Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis.

BACKGROUND & AIMS: We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. METHODS: A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. RESULTS: A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). CONCLUSIONS: Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.

Is Noninferior Not Inferior?

Is Noninferior Not Inferior? What is a non-inferiority trial margin? To answer this, ask whether you have ever weighed a tradeoff between the best version of something and an acceptable alternative. Restated, in a choice between two decisions, is one option not inferior to the other? Watch an animated video that explores the basis for non-inferiority trials, the meaning of non-inferiority margins, and the interpretation of a non-inferiority trial's results.

NEJM Evidence - A New Journal in the NEJM Group Family.

NEJM Evidence - A New Journal in the NEJM Group Family In January 2022, the NEJM Group will be publishing a new journal, NEJM Evidence. This monthly, peer-reviewed, online-only, general medical journal will publish original research, along the full spectrum of clinical investigation, that takes ideas and turns them into reality.

Skin sympathetic nerve activity as a biomarker of fitness.

BACKGROUND: Exercise stress testing is frequently used to expose cardiac arrhythmias. Aerobic exercise conditioning has been used as a nonpharmacologic antiarrhythmic intervention. OBJECTIVE: The purpose of this study was to test the hypothesis that noninvasively recorded skin sympathetic nerve activity (SKNA) is increased during exercise and that SKNA response varies according to fitness levels. METHODS: Oxygen consumption (VO2) and SKNA were recorded in 39 patients undergoing an incremental exercise test. Patients were grouped by 5 levels of fitness based on age, sex, and VO2max. RESULTS: With exercise, all patients had a significant increase in average SKNA (aSKNA) (1.58 ± 1.12 µV to 4.50 ± 3.06 µV, P = .000) and heart rate (HR) (87.40 ± 20.42 bpm to 154.13 ± 16.82 bpm, P = .000). A mixed linear model of aSKNA was used with fixed effects of fitness, exercise time, and recovery time, and random effects of subject level intercept and slopes for exercise time and recovery times. The poor fitness group had significantly higher aSKNA than the other groups (P = .0273). For all subjects studied, aSKNA increased by 5% per minute with progression of exercise and decreased by 15% per minute with progression of recovery. The fitness variable encodes information on both comorbidities and body mass index (BMI). Once fitness level is known, comorbidities and BMI are not significantly associated with aSKNA. In all groups, aSKNA positively correlated with HR (R2 = 0.47 ± 0.23) and VO2 (R2 = 0.68 ± 0.25). CONCLUSION: Fitness level determines the magnitude and time course of SKNA increase during exercise. SKNA may be a useful fitness biomarker in exercise stress testing.

Cocaine Positivity in ST-Elevation Myocardial Infarction: A True or False Association.

INTRODUCTION: Every year, more than 500,000 US Emergency Department visits are associated with cocaine use. People who use cocaine tend to have a lower incidence of true ST-elevation myocardial infarction (STEMI). OBJECTIVE: To identify the factors associated with true STEMI in patients with cocaine-positive (CPos) findings. METHODS: We retrospectively analyzed 1144 consecutive patients with STEMI between 2008 and 2013. True STEMI was defined as having a culprit lesion on coronary angiogram. Multivariate and univariate analyses were used to identify risk factors and create a predictive model. RESULTS: A total of 64 patients with suspected STEMI were CPos (mean age 53.1 ± 11.2 years; male = 80%). True STEMI was diagnosed in 34 patients. Patients with CPos true STEMI were more likely to be uninsured than those with false STEMI (61.8% vs 34.5%, p = 0.03) and have higher peak troponin levels (21.1 ng/mL vs 2.12 ng/mL, p = < 0.01) with no difference in mean age between the 2 groups (p = 0.24). In multivariate analyses, independent predictors of true STEMI in patients with CPos findings included age older than 65 years (odds ratio [OR] = 19.3, 95% confidence iterval [CI] = 1.2-318.3), lack of health insurance (OR = 4.9, 95% CI = 1.2-19.6), and troponin level higher than 0.05 (OR = 24.0, 95% CI = 2.6-216.8) (all p < 0.05). A multivariate risk score created with a C-statistic of 82% (95% CI = 71-93) significantly improved the identification of patients with true STEMI. CONCLUSION: Among those with suspected STEMI, patients with CPos findings had a higher incidence of false STEMI. Older age, lack of health insurance, and troponin levels outside of defined limits were associated with true STEMI in this group.

Outcomes following transcatheter aortic valve replacement in patients with native aortic valve regurgitation.

Due to the absence of annular calcification for device anchoring, it is presumed that transcatheter aortic valve replacement (TAVR) is not suitable for the treatment of native aortic valve regurgitation (NAVR) resulting in very limited data and experience concerning its safety and efficacy. We sought to review published data on the safety and efficacy of TAVR in high-risk patients with NAVR. Studies including case reports, case series and original articles published between 2002 and 2016 on TAVR in patients with NAVR were identified with a systematic electronic search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Only studies reporting data on demographic and procedural characteristics, management and follow up outcomes were analyzed. A total of 30 publications describing 182 patients were identified. Most patients (54%) were men, with a mean age of 70.1±2.6 years, mean logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE) of 21.8%±4.5% and mean Society of Thoracic Surgeons (STS) score of 8%±1.8% for mortality. The majority (87%) of patients had severe NAVR with no valvular calcification. TAVR was mostly performed through the femoral (58.8%) and apical (33.1%) approach. Device success, defined by VARC-2, was achieved in 86.3% of our study population. A second valve was required in 17 patients (9.3%) during the index procedure for residual aortic regurgitation or malposition. Post-procedure aortic regurgitation of grade 1 or less was present in 80 patients (81%). Pacemaker implantation was required post procedure in 17 patients (9.3%). The 30-day and 1-year mortality was 11.9% and 16.2%, respectively. TAVR is associated with favorable pacemaker implantation and 1-year mortality rates with a high 30-day mortality among selected patients with NAVR.

Unusual Presentation of Duodenal Ulcer Presenting with Duodenal Intussusception.

We present a unique case of duodeno-duodenal intussusception from a duodenal bulb ulcer. A 38-year-old man presented with nausea, vomiting, and abdominal pain. Computed tomography showed duodenal intussusception. Esophagogastroduodenoscopy (EGD) showed a linear gastric ulcer and a duodenal bulb ulcer with an overlying blood clot. Helicobacter pylori status was positive. Intussusception resolved spontaneously without intervention. He completed treatment for H. pylori infection, and repeat EGD showed ulcer healing. Duodenal intussusception is rarely reported; intussusception from an edematous duodenal ulcer with an overlying blood clot mimicking a mass lesion acting as lead point has never been reported to our knowledge.