Primecuts-This Week in the Journals

December 18, 2018

By: Siyuan Cao, MD

Peer Reviewed

With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature. This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature fire hose.

Death and Readmissions after Hospital Discharge During the December Holiday period [1]

With the arrival of the December holiday season, there is also rising concern over adequate access to healthcare. This population based retrospective cohort study analyzed death and readmission rates in patients who were discharged from the hospital during the two-week December holiday window (N=217,305), encompassing Christmas and New Year’s day. These results were compared to outcomes during two control periods (N=453,641), both separated from the December holiday window by four weeks.

Patients who were discharged during the December holiday window were at increased risk of death or readmission within 30 days (25.9% compared to 24.7%, adjusted odds ratio 1.09 [95% CI 1.07-1.10]) and were less likely to have outpatient follow up within seven days of discharge (36.3% compared to 47.8%, adjusted odds ratio 0.61 [95% CI 0.60-0.62]). These results were despite of the finding that patients discharged during the December holiday window had lower overall baseline risk of readmission or death at 30 days.

These results suggest that physicians need to better risk stratify patients who are discharged during the December holiday period. Given the decreased ability to make outpatient appointment, decreased availability of outpatient providers, and decreased patient desire to see doctors during the holiday period, not all patients can be safely discharged despite clinical stability.

Role of High-Dose Beta-Blockers in Patients with Heart Failure with Preserved Ejection Fraction and Elevated Heart Rate [2]

Beta-blockers are a mainstay of medical therapy for heart failure with reduced ejection fraction, but their use in heart failure with preserved ejection fraction (HFpEF) is less clear. This study included 2592 HFpEF patients from the OPTIMIZE-HF registry who had a discharge heart rate ≥70 beats per minute and had no contraindications to beta-blockers. From this sample, 730 patients received high-dose beta-blockers and of these 640 were matched with patients who did not receive a beta-blocker to build a matched cohort of 1280 patients. High-dose beta-blocker was defined as carvedilol ≥50 mg, metoprolol succinate ≥200 mg, metoprolol tartrate ≥200 mg, bisoprolol ≥10 mg, and atenolol ≥100 mg daily.

All-cause mortality was lower in patients who were prescribed a high-dose beta-blocker at 6 years (63% compared to 68%, hazard ratio 0.86 [95% CI 0.75-0.98]), suggesting that high-dose beta-blockers are associated with better outcomes in HFpEF. However, it is likely premature to routinely use beta-blockers in HFpEF, since currently there are no randomized controlled trials to assess for a causal relationship. Furthermore, it is also unclear how well beta-blockers are tolerated in HFpEF patients. HFpEF patients are more likely than healthy individuals to have chronotrophic incompetence [3], and it is unclear how this underlying condition will interact with the negative chronotropic effects of beta-blockers.

Effect of a Program Combining Transitional Care and Long-term Self-management Support on Outcomes of Hospitalized Patients with Chronic Obstructive Pulmonary Disease [4]

COPD can be a difficult and frustrating disease to manage, for both the clinician and the patient, due to its propensity for exacerbations, its dependence on patient behaviors, and its overall impact on patients’ quality of life. This single-center, single-blind randomized clinical trialed evaluated the effect of a three-month COPD self-management program on incidence of COPD-related acute care events, defined as ED visit or hospitalization, and patients’ quality of life. Of the 240 patients enrolled, 120 were randomized to the intervention arm, which included transition support with COPD nurses, standardized self-management support consisting of education on medication management and recognition of COPD exacerbations, and motivational interviewing.

At 6 months, participants in the COPD self-management program had fewer COPD-related acute care events per patient (0.72 compared to 1.40, difference 0.68 [95% CI 0.22-1.15]). Patient’s health-related quality of life was also statistically significantly better in the intervention group, although interpretation of this effect is limited by the wide confidence intervals.

These results suggest that increased patient education and post-discharge support allow patients to take ownership of their own health, improve their quality of life, and decrease healthcare utilization. Further studies should stratify based on GOLD staging to assess for the generalizability of these findings.

FOCUS Trial Collaboration. Effects of Fluoxetine on Functional Outcomes after Acute Stroke [5]

Stroke can be a debilitating illness that severely reduces patients’ independence, function, and overall quality of life. The FLAME trial suggested a beneficial effect of early fluoxetine use on post-ischemic stroke functional status at 3 months; while the mechanism for this effect is unclear, researcher hypothesized that it may be due to the anti-inflammatory effects of SSRIs or serotonin’s role in modulating motor outputs and neural plasticity. However, this beneficial effect of fluoxetine in stroke patients has yet to be shown in a large clinical trial.

The FOCUS trial is one of the first large, randomized, double-blind, placebo-controlled trial aimed to quantify the effects of fluoxetine on post-stroke functional outcomes [6]. This trial enrolled 3127 adult patients with ischemic or hemorrhagic stroke and resulting focal neurologic deficits who were randomized to fluoxetine 20 mg or placebo daily starting at day 2-15 after stroke onset. There was no significant difference in functional status between treatment and control groups (odds ratio 0.951 [95% CI 0.839-1.079]). The treatment group had a lower rate of new depression compared to that of the control group, but was also more likely to have bone fractures. The study was limited by moderate adherence to the medication, which can lead to overall underestimation of the effect; however; the data also did not show a positive correlation between effect and adherence.

These results suggest fluoxetine does not improve post-stroke functional status and its role in treating post-stroke depression may be limited by side effects. Additional trials on this topic include the AFFINITY and EFFECTS trials, which are currently ongoing [6].


Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation [7]

The MITRA-FR trial did not find a statistically significant difference in all-cause mortality or hospitalization rate in secondary mitral regurgitation patients who received transcatheter mitral-valve repair in addition to medical therapy; these results are in contrast to the findings from the COAPT trial, which found lower rates of both outcome measures. Severity of patient illness may be one of the explanations for these different findings, suggesting that patients should have a trial of optimal medical therapy prior to percutaneous repair.

Reduced Cost of Specialty Care Using Electronic Consultations for Medicaid Patients [8]

The demand for specialty care is at an all time high, but supply of care is constrained by limited access and high costs; one potential solution is the use of electronic consultations (eConsults) whereby information exchange can occur electronically. This study found a decrease in health care costs from implementation of an eConsult platform in a statewide health center caring for primarily underserved Medicaid patients.

Sleep Apnea Increases the Risk of New Hospitalized Atrial Fibrillation [9]

Obstructive sleep apnea and atrial fibrillation often afflict the same patient population, although there is debate over whether this relationship is due to causation or correlation. In this historical cohort of arrhythmia-free patients, nocturnal hypoxemia was independently associated with new-onset atrial fibrillation after controlling for confounders, which may illuminate the mechanism through which patients with OSA develop atrial fibrillation.

Siyuan Cao is a 1st-year internal medicine resident at NYU Langone Health

Peer reviewed by Neil Shapiro, MD, Editor-in-Chief, Clinical Correlations, Associate Professor, Department of Medicine, NYU Langone Health

Image courtesy of Wikimedia Commons By Lotus Head from Johannesburg, Gauteng, South Africa 


  1. Lapointe-Shaw L, Austin PC, Ivers, NM, et al. Death and readmissions after hospital discharge during the December holiday period: Cohort study. BMJ 2018;363;k4481.
  2. Lam PH, Gupta N, Dooley DJ, et al. Role of high-dose beta-blockers in patients with heart failure with preserved ejection fraction and elevated heart rate. Am J Med. 2018;131(12):1473-81.
  1. Phan TT, Shivu GN, Abozguia K, et al. Impaired heart rate recovery and chronotropic incompetence in patients with heart failure with preserved ejection fraction. Circ Heart Fail. 2009;3(1):29-34.
  2. Aboumatar H, Naqibuddin M, Chung, S, et al. Effect of a program combining transitional care and long-term self-management support on outcomes of hospitalized patients with chronic obstructive pulmonary disease. JAMA. 2018;320(22):2335-43.
  3. FOCUS Trial Collaboration. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. Lancet. 2018; (published online Dec 5). DOI: 10.1016/S0140-6736(18)32823-X.
  1. Mead G, Hackett ML, Lundström E, et al. The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: a study protocol for three multicentre randomised controlled trials. Trials. 2015;16:369.
  2. Obadia J-F, Messika-Zeitoun D, Leurent G, et al. Percutaneous repair or medical treatment for secondary mitral regurgitation. N Engl J Med 2018;379:2297-2306.
  3. Daren A, Victor GV, Emil C, et al. Reduced cost off specialty care using electronic consultations for Medicaid patients. Health Affairs. 2018;37(12):2031–6.
  4. Kendzerska T, Gershon AS, Atzema C, et al. Sleep apnea increases the risk of new hospitalized atrial fibrillation: A historical cohort. Chest. 2018;154(6):1330-9.