Primecuts – This Week In The Journals

February 9, 2016

Rally_to_support_Planned_ParenthoodBy Nicole Van Groningen, MD

Peer Reviewed

Last week we watched Hillary Clinton become the democratic favorite in the Iowa caucus – only narrowly avoiding getting Bern’ed. On the GOP side, Rand Paul, Mike Huckabee and Rick Santorum pulled out of the Republican race and Donald Trump, who came in second to Ted Cruz, demanded a do-over [1]. The New England Journal of Medicine maintained political relevance this week with its release of a study examining the impact of Texas’ ban on Planned Parenthood services. Also in the journals this week, we learned about the surprising benefits of waiving certain resident duty-hours restrictions, the role of azithromycin in treating (some) people with chronic cough, and the lesser-known benefits of angiotensin receptor blockers.

The impact of Texas’ ban on planned parenthood 

Legislation aimed at excluding Planned Parenthood affiliated providers from participating in state-administered, federally funded family-planning programs is now in various stages of development in 17 states [2]. In 2013, Texas became the first state to enforce such a law. A study published this week examined claims data for all participants in the state-funded Texas Women’s Health Program to ascertain whether the exclusion of Planned Parenthood affiliates had an impact on the provision of contraception and rates of childbirth [3].

In the three months after the Planned Parenthood exclusion, there was a sharp decrease in claims for both long-acting reversible contraceptives (LARC), from 1042 to 672, and injectable contraceptives, from 6832 to 4708, corresponding with relative reductions of 35.5% and 31.1%, respectively. Counties that didn’t have Planned Parenthood services to begin with – serving as a “control” group in the study – showed no change in the provision of either of these contraceptive methods. The difference in the differences was statistically significant (p < 0.001), suggesting a drop in utilization of contraception related to the Planned Parenthood withdrawal. The study’s most stark finding, however, was that 18 months after the withdrawal of Planned Parenthood in counties where Planned Parenthood previously operated, the percentage of women on injectable contraception who underwent childbirth covered by Medicaid increased from 7% to 8.4%, a relative increase of 27.1%. Again, this difference, when compared to that of counties who did not previously offer Planned Parenthood services, was statistically significant.

The observational study is limited by its inability to show causality, lack of adjustment for other county-level changes, and absent data on women who paid out-of-pocket for contraception or used private insurance for childbirth. Still, its findings raise concern that Texas’ divorce from Planned Parenthood may have hurt low-income Texan women by decreasing access to contraception.

Duty hour restrictions make no difference in well-being of America surgical residents

Another NEJM article published this week argues against the benefit of ACGME duty hour restrictions imposed between 2003 and 2011. Although prior studies among surgical residents have failed to show a difference in patient post-operative outcomes in the post-duty hour restriction era, promoters of the hour restrictions maintain that resident well-being and fatigue are bolstered under the regulations [4]. The Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) trial challenged this idea [5]. Investigators randomly assigned 118 ACGME-accredited general surgery residency programs to a flexible-policy (intervention) group, in which no restrictions on shift lengths were imposed, or a standard-policy (control) group, which followed all current ACGME duty hour regulations.

The study’s primary patient-centered outcome, the rate of death or serious complications, didn’t differ between the groups (9.1% in flexible-policy group versus 9.0% in the standard-policy group, p = 0.92), confirming previous reports. However, the study’s surprising finding was that among the 4330 residents surveyed, there was no significant difference between the flexible-policy residents and the standard-policy residents in terms of the resident-centered primary outcomes, which included dissatisfaction with educational quality (11.0% versus 10.7% respectively, p=0.86) and overall well-being (14.9% and 12.0%, p=0.10). Fexible-policy residents were more satisfied with continuity of care and quality of hand-offs, were significantly less likely to leave during an operation, miss an operation, or hand off an active patient care issue. The study highlights residents’ dissatisfaction in transitions of care in standard duty-hours programs, and makes the novel point that residents without shift-length regulations do not experience decreased well-being or educational satisfaction. Still, the study’s lack of generalizability to other specialties limits any potential impact on duty-hour restrictions anytime soon.

Azithromycin Investigated in the Treatment-resistant cough  

Last week, Clinical Correlations reported on strategies to decrease antibiotic use in upper respiratory infections. Now, a study published in Chest questions the role of azithromycin in treating a common non-infectious respiratory condition, the treatment-resistant cough [6]. The study enrolled 54 patients with treatment-resistant cough, a condition occurring in patients with structurally normal lungs after common causes of chronic cough (asthma, GERD, and rhinitis) have been ruled out. Participants were randomly assigned to receive azithromycin (500mg for 3 days, followed by 250mg three times weekly for 8 weeks) or placebo.   The supposed benefit of the macrolide was its anti-neutrophil and anti-inflammatory effects, previously shown to be independent of its antimicrobial effect.[7]

After 4 weeks, the treatment group experienced a clinically and statistically significant improvement in symptoms as measured by the LCQ score, a self-reported quality of life measure in chronic cough (mean change 2.4 vs. 0.7, p=0.01). Among treatment-group patients there was a nearly 20% decrease in exhaled nitric oxide, indicating decreased airway inflammation (p = 0.01). But before prescribing azithromycin to all-comers with chronic cough, consider this: azithromycin’s therapeutic effect was driven almost entirely by the sub-group of patients with asthma. Of the 7 asthmatics included in the study, all had a response to azithromycin, with strikingly high improvements in LCS scores (mean improvement of 6.19, p = 0.01). Given that these patients had failed to improve with usual asthma care, the study invites further investigation of azithromycin’s role in the management of treatment-resistant cough in asthma.

ACE Inhibitors and Angiotensin Receptor Blockers provide similar benefit, in contrast to previous thought 

The benefit of a renin-angiotensin-aldosterone system blockade in improving outcomes in patients with CVD or multiple other cardiovascular risk factors has long been established. But the relative advantages of ACEIs and ARBs have been debated, with ACEIs historically winning out as first-line therapy.

A recent meta-analysis published in the Mayo Clinic Proceedings argues differently [8]. The study identified 106 randomized trials including a total of 254,301 patients without heart failure that compared either ACEIs or ARBs to placebo, ACEI or ARB to active controls, or head-to-head comparisons of ACEIs to ARBs. Compared to placebo, ACEIs conferred a significant reduction in all-cause mortality (RR 0.91; 95% CI 0.86-0.96), cardiovascular death (RR 0.85; 95% CI 0.79-0.92), and MI (RR 0.83; 95% CI 0.78-0.90) whereas ARBs did not. Still, the authors questioned whether ACEIs were truly superior. In a meta-regression analysis, they showed that the placebo event rate had a significant effect on the apparent efficacy of ACEIs and ARBs. The ARB trials, which were conducted around 10 years after the majority of ACEI trials, in an era where cardiovascular risk profiles were better optimized by other factors, had significantly lower placebo event rates, around 5%, compared to 10.5% for most ACEI trials. The authors therefore argue that the lower placebo event rate in the ARB trials is responsible for the apparent lack of efficacy in reducing all-cause and cardiovascular mortality. The authors further support this claim by a meta-analysis of head-to-head comparison trials between ACEIs and ARBs, which showed similar risk for all outcomes, including all-cause mortality and cardiovascular death, between ACEIs and ARBs. Importantly, these trials also found that ARBs were associated with a 28% lower rate of adverse events, such as hyperkalemia, (RR, 0.72, CI, 0.65-0.81) when compared to ACEIs. Great news for drug companies who manufacture ARBs.

Skimmed off the top of other journals: 

Fruits and vegetables may have an impact on body weight independent of their calorie content, according to a recent observational study of participants in the Nurse’s Health Study and the Health Professionals Follow-Up Study. Participants who consumed high levels flavonoids, found in blueberries, citrus fruits, green tea, and various other types of produce, self-reported significantly lower levels of weight gain over 4-year intervals than those who filled their plates with meat and potatoes [9].

The BMJ reported that a vaccine for the Zika virus could be in production by the end of 2016, marketed by Invovio Pharmaceuticals. Public health officials, however, doubt this bold prediction, and insist that the focus must remain on battling mosquitos. The Unites States and Brazil are reportedly “examining approaches that involve the release of genetically modified male mosquitos to interrupt reproduction [10].”

Proenkephalin (proENK) is a novel biomarker that may become beneficial in estimating prognosis in patients with heart failure. A 4-year single center prospective cohort study of 200 participants with heart failure found that those with higher proENK levels at the beginning of the study had a significantly increased rate of cardiovascular-related hospital admission or death at follow up (HR 3, 95% CI, 1.4-6.7) [11].

The CDC recommended that all sexually active women not on contraceptives abstain from alcohol in order to prevent fetal alcohol syndrome. Literal buzzkill [12].


Dr. Nicole Van Groningen is a 3rd year resident at NYU Langone Medical Center

Peer reviewed by Matthew Dallos, MD, chief resident, internal medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons


  1. Donald Trump accuses Ted Cruz of Fraud in Iowa, calls for new election. CBS News. February 3, 2016.
  2. Medicaid family planning eligibility expansions. New York: Guttmacher Institute. January 2016.
  3. Stevenson AJ, Flores-Vazquez IM, Allgeyer RL, Schenkkan PJD, Potter JE. Effect of Removal of Planned Parenthood from the Texas Women’s Health Program. N Engl J Med. 2016 Feb 2 [Epub ahead of print].
  4. Effects of resident duty hour reform on surgical and procedural patient safety indicators among hospitalized Veterans Health Administration and Medicare patients. Med Care. 2009; 47: 723-731.
  5. Billmoria KY, Chung JW, Hedges LV et al. National cluster-randomized trial of duty-hour flexibility in surgical training. N Engl J Med. 2016 Feb 2 [Epub ahead of print].
  6. Hodgson D, Anderson J, Reynolds C, et al. The Effects of Azithromycin In Treatment Resistant Cough: A Randomised, Double Blind, Placebo Controlled Trial. Chest. 2016 January [published online].
  7. Ianaro A, Ialenti A, Maffia P, et al. Anti-inflammatory activity of macrolide antibiotics. J Pharmacol Exp Ther. 2000 Jan; 292(1): 156-63.
  8. Bangalore S, Fakheri R, Toklu B, Ogedegbe G, Weintraub H, Messerli FH. Angiotensin-Converting Enzym Inhibiros or Angiotensin Receptor Blockers in Patients Without Heart Failure? Insights From 254,301 Patients From Randomized Trials. Mayo Clinic Proceedings. 2016; 91(1): 51-60.
  9. Bertoia ML, Rimm EB, Mukamal KJ, et al. Dietary flavonoid intake and weight maintenance: three prospective cohorts of 124 086 US men and women followed for up to 24 years. BMJ. 2016; 352: i17.
  10. Dyer O. Zika vaccine could be in production by year’s end, says maker. BMJ. 2016; 352 :i630.
  11. Arbit B, Marston N, Shah K, et al. Prognostic Usefulness of Proenkephalin in Stable Ambulatory Patients with Heart Failure. American Journal of Cardiology. [Article in Press].

12. Vital Signs: Alcohol and Pregnancy. The Centers for Disease Control and Prevention. February 2, 2016.