Hormonal Treatments and Vaginal Moisturizers for Genitourinary Syndrome of Menopause : A Systematic Review.

BACKGROUND: Postmenopausal women commonly experience vulvovaginal, urinary, and sexual symptoms associated with genitourinary syndrome of menopause (GSM). PURPOSE: To evaluate effectiveness and harms of vaginal estrogen, nonestrogen hormone therapies, and vaginal moisturizers for treatment of GSM symptoms. DATA SOURCES: Medline, Embase, and CINAHL through 11 December 2023. STUDY SELECTION: Randomized controlled trials (RCTs) of at least 8 weeks' duration enrolling postmenopausal women with at least 1 GSM symptom and reporting effectiveness or harms of hormonal interventions or vaginal moisturizers. DATA EXTRACTION: Risk of bias and data extraction were performed by one reviewer and verified by a second reviewer. Certainty of evidence (COE) was assessed by one reviewer and verified by consensus. DATA SYNTHESIS: From 11 993 citations, 46 RCTs evaluating vaginal estrogen (k = 22), nonestrogen hormones (k = 16), vaginal moisturizers (k = 4), or multiple interventions (k = 4) were identified. Variation in populations, interventions, comparators, and outcomes precluded meta-analysis. Compared with placebo or no treatment, vaginal estrogen may improve vulvovaginal dryness, dyspareunia, most bothersome symptom, and treatment satisfaction. Compared with placebo, vaginal dehydroepiandrosterone (DHEA) may improve dryness, dyspareunia, and distress, bother, or interference from genitourinary symptoms; oral ospemifene may improve dryness, dyspareunia, and treatment satisfaction; and vaginal moisturizers may improve dryness (all low COE). Vaginal testosterone, systemic DHEA, vaginal oxytocin, and oral raloxifene or bazedoxifene may provide no benefit (low COE) or had uncertain effects (very low COE). Although studies did not report frequent serious harms, reporting was limited by short-duration studies that were insufficiently powered to evaluate infrequent serious harms. LIMITATIONS: Most studies were 12 weeks or less in duration and used heterogeneous GSM diagnostic criteria and outcome measures. Few studies enrolled women with a history of cancer. CONCLUSION: Vaginal estrogen, vaginal DHEA, oral ospemifene, and vaginal moisturizers may improve some GSM symptoms in the short term. Few long-term data exist on efficacy, comparative effectiveness, tolerability, and safety of GSM treatments. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42023400684).

Simultaneous evaluation of the imprecision and inconsistency domains of GRADE can be performed using prediction intervals.

OBJECTIVES: To explore the use of prediction interval (PI) for the simultaneous evaluation of the imprecision and inconsistency domains of Grading of Recommendations, Assessment, and Evaluation using stakeholder-provided decision thresholds. STUDY DESIGN AND SETTING: We propose transforming the PI of a meta-analysis from a relative risk scale to an absolute risk difference using an appropriate baseline risk. The transformed PI is compared to stakeholder-provided thresholds on an absolute scale. We applied this approach to a large convenience sample of meta-analyses extracted from the Cochrane Database of Systematic Reviews and compared it against the traditional approach of rating imprecision and inconsistency separately using confidence intervals and statistical measures of heterogeneity, respectively. We used empirically derived thresholds following Grading of Recommendations, Assessment, and Evaluation guidance. RESULTS: The convenience sample consisted of 2516 meta-analyses (median of 7 studies per meta-analysis; interquartile range: 5-11). The main analysis showed the percentage of meta-analyses in which both approaches had the same number of certainty levels rated down was 59%. The PI approach led to more levels of rating down (lower certainty) in 27% and to fewer levels of rating down (higher certainty) in 14%. Multiple sensitivity analyses using different thresholds showed similar results, but the PI approach had particularly increased width with a larger number of included studies and higher I2 values. CONCLUSION: Using the PI for simultaneous evaluation of imprecision and inconsistency seems feasible and logical but can lead to lower certainty ratings. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria. PLAIN LANGUAGE SUMMARY: The prediction interval (PI) addresses both the imprecision and inconsistency domains of certainty. In this study, we applied this PI approach to simultaneously judge both domains and compared this to the traditional approach of making these separate judgments. The 2 approaches had moderate agreement. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria.

Prostate cancer screening with MRI does not differ from PSA only for detection but reduces biopsies and overdiagnosis.

SOURCE CITATION: Fazekas T, Shim SR, Basile G, et al. Magnetic resonance imaging in prostate cancer screening: a systematic review and meta-analysis. JAMA Oncol. 2024;10:745-754. 38576242.

Impact of the diagnostic label for a low-risk prostate lesion: protocol for two online factorial randomised experiments.

INTRODUCTION: Many types of prostate cancer present minimal risk to a man's lifespan or well-being, but existing terminology makes it difficult for men to distinguish these from high-risk prostate cancers. This study aims to explore whether using an alternative label for low-risk prostate cancer influences management choice and anxiety levels among Australian men and their partners. METHODS AND ANALYSIS: We will run two separate studies for Australian men and Australian women with a male partner. Both studies are between-subjects factorial (3×2) randomised online hypothetical experiments. Following consent, eligible participants will be randomised 1:1:1 to three labels: 'low-risk prostate cancer, Gleason Group 1', 'low-risk prostate neoplasm' or 'low-risk prostate lesion'. Participants will then undergo a second randomisation step with 1:1 allocation to the provision of detailed information on the benefits and harms of different management choices versus the provision of less detailed information about management choices. The required sample sizes are 1290 men and 1410 women. The primary outcome is the participant choice of their preferred management strategy: no immediate treatment (prostate-specific antigen (PSA)-based monitoring or active surveillance using PSA, MRI, biopsy with delayed treatment for disease progression) versus immediate treatment (prostatectomy or radiation therapy). Secondary outcomes include preferred management choice (from the four options listed above), diagnosis anxiety, management choice anxiety and management choice at a later time point (for participants who initially choose a monitoring strategy). ETHICS AND DISSEMINATION: Ethics approval has been received from The University of Sydney Human Research Ethics Committee (2023/572). The results of the study will be published in a peer-reviewed medical journal and a plain language summary of the findings will be shared on the Wiser Healthcare publications page http://www.wiserhealthcare.org.au/category/publications/ TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trials Registry (ID 386701 and 386889).

Estimating the Effect of Radical Prostatectomy: Combining Data From the SPCG4 and PIVOT Randomized Trials With Contemporary Cohorts.

PURPOSE: Two randomized trials (SPCG4 and PIVOT) have compared surgery to conservative management for localized prostate cancer. The applicability of these trials to contemporary practice remains uncertain. We aimed to develop an individualized prediction model for prostate cancer mortality comparing immediate surgery at a high-volume center to active surveillance. MATERIALS AND METHODS: We determined whether the relative risk of prostate cancer mortality with surgery vs observation varied by baseline risk. We then used various estimates of relative risk to estimate 15-year mortality with and without surgery using, as a predictor, risk of biochemical recurrence calculated from a model. RESULTS: We saw no evidence that relative risk varied by baseline risk, supporting the use of a constant relative risk. Compared with observation, surgery was associated with negligible benefit for patients with Grade Group (GG) 1 disease (0.2% mortality reduction at 15 years) and small benefit for patients with GG2 with lower PSA and stage (≤5% mortality reduction). Benefit was greater (6%-9%) for patients with GG3 or GG4 though still modest, but effect estimates varied widely depending on choice of hazard ratio for surgery (6%-36% absolute risk reduction). CONCLUSIONS: Surgery should be avoided for men with low-risk (GG1) prostate cancer and for many men with GG2 disease. Surgical benefits are greater in men with higher-risk disease. Integration of findings with a life expectancy model will allow patients to make informed treatment decisions given their oncologic risk, risk of death from other causes, and estimated effects of surgery.

Cytoreductive nephrectomy in metastatic renal cell carcinoma.

BACKGROUND: Nephrectomy is the surgical removal of all or part of a kidney. When the aim of nephrectomy is to reduce tumor burden in people with established metastatic disease, the procedure is called cytoreductive nephrectomy (CN). CN is typically combined with systemic anticancer therapy (SACT). SACT can be initiated before or immediately after the operation or deferred until radiological signs of disease progression. The benefits and harms of CN are controversial. OBJECTIVES: To assess the effects of cytoreductive nephrectomy combined with systemic anticancer therapy versus systemic anticancer therapy alone or watchful waiting in newly diagnosed metastatic renal cell carcinoma. SEARCH METHODS: We performed a comprehensive search in the Cochrane Library, MEDLINE, Embase, Scopus, two trial registries, and other gray literature sources up to 1 March 2024. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated SACT and CN versus SACT alone or watchful waiting. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. Primary outcomes were time to death from any cause and quality of life. Secondary outcomes were time to disease progression, treatment response, treatment-related mortality, discontinuation due to adverse events, and serious adverse events. We performed statistical analyses using a random-effects model. We rated the certainty of evidence using the GRADE approach. MAIN RESULTS: Our search identified 10 records of four unique RCTs that informed two comparisons. In this abstract, we focus on the results for the two primary outcomes. Cytoreductive nephrectomy plus systemic anticancer therapy versus systemic anticancer therapy alone Three RCTs informed this comparison. Due to the considerable heterogeneity when pooling across these studies, we decided to present the results of the prespecified subgroup analysis by type of systemic agent. Cytoreductive nephrectomy plus interferon immunotherapy versus interferon immunotherapy alone CN plus interferon immunotherapy compared with interferon immunotherapy alone probably increases time to death from any cause (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.51 to 0.89; I²= 0%; 2 studies, 326 participants; moderate-certainty evidence). Assuming 820 all-cause deaths at two years' follow-up per 1000 people who receive interferon immunotherapy alone, the effect estimate corresponds to 132 fewer all-cause deaths (237 fewer to 37 fewer) per 1000 people who receive CN plus interferon immunotherapy. We found no evidence to assess quality of life. Cytoreductive nephrectomy plus tyrosine kinase inhibitor therapy versus tyrosine kinase inhibitor therapy alone We are very uncertain about the effect of CN plus tyrosine kinase inhibitor (TKI) therapy compared with TKI therapy alone on time to death from any cause (HR 1.11, 95% CI 0.90 to 1.37; 1 study, 450 participants; very low-certainty evidence). Assuming 574 all-cause deaths at two years' follow-up per 1000 people who receive TKI therapy alone, the effect estimate corresponds to 38 more all-cause deaths (38 fewer to 115 more) per 1000 people who receive CN plus TKI therapy. We found no evidence to assess quality of life. Immediate cytoreductive nephrectomy versus deferred cytoreductive nephrectomy One study evaluated CN followed by TKI therapy (immediate CN) versus three cycles of TKI therapy followed by CN (deferred CN). Immediate CN compared with deferred CN may decrease time to death from any cause (HR 1.63, 95% CI 1.05 to 2.53; 1 study, 99 participants; low-certainty evidence). Assuming 620 all-cause deaths at two years' follow-up per 1000 people who receive deferred CN, the effect estimate corresponds to 173 more all-cause deaths (18 more to 294 more) per 1000 people who receive immediate CN. We found no evidence to assess quality of life. AUTHORS' CONCLUSIONS: CN plus SACT in the form of interferon immunotherapy versus SACT in the form of interferon immunotherapy alone probably increases time to death from any cause. However, we are very uncertain about the effect of CN plus SACT in the form of TKI therapy versus SACT in the form of TKI therapy alone on time to death from any cause. Immediate CN versus deferred CN may decrease time to death from any cause. We found no quality of life data for any of these three comparisons. We also found no evidence to inform any other comparisons, in particular those involving newer immunotherapy agents (programmed death receptor 1 [PD-1]/programmed death ligand 1 [PD-L1] immune checkpoint inhibitors), which have become the backbone of SACT for metastatic renal cell carcinoma. There is an urgent need for RCTs that explore the role of CN in the context of contemporary forms of systemic immunotherapy.

Under-representation of Diversity on American Urological Association and European Association of Urology Guideline Panels.

OBJECTIVE: To assess the panel composition of the 2 most important guideline developers in urology as equity and acceptability, important domains in clinical guideline development, require broad stakeholder representation. METHODS: Following a predefined protocol, we identified all current AUA and EAU guideline documents. Two authors independently abstracted data including guideline topic, number and roles of panel members, voting status, and academic rank. We determined panel member's gender (woman, man, or nonbinary) and racialization (White or non-White) status based on name, internet picture, pronouns used, bios available, and gender listed on their profile. RESULTS: We identified 31 AUA and 20 EAU guidelines for inclusion. Median panel size was 19 (interquartile range [IQR]: 17; 21) with 12 (IQR: 10; 14) voting members. The average composition of voting panels was predominantly male (81.8%) and White (86.8%). Eleven guideline panels (21.6%) did not include any women, and 9 (17.6%) panels had no representation of individuals from non-White groups. While gender distribution was similar among guidelines of the 2 organizations, the AUA included more voting members from non-White groups (14.3% vs 8.0%; P = .010). Analysis of the AUA panel composition over time revealed stable proportions of female and non-White individuals. CONCLUSION: Both AUA and EAU guidelines exhibit insufficient representation of females and non-White individuals, with no evident improvement observed over time. Implementing more transparent processes that advocate for diverse panel representation may enhance the incorporation of stakeholder values and preferences, thereby improving the dissemination and adoption of guidelines.

Immunotherapy for advanced or metastatic urothelial carcinoma: an abridged Cochrane review.

OBJECTIVES: To assess the effects of immunotherapy compared to chemotherapy as first- and second-line treatment of advanced or metastatic urothelial carcinoma. METHODS: Based on a published protocol, we performed a systematic search of multiple databases. Two review authors independently performed the literature selection, identified relevant studies, assessed the eligibility of studies for inclusion, and extracted data. We performed statistical analyses using a random-effects model and assessed the quality of the evidence on a per-outcome basis according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included five randomised controlled trials and also identified seven single-arm studies. When used as first-line therapy, immunotherapy probably has little to no effect on the risk of death from any cause compared to chemotherapy (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.87-1.07; moderate-certainty evidence). immunotherapy probably has little to no effect on health-related quality of life (mean difference [MD] 4.10, 95% CI 3.83-4.37; moderate). Immunotherapy probably reduces grade 3-5 adverse events (risk ratio [RR] 0.47, 95% CI 0.29-0.75; moderate). In the second-line setting immunotherapy may reduce the risk of death from any cause (HR 0.72, 95% CI 0.63-0.81; low). Immunotherapy may have little to no effect on health-related quality of life when compared to chemotherapy (MD 4.82, 95% CI -3.11 to 12.75; low). Immunotherapy may reduce grade 3-5 adverse events (RR 0.89, 95% CI 0.81-0.97; low). CONCLUSIONS: Compared to chemotherapy, immunotherapy has little to no effect on the risk of death from any cause in a first-line setting. Nevertheless, it may reduce the risk of death from any cause when used as second-line therapy. The health-related quality of life of participants receiving first- and second-line therapy does not appear to be affected by immunotherapy. Immunotherapy probably reduces or may reduce grade 3-5 adverse events when used as first- and second-line therapy, respectively.

GRADE guidance 37: rating imprecision in a body of evidence on test accuracy.

OBJECTIVES: To provide guidance on rating imprecision in a body of evidence assessing the accuracy of a single test. This guide will clarify when Grading of Recommendations Assessment, Development and Evaluation (GRADE) users should consider rating down the certainty of evidence by one or more levels for imprecision in test accuracy. STUDY DESIGN AND SETTING: A project group within the GRADE working group conducted iterative discussions and presentations at GRADE working group meetings to produce this guidance. RESULTS: Before rating the certainty of evidence, GRADE users should define the target of their certainty rating. GRADE recommends setting judgment thresholds defining what they consider a very accurate, accurate, inaccurate, and very inaccurate test. These thresholds should be set after considering consequences of testing and effects on people-important outcomes. GRADE's primary criterion for judging imprecision in test accuracy evidence is considering confidence intervals (i.e., CI approach) of absolute test accuracy results (true and false, positive, and negative results in a cohort of people). Based on the CI approach, when a CI appreciably crosses the predefined judgment threshold(s), one should consider rating down certainty of evidence by one or more levels, depending on the number of thresholds crossed. When the CI does not cross judgment threshold(s), GRADE suggests considering the sample size for an adequately powered test accuracy review (optimal or review information size [optimal information size (OIS)/review information size (RIS)]) in rating imprecision. If the combined sample size of the included studies in the review is smaller than the required OIS/RIS, one should consider rating down by one or more levels for imprecision. CONCLUSION: This paper extends previous GRADE guidance for rating imprecision in single test accuracy systematic reviews and guidelines, with a focus on the circumstances in which one should consider rating down one or more levels for imprecision.

Uncovering gaps in GRADE reporting of Eastern Association for the Surgery of Trauma (EAST) guidelines.

OBJECTIVES: To formally evaluate the uptake and reporting of the Grading of Recommendation Assessments, Development and Evaluation (GRADE) approach in clinical practice guidelines (CPGs) developed by the Eastern Association for the Surgery of Trauma (EAST). STUDY DESIGN AND SETTING: Based on an a priori, written protocol, we developed a dedicated data abstraction form that included the six suggested criteria for using and applying GRADE. By searching the EAST website, we identified all EAST guidelines that referenced the use of GRADE. All steps of the data abstraction process were completed independently and in duplicate by two members of the research team. RESULTS: We identified a total of 48 CPGs that used GRADE. Trauma and violence prevention (n = 11; 23.9%) was the most common topic. The median number of patient/population, intervention, comparison, and outcomes (PICO) questions addressed was 3 (interquartile range: 2; 4) with a median of 2.5 (interquartile range: 1; 4) critical outcomes. A conditional/weak recommendation was provided for n = 79 (51.4%) PICOs, whereas a strong recommendation was provided for 33 PICOs (23.9%). For 22 PICOs (15.9%), no recommendation was made. Nearly all guideline documents provided search dates (n = 44; 95.7%) and a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram (n = 44; 95.7%). Most described categories for rating down (n = 35; 76.1%). GRADE decision-making domains related to the ratio of benefits to harms, values and preferences, and resource utilization were referenced by 43.5% (n = 20), 43.5% (n = 20), and 30.4% (n = 14) of CPGs, respectively. For nearly half of PICO questions (n = 59; 44.2%) authors did not provide an evidence profile or summary of findings table. Comparing time periods from 2014-2018 to 2019-2022, the proportion of recommendations with an overall certainty of evidence increased (52.4% vs 83.9%; P < 0.001). CONCLUSION: EAST has successfully adopted GRADE to develop many trauma-related guidelines, each addressing a finite number of focused clinical questions based on systematic reviews conducted in-house. Overall reporting improved over time. There is for improvement when it comes to consistent provision of an overall certainty of evidence, the reporting of the evidence to decision-making process, and the justification of strong recommendations based on low/very low certainty evidence.

Testosterone replacement in men with sexual dysfunction.

BACKGROUND: Clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with sexual dysfunction and testosterone deficiency. However, TRT is commonly promoted in men without testosterone deficiency and existing trials often do not clearly report participants' testosterone levels or testosterone-related symptoms. This review assesses the potential benefits and harms of TRT in men presenting with complaints of sexual dysfunction. OBJECTIVES: To assess the effects of testosterone replacement therapy compared to placebo or other medical treatments in men with sexual dysfunction. SEARCH METHODS: We performed a comprehensive search of CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and the trials registries ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform, with no restrictions on language of publication or publication status, up to 29 August 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in men (40 years or over) with sexual dysfunction. We excluded men with primary or secondary hypogonadism. We compared testosterone or testosterone with phosphodiesterase-5 inhibitors (PDEI5I) to placebo or PDE5I alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, assessed the risk of bias, extracted data, and rated the certainty of evidence (CoE) according to GRADE using a minimally contextualized approach. We performed statistical analyses using a random-effects model and interpreted them according to standard Cochrane methodology. Predefined primary outcomes were self-reported erectile dysfunction assessed by a validated instrument, sexual quality of life assessed by a validated instrument, and cardiovascular mortality. Secondary outcomes were treatment withdrawal due to adverse events, prostate-related events, and lower urinary tract symptoms (LUTS). We distinguished between short-term (up to 12 months) and long-term (> 12 months) outcomes. MAIN RESULTS: We identified 43 studies with 11,419 randomized participants across three comparisons: testosterone versus placebo, testosterone versus PDE5I, and testosterone with PDE5I versus PDE5I alone. This abstract focuses on the most relevant comparison of testosterone versus placebo. Testosterone versus placebo (up to 12 months) Based on a predefined sensitivity analysis of studies at low risk of bias, and an analysis combing data from the similar International Index of Erectile Function (IIEF-EF) and IIEF-5 instruments, TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference (MD) 2.37, 95% confidence interval (CI) 1.67 to 3.08; I² = 0%; 6 RCTs, 2016 participants; moderate CoE) on a scale from 6 to 30 with larger values reflecting better erectile function. We assumed a minimal clinically important difference (MCID) of greater than or equal to 4. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD -2.31, 95% CI -3.63 to -1.00; I² = 0%; 5 RCTs, 1030 participants; moderate CoE) on a scale from 17 to 85 with larger values reflecting worse sexual quality of life. We assumed a MCID of greater than or equal to 10. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio (RR) 0.83, 95% CI 0.21 to 3.26; I² = 0%; 10 RCTs, 3525 participants; moderate CoE). Based on two cardiovascular deaths in the placebo group and an assumed MCID of 3%, this would correspond to no additional deaths per 1000 men (95% CI 1 fewer to 4 more). TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or LUTS. Testosterone versus placebo (later than 12 months) We are very uncertain about the longer-term effects of TRT on erectile dysfunction assessed with the IIEF-EF (MD 4.20, 95% CI -2.03 to 10.43; 1 study, 42 participants; very low CoE). We did not find studies reporting on sexual quality of life or cardiovascular mortality. We are very uncertain about the effect of testosterone on treatment withdrawal due to adverse events. We found no studies reporting on prostate-related events or LUTS. AUTHORS' CONCLUSIONS: In the short term, TRT probably has little to no effect on erectile function, sexual quality of life, or cardiovascular mortality compared to a placebo. It likely results in little to no difference in treatment withdrawals due to adverse events, prostate-related events, or LUTS. In the long term, we are very uncertain about the effects of TRT on erectile function when compared to placebo; we did not find data on its effects on sexual quality of life or cardiovascular mortality. The certainty of evidence ranged from moderate (signaling that we are confident that the reported effect size is likely to be close to the true effect) to very low (indicating that the true effect is likely to be substantially different). The findings of this review should help to inform future guidelines and clinical decision-making at the point of care.

Tranexamic acid for percutaneous nephrolithotomy: an abridged Cochrane review.

OBJECTIVE: To assess the effects of tranexamic acid (TXA) in individuals with kidney stones undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We performed a literature search of Cochrane Library, PubMed (including MEDLINE), Embase, Scopus, Global Index Medicus, trials registries, grey literature, and conference proceedings. We included randomised controlled trials (RCTs) that compared treatment with PCNL with administration of TXA to placebo (or no TXA) for patients aged ≥18 years. Two review authors independently classified studies and abstracted data. Primary outcomes were blood transfusion, stone-free rate (SFR), thromboembolic events (TEE). We rated the certainty of evidence (CoE) according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach using a minimally contextualised approach with pre-defined thresholds for minimally clinically important differences (MCID). RESULTS: We included 10 RCTs assessing the effect of systemic TXA in PCNL vs placebo (or no TXA). Eight studies were published as full text. Based on an adjusted baseline risk of blood transfusion of 5.7%, systemic TXA may reduce blood transfusions (risk ratio [RR] 0.45, 95% confidence interval [CI] 0.27-0.76). Based on an adjusted baseline SFR of 75.7%, systemic TXA may increase SFR (RR 1.11, 95% CI 0.98-1.27). There is probably no difference in TEEs (risk difference 0.001, 95% CI -0.01 to 0.01). Systemic TXA may increase adverse events (AEs) (RR 5.22, 95% CI 0.52-52.72). Systemic TXA may have little to no effect on secondary interventions (RR 1.15, 95% CI 0.84-1.57). The CoE for most outcomes was assessed as low or very low. CONCLUSIONS: Based on a body of evidence of 10 RCTs, we found that systemic TXA in PCNL may reduce blood transfusions, major surgical complications, and hospital length of stay, as well as improve the SFR; however, it may increase AEs. These findings should inform urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL.

Percutaneous nephrolithotomy vs retrograde intrarenal surgery for renal stones: a Cochrane Review.

OBJECTIVES: To assess the effects of percutaneous nephrolithotomy (PCNL) vs retrograde intrarenal surgery (RIRS) for the treatment of renal stones in adults. METHODS: We performed a comprehensive search of the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of the grey literature, and conference proceedings up to 23 March 2023. We applied no restrictions on publication language or status. Screening, data extraction, risk-of-bias assessment, and certainty of evidence (CoE) rating using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach were done in duplicate by two independent reviewers. This co-publication focuses on the primary outcomes of this review only. RESULTS: We included 42 trials that met the inclusion criteria. Stone-free rate (SFR): PCNL may improve SFRs (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.08-1.18; I2 = 71%; 39 studies, 4088 participants; low CoE). Major complications: PCNL probably has little to no effect on major complications (RR 0.86, 95% CI 0.59-1.25; I2 = 15%; 34 studies, 3649; participants; moderate CoE) compared to RIRS. Need for secondary interventions: PCNL may reduce the need for secondary interventions (RR 0.31, 95% CI 0.17-0.55; I2 = 61%; 21 studies, 2005 participants; low CoE) compared to RIRS. CONCLUSION: Despite shortcomings in most studies that lowered our certainty in the estimates of effect to mostly very low or low, we found that PCNL may improve SFRs and reduce the need for secondary interventions while not impacting major complications. Ureteric stricture rates may be similar compared to RIRS. We expect the findings of this review to be helpful for shared decision-making about management choices for individuals with renal stones.

Certainty of Evidence Assessment in Systematic Reviews Published by High-Impact Sports Science Journals: A Meta-epidemiological Study.

BACKGROUND: Assessing certainty of evidence is a key element of any systematic review. The aim of this meta-epidemiology study was to understand the frequency and ways with which certainty of evidence is assessed in contemporary systematic reviews published in high-impact sports science journals. METHODS: We searched PubMed and relevant journal web sites from 1 August 2016 to 11 October 2022 for systematic reviews published in the top-ten highest-impact journals within the 2020 Journal Citation Report for the Sports Sciences category. Pairs of independent reviewers screened items using a priori established criteria. RESULTS: Of 1250 eligible documents, 258 (20.6%) assessed the certainty of evidence, defined as using two or more distinct domains to provide an overall rating of the trustworthiness of findings across studies. Nine methods were cited for assessing certainty, with the most common being the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach (61.6%). The proportion of systematic reviews assessing certainty of evidence appeared to increase over the 6-year timeframe analyzed. Across all reviews analyzed, a large majority addressed the domains of risk of bias, imprecision, and inconsistency of the results. Other certainty domains including indirectness/applicability were less commonly assessed. DISCUSSION: Only one in five recent contemporary systematic reviews in the field of exercise and sports science assessed certainty of evidence. Organizational and institutional education on methods for assessing evidence may help further increase uptake of these methods and improve both the quality and clinical impact of systematic reviews in the field.