The effects of nonpharmacological sleep hygiene on sleep quality in nonelderly individuals: A systematic review and network meta-analysis of randomized controlled trials.

The prevalence of locomotive syndrome naturally increases with age, but approximately half of nonelderly individuals also meet the criteria for locomotive syndrome, suggesting that even younger people need to pay attention to their own health status. Sleep is important for physical, cognitive, and psychological health. Some individuals with poor sleep quality may be at risk of developing negative health status. Although the effects of sleep hygiene strategies for elderly individuals have been well investigated, optimal nonpharmacological sleep hygiene strategies for improving sleep quality in nonelderly individuals has not been identified. We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials aimed to elucidate the effects of various nonpharmacological interventions on sleep quality in nonelderly individuals and to identify the optimal intervention. Cochrane Central Register of Controlled Trials, Medline, Cumulative Index to Nursing and Allied Health Literature, Physiotherapy Evidence Database, and Scopus were comprehensively searched. We identified 27 studies focusing on the effects of various nonpharmacological sleep hygiene strategies in nonelderly individuals, and 24 studies were applied into NMA. The present results showed that resistance training was the most effective intervention for improving sleep quality in nonelderly individuals. In addition, this study revealed the effects of nonpharmacological interventions, such as physical activity, nutritional intervention, as well as exercise interventions. This is the first report that utilized NMA to compare the effects of various nonpharmacological interventions on sleep quality in nonelderly individuals.

The efficacy and acceptability of pharmacological monotherapies and e-cigarette on smoking cessation: a systemic review and network meta-analysis.

Background and aims: Several pharmacological interventions, such as nicotine replacement therapy (NRT), varenicline, and bupropion, have been approved for clinical use of smoking cessation. E-cigarettes (EC) are increasingly explored by many RCTs for their potentiality in smoking cessation. In addition, some RCTs are attempting to explore new drugs for smoking cessation, such as cytisine. This network meta-analysis (NMA) aims to investigate how these drugs and e-cigarettes compare regarding their efficacy and acceptability. Materials and methods: This systematic review and NMA searched all clinical studies on smoking cessation using pharmacological monotherapies or e-cigarettes published from January 2011 to May 2022 using MEDLINE, COCHRANE Library, and PsychINFO databases. NRTs were divided into transdermal (TDN) and oronasal nicotine (ONN) by administrative routes, thus 7 network nodes were set up for direct and indirect comparison. Two different indicators measured the efficacy: prevalent and continuous smoking abstinence. The drop-out rates measured the acceptability. Results: The final 40 clinical studies included in this study comprised 77 study cohorts and 25,889 participants. Varenicline is more effective intervention to assist in smoking cessation during 16-32 weeks follow-up, and is very likely to prompt dropout. Cytisine shows more effectiveness in continuous smoking cessation but may also lead to dropout. E-cigarettes and oronasal nicotine are more effective than no treatment in encouraging prevalent abstinence, but least likely to prompt dropout. Finally, transdermal nicotine delivery is more effective than no treatment in continuous abstinence, with neither significant effect on prevalent abstinence nor dropout rate. Conclusion: This review suggested and agreed that Varenicline, Cytisine and transdermal nicotine delivery, as smoking cessation intervention, have advantages and disadvantages. However, we had to have reservations about e-cigarettes as a way to quit smoking in adolescents.

Optimal dose and type of exercise to improve depressive symptoms in older adults: a systematic review and network meta-analysis.

BACKGROUND: Depression is a prevalent issue among older adults, affecting their quality of life and overall well-being. Exercise is an effective means of relieving depressive symptoms in older adults, but the optimal dose for different exercise types remains unclear. As such, the aim of this meta-analysis was to examine the dose-response relationship between overall and specific types of exercise with depression symptoms in older adults. METHODS: This systematic review and network meta-analysis included a search of PubMed, Medline, Embase, PsycINFO, Cochrane library, and Web of Science for randomized controlled trials of exercise in older adults with depression symptoms from inception to 15 July 2023. Comprehensive data extraction covered dose, treatment regimen, demographics and study duration. Dosage metrics, encompassing METs-min/week, were scrutinized in correlation with the Minimal Clinically Importance Difference (MCID). RESULTS: A total of 47 studies involving 2895 participants and 7 kinds of exercise were included in the review. Without considering the dose, the results of our network meta-analysis indicated that Walking was the most effective in alleviating depression in older adults, in addition to Aerobic exercise (AE), Yoga, Qigong, Resistance training (RT), and Tai Chi (TC), which were equally effective. However, the results of the dose-response analysis found that Aerobic exercise was most effective at a dose of 1000 METs-min/week. It is noteworthy that Walking is significantly effective in alleviating depressive symptoms in older adults at very low doses. In terms of clinical benefits, we found that overall exercise doses in the range of 600 ~ 970 METs-min/week were clinically effective. Considering the specific types of exercise, Aerobic exercise, Resistance training, Walking, and Yoga were found to be effective at doses ranging from 820 ~ 1000 METs-min/week, 520 ~ 1000 METs-min/week, 650 ~ 1000 METs-min/week, 680 ~ 1000 METs-min/week, respectively. At the same time, we found that when the age exceeded 81 years, even when participating in exercise, it did not achieve the effect of alleviating depressive symptoms in older adults. CONCLUSIONS: In conclusion, including Walking, AE, Yoga, Qigong, RT, and TC, effectively alleviate depressive symptoms in older adults. Furthermore, we established statistically and clinically significant threshold doses for various exercise types. Early initiation of exercise is beneficial, but its efficacy diminishes from the age of 80, and beyond 81, exercise no longer significantly alleviates depressive symptoms.

Effectiveness of zygomatic-implant fixed rehabilitation for the atrophic edentulous maxilla: protocol for a systematic review and network meta-analysis.

BACKGROUND: Atrophic edentulous maxilla is a debilitating condition caused by the progressive and irreversible bone resorption following loss of teeth, that results in bone of inadequate volume and density. This makes conventional implant therapy extremely challenging without complex reconstructive procedures. Several techniques such as sinus augmentation, short implants, and tilted implants have been used for the rehabilitation of the atrophic maxilla. In recent years, zygomatic implants have emerged as a graftless rehabilitation technique. However, few studies compare zygomatic-implant fixed rehabilitation with other fixed rehabilitation techniques. The existing body of evidence on zygomatic implants is largely based on clinical and disease-oriented outcomes. METHODS: A network meta-analysis (NMA) will be conducted in order to compare the effectiveness of zygomatic-implant fixed rehabilitation with the other rehabilitation techniques. Experimental and observational studies comparing different implant-assisted fixed rehabilitation in adults with atrophic maxilla will be included. The primary and secondary outcomes will be patient's satisfaction and quality of life respectively. Additional outcomes include the implant's survival/success, and biological and prosthetic complications. An electronic search will be performed through various databases for articles in English and French, without time limits. Risk of bias will be assessed using the Revised Cochrane Risk-of-Bias tool for randomized controlled trials, and ROBINS-I for non-randomized and observational studies. Two independent reviewers will screen the titles and abstracts and extract data. Any discrepancy between reviewers will be discussed and resolved through consensus or with the help of a third reviewer. Pairwise meta-analyses will be performed using a random effects model. I2, τ2, transitivity, subgroup/meta-regression analyses will assess and explain heterogeneity and distribution of effect modifiers. A network plot will be created to connect the different interventions directly and indirectly. Interventions will be ranked using the surface under cumulative ranking curve. Confidence in the results of the NMA will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). DISCUSSION: This study will be the first to assess the effectiveness of zygomatic-implant fixed rehabilitation for the atrophic maxilla using NMA. The evidence obtained will aid clinical decision-making and will advance the knowledge of the rehabilitation techniques for the atrophic maxilla. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023353303.

The efficacy and safety of PARP inhibitors in mCRPC with HRR mutation in second-line treatment: a systematic review and bayesian network meta-analysis.

BACKGROUND: Poly (ADP- ribose) polymerase inhibitors (PARPi) has been increasingly adopted for metastatic castration-resistance prostate cancer (mCRPC) patients with homologous recombination repair deficiency (HRD). However, it is unclear which PARPi is optimal in mCRPC patients with HRD in 2nd -line setting. METHOD: We conducted a systematic review of trials regarding PARPi- based therapies on mCRPC in 2nd -line setting and performed a Bayesian network meta-analysis (NMA). Radiographic progression-free survival (rPFS) was assessed as primary outcome. PSA response and adverse events (AEs) were evaluated as secondary outcomes. Subgroup analyses were performed according to specific genetic mutation. RESULTS: Four RCTs comprised of 1024 patients (763 harbored homologous recombination repair (HRR) mutations) were identified for quantitative analysis. Regarding rPFS, olaparib monotherapy, rucaparib and cediranib plus olaparib showed significant improvement compared with ARAT. Olaparib plus cediranib had the highest surface under cumulative ranking curve (SUCRA) scores (87.5%) for rPFS, followed by rucaparib, olaparib and olaparib plus abiraterone acetate prednisone. For patients with BRCA 1/2 mutations, olaparib associated with the highest probability (98.1%) of improved rPFS. For patients with BRCA-2 mutations, olaparib and olaparib plus cediranib had similar efficacy. However, neither olaparib nor rucaparib showed significant superior effectiveness to androgen receptor-axis-targeted therapy (ARAT) in patients with ATM mutations. For safety, olaparib showed significantly lower ≥ 3 AE rate compared with cediranib plus olaparib (RR: 0.72, 95% CI: 0.51, 0.97), while olaparib plus cediranib was associated with the highest risk of all-grade AE. CONCLUSION: PARPi-based therapy showed considerable efficacy for mCRPC patients with HRD in 2nd -line setting. However, patients should be treated accordingly based on their genetic background as well as the efficacy and safety of the selected regimen. TRIAL REGISTRATION: CRD42023454079.

Induction chemotherapy regimes in first-line treatment for locoregionally advanced nasopharyngeal carcinoma: A network meta-analysis and cost-effectiveness analysis.

OBJECTIVE: The aim of this study is to evaluate the efficacy and cost-effectiveness of various induction chemotherapy (IC) regimens as first-line treatment for Locoregionally advanced nasopharyngeal carcinoma (LA-NPC), aiming to provide clinicians and patients with informed insights to aid in treatment decision-making. PATIENTS AND METHODS: We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based on data from 10 clinical trials investigating IC regimens for the treatment of LA-NPC. A Bayesian NMA was performed, with the primary outcomes being hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS). To model the disease progression of LA-NPC, we developed a dynamic partitioned survival model consisting of three disease states: progression-free survival (PFS), progression disease (PD), and death. The model was run on a 3-week cycle for a research period of 10 years, with quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) serving as outcome measures. RESULTS: According to the surface under the cumulative ranking curve (SUCRA) estimates derived from the NMA, TPC and TP, as IC regimens, appear to exhibit superior efficacy compared to other treatment modalities. In terms of CEA, concurrent chemoradiotherapy (CCRT), TPF + CCRT, and GP + CCRT were found to be dominated (more costs and less QALYs). Comparatively, TPC + CCRT emerged as a cost-effective option with an ICER of $1260.57/QALY when compared to PF + CCRT. However, TP + CCRT demonstrated even greater cost-effectiveness than TPC + CCRT, with an associated increase in costs of $3300.83 and an increment of 0.1578 QALYs per patient compared to TPC + CCRT, resulting in an ICER of $20917.62/QALY. CONCLUSION: Based on considerations of efficacy and cost-effectiveness, the TP + CCRT treatment regimen may emerge as the most favorable first-line therapeutic approach for patients with LA-NPC.

Network meta-analysis of four common immunomodulatory therapies for the treatment of patients with thin endometrium.

OBEJECTIVE: To compare the effectiveness of endometrial receptivity and pregnancy outcomes of four common immunomodulatory therapies for patients with thin endometrium. METHOD: This systematic review and network meta-analysis using a literature search up to January 2024, to identify relevant trials comparing endometrial receptivity and pregnancy outcomes of human chorionic gonadotropin (hCG), platelet-rich plasma (PRP), infusion of granulocyte colony-stimulating factor (IG-CSF), and peripheral blood mononuclear cell (PBMC) for patients with thin endometrium. We used surface under the cumulative ranking (SUCRA) to ranked four common immunomodulatory therapies on endometrium thickness, implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR). RoB2 and ROBINS-I were used to assess the certainty of evidence. RESULTS: The pooled results of 22 studies showed that hCG (mean difference [MD]: 3.05, 95% confidence interval [CI]: 1.46-4.64) and PRP (MD: 0.98, 95% CI: 0.20-1.76) significantly increase endometrium thickness. The hCG was the best among the IG-CSF (MD = -2.56, 95% CI = -4.30 to -0.82), PBMC (MD = -2.75, 95% CI = -5.49 to -0.01), and PRP (MD = -2.07, 95% CI = -3.84 to -0.30) in increasing endometrium thickness. However, IG-CSF and PRP significantly improved IR (IG-CSF: risk ratio (RR; IG-CSF: RR = 1.33, 95% CI = 1.06-1.67; PRP: RR = 1.63, 95% CI = 1.19-2.23), and LBR (IG-CSF: RR = 1.53, 95% CI = 1.16-2.02; PRP: RR = 1.59, 95% CI = 1.08-2.36). CONCLUSIONS: Available evidence reveals that hCG and subcutaneous or intrauterine CSF (SG-CSF) may be the best treatment options for current thin endometrium patients. However, future high-quality and large-scale studies are necessary to validate our findings.

Comparison for the diagnostic performance of early diagnostic methods for biliary atresia: a systematic review and network meta-analysis.

BACKGROUND: Biliary atresia (BA), a progressive condition affecting canalicular-bile duct function/anatomy, requires prompt surgical intervention for favorable outcomes. Therefore, we conducted a network meta-analysis of common diagnostic methods to assess their performance and provide evidence-based support for clinical decision-making. METHODS: We reviewed literature in PubMed, EMBASE, and Cochrane for BA diagnostics. The search included gamma-glutamyl transferase (GGT), direct/combined bilirubin, matrix metalloproteinase 7 (MMP-7), ultrasonic triangular cord sign (TCS), hepatic scintigraphy (HS), and percutaneous cholangiocholangiography/percutaneous transhepatic cholecysto-cholangiography (PCC/PTCC). QUADAS-2 assessed study quality. Heterogeneity and threshold effect were evaluated using I2 and Spearman's correlation. We combined effect estimates, constructed SROC models, and conducted a network meta-analysis based on the ANOVA model, along with meta-regression and subgroup analysis, to obtain precise diagnostic performance assessments for BA. RESULTS: A total of 40 studies were included in our analysis. GGT demonstrated high diagnostic accuracy for BA with a sensitivity of 81.5% (95% CI 0.792-0.836) and specificity of 72.1% (95% CI 0.693-0.748). Direct bilirubin/conjugated bilirubin showed a sensitivity of 87.6% (95% CI 0.833-0.911) but lower specificity of 59.4% (95% CI 0.549-0.638). MMP-7 exhibited a total sensitivity of 91.5% (95% CI 0.893-0.934) and a specificity of 84.3% (95% CI 0.820-0.863). TCS exhibited a sensitivity of 58.1% (95% CI 0.549-0.613) and high specificity of 92.9% (95% CI 0.911-0.944). HS had a high sensitivity of 98.4% (95% CI 0.968-0.994) and moderate specificity of 79.0% (95% CI 0.762-0.816). PCC/PTCC exhibited excellent diagnostic performance with a sensitivity of 100% (95% CI 0.900-1.000) and specificity of 87.0% (95% CI 0.767-0.939). Based on the ANOVA model, the network meta-analysis revealed that MMP-7 ranked second overall, with PCC/PTCC ranking first, both exhibiting superior diagnostic accuracy compared to other techniques. Our analysis showed no significant bias in most methodologies, but MMP-7 and hepatobiliary scintigraphy exhibited biases, with p values of 0.023 and 0.002, respectively. CONCLUSION: MMP-7 and ultrasound-guided PCC/PTCC show diagnostic potential in the early diagnosis of BA, but their clinical application is restricted due to practical limitations. Currently, the cutoff value of MMP-7 is unclear, and further evidence-based medical research is needed to firmly establish its diagnostic value. Until more evidence is available, MMP-7 is not suitable for widespread diagnostic use. Therefore, considering cost and operational simplicity, liver function tests combined with ultrasound remain the most clinically valuable non-invasive diagnostic methods for BA.

Efficacy of daprodustat for patients on dialysis with anemia: systematic review and network meta-analysis.

Chronic kidney disease (CKD) is commonly complicated by anemia. Treating dialysis-dependent patients with anemia, including daprodustat and other inhibitors of prolyl hydroxylase of hypoxia-inducible factor, recombinant human erythropoietin (rhEPO), and iron supplements. We conducted this study to test our postulation; daprodustat is superior to rhEPO and other conventional treatments respecting efficacy and safety parameters. We made systematic search through PubMed, Web of Science, Scopus, and Cochrane. Seven unique trials were eventually included for systematic review; six of them with a sample size of 759 patients entered our network meta-analysis (NMA). Daprodustat 25-30 mg was associated with the greatest change in serum hemoglobin (MD=1.86, 95%CI= [1.20; 2.52]), ferritin (MD= -180.84, 95%CI= [-264.47; -97.20]), and total iron binding capacity (TIBC) (MD=11.03, 95%CI= [3.15; 18.92]) from baseline values. Dialysis-dependent patients with anemia had a significant increment in serum Hemoglobin and TIBC and a reduction in serum ferritin, in a dose-dependent manner, when administered daprodustat.

The Diagnostic Accuracy of SPECT Imaging in Patients With Suspected Pulmonary Embolism: Systematic Review and Network Meta-analysis.

BACKGROUND: This meta-analysis and systematic review assessed the diagnostic accuracy of lung SPECT compared with lung planar imaging in patients with suspected acute pulmonary embolism (PE) or chronic thromboembolic pulmonary hypertension. PATIENTS AND METHODS: A search of Medline, Embase, and Cochrane databases identified suitable articles published before October 2023. Meta-analyses were performed to determine the diagnostic accuracy of SPECT imaging modalities, including perfusion (Q) SPECT, ventilation (V)/Q SPECT, Q SPECT/CT, and V/Q SPECT/CT. Network meta-analyses were performed to compare the diagnostic accuracy of SPECT and planar imaging in paired-design studies. RESULTS: Twenty-four articles (total n = 6576) were included in the analysis. For suspected acute PE, the respective sensitivity and specificity of SPECT imaging modalities were as follows: Q SPECT, 0.93 (95% confidence interval [CI], 0.87-0.99; I2 = 49%) and 0.72 (95% CI, 0.54-0.95; I2 = 94%); V/Q SPECT, 0.96 (95% CI, 0.94-0.98; I2 = 51%) and 0.95 (95% CI, 0.92-0.98; I2 = 80%); Q SPECT/CT, 0.93 (95% CI, 0.87-0.98; I2 = 66%) and 0.82 (95% CI, 0.70-0.96; I2 = 87%); and V/Q SPECT/CT, 0.97 (95% CI, 0.93-1.00; I2 = 7%) and 0.98 (95% CI, 0.97-1.00; I2 = 31%). The relative sensitivity and specificity of SPECT compared with planar imaging were 1.17 (95% CI, 1.06-1.30; P < 0.001) and 1.14 (95% CI, 1.00-1.29; P = 0.05), respectively. For suspected chronic thromboembolic pulmonary hypertension, the pooled sensitivity and specificity of SPECT imaging were 0.97 (95% CI, 0.95-1.00; I2 = 0%) and 0.91 (95% CI, 0.87-0.94; I2 = 0%), respectively. CONCLUSIONS: SPECT exhibited superior diagnostic performance for PE. V/Q SPECT/CT was the most accurate modality.

Effective dosage and mode of exercise for enhancing cognitive function in Alzheimer's disease and dementia: a systematic review and Bayesian Model-Based Network Meta-analysis of RCTs.

OBJECTIVE: Research the dose-response relationship between overall and certain types of exercise and cognitive function in older adults with Alzheimer's disease and dementia. DESIGN: Systemic and Bayesian Model-Based Network Meta-Analysis. METHODS: In our study, we analyzed data from randomized controlled trials investigating the effects of different exercises on cognitive outcomes in older adults with AD. We searched the Web of Science, PubMed, Cochrane Central Register of Controlled Trials, and Embase up to November 2023. Using the Cochrane Risk of Bias tool (Rob2) for quality assessment and R software with the MBNMA package for data analysis, we determined standard mean differences (SMDs) and 95% confidence intervals (95%CrI) to evaluate exercise's impact on cognitive function in AD. RESULTS: Twenty-seven studies with 2,242 AD patients revealed a nonlinear relationship between exercise and cognitive improvement in AD patients. We observed significant cognitive enhancements at an effective exercise dose of up to 1000 METs-min/week (SMDs: 0.535, SD: 0.269, 95% CrI: 0.023 to 1.092). The optimal dose was found to be 650 METs-min/week (SMDs: 0.691, SD: 0.169, 95% CrI: 0.373 to 1.039), with AE (Aerobic exercise) being particularly effective. For AE, the optimal cognitive enhancement dose was determined to be 660 METs-min/week (SMDs: 0.909, SD: 0.219, 95% CrI: 0.495 to 1.362). CONCLUSION: Nonlinear dose-response relationship between exercise and cognitive improvement in Alzheimer's disease, with the optimal AE dose identified at 660 METs-min/week for enhancing cognitive function in AD.

Treatment of Locally Advanced Rectal Cancer in the Era of Total Neoadjuvant Therapy: A Systematic Review and Network Meta-Analysis.

Importance: Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates. Objective: To assess the efficacy and tolerability of TNT protocols for LARC. Data Sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024. Study Selection: Randomized clinical trials including adults with LARC who underwent rectal resection as a final treatment were included. Studies including nonoperative treatment (watch-and-wait strategy), treatments other than rectal resection, immunotherapy, or antiangiogenic agents were excluded. Among the initially identified studies, 2.9% met the selection criteria. Data Extraction and Synthesis: Two authors independently screened the records and extracted data. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant pairwise and network meta-analyses with a random-effects model were performed in a frequentist framework, and the certainty of evidence was assessed according to the confidence in network meta-analysis approach. Main Outcomes and Measures: The primary outcome was pCR, defined as the absence of residual tumor at pathological assessment after surgery. Secondary outcomes included tolerability, toxic effects, perioperative outcomes, and long-term survival. Results: Of 925 records identified, 27 randomized clinical trials, including 13 413 adults aged 18 years or older (median age, 60.0 years [range, 42.0-63.5 years]; 67.2% male) contributed to the primary network meta-analysis. With regard to pCR, long-course chemoradiotherapy (L-CRT) plus consolidation chemotherapy (relative risk [RR], 1.96; 95% CI, 1.25-3.06), short-course radiotherapy (S-RT) plus consolidation chemotherapy (RR, 1.76; 95% CI, 1.34-2.30), and induction chemotherapy plus L-CRT (RR, 1.57; 95% CI, 1.09-2.25) outperformed standard L-CRT with single-agent fluoropyrimidine-based chemotherapy. Considering 3-year disease-free survival, S-RT plus consolidation chemotherapy (RR, 1.08; 95% CI, 1.01-1.14) and induction chemotherapy plus L-CRT (RR, 1.12; 95% CI, 1.01-1.24) outperformed L-CRT, in spite of an increased 5-year locoregional recurrence rate of S-RT plus consolidation chemotherapy (RR, 1.65; 95% CI, 1.03-2.63). Conclusions and Relevance: In this systematic review and network meta-analysis, 3 TNT protocols were identified to outperform the current standard of care in terms of pCR rates, with good tolerability and optimal postoperative outcomes, suggesting they should be recognized as first-line treatments.

Compare the efficacy of antifungal agents as primary therapy for invasive aspergillosis: a network meta-analysis.

BACKGROUND: Several antifungal agents are available for primary therapy in patients with invasive aspergillosis (IA). Although a few studies have compared the effectiveness of different antifungal agents in treating IA, there has yet to be a definitive agreement on the best choice. Herein, we perform a network meta-analysis comparing the efficacy of different antifungal agents in IA. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Clinical Trials databases to find studies (both randomized controlled trials [RCTs] and observational) that reported on treatment outcomes with antifungal agents for patients with IA. The study quality was assessed using the revised tool for risk of bias and the Newcastle Ottawa scale, respectively. We performed a network meta-analysis (NMA) to summarize the evidence on antifungal agents' efficacy (favourable response and mortality). RESULTS: We found 12 studies (2428 patients) investigating 11 antifungal agents in the primary therapy of IA. There were 5 RCTs and 7 observational studies. When treated with monotherapy, isavuconazole was associated with the best probability of favourable response (SUCRA, 77.9%; mean rank, 3.2) and the best reduction mortality against IA (SUCRA, 69.1%; mean rank, 4.1), followed by voriconazole and posaconazole. When treated with combination therapy, Liposomal amphotericin B plus caspofungin was the therapy associated with the best probability of favourable response (SUCRA, 84.1%; mean rank, 2.6) and the best reduction mortality (SUCRA, 88.2%; mean rank, 2.2) against IA. CONCLUSION: These findings suggest that isavuconazole, voriconazole, and posaconazole may be the best antifungal agents as the primary therapy for IA. Liposomal amphotericin B plus caspofungin could be an alternative option.

Comparative physiological effects of antipsychotic drugs in children and young people: a network meta-analysis.

BACKGROUND: The degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents. With network meta-analysis, we aimed to investigate the effects of various antipsychotic medications on physiological variables in children and adolescents with neuropsychiatric and neurodevelopmental conditions. METHODS: For this network meta-analysis, we searched Medline, EMBASE, PsycINFO, Web of Science, and Scopus from database inception until Dec 22, 2023, and included randomised controlled trials comparing antipsychotics with placebo in children or adolescents younger than 18 years with any neuropsychiatric and neurodevelopmental condition. Primary outcomes were mean change from baseline to end of acute treatment in bodyweight, BMI, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, prolactin, heart rate, systolic blood pressure (SBP), and QT interval corrected for heart rate (QTc) for patients receiving either active treatment or placebo. For multigroup trials reporting several doses, we calculated a summary value for each physiological variable for all doses. After transitivity assessment, we fitted frequentist random-effects network meta-analyses for all comparisons in the network. A Kilim plot was used to summarise the results for all treatments and outcomes, providing information regarding the strength of the statistical evidence of treatment effects, using p values. Network heterogeneity was assessed with τ, risk of bias of individual trials was assessed with the Cochrane Collaboration's Tool for Assessing Risk of Bias, and the credibility of findings from each network meta-analysis was assessed with the Confidence in Network Meta-Analysis (CINEMA) app. This study is registered on PROSPERO (CRD42021274393). FINDINGS: Of 6676 studies screened, 47 randomised controlled trials were included, which included 6500 children (mean age 13·29 years, SD 2·14) who received treatment for a median of 7 weeks (IQR 6-8) with either placebo (n=2134) or one of aripiprazole, asenapine, blonanserin, clozapine, haloperidol, lurasidone, molindone, olanzapine, paliperidone, pimozide, quetiapine, risperidone, or ziprasidone (n=4366). Mean differences for bodyweight change gain compared with placebo ranged from -2·00 kg (95% CI -3·61 to -0·39) with molindone to 5·60 kg (0·27 to 10·94) with haloperidol; BMI -0·70 kg/m2 (-1·21 to -0·19) with molindone to 2·03 kg/m2 (0·51 to 3·55) with quetiapine; total cholesterol -0·04 mmol/L (-0·39 to 0·31) with blonanserin to 0·35 mmol/L (0·17 to 0·53) with quetiapine; LDL cholesterol -0·12 mmol/L (-0·31 to 0·07) with risperidone or paliperidone to 0·17 mmol/L (-0·06 to 0·40) with olanzapine; HDL cholesterol 0·05 mmol/L (-0·19 to 0·30) with quetiapine to 0·48 mmol/L (0·18 to 0·78) with risperidone or paliperidone; triglycerides -0·03 mmol/L (-0·12 to 0·06) with lurasidone to 0·29 mmol/L (0·14 to 0·44) with olanzapine; fasting glucose from -0·09 mmol/L (-1·45 to 1·28) with blonanserin to 0·74 mmol/L (0·04 to 1·43) with quetiapine; prolactin from -2·83 ng/mL (-8·42 to 2·75) with aripiprazole to 26·40 ng/mL (21·13 to 31·67) with risperidone or paliperidone; heart rate from -0·20 bpm (-8·11 to 7·71) with ziprasidone to 12·42 bpm (3·83 to 21·01) with quetiapine; SBP from -3·40 mm Hg (-6·25 to -0·55) with ziprasidone to 10·04 mm Hg (5·56 to 14·51) with quetiapine; QTc from -0·61 ms (-1·47 to 0·26) with pimozide to 0·30 ms (-0·05 to 0·65) with ziprasidone. INTERPRETATION: Children and adolescents show varied but clinically significant physiological responses to individual antipsychotic drugs. Treatment guidelines for children and adolescents with a range of neuropsychiatric and neurodevelopmental conditions should be updated to reflect each antipsychotic drug's distinct profile for associated metabolic changes, alterations in prolactin, and haemodynamic alterations. FUNDING: UK Academy of Medical Sciences, Brain and Behaviour Research Foundation, UK National Institute of Health Research, Maudsley Charity, the Wellcome Trust, Medical Research Council, National Institute of Health and Care Research Biomedical Centre at King's College London and South London and Maudsley NHS Foundation Trust, the Italian Ministry of University and Research, the Italian National Recovery and Resilience Plan, and Swiss National Science Foundation.

A Comparison of Surgical Approaches for Hip Hemiarthroplasty Performed for the Treatment of Femoral Neck Fracture: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Multiple hemiarthroplasty (HA) approaches exist for femoral neck fracture (FNF) treatment. However, there is no consensus on the superiority of one approach for postoperative outcomes. This study assessed outcomes among randomized controlled trials (RCTs) comparing the posterior approach (PA), direct lateral approach (DLA), anterolateral approach (ALA), and the direct anterior approach (DAA) in HA for FNF. METHODS: PubMed, Ovid/MEDLINE, Scopus, Cochrane Central Registry of Controlled Trials, and Cochrane Database of Systematic Reviews were queried in February 2024. A frequentist model network meta-analysis of eligible prospective RCTs compared outcomes among approaches using P-scores. RESULTS: Of 1,481 retrieved studies, 11 RCTs totaling 1,513 FNF patients who underwent HA through a PA (n = 446; 29.5%), DLA (n = 481; 31.8%), ALA (n = 296; 19.6%), or DAA (n = 290; 19.2%) with median (interquartile range) follow-up of 6 (4.5-12.0) months were included for meta-analysis. DAA was associated with statistically increased operative duration (mean difference [MD], 1.89 minutes; 95% CI, 0.08 to 3.69 minutes; p < 0.001) compared with a PA, whereas an ALA was associated with statistically greater blood loss compared with a PA (MD, 5.81 mL; 95% CI, 4.11 to 7.50 mL; p < 0.001). There were no differences in the incidence of fracture, dislocation, infection, complications, revision, nor 1-year mortality among approaches. There were also no differences in hip nor pain score improvement at latest follow-up, although with high heterogeneity (I2 = 85.7% and 94.2%, respectively). CONCLUSION: This study found no clinical difference in improvement in pain, function, nor in revision outcomes and operative characteristics among HA approaches for FNF, and each approach had a similar adverse event profile. Despite limited randomized evidence, these findings suggest comparable short-term efficacy and safety of all approaches. LEVEL OF EVIDENCE: Therapeutic, Level I. See Instructions for Authors for a complete description of levels of evidence.

Efficacy and Safety of Oral Tranexamic Acid vs. Other Routes in Total Joint Arthroplasty: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Total joint arthroplasty (TJA) is often associated with significant blood loss, leading to complications such as acute anemia and increased risk of infection and mortality. Tranexamic acid (TXA), an antifibrinolytic agent, has been recognized for effectively reducing blood loss during TJA. This systematic review and network meta-analysis aims to evaluate the efficacy and safety of oral TXA compared with other administration routes in TJA. METHODS: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, Embase, and Web of Science, focusing on randomized clinical trials involving oral TXA in TJA. The studies were assessed for quality using the Cochrane risk assessment scale. Data synthesis involved network meta-analyses, comparing outcomes including hemoglobin drop, estimated blood loss (EBL), transfusion rate, and deep vein thrombosis (DVT) rate. RESULTS: Our comprehensive literature search incorporated 39 studies with 7,538 participants, focusing on 8 TXA administration methods in TJA. The combination of oral and intra-articular (oral + IA) TXA markedly reduced hemoglobin drop more effectively than oral, intravenous (IV), and IA alone, but the difference was not significant. Oral + IA TXA significantly reduced EBL more effectively than oral + IV, IA + IV, and oral, IV, and IA alone. Perioperative transfusion rates with oral + IA TXA was significantly lower than that of oral, IA, and IV alone. The DVT rate with oral + IA was significantly lower than that with all other routes, including oral + IV, IA + IV, and oral, IA, and IV alone. CONCLUSION: Oral TXA, particularly in combination with IA administration, demonstrates significantly higher efficacy in reducing blood loss and transfusion rates in TJA, with a safety profile comparable with that of other administration routes. The oral route, offering lower costs and simpler administration, emerges as a viable and preferable option in TJA procedures. LEVEL OF EVIDENCE: Level I. See Instructions for Authors for a complete description of levels of evidence.

The optimal second-line therapy for older adults with type 2 diabetes mellitus: protocol for a systematic review and network meta-analysis using individual participant data (IPD).

BACKGROUND: Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. METHODS: All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. DISCUSSION: With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021272686.

Protocol for a systematic review and network meta-analysis of the use of prophylactic antibiotics in hand trauma surgery.

BACKGROUND: The use of prophylactic antibiotics in surgery is contentious. With the rise in antimicrobial resistance, evidence-based antibiotic use should be followed. This systematic review and network meta-analysis will assess the effectiveness of different antibiotics on the prevention of surgical site infection (SSI) following hand trauma surgery. METHODS AND ANALYSIS: The databases Embase, MEDLINE, CINAHL and CENTRAL, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform will be searched. Abstracts will be screened by two persons independently to identify eligible studies. This systematic review will include both randomised and non-randomised prospective comparative studies in participants with hand and/or wrist injuries requiring surgery; bite injuries will be excluded. The network meta-analysis will compare the use of different prophylactic antibiotics against each other, placebo and/or no antibiotics on the development of SSI within 30 days of surgery (or 90 days if there is an implanted device). The Cochrane risk-of-bias tool 2 will be used to assess the risk of methodological bias in randomised controlled trials, and the Newcastle-Ottowa scale (NOS) will be used to assess the risk of bias in non-randomised studies. A random-effects network meta-analysis will be conducted along with subgroup analyses looking at antibiotic timing, injury type, and operation location. Sensitivity analyses including only low risk-of-bias studies will be conducted, and the confidence in the results will be assessed using Confidence in Network Meta-Analysis (CINEMA). DISCUSSION: This systematic review and network meta-analysis aims to provide an up-to-date synthesis of the studies assessing the use of antibiotics following hand and wrist trauma to enable evidence-based peri-operative prescribing. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023429618.

Long-term effects of different hypoglycemic drugs on carotid intima-media thickness progression: a systematic review and network meta-analysis.

Objective: The progression of carotid intima-media thickness (cIMT) can partially predict the occurrence of future cardiovascular events. This network meta-analysis compared the effects of 14 antidiabetic drugs (acarbose, alogliptin, exenatide, glibenclamide, glimepiride, ipragliflozin, metformin, nateglinide, pioglitazone, rosiglitazone, sitagliptin, tofoglifozin, troglitazone, voglibose) on the progression of cIMT. Method: PubMed, EMBASE, Cochrane Library, and Web of Science were searched to screen all clinical trials of treatment of cIMT with hypoglycemic agents before March 1, 2024. The differences in the changes in cIMT between the treatment group and control group were evaluated. Result: After screening 8395 citations, 25 studies (6675 patients) were included. The results indicated that exenatide had the best efficacy in slowing down cIMT progress, and exenatide [MD=-0.13,95%CI (-0.25, -0.01)], alogliptin [MD=-0.08,95%CI (-0.13, -0.02)] and metformin [MD=-0.05, 95%CI (-0.09, -0.02)] are more effective than placebo. Conclusion: Long-term treatment of exenatide, alogliptin, and metformin may be more effective than other hypoglycemic drugs in slowing the progression of cIMT. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024519474.

A bayesian network meta-analysis to explore modifying factors in randomized controlled trials: what works for whom to reduce depression in nursing home residents?

BACKGROUND: Reviews of depression interventions in nursing home residents resulted in positive findings. However, because of the heterogeneity of the studies, it remains unclear what works for whom. Considering moderator effects may contribute to a comprehensive understanding of depression treatment in residents. Therefore, this study aims to review depression interventions, examining moderator effects of (1) residents' factors, and (2) components specific of interventions. METHODS: A Bayesian network meta-analysis of randomized controlled trials primarily aimed at reducing depressive symptoms among residents was conducted. First, intervention types, e.g., exercise interventions, were compared to care as usual. Second, meta-regression analyses were conducted for moderator effects of residents' factors (i.e., severity of depressive symptoms, physical dependency, and cognitive impairment) and components identified as specific to an intervention (e.g., music, creativity, positivity). RESULTS: Our search across six databases resulted in 118 eligible studies: 16 on neurobiological interventions, 102 on non-pharmacological interventions. Compared to care as usual, cognitive interventions, such as cognitive behavioral therapy and goal-oriented therapy, showed the strongest effects (MD = -1.00, 95% CrI [-1.40 to -0.66]). Furthermore, the severity of depressive symptoms moderated the effect of interventions (ƅ = -0.63, CrI 95% [-1.04 to -0.22]), while none of fifteen identified intervention-specific components did. In residents with a depression diagnosis, there were larger effect sizes for interventions including daily structure, psychoeducation, healthy food, creativity, positivity, and an activating/encouraging environment, whereas interventions focusing on distraction and relaxation had larger effect sizes in those residents without. CONCLUSIONS: By examining the moderator effects, we provided an integrative perspective on the observed variations in effects across different target groups, and components of depression interventions. This approach underscores the complex nature of interventions, emphasizing the need for continued transdisciplinary research, and the exploration of potential moderators. Future investigations should carefully assess residents' factors and choose interventions and their components accordingly.