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Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis.

INTRODUCTION: The purpose of this study was to perform a systematic review and meta-analysis of exogenous surfactant administration to assess whether this therapy may be useful in adult patients with acute respiratory distress syndrome. METHODS: We performed a computerized literature search from 1966 to December 2005 to identify randomized clinical trials. The primary outcome measure was mortality 28-30 days after randomization. Secondary outcome measures included a change in oxygenation (PaO2:FiO2 ratio), the number of ventilation-free days, and the mean duration of ventilation. Meta-analysis was performed using the inverse variance method. RESULTS: Two hundred and fifty-one articles were identified. Five studies met our inclusion criteria. Treatment with pulmonary surfactant was not associated with reduced mortality compared with the control group (odds ratio 0.97; 95% confidence interval (CI) 0.73, 1.30). Subgroup analysis revealed no difference between surfactant containing surface protein or not - the pooled odds ratio for mortality was 0.87 (95% CI 0.48, 1.58) for trials using surface protein and the odds ratio was 1.08 (95% CI 0.72, 1.64) for trials without surface protein. The mean difference in change in the PaO2:FiO2 ratio was not significant (P = 0.11). There was a trend for improved oxygenation in the surfactant group (pooled mean change 13.18 mmHg, standard error 8.23 mmHg; 95% CI -2.95, 29.32). The number of ventilation-free days and the mean duration of ventilation could not undergo pooled analysis due to a lack of sufficient data. CONCLUSION: Exogenous surfactant may improve oxygenation but has not been shown to improve mortality. Currently, exogenous surfactant cannot be considered an effective adjunctive therapy in acute respiratory distress syndrome.

Adult↗

Is there a delay in the antidepressant effect? A meta-analysis.

OBJECTIVES: It has long been thought that there is a delay of several weeks before a true antidepressant effect occurs, although this theory has increasingly come into question. The goals of this meta-analysis were to determine whether significant drug-placebo separation occurs during the first 2 weeks of treatment and to ascertain whether the timing of response to antidepressant medication and placebo is distinct. DATA SOURCES: Seventy-six double-blind, placebo-controlled trials conducted between 1981 and 2000, included in a recently published meta-analysis that evaluated placebo response rates in depressed outpatients, were reviewed. In addition, each issue of 6 psychiatric journals from January 1992 through December 2001 was reviewed. STUDY SELECTION: Forty-seven studies that evaluated antidepressant medications with established efficacy, performed weekly or biweekly (every other week) evaluations, and presented the time course of improvement as measured by the Hamilton Rating Scale for Depression were included in our meta-analysis. DATA SYNTHESIS: The time course of improvement on active medication and placebo was nearly identical, as 60.2% and 61.6% of the improvement that occurred on active medication and placebo, respectively, took place during the first 2 weeks of treatment. Drug-placebo differences were not only present but were most pronounced during the first 2 weeks of treatment and diminished in a stepwise fashion thereafter. A series of subanalyses confirmed that this early drug-placebo separation was clinically observable and represented a true drug effect. CONCLUSION: These results challenge the notion that a delay exists before a true antidepressant effect occurs.

Antidepressive Agents↗

A systematic review and meta-analysis comparing outcome of severely injured patients treated in trauma centers following the establishment of trauma systems.

BACKGROUND: The establishment of trauma systems was anticipated to improve overall survival for the severely injured patient. We systematically reviewed the published literature to assess if outcome from severe traumatic injury is improved for patients following the establishment of a trauma system. METHODS: A systematic literature review of all population-based studies that evaluated trauma system performance was conducted. A qualitative analysis of each study's design and methodology and a meta-analysis was performed to evaluate the evidence to date of trauma system effectiveness. RESULTS: A search of the literature yielded 14 published articles. Trauma systems demonstrated improved odds of survival in 8 of the 14 reports. The overall quality-weighted odds ratio was 0.85 lower mortality following trauma system implementation. CONCLUSIONS: The results of the meta-analysis showed a 15% reduction in mortality in favor of the presence of a trauma system. Evaluation of trauma system effectiveness must remain an uncompromising commitment to optimal outcome for the injured patient.

Benchmarking↗

Estrogen therapy in the management of urinary incontinence in postmenopausal women: a meta-analysis. First report of the Hormones and Urogenital Therapy Committee.

OBJECTIVE: To apply a meta-analysis to available data to evaluate the efficacy of estrogen therapy in the management of postmenopausal women with urinary incontinence. METHODS: The literature review incorporated English language articles based on a search of EXCERPTA MEDICA, BIOSIS, and MEDLINE from January 1969 to June 1992. Criteria included: peer-reviewed original article, confirmed diagnosis of urinary incontinence, an estrogen-treated group, and outcome data on subjective improvement, quantitation of fluid loss, or maximum urethral closure pressure. In addition, the data had to allow comparison between treated and control groups in controlled trials or an estimated change in uncontrolled series. meta-analytic methods were applied only to studies considered to be controlled clinical trials. RESULTS: Of 166 articles reviewed, 143 did not meet the entry criteria; six were considered controlled clinical trials and 17 were uncontrolled series. Meta-analysis found an overall significant effect of estrogen therapy on subjective improvement for all subjects (P < .01) and for subjects with genuine stress incontinence alone (P < .05). The results showed no significant effect on quantity of fluid loss but a significant effect (P < .05) on maximum urethral closure pressure. However, the latter result was influenced by only one study showing a large effect. CONCLUSION: It appears from this analysis that estrogen subjectively improves urinary incontinence in postmenopausal women. However, the studies included nonhomogeneous groups, and the diagnostic criteria, therapeutic interventions, and outcome assessments varied considerably.

Aged↗

Association between youth athletes' sports specialization and injuries: a systematic review and meta-analysis.

INTRODUCTION: The purpose of this study was to conduct a systematic review and meta-analysis to examine the specialization-injury relationship, and explore whether the specialization-injury relationship is moderated by study design, sport type, age, sex, and injury measurement type, injury mechanism, and anatomical location. METHODS: We searched eight databases by related keywords and assessed the quality of the included studies using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies and the Newcastle-Ottawa Scale. The Comprehensive Meta-Analysis (CMA) statistical software 3.7 examined heterogeneity, sensitivity, publication bias, overall effect size of specialization-injury relationship, and moderation effects. This review was prospectively registered in PROSPERO (CRD420251233318). Searches were conducted in eight electronic databases from inception to March, 2026. RESULTS: The 15 included studies showed moderate heterogeneity, stable sensitivity analyses, and no publication bias. The overall odds ratio of the sports specialization-injury relationship was 2.00 (95% confidence interval [1.58-2.55], p&#xa0;<&#xa0;.001). Moderation analyses indicated that sport type significantly influenced the specialization-injury relationship, whereas no significant moderation effects were observed for study design, sex, age, injury measurement type, injury mechanism, and injury anatomical location. CONCLUSIONS: The findings indicate a positive association between sport specialization and injury risk among youth athletes, with variation across sport participation contexts. Specifically, athletes in both contact and non-contact sports demonstrated higher pooled odds of injury than those involved in multiple sports. Although the evidence is heterogeneous and should be interpreted with caution, these findings highlight the potential role of diversified sport participation in relation to injury.

Humans↗

The risk of lymphoma development in autoimmune diseases: a meta-analysis.

BACKGROUND: The risk of development of non-Hodgkin lymphoma (NHL) in autoimmune patients has been investigated in several cohort studies. These studies revealed inconclusive results. To shed some light on this controversy, we conducted a meta-analysis of all available cohort studies linking systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren syndrome (pSS) to the risk of NHL development. METHODS: We searched the PubMed database (1974 to April 2005) for English-language cohort studies using the key words systemic lupus erythematosus, SLE, rheumatoid arthritis, RA, Sjögren syndrome, or SS; non-Hodgkin lymphoma; and relative risk, RR, standardized incidence rate, or SIR. All cohort studies that used established diagnostic criteria for SLE, RA, and pSS; had histologic confirmation of NHL; and provided standardized incidence rates (SIRs) were included in the meta-analysis. RESULTS: The 20 studies chosen for the analysis included 6 for SLE, 9 for RA, and 5 for pSS. Overall, the meta-analysis suggested extreme heterogeneity among the studies (P < .01; I2 > 70%), high risk of NHL development for pSS (random effects SIR, 18.8; 95% confidence interval [CI], 9.5-37.3); moderate risk for SLE (random effects SIR, 7.4; 95% CI, 3.3-17.0); and lower risk for RA (random effects SIR, 3.9; 95% CI, 2.5-5.9). In RA, the random effects SIRs of NHL with conventional antirheumatic treatment, cytotoxic treatment, and treatment with a biological agent were 2.5 (95% CI, 0.7-9.0), 5.1 (95% CI, 0.9-28.6), and 11.5 (95% CI, 3.7-26.9), respectively. CONCLUSIONS: Rheumatic disease may present a potential risk factor for development of NHL. In this regard, we focused on the underlying pathophysiologic mechanisms related to lymphomagenesis in pSS, SLE, and RA, to justify the varying potential for and background of NHL development.

Antirheumatic Agents↗

Bayesian approaches to random-effects meta-analysis: a comparative study.

Current methods for meta-analysis still leave a number of unresolved issues, such as the choice between fixed- and random-effects models, the choice of population distribution in a random-effects analysis, the treatment of small studies and extreme results, and incorporation of study-specific covariates. We describe how a full Bayesian analysis can deal with these and other issues in a natural way, illustrated by a recent published example that displays a number of problems. Such analyses are now generally available using the BUGS implementation of Markov chain Monte Carlo numerical integration techniques. Appropriate proper prior distributions are derived, and sensitivity analysis to a variety of prior assumptions carried out. Current methods are briefly summarized and compared to the full Bayes analysis.

Bayes Theorem↗

Impact of long-term inhaled corticosteroid therapy on bone mineral density: results of a meta-analysis.

BACKGROUND: The impact of long-term inhaled corticosteroid (ICS) therapy on bone mineral density (BMD) is poorly understood. OBJECTIVE: To evaluate the impact of long-term ICS use on BMD. METHODS: Random-effects meta-analysis. Published and unpublished literature were identified by searches of MEDLINE and EMBASE databases and consultation with experts. Studies reporting BMD among adult asthma and chronic obstructive pulmonary disease (COPD) patients using ICS and non-ICS controls were identified. Studies selected for review included at least 1 year of follow-up. Two independent reviewers evaluated studies; data from those meeting specified inclusion criteria were abstracted for inclusion in the meta-analysis. RESULTS: Fourteen (5.3%) of 266 reviewed studies met specified inclusion criteria. Sufficient data were available to perform meta-analysis on 3 measures for ICS-using patients (lumbar, femoral neck, and major trochanter BMD) and 1 measure (lumbar BMD) for non-ICS-using controls. Using current National Asthma Education and Prevention Program definitions, the majority of studies (12 of 14) included patients receiving moderate to high doses of ICSs. Among ICS users, annual changes from baseline in lumbar, femoral neck, and major trochanter BMD (-0.23%, -0.17%, and +1.46%, respectively) were not statistically significant. Mean changes in lumbar BMD were also not significantly different from controls (-0.02%). Further, annual changes in lumbar BMD were not statistically significant for subgroups of patients with asthma or COPD. CONCLUSIONS: Long-term use of ICSs in patients with asthma or COPD was not associated with significant changes in BMD.

Administration, Inhalation↗

Meta-analysis of cancer trials: a new approach to the assessment of treatment.

Meta-analysis of clinical trials offers the opportunity to pool results from a number of randomised studies so increasing the statistical ability to detect the value of treatment. More accurate estimates of the likely size of such effects can also be obtained. Subset analysis, which is seldom reliable in individual clinical trials, can be made more trustworthy. Meta-analysis of randomised trials of adjuvant therapy in early breast cancer illustrates the value of such analyses. These have helped not only routine clinical practice but also thrown light upon biological mechanisms and directed future research. Meta-analyses or overviews are playing an increasingly prominent role in cancer research. They offer the opportunity to maximise the use of information about a given treatment by combining the results from multiple randomised trials in a meaningful way. Whilst data from studies examining the same issue cannot simply be combined (due to trial heterogeneity), summation of the treatment effect across trials can be performed. It is reasonably assumed that differences between studies are differences in magnitude rather than differences in direction. The net result of such a process is to produce a result which is more accurate in its estimate of treatment benefit than its component parts.

Breast Neoplasms↗

The nocturnal jejunal migrating motor complex: defining normal ranges by study of 51 healthy adult volunteers and meta-analysis.

Interdigestive human small bowel motility is characterized by the migrating motor complex (MMC). The aims of this study were to: (i) establish the normal range of variables of the nocturnal jejunal MMC and (ii) incorporate these data in a subsequent meta-analysis. Eighty-one recordings were performed by prolonged (24 h) ambulatory manometry in 51 subjects in two centres. Quantitative analysis was undertaken of 419 Phase III and 332 Phase II episodes. Adjusted mean values of seven variables were calculated using a mixed-effects model. Meta-analysis of pooled published data to generate a reliable 95% reference range was also performed. Adjusted mean values and confidence intervals are presented for all seven variables. Intrasubject variances were large in comparison with intersubject. Meta-analysis of 19 studies (356 pooled patients) meeting inclusion criteria produced wide reference ranges. At least five such ranges are useful for the detection of abnormality in the individual. This is the largest study of normal volunteers presented to date, with ranges for many variables produced using appropriate statistical methodology. A model for definition of abnormality has been proposed. We recommend that these data may be used by investigators in this field as a complement to other existing indicators of small bowel dysmotility.

Adolescent↗

A practical guide to meta-analysis.

The wealth of medical research published on a yearly basis demands methods to summarize the literature. Narrative or expert reviews were the traditional method to provide this summary; however, biases associated with narrative reviews raise questions regarding whether this process provides sufficient evidence to guide practice. Meta-analysis is becoming increasingly popular because it can combine results from similar studies to calculate an overall estimate of a treatment effect. Although meta-analysis has its limitations, a thoughtful and well-planned analysis is a valuable tool in providing a high level of evidence. We discuss the steps needed to perform a meta-analysis as a guideline for those interested in pursuing this type of research.

Clinical Trials as Topic↗

Endoscopically directed middle meatal cultures versus maxillary sinus taps in acute bacterial maxillary rhinosinusitis: a meta-analysis.

OBJECTIVE: The aim of this study was to verify the correlation of endoscopically directed middle meatal (EDMM) cultures with maxillary sinus tap and culture (MST) in acute bacterial rhinosinusitis (ABRS). STUDY DESIGN AND METHODS: Meta-analysis of the previous literature, unpublished data, and a prospective trial supported by the Sinus & Allergy Health Partnership. EDMM and MST cultures were obtained and their results compared. Inclusion for both the unpublished and prospective trial as well as prior published literature in the meta-analysis required the studies to compare EDMM versus MST in the acute setting of bacterial rhinosinusitis with both symptomatic and radiologic evidence of ABRS. RESULTS: Three articles and 1 national presentation were identified for inclusion. Additional data from unpublished studies and the prospective trial were combined. The pooled data consisted of 126 patients with 131 culture pairs. For known pathogenic bacteria for ABRS and in comparison to MST, EDMM had a sensitivity of 80.9%, a specificity of 90.5%, a positive predictive value of 82.6%, a negative predictive value of 89.4%, and an overall accuracy of 87.0% (95% confidence interval, 81.3%-92.8%); 70.5% (12/17) of false positive culture pairs were of known pathogens for ABRS that would not be expected to be contaminants. CONCLUSIONS AND SIGNIFICANCE: This meta-analysis shows that EDMM is a highly sensitive and accurate culture method for acute ABRS and may be more sensitive than MST given the presence of pathogenic bacteria not found on antral lavage. EDMM is a viable, and possibly preferred, culture method for determining antimicrobial efficacy and bacterial resistance patterns. EBM RATING: A-1a.

Endoscopy↗

Osteopathic manipulative treatment for low back pain: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Osteopathic manipulative treatment (OMT) is a distinctive modality commonly used by osteopathic physicians to complement their conventional treatment of musculoskeletal disorders. Previous reviews and meta-analyses of spinal manipulation for low back pain have not specifically addressed OMT and generally have focused on spinal manipulation as an alternative to conventional treatment. The purpose of this study was to assess the efficacy of OMT as a complementary treatment for low back pain. METHODS: Computerized bibliographic searches of MEDLINE, EMBASE, MANTIS, OSTMED, and the Cochrane Central Register of Controlled Trials were supplemented with additional database and manual searches of the literature. Six trials, involving eight OMT vs control treatment comparisons, were included because they were randomized controlled trials of OMT that involved blinded assessment of low back pain in ambulatory settings. Data on trial methodology, OMT and control treatments, and low back pain outcomes were abstracted by two independent reviewers. Effect sizes were computed using Cohen's d statistic and meta-analysis results were weighted by the inverse variance of individual comparisons. In addition to the overall meta-analysis, stratified meta-analyses were performed according to control treatment, country where the trial was conducted, and duration of follow-up. Sensitivity analyses were performed for both the overall and stratified meta-analyses. RESULTS: Overall, OMT significantly reduced low back pain (effect size, -0.30; 95% confidence interval, -0.47 - -0.13; P = .001). Stratified analyses demonstrated significant pain reductions in trials of OMT vs active treatment or placebo control and OMT vs no treatment control. There were significant pain reductions with OMT regardless of whether trials were performed in the United Kingdom or the United States. Significant pain reductions were also observed during short-, intermediate-, and long-term follow-up. CONCLUSION: OMT significantly reduces low back pain. The level of pain reduction is greater than expected from placebo effects alone and persists for at least three months. Additional research is warranted to elucidate mechanistically how OMT exerts its effects, to determine if OMT benefits are long lasting, and to assess the cost-effectiveness of OMT as a complementary treatment for low back pain.

Humans↗

Smoking and in vitro fertilization: a meta-analysis.

PURPOSE: Including our own data and seven relevant publications from the literature, this meta-analysis aimed to establish the influence of the status of female smokers on the clinical pregnancy rate after the first attempt at in vitro fertilization-embryo transfer (IVF-ET). METHODS: We started to collect information about our own patient's smoking habits in January 1996 to evaluate prospectively the influence on IVF success. Information regarding 799 patients (607 nonsmokers and 192 smokers) was obtained. Additionally we retrieved seven relevant publications from the unabridged MEDLINE 1982-1996. They were recalculated to first cycles, because from a biometrical point of view, only the results of the first IVF cycle are really well comparable, as the number of necessary IVF cycles always correlates with the number of pregnancies. These data were compared in the nonparametric sign test according to Dixon-Mood and calculated as relative success ratios, defined as the quotient of the probability of IVF-ET success of nonsmokers divided by that of smokers for each publication. RESULTS: This meta-analysis, based on a total of 2314 first IVF-ET treatments, showed that almost twice as many IVF-ET cycles were needed for smokers as for nonsmokers to become pregnant. For the success quotient, we obtained a ratio of 1.79, with an associated 95% confidence interval of from 1.24 to 2.59. The total analysis shows, with a P value of less than 0.01, significantly higher pregnancy rates (21%) in nonsmokers compared to smokers (14%). CONCLUSIONS: Based on the analyzed data there exists--from a statistical point of view--a significant negative effect on the chances of success for smokers to become pregnant compared to nonsmokers.

Embryo Transfer↗

A meta-analysis of the literature on distal radius fractures: review of 615 articles.

A structured meta-analysis of the available literature was performed to evaluate the outcome of the treatment of displaced intra-articular fractures of the distal radius. A comprehensive search of Medline using the key words "radius" and "fracture" revealed over 4,000 articles. After limiting the search to clinical trials in English and excluding pediatric and geriatric age groups as well as biomechanical and animal studies, 615 abstracts were identified in the period from 1976 to May 1998. Thirty-one articles met the inclusion and exclusion criteria. These included two prospective randomized comparative trials, two non-randomized comparative trials, one half prospective case series and half historical control, and 27 papers on case series. Four papers dealt with external fixation versus closed reduction and cast treatment and one paper looked at open reduction internal fixation with or without additional external fixation. There was insufficient data to perform a scientific meta-analysis because of the poor quality of the studies and lack of a uniform method of outcome assessment. However, the data from the comparative trials showed that external fixation was favored over closed reduction and casting. Additionally, comparing the results of the case series showed that external fixation was superior to internal fixation.

Casts, Surgical↗

Intravesical chemotherapy prophylaxis in primary superficial bladder cancer: a meta-analysis of 3703 patients from 11 randomized trials.

The impact of intravesical chemotherapy prophylaxis on recurrence of superficial transitional cell carcinoma of the bladder is poorly defined. The objective of this report is to present a meta-analysis of the available clinical trial data to quantify the effect of intravesical chemotherapy on tumor recurrence following complete transurethral resection (TURB) in patients with newly diagnosed superficial bladder cancer. A prospective protocol outlining the above meta-analysis was initially developed followed by a thorough search of the existing published literature using strict eligibility criteria. Eleven randomized trials were found that met protocol specifications. These studies contained data on 3703 patients that were statistically combined using a fixed effects model (Peto). The outcome of interest was the proportion of patients recurring at 1, 2, and 3 years post-TURB. Combining all 11 studies using 1-year recurrence as the outcome measure yielded a Peto odds ratio (ORp) of 0.56, demonstrating a 44% reduction in 1-year recurrence among patients treated with intravesical chemotherapy versus those treated with TURB alone. A statistical test for heterogeneity (Q) showed these data to be heterogenous (the studies are not measuring an effect of the same size). Sensitivity analyses were performed to determine sources of heterogeneity. These tests suggest that chemotherapy treatment schedule may account for the wide variation in tumor recurrence rates across studies. When the available clinical trial data were stratified by duration of treatment, the meta-analysis showed that intravesical chemotherapy decreased tumor recurrence from 30% to 80% depending on the outcome of interest (i.e., recurrence at 1, 2, or 3 years post-TURB). Intravesical chemotherapy appears to have a major impact on decreasing the chance of recurrence of superficial transitional cell carcinoma of the bladder. This is in contrast to prior analyses suggesting only modest efficacy in this clinical setting (i.e., on the order of a 14% reduction in recurrence).

Administration, Intravesical↗

The influence of growth hormone (GH) substitution on patient-reported outcomes and cognitive functions in GH-deficient patients: a meta-analysis.

OBJECTIVE: The influence of growth hormone (GH) replacement on patient-reported outcomes (i.e., quality of life, health status and well-being) and cognitive functioning in GH-deficient adults is controversial. DESIGN: We carried out a meta-analysis of clinical trials concerning the influence of GH substitution on patient-reported outcomes and cognitive functions (studies were selected from 1985 to 2004). The results of individual studies were combined in a series of meta-analyses using a random effects model. Effects of GH replacement in GH-deficient adults were compared to baseline and/or placebo. RESULTS: Fifteen studies on GH and patient-reported outcomes were included (830 patients, follow-up 3-50 months). Four of these studies also provided data on cognitive functions (85 patients, follow-up 6-12 months). Relative to baseline, GH treatment is found to have a large effect on patient-reported outcomes at 3 months, a medium effect at 6 months and a small effect at 12 months. With respect to the median treatment duration of 6 months placebo appears to be as effective as GH substitution. Cognitive functioning does not improve after 6 months of GH substitution, relative to baseline. CONCLUSION: This meta-analysis provides no evidence that GH improves patient-reported outcomes in GH-deficient patients. As the amount of cognitive data was too limited to allow for comparisons with placebo, from the present meta-analysis no conclusions can be drawn with respect to the impact of GH treatment on cognition.

Adolescent↗

Comparative Effectiveness of Exercise Interventions for Hamstring Injury Prevention in Football Players: A Systematic Review and Network Meta-analysis.

BACKGROUND: Hamstring strain injury is a leading time-loss injury in football, yet trials have evaluated diverse exercise-based prevention programs with limited direct head-to-head evidence. This systematic review and network meta-analysis aimed to compare the effectiveness of exercise-based interventions for preventing hamstring injuries in football players using exposure-adjusted incidence rate ratios. METHODS: We conducted a PRISMA-aligned systematic review and random-effects network meta-analysis of randomized controlled trials in football players comparing exercise-based interventions to prevent hamstring injuries. Searches covered PubMed, Cochrane Library, Embase and Web of Science from inception to January 5, 2026. Interventions were modeled as separate nodes (Nordic hamstring exercise [NHE], FIFA 11, FIFA 11&#x2009;+&#x2009;, FIFA 11&#x2009;+&#x2009;Kids, bounding exercise program [BEP], usual training). The primary effect measure was incidence rate ratio (IRR) versus usual training, with ranking by P-scores; exploratory subgroup analyses were conducted by sex-restricted male-only evidence and age group. RESULTS: Eleven randomized controlled trials involving 9,282 participants were included. The network was connected but largely star-shaped, with most evidence comparing active interventions against usual training and no direct active-active comparisons. FIFA 11&#x2009;+&#x2009;showed the most consistent exposure-adjusted association with reduced hamstring injury incidence versus usual training (IRR&#x2009;=&#x2009;0.55, 95% CI 0.31-0.98; P-score&#x2009;=&#x2009;0.84). FIFA 11&#x2009;+&#x2009;Kids showed a favorable but imprecise estimate, whereas NHE showed a modest non-significant reduction and FIFA 11 and BEP showed no clear benefit. Male-only findings were broadly consistent with the primary analysis. Age-stratified analyses suggested that the apparent hierarchy was not fully identical across age strata, but subgroup networks were sparse and exploratory. RoB 2 judged three studies as high risk and eight as having some concerns; no trial was judged as overall low risk. Between-study heterogeneity was substantial, and treatment rankings were, therefore, interpreted cautiously. CONCLUSIONS: In this IRR-based network meta-analysis, FIFA 11&#x2009;+&#x2009;showed the most consistent exposure-adjusted association with reduced hamstring injury incidence compared with usual training. However, certainty across the primary comparisons ranged from low to very low because of clinical and methodological heterogeneity, sparse direct evidence for several nodes, reliance on indirect active-active comparisons, substantial between-study heterogeneity, and moderate-to-high risk of bias across the included studies. The treatment hierarchy should, therefore, be interpreted as a low-to-very-low-certainty, population-level summary rather than as a basis for firm recommendations. Further well-reported, age- and population-specific head-to-head trials with consistent exposure, injury-definition, adherence, and intervention-dose reporting are needed. Registration Systematic review registration PROSPERO (CRD420251243576).

FIFA 11&#x2009;+&#x2009;↗