Fascial Defect Closure During Ventral Hernia Repair: A Systematic Review of Randomized Controlled Trials.

Background: During minimally invasive ventral hernia repair (VHR) it is unknown if a fascial defect closure, as opposed to a bridged repair (current care), is beneficial for patients. We sought to systematically review the published literature on the role of fascial defect closure during minimally invasive VHR. Methods: PubMed, Embase, Scopus, Cochrane, and Clinicaltrials.gov were reviewed for randomized controlled trials (RCTs) that compared fascial defect closure with bridged repair. The primary outcome was major complications defined as deep/organ-space surgical site infections (SSIs), reoperations, hernia recurrences, or deaths. Secondary outcomes included SSI, seroma, eventration, hernia recurrence, post-operative pain, and quality of life (QOL). Pooled risk ratios with 95% confidence intervals were obtained through random effect meta-analyses. Results: Of 579 screened articles, 6 publications of 5 RCTs were included. No significant difference in major complications (10.6% vs 10.4%, RR=1.05, 95% CI=0.51-2.14, P=.90) or recurrences (9.0% vs 10.6%, RR=0.92, 95% CI=0.32-2.61, P=.87) were found between groups. Fascial defect closure decreased the risk of seromas (22.9% vs 34.2%, RR=0.60, 95% CI=0.37-0.97, P=.04) and may decrease the risk of eventrations (6.7% vs 9.0%, RR=0.74, 95% CI=0.37-1.50, P=.41) at the expense of potentially increasing the risk of SSI (3.2% vs 1.4%, RR=1.89, 95% CI=0.60-5.93; P=.28). Reporting of pain and QOL scores was inconsistent. Conclusion: While most individual RCTs demonstrated benefit with fascial defect closure during minimally invasive VHR, our meta-analysis of fascial defect closure demonstrated only a statistically significant difference in seromas compared to bridged repair. Large, multi-center RCTs are needed.

Mesh Type With Ventral Hernia Repair: A Systematic Review and Meta-analysis of Randomized Trials.

INTRODUCTION: Synthetic mesh is widely utilized for clean ventral hernia repair; however, it is unclear if synthetic mesh provides the same benefits with high-risk patients or during contaminated cases. Many surgeons use biologic mesh in these settings, but there is little evidence to support this practice. Our objective was to compare the clinical outcomes of utilizing biologic mesh versus synthetic mesh during ventral hernia repair. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a review of the literature was conducted using Cochrane library, EMBASE, Clinicaltrials.gov, and PubMed for randomized controlled trials published that compared biologic versus synthetic mesh during ventral hernia repair. The primary outcome was major complications defined as deep or organ space surgical site infection, reoperations, and hernia recurrences. RESULTS: Of 1889 manuscripts screened, four publications were included. The four studies included a total of 758 patients, with 381 receiving biologic mesh and 377 receiving synthetic mesh. Compared to biologic mesh, synthetic mesh had lower rates of major complications (38.6% versus 23.4, risk ratio = 0.55, 95% confidence interval = 0.35 to 0.86, P = 0.009) and hernia recurrence (24.5 % versus 10.3%, risk ratio = 0.44, 95% confidence interval = 0.28 to 0.69, P = 0.004). In addition, there was a lower percentage of surgical site infection and reoperation in the synthetic mesh group. CONCLUSIONS: Contrary to current surgical teaching, placement of permanent synthetic mesh into a contaminated field yielded rates of complications that were comparable or reduced compared to biologic mesh.

Accidental Extravasation of Mitomycin C into the Subcutaneous Tissue.

Introduction: Mitomycin C (MMC) is a common chemotherapeutic agent used to treat a variety of solid tumors. Cutaneous adverse events are rare, but MMC is a known vesicant reported to cause tissue necrosis and sloughing, erythema, and ulceration if incorrectly infused into the subcutaneous tissue. Definitive treatment of extravasation injuries due to MMC depends on the severity of the cutaneous manifestation, which includes stopping the infusion, removing the catheter, or possible debridement. Case Presentation: We present the case of a 70-year-old female with extensive soft-tissue injury secondary to extravasation of MMC that required hospital admission and surgical intervention to remove the implantable venous access device. Conclusion: Extravasation injuries caused by vesicant drugs, such as MMC, often present as local skin irritation and inflammation. MMC extravasation may present a wide range of skin and soft tissue manifestations, ranging from erythema to ulcerations to necrosis. This rare but potentially detrimental complication of chemotherapy infusions should be recognized in cancer patients.

The Role of Biologic Mesh and Fundoplication in the Surgical Management of Hiatal Hernias: A Multicenter Evaluation.

INTRODUCTION: Hiatal hernia repair is associated with substantial recurrence of both hiatal hernia and symptoms of gastroesophageal reflux (GER). While small randomized controlled trials demonstrate limited differences in outcomes with use of mesh or fundoplication type, uncertainty remains. METHODS: A multicenter, retrospective review of patients undergoing surgical treatment of hiatal hernias between 2015 and 2020 was performed. Patients with mesh and with suture-only repair were compared, and partial versus complete fundoplication was compared. Primary outcomes were hernia recurrence and occurrence of postoperative GER symptoms and dysphagia. Multivariable regression was performed to assess the effect of each intervention on clinical outcomes. RESULTS: A total of 453 patients from four sites were followed for a median (IQR) of 17 (13) months. On multivariate analysis, mesh had no impact on hernia recurrence (odds ratio 0.993, 95% CI: 0.53-1.87, p = 0.982), and fundoplication type did not impact recurrence of postoperative GER symptoms (complete: odds ratio 0.607, 95% CI: 0.33-1.12, p = 0.112) or dysphagia (complete: odds ratio 1.17, 95% CI: 0.56-2.43, p = 0.677). CONCLUSION: During hiatal hernia repair, mesh and fundoplication type do not appear to have substantial impact on GER symptoms, dysphagia, or hernia recurrence. This multicenter study provides real-world evidence to support the findings of small RCTs.

Hernia Prevention Using Biologic Mesh and/or Small Bites: A Multispecialty 2 × 2 Factorial Randomized Controlled Trial.

BACKGROUND: Ventral incisional hernias are the most common complication after abdominal operation. Randomized trials have shown efficacy of prophylactic synthetic mesh and small bites. Adoption of these practices has been limited due to concerns with placement of synthetic mesh in contaminated cases and small bites in an overweight population. We sought to assess the efficacy of prophylactic biologic mesh and small bites to prevent postoperative major complications: ventral incisional hernias, surgical site infection, reoperation, and death. STUDY DESIGN: High-risk patients (overweight/obese, current smoker) undergoing abdominal operation with a midline incision (5 cm or greater) were randomized (2 × 2 factorial trial) to receive either sublay biologic mesh or no mesh and either small bites (0.5 × 0. 5cm) or large bites (1 × 1 cm) fascial closure. The primary outcome measure was major complications at 1 year postoperative. CONSORT guidelines were followed, and this study was registered on clinicaltrials.gov (NCT03148496). Assuming α = 0.05, ß = 0.20, and Δ = 20%, it was estimated that 105 patients were needed. Primary outcome was assessed using Fisher's exact test. RESULTS: A total of 107 patients were randomized: 52 (49%) to mesh, 55 (51%) to no mesh, 55 (51%) to small bites, and 52 (49%) to large bites. Of the patients, 16% were smokers, 31% were overweight, and 55% were obese. At 1 year postoperative, there were no differences in major complications between groups (mesh vs no mesh 21% vs 16%, p = 0.62; small vs large bites 18% vs 19%, p = 1.00). CONCLUSIONS: In this trial, biologic mesh and small bites appear to have no benefit. Further randomized trials are needed among high-risk patients before widespread adoption of prophylactic biologic mesh or small bites.

Biologic Versus Synthetic Mesh in Ventral Hernia Repair: Participant-Level Analysis of Two Randomized Controlled Trials at Twenty-Four to Thirty-Six Months.

Background: Biologic mesh has been used increasingly in complex ventral hernia repair despite limited evidence at low risk of bias supporting its use. Patients and Methods: We performed a participant-level analysis of published randomized controlled trials (RCTs) comparing biologic to synthetic mesh with complex ventral hernia repair at 24 to 36 months. Primary outcome was major complication (composite of mesh infection, recurrence, reoperation, or death) at 24 to 36 months post-operative. Secondary outcomes included length of index hospital stay, surgical site occurrence, surgical site infection, and death. Outcomes were assessed using both frequentist and Bayesian generalized linear regression models. Results: A total of 252 patients from two RCTs were included, 126 patients randomized to the intervention arm of biologic and 126 patients to the control of synthetic mesh with median follow-up of 29 (23, 38) months. Major complication occurred in 33 (33%) patients randomized to biologic, and 39 (38%) patients randomized to synthetic mesh, (relative risk [RR] 0.91, 95% confidence interval [CI] 0.63-1.31; p value = 0.600). Bayesian analysis demonstrated that compared with synthetic mesh, biologic mesh had similar probability of major complications at 24 to 36 months post-operative. The remainder of outcomes demonstrated slight benefit with synthetic mesh as opposed to biologic mesh except for mesh infection. However, under a frequentist framework, no outcome was statistically different. Conclusions: In patients undergoing open ventral hernia repair, there was no benefit for patients receiving biologic versus synthetic mesh at 24 to 36 months post-operative.

Trial Participation and Outcomes Among English-Speaking and Spanish-Speaking Patients With Appendicitis Randomized to Antibiotics: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: Spanish-speaking participants are underrepresented in clinical trials, limiting study generalizability and contributing to ongoing health inequity. The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial intentionally included Spanish-speaking participants. Objective: To describe trial participation and compare clinical and patient-reported outcomes among Spanish-speaking and English-speaking participants with acute appendicitis randomized to antibiotics. Design, Setting, and Participants: This study is a secondary analysis of the CODA trial, a pragmatic randomized trial comparing antibiotic therapy with appendectomy in adult patients with imaging-confirmed appendicitis enrolled at 25 centers across the US from May 1, 2016, to February 28, 2020. The trial was conducted in English and Spanish. All 776 participants randomized to antibiotics are included in this analysis. The data were analyzed from November 15, 2021, through August 24, 2022. Intervention: Randomization to a 10-day course of antibiotics or appendectomy. Main Outcomes and Measures: Trial participation, European Quality of Life-5 Dimensions (EQ-5D) questionnaire scores (higher scores indicating a better health status), rate of appendectomy, treatment satisfaction, decisional regret, and days of work missed. Outcomes are also reported for a subset of participants that were recruited from the 5 sites with a large proportion of Spanish-speaking participants. Results: Among eligible patients 476 of 1050 Spanish speakers (45%) and 1076 of 3982 of English speakers (27%) consented, comprising the 1552 participants who underwent 1:1 randomization (mean age, 38.0 years; 976 male [63%]). Of the 776 participants randomized to antibiotics, 238 were Spanish speaking (31%). Among Spanish speakers randomized to antibiotics, the rate of appendectomy was 22% (95% CI, 17%-28%) at 30 days and 45% (95% CI, 38%-52%) at 1 year, while in English speakers, these rates were 20% (95% CI, 16%-23%) at 30 days and 42% (95% CI 38%-47%) at 1 year. Mean EQ-5D scores were 0.93 (95% CI, 0.92-0.95) among Spanish speakers and 0.92 (95% CI, 0.91-0.93) among English speakers. Symptom resolution at 30 days was reported by 68% (95% CI, 61%-74%) of Spanish speakers and 69% (95% CI, 64%-73%) of English speakers. Spanish speakers missed 6.69 (95% CI, 5.51-7.87) days of work on average, while English speakers missed 3.76 (95% CI, 3.20-4.32) days. Presentation to the emergency department or urgent care, hospitalization, treatment dissatisfaction, and decisional regret were low for both groups. Conclusions and Relevance: A high proportion of Spanish speakers participated in the CODA trial. Clinical and most patient-reported outcomes were similar for English- and Spanish-speaking participants treated with antibiotics. Spanish speakers reported more days of missed work. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Robotic Versus Laparoscopic Ventral Hernia Repair: Two-Year Results From a Prospective, Multicenter, Blinded Randomized Clinical Trial.

OBJECTIVE: Report the 2-year outcomes of a multicenter randomized controlled trial comparing robotic versus laparoscopic intraperitoneal onlay mesh ventral hernia repair. BACKGROUND: Ventral hernia repair is one of the most common operations performed by general surgeons. To our knowledge, no studies have been published to date comparing long-term outcomes of laparoscopic versus robotic ventral hernia repair. METHODS: The trial was registered at clinicaltrials.gov (NCT03490266). Clinical outcomes included surgical site infection, surgical site occurrence, hernia occurrence, readmission, reoperation, and mortality. RESULTS: A total of 175 consecutive patients were approached that were deemed eligible for elective minimally invasive ventral hernia repair. In all, 124 were randomized and 101 completed follow-up at 2 years. Two-year follow-up was completed in 54 patients (83%) in the robotic arm and 47 patients (80%) in the laparoscopic arm. No differences were seen in surgical site infection or surgical site occurrence. Hernia recurrence occurred in 2 patients (4%) receiving robotic repair versus in 6 patients (13%) receiving laparoscopic repair (relative risk: 0.3, 95% CI: 0.06-1.39; P =0.12). No patients (0%) required reoperation in the robotic arm whereas 5 patients (11%) underwent reoperation in the laparoscopic arm ( P =0.019, relative risk not calculatable due to null outcome). CONCLUSIONS: Robotic ventral hernia repair demonstrated at least similar if not improved outcomes at 2 years compared with laparoscopy. There is potential benefit with robotic repair; however, additional multi-center trials and longer follow-up are needed to validate the hypothesis-generating findings of this study.

Evaluation of ICARUS Guidelines and Recommendations Not Supported by Randomized Controlled Trials.

BACKGROUND: The ICARUS guidelines are a systematic review and Delphi process that provide recommendations in the treatment and management of patients with gastroesophageal reflux disease (GERD). Many of the recommendations were supported by randomized trials; some were not. This study assesses guidelines with limited evidence and weak endorsement. METHODS: Four ICARUS guidelines were chosen: the role of fundoplication for patients with BMI > 35, regurgitation, chest pain, and extra-esophageal symptoms. A multicenter database of patients undergoing fundoplication surgery for GERD between 2015 and 2020 was used. Outcomes assessed were anatomic failure and symptom recurrence. Multivariable regression was performed. RESULTS: Five institutions performed a fundoplication on 461 patients for GERD with a median of follow-up of 14.7 months (IQR 14.2). On multivariate analysis, patients with the chosen pre-operative comorbidities achieved comparable post-operative benefits. Patients with a BMI > 35 were not more likely to experience anatomic failure. Patients with pre-operative regurgitation had similar symptom recurrence rates to those without. Patients with non-cardiac chest pain had comparable rates of symptom recurrence to those without. Reporting a pre-operative chronic cough attributable to reflux was not associated with higher rates of post-operative symptom recurrence. DISCUSSION: Among the ICARUS guidelines and recommendations, a small proportion was lacking evidence at low risk for bias and endorsement. The results of this multicenter study evaluated outcomes of patients with various pre-operative conditions: BMI > 35, chest pain attributable to reflux, extra-esophageal symptoms attributable to reflux, and regurgitation. Our findings endorse patients with these characteristics as candidates for anti-reflux surgery.

Systematic Review of Treatment of Patients with Achalasia: Heller Myotomy, Pneumatic Dilation, and Peroral Endoscopic Myotomy.

BACKGROUND: The aim of this systematic review is to assess all comparative randomized controlled trials evaluating Heller myotomy, pneumatic dilation, and peroral endoscopic myotomy. STUDY DESIGN: Achalasia is an esophageal motility disorder associated with degeneration of the myenteric plexus; it causes significant symptoms and impacts patient quality of life (QOL). The optimal treatment for patients with achalasia and the impact of these interventions on QOL remain unclear. PubMed, Embase, Scopus, and Cochrane were searched from inception to April 2020. Randomized controlled trials that compared the 3 interventions were included. Primary outcome was QOL at 12 to 36 months after the operation. Secondary outcomes included reintervention, dysphagia, leak/perforation, and GERD recurrence. RESULTS: Nine publications of 6 studies were included. Of the 9 publications, there was no significant difference in QOL at 12 to 36 months except for one study in which QOL was significantly higher in patients who underwent Heller myotomy as opposed to pneumatic dilation at 3 years; however, at 5 years there was no difference. Pneumatic dilation was associated with the highest rates of dysphagia recurrence and reintervention, but peroral endoscopic myotomy had the lowest. CONCLUSIONS: The treatment of achalasia should be chosen in accordance with patient goals. After any of the 3 interventions, QOL appears to be similar. However, peroral endoscopic myotomy may be associated with the lowest rates of perforation/leak, dysphagia, and reintervention and may be the lowest risk option. However, there are barriers to widespread use due to challenges in training and adoption.

Safety and Feasibility of Performing Antireflux Procedures at a Safety Net Hospital.

INTRODUCTION: One-half of Americans have limited access to health care; these patients often receive care through safety net hospitals, which are associated with worse medical outcomes. This study aims to compare the outcomes of patients who received foregut surgery at a safety net hospital to those at a private or university hospital. We hypothesized that patients treated at the safety net hospital will have a greater rate of radiographic recurrence and reoperations. METHODS: A retrospective study was conducted on patients who underwent hiatal hernia repair or fundoplication for gastroesophageal reflux disease at an affiliated safety net, private, or university hospital from June 2015 to May 2020. The primary outcome was radiographic recurrence. The secondary outcomes included reoperation and symptom recurrence. Analysis was performed using analysis of variance, chi-square, and logistic regression. RESULTS: A total of 499 patients were identified: 157 at a safety net hospital, 233 at a private hospital, and 119 at a university hospital. The median (interquartile range) follow-up was 16 (13) mo. The safety net hospital treated more Hispanics, females, and patients with comorbidities. Large hiatal hernias were more common at the safety net and private hospitals. Robotic surgery was more frequently at the university hospital. There was no difference in radiographic recurrence (13.4% versus 19.7% versus 17.6%; P = 0.269), reoperation (3.8% versus 7.2% versus 6.7%; P = 0.389), or postoperative dysphagia (15.3% versus 12.6% versus 15.1%; P = 0.696). On logistic regression, there were no differences in outcomes among institutions. CONCLUSIONS: This study suggests that despite the challenges faced at safety net hospitals, it could be feasible to safely perform minimally invasive foregut surgery with similar outcomes to private and university hospitals.

Perception of Treatment Success and Impact on Function with Antibiotics or Appendectomy for Appendicitis: A Randomized Clinical Trial with an Observational Cohort.

OBJECTIVE: To compare secondary patient reported outcomes of perceptions of treatment success and function for patients treated for appendicitis with appendectomy vs. antibiotics at 30 days. SUMMARY BACKGROUND DATA: The Comparison of Outcomes of antibiotic Drugs and Appendectomy trial found antibiotics noninferior to appendectomy based on 30-day health status. To address questions about outcomes among participants with lower socioeconomic status, we explored the relationship of sociodemographic and clinical factors and outcomes. METHODS: We focused on 4 patient reported outcomes at 30 days: high decisional regret, dissatisfaction with treatment, problems performing usual activities, and missing >10 days of work. The randomized (RCT) and observational cohorts were pooled for exploration of baseline factors. The RCT cohort alone was used for comparison of treatments. Logistic regression was used to assess associations. RESULTS: The pooled cohort contained 2062 participants; 1552 from the RCT. Overall, regret and dissatisfaction were low whereas problems with usual activities and prolonged missed work occurred more frequently. In the RCT, those assigned to antibiotics had more regret (Odd ratios (OR) 2.97, 95% Confidence intervals (CI) 2.05-4.31) and dissatisfaction (OR 1.98, 95%CI 1.25-3.12), and reported less missed work (OR 0.39, 95%CI 0.27-0.56). Factors associated with function outcomes included sociodemographic and clinical variables for both treatment arms. Fewer factors were associated with dissatisfaction and regret. CONCLUSIONS: Overall, participants reported high satisfaction, low regret, and were frequently able to resume usual activities and return to work. When comparing treatments for appendicitis, no single measure defines success or failure for all people. The reported data may inform discussions regarding the most appropriate treatment for individuals. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02800785.

Prophylactic Mesh Reinforcement for Prevention of Midline Incisional Hernias: A Publication Bias Adjusted Meta-analysis.

OBJECTIVE: To systematically review the published literature on the use of prophylactic mesh reinforcement of midline laparotomy closures for prevention of VIH. SUMMARY OF BACKGROUND DATA: VIH are common complications of abdominal surgery. Prophylactic mesh has been proposed as an adjunct to prevent their occurrence. METHODS: PubMed, Embase, Scopus, and Cochrane were reviewed for RCTs that compared prophylactic mesh reinforcement versus conventional suture closure of midline abdominal surgery. Primary outcome was the incidence of VIH at postoperative follow-up ≥24 months. Secondary outcomes included surgical site infection and surgical site occurrence (SSO). Pooled risk ratios were obtained through random effect meta-analyses and adjusted for publication bias. Network meta-analyses were performed to compare mesh types and locations. RESULTS: Of 1969 screened articles, 12 RCTs were included. On meta-analysis there was a lower incidence of VIH with prophylactic mesh [11.1% vs 21.3%, Relative risk (RR) = 0.32; 95% confidence interval (CI) = 0.19-0.55, P < 0.001), however, publication bias was highly likely. When adjusted for this bias, prophylactic mesh had a more conservative effect (RR = 0.52; 95% CI = 0.39-0.70). There was no difference in risk of surgical site infection (9.1% vs 8.9%, RR = 1.08, 95% CI = 0.82-1.43; P = 0.118), however, prophylactic mesh increased the risk of SSO (14.2% vs 8.9%, RR = 1.57, 95% CI = 1.19-2.05; P < 0.001). CONCLUSION: Current RCTs suggest that in mid-term follow-up prophylactic mesh prevents VIH with increased risk for SSO. There is limited long-term data and substantial publication bias.

Expert Consensus for Key Features of Operative Reports of Ventral Hernia.

BACKGROUND: Operative reports are important documents; however, standards for critical elements of operative reports are general and often vague. Hernia surgery is one of the most common procedures performed by general surgeons, so the aim of this project was to develop a Delphi consensus on critical elements of a ventral hernia repair operative report. STUDY DESIGN: The Delphi method was used to establish consensus on key features of operative reports for ventral hernia repair. An expert panel was selected and questionnaires were distributed. The first round of voting was open-ended to allow participants to recommend what details should be included. For the second round the questionnaire was distributed with the items that did not have unanimous responses along with free text comments from the first round. RESULTS: Eighteen surgeons were approached, of which 11 completed both rounds. Twenty items were on the initial questionnaire, of which 11 had 100% agreement. Of the remaining 9 items, after the second questionnaire an additional 7 reached consensus. CONCLUSION: Ventral hernia repairs are a common and challenging problem and often require reoperations. Surgeons frequently refer to previous operative notes to guide future procedures, which requires detailed and comprehensive operative reports. This Delphi consensus was able to identify key components needed for an operative report describing ventral hernia repair.

The Food and Drug Administration's (FDA's) 510(k) Process: A Systematic Review of 1000 Cases.

BACKGROUND: The vast majority of devices cleared by the Food and Drug Administration (FDA) are through the 510(k) process, which allows medical devices to be quickly introduced into the market. The FDA 510(k) process is designed to minimize the burden and expense of bringing new devices to market; however, as a result, the FDA may be limited in its ability to establish the safety of these devices. METHODS: The FDA 510(k) online archives were searched for devices cleared from 2013 to 2014. One thousand devices were randomly selected. PubMed was searched for each device to identify publications about the devices. The primary outcome was the percentage of devices cleared through the 510(k) process with no published research. Secondary outcomes included: conflict of interest (COI) of authors and outcomes of published studies on the devices. RESULTS: A total of 6152 devices were cleared through the 510(k) process in 2013-2014. Of the 1000 randomly selected devices, 17.8% had published research. There were 375 manuscripts, of which 47 (12.5%) were randomized controlled trials. One-fourth (25.1%) of studies had a clearly identifiable COI, while COI was unclear for half (49.9%). CONCLUSION AND RELEVANCE: There is limited evidence examining the safety and effectiveness of devices cleared via the 510(k) process. Thousands of devices are cleared through the FDA's 510(k) process each year with limited or no evidence publicly available. This has led to the market being introduced to potentially costly, nonbeneficial, or harmful devices. Devices, like prescription drugs, should undergo a more rigorous clearance process.

Association of Patient Belief About Success of Antibiotics for Appendicitis and Outcomes: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials. Objective: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial. Design, Setting, and Participants: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive antibiotics in the CODA trial. After informed consent but before randomization, participants who were assigned to receive antibiotics responded to a baseline survey including a question about how successful they believed antibiotics could be in treating their appendicitis. Interventions: Participants were categorized based on baseline survey responses into 1 of 3 belief groups: unsuccessful/unsure, intermediate, and completely successful. Main Outcomes and Measures: Three outcomes were assigned at 30 days: (1) appendectomy, (2) high decisional regret or dissatisfaction with treatment, and (3) persistent signs and symptoms (abdominal pain, tenderness, fever, or chills). Outcomes were compared across groups using adjusted risk differences (aRDs), with propensity score adjustment for sociodemographic and clinical factors. Results: Of the 776 study participants who were assigned antibiotic treatment in CODA, a total of 425 (mean [SD] age, 38.5 [13.6] years; 277 male [65%]) completed the baseline belief survey before knowing their treatment assignment. Baseline beliefs were as follows: 22% of participants (92 of 415) had an unsuccessful/unsure response, 51% (212 of 415) had an intermediate response, and 27% (111 of 415) had a completely successful response. Compared with the unsuccessful/unsure group, those who believed antibiotics could be completely successful had a 13-percentage point lower risk of appendectomy (aRD, -13.49; 95% CI, -24.57 to -2.40). The aRD between those with intermediate vs unsuccessful/unsure beliefs was -5.68 (95% CI, -16.57 to 5.20). Compared with the unsuccessful/unsure group, those with intermediate beliefs had a lower risk of persistent signs and symptoms (aRD, -15.72; 95% CI, -29.71 to -1.72), with directionally similar results for the completely successful group (aRD, -15.14; 95% CI, -30.56 to 0.28). Conclusions and Relevance: Positive patient beliefs about the likely success of antibiotics for appendicitis were associated with a lower risk of appendectomy and with resolution of signs and symptoms by 30 days. Pathways relating beliefs to outcomes and the potential modifiability of beliefs to improve outcomes merit further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Reproducing Statistics Performed in Published Randomized Controlled Trials.

INTRODUCTION: Randomized controlled trials (RCT) represent evidence at the lowest potential risk for bias. Clinicians in all specialties depend upon RCTs to guide patient care. Issues such as statistical discordance, or reporting statistical results that cannot be reproduced, should be uncommon. Our aim was to confirm the statistical reproducibility of published RCTs. METHODS: PubMed was searched using "randomized controlled trial." Studies were selected using a random number generator. Studies were included if the primary outcome could be reproduced using the data and statistical test reported in the manuscript. The reproduced p-value from our analysis and the published p-value were compared. Primary outcome was the number of studies that reported p-values that differed in statistical significance (crossed p-value=0.05) from the reproduction analysis. Assuming an alpha of 0.05, a beta of 0.80, an estimated rate of statistical discordance of 5% for RCTs, a total of at least 568 studies were required. RESULTS: Overall, 572 RCTs were selected involving six specialties. Of these, 45% were positive (p<0.05) studies. Eleven (2%) published results that differed from the reproduction analysis and crossed the p=0.05 threshold. All 11 studies were positive studies (while the reproduction analysis demonstrated p≥0.05). CONCLUSION: Less than 5% of published RCTs reported a discordant p-value that crossed the "p=0.05" threshold. Although the occurrence is uncommon, the existence of even one RCT publishing nonreproducible results is concerning. Future studies should seek to identify why some RCTs report discordant statistics and how to prevent this from occurring.