Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Factors That Influence Discharge Opioid Prescribing among Bariatric Surgeons across Michigan

Introduction: Opioid prescribing after bariatric surgery has been an area of focus due to its association with new persistent opioid use (NPOU) and worse outcomes. The development of statewide guidelines has led to a reduction in discharge opioid prescribing, but there remains variation in the number of opioids prescribed by surgeons after bariatric surgery. Understanding the factors underlying this variation may be another way to further improve practices around opioid prescribing. Methods: We conducted interviews with 20 bariatric surgeons across Michigan to explore factors that influence discharge opioid prescribing after bariatric surgery. All interviewed surgeons participate in a statewide bariatric surgery focused quality improvement collaborative. Transcripts were analyzed using descriptive content analysis. Results: Surgeons identified factors that influence their decision- making at the patient, provider, institution, and collaborative level. At the patient level, surgeons described the role of surgical history, addiction history, and pain tolerance. At the provider level, surgeons discussed patient dissatisfaction, provider reputation, workload, and involvement with research. At the institution level, surgeons discussed the influence of colleagues, variation in resources, and pressure from administration. At a collaborative level, surgeons described the role of evidence and performance measures. Notably, there was lack of consensus on whether NPOU is a problem facing patients undergoing bariatric surgery. Conclusion: Despite efforts aimed at addressing opioid prescribing, variability exists in prescribing practices and beliefs among bariatric surgeons across Michigan. Understanding determinants that impact stakeholder alignment and proficiency is critical to the development of tailored intervention aimed at increasing adherence to guideline-concordant care

Life after no : barriers to behavior change for persons declined hernia repair due to high-risk features

INTRODUCTION: Delaying an elective operation to mitigate risk factors improves patient outcomes. Elective ventral hernia repair is one such example. To address this issue, we developed a pre-operative optimization clinic to support high-risk patients seeking elective ventral hernia repair. Unfortunately, few patients progressed to surgery. Within this context, we sought to understand the barriers to behavior change among these patients with the goal of improving care for patients undergoing elective surgery. METHODS: We performed semi-structured, qualitative interviews with 20 patients who were declined ventral hernia repair due to either active tobacco use or obesity. Patients were recruited from a pre-operative optimization clinic at an academic hospital. Interviews sought to characterize patients\u27 perceived barriers to behavior change. Interviews were concluded once thematic saturation was reached. We used an inductive thematic analysis to analyze the data. All data analysis was performed using MAXQDA software. RESULTS: Among 20 patients (mean age 50, 65% female, 65% White), none had yet undergone ventral hernia repair. While most patients had a positive experience in the clinic, among those who did not, we found three dominant themes around behavior change: (1) Patient\u27s role in behavior change: how the patient perceived their role in making behavior changes optimize their health for surgery; (2) Obtainability of offered resources: the need for more support for patients to access the recommended healthcare; and (3) Patient-provider concordance: the extent to which patients and providers agree on the relative importance of different attributes of their care. CONCLUSION: Behavior change prior to elective surgery is complex and multifaceted. While improving access to tobacco cessation resources and obesity management may improve outcomes for some, patients may benefit from increased on-site facilitation to promote access to resources as well as the use of patient-facing decision support tools to promote patient-provider concordance

Optimizing Surgeon Well-Being

Objective:. Through a systematic review and mixed-methods meta-synthesis of the existing literature on surgeon well-being, we sought to identify the specific elements of surgeon well-being, examine factors associated with suboptimal well-being, and highlight opportunities to promote well-being. Background:. Suboptimal surgeon well-being has lasting and substantial impacts to the individual surgeon, patients, and to society as a whole. However, most of the existing literature focuses on only 1 aspect of well-being—burnout. While undoubtedly a crucial component of overall well-being, the mere absence of burnout does not fully consider the complexities of being a surgeon. Methods:. We performed a literature search within Ovid Medline, Elsevier Excerpta Medica dataBASE, EBSCOhost Cumulative Index to Nursing and Allied Health Literature, and Clarivate Web of Science from inception to May 7, 2020, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies with primary data examining surgeon well-being were included. Using a predetermined instrument, data were abstracted from each study and compared using thematic analysis. Results:. A total of 5369 abstracts were identified and screened, with 184 full articles (172 quantitative, 3 qualitative, 9 mixed methods) selected for analysis. Among these, 91 articles measured burnout, 82 examined career satisfaction, 95 examined work-related stressors, 44 explored relationships and families, and 85 assessed emotional and physical health. Thematic analysis revealed 4 themes: professional components, personal components, work-life balance, and impacts to well-being. Conclusions:. Surgeon well-being is complex and multifaceted. This nuanced examination of surgeon well-being highlights the critical need to develop and provide more long-term support to surgeons—with interventions being tailored based on individual, institutional, and systemic factors

The Best Gift You Could Give a Resident

Background:. In recent years, there has been increasing focus on the well-being of resident physicians. Considering the persistent problem of burnout and attrition particularly among surgical trainees, this is a well-warranted and laudable area of focus. However, despite the widespread adoption of resources available to residents through individual institutions, there is little understanding of how and why these resources are engaged or not during particularly vulnerable moments, such as following an unwanted patient event including postoperative complications and deaths. Methods:. This qualitative study explored access to and usage of resources to promote well-being following an unwanted patient outcome through semi-structured interviews of 28 general surgery residents from 14 residency programs across the United States, including community, academic, and hybrid programs. A qualitative descriptive approach was used to analyze transcripts. Results:. Residents described 3 main types of institutional resources available to them to promote well-being, including counseling services, support from program leadership, and wellness committees. Residents also described important barriers to use for each of these resources, which limited their access and value of these resources. Finally, residents shared their recommendations for future initiatives, including additional protected time off during weekdays and regular usage of structured debrief sessions following adverse patient outcomes. Conclusions:. While institutional resources are commonly available to surgery residents, there remain important limitations and barriers to use, which may limit their effectiveness in supporting resident well-being in times of need. These barriers should be addressed at the program level to improve services and accessibility for residents

The ISMRM Open Science Initiative for Perfusion Imaging (OSIPI):Results from the OSIPI-Dynamic Contrast-Enhanced challenge

Purpose: (Formula presented.) has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for (Formula presented.) quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging–Dynamic Contrast-Enhanced (OSIPI-DCE) challenge was designed to benchmark methods to better help the efforts to standardize (Formula presented.) measurement. Methods: A framework was created to evaluate (Formula presented.) values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for (Formula presented.) quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' (Formula presented.) values, the applied software, and a standard operating procedure. These were evaluated using the proposed (Formula presented.) score defined with accuracy, repeatability, and reproducibility components. Results: Across the 10 received submissions, the (Formula presented.) score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0–1 = lowest–highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in (Formula presented.) analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. Conclusions: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within (Formula presented.) estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology.</p