Primecuts – This Week In The Journals

August 1, 2011

By Anjali Nigalaye, MD

Faculty Peer Reviewed

In keeping with the trend of current times, this week’s Primecuts begins and ends with Washington.  Love it or hate it, the political atmosphere is tense and the issues of debate are all-pervasive, no less in the business of our daily lives as health care professionals.  Paying credence to this fact is new data published this week in Health Affairs [1] that estimates government spending to account for about half of annual health dollars spent by the year 2020.   In 2010, 45% of the 2.6 trillion spent on health care came from government pockets.  This share is expected to grow to 49%, roughly $2.28 trillion, in 2020.   The authors of the report – economists and actuaries from the Centers for Medicare and Medicaid services – attribute this rise to decreased spending on the part of private employers as a result of provisions in President Obama’s 2010 Affordable Care Act.  This legislation may exempt certain large employers from having to provide health insurance to low-wage workers, a segment of the population that will increasingly be covered by federal government subsidized insurance plans.   Another source for the rise in government spending is the growing Medicare population.   Of course, these estimates are subject to much variability, not the least of which is speculation regarding which parts of the health bill, if any, will actually go into effect in 2014.   And given the stalemate we’ve seen in Congress over the past few weeks with regards to the budget ceiling, speculation remains just that – speculation.  As we continue to watch the rumblings in Washington, a look at this week’s major medical journals offers insight on how we might help trim the fat on spending by providing more efficient and effective health care, especially to our growing and aging population (hitting 7 billion total this week!).

Speaking of trimming the fat, exercise remains the mainstay of physician counseling for weight loss, blood pressure control, and general cardioprotection.  A study released in this week’s Archives of Internal Medicine [2] may give yet another indication for which to prescribe exercise as primary prevention – dementia.  This subgroup analysis of the larger Health Aging and Body Composition (Health ABC) prospective cohort study enrolled 197 black and white participants between the ages of 70 and 79 to partake in energy expenditure analysis and cognitive assessment over a five year span.  At baseline, participants’ cognitive function was assessed using the modified mini-mental state examination.  Energy expenditure was calculated using doubly labeled water, which was ingested at the first visit and then measured in urine at 2, 3, and 4 hours after ingestion and again measured at 2 week follow-up visit.  This method allows for calculation of total energy expenditure using a biophysical equation, the Weir equation. Resting metabolic rate was also calculated at the first visit using indirect calorimetry.  Researchers then calculated Active Energy Expenditure (AEE) as 90% of total energy expenditure minus the resting metabolic rate.  Other measures recorded were self-reported physical activity, smoking history, hours per day sleeping, depressive symptoms, history of hypertension and diabetes, fat-free mass, and usual eating habits during the previous year. Participants were then divided in to tertiles based on AEE as well as self-reported physical activity and followed for two to five years.  The primary outcome of the study was cognitive impairment which was defined as a decline of 1 SD on the MMS.  The study found a significant association between AEE and the likelihood cognitive impairment, with the lowest AEE tertile showing the greatest decline (16.9%), followed by the middle tertile (4.5%), and the highest turtle of AEE showing the smallest decline (1.5%).  Even after controlling for baseline cognition and factors associated with tertile of AEE such as fat-free mass, sleep duration, and diabetes, the association remained significant.  Interestingly, there was no association between self-reported physical activity and the likelihood of cognitive impairment.  This is likely due to the under-reporting of activities that contribute to energy expenditure, like gardening and fidgeting, which are accounted for in more objective measures of energy expenditure as were used in this study.   While it is unrealistic to routinely measure and monitor physical activity so precisely in our practices, this study gives us a basis to encourage our patients to keep moving, in whatever way, to keep both their bodies and minds in good shape.

For patients who already suffer the consequences of cognitive impairment, results of a large study published this week in the Lancet [3] may prove quite important. While it is known that 20% of the 36 million people with dementia suffer from depression, it’s management in Alzheimer’s patients had been poorly studied until recently. The UK Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) is the largest study to date on the issue.  In this randomized, double-blind, placebo-controlled trial, 326 patients, with a mean age of 80, were included on the basis of possible or probable Alzheimer’s and depression on the basis of a Cornell scale for depression in dementia (CSDD) score of 8 or more.   These patients were randomly assigned to sertraline, mirtazapine or placebo and were followed for 39 weeks.  Primary outcome for the study was a reduction in CSDD score at 13 weeks; other outcomes included CSDD at 39 weeks, health-related quality of life, generic quality of life, withdrawal from treatment, cognition by MMSE, adverse events, behavioral disorders, among others.  At the 13 weeks, data showed that depression had decreased in all three groups, however there was no statistically significant difference in CSDD score reduction across all three groups with a mean difference of 1.17, 95% CI -0.23 to 2.58, p value 0.10.   On the contrary, treatment groups showed an overall higher rate of adverse effects by week 39 (43% in the sertraline group and 41% in the mirtazapine group compared to 26% in placebo) with GI upset and nausea being the most common in sertraline group (24%) and psychological in the mirtazapine group (44%).  This was augmented by a severity relationship, with patients describing adverse events as more severe in the treatment groups as compared to the placebo groups.  Given that psychotropic medications have been first-line in the treatment of depression in dementia, the negative results of this study are important and suggest that perhaps other modalities of treatment such as watchful waiting and low-intensity psychosocial interventions should be attempted first.  Another lesson in ‘less is more.’

That being said, the next article that I review today shows that sometimes action in the short term can lead to better outcomes in the long term.   A study published this week in the British Journal of Medicine [4] detailed the utility of systematic pain control in preventing agitation in nursing home residents with severe dementia.  352 residents across 18 nursing homes in western Norway were randomized to cluster groups employing either a stepwise protocol for pain management or treatment as usual.  Patients were followed for 8 weeks and again at 4 week post-treatment follow-up.  Inclusion criteria were age 65 or more, dementia by DSM-IV functional stage of more than 4, and behavioral disturbance defined as a score of 39 or more by Cohen-Mansfield Agitation Inventory for at least one week.  Patients with a life expectancy of less than six month on the basis of advanced medical disease were excluded, along with patients with a history of severe agitation, liver or renal failure, injury, anemia, and known allergy to acetaminophen, morphine, buprenorphine, or pregabaline.  The protocol employed in the intervention group was based on recommendations by the American Geriatrics Society in which pain control was managed in a stepwise manner: step 1 – incremental acetaminophen dosing up to 3 grams per day; step 2 – oral morphine to a max of 20mg day; step 3 – buprenorphine transdermal patch, max 10ug/hour; and finally step 4 – oral pregabaline to max of 300mg per day.  Prior to randomization, patients’ current medical treatment was assessed to determine which step they would begin if randomized to the intervention group.  Patients in the intervention group were offered analgesic medication at breakfast, lunch and dinner as per their individualized step. Combination therapy was permitted in the intervention group; in cases of low tolerability of medication, dosages were decreased or patients were withdrawn from the study. Patients were assessed through eight weeks of treatment by blinded research assistants and caregivers.  Notably, clinically significant pain was prevalent and equal in both groups – 59% in treatment and 55% in control.  63% of the intervention group received step 1 management with simple paracetamol (acetaminophen) for the duration of the treatment.  At the conclusion of the study, authors report a 17% reduction in agitation scores, 7% treatment effect estimate as compared to placebo (95% CI -.37 to -10.3) with statistically significant reductions in severity of neuropsychiatric symptoms and pain.  While we must always beware of organic causes of altered mental status and agitation in the elderly, this study points to two significant points – one being the importance of pain control and how this can be achieved with relatively safe and simple medications.  Second, it again emphasizes the importance of standardized and systems-based practice in effecting change.

The final study we look at this week also highlights the importance of systems-based change, in this case the system being the federal government.   For most of us, Medicare Part D and the debate surrounding it’s “doughnut hole” are a distant memory from the fall of 2003.  But for many of our elderly patients, this prescription drug coverage program has been front and center since its implementation in 2006.  Research has shown that Medicare Part D has indeed increased prescription drug use and adherence, but how this translates into outcomes has yet to be shown.  A study published in this week’s JAMA[5] begins to investigate this link.  Data from the Health and Retirement Study were used to examine a cohort of 6000 Medicare beneficiaries two years prior to and two years after the implementation of Medicare Part D.  Study participants were divided into generous coverage prior to Medicare Part D versus limited coverage prior to Part D based on self-reported perceptions of coverage prior to 2006.  Given that seniors in the generous coverage group were less likely to enroll in Medicare Part D, this group was deemed the control group, i.e. “not affected by Medicare Part D.”  The primary outcome of this study was non-drug medical spending, including inpatient, outpatient and skilled nursing expenditure, which was assessed via review of Medicare claims processed during the study period.  Results from this review indicate that in beneficiaries with prior limited coverage, the prescription drug program has resulted in lower non-drug expenditure in the form of inpatient or acute care visits and nursing home care (−$306/quarter, 95% C −$586 to −$5;  P=.02).  There was no difference in spending on outpatient physician services across all groups.  While this study makes several assumptions, first and foremost being who is and who is not affected by Medicare Part D, and also leaves out key analyses such as which medications are driving are increasingly being used, one cannot ignore the overall decrease in non-drug expenditure that coincides with the implementation of this nationwide legislation.  It remains to be seen whether the Affordable Health Care Act of 2010 will close Part D’s doughnut hole which excludes many seniors from prescription drug coverage if they fall within a certain spending range.  But it is reassuring to see objective data showing that even some form of increased access can result in savings… how this savings compares to the cost of providing access is a topic we are sure to see hotly debated on the airwaves, especially as the budget wars ensue.

So as promised, we arrive back in the nation’s capital.  The countdown continues.  And the train of scientific discovery chugs along.

Dr. Anjali Nigalaye is a 3rd year resident at NYU Langone Medical Center

Peer reviewed by Barbara Porter, MD, Section Editor, Clinical Correlations

Image courtesy of Wikimedia Commons


1. Keehan S, Sisko A, Truffer J, Poisal J, Cuckler G, Madison A, Lizonitz J, Smith S. “National Health Spending Projections Through 2020: Economic Recovery and Reform Drive Faster Spending Growth.” Health Affairs. 2011 Jul 28. Published online.

2.  Middleton L, Manini T, Simonsick E, Harris T, Barnes D, Tylavsky F, Brach J, Everhart J, Yaffe K. “Activity Energy Expenditure and Incident Cognitive Impairment in Older Adults.” Arch Intern Med. 2011 Jul 25; 171(14):1251-1257.

3.  Banerjee S, Hellier J, Dewey M, Romeo R, Ballard C, Baldwn R, Bentham P, Fox C, Holmes C, Katona C, Knapp M, Lawton C, Lindesay J, Livingston G, McCrae N, Moniz-Cook E, Murray J, Nurock S, Orrell M, O’Brien J, et al. “Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial” The Lancet.  2011 July 30; 373 (9789): 403-411.

4. Husebo B, Ballard C, Sandvik R, Nilsen O, Aarsland D. “Efficacy of treating pain to reduce behavioral disturbances in residents of nursing homes with dementia: cluster randomized clinical trial.” BMJ 2011 Jul 17. 343:d4065.

5.  McWilliams J, Zaslavsky A, Huskamp H. “Implementation of Medicare Part D and Nondrug Medical Spending for Elderly Adults with Limited Prior Drug Coverage.” JAMA 2011 Jul 27. 306(4): 402-409.