CLOSE protocol versus lower ablation index value for paroxysmal atrial fibrillation: A randomized noninferior clinical trial.

INTRODUCTION: The optimized ablation index (AI) value for catheter ablation of atrial fibrillation (AF) remains to be defined. We aimed to compare the efficacy and safety of CLOSE protocol and lower AI protocol in paroxysmal AF. METHODS AND RESULTS: Patients with symptomatic, drug-resistant paroxysmal AF for first ablation were prospectively enrolled from September 2020 to January 2022. The patients were randomly divided into CLOSE group (AI ≥ 550 for anterior/roof segments and ≥400 for posterior/inferior segments) and lower AI group (AI ≥ 450 for anterior/roof segments and ≥350 for posterior/inferior segments). First-pass isolation, acute pulmonary vein (PV) reconnections, 1-year arrhythmia recurrence, and major complications were assessed. Of the 270 enrolled patients, 238 completed 1-year follow-up (118 in CLOSE group and 120 in lower AI group). First-pass isolation in left PVs was higher in CLOSE group (71.2% vs. 53.3%, p = .005). Acute PV reconnections were comparable between groups (9.3% vs. 14.2%, p = .246). At 1 year, 86.4% in CLOSE group versus 81.7% in lower AI group were free from atrial arrhythmia (log rank p = .334). The proportion difference was -4.8% (95% CI: -14.1% to 4.6%), and p = .475 for noninferiority. Stroke occurred in four patients of lower AI group, and no cardiac tamponade, atrioesophageal fistula, major bleeding or death occurred post procedure. CONCLUSION: For patients with paroxysmal AF and treated by AI-guided PV ablation, lower AI is not noninferior to CLOSE protocol.

Safety and Efficacy of Ceftriaxone in the Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections: A Noninferiority Retrospective Cohort Study.

BACKGROUND: Antistaphylococcal penicillins and cefazolin are the treatments of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections, requiring multiple doses daily. At Parkland, eligible uninsured patients with MSSA bloodstream infections (BSI) receive self-administered outpatient parenteral antimicrobial therapy (S-OPAT). Ceftriaxone was used in a cohort of S-OPAT patients for ease of once-daily dosing. OBJECTIVE: A retrospective study was conducted to evaluate clinical outcomes for patients discharged with ceftriaxone versus cefazolin to treat MSSA BSI. METHODS: A retrospective cohort noninferiority study design was used to assess treatment efficacy of ceftriaxone versus cefazolin among Parkland S-OPAT patients treated from April 2012 to March 2020. Demographic, clinical, and treatment-related adverse events data were collected. Clinical outcomes included treatment failure as defined by repeat positive blood culture or retreatment within 6 months, all-cause 30-day readmission rates, and central line-associated bloodstream infection (CLABSI) rates. RESULTS: Of 368 S-OPAT patients with MSSA BSI, 286 (77.7%) received cefazolin, and 82 (22.3%) received ceftriaxone. Demographics and comorbidities were similar for both groups. There were no treatment failures in the ceftriaxone group compared with 4 (1%) in the cefazolin group (P = 0.58). No difference in 30-day readmission rate between groups was found. The CLABSI rates were lower in ceftriaxone group (2%) compared with cefazolin (11%; P = 0.02). Limitations include retrospective cohort design. CONCLUSIONS: Ceftriaxone was found to be noninferior to cefazolin in this study. Our findings suggest that ceftriaxone is a safe and effective treatment of MSSA BSI secondary to osteoarticular or skin and soft tissue infections when used in the S-OPAT setting. POSTER ABSTRACT: OFID on 2018 Nov; 5(Suppl 1): S316: doi: 10.1093/ofid/ofy210.894.

Local infiltration analgesia versus interscalene nerve block for postoperative pain control after shoulder arthroplasty: a prospective, randomized, comparative noninferiority study involving 99 patients.

BACKGROUND: The aim of this study was to compare the efficacy of local infiltration analgesia (LIA) and interscalene nerve block (ISB) for early postoperative pain control after total shoulder arthroplasty (TSA). The hypothesis was that LIA is not inferior to ISB. METHODS: A prospective, randomized controlled study was performed in 2014-2016. All patients who underwent TSA for shoulder osteoarthritis were included. Patients in the ISB group received a continuous infusion of 0.2% ropivacaine by perineural catheter for 48 hours. The surgeon injected 110 mL of 0.2% ropivacaine, 30 mg of ketoprofen, and 0.5 mg of epinephrine before TSA in the LIA group and inserted a catheter into the glenohumeral joint. The next morning, 10 mL of 0.2% ropivacaine, 30 mg of ketoprofen, and epinephrine were injected through the catheter, which was then removed. The primary outcome was the mean shoulder pain score for the 48-hour postoperative period on a numerical scale (0-10). The secondary outcomes were postoperative opioid requirements, complications, and shoulder function at the 1-month follow-up visit. The sample size was calculated for a noninferiority study. RESULTS: The study included 99 patients (50 LIA and 49 ISB patients) with a mean age of 72 ± 9.6 years. Although no significant difference in the mean pain score was found between the 2 groups for the 48-hour postoperative period (1.4 ± 0.9 for LIA vs 1.7 ± 1 for ISB, P = .19), the LIA group had significantly less severe pain (P = .003) and less opioid consumption (P = .01) in the recovery room. No complications occurred. A negative but nonsignificant correlation was found between postoperative pain and Constant score at the 1-month follow-up. CONCLUSION: LIA is not less effective than ISB for early postoperative pain control after TSA.

On the restricted mean survival time curve in survival analysis.

For a study with an event time as the endpoint, its survival function contains all the information regarding the temporal, stochastic profile of this outcome variable. The survival probability at a specific time point, say t, however, does not transparently capture the temporal profile of this endpoint up to t. An alternative is to use the restricted mean survival time (RMST) at time t to summarize the profile. The RMST is the mean survival time of all subjects in the study population followed up to t, and is simply the area under the survival curve up to t. The advantages of using such a quantification over the survival rate have been discussed in the setting of a fixed-time analysis. In this article, we generalize this approach by considering a curve based on the RMST over time as an alternative summary to the survival function. Inference, for instance, based on simultaneous confidence bands for a single RMST curve and also the difference between two RMST curves are proposed. The latter is informative for evaluating two groups under an equivalence or noninferiority setting, and quantifies the difference of two groups in a time scale. The proposal is illustrated with the data from two clinical trials, one from oncology and the other from cardiology.

Student Perception of Case-based Teaching by Near-Peers and Faculty during the Internal Medicine Clerkship: A Noninferiority Study.

INTRODUCTION: Third-year medical students traditionally receive their didactic or small group teaching sessions from clinical faculty during clerkship rotations. Near-peer teaching is increasingly recognized as an acceptable method for teaching, however most near-peer teaching takes place during the pre-clinical curriculum. We sought to determine if fourth year medical students were noninferior to faculty in facilitating small group discussions during clerkship rotations. METHODS: Seventy-five third-year medical students participated in a small group session focused on rheumatologic diseases during their internal medicine clerkship rotation. Students were taught by fourth-year medical students who self-selected to participate as near-peer teachers at 1 clinical site (near-peers, N = 36) and by clinical faculty at another site (N = 39). At the end of the session, third-year medical students completed a survey evaluating teacher performance and effectiveness. RESULTS: There was no significant difference between the 2 groups on each of the 17 survey items assessing teacher performance, the total teaching performance score, and the teaching effectiveness rating (all P-values >.05). A mean between-group difference of 2% in favor of the near-peers indicated noninferiority of the near-peer teachers compared with faculty teachers on the total teaching performance score. An absolute difference of 14% in favor of the near-peers indicated noninferiority of the near-peer teachers compared with faculty teachers on the teaching effectiveness score. Near-peer teachers reported several benefits, including improving their own medical knowledge and skills as a future educator. DISCUSSION: Our data supports the noninferiority of the perceived performance and effectiveness of near-peer teachers compared to faculty teachers in the clerkship setting. Adding near-peer teachers to the clerkship setting is feasible and can be beneficial to all stakeholders.

Efficacy and safety of a novel skin cleansing formulation versus chlorhexidine gluconate.

BACKGROUND: This study evaluated whether a multi-ingredient surfactant colloidal silver technology was noninferior to a 4% chlorhexidine gluconate (CHG) antiseptic on immediate and persistent antimicrobial activity. METHODS: The inguinal regions of 81 healthy adults were demarcated into 4 quadrants, and 3 were used for testing each product at baseline, 10 minutes, and 6 hours postapplication. The log of the number of colony forming units was obtained using a cylinder sampling technique. The 95% confidence interval of the test product to the control product with a margin of 0.65 was established as the upper limit of noninferiority. RESULTS: A total of 81 individuals were enrolled. The colloidal silver product was found to be noninferior to 4% CHG at both 10 minutes and 6 hours postapplication. CONCLUSIONS: The colloidal silver-based product was noninferior to the 4% CHG product at 10 minutes and 6 hours postapplication.

The choice of the noninferiority margin in clinical trials was driven by baseline risk, type of primary outcome, and benefits of new treatment.

OBJECTIVES: To explore characteristics of clinical trials that influence the choice of the noninferiority margin (NIM) when planning the trial. STUDY DESIGN AND SETTING: We conducted an experimental survey among corresponding authors of randomized controlled trials indexed in MEDLINE. We described two hypothetical studies and asked the respondents' opinion on the largest loss of effectiveness that is clinically negligible (or the smallest lost of effectiveness that is clinically important in the superiority scenario). We randomly manipulated four study attributes in each vignette, using a factorial design. RESULTS: A total of 364 researchers participated. The values for NIMs were significantly lower than the differences to be detected in a superiority trial. The NIM was smaller when the primary outcome was mortality compared with treatment failure, when baseline risk in the control arm was lower, and when the advantage of the new treatment was a lower cost compared with having fewer side effects. In contrast, the population age group under study and the difficulty to recruit patients showed no effect on the choice of the NIM. CONCLUSION: In our experimental study, the factors associated with lower NIMs were mortality as a primary outcome, low baseline risk, and a less costly new treatment.