This study aimed to evaluate and rank the effectiveness of pharmacological and non-pharmacological interventions for managing dyspnea severity, anxiety, exercise capacity, and health-related quality of life (HRQoL) in patients with advanced cancer.

A comprehensive search of PUBMED, HINARI, CENTRAL, and ResearchGate was conducted to identify randomized controlled trials (RCTs) published up to March 2024. Network meta-analysis was performed to compare interventions, calculating mean differences (MD) and standardized mean differences (SMD) with 95% confidence intervals (CI). P-scores were used to rank the interventions. Risk of bias was assessed using the Cochrane tool, and the quality of evidence (QOE) was evaluated using the GRADE framework.

A total of 42 RCTs, encompassing 3,832 patients, were included in the analysis. Among the evaluated interventions, high-flow nasal cannula (HFNC) demonstrated the most significant improvement in dyspnea relief (SMD = -1.91; 95% CI: -3.32 to -0.49; QOE: moderate), followed by acupressure/reflexology (SMD = -1.04; 95% CI: -2.02 to -0.06; QOE: very low). Activity rehabilitation was the only intervention that significantly reduced anxiety compared to the control group (SMD = -0.64; 95% CI: -0.97 to -0.32; QOE: very low). While all interventions showed trends of improving exercise capacity, none reached statistical significance. Notably, acupressure/reflexology significantly enhanced HRQoL (SMD = 1.55; 95% CI: 0.22 to 2.88; QOE: moderate).

Non-pharmacological interventions, particularly HFNC and acupressure/reflexology, were more effective than pharmacological approaches in improving dyspnea relief and HRQoL. However, the low quality of evidence underscores the need for high-quality, large-scale trials to confirm these findings and refine treatment strategies for dyspnea management in advanced cancer patients.

PROSPERO CRD42023479041.

Despite limited breakthroughs in COPD pharmacotherapy, recent trials have shown promising results for biologics in COPD patients. However, robust evidence synthesis in this area is currently lacking.

We conducted a systematic review of MEDLINE, EMBASE, and Cochrane CENTRAL from inception to July 17, 2024, to identify randomized trials of biologic medications in patients with COPD. We performed a random effects frequentist network meta-analysis and present the results using relative risk (RR) and 95% confidence intervals (CI). We used the GRADE framework to rate the certainty of the evidence. Outcomes of interest included exacerbations, change in FEV1, change in quality of life, and serious adverse events.

Dupilumab reduced exacerbations as compared to placebo (RR 0.68 [95% CI 0.59 to 0.79]) (high certainty). Benralizumab (RR 0.89 [95% CI 0.78 to 1]), itepekimab (RR 0.81 [95% CI 0.61 to 1.07]) and tezepelumab (RR 0.83 [95% CI 0.61 to 1.12]) may reduce exacerbations as compared to placebo (all low certainty). Dupilumab probably reduced exacerbations more than mepolizumab (RR 0.74 [95% CI 0.62 to 0.89]) (moderate certainty). Dupilumab may reduce exacerbations more than tezepelumab (RR 0.82 [95% CI 1.14]) (low certainty). For all patients, no treatment improved FEV1 above the pre-specified minimal clinically important difference (MCID) of 0.1 L. Dupilumab probably has no meaningful effect on FEV1 compared to placebo (MD 0.07 [95% CI 0.02 to 0.13]) (moderate certainty). However, in the subgroup of patients with blood eosinophils ≥300/mcL, both tezepelumab (MD 0.15 [95% CI 0.05 to 0.26]) and dupilumab (MD 0.13 [95% CI 0.06 to 0.19]) probably improved FEV1 above the MCID.

Dupilumab is effective at improving patient-relevant outcomes in COPD with higher eosinophil levels. Other biological therapies, including tezepelumab, have no important effect on patient-relevant outcomes.

To comprehensively compare and rank hormone therapy for patients with perimenopausal syndrome.

A comprehensive search was conducted on PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, and Wanfang databases from inception to August 20, 2024. The quality of the included randomized controlled trials (RCTs) were measured by the Cochrane risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was applied to grade the quality of evidence in this network meta-analysis. Network plots were depicted to show direct and indirect comparisons of hormone therapy for each outcome. The influences of different hormone therapy on the outcomes were illustrated via forest plots and league tables. Rank probabilities showed the ranking of different administration routes.

Seven studies involving 704 perimenopausal syndrome patients were included. The rank probabilities suggested that oral estradiol (E2) combined with medroxyprogesterone and general health guidance had the highest likelihood to be the optimal therapy for the severity of menopausal syndrome. General health guidance combined with oral E2 was less likely to have a nausea and vomiting, and breast pain.

Oral E2 and medroxyprogesterone or general health guidance combined with oral E2 may be the effective and safe option for the management of perimenopausal syndrome.

This study evaluates and compares the effectiveness and safety of febuxostat and allopurinol in chronic kidney disease (CKD) stages 3-5 patients with asymptomatic hyperuricemia using a network meta-analysis.

A systematic review and network meta-analysis were conducted, adhering to PRISMA-NMA guidelines. Searches included PubMed, Embase, Cochrane Library, and Chinese databases up to June 2024. Randomized controlled trials (RCTs) and cohort studies were assessed for methodological rigor using GRADE.

A total of 12 RCTs and 4 cohort studies (n = 2,423 participants) were included. Febuxostat was associated with greater improvements in estimated glomerular filtration rate compared to allopurinol (MD, 4.99 mL/min/1.73 m2; 95%CI -0.65 to 10.78; certainty: low) and placebo (MD, 4.72 mL/min/1.73 m2; 95%CI 0.67 to 8.82; low). Serum uric acid reduction was also more pronounced with febuxostat (MD, -0.61 mg/dL; 95%CI -1.15 to -0.05; moderate). Safety outcomes, including major cardiovascular events and adverse events, showed no significant differences between febuxostat and allopurinol. Subgroup analyses revealed enhanced effectiveness of febuxostat at six months of treatment.

This analysis provides robust evidence that febuxostat might offers greater improvements in kidney function and uric acid levels compared to allopurinol or placebo in asymptomatic hyperuricemia with CKD stage 3-5 patients, without compromising safety. These findings can guide clinical decision-making and treatment optimization.

Chronic lower back pain (CLBP) severely affects an individual's quality of life and increases reliance on healthcare services. Previous meta-analyses have primarily examined the effects of essential oils and herbal remedies separately, without considering their combined therapeutic potential. The present meta-analysis integrated both treatment modalities to evaluate the efficacy of botanical extract-based therapies for CLBP management. A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with data extracted from randomized controlled trials (RCTs) conducted up to July 2024. A comprehensive search of several databases identified 13 RCTs that met the inclusion criteria, focusing on interventions using plant extracts, including various herbal formulations and essential oils. The meta-analysis demonstrated that botanical extract-based treatments, whether applied topically, combined with massage or administered orally, were more effective compared with a placebo in reducing pain, enhancing lumbar flexibility and extending walking duration in patients with CLBP. These findings support the role of botanical extracts as viable therapeutic options for CLBP management, emphasizing their potential integration into comprehensive pain management strategies. However, further research is necessary to explore their long-term efficacy and underlying mechanisms. The present study is registered in PROSPERO (registration no. CRD42024554015).

Metabolic dysfunction associated steatotic liver disease (MASLD) is a universal hepatic disease, and many recent randomized clinical trials (RCTs) have explored whether hypoglycemic agents may be beneficial for its treatment. This study aimed to assess the relative effectiveness of each hypoglycemic agent for MASLD.

China National Knowledge Infrastructure（CNKI）, WanFang, Weipu, PubMed, Embase, The Cochrane Library, and Web of Science Core Collection were searched for RCTs on the efficacy of hypoglycemic agents in MASLD published up to December 31, 2024. All statistical analyses were performed using R version 4.3.3. The network meta-analysis was conducted using Bayesian statistical methods.

A total of 26 hypoglycemic agents for treating MASLD in 37 studies with 2406 participants were included. Empagliflozin was most effective in improving liver stiffness measurement (LSM), whereas liraglutide showed significant benefits in body weight, body mass index (BMI), and waist circumference. Both sodium-glucose co-transporter 2 (SGLT-2) inhibitors (e.g., empagliflozin) and glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide) improved liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [GGT]), glucose metabolism (fasting plasma glucose [FPG], and homeostasis model assessment of insulin resistance [HOMA-IR]), and lipid profiles. Pioglitazone had limited benefits in these outcomes. Secondary outcomes such as inflammatory markers and fibrosis showed minimal changes.

Several hypoglycemic agents can improve laboratory and imaging indicators in adult patients with MASLD. Liraglutide is more effective than other agents, whereas empagliflozin emerged as the most effective for reducing LSM. However, different agents have different effects on the indicators; therefore, the relevant agents must be selected according to the specific patient condition.

Seagrass forest restoration programs have become a global priority to reverse their decline and regain their ecosystem services. However, defining the restoration effectiveness has remained controversial, probably due to the wide selection of procedures experienced mainly on short-term periods and local scales. Here, scientific literature from 40 years of experience on experimental works and active restoration interventions of the Mediterranean foundation seagrass Posidonia oceanica has been systematically summarized through a meta-analysis. Twenty-five variables concerning the characteristics of the site selection, procedural context, and plant performance evidenced the best practices for the seagrass restoration. Results have evidenced the importance of the correct selection of the donor and receiving site, the use of plagiotropic cuttings bearing at least three shoots, and the need of monitoring the total extent of restored area for long term periods, considering more than one plant trait to define the plant performance. Higher biological levels should be also considered to estimate the recovery of the habitat structure and ecosystem functioning.

Tranexamic acid (TXA) has been used to treat traumatic brain injury (TBI); however, no definitive conclusions have been drawn regarding its effectiveness or dosage. This study evaluated the optimal TXA dose for treating TBI using a network meta-analysis (NMA).

Five databases were searched for peer-reviewed randomized controlled trials (RCTs) published from inception to May 2024. The inclusion criteria were as follows: (1) RCTs, (2) patients older than 1 month with TBI, (3) interventions of TXA and control, (4) primary outcomes of mortality and poor neurological outcomes and secondary outcomes of vascular occlusive events, and (5) full-text peer-reviewed articles. Two reviewers independently screened and extracted the data and assessed the risk of bias. Frequency-based NMA was performed using the Grading of Recommendations, Assessment, Development, and Evaluation working-group approach.

We included 10 RCTs comprising 11,237 patients with TBI. Placebo showed higher mortality compared with that of a 2-g bolus of TXA (risk ratio, 1.53; 95% confidence interval, 1.08-2.17). Higher mortality was observed with a 1-g bolus of TXA followed by 1-g maintenance TXA compared with that of a 2-g bolus of TXA (risk ratio, 1.44; 95% confidence interval, 1.02-2.03). No significant differences in poor neurological outcomes or vascular occlusive events were observed between the treatment groups.

Placebo and a 1-g bolus followed by 1-g maintenance TXA were associated with higher mortality rates than those of a 2-g bolus of TXA. No difference in vascular occlusive events was observed with either treatment, indicating that our NMA recommends 2 g of TXA. However, the data for the 2-g bolus of TXA were from a single study, and further research is needed to draw definitive conclusions.

Systematic Review/Meta-Analysis; Level III.

Multiple pharmacological interventions have been studied for managing eosinophilic esophagitis (EoE). We performed a comprehensive systematic review and network meta-analysis of all available randomized controlled trials (RCT) to assess the efficacy and safety of these interventions in EoE in adults and children.

We performed a comprehensive review of Embase, PubMed, MEDLINE OVID, Cochrane CENTRAL, and Web of Science through May 10, 2023. We performed frequentist approach network meta-analysis using random effects model. We calculated the odds ratio (OR) with 95% CI for dichotomous outcomes.

Our search yielded 25 RCTs with 25 discrete interventions and 2067 patients. Compared with placebo, the following interventions improved histology (using study definitions) in decreasing order on ranking: orodispersible budesonide (ODB) low dose, ODB high dose, oral viscous budesonide (OVB) high dose, fluticasone tablet 1.5 mg twice daily, fluticasone 3 mg twice daily, esomeprazole, dupilumab every 2 weeks, dupilumab weekly, OVB medium dose, fluticasone 3 mg daily, cendakimab 180 mg, prednisone, swallowed fluticasone, fluticasone tablet 1.5 mg daily, OVB low dose, reslizumab 3 mg/kg, reslizumab 1 mg/kg, and reslizumab 2 mg/kg.

Network meta-analysis demonstrates histological efficacy of multiple medications for EoE. Because of the heterogeneity and large effect size, we recommend more trials comparing pharmacotherapeutic interventions with each other and placebo. An important limitation of this study is absence of clinical efficacy data due to insufficient data. Other limitations include heterogeneity of operator, population, and outcome analysis.

This systematic review and meta-analysis compares the complications and effects of photobiomodulation (PBM) therapy with sham treatment in patients with age-related macular degeneration (AMD). AMD is a leading cause of visual impairment in older adults, with current treatments primarily focusing on symptom management. PBM therapy is emerging as a potential intervention to improve clinical and anatomical outcomes in patients with AMD, necessitating a comparative analysis with sham treatment to determine its efficacy and safety.

A systematic search was conducted across PubMed/Medline, Google Scholar and the Cochrane Library from inception to January 13, 2025. Randomised controlled trials (RCTs) meeting predefined inclusion criteria were selected. Meta-analysis employed random-effects models. The risk of bias in the included studies was assessed using Cochrane tools.

A total of six studies, comprising 360 patients and 477 eyes, focused on PBM for dry AMD. Five studies were eligible for meta-analysis. Best-corrected visual acuity (BCVA) showed no significant improvement with PBM (SMD - 0.30, 95% CI - 0.85 to 0.26, p = 0.30), with high heterogeneity (I2 = 83%). Macular drusen volume also showed no significant change (SMD - 0.08, 95% CI - 0.52 to 0.37, p = 0.74), with moderate heterogeneity (I2 = 48%). A single study reported no significant effect on geographic atrophy (SMD - 0.28, 95% CI - 1.26 to 0.71, p = 0.58). Central subfield thickness (SMD 0.11, 95% CI - 0.25 to 0.47, p = 0.58) and microperimetry (SMD - 0.02, 95% CI - 0.48 to 0.44, p = 0.94) also showed no significant changes. The adverse events analysis indicated a statistically significant increase in adverse events in the sham group within 6 months (RR 0.48, 95% CI 0.29-0.82, p = 0.007), while the overall effect on adverse events was non-significant (RR 1.04, 95% CI 0.51-2.12, p = 0.91, I2 = 78%). Qualitative analysis suggested that PBM might enhance quality of life and clinical and anatomical outcomes compared to sham treatment.

This meta-analysis suggests that, to date, there are no significant clinical benefits of PBM therapy for patients with AMD. Further long-term studies are needed to establish its clinical relevance and safety profile.

The objective of this systematic review was to synthesize evidence from randomized controlled trials (RCTs) regarding the efficacy of music-based interventions (MBIs) in improving anxiety and depression in older adults with dementia.

Relevant RCTs were identified through searches in electronic databases, including PubMed, Embase, EBSCOhost, Scopus, Web of Science, APA PsycINFO, and Google. The Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) was used to evaluate the risk of bias in the included trials. A narrative synthesis of the included trials was conducted.

Nine RCTs involving 496 patients met the inclusion criteria; five trials evaluated the efficacy of MBIs for anxiety, and six trials evaluated their efficacy for depression in older adults with dementia. Of the nine trials, two reported significant improvements in anxiety in older adults with dementia following MBIs (Cohen's d = -1.71 to -2.48), while one trial reported significant improvements in depression (Cohen's d = -0.66).

Only a few trials support the efficacy of MBIs in alleviating negative emotions in older adults with dementia, as evidenced by three out of the nine trials. However, due to the small sample sizes and heterogeneity in dementia types, stages, and interventions, quantitative results were not pooled, making it challenging to draw reliable conclusions. Further validation and examination of the findings presented in this study are warranted to strengthen the evidence base for integrating MBIs into dementia care and treatment protocols.

Premature ovarian failure (POF) is becoming more common and has a major negative impact on women's mental and physical well-being. The use of acupuncture therapies to treat POF has gained popularity. However, the optimal treatment remains uncertain. This study aimed to systematically review the literature and conduct a network meta-analysis (NMA) to compare the efficacy of different acupuncture and related therapies and identify methodologic weaknesses in previous studies.

We systematically searched six databases from their inception to April 2024 for randomized controlled trials (RCTs) of acupuncture therapies for POF. We assessed methodological quality and risk of bias using the RoB 2.0 tool. The NMA was conducted using R and STATA software based on frequency theory, focusing on overall effectiveness rates and hormone levels. Additionally, we critically reviewed methodological limitations and potential biases in the studies included.

Thirty-seven eligible studies involving 2419 patients were included in this NMA. The NMA results indicated that moxibustion_catgut implantation at acupoint (MB_CIA) (P-score = 0.88; pooled mean difference (95 % CI): 22.07 (1.61-302.48)) showed the highest improvement in overall effectiveness, while warming acupuncture (WA) (0.95; -27.56 (-45.35 to -9.78)) improved follicle-stimulating hormone (FSH) levels best. WA_MB (0.85; -9.35 (-15.08 to -3.62)) and WA (P-score = 0.77) were most effective for luteinizing hormone (LH) and estradiol (E2) levels, respectively. Confidence in evidence ranged from moderate to very low, with low overall confidence. Key methodologic weaknesses included insufficient allocation concealment, lack of blinding, and small sample sizes.

Acupuncture therapies may effectively improve POF. MB_CIA, WA, and WA_MB seem to be the most effective. However, severe methodological constraints, such as insufficient randomization and a lack of blinding, may reduce trust in these results. To offer robust evidence, high-quality RCTs must overcome these limitations.

[PROSPERO], identifier [CRD42024550180].

This study aims to compare and rank the effects of acoustic stimulation on painful procedures in both preterm and full-term infants.

Six databases including Medline, Web of Science, the Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Embase, and SinoMed, were searched from inception to July, 2023. A Bayesian network meta-analysis with random effects models was performed using R software and Stata 15.0. The quality of included studies was assessed using the Cochrane Collaboration's tool. The study protocol was registered at PROSPERO (Registration number: CRD42023451102).

A total of 28 studies involving 2624 preterm and full-term infants were included and 8 acoustic stimulation interventions were identified. Regarding pain levels during procedures, maternal voice, maternal voice plus, music therapy and maternal voice plus, music therapy plus, other pharmaceutical interventions, vocal music therapy, white noise, and white noise plus were significantly more effective than control group [standardized mean differences (SMD) ranged from -2.6 to -0.87]. White noise plus was the most effective intervention for reducing pain levels during procedures (90.6 %). Regarding pain levels after procedures (no specific time mentioned), maternal voice, maternal voice plus, music therapy and maternal voice plus, music therapy plus, other pharmaceutical interventions, other non-pharmaceutical interventions, routine care, vocal music therapy, and white noise plus were significantly more effective than control group (SMD ranged from -4.7 to -1.6). Music therapy and maternal voice plus was the most effective intervention for reducing pain levels after procedures, without specific time mentioned (95.29 %). Regarding pain levels 1 min after procedures, only music therapy plus and other pharmaceutical interventions were effective (SMD ranged from -4.5 to -4.9) and music therapy plus was the most effective intervention (93.41 %). No interventions had significant effects on pain levels 3, 5, and 10 min after procedures. Regarding heart rate, only white noise plus could provide a lower increase during procedures. For oxygen saturation, only vocal music therapy could provide a lower decrease after painful procedures (no specific time mentioned). No interventions had significant effects on stabilizing respiratory rate.

This review suggests that multiple acoustic stimulation interventions are effective for pain relief in both preterm and full-term infants undergoing painful procedures. More high quality studies with larger sample size are required to generate evidence regarding the short- and long-term effectiveness and safety of acoustic stimulation interventions on painful procedures.

Concerns about the cardiovascular safety of medications used for the treatment of attention-deficit hyperactivity disorder (ADHD) remain. We aimed to compare the effects of pharmacological treatments for ADHD on haemodynamic values and electrocardiogram (ECG) parameters in children, adolescents, and adults.

For this systematic review and network meta-analysis, we searched 12 electronic databases, including Cochrane CENTRAL, Embase, PubMed, and the WHO International Clinical Trials Registry Platform, from database inception to Jan 18, 2024, for published and unpublished randomised controlled trials comparing amphetamines, atomoxetine, bupropion, clonidine, guanfacine, lisdexamfetamine, methylphenidate, modafinil, or viloxazine against each other or placebo. Primary outcomes were change in systolic blood pressure (SBP) and diastolic blood pressure (DBP), measured in mm Hg, and pulse, measured in beats per minute, at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. Summary data were extracted and pooled in random-effects network meta-analyses. Certainty of evidence was assessed with the Confidence in Network Meta-Analysis (CINeMA) framework. This study was registered with PROSPERO, CRD42021295352. Before study initiation, we contacted representatives of a UK-based charity of people with lived experience of ADHD-the ADHD Foundation-regarding the relevance of the topic and the appropriateness of the outcomes chosen.

102 randomised controlled trials with short-term follow-up (median 7 weeks [IQR 5-9]) were included, encompassing 13 315 children and adolescents (aged ≥5 years and <18 years; mean age 11 years [SD 3]; of available data, 9635 [73%] were male and 3646 [27%] were female; of available data, 289 [2%] were Asian, 1719 [15%] were Black, and 8303 [71%] were White) and 9387 adults (≥18 years, mean age 35 years [11]; of available data, 5064 [57%] were male and 3809 [43%] were female; of available data, 488 [6%] were Asian, 457 [6%] were Black, and 6372 [79%] were White). Amphetamines, atomoxetine, lisdexamfetamine, methylphenidate, and viloxazine led to increments in haemodynamic values in children and adolescents, adults, or both. In children and adolescents, mean increase against placebo ranged from 1·07 (95% CI 0·36-1·79; moderate CINeMA confidence) with atomoxetine to 1·81 (1·05-2·57; moderate) with methylphenidate for SBP; from 1·93 (0·74-3·11; high) with amphetamines to 2·42 (1·69-3·15; low) with methylphenidate for DBP; and from 2·79 (1·05-4·53; moderate) with viloxazine to 5·58 (4·67-6·49; high) with atomoxetine for pulse. In adults, mean increase against placebo ranged from 1·66 (95% CI 0·38-2·93; very low) with methylphenidate to 2·3 (0·66-3·94; very low) with amphetamines for SBP; from 1·60 (0·29-2·91; very low) with methylphenidate to 3·07 (0·69-5·45; very low) with lisdexamfetamine for DBP; and from 4·37 (3·16-5·59; very low) with methylphenidate to 5·8 (2·3-9·3; very low) with viloxazine for pulse. Amphetamines, lisdexamfetamine, or methylphenidate were not associated with larger increments in haemodynamic values compared with atomoxetine or viloxazine in either children and adolescents or adults. Guanfacine was associated with decrements in haemodynamic values in children and adolescents (mean decrease against placebo of -2·83 [95% CI -3·8 to -1·85; low CINeMA confidence] in SBP, -2·08 [-3 to -1·17; low] in DBP, and -4·06 [-5·45 -2·68; moderate] in pulse) and adults (mean decrease against placebo of -10·1 [-13·76 to -6·44; very low] in SBP, -7·73 [-11·88 to -3·58; very low] in DBP, and -6·83 [-10·85 to -2·81; very low] in pulse). Only four RCTs informed on effects in the medium term and none on the long term.

Practitioners should monitor blood pressure and pulse in patients with ADHD treated with any pharmacological intervention, and not stimulants only. Given the short duration of available randomised controlled trials, new research providing insights on the causal effects of ADHD medications on cardiovascular parameters in the longer term should be funded.

National Institute for Health and Care Research.

BackgroundPatient decision aids (PtDAs) are effective interventions to help people participate in health care decisions. Although there are quality standards, PtDAs are complex interventions with variability in their attributes.PurposeTo determine and compare the effects of PtDA attributes (e.g., content elements, delivery timing, development) on primary outcomes for adults facing health care decisions.Data SourcesA systematic review of randomized controlled trials (RCTs) comparing PtDAs to usual care.Study SelectionEligible RCTs measured at least 1 primary outcome: informed values choice, knowledge, accurate risk perception, decisional conflict subscales, and undecided.Data AnalysisA network meta-analysis evaluated direct and indirect effects of PtDA attributes on primary outcomes.Data SynthesisOf 209 RCTs, 149 reported eligible outcomes. There was no difference in outcomes for PtDAs using implicit compared with explicit values clarification. Compared with PtDAs with probabilities, PtDAs without probabilities were associated with poorer patient knowledge (mean difference [MD] -3.86; 95% credible interval [CrI] -7.67, -0.03); there were no difference for other outcomes. There was no difference in outcomes when PtDAs presented information in ways that decrease cognitive demand and mixed results when PtDAs used strategies to enhance communication. Compared with PtDAs delivered in preparation for consultations, PtDAs used during consultations were associated with poorer knowledge (MD -4.34; 95% CrI -7.24, -1.43) and patients feeling more uninformed (MD 5.07; 95% CrI 1.06, 9.11). Involving patients in PtDA development was associated with greater knowledge (MD 6.56; 95% CrI 1.10, 12.03) compared with involving health care professionals alone.LimitationsThere were no direct comparisons between PtDAs with/without attributes.ConclusionsImprovements in knowledge were influenced by some PtDA content elements, using PtDA content before the consultation, and involving patients in development. There were few or no differences on other outcomes.HighlightsThis is the first known network meta-analysis conducted to determine the contributions of the different attributes of patient decision aids (PtDAs) on patient outcomes.There was no difference in outcomes when PtDAs used implicit compared with explicit values clarification.There were greater improvements in knowledge when PtDAs included information on probabilities, PtDAs were used in preparation for the consultation or development included patients on the research team.There was no difference in outcomes when PtDAs presented information in ways that decrease cognitive demand and mixed results when PtDAs used strategies to enhance communication.

There is tentative evidence to support the analgesic effects of noninvasive brain stimulation (NiBS) in fibromyalgia (FM), but a comprehensive synthesis is lacking. This systematic review with network meta-analysis (NMA) aimed to determine the relative effectiveness of different NiBS techniques, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in FM, and to identify the optimal stimulation location and intensity/frequency.

Four databases were searched until July 9, 2023 for randomized trials (RCTs) comparing NiBS in FM. Pain was the primary outcome, while fatigue and sleep were secondary outcomes. A frequentist NMA calculated standardized-mean-differences (SMDs) for pain, with pairwise meta-analysis for fatigue and sleep. Bias was assessed with the Cochrane-risk-of-bias-tool (RoB-2.0), and evidence certainty through confidence-in-NMA.

Forty-three RCTs with 2120 participants were included. NMA showed that low frequency (LF)-rTMS (SMD: -1.20, 95% CI: -1.82 to -0.58), dual tDCS (SMD: -0.91, 95% CI: -1.82 to -0.58), and high frequency (HF)-rTMS (SMD: -0.58, 95% CI: -1.00 to -0.17) likely results in a reduction in pain intensity at the end of intervention compared with sham stimulation. For stimulation location, right dorsolateral prefrontal cortex (DLPFC)(SMD: -1.42, 95% CI: -2.69 to -0.15), bilateral DLPFC (SMD: -0.94, 95% CI: -1.82 to -0.05), and left primary motor cortex (M1)(SMD: -0.49, 95% CI: -0.85 to -0.14) likely results in reduction in pain intensity at the end of intervention, with DLPFC maintaining effects in short-term. LF-rTMS over DLPFC (SMD: -1.42, 95% CI: -2.69 to -0.15) and HF-rTMS over M1 (SMD: -0.78, 95% CI: -1.39 to -0.18) likely results in the reduction in pain intensity at the end of intervention, with LF-rTMS over right DLPFC maintaining effects in the short term. NiBS appears to be safe and may reduce fatigue and improve sleep quality.

Excitatory stimulation like HF-rTMS over M1 and inhibitory like LF-rTMS over DLPFC may yield better results.

The role of a minimally invasive approach (MI) in patients who underwent pancreatoduodenectomy (PD) remained unclear.

A systematic search of randomized controlled trials was conducted. A random-effects meta-analysis was conducted, reporting risk ratio (RR) or mean difference (MD). The primary endpoints were the morbidity, mortality, and R1 rate. The secondary endpoints were clinically relevant postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), biliary fistula, reoperation, length of stay (LOS), time to functional recovery (TFR), and readmission.

The meta-analysis includes seven studies and 1428 patients: 618 (46.5%) in the OPD arm and 711 (53.5%) in minimally invasive pancreaticoduodenectomy (MIPD). The mortality rate was 2.9% for MIPD and 2.6% for OPD (RR 1.11 [range 0.53-2.29]). The major morbidity rate was 29.4% for MIPD and 25.6% for OPD (RR 1.11 [range 0.53-2.29]). The R1 rate was 6.2% for MIPD and 7% for OPD (RR 0.80 [0.54-1.20]). The operative time, comprehensive complication index score, POPF, PPH, DGE, biliary fistula, reoperation, readmission, LOS, TFR, and harvested lymph nodes were similar. Greater than 25% of heterogeneity was observed for major morbidity, operative time, POPF, LOS, TFR, and harvested lymph nodes. No publication bias was registered.

Minimally invasive pancreaticoduodenectomy was not superior to OPD and provided marginal advantages in short-term results. Further efforts should be addressed to clarify the impact of learning curve in MIPD results and the economic sustainability of MIPD, particularly robotic approach.

Pulsed field ablation (PFA) and high-power short-duration radiofrequency ablation (HPSD) are emerging techniques for treating atrial fibrillation (AF), offering promising results compared to cryoballoon ablation (CBA). This network meta-analysis aims to evaluates the efficacy and safety of PFA, HPSD, and CBA.

PubMed, Scopus and Cochrane Central Register of Controlled Trials were systematically searched for relevant studies until October 2024. The primary outcome is freedom from atrial arrhythmia. A random-effects model was used for data synthesis, and P-scores were employed for outcome ranking. Point estimation (odd ratios) was calculated for comparisons.

Eighteen studies were included in our network meta-analysis, involving 7,071 atrial fibrillation patients. Among them, 2,023 (29%), 3,725 (53%), and 1,323 (18%) patients underwent PFA, CBA, and HPSD, respectively. PFA demonstrated a higher freedom from atrial arrhythmia, with an odds ratio (OR) of 3.63 (95% CI: 2.95-4.46) compared to CBA and 1.89 (95% CI: 1.47-2.43) compared to HPSD. However, PFA was associated with a higher risk of complications (OR = 6.54, 95% CI: 2.13-20.00) compared to CBA, while HPSD showed an insignificant association with a lower risk of complications compared to CBA (OR = 0.61, 95% CI: 0.15-2.42). PFA had the shortest procedural time (P-score: 100%), while HPSD had the longest (P-score: 0%). In contrast, HPSD had the shortest fluoroscopic time, with P-scores of 100%, 46%, and 3% for HPSD, PFA, and CBA, respectively.

PFA demonstrated higher efficacy but also a higher risk of complications compared to HPSD and CBA. HPSD showed greater efficacy with comparable safety to CBA.

To compare the diagnostic yield of various bioinformatics tools for predicting Mycobacterium tuberculosis drug resistance. A systematic review of PubMed, Embase, Scopus, Web of Science, CINAHL and the Cochrane Library was performed to identify studies reporting the effectiveness of bioinformatic tools for predicting resistance to anti-tuberculosis (TB) drugs. Data were collected and pooled using random-effects meta-analysis and Bayesian network meta-analysis (NMA). Summary receiver operating characteristic curves (SROCs) analysis were performed, and superiority index (SI) and area under the curve (AUC) were calculated. Thirty-three studies evaluated 9 different bioinformatics tools for predicting resistance to 14 anti-TB drugs. NMA and SROCs demonstrated that TBProfiler, TGS-TB, Mykrobe, PhyResSE, and SAM-TB all exhibited satisfactory performance. Remarkably, TBProfiler stood out with its exceptional ability to predict resistance to the majority of anti-TB drugs, including isoniazid (SI: 3.39 [95% confidence interval (CI): 0.20, 11.00]; AUC: 0.97 [0.95, 0.98]), rifampicin (SI: 6.38 [0.60, 15.00]; AUC: 0.99 [0.98, 1.00]), ethambutol (SI: 5.15 [0.60, 13.00]; AUC: 0.96 [0.94, 0.97]), streptomycin (SI: 3.67 [0.60, 11.00]; AUC: 0.97 [0.95, 0.98], amikacin (SI: 2.49 [0.14, 11.00]; AUC: 0.97 [0.96, 0.99]), kanamycin (SI: 2.26 [0.14, 9.00]; AUC: 0.98 [0.97, 0.99]), levofloxacin (SI: 1.87 [0.11, 9.00]; AUC: 0.95 [0.93, 0.97]), and prothionamide (SI: 2.73 [0.20, 7.00]; AUC: 0.87 [0.84, 0.90]). Meanwhile, Mykrobe demonstrated superior accuracy specifically for moxifloxacin (SI: 3.96 [0.11, 13.00]; AUC: 0.97 [0.95, 0.98]). Lastly, TGS-TB had the best efficacy in predicting resistance to pyrazinamide (SI: 12.53 [1.67, 17.00]; AUC: 0.97 [0.95, 0.98]), capreomycin (SI: 4.22 [0.08, 15.00]; AUC: 1.00 [0.98, 1.00]), and ethionamide (SI: 2.15 [0.33, 7.00]; AUC: 0.96 [0.94, 0.98]). TBProfiler, TGS-TB, Mykrobe, PhyResSE and SAM-TB have all demonstrated outstanding accuracy in predicting resistance to anti-TB drugs. In particular, TBProfiler stood out for its exceptional performance in predicting resistance to most anti-TB drugs, while TGS-TB excelled in predicting resistance to pyrazinamide and certain second-line drugs. The efficacy of SAM-TB requires further investigation to fully establish its reliability and effectiveness. To ensure the accuracy and reliability of genotypic drug susceptibility testing, bioinformatics tools should be refined and adapted continuously to accommodate novel and current resistance-associated mutations.

The effectiveness of exercise for tension-type headache (TTH) is unclear because of the complexity of exercise regimens-usually the combination of different types of exercise. We aimed to estimate the effectiveness of exercise for TTH and to test the incremental effect of each type of exercise by component network meta-analysis (CNMA).

We searched Ovid Medline, Embase, and the Cochrane Library from database inception to 25 December 2023, and a supplementary search was conducted on 10 February 2025. We included randomized controlled trials of exercise, including aerobic, resistance, and stretching exercise, in adults with TTH. The primary outcome was headache frequency, and secondary outcomes were headache intensity and medication use.

Twelve trials with 759 participants were included. There were no significant differences between exercise and usual care in reducing headache frequency at the end of treatment with very low certainty evidence (mean difference [MD] -2.30, 95% [confidence interval] CI -8.86 to 4.26), while CNMA suggested that resistance exercise significantly reduced headache frequency (incremental mean difference [iMD] -6.00, 95% CI -9.10 to -2.90) and stretching exercise increased headache frequency (iMD 4.60, 95% CI 1.20 to 8.00). Exercise was better than usual care in reducing headache intensity (MD -2.29, 95% CI -3.23 to -1.34); the CNMA suggested that no single type of exercise had the greatest effect.

Resistance exercise could be considered an effective and accessible treatment for patients with TTH. But our study was limited by heterogeneity and inconsistency of results, and more studies are warranted.

Many systematic reviews and meta-analyses (SRs/MAs) have evaluated the efficacy of biologic therapies for severe asthma. However, the overall quality of these SRs/MAs is unclear, which may influence the selection of biologics and lead to misleading clinical decisions. This umbrella review aims to objectively evaluate the overall quality of these SRs/MAs and reassess the efficacy of biologic therapies for severe asthma. Thus, this study will provide reliable evidence for clinical practice.

A systematic search will be performed in PubMed, Embase, Cochrane Library, Web of Science, Scopus and conference abstracts up to 1 March 2025. Literature screening and data extraction will be conducted according to predefined inclusion and exclusion criteria. We will evaluate the reporting quality, methodological quality and evidence quality of these SRs/MAs using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, PRISMA for Network Meta-Analysis 2015 checklist, A MeaSurement Tool to Assess Systematic Reviews 2, Cochrane Risk of Bias 1.0 and Grading of Recommendations Assessment, Development and Evaluation system. Additionally, the re-analysis of outcomes will be performed using R software (V.4.3.3).

Since this umbrella review will use publicly available data, ethics approval is not required. The results of this study will be disseminated through publication in a peer-reviewed journal.

CRD42024607393.

Diabetes mellitus is a highly burdensome metabolic disorder, affecting over 100 million people worldwide and leading to numerous complications. Among these, diabetic neuropathy is one of the most common, with approximately 60% of individuals with diabetes developing this condition. Current pharmacological treatments for diabetic neuropathy are often inadequate, providing limited efficacy and accompanied by a range of adverse effects. Non-invasive brain and nerve stimulation techniques have been proposed as potentially beneficial for diabetic neuropathy, though existing evidence remains inconclusive. This systematic review and network meta-analysis (NMA) aimed to evaluate the comparative efficacy of various non-invasive brain and nerve stimulation interventions in patients with diabetic neuropathy.

A systematic search of electronic databases was conducted to identify randomized controlled trials (RCTs) of non-invasive brain or nerve stimulation in patients with diabetic neuropathy, from inception to September 6, 2024. The primary outcome was the change in pain severity, while secondary outcomes included changes in quality of life and sleep disturbance. Acceptability was assessed through dropout rates (i.e., withdrawal from the study before completion for any reason). A frequentist-based NMA was performed, utilizing odds ratios (OR) and standardized mean differences (SMD) with 95% confidence intervals (95%CIs) as effect size measures.

The NMA, which included 15 RCTs (totaling 1,139 participants, with a mean age of 61.2 years and a mean female proportion of 53.8%), evaluated 10 experimental interventions (1 control group, 4 non-invasive brain stimulation methods, and 5 non-invasive nerve stimulation methods). The analysis revealed that only transcutaneous electrical nerve stimulation (TENS) was associated with significantly greater improvements in pain severity (SMD = - 1.67, 95%CIs = - 2.64 to - 0.71) and sleep disruption (SMD = - 1.63, 95%CIs = - 2.27 to - 0.99) compared to the control group. None of the studied interventions showed significant differences in dropout rates or all-cause mortality compared to the control group.

This study provides comparative evidence supporting the use of specific brain and nerve stimulation interventions in managing diabetic neuropathy. Future well-designed RCTs with longer treatment durations are recommended to further validate the long-term efficacy of these interventions. Trial registration PROSPERO CRD42024587660.

Patients with irritable bowel syndrome (IBS) are often interested in dietary interventions as a means of managing their symptoms. However, the relative efficacy of available diets for the management of IBS is unclear. We aimed to examine the relative efficacy of various dietary interventions in IBS.

For this systematic review and network meta-analysis we searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane Central Register of Controlled Trials from database inception to Feb 7, 2025, to identify randomised controlled trials comparing an active dietary intervention requiring changes to the intake of more than one food in IBS with either a control intervention, such as a habitual diet, sham diet, a high fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, or alternative miscellaneous dietary advice, or any other active dietary intervention requiring changes to the intake of more than one food. We assessed efficacy using dichotomous assessments of improvement in global IBS symptoms or improvement in individual IBS symptoms, including abdominal pain, abdominal bloating or distension, and bowel habit. We pooled data using a random-effects model, with the efficacy of each intervention reported as pooled relative risks (RRs) with 95% CIs. We ranked interventions according to their P-score, which measures the mean extent of certainty that one intervention is better than another, averaged over all competing interventions.

We identified 28 eligible randomised controlled trials (comprising 2338 patients) of 11 different dietary interventions compared with four control interventions, of which six (low FODMAP diet, British Dietetic Association/National Institute for Health and Care Excellence [BDA/NICE] diet, lactose-reduced diet, starch-reduced and sucrose-reduced diet, a personalised diet, and a Mediterranean diet) were studied in more than one trial. For global IBS symptoms, assessed in 28 randomised controlled trials and when considering only the dietary interventions studied in more than one trial, a starch-reduced and sucrose-reduced diet ranked first (RR of global IBS symptoms not improving 0·41 [95% CI 0·26-0·67]; P-score 0·84; two trials), a low FODMAP diet ranked fourth (0·51 [0·37-0·70]; P-score 0·71; 24 trials), and a BDA/NICE diet ranked tenth (0·62 [0·43-0·90]; P-score 0·44; eight trials), versus a habitual diet. For abdominal pain, assessed in 26 trials and when considering only the dietary interventions studied in more than one randomised controlled trial, a starch-reduced and sucrose-reduced diet ranked second (RR of abdominal pain not improving 0·54 [95% CI 0·33-0·90]; P-score 0·73; two trials), and a low FODMAP diet ranked fifth (0·61 [0·42-0·89]; P-score 0·64; 23 trials), versus a habitual diet. For abdominal bloating or distension, assessed in 26 trials and when considering only the dietary interventions studied in more than one randomised trial, only a low FODMAP diet (RR of abdominal bloating or distension not improving 0·55 [95% CI 0·37-0·80]; P-score 0·64; 23 trials) was superior to a habitual diet and ranked fourth. For bowel habit, assessed in 23 randomised trials, none of the dietary interventions was superior to any of the control interventions, but a low FODMAP diet was superior to a BDA/NICE diet (RR of bowel habit not improving 0·79 [95% CI 0·63-0·99]). All comparisons across the network were rated as low or very low confidence, except for direct comparisons between a low FODMAP diet or a starch-reduced and sucrose-reduced diet and habitual diet, both of which were rated as moderate confidence.

In terms of dietary interventions for IBS, the most evidence exists for a low FODMAP diet, but other promising therapies are emerging and should be the subject of further study.

None.

Knee osteoarthritis (KOA) is a prevalent chronic joint disease. Due to the risks of opioid use and limited pharmacological effectiveness, mind-body exercise (MBE) therapy and other non-pharmacological interventions have emerged as first-line treatments for this condition. However, the optimal MBE modes for KOA remain undetermined. This systematic review and network meta-analysis (NMA) aims to compare the efficacy of different MBE modes, including Pilates, Tai Chi, Yoga, and Qigong, in managing KOA.

We searched PubMed, Embase, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), Wanfang Database from inception to 25 April 2024. Randomized clinical trials comparing MBE interventions for pain, physical function and quality of life (QoL) in KOA patients were eligible. The Cochrane Risk-of-Bias Tool 2.0 and Grading of Recommendations, Assessment, Development & Evaluation (GRADE) approach were used to assess literature quality and evidence certainty for each outcome.

A total of 38 studies (N = 2561) were included, with 38 for pain, 36 for physical function, and 12 for QoL in the NMA. With moderate-certainty, both Pilates and TC showed significant improvements in pain reduction [Pilates: standardized mean difference (SMD) =  - 1.19, 95% confidence intervals (95% CI): - 1.92 to - 0.46; TC: SMD =  - 0.78, 95% CI - 0.97 to - 0.59] and physical function (Pilates: SMD =  - 1.37, 95% CI - 2.13 to - 0.50; TC: SMD =  - 0.85, 95% CI - 1.08 to - 0.63) compared to the usual care group, while TC [SMD =  - 0.57, 95% CI = (- 1.07 to - 0.06)] showed statistically significant efficacy in improving QoL compared to the usual care group.

There is moderate-certainty evidence that Pilates and Tai Chi may be the most effective mind-body exercises for improving pain and physical function in knee osteoarthritis, while Tai Chi may be the best for improving quality of life. These findings may help clinicians guide their prescription of exercise types with respect to treatment outcomes. The limited number of large sample studies and the few studies with low bias risk are limitations. Trial registration The protocol for NMA has been registered with PROSPERO (CRD42024531878).

Tobacco use is a global issue, and non-combustible nicotine products (NCNPs) like electronic nicotine delivery systems, nicotine pouches, snus, and nicotine replacement therapies offer potential risk/harm reduction for smokers unable or unwilling to quit. Although NCNPs are less harmful than tobacco smoking, their impact on oral health remains unclear. A systematic review and network meta-analysis will be conducted to answer the research question: What are the oral signs and symptoms associated with NCNPs as both monotherapies and combination therapies compared to each other, placebo, standard care, no drug treatment, and combustible cigarette smoking?

We will search PubMed and Scopus databases, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to August 2024. This review will focus on randomized controlled trials (RCTs) with a minimum follow-up period of 1 month, comparing any NCNPs versus placebo, standard care, no drug treatment, combustible cigarette smoking or to each other in adult smokers. Our primary outcomes will be the number of participants reporting any oral side effect, aphthous ulcers, dry mouth and mouth irritation. Studies will be excluded if they involve: non-smokers, pregnant women, individuals with mental health or neurological disorders, participants consuming alcohol or other substances. Data will be analyzed using a network meta-analysis framework, estimating odds ratios with 95% confidence intervals. Risk of bias will be determined using the Cochrane risk of bias tool-version 2.0 for included RCTs and the Confidence In Network Meta-Analysis tool will be employed to assess the confidence of evidence contributing to each network estimate.

Our findings will provide critical insights into the oral health implications of NCNPs, informing clinical and public health decisions. Results are expected by May 2025 and will be disseminated through publications and presentations to guide tobacco harm reduction strategies.

PROSPERO CRD42024565118.

This systematic review and network meta-analysis aims to investigate the comparative effectiveness of six biophysical agents, including Transcutaneous electrical nerve stimulation (TENS), interferential current (IFC), extracorporeal shockwave therapy (ESWT), therapeutic ultrasound, low-level laser therapy (LLLT), and high-intensity laser therapy (HILT) on neck pain rehabilitation.

Three bibliographic databases, PubMed, Embase, and Scopus were searched from inception to July 30, 2024. Randomized controlled trials comparing a single biophysical agent with placebo control or another biophysical agent on neck pain intensity as an outcome were selected. Two independent reviewers independently conducted study selection, data extraction, and quality assessment. The methodological quality of included randomized controlled trials was assessed using the Physiotherapy Evidence Database scale.

A total of 34 randomized controlled trials with 2141 patients with neck pain were included, and all included studies had good or above quality. A random-effects frequentist network meta-analysis, assuming a common random-effects standard deviation for all comparisons in the network. Effects of biophysical agents on neck pain intensity were estimated as mean differences with 95% confidence intervals. League tables were created to display the relative degree of neck pain for all comparisons among the six biophysical agents.

This study suggests that rehabilitation of neck pain using biophysical agents should be prioritized in the following ranks: HILT, ESWT, IFC, TENS, LLLT, and therapeutic ultrasound. The results clarified how different biophysical agents may influence neck pain outcomes and provided proper evidence to inform clinicians to select biophysical agents prudently for neck pain management.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Primary objective To evaluate the relative benefits and harms of therapy with glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter-2 inhibitors (SGLT2i), and their combination in adults with type 2 diabetes mellitus. Secondary objectives To determine the relative rankings of GLP-1RA, SGLT2i, and their combination, according to their comparative efficacy for the critical outcomes identified in this review through a network meta-analysis.

Sepsis affects approximately 50 million people worldwide, resulting in 11 million deaths annually. Conflicting results and insufficient evidence comparing performance biomarkers exist. The study aimed to comprehensively compare available biomarkers and clinical scores for detecting sepsis since its redefinition in 2016 with this systematic review and Bayesian diagnostic test accuracy network meta-analysis.

We conducted searches in the PubMed, EMBASE, and Scopus databases between January 2016 and December 2023. Eligible studies assessed the diagnostic accuracies of biomarkers, the quick Sequential Organ Failure Assessment (qSOFA) score, or Systemic Inflammatory Response Syndrome (SIRS) criteria in detecting sepsis. Bivariate hierarchical random effects arm-based beta-binomial models were used for quantitative synthesis (PROSPERO Registration Number: CRD42018086545).

We included 78 studies representing 34,234 patients and compared qSOFA score, SIRS criteria alongside seven of the most studied biomarkers: procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), presepsin (cluster of differentiation 14 subtypes), CD64, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), and lipopolysaccharide-binding protein (LBP). CD64 demonstrated the highest superiority index, followed by sTREM-1 and presepsin (diagnostic odds ratio: 20.17 vs 18.73 and 10.04, 95 % credible interval [CrI]: 8.39-38.61 vs 1.31-83.98 and 6.71-14.24; quality of evidence: moderate vs low and low). Multivariable meta-regression analysis identified significant sources of heterogeneity, including study design, proportion of sepsis, sample size, and the risk of bias (patient selection).

The best diagnostic accuracy for sepsis was shown by CD64, with a moderate quality of evidence. Compared to CD64, sTREM-1 and presepsin provided suboptimal and low evidence. These biomarkers were more effective at identifying updated sepsis than clinical scores. We recommend re-considering the addition of biomarkers in screening for sepsis or sepsis-related conditions, as this could lead to more accurate and timely decisions for future clinical interventions.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with a median age at diagnosis of 68 years. The outcomes in older or unfit AML patients on intensive chemotherapy are poor, and thus, it is necessary to explore alternative strategies. In recent years, non-intensive therapies have transformed the standard of care for this population. Despite the increasing number of randomized clinical trials (RCTs) and cohort studies in this area, the optimal treatment approach remains unclear.

We sourced four databases, PubMed, Embase, Cochrane, and Web of Science, until July 07, 2024, to identify all Phase II/III randomized controlled trials (RCTs) and cohort studies evaluating low-intensity treatments for older AML patients. Overall survival (OS), recurrence-free survival (RFS), complete remission (CR), complete remission with incomplete hematologic recovery (CRi), overall response rate (ORR), and adverse events (AEs) graded ≥ 3 were analyzed using a Bayesian fixed-effects network meta-analysis (NMA).

A total of 4920 patients across 26 trials were included. In terms of improving OS, AZA + VEN, LDAC + glasdegib, and LDAC + VEN (SUCRA = 0.936, 0.898, and 0.718, respectively) were the most effective treatments. For CR, ORR, and CRi, AZA + VEN ranked highest among all therapies (SUCRA = 0.836, 0.911, and 0.829, respectively).

This systematic review and network meta-analysis suggest that AZA + VEN is superior to the current standard of care, particularly in improving OS, CR, ORR, and CRi. LDAC + glasdegib also demonstrated promising efficacy and warrants further investigation.

In recent years, many pharmacological agents for the prevention of delirium have emerged; however, the efficacy of these agents in preventing delirium remains unclear.

To compare and rank the efficacy of different pharmacological interventions for the prevention of delirium.

A systematic review and network meta-analysis.

Relevant randomized controlled trials on drug prevention of delirium were extracted from three electronic databases. A network meta-analysis was then conducted to assess the relative efficacy of drug interventions in preventing delirium. The quality of the data was evaluated using the Cochrane Risk of Bias tool.

A total of 80 randomized controlled trials on drug interventions were included in the final analysis. Treatment with dexmedetomidine can prevent delirium.

Dexmedetomidine treatment can prevent delirium and reduce patient suffering. Healthcare professionals should be encouraged to use dexmedetomidine for delirium prevention.

This network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to identify effective initial conservative treatment strategies for patients with temporomandibular joint disorders (TMD).

RCTs comparing treatment options for TMD published between January 2000 and July 2021 were retrieved from the databases of PubMed and Embase via a comprehensive electronic search. Patients diagnosed with myalgia (muscle pain) or arthralgia (joint pain) according to pain-related Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were eligible for inclusion. Twelve treatment options and a placebo were included in the mutual comparisons. The risk of bias was assessed using Risk of Bias 2.0. Forest plots of direct comparisons between individual studies were created using MetaInsight. NMA was performed using R statistical software (netmeta).

Twenty-four RCTs involving 1336 patients assessing pain and 12 RCTs involving 614 patients assessing maximal mouth opening were identified. Low-level laser therapy (standard mean difference [SMD]: -2.12, 95% confidence interval [CI]: -3.18, -1.06), self-exercise (SMD: -1.51, 95% CI: -2.82, -0.2), and stabilization splints (SMD: -1.16, 95% CI: -2.02, -0.29) were effective in improving pain; however, the certainty of evidence was very low. Self-exercise (SMD: 0.71, 95% CI: -0.58, 2.01), stabilization splints (SMD: 0.65, 95% CI: -0.09, 1.39), and low-level laser therapy (SMD: 0.63, 95% CI: -0.34, 1.6) were effective in improving maximal mouth opening; however, the certainty of evidence was very low.

Stabilization splints, self-exercise, and low-level laser therapy may be effective in the initial treatment of TMD.

Hormone pre-treatment is still used before assisted reproductive technique (ART) in endometriotic women, but evidence supporting this recommendation is conflicting.

To evaluate whether hormone pre-treatment with gonadotropin-releasing hormone (GnRH) agonists or progestogens could improve fertility in women with endometriosis undergoing ART.

MEDLINE, LILACS, EMBASE, Scielo.br, PROSPERO, Cochrane at the CENTRAL Register of Controlled Trials, conference abstracts, and international controlled trials registries were searched without temporal, geographic, and language limitations.

Randomized controlled trials that enrolled infertile women with endometriosis undergoing in vitro fertilization/intracytoplasmic sperm injection after the application of a stimulation protocol with hormone pre-treatment were selected and included.

We conducted a network meta-analysis based on the random-effects model for mixed multiple treatment comparisons to rank the available hormone pre-treatment by the surface under the cumulative ranking curve area (SUCRA) following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension statement for network meta-analyses. Quality assessment was carried out using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Egger test and funnel plot analysis were used for publication bias assessment. The primary outcome was clinical pregnancy rate (CPR). Secondary outcomes were live birth rate (LBR), pregnancy loss rate (PLR), and implantation rate (IR).

Nine studies with 2087 women were included. Ultralong (3 months GnRH agonist) (SUCRA 24.5%) and long protocols (1 month GnRH agonist) (SUCRA 24.9%) as well as progestins (SUCRA 28.8%) showed similar results to no treatment (SUCRA 21.8%) in terms of post-ART CPR. Regarding the LBR, no treatment (SUCRA 50.0%) showed highest rates relative to progestins (SUCRA 7.0%), and long (SUCRA 36.6%) and ultralong (SUCRA 6.4%) protocols. For PLR, no treatment (SUCRA 57.9%), followed by long protocol (SUCRA 18.4%), ultralong protocol (SUCRA 12.3%), and progestins (SUCRA 11.4%) showed the greatest degree of reduction. The long (SUCRA 45.0%) and ultralong (SUCRA 39.5%) protocols seemed more effective in increasing IR than did than progestins (SUCRA 15.5%).

The increased number of implanted pregnancies using a GnRH agonist protocol does not lead to higher clinical pregnancies or live births. Currently, there is no indication for hormone pre-treatment before ART in women with endometriosis as it does not increase fertility chances.

Cerebellum has been a emerging target for non-invasive brain stimulation (NIBS) on post-stroke patients in recent years. While research is emerging on the impact of cerebellar repetitive transcranial magnetic stimulation (rTMS) on post-stroke patients, and its integrated effect remain unclear.

The objective of this review is to evaluate the efficacy of cerebellar rTMS on stroke rehabilitation.

We searched PubMed, EMBASE, and Web of Science databases from inception to 31 March 2024 for randomized controlled trials (RCTs) and case studies reporting effects of cerebellar rTMS on patients with stroke.

This review included 18 studies (n = 638 participants), consisting of 14 RCTs and 4 case reports. A total of 6 studies focused on post-stroke dysphagia, while 12 studies investigated post-stroke motor dysfunction. Comparative analysis between treatment and control groups revealed statistically significant improvements in swallowing function, as measured by the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) (P = 0.02), the Penetration Aspiration Scale (PAS) (P < 0.001), and the Standardised Swallowing Assessment (SSA) (P < 0.001). Moreover, cerebellar rTMS treatment showed significant enhancements in balance abilities and activity of daily living among stroke patients, as indicated by significant increases in the Berg Balance Scale (BBS) (P = 0.003) and the Barthel Index (BI) (P = 0.04) compared to the control group.

Existing evidence suggests that cerebellar rTMS holds promise in mitigating post-stroke swallowing dysfunction and motor dysfunction. Stimulation by cerebellar rTMS appears to be an efficacious technique for enhancing stroke rehabilitation.

Small subcortical infarction (SSI) accounts for approximately 25% of ischemic strokes and shares a comparable recurrence rate of cardiovascular events with other stroke subtypes. This study aimed to evaluate the efficacy and safety of various antiplatelet for secondary prevention of SSI by network meta-analysis (NMA).

We systematically searched Medline, Embase, Cochrane Library, and Web of Science from inception to October 2024 for randomized controlled trials (RCTs). Efficacy outcomes included: incidence of major adverse cardiovascular events (MACEs), rates of any stroke and ischemic stroke recurrence. Safety outcomes included: incidence of intracranial hemorrhage, severe bleeding, any bleeding events, and mortality.

A total of 24 RCTs involving 47,507 SSI patients were included in systematic review. The NMA included 19 RCTs (39,137 patients). The NMA demonstrated that Cilostazol showed the best efficacy in preventing MACEs (surface under the cumulative ranking curve (SUCRA): 90.0%). cilostazol significantly reduced the incidence of MACEs compared to aspirin (OR, 0.66; 95% CI, 0.49-0.89), ticlopidine (OR, 0.65; 95% CI, 0.43-1.00), dipyridamole (OR, 0.61; 95% CI, 0.42-0.90), vorapaxar (OR, 0.51; 95% CI, 0.35-0.74), Sarpogrelate (OR, 0.62; 95% CI, 0.40-0.97), and placebo (OR, 0.51; 95% CI, 0.37-0.71). Regarding safety, aspirin plus clopidogrel and vorapaxar was associated with a significantly increased risk of severe bleeding events compared to the control.

Cilostazol may be the most effective agent for preventing cardiovascular event recurrence. Aspirin plus clopidogrel and vorapaxar may be not recommended due to heightened bleeding risks.

International prospective register of systematic reviews (PROSPERO) - CRD42024607819.

Poor sleep quality not only diminishes people's quality of life and work efficiency but is also closely associated with various diseases. A reasonable exercise regimen can improve sleep quality to some extent, but there is a lack of comparative studies on the effects of different types of exercise, especially varying exercise doses, on sleep quality.

To systematically evaluate the effects of different exercise modalities and doses on sleep quality.

A search was conducted in PubMed, Web of Science, EBSCO, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases for randomized controlled trials (RCTs) on the effects of different exercise modalities on sleep quality, from database inception to November 2024. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Network meta-analysis and dose-response analysis were performed using Stata 16.0 and R software with a random-effects model.

A total of 86 RCTs involving 7,276 participants were included. Six types of interventions were assessed: Aerobic Exercise (AE), Resistance Training (RT), Combined Aerobic and Resistance training (AE + RT), Yoga, Pilates, and Traditional Chinese Sports (TCS). The network meta-analysis results showed that compared to the control group, AE (SMD = -1.21, 95% CI: -1.50, -0.91, P < 0.01), RT (SMD = -1.12, 95% CI: -1.80, -0.44, P < 0.01), AE + RT (SMD = -1.11, 95% CI: -1.56, -0.66, P < 0.01), YOGA (SMD = -0.82, 95% CI: -1.22, -0.42, P < 0.01), Pilates (SMD = -1.65, 95% CI: -2.42, -0.88, P < 0.01), and TCS (SMD = -0.94, 95% CI: -1.28, -0.60, P < 0.01) all significantly improved sleep quality. The cumulative ranking probability (SUCRA) ranking showed that Pilates (91.7%) was the most effective, followed by AE (69.7%), AE + RT (59.4%), RT (58.6%), TCS (40.5%), and YOGA (30.1%). Additionally, the relationship between exercise dose and sleep quality was nonlinear, following a U-shaped curve. The overall optimal exercise dose for improving sleep quality was 920 MET-min/week. The optimal doses varied across exercise types, ranging from 390 MET-min/week for Pilates to 1,100 MET-min/week for aerobic exercise.

This study provides strong support for non-pharmacological interventions to improve sleep quality. For individuals aiming to improve their sleep through exercise, Pilates and aerobic exercise are recommended as the preferred options. Additionally, controlling the exercise dose within the optimal range (e.g., 920 MET-min/week) can significantly enhance the intervention effect.

Not applicable.

Deep brain stimulation (DBS) and infusion therapies are effective treatments for the motor complications of Parkinson's disease (PD), but less established is their role in fall prevention. This systematic review and network meta-analysis (NMA) aimed to evaluate the risk of falls associated with advanced therapies in PD.

Following PRISMA-NMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-analyses) guidelines, we searched PubMed, Medline, Embase and CINAHL up to 20 March 2024. Eligibility criteria based on PICOS (Population Intervention Control Outcome Study design) framework were used for DBS of the subthalamic nucleus (STN) or globus pallidus pars interna (GPi), or infusion therapies, compared with best medical treatment (BMT) or sham stimulation. Pairwise meta-analysis was conducted using RevMan V.5.4, and NMA using the netmeta package in R software.

Fourteen studies were included. A higher number of falls were observed in the DBS group compared with BMT, although the difference was not significant. Sensitivity analysis excluding a heterogeneity-contributing study showed a significantly higher fall risk in the DBS group (Risk Ratio (RR)=2.74, 95% CI 1.60, 4.67, p=0.0002). Subgroup analyses indicated that levodopa-carbidopa intestinal gel tended towards increased fall risk, while continuous subcutaneous infusion of (fos)levodopa (CSCI) significantly decreased risk with high certainty of evidence. NMA showed CSCI as the most effective in reducing falls, while STN DBS was associated with the highest risk.

DBS, especially targeting the STN, may increase fall risk compared with other advanced non-DBS procedures. While LCIG might not alter fall risk, preliminary evidence suggests that CSCI positively affects fall prevention.

CRD42023420637.

Residual sleepiness can occur in adult patients with obstructive sleep apnea (OSA) despite adequate treatment with continuous positive airway pressure (CPAP). Various wake-promoting agents (WPAs) have been shown to reduce residual sleepiness in CPAP-treated patients with OSA. This systematic review and network meta-analysis aimed to compare the efficacy and safety of WPAs in this setting.

We searched MEDLINE, Scopus, and ClinicalTrials.gov up to 9 January 2025 for randomized controlled trials (RCTs) examining WPAs for treating sleepiness in patients with OSA. Included were all RCTs that explored the efficacy and/or safety of any approved WPAs (i.e., modafinil, armodafinil, solriamfetol, or pitolisant) in patients with OSA (aged ≥ 18 years) treated with CPAP but who are still sleepy [Epworth sleepiness scale (ESS) score ≥10]. Studies that were conducted in patients whose comorbidities cause daytime somnolence [i.e., psychiatric conditions (other than depression), other sleep disorders, medical or surgical conditions], open label extension studies, and studies published in a language other than English were excluded. The primary outcomes included ESS, maintenance of wakefulness test (MWT), and adverse events. Two authors independently assessed the risk of bias using the revised Cochrane risk-of-bias tool for randomized trials 2.0.

In total, 14 RCTs studying four WPAs (total N = 2969) including modafinil (six RCTs; 200-400 mg/day), armodafinil (four RCTs; 150-250mg/day), solriamfetol (two RCTs; 37.5-300 mg/day), and pitolisant (two RCTs; 5-40 mg/day) were included. Solriamfetol, modafinil, and armodafinil were efficacious in reducing subjective sleepiness as measured by ESS [mean difference (95% confidence interval) at ≤ 4 weeks: -3.84 (-5.60, -2.07), -2.44 (-3.38, -1.49), and -2.41 (-3.60, -1.21) for solriamfetol, modafinil, and armodafinil, respectively; at > 4 weeks: -4.11 (-6.14, -2.08), -2.88 (-3.85, -1.91), -2.46 (-3.68, -1.24) for solriamfetol, armodafinil, and modafinil, respectively] and clinical global impression of change, as well as the objective MWT [at ≤ 4 weeks: 11.66 min (9.70, 13.61), 3.61 min (2.48, 4.73), and 2.52 min (1.27, 3.76) for solriamfetol, modafinil, and armodafinil, respectively; at > 4 weeks: 10.34 min (4.16, 16.52) for solriamfetol]. Pitolisant showed later improvements in ESS [at > 4 weeks: -2.70 (-3.66, -1.73)], with limited data on MWT. Sensitivity analyses restricted to U.S. Food and Drug Administration-approved solriamfetol dosages (37.5-150 mg/day) still showed higher efficacy, but lower anxiety risk.

Among all WPAs, solriamfetol demonstrated the highest efficacy on ESS and MWT, with the latter being significant. Modafinil demonstrated the best clinician impression, albeit not statistically significant. All four WPAs were associated with a low risk of serious or adverse events.

PROSPERO registration number, CRD42022359237.

Several studies have indicated that transcutaneous electrical nerve stimulation, functional electrical stimulation, neuromuscular electrical stimulation and electroacupuncture exhibit certain therapeutic effects in the treatment of rheumatoid arthritis (RA). However, definitive proof of the effectiveness of different types of electrical stimulation in relieving the different symptomatic manifestations of RA is required. This study aims to analyse the efficacy (health assessment questionnaire, visual analogue scale, etc), safety (adverse reactions) of electrical stimulation for functional impairment (morning stiffness and decreased muscle strength) and pain (joint tenderness and swelling) of RA, and to explore their comparative advantages and potential benefits for patients.

We will conduct a systematic and comprehensive search of eight databases, and the search will proceed from the beginning to 5 September 2024. Two reviewers will independently screen the retrieved literature to determine the final included studies. Two reviewers will independently assess the risk of bias for all included eligible studies using the Cochrane Risk of Bias tool (V.2.0). Data synthesis will be performed using a random-effects model for network meta-analysis to compare the efficacy and safety of different electrical stimulations. The surface under the cumulative ranking curve will be used to demonstrate the probability of the benefits and harms of interventions. Funnel plots will be used to detect potential publication bias and small sample study effects. The strength of the evidence will be assessed through the Grading of Recommendations, Assessment, Development and Evaluation framework.

Our study data comes from public databases, and the entire study does not directly involve patients and the public, so ethical approval is not required. The final study results will be peer-reviewed and published in a journal.

CRD42024586835.

Perioperative anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) immune checkpoint inhibitors improve outcomes, but optimal selection between agents remains debated. We compared the efficacy and safety of anti-PD-1 versus anti-PD-L1 in neoadjuvant/adjuvant settings.

PubMed, Embase, Cochrane CENTRAL, and major oncology conferences (up to May 20, 2024) were systematically searched for randomized trials comparing anti-PD-1/PD-L1 with standard perioperative therapy. Data extraction followed PRISMA guidelines, including trial characteristics, efficacy outcomes (pathological response and survival outcome), and safety profiles. Indirect comparisons between agents were conducted through network meta-analysis employing the mirror principle, utilizing both frequentist and Bayesian methodologies.

Thirty-one trials (14,974 patients) were analyzed. Anti-PD-1 demonstrated superior pathological complete response (relative risk [RR]: 1.65, 95% confidence interval [CI]: 1.18-2.29, p = 0.003), major pathological response (RR: 1.43, 95% CI: 1.04-1.96, p = 0.026), and disease-free survival (hazard ratio [HR] = 0.82, 95% CI: 0.71-0.96, p = 0.0106) versus anti-PD-L1. Safety profiles were comparable overall, though anti-PD-1 correlated with higher grade 3-5 immune-related adverse events (irAEs). Frequentist and Bayesian analyses yielded consistent results.

Perioperative anti-PD-1 therapy shows enhanced efficacy but increased severe irAEs compared to anti-PD-L1, supporting agent-specific considerations in clinical practice. Further tumor-specific evaluations and mature data are warranted.

This work is supported in part by the CAMS Innovation Fund for Medical Sciences (2024-I2M-ZD-004) and so on.

Dosing and types of local anesthetic agents for spinal anesthesia in ambulatory settings vary significantly. We sought to conduct a network meta-analysis to evaluate the effect of the type and dose of local anesthetic on outcomes in patients undergoing ambulatory surgery.

After PROSPERO registration (CRD42023399356), we searched various databases for randomized controlled trials (RCTs) evaluating adult patients undergoing daycare surgery under spinal anesthesia. Most included trials focused on patients undergoing knee arthroscopy, while other covered procedures were perineal, lower abdominal, and limb surgeries. Unfortunately, we could not include trials on arthroplasty surgery owing to the lack of RCTs in this area. We used Confidence in Network Meta-Analysis (CINeMA) to assess the confidence in the estimates, and we used surface under the cumulative ranking curve (SUCRA) to determine the probability rank order. The primary outcome was the time to discharge. Intraoperative effectiveness of anesthetic, sensory, and motor blockade duration; time to first micturition; time to ambulation; and adverse effects such as urinary retention and transient neurologic symptoms (TNS) were the secondary outcomes.

Overall, this study included 44 trials comprising 3,299 patients, each comprising 11 distinct agents (2-chloroprocaine, articaine, high-dose bupivacaine, low-dose bupivacaine, lidocaine, high-dose levobupivacaine, low-dose levobupivacaine, mepivacaine, prilocaine, high-dose ropivacaine, and low-dose ropivacaine). Low- to moderate-certainty evidence showed that 2-chloroprocaine, lidocaine, and mepivacaine were superior for discharge readiness, while 2-chloroprocaine ranked highest for other outcomes (sensory and motor block duration, time to first ambulation, and spontaneous voiding).

Evidence supports 2-chloroprocaine for short-duration spinal anesthesia in the ambulatory setting.

PROSPERO ( CRD42023399356 ); first submitted 13 February 2023.

This systematic review and network meta-analysis (NMA) was to investigate the effects of different exercise modalities on inflammatory markers in cancer patients. Using the standardized mean difference (SMD) as the effect size, a Bayesian random-effects network meta-analysis and regression analysis were conducted. Searches were performed across five databases for randomized controlled trials (RCTs) involving cancer patients, with exercise as the intervention, reported outcomes related to inflammatory markers, and interventions lasting more than four weeks, up to June 2024. A total of 57 RCTs (3106 patients) were included. The Cochrane risk of Bias Tool was utilized to assess the RCTs, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was employed to evaluate the quality of evidence. NMA results indicate that regular exercise is effective in reducing inflammation in cancer patients, with combined high-intensity aerobic and resistance exercises proving to be the most beneficial. The type, intensity, and total volume of exercise are critical factors in achieving positive outcomes. It is recommended to design exercise programs for cancer patients that combine aerobic and resistance training, with a gradual increase in intensity to ensure safety.

Dysfunction of the autonomic nervous system (characterized by excessive sympathetic activation and reduced parasympathetic activity) is regarded as one of the primary mechanisms of heart failure. Theoretically, nerve stimulation or modulation targeting this autonomic imbalance could improve outcomes in heart failure, but current evidence is inconclusive.

This systematic review and network meta-analysis (NMA) aimed to compare the efficacy of various nerve stimulation/modulation approaches in patients with heart failure.

We conducted a frequentist-based NMA of randomized controlled trials (RCTs) investigating nerve stimulation or modulation techniques for heart failure management. The primary outcomes included objective measures (such as brain natriuretic peptide [BNP] serum levels) and subjective measures (such as psychosocial functioning and quality of life).

Interventions targeting both arms of the autonomic nervous system, including sympathetic and parasympathetic nervous systems, and the vasculature (carotid or renal arteries) demonstrated preferable results. Interventions dealing only with the autonomic nervous system did not provide significant results. Specifically, only renal sympathetic denervation was significantly associated with a more significant reduction in BNP levels than the control group. Additionally, baroreflex activation therapy was the only treatment significantly associated with improving quality of life.

This study provides comparative evidence supporting the use of specific nerve stimulation/modulation techniques in treating heart failure. Further well-designed RCTs, incorporating appropriate blinding, are recommended to minimize potential biases.