less as well as normal stable renal function (estimated glomerular filtration rate of 60 mL/min per 1.73 m² or greater or no confirmed decrease from baseline in eGFR of 20% or greater) – occurred in 32.6% of patients who were randomized to take 23.7 mg of voclosporin twice daily, which was significantly higher than the 19.3% rate observed in the placebo-treated group. The rate was 27.3% in a higher-dose group that received 39.5 mg of voclosporin twice daily.

©London_England/Thinkstock

Serious adverse events occurred at higher rates in both voclosporin arms of the trial than in the placebo arm, but Aurinia said in its statement announcing the results that the nature of the events was consistent with highly active lupus nephritis. A total of 13 deaths occurred, including 2 in the high-dose arm, 10 in the low-dose arm, and 1 in the placebo arm, but the company said that the investigator deemed the deaths as unrelated to voclosporin. Eleven of the deaths occurred in Asia.

Both low- and high-dose voclosporin arms attained a partial response by 24 weeks (50% drop in urine protein per creatinine ratio) in a significantly higher percentage of patients than did the placebo arm (69.7% and 65.9%, respectively, vs. 49.4%).

The Lupus Research Alliance welcomed the results of the study but noted that more needs to be known about the risk-benefit profile of the drug, specifically in reference to the 12 deaths reported in those who took voclosporin. “The magnitude of benefit is quite striking and unprecedented in lupus nephritis, but the number of deaths is a concern that must be taken seriously. We are very hopeful that further analysis of the safety data will confirm that voclosporin can provide a safe and effective treatment,” Margaret G. Dowd, co–chief executive officer of the Lupus Research Alliance, said in a statement.

The trial enrolled and randomized 265 patients diagnosed with highly active lupus nephritis (according to clinical signs and renal biopsy features) across centers in more than 20 countries. Besides being randomized to either active treatment arm or placebo, all patients received mycophenolate mofetil (CellCept) and oral corticosteroids that started at 20-25 mg/daily and then tapered down to 5 mg daily by week 8 and 2.5 mg daily by week 16. All patients also had an initial 500-1,000 mg intravenous dose of steroids.

Aurinia said that the study will continue to 48 weeks, and these data will be available in early 2017.

[email protected]

Patients with highly active lupus nephritis who took the investigational oral calcineurin inhibitor voclosporin plus mycophenolate mofetil and tapered corticosteroids were twice as likely to achieve complete remission by 24 weeks, compared against placebo-treated patients who also received standard of care treatment in a phase IIb study trial reported by Aurinia Pharmaceuticals.

The 24-week complete remission primary endpoint of the AURA-LV(Aurinia Urinary Protein Reduction Active–Lupus With Voclosporin) study – defined as a urine protein/creatinine ratio of 0.5 mg/mg or less as well as normal stable renal function (estimated glomerular filtration rate of 60 mL/min per 1.73 m² or greater or no confirmed decrease from baseline in eGFR of 20% or greater) – occurred in 32.6% of patients who were randomized to take 23.7 mg of voclosporin twice daily, which was significantly higher than the 19.3% rate observed in the placebo-treated group. The rate was 27.3% in a higher-dose group that received 39.5 mg of voclosporin twice daily.

©London_England/Thinkstock

Serious adverse events occurred at higher rates in both voclosporin arms of the trial than in the placebo arm, but Aurinia said in its statement announcing the results that the nature of the events was consistent with highly active lupus nephritis. A total of 13 deaths occurred, including 2 in the high-dose arm, 10 in the low-dose arm, and 1 in the placebo arm, but the company said that the investigator deemed the deaths as unrelated to voclosporin. Eleven of the deaths occurred in Asia.

Both low- and high-dose voclosporin arms attained a partial response by 24 weeks (50% drop in urine protein per creatinine ratio) in a significantly higher percentage of patients than did the placebo arm (69.7% and 65.9%, respectively, vs. 49.4%).

The Lupus Research Alliance welcomed the results of the study but noted that more needs to be known about the risk-benefit profile of the drug, specifically in reference to the 12 deaths reported in those who took voclosporin. “The magnitude of benefit is quite striking and unprecedented in lupus nephritis, but the number of deaths is a concern that must be taken seriously. We are very hopeful that further analysis of the safety data will confirm that voclosporin can provide a safe and effective treatment,” Margaret G. Dowd, co–chief executive officer of the Lupus Research Alliance, said in a statement.

The trial enrolled and randomized 265 patients diagnosed with highly active lupus nephritis (according to clinical signs and renal biopsy features) across centers in more than 20 countries. Besides being randomized to either active treatment arm or placebo, all patients received mycophenolate mofetil (CellCept) and oral corticosteroids that started at 20-25 mg/daily and then tapered down to 5 mg daily by week 8 and 2.5 mg daily by week 16. All patients also had an initial 500-1,000 mg intravenous dose of steroids.

Aurinia said that the study will continue to 48 weeks, and these data will be available in early 2017.

[email protected]

The first article during my tenure as editor of the “Practice Management: The Road Ahead” section of Clinical Gastroenterology and Hepatology published in July 2012 (Clin Gastroenterol Hepatol. 2012;10:692-6) outlined anticipated changes in health care delivery, due in large part to mandates or trends contained in the Patient Protection and Affordable Care Act. A second article was published in 2013 (Health care reform 3.0: The road gets bumpy. Clin Gastroenterol Hepatol. 2013;11:1527-8). In this month’s column, Spencer D. Dorn, MD, MPH, MHA, of the University of North Carolina at Chapel Hill, adds a third update with an article focused on alternative payment models. These new reimbursement models are becoming common and will be part of all of our practice strategies in the years to come. No matter what occurs in the 2016 election, the movement from volume- to value-based payment will continue relentlessly, and practices that do not understand how to respond will struggle. We hope these articles will kick-start conversations in your practice.

Fee-for-service (FFS) reimbursement has been criticized for encouraging quantity over quality, favoring procedures over cognitive services, and fragmenting care.1 The landmark Patient Protection and Affordable Care Act (ACA) and more recent Medicare Access and Children’s Health Insurance Program Reauthorization Act (MACRA) modify Medicare’s FFS and encourage alternative payment models (APMs) that better reward value than volume.

Prior articles in this series have identified the specific trends driving gastroenterology practice strategies and business decisions,2 including an increasing need to demonstrate value, an emphasis on improved population health, an increasing number of practices becoming employees of large integrated delivery networks, reduced FFS reimbursements that are more closely linked to performance metrics, and increasing demands for risk-based contracts.3 In this article, I dive more deeply into these last two trends (declining FFS and the rise of APMs) and consider strategies gastroenterology practices can take in response.

Changes in fee for service

The ACA directed the secretary of Health and Human Services to establish a formal process to review potentially misvalued procedure codes. Compared with the pre-ACA fee schedule, the final 2016 Medicare Physician Fee Schedule includes cuts to professional fees for upper endoscopy, endoscopic retrograde cholangiopancreatography, endoscopic ultrasound, and colonoscopy. At the same time, over the past decade, facility fees paid for procedures performed in hospital outpatient departments have increased. Those to ambulatory surgery centers have gradually increased, although they still remain far below pre-2008 levels. Thus, the full economic impact of fee revaluation on an individual gastroenterology practice depends on whether it collects associated facility and ancillary fees.4

In addition, in the 2016 fee schedule, the Centers for Medicare & Medicaid Services described its intention to remove the value of moderate sedation from all gastrointestinal procedures. This is to prevent paying twice for sedation in procedures that involve anesthesiology professionals (i.e., one payment to the endoscopist as part of the overall procedure fee and a separate payment to the anesthesia professional for sedation they provide and bill for separately). The American Medical Association/Specialty Society Relative Value Scale Update Committee, using survey data from the GI specialty societies and other specialties that perform their own moderate sedation, has submitted recommendations for the value of a new set of moderate sedation Current Procedural Terminology codes to the CMS. The agency is expected to provide the specifics on how it will remove moderate sedation from the GI procedure codes in the 2017 Medicare Physician Fee Schedule Proposed Rule. The more that moderate sedation is valued, the less that endoscopic procedures will be valued. Consequently, gastroenterologists who rely on anesthesiology professionals to sedate their patients will generate less revenue per procedure, unless they rearrange contracts with anesthesia providers. Gastroenterologists who perform moderate sedation will not be impacted, because the sum of the value of the new moderate sedation code plus the underlying endoscopic procedure code will equal the original value of the procedure.

Beyond revaluing services, the CMS outlined its rather ambitious goal “to have 85% of all Medicare fee-for-service (FFS) payments tied to quality or value by 2016, and 90% by 2018.”5 Currently this includes the Physician Quality Reporting System (PQRS), which requires gastroenterologists to report performance on either three or more individual PQRS measures or one PQRS measures group (collection of related individual measures) or face a 2% Medicare payment penalty. It also includes the value-based payment modifier, through which by 2017 all practices with better-than-average quality (linked to PQRS measures) and lower costs will receive bonus payments, whereas those with worse-than-average performance (or who choose not to report) will be penalized.

MACRA changes all of this. Starting in 2019, the meaningful use incentive program, PQRS, and value-based payment modifier will be consolidated into the Merit-Based Incentive Payment System (MIPS). Physicians who elect to remain on an FFS tract will receive a 0-100 composite performance score based on quality (30%), resource use (30%), meaningful use (25%), and clinical practice improvement activities (15%). At the start of a performance period, a composite threshold necessary to achieve incentive payments and avoid penalties will be determined. Throughout the performance period, physicians will receive timely feedback on their performance. At year’s end, those below the threshold will face penalties proportionate to their performance (as much as 4% in 2019 and going up to 9% in 2022), those at threshold will not receive a payment adjustment, and those above threshold will receive bonuses proportionate to their performance (although overall payments will be capped at $500 million).

Alternative payment models

The CMS’s ultimate goal is to move beyond FFS and have “30% of Medicare payments tied to quality or value through APMs by the end of 2016 and 50% of payments by the end of 2018.”5 MACRA supports this ambitious goal: Starting in 2019, providers who “sufficiently” participate in APMs will receive 5% across-the-board bonuses. The three main APMs are bundled payments, accountable care organizations (ACOs), and patient-centered medical homes.

A bundled payment is a single fixed price paid to cover services for a specific episode of care. Depending on how an episode is defined, the bundle may encompass all professional fees, facility fees, and medical device and supply costs for a given service, including postacute care and any complications. If costs are reduced beyond the already discounted price of the bundle and quality metrics are achieved, then participants share the savings. Conversely, if costs exceed the bundled payment amount, then participants lose money. Unlike FFS, bundling incentivizes participants to coordinate care, reduce complications and unnecessary services, and cut purchasing costs.

To date, the CMS has launched three bundling programs. The Acute Care Episode Demonstration Project provided hospitals and clinicians a bundled payment to cover orthopedic and cardiovascular procedure–related episodes of care. This program reduced Medicare costs, primarily because the bundle payment was lower than what the sum of individual payments would have been. Providers were able to cope mainly by reducing their surgical implant costs. Second, more than 6,000 providers are currently participating in Medicare’s Bundled Payments for Care Improvement Program. The results of this program have not yet been released. Third, the CMS recently announced the Comprehensive Care for Joint Replacement Program under which hospitals and physicians in 67 metropolitan areas will be required to participate. Mandatory participation signals the CMS’s strong motivation to shift away from FFS. Beyond Medicare, many commercial insurers offer bundled payment programs, primarily for cardiovascular and orthopedic conditions.⁶ Although these programs are promising, it is technically challenging to define what is in a bundle, and to adequately risk adjust and mitigate random variation in spending for certain episodes of care. Providers are also challenged to find ways to divide payment among participants, coordinate all care, and accept financial risk.^7,8 The American Gastroenterological Association recently published a bundled payment framework for screening and surveillance colonoscopy.⁹ Bundling other gastroenterology services will be more challenging.

Whereas bundled-care programs focus on a discrete service (e.g., knee replacement or colonoscopy), ACOs are integrated groups of providers who jointly assume responsibility for the cost and quality of all care delivered to a defined population. The ACA requires ACOs to have formal legal, leadership, and management structures; care for at least 5,000 Medicare beneficiaries; fulfill certain patient-centeredness criteria; measure and report quality and cost data; and coordinate care. Different payment models incentivize ACOs to reduce costs and improve quality of care. ACOs operating under a one-sided shared savings model receive FFS payments for each service delivered, along with a bonus for reducing costs below a spending target and meeting quality requirements. There are no potential financial penalties. Alternatively, ACOs operating under a two-sided risk-savings model share a greater proportion of cost savings, in exchange for potential financial penalties if the cost of care exceeds target spending.

To date, Medicare-sponsored ACOs have produced mixed results. In 2014 only 92 of the 322 Medicare Shared Savings ACOs were able to reduce spending below a predetermined benchmark by a predetermined amount (2%-3%) while meeting quality scores, thereby earning a bonus ($341 million in total). Similarly, of the original 32 pioneer ACOs, which by definition are more experienced at managing population health and more willing to take on financial risk, 13 dropped out of the program, and in 2014, only 11 generated enough savings to earn a payout ($82 million in total), whereas 5 incurred financial penalties ($9 million in total) for costs exceeding target thresholds.¹⁰ In total, after paying out bonuses, the ACO program cost Medicare a net loss of nearly $3 million, far from the $10-$240 million Medicare had previously projected it would save through the ACO program.¹¹ Clearly, ACOs are not a quick fix for all that ails health care. For many ACOs, the major start-up requirements (time, capital investments, and so forth) needed to manage a population may not be worthwhile.¹² Nonetheless, the CMS recently launched the Next Generation ACO model through which 21 participating ACOs will assume higher levels of financial risk (possibly capitated payments) in exchange for greater potential rewards. Similarly, beyond Medicare, there are also many Medicaid-sponsored ACOs and hundreds of commercial payer-sponsored ACOs.¹³

Finally, practices can qualify for APM status without accepting bundled payments or joining an ACO by qualifying as a patient-centered medical home. One option for gastroenterologists and other specialists is the National Committee for Quality Assurance’s patient-centered specialty practice designation, available to practices that successfully demonstrate their ability to track and coordinate care with primary care providers and other specialists, offer timely appointments and responses to telephone and electronic messages, use evidence-based tools to manage care for specific patient populations, develop patient-centered care plans, and measure and improve performance.¹⁴

Consolidation

Health insurers are merging to increase scale (and negotiating power), enhance efficiency (reducing administrative costs makes more room for profits), and diversify their businesses. Recently proposed acquisitions will bring “the big five” health insurers to the “big three.” Likewise, health care systems are rapidly acquiring hospitals and physician groups, so much so that today half of all American health care markets are now considered highly concentrated, and none are considered highly competitive.¹⁵ Today only 35% of all physicians are independently employed.¹⁶ Physicians employed by health systems trade their complete autonomy to offset declining reimbursement, reduce operating expenses (including health information technology costs), improve work-life balance, and mitigate unknown risks.

Proponents contend that these mergers allow health care systems to better coordinate care, improve care experiences, accommodate new payment models, and assemble the building blocks needed to form ACOs and other integrated care models. Critics argue that locally dominant systems drive volume (by tightening referral relationships and gaining new market share) and increase costs (through enhanced negotiating leverage and by reclassifying newly acquired physician practices as part of the hospital, thereby generating facility fees). It is unclear whether consolidation results in better outcomes or simply increases overall costs.¹⁷

Strategic imperatives

What should gastroenterologists do? First, recognize that FFS is not going away anytime soon.¹⁸ Most APMs are still largely in their experimentation phase, and it remains unclear which models will work and which will be broadly adopted. Still, it is unrealistic to expect FFS to indefinitely persist as the dominant payment model. For some services FFS may no longer be a payment option (e.g., Medicare’s BCPI [Bundled Payments for Care Improvement]). For others, FFS rates may become so unattractive that APMs seem necessary. Finally, APMs may allow some practices to capture a greater proportion of overall clinical revenue (e.g., academic practices that perform endoscopic procedures within hospital outpatient departments) and to develop new models that meaningfully improve care. Today’s gastroenterology practices must therefore operate on two separate tracks: an FFS track that rewards volume (most practices are optimized for this) and an alternative payment track that rewards value (few practices can accommodate these on their own). The degree and speed with which practices should reorient to the alternative payment track depends on the type of practice and the specific local health care market. But even practices operating in slower-to-evolve markets should start preparing for the APMs, no matter how far off in the distance they may seem. I recommend the following six steps:

1. Integrate. To participate in APMs, preserve referral streams, and maintain negotiating leverage with health plans, independent, community-based practices may need to affiliate or merge with other physician groups, or align with or be acquired by a health care system.¹⁹ Academic practices are challenged to define their role within health care systems that are rapidly adding primary care practices, and often community gastroenterology practices, too.

2. Collaborate and communicate. To deliver high-value care to populations of patients, gastroenterologists must closely collaborate and clearly communicate with primary care physicians and other specialists. Collaborative care agreements can help guide these relationships.²⁰3. Develop new models of care. Patients with more routine GI and liver-related problems may be served more cost effectively by midlevel providers²¹ or innovative solutions, such as e-consultations.²² Patients with complex, chronic GI and liver diseases may be best served by multidisciplinary care teams (e.g., gastroenterologists alongside midlevel providers, nurses, care managers, psychologists, and/or pharmacists) who use clinical information systems to identify high-risk patients and to encourage evidence-based decision making, and who support patients to self-manage their own conditions.²³ Previously infeasible in a purely FFS world, these models are encouraged by APMs.

4. Care for common, costly conditions. Most gastroenterology practices have built robust colorectal cancer screening programs, sometimes at the expense of cognitive-based services. In today’s more accountable world, practices that can effectively manage common, costly conditions, such as inflammatory bowel disease, functional GI disorders, and advanced liver diseases, will be rewarded better than before and will be more highly sought as partners.

5. Understand and contain costs. The timely, accurate data needed to effectively respond to APMs are challenging to come by.¹⁹ Individual clinicians and group practices can roughly gauge their costs of care for Medicare beneficiaries, compared with other practices, using CMS Quality Resource Utilization Reports. Local commercial insurers may be willing to share cost profiles with interested practices. Strategies to reduce costs may include shifting clinically appropriate patients to more cost-effective settings (especially important for academic practices that see the bulk of their patients in costly hospital outpatient departments), standardizing endoscopy supplies and devices, using anesthesia services more selectively, and preferentially prescribing generic drugs, among others.

6. Measure and demonstrate value. Despite the inherent limitations of performance measurement,²⁴ it is imperative that practices measure and report the value of care to their patients, community, and payers so that they are preferred partners and not locked out of insurance or referral networks. Improving patient experiences is intrinsically worthwhile²⁵ and also makes good business sense.²⁶

References

1. Miller, H.D. Creating payment systems to accelerate value-driven health care: Issues and options for policy reform. New York: The Commonwealth Fund, 2007.

2. Allen, J.I. The road ahead. Clin Gastroenterol Hepatol. 2012;10:692–6.

3. Allen, J.I. Health care reform 3.0: The road gets bumpy. Clin Gastroenterol Hepatol. 2013;11:1527-8.

4. Dorn, S.D., Vesy C.J. Medicare’s revaluation of gastrointestinal endoscopic procedures: Implications for academic and community-based practices. Clin Gastroenterol Hepatol. 2016 (in press).

5. Burwell, S.M. Setting value-based payment goals: HHS efforts to improve U.S. health care (N Engl J Med. 2015;372:897–9).

6. The Advisory Board Company. Commercial Bundled Payment Tracker, 2016.

7. Mechanic, R.E. Mandatory Medicare bundled payment – is it ready for prime time? N Engl J Med. 2015;373:1291–3.

8. The National Commission on Physician Payment Reform. Physician Payment Report, 2013.

9. Brill, J.V., Jain, R., Margolis, P.S., et al. A bundled payment framework for colonoscopy performed for colorectal cancer screening or surveillance. Gastroenterology. 2014;146:849–53, e9.

10. Evans, M. Few Medicare ACOs earned bonuses in 2014. Mod Healthc (2015). Available at: www.modernhealthcare.com/article/20150825/NEWS/150829922. Accessed Nov. 14, 2015.

11. Rau, J., Gold, J. Medicare yet to save money through heralded medical payment model. Kaiser Health News. Available at: http://khn.org/news/medicare-yet-to-save-money-through-heralded-medical-payment-model. Accessed Nov. 14, 2015.

12. Goldmsith, J., Kaufman, N. Pioneer ACOs: Anatomy of a victory. Health Affairs Blog, 2015.

13. Tu, T., Muhlestein, D., Kocot, S.L., et al. The impact of accountable care: Origins and future of accountable care organizations. Washington, D.C.: Brookings Institution, 2015.

14. NCQA. Patient-centered specialty practice frequently asked questions.

15. Xu, T., Wu, A.W., Makary, M.A. The potential hazards of hospital consolidation: Implications for quality, access, and price. JAMA. 2015;314:1337–8.

16. The Physician’s Foundation. 2014 survey of America’s physicians. Practice patterns & perspectives: The Physician’s Foundation.

17. Tsai, T.C., Jha, A.K. Hospital consolidation, competition, and quality: Is bigger necessarily better? JAMA. 2014;312:29–30.

18. Ginsburg, P.B. Fee-for-service will remain a feature of major payment reforms, requiring more changes in Medicare physician payment. Health Aff (Millwood). 2012;31:1977–83.

19. Friedberg, M.W., Chen, P.G., White, C., et al. Effects of health care payment models on physician practice in the United States. Santa Monica, Calif.: RAND Corp., 2015.

20. Greenberg, J.O., Barnett, M.L., Spinks, M.A., et al. The “medical neighborhood”: Integrating primary and specialty care for ambulatory patients. JAMA Intern Med. 2014;174:454–7.

21. Dorn, S.D. Mid-level providers in gastroenterology. Am J Gastroenterol. 2010;105:246–51.

22. Wasfy, J.H., Rao, S.K., Kalwani, N., et al. Longer term impact of cardiology e-consults. Am Heart J. 2016;173:86–93.

23. Coleman, K., Austin, B.T., Brach, C., et al. Evidence on the chronic care model in the new millennium. Health Aff (Millwood). 2009;28:75–85.

24. Dorn, S.D. Quality measurement in gastroenterology: confessions of a realist. Clin Gastroenterol Hepatol. 2016;14:648–50.

25. Berwick, D.M. Measuring physicians’ quality and performance: adrift on Lake Wobegon. JAMA. 2009;302:2485-6.

26. Browne, K., Roseman, D., Shaller, D., et al. Analysis & commentary. Measuring patient experience as a strategy for improving primary care. Health Aff (Millwood). 2010;29:921–5.

Dr. Dorn is vice chief, division of gastroenterology and hepatology, associate professor of medicine, health policy & management, University of North Carolina at Chapel Hill. He has received honoraria for consulting and presentations on health reform from AbbVie and Olympus.

The first article during my tenure as editor of the “Practice Management: The Road Ahead” section of Clinical Gastroenterology and Hepatology published in July 2012 (Clin Gastroenterol Hepatol. 2012;10:692-6) outlined anticipated changes in health care delivery, due in large part to mandates or trends contained in the Patient Protection and Affordable Care Act. A second article was published in 2013 (Health care reform 3.0: The road gets bumpy. Clin Gastroenterol Hepatol. 2013;11:1527-8). In this month’s column, Spencer D. Dorn, MD, MPH, MHA, of the University of North Carolina at Chapel Hill, adds a third update with an article focused on alternative payment models. These new reimbursement models are becoming common and will be part of all of our practice strategies in the years to come. No matter what occurs in the 2016 election, the movement from volume- to value-based payment will continue relentlessly, and practices that do not understand how to respond will struggle. We hope these articles will kick-start conversations in your practice.

Fee-for-service (FFS) reimbursement has been criticized for encouraging quantity over quality, favoring procedures over cognitive services, and fragmenting care.1 The landmark Patient Protection and Affordable Care Act (ACA) and more recent Medicare Access and Children’s Health Insurance Program Reauthorization Act (MACRA) modify Medicare’s FFS and encourage alternative payment models (APMs) that better reward value than volume.

Prior articles in this series have identified the specific trends driving gastroenterology practice strategies and business decisions,2 including an increasing need to demonstrate value, an emphasis on improved population health, an increasing number of practices becoming employees of large integrated delivery networks, reduced FFS reimbursements that are more closely linked to performance metrics, and increasing demands for risk-based contracts.3 In this article, I dive more deeply into these last two trends (declining FFS and the rise of APMs) and consider strategies gastroenterology practices can take in response.

Changes in fee for service

The ACA directed the secretary of Health and Human Services to establish a formal process to review potentially misvalued procedure codes. Compared with the pre-ACA fee schedule, the final 2016 Medicare Physician Fee Schedule includes cuts to professional fees for upper endoscopy, endoscopic retrograde cholangiopancreatography, endoscopic ultrasound, and colonoscopy. At the same time, over the past decade, facility fees paid for procedures performed in hospital outpatient departments have increased. Those to ambulatory surgery centers have gradually increased, although they still remain far below pre-2008 levels. Thus, the full economic impact of fee revaluation on an individual gastroenterology practice depends on whether it collects associated facility and ancillary fees.4

In addition, in the 2016 fee schedule, the Centers for Medicare & Medicaid Services described its intention to remove the value of moderate sedation from all gastrointestinal procedures. This is to prevent paying twice for sedation in procedures that involve anesthesiology professionals (i.e., one payment to the endoscopist as part of the overall procedure fee and a separate payment to the anesthesia professional for sedation they provide and bill for separately). The American Medical Association/Specialty Society Relative Value Scale Update Committee, using survey data from the GI specialty societies and other specialties that perform their own moderate sedation, has submitted recommendations for the value of a new set of moderate sedation Current Procedural Terminology codes to the CMS. The agency is expected to provide the specifics on how it will remove moderate sedation from the GI procedure codes in the 2017 Medicare Physician Fee Schedule Proposed Rule. The more that moderate sedation is valued, the less that endoscopic procedures will be valued. Consequently, gastroenterologists who rely on anesthesiology professionals to sedate their patients will generate less revenue per procedure, unless they rearrange contracts with anesthesia providers. Gastroenterologists who perform moderate sedation will not be impacted, because the sum of the value of the new moderate sedation code plus the underlying endoscopic procedure code will equal the original value of the procedure.

Beyond revaluing services, the CMS outlined its rather ambitious goal “to have 85% of all Medicare fee-for-service (FFS) payments tied to quality or value by 2016, and 90% by 2018.”5 Currently this includes the Physician Quality Reporting System (PQRS), which requires gastroenterologists to report performance on either three or more individual PQRS measures or one PQRS measures group (collection of related individual measures) or face a 2% Medicare payment penalty. It also includes the value-based payment modifier, through which by 2017 all practices with better-than-average quality (linked to PQRS measures) and lower costs will receive bonus payments, whereas those with worse-than-average performance (or who choose not to report) will be penalized.

MACRA changes all of this. Starting in 2019, the meaningful use incentive program, PQRS, and value-based payment modifier will be consolidated into the Merit-Based Incentive Payment System (MIPS). Physicians who elect to remain on an FFS tract will receive a 0-100 composite performance score based on quality (30%), resource use (30%), meaningful use (25%), and clinical practice improvement activities (15%). At the start of a performance period, a composite threshold necessary to achieve incentive payments and avoid penalties will be determined. Throughout the performance period, physicians will receive timely feedback on their performance. At year’s end, those below the threshold will face penalties proportionate to their performance (as much as 4% in 2019 and going up to 9% in 2022), those at threshold will not receive a payment adjustment, and those above threshold will receive bonuses proportionate to their performance (although overall payments will be capped at $500 million).

Alternative payment models

The CMS’s ultimate goal is to move beyond FFS and have “30% of Medicare payments tied to quality or value through APMs by the end of 2016 and 50% of payments by the end of 2018.”5 MACRA supports this ambitious goal: Starting in 2019, providers who “sufficiently” participate in APMs will receive 5% across-the-board bonuses. The three main APMs are bundled payments, accountable care organizations (ACOs), and patient-centered medical homes.

A bundled payment is a single fixed price paid to cover services for a specific episode of care. Depending on how an episode is defined, the bundle may encompass all professional fees, facility fees, and medical device and supply costs for a given service, including postacute care and any complications. If costs are reduced beyond the already discounted price of the bundle and quality metrics are achieved, then participants share the savings. Conversely, if costs exceed the bundled payment amount, then participants lose money. Unlike FFS, bundling incentivizes participants to coordinate care, reduce complications and unnecessary services, and cut purchasing costs.

To date, the CMS has launched three bundling programs. The Acute Care Episode Demonstration Project provided hospitals and clinicians a bundled payment to cover orthopedic and cardiovascular procedure–related episodes of care. This program reduced Medicare costs, primarily because the bundle payment was lower than what the sum of individual payments would have been. Providers were able to cope mainly by reducing their surgical implant costs. Second, more than 6,000 providers are currently participating in Medicare’s Bundled Payments for Care Improvement Program. The results of this program have not yet been released. Third, the CMS recently announced the Comprehensive Care for Joint Replacement Program under which hospitals and physicians in 67 metropolitan areas will be required to participate. Mandatory participation signals the CMS’s strong motivation to shift away from FFS. Beyond Medicare, many commercial insurers offer bundled payment programs, primarily for cardiovascular and orthopedic conditions.⁶ Although these programs are promising, it is technically challenging to define what is in a bundle, and to adequately risk adjust and mitigate random variation in spending for certain episodes of care. Providers are also challenged to find ways to divide payment among participants, coordinate all care, and accept financial risk.^7,8 The American Gastroenterological Association recently published a bundled payment framework for screening and surveillance colonoscopy.⁹ Bundling other gastroenterology services will be more challenging.

Whereas bundled-care programs focus on a discrete service (e.g., knee replacement or colonoscopy), ACOs are integrated groups of providers who jointly assume responsibility for the cost and quality of all care delivered to a defined population. The ACA requires ACOs to have formal legal, leadership, and management structures; care for at least 5,000 Medicare beneficiaries; fulfill certain patient-centeredness criteria; measure and report quality and cost data; and coordinate care. Different payment models incentivize ACOs to reduce costs and improve quality of care. ACOs operating under a one-sided shared savings model receive FFS payments for each service delivered, along with a bonus for reducing costs below a spending target and meeting quality requirements. There are no potential financial penalties. Alternatively, ACOs operating under a two-sided risk-savings model share a greater proportion of cost savings, in exchange for potential financial penalties if the cost of care exceeds target spending.

To date, Medicare-sponsored ACOs have produced mixed results. In 2014 only 92 of the 322 Medicare Shared Savings ACOs were able to reduce spending below a predetermined benchmark by a predetermined amount (2%-3%) while meeting quality scores, thereby earning a bonus ($341 million in total). Similarly, of the original 32 pioneer ACOs, which by definition are more experienced at managing population health and more willing to take on financial risk, 13 dropped out of the program, and in 2014, only 11 generated enough savings to earn a payout ($82 million in total), whereas 5 incurred financial penalties ($9 million in total) for costs exceeding target thresholds.¹⁰ In total, after paying out bonuses, the ACO program cost Medicare a net loss of nearly $3 million, far from the $10-$240 million Medicare had previously projected it would save through the ACO program.¹¹ Clearly, ACOs are not a quick fix for all that ails health care. For many ACOs, the major start-up requirements (time, capital investments, and so forth) needed to manage a population may not be worthwhile.¹² Nonetheless, the CMS recently launched the Next Generation ACO model through which 21 participating ACOs will assume higher levels of financial risk (possibly capitated payments) in exchange for greater potential rewards. Similarly, beyond Medicare, there are also many Medicaid-sponsored ACOs and hundreds of commercial payer-sponsored ACOs.¹³

Finally, practices can qualify for APM status without accepting bundled payments or joining an ACO by qualifying as a patient-centered medical home. One option for gastroenterologists and other specialists is the National Committee for Quality Assurance’s patient-centered specialty practice designation, available to practices that successfully demonstrate their ability to track and coordinate care with primary care providers and other specialists, offer timely appointments and responses to telephone and electronic messages, use evidence-based tools to manage care for specific patient populations, develop patient-centered care plans, and measure and improve performance.¹⁴

Consolidation

Health insurers are merging to increase scale (and negotiating power), enhance efficiency (reducing administrative costs makes more room for profits), and diversify their businesses. Recently proposed acquisitions will bring “the big five” health insurers to the “big three.” Likewise, health care systems are rapidly acquiring hospitals and physician groups, so much so that today half of all American health care markets are now considered highly concentrated, and none are considered highly competitive.¹⁵ Today only 35% of all physicians are independently employed.¹⁶ Physicians employed by health systems trade their complete autonomy to offset declining reimbursement, reduce operating expenses (including health information technology costs), improve work-life balance, and mitigate unknown risks.

Proponents contend that these mergers allow health care systems to better coordinate care, improve care experiences, accommodate new payment models, and assemble the building blocks needed to form ACOs and other integrated care models. Critics argue that locally dominant systems drive volume (by tightening referral relationships and gaining new market share) and increase costs (through enhanced negotiating leverage and by reclassifying newly acquired physician practices as part of the hospital, thereby generating facility fees). It is unclear whether consolidation results in better outcomes or simply increases overall costs.¹⁷

Strategic imperatives

What should gastroenterologists do? First, recognize that FFS is not going away anytime soon.¹⁸ Most APMs are still largely in their experimentation phase, and it remains unclear which models will work and which will be broadly adopted. Still, it is unrealistic to expect FFS to indefinitely persist as the dominant payment model. For some services FFS may no longer be a payment option (e.g., Medicare’s BCPI [Bundled Payments for Care Improvement]). For others, FFS rates may become so unattractive that APMs seem necessary. Finally, APMs may allow some practices to capture a greater proportion of overall clinical revenue (e.g., academic practices that perform endoscopic procedures within hospital outpatient departments) and to develop new models that meaningfully improve care. Today’s gastroenterology practices must therefore operate on two separate tracks: an FFS track that rewards volume (most practices are optimized for this) and an alternative payment track that rewards value (few practices can accommodate these on their own). The degree and speed with which practices should reorient to the alternative payment track depends on the type of practice and the specific local health care market. But even practices operating in slower-to-evolve markets should start preparing for the APMs, no matter how far off in the distance they may seem. I recommend the following six steps:

1. Integrate. To participate in APMs, preserve referral streams, and maintain negotiating leverage with health plans, independent, community-based practices may need to affiliate or merge with other physician groups, or align with or be acquired by a health care system.¹⁹ Academic practices are challenged to define their role within health care systems that are rapidly adding primary care practices, and often community gastroenterology practices, too.

2. Collaborate and communicate. To deliver high-value care to populations of patients, gastroenterologists must closely collaborate and clearly communicate with primary care physicians and other specialists. Collaborative care agreements can help guide these relationships.²⁰3. Develop new models of care. Patients with more routine GI and liver-related problems may be served more cost effectively by midlevel providers²¹ or innovative solutions, such as e-consultations.²² Patients with complex, chronic GI and liver diseases may be best served by multidisciplinary care teams (e.g., gastroenterologists alongside midlevel providers, nurses, care managers, psychologists, and/or pharmacists) who use clinical information systems to identify high-risk patients and to encourage evidence-based decision making, and who support patients to self-manage their own conditions.²³ Previously infeasible in a purely FFS world, these models are encouraged by APMs.

4. Care for common, costly conditions. Most gastroenterology practices have built robust colorectal cancer screening programs, sometimes at the expense of cognitive-based services. In today’s more accountable world, practices that can effectively manage common, costly conditions, such as inflammatory bowel disease, functional GI disorders, and advanced liver diseases, will be rewarded better than before and will be more highly sought as partners.

5. Understand and contain costs. The timely, accurate data needed to effectively respond to APMs are challenging to come by.¹⁹ Individual clinicians and group practices can roughly gauge their costs of care for Medicare beneficiaries, compared with other practices, using CMS Quality Resource Utilization Reports. Local commercial insurers may be willing to share cost profiles with interested practices. Strategies to reduce costs may include shifting clinically appropriate patients to more cost-effective settings (especially important for academic practices that see the bulk of their patients in costly hospital outpatient departments), standardizing endoscopy supplies and devices, using anesthesia services more selectively, and preferentially prescribing generic drugs, among others.

6. Measure and demonstrate value. Despite the inherent limitations of performance measurement,²⁴ it is imperative that practices measure and report the value of care to their patients, community, and payers so that they are preferred partners and not locked out of insurance or referral networks. Improving patient experiences is intrinsically worthwhile²⁵ and also makes good business sense.²⁶

References

1. Miller, H.D. Creating payment systems to accelerate value-driven health care: Issues and options for policy reform. New York: The Commonwealth Fund, 2007.

2. Allen, J.I. The road ahead. Clin Gastroenterol Hepatol. 2012;10:692–6.

3. Allen, J.I. Health care reform 3.0: The road gets bumpy. Clin Gastroenterol Hepatol. 2013;11:1527-8.

4. Dorn, S.D., Vesy C.J. Medicare’s revaluation of gastrointestinal endoscopic procedures: Implications for academic and community-based practices. Clin Gastroenterol Hepatol. 2016 (in press).

5. Burwell, S.M. Setting value-based payment goals: HHS efforts to improve U.S. health care (N Engl J Med. 2015;372:897–9).

6. The Advisory Board Company. Commercial Bundled Payment Tracker, 2016.

7. Mechanic, R.E. Mandatory Medicare bundled payment – is it ready for prime time? N Engl J Med. 2015;373:1291–3.

8. The National Commission on Physician Payment Reform. Physician Payment Report, 2013.

9. Brill, J.V., Jain, R., Margolis, P.S., et al. A bundled payment framework for colonoscopy performed for colorectal cancer screening or surveillance. Gastroenterology. 2014;146:849–53, e9.

10. Evans, M. Few Medicare ACOs earned bonuses in 2014. Mod Healthc (2015). Available at: www.modernhealthcare.com/article/20150825/NEWS/150829922. Accessed Nov. 14, 2015.

11. Rau, J., Gold, J. Medicare yet to save money through heralded medical payment model. Kaiser Health News. Available at: http://khn.org/news/medicare-yet-to-save-money-through-heralded-medical-payment-model. Accessed Nov. 14, 2015.

12. Goldmsith, J., Kaufman, N. Pioneer ACOs: Anatomy of a victory. Health Affairs Blog, 2015.

13. Tu, T., Muhlestein, D., Kocot, S.L., et al. The impact of accountable care: Origins and future of accountable care organizations. Washington, D.C.: Brookings Institution, 2015.

14. NCQA. Patient-centered specialty practice frequently asked questions.

15. Xu, T., Wu, A.W., Makary, M.A. The potential hazards of hospital consolidation: Implications for quality, access, and price. JAMA. 2015;314:1337–8.

16. The Physician’s Foundation. 2014 survey of America’s physicians. Practice patterns & perspectives: The Physician’s Foundation.

17. Tsai, T.C., Jha, A.K. Hospital consolidation, competition, and quality: Is bigger necessarily better? JAMA. 2014;312:29–30.

18. Ginsburg, P.B. Fee-for-service will remain a feature of major payment reforms, requiring more changes in Medicare physician payment. Health Aff (Millwood). 2012;31:1977–83.

19. Friedberg, M.W., Chen, P.G., White, C., et al. Effects of health care payment models on physician practice in the United States. Santa Monica, Calif.: RAND Corp., 2015.

20. Greenberg, J.O., Barnett, M.L., Spinks, M.A., et al. The “medical neighborhood”: Integrating primary and specialty care for ambulatory patients. JAMA Intern Med. 2014;174:454–7.

21. Dorn, S.D. Mid-level providers in gastroenterology. Am J Gastroenterol. 2010;105:246–51.

22. Wasfy, J.H., Rao, S.K., Kalwani, N., et al. Longer term impact of cardiology e-consults. Am Heart J. 2016;173:86–93.

23. Coleman, K., Austin, B.T., Brach, C., et al. Evidence on the chronic care model in the new millennium. Health Aff (Millwood). 2009;28:75–85.

24. Dorn, S.D. Quality measurement in gastroenterology: confessions of a realist. Clin Gastroenterol Hepatol. 2016;14:648–50.

25. Berwick, D.M. Measuring physicians’ quality and performance: adrift on Lake Wobegon. JAMA. 2009;302:2485-6.

26. Browne, K., Roseman, D., Shaller, D., et al. Analysis & commentary. Measuring patient experience as a strategy for improving primary care. Health Aff (Millwood). 2010;29:921–5.

Dr. Dorn is vice chief, division of gastroenterology and hepatology, associate professor of medicine, health policy & management, University of North Carolina at Chapel Hill. He has received honoraria for consulting and presentations on health reform from AbbVie and Olympus.

The first article during my tenure as editor of the “Practice Management: The Road Ahead” section of Clinical Gastroenterology and Hepatology published in July 2012 (Clin Gastroenterol Hepatol. 2012;10:692-6) outlined anticipated changes in health care delivery, due in large part to mandates or trends contained in the Patient Protection and Affordable Care Act. A second article was published in 2013 (Health care reform 3.0: The road gets bumpy. Clin Gastroenterol Hepatol. 2013;11:1527-8). In this month’s column, Spencer D. Dorn, MD, MPH, MHA, of the University of North Carolina at Chapel Hill, adds a third update with an article focused on alternative payment models. These new reimbursement models are becoming common and will be part of all of our practice strategies in the years to come. No matter what occurs in the 2016 election, the movement from volume- to value-based payment will continue relentlessly, and practices that do not understand how to respond will struggle. We hope these articles will kick-start conversations in your practice.

Fee-for-service (FFS) reimbursement has been criticized for encouraging quantity over quality, favoring procedures over cognitive services, and fragmenting care.1 The landmark Patient Protection and Affordable Care Act (ACA) and more recent Medicare Access and Children’s Health Insurance Program Reauthorization Act (MACRA) modify Medicare’s FFS and encourage alternative payment models (APMs) that better reward value than volume.

Prior articles in this series have identified the specific trends driving gastroenterology practice strategies and business decisions,2 including an increasing need to demonstrate value, an emphasis on improved population health, an increasing number of practices becoming employees of large integrated delivery networks, reduced FFS reimbursements that are more closely linked to performance metrics, and increasing demands for risk-based contracts.3 In this article, I dive more deeply into these last two trends (declining FFS and the rise of APMs) and consider strategies gastroenterology practices can take in response.

Changes in fee for service

The ACA directed the secretary of Health and Human Services to establish a formal process to review potentially misvalued procedure codes. Compared with the pre-ACA fee schedule, the final 2016 Medicare Physician Fee Schedule includes cuts to professional fees for upper endoscopy, endoscopic retrograde cholangiopancreatography, endoscopic ultrasound, and colonoscopy. At the same time, over the past decade, facility fees paid for procedures performed in hospital outpatient departments have increased. Those to ambulatory surgery centers have gradually increased, although they still remain far below pre-2008 levels. Thus, the full economic impact of fee revaluation on an individual gastroenterology practice depends on whether it collects associated facility and ancillary fees.4

In addition, in the 2016 fee schedule, the Centers for Medicare & Medicaid Services described its intention to remove the value of moderate sedation from all gastrointestinal procedures. This is to prevent paying twice for sedation in procedures that involve anesthesiology professionals (i.e., one payment to the endoscopist as part of the overall procedure fee and a separate payment to the anesthesia professional for sedation they provide and bill for separately). The American Medical Association/Specialty Society Relative Value Scale Update Committee, using survey data from the GI specialty societies and other specialties that perform their own moderate sedation, has submitted recommendations for the value of a new set of moderate sedation Current Procedural Terminology codes to the CMS. The agency is expected to provide the specifics on how it will remove moderate sedation from the GI procedure codes in the 2017 Medicare Physician Fee Schedule Proposed Rule. The more that moderate sedation is valued, the less that endoscopic procedures will be valued. Consequently, gastroenterologists who rely on anesthesiology professionals to sedate their patients will generate less revenue per procedure, unless they rearrange contracts with anesthesia providers. Gastroenterologists who perform moderate sedation will not be impacted, because the sum of the value of the new moderate sedation code plus the underlying endoscopic procedure code will equal the original value of the procedure.

Beyond revaluing services, the CMS outlined its rather ambitious goal “to have 85% of all Medicare fee-for-service (FFS) payments tied to quality or value by 2016, and 90% by 2018.”5 Currently this includes the Physician Quality Reporting System (PQRS), which requires gastroenterologists to report performance on either three or more individual PQRS measures or one PQRS measures group (collection of related individual measures) or face a 2% Medicare payment penalty. It also includes the value-based payment modifier, through which by 2017 all practices with better-than-average quality (linked to PQRS measures) and lower costs will receive bonus payments, whereas those with worse-than-average performance (or who choose not to report) will be penalized.

MACRA changes all of this. Starting in 2019, the meaningful use incentive program, PQRS, and value-based payment modifier will be consolidated into the Merit-Based Incentive Payment System (MIPS). Physicians who elect to remain on an FFS tract will receive a 0-100 composite performance score based on quality (30%), resource use (30%), meaningful use (25%), and clinical practice improvement activities (15%). At the start of a performance period, a composite threshold necessary to achieve incentive payments and avoid penalties will be determined. Throughout the performance period, physicians will receive timely feedback on their performance. At year’s end, those below the threshold will face penalties proportionate to their performance (as much as 4% in 2019 and going up to 9% in 2022), those at threshold will not receive a payment adjustment, and those above threshold will receive bonuses proportionate to their performance (although overall payments will be capped at $500 million).

Alternative payment models

The CMS’s ultimate goal is to move beyond FFS and have “30% of Medicare payments tied to quality or value through APMs by the end of 2016 and 50% of payments by the end of 2018.”5 MACRA supports this ambitious goal: Starting in 2019, providers who “sufficiently” participate in APMs will receive 5% across-the-board bonuses. The three main APMs are bundled payments, accountable care organizations (ACOs), and patient-centered medical homes.

A bundled payment is a single fixed price paid to cover services for a specific episode of care. Depending on how an episode is defined, the bundle may encompass all professional fees, facility fees, and medical device and supply costs for a given service, including postacute care and any complications. If costs are reduced beyond the already discounted price of the bundle and quality metrics are achieved, then participants share the savings. Conversely, if costs exceed the bundled payment amount, then participants lose money. Unlike FFS, bundling incentivizes participants to coordinate care, reduce complications and unnecessary services, and cut purchasing costs.

To date, the CMS has launched three bundling programs. The Acute Care Episode Demonstration Project provided hospitals and clinicians a bundled payment to cover orthopedic and cardiovascular procedure–related episodes of care. This program reduced Medicare costs, primarily because the bundle payment was lower than what the sum of individual payments would have been. Providers were able to cope mainly by reducing their surgical implant costs. Second, more than 6,000 providers are currently participating in Medicare’s Bundled Payments for Care Improvement Program. The results of this program have not yet been released. Third, the CMS recently announced the Comprehensive Care for Joint Replacement Program under which hospitals and physicians in 67 metropolitan areas will be required to participate. Mandatory participation signals the CMS’s strong motivation to shift away from FFS. Beyond Medicare, many commercial insurers offer bundled payment programs, primarily for cardiovascular and orthopedic conditions.⁶ Although these programs are promising, it is technically challenging to define what is in a bundle, and to adequately risk adjust and mitigate random variation in spending for certain episodes of care. Providers are also challenged to find ways to divide payment among participants, coordinate all care, and accept financial risk.^7,8 The American Gastroenterological Association recently published a bundled payment framework for screening and surveillance colonoscopy.⁹ Bundling other gastroenterology services will be more challenging.

Whereas bundled-care programs focus on a discrete service (e.g., knee replacement or colonoscopy), ACOs are integrated groups of providers who jointly assume responsibility for the cost and quality of all care delivered to a defined population. The ACA requires ACOs to have formal legal, leadership, and management structures; care for at least 5,000 Medicare beneficiaries; fulfill certain patient-centeredness criteria; measure and report quality and cost data; and coordinate care. Different payment models incentivize ACOs to reduce costs and improve quality of care. ACOs operating under a one-sided shared savings model receive FFS payments for each service delivered, along with a bonus for reducing costs below a spending target and meeting quality requirements. There are no potential financial penalties. Alternatively, ACOs operating under a two-sided risk-savings model share a greater proportion of cost savings, in exchange for potential financial penalties if the cost of care exceeds target spending.

To date, Medicare-sponsored ACOs have produced mixed results. In 2014 only 92 of the 322 Medicare Shared Savings ACOs were able to reduce spending below a predetermined benchmark by a predetermined amount (2%-3%) while meeting quality scores, thereby earning a bonus ($341 million in total). Similarly, of the original 32 pioneer ACOs, which by definition are more experienced at managing population health and more willing to take on financial risk, 13 dropped out of the program, and in 2014, only 11 generated enough savings to earn a payout ($82 million in total), whereas 5 incurred financial penalties ($9 million in total) for costs exceeding target thresholds.¹⁰ In total, after paying out bonuses, the ACO program cost Medicare a net loss of nearly $3 million, far from the $10-$240 million Medicare had previously projected it would save through the ACO program.¹¹ Clearly, ACOs are not a quick fix for all that ails health care. For many ACOs, the major start-up requirements (time, capital investments, and so forth) needed to manage a population may not be worthwhile.¹² Nonetheless, the CMS recently launched the Next Generation ACO model through which 21 participating ACOs will assume higher levels of financial risk (possibly capitated payments) in exchange for greater potential rewards. Similarly, beyond Medicare, there are also many Medicaid-sponsored ACOs and hundreds of commercial payer-sponsored ACOs.¹³

Finally, practices can qualify for APM status without accepting bundled payments or joining an ACO by qualifying as a patient-centered medical home. One option for gastroenterologists and other specialists is the National Committee for Quality Assurance’s patient-centered specialty practice designation, available to practices that successfully demonstrate their ability to track and coordinate care with primary care providers and other specialists, offer timely appointments and responses to telephone and electronic messages, use evidence-based tools to manage care for specific patient populations, develop patient-centered care plans, and measure and improve performance.¹⁴

Consolidation

Health insurers are merging to increase scale (and negotiating power), enhance efficiency (reducing administrative costs makes more room for profits), and diversify their businesses. Recently proposed acquisitions will bring “the big five” health insurers to the “big three.” Likewise, health care systems are rapidly acquiring hospitals and physician groups, so much so that today half of all American health care markets are now considered highly concentrated, and none are considered highly competitive.¹⁵ Today only 35% of all physicians are independently employed.¹⁶ Physicians employed by health systems trade their complete autonomy to offset declining reimbursement, reduce operating expenses (including health information technology costs), improve work-life balance, and mitigate unknown risks.

Proponents contend that these mergers allow health care systems to better coordinate care, improve care experiences, accommodate new payment models, and assemble the building blocks needed to form ACOs and other integrated care models. Critics argue that locally dominant systems drive volume (by tightening referral relationships and gaining new market share) and increase costs (through enhanced negotiating leverage and by reclassifying newly acquired physician practices as part of the hospital, thereby generating facility fees). It is unclear whether consolidation results in better outcomes or simply increases overall costs.¹⁷

Strategic imperatives

What should gastroenterologists do? First, recognize that FFS is not going away anytime soon.¹⁸ Most APMs are still largely in their experimentation phase, and it remains unclear which models will work and which will be broadly adopted. Still, it is unrealistic to expect FFS to indefinitely persist as the dominant payment model. For some services FFS may no longer be a payment option (e.g., Medicare’s BCPI [Bundled Payments for Care Improvement]). For others, FFS rates may become so unattractive that APMs seem necessary. Finally, APMs may allow some practices to capture a greater proportion of overall clinical revenue (e.g., academic practices that perform endoscopic procedures within hospital outpatient departments) and to develop new models that meaningfully improve care. Today’s gastroenterology practices must therefore operate on two separate tracks: an FFS track that rewards volume (most practices are optimized for this) and an alternative payment track that rewards value (few practices can accommodate these on their own). The degree and speed with which practices should reorient to the alternative payment track depends on the type of practice and the specific local health care market. But even practices operating in slower-to-evolve markets should start preparing for the APMs, no matter how far off in the distance they may seem. I recommend the following six steps:

1. Integrate. To participate in APMs, preserve referral streams, and maintain negotiating leverage with health plans, independent, community-based practices may need to affiliate or merge with other physician groups, or align with or be acquired by a health care system.¹⁹ Academic practices are challenged to define their role within health care systems that are rapidly adding primary care practices, and often community gastroenterology practices, too.

2. Collaborate and communicate. To deliver high-value care to populations of patients, gastroenterologists must closely collaborate and clearly communicate with primary care physicians and other specialists. Collaborative care agreements can help guide these relationships.²⁰3. Develop new models of care. Patients with more routine GI and liver-related problems may be served more cost effectively by midlevel providers²¹ or innovative solutions, such as e-consultations.²² Patients with complex, chronic GI and liver diseases may be best served by multidisciplinary care teams (e.g., gastroenterologists alongside midlevel providers, nurses, care managers, psychologists, and/or pharmacists) who use clinical information systems to identify high-risk patients and to encourage evidence-based decision making, and who support patients to self-manage their own conditions.²³ Previously infeasible in a purely FFS world, these models are encouraged by APMs.

4. Care for common, costly conditions. Most gastroenterology practices have built robust colorectal cancer screening programs, sometimes at the expense of cognitive-based services. In today’s more accountable world, practices that can effectively manage common, costly conditions, such as inflammatory bowel disease, functional GI disorders, and advanced liver diseases, will be rewarded better than before and will be more highly sought as partners.

5. Understand and contain costs. The timely, accurate data needed to effectively respond to APMs are challenging to come by.¹⁹ Individual clinicians and group practices can roughly gauge their costs of care for Medicare beneficiaries, compared with other practices, using CMS Quality Resource Utilization Reports. Local commercial insurers may be willing to share cost profiles with interested practices. Strategies to reduce costs may include shifting clinically appropriate patients to more cost-effective settings (especially important for academic practices that see the bulk of their patients in costly hospital outpatient departments), standardizing endoscopy supplies and devices, using anesthesia services more selectively, and preferentially prescribing generic drugs, among others.

6. Measure and demonstrate value. Despite the inherent limitations of performance measurement,²⁴ it is imperative that practices measure and report the value of care to their patients, community, and payers so that they are preferred partners and not locked out of insurance or referral networks. Improving patient experiences is intrinsically worthwhile²⁵ and also makes good business sense.²⁶

References

1. Miller, H.D. Creating payment systems to accelerate value-driven health care: Issues and options for policy reform. New York: The Commonwealth Fund, 2007.

2. Allen, J.I. The road ahead. Clin Gastroenterol Hepatol. 2012;10:692–6.

3. Allen, J.I. Health care reform 3.0: The road gets bumpy. Clin Gastroenterol Hepatol. 2013;11:1527-8.

4. Dorn, S.D., Vesy C.J. Medicare’s revaluation of gastrointestinal endoscopic procedures: Implications for academic and community-based practices. Clin Gastroenterol Hepatol. 2016 (in press).

5. Burwell, S.M. Setting value-based payment goals: HHS efforts to improve U.S. health care (N Engl J Med. 2015;372:897–9).

6. The Advisory Board Company. Commercial Bundled Payment Tracker, 2016.

7. Mechanic, R.E. Mandatory Medicare bundled payment – is it ready for prime time? N Engl J Med. 2015;373:1291–3.

8. The National Commission on Physician Payment Reform. Physician Payment Report, 2013.

9. Brill, J.V., Jain, R., Margolis, P.S., et al. A bundled payment framework for colonoscopy performed for colorectal cancer screening or surveillance. Gastroenterology. 2014;146:849–53, e9.

10. Evans, M. Few Medicare ACOs earned bonuses in 2014. Mod Healthc (2015). Available at: www.modernhealthcare.com/article/20150825/NEWS/150829922. Accessed Nov. 14, 2015.

11. Rau, J., Gold, J. Medicare yet to save money through heralded medical payment model. Kaiser Health News. Available at: http://khn.org/news/medicare-yet-to-save-money-through-heralded-medical-payment-model. Accessed Nov. 14, 2015.

12. Goldmsith, J., Kaufman, N. Pioneer ACOs: Anatomy of a victory. Health Affairs Blog, 2015.

13. Tu, T., Muhlestein, D., Kocot, S.L., et al. The impact of accountable care: Origins and future of accountable care organizations. Washington, D.C.: Brookings Institution, 2015.

14. NCQA. Patient-centered specialty practice frequently asked questions.

15. Xu, T., Wu, A.W., Makary, M.A. The potential hazards of hospital consolidation: Implications for quality, access, and price. JAMA. 2015;314:1337–8.

16. The Physician’s Foundation. 2014 survey of America’s physicians. Practice patterns & perspectives: The Physician’s Foundation.

17. Tsai, T.C., Jha, A.K. Hospital consolidation, competition, and quality: Is bigger necessarily better? JAMA. 2014;312:29–30.

18. Ginsburg, P.B. Fee-for-service will remain a feature of major payment reforms, requiring more changes in Medicare physician payment. Health Aff (Millwood). 2012;31:1977–83.

19. Friedberg, M.W., Chen, P.G., White, C., et al. Effects of health care payment models on physician practice in the United States. Santa Monica, Calif.: RAND Corp., 2015.

20. Greenberg, J.O., Barnett, M.L., Spinks, M.A., et al. The “medical neighborhood”: Integrating primary and specialty care for ambulatory patients. JAMA Intern Med. 2014;174:454–7.

21. Dorn, S.D. Mid-level providers in gastroenterology. Am J Gastroenterol. 2010;105:246–51.

22. Wasfy, J.H., Rao, S.K., Kalwani, N., et al. Longer term impact of cardiology e-consults. Am Heart J. 2016;173:86–93.

23. Coleman, K., Austin, B.T., Brach, C., et al. Evidence on the chronic care model in the new millennium. Health Aff (Millwood). 2009;28:75–85.

24. Dorn, S.D. Quality measurement in gastroenterology: confessions of a realist. Clin Gastroenterol Hepatol. 2016;14:648–50.

25. Berwick, D.M. Measuring physicians’ quality and performance: adrift on Lake Wobegon. JAMA. 2009;302:2485-6.

26. Browne, K., Roseman, D., Shaller, D., et al. Analysis & commentary. Measuring patient experience as a strategy for improving primary care. Health Aff (Millwood). 2010;29:921–5.

Dr. Dorn is vice chief, division of gastroenterology and hepatology, associate professor of medicine, health policy & management, University of North Carolina at Chapel Hill. He has received honoraria for consulting and presentations on health reform from AbbVie and Olympus.

Maternal antibodies against hepatitis blunt the immune response to the hepatitis B vaccine in newborns, but the booster dose is unaffected by maternal antibodies, a study found.

Previous research also has identified a suppressed response to vaccination due to maternal antibodies with vaccines such as the measles, hepatitis A, mumps and tetanus vaccines.

CDC/Dr. Erskine Palmer

“Maternal antibodies are a double-edged sword for infants,” wrote X. Chen of the Zhongnan Hospital of Wuhan (China) University, and colleagues (J Viral Hepat. 2016 Jul 29. doi: 10.1111/jvh.12572). “These neutralizing antibodies can protect neonates against most infectious diseases in early life; however, as shown in the study here, these antibodies can also suppress the immune response of infants to vaccines.”

The researchers first assessed transplacental transfer of antibodies by measuring anti–hepatitis B antibodies in 90 mothers and their newborns. The mothers were all positive for anti–hepatitis B antibodies with a median titer of 250. Before the infants had been vaccinated, 97% were positive for anti–hepatitis B antibodies. Among infants whose mothers had titers above 100 IU/L, 100% were positive for antibodies.

Then the researchers measured titers and rate of anti–hepatitis B positivity in 1,055 mothers and their 1,063 infants, aged 7-24 months, after the babies had received doses of the 10 mcg HBV vaccine at ages 0, 1 and 6 months, per the recommended schedule in China. In the United States, infants are recommended to receive the vaccine at birth, at 1-4 months, and then at 6-18 months.

Among the 405 mothers with antibodies of less than 10 IU/L, 89% of their newborns responded sufficiently to the vaccine to be positive for anti–hepatitis B antibodies. Among the 451 mothers with antibodies from 10-499 IU/L, 85% of the infants had positivity, and among the 207 mothers with antibodies of 500 IU/L and higher, 77% of the infants were positive for anti–hepatitis B antibodies.

Titers followed the same inverse pattern. The median titer was 169 in infants whose mothers had low titers, but the median titer was 79 in infants of mothers with high titers. When mothers with titers in the middle range, the infants’ median titer was 141.

Among 162 newborns who tested negative for anti–hepatitis B antibodies after receiving all three doses of the vaccine, 92% showed positivity for the antibodies after receiving a “catch-up” booster dose, without significant interference from maternal antibodies. Of another 11 infants still lacking positivity, 8 assessed 1 month later, achieved it after a second catch-up booster, suggesting “the suppression effects of the maternal anti-HBVs can be overcome.”

The research was funded by the Hongkong Zeshan Foundation, and the authors reported having no disclosures.

Maternal antibodies against hepatitis blunt the immune response to the hepatitis B vaccine in newborns, but the booster dose is unaffected by maternal antibodies, a study found.

Previous research also has identified a suppressed response to vaccination due to maternal antibodies with vaccines such as the measles, hepatitis A, mumps and tetanus vaccines.

CDC/Dr. Erskine Palmer

“Maternal antibodies are a double-edged sword for infants,” wrote X. Chen of the Zhongnan Hospital of Wuhan (China) University, and colleagues (J Viral Hepat. 2016 Jul 29. doi: 10.1111/jvh.12572). “These neutralizing antibodies can protect neonates against most infectious diseases in early life; however, as shown in the study here, these antibodies can also suppress the immune response of infants to vaccines.”

The researchers first assessed transplacental transfer of antibodies by measuring anti–hepatitis B antibodies in 90 mothers and their newborns. The mothers were all positive for anti–hepatitis B antibodies with a median titer of 250. Before the infants had been vaccinated, 97% were positive for anti–hepatitis B antibodies. Among infants whose mothers had titers above 100 IU/L, 100% were positive for antibodies.

Then the researchers measured titers and rate of anti–hepatitis B positivity in 1,055 mothers and their 1,063 infants, aged 7-24 months, after the babies had received doses of the 10 mcg HBV vaccine at ages 0, 1 and 6 months, per the recommended schedule in China. In the United States, infants are recommended to receive the vaccine at birth, at 1-4 months, and then at 6-18 months.

Among the 405 mothers with antibodies of less than 10 IU/L, 89% of their newborns responded sufficiently to the vaccine to be positive for anti–hepatitis B antibodies. Among the 451 mothers with antibodies from 10-499 IU/L, 85% of the infants had positivity, and among the 207 mothers with antibodies of 500 IU/L and higher, 77% of the infants were positive for anti–hepatitis B antibodies.

Titers followed the same inverse pattern. The median titer was 169 in infants whose mothers had low titers, but the median titer was 79 in infants of mothers with high titers. When mothers with titers in the middle range, the infants’ median titer was 141.

Among 162 newborns who tested negative for anti–hepatitis B antibodies after receiving all three doses of the vaccine, 92% showed positivity for the antibodies after receiving a “catch-up” booster dose, without significant interference from maternal antibodies. Of another 11 infants still lacking positivity, 8 assessed 1 month later, achieved it after a second catch-up booster, suggesting “the suppression effects of the maternal anti-HBVs can be overcome.”

The research was funded by the Hongkong Zeshan Foundation, and the authors reported having no disclosures.

Maternal antibodies against hepatitis blunt the immune response to the hepatitis B vaccine in newborns, but the booster dose is unaffected by maternal antibodies, a study found.

Previous research also has identified a suppressed response to vaccination due to maternal antibodies with vaccines such as the measles, hepatitis A, mumps and tetanus vaccines.

CDC/Dr. Erskine Palmer

“Maternal antibodies are a double-edged sword for infants,” wrote X. Chen of the Zhongnan Hospital of Wuhan (China) University, and colleagues (J Viral Hepat. 2016 Jul 29. doi: 10.1111/jvh.12572). “These neutralizing antibodies can protect neonates against most infectious diseases in early life; however, as shown in the study here, these antibodies can also suppress the immune response of infants to vaccines.”

The researchers first assessed transplacental transfer of antibodies by measuring anti–hepatitis B antibodies in 90 mothers and their newborns. The mothers were all positive for anti–hepatitis B antibodies with a median titer of 250. Before the infants had been vaccinated, 97% were positive for anti–hepatitis B antibodies. Among infants whose mothers had titers above 100 IU/L, 100% were positive for antibodies.

Then the researchers measured titers and rate of anti–hepatitis B positivity in 1,055 mothers and their 1,063 infants, aged 7-24 months, after the babies had received doses of the 10 mcg HBV vaccine at ages 0, 1 and 6 months, per the recommended schedule in China. In the United States, infants are recommended to receive the vaccine at birth, at 1-4 months, and then at 6-18 months.

Among the 405 mothers with antibodies of less than 10 IU/L, 89% of their newborns responded sufficiently to the vaccine to be positive for anti–hepatitis B antibodies. Among the 451 mothers with antibodies from 10-499 IU/L, 85% of the infants had positivity, and among the 207 mothers with antibodies of 500 IU/L and higher, 77% of the infants were positive for anti–hepatitis B antibodies.

Titers followed the same inverse pattern. The median titer was 169 in infants whose mothers had low titers, but the median titer was 79 in infants of mothers with high titers. When mothers with titers in the middle range, the infants’ median titer was 141.

Among 162 newborns who tested negative for anti–hepatitis B antibodies after receiving all three doses of the vaccine, 92% showed positivity for the antibodies after receiving a “catch-up” booster dose, without significant interference from maternal antibodies. Of another 11 infants still lacking positivity, 8 assessed 1 month later, achieved it after a second catch-up booster, suggesting “the suppression effects of the maternal anti-HBVs can be overcome.”

The research was funded by the Hongkong Zeshan Foundation, and the authors reported having no disclosures.

Myeloma-induced osteolytic bone lesions were reduced by suppressing expression of thymidine phosphorylase (TP), according to Huan Liu of the University of Texas MD Anderson Cancer Center in Houston and associates.

In osteoblast progenitors, methylation of alpha-1/runt-related transcription factor 2 (RUNX2) and osterix was upregulated by TP, resulting in decreased bone formation. TP also upregulated methylation of interferon regulatory factor 8 (IRF8) and enhanced nuclear factor of activated T cells, cytoplasmic 1 protein (NFATc1), which increased bone resorption. Thymidine was catalyzed into thymine and 2-deoxy-d-ribose, which bound to integrins alphavbeta3 and alpha5beta1, activated PI3K/Akt signaling, and increased DNA methyltransferase 3A (DNMT3A) expression, the investigators found.

In an experiment, myeloma was established in severe combined immunodeficient mice, and the mice were injected with ARP-1 cells, which produce high levels of TP. The mice were then treated with 7-deazaxanthine or tipiracil hydrochloride, which reduced ARP-1-induced bone lesions, DNMT3A expression, and 2DDR levels in the serum of tumor-bearing mice.

“This model could facilitate the translation of these inhibitors into human studies of myeloma bone disease. Because TP is often expressed by other malignancies including breast, prostate, and lung cancer, these findings may also have broader implications for the genesis of bone metastasis caused by these and other tumors,” the investigators concluded.

Find the full study in Science Translational Medicine (doi:10.1126/scitranslmed.aad8949)

[email protected]

Myeloma-induced osteolytic bone lesions were reduced by suppressing expression of thymidine phosphorylase (TP), according to Huan Liu of the University of Texas MD Anderson Cancer Center in Houston and associates.

In osteoblast progenitors, methylation of alpha-1/runt-related transcription factor 2 (RUNX2) and osterix was upregulated by TP, resulting in decreased bone formation. TP also upregulated methylation of interferon regulatory factor 8 (IRF8) and enhanced nuclear factor of activated T cells, cytoplasmic 1 protein (NFATc1), which increased bone resorption. Thymidine was catalyzed into thymine and 2-deoxy-d-ribose, which bound to integrins alphavbeta3 and alpha5beta1, activated PI3K/Akt signaling, and increased DNA methyltransferase 3A (DNMT3A) expression, the investigators found.

In an experiment, myeloma was established in severe combined immunodeficient mice, and the mice were injected with ARP-1 cells, which produce high levels of TP. The mice were then treated with 7-deazaxanthine or tipiracil hydrochloride, which reduced ARP-1-induced bone lesions, DNMT3A expression, and 2DDR levels in the serum of tumor-bearing mice.

“This model could facilitate the translation of these inhibitors into human studies of myeloma bone disease. Because TP is often expressed by other malignancies including breast, prostate, and lung cancer, these findings may also have broader implications for the genesis of bone metastasis caused by these and other tumors,” the investigators concluded.

Find the full study in Science Translational Medicine (doi:10.1126/scitranslmed.aad8949)

[email protected]

Myeloma-induced osteolytic bone lesions were reduced by suppressing expression of thymidine phosphorylase (TP), according to Huan Liu of the University of Texas MD Anderson Cancer Center in Houston and associates.

In osteoblast progenitors, methylation of alpha-1/runt-related transcription factor 2 (RUNX2) and osterix was upregulated by TP, resulting in decreased bone formation. TP also upregulated methylation of interferon regulatory factor 8 (IRF8) and enhanced nuclear factor of activated T cells, cytoplasmic 1 protein (NFATc1), which increased bone resorption. Thymidine was catalyzed into thymine and 2-deoxy-d-ribose, which bound to integrins alphavbeta3 and alpha5beta1, activated PI3K/Akt signaling, and increased DNA methyltransferase 3A (DNMT3A) expression, the investigators found.

In an experiment, myeloma was established in severe combined immunodeficient mice, and the mice were injected with ARP-1 cells, which produce high levels of TP. The mice were then treated with 7-deazaxanthine or tipiracil hydrochloride, which reduced ARP-1-induced bone lesions, DNMT3A expression, and 2DDR levels in the serum of tumor-bearing mice.

“This model could facilitate the translation of these inhibitors into human studies of myeloma bone disease. Because TP is often expressed by other malignancies including breast, prostate, and lung cancer, these findings may also have broader implications for the genesis of bone metastasis caused by these and other tumors,” the investigators concluded.

Find the full study in Science Translational Medicine (doi:10.1126/scitranslmed.aad8949)

[email protected]

Early and aggressive therapy may prevent or stabilize organ damage and disease-related complications in patients with juvenile dermatomyositis, according to new consensus-based recommendations for the management of the disorder.

Overall, the recommendations – a project of the Single Hub and Access Point for Pediatric Rheumatology in Europe (SHARE) initiative – include 7 overarching principles, 33 recommendations on diagnosis, and 19 recommendations on therapy that were accepted with greater than 80% agreement among experts. The recommendations, which address the assessment of skin, muscle, and major organ involvement and treatment suggestions at disease onset and in refractory cases, fill a void in the area of evidence-based guidelines for this rare disease within the group of pediatric rheumatic diseases, according to Felicitas Bellutti Enders, MD, of University Medical Center Utrecht (the Netherlands) and her colleagues.

Elizabeth M. Dugan, Adam M. Huber, Frederick W. Miller, Lisa G. Rider / CC-BY-SA-3.0

“Clear recommendations can help clinicians in the care of patients with JDM [juvenile dermatomyositis] as no international consensus regarding diagnosis and treatment is currently available and management therefore varies,” they wrote (Ann Rheum Dis. 2016 Aug 11. doi: 10.1136/annrheumdis-2016-209247).

The consensus committee, including 19 experienced pediatric rheumatologists and 2 experts in pediatric exercise physiology and physical therapy, developed recommendations based on a validated systematic literature review. The recommendations were evaluated by an online survey and then discussed at two subsequent consensus meetings.

The overarching principles accepted by more than 80% of respondents (100% in all but number 4 below), hold that:

1) All children with suspected idiopathic inflammatory myopathies should be referred to a specialized center.

2) High-risk patients need immediate/urgent referral to a specialized center.

3) Patient-/parent-reported outcomes measures are helpful when assessing disease activity and should be used at diagnosis and during disease monitoring.

4) Validated tools such as the Childhood Health Assessment Questionnaire, patient/parent visual analog scale and Juvenile Dermatomyositis Multi-dimensional Assessment Report should be used to measure health status.

5) All children with JDM should have disease activity (muscle, skin, major organ) assessed regularly in a standardized way, using tools such as the Disease Activity Score.

6) All children with JDM should have disease damage assessed at least yearly using a standardized disease damage measure, such as the Myositis Damage index.

7) All patients with JDM should have the opportunity to be registered within a research registry/repository such as the Euromyositis registry.

The consensus process also yielded both general and specific recommendations for diagnosis and management – also with 100% agreement in almost all cases – addressing investigations to consider in all those with a JDM diagnosis (muscle enzymes, full blood count, renal function and liver function tests, and infection screen – to name a few), ways that MRI can be used (both for diagnosis and disease activity monitoring), the use of muscle biopsy (use in all cases involving atypical presentation), and assessment of calcinosis and skin, lung, and cardiac involvement.

Treatment recommendations address sun protection (encourage routine use of sunblock), exercise (should be safe and appropriate and monitored by a physiotherapist), corticosteroid use (administer systematically either orally or intravenously in moderate to severe JDM and wean as the patient shows clinical improvement), use of intravenous immunoglobulin (a useful adjunct for resistant disease, especially when skin features are prominent), and the use of anti–tumor necrosis factor therapies (consider in refractory disease; infliximab or adalimumab are favored over etanercept), as well as other treatments.

The recommendations state that while there is no high-level evidence of when to stop therapy, consideration may be given to withdrawing treatment if a patient has been off steroids and in remission on methotrexate or an alternative disease-modifying antirheumatic drug [DMARD] for at least 1 year.

The management of JDM is complex and warrants a multidisciplinary approach, involving physiotherapists, specialist nurses, pediatric rheumatologists, and other specialists as needed, the authors wrote, noting that the mainstay of therapy is high-dose corticosteroids initially in combination with DMARDS.

However, the evidence base for treatment is limited and “often confined to small case-controlled studies, with the exception of two randomized controlled trials,” they said.

Similarly, there is no high-level evidence regarding when to stop immunosuppressive therapy, but the expert group suggested considering the withdrawal of methotrexate or alternative DMARD once the patient is in remission and off steroids for a minimum of 1 year.

The authors concluded that “this SHARE initiative is based on expert opinion informed by the best available evidence and provides recommendations ... with a view to improving the outcome for patients with JDM in Europe.

“It will now be important to broaden discussion and test acceptability of these to the wider community,” they wrote.

The SHARE initiative is funded by a grant from the European Agency for Health and Consumers. Dr. Enders disclosed a relationship with the Valeria e Ettore Bossi Foundation. Her coauthors reported financial or other relationships with Roche/Chugai, AbbVie, Pfizer, Novartis, Bristol-Myers Squibb, SOBI, Medac, The Myositis Association, Neopharm, GlaxoSmithKline, and/or Genzyme.

[email protected]

Early and aggressive therapy may prevent or stabilize organ damage and disease-related complications in patients with juvenile dermatomyositis, according to new consensus-based recommendations for the management of the disorder.

Overall, the recommendations – a project of the Single Hub and Access Point for Pediatric Rheumatology in Europe (SHARE) initiative – include 7 overarching principles, 33 recommendations on diagnosis, and 19 recommendations on therapy that were accepted with greater than 80% agreement among experts. The recommendations, which address the assessment of skin, muscle, and major organ involvement and treatment suggestions at disease onset and in refractory cases, fill a void in the area of evidence-based guidelines for this rare disease within the group of pediatric rheumatic diseases, according to Felicitas Bellutti Enders, MD, of University Medical Center Utrecht (the Netherlands) and her colleagues.

Elizabeth M. Dugan, Adam M. Huber, Frederick W. Miller, Lisa G. Rider / CC-BY-SA-3.0

“Clear recommendations can help clinicians in the care of patients with JDM [juvenile dermatomyositis] as no international consensus regarding diagnosis and treatment is currently available and management therefore varies,” they wrote (Ann Rheum Dis. 2016 Aug 11. doi: 10.1136/annrheumdis-2016-209247).

The consensus committee, including 19 experienced pediatric rheumatologists and 2 experts in pediatric exercise physiology and physical therapy, developed recommendations based on a validated systematic literature review. The recommendations were evaluated by an online survey and then discussed at two subsequent consensus meetings.

The overarching principles accepted by more than 80% of respondents (100% in all but number 4 below), hold that:

1) All children with suspected idiopathic inflammatory myopathies should be referred to a specialized center.

2) High-risk patients need immediate/urgent referral to a specialized center.

3) Patient-/parent-reported outcomes measures are helpful when assessing disease activity and should be used at diagnosis and during disease monitoring.

4) Validated tools such as the Childhood Health Assessment Questionnaire, patient/parent visual analog scale and Juvenile Dermatomyositis Multi-dimensional Assessment Report should be used to measure health status.

5) All children with JDM should have disease activity (muscle, skin, major organ) assessed regularly in a standardized way, using tools such as the Disease Activity Score.

6) All children with JDM should have disease damage assessed at least yearly using a standardized disease damage measure, such as the Myositis Damage index.

7) All patients with JDM should have the opportunity to be registered within a research registry/repository such as the Euromyositis registry.

The consensus process also yielded both general and specific recommendations for diagnosis and management – also with 100% agreement in almost all cases – addressing investigations to consider in all those with a JDM diagnosis (muscle enzymes, full blood count, renal function and liver function tests, and infection screen – to name a few), ways that MRI can be used (both for diagnosis and disease activity monitoring), the use of muscle biopsy (use in all cases involving atypical presentation), and assessment of calcinosis and skin, lung, and cardiac involvement.

Treatment recommendations address sun protection (encourage routine use of sunblock), exercise (should be safe and appropriate and monitored by a physiotherapist), corticosteroid use (administer systematically either orally or intravenously in moderate to severe JDM and wean as the patient shows clinical improvement), use of intravenous immunoglobulin (a useful adjunct for resistant disease, especially when skin features are prominent), and the use of anti–tumor necrosis factor therapies (consider in refractory disease; infliximab or adalimumab are favored over etanercept), as well as other treatments.

The recommendations state that while there is no high-level evidence of when to stop therapy, consideration may be given to withdrawing treatment if a patient has been off steroids and in remission on methotrexate or an alternative disease-modifying antirheumatic drug [DMARD] for at least 1 year.

The management of JDM is complex and warrants a multidisciplinary approach, involving physiotherapists, specialist nurses, pediatric rheumatologists, and other specialists as needed, the authors wrote, noting that the mainstay of therapy is high-dose corticosteroids initially in combination with DMARDS.

However, the evidence base for treatment is limited and “often confined to small case-controlled studies, with the exception of two randomized controlled trials,” they said.

Similarly, there is no high-level evidence regarding when to stop immunosuppressive therapy, but the expert group suggested considering the withdrawal of methotrexate or alternative DMARD once the patient is in remission and off steroids for a minimum of 1 year.

The authors concluded that “this SHARE initiative is based on expert opinion informed by the best available evidence and provides recommendations ... with a view to improving the outcome for patients with JDM in Europe.

“It will now be important to broaden discussion and test acceptability of these to the wider community,” they wrote.

The SHARE initiative is funded by a grant from the European Agency for Health and Consumers. Dr. Enders disclosed a relationship with the Valeria e Ettore Bossi Foundation. Her coauthors reported financial or other relationships with Roche/Chugai, AbbVie, Pfizer, Novartis, Bristol-Myers Squibb, SOBI, Medac, The Myositis Association, Neopharm, GlaxoSmithKline, and/or Genzyme.

[email protected]

Early and aggressive therapy may prevent or stabilize organ damage and disease-related complications in patients with juvenile dermatomyositis, according to new consensus-based recommendations for the management of the disorder.

Overall, the recommendations – a project of the Single Hub and Access Point for Pediatric Rheumatology in Europe (SHARE) initiative – include 7 overarching principles, 33 recommendations on diagnosis, and 19 recommendations on therapy that were accepted with greater than 80% agreement among experts. The recommendations, which address the assessment of skin, muscle, and major organ involvement and treatment suggestions at disease onset and in refractory cases, fill a void in the area of evidence-based guidelines for this rare disease within the group of pediatric rheumatic diseases, according to Felicitas Bellutti Enders, MD, of University Medical Center Utrecht (the Netherlands) and her colleagues.

Elizabeth M. Dugan, Adam M. Huber, Frederick W. Miller, Lisa G. Rider / CC-BY-SA-3.0

“Clear recommendations can help clinicians in the care of patients with JDM [juvenile dermatomyositis] as no international consensus regarding diagnosis and treatment is currently available and management therefore varies,” they wrote (Ann Rheum Dis. 2016 Aug 11. doi: 10.1136/annrheumdis-2016-209247).

The consensus committee, including 19 experienced pediatric rheumatologists and 2 experts in pediatric exercise physiology and physical therapy, developed recommendations based on a validated systematic literature review. The recommendations were evaluated by an online survey and then discussed at two subsequent consensus meetings.

The overarching principles accepted by more than 80% of respondents (100% in all but number 4 below), hold that:

1) All children with suspected idiopathic inflammatory myopathies should be referred to a specialized center.

2) High-risk patients need immediate/urgent referral to a specialized center.

3) Patient-/parent-reported outcomes measures are helpful when assessing disease activity and should be used at diagnosis and during disease monitoring.

4) Validated tools such as the Childhood Health Assessment Questionnaire, patient/parent visual analog scale and Juvenile Dermatomyositis Multi-dimensional Assessment Report should be used to measure health status.

5) All children with JDM should have disease activity (muscle, skin, major organ) assessed regularly in a standardized way, using tools such as the Disease Activity Score.

6) All children with JDM should have disease damage assessed at least yearly using a standardized disease damage measure, such as the Myositis Damage index.

7) All patients with JDM should have the opportunity to be registered within a research registry/repository such as the Euromyositis registry.

The consensus process also yielded both general and specific recommendations for diagnosis and management – also with 100% agreement in almost all cases – addressing investigations to consider in all those with a JDM diagnosis (muscle enzymes, full blood count, renal function and liver function tests, and infection screen – to name a few), ways that MRI can be used (both for diagnosis and disease activity monitoring), the use of muscle biopsy (use in all cases involving atypical presentation), and assessment of calcinosis and skin, lung, and cardiac involvement.

Treatment recommendations address sun protection (encourage routine use of sunblock), exercise (should be safe and appropriate and monitored by a physiotherapist), corticosteroid use (administer systematically either orally or intravenously in moderate to severe JDM and wean as the patient shows clinical improvement), use of intravenous immunoglobulin (a useful adjunct for resistant disease, especially when skin features are prominent), and the use of anti–tumor necrosis factor therapies (consider in refractory disease; infliximab or adalimumab are favored over etanercept), as well as other treatments.

The recommendations state that while there is no high-level evidence of when to stop therapy, consideration may be given to withdrawing treatment if a patient has been off steroids and in remission on methotrexate or an alternative disease-modifying antirheumatic drug [DMARD] for at least 1 year.

The management of JDM is complex and warrants a multidisciplinary approach, involving physiotherapists, specialist nurses, pediatric rheumatologists, and other specialists as needed, the authors wrote, noting that the mainstay of therapy is high-dose corticosteroids initially in combination with DMARDS.

However, the evidence base for treatment is limited and “often confined to small case-controlled studies, with the exception of two randomized controlled trials,” they said.

Similarly, there is no high-level evidence regarding when to stop immunosuppressive therapy, but the expert group suggested considering the withdrawal of methotrexate or alternative DMARD once the patient is in remission and off steroids for a minimum of 1 year.

The authors concluded that “this SHARE initiative is based on expert opinion informed by the best available evidence and provides recommendations ... with a view to improving the outcome for patients with JDM in Europe.

“It will now be important to broaden discussion and test acceptability of these to the wider community,” they wrote.

The SHARE initiative is funded by a grant from the European Agency for Health and Consumers. Dr. Enders disclosed a relationship with the Valeria e Ettore Bossi Foundation. Her coauthors reported financial or other relationships with Roche/Chugai, AbbVie, Pfizer, Novartis, Bristol-Myers Squibb, SOBI, Medac, The Myositis Association, Neopharm, GlaxoSmithKline, and/or Genzyme.

[email protected]

VANCOUVER—Medications can help manage symptoms and prolong function in patients with dementia, even if the effects are modest and do not affect the underlying disease, according to an overview of dementia management provided at the 68th Annual Meeting of the American Academy of Neurology. Neurologists should bear in mind drug indications and patient diagnoses because certain drugs are indicated for Alzheimer’s disease dementia only, and it is unclear if they provide benefit in other forms of dementia.

Psychotropic medications also may play a role in treating behavioral and psychiatric symptoms, although it is important to first identify underlying causes that could trigger these symptoms, said Gregory S. Day, MD, MSc, Instructor in Neurology at Washington University in St. Louis.

Two Drug Types

Two types of medications are FDA-approved for the treatment of dementia: acetylcholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) and memantine, a partial NMDA-receptor antagonist. The FDA first approved an acetylcholinesterase inhibitor to treat dementia in 1993. Memantine was approved in 2003.

More recently, new formulations and dosages of those four drugs have been approved by the FDA, including a rivastigmine transdermal patch, a once-daily dose of memantine, and a donepezil and memantine combination pill.

Each medication requires a dose titration schedule. Donepezil is taken once daily; rivastigmine, galantamine, and memantine have once- and twice-daily formulations.

The acetylcholinesterase inhibitors are approved for the treatment of dementia due to Alzheimer’s disease. Rivastigmine also is FDA-approved for Parkinson’s disease dementia. Each drug also is used off label for the treatment of other forms of dementia, particularly dementia with Lewy bodies, Parkinson’s disease dementia, and vascular dementia, although it is unclear if off-label use in other forms of dementia provides benefit, Dr. Day said.

Donepezil and rivastigmine are approved for all stages of dementia, whereas galantamine is not approved for severe dementia because a controlled trial was never conducted in that patient population. A systematic review found no measurable effect of acetylcholinesterase inhibitors in patients with undifferentiated mild cognitive impairment.

In clinical trials, individuals with mild to moderate dementia due to Alzheimer’s disease taking acetylcholinesterase inhibitors had a modest benefit in function and cognition, compared with those taking placebo. “That benefit is relatively sustained throughout the course of the trial, but it is modest at best,” he said.

Adverse Events

Side effects of acetylcholinesterase inhibitors occur in 10% to 20% of patients. Gastrointestinal side effects (eg, nausea, vomiting, diarrhea, or anorexia) are the most common. Starting patients at a lower dose, varying the time of day the medication is taken, and taking the medication with food may alleviate some of these symptoms. Side effects may subside after one or two weeks, so it may be worth continuing the medication if the side effects are not severe, Dr. Day said.

Serious side effects can include syncope, convulsive seizures, loss of consciousness, and rhabdomyolysis. Less common side effects can include changes in cognitive or psychiatric comportment and cardiac complications. Rivastigmine in the transdermal formulation has an additional caveat because the patches can cause hypersensitivity reactions on the skin.

A 2015 review of drug prescribing records in North America found an increased risk of death in individuals taking acetylcholinesterase inhibitors. “Digging a little deeper, we see that this risk is almost entirely accounted for by rivastigmine,” Dr. Day said. “If anything, we could argue that people prescribed donepezil and galantamine have a lower risk of death than those not on these medications.”

Various factors could account for the elevated risk with rivastigmine. The drug has a slightly different mechanism of action and a longer half-life. Perhaps more importantly, as the only medication that can be delivered via transdermal patch, it may be prescribed to people with more severe forms of dementia who are no longer able to take medications by mouth, or who have agitation or psychoses. In addition, patients may forget to remove a patch and end up wearing multiple patches. Finally, rivastigmine is FDA-approved for Parkinson’s disease dementia, and the risk of death may be higher in those patients, Dr. Day said.

Memantine Alone and in Combination

Memantine is FDA-approved for patients with moderate to severe dementia due to Alzheimer’s disease. Pooled data indicate a small beneficial effect on cognition, activities of daily living, and behavior in this population. Despite multiple trials, there is no evidence of benefit of memantine in patients with mild dementia due to Alzheimer’s disease, and there is no convincing evidence to support the use of memantine in other forms of dementia.

Memantine is associated with fewer side effects than acetylcholinesterase inhibitors. Side effects can include dizziness, headache, and confusion. In clinical trials, more people taking placebo experienced side effects than those taking memantine. In patients with moderate to severe Alzheimer’s disease dementia receiving donepezil, the addition of memantine resulted in significantly better cognitive outcomes, function, and behavior. The addition of memantine is well tolerated in patients who are stable on an acetylcholinesterase inhibitor, said Dr. Day.

When to Stop Medication

Long-term observational data suggest a persistent effect of acetylcholinesterase inhibitors in Alzheimer’s disease dementia, with about five years of benefit in some trials. In a study that used admission to a nursing home as an outcome, the median time to admission in individuals not prescribed medication was around four to five years. The median time to admission in patients taking an acetylcholinesterase inhibitor was between eight and 10 years. There were not enough data for patients receiving combination therapy, but they may stay out of nursing homes a little longer. “There is this suggestion that use of these medications may delay admission to a nursing home,” he said.

Recommendations regarding stopping treatment vary. Some recommendations suggest that it is reasonable to discontinue these medications in patients who have transitioned to a severe dementia stage, while other recommendations suggest continuing the drugs indefinitely.

The American College of Physicians and American Academy of Family Physicians argue that if slowing decline is no longer a goal of treatment, memantine or acetylcholinesterase inhibitors are no longer appropriate.

If the family or patient’s “focus is shifting away from, ‘Let’s keep them as good as possible for as long as possible,’ to more, ‘Let’s keep them comfortable,’ then maybe removing a medication is part of that. I think it is very reasonable to consider,” Dr. Day said.

When considering stopping treatment, patients can stop medication for two weeks, and the patient and a caregiver can assess perceived cognition, function, and behaviors. If there is not a noticeable change, there is no need to restart the medication. “If they do perceive a decline, I think it is reasonable in that case to restart therapy if that is what they would like to do,” Dr. Day said. “Restarting, you simply revert back to the titration schedule that we would start whenever we’re prescribing these medications.”

Behavioral and Psychiatric Symptoms

Behavioral and psychiatric symptoms may occur in 60% to 90% of patients with dementia. These symptoms are distressing, add to caregiver burden, and are a major reason for institutionalization, Dr. Day said. Symptoms fall into four main categories: agitation, depression, apathy, and psychoses.

First, neurologists should screen for and treat any provoking causes, Dr. Day said. If a patient with a mild dementia syndrome suddenly presents with new agitation, delusions, or hallucinations, neurologists should investigate for oral ulceration, tooth problems, skin breakdown, urinary tract infection, dehydration, or visual or auditory impairment, which may contribute to or trigger these symptoms.

Otherwise, first-line treatment of agitation and psychoses entails atypical antipsychotic medication, although these treatments are not FDA-approved in patients with dementia. In patients with agitation alone, first-line therapy is behavioral interventions, although antipsychotic medications, mood stabilizers, or serotonergic compounds also can be considered. Depression and apathy may respond well to serotonergic compounds.

Black Box Warning

“Anytime we are prescribing antipsychotic medications to our patients with dementia, we need to be cognizant of the fact that these medications are prescribed off label and that they come with a black box warning,” Dr. Day said. Patients with dementia treated with antipsychotic drugs are at an increased risk of death. The risk of death appears to be greatest in those who are continued on antipsychotic medications across a three-month period. In addition, before prescribing antipsychotic medication, “you need to ask yourself—and maybe a nurse and a medical student—do you think that this patient could have dementia with Lewy bodies?” Patients with cortical Lewy bodies can experience significant morbidity or mortality due to severe neuroleptic sensitivity reactions.

Behavioral modification techniques are as effective as antipsychotic and antidepressant drugs, with fewer adverse effects, although they can be challenging to implement in a household environment.

Other Recommendations

When patients ask what else they can do to slow the progression of dementia, Dr. Day refers to seven modifiable risk factors identified in a 2014 Lancet Neurology article. These modifiable risk factors include physical inactivity, depression, midlife hypertension, midlife obesity, smoking, low educational attainment, and diabetes. In promoting physical activity, the CDC recommends a weekly exercise schedule of 150 minutes of moderate intensity activity or 75 minutes of more strenuous activity for individuals 65 and older. “That is a reasonable place to start,” Dr. Day said.

There is no clear demonstration of benefit of cognitive training, nor is there evidence to suggest that one cognitive training strategy is better than another. “If [patients] like doing sudoku or they like doing puzzles, Scrabble, or cards, that is what I am going to emphasize,” he said. “It is very reasonable to recommend that our patients remain cognitively and socially engaged, whatever that means for the individual patient.”

In addition, a Mediterranean-type diet high in olive oil, fresh vegetables, and fish may be worth recommending to patients and their caregivers, as it has been associated in studies with a lower risk of Alzheimer’s disease and mild cognitive impairment. Furthermore, neurologists should screen patients for sleep dysfunction, excessive alcohol intake, thyroid dysfunction, vitamin B12 deficiency, stroke risk factors, and medications that may impair cognition.

Other potential dementia therapies, including numerous interventions promoted online, have little or no evidence to support them. “We have a responsibility, in my opinion, to step in and provide some counseling regarding that to save our patients from committing to potentially expensive treatments with questionable efficacy,” said Dr. Day.

—Jake Remaly

VANCOUVER—Medications can help manage symptoms and prolong function in patients with dementia, even if the effects are modest and do not affect the underlying disease, according to an overview of dementia management provided at the 68th Annual Meeting of the American Academy of Neurology. Neurologists should bear in mind drug indications and patient diagnoses because certain drugs are indicated for Alzheimer’s disease dementia only, and it is unclear if they provide benefit in other forms of dementia.

Psychotropic medications also may play a role in treating behavioral and psychiatric symptoms, although it is important to first identify underlying causes that could trigger these symptoms, said Gregory S. Day, MD, MSc, Instructor in Neurology at Washington University in St. Louis.

Two Drug Types

Two types of medications are FDA-approved for the treatment of dementia: acetylcholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) and memantine, a partial NMDA-receptor antagonist. The FDA first approved an acetylcholinesterase inhibitor to treat dementia in 1993. Memantine was approved in 2003.

More recently, new formulations and dosages of those four drugs have been approved by the FDA, including a rivastigmine transdermal patch, a once-daily dose of memantine, and a donepezil and memantine combination pill.

Each medication requires a dose titration schedule. Donepezil is taken once daily; rivastigmine, galantamine, and memantine have once- and twice-daily formulations.

The acetylcholinesterase inhibitors are approved for the treatment of dementia due to Alzheimer’s disease. Rivastigmine also is FDA-approved for Parkinson’s disease dementia. Each drug also is used off label for the treatment of other forms of dementia, particularly dementia with Lewy bodies, Parkinson’s disease dementia, and vascular dementia, although it is unclear if off-label use in other forms of dementia provides benefit, Dr. Day said.

Donepezil and rivastigmine are approved for all stages of dementia, whereas galantamine is not approved for severe dementia because a controlled trial was never conducted in that patient population. A systematic review found no measurable effect of acetylcholinesterase inhibitors in patients with undifferentiated mild cognitive impairment.

In clinical trials, individuals with mild to moderate dementia due to Alzheimer’s disease taking acetylcholinesterase inhibitors had a modest benefit in function and cognition, compared with those taking placebo. “That benefit is relatively sustained throughout the course of the trial, but it is modest at best,” he said.

Adverse Events

Side effects of acetylcholinesterase inhibitors occur in 10% to 20% of patients. Gastrointestinal side effects (eg, nausea, vomiting, diarrhea, or anorexia) are the most common. Starting patients at a lower dose, varying the time of day the medication is taken, and taking the medication with food may alleviate some of these symptoms. Side effects may subside after one or two weeks, so it may be worth continuing the medication if the side effects are not severe, Dr. Day said.

Serious side effects can include syncope, convulsive seizures, loss of consciousness, and rhabdomyolysis. Less common side effects can include changes in cognitive or psychiatric comportment and cardiac complications. Rivastigmine in the transdermal formulation has an additional caveat because the patches can cause hypersensitivity reactions on the skin.

A 2015 review of drug prescribing records in North America found an increased risk of death in individuals taking acetylcholinesterase inhibitors. “Digging a little deeper, we see that this risk is almost entirely accounted for by rivastigmine,” Dr. Day said. “If anything, we could argue that people prescribed donepezil and galantamine have a lower risk of death than those not on these medications.”

Various factors could account for the elevated risk with rivastigmine. The drug has a slightly different mechanism of action and a longer half-life. Perhaps more importantly, as the only medication that can be delivered via transdermal patch, it may be prescribed to people with more severe forms of dementia who are no longer able to take medications by mouth, or who have agitation or psychoses. In addition, patients may forget to remove a patch and end up wearing multiple patches. Finally, rivastigmine is FDA-approved for Parkinson’s disease dementia, and the risk of death may be higher in those patients, Dr. Day said.

Memantine Alone and in Combination

Memantine is FDA-approved for patients with moderate to severe dementia due to Alzheimer’s disease. Pooled data indicate a small beneficial effect on cognition, activities of daily living, and behavior in this population. Despite multiple trials, there is no evidence of benefit of memantine in patients with mild dementia due to Alzheimer’s disease, and there is no convincing evidence to support the use of memantine in other forms of dementia.

Memantine is associated with fewer side effects than acetylcholinesterase inhibitors. Side effects can include dizziness, headache, and confusion. In clinical trials, more people taking placebo experienced side effects than those taking memantine. In patients with moderate to severe Alzheimer’s disease dementia receiving donepezil, the addition of memantine resulted in significantly better cognitive outcomes, function, and behavior. The addition of memantine is well tolerated in patients who are stable on an acetylcholinesterase inhibitor, said Dr. Day.

When to Stop Medication

Long-term observational data suggest a persistent effect of acetylcholinesterase inhibitors in Alzheimer’s disease dementia, with about five years of benefit in some trials. In a study that used admission to a nursing home as an outcome, the median time to admission in individuals not prescribed medication was around four to five years. The median time to admission in patients taking an acetylcholinesterase inhibitor was between eight and 10 years. There were not enough data for patients receiving combination therapy, but they may stay out of nursing homes a little longer. “There is this suggestion that use of these medications may delay admission to a nursing home,” he said.

Recommendations regarding stopping treatment vary. Some recommendations suggest that it is reasonable to discontinue these medications in patients who have transitioned to a severe dementia stage, while other recommendations suggest continuing the drugs indefinitely.

The American College of Physicians and American Academy of Family Physicians argue that if slowing decline is no longer a goal of treatment, memantine or acetylcholinesterase inhibitors are no longer appropriate.

If the family or patient’s “focus is shifting away from, ‘Let’s keep them as good as possible for as long as possible,’ to more, ‘Let’s keep them comfortable,’ then maybe removing a medication is part of that. I think it is very reasonable to consider,” Dr. Day said.

When considering stopping treatment, patients can stop medication for two weeks, and the patient and a caregiver can assess perceived cognition, function, and behaviors. If there is not a noticeable change, there is no need to restart the medication. “If they do perceive a decline, I think it is reasonable in that case to restart therapy if that is what they would like to do,” Dr. Day said. “Restarting, you simply revert back to the titration schedule that we would start whenever we’re prescribing these medications.”

Behavioral and Psychiatric Symptoms

Behavioral and psychiatric symptoms may occur in 60% to 90% of patients with dementia. These symptoms are distressing, add to caregiver burden, and are a major reason for institutionalization, Dr. Day said. Symptoms fall into four main categories: agitation, depression, apathy, and psychoses.

First, neurologists should screen for and treat any provoking causes, Dr. Day said. If a patient with a mild dementia syndrome suddenly presents with new agitation, delusions, or hallucinations, neurologists should investigate for oral ulceration, tooth problems, skin breakdown, urinary tract infection, dehydration, or visual or auditory impairment, which may contribute to or trigger these symptoms.

Otherwise, first-line treatment of agitation and psychoses entails atypical antipsychotic medication, although these treatments are not FDA-approved in patients with dementia. In patients with agitation alone, first-line therapy is behavioral interventions, although antipsychotic medications, mood stabilizers, or serotonergic compounds also can be considered. Depression and apathy may respond well to serotonergic compounds.

Black Box Warning

“Anytime we are prescribing antipsychotic medications to our patients with dementia, we need to be cognizant of the fact that these medications are prescribed off label and that they come with a black box warning,” Dr. Day said. Patients with dementia treated with antipsychotic drugs are at an increased risk of death. The risk of death appears to be greatest in those who are continued on antipsychotic medications across a three-month period. In addition, before prescribing antipsychotic medication, “you need to ask yourself—and maybe a nurse and a medical student—do you think that this patient could have dementia with Lewy bodies?” Patients with cortical Lewy bodies can experience significant morbidity or mortality due to severe neuroleptic sensitivity reactions.

Behavioral modification techniques are as effective as antipsychotic and antidepressant drugs, with fewer adverse effects, although they can be challenging to implement in a household environment.

Other Recommendations

When patients ask what else they can do to slow the progression of dementia, Dr. Day refers to seven modifiable risk factors identified in a 2014 Lancet Neurology article. These modifiable risk factors include physical inactivity, depression, midlife hypertension, midlife obesity, smoking, low educational attainment, and diabetes. In promoting physical activity, the CDC recommends a weekly exercise schedule of 150 minutes of moderate intensity activity or 75 minutes of more strenuous activity for individuals 65 and older. “That is a reasonable place to start,” Dr. Day said.

There is no clear demonstration of benefit of cognitive training, nor is there evidence to suggest that one cognitive training strategy is better than another. “If [patients] like doing sudoku or they like doing puzzles, Scrabble, or cards, that is what I am going to emphasize,” he said. “It is very reasonable to recommend that our patients remain cognitively and socially engaged, whatever that means for the individual patient.”

In addition, a Mediterranean-type diet high in olive oil, fresh vegetables, and fish may be worth recommending to patients and their caregivers, as it has been associated in studies with a lower risk of Alzheimer’s disease and mild cognitive impairment. Furthermore, neurologists should screen patients for sleep dysfunction, excessive alcohol intake, thyroid dysfunction, vitamin B12 deficiency, stroke risk factors, and medications that may impair cognition.

Other potential dementia therapies, including numerous interventions promoted online, have little or no evidence to support them. “We have a responsibility, in my opinion, to step in and provide some counseling regarding that to save our patients from committing to potentially expensive treatments with questionable efficacy,” said Dr. Day.

—Jake Remaly

VANCOUVER—Medications can help manage symptoms and prolong function in patients with dementia, even if the effects are modest and do not affect the underlying disease, according to an overview of dementia management provided at the 68th Annual Meeting of the American Academy of Neurology. Neurologists should bear in mind drug indications and patient diagnoses because certain drugs are indicated for Alzheimer’s disease dementia only, and it is unclear if they provide benefit in other forms of dementia.

Psychotropic medications also may play a role in treating behavioral and psychiatric symptoms, although it is important to first identify underlying causes that could trigger these symptoms, said Gregory S. Day, MD, MSc, Instructor in Neurology at Washington University in St. Louis.

Two Drug Types

Two types of medications are FDA-approved for the treatment of dementia: acetylcholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) and memantine, a partial NMDA-receptor antagonist. The FDA first approved an acetylcholinesterase inhibitor to treat dementia in 1993. Memantine was approved in 2003.

More recently, new formulations and dosages of those four drugs have been approved by the FDA, including a rivastigmine transdermal patch, a once-daily dose of memantine, and a donepezil and memantine combination pill.

Each medication requires a dose titration schedule. Donepezil is taken once daily; rivastigmine, galantamine, and memantine have once- and twice-daily formulations.

The acetylcholinesterase inhibitors are approved for the treatment of dementia due to Alzheimer’s disease. Rivastigmine also is FDA-approved for Parkinson’s disease dementia. Each drug also is used off label for the treatment of other forms of dementia, particularly dementia with Lewy bodies, Parkinson’s disease dementia, and vascular dementia, although it is unclear if off-label use in other forms of dementia provides benefit, Dr. Day said.

Donepezil and rivastigmine are approved for all stages of dementia, whereas galantamine is not approved for severe dementia because a controlled trial was never conducted in that patient population. A systematic review found no measurable effect of acetylcholinesterase inhibitors in patients with undifferentiated mild cognitive impairment.

In clinical trials, individuals with mild to moderate dementia due to Alzheimer’s disease taking acetylcholinesterase inhibitors had a modest benefit in function and cognition, compared with those taking placebo. “That benefit is relatively sustained throughout the course of the trial, but it is modest at best,” he said.

Adverse Events

Side effects of acetylcholinesterase inhibitors occur in 10% to 20% of patients. Gastrointestinal side effects (eg, nausea, vomiting, diarrhea, or anorexia) are the most common. Starting patients at a lower dose, varying the time of day the medication is taken, and taking the medication with food may alleviate some of these symptoms. Side effects may subside after one or two weeks, so it may be worth continuing the medication if the side effects are not severe, Dr. Day said.

Serious side effects can include syncope, convulsive seizures, loss of consciousness, and rhabdomyolysis. Less common side effects can include changes in cognitive or psychiatric comportment and cardiac complications. Rivastigmine in the transdermal formulation has an additional caveat because the patches can cause hypersensitivity reactions on the skin.

A 2015 review of drug prescribing records in North America found an increased risk of death in individuals taking acetylcholinesterase inhibitors. “Digging a little deeper, we see that this risk is almost entirely accounted for by rivastigmine,” Dr. Day said. “If anything, we could argue that people prescribed donepezil and galantamine have a lower risk of death than those not on these medications.”

Various factors could account for the elevated risk with rivastigmine. The drug has a slightly different mechanism of action and a longer half-life. Perhaps more importantly, as the only medication that can be delivered via transdermal patch, it may be prescribed to people with more severe forms of dementia who are no longer able to take medications by mouth, or who have agitation or psychoses. In addition, patients may forget to remove a patch and end up wearing multiple patches. Finally, rivastigmine is FDA-approved for Parkinson’s disease dementia, and the risk of death may be higher in those patients, Dr. Day said.

Memantine Alone and in Combination

Memantine is FDA-approved for patients with moderate to severe dementia due to Alzheimer’s disease. Pooled data indicate a small beneficial effect on cognition, activities of daily living, and behavior in this population. Despite multiple trials, there is no evidence of benefit of memantine in patients with mild dementia due to Alzheimer’s disease, and there is no convincing evidence to support the use of memantine in other forms of dementia.

Memantine is associated with fewer side effects than acetylcholinesterase inhibitors. Side effects can include dizziness, headache, and confusion. In clinical trials, more people taking placebo experienced side effects than those taking memantine. In patients with moderate to severe Alzheimer’s disease dementia receiving donepezil, the addition of memantine resulted in significantly better cognitive outcomes, function, and behavior. The addition of memantine is well tolerated in patients who are stable on an acetylcholinesterase inhibitor, said Dr. Day.

When to Stop Medication

Long-term observational data suggest a persistent effect of acetylcholinesterase inhibitors in Alzheimer’s disease dementia, with about five years of benefit in some trials. In a study that used admission to a nursing home as an outcome, the median time to admission in individuals not prescribed medication was around four to five years. The median time to admission in patients taking an acetylcholinesterase inhibitor was between eight and 10 years. There were not enough data for patients receiving combination therapy, but they may stay out of nursing homes a little longer. “There is this suggestion that use of these medications may delay admission to a nursing home,” he said.

Recommendations regarding stopping treatment vary. Some recommendations suggest that it is reasonable to discontinue these medications in patients who have transitioned to a severe dementia stage, while other recommendations suggest continuing the drugs indefinitely.

The American College of Physicians and American Academy of Family Physicians argue that if slowing decline is no longer a goal of treatment, memantine or acetylcholinesterase inhibitors are no longer appropriate.

If the family or patient’s “focus is shifting away from, ‘Let’s keep them as good as possible for as long as possible,’ to more, ‘Let’s keep them comfortable,’ then maybe removing a medication is part of that. I think it is very reasonable to consider,” Dr. Day said.

When considering stopping treatment, patients can stop medication for two weeks, and the patient and a caregiver can assess perceived cognition, function, and behaviors. If there is not a noticeable change, there is no need to restart the medication. “If they do perceive a decline, I think it is reasonable in that case to restart therapy if that is what they would like to do,” Dr. Day said. “Restarting, you simply revert back to the titration schedule that we would start whenever we’re prescribing these medications.”

Behavioral and Psychiatric Symptoms

Behavioral and psychiatric symptoms may occur in 60% to 90% of patients with dementia. These symptoms are distressing, add to caregiver burden, and are a major reason for institutionalization, Dr. Day said. Symptoms fall into four main categories: agitation, depression, apathy, and psychoses.

First, neurologists should screen for and treat any provoking causes, Dr. Day said. If a patient with a mild dementia syndrome suddenly presents with new agitation, delusions, or hallucinations, neurologists should investigate for oral ulceration, tooth problems, skin breakdown, urinary tract infection, dehydration, or visual or auditory impairment, which may contribute to or trigger these symptoms.

Otherwise, first-line treatment of agitation and psychoses entails atypical antipsychotic medication, although these treatments are not FDA-approved in patients with dementia. In patients with agitation alone, first-line therapy is behavioral interventions, although antipsychotic medications, mood stabilizers, or serotonergic compounds also can be considered. Depression and apathy may respond well to serotonergic compounds.

Black Box Warning

“Anytime we are prescribing antipsychotic medications to our patients with dementia, we need to be cognizant of the fact that these medications are prescribed off label and that they come with a black box warning,” Dr. Day said. Patients with dementia treated with antipsychotic drugs are at an increased risk of death. The risk of death appears to be greatest in those who are continued on antipsychotic medications across a three-month period. In addition, before prescribing antipsychotic medication, “you need to ask yourself—and maybe a nurse and a medical student—do you think that this patient could have dementia with Lewy bodies?” Patients with cortical Lewy bodies can experience significant morbidity or mortality due to severe neuroleptic sensitivity reactions.

Behavioral modification techniques are as effective as antipsychotic and antidepressant drugs, with fewer adverse effects, although they can be challenging to implement in a household environment.

Other Recommendations

When patients ask what else they can do to slow the progression of dementia, Dr. Day refers to seven modifiable risk factors identified in a 2014 Lancet Neurology article. These modifiable risk factors include physical inactivity, depression, midlife hypertension, midlife obesity, smoking, low educational attainment, and diabetes. In promoting physical activity, the CDC recommends a weekly exercise schedule of 150 minutes of moderate intensity activity or 75 minutes of more strenuous activity for individuals 65 and older. “That is a reasonable place to start,” Dr. Day said.

There is no clear demonstration of benefit of cognitive training, nor is there evidence to suggest that one cognitive training strategy is better than another. “If [patients] like doing sudoku or they like doing puzzles, Scrabble, or cards, that is what I am going to emphasize,” he said. “It is very reasonable to recommend that our patients remain cognitively and socially engaged, whatever that means for the individual patient.”

In addition, a Mediterranean-type diet high in olive oil, fresh vegetables, and fish may be worth recommending to patients and their caregivers, as it has been associated in studies with a lower risk of Alzheimer’s disease and mild cognitive impairment. Furthermore, neurologists should screen patients for sleep dysfunction, excessive alcohol intake, thyroid dysfunction, vitamin B12 deficiency, stroke risk factors, and medications that may impair cognition.

Other potential dementia therapies, including numerous interventions promoted online, have little or no evidence to support them. “We have a responsibility, in my opinion, to step in and provide some counseling regarding that to save our patients from committing to potentially expensive treatments with questionable efficacy,” said Dr. Day.

—Jake Remaly

HILTON HEAD, SC—An expanded indication for deep brain stimulation (DBS) in mid-stage Parkinson’s disease, approved by the FDA in November 2015, is “a big step” toward use of DBS earlier in the disease, said David Charles, MD, Professor and Vice-Chair of Neurology at Vanderbilt University in Nashville and Chief Medical Officer of the Vanderbilt Neuroscience Institute.

Results from a pilot trial of DBS in early Parkinson’s disease suggest that early treatment may slow the progression of tremor, a finding discovered by Mallory Hacker, PhD, Assistant Professor of Neurology at Vanderbilt University. “If this finding holds up in a pivotal trial, this would be the first therapy shown to slow the progression of anything in Parkinson’s disease,” Dr. Charles said.

Expanded Indication

Since 2002, DBS has been indicated for advanced Parkinson’s disease when symptoms are no longer adequately controlled with medicine. This year, Dublin-based Medtronic announced that the FDA had approved an expanded indication for its DBS therapy. Bilateral stimulation of the subthalamic nucleus or internal globus pallidus gained an indication for adjunctive therapy in patients with Parkinson’s disease duration of at least four years and at least four months of motor complications.

This expanded indication was based on results from the EARLYSTIM clinical trial published in the New England Journal of Medicine in 2013. The trial enrolled 251 participants with disease duration of at least four years and the presence of dyskinesias or other motor fluctuations. Patients treated with DBS and medical therapy reported an average 26% improvement in disease-related quality of life at two years, compared with a 1% decline in patients treated with medical therapy alone.

Researchers have hypothesized that early treatment with DBS might slow the progression of Parkinson’s disease, and preclinical studies suggest a possible mechanism by which DBS could have this effect, said Dr. Charles. Caryl Sortwell, PhD, Professor of Translational Science and Molecular Medicine at Michigan State University in Grand Rapids, and colleagues have shown in animal models that brain-derived neurotrophic growth factor (BDNF) is upregulated in the substantia nigra when the subthalamic nucleus undergoes stimulation. This increased production of BDNF may be therapeutic and also neuroprotective, Dr. Charles said.

Four Patients in Pilot Study Improved

In 2006, researchers at Vanderbilt University initiated a pilot study in 30 patients with early Parkinson’s disease to evaluate the safety and tolerability of DBS. Participants were between the ages of 50 and 75, had received medication for at least six months but not more than four years, and had no history of dyskinesias or other motor fluctuations. Participants had an average age of 60 and had been on medication for an average of about two years. Half of the participants received DBS plus medicine, and half received standard medication only. They were followed for 24 months. Researchers observed a trend toward better motor outcomes in the DBS group, compared with the medication-only group, but the differences were not statistically significant. In addition, the DBS group took less medication than the medication-only group at every time point. At two years, the medication-only group began to experience complications of therapy (eg, fluctuations or dyskinesias), whereas the DBS group did not.

Every six months during the study, patients were admitted to the hospital and stopped all medicine (and stimulation, if present) for a week. Motor scores after the washout periods in the DBS group trended better than those in the medicine group at 24 months. When researchers evaluated patients’ motor scores after each washout period individually, all 14 patients in the medication-only group worsened over two years. In the DBS group, five of 14 patients did not worsen; four patients actually improved. “That should not happen,” Dr. Charles said. These results from the pilot study suggest “a nearly fourfold increase in the chance of not worsening if you give DBS plus medicine early,” he said.

In addition, when researchers examined patients’ tremor after the seven-day washout, tremor scores in the DBS group did not worsen, whereas tremor scores in patients who received medication only slowly worsened over time as expected.

Planned Pivotal Trial

In the phase III trial of DBS in early Parkinson’s disease, investigators plan to enroll 280 patients at 18 centers. Eligible patients will have received medication for Parkinson’s disease for at least one year but less than four years and have no history of motor fluctuations. All participants will undergo DBS surgery and be randomized to have their stimulator kept off and continue on standard medical therapy, or to have their stimulator turned on in addition to receiving medical therapy. Researchers will follow the participants for two years.

The primary end point for the trial will be a composite measure that assesses whether, at 24 months, a patient worsened or not. Worsening will be defined as a three-point increase in the Unified Parkinson’s Disease Rating Scale (UPDRS) III on-treatment motor score, combined with a one-point increase in the UPDRS IV complications of therapy score, Dr. Charles said.

—Jake Remaly

HILTON HEAD, SC—An expanded indication for deep brain stimulation (DBS) in mid-stage Parkinson’s disease, approved by the FDA in November 2015, is “a big step” toward use of DBS earlier in the disease, said David Charles, MD, Professor and Vice-Chair of Neurology at Vanderbilt University in Nashville and Chief Medical Officer of the Vanderbilt Neuroscience Institute.

Results from a pilot trial of DBS in early Parkinson’s disease suggest that early treatment may slow the progression of tremor, a finding discovered by Mallory Hacker, PhD, Assistant Professor of Neurology at Vanderbilt University. “If this finding holds up in a pivotal trial, this would be the first therapy shown to slow the progression of anything in Parkinson’s disease,” Dr. Charles said.

Expanded Indication

Since 2002, DBS has been indicated for advanced Parkinson’s disease when symptoms are no longer adequately controlled with medicine. This year, Dublin-based Medtronic announced that the FDA had approved an expanded indication for its DBS therapy. Bilateral stimulation of the subthalamic nucleus or internal globus pallidus gained an indication for adjunctive therapy in patients with Parkinson’s disease duration of at least four years and at least four months of motor complications.

This expanded indication was based on results from the EARLYSTIM clinical trial published in the New England Journal of Medicine in 2013. The trial enrolled 251 participants with disease duration of at least four years and the presence of dyskinesias or other motor fluctuations. Patients treated with DBS and medical therapy reported an average 26% improvement in disease-related quality of life at two years, compared with a 1% decline in patients treated with medical therapy alone.

Researchers have hypothesized that early treatment with DBS might slow the progression of Parkinson’s disease, and preclinical studies suggest a possible mechanism by which DBS could have this effect, said Dr. Charles. Caryl Sortwell, PhD, Professor of Translational Science and Molecular Medicine at Michigan State University in Grand Rapids, and colleagues have shown in animal models that brain-derived neurotrophic growth factor (BDNF) is upregulated in the substantia nigra when the subthalamic nucleus undergoes stimulation. This increased production of BDNF may be therapeutic and also neuroprotective, Dr. Charles said.

Four Patients in Pilot Study Improved

In 2006, researchers at Vanderbilt University initiated a pilot study in 30 patients with early Parkinson’s disease to evaluate the safety and tolerability of DBS. Participants were between the ages of 50 and 75, had received medication for at least six months but not more than four years, and had no history of dyskinesias or other motor fluctuations. Participants had an average age of 60 and had been on medication for an average of about two years. Half of the participants received DBS plus medicine, and half received standard medication only. They were followed for 24 months. Researchers observed a trend toward better motor outcomes in the DBS group, compared with the medication-only group, but the differences were not statistically significant. In addition, the DBS group took less medication than the medication-only group at every time point. At two years, the medication-only group began to experience complications of therapy (eg, fluctuations or dyskinesias), whereas the DBS group did not.

Every six months during the study, patients were admitted to the hospital and stopped all medicine (and stimulation, if present) for a week. Motor scores after the washout periods in the DBS group trended better than those in the medicine group at 24 months. When researchers evaluated patients’ motor scores after each washout period individually, all 14 patients in the medication-only group worsened over two years. In the DBS group, five of 14 patients did not worsen; four patients actually improved. “That should not happen,” Dr. Charles said. These results from the pilot study suggest “a nearly fourfold increase in the chance of not worsening if you give DBS plus medicine early,” he said.

In addition, when researchers examined patients’ tremor after the seven-day washout, tremor scores in the DBS group did not worsen, whereas tremor scores in patients who received medication only slowly worsened over time as expected.

Planned Pivotal Trial

In the phase III trial of DBS in early Parkinson’s disease, investigators plan to enroll 280 patients at 18 centers. Eligible patients will have received medication for Parkinson’s disease for at least one year but less than four years and have no history of motor fluctuations. All participants will undergo DBS surgery and be randomized to have their stimulator kept off and continue on standard medical therapy, or to have their stimulator turned on in addition to receiving medical therapy. Researchers will follow the participants for two years.

The primary end point for the trial will be a composite measure that assesses whether, at 24 months, a patient worsened or not. Worsening will be defined as a three-point increase in the Unified Parkinson’s Disease Rating Scale (UPDRS) III on-treatment motor score, combined with a one-point increase in the UPDRS IV complications of therapy score, Dr. Charles said.

—Jake Remaly

HILTON HEAD, SC—An expanded indication for deep brain stimulation (DBS) in mid-stage Parkinson’s disease, approved by the FDA in November 2015, is “a big step” toward use of DBS earlier in the disease, said David Charles, MD, Professor and Vice-Chair of Neurology at Vanderbilt University in Nashville and Chief Medical Officer of the Vanderbilt Neuroscience Institute.

Results from a pilot trial of DBS in early Parkinson’s disease suggest that early treatment may slow the progression of tremor, a finding discovered by Mallory Hacker, PhD, Assistant Professor of Neurology at Vanderbilt University. “If this finding holds up in a pivotal trial, this would be the first therapy shown to slow the progression of anything in Parkinson’s disease,” Dr. Charles said.

Expanded Indication

Since 2002, DBS has been indicated for advanced Parkinson’s disease when symptoms are no longer adequately controlled with medicine. This year, Dublin-based Medtronic announced that the FDA had approved an expanded indication for its DBS therapy. Bilateral stimulation of the subthalamic nucleus or internal globus pallidus gained an indication for adjunctive therapy in patients with Parkinson’s disease duration of at least four years and at least four months of motor complications.

This expanded indication was based on results from the EARLYSTIM clinical trial published in the New England Journal of Medicine in 2013. The trial enrolled 251 participants with disease duration of at least four years and the presence of dyskinesias or other motor fluctuations. Patients treated with DBS and medical therapy reported an average 26% improvement in disease-related quality of life at two years, compared with a 1% decline in patients treated with medical therapy alone.

Researchers have hypothesized that early treatment with DBS might slow the progression of Parkinson’s disease, and preclinical studies suggest a possible mechanism by which DBS could have this effect, said Dr. Charles. Caryl Sortwell, PhD, Professor of Translational Science and Molecular Medicine at Michigan State University in Grand Rapids, and colleagues have shown in animal models that brain-derived neurotrophic growth factor (BDNF) is upregulated in the substantia nigra when the subthalamic nucleus undergoes stimulation. This increased production of BDNF may be therapeutic and also neuroprotective, Dr. Charles said.

Four Patients in Pilot Study Improved

In 2006, researchers at Vanderbilt University initiated a pilot study in 30 patients with early Parkinson’s disease to evaluate the safety and tolerability of DBS. Participants were between the ages of 50 and 75, had received medication for at least six months but not more than four years, and had no history of dyskinesias or other motor fluctuations. Participants had an average age of 60 and had been on medication for an average of about two years. Half of the participants received DBS plus medicine, and half received standard medication only. They were followed for 24 months. Researchers observed a trend toward better motor outcomes in the DBS group, compared with the medication-only group, but the differences were not statistically significant. In addition, the DBS group took less medication than the medication-only group at every time point. At two years, the medication-only group began to experience complications of therapy (eg, fluctuations or dyskinesias), whereas the DBS group did not.

Every six months during the study, patients were admitted to the hospital and stopped all medicine (and stimulation, if present) for a week. Motor scores after the washout periods in the DBS group trended better than those in the medicine group at 24 months. When researchers evaluated patients’ motor scores after each washout period individually, all 14 patients in the medication-only group worsened over two years. In the DBS group, five of 14 patients did not worsen; four patients actually improved. “That should not happen,” Dr. Charles said. These results from the pilot study suggest “a nearly fourfold increase in the chance of not worsening if you give DBS plus medicine early,” he said.

In addition, when researchers examined patients’ tremor after the seven-day washout, tremor scores in the DBS group did not worsen, whereas tremor scores in patients who received medication only slowly worsened over time as expected.

Planned Pivotal Trial

In the phase III trial of DBS in early Parkinson’s disease, investigators plan to enroll 280 patients at 18 centers. Eligible patients will have received medication for Parkinson’s disease for at least one year but less than four years and have no history of motor fluctuations. All participants will undergo DBS surgery and be randomized to have their stimulator kept off and continue on standard medical therapy, or to have their stimulator turned on in addition to receiving medical therapy. Researchers will follow the participants for two years.

The primary end point for the trial will be a composite measure that assesses whether, at 24 months, a patient worsened or not. Worsening will be defined as a three-point increase in the Unified Parkinson’s Disease Rating Scale (UPDRS) III on-treatment motor score, combined with a one-point increase in the UPDRS IV complications of therapy score, Dr. Charles said.

—Jake Remaly

In a peer-to-peer audiocast, Ms. DiVenere probed Dr. Smith for the problem areas that appear in the early to late stages of burnout. He spoke to the stressors that residents experience in the learning situation and that ObGyns must deal with in practice, as well as described strategies to deal with that stress.   

Have you read "ObGyn burnout: ACOG takes aim," by Lucia DiVenere, MA (September 2016)?

In a peer-to-peer audiocast, Ms. DiVenere probed Dr. Smith for the problem areas that appear in the early to late stages of burnout. He spoke to the stressors that residents experience in the learning situation and that ObGyns must deal with in practice, as well as described strategies to deal with that stress.   

Have you read "ObGyn burnout: ACOG takes aim," by Lucia DiVenere, MA (September 2016)?

In a peer-to-peer audiocast, Ms. DiVenere probed Dr. Smith for the problem areas that appear in the early to late stages of burnout. He spoke to the stressors that residents experience in the learning situation and that ObGyns must deal with in practice, as well as described strategies to deal with that stress.   

Have you read "ObGyn burnout: ACOG takes aim," by Lucia DiVenere, MA (September 2016)?

TORONTO—A behavioral syndrome called mild behavioral impairment (MBI) may be a forerunner of Alzheimer’s disease and other neurodegenerative diseases, according to research described at the Alzheimer’s Association International Conference. Investigators have developed a tool for diagnosing it.

MBI, according to the researchers, is a syndrome characterized by new-onset neuropsychiatric symptoms that are sustained for at least six months in patients without dementia who are older than 50. Symptoms can occur in any of the following five domains: motivation, mood, impulse control, social appropriateness, and psychosis.

Zahinoor Ismail, MD, Assistant Professor of Psychiatry and Neurology at the Hotchkiss Brain Institute of the University of Calgary in Canada, described MBI at the conference and unveiled the MBI Checklist (MBI-C), a two-page screen that identifies and scores these symptoms. The MBI-C is a project of the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART).

Family members or informants rate the presence and severity of their symptoms on a three-point scale. The researchers who developed the MBI-C chose age 50 as the lower age limit because symptoms that emerge at that age can herald the onset of frontotemporal dementia. While the MBI-C is available for clinical and research use, the scoring risk stratification is still being validated. At present, the MBI-C identifies symptoms of concern and monitors change over time, said Dr. Ismail.

Changes in personality are often the earliest signs of an emerging neurocognitive disorder and appear well before any problems with memory or cognition. The MBI-C is intended to identify and track these changes in patients.

“We can now describe this preclinical dementia phenotype and use this tool to diagnose it and to capture change over time,” said Dr. Ismail.

Checklist May Aid Research

In addition to being clinically useful, the checklist will aid research, he added. It could identify a population at greatest risk for neurocognitive decline at a time when any nonpharmacological interventions or future disease-modifying drugs could be most beneficial.

“We all know that dementia is much more than memory or cognitive impairment alone. The neuropsychiatric symptoms of dementia are associated with functional impairment, caregiver burden, institutionalization, accelerated rates of progression, and a greater burden of plaques and tangles. There is a great need to identify people early on, people in whom we might be able to change the course of illness. These patients who present with early neuropsychiatric symptoms may be a population we can examine to see if that is possible,” said Dr. Ismail.

Previous studies have linked new-onset neuropsychiatric symptoms with neurocognitive disease, particularly frontotemporal dementia. One study included about 500 subjects enrolled in the ongoing Mayo Clinic Study of Aging. Investigators followed these participants for five years. This study found that the emergence of neuropsychiatric symptoms in cognitively normal older adults was associated with significant increases in the risk of developing mild cognitive impairment (MCI). Agitation conferred the highest risk (hazard ratio [HR], 3.06), followed by apathy (HR, 2.6), anxiety (HR, 1.87), irritability (HR, 1.84), and depression (HR, 1.63).

New-onset neuropsychiatric symptoms are common by the time patients enter care for memory concerns. Dr. Ismail presented data on a group of about 300 patients with MCI who attended a memory clinic. About 82% of patients endorsed at least one neuropsychiatric symptom. As measured by the MBI-C, 78% of patients reported mood symptoms, 64% reported impulse-control symptoms, 52% reported apathy, 28% reported social appropriateness, and 9% reported psychotic symptoms.

Validation of MBI-C Is Ongoing

“Our study suggests that this concept of MBI may be a common and clinically relevant syndrome, particularly given that neuropsychiatric symptoms are associated with greater caregiver burden,” said Dr. Ismail.

“This idea of symptoms persisting for at least six months is important,” he continued. “What we’re talking about is a sustained change from baseline personality. But these are still patients without dementia. Function is maintained. Independent activities of daily living are intact.”

The most comprehensive domain encompasses impulse control, agitation, and reward. “This [domain] captures a lot of function with regard to agitation in dementia, new-onset substance abuse, irritability, new-onset road rage … things we might not otherwise capture,” said Dr. Ismail.

The social appropriateness domain examines symptoms like a loss of the ability to share appropriately, acting out sexually, and loss of social judgment. The psychosis domain inquires about feelings of aggrandizement, persecution, and suspicion, as well as auditory and visual hallucinations.

The mood domain asks about new-onset anxiety, panic, and depression. The motivation domain asks about the development of apathy or disinterest in family, friends, and activities.

Validation studies in large cohorts are ongoing, as are studies that Dr. Ismail hopes will link these early behavioral changes to well-established Alzheimer’s disease biomarkers. The checklist is availablefor free by request emailed to [email protected].

—Michele G. Sullivan

TORONTO—A behavioral syndrome called mild behavioral impairment (MBI) may be a forerunner of Alzheimer’s disease and other neurodegenerative diseases, according to research described at the Alzheimer’s Association International Conference. Investigators have developed a tool for diagnosing it.

MBI, according to the researchers, is a syndrome characterized by new-onset neuropsychiatric symptoms that are sustained for at least six months in patients without dementia who are older than 50. Symptoms can occur in any of the following five domains: motivation, mood, impulse control, social appropriateness, and psychosis.

Zahinoor Ismail, MD, Assistant Professor of Psychiatry and Neurology at the Hotchkiss Brain Institute of the University of Calgary in Canada, described MBI at the conference and unveiled the MBI Checklist (MBI-C), a two-page screen that identifies and scores these symptoms. The MBI-C is a project of the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART).

Family members or informants rate the presence and severity of their symptoms on a three-point scale. The researchers who developed the MBI-C chose age 50 as the lower age limit because symptoms that emerge at that age can herald the onset of frontotemporal dementia. While the MBI-C is available for clinical and research use, the scoring risk stratification is still being validated. At present, the MBI-C identifies symptoms of concern and monitors change over time, said Dr. Ismail.

Changes in personality are often the earliest signs of an emerging neurocognitive disorder and appear well before any problems with memory or cognition. The MBI-C is intended to identify and track these changes in patients.

“We can now describe this preclinical dementia phenotype and use this tool to diagnose it and to capture change over time,” said Dr. Ismail.

Checklist May Aid Research

In addition to being clinically useful, the checklist will aid research, he added. It could identify a population at greatest risk for neurocognitive decline at a time when any nonpharmacological interventions or future disease-modifying drugs could be most beneficial.

“We all know that dementia is much more than memory or cognitive impairment alone. The neuropsychiatric symptoms of dementia are associated with functional impairment, caregiver burden, institutionalization, accelerated rates of progression, and a greater burden of plaques and tangles. There is a great need to identify people early on, people in whom we might be able to change the course of illness. These patients who present with early neuropsychiatric symptoms may be a population we can examine to see if that is possible,” said Dr. Ismail.

Previous studies have linked new-onset neuropsychiatric symptoms with neurocognitive disease, particularly frontotemporal dementia. One study included about 500 subjects enrolled in the ongoing Mayo Clinic Study of Aging. Investigators followed these participants for five years. This study found that the emergence of neuropsychiatric symptoms in cognitively normal older adults was associated with significant increases in the risk of developing mild cognitive impairment (MCI). Agitation conferred the highest risk (hazard ratio [HR], 3.06), followed by apathy (HR, 2.6), anxiety (HR, 1.87), irritability (HR, 1.84), and depression (HR, 1.63).

New-onset neuropsychiatric symptoms are common by the time patients enter care for memory concerns. Dr. Ismail presented data on a group of about 300 patients with MCI who attended a memory clinic. About 82% of patients endorsed at least one neuropsychiatric symptom. As measured by the MBI-C, 78% of patients reported mood symptoms, 64% reported impulse-control symptoms, 52% reported apathy, 28% reported social appropriateness, and 9% reported psychotic symptoms.

Validation of MBI-C Is Ongoing

“Our study suggests that this concept of MBI may be a common and clinically relevant syndrome, particularly given that neuropsychiatric symptoms are associated with greater caregiver burden,” said Dr. Ismail.

“This idea of symptoms persisting for at least six months is important,” he continued. “What we’re talking about is a sustained change from baseline personality. But these are still patients without dementia. Function is maintained. Independent activities of daily living are intact.”

The most comprehensive domain encompasses impulse control, agitation, and reward. “This [domain] captures a lot of function with regard to agitation in dementia, new-onset substance abuse, irritability, new-onset road rage … things we might not otherwise capture,” said Dr. Ismail.

The social appropriateness domain examines symptoms like a loss of the ability to share appropriately, acting out sexually, and loss of social judgment. The psychosis domain inquires about feelings of aggrandizement, persecution, and suspicion, as well as auditory and visual hallucinations.

The mood domain asks about new-onset anxiety, panic, and depression. The motivation domain asks about the development of apathy or disinterest in family, friends, and activities.

Validation studies in large cohorts are ongoing, as are studies that Dr. Ismail hopes will link these early behavioral changes to well-established Alzheimer’s disease biomarkers. The checklist is availablefor free by request emailed to [email protected].

—Michele G. Sullivan

TORONTO—A behavioral syndrome called mild behavioral impairment (MBI) may be a forerunner of Alzheimer’s disease and other neurodegenerative diseases, according to research described at the Alzheimer’s Association International Conference. Investigators have developed a tool for diagnosing it.

MBI, according to the researchers, is a syndrome characterized by new-onset neuropsychiatric symptoms that are sustained for at least six months in patients without dementia who are older than 50. Symptoms can occur in any of the following five domains: motivation, mood, impulse control, social appropriateness, and psychosis.

Zahinoor Ismail, MD, Assistant Professor of Psychiatry and Neurology at the Hotchkiss Brain Institute of the University of Calgary in Canada, described MBI at the conference and unveiled the MBI Checklist (MBI-C), a two-page screen that identifies and scores these symptoms. The MBI-C is a project of the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART).

Family members or informants rate the presence and severity of their symptoms on a three-point scale. The researchers who developed the MBI-C chose age 50 as the lower age limit because symptoms that emerge at that age can herald the onset of frontotemporal dementia. While the MBI-C is available for clinical and research use, the scoring risk stratification is still being validated. At present, the MBI-C identifies symptoms of concern and monitors change over time, said Dr. Ismail.

Changes in personality are often the earliest signs of an emerging neurocognitive disorder and appear well before any problems with memory or cognition. The MBI-C is intended to identify and track these changes in patients.

“We can now describe this preclinical dementia phenotype and use this tool to diagnose it and to capture change over time,” said Dr. Ismail.

Checklist May Aid Research

In addition to being clinically useful, the checklist will aid research, he added. It could identify a population at greatest risk for neurocognitive decline at a time when any nonpharmacological interventions or future disease-modifying drugs could be most beneficial.

“We all know that dementia is much more than memory or cognitive impairment alone. The neuropsychiatric symptoms of dementia are associated with functional impairment, caregiver burden, institutionalization, accelerated rates of progression, and a greater burden of plaques and tangles. There is a great need to identify people early on, people in whom we might be able to change the course of illness. These patients who present with early neuropsychiatric symptoms may be a population we can examine to see if that is possible,” said Dr. Ismail.

Previous studies have linked new-onset neuropsychiatric symptoms with neurocognitive disease, particularly frontotemporal dementia. One study included about 500 subjects enrolled in the ongoing Mayo Clinic Study of Aging. Investigators followed these participants for five years. This study found that the emergence of neuropsychiatric symptoms in cognitively normal older adults was associated with significant increases in the risk of developing mild cognitive impairment (MCI). Agitation conferred the highest risk (hazard ratio [HR], 3.06), followed by apathy (HR, 2.6), anxiety (HR, 1.87), irritability (HR, 1.84), and depression (HR, 1.63).

New-onset neuropsychiatric symptoms are common by the time patients enter care for memory concerns. Dr. Ismail presented data on a group of about 300 patients with MCI who attended a memory clinic. About 82% of patients endorsed at least one neuropsychiatric symptom. As measured by the MBI-C, 78% of patients reported mood symptoms, 64% reported impulse-control symptoms, 52% reported apathy, 28% reported social appropriateness, and 9% reported psychotic symptoms.

Validation of MBI-C Is Ongoing

“Our study suggests that this concept of MBI may be a common and clinically relevant syndrome, particularly given that neuropsychiatric symptoms are associated with greater caregiver burden,” said Dr. Ismail.

“This idea of symptoms persisting for at least six months is important,” he continued. “What we’re talking about is a sustained change from baseline personality. But these are still patients without dementia. Function is maintained. Independent activities of daily living are intact.”

The most comprehensive domain encompasses impulse control, agitation, and reward. “This [domain] captures a lot of function with regard to agitation in dementia, new-onset substance abuse, irritability, new-onset road rage … things we might not otherwise capture,” said Dr. Ismail.

The social appropriateness domain examines symptoms like a loss of the ability to share appropriately, acting out sexually, and loss of social judgment. The psychosis domain inquires about feelings of aggrandizement, persecution, and suspicion, as well as auditory and visual hallucinations.

The mood domain asks about new-onset anxiety, panic, and depression. The motivation domain asks about the development of apathy or disinterest in family, friends, and activities.

Validation studies in large cohorts are ongoing, as are studies that Dr. Ismail hopes will link these early behavioral changes to well-established Alzheimer’s disease biomarkers. The checklist is availablefor free by request emailed to [email protected].

—Michele G. Sullivan

DENVER—Sleep medication, when administered in recommended dosages at bedtime, can significantly impair next-morning short- and long-term memory, according to data presented at the 30th Anniversary Meeting of the Associated Professional Sleep Societies. Additionally, the medication significantly impairs psychomotor speed in healthy adults, but not in the elderly.

Joris C. Verster, PhD, Associate Professor in the Division of Pharmacology at Utrecht University in the Netherlands, and colleagues conducted two meta-analyses on the next-morning effects of hypnotic drugs. In one analysis, they looked at the drugs’ effects on short- and long-term memory functioning in healthy adults and in the elderly. In another study, they examined the next-morning effects on psychomotor speed and motor control in the same two age groups. For these meta-analyses, Dr. Verster and colleagues identified 33,969 potentially relevant articles.

Morning-After Effects on Memory

Studies were included if they assessed next-morning short- and long-term memory after bedtime administration of recommended dosages of hypnotic drugs and were double-blind, placebo-controlled, and conducted in healthy volunteers, and if sufficient data were reported. Separate analyses were performed for adults (ages 18 to 65) and for elderly healthy volunteers (age 65 or older).

In adults, eight studies assessing next-morning short-term memory (after bedtime administration of nitrazepam, triazolam, temazepam, flurazepam, melatonin, zaleplon, lormetazepam, or zolpidem) and five studies assessing long-term memory (after bedtime administration of triazolam, nitrazepam, zopiclone, flurazepam, or zolpidem) were included in the meta-analysis. The analysis revealed that next-morning short- and long-term memory were significantly impaired.

In the elderly, three studies assessing next-morning short-term memory (after bedtime administration of flurazepam, zolpidem, or temazepam) and three studies assessing long-term memory (after bedtime administration of flurazepam, zolpidem, or temazepam) were included in the meta-analysis. This analysis revealed that in the elderly, next-morning short-term memory was significantly impaired, but no significant impairment was detected in long-term memory.

Morning-After Effects on Psychomotor Speed and Motor Control

Studies were included in the analysis if they assessed next-morning effects on psychomotor speed or motor control after bedtime administration of recommended dosages of hypnotic drugs. As in the meta-analyses described above, studies also had to be double-blind, placebo-controlled, and conducted in healthy subjects, and to provide sufficient data.

In adults, 15 studies assessing next-morning psychomotor speed and five studies assessing next-morning motor control were included in the meta-analysis. This analysis revealed that next-morning psychomotor speed was significantly impaired, whereas next-morning motor control was not.

In the elderly, six studies assessing next-morning psychomotor speed and three studies assessing next-morning motor control were included in the meta-analysis. This analysis revealed that in the elderly, next-morning psychomotor speed and motor control were not significantly impaired. Taken together, the analyses show that skills and abilities that are relevant to daily activities such as driving a car or job performance may be impaired the day after using hypnotic drugs.

—Glenn S. Williams

DENVER—Sleep medication, when administered in recommended dosages at bedtime, can significantly impair next-morning short- and long-term memory, according to data presented at the 30th Anniversary Meeting of the Associated Professional Sleep Societies. Additionally, the medication significantly impairs psychomotor speed in healthy adults, but not in the elderly.

Joris C. Verster, PhD, Associate Professor in the Division of Pharmacology at Utrecht University in the Netherlands, and colleagues conducted two meta-analyses on the next-morning effects of hypnotic drugs. In one analysis, they looked at the drugs’ effects on short- and long-term memory functioning in healthy adults and in the elderly. In another study, they examined the next-morning effects on psychomotor speed and motor control in the same two age groups. For these meta-analyses, Dr. Verster and colleagues identified 33,969 potentially relevant articles.

Morning-After Effects on Memory

Studies were included if they assessed next-morning short- and long-term memory after bedtime administration of recommended dosages of hypnotic drugs and were double-blind, placebo-controlled, and conducted in healthy volunteers, and if sufficient data were reported. Separate analyses were performed for adults (ages 18 to 65) and for elderly healthy volunteers (age 65 or older).

In adults, eight studies assessing next-morning short-term memory (after bedtime administration of nitrazepam, triazolam, temazepam, flurazepam, melatonin, zaleplon, lormetazepam, or zolpidem) and five studies assessing long-term memory (after bedtime administration of triazolam, nitrazepam, zopiclone, flurazepam, or zolpidem) were included in the meta-analysis. The analysis revealed that next-morning short- and long-term memory were significantly impaired.

In the elderly, three studies assessing next-morning short-term memory (after bedtime administration of flurazepam, zolpidem, or temazepam) and three studies assessing long-term memory (after bedtime administration of flurazepam, zolpidem, or temazepam) were included in the meta-analysis. This analysis revealed that in the elderly, next-morning short-term memory was significantly impaired, but no significant impairment was detected in long-term memory.

Morning-After Effects on Psychomotor Speed and Motor Control

Studies were included in the analysis if they assessed next-morning effects on psychomotor speed or motor control after bedtime administration of recommended dosages of hypnotic drugs. As in the meta-analyses described above, studies also had to be double-blind, placebo-controlled, and conducted in healthy subjects, and to provide sufficient data.

In adults, 15 studies assessing next-morning psychomotor speed and five studies assessing next-morning motor control were included in the meta-analysis. This analysis revealed that next-morning psychomotor speed was significantly impaired, whereas next-morning motor control was not.

In the elderly, six studies assessing next-morning psychomotor speed and three studies assessing next-morning motor control were included in the meta-analysis. This analysis revealed that in the elderly, next-morning psychomotor speed and motor control were not significantly impaired. Taken together, the analyses show that skills and abilities that are relevant to daily activities such as driving a car or job performance may be impaired the day after using hypnotic drugs.

—Glenn S. Williams

DENVER—Sleep medication, when administered in recommended dosages at bedtime, can significantly impair next-morning short- and long-term memory, according to data presented at the 30th Anniversary Meeting of the Associated Professional Sleep Societies. Additionally, the medication significantly impairs psychomotor speed in healthy adults, but not in the elderly.

Joris C. Verster, PhD, Associate Professor in the Division of Pharmacology at Utrecht University in the Netherlands, and colleagues conducted two meta-analyses on the next-morning effects of hypnotic drugs. In one analysis, they looked at the drugs’ effects on short- and long-term memory functioning in healthy adults and in the elderly. In another study, they examined the next-morning effects on psychomotor speed and motor control in the same two age groups. For these meta-analyses, Dr. Verster and colleagues identified 33,969 potentially relevant articles.

Morning-After Effects on Memory

Studies were included if they assessed next-morning short- and long-term memory after bedtime administration of recommended dosages of hypnotic drugs and were double-blind, placebo-controlled, and conducted in healthy volunteers, and if sufficient data were reported. Separate analyses were performed for adults (ages 18 to 65) and for elderly healthy volunteers (age 65 or older).

In adults, eight studies assessing next-morning short-term memory (after bedtime administration of nitrazepam, triazolam, temazepam, flurazepam, melatonin, zaleplon, lormetazepam, or zolpidem) and five studies assessing long-term memory (after bedtime administration of triazolam, nitrazepam, zopiclone, flurazepam, or zolpidem) were included in the meta-analysis. The analysis revealed that next-morning short- and long-term memory were significantly impaired.

In the elderly, three studies assessing next-morning short-term memory (after bedtime administration of flurazepam, zolpidem, or temazepam) and three studies assessing long-term memory (after bedtime administration of flurazepam, zolpidem, or temazepam) were included in the meta-analysis. This analysis revealed that in the elderly, next-morning short-term memory was significantly impaired, but no significant impairment was detected in long-term memory.

Morning-After Effects on Psychomotor Speed and Motor Control

Studies were included in the analysis if they assessed next-morning effects on psychomotor speed or motor control after bedtime administration of recommended dosages of hypnotic drugs. As in the meta-analyses described above, studies also had to be double-blind, placebo-controlled, and conducted in healthy subjects, and to provide sufficient data.

In adults, 15 studies assessing next-morning psychomotor speed and five studies assessing next-morning motor control were included in the meta-analysis. This analysis revealed that next-morning psychomotor speed was significantly impaired, whereas next-morning motor control was not.

In the elderly, six studies assessing next-morning psychomotor speed and three studies assessing next-morning motor control were included in the meta-analysis. This analysis revealed that in the elderly, next-morning psychomotor speed and motor control were not significantly impaired. Taken together, the analyses show that skills and abilities that are relevant to daily activities such as driving a car or job performance may be impaired the day after using hypnotic drugs.

—Glenn S. Williams