Primecuts – This Week in the Journals

May 15, 2018

By Michael Tamimi, MD

Peer Reviewed

At a mere 104 years old, famed ecologist and botanist David Goodall, who was frequently touted as Australia’s oldest scientist, ended his own life via assisted suicide in Switzerland with family and friends at bedside. A proponent of Exit International, Dr. Goodall, just prior to his death, spoke about how he “regret[ed] reaching that age,” and noted the “sadness” attributed to his wishes, is not sadness in the desire to die, but rather the fact that “one is prevented” from doing so [1].

Perhaps his death will once again open up the euthanasia and assisted suicide debate among developed nations, particularly in his home Australia and The United States, where only one state and six states, respectively, have some form of “death-with-dignity” laws in place. All of which are largely only applicable to terminally ill patients.

We are left to wonder whether Dr. Goodall’s actions will become a marker for progression or an insignificant blip in the legislation reform of these nations, which in this domain, seem to significantly lag behind their Western European counterparts.

And with that, let’s transition to new developments in medical literature during this past week with a special mini-cuts piece relating to euthanasia and physician assisted suicide.

Dialysis Initiation and Mortality Among Older Veterans With Kidney Failure Treated in Medicare vs the Department of Veterans Affairs

The mortality benefit of dialysis in older patients remains controversial, especially in the setting of multiple co-morbidities [2-4]. The capitated Veterans Affairs Healthcare System and the fee-for-service Medicare system, both of with have their fair share of criticisms, provide a large portion of care for these patients. A retrospective cohort study in JAMA Internal Medicine looked at 11,215 veterans, aged 67+, with kidney failure who received pre-ESRD care exclusively at either The Veterans Affairs Healthcare System or through Medicare and measured dialysis treatment and mortality within two years [5].

In terms of initiation, almost 82% of patients who received care via Medicare had started dialysis within two years of kidney failure, compared to about 53% in The VA group. This increased rate did not however increase mortality benefit, as roughly 53% of the Medicare group died within two years of kidney failure, compared to 44% of The VA group.
Due to varying socio-demographic differences in those patients who used Medicare over The VA, propensity matched analysis between the two groups was also used to minimize possible confounders. These rates proved similar after propensity matching as well. Limitations with this study, as with any observational study, include the possibility of confounding bias. Overall, the notion of worsening outcomes despite increased initiation of dialysis is consistent with prior literature that looked at overall dialysis initiation and mortality rates in the United States versus abroad [6].

Bottom Line: Dialysis initiation was both more frequent and associated with higher mortality in Veterans with ESRD who received pre-ESRD care via Medicare when compared to their counterparts receiving care at The VA.

Association of Mild Traumatic Brain Injury With and Without Loss of Consciousness With Dementia in US Military Veterans
The link between traumatic brain injury (TBI) and the development of dementia has been known for quite some time, particularly in those with the classification of moderate to severe TBI under the criteria set forth by the Department of Defense and Defense and Brain Injury Center classification system [7-15]. However, what remained to be seen, was if mild TBI without LOC put individuals at a statistically significant increased risk of developing dementia, when mild TBI was diagnosed clinically and obtained through medical records rather than self-reported [16].

This retrospective cohort study sought to answer that very question. By design, 178,799 veterans of varying age, sex, social demographics, medical and psychiatric comorbidities, with varying degrees of diagnosed TBI were matched to an equal number of TBI-free controls, all of whom were enrolled in the VHA Healthcare system, in an attempt to find a causal link. Two large databases, National Patient Care Databases and The Comprehensive Traumatic Brain Injury Evaluation database, were used to obtain data on VHA patients over a thirteen year span.

In total, roughly 2.5% and 6% of patients from the non-TBI group and TBI group, respectively, were diagnosed with Dementia [16]. After adjustments were made for varying age as well as medical and psychiatric co-morbidities, a Hazard Ratio of 2.36 (CI 2.10-2.66) was seen for diagnosis of dementia in patients with mild TBI without LOC [16]. A dose-response association between severity and diagnosis was also noted as severity increased [16].

Notable limitations included applicability to the general civilian population as well as extrapolation methods, as this study was limited to veterans who sought medical attention for their TBI, regardless of severity, leaving out many mild cases undiagnosed, possibly limiting to only the most severe of the mild cases [16].

Bottom Line: Any form of TBI, regardless if loss of consciousness occurred, puts veterans at an increased risk of being diagnosed with dementia.

Association Between Psychological Interventions and Chronic Pain Outcomes in Older Adults
Cognitive Behavioral Therapy, as a means to combat chronic pain, has increased substantially as our nation has faced a growing opioid epidemic, albeit with mixed results [17]. This meta-anylysis of 238 articles evaluated the efficacy of CBT on older adults, defined as a median age of 60, with various types of physical pain, the majority of which were musculoskeletal in nature.

The approach taken incorporated a systematic review of clinical trials via MEDLINE, Embase, PsycINFO and the Cochrane Library, which had at least one psychological intervention, modalities of which included Behavioral and Cognitive coping skills training, Acceptance, Behavioral Activation, and Cognitive Restructuring. Data was taken from one of ten outcomes, which were changes in pain intensity, pain interference, depressive symptoms, anxiety, catastrophizing beliefs, self-efficacy for managing pain, self reported physical function and health, pain medication, and adverse events. Said outcomes, excluding adverse events and medication changes, were chosen based on previous positive effects by psychological therapies [18-22].

In all, 238 articles were reviewed, which had an average CBT treatment time of about nine weeks, composed of either group therapy or single sessions. As varying instrumentations for measurements were used amongst the studies, this meta-analysis reported findings as Differences of Standard Mean Differences, dubbed dD. Significant findings were noted only for pain intensity (dD -0.18, p 0.006) catastrophizing beliefs (dD. -0.18, p 0.046) and self-efficacy for managing pain (dD 0.193, p 0.02).

Limitations included unclear effect of other confounding modalities on reported changes in pain (ie those studies which had both psychological modalities and physical modalities such as exercise) as well as limited applicability, as most patients were Caucasians, and limited long-term efficacy, as most studies were did not evaluate past six months.

Bottom Line: Psychological interventions have at best, a small benefit in older adults with chronic pain. These benefits are most pronounced in improving patient self-efficacy for managing pain, reducing pain intensity, and reducing catastrophizing beliefs. Reduction of pain intensity being the only modality that showed continued benefit at six months post treatment.

Association of Timing of Aortic Valve Replacement Surgery After Stroke With Risk of Recurrent Stroke and Mortality
Previous studies have shown that a prior stroke increases risk of recurrent peri-procedural stroke in patients undergoing aortic valve replacement surgery [23-25]. However, what has been studied less, is whether specific timing intervals post stroke have significantly increased risks for recurrent stroke and if an “optimal” procedure time exists [26].

A cohort study in JAMA Cardiology evaluated the risk of 30 day peri-operative ischemic stroke, major adverse cardiovascular events (defined as ischemic stroke in addition to non-fatal MI and all fatal cardiovascular events), and all-cause mortality in patients who underwent surgical aortic valve replacements who also had a previous stroke time of less than 3 months, 3-12 months, and over 12 months. A control of no previous stroke was also included.

Recurrent stroke risk was inversely related to time of aortic valve replacement, with about a fourteen fold [OR 14.69 (CI 9.69-22.27) ] and a four fold [OR 3.96 (CI 1.63-9.59)] higher risk of recurrent stroke when the procedure was performed at less than three months and three to 12 months, respectively. The risk of recurrent stroke after the 12 month mark, reduced to two fold [OR 2.29 (CI 1.16-4.51). Statistically significant increases in risk were also noted for adverse cardiovascular events, but not for all cause mortality.

Limitations included a small, homogenous population sample size (an n of 132 which were predominately Caucasian Danes) allowing for type 2 error and poor applicability to other races and ethnic groups, respectively.

Bottom Line: A prior stroke put patients undergoing surgical aortic valve replacement at increased risk for recurrent stroke, most pronounced in the first three months post insult. However, postponement of surgical aortic valve replacement for at least three months cannot definitively be said to reduce the risk of recurrent stroke without further investigation through randomized control studies.

And alas, here are your Minicuts for the week…


1) This meta-analysis unanimously showed the benefits of Resistance training in contesting depressive symptoms, perhaps, allowing for consideration of resistance based exercise as adjuvant therapy in combating depression, however with notable limitations [27].

2) Due to diminishing costs, BRCA1/2 only testing has long given way to multiple-gene sequencing, the latter which according to this population based study appears to detect pathogenic variants better than BRCA 1/2 only testing and without a notable change in prophylactic mastectomy rates [28].

3) Within one year of initiation, three tested smoking cessation agents (Varenicline, Bupropion, and Nicotine Patches) showed no statistically significant increased risk in adverse cardiovascular events, according to this Pfizer and GlaxoSmithKline supported randomized clinical trial [29]. This may further encourage physicians, who might have been once hesitant due to conflicting previous studies, to offer these pharmacotherapy based tobacco cessation agents to their patients.

4) This special communication piece, relating to our introduction, touches on relatively recent (2016) attitudes and implementations of euthanasia and physician assisted suicide in North America and Europe, noting ever evolving opinions of the general public and physicians when it comes to this controversial topic [30].

Dr. Michael Tamimi is a 1st year internal medicine resident at  NYU Langone Health

Peer reviewed by Ian Henderson, MD, Editor, Clinical Correlations, internal medicine, a chief resident, NYU Langone Health


1. Bever, Lindsey. “David Goodall, 104, just took his own life, after making a powerful statement about assisted death” The Washington Post May 2018. Web. 10 May 2018

2. Williams AW, Dwyer AC, Eddy AA, et al; American Society of Nephrology Quality, and Patient Safety Task Force. Critical and honest conversations: the evidence behind the “Choosing Wisely” campaign recommendations by the American Society of Nephrology. Clin J Am Soc Nephrol. 2012;7(10):1664-1672.

3. Kurella Tamura M, Covinsky KE, Chertow GM, Yaffe K, Landefeld CS, McCulloch CE. Functional status of elderly adults before and after initiation of dialysis. N Engl J Med. 2009;361(16):1539-1547.

4. Carson RC, Juszczak M, Davenport A, Burns A. Is maximum conservative management an equivalent treatment option to dialysis for elderly patients with significant comorbid disease? Clin J Am Soc Nephrol. 2009;4(10):1611-1619.

5. Tamura MK, Chun Thomas I, Montez-Rath M, Dialysis Initiation and Mortality Among Older Veterans with Kidney Failure Treated in Medicare vs The Department of Veterans Affairs. JAMA Intern Med. 2018;178(5):657-664. doi:10.1001/jamainternmed.2018.0411

6. Robinson BM, Akizawa T, Jager KJ, Kerr PG, Saran R, Pisoni RL. Factors affecting outcomes in patients reaching end-stage kidney disease worldwide: differences in access to renal replacement therapy, modality use, and haemodialysis practices. Lancet. 2016;388(10041):294-306.

7.Mayeux R, Ottman R, Maestre G, et al. Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer’s disease. Neurology. 1995;45(3 pt 1):555-557.

8.Schofield PW, Tang M, Marder K, et al. Alzheimer’s disease after remote head injury: an incidence study. J Neurol Neurosurg Psychiatry. 1997;62(2):119-124.

9.Nemetz PN, Leibson C, Naessens JM, et al. Traumatic brain injury and time to onset of Alzheimer’s disease: a population-based study. Am J Epidemiol. 1999;149(1):32-40.

10.Plassman BL, Havlik RJ, Steffens DC, et al. Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias. Neurology. 2000;55(8):1158-1166.

11.Wang HK, Lin SH, Sung PS, et al. Population based study on patients with traumatic brain injury suggests increased risk of dementia. J Neurol Neurosurg Psychiatry. 2012;83(11):1080-1085

12.Lee YK, Hou SW, Lee CC, Hsu CY, Huang YS, Su YC. Increased risk of dementia in patients with mild traumatic brain injury: a nationwide cohort study. PLoS One. 2013;8(5):e62422.

13.Barnes DE, Kaup A, Kirby KA, Byers AL, Diaz-Arrastia R, Yaffe K. Traumatic brain injury and risk of dementia in older veterans. Neurology. 2014;83(4):312-319.

14.Gardner RC, Burke JF, Nettiksimmons J, Kaup A, Barnes DE, Yaffe K. Dementia risk after traumatic brain injury vs nonbrain trauma: the role of age and severity. JAMA Neurol. 2014;71(12):1490-1497.

15.Chu SF, Chiu WT, Lin HW, Chiang YH, Liou TH. Hazard ratio and repeat injury for dementia in patients with and without a history of traumatic brain injury: a population-based secondary data analysis in Taiwan. Asia Pac J Public Health. 2016;28(6):519-527.

16. Barnes, Deborah, et al. Association of Mild Traumatic Brain Injury With and Without Loss of Consciousness With Dementia in US Military Veterans. JAMA Neurology 2018 E1-E7

17. Niknejad B, Bolier R, Henderson Jr CR, et al. Association Between Psychological interventions and Chronic Pain Outcomes in Older Adults. JAMA Intern Med. Published online May 7, 2018. doi:10.1001/jamainternmed.2018.0756

18. Williams AC, Eccleston C, Morley S. Psychological therapies for the management of chronic pain (excluding headache) in adults. Cochrane Database Syst Rev. 2012;11(11):CD007407.

19. Lunde LH, Nordhus IH, Pallesen S. The effectiveness of cognitive and behavioural treatment of chronic pain in the elderly: a quantitative review. J Clin Psychol Med Settings. 2009;16(3):254-262.

20. McGuire BE, Nicholas MK, Asghari A, Wood BM, Main CJ. The effectiveness of psychological treatments for chronic pain in older adults: cautious optimism and an agenda for research. Curr Opin Psychiatry. 2014;27(5):380-384.

21. Ehde DM, Dillworth TM, Turner JA. Cognitive-behavioral therapy for individuals with chronic pain: efficacy, innovations, and directions for research. Am Psychol. 2014;69(2):153-166.

22. Nicholas MK, Asghari A, Blyth FM, et al. Self-management intervention for chronic pain in older adults: a randomised controlled trial. Pain. 2013;154(6):824-835.

23. Miller DC, Blackstone EH, Mack MJ, et al; PARTNER Trial Investigators and Patients; PARTNER Stroke Substudy Writing Group and Executive Committee. Transcatheter (TAVR) versus surgical (AVR) aortic valve replacement: occurrence, hazard, risk factors, and consequences of neurologic events in the PARTNER trial. J Thorac Cardiovasc Surg. 2012;143(4):832-843.e13.

24. Brown JM, O’Brien SM, Wu C, Sikora JAH, Griffith BP, Gammie JS. Isolated aortic valve replacement in North America comprising 108,687 patients in 10 years: changes in risks, valve types, and outcomes in the Society of Thoracic Surgeons National Database. J Thorac Cardiovasc Surg. 2009;137(1):82-90.

25. Bucerius J, Gummert JF, Borger MA, et al. Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg. 2003;75(2):472-478.

26. Andreasen C, Jorgensen E, Gislason G, et al. Association of Timing of Aortic Valve Replacement Surgery After Stroke With Risk of Recurrent Stroke and Mortality. JAMA Cardiol. Published online April 25, 2018. doi:10.1001/jamacardio.2018.0899

27. Gordon BR, McDowell C, Hallgren M, et al. Association of Efficacy of Resistance Exercise Training with Depressive Symptoms. JAMA Psychiatry. Published online May 9, 2018. doi:10.1001/jamapsychiatry.2018.0572

28. Kurian A, Ward K, Hamilton A, et al. Uptake, Results, and Outcomes of Germline Multiple-Gene Sequencing after Diagnosis of Breast Cancer. JAMA Oncol. Published online May 10, 2018. doi:10.1001/jamaoncol.2018.0644

29. Benowitz N, Pipe A, West R, Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers. JAMA Intern Med. 2018;178(5):622-631. doi:10.1001/jamainternmed.2018.0397

30. Emanuel E, Onwuteaka-Philipsen B, Urwin J, et al. Attitudes and practices of Euthanasia and Physician-Assisted Suicide in the United States, Canada, and Europe. JAMA. 2016;316(1):79-90. doi:10.1001/jama.2016.8499