Primecuts-This Week in the Journals

March 15, 2016

1024px-Just_Say_NoBy Jafar Al-Mondhiry, MD MA

This week saw the passing of former first lady Nancy Reagan, a national icon during and after her time, and a pioneer of many social and health-related movements.  Her “Just Say No” campaign became an international catch phrase, something featured in newspapers, magazines, TV commercials, and even music videos [1]. Even while the nation struggles more than ever with drug abuse and new ways to address it – now with drug overdose eclipsing car accidents as the leading cause of injury death– we remember her dedication to helping at risk youth [2].  Her influence in medicine went far beyond her time living in the White House, with personal and public advocacy in areas of breast cancer, Alzheimer’s disease, and stem cell research.  She was remembered fondly this week by many on her way to her final resting place in southern California, and even on stage by the Beach Boys as a true California Girl [3].

Early invasive strategies for patients over 80 years old with NSTEMI or unstable angina prove to be superior to conservative strategies in a Norwegian study (“After Eighty Study”) [4]

In this open-label randomized controlled multicentre trial, 457 patients aged 80 years or older presenting with an NSTEMI or unstable angina were randomly assigned to an invasive strategy (including early coronary angiography with immediate assessment for percutaneous coronary intervention, coronary artery bypass graft, and optimum medical treatment) or to a conservative strategy (optimum medical treatment alone). The patients were admitted to 16 hospitals in the South-East Health Region of Norway. The primary outcome was a composite of myocardial infarction, need for urgent revascularization, stroke, and death and with a medial follow-up time of 1.53 years. The primary outcome occurred in 40.6% patients assigned to the invasive group and 61.4% patients assigned to the conservative group (HR 0.53 [95% CI 0·41–0·69], p<0·0001; NNT = 4.8).  Specifically, HRs for the four components of the primary composite endpoint were 0.52 (0·35–0·76; p=0·0010) for myocardial infarction, 0.19 (0·07–0·52; p=0·0010) for the need for urgent revascularization, 0.60 (0·25–1·46; p=0·2650) for stroke, and 0.89 (0·62–1·28; p=0·5340) for death from any cause. The two strategies did not differ in terms of bleeding complications. Treatment efficacy was diluted with increasing age, and the study excluded patients with short life expectancy (<12 months), clinical instability, or severe mental disorders, including dementia, which would interfere with compliance.   Overall, however, these findings support the use of invasive strategies for the elderly, a group previously excluded from many important clinical trials.

Kidney transplants from HLA-incompatible live donors show survival benefit over wait-list deceased donor transplants [5]

Expanding on data from a large single-center study from Johns Hopkins, this paper tracked survival of kidney transplant recipients from 22 centers receiving kidneys from HLA-incompatible donors.  These recipients included 1025 patients who underwent perioperative desensitization therapy for donor-specific antibodies along with transplantation, who were cross-matched and categorized as having low, medium, or high donor-specific antibody levels. Two sets of matched controls were drawn from the Scientific Registry of Transplant Recipients (SRTR) waiting list. The first group consisted of 5125 wait-listed patients, some of whom subsequently received a transplant from a deceased donor (waiting-list-or-transplant control group). The second group consisted of 5125 wait-listed patients who never underwent kidney transplantation (waiting-list-only control group).

Recipients of kidney transplants from incompatible live donors had a significant survival benefit at all time points (1, 3, 5 and 8 years) as compared with the waiting-list-or-transplant control group and the waiting-list-only control group (P<0.001 for both comparisons). Receiving a kidney from an incompatible live donor was associated with an absolute increase of 13.6% survival at 8 years, as compared with remaining on the waiting list or receiving a transplant from a deceased donor (NNT = 7.35), and 32.6% survival increase, as compared with remaining on the waiting list and not receiving a transplant from a deceased donor (NNT = 3.06). This survival benefit was seen across all donor-specific antibody levels, but were especially pronounced in those matched with lower antibody levels.  These findings support the generalizability of the former single-center study, and pave the road for more successful and timely renal transplantation in the United States.

A randomized clinical trial of vitamin D supplementation failed to produce benefit on tibial cartilage volume or knee pain among patients with symptomatic knee osteoarthritis with vitamin D deficiency [6]

A multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia enrolled 413 patients with symptomatic knee osteoarthritis and low levels 25-hydroxyvitamin D (12.5-60 nmol/L) to participate in a trial investigating the benefits of vitamin D supplementation on pain scores or tibial cartilage volume.  Patients were either randomized to receive monthly treatment with oral vitamin D3 (50 000 IU; n = 209) or an identical placebo (n = 204) for 2 years.  Primary outcomes were pain scores were measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and tibial cartilage volume was assessed using MRI at baseline and 24 months, with cartilage defects and bone marrow lesions also assessed by MRI as secondary outcomes.

Despite significant increase in the level of 25-hydroxyvitamin D between the two groups at the end of the trial (40.6 vs. 6.7, p<0.001), there were no significant differences in annual change of tibial cartilage volume (−3.4% in the vitamin D group vs −4.2% in the placebo group (p = 0.13) or WOMAC pain score (−49.9 in the vitamin D group vs −35.1 in the placebo group (p=0.10).  There were also no significant differences in change of tibiofemoral cartilage defects (0.3 in the vitamin D group vs 0.5 in the placebo group, p=0.21) or change in tibiofemoral bone marrow lesions (−0.1 in the vitamin D group vs 0.3 in the placebo group, p=0.06).  Although scores trended towards significance, these findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving knee pain in patients with knee osteoarthritis, and challenge a widely held practice in osteoarthritis.

Mindfulness-based cognitive therapy proves to be a viable alternative to maintenance antidepressant treatment in the prevention of depressive relapse or recurrence among primary care patients [7]

In a single-blind, parallel, randomized clinical trial of primary care patients in the UK, mindfulness-based cognitive therapy (MBCT) was studied as an alternative to maintenance antidepressants for patients with recurrent depression.  In this study, 424 patients from 95 clinical practices in rural and urban settings were randomly assigned to either MBCT and tapering or discontinuing of their current antidepressant or continuing with maintenance doses of their antidepressant. Participants were aware of treatment allocation and research assessors were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with patients followed across a 24-month study period. The time to relapse or recurrence of depression did not differ between MBCT and maintenance antidepressants over 24 months (hazard ratio 0.89, 95% CI 0·67–1·18; p=0·43), nor did the number of serious adverse events.  While not superior to maintenance antidepressants, previous studies have confirmed the superiority of MBCT vs. no MBCT in tapering or discontinuing antidepressants, and this study at least confirms the safety of using this technique in patients who wish to stop their antidepressants.  This paper contributes to the widening base of mindfulness-related benefits in many medical conditions, and provides a cost-effective alternative to traditional medical interventions.

Best of the rest…

A retrospective study of patients with acute pulmonary embolism diagnosed on CT pulmonary angiography showed that decreased LA volume is associated with higher mortality.  Specifically, mortality was higher for LA volume ≤62 mL compared with those with an LA volume >62 mL (19.6% vs 8.9%, respectively; HR, 2.44; P < .001), a left ventricle volume ≤67 mL (16.4% vs 8.3%; HR, 1.8; P = .024) and a right atrium/LA volume ratio >1.2 (17% vs 9.4%; HR, 2.1; P = .002) [8].

A major double-blind, placebo-controlled trial looking at the risk of major adverse cardiovascular events associated with the use of naltrexone-buproprion therapy for overweight and obese patients was published, although the trial was terminated early [9].

A meta-analysis of 23 studies on cardiovascular risk associated moderate compared to heavy alcohol intake showed increased cardiovascular risk for myocardial infarction, ischemic stroke, and hemorrhagic stroke for both groups within 24 hours.  However, moderate alcohol intake was associated with a protective effect for myocardial infarction and hemorrhagic stroke (≈2–4 drinks: relative risk=30% lower risk), while heavy alcohol drinking was associated with higher cardiovascular risk in the following day (≈6–9 drinks: RR=1.3–2.3) and week (≈19–30 drinks: RR=2.25–6.2)(10).

Endoscopic ultrasonography-guided double-balloon-occluded gastrojejunostomy bypass (EPASS) has been proving technical success for malignant gastric outlet obstruction in prospective trials.  This is the first evaluation of the procedure in clinical subjects, and provides more long-term efficacy over traditional gastric outlet stents, while maintaining an endoscopic approach over traditional surgical gastrojejunostomy [11].

Jafar Al-Mondhiry, MD MA, is a 1st-year internal medicine resident with NYU School of Medicine.

Peer Reviewed by Karin Katz, MD, Associate Editor, Clinical Correlations

Picture from the Reagan Library Courtesy of Wikimedia Commons



Beach Boys to Bon Jovi: Nancy Reagan’s rock ‘n’ roll life.

        March 9, 2016.

46,471: Drug Overdoses Killed More Americans Than Car Crashes or Guns.

        Nov 5, 2016.  CNS News.

Watch Beach Boys’ Touching Tribute to Nancy Reagan.

         March 7, 2015.  Rolling Stone Magazine.
        4.    Tegn N, Abdelnoor M, Aaberge L, et al.

Invasive versus conservative strategy in patients aged 80 years or older

        with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial.  The Lancet.  2016; 387(10023): 1057-1065.
        5.     Orandi BJ, Luo X, Massie AB, et al.

Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors

        . NEJM.  2016; 374: 940-950.
        6.     Jin X, Jones G, Cicuttini F, et al.

Effect of Vitamin D Supplementation

      on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis:  A Randomized Clinical Trial.  JAMA. 2016; 315(10): 1005-1013.
        7.     Kuyken W, Hayes R, Barrett B, et al.

Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy

        compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial.  The Lancet.  2015; 386(9988): 63-73.
        8.     Aviram G, Soikher E, Bendet A, et al.

Prediction of Mortality in Pulmonary Embolism

        Based on Left Atrial Volume Measured on CT Pulmonary Angiography.  Chest. 2016; 149(3): 667-675.
        9.     Nissen SE, Wolski KE, Prcela L.

Effect of Naltrexone-Bupropion

      on Major Adverse Cardiovascular Events in Overweight and Obese Patients With Cardiovascular Risk FactorsA Randomized Clinical Trial. JAMA. 2016; 315(10): 990-1004
        10.  Mostofsky E, Chahal HS, Mukamal KJ, et al.

Alcohol and Immediate Risk

        of Cardiovascular Events:  A Systematic Review and Dose–Response Meta-Analysis. Circulation. 2016; 133: 979-987.
        11.  Itoi T, Ishii K, Ikeuchi N, et al.

Prospective evaluation of endoscopic ultrasonography-guided double-balloon-occluded gastrojejunostomy bypass

        (EPASS) for malignant gastric outlet obstruction. Gut. 2016; 65: 193-195.