PCN287 THE ROLE OF EFFICACY AND EFFECTIVENESS ANALYSES IN HEALTH TECHNOLOGY ASSESSMENTS IN DETERMINING TENDERING RANKS FOR ONCOLOGY DRUGS IN DENMARK & NORWAY

Background We performed a systematic review and network meta-analysis to compare probiotics to current therapies in the induction and maintenance of remission in ulcerative colitis (UC). Methods We systematically searched Medline, Embase, CENTRAL up to November 2018. We included randomised controlled trials (RCTs) in patients with mild to moderate UC that compared probiotics, sulfasalazine, mesalamine (low dose <2 g/day, standard dose ≥ 2 g/day), olsalazine, balsalazide, budesonide, budesonide MMX and beclomethasone either alone or in combination with topical therapy, to each other or placebo. We excluded trials where <50% of the population had extensive or left-sided colitis. Outcomes were remission (induction studies), relapse (maintenance studies) and discontinuation due to adverse events (tolerability). We conducted random-effects network meta-analysis and ranked treatments based on the surface under the cumulative ranking (SUCRA) probabilities. Results Forty-eight trials (probiotics 6 trials) of induction therapy and 30 trials (probiotics 6 trials) of maintenance therapy were included in the analysis. In studies with probiotics concomitant treatment, mainly mesalamine, were allowed. At induction, probiotics were not superior to placebo (OR 1.43; 95%CI 0.84–2.42) and they were inferior to combined oral and topical mesalamine therapy (OR 0.28; 95%CI 0.12–0.66) and combined mesalamine and beclomethasone therapy (OR 0.27; 95%CI 0.09–0.83). On SUCRA analysis, combination therapies (SUCRA 0.92 and 0.93) were ranked the highest followed by balsalazide (SUCRA 0.71), budesonide ΜΜΧ (SUCRA 0.68), standard dose mesalamine (SUCRA 0.52), beclomethasone (SUCRA 0.50), olsalazine (SUCRA 0.41), probiotics (SUCRA 0.29), low dose mesalamine (SUCRA 0.26) and sulfasalazine (SUCRA 0.23) in terms of inducing remission. Probiotics were well tolerated. At maintenance, probiotics (OR 0.35; 95%CI 0.19–0.62) and their combination with mesalamine (OR 0.38; 95%CI 0.15–0.99) had lower rate of relapse compared with placebo, but there were no differences when compared with other treatments. On SUCRA analysis, probiotics either alone or combined with mesalamine had comparable SUCRA values to standard dose mesalamine (SUCRA 0.59) and sulfasalazine (SUCRA 0.68). The combination of oral and rectal mesalamine was superior to placebo (OR 0.10; 95%CI 0.04–0.26) and all other treatments and it was ranked highest (SUCRA 0.99). Probiotics were ranked the best tolerated option in terms of discontinuation due to adverse events (SUCRA 0.80). Conclusion Probiotics are well tolerated but they are not effective in inducing remission in active UC. They may be effective when added to mesalamine therapy in preventing relapse of quiescent UC, but large, well-designed RCTs are needed.

BackgroundVarious surgical techniques and conservative therapies are useful tools for treating proximal humerus fractures (PHFs), but it is important to understand how to properly utilize them. Therefore, we performed a systematic review and network meta-analysis to compare and rank the efficacy and safety of medical treatments for PHF.MethodsPubMed, Embase, the Cochrane Library, and the ClinicalTrials.gov databases were systematically searched for eligible randomized controlled trials (RCTs) from inception until June 2022. Conservative therapy-controlled or head-to-head RCTs of open reduction internal fixation (ORIF), intramedullary nailing (IMN), hemiarthroplasty (HA), and reverse total shoulder arthroplasty (RTSA) used for the treatment of adult patients with PHF were included. The surface under the cumulative ranking (SUCRA) probabilities were applied to compare and rank the effects of medical treatments for PHF.ResultsEighteen RCTs involving 1,182 patients with PHF were selected for the final analysis. Mostly baseline characteristics among groups were well balanced, and the imbalanced factors only included age, injury type, medial comminution, blood loss, and cognitive function in single trial. The SUCRA probabilities found that RTSA provided the best effect on the Constant-Murley score (SUCRA: 100.0%), and the disabilities of the arm, shoulder and hand (DASH) score (SUCRA: 99.0%). Moreover, HA (SUCRA: 85.5%) and RTSA (SUCRA: 68.0%) had a relatively better effect on health-related quality of life than the other treatment modalities. Furthermore, conservative therapy (SUCRA: 84.3%) and RTSA (SUCRA: 80.7%) were associated with a lower risk of secondary surgery. Finally, the best effects on the risk of complications are varied, including infection was observed with conservative therapy (SUCRA: 94.2%); avascular necrosis was observed in HA (SUCRA: 78.1%), nonunion was observed in RTSA (SUCRA: 69.6%), and osteoarthritis was observed in HA (SUCRA: 93.9%).ConclusionsThis study found that RTSA was associated with better functional outcomes, while the comparative outcomes of secondary surgery and complications varied. Optimal treatment for PHF should consider patient-specific factors.

A 2021 survey by the World Health Organization showed that 27% of the global population experiences sleep problems and that middle-aged and older adults are more likely to have sleep disorders. Sleep deprivation increases cardiovascular disease risk. This study aimed to assess the effects of aerobic exercise, resistance exercise, combined training, and yoga on the quality of sleep in middle-aged and older adults through their effects on the Pittsburgh Sleep Quality Index (PSQI) and its components. Direct and indirect comparisons were used to determine which exercise modality most effectively improves sleep quality in middle-aged and older adults. This study conducted a systematic review and frequency network meta-analysis of all randomized controlled trials comparing the effects of aerobic exercise, resistance exercise, combined training, and yoga with a control group on sleep quality in middle-aged and older adults. We included 28 studies involving 3,460 participants. According to the surface under the cumulative ranking (SUCRA) curve results, aerobic exercise was the most effective in improving total PSQI score (SUCRA = 93.2%), sleep latency (SUCRA = 96.8%), and sleep medication use (SUCRA = 77.1%). In addition, yoga was the most effective in improving sleep disorders (SUCRA = 90.4%), sleep efficiency (SUCRA = 95.9%), sleep duration (SUCRA = 93.8%), and daytime dysfunction (SUCRA = 98.3%). Aerobic exercise is the most effective exercise modality for improving PSQI total score in middle-aged and older adults. Registry: PROSPERO; Identifier: CRD42023454237. Gao X, Qiao Y, Chen Q, Wang C, Zhang P. Effects of different types of exercise on sleep quality based on Pittsburgh Sleep Quality Index in middle-aged and older adults: a network meta-analysis. J Clin Sleep Med. 2024;20(7):1193-1204.

The burden of metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis is rapidly rising globally. There are several therapeutic agents under clinical development for the treatment of cirrhosis due to MASH; however, their relative efficacy has not been systematically assessed. This systematic review and network meta-analysis was performed to compare the histological efficacy of available therapeutic agents for compensated MASH cirrhosis. PubMed and Cochrane Library databases were searched from inception to May 25, 2025, for randomised controlled trials (RCTs) evaluating pharmacological treatments in patients with biopsy-proven compensated MASH cirrhosis (F4c). The primary endpoint was fibrosis regression of at least one stage without MASH worsening, and the secondary endpoint was MASH resolution. Treatment comparisons were conducted via network meta-analysis, and ranking probabilities were estimated using the surface under the cumulative ranking (SUCRA) curve analysis. Nine RCTs with 3266 participants met the eligibility criteria. Efruxifermin was the only intervention significantly superior to placebo for ≥ 1-stage fibrosis improvement without worsening of MASH. The highest-ranked interventions for fibrosis improvement were efruxifermin (SUCRA: 77.44), cilofexor + firsocostat (SUCRA: 72.38) and aldafermin (SUCRA: 71.27). For MASH resolution, efruxifermin, semaglutide + cilofexor + firsocostat and semaglutide were significantly superior to placebo. Efruxifermin (SUCRA: 81.38), semaglutide + cilofexor + firsocostat (SUCRA: 74.07) and semaglutide (SUCRA: 63.88) had the highest probability of ranking best for MASH resolution. This network meta-analysis provides relative rank-order estimates of the histological efficacy of available pharmacological therapies for compensated MASH cirrhosis. These data may have implications for the design of future clinical trials.

Comparative efficacy and safety among different doses of tenecteplase for acute ischemic stroke: A systematic review and network meta-analysis

BackgroundMalignant pleural effusion (MPE) is a common complication in patients with advanced lung cancer that can severely compromise the quality of life and limit life expectancy. Randomized controlled trials (RCTs) have shown that Chinese herbal injections (CHIs) may be beneficial in improving quality of life. This network meta-analysis (NMA) aims to explore several CHIs used for lung cancer patients with MPE.MethodsSeven databases were systematically searched for eligible RCTs from inception to November 2021. The primary outcome was the clinical effective rate. Secondary outcomes were the improvement rate of Karnofsky performance status (KPS) score and incidence of adverse events (AEs). The Cochrane risk of bias 2 tool was used to assess the quality of included studies. Data analysis was performed using STATA 16.0 and R software 4.1.0. Both pairwise meta-analysis and Bayesian NMA were conducted. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Evidence grading was evaluated using the Confidence in Network Meta-Analysis online software (https://cinema.ispm.unibe.ch/).ResultsA total of 44 studies involving 2,573 patients were included. The combined Huachansu injection (HCS) with intrapleural cisplatin (cis-diamminedichloro-platinum, DDP) had the highest probability of improving the clinical effective rate (SUCRA, 84.33%). The Kangai injection (KA) combined with DDP had the most improvement rate of KPS score (SUCRA, 80.82%), while the Fufangkushen injection (FFKS) alone was more likely to reduce AEs including gastrointestinal reactions (SUCRA, 89.92%), leukopenia (SUCRA, 91.85%), and chest pain (SUCRA, 98.17%). FFKS combined with DDP ranked the best in reducing the incidence of fever (SUCRA, 75.45%).ConclusionsOur NMA showed that CHIs alone or combined with DDP could improve clinical effectiveness and quality of life and reduce AEs, compared to DDP alone. HSC and KA, combined with DDP, may be the most effective considering clinical effective rate and improvement of KPS score, respectively. FFKS, either used alone or in combination therapy with DDP, may be the best in reducing AEs. However, high-quality RCTs with larger sample sizes are needed to further support the evidence.Systematic review registrationPROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021285275.

Objective: The purpose of this study was to evaluate the rehabilitation effects of four common interventions (BA: body acupuncture, SA: scalp acupuncture, TA: tongue acupuncture, SLT: speech and language training) used singly or in combination with language function in patients with post-stroke aphasia (PSA). Design: We systematically searched PubMed, EMBASE, Cochrane Library, Ovid, Web of Science, CNKI, VIP, and Wanfang from inception to 4 April 2022. Only randomized controlled trials that met the eligibility criteria were included. The risk of bias of studies included was assessed using the RoB-2 tool. The effects of different interventions for PSA patients were analyzed and ranked according to the surface under the cumulative ranking (SUCRA) analysis. Results: A total of 69 RCTs were included, including 5097 total participants. According to the results of the SUCRA curves, TA ranked highest in improving overall efficacy (SUCRA = 86%) and oral expression score (SUCRA = 86%). BA + TA ranked highest in increasing the comprehension score (SUCRA = 74.9%). BA + SA ranked highest in improving aphasia patients’ repetition (SUCRA = 89.2%) and denomination scores (SUCRA = 93%). Conclusions: Results of our network meta-analysis and SUCRA ranking showed that tongue acupuncture, body acupuncture + tongue acupuncture, and body acupuncture + scalp acupuncture seem to offer better advantages than other interventions for improving the language function in PSA patients. Moreover, it is noteworthy that our results are limited to the Chinese population, since all eligible studies are from China. Future well-designed studies with larger sample sizes and more ethnic groups are required to further verify these findings.

Efficacy and safety of frontline regimens for older transplant-ineligible patients with multiple myeloma: A systematic review and meta-analysis

ObjectivesThis study aimed to compare the effects of different exercise interventions on brain-derived neurotrophic factor (BDNF) levels in patients with neurodegenerative diseases and to explore regulatory factors.MethodsSearched PubMed, Scopus, Web of Science Core Collection, CNKI and Cochrane Library databases up to March 15, 2025. Bayesian network meta-analysis was conducted using R software, and meta-regression analyzed the moderating effects of training period and frequency.Results42 randomized controlled trials covering 1482 patients were included. The Surface Under the Cumulative Ranking (SUCRA) indicated that stretching training (SUCRA = 78.92) and high-intensity interval training (SUCRA = 69.73) were ranked higher than other exercise modalities and exhibited more favorable effect on BDNF enhancement, although neither demonstrated statistically significant superiority over the blank control. In contrast, combined training (SUCRA = 35.58), aerobic training (SUCRA = 35.17), and resistance training (SUCRA = 12.98) showed relatively lower potential for BDNF enhancement (blank control SUCRA = 67.62). Meta-regression analysis showed that the effect of combined training was significantly and positively correlated with intervention period (P < 0.01).ConclusionsStretching training and high-intensity interval training appear promising for enhancing BDNF level in neurodegenerative diseases, while isolated aerobic or resistance training show relatively lower potential on improving BDNF. Combined training requires sustained implementation for significant benefits. These findings highlight the importance of tailored exercise prescription for improving BDNF levels.

Introduction: Secondary progressive multiple sclerosis (SPMS) represents a disabling stage of multiple sclerosis (MS) with limited treatment options. The evidence regarding the effectiveness of disease-modifying therapies (DMTs) in SPMS remains uncertain. This study evaluated the comparative efficacy and safety of DMTs in SPMS using a network meta-analysis (NMA). Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane databases was conducted from January 2000 to May 2025 to identify randomized controlled trials (RCTs) involving adults with SPMS. The outcomes of interest were confirmed disability progression (CDP) and serious adverse events (SAEs). A frequentist random-effects NMA was performed to estimate odds ratios (ORs) and rank treatments using surface under the cumulative ranking (SUCRA) values. Results: Seven RCTs involving 5,872 patients with SPMS were included in the final analysis. Approximately 60% of participants were women, with a mean age ranging from 39.9 to 48.9 years and a baseline Expanded Disability Status Scale (EDSS) score between 3.0 and 6.5. Tolebrutinib (OR 0.66, 95% confidence interval [CI] 0.50–0.87; SUCRA 0.713) and siponimod (OR 0.72, 95% CI 0.57–0.92; SUCRA 0.606) significantly reduced 6-month CDP compared with placebo. At 3 months, interferon beta-1b (OR 0.64, 95% CI 0.43–0.97; SUCRA 0.663), tolebrutinib (OR 0.73, 95% CI 0.56–0.96; SUCRA 0.554), and siponimod (OR 0.76, 95% CI 0.61–0.96; SUCRA 0.497) showed significant benefits. In terms of safety, tolebrutinib was associated with a higher risk of SAEs (OR 1.53, 95% CI 1.04–2.25), whereas the other agents had safety profiles comparable to placebo. Conclusion: This NMA found that tolebrutinib, IFN-β-1b, and siponimod delay disability progression in SPMS, with IFN-β-1b and siponimod remaining the most practical options. The conclusions should be interpreted cautiously given bias risk, moderate evidence certainty, limited safety data, and clinical heterogeneity.

Identifying the superior surgical procedure for endometrial polypectomy: A network meta-analysis

BackgroundThere are many surgical methods of sphincter preservation in treating complex anal fistula, but the therapeutic effects of each operation are different. Therefore, this study aimed to compare the impact of other treatment methods through a network meta-analysis to evaluate the best sphincter preservation method for treating complex anal fistula.MethodsWe searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Journal Database, and the Wanfang Database to collate randomized controlled trials on sphincter-preserving surgery for complex anal fistula.ResultsA total of 29 articles were included in this meta-analysis. The cure rates showed no statistically significant differences between any two interventions (P > 0.05). The recurrence rate results showed that the rate of patients after Fistulectomy was higher than others (P < 0.05). The incidence rate of complications showed that the incidence rate after fistulectomy treatment was higher than that of others (P < 0.05). The surface under the cumulative ranking (SUCRA) was used to arrange their advantages and disadvantages, and a larger SUCRA value indicates that the intervention may be more effective. The results showed that TROPIS may have the highest cure rate (SUCRA = 78.6%), stem cell transplantation (SCT) may have the lowest recurrence rate (SUCRA = 85.5%), and imLIFT may have the least complications (SUCRA = 88.2%).ConclusionAccording to the existing literature data, for patients with complex anal fistula, TROPIS may be the surgical method with the highest cure rate, SCT may be the treatment method with the lowest recurrence rate, and imLIFT may be the surgical method with the lowest incidence of postoperative complications.Systematic Review RegistrationPROSPERO, identifier: CRD42020221907.

To compare the efficacy and safety of silodosin-a highly selective α₁A-adrenoceptor antagonist-with placebo, tamsulosin, naftopidil, and alfuzosin in men with benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS). We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials retrieved from EMBASE, PubMed, Cochrane Library, ScienceDirect, and Web of Science until February 2024. Studies were selected based on predefined PICOS criteria. Two reviewers independently extracted data and assessed risk of bias using the Cochrane RoB tool. A frequentist random-effects NMA was performed; heterogeneity was evaluated with I 2 statistic, and publication bias was assessed using Egger's and Begg's tests. Treatment rankings were based on surface under the cumulative ranking (SUCRA) probabilities. Twenty-five RCTs (n=6,831) were included. NMA showed silodosin significantly improved voiding symptoms versus tamsulosin (MD=0.52, 95% CI: 0.01-0.56) and total IPSS versus naftopidil (P < 0.001). Silodosin monotherapy ranked highest for symptom improvement (SUCRA: 93.3-97.5%). However, it was associated with higher overall adverse events versus tamsulosin (RR=1.26, P < 0.001) and significantly increased risk of retrograde ejaculation versus placebo (RR=24.94, P < 0.001). Combination therapy with tadalafil improved urinary flow (SUCRA=56.7%). Silodosin is highly effective for BPH-LUTS, particularly for voiding symptoms, but carries a elevated risk of ejaculatory dysfunction. Combination with tadalafil may enhance urinary flow. Clinicians should weigh efficacy against adverse events; further trials are needed to confirm long-term benefits.

The objective was to systematically compare the effects of speed, agility, and quickness (SAQ) training, high-intensity interval training (HIIT), and small-sided games (SSG) training on sprint and change of direction (COD) performance in soccer players through pairwise and network meta-analyses. A comprehensive search of five electronic databases (PubMed, Web of Science, Embase, Cochrane, and EBSCO) was conducted during June 2025 to identify controlled trials involving SAQ, HIIT, or SSG training interventions. Studies meeting predefined eligibility criteria underwent pairwise meta‑analysis (PMA) to calculate standardized mean differences (SMDs) against control conditions, and network meta‑analysis (NMA) to estimate comparative efficacy across all three modalities. Surface under the cumulative ranking (SUCRA) values were computed to establish an intervention hierarchy. Twenty-three studies involving 914 participants were included. Pairwise meta-analysis (PMA) results showed that, compared with the control groups, only SAQ training significantly improved sprint (SMD = –1.23, 95% CI: –1.85 to –0.60, p&amp;lt;.001) and COD performance (SMD = –1.09, 95% CI: –1.69 to –0.48, p&amp;lt;.001). In network meta-analysis (NMA), SAQ ranked highest for sprint performance (SUCRA = 98.2%), followed by Conventional Training (CT) (57.0%), HIIT (36.7%), and SSG (8.1%). For COD performance, HIIT (SUCRA = 67.3%) ranked highest, followed by SSG (65.9%), SAQ (63.1%) and CT (3.7%). SAQ training demonstrated the most robust enhancement of sprint speed among the examined modalities. Although direct comparisons indicated benefits of SAQ for COD performance, its superiority was not confirmed in the network analysis, likely due to limited head-to-head data and study heterogeneity. A training strategy centered on SAQ, with supplemental HIIT and SSG components, is therefore recommended to optimize both sprint and COD adaptations in soccer players. PROSPERO: CRD42024583586

A Systematic Review With Pairwise and Network Meta-analysis of Closed Reduction Methods for Anterior Shoulder Dislocation.