NEJM Evidence

Understanding the principles of exercise physiology is essential for clinicians. Cardiorespiratory fitness (CRF), one of the key outcomes of an exercise test, is an indicator of future cardiac, metabolic, and other health events.?? ? In 2016, the American Heart Association recommended that CRF be added as a vital sign, given its?importance in predicting cardiovascular disease and all-cause mortality.? ? Knowledge of a patient’s CRF also informs the implementation of lifestyle-based strategies to reduce cardiovascular risk and can empower patients to effect behavioral changes. Yet CRF remains?undervalued and underutilized in cardiovascular disease prevention and management.? ? Continue reading the Review Article: “Physiological Principles of Exercise” by Tiffany L. Brazile, MD, Benjamin D. Levine, MD, and Keri Shafer, MD: https://eviden.cc/3Pe9Ay8? ? #Cardiology?

Clinical guidelines have concluded that there are insufficient data to provide recommendations for the hemoglobin threshold for the use of red cell transfusion in patients with acute myocardial infarction (MI) and anemia.?? ? After the recent publication of the Myocardial Infarction and Transfusion (MINT) trial, Carson and colleagues performed an individual patient-level data meta-analysis to evaluate the effect of restrictive versus liberal blood transfusion strategies. The results are now published in NEJM Evidence.? ? The investigators conducted searches in major databases. Eligible trials randomly assigned patients with MI and anemia to either a restrictive (i.e., transfusion threshold of 7–8 g/dl) or liberal (i.e., transfusion threshold of 10 g/dl) red cell transfusion strategy.? ? The authors used individual patient data from each trial. The primary outcome was a composite of 30-day mortality or MI.? ? They included 4311 patients from four trials. The primary outcome occurred in 334 patients (15.4%) in the restrictive strategy and 296 patients (13.8%) in the liberal strategy (relative risk [RR] 1.13, 95% confidence interval [CI], 0.97 to 1.30).?? ? Death at 30 days occurred in 9.3% of patients in the restrictive strategy and in 8.1% of patients in the liberal strategy (RR 1.15, 95% CI, 0.95 to 1.39). Cardiac death at 30 days occurred in 5.5% of patients in the restrictive strategy and in 3.7% of patients in the liberal strategy (RR 1.47, 95% CI, 1.11 to 1.94).? ? Heart failure (RR 0.89, 95% CI, 0.70 to 1.13) was similar in the transfusion strategies. All-cause mortality at 6 months occurred in 20.5% of patients in the restrictive strategy compared with 19.1% of patients in the liberal strategy (hazard ratio 1.08, 95% CI, 1.05 to 1.11).? ? Pooling individual patient data from four trials did not find a definitive difference in the primary composite outcome of MI or death at 30 days. At 6 months, a restrictive transfusion strategy was associated with increased all-cause mortality.? ? Read the Original Article “Restrictive versus Liberal Transfusion in Myocardial Infarction — A Patient-Level Meta-Analysis" by J.L. Carson et al.: https://eviden.cc/4gGsUjl? ? ?????????????? ???????????????? Editorial by Sheharyar Raza, MD, FRCPC, and Jeremy Jacobs, MD, MHS: Transfusion Strategies in Myocardial Ischemia — Treat Patients, Not Numbers https://eviden.cc/4gajcVS? ? #Cardiology #ClinicalTrials?

Larsucosterol is a DNA methyltransferase inhibitor in development for alcohol-associated hepatitis (AH), a disease for which there is no approved therapy.? ? In a phase 2b trial, the results of which are published in NEJM Evidence, patients with severe AH were randomly assigned 1:1:1 to receive 30 mg or 90 mg of larsucosterol or placebo; a second dose was administered after 72 hours if the patient remained hospitalized.?? ? All patients received supportive care as determined by investigators. Patients in the placebo group, if prescribed, received 32 mg of methylprednisolone, while patients in the larsucosterol groups received matching placebo capsules.?? ? The primary end point was 90-day mortality or liver transplant (LT) rate. The key secondary end point was 90-day mortality. We prespecified the reporting of U.S. results separately.? ? Among 307 enrolled patients, 301 received at least one treatment dose. The difference in 90-day mortality or LT between the 30-mg or 90-mg larsucosterol and placebo groups did not reach statistical significance.?? ? Ninety-day mortality in the placebo and the 30-mg and 90-mg groups was 25 out of 103, 15 out of 102, and 17 out of 102, respectively.? ? Among U.S. patients (76% of all enrolled patients), there were 21 deaths and 4 LTs among 77 patients in the placebo group, 8 deaths and 5 LTs among 73 patients in the 30-mg larsucosterol group, and 10 deaths and 8 LTs among 77 patients in the 90-mg larsucosterol group.?? ? In patients who were treated within less than 10 days of hospitalization (75%), mortality in the placebo group was 20 out of 79 (U.S. patients 17/57), mortality in the 30-mg larsucosterol group was 7 out of 74 (U.S. patients 4/57), and mortality in the 90-mg larsucosterol group was 13 out of 77 (U.S. patients 9/66).? ? Most adverse events arising during treatment were attributable to hepatic disease, and there was no imbalance in adverse events that could not be ascribed to liver disease.? ? The trial did not meet the primary end point of showing a beneficial effect of larsucosterol on 90-day mortality or LT in patients with severe AH. Equipoise has been established for a further trial of larsucosterol on AH survival.? ? Read the Original Article “Larsucosterol for the Treatment of Alcohol-Associated Hepatitis” by M. Shiffman et al.: https://eviden.cc/3EehUvJ? ?? ?????????????? ???????????????? Editorial by Praveena Narayanan, MD, and Michael Lucey, MD:?Larsucosterol Moves Forward as a Treatment Contender for Alcohol-Associated Hepatitis: https://eviden.cc/4jB8Ktm? ? Mitchell Shiffman #ClinicalTrials #Gastroenterology?

Read the Original Article "Clinical Use of ZSCAN4 for Telomere Elongation in Hematopoietic Stem Cells" by Dr. Kasiani Myers and colleagues published in NEJM Evidence: https://eviden.cc/3QjLjYe Elixirgen Therapeutics, Inc. Cincinnati Children's #ClinicalTrials #MedicalResearch

Volume 4 Issue 3 of ???????? ???????????????? is now available! Here is a preview of the latest content:?? ?? ???????????????? ????????????????? Peanut Oral Immunotherapy in Children with High-Threshold Peanut Allergy https://eviden.cc/3WMQwLF? ?? Clinical Use of ZSCAN4 for Telomere Elongation in Hematopoietic Stem Cells https://eviden.cc/3QjLjYe? ? Haploidentical Bone Marrow Transplantation for Sickle Cell Disease https://eviden.cc/3Qwv1eF? ? Nirsevimab Effectiveness at Preventing RSV-Related Hospitalization in Infants https://eviden.cc/4i62LuX? ? Alcohol Sales and Adverse Events During the Covid-19 Pandemic https://eviden.cc/4ievTAz? ? ???????????? ??????????????? Enhanced Recovery After Surgery — Evidence and Practice https://eviden.cc/4gUqnSo? ??? ?????????????? ?????????????? A 59-Year-Old Man with Fatigue and Abdominal Pain https://eviden.cc/4hU63lE? ? Explore all the latest #MedicalResearch and specialty articles in the March issue: https://eviden.cc/current? #ClinicalTrials

In a new interview, Dr. Francois Lamontagne, coauthor of a new article on blood pressure targets for adults with vasodilatory shock, discusses with Drs. Corey Hardin and Rob Mac Sweeney the rationale for targeting a lower BP targets for those patients. Listen to the full interview: https://eviden.cc/4gKkbNd #ClinicalTrials #CriticalCare

How much training do you need to do to run a 5K? ?? The NEJM Evidence team aims to find out in this Stats, STAT! animated video on linear regression.? Watch the full video: https://lnkd.in/epCBiUfU? #MedicalResearch

In NEJM Evidence, Winikoff et al. report on the first study in humans of ulipristal acetate used for medication abortion.?? ? The researchers found that ulipristal acetate 60 mg used together with a single dose of misoprostol 800 μg was 97.0% (95% confidence interval, 94.1 to 99.9%) effective to induce a complete abortion up to 63 days of pregnancy.?? ? Although the study is small and lacks a concurrent comparison group, the findings suggest that this regimen may be effective for medication abortion, and more research is warranted.? ? Read the editorial by Daniel Grossman, MD: “New Data on Ulipristal Acetate and Misoprostol for Medication Abortion — A Step Forward?” https://eviden.cc/4hoymaZ? ? ?????????????? ??????????????? Original Article by Winikoff et al.:?A Proof-of-Concept Study of Ulipristal Acetate for Early Medication Abortion https://eviden.cc/4apayla? ? #ClinicalTrials #OBGYN Beverly Winikoff Manuel Bousieguez Ilana Dzuba?

The authors of a meta-analysis, the results of which are published in NEJM Evidence, sought to estimate whether a lower mean arterial blood pressure target, compared with a higher mean arterial blood pressure target, reduced 90-day all-cause mortality among critically ill adult patients with vasodilatory shock.? ? Angriman et al. conducted an individual patient data meta-analysis of randomized controlled trials that evaluated the effect of distinct thresholds of mean arterial blood pressure to guide vasopressor support among critically ill adults identified in a systematic literature search.?? ? The main exposure was a lower mean arterial pressure target compared with a higher mean arterial pressure target (including usual care). The primary outcome was 90-day all-cause mortality. The authors used a Bayesian random effects log-binomial model to estimate risk ratios with 95% credible intervals (CrIs).? ? Between 2010 and 2019, 3352 patients were randomly assigned in three trials (SEPSISPAM, OVATION pilot trial, and 65-Trial) across 103 hospitals from the United Kingdom, France, and Canada. When compared with a higher mean arterial blood pressure target or usual care, the risk ratio for 90-day all-cause mortality associated with a lower blood pressure target was 0.93 (95% global: CrI, 0.76 to 1.07; low certainty, posterior probability of benefit 87%).?? ? Results were consistent across multiple secondary and sensitivity analyses, including adjustment for prognostically important baseline covariates and alternative modeling techniques. Multiple approaches to evaluate the heterogeneity of treatment effect did not identify any subgroups that may potentially benefit from higher mean arterial blood pressure targets.? ? Targeting a lower mean arterial blood pressure for vasopressor therapy in critically ill patients with vasodilatory shock possibly reduced 90-day all-cause mortality. However, the certainty of evidence is low, and this analysis does not exclude the possibility that lower targets may cause harm overall.? ? Read the Original Article “Blood Pressure Targets for Adults with Vasodilatory Shock — An Individual Patient Data Meta-Analysis” by F. Angriman et al.: https://eviden.cc/3Z7RfIT? ? ???Listen to the NEJM Evidence audio interview about the article with Rob Mac Sweeney, PhD, MRCP,?C. Corey Hardin, MD, PhD, and Fran?ois Lamontagne, MD, MSc: https://eviden.cc/4gKkbNd? ? ?????????????? ?????????????? ? Editorial by Jehan Alladina, MD:?When Less Is More — Revisiting Hemodynamic Targets in Vasodilatory Shock https://eviden.cc/4fqXGvG? ? #ClinicalTrials #CriticalCare?

Approved therapeutics for peanut allergy are not designed for the many patients with allergic reactions to more than one peanut.? ? In a new trial, the results of which are now published in NEJM Evidence, Sicherer and colleagues randomly assigned (1:1) participants 4 to 14 years of age reacting to a challenge of between 443 mg and 5043 mg of peanut protein to peanut oral immunotherapy (P-OIT) using home-measured peanut butter versus peanut avoidance.?? ? The primary end point was the difference between groups in the proportion tolerating a two-dose-level increase or 9043 mg of peanut protein.?? ? For ingestion participants tolerating 9043 mg, sustained unresponsiveness (tolerance off treatment), which was tested after 16 weeks of ad lib ingestion followed by 8 weeks of abstinence.? ? Of 73 participants, 38 were randomly assigned to P-OIT and 35 to avoidance. Thirty-two of 38 participants in the ingestion group (84.2%) and 30 of 35 in the avoidance group (85.7%) underwent the primary outcome food challenge.?? ? The primary analysis with prespecified multiple imputation for missing values showed 100% success for ingestion versus 21.0% for avoidance (between-group difference, 79.0 percentage points; 95% confidence interval [CI], 64.6 to 93.5; P<0.001). All 32 treated and 3 out of 30 avoiders (10%) tolerated 9043 mg.?? ? In the intention-to-treat analysis, sustained unresponsiveness occurred in 68.4% (26/38) on P-OIT versus 8.6% (3/35) tolerating 9043 mg among those avoiding (between-group difference, 59.9 percentage points; 95% CI, 42.4 to 77.3). No dosing reactions were greater than grade 1 severity, and no serious adverse events were reported.? ? In this trial of P-OIT using store-bought, home-measured peanut versus peanut avoidance in high-threshold peanut allergy, those treated achieved significantly higher rates of desensitization with a durable response off treatment.? Read the Original Article "Peanut Oral Immunotherapy in Children with High-Threshold Peanut Allergy" by S.H. Sicherer et al. in NEJM Evidence: https://eviden.cc/3WMQwLF Icahn School of Medicine at Mount Sinai #ClinicalTrials #Immunology