Clinical Phenotypes of Immediate First-Dose Reactions to mRNA COVID-19: A Multicenter Latent Class Analysis.

BACKGROUND: Although immediate potentially allergic reactions have been reported after dose 1 of mRNA coronavirus disease 2019 (COVID-19) vaccines, comprehensively defined subtypes have not been clearly distinguished. OBJECTIVE: To define distinct clinical phenotypes of immediate reactions after dose 1 of mRNA COVID-19 vaccination, and to assess the relation of clinical phenotype to mRNA COVID-19 vaccine second dose tolerance. METHODS: This retrospective study included patients with 1 or more potentially allergic symptoms or signs within 4 hours of receiving dose 1 of an mRNA COVID-19 vaccine and assessed by allergy/immunology specialists from 5 U.S. academic medical centers (January-June 2021). We used latent class analysis-an unbiased, machine-learning modeling method-to define novel clinical phenotypes. We assessed demographic, clinical, and reaction characteristics associated with phenotype membership. Using log-binomial regression, we assessed the relation between phenotype membership and second dose tolerance, defined as either no symptoms or mild, self-limited symptoms resolving with antihistamines alone. A sensitivity analysis considered second dose tolerance as objective signs only. RESULTS: We identified 265 patients with dose-1 immediate reactions with 3 phenotype clusters: (1) Limited or Predominantly Cutaneous, (2) Sensory, and (3) Systemic. A total of 223 patients (84%) received a second dose and 200 (90%) tolerated their second dose. Sensory cluster (all patients had the symptom of numbness or tingling) was associated with a higher likelihood of second dose intolerance, but this finding did not persist when accounting for objective signs. CONCLUSIONS: Three novel clinical phenotypes of immediate-onset reactions after dose 1 of mRNA COVID-19 vaccines were identified using latent class analysis: (1) Limited or Predominantly Cutaneous, (2) Sensory, and (3) Systemic. Whereas these clinical phenotypes may indicate differential mechanistic etiologies or associations with subsequent dose tolerance, most individuals proceeding to their second dose tolerated it.

Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors: A Systematic Review and Meta-analysis.

Importance: The safety profile of interleukin (IL) inhibitors is not well established. Objective: To assess the risk of serious infections, opportunistic infections, and cancer in patients with rheumatologic diseases treated with IL inhibitors. Data Sources: Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations; Ovid MEDLINE Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus were searched (inception to November 30, 2018). Study Selection: Randomized, placebo-controlled trials that evaluated IL inhibitor therapies in rheumatic diseases and reported safety data were included in the analyses. Data Extraction and Synthesis: This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Two investigators independently extracted study data and assessed risk of bias and certainty in the evidence. Fixed-effects meta-analysis was conducted to pool odds ratios (ORs) for serious infections, opportunistic infections, and cancers for IL inhibitors vs placebo. Main Outcomes and Measures: The outcomes of interest were the number of serious infections, opportunistic infections, and cancers in individuals receiving IL inhibitor therapies compared with placebo. Results: In this meta-analysis, 74 studies comprising 29 214 patients (24 236 patients for serious infections, 9998 for opportunistic infections, and 21 065 for cancer [number of patients overlaps for each outcome]) were included. Patients receiving IL inhibitors had a higher risk of serious infections (OR, 1.97; 95% CI, 1.58-2.44; P < .001, I2 = 0%; high certainty), opportunistic infections (OR, 2.35; 95% CI, 1.09-5.05; P = .03, I2 = 0%; moderate certainty), and cancer (OR, 1.52; 95% CI, 1.05-2.19; P = .03, I2 = 11%; moderate certainty). Conclusions and Relevance: The risk of serious infections, opportunistic infections, and cancer appears to be increased in patients with rheumatologic diseases who are treated with IL inhibitors compared with placebo.

Colchicine for Prevention of Post-Operative Atrial Fibrillation: A Meta-Analysis.

OBJECTIVES: This study sought to investigate the efficacy and safety of colchicine for prevention of post-operative atrial fibrillation. BACKGROUND: Proinflammatory processes induced during cardiac surgery may contribute toward post-operative atrial fibrillation (AF). Colchicine is a potent anti-inflammatory agent, which may have a role in post-operative AF prevention. METHODS: We searched PubMed, EMBASE, Web of Science, CINAHL, ClinicalTrials.gov, and the Cochrane Library databases for randomized controlled trials (RCT) comparing colchicine versus placebo for prevention of post-operative AF. The main outcome measure of interest was the development of AF within 12 months after cardiac surgery. The overall risk ratio (RR) for the development of post-operative AF was computed using a random-effects model. RESULTS: Data analyzed from 3 randomized studies with a total of 912 patients, where 457 patients received colchicine and 455 patients received placebo, showed that perioperative colchicine therapy was associated with a reduced incidence of post-operative AF (RR: 0.65; 95% confidence interval [CI]: 0.46 to 0.91; p < 0.01). Although colchicine therapy was associated with increased incidence of gastrointestinal intolerance (RR: 2.20; 95% CI: 1.31 to 3.70; p = 0.003), it was not associated with early treatment discontinuation (RR: 1.37; 95% CI: 0.95 to 1.96; p = 0.09). CONCLUSIONS: In conclusion, current evidence suggests that colchicine therapy is efficacious for the prevention of post-operative AF, and may be considered as adjunctive prophylaxis. Further studies may be required to determine the optimal treatment protocol to reduce the incidence of gastrointestinal intolerance.

Professional Demands and Job Satisfaction in Orthopaedic Trauma: An OTA Member Survey.

OBJECTIVES: The goal of this study was to examine the factors that affect career satisfaction in orthopaedic traumatologists. We hypothesize that the level of stress and career satisfaction in orthopaedic traumatology would be affected by increased number of call nights and work hours. DATA SOURCES: A 30-question survey was emailed to members of the OTA. The survey evaluated 5 critical areas: training/experience, practice characteristics, demands, stress management strategies, and satisfaction. STUDY SELECTION: After approval by the OTA research committee, all active and associate US members of the OTA were contacted. DATA EXTRACTION: The survey was open to the OTA members from July through November of 2012. DATA SYNTHESIS: Of 1031 members of the OTA, 263 members responded for an overall response rate of 25.5%. Most respondents were fellowship-trained (218, 82.9%) and predominantly young (<5 years in practice, 34.4%) or established surgeons (>15 years in practice, 28.5%). Most surgeons were married (229, 87.1%) and have not been divorced (226, 85.9%). Career satisfaction was statistically improved by belonging to larger practice (P = 0.016), decreased by work for more hours per week (P = 0.001), and improved by taking more call (P = 0.014). CONCLUSIONS: Career satisfaction among orthopaedic trauma surgeons was extremely high. Our results indicate that young surgeons may improve their job satisfaction and potentially prolong their career by limiting the numbers of hours worked, taking a consistent number of calls and joining a larger group. LEVEL OF EVIDENCE: Prognostic Level V. See Instructions for Authors for a complete description of levels of evidence.

Composite outcomes in 2.25-mm drug eluting stents: a systematic review.

BACKGROUND: Coronary atherosclerosis often involves small-caliber coronaries, yet the safety and efficacy of 2.25-mm DES have been poorly defined, with a general lack of separation of 2.25 with 2.5-mm performance. No randomized head-to-head 2.25 mm DES studies have been reported. There are several single-arm prospective studies, and we aim to systematically review all published specific 2.25-mm data to estimate composite DES-specific performance and highlight current knowledge gaps. METHODS: We performed a systematic literature search of PubMed, EMBASE, Web of Science and Cochrane database for clinical trials of 2.25-mm DES. Angiographic and composite clinical outcomes were compared with descriptive statistics. RESULTS: 2.25 mm-Paclitaxel (PES), sirolimus (SES), everolimus (EES) and platinum chromium EES DES-specific outcomes have been reported. Death at 12 months for SES, PES, EES and platinum chromium EES was 1.3%, 3.0%, 1.5%, and 4.4%. Rates of target vessel revascularization at 12 months for SES, PES, EES and platinum chromium EES were 5.7%, 13.3%, 8.8%, and 3.3%. Angiographic outcomes at 9 months to one year were as follows: mean late lumen loss (LLL) for SES, PES, and EES was 0.15 ± 0.11-mm, 0.28 ± 0.11-mm, and 0.16 ± 0.41-mm and mean diameter restenosis for SES, PES, and EES were 29.5 ± 6.2%, 34.7 ± 4.2%, and 20.9 ± 22.5%. Reported stent thrombosis rates for 2.25-mm DES were low ranging from 0% to 2.2% in up to 24-months of follow-up. CONCLUSIONS: This systematic review summarizes and tabulates all available specific data on 2.25-mm DES. Based on our descriptive analysis, 2.25-mm DESs have a favorable safety and efficacy profile for the treatment of very small coronary lesions.