Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 11 appraisals
Journal of global health
Plasma proteomic signatures predict incident benign prostatic hyperplasia: a prospective cohort study of 20 996 men
BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent disease in elderly men. However, the plasma proteomic signatures for incident BPH are absent, hindering early prediction and risk stratification. We aimed to identify plasma proteins associated with incident BPH and the implicated biological pathways. METHODS: This prospective cohort was constructed based on the UK Biobank, enrolling 20 996 BPH-free males at baseline. We used the Olink Explore platform to determine the abundances of 2920 plasma proteins. We used Cox regression models to evaluate associations and the Extreme Gradient Boosting model to perform feature selection and predictive modelling. We performed pathway enrichment and Mendelian randomisation analyses to elucidate the molecular pathways involved and assess causality. RESULTS: During the median follow-up period of 13.38 years, 2405 incident BPH cases were recorded. Cox regression identified 92 plasma proteins significantly associated with BPH risk (false discovery rate <0.05). Extreme Gradient Boosting model prioritised a three-protein signature: TSPAN1 (hazard ratio (HR) = 1.24) and KLK3 (HR = 1.34) as risk factors, and EDA2R (HR = 0.83) as a protective factor. This three-protein panel achieved an AUC of 0.71 (95% confidence interval = 0.69-0.73) for predicting BPH onset. Enrichment analysis revealed the associated proteins were mainly involved in immune-inflammatory pathways and stromal remodelling. As revealed by Mendelian randomisation, TSPAN1 and KLK3 were causally associated with incident BPH. CONCLUSIONS: We identified a three-protein panel (TSPAN1, KLK3, EDA2R) which can predict incident BPH. The findings highlight potential targets for non-invasive risk assessment and therapy.
15 June 2026
Read appraisal →World journal of urology
The urologic impact of long-term finasteride 1-mg use for androgenic alopecia: a matched-cohort database analysis
INTRODUCTION AND OBJECTIVES: Since its approval in 1997, finasteride-1 mg (F1) can be taken daily to treat androgenic alopecia (AA) by reducing serum dihydrotestosterone (DHT). When finasteride is prescribed at the 5 mg dosage, the DHT reduction is known to affect sexual function, reduce serum prostate-specific antigen (PSA) levels and treat benign prostatic hyperplasia (BPH). However, there is no literature on the urologic function of men using long-term F1. Thus, we aimed to address this knowledge gap by analyzing a database for the impact of F1 on urologic function. METHODS: Using the Truveta database, we identified men aged 18 + diagnosed with AA per International Classification of Diseases (ICD) coding, with at least 90 days of F1 use and ≥ 5 years of follow-up. Exclusions included patients with a history of anti-depressant usage, prior diagnosis (Dx) or treatment (Tx) of erectile dysfunction (ED), BPH, or prostate cancer (PC). A control cohort with AA but no F1 use was matched based on age, race, ethnicity, and marital status. We compared Dx rates, Tx rates, and time to Dx or Tx using Chi-square and Kruskal-Wallis Rank sum tests. Survival analysis was performed with restricted mean survival time. RESULTS: We identified 3470 patients with long-term F1 use and 3470 matched patients with AA but no F1 use. The average age for the F1 group was 40.59 and 39.75 for the control. Average F1 use duration was 2011.5 days. Median follow-up was 2554.7 days for the F1 group, and 3129.5 days for the control. The F1 group had higher phosphodiesterase type 5 inhibitor (PDE5i) prescription rate (13.6% vs. 10.5%, p < 0.001) and earlier prescription by 238.6 days (95% CI -304.3, -172.9, p < 0.0001). The control group had a higher -blocker prescription rate (4.4% vs. 2.9%, p = 0.001). There were no significant differences in ED diagnosis, BPH Dx rates or time-to BPH diagnosis or α-blocker prescription. The F1 group had lower elevated PSA Dx and PC Dx rates (2.9% vs. 4.4%, p < 0.001; 0.9% vs. 1.8%, p = 0.001). CONCLUSIONS: Though ED diagnosis did not differ significantly, patients on long-term F1 for AA were more likely to be prescribed PDE5i and sooner by approximately 230 days, compared to non-F1 users. F1 did not significantly affect BPH Dx or Tx rates. F1 use was associated with decreased PC and elevated PSA Dx rates. More research on urologic effects of chronic F1 use in AA patients is needed.
9 June 2026
Read appraisal →Chinese medical journal
Estimating minimal, moderate, and marked clinically important differences for patient reported outcome measure in randomised controlled trial
BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly used in clinical trials, yet thresholds that define clinically important difference (CID) within patients and treatment effects beyond placebo remain inconsistently reported, limiting its utility in clinical research and practice. Using chronic pelvic pain and its core PROM as a worked example, the study aims to present a structured framework for CID thresholds that separates within-group change from between-group difference in treatment effect, each further stratified as minimal, moderate, and marked. METHODS: We used data from a multicenter randomized controlled trial of acupuncture vs . sham acupuncture in 440 men with chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) conducted from October 2017 to April 2019. National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) served as the PROM and the Patient Global Impression of Change (PGI-C) as the anchor. CIDs were estimated using a linear mixed-effects model to assess changes in NIH-CPSI scores across PGI-C categories. RESULTS: At the end of treatment, 12.3% (51/414) participants reported no change, 34.1% (141/414) slight improvement, 32.1% (133/414) moderate improvement, and 19.6% (81/414) marked improvement; and 1.9% (8/414) reported worsening. The estimated Clinically important within-group difference (CIDs within-group ) in NIH-CPSI total score was 4.6 points for minimal, 6.0 points for moderate, and 7.3 points for marked improvement. The corresponding Clinically important between-group difference (CIDs between-group ) were 1.4, 2.7, and 4.1 points, respectively. CONCLUSIONS: In this methodological study, we proposed a pragmatic and scalable operational framework to derive thresholds for minimal, moderate, and marked CIDs. By explicitly distinguishing CIDs within-group and CIDs between-group , the approach clarifies two frequently conflated terms that serve distinct purposes in interpretation and decision-making. This framework offers benchmarks to strengthen inference on treatment response, trial design, and guideline decision thresholds.
21 May 2026
Read appraisal →Journal of robotic surgery
NeuroSAFE-guided robot-assisted radical prostatectomy versus standard RARP: systematic review and meta-analysis of comparative studies
Prostate cancer is the most common male malignancy, and although robotic-assisted radical prostatectomy (RARP) is widely used, urinary incontinence and erectile dysfunction remain significant issues. NeuroSAFE, an intraoperative frozen section technique aimed at optimizing nerve preservation without compromising cancer control, is increasingly used, but its overall impact on outcomes remains unclear.To systematically evaluate the effectiveness and safety of the NeuroSAFE technique during RARP, comparing functional recovery and oncologic outcomes with non-NeuroSAFE approaches.This systematic review and meta-analysis followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251032774). A comprehensive search of Embase, MEDLINE, and ClinicalTrials.gov (March, 2026) identified studies reporting oncologic and/or functional outcomes in men undergoing RARP with NeuroSAFE. Two reviewer teams independently conducted study selection, data extraction, and risk-of-bias assessment using ROBINS-I tool. Random-effects meta-analyses estimated pooled odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was quantified with the I2 statistic, and publication bias was evaluated using Egger's test.Thirteen studies (2 randomized controlled trials and 11 observational cohorts) comprising 22,183 patients met the inclusion criteria. NeuroSAFE was associated with significantly improved postoperative erectile function (OR 2.00; 95% CI 1.46-2.74) and urinary continence recovery (OR 1.36; 95% CI 1.05-1.76). Positive surgical margins were significantly reduced in the NeuroSAFE group (OR 0.73; 95% CI 0.59-0.89). No differences in biochemical recurrence were observed (OR 0.81; 95% CI 0.43-1.56). Heterogeneity was substantial for some outcomes, and most nonrandomized studies carried a serious risk of bias, which limits causal inference.This systematic review and meta-analysis, including randomized evidence, demonstrates that NeuroSAFE is a safe and effective intraoperative strategy that is associated with improved erectile function, enhanced continence recovery, and negative surgical margins without compromising oncologic outcomes. These findings support integrating NeuroSAFE into surgical decision-making for patients undergoing RARP, particularly when nerve preservation can be achieved without compromising oncologic outcomes.In this study, we compared a surgical approach that uses real-time analysis during prostate cancer surgery with the standard technique. This method helps surgeons decide how much tissue to preserve while the operation is still ongoing. We found that this approach is safe and may improve recovery of urinary continence and sexual function, while also reducing the risk of leaving cancer behind, without compromising cancer control.
14 May 2026
Read appraisal →World journal of urology
Thulium fiber laser versus Holmium laser enucleation of the prostate: 24-month outcomes from a prospective randomized non-inferiority trial
PURPOSE: To compare 24-month outcomes of Thulium fiber laser enucleation of the prostate (ThuFLEP) and Holmium laser enucleation of the prostate (HoLEP). METHODS: A 24-month follow-up analysis of a prospective randomized trial including 150 patients (ThuFLEP n = 74, HoLEP n = 76) was conducted. Primary outcome was non-inferior International Prostate Symptom Score (IPSS) and quality of life (QoL) reduction. Secondary outcomes included urinary continence, medication use reduction, erectile and ejaculatory function, and late adverse events. RESULTS: At 24 months, non-inferiority of ThuFLEP regarding IPSS and QoL was confirmed (p = 0.03). Median IPSS improved from 21 preoperatively to 3 after ThuFLEP and from 20 to 4 after HoLEP (p < 0.001), with no significant intergroup differences at any time point (all p > 0.1). Median QoL improved from 4 to 1 in both groups (p < 0.001), likewise without significant differences at any time point (all p > 0.3). Continence rates improved from 74.0% preoperatively to 90.0%, pad usage decreased from 89.8% to 25.4% and ICIQ-SF decreased from 5 to 3 points (all p < 0.001), without intergroup differences (all p > 0.1). Use of medication for lower urinary tract symptoms decreased from 89.4% to 7.7% (p < 0.001). Ejaculatory function declined, while ejaculation-related bother remained unchanged and erectile function improved modestly, all without intergroup differences (all p > 0.1). Three late adverse events occurred exclusively in the ThuFLEP group, without statistical significance (p > 0.1). CONCLUSION: ThuFLEP remains non-inferior to HoLEP for patient-reported functional outcomes at 24 months and demonstrates comparable safety, continence, medication use reduction, and sexual function results over time. Both techniques represent effective, durable and safe surgical options for treating benign prostatic obstruction. TRIAL REGISTRATION NUMBER: DRKS00032699 (18.09.2023, retrospectively registered).
3 May 2026
Read appraisal →The New England journal of medicine
Transdermal Estradiol Patches in Locally Advanced Prostate Cancer
BACKGROUND: Transdermal estradiol (tE2) is an alternative to luteinizing hormone-releasing hormone (LHRH) agonists as androgen-deprivation therapy in patients with prostate cancer. With tE2, testosterone is suppressed, and the side effects of estrogen depletion due to LHRH agonists and the thromboembolic side effects of oral estrogen are mitigated. METHODS: In this phase 3, noninferiority, randomized trial, we assigned men with locally advanced (M0 and N0 or N+) prostate cancer to receive tE2 patches (100 μg of estradiol every 24 hours) or LHRH agonists. The primary outcome was 3-year metastasis-free survival. The noninferiority margin was 4 percentage points; this corresponded to a target hazard ratio of 1.31, as derived from the observed 3-year metastasis-free survival in the LHRH agonist group. Secondary outcomes included castrate levels of testosterone (<1.7 nmol per liter), overall survival, and safety. RESULTS: Between 2007 and 2022, we recruited 1360 patients at 75 U.K. centers. The median age of the patients was 72 years (interquartile range, 68 to 77); 85% had a T3 tumor stage and 65% an N0 nodal stage. Observed 3-year metastasis-free survival was 87.1% with tE2 and 85.9% with LHRH agonists (hazard ratio for confirmed metastasis or death, 0.96; upper limit of the one-sided 95% confidence interval [CI], 1.11, which met the criterion for noninferiority). Among patients continuing the assigned treatment, castrate levels of testosterone were sustained during the first year after randomization in 85% in each group. Observed 5-year overall survival was 81.1% with tE2 and 79.2% with LHRH agonists (hazard ratio for death, 0.90; 95% CI, 0.75 to 1.07). During treatment, hot flashes occurred in 44% of the patients who received tE2 and 89% of those who received LHRH agonists (grade ≥2 events, 8% and 37%, respectively) and gynecomastia in 85% and 42% (grade ≥2 events, 37% and 9%). CONCLUSIONS: In patients with locally advanced prostate cancer, tE2 was noninferior to LHRH agonists for 3-year metastasis-free survival, with a lower incidence of hot flashes but a higher incidence of gynecomastia. (Funded by Cancer Research U.K. and the U.K. Research Institute Medical Research Council; PATCH ClinicalTrials.gov number, NCT00303784; STAMPEDE-1 ClinicalTrials.gov number, NCT00268476.).
24 Apr 2026
Read appraisal →The aging male : the official journal of the International Society for the Study of the Aging Male
The effect of dutasteride on storage symptoms in men with lower urinary tract symptoms: a REDUCE trial analysis
BACKGROUND: Dutasteride is used to treat voiding symptoms; its impact on storage symptoms is unclear. METHODS: We reviewed 8122 men in the placebo and dutasteride arms from the REDUCE trial. Lower urinary tract symptoms outcomes were measured with international prostate symptom score and subscores. RESULTS: At 2-year follow-up, dutasteride significantly reduced the total International Prostate Symptom Score and voiding subscore versus placebo (both p < 0.001), but not storage symptoms (p = 0.09) or nocturia (p = 0.2). By 4 years, improvements in the total score and voiding subscores remained, but now extended to storage symptoms (p < 0.001) and nocturia (p = 0.003), though the impact on storage symptoms was modest (0.62 points improvement). CONCLUSION: While dutasteride reduces storage symptoms, it takes several years, and the overall effect is modest and unlikely to be clinically meaningful. Timely, comprehensive lower urinary tract symptoms management may require additional therapy.
22 Apr 2026
Read appraisal →JMIR research protocols
Integrating Sperm Microscopy, Environmental Exposures, and Lifestyle Factors for Male Fertility Analysis: Protocol for the Nippon Semen and Environmental Exposure Database (N-SEED) Cross-Sectional Study
BACKGROUND: Conventional semen analysis does not fully capture male reproductive potential. The sperm DNA fragmentation index (DFI) may detect latent infertility, although the sperm chromatin structure assay (SCSA) is costly and technically demanding. Image-based analysis of semen microscopy, including artificial intelligence (AI), may enable lower-cost noninvasive assessment. However, progress is limited by a lack of standardized multimodal datasets linking sperm images with the DFI and relevant covariates. OBJECTIVE: This protocol describes the initial phase of the Nippon Semen and Environmental Exposure Database (N-SEED) initiative. The study aims to (1) establish standardized acquisition and quality control procedures for sperm microscopy/video and DFI measurement; (2) evaluate the feasibility and magnitude of associations between predefined image-/video-derived variables and the DFI; and (3) characterize clinical, environmental, physical, and lifestyle factors that may act as candidate correlates or confounders for subsequent image-based fertility research. METHODS: This multi-institutional cross-sectional study centralized clinical assessment and specimen collection at a single site in Japan. The prespecified group-specific enrollment targets were 25 for group 1 (a relatively homogeneous low-risk cohort for DFI quality control) and 100 for group 2 (apparently healthy community-based adult volunteers for exploratory association analyses). Microscopic sperm videos, automated semen parameters, and sperm oxidative stress data were obtained at collection. SCSA-based DFI assays are currently being performed sequentially. Group 2 participants additionally provided fasting blood and early-morning urine samples for endocrine, metabolic, environmental chemical, and elemental assays. They also underwent physical measurements and completed structured questionnaires/interviews on lifestyle, nutrition, sleep, psychological status, sexual function, and collection conditions. The primary outcome measure is the continuous DFI assessed with SCSA. Group 1 data will be used to evaluate intraday, interday, and interfacility variability and to fix flow cytometry gating settings. In groups 1 and 2, predefined image-/video-derived summary variables after standardized preprocessing will be analyzed against the continuous DFI using correlation analyses and simple linear regression to assess whether sperm microscopy data contain information relevant to sperm DNA integrity. Exploratory categorical DFI analyses will use simple logistic regression. Secondary exploratory analyses will examine candidate covariates and data completeness, including sensitivity analyses. RESULTS: The study was registered in the University Hospital Medical Information Network Clinical Trials Registry on January 18, 2026. Between January 18 and February 21, 2026, 124 unique participants were recruited (group 1: n=25; group 2: n=103; both groups: n=4). Sample and data collection were completed on February 21, 2026. Biospecimen assays and primary association analyses are expected to be completed by March 2028. CONCLUSIONS: This initial N-SEED phase will deliver a standardized, quality-controlled multimodal resource linking sperm microscopy/video data with the DFI and broader physiological and environmental measures. Its immediate contribution is not to provide an immediately deployable clinical AI tool but rather to support feasibility assessment, confounder identification, and planning for subsequent database expansion and external validation of image-based male fertility assessment methods. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000060395; https://tinyurl.com/mryfymw5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/93803.
19 Apr 2026
Read appraisal →Biology of reproduction
The relationship between seminal microbiome and male reproductive wellness: a systematic review
The seminal microbiome, which is composed of different types of bacteria in semen and seminal plasma, has a significant impact on male reproductive health by changing the quality of semen and fertility. Previously regarded as sterile, the male reproductive tract contains microbes originating from the gastrointestinal tract, reproductive organs, and external sources such as sexual partners. Dysbiosis alters sperm parameters, triggers inflammation and oxidative stress, and is associated with conditions such as infertility, HPV infection, prostatitis, prostate cancer, and azoospermia. This systematic review adhered to the PRISMA 2020 guidelines (with 2025 extensions for reproducibility) and examined studies from PubMed, Scopus, and Science Direct (2015-2025, with prior context), concentrating on human, in vitro, and rodent models. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes are among the most important phyla. Beneficial genera, such as Lactobacillus, improve sperm motility, concentration, and DNA integrity, whereas dysbiotic taxa, such as Prevotella, Pseudomonas, and Ureaplasma, are associated with declines. Sexual activity facilitates bidirectional microbial transfer, modifying diversity and fostering the dysbiosis. Inflammatory cytokines, reactive oxygen species, and metabolic disruptions are all involved in this process. Changes that are specific to a disease, such as higher levels of Fusobacterium in HPV-positive samples, worsen the situation. This review highlights how the microbiome alters sperm function and causes infertility. Standardized methods and long-term studies are needed to prove causality. Probiotics and other therapeutic interventions show promise in restoring balance and boosting fertility.
16 Apr 2026
Read appraisal →Chinese medical journal
Efficacy and safety of topical finasteride spray solution in the treatment of Chinese men with androgenetic alopecia: A phase III, multicenter, randomized, double-blind, placebo-controlled study
BACKGROUND: Topical finasteride is a novel treatment for men with androgenetic alopecia (AGA). This study aimed to evaluate the efficacy and safety of topical finasteride spray solution in Chinese men with AGA. METHODS: This randomized, double-blind, placebo-controlled, phase III trial enrolled 270 individuals with AGA from 16 sites across China between December 2021 and March 2023. The participants were randomized at a ratio of 2:1 to receive either topical finasteride or placebo treatment once daily for 24 weeks. The primary endpoint was the change from baseline in target area (0.903 cm 2 area) hair count at week 24. The secondary endpoints were change from baseline in target area hair count at week 12, target area terminal hair count at weeks 12 and 24, target area terminal hair width at week 24, and target area hair width at week 24; an improvement of vertex hair growth assessed by the investigator at week 24; and the patient-assessed scores on the Male Hair Growth Questionnaire at week 24. RESULTS: A total of 270 individuals were enrolled and randomized, and 251 completed the study (165 in topical finasteride group, 86 in placebo group). Compared with the placebo group, in the topical finasteride group, the change from baseline in target area hair count was significantly higher at week 24 ( P <0.05), although it was only numerically higher at week 12 ( P = 0.0688). Significant differences favoring topical finasteride over placebo were observed for change from baseline in target area terminal hair count at weeks 12 ( P <0.05) and 24 ( P <0.01). The improvement of vertex hair growth assessed by the investigator was significantly greater in the topical finasteride group vs. the placebo group at week 24 ( P <0.01). Topical finasteride was generally safe and well-tolerated. CONCLUSIONS: In Chinese men with AGA, topical finasteride spray solution increased hair growth and showed good safety and tolerability profile during a 24-week treatment period. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05135468.
5 Apr 2026
Read appraisal →Sexual medicine reviews
Internet-based cognitive behavioral therapy, web-based counseling, and online/digital psychoeducation for male sexual dysfunction: a systematic review
INTRODUCTION: Male sexual dysfunctionhas a substantial impact on psychological well-being and intimate partner relationships. The expanding availability of digital health services has enabled online interventions, such as internet-based cognitive behavioral therapy (ICBT), digital psychoeducation, and web-based counseling, to emerge as alternatives to conventional therapies. OBJECTIVE: To evaluate the effectiveness, feasibility, and acceptability of digital and online interventions for male sexual dysfunction, and to synthesize evidence from randomized, non-randomized, and observational studies on clinical outcomes and patterns of digital engagement. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search was conducted across several databases using predefined keywords. Eligible studies included randomized controlled trials, experimental studies, and analytical observational studies published between 2007 and 2024. Extracted data comprised country, participant characteristics, type and duration of intervention, control conditions, outcome measures, and main findings. The primary outcome was improvement in erectile/sexual function using certain parameters, while secondary outcomes included relationship satisfaction, anxiety, and depression. RESULTS: Of 2482 records identified, and 21 met the inclusion criteria. Overall, web-based ICBT and psychoeducational interventions improved erectile function and sexual satisfaction compared with control conditions. Most interventions lasted 6-12 weeks and incorporated therapist feedback or automated systems. Remission rates for erectile dysfunction ranged from 20% to 30%; however, participant adherence was low (<60%). Several studies also reported reductions in performance anxiety and improvements in sexual confidence, with no serious adverse effects. CONCLUSION: Online interventions are promising approaches for managing male sexual dysfunction. Nevertheless, low adherence rates and heterogeneity in intervention formats remain major challenges. The findings also suggest heterogeneous benefits of digital interventions, alongside improved accessibility, reduced stigma, and increased engagement in help-seeking among men with sexual dysfunction. Future research should prioritize strategies to enhance adherence, integrate mobile health technologies, and assess long-term outcomes through large-scale clinical trials.
4 Apr 2026
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