Meta-analyses, which present the best source of information on the effectiveness of interventions, are influenced by several biases. One category relates to the convenience of selective inclusion of those primary studies, which are more easily available than others. This availability bias includes bias from excluding the grey literature, bias from excluding non-English literature, and bias from excluding older studies. Existing studies are not conclusive about the impacts of this bias; in addition, none of them focus on road safety meta-analyses. To fill this gap, the present paper consisted of two studies: (1) exploring the presence of availability bias in road safety meta-analyses, and (2) demonstrating the impact of availability bias in several example meta-analyses. Based on an analysis of 80 existing meta-analyses, the first study concluded that compared to the medicine meta-analyses, the road safety meta-analyses use a longer time range, are more often restricted in terms of language, and less often involve the grey literature. The second study utilized selected unrestricted data samples to demonstrate the impact of availability bias in seven meta-analyses. The differences in intervention effectiveness in terms of crash frequency changes between unrestricted and restricted scenarios were identified. This shows that the search restrictions clearly lead to availability bias, which influences the differences in meta-analysis results.

• Klíčová slova
• Availability bias, Meta-analysis, Road safety, Systematic review,
• MeSH
• bezpečnost * MeSH
• dopravní nehody * prevence a kontrola   statistika a číselné údaje   MeSH
• lidé MeSH
• metaanalýza jako téma * MeSH
• přehledová literatura jako téma MeSH
• zkreslení výsledků (epidemiologie) MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Androgen-receptor signaling inhibitors (ARSIs) significantly improve survival in systemic therapy for advanced/metastatic prostate cancer (PCa) patients; however possible central nervous system (CNS) toxicity is an unaddressed concern. We aimed to assess and compare the incidence of CNS-related adverse events (AEs) secondary to the treatment of PCa patients with different ARSIs. MATERIALS: In August 2023, a comprehensive seach was conducted in three databases for randomized controlled trials (RCTs) of PCa patients receiving ARSIs plus ADT. The primary endpoints included mental impairment, cognitive impairment, seizure, fatigue, and falls. RESULTS: Twenty-six RCTs, comprising 20,328 patients, were included in meta-analyses and network meta-analyses (NMAs). ARSIs increased the risk of mental impairment (RR: 1.72; 95% CI, 1.09-2.71), cognitive impairment (RR: 2.25; 95% CI, 1.78-2.86), seizure (RR: 2.20, 95% CI, 1.09-4.45), fatigue (RR: 1.31, 95% CI, 1.20-1.43), and falls (RR: 2.07, 95% CI, 1.60-2.67) compared to standard of care (SOC). Based on NMAs, Enzalutamide showed a significant increase in risk for all assessed CNS-related AEs, while Abiraterone demonstrated significant risk increases in cognitive impairment, fatigue, and falls. Conversely, Darolutamide did not exhibit significant increases in risk for any CNS-related AEs, except for fatigue. CONCLUSIONS: The addition of ARSIs to ADT increased all examined CNS-related AEs compared to SOC. Each ARSI is associated with a distinct profile of CNS-related AEs. Careful patient selection and monitoring for CNS sequelae is necessary to achieve the best quality of life in patients on ARSI + ADT for PCa.

• Klíčová slova
• ARSI, Central Nervous System, Meta-analysis, Network Meta-analysis, Prostate Cancer,
• MeSH
• antagonisté androgenních receptorů * škodlivé účinky   MeSH
• lidé MeSH
• nádory prostaty * farmakoterapie   MeSH
• nemoci centrálního nervového systému * chemicky indukované   epidemiologie   MeSH
• randomizované kontrolované studie jako téma MeSH
• síťová metaanalýza MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• antagonisté androgenních receptorů * MeSH

OBJECTIVES: To assess the efficacy and safety of pharmacological interventions for preventing upper gastrointestinal (GI) bleeding in people admitted to intensive care units (ICUs). DESIGN AND SETTING: Systematic review and frequentist network meta-analysis using standard methodological procedures as recommended by Cochrane for screening of records, data extraction and analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. PARTICIPANTS: Randomised controlled trials involving patients admitted to ICUs for longer than 24 hours were included. SEARCH METHODS: The Cochrane Gut Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Latin American and Caribbean Health Science Information database (LILACS) databases were searched from August 2017 to March 2022. The search in MEDLINE was updated in April 2023. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). MAIN OUTCOME MEASURES: The primary outcome was the prevention of clinically important upper GI bleeding. RESULTS: We included 123 studies with 46 996 participants. Cimetidine (relative risk (RR) 0.56, 95% CI 0.40 to 0.77, moderate certainty), ranitidine (RR 0.54, 95% CI 0.38 to 0.76, moderate certainty), antacids (RR 0.48, 95% CI 0.33 to 0.68, moderate certainty), sucralfate (RR 0.54, 95% CI 0.39 to 0.75, moderate certainty) and a combination of ranitidine and antacids (RR 0.13, 95% CI 0.03 to 0.62, moderate certainty) are likely effective in preventing upper GI bleeding.The effect of any intervention on the prevention of nosocomial pneumonia, all-cause mortality in the ICU or the hospital, duration of the stay in the ICU, duration of intubation and (serious) adverse events remains unclear. CONCLUSIONS: Several interventions seem effective in preventing clinically important upper GI bleeding while there is limited evidence for other outcomes. Patient-relevant benefits and harms need to be assessed under consideration of the patients' underlying conditions.

• Klíčová slova
• Drug-Related Side Effects and Adverse Reactions, Gastrointestinal Diseases, Hematology, Systematic Reviews as Topic,
• MeSH
• cimetidin terapeutické užití   MeSH
• gastrointestinální krvácení * prevence a kontrola   MeSH
• inhibitory protonové pumpy terapeutické užití   MeSH
• jednotky intenzivní péče * MeSH
• lidé MeSH
• protivředové látky terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• síťová metaanalýza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• cimetidin MeSH
• inhibitory protonové pumpy MeSH
• protivředové látky MeSH

CONTEXT: Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens. OBJECTIVE: To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials. EVIDENCE ACQUISITION: In April 2024, three databases were searched for eligible randomized controlled trials that evaluated oncologic outcomes in patients with MIUC treated with adjuvant ICIs. Pairwise meta-analysis (MA) and network meta-analyses were performed to compare the hazard ratios of oncological outcomes, including disease-free survival (DFS), overall survival (OS), and adverse events. Subgroup analyses were conducted on the basis of predefined clinicopathological features. EVIDENCE SYNTHESIS: Three randomized controlled trials that assessed the efficacy of adjuvant nivolumab, pembrolizumab, and atezolizumab were included in the MAs and network meta-analyses groups. Pairwise MAs showed that treatment with adjuvant ICIs significantly improved DFS [hazards ratio: 0.77, 95% confidence interval (CI): 0.66-0.90] as well as OS (hazards ratio: 0.87, 95% CI 0.76-1.00) in patients with MIUC compared with in the placebo/observation group. The DFS benefit was prominent in patients who underwent neoadjuvant chemotherapy (P = 0.041) and in those with bladder cancer (P = 0.013) but did not differ across programmed death-ligand 1 and lymph node status. Adjuvant ICI therapy was associated with increased risk of any (OR: 2.98, 95% CI 2.06-4.33) and severe adverse events (OR: 1.78, 95% CI 1.49-2.13). The treatment rankings revealed that pembrolizumab for DFS (84%) and nivolumab for OS (93%) had the highest likelihood of improving survival. CONCLUSIONS: Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.

• MeSH
• adjuvantní chemoterapie metody   MeSH
• inhibitory kontrolních bodů * terapeutické užití   farmakologie   MeSH
• karcinom z přechodných buněk * farmakoterapie   patologie   MeSH
• lidé MeSH
• nádory močového měchýře * farmakoterapie   patologie   MeSH
• síťová metaanalýza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• inhibitory kontrolních bodů * MeSH

This study conducted pairwise and network meta-analysis to evaluate the effectiveness of three mind-body exercise interventions (Tai Chi, Qigong, and yoga) on physical capacity, psychological well-being, and quality of life in stroke patients. The research encompassed 30 studies involving 2107 participants and utilized the Risk of Bias 2.0 tool for quality assessment. Pairwise analysis revealed that all three mind-body exercises significantly enhanced patients' quality of life. Tai Chi demonstrated the most comprehensive improvements in balance, limb motor function, activities of daily living, and depression. Network meta-analysis indicated that Qigong was the most effective in improving balance and quality of life for post-stroke patients, followed by Tai Chi. These findings underscore the positive impact of mind-body exercises on both physical and psychosocial outcomes in stroke patients. However, further research involving rigorously designed and adequately powered trials is necessary to enhance the level of evidence in this area.

• Klíčová slova
• Mind-body exercise, Network meta-analysis, Stroke, Systematic review,
• MeSH
• cévní mozková příhoda * MeSH
• činnosti denního života MeSH
• kvalita života MeSH
• lidé MeSH
• síťová metaanalýza MeSH
• taiči * MeSH
• terapie cvičením MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH

• MeSH
• anemie z nedostatku železa farmakoterapie   MeSH
• aplikace orální MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• potravní doplňky * MeSH
• randomizované kontrolované studie jako téma MeSH
• sportovci * MeSH
• systematický přehled jako téma MeSH
• železo * aplikace a dávkování   krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• Názvy látek
• železo * MeSH

BACKGROUND: Laser therapy has emerged as a promising treatment modality for improving the appearance and symptoms associated with hypertrophic and keloid scars. In this network meta-analysis, we aimed to evaluate the efficacy of different laser types in treating hypertrophic and keloid scars. METHODS: A comprehensive search of four databases was conducted to identify relevant studies published up until July 2023. Data were extracted from eligible studies and pooled as mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous data in a network meta-analysis (NMA) model, using R software. RESULTS: A total of 18 studies, comprising 550 patients, were included in the analysis. Pooling our data showed that fractional carbon dioxide (FCO2) plus 5-fluorouracil (5-FU) was superior to control in terms of Vancouver Scar Scale (VSS), pliability score, and thickness; [MD = - 5.97; 95% CI (- 7.30; - 4.65)], [MD = - 2.68; 95% CI (- 4.03; - 1.33)], [MD = - 2.22; 95% CI (- 3.13; - 1.31)], respectively. However, insignificant difference was observed among FCO2 plus 5-FU compared to control group in terms of erythema, vascularity, redness and perfusion, and pigmentation [MD = - 0.71; 95% CI (- 2.72; 1.30)], [MD = - 0.44; 95% CI (- 1.26; 0.38)], respectively. CONCLUSION: Our NMA found that the FCO2 plus 5-FU was the most effective intervention in decreasing the VSS and thickness, while FCO2 plus CO2 was the most effective intervention in decreasing the pliability score. Further research is needed to determine the optimal laser parameters and long-term efficacy of laser therapy in hypertrophic and keloid scars. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

• Klíčová slova
• Hypertrophic scars, Keloid scars, Laser therapy, Network meta-analysis,
• MeSH
• jizva hypertrofická * diagnóza   terapie   MeSH
• keloid * diagnóza   terapie   MeSH
• laserová terapie škodlivé účinky   přístrojové vybavení   metody   MeSH
• lidé MeSH
• síťová metaanalýza MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

OBJECTIVE: To compare the differential efficacy of first-line immune checkpoint inhibitor (ICI)-based combined therapies among patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC), as recently, the efficacy of triplet therapy comprising nivolumab plus ipilimumab plus cabozantinib has been published. PATIENTS AND METHODS: Three databases were searched in December 2022 for randomised controlled trials (RCTs) analysing oncological outcomes in patients with mRCC treated with first-line ICI-based combined therapies. We performed network meta-analysis (NMA) to compare the outcomes, including progression-free survival (PFS) and objective response rates (ORRs), in patients with intermediate- and poor-risk mRCC; we also assessed treatment-related adverse events. RESULTS: Overall, seven RCTs were included in the meta-analyses and NMAs. Treatment ranking analysis revealed that pembrolizumab + lenvatinib (99%) had the highest likelihood of improved PFS, followed by nivolumab + cabozantinib (79%), and nivolumab + ipilimumab + cabozantinib (77%). Notably, compared to nivolumab + cabozantinib, adding ipilimumab to nivolumab + cabozantinib did not improve PFS (hazard ratio 1.02, 95% confidence interval 0.72-1.43). Regarding ORRs, treatment ranking analysis also revealed that pembrolizumab + lenvatinib had the highest likelihood of providing better ORRs (99.7%). The likelihoods of improved PFS and ORRs of pembrolizumab + lenvatinib were true in both International Metastatic RCC Database Consortium (IMDC) risk groups. CONCLUSIONS: Our analyses confirmed the robust efficacy of pembrolizumab + lenvatinib as first-line treatment for patients with intermediate or poor IMDC risk mRCC. Triplet therapy did not result in superior efficacy. Considering both toxicity and the lack of mature overall survival data, triplet therapy should only be considered in selected patients.

• Klíčová slova
• cabozantinib, immune checkpoint inhibitors, ipilimumab, metastasis, nivolumab, renal cell carcinoma,
• MeSH
• anilidy * terapeutické užití   MeSH
• chinoliny terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• fenylmočovinové sloučeniny terapeutické užití   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunoterapie metody   MeSH
• inhibitory kontrolních bodů * terapeutické užití   MeSH
• ipilimumab terapeutické užití   MeSH
• karcinom z renálních buněk * farmakoterapie   mortalita   sekundární   MeSH
• lidé MeSH
• nádory ledvin * farmakoterapie   mortalita   patologie   MeSH
• nivolumab terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• pyridiny terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• síťová metaanalýza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• anilidy * MeSH
• cabozantinib MeSH Prohlížeč
• chinoliny MeSH
• fenylmočovinové sloučeniny MeSH
• humanizované monoklonální protilátky MeSH
• inhibitory kontrolních bodů * MeSH
• ipilimumab MeSH
• lenvatinib MeSH Prohlížeč
• nivolumab MeSH
• pembrolizumab MeSH Prohlížeč
• pyridiny MeSH

CONTEXT: The optimal therapeutic agent with respect to metastatic sites is unclear in advanced urothelial carcinoma (UC). OBJECTIVE: To investigate the metastatic organotropism differential treatment response in patients with advanced or metastatic UC. EVIDENCE ACQUISITION: A systematic search and network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The primary endpoints of interest were the objective response rate, overall survival (OS), and progression-free survival with respect to different metastatic sites. EVIDENCE SYNTHESIS: Twenty-six trials comprising 9082 patients met our eligibility criteria, and a formal NMA was conducted. Durvalumab plus tremelimumab as first-line systemic therapy was significantly associated with better OS than chemotherapy in visceral metastasis (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.67-0.98). Pembrolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with visceral metastasis (HR 0.75, 95% CI 0.60-0.95). Atezolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with liver metastasis (in the population of >5% of tumor-infiltrating immune cells) and lymph node metastasis (HR 0.51, 95% CI 0.28-0.96, and HR 0.59, 95% CI 0.37-0.96, respectively). CONCLUSIONS: Administration of immune-oncology treatments with respect to metastatic sites in patients with advanced or metastatic UC might have a positive impact on survival outcomes in both the first- and the second-line setting. Nevertheless, further investigations focusing on metastatic organotropism differential response with reliable oncological outcomes are needed to identify the optimal management strategy for these patients. PATIENT SUMMARY: Although the supporting evidence for oncological benefits of therapeutic systemic agents with respect to metastatic sites is not yet strong enough to provide a recommendation in advanced or metastatic urothelial carcinoma, clinicians may take into account tumor organotropism only in discussion with the patient fully informed on the optimal treatment decision to be taken.

• Klíčová slova
• Bladder cancer, Chemotherapy, Immunotherapy, Metastatic urothelial carcinoma, Organotropism,
• MeSH
• karcinom z přechodných buněk * farmakoterapie   sekundární   mortalita   patologie   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• randomizované kontrolované studie jako téma * MeSH
• síťová metaanalýza * MeSH
• urologické nádory farmakoterapie   patologie   mortalita   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

BACKGROUND: Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear. METHODS: We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist. RESULTS: Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64-0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52-0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease. CONCLUSIONS: Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.

• Klíčová slova
• Androgen receptor signaling inhibitor, Docetaxel, High-volume, Low-volume, Metastatic hormone-sensitive prostate cancer,
• MeSH
• antagonisté androgenních receptorů terapeutické užití   MeSH
• antagonisté androgenů * terapeutické užití   MeSH
• docetaxel * terapeutické užití   aplikace a dávkování   MeSH
• lidé MeSH
• nádory prostaty * farmakoterapie   mortalita   patologie   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• síťová metaanalýza * MeSH
• tumor burden MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• antagonisté androgenních receptorů MeSH
• antagonisté androgenů * MeSH
• docetaxel * MeSH