Primecuts – This Week In The Journals

December 8, 2016

Tobacco-free_zoneBy Robert Freilich, MD

Peer Reviewed

Levels of smoking have dropped to record lows in the United states. Per a NY Times article1, the CDC reports that smoking levels are down in Americans from 21% in 2005 to 15% in 2015. This represents a reduction of almost 9 million Americans who are smoking. Encouragingly, smoking declined the greatest among the youngest age groups. Fifteen percent is the lowest level since the US began recording levels of smoking 50 years ago. Moving from population changes leading to better health outcomes to medical research into future health improving interventions, here are this week’s Prime Cuts:

Patient Outcomes in Patients Receiving Palliative Care

Palliative care, a scary and difficult to understand consultation for patients, is defined as patient and family-centered care that optimizes quality of life by anticipating, preventing, and treating suffering2. This past week in JAMA, Kavalieratos, et al. attempt to estimate the association of palliative care with patient Quality of Life (QoL), symptom burden and survival3. The authors performed systematic review of 23 palliative care randomized-controlled trials from 2008 to present and included 12,731 patients a meta-analysis. Each trial underwent an independent review by at least 2 investigators and assessed a risk of bias (high, low, or unclear) as part of the data stratification process.  Due to the variety of instruments used to evaluate QoL and symptom burden, pooled effects were summarized as Standard mean differences (SMDs).  The study was separated into 1-3 month follow-up and more longer term look at 4-6 month follow-up.  After adjusting for risk of bias, this study demonstrated that Palliative care was associated with improved patient QoL (SMD 0.20; 95% CI, 0.06 to 0.34), but not symptoms burden or survival (SMD −0.21; 95% CI, −0.42 to 0.00; HR 0.90; 95% CI, 0.69 to 1.17). This study suggests that palliative care services are only partially achieving their defined outcomes, specifically not providing adequate symptom relief. Given the significant variation in study designs, the associations found is this study are weak. Overall, the study shows that current palliative care services improve QoL all patients with severe or life-threatening illness, and can for some patients help address symptom burden and possibly extend survival.

Goals of Care Discussion in Advanced Dementia

Discussions of code status, health care proxy, and desired interventions, frequently called Goals of Care(GOC), are increasingly important in an aging American population. Despite this many patients do not have such conversations. In a JAMA Internal Medical article, Hanson, et al. performed a single-blind cluster randomized clinical4 trial focused at patients with advanced dementia and their family/caregivers with an intervention associated with Goals of Care (GOC).   Hanson et el. point out that from the CASCADE study only 38% of decision makers ever recalled any discussion about Goals of care.  This study compares a GOC intervention, comprising of a video discussion aid describing common GOC elements (end of life care, dementia information, treatment options… ect.) and a structured care plan meeting for family decision to and attention control.   Outcomes were measured at 3, 6, 9 months or death, which looked at quality of communication, concordance of GOCs with caregivers, and an Advanced Care Planning problem score.  In the study, 22 nursing homes participated and 302 Dyads (patient and family/caregivers) were enrolled in both arms of the study.  However, only 128 in the intervention group and 127 in the control group completed 9 month follow up with a total of 60 deaths combined groups completed the study. The study found that the intervention group had Family decision makers reported better quality of communications and better end-of-life communications.  Goal concordance at three months did not differ but after 9 months was better than control.  Ultimately, this study demonstrated that this brief GOC intervention improved end-of-life communications for nursing home residents with dementia and their family/caregivers.

Comparison of The Efficacy and Safety of a Novel P2Y12 Inhibitor with Current Therapy

P2Y12 inhibitors, a class of anti-platelet agents, play a major role in the management of atherothrombotic disease and have reduced the mortality of several forms of cardiovascular disease. Since there initial use numerous new, more potent P2Y12 inhibitors have been developed. Vaduganathan, et al. compare the ischemic and bleeding risks between a newer more potent P2Y12 inhibitor, Cangrelor, and Glycoprotien IIb/IIIa inhibitors (GPIs) plus Clopidogrel5. The author’s pool results from three previous phase III trials from “The Cangrelor vs. Standard Therapy to Achieve optimal Management of Platelet Inhibition program” the CHAMPION trials. Study subjects were >18 YO requiring PCI for Stable angina, non-ST elevation acute coronary syndrome (ACS).  Patients who had received either other P2Y12 inhibitor or abciximab within 5-7 days, or eptifibatide, tirofiban or fibrinolytic therapy within 12 hours were excluded.   A key aspect of this studies design was noting that the original CHAMPION trial had an imbalance between the two groups. For example, the Clopidogrel-GPI group was slightly younger and carried a lower comorbid disease (diabetes, PAD, or Heart failure) burden when compared with the Cangrelor group. To account for difference in baseline risk profile imbalances and other confounders, a propensity score (PS)-matched analysis was performed that found 1021 unique matched pairs to compare.  Overall, when using the PS-Matched analysis the study found  .  This contradicts previous results that showed there was higher risk of bleeding which the authors adjusted to remove any discrepancies in patient profiles.

PCSK9 Inhibitors for CVD Risk Reduction: A Genetic Approach

In NEJM this past week6, Ference, et al. demonstrates that inhibition of Proprotein convertase subtilisin–kexin type 9 (PCSK9), known to already lower LDL levels by ~50-60%, also reduces the risk of cardiovascular events or diabetes similar to Statins.  More importantly the authors sought to determine causality by performing a “Medelian randomization” approach at both the PCSK9 and 3-hydroxy-3-methyl-glutaryl–coenzyme A reductase (HMCR) genes. In short, Ference et al. constructed genetic scoring based which gene allele(s) were associated with lower LDL cholesterol levels, thus mimicking chemical inhibition of either the PCSK9 or HMGCR genes.  Primary cardiovascular outcomes were defined as the initial myocardial infarct (MI), death from coronary heart disease, stroke, and other vascular events.  Diabetes was determined by A1C levels and was defined as a primary safety outcome.  The study was performed on 62,240 case patients and 127,299 controls without such disease. Ference, et al demonstrated that the groups with either higher PCSK9 or HMGCR genetic scores had an 8.4% or 6.6 % respectively of lower risk of MI or death from coronary heart disease (OR, 0.92; 95% confidence interval [CI], 0.88 to 0.95/ OR 0.93; 95% CI, 0.90 to 0.97 respectively). Further, Ference, et al also demonstrate a dose–response analyses with either increasing PCSK9 or HMGCR scores were associated with a stepwise decrease in LDL cholesterol levels and a corresponding stepwise decrease in the risk of MI or death from coronary heart disease. Interestingly, increasing PCSK9 or HMGCR scores were associated with a 6.1% higher risk for diabetes, which the authors noted as appearing to be confined to persons with impaired fasting glucose. Overall, this study takes large steps at establishing causality between variations in either PCSK9 or HMGCR gene and LDL levels and cardiovascular events.

Mini Cuts

In a meta-analysis published in JAMA Internal Medicine7, the authors found existing interventions to reduce burnout in physicians were only associated with small benefits. The strongest evidence was found for organization-direction interventions.

This observational cohort study8 of more than 21,000 US adults aged 65 or older demonstrated a 2.8% reduction in the prevalence of Dementia from 2000 to 2012.

A study in JAMA Oncology9 showed a 33% increase in incidence in cancer when compared to 2005 levels. These estimates were made by applying the Global Burden of Disease methodology.

Dr. Robert Freilich is a 2nd year internal medicine resident at NYU Langone Medical Center

Peer reviewed by Ian Henderson, internal medicine resident, NYU Langone Medical Center and contributing editor, Clinical Correlations

Image courtesy of Wikimedia Commons


  1. Bakalar, Nicholas. (2016, December 5). A New Low for Cigarette Smoking. New York Times.®ion=stream&module=stream_unit&version=latest&contentPlacement=1&pgtype=sectionfront


  1. Definition of Palliative Care. Center for Medicare and Medicaid Services. Federal Register 2008 – 73 FR 32204, June 5, 2008.


  1. Kavalieratos, D. PhD; et al. Association Between Palliative Care and Patient and Caregiver Outcomes: A Systematic Review and Meta-analysis. JAMA. 2016;316(20):2104-2114
  2. Hanson LC, Zimmerman S, Song M, Lin F, Rosemond C, Carey TS, Mitchell SL. Effect of the Goals of Care Intervention for Advanced DementiaA Randomized Clinical Trial. JAMA Intern Med.Published online November 28, 2016.
  3. Vaduganathan M, Harrington RA, Stone GW, Deliargyris EN, Steg PG, Gibson CM, Hamm CW, Price MJ, Menozzi A, Prats J, Elkin S, Mahaffey KW, White HD, Bhatt DL. Evaluation of Ischemic and Bleeding Risks Associated With 2 Parenteral Antiplatelet Strategies Comparing Cangrelor With Glycoprotein IIb/IIIa InhibitorsAn Exploratory Analysis From the CHAMPION Trials. JAMA Cardiol.Published online November 30, 2016.
  4. Brian Ference, MD; et al. Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes. N Engl J Med 2016; 375:2144-2153.
  5. Panagioti M, Panagopoulou E, Bower P, Lewith G, Kontopantelis E, Chew-Graham C, Dawson S, van Marwijk H, Geraghty K, Esmail A. Controlled Interventions to Reduce Burnout in PhysiciansA Systematic Review and Meta-analysis. JAMA Intern Med.Published online December 05, 2016.


  1. Langa KM, Larson EB, Crimmins EM, Faul JD, Levine DA, Kabeto MU, Weir DR. A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012. JAMA Intern Med.Published online November 21, 2016.  
  2. Global Burden of Disease Cancer Collaboration. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol.Published online December 03, 2016.