Fungicides as a risk factor for the development of neurological diseases and disorders in humans: a systematic review.

Although studies show that pesticides, especially insecticides, may be toxic to humans, publications on the neurological effects of fungicides are scarce. As fungicides are used widely in Brazil, it is necessary to gather evidence to support actions aimed at safely using of these chemicals. We investigated through a systematic review of publications on the use of fungicides and consequences of exposure related to nervous system diseases or neurological disorders in humans. The protocol review was registered on PROSPERO and followed the guidelines of the PRISMA-Statement. As far as it is known, there is no apparent systematic review in the literature on this topic. The search was comprised of the following databases: PubMed; Web of Science; Scopus and EMBASE, using groups of Mesh terms and strategies specific to each database. Thirteen articles were selected for this review. Regarding the substances analyzed in the studies, some reported the use of fungicides in general, without separating them by type, while others summarized the categories of all pesticides by their function (insecticides, herbicides, fungicides, etc.) or chemical class (dithiocarbamate, dicarboximide, inorganic, etc.). However, most of the articles referred to fungicides that contain the metal manganese (Mn) in their composition. As for neurological disorders, articles addressed Parkinson's disease (PD), neurodevelopmental outcomes, extrapyramidal syndrome resembling PD, cognitive disorders, depression, neural tube defects, motor neurone disease, and amyotrophic lateral sclerosis. Most investigations pointed to exposure to fungicides, mainly maneb and mancozeb, leading to the development of at least one neurological disease, which suggests the need for further multicentric clinical trials and prospective studies for greater clarity of the research problem.

Prophylactic ureteric catheterisation during complex gynaecological surgery: A systematic review and meta-analysis.

BACKGROUND: There is a lack of robust evidence to recommend the use of perioperative ureteric catheterisation or stenting in complex gynaecological surgery. OBJECTIVES: To evaluate the evidence on the benefits and risks of perioperative ureteric catheterisation or stenting in complex gynaecological surgery. SEARCH STRATEGY: A literature search was performed in CINAHL, the Cochrane Library, Embase and MEDLINE, from 1946 to January 2024, using a combination of keywords and Medical Subject Headings (MeSH) terminology. SELECTION CRITERIA: Randomised controlled trials (RCTs) and observational studies were included. DATA COLLECTION AND ANALYSIS: Meta-analysis of the RCTs and observational studies were performed separately. Cochrane RevMan 6.5.1 was used to undertake meta-analysis. Risk ratios with 95% CIs were calculated for the outcome measures. MAIN RESULTS: Ten studies were included: three RCTs and seven observational studies, comprising 8661 patients. The three RCTs, comprising a total of 3277 patients, showed no difference in the risk of immediate complications in the form of ureteric injury between the ureteric stent and the control groups (RR 0.9, 95% CI 0.49-1.65). The observational studies included 5384 patients. Four studies that explored the ureteric injury as an outcome did not show any difference between the two groups (RR 0.76, 95% CI 0.27-2.16). One case-control study with 862 participants found that the rate of ureteric injury was higher in the non-stented group, although this was observed in only three patients. The risk of urinary tract infection (UTI) was increased in the stent group, although not with statistical significance (RR 1.84, 95% CI 0.47-7.17). There was no significant difference in the risk of ureteric fistulae (RR 1.91, 95% CI 0.62-5.83), although the number of studies was limited. CONCLUSIONS: Prophylactic ureteric catheterisation or stenting for complex gynaecological surgery is not associated with a lower risk of ureteric injury.

Transabdominal pre-peritoneal (TAPP) versus totally extraperitoneal (TEP) laparoscopic techniques for inguinal hernia repair.

BACKGROUND: An inguinal hernia occurs when part of the intestine protrudes through the abdominal muscles. In adults, this common condition is much more likely in men than in women. Inguinal hernia can be monitored by 'watchful waiting', but if symptoms persist or worsen, surgery is usually required, which can be open or laparoscopic. Laparoscopic (keyhole) repair of inguinal hernias in adults is generally performed using either the transabdominal preperitoneal (TAPP) or the totally extraperitoneal (TEP) method. Both methods include the use of mesh placed in front of the peritoneal lining of the abdominal wall, but for the TAPP technique, the abdominal cavity needs to be entered to place the mesh, and for the TEP technique, the whole procedure is done on the outside of the peritoneal lining of the abdominall wall. Whether one method is superior to the other has not been established, and there is debate about their relative benefits and harms. An advantage of TEP is its avoidance of the abdominal cavity; the downside is that it requires a steeper learning curve for clinicians. TAPP is considered simpler and makes it possible to inspect the contralateral side, but TAPP may have a higher risk of visceral injury compared to TEP. This is an update of a Cochrane review first published in 2005. OBJECTIVES: To compare the benefits and harms of laparoscopic TAPP technique versus laparoscopic TEP technique for inguinal hernia repair in adults. SEARCH METHODS: On 25 October 2022, the authors searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); and Ovid Embase, for published randomised controlled trials. To identify studies in progress, we searched ClinicalTrials.gov and the WHO International Clinical Trial Registry Platform (ICTRP). SELECTION CRITERIA: All prospective randomised, quasi-randomised, and cluster-randomised trials that compared the laparoscopic TAPP technique with the laparoscopic TEP technique for inguinal hernia repair in adults were eligible for inclusion. We included studies that involved a mix of different types of groin hernia if we could extract data for the inguinal hernias. Studies may have also included a group of participants receiving hernia repair by open surgery, but these groups were not included in our review. DATA COLLECTION AND ANALYSIS: Both review authors independently evaluated trial eligibility, extracted data from included studies, and assessed the risk of bias in the included studies. The review's primary outcomes were serious adverse events, chronic pain (persisting for at least six months after surgery), and hernia recurrence. We also assessed a variety of secondary outcomes at perioperative, early postoperative, and late postoperative time points. We performed statistical analyses using the random-effects model, and expressed the results as odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, with their respective 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for key outcomes as high, moderate, low or very low. MAIN RESULTS: We included 23 studies in this review update, which randomised 1156 people to TAPP and 1110 people to TEP, all requiring repair of inguinal hernias. Study sample sizes varied from 40 to 316 participants. The vast majority of study participants were male. We judged most studies to be at 'high' or 'unclear' risk of bias. Our judgements of the certainty of the evidence were low or very low for all outcomes we assessed. There may be little to no difference between TAPP and TEP laparoscopic techniques for serious adverse events (0.4% versus 0.7%; OR 0.58, 95% CI 0.15 to 2.32, P = 0.45, I2 = 0%; 19 studies, 1735 participants; low certainty of evidence); and hernia recurrence (1.2% versus 1.1%; OR 1.14, 95% CI 0.49 to 2.62, P = 0.97, I2 = 0%; 17 studies, 1712 participants; low certainty of evidence). The evidence is very uncertain about the effects of TAPP versus TEP techniques on chronic pain (OR 0.62, 95% CI 0.20 to 1.97, P = 0.68, I2 = 0%; 6 studies, 860 participants; very low certainty of evidence). In terms of secondary outcomes, the evidence is very uncertain for TAPP versus TEP techniques for perioperative visceral and vascular injury (15 studies, 1523 participants; very low certainty of evidence), and for haematoma or seroma during the early (≤ 30 days) postoperative phase (OR 0.86, 95% CI 0.54 to 1.37, P = 0.3861, I2 = 0%; 15 studies, 1423 participants; very low certainty of evidence). TEP technique may carry a higher risk of conversion to another hernia repair method (either TAPP technique or open surgery) when compared to TAPP (2.5% versus 0.7%; OR 0.28, 95% CI 0.09 to 0.84, P = 0.02, I2 = 0%; 13 studies, 1178 participants; low certainty of evidence). Only two studies (474 participants) reported quality of life in the late (> 30 days) postoperative phase; overall, there was an improvement in quality of life from the pre- to post-operative assessment, but the evidence suggests little to no difference between the techniques (low certainty of evidence). AUTHORS' CONCLUSIONS: This review update found that there may be little to no difference between the TAPP and TEP techniques for serious adverse events, hernia recurrence, or chronic pain (low- to very-low-certainty evidence). Decisions about which method to use will most likely reflect surgeon and patient preference until high-certainty evidence becomes available. There may be a higher risk of needing to convert from TEP to TAPP or open surgery when compared to the risk of needing to convert from TAPP to open surgery (low-certainty evidence). If surgeons opt for TEP as their standard laparoscopic method, they could consider having a strategy for how to handle the potential need for conversion. This might include proficiency in the TAPP approach or having informed the patient about the risk of conversion to open surgery. For surgeons or surgical departments, the choice of a laparoscopic technique should involve shared decision-making with patients and their families or carers. Future research could focus on patient-reported outcomes, such as quality of life.

Autologous Fascial Slings for Stress Urinary Incontinence: a 17-year Follow-up of a Randomised Controlled Study.

INTRODUCTION AND HYPOTHESIS: Safety concerns with the use of mesh in vaginal surgery have been ongoing. Autologous fascial slings (AFS) avoid foreign body complications. We compared the long-term (17-year) outcomes of two AFS repair methods-the standard sling and short sling (sling-on-string), and assessed durability and patient satisfaction of these for the treatment of stress urinary incontinence (SUI). METHODS: A total of 107 patients from three urogynaecology units who had participated in a randomised controlled trial assessing standard (n = 52) and short (n = 55) slings were followed up for a median period of 17 years. Primary outcomes were Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) scores to assess the impact on the quality of life and symptom distress. Logistic quantile regression was employed to compare the two methods. Secondary outcomes included long-term complications and patient satisfaction. RESULTS: Mean scores showed no statistically significant difference between the standard and short slings at the 17-year follow-up relating to IIQ and UDI scores, leakage or urgency (p > 0.05). Improved bladder function was observed at 17 years compared with baseline (standard sling-IIQ scores mean difference [MD] 1.22 [CI: 0.69, 1.74], UDI scores MD 0.83 [CI: 0.70, 0.97]; short sling-IIQ score MD 1.14 [CI: 0.73, 1.54], UDI scores MD 0.54 [CI: 0.40, 0.67]) with age-related deterioration over time. Re-operation rates were low and patient satisfaction rates were high (67.2%) at follow-up. CONCLUSIONS: Autologous fascial slings are an effective and durable option for management of SUI and the short sling procedure can be recommended owing to plausible surgical advantages.

Assessing the Content and Effect of Web-Based Decision Aids for Postmastectomy Breast Reconstruction: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Web-based decision aids have been shown to have a positive effect when used to improve the quality of decision-making for women facing postmastectomy breast reconstruction (PMBR). However, the existing findings regarding these interventions are still incongruent, and the overall effect is unclear. OBJECTIVE: We aimed to assess the content of web-based decision aids and its impact on decision-related outcomes (ie, decision conflict, decision regret, informed choice, and knowledge), psychological-related outcomes (ie, satisfaction and anxiety), and surgical decision-making in women facing PMBR. METHODS: This systematic review and meta-analysis followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 6 databases, PubMed, Embase, Cochrane Library, CINAHL, PsycINFO, and Web of Science Core Collection, were searched starting at the time of establishment of the databases to May 2023, and an updated search was conducted on April 1, 2024. MeSH (Medical Subject Headings) terms and text words were used. The Cochrane Risk of Bias Tool for randomized controlled trials was used to assess the risk of bias. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: In total, 7 studies included 579 women and were published between 2008 and 2023, and the sample size in each study ranged from 26 to 222. The results showed that web-based decision aids used audio and video to present the pros and cons of PMBR versus no PMBR, implants versus flaps, and immediate versus delayed PMBR and the appearance and feel of the PMBR results and the expected recovery time with photographs of actual patients. Web-based decision aids help improve PMBR knowledge, decisional conflict (mean difference [MD]=-5.43, 95% CI -8.87 to -1.99; P=.002), and satisfaction (standardized MD=0.48, 95% CI 0.00 to 0.95; P=.05) but have no effect on informed choice (MD=-2.80, 95% CI -8.54 to 2.94; P=.34), decision regret (MD=-1.55, 95% CI -6.00 to 2.90 P=.49), or anxiety (standardized MD=0.04, 95% CI -0.50 to 0.58; P=.88). The overall Grading of Recommendations, Assessment, Development, and Evaluation quality of the evidence was low. CONCLUSIONS: The findings suggest that the web-based decision aids provide a modern, low-cost, and high dissemination rate effective method to promote the improved quality of decision-making in women undergoing PMBR. TRIAL REGISTRATION: PROSPERO CRD42023450496; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=450496.

Assessing the efficacy of Laser pulpotomy versus conventional pulpotomy in primary teeth: A systematic review and meta-analysis of clinical trials.

PURPOSE: This study systematically reviewed the clinical and radiographic outcomes of laser versus conventional pulpotomy in primary teeth. It also compared the success and effectiveness of different lasers to enhance the understanding and use of laser pulpotomy as an alternative treatment. METHODOLOGY: An electronic search was carried out in PubMed and Cochrane from 1st January 1999 to 31st December 2023. The published articles in the English language were searched using MeSH terms and text words. Only randomized controlled trials with a sample size of more than 10 and follow-ups over 6 months were included. Meta-analysis and forest plots were evaluated by utilizing Review Manager 5.4 software. Two reviewers assessed the risk of bias using the RoB 2 tool and discrepancies were resolved by the third reviewer. The success rates were combined using a random effects model to determine clinical and radiographic outcomes. We used risk ratios with 95% confidence intervals (CI) as the primary effect measures and set the significance level at 0.05. RESULTS: Only 18 studies met the inclusion criteria after an electronic search. Among them, 13 studies evaluated the clinical and radiographic outcomes of laser with formocresol pulpotomy, 2 studies compared with ferric sulfate pulpotomy, and the remaining studies with Mineral trioxide aggregate (MTA) pulpotomy. The various studies showed different levels of bias. There was no significant difference in the clinical success rate (p = 0.47; RR: 1.01; 95% CI 0.98-1.04; I2 = 0%; p = 0.70) and radiographic success rate (p = 0.94; RR: 1.00; 95% CI 0.91-1.09; I2 = 64%; p = 0.001) between laser pulpotomy and formocresol. Similarly, there was no significant difference between laser pulpotomy and ferric sulfate or MTA pulpotomy. CONCLUSION: Diode laser and LLLT can be considered as alternative pulpotomy agents to formocresol in primary teeth. However, high-quality trials are needed to confirm the accuracy and reliability of these findings.

A Systematic Review of Registered Clinical Trials for Peripheral Nerve Injuries.

ABSTRACT: Upper extremity peripheral nerve injuries (PNIs) significantly impact daily functionality and necessitate effective treatment strategies. Clinical trials play a crucial role in developing these strategies. However, challenges like retrospective data collection, reporting biases, inconsistent outcome measures, and inadequate data sharing practices hinder effective research and treatment advancements. This review aims to analyze the landscape of reporting, methodological design, outcome measures, and data sharing practices in registered clinical trials concerning upper extremity PNIs. It seeks to guide future research in this vital area by identifying current trends and gaps.A systematic search was conducted on ClinicalTrials.gov and WHO International Clinical Trials Registry Platform up to November 10, 2023, using a combination of MeSH terms and keywords related to upper extremity nerve injury. The PRISMA 2020 guidelines were followed, and the studies were selected based on predefined inclusion and exclusion criteria. A narrative synthesis of findings was performed, with statistical analysis for associations and completion rates.Of 3051 identified studies, 96 met the inclusion criteria. These included 47 randomized controlled trials, 27 nonrandomized trials, and others. Sensory objective measures were the most common primary outcomes. Only 13 studies had a data sharing plan. The analysis revealed varied intervention methods and inconsistencies in outcome measures. There was a significant association between study funding, design, and completion status, but no association between enrollment numbers and completion.This review highlights the need for standardized outcome measures, patient-centered assessments, and improved data sharing in upper extremity PNI trials. The varied nature of interventions and inconsistency in outcome measures indicate the necessity for more rigorous and transparent research practices to strengthen the evidence base for managing these injuries.

Industry Sponsorship Bias in Collagenase Clinical Trials for Dupuytren Disease: A Meta-analysis.

BACKGROUND: Collagenase clostridium histolyticum (collagenase) was introduced in 2010 creating a nonoperative treatment option for Dupuytren disease with promising results in sponsored clinical trials. A meta-analysis was performed to investigate industry sponsorship bias. METHODS: A systematic review of collagenase treatment of Dupuytren contracture was conducted. Articles containing mesh terms including "microbial collagenase" and "Dupuytren's contracture" were searched and limited to only clinical trials with similar protocols for inclusion. Meta-analysis of treatment endpoints of correction of contracture to 0-5 degrees after first and last injection was conducted comparing sponsored versus nonsponsored studies. RESULTS: Sixteen of the 29 identified articles met criteria for inclusion. Nonsponsored studies reported a significantly higher rate of meeting the primary treatment endpoint compared to sponsored studies after single injection for all joints (69.6% vs 56% P < 0.01), metacarpophalangeal joint (96% vs 64% P < 0.01), and proximal interphalangeal joint (67% vs 36% P = 0.011). The correction in contracture rates was similar between groups with studies evaluating more than one injection. CONCLUSIONS: Nonsponsored studies published higher success rates in meeting the primary endpoint of full correction after single injection than sponsored studies; however, similar results with multiple injections. This study demonstrated that sponsored studies of collagenase produced highly powered studies that may be reliably depended on for evidence-based clinical application.

Importance of sex and gender differences in enrollment and interpretation of stroke clinical trials.

OBJECTIVES: This review aims to reinforce the importance of improving sex balance in preclinical trials and sex and gender diversity and proportional balance in clinical trials enrollment and how this influences interpretation of stroke clinical trials. It also aims to identify strategies for improvement in data collection. MATERIALS AND METHODS: A PubMed search was conducted of publications in English, using MeSH terms sex, sex characteristics, gender identity, transgender, gender-nonconforming persons, clinical trials as topic, stroke. Of 249 search results, 217 were human or animal studies related to stroke, the majority of which were reviews, secondary analyses of stroke clinical trials, meta analyses, or retrospective studies, subject to the methods of sex and gender acquisition per the primary data source. Articles were reviewed, noting inclusion or absence of sex and gender definitions and trial design. Selected articles were supplemented with United States Food and Drug Administration, National Institutes of Health, and National Academy of Science, Engineering, and Medicine publications. RESULTS: The majority of preclinical studies continue to report sex as a binary variable, and the majority of stroke clinical trials report sex and gender as interchangeable and binary. Mindful trial design and statistical analysis can improve accuracy in the interpretation of sex and gender differences. Guidance exists to improve reporting on currently accepted sex and gender definitions, recommended data collection instruments, and appropriate statistical analyses. CONCLUSIONS: Despite acknowledgement of having failed to achieve diverse and proportionally balanced enrollment, sex and gender imbalance across the research continuum remains prevalent. Responsible incorporation of sex and gender in stroke clinical trials can be achieved through thoughtful study design, use of contemporary sex and gender definitions, inclusive prospective data collection, balanced enrollment with prespecified goals, and appropriate statistical analysis.

The Effectiveness of Cyanoacrylates versus Sutures for Mesh Fixation after Lichtenstein Repair (SCyMeLi STUDY) A Systematic Review and Meta-Analyze of Randomized Controlled Trials.

Background: Chronic postoperative inguinal pain (CPIP) is still the most frequent complication after open Lichtenstein repair and any strategy to reduce its incidence and implications is a step forward to better outcomes. Between the means of mesh fixation atraumatic glue fixation has been explored as such possibility. A meta-analysis of randomized controlled trials comparing the performance of cyanoacrylate glue versus sutures fixation was conducted. Methods: the meta-analysis was conducted according to the PRISMA guidelines. Randomized controlled trials (RCTs) published between January 2000 and December 2021 were searched for in MEDLINE, PubMed, Web of Science, and Google Scholars. The quality of RCTs and the potential risk of bias were assessed using MINORS criteria and the Cochrane risk of bias tool. Results: of 269 papers the meta-analysis was performed on 19 RCTs including 3578 patients. In the glue fixation group, the operation was shorter (mean pooled difference 6 minutes; SE = 0.47; 95% CI = - 6.77 - - 4.92; t test = -12.36; p 0.0001) and immediate postoperative pain was lower (2.37% vs 13.3%OR - 0.158; 95% CI = 0.064 0.386; p = 0.0001). There was no difference in terms of chronic pain, recurrence rate and wound events. Conclusion: glue fixation of mesh in elective Lichtenstein repair of inguinal hernia seems to be a valid choice for a painful and safe procedure without increasing risk of recurrence.

The effectiveness of customised 3D-printed insoles on perceived pain, comfort, and completion time among frequent Park Runners: Study protocol for a pragmatic randomised controlled trial (The ZOLES RCT).

BACKGROUND: Running, a popular recreational activity, often leads to the experience of pain and discomfort among participants impacting performance and participation longevity. The ZOLES trial evaluates customised 3D-printed insoles for reducing pain in frequent parkrunners aged 35 and over. An innovative process of foot-scanning and responses to questions relating to size, pain, discomfort, and previous medical conditions are combined leading to the production of personalised 3D-printed orthotics. METHODS: The ZOLES trial is a pragmatic, outcome assessor blinded, randomised, controlled, superiority trial involving 200 recreational runners, randomised to receive either customised 3D-printed insoles (ZOLES) or to a "do-as-usual" control group. The study follows a robust protocol, ensuring adherence to established guidelines for clinical trials, and is based at St Mary's University, Twickenham, London. The primary outcome is change in running-related pain over a 10-week period, assessed using an 11-point Numeric Rating Scale. Secondary outcomes include overall pain and discomfort, running-related comfort, 5k-completion time, time-loss due to injuries, running exposure, and adherence to the intervention. A balanced-block randomisation process is stratified by sex and parkrun location, and an intention-to-treat analyses will be employed on all outcomes in the primary trial report. The trial includes a 52-week post-market surveillance to assess long-term effects of the customised insoles. DISCUSSION: The ZOLES trial aims to provide insights into real-world applicability and effectiveness of customised 3D-printed insoles in reducing running-related pain and enhancing overall running experience. Despite the limitation of a subjective primary outcome measure without participant blinding, the methodological rigor, including external outcome assessment and data handling, we anticipate results that are academically credible and applicable in real-world settings The results of this trial may have important implications for runners, clinicians, and the sports footwear industry, as evidence for the use of individualised insoles to improve running experience and prevention of pain may become evident. TRIAL REGISTRATION: The trial was pre-registered at ClinicalTrials.gov with the trial identifier NCT06034210 on September 4, 2023, and publicly posted on September 13, 2023 (https://clinicaltrials.gov/study/NCT06034210). PROTOCOL VERSION: Version 1, September 27, 2023.

Effects of long and short ejaculatory abstinence on sperm parameters: a meta-analysis of randomized-controlled trials.

Purpose: This study aimed to investigate the effects of ejaculatory abstinence on sperm parameters. Methods: This analysis was registered in PROSPERO (CRD42023472124). We performed a search on PubMed using the following text terms: (("sperm parameters" OR "sperm analysis" [Mesh]) AND ("sperm DNA fragmentation" OR "DNA fragmentation" [Mesh]) AND ("sexual abstinence" [Mesh] OR "abstinence")) and an advanced search in Scopus using the terms ("sperm parameters" OR "sperm parameters" OR "DNA fragmentation") AND ("abstinence"). The sperm parameters that were investigated were sperm volume, total sperm motility, progressive sperm motility, sperm concentration, sperm morphology, and sperm DNA fragmentation (SDF). A two-day cut-off as a "short" or "long" abstinence period has been defined. Results: Thirteen studies published between 2013 and 2022 were included in this meta-analysis. A total of 2,315 patients, ranging from 6 to 836 from each cohort, were enrolled in the study. We showed that longer abstinence time was associated with greater sperm concentration (mean difference [MD]: 8.19; p <0.01), sperm volume (MD: 0.96; p <0.01), and higher SDF (MD: 3.46; p <0.01), but lower progressive sperm motility (MD: -1.83; p <0.01). Otherwise, no statistically significant difference was observed in patients with longer vs. shorter abstinence times regarding total sperm motility (MD: -1.83; p = 0.06). Meta-regression analysis showed that days of abstinence were positively and linearly related to sperm concentration (slope: 3.74; p <0.01) and SDF (slope: 0.65; p = 0.044). Conclusions: According to our data, short ejaculatory abstinence is associated with better sperm quality. Indeed, a higher percentage of progressive sperm motility and lower levels of SDF have been reported in a short abstinence cohort. In contrast, the long abstinence group reported a higher sperm concentration. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023472124.

Registry-based randomised controlled trials: conduct, advantages and challenges-a systematic review.

BACKGROUND: Registry-based randomised controlled trials (rRCTs) have been described as pragmatic studies utilising patient data embedded in large-scale registries to facilitate key clinical trial procedures including recruitment, randomisation and the collection of outcome data. Whilst the practice of utilising registries to support the conduct of randomised trials is increasing, the use of the registries within rRCTs is inconsistent. The purpose of this systematic review is to explore the conduct of rRCTs using a patient registry to facilitate trial recruitment and the collection of outcome data, and to discuss the advantages and challenges of rRCTs. METHODS: A systematic search of the literature was conducted using five databases from inception to June 2020: PubMed, Embase (through Ovid), CINAHL, Scopus and the Cochrane Controlled Register of Trials (CENTRAL). The search strategy comprised of MESH terms and key words related to rRCTs. Study selection was performed independently by two reviewers. A risk of bias for each study was completed. A narrative synthesis was conducted. RESULTS: A total 47,862 titles were screened and 24 rRCTs were included. Eleven rRCTs (45.8%) used more than one registry to facilitate trial conduct. Six rRCTs (25%) randomised participants via a specific randomisation module embedded within a registry. Recruitment ranged between 209 to 106,000 participants. Advantages of rRCTs are recruitment efficiency, shorter trial times, cost effectiveness, outcome data completeness, smaller carbon footprint, lower participant burden and the ability to conduct multiple trials from the same registry. Challenges are data collection/management, quality assurance issues and the timing of informed consent. CONCLUSIONS: Optimising the design of rRCTs is dependent on the capabilities of the registry. New registries should be designed and existing registries reviewed to enable the conduct of rRCTs. At all times, data management and quality assurance of all registry data should be given key consideration. We suggest the inclusion of the term 'registry-based' in the title of all rRCT manuscripts and a clear simple breakdown of the registry-based conduct of the trial in the abstract to facilitate indexing in the major databases.

Protocol for an independent patient data meta-analysis of prophylactic mesh placement for incisional hernia prevention after abdominal aortic aneurysm surgery: a collaborative European Hernia Society project (I-PREVENT-AAA).

INTRODUCTION: Incisional hernia (IH) is a prevalent and potentially dangerous complication of abdominal surgery, especially in high-risk groups. Mesh reinforcement of the abdominal wall has been studied as a potential intervention to prevent IHs. Randomised controlled trials (RCTs) have demonstrated that prophylactic mesh reinforcement after abdominal surgery, in general, is effective and safe. In patients with abdominal aortic aneurysm (AAA), prophylactic mesh reinforcement after open repair has not yet been recommended in official guidelines, because of relatively small sample sizes in individual trials. Furthermore, the identification of subgroups that benefit most from prophylactic mesh placement requires larger patient numbers. Our primary aim is to evaluate the efficacy and effectiveness of the use of a prophylactic mesh after open AAA surgery to prevent IH by performing an individual patient data meta-analysis (IPDMA). Secondary aims include the evaluation of postoperative complications, pain and quality of life, and the identification of potential subgroups that benefit most from prophylactic mesh reinforcement. METHODS AND ANALYSIS: We will conduct a systematic review to identify RCTs that study prophylactic mesh placement after open AAA surgery. Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase, Web of Science Core Collection and Google Scholar will be searched from the date of inception onwards. RCTs must directly compare primary sutured closure with mesh closure in adult patients who undergo open AAA surgery. Lead authors of eligible studies will be asked to share individual participant data (IPD). The risk of bias (ROB) for each included study will be assessed using the Cochrane ROB tool. An IPDMA will be performed to evaluate the efficacy, with the IH rate as the primary outcome. Any signs of heterogeneity will be evaluated by Forest plots. Time-to-event analyses are performed using Cox regression analysis to evaluate risk factors. ETHICS AND DISSEMINATION: No new data will be collected in this study. We will adhere to institutional, national and international regulations regarding the secure and confidential sharing of IPD, addressing ethics as indicated. We will disseminate findings via international conferences, open-source publications in peer-reviewed journals and summaries posted online. PROSPERO REGISTRATION NUMBER: CRD42022347881.

Characterisation of digital therapeutic clinical trials: a systematic review with natural language processing.

Digital therapeutics (DTx) are a somewhat novel class of US Food and Drug Administration-regulated software that help patients prevent, manage, or treat disease. Here, we use natural language processing to characterise registered DTx clinical trials and provide insights into the clinical development landscape for these novel therapeutics. We identified 449 DTx clinical trials, initiated or expected to be initiated between 2010 and 2030, from ClinicalTrials.gov using 27 search terms, and available data were analysed, including trial durations, locations, MeSH categories, enrolment, and sponsor types. Topic modelling of eligibility criteria, done with BERTopic, showed that DTx trials frequently exclude patients on the basis of age, comorbidities, pregnancy, language barriers, and digital determinants of health, including smartphone or data plan access. Our comprehensive overview of the DTx development landscape highlights challenges in designing inclusive DTx clinical trials and presents opportunities for clinicians and researchers to address these challenges. Finally, we provide an interactive dashboard for readers to conduct their own analyses.