Antibiotic resistance is a global health crisis that requires urgent action to stop its spread. To counteract the spread of antibiotic resistance, we must improve our understanding of the origin and spread of resistant bacteria in both community and healthcare settings. Unfortunately, little attention is being given to contain the spread of antibiotic resistance in community settings (i.e., locations outside of a hospital inpatient, acute care setting, or a hospital clinic setting), despite some studies have consistently reported a high prevalence of antibiotic resistance in the community settings. This study aimed to investigate the prevalence of antibiotic resistance in commensal Escherichia coli isolates from healthy humans in community settings in LMICs. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we synthesized studies conducted from 1989 to May 2020. A total of 9363 articles were obtained from the search and prevalence data were extracted from 33 articles and pooled together. This gave a pooled prevalence of antibiotic resistance (top ten antibiotics commonly prescribed in LMICs) in commensal E. coli isolates from human sources in community settings in LMICs of: ampicillin (72% of 13,531 isolates, 95% CI: 65-79), cefotaxime (27% of 6700 isolates, 95% CI: 12-44), chloramphenicol (45% of 7012 isolates, 95% CI: 35-53), ciprofloxacin (17% of 10,618 isolates, 95% CI: 11-25), co-trimoxazole (63% of 10,561 isolates, 95% CI: 52-73), nalidixic acid (30% of 9819 isolates, 95% CI: 21-40), oxytetracycline (78% of 1451 isolates, 95% CI: 65-88), streptomycin (58% of 3831 isolates, 95% CI: 44-72), tetracycline (67% of 11,847 isolates, 95% CI: 59-74), and trimethoprim (67% of 3265 isolates, 95% CI: 59-75). Here, we provided an appraisal of the evidence of the high prevalence of antibiotic resistance by commensal E. coli in community settings in LMICs. Our findings will have important ramifications for public health policy design to contain the spread of antibiotic resistance in community settings. Indeed, commensal E. coli is the main reservoir for spreading antibiotic resistance to other pathogenic enteric bacteria via mobile genetic elements.

Host genetic factors have frequently been implicated in respiratory infectious diseases, often with inconsistent results in replication studies. We identified 386 studies from the total of 24,823 studies identified in a systematic search of four bibliographic databases. We performed meta-analyses of studies on tuberculosis, influenza, respiratory syncytial virus, SARS-Coronavirus and pneumonia. One single-nucleotide polymorphism from IL4 gene was significant for pooled respiratory infections (rs2070874; 1.66 [1.29-2.14]). We also detected an association of TLR2 gene with tuberculosis (rs5743708; 3.19 [2.03-5.02]). Subset analyses identified CCL2 as an additional risk factor for tuberculosis (rs1024611; OR = 0.79 [0.72-0.88]). The IL4-TLR2-CCL2 axis could be a highly interesting target for translation towards clinical use. However, this conclusion is based on low credibility of evidence - almost 95% of all identified studies had strong risk of bias or confounding. Future studies must build upon larger-scale collaborations, but also strictly adhere to the highest evidence-based principles in study design, in order to reduce research waste and provide clinically translatable evidence.

There is controversy whether IL-6 (receptor) antagonists are beneficial in treating COVID-19 patients. We therefore update our systematic review to answer the following research questions: (1) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have lower mortality compared to standard of care? (2) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have more side effects compared to standard of care? The following databases were search up to December 1st 2020: PubMed, PMC PubMed Central, MEDLINE, WHO COVID-19 Database, Embase, Web-of-Science, COCHRANE LIBRARY, Emcare and Academic Search Premier. In order to pool the risk ratio (RR) and risk difference of individual studies we used random effects meta-analysis. The search strategy retrieved 2975 unique titles of which 71 studies (9 RCTs and 62 observational) studies comprising 29,495 patients were included. Mortality (RR 0.75) and mechanical ventilation (RR 0.78) were lower and the risk of neutropenia (RR 7.3), impaired liver function (RR 1.67) and secondary infections (RR 1.26) were higher for patients treated with IL-6 (receptor) antagonists compared to patients not treated with treated with IL-6 (receptor) antagonists. Our results showed that IL-6 (receptor) antagonists are effective in reducing mortality in COVID-19 patients, while the risk of side effects was higher. The baseline risk of mortality was an important effect modifier: IL-6 (receptor) antagonists were effective when the baseline mortality risk was high (e.g. ICU setting), while they could be harmful when the baseline mortality risk was low.

In recent years, there has been a growing interest in understanding the relationship between sleep and suicide. Although sleep disturbances are commonly cited as critical risk factors for suicidal thoughts and behaviours, it is unclear to what degree sleep disturbances confer risk for suicide. The aim of this meta-analysis was to clarify the extent to which sleep disturbances serve as risk factors (i.e., longitudinal correlates) for suicidal thoughts and behaviours. Our analyses included 156 total effects drawn from 42 studies published between 1982 and 2019. We used a random effects model to analyse the overall effects of sleep disturbances on suicidal ideation, attempts, and death. We additionally explored potential moderators of these associations. Our results indicated that sleep disturbances are statistically significant, yet weak, risk factors for suicidal thoughts and behaviours. The strongest associations were found for insomnia, which significantly predicted suicide ideation (OR 2.10 [95% CI 1.83-2.41]), and nightmares, which significantly predicted suicide attempt (OR 1.81 [95% CI 1.12-2.92]). Given the low base rate of suicidal behaviours, our findings raise questions about the practicality of relying on sleep disturbances as warning signs for imminent suicide risk. Future research is necessary to uncover the causal mechanisms underlying the relationship between sleep disturbances and suicide.

Prematurity is the leading cause of perinatal mortality and the morbidity among children under the age of 5. The prevalence of preterm birth is between 5 and 18% worldwide. Approximately 30% of preterm deliveries occur as a consequence of fetal or maternal infections. Bacterial vaginosis can increase the risk of ascending infections. However, there is no recommendation or protocol for screening of abnormal vaginal flora. The aim of this systematic review was to investigate the effectiveness of routine screening of abnormal vaginal flora during pregnancy care. We conducted our systematic search in the following databases: MEDLINE via PubMed, Embase, and Cochrane Library. Studies reporting on pregnant women with no symptoms of bacterial vaginosis were included in our analysis if they provided data on the outcome of their pregnancy. The intervention group went through screening of abnormal vaginal flora in addition to routine pregnancy care. Odds ratio (OR) with 95% confidence intervals (CIs) was used as effect size measure. From each study the total number of patients and number of events was extracted in both the intervention and control arm to calculate OR. Altogether we included 13 trials with 143,534 patients. The screening methods were Gram stain, pH screening, pH self-screening and pH screening combined with Gram stain. Regular screening of vaginal flora compared to no screening significantly reduces the odds of preterm birth before 37 weeks (8.98% vs 9.42%; OR 0.71, CI 0.57-0.87), birthweight under 2500 g (6.53% vs 7.24%; OR 0.64, CI 0.50-0.81), preterm birth before 32 weeks (1.35% vs 2.03%; OR 0.51, CI 0.31-0.85) and birthweight under 1000 g (0.86% vs 2.2%; OR 0.33, CI 0.19-0.57). In conclusion, the routine screening of abnormal vaginal flora might prevent preterm birth, extreme preterm birth, low birthweight deliveries and very low birthweight deliveries. Further research is needed to assess the problem more accurately.

This meta-analysis aimed to investigate the protective effects of bovine colostrum against childhood infectious diarrhea. A systematic search was conducted using PubMed, Cochrane Library databases and clinicaltrial.gov. Among 166 research articles, only five RCTs were included into final analysis. Review manager (version 5.2) was used to pool the effect-size across studies. Sensitivity and risk of bias were estimated accordingly. Under a pooled analysis, bovine colostrum consumption correlated with a significant reduction in stool frequency of infectious diarrhea, by 1.42 times per day (95% CI: -2.70, -0.14). Bovine colostrum intervention also reduced occurrence of diarrhea by 71% (pooled OR = 0.29, 95%CI 0.16, 0.52). The OR of positive detection of pathogen in the stool was 0.29 (95%CI 0.08, 0.71) in bovine colostrum treated group, compared with placebo group. In the sensitivity analysis of studies with low risk of biases, bovine colostrum significantly reduced stool frequency, occurrence of diarrhea and pathogen detection. BC and related products have a significant benefit in reducing the frequency and relieving the symptoms of childhood infectious diarrhea.

The stethoscope is used as first line diagnostic tool in assessment of patients with pulmonary symptoms. However, there is much debate about the diagnostic accuracy of this instrument. This meta-analysis aims to evaluate the diagnostic accuracy of lung auscultation for the most common respiratory pathologies. Studies concerning adult patients with respiratory symptoms are included. Main outcomes are pooled estimates of sensitivity and specificity with 95% confidence intervals, likelihood ratios (LRs), area under the curve (AUC) of lung auscultation for different pulmonary pathologies and breath sounds. A meta-regression analysis is performed to reduce observed heterogeneity. For 34 studies the overall pooled sensitivity for lung auscultation is 37% and specificity 89%. LRs and AUC of auscultation for congestive heart failure, pneumonia and obstructive lung diseases are low, LR- and specificity are acceptable. Abnormal breath sounds are highly specific for (hemato)pneumothorax in patients with trauma. Results are limited by significant heterogeneity. Lung auscultation has a low sensitivity in different clinical settings and patient populations, thereby hampering its clinical utility. When better diagnostic modalities are available, they should replace lung auscultation. Only in resource limited settings, with a high prevalence of disease and in experienced hands, lung auscultation has still a role.

Posterior cruciate ligament (PCL) reconstruction can be performed using single bundle (SB) and double bundle (DB) techniques. The present study investigated whether DB PCL reconstruction is superior to SB reconstruction in terms of patient reported outcome measures (PROMs) and joint stability. In December 2021 Embase, Google Scholar, Pubmed, Scopus databases were accessed. All clinical trials comparing SB versus DB reconstruction to address PCL insufficiency in skeletally mature patients were considered. Data from 483 procedures were retrieved. The mean follow-up was 31.0 (28.0 to 107.6) months, and the mean timespan between injury and surgery was 11.3 (6 to 37) months. The mean age of the patients was 29.3 ± 3.8 years. 85 of 483 patients (18%) were women. At a mean of 31.0 months post reconstruction, ROM (P = 0.03) was slightly greater in the SB group, while the Tegner score (P = 0.03) and the Telos stress (P = 0.04) were more favorable in the DB cohort. Similarity was found in instrumental laxity (P = 0.4) and Lysholm score (P = 0.3). The current evidence does not support the use of DB techniques for PCL reconstruction. Both methods could restore knee stability and motion with satisfactory short term patient reported outcome measures. Further high quality clinical trials are required to validate these results on a larger scale.

Insight into the clinical potential of convalescent plasma in patients with coronavirus disease (COVID-19) is important given the severe clinical courses in unvaccinated and seronegative individuals. The aim of the study was to investigate whether there is a survival benefit of convalescent plasma therapy in COVID-19 patients. The authors independently assessed randomized controlled trials (RCTs) identified by the search strategy for inclusion, extracted data, and assessed risk of bias. The binary primary outcome was all-cause mortality. Risk ratio (RR) of the convalescent plasma treatment (vs. best standard care) and its associated standard error (effect size) were calculated. A random-effects model was employed to statistically pool the effect sizes of the selected studies. We included 19 RCTs with 17,021 patients. The random-effects model resulted in an estimated pooled RR of 0.94 (95% CI 0.81-1.08, p = 0.33), showing no statistical evidence of the benefit of convalescent plasma therapy on all-cause mortality. Convalescent plasma therapy was not found to be effective in reducing all-cause mortality in COVID-19 patients. Further studies are needed to determine in which patients convalescent plasma therapy may lead to a reduction in mortality.

Cardiac natriuretic peptides (NPs) play a fundamental role in maintaining cardiovascular (CV) and renal homeostasis. Moreover, they also affect glucose and lipid metabolism. We performed a systematic review and meta-analysis of studies investigating the association of NPs with serum lipid profile. A PubMed and Scopus search (2005-2018) revealed 48 studies reporting the association between NPs and components of lipid profile [total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and triglycerides (TG)]. Despite high inconsistency across studies, NPs levels were inversely associated with TC [k = 32; pooled r = -0.09; I2 = 90.26%], LDLc [k = 31; pooled r = -0.09; I2 = 82.38%] and TG [k = 46; pooled r = -0.11; I2 = 94.14%], while they were directly associated with HDLc [k = 41; pooled r = 0.06; I2 = 87.94%]. The relationship with LDLc, HDLc and TG lost significance if only studies on special populations (works including subjects with relevant acute or chronic conditions that could have significantly affected the circulating levels of NPs or lipid profile) or low-quality studies were taken into account. The present study highlights an association between higher NP levels and a favorable lipid profile. This confirms and extends our understanding of the metabolic properties of cardiac NPs and their potential in CV prevention.

In order to investigate the association between the iNOS gene polymorphisms and susceptibility to cancer, a search of English papers was done using Pubmed, the Cochrane Library, Embase, ISI Web of Science, Google (scholar) database, and all Chinese reports were conducted using CBMDisc, Chongqing VIP database, and CNKI database. A total of eight studies were included in this meta-analysis including 1,920 cases and 2,373 controls. The results indicated that the polymorphisms in iNOS gene (C150T(Ser(608) Leu) polymorphism and polymorphic (CCTTT)n repeats) had no association with cancer risk for all genetic models. This meta-analysis suggested that the polymorphisms in the iNOS gene were not associated with cancer risk.

We systematically reviewed observational and clinical trials (baseline) studies examining differences in gait parameters between Parkinson's disease (PD) in on-medication state and healthy control. Four electronic databases were searched (November-2018 and updated in October-2020). Independent researchers identified studies that evaluated gait parameters measured quantitatively during self-selected walking speed. Risk of bias was assessed using an instrument proposed by Downs and Black (1998). Pooled effects were reported as standardized mean differences and 95% confidence intervals using a random-effects model. A total of 72 studies involving 3027 participants (1510 with PD and 1517 health control) met the inclusion criteria. The self-selected walking speed, stride length, swing time and hip excursion were reduced in people with PD compared with healthy control. Additionally, PD subjects presented higher cadence and double support time. Although with a smaller difference for treadmill, walking speed is reduced both on treadmill (.13 m s-1) and on overground (.17 m s-1) in PD. The self-select walking speed, stride length, cadence, double support, swing time and sagittal hip angle were altered in people with PD compared with healthy control. The precise determination of these modifications will be beneficial in determining which intervention elements are most critical in bringing about positive, clinically meaningful changes in individuals with PD (PROSPERO protocol CRD42018113042).

This study compared weight and cardiometabolic changes after short-term treatment of olanzapine/samidorphan and olanzapine. Eligible criteria for an included trial were ≤ 24 weeks, randomized controlled trials (RCTs) that compared olanzapine/samidorphan and olanzapine treatments in patients/healthy volunteers and reported weight or cardiometabolic outcomes. Three databases were searched on October 31, 2020. Primary outcomes included weight changes and all-cause dropout rates. Standardized mean differences (SMDs) and risk ratios (RRs) were computed and pooled using a random-effect model. This meta-analysis included four RCTs (n = 1195). The heterogeneous data revealed that weight changes were not significantly different between olanzapine/samidorphan and olanzapine groups (4 RCTs, SDM = - 0.19, 95% CI - 0.45 to 0.07, I2 = 75%). The whole-sample, pooled RR of all-cause dropout rates (4 RCTs, RR = 1.02, 95% CI 0.84 to 1.23, I2 = 0%) was not significant different between olanzapine/samidorphan and olanzapine groups. A lower percentage of males and a lower initial body mass index were associated with the greater effect of samidorphan in preventing olanzapine-induced weight gain. Current evidence is insufficient to support the use of samidorphan to prevent olanzapine-induced weight gain and olanzapine-induced cardiometabolic abnormalities. Samidorphan is well accepted by olanzapine-treated patients.

Diabetes is a serious threat to global health and among the top 10 causes of death, with nearly half a billion people living with it worldwide. Treating patients with diabetes tend to become more challenging due to the progressive nature of the disease. The role and benefits of combination therapies for the management of type 2 diabetes are well-documented, while the comparative safety and efficacy among the different combination options have not been elucidated. We aimed to systematically synthesize the evidence on the comparative cardiovascular safety and efficacy of combination therapy with metformin-sodium-glucose cotransporter-2 inhibitors versus metformin-sulfonylureas in patients with type 2 diabetes. We searched MEDLINE-PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to 15 August 2019 without restriction in the year of publication. We included randomized controlled trials of patients with type 2 diabetes who were on metformin-sodium-glucose cotransporter-2 inhibitors or metformin-sulphonylureas combination therapy at least for a year. The primary endpoints were all-cause mortality and serious adverse events, and the secondary endpoints were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hypoglycemia, and changes in glycated hemoglobin A1c (HbA1c), body weight, fasting plasma glucose, blood pressure, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We used a random-effects meta-analysis model to estimate mean differences for continuous outcomes and risk ratio for dichotomous outcomes. We followed PICOS description model for defining eligibility and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for reporting results. Of 3,190 citations, we included nine trials involving 10,974 participants. The pooled analysis showed no significant difference in all-cause mortality (risk ration [RR] = 0.93, 95% CI [0.52, 1.67]), serious adverse events (RR = 0.96, 95% CI [0.79, 1.17]) and adverse events (RR = 1.00, 95% CI [0.99, 1.02]) between the two, but in hypoglycemia (RR = 0.13, 95% CI [0.10, 0.17], P < 0.001). Participants taking metformin-sodium glucose cotransporter-2 inhibitors showed a significantly greater reduction in HbA1c (mean difference [MD] = - 0.10%, 95% CI [- 0.17, - 0.03], body weight (MD = - 4.57 kg, 95% CI [- 4.74, - 4.39], systolic blood pressure (MD = - 4.77 mmHg, 95% CI [- 5.39, - 4.16]), diastolic blood pressure (MD = - 2.07 mmHg, 95% CI [- 2.74, - 1.40], and fasting plasma glucose (MD = - 0.55 mmol/L, 95% CI [- 0.69, - 0.41]), p < 0.001. Combination therapy of metformin and sodium-glucose cotransporter-2 inhibitors is a safe and efficacious alternative to combination therapy of metformin and sulphonylureas for patients with type 2 diabetes who are at risk of cardiovascular comorbidity. However, there remains a need for additional long-term randomized controlled trials as available studies are very limited and heterogeneous.

Time-of-day dependent fluctuations in exercise performance have been documented across different sports and seem to affect both endurance and resistance modes of exercise. Most of the studies published to date have shown that the performance in short-duration maximal exercises (i.e. less than 1 min - e.g. sprints, jumps, isometric contractions) exhibits diurnal fluctuations, peaking between 16:00 and 20:00 h. However, the time-of-day effects on short duration exercise performance may be minimized by the following factors: (1) short exposures to moderately warm and humid environments; (2) active warm-up protocols; (3) intermittent fasting conditions; (4) warming-up while listening to music; or (5) prolonged periods of training at a specific time of day. This suggests that short-duration maximal exercise performance throughout the day is controlled not only by body temperature, hormone levels, motivation and mood state but also by a versatile circadian system within skeletal muscle. The time of day at which short-duration maximal exercise is conducted represents an important variable for training prescription. However, the literature available to date lacks a specific review on this subject. Therefore, the present review aims to (1) elucidate time-of-day specific effects on short-duration maximal exercise performance and (2) discuss strategies to promote better performance in short-duration maximal exercises at different times of the day.

Total hip arthroplasty (THA) is a common procedure for patients suffering from hip pain e.g. from osteoarthritis, osteonecrosis, or hip fractures. The satisfaction of patients undergoing THA is influenced by the choice of implant type and material, with one key factor being the selection of the appropriate material combination for the bearing surface. In this Bayesian network meta-analysis, we investigated the impact of material combinations for the bearing surface on the longevity of hip implants. The wear penetration rate per year and the total wear penetration in the liner resulting from different material combinations, as well as the survival rate at last follow-up, were examined. We analyzed a total of 663,038 THAs, with 55% of patients being women. Mean patient age was 59.0 ± 8.1 years and mean BMI 27.6 ± 2.6 kg/m2. The combination of an aluminium oxide (Al2O3) head and an Al2O3 liner demonstrated the lowest wear penetration at last follow-up and the lowest rate of wear penetration per year. Additionally, the combination of a crosslinked polyethylene (XLPE) liner and a zircon oxide (ZrO2) head demonstrated the lowest rate of revision at last follow-up. These findings underscore the importance of careful material selection for hip implant bearing surfaces to optimize their longevity and patient satisfaction after THA.

Bone-patellar tendon-bone (BPTB), two- and four-strand hamstring tendon (4SHT and 2SHT, respectively) are the most common autografts used for anterior cruciate ligament (ACL) reconstruction. The present study compared BPTB, 2SHT, and 4SHT for ACL reconstruction in terms of joint laxity, patient reported outcome measures (PROMs), rate of failure and anterior knee pain (AKP). The time to return to sport and the peak torque between the autografts were also compared. Finally, prognostic factors leading to worse outcomes were also investigated. It was hypothesized that all grafts yield similar proprieties in terms of joint laxity, patient reported outcome measures (PROMs) and rate of failure, but that the BPTB autograft causes a greater rate of anterior knee pain (AKP). The literature search was conducted. All clinical trials comparing BTPB and/or 2SHT, and/or 4SHT were accessed. Grafts other than BTPB and/or 4SHT and/or 2SHT were not considered. Articles reporting outcomes of allografts or synthetic grafts were not eligible, nor were those concerning revision settings. Articles reporting ACL reconstruction in patients with multi-ligament damage were also not eligible. Data from 95,575 procedures were retrieved. The median length of follow-up was 36 months. The median age of the patients was 27.5 years. With regard to joint laxity, similarity was found in terms of Lachman and Pivot shift tests between all three autografts. The BPTB demonstrated the greatest stability in terms of instrumental laxity. BPTB demonstrated the greatest PROMs. BPTB demonstrated the greatest rate of AKP, while AKP in 2SHT and 4SHT was similar. Concerning failure, statistically significant inconsistency was found (P = 0.008). The 4SHT demonstrated the quickest return to sport, followed by BPTB, and 2SHT. There was evidence of a negative association between the time span between injury to surgery, Lysholm score (P = 0.04), and Tegner scale (P = 0.04). Furthermore, there was evidence of a weak positive association between the time span between injury to surgery and return to sport (P = 0.01). BPTB may result in lower joint laxity, greater PROMs, and greater peak flexion torque compared to 2SHT and 4SHT autografts. On the other hand, BPTB reported the lowest peak extension torque and the greatest rate of AKP. Finally, a longer time span between injury and surgery negatively influences outcome.

The combination of mirror therapy (MT) and neuromuscular electrical stimulation (NMES) has been devised as an intervention method in stroke rehabilitation; however, few studies have investigated its efficacy in lower extremity motor function recovery. In this systematic review and meta-analysis, we examined the effectiveness of combined MT and NMES therapy in improving poststroke walking speed, spasticity, balance and other gait parameters. Randomized controlled trials (RCTs) were selected from PubMed, Cochrane Library, EMBASE, and Scopus databases. In total, six RCTs which involving 181 participants were included. Our findings indicate that MT combined with NMES elicits greater improvement relative to control group in walking speed (SMD = 0.67, 95% confidence interval [CI] 0.26-1.07, P = 0.001), Berg Balance Scale (SMD = 0.72; 95% CI 0.31-1.13; P = 0.0007), cadence (SMD = 0.59, 95% CI 0.02-1.16, P = 0.04), step length (SMD = 0.94, 95% CI 0.35-1.53, P = 0.002), and stride length (SMD = 0.95, 95% CI 0.36-1.54, P = 0.002) but not in modified Ashworth scale (SMD =  - 0.40, 95% CI - 1.05 to 0.26, P = 0.23). Our findings suggest that MT combined with NMES may be a suitable supplemental intervention to conventional therapy in stroke survivors.

Inconsistent reporting of clinical trials is well-known in the literature. Despite this, factors associated with poor practice such as outcome switching in clinical trials are poorly understood. We performed a cross-sectional analysis to evaluate the prevalence of, and the factors associated with outcome switching. PubMed and Embase were searched for pharmaceutical randomized controlled trials (RCTs) in oncology reporting on a surrogate primary outcome published in 2015. Outcome switching was present in 18% (39/216). First-author male sex was significantly more likely associated with outcome switching compared to female sex with an OR of 3.05 (95% CI 1.07-8.64, p = 0.04) after multivariable adjustment. For-profit funded RCTs were less likely associated with outcome switching compared to non-profit funded research with an OR of 0.22 (95% CI 0.07-0.74, p = 0.01). First author male sex was more likely associated with outcome switching compared to female sex in drug oncology RCTs reporting on a primary surrogate endpoint. For-profit funded research was less likely associated with outcome switching compared to research funded by non-profit organizations. Furthermore, 18 percent of drug oncology trials reporting on a surrogate endpoint could have a higher risk of false positive results due to primary outcome switching.

Pilonidal sinus disease (PSD) is increasing globally. A recent meta-analysis and merged-data analysis showed that recurrence rates in PSD depend essentially on follow-up time and specific surgical procedures. However, the global distribution of surgical approaches and respective recurrence rates have never been studied in PSD. We aimed at studying the impact of geographic distribution of surgical approaches to treat PSD and subsequent geography-specific recurrence rates. We searched relevant databases as described previously. Recurrence rates were then associated with reported follow-up times and geographic origin. We simulated individual patients to enable analogy across data. Globally, recurrence rates range from 0.3% for Limberg/Dufourmentel approaches (95% CI 0.2-0.4) and flaps (95% CI 0.1-0.5) and up to 6.3% for incision (95% CI 3.2-9.3) at 12 months. Recurrence rates range from 0.3% for Karydakis/Bascom approaches (95% CI 0.0-0.8) up to 67.2% for incision (95% CI 7.5-100) in the USA, and 0.0% for primary asymmetric closure in Germany (95% CI 0.0-0.0). Our analysis shows that recurrence rates in PSD not only depend on therapeutic approaches and follow-up time but also on geography. Primary asymmetric closure and various flap techniques remain superior regardless of the geographical region. Some approaches have extraordinarily good outcomes in specific countries.