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 firehose.
There are over 15 million Americans living with COPD , and each year nearly half will have at least one acute exacerbation (AECOPD) . Current guidelines recommend that clinical criteria guide antibiotic prescribing practices in AECOPD, but previous studies have suggested adding laboratory data may better predict who will benefit from antibiotic therapy [3, 4].
The PACE trial randomized 653 patients across 86 outpatient general medical practices in the UK to usual care guided by point-of-care CRP (POCCRP) testing or usual care alone. Eligible patients were aged 40 or over, presenting with AECOPD of 1-21 days duration. Exclusion criteria included the need for hospitalization and history of respiratory failure. There were two primary outcomes: patient-reported use of antibiotics within 4 weeks of randomization and patient-reported health status after 2 weeks, measured with the Clinical COPD Questionnaire.
Fewer patients reported receiving antibiotics in the POCCRP group (57%) compared to control (77.4%) (adjusted odds ratio, 0.31; 95% CI, 0.20–0.47). Scores on the Clinical COPD Questionnaire were statistically equivalent at the time of randomization (POCCRP 3.2 ± 1.16; Control 3.3 ± 1.11) and at 2-week follow-up (POCCRP, 2.6 ± 1.23; Control 2.8 ± 1.29).
Physicians in this study were offered guidance regarding incorporation of POCCRP results into decision making: the likelihood of benefit with antibiotics was low if CRP < 20, intermediate if 20 ≤ CRP ≤ 40, and high if > 40. Antibiotic prescribing for these groups was 33%, 84% and 95%, respectively. Previous studies suggest that primarily patients with purulent sputum in the intermediate group would benefit from antibiotics [2,3]; therefore, this group was likely over-treated. A valuable follow-up study would randomize patients with AECOPD, 20 ≤ CRP ≤ 40 and non-purulent sputum to antibiotic treatment or placebo to verify safety of foregoing antibiotic treatment in this group.
Approximately 2-13% of people with Stage 3 CKD and 19-37% of people with Stage 4 CKD have chronic metabolic acidosis [6,7]. Options for therapy are currently limited to oral alkali supplements (e.g., sodium bicarbonate) and dietary changes, but veverimer is a newly studied polymer that binds hydrochloric acid in the gastrointestinal lumen and inhibits its absorption.
Researchers selected adults in Eastern Europe and the US with serum bicarbonate between 12–20 mmol/L and eGFR 20–40 mL/min/1.73m2. Patients were randomized to veverimer or placebo and followed for 52 weeks. The primary outcome was incidence of adverse events (AEs). Secondary outcomes included change in serum bicarbonate.
In the first 12 weeks, there was a significant increase in GI AEs in the veverimer group (17%) compared to placebo (9%) . After 12 weeks, there were no differences in any AEs, serious AEs or withdrawals due to AEs between groups. Patients taking veverimer were significantly more likely to have an increase in serum bicarbonate of at least 4mmol/L or normalization of serum bicarbonate (63% vs. 38%, difference between groups 25%; 95% CI 10-39%).
While oral alkali has its limitations (GI side effects, sodium load), it is the standard of treatment, and this study failed to compare the two. The company behind veverimer – Tricida – is seeking accelerated approval from the FDA; they funded this study, and the authors include the CEO & President and multiple members of the advisory board. A better study would have compared veverimer head-to-head with sodium citrate, or would have selected patients who were acidotic despite maximal oral alkali load, or who didn’t tolerate it due to side effects, and then randomized them to veverimer or placebo.
Ambulatory blood pressure monitoring (ABPM) is recommended by the AHA, ACC and USPSTF, but clinicians have been reluctant to adopt the practice. Banegas, et al. made a splash last year when they published an association between white coat hypertension (WCH) and all-cause mortality (HR 2.24, 95% CI 1.74–2.88) . What’s the utility of ABPM in WCH if in-office hypertension alone predicts mortality?
This meta-analysis looked at 27 studies comprising over 25,000 patients with either WCH or white coat elevation (WCH in patients on anti-hypertensives) (WCE) and nearly 35,000 with normal BP who were followed for a mean of at least 3 years. WCH was defined by each study as elevated office blood pressure and normal ABPM or home blood pressure monitoring (HBPM). All studies were controlled for age, sex, previous major adverse cardiovascular events, and antihypertensive medication. The primary outcomes assessed were all-cause mortality and cardiovascular events.
WCH was associated with cardiovascular events compared to normotension (HR 1.36, 95% CI 1.03–2.00), while WCE had no such association (HR 1.12, 95% CI 0.91–1.39). WCH was also associated with all-cause mortality (HR 1.33, 95% CI 1.07–1.67) and WCE was not (HR 1.11, 95% CI 0.89–1.46).
Some suggest that based on this study, patients with WCH deserve antihypertensive therapy while those with WCE do not need further titration of their antihypertensive regimen – thus identifying one patient group that would truly benefit from ABPM/HBPM. Clarity might come in the form of two trials: one randomizing patients with WCH to antihypertensive treatment or placebo, and another where patients with WCE are randomized to further uptitration of antihypertensives or placebo. Until then, expect this topic to continue generating debate.
1 mmHg is worth a pound of cure – isn’t that what cardiologists say? Observational studies have shown an association between elevated systolic blood pressure and valvular heart disease (VHD). The question remains: does lowering blood pressure reduce the risk of VHD?
329,237 white British individuals were selected from the U.K. Biobank. Researchers used previous GWAS meta-analyses to identify 130 single-nucleotide polymorphisms (SNPs) associated with systolic blood pressure and turned them into a genetic risk score (GRS) where each SNP was worth 0, 1 or 2 based on an individual’s genotype and each SNP was weighted based on its effect on SBP. Primary outcomes were VHDs as a composite and as individual entities.
For each genetically-associated increase in blood pressure of 20mmHg there was an association with the composite outcome of VHD (OR 2.85, 95% CI 1.69–4.78), as well as aortic stenosis (OR 3.29, 95% CI 1.52–7.12) and mitral regurgitation (OR 2.22, 95% CI 1.09–4.52). The association with aortic regurgitation was not statistically significant (OR 2.59, 95% CI 0.75–8.92).
This study adds to the body of data pointing to an association between hypertension and VHD. A randomized, controlled trial testing this hypothesis will not occur, as the other known advantages of blood pressure lowering would make withholding treatment unethical. Yet the plausibility of this connection may provide further motivation for patients to take their blood pressure-lowering medications.
This study randomized 71 patients with hypertension on outpatient hemodialysis to lung ultrasound-guided estimation of dry weight or usual care and underwent 48-hour ABPM at baseline and after 8 weeks. At the end of the trial, the treatment group had significant reductions in SBP (–6.61mmHg vs. –0.67mmHg; p=0.033) and DBP (–3.85mmHg vs. –0.55mmHg; p=0.031) as well as fewer intradialytic hypotensive episodes than the control group (34.3% vs. 55.6%; p=0.072).
This study created a synthetic population with comorbidities representative of the U.S. and simulated outcomes if patients resumed apixaban or warfarin after an upper gastrointestinal bleed over each of the 60 days following resolution of the bleed. Quality-adjusted life years peaked when apixaban was restarted on day 32 and warfarin on day 41.
HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial 
Observational and in vitro studies raised concerns that intramuscular depot medroxyprogesterone acetate (DMPA-IM) might increase women’s susceptibility to HIV acquisition. This study randomized nearly 8,000 HIV seronegative women to DMPA-IM, copper IUD or levonorgestrel implant and found no difference in rates of HIV acquisition between the different methods after 18 months.
This retrospective study looked at over 6,000 patients admitted to general hospital floors with community-acquired pneumonia and found that 67.8% received antibiotics for longer than the shortest effective duration recommended by guidelines. Longer treatment was not associated with improvements in 30-day mortality or readmission, but odds of patient-reported adverse events were 5% greater (95% CI, 2%–8%) for each day of excess antibiotic treatment.
Dr. Charles Gillihan is a physician resident at NYU Langone Health
Peer reviewed by Christian Torres, MD, chief resident, internal medicine, NYU School of Medicine
Image courtesy of Wikimedia Commons
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 Kraut, Jeffrey A., and Madias, Nicolaos E. Metabolic Acidosis of CKD: An Update. AJKD 67.2 (2016): 307–317. https://www.ajkd.org/article/S0272-6386(15)01211-1/fulltext
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 Cardiovascular Events and Mortality in White Coat Hypertension: A Systematic Review and Meta-analysis https://annals.org/aim/fullarticle/2735719/cardiovascular-events-mortality-white-coat-hypertension-systematic-review-meta-analysis
 Banegas, Jose R., et al. Relationship between Clinic and Ambulatory Blood-Pressure Measurements and Mortality. NEJM 378.16 (2018): 1509–1520. https://www.nejm.org/doi/full/10.1056/NEJMoa1712231
 Nazarzadeh, Milad, et al. Systolic Blood Pressure and Risk of Valvular Heart Disease. JAMA Cardiol Epub ahead of print (2019) E1–E8. https://jamanetwork.com/journals/jamacardiology/fullarticle/2737872
 Loutradis, Charalampos, et al. The effect of dry-weight reduction guided by lung ultrasound on ambulatory blood pressure in hemodialysis patients: a randomized controlled trial. Kidney International 95.6 (2019): 1505–1513. https://www.sciencedirect.com/science/article/pii/S0085253819302704
 Pappas, Matthew A., et al. Resuming Anticoagulation following Upper Gastrointestinal Bleeding among Patients with Nonvalvular Atrial Fibrillation—A Microsimulation Analysis. J Hosp Med 14.7 (2019): 394–400. https://www.journalofhospitalmedicine.com/jhospmed/article/198304/hospital-medicine/resuming-anticoagulation-following-upper-gastrointestinal
 Ahmed, Khatija, et al. HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial. Lancet E pub ahead of print (2019). https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31288-7/fulltext
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