By Zoe Lawrence, 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 firehose.
Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia (REDUCE_IT) [1]
Patients with cardiovascular risk factors or known coronary heart disease treated with statins have a decrease in LDL, however those patients who continue to have elevated triglycerides are still at increased risk for long-term mortality [2]. In this randomized, double-blinded trial, patients were randomized to receive either placebo or icosapent ethyl (Vascepa), an omega-3 fatty acid with potential anti-inflammatory and plaque-stabilizing properties The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina.
This study randomized 8179 patients who were ≥ 45 with established cardiovascular disease or ≥ 50 with diabetes and at least one other risk factor. In total, 70.7% were enrolled for secondary prevention and 29.3% for primary prevention. Patients had LDL 41-100 mg/dl (median 75) on a stable dose of a statin, and triglycerides 150-499 mg/dl (median 216). This study found a significant reduction in events in the treatment group (17.2% vs 22.0%, HR 0.75, 95% CI 0.68-0.83, p<0.001) with a number needed to treat of 21 over a median follow-up of 4.9 years. Interestingly this risk reduction was independent of attained triglyceride levels, suggesting additional benefit beyond triglyceride lowering. The overall rates of adverse events did not differ significantly between the two arms. Notably, Amarin Pharma, the company that produces Vascepa, sponsored this trial. Despite this clear bias, the trial is a well-designed study that supports the use of a relatively low-risk supplement to reduce cardiovascular risk.
Fracture Prevention with Zoledronate in Older Women with Osteopenia [3]
Bisphosphonates are the mainstay of treatment for osteoporosis, but patients with osteopenia are also at increased risk for fracture and are not routinely placed on bisphosphonate therapy. This randomized, double-blind, placebo-controlled trial set out to determine the efficacy of zolendronate in the prevention of fractures in post-menopausal women older than 65 with osteopenia. The 2000 participants were randomized to receive four zolendronate infusions at 18-month intervals versus infusions of normal saline. They were followed over six years, and the number of fragility fractures was lower in the treatment group (122 women with 131 fractures) than in the placebo group (190 women with 227 fractures) with a hazard ratio of 0.63 (95% CI 0.50-0.79, p<0.001). The number needed to treat to prevent the occurrence of a single fragility fracture was 10. Notably, the odds ratio for cancer with zolendronate was 0.67 (95% CI 0.50-0.89) but no other adverse events were significantly different between groups.
Patients with osteopenia in the hip or either femoral neck as well as osteoporosis in one site were eligible for inclusion, which may have skewed the results given that zolendronate has already been proven effective in osteoporosis. However, the results were still significant when these patients were excluded. This trial provides good evidence for the use of zolendronate in post-menopausal women age 65 or older with osteopenia.
Fecal microbiota transplant (FMT) has been shown to be an effective treatment for recurrent C. difficile infections. But far more common than C. difficile is Irritable Bowel Syndrome (IBS) which affects up to one in five people at some point in their lives [5]. This study investigates the effects of FMT on symptoms and gut microbiota in patients with IBS of all subtypes. In this double-blinded study, 52 Danish patients with IBS were randomized to treatment with FMT capsules or placebo capsules for 12 days and followed for 6 months. The primary endpoint was reduction of IBS symptoms at 3 months as measured by the IBS-severity scoring system (IBS-SSS). Four healthy fecal donors provided samples for use. At three months, the patients in the placebo arm had a significant improvement in symptoms relative to the FMT arm (IBS-SSS score change -125.71 vs. -52.45, p= 0.012). The FMT recipients had an increase in biodiversity of the microbiome that was not seen in the placebo recipients, however this change did not correlate with symptom improvement. Similar results were found with IBS-specific quality of life questionnaires. Side effects were similar between groups except that the FMT patients had diarrhea during treatment while the placebo patients did not (6 vs. 0 patients).
This study was small, did not discriminate based on IBS subtype, and used a limited number of stool donors. However, it was well designed and the results for the primary endpoint reached statistical significance. FMT likely does not work for treatment of IBS and further research on other treatment options is needed.
Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility [6]
The first successful live birth from a deceased donor uterine transplantation occurred in Brazil in September 2016, and this article detailing this proof of concept was published in December 2018. Although there have previously been a couple cases of successful live births from living donor uterus transplantations, this event marks the first deceased donor success. The patient is a 32-year-old woman with uterine agenesis and the donor was a 45-year-old woman with a history of three vaginal deliveries who died from a subarachnoid hemorrhage.
The recipient’s surgery lasted for 10 hours and 30 minutes and the uterus had a total duration of ischemia of 7 hours and 50 minutes, measured from harvest from the donor until vascular anastomosis in the recipient. A conservative immunosuppression regimen was prescribed given the lack of prior evidence on which to base the regimen. The patient was initially on tacrolimus and mycophenolate mofetil (MMF) but at 5 months, MMF was replaced with azathioprine and prednisone to prepare for pregnancy. The recipient had undergone one cycle of IVF pre-transplant, and the embryo transfer was done 7 months after transplantation. At 35 weeks and 3 days, a healthy baby girl and a normal placenta were delivered via Caesarean. The uterus was removed at the time of delivery and had no evidence of rejection.
Minicuts
This prospective multicenter cohort study found that the nasal microbiota of patients with severe obstructive apnea (OSA) had enriched levels of oral commensal bacteria as well as higher levels of inflammatory biomarkers such as IL-6 and IL-8 relative to patients without OSA. Treatment with CPAP for three months in a subgroup with OSA did not change the composition of the nasal microbiota. While the causes and clinical implications of this finding are unclear, it opens the way for additional research on the relevance of the microbiome in OSA.
Shifting Hepatitis A Epidemiology [8]
Hepatitis A outbreaks are usually associated with contaminated food, however large outbreaks in multiple states across the US recently have disproportionately affected homeless patients and those engaging in drug use, raising concern for person-to-person rather than foodborne transmission. As a result, the CDC’s Advisory Committee on Immunization Practices (ACIP) has revised its recommendations to include homelessness as an indication for hepatitis A vaccination.
This meta-analysis investigates the association of long-term exercise with the risk of falls in older adults. Overall, there was a reduction in patients who fell (RR 0.88, 95% CI 0.79-0.98, p=0.02) and in patients who had injurious falls (RR 0.74, 95% CI 0.62-0.88, p= 0.001) in the exercise group. There was also a trend towards reduction in fractures (RR 0.84. 95% CI 0.71-1.00, p=0.054) in the exercise group. The results of this study are compelling evidence for continuation of exercise in older adults in order to reduce falls and injuries.
Dr. Zoe Lawrence is a resident physician at NYU Langone Health
Peer reviewed by Scott Statman, MD, Chief Resident, Internal Medicine, NYU School of Medicine, NYU Langone Health
References
1 Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019;380:11–22. doi:10.1056/NEJMoa1812792 https://www.ncbi.nlm.nih.gov/pubmed/30415628
2 Klempfner R, Erez A, Sagit B-Z, et al. Elevated Triglyceride Level Is Independently Associated With Increased All-Cause Mortality in Patients With Established Coronary Heart Disease: Twenty-Two-Year Follow-Up of the Bezafibrate Infarction Prevention Study and Registry. Circ Cardiovasc Qual Outcomes 2016;9:100–8. doi:10.1161/CIRCOUTCOMES.115.002104 https://www.ncbi.nlm.nih.gov/pubmed/26957517
3 Reid IR, Horne AM, Mihov B, et al. Fracture Prevention with Zoledronate in Older Women with Osteopenia. N Engl J Med 2018;379:2407–16. doi:10.1056/NEJMoa1808082 https://www.ncbi.nlm.nih.gov/pubmed/30575489
4 Halkjær SI, Christensen AH, Lo BZS, et al. Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study. Gut 2018;67:2107–15. doi:10.1136/gutjnl-2018-316434 https://www.ncbi.nlm.nih.gov/pubmed/29980607
5 Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: a clinical review. JAMA 2015;313:949–58. doi:10.1001/jama.2015.0954 https://www.ncbi.nlm.nih.gov/pubmed/25734736
6 Ejzenberg D, Andraus W, Baratelli Carelli Mendes LR, et al. Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility. Lancet Published Online First: 4 December 2018. doi:10.1016/S0140-6736(18)31766-5 https://www.ncbi.nlm.nih.gov/pubmed/30527853
7 Wu BG, Sulaiman I, Wang J, et al. Severe Obstructive Sleep Apnea Is Associated with Alterations in the Nasal Microbiome and an Increase in Inflammation. Am J Respir Crit Care Med 2019;199:99–109. doi:10.1164/rccm.201801-0119OC https://www.ncbi.nlm.nih.gov/pubmed/29969291
8 Kuehn B. Shifting Hepatitis A Epidemiology . JAMA 2018;320:2522. https://www.ncbi.nlm.nih.gov/pubmed/30575889
9 de Souto Barreto P, Rolland Y, Vellas B, et al. Association of Long-term Exercise Training With Risk of Falls, Fractures, Hospitalizations, and Mortality in Older Adults: A Systematic Review and Meta-analysis. JAMA Intern Med Published Online First: 28 December 2018. doi:10.1001/jamainternmed.2018.5406 https://www.ncbi.nlm.nih.gov/pubmed/30592475