Comparative effects of different treatments based on the levonorgestrel intrauterine system in endometrial carcinoma and endometrial hyperplasia patients: a network meta-analysis.

OBJECTIVE: Levonorgestrel intrauterine system (LNG-IUS) has been widely used in patients with endometrial carcinoma (EC), endometrial hyperplasia without atypical (EH), and atypical endometrial hyperplasia (AEH). The purpose of our Network meta-analysis (NMA) is to evaluate the efficacy of the treatments based on the LNG-IUS in patients with EC and EH with or without atypical. METHODS: We examined PubMed, EMBASE, Web of Science and the Cochrane Library up to 22 April 2024 to determine studies reporting treatment outcomes in EC and EH patients receiving LNG-IUS therapy, LNG-IUS + metformin (MET), oral progestins (OP), etc. We used EndNote 9 to select studies, Jadad scale and NOS scale to assess quality, stata(16.0) and R (4.3.1) to analysis the data. RESULTS: Overall, 28 studies involving 3752 patients were included in our NMA. As for EH patients, LNG-IUS (RR 1.21; 95% CrI [1.11, 1.34]) and LNG-IUS + MET (RR 323.57; 95% CrI [1.61, 214,223,188.1])] significantly increased CR rate in comparison with OP. Based on SUCRA, LNG-IUS + OP was the best treatment to improve CR(SUCRA = 67.2%) in patients with EC, whereas LNG-IUS + MET was superior in increasing CR (SUCRA = 99.8%) than any other treatments for EH patients. Besides, the ranking based on SUCRA illustrated that LNG-IUS alone was the best choice to raise CR rates (SUCRA = 76.7%) for AEH patients. In head-to-head meta-analysis, OP has a higher progression rate (RR 4, 95% CI 1.89-8.46, p = 0.062; I2 = 71.3%), a higher nausea rate (RR 1.93, 95% CI 1.24-3.01, p = 0.187; I2 = 40.4%) than LNG-IUS in patients with EH. In contrast, LNG-IUS had a irregular vaginal bleeding rates (RR 0.76, 95% CI 0.64-0.90, p = 0.034; I2 = 77.7%) than OP in EH patients. In addition, as for AEH patients, OP has a higher persistence rate (RR 4.31, 95% CI 1.43-13.00, p = 0.93; I2 = 0.0%) than LNG-IUS. CONCLUSION: According to the NMA, LNG-IUS related studies are feasible for conservative therapy in patients with EC and EH with or without atypical. Therefore, concerning the curative effect, we recommend LNG-IUS-based treatments as the best conservative therapy for EC and EH patients. However, future studies require large sample sizes and more outcomes to further evaluate the differences of treatment selections based on LNG-IUS.

Risk of limb amputation and bone fractures with sodium glucose cotransporter-2 inhibitors: a network meta-analysis and meta-regression.

BACKGROUND: Sodium glucose cotransporter-2 inhibitors (SGLT2is) have gained immense attention for a variety of indications. Limb amputations (LA) and fractures were reported in clinical trials. This network meta-analysis and meta-regression were carried out to quantify the risks of these events. RESEARCH DESIGN AND METHODS: Randomized clinical trials evaluating SGLT2is and reporting patients developing LA/fracture were included. Odds ratios (OR) with 95% confidence intervals (95% CI) were the effect estimates. Sub-group analyses and meta-regression analysis were carried out. RESULTS: Ninety articles were included (LA: 36 studies; 96522 participants and fracture: 66 studies; 102,862 participants). An increased risk of LA (OR: 1.2; 95% CI: 1.1, 1.3) was observed. Amongst SGLT2is, canagliflozin was associated with increased risk of LA (OR: 1.6, 95% CI: 1.1, 2.4) while dapagliflozin with fracture (OR: 1.1, 95% CI: 1, 1.2). Sub-group analysis revealed increased risk of LA with an OR of 1.3 among those in the age group of > 40 to < 65, body-mass index of > 30 kg/m2, HbA1c category of > 7%, duration of diabetes of > 10 years, type 2 diabetes, and an OR of 1.2 for SGLT2is administration of > 6 months. CONCLUSIONS: SGLT2is were observed with an increased risk of LA. High- risk categories were identified for which precautions should be recommended in the standard treatment guidelines. PROTOCOL REGISTRATION: Open Science Framework (https://osf.io/5fwyk).

Compared to exercise, the effects of exercise combined with cognitive training in people with mild cognitive impairment: a network meta-analysis.

OBJECTIVES: The study aimed to evaluate the relative effectiveness of exercise combined with cognitive training (E&CT) in improving cognitive function compared to exercise alone. METHOD: PubMed, Embase, Cochrane Central Register of Controlled Trials, SPORTDiscus, and OpenGrey were systematically searched. Additional screenings were performed by reviewing citations of relevant articles. Studies were included if they met inclusion criteria. Both pairwise and network meta-analyses were performed using a random effects model in Stata 15.0. RESULTS: Totally, 46 trials from 54 literature (n = 2846) were eligible for inclusion in the meta-analysis. The network meta-analysis indicated that exercise alone was more efficacious than E&CT in improving global cognition and multicomponent exercise exhibited the highest likelihood (SUCRA value= 89.0%) of being the most effective type. Regarding memory function, E&CT presented greater potential than exercise alone, with the interactive modality ranking first (SUCRA value = 88.4%). Multicomponent exercise was identified as the top intervention for enhancing executive function. The overall quality of the included studies was rated as moderate, and the certainty of evidence ranged from low to high. CONCLUSION: Multicomponent exercise emerged as the optimal intervention for improving global cognition and executive function. Nevertheless, for memory function, the interactive modality of E&CT demonstrated the highest probability of being the most effective choice.

Comparative efficacy and safety of Chinese patent medicines of iron deficiency anemia during pregnancy: A network meta-analysis.

BACKGROUND: Iron deficiency anemia (IDA) is a prevalent nutritional disorder during pregnancy. Clinical studies indicate that incorporating Chinese patent medicines (CPMs) with oral iron (OI) in treating IDA in pregnancy can reduce adverse effects and improve clinical outcomes. Nonetheless, the comparative efficacy of different CPMs remains unclear. AIM: To assess the safety and effectiveness of different CPMs for treating IDA during pregnancy using network meta-analysis. METHODS: We conducted a search for randomized controlled trials (RCTs) that combined CPM and OI for IDA treatment in pregnancy, spanning from 2013 to the present. Data analysis was performed using Rev Man 5.3 and Stata 14.0 on literature that satisfied the quality criteria. RESULTS: The analysis included 45 RCTs, encompassing 4422 pregnant patients with IDA. Six CPMs were examined, including Shengxuebao Mixture, Shengxuening Tablets (SXN), Yiqi Weixue CPMs (YQWX), Jianpi Shengxue CPMs (JPSX), Yiqi Buxue Tablets, and Compound Hongyi Buxue Oral Liquid (FFHY). Findings indicated that FFHY + OI significantly improved the clinical effective rate. SXN + OI was most effective in boosting red blood cells counts and hemoglobin levels. YQWX + OI showed superior results in improving serum ferritin, and SXN + OI was most effective in increasing serum iron levels. JPSX + OI was optimal in reducing adverse pregnancy outcomes, while YQBX + OI effectively minimized adverse events. A cluster analysis suggested that SXN + OI could be the potentially optimal therapeutic regimen for IDA in pregnancy. CONCLUSION: This study demonstrates that the combination of OI with CPMs offers better outcomes than OI alone. Based on clinical efficacy and other measured outcomes, SXN + OI emerges as the most effective treatment modality for improving the health of pregnant patients with IDA.

Network meta-analysis made simple: a composite likelihood approach.

Network meta-analysis, also known as mixed treatments comparison meta-analysis or multiple treatments meta-analysis, extends conventional pairwise meta-analysis by simultaneously synthesizing multiple interventions in a single integrated analysis. Despite the growing popularity of network metaanalysis within comparative effectiveness research, it comes with potential challenges. For example, within-study correlations among treatment comparisons are rarely reported in the published literature. Yet, these correlations are pivotal for valid statistical inference. As demonstrated in earlier studies, ignoring these correlations can inflate mean squared errors of the resulting point estimates and lead to inaccurate standard error estimates. This paper introduces a composite likelihood-based approach that ensures accurate statistical inference without requiring knowledge of the within-study correlations. The proposed method is computationally robust and efficient, with substantially reduced computational time compared to the state-of-the-science methods implemented in R packages. The proposed method was evaluated through extensive simulations and applied to two important applications including a network meta-analysis comparing interventions for primary open-angle glaucoma, and another comparing treatments for chronic prostatitis and chronic pelvic pain syndrome.

Comparative efficacy of exercise modalities for general risk factors, renal function, and physical function in non-dialysis chronic kidney disease patients: a systematic review and network meta-analysis.

BACKGROUND: Exercise therapy can effectively manage chronic kidney disease (CKD) risk factors and improve renal function and physical fitness, but the challenge lies in choosing the right exercise type tailored to patients' condition. METHODS: An electronic search of databases including PubMed, The Cochrane Library, EMBASE, Web of Science, VIP, WanFang, and CNKI was performed. The random effects model was used. Mean difference was employed as the effect size for continuous variables, with 95% confidence interval (CI) provided. RESULTS: A total of 36 RCTs were included in this study. Compared to conventional therapy (CT), the combination of three exercise therapies with CT resulted in notable benefits in enhancing six minutes walk test (6MWT) capacity, 24-h urinary protein quantity (24hUTP), systolic blood pressure (SBP), diastolic blood pressure (DBP). Resistance exercise therapy (RT) + CT were more effective than CT to reduce serum creatinine (Scr), body mass index (BMI), and hemoglobin A1c (HbA1c) and improve estimated glomerular filtration rate (eGFR). In terms of improving peak oxygen uptake (VO2 peak), only two exercise modalities were involved, aerobic exercise therapy (AT) and combined (Resistance-Aerobic) exercise therapy (CBT), both of which were more efficacious than CT. The efficacy ranking overall demonstrated clear benefits for RT in enhancing eGFR and 6MWT, decreasing Scr, BMI, SBP, DBP, and HbA1c, while AT was more suitable for boosting VO2 peak, and CBT had greater potential for reducing 24hUTP. CONSLUSIONS: Exercise therapy combined with CT offers significant advantages over CT in many cases, but no single exercise modality is universally effective for all indicators.

Discrepancies between self-reported medication in adherence and indirect measurement adherence among patients undergoing antiretroviral therapy: a systematic review.

BACKGROUND: Given the critical importance of medication adherence in HIV/AIDS treatment, this study aims to compare medication adherence measured by self-report (SR) and indirect measurement among antiretroviral therapy (ART) patients, exploring the differences of adherence results measured by different tools. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library to identify all relevant literature published up to November 22, 2023, without language restrictions, reporting adherence to ART measured by both SR and indirect measurement methods, while also analyzing individual and group adherence separately. Discrepancies between SR and indirect measurement results were assessed using the Mann-Whitney U test or Wilcoxon signed-rank test, with correlations evaluated using the Pearson correlation coefficient. Following one-to-one comparisons, meta-epidemiological one-step analysis was conducted, and network meta-analysis techniques were applied to compare results obtained through specific adherence assessment tools reported in the identified articles. RESULTS: The analysis encompassed 65 original studies involving 13,667 HIV/AIDS patients, leading to 112 one-to-one comparisons between SR and indirect measurement tools. Statistically significant differences were observed between SR and indirect measurement tools regarding both individual and group adherence (P < 0.05), with Pearson correlation coefficients of 0.843 for individual adherence and 0.684 for group adherence. During meta-epidemiological one-step analysis, SR-measured adherence was determined to be 3.94% (95% CI: -4.48-13.44%) higher for individual adherence and 16.14% (95% CI: 0.81-18.84%) higher for group adherence compared to indirectly measured results. Subgroup analysis indicated that factors such as the year of reporting and geographic region appeared to influence the discrepancies between SR and indirect measurements. Furthermore, network meta-analysis revealed that for both individual and group adherence, the results obtained from most SR and indirect measurement tools were higher than those from electronic monitoring devices, with some demonstrating statistical significance (P < 0.05). CONCLUSIONS: The findings underscored the complexity of accurately measuring medication adherence among ART patients. Significant variability was observed across studies, with self-report methods showing a significant tendency towards overestimation. Year of reporting, geographic region, and adherence measurement tools appeared to influence the differences between SR and indirect measurements. Future research should focus on developing and validating integrated adherence measurements that can combine SR data with indirect measures to achieve a more comprehensive understanding of adherence behaviors.

Effects of exercise on depression and anxiety in postmenopausal women: a pairwise and network meta-analysis of randomized controlled trials.

BACKGROUND: Exercise has been identified as a promising non-pharmacological therapy for the management of depression, but there is still controversy over which type is most effective. We aimed to compare and rank the types of exercise that improve depression in postmenopausal women by quantifying information from randomized controlled trials (RCTs). METHODS: The PubMed, Web of Science, SPORTDiscus, CNKI, The Cochrane Library, PsycINFO, EMBASE, and CINAHL Plus databases were searched to identify articles published from inception to 1 March 2024 reporting RCTs that examined the effectiveness of exercise on depression in postmenopausal women. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for RCTs. The quality of the evidence for each comparison was graded using the online confidence in network meta-analysis tool (CINeMA). Standardized mean differences (SMDs) were calculated using the mean and standard deviation of pre-to-post intervention changes and then pooled using a random effects model in a pairwise meta-analysis using Review Manager 5.4. Then, a frequentist network meta-analysis was conducted using a random effects model was conducted to evaluate the efficacy of different exercise types using the network package of Stata 15. RESULTS: This study included 26 studies involving 2,170 participants. The pairwise meta-analysis revealed that exercise had a significant positive effect on depression in postmenopausal women (SMD = -0.71, 95% confidence interval [CI] = -0.94 to -0.48; I2 = 78%). The network meta-analysis revealed that mind-body exercise (SMD = -0.97, 95% CI = -1.28 to -0.67), aerobic exercise (SMD = -0.58, 95% CI = -0.88 to -0.27) and multicomponent exercise (SMD = -0.57, 95% CI = -1.15 to -0.002) significantly reduced depression compared to the control intervention. Mind-body exercise had the highest probability of being the most effective intervention. Exercise interventions also showed positive effects on anxiety. Most studies were judged to have some concerns regarding their risk of bias, and the confidence in evidence was often very low according to CINeMA. CONCLUSION: For postmenopausal women, there is very low to moderate quality evidence that exercise interventions are an effective antidepressant therapy, with mind-body exercise most likely being the optimal type. TRIAL REGISTRATION: This meta-analysis was prospectively registered with PROSPERO (registration number: CRD42024505425).

Rescue Therapies for Steroid-Refractory Acute Severe Ulcerative Colitis: A Systemic Review and Network Meta-analysis.

BACKGROUND AND AIMS: Approximately 40% of patients with steroid-refractory acute severe ulcerative colitis (steroid-refractory (SR) ASUC) requires colectomies. Advanced therapies may reduce the short-term colectomy rates in patients with SR ASUC. However, comparative clinical studies evaluating the effectiveness of these rescue therapies are lacking. Therefore, we conducted a network meta-analysis to study the effectiveness of rescue therapies for SR ASUC. METHODS: Six randomized controlled trials and 15 cohort studies including 2,004 patients were analyzed. Rescue drugs included tofacitinib, infliximab with a 5 or 10 mg/kg induction dose at 0, 2, and 6 weeks (IFX and IFX10, respectively), IFX with an accelerated regimen of three 5 mg/kg induction doses timed according to clinical need (accelerated IFX), tacrolimus, cyclosporine (CyA), ustekinumab, and adalimumab. Treatments were compared with a placebo. RESULTS: Tofacitinib (odds ratio [OR]: 0.09 [95% confidence interval [CI]: 0.02-0.52]), accelerated IFX (OR: 0.16 [95% CI: 0.03-0.94]), IFX (OR: 0.2 [95% CI: 0.07-0.58]), and tacrolimus (OR: 0.24 [95% CI: 0.06-0.96]) significantly reduced the short-term colectomy rates compared with placebo. IFX10 and CyA tended to prevent colectomies. However, ustekinumab and adalimumab did not significantly affect the colectomy rates. CONCLUSION: This is the first network meta-analysis to investigate the efficacy of advanced therapies in reducing short-term colectomy rates in patients with SR ASUC. Tofacitinib, accelerated IFX, standard IFX, and tacrolimus significantly reduced the colectomy rates in SR ASUC patients compared with placebo. Thus, advanced therapies should be considered for rescue therapies in patients with SR ASUC.

Efficacy and safety of first-line regimens for advanced HER2-positive breast cancer: A Bayesian network meta-analysis.

Background: The current standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is pertuzumab plus trastuzumab and docetaxel as first-line therapy. However, with the development of newer treatment regimens, there is a lack of evidence regarding which is the optimal treatment strategy. The aim of this network meta-analysis was to evaluate the efficacy and safety of first-line regimens for advanced HER2-positive breast cancer by indirect comparisons. Methods: A systematic review and Bayesian network meta-analysis were conducted. The PubMed, EMBASE, and Cochrane Library databases were searched for relevant articles published through to December 2023. The hazard ratio (HR) and 95% credible interval (CrI) were used to compare progression-free survival (PFS) between treatments, and the odds ratio and 95% CrI were used to compare the objective response rate (ORR) and safety. Results: Twenty randomized clinical trials that included 15 regimens and 7094 patients were analyzed. Compared with the traditional trastuzumab and docetaxel regimen, PFS was longer on the pyrotinib and trastuzumab plus docetaxel regimen (HR: 0.41, 95% CrI: 0.22-0.75) and the pertuzumab and trastuzumab plus docetaxel regimen (HR: 0.65, 95% CrI: 0.43-0.98). Consistent with the results for PFS, the ORR was better on the pyrotinib and trastuzumab plus docetaxel regimen and the pertuzumab and trastuzumab plus docetaxel regimen than on the traditional trastuzumab and docetaxel regimen. The surface under the cumulative ranking curve indicated that the pyrotinib and trastuzumab plus docetaxel regimen was most likely to rank first in achieving the best PFS and ORR. Comparable results were found for grade ≥3 AE rates of ≥10%. Conclusions: Our results suggest that the pyrotinib and trastuzumab plus docetaxel regimen is most likely to be the optimal first-line therapy for patients with HER2-positive breast cancer.

Comparative Efficacy of Omega-3 Fatty Acid with Other Interventions for Depression in Children and Adolescents: A Systematic Review and Network Meta-Analysis.

Background: The administration of omega-3 polyunsaturated fatty acid supplements is recommended as an adjuvant therapy for adults diagnosed with major depressive disorder. The evaluation of replicated data in combination treatment with omega-3 has been extensively conducted in adults over the past decade. However, the generalizability of these findings to pediatric groups is still uncertain. The objectives of this evaluation were twofold: (1) to evaluate the effectiveness of omega-3 and associated combination therapies in reducing the severity of depressive symptoms, and (2) to include remission rates (i.e., reduction of more than 50% in depression symptoms) as a measure of therapeutic efficacy. Methods: We conducted a literature search on PubMed/EMBASE from inception to October 2023. Data analyses were conducted using Stata (version 17.0). Results: We identified a total of 3168 articles. After eligibility screening of identified studies, nine studies (n = 561 participants) were included in our analysis herein. Pairwise comparisons revealed no significant improvement in depression symptoms for any intervention versus placebo. However, a clustered ranking plot identified omega-3 plus inositol as the most effective treatment for pediatric depression (77.3% efficacy). Omega-3 paired with psychoeducational psychotherapy significantly lowered the remission rate compared to placebo (standardized mean difference = 0.44, 95% confidence interval: 0.00-0.87, p = 0.048), resulting in a 91.5% remission rate, making it the most effective treatment in the study. Conclusions: Taken together, this network meta-analysis presents compelling evidence supporting the antidepressant effects of omega-3 in pediatric groups with depression. Future research should aim to investigate omega-3 as monotherapy for young individuals with depression, as well as investigate the efficacy of omega-3 in comparison to psychosocial interventions for affected individuals.

Which intervention is optimal to control blood glucose and improve physical performance in the elderly living with type 2 diabetes mellitus? A network meta-analysis.

BACKGROUND AND OBJECTIVES: This study aimed to find the optimal intervention available to both control blood glucose and improve physical function in the geriatric population with T2DM. METHODS AND STUDY DESIGN: A systemic review and network meta-analysis (NMA) was conducted to assess and rank the comparative efficacy of different interventions on glycosylated hemoglobin A1c (HbAc1), fasting blood glucose (FBG), muscle mass, grip strength, gait speed, lower body muscle strength, and dynamic balance. A total of eight databases were searched for eligible randomized controlled trials (RCTs) that the elderly aged more than 60 years or with mean age ≥ 55 years, the minimal duration of the RCT intervention was 6 weeks, and those lacking data about glycemic level and at least one indicator of physical performance were excluded. The Cochrane risk of bias tool was used to assess the bias of each study included. Bayesian NMA was performed as the main results, the Bayesian meta regression and the frequentist NMA as sensitivity analysis. RESULTS: Of the 2266 literature retrieved, 27 RCTs with a total of 2289 older adults were included. Health management provided by health workers exerts beneficial effects that is superior to other interventions at achieving glycemic control, but less marked improvement in physical performance. Exercise combined with cognitive training showed more pronounced improvement in muscle strength, gait speed, and dynamic balance, but ranked behind in decreasing the HbAc1 and FBG. CONCLUSIONS: Personalized health management combined with physical and cognitive training might be the optimal intervention to both accomplish glycemic control and improvement of physical performance. Further RCTs are needed to validate and assess the confidence of our results from this NMA.

Anti-PD-1/L1 antibody plus anti-VEGF antibody vs. plus VEGFR-targeted TKI as first-line therapy for unresectable hepatocellular carcinoma: a network meta-analysis.

Background: This article is based on our previous research, which was presented at the 2023 ASCO Annual Meeting I and published in Journal of Clinical Oncology as Conference Abstract (JCO. 2023;41:e16148. doi: 10.1200/JCO.2023.41.16_suppl.e16148). Both anti-programmed death 1/ligand-1 (PD-1/L1) antibody + anti-vascular endothelial growth factor (VEGF) antibody (A + A) and anti-PD-1/L1 antibody + VEGF receptor (VEGFR)-targeted tyrosine kinase inhibitor (A + T) are effective first-line therapies for unresectable hepatocellular carcinoma. However, there lacks evidence from head-to-head comparisons between these two treatments. We conducted a network meta-analysis on the efficacy and safety of them. Methods: After a rigorous literature research, 6 phase III trials were identified for the final analysis, including IMbrave150, ORIENT-32, COSMIC-312, CARES-310, LEAP-002, and REFLECT. The experiments were classified into three groups: A + A, A + T, and intermediate reference group. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and incidence of treatment-related adverse events (TRAEs). Hazard ratio (HR) with 95% confidence intervals (CI) for OS and PFS, odds ratio (OR) for ORR, and relative risk (RR) for all grade and grade ≥3 TRAEs were calculated. Under Bayesian framework, the meta-analysis was conducted using sorafenib as intermediate reference. Results: With the rank probability of 96%, A + A showed the greatest reduction in the risk of death, without significant difference from A + T (HR: 0.82, 95% CI: 0.65-1.04). A + T showed the greatest effect in prolonging PFS and improving ORR with the rank probability of 77%, but there were no statistical differences with A + A. A + A was safer than A + T in terms of all grade of TRAEs (RR: 0.91, 95% CI: 0.82-1.00) and particularly in those grade ≥3 (RR: 0.65, 95% CI: 0.54-0.77). Conclusions: A + A had the greatest probability of delivering the longest OS, while A + T was correlated with larger PFS benefits at the cost of a lower safety rate.

Safety Profile of First-Line Targeted Therapies in Elderly and/or Comorbid Chronic Lymphocytic Leukaemia Patients (Unfit Subpopulation). A Systematic Review and Network Meta-Analysis.

This systematic literature review (CRD42023393903) and a Bayesian network meta-analysis (NMA) aimed to assess the relative safety profile of first-line targeted therapies (acalabrutinib, ibrutinib, obinutuzumab, ofatumumab, pirtobrutinib, ublituximab, umbralisib, venetoclax, zanubrutinib) in chronic lymphocytic leukaemia (CLL) patients with advanced age and/or comorbidities. The NMA revealed that zanubrutinib was the safest treatment option in terms of the overall safety profile (e.g., serious adverse events [AEs] grade 1-5), followed by venetoclax-obinutuzumab, which showed an advantage in terms of AEs grade 1-5. The use of Bruton's tyrosine kinase inhibitor (BTKi) monotherapy was more favourable in terms of the risk of haematological AEs, but chemoimmunotherapy showed advantages in terms of cardiovascular, gastrointestinal, and infectious AEs. The risk of secondary cancers was similar between treatments. In conclusion, targeted therapies are associated with variable and clinically relevant AEs. The therapies appear to be safer when used as monotherapy rather than in combination with immunological agents in naïve CLL patients with advanced age and/or comorbidities.

Efficacy and safety of different pharmacological interventions in the treatment of tardive dyskinesia: a systematic review and network meta-analysis.

OBJECTIVES: The aim of this study is to indirectly compare and rank the different drugs that have been studied in randomized clinical trials (RCTs) in patients with tardive dyskinesia (TD) in terms of their efficacy in ameliorating the symptoms of TD and safety. DESIGN: A network meta-analysis and a systematic review were registered prospectively on PROSPERO under the ID: CRD42023407823 and were conducted in accordance with the PRISMA-NMA guidelines. DATA SOURCES: PubMed, Scopus, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Sciences, and Clinicaltrials.gov were searched to identify relevant records. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Any parallel randomized blinded controlled clinical trials that studied the use of any medications in treating TD and assessed the symptoms using a functional scale that has been previously validated. DATA EXTRACTION: The standardized mean difference of improvement along with the reported adverse events for each drug was extracted from each trial, and a network meta-analysis was conducted using a random-effects model. RESULTS: One thousand eight hundred seventeen patients in 33 RCTs were included in the analysis. Twenty-three different drugs were compared to placebo in terms of reduction in TD symptoms. Among these, valbenazine 80 mg (SMD = - 1.66, 95%CI = [- 2.55; - 0.78]), valbenazine 40 mg (- 1.00, [- 1.89; - 0.11]), and vitamin E (- 0.77, [- 1.45; - 0.1]) significantly reduced TD symptoms in comparison to placebo, while deutetrabenazine 36 mg (- 1.00, [- 2.12; 0.11]) and reserpine (- 0.54, [- 1.09; 0.02]) did not significantly reduce symptoms. Some serious adverse events were reported for valbenazine and deutetrabenazine, which included mainly psychiatric symptoms such as depression, worsening of schizophrenia, and suicidal ideation, while mild adverse events were reported for other drugs, and their incidence in the treatment arms was comparable to those in the placebo arm. CONCLUSIONS: Valbenazine (80 and 40 mg) and vitamin E demonstrated efficacy in treating tardive dyskinesia. However, the significant side effects of valbenazine should prompt further investigation of alternative treatment modalities.

Association between spontaneous breathing trial methods and reintubation in adult critically ill patients: A systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Reintubation is associated with higher risk of mortality. There is no clear evidence on the best spontaneous breathing trial (SBT) method to reduce the risk of reintubation. RESEARCH QUESTION: Are different methods of conducting SBT in critically ill patients associated with different risk of reintubation compared to T-tube? STUDY DESIGN AND METHODS: We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials (RCTs) investigating the effects of different SBT methods on reintubation. We surveyed PubMed, MEDLINE, CINAHL and CENTRAL databases from inception to 26th January 2024. The Surface Under the Cumulative Ranking curve (SUCRA) was used to determine the likelihood that an intervention was ranked as the best. Pairwise comparisons were also investigated by frequentist meta-analysis. Certainty of the evidence was assessed according to the GRADE approach. RESULTS: A total of 22 RCTs were included, for a total of 6196 patients. The network included nine nodes, with 13 direct pairwise comparisons. About 71% of the patients were allocated to T-tube and PSV-ZEEP, with 2135 and 2101 patients, respectively. The only intervention with a significantly lower risk of reintubation compared to T-tube was high flow oxygen (HFO) (RR 0.23, CrI 0.09 to 0.51, moderate quality evidence). HFO was associated with the highest probability of being the best intervention for reducing the risk of reintubation (81.86%, SUCRA 96.42), followed by continuous positive airway pressure (11.8%, SUCRA 76.75). INTERPRETATION: HFO SBT was associated with a lower risk of reintubation in comparison to other SBT methods. The results of our analysis should be considered with caution due to the low number of studies that investigated HFO SBT, and potential clinical heterogeneity related to co-interventions. Further trials should be performed to confirm the results on larger cohorts of patients and assess specific subgroups.

The effects of music-based interventions on behavioural and psychological symptoms of people living with dementia: a systematic review and network meta-analysis protocol.

OBJECTIVES: People living with dementia often experience behavioural and psychological symptoms of dementia (BPSD), which severely affect their well-being during the course of the disease. Particularly for BPSD outcomes, there is a high demand for increasing the evidence-based knowledge of non-pharmacological approaches, such as music-based interventions. Although previous reviews emphasize the potential effects of music-based interventions in people with dementia, they cover a wide range of different interventions and outcomes. METHOD: Therefore, this systematic review (SR) and network meta-analysis (NMA) aims to not only investigate the efficacy of music-based interventions on BPSD, but also to compare the impact of different types of music-based interventions on outcomes. Preferred reporting items for SR and meta-analysis protocols (PRISMA-P) and the PRISMA NMA extension were followed. Several databases will be searched from inception to the date the search will be performed, for relevant randomized or non-randomized controlled trials comparing a music-based intervention with treatment as usual, active controls, or another music-based intervention. Multivariate pairwise meta-analyses will be conducted for each outcome. NMA based on a frequentist random-effects model will be used to estimate the comparative effects of each type of music-based intervention and related components across outcomes. Heterogeneity will be investigated by meta-regression models. CONCLUSION: Based on our knowledge, this may be the first SR and NMA study to compare the efficacy of different types of music-based interventions. In addition, combined with our multivariate analysis approach, it will allow us to identify potential effect modifiers in music-based intervention for treating BPSD.

Psychotherapies for prolonged grief disorder in adults: A systematic review and network meta-analysis.

BACKGROUND: Prolonged grief disorder (PGD), a condition characterized by severe, persistent, and disabling grief, is newly included in ICD-11 and DSM-5-TR. Psychotherapies are among the most recommended treatments for PGD, but which should be considered as first-line treatment needs to be clarified. The purpose of this systematic review and network meta-analysis was to synthesize the available evidence to compare five outcomes of different psychotherapies on PGD in adults and identify the optimal psychotherapy modality to inform clinical decision-making for the treatment of PGD. METHOD: A comprehensive search was conducted in 7 databases from inception until March 20th, 2023. In the frequentist framework, pairwise and network meta-analyses using random-effects models were performed for outcomes with 95 % confidence interval (CI). RESULTS: There were 2962 records found and 55 studies (1,0330 participants) assessing 11 different psychological interventions were included. Compared with the waiting list, behavioral therapy (SMD=-1.05; 95 %CI=-1.71, -0.38), third-wave cognitive behavior therapy (SMD=-1.00; 95 %CI =-1.41, -0.58), family therapy (SMD=-0.87; 95 %CI=-1.59, -0.16), psychodynamic therapy (SMD=-0.88; 95 %CI=-1.67, -0.10) and cognitive therapy (SMD=-0.84; 95 %CI=-1.57, -0.12) were statistically effective in reducing grief symptom. Only cognitive behavior therapy (OR =0.48; 95 %CI = 0.27, 0.85) was more acceptable than waiting list. In terms of secondary outcome, third-wave CBT can statistically significantly reduce depression (SMD= -0.60; 95 %CI =- 0.84, -0.36), PTSD (SMD=-0.99; 95 %CI =- 1.62, -0.36) and anxiety (SMD= -1.44; 95 %CI =-2.63, -0.25) respectively. CONCLUSIONS: Most psychological interventions are effective, but only cognitive behavior therapy has the highest acceptability. Third-wave CBT with higher efficacy rates may be more beneficial for reducing secondary outcomes. To provide more robust evidence, high-quality trials should be conducted in the future.

A comparison of two models for detecting inconsistency in network meta-analysis.

The application of network meta-analysis is becoming increasingly widespread, and for a successful implementation, it requires that the direct comparison result and the indirect comparison result should be consistent. Because of this, a proper detection of inconsistency is often a key issue in network meta-analysis as whether the results can be reliably used as a clinical guidance. Among the existing methods for detecting inconsistency, two commonly used models are the design-by-treatment interaction model and the side-splitting models. While the original side-splitting model was initially estimated using a Bayesian approach, in this context, we employ the frequentist approach. In this paper, we review these two types of models comprehensively as well as explore their relationship by treating the data structure of network meta-analysis as missing data and parameterizing the potential complete data for each model. Through both analytical and numerical studies, we verify that the side-splitting models are specific instances of the design-by-treatment interaction model, incorporating additional assumptions or under certain data structure. Moreover, the design-by-treatment interaction model exhibits robust performance across different data structures on inconsistency detection compared to the side-splitting models. Finally, as a practical guidance for inconsistency detection, we recommend utilizing the design-by-treatment interaction model when there is a lack of information about the potential location of inconsistency. By contrast, the side-splitting models can serve as a supplementary method especially when the number of studies in each design is small, enabling a comprehensive assessment of inconsistency from both global and local perspectives.

Comparison of the efficacy and safety of vertebroplasty with different pedicle approaches for osteoporotic vertebral.

OBJECTIVE: To compare the efficacy and safety of vertebroplasty through different pedicle approaches in the treatment of osteoporotic vertebral compression fracture osteoporotic vertebral compression fractures (OVCF) by network meta-analysis. METHODS: Pubmed, Embase, Cochrane Library, Web of Science. Database for literature retrieval, retrieval time from the establishment of the database to April 2023, the randomized controlled trials of unilateral vertebroplasty (UVP), bilateral vertebroplasty (BVP), unilateral kyphoplasty (UKP), bilateral kyphoplasty (BKP), curved vertebroplasty (CVP) and curved kyphoplasty (CKP) were screened, evaluated and the data were extracted and included in the analysis. STATA 15.0 and ReMan 5.3 were used for data analysis. This study was registered in the National Institute for Health Research (NIHR) with the registration number CRD42023405181. RESULTS: This study included 16 articles with a total of 1712 patients. The order of visual analogue scale (VAS) improvement from good to bad is CVP > BVP > UVP > CKP > BKP > UKP. The order of kyphotic angles improvement from good to bad is CKP > UKP > UKP > UVP > BVP > CVP. The order of bone cement injection from less to more is UVP > CVP > UKP > CKP > BVP > BKP. The order of bone cement leakage rate from less to more is CKP > CVP > UKP > BKP > UVP > BVP. The order of X-ray exposure time from less to more is CKP > CVP > UVP > BVP > UKP > BKP. The order of operation time from less to more is CVP > UVP > UKP > CKP > BVP > BKP. CONCLUSION: For patients with kyphotic angles, kyphoplasty has unique advantages in improving kyphotic angles. But generally speaking, curved approach can optimize the distribution of bone cement through unilateral approach to achieve the orthopedic effect of bilateral approach, which is a minimally invasive technique with better curative effect and higher safety in the treatment of OVCF.