Surface Under The Cumulative Ranking Area Research Articles

Comparative Efficacy and Safety of Monoclonal Antibodies for Cognitive Decline in Patients with Alzheimer's Disease: A Systematic Review and Network Meta-Analysis.

Recent clinical trials of anti-Aβ monoclonal antibodies (mAbs) in the treatment of early Alzheimer's disease (AD) have produced encouraging cognitive and clinical results. The purpose of this network meta-analysis (NMA) was to compare and rank mAb drugs according to their efficacy and safety. PubMed, Embase, Web of Science, and the Cochrane Library were searched for randomized controlled trials testing various mAbs for the treatment of cognitive decline in patients with AD, up to March 31, 2023. R software (version 4.2.3) along with JAGS and STATA software (version 15.0) were used for statistical analysis. Odds ratio (OR) for binary variables, mean difference (MD) for continuous variables, and their 95% confidence intervals (CI) were utilized to estimate treatment effects and rank probabilities for each mAb in terms of safety and efficacy outcomes. We calculated the surface under the cumulative ranking area (SUCRA) to evaluate each mAb, with higher SUCRA values indicating better efficacy or lower likelihood of adverse events. Thirty-three randomized controlled trials with a total of 21,087 patients were included in the current NMA, involving eight different mAbs. SUCRA values showed that aducanumab (87.01% and 99.37%, respectively) was the most likely to achieve the best therapeutic effect based on the changes of Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale Sum of Boxes (CDR-SB) scores. Donanemab (88.50% and 99.00%, respectively) performed better than other therapies for Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Positron Emission Tomography-Standardized Uptake Value ratio (PET-SUVr). Lecanemab (87.24%) may be the most promising way to slow down the decrease of Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score. In the analysis of the incidence of adverse events (subjects with any treatment-emergent adverse event), gantenerumab (89.12%) had the least potential for adverse events, while lecanemab (0.79%) may cause more adverse events. Solanezumab (95.75% and 80.38%, respectively) had the lowest incidence of amyloid-related imaging abnormalities characterized by edema and effusion (ARIA-E) and by cerebral microhemorrhages (ARIA-H) of the included immunotherapies. While SUCRA values provided a comprehensive measure of treatment efficacy, the inherent statistical uncertainty required careful analysis in clinical application. Despite immunotherapies significantly increasing the risks of adverse events and ARIA, the data suggest that mAbs can effectively improve the cognitive function of patients with mild and moderate AD. According to the NMA, aducanumab was the most likely to achieve significant improvements in different cognitive and clinical assessments (statistically improved MMSE and CDR-SB), followed by donanemab (statistically improved ADAS-Cog, and PET-SUVr) and lecanemab (statistically improved ADCS-ADL).

Clinical effectiveness of pharmacological interventions for managing chronic migraine in adults: a systematic review and network meta-analysis

BackgroundChronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication is the most effective. We present a network meta-analysis to determine the effectiveness and rank of preventive drugs for chronic migraine in adults.MethodsWe identified, reviewed, and extracted data from randomised controlled trials (RCTs) of preventive drugs for chronic migraine with at least 200 participants. Data were analysed using network meta-analysis.FindingsWe included 12 RCTs of six medications (Eptinezumab, Erenumab, Fremanezumab, Galcanezumab, Onabotulinumtoxin A, and Topiramate) compared to placebo or each other. All drugs effectively reduced monthly headache and migraine days compared with placebo. The most effective drug for monthly headache days was Eptinezumab 300mg, with a mean difference of -2.46 days, 95% Credible Interval (CrI): -3.23 to -1.69. On the Surface Under the Cumulative Ranking Area (SUCRA) analysis, the probability that Eptinezumab 300mg was ranked highest was 0.82. For monthly migraine days, the most effective medication was Fremanezumab-monthly, with a mean difference: -2.77 days, 95% CrI: -3.36 to -2.17, and 0.98 probability of being ranked the highest. All included drugs, except Topiramate, improved headache-related quality of life. No eligible studies were identified for the other common preventive oral medications such as Amitriptyline, Candesartan, and Propranolol. The main reasons were that the studies did not define chronic migraine, were undertaken before the definition of chronic migraine, or were too small.InterpretationAll six medications were more effective than the placebo on monthly headache and migraine days. The absolute differences in the number of headache/migraine days are, at best, modest. No evidence was found to determine the relative effectiveness of the six included drugs with other oral preventive medications.RegistrationPROSPERO (number CRD42021265990).

Network Meta-analysis of Intraocular Lens Power Calculation Formula Accuracy in 1016 Eyes With Long Axial Length

To systematically review the literature and quantitatively synthesize the currently available evidence to compare the accuracy of different intraocular lens calculation formulas in eyes with long axial length (AL). Network meta-analysis. PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for studies published between January 2000 and June 2022. Included were prospective or retrospective clinical studies reporting the following outcomes in cataract patients with long AL (AL ≥ 26 mm): percentage of eyes with a prediction error (PE) within ±0.25, ±0.50 and ±1.00 diopters (D). Network meta-analysis was conducted using R software (version 4.2.1). 10 prospective or retrospective clinical studies, including 1016 eyes and 11 calculation formulas, were identified. A traditional meta-analysis showed that for the percentage of eyes with PE within ±0.25 D and ±0.50 D, the Olsen, Kane and Emmetropia Verifying Optical (EVO) all had insignificantly higher percentages compared to others. Considering the percentage of eyes with PE within ±1.00 D, the original and modified Wang-Koch adjustment formulas for Holladay 1 (H1-WK and H1-MWK) and EVO formulas showed superiority, but the difference was insignificant. This network meta-analysis revealed that compared with the widely used Barrett Universal II (BUII) formula, the Olsen, Kane and EVO formulas had higher percentages of eyes with PE within ±0.25 D, ±0.50 D and ±1.00 D (all OR > 1 but P > 0.05). Based on the surface under the cumulative ranking area (SUCRA) values for the percentage of eyes with PE within ±0.25 D, the Olsen (96.4%), Kane (77.5%) and EVO (75.9%) formulas had the highest probability of being in the top three of the 11 formulas. The Olsen, Kane and EVO formulas may perform better than others in calculating IOL power in eyes with long AL. Nevertheless, there is still considerable uncertainty in this regard and the accuracy of these formulas in highly myopic eyes should be confirmed in studies based on large multicenter registries.

Efficacy and safety of Tripterygium wilfordii multiglucoside for idiopathic membranous nephropathy: a systematic review with bayesian meta-analysis.

Background: Currently, the optimal therapy plan for idiopathic membranous nephropathy (IMN) remains controversial as there has been no comprehensive and systematic comparison of therapy plans for IMN. Therefore, in this study, a Bayesian meta-analysis was used to systematically evaluate the clinical efficacy and safety of various intervention plans involving traditional Chinese medicine TWM in the treatment of IMN. Methods: An electronic search in 7 databases was conducted from their inception to August 2022 for all published randomized controlled trials (RCTs) of various intervention plans for IMN. Network meta-analysis (NMA) was performed by using software R, and the surface under the cumulative ranking area (SUCRA) probability curve was plotted for each outcome indicator to rank the efficacy and safety of different intervention plans. Results: A total of 30 RCTs were included, involving 13 interventions. The results showed that (1) in terms of total remission (TR), ① GC + CNI + TWM was the best effective among all plans, and the addition and subtraction plan of CNI + TWM was the best effective for IMN; ② All plans involving TWM were more effective than GG; ③ Among monotherapy plans for IMN, TWM was more effective distinctly than GC, while TWM and CNI were similarly effective; ④ Among multidrug therapy plans for IMN, the addition of TWM to previously established therapy plans made the original plans more effective; ⑤The efficacy of combining TWM with other plans was superior to that of TWM alone. (2) In terms of lowering 24h-UTP, GC + TWM was the best effective and more effective than TWM. (3) In terms of safety, there was no statistically significant difference between all groups. However, CNI + TWM was the safest. No serious adverse events (AEs) occurred in all the included studies. Conclusion: The addition of TWM may be beneficial to patients with IMN. It may enhance the efficacy of previously established treatment protocols without leading to additional safety risks. In particular, GC + CNI + TWM, GC + TWM, and CNI + TWM with better efficacy and higher safety can be preferred in clinical decision-making as the therapy plans for IMN.

Comparison of different surgical techniques for chronic subdural hematoma: a network meta-analysis.

Chronic subdural hematoma (CSDH) is a neurosurgical condition with high prevalence. Many surgical approaches are recommended for treating CSDH, but there needs to be a consensus on the optimal technique. This network meta-analysis (NMA) compared the efficacy and safety of different surgical treatments for CSDH. Electronic databases, including PubMed, Embase, and the Cochrane Library, were searched for relevant studies up to February 2023. An NMA was performed to compare the outcomes of patients with CSDH treated by single-hole or double-hole craniotomy (SBHC and DBHC, respectively), twist-drill craniotomy (TDC), mini-craniotomy, and craniotomy. The NMA protocol was registered at INPLASY (registration no. 202320114). The NMA included 38 studies with 7,337 patients. For efficacy outcomes, DBHC showed the highest surface under the cumulative ranking area (SUCRA) values for recurrence (96.3%) and reoperation (87.4%) rates. DBHC differed significantly from mini-craniotomy in recurrence rate (odds ratio [OR] = 0.58, 95% confidence interval [CI]: 0.35, 0.97) and from SBHC (OR = 0.48, 95% CI: 0.25, 0.91) and TDC (OR = 0.40, 95% CI: 0.20, 0.82) in reoperation rate. For operative time, TDC was superior to SBHC (mean difference [MD] = -2.32, 95% CI: -3.78 to -0.86), DBHC (MD = -3.61, 95% CI: -5.55, -1.67), and mini-craniotomy (MD = -3.39, 95% CI: -5.70, -1.08). Patients treated by TDC had a shorter hospital stay than those treated by SBHC (MD = -0.82, 95% CI: -1.51, -0.12). For safety outcomes, there were no significant differences between groups in mortality and complication rates; however, mini-craniotomy (79.8%) and TDC (78.1%) had the highest SUCRAs. DBHC may be the most effective surgical treatment for CSDH based on the low recurrence and reoperation rates, although all examined techniques were relatively safe. https://inplasy.com/inplasy-2023-2-0114/.

Catheter ablation as first-line treatment in patients with atrial fibrillation: a Bayesian network meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Clinical trials suggest that early catheter ablation (CA) can be superior to anti-arrhythmic drugs (AADs) in "naïve" patients with AF. A low power to examine the outcomes, the use of a single technology ablation, and the short follow-up period are significant limitations of the studies. The EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) trial recently reported the results over three years of follow-up. Our research aims to update the comparison among different CA technologies with AADs as reference treatment. Interest outcomes included freedom from atrial tachycardia recurrences (ATRs) for efficacy and serious adverse events (AEs) for safety. Methods A systematic literature search was carried out up to Oct 31, 2022. We considered studies of patients with untreated atrial fibrillation who were enrolled in a trial in which they had been assigned to undergo initial rhythm-control therapy with cryoballoon (CRYO) or radiofrequency (RF) CA in at least one arm or to receive antiarrhythmic drugs (AADs). A Bayesian random-effects network meta-analysis (NMA) model comparing ATRs and AEs among the treatment arms was performed using MetaInsight V 4.0.0 web-based tool. Estimates are presented as Odds Ratio (OR) with a 95% Credible Interval (CrI). The surface under the cumulative ranking area (SUCRA) probabilities was selected to calculate the ranking and hierarchy of the different treatments. The larger SUCRA indicates the greater likelihood of becoming the best intervention. Results Six randomised control trials (RCTs) and one observational study (OBS) with 1,418 patients (mainly paroxysmal AF) were included. The follow-up period ranged from 12 to 36 months. The NMA demonstrates that ATRs were significantly lower with CRYO (OR [95% CrI], 0.36 [0.17-0.72]) and RF (OR [95% CrI], 0.39 [0.16-0.72]) compared with AADs. No significant difference was observed between CRYO and RF (OR [95% CrI], 1.09 [0.39-2.4]). The higher SUCRA value for CRYO (79%) indicated the likelihood that the treatment is the best, followed by RF (70%) and AADs (8%) (Figure 1). A total of 228 AEs were observed in 1,565 patients. The cumulative AEs associated with RF (OR [95% CrI], 1.31 [0.65-2.72]) and CRYO (OR [95% CrI], 0.72 [0.39-1.29]) were statistically similar in comparison with AADs. The indirect comparison showed no significant difference between the two ablative techniques. The probability of avoiding an AE was highest for CRYO (91%), followed by AADs (45%) and RF (14%) (Figure 2). In both analyses, the assessment of inconsistency for all studies was not significant (P > 0.05). Conclusions Our NMA demonstrated a lower rate of ATRs in patients treated with CRYO or RF CA than AADs. Furthermore, CA had a safety profile comparable to AADs. These results suggest recommending CA as a first-line treatment when early rhythm control is warranted, mainly in patients with paroxysmal AF.

Permanent pacemaker implantation following transcatheter aortic valve implantation: a systematic review and Bayesian network meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Permanent pacemaker implantation (PPI) remains a common complication after transcatheter aortic valve implantation (TAVI). Different transcatheter heart valves (THVs) exist, and newly approved devices are growing. A comparison according to the mechanisms of TAVI prosthesis with longer follow-up needs to be made. We address this issue using a systematic review and a Bayesian network meta-analysis (NMA). Methods A systematic literature review was carried out up to Oct 31, 2022, to identify studies reporting the use of balloon-expandable valves (BEVs), self-expandable valves (SEVs), and mechanically expandable valves (MEVs). We compared the various THVs, or standard medical treatment (STD), with a common comparator of surgical aortic valve replacement (SAVR) concerning PPI. Data at the most extended follow-up for each study were extracted. A random-effects Bayesian NMA was used to calculate odds ratios (OR) and 95% credible intervals (CrI) using MetInsight V4.0.0. The surface under the cumulative ranking area (SUCRA) probabilities was selected to calculate the ranking and hierarchy of the different treatments. The larger SUCRA indicates the greater likelihood of becoming the best intervention. Results We included 15 RCTs comprising 12.783 patients, among whom 8.585 underwent TAVI using various commercially available THVs, including BEVs (Sapien & Sapien XT, Sapien 3), MEVs (Corevalve, Evolut & Pro/R, Acurate Neo, Portico), and MEVs (Lotus). The median follow-up was 2.5 years (IQR 1-5). No significant differences in the risk of PPI were observed between STD: 1.70 [0.556, 5.39], Sapien & Sapien XT: 1.39 [0.834, 2.41], Sapien 3: 1.70 [0.977, 2.88], and Acurate Neo: 1.68 [0.768, 3.789], compared with SARV. All the other THVs (Corevalve: 3.07 [1.99. 4.959]; Evolut & Pro/R: 3.19 [1.80, 6.03]; Lotus: 5.22 [2.08, 13.7]; Portico: 7.22 [2.85, 19.4]) showed significant differences in the risk of PPI compared with SARV. In Bayesian ranking results, Sapien & Sapien XT had the highest chance (77%) of providing a lower PPI rate. Meanwhile, Portico THV was ranked the worst (5%) regarding the likelihood of PPI rate (Figure 1). According to the mechanism, all the THVs showed a higher risk for PPI than SARV (BEVs: 1.60 [1.01, 2.54]; SEVs: 3.09 [1.97, 4.96]; and MEV: 5.30 [1.62, 17.7]). STD: 1.92 [0.518, 7.14] had a non-significant PPI rate compared with SARV. SUCRA plot showed that SARV was the intervention with the lowest (95%) probability of PPI, followed by BEVs (65%), STD (55%), SEVs (27%) and MEVs (7%) (Figure 2). In both analyses, the assessment of inconsistency between direct and indirect estimates was not significant (P > 0.05). Conclusions This NMA of RCTs includes a more significant number of patients with longer follow-up. We demonstrated that BEVs are associated with lower PPI rates than SEVs and MEVs. Some newer generations of THVs (Acurate Neo, Evolut R/Pro) performed better than the older ones, reducing the PPI rate.

Comparative short-term risks of infection and serious infection in patients receiving biologic and small-molecule therapies for psoriasis and psoriatic arthritis: a systemic review and network meta-analysis of randomized controlled trials.

Infection events are a major concern for patients and physicians when making psoriasis treatment decisions. To estimate the relative short-term risks of infection and serious infection for biologic and small molecule therapies in the treatment of moderate-to-severe plaque psoriasis (PsO) and psoriatic arthritis (PsA). A systematic literature search of the PubMed, EMBASE, and Web of Science databases was conducted on 17 June 2022. We included phase II, III, or IV randomized controlled trials (RCTs) of biologic and small-molecule therapies that are licensed or likely to gain approval soon for PsO and PsA, as well as infection data reports. Two investigators independently extracted the data based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Network meta-analysis (NMA) was performed to estimate the pooled relative risks (RRs) and corresponding 95% confidence intervals of total infections and serious infections for treatments during placebo-controlled phases of RCTs. The surface under the cumulative ranking area (SUCRA) was calculated to rank the infection risk for each treatment. A total of 94 RCTs with a total of 19 treatment arms involving 54,369 participants were analyzed. For patients with PsO, bimekizumab, secukizumab, risankizumab, ustekinumab, apremilast, guselkumab, and adalimumab were associated with significantly higher risks of infection than placebo; SUCRA ranked infliximab, deucravacitinib, and bimekizumab with the highest risks of infection. For patients with PsA, bimekizumab, apremilast, and upadacitinib (30 mg daily) were associated with higher risks of infection; SUCRA ranked bimekizumab with the highest risk of infection. No treatments, except for upadacitinib (30 mg daily), were associated with a higher risk of serious infection than placebo in PsA. This NMA provides a comprehensive assessment of the comparative short-term risks of infection, which could help physicians and patients to select individualized treatments for psoriasis. CRD42022359873.

Efficacy of low or heavy rituximab‑based protocols and comparison with seven regimens in idiopathic membranous nephropathy: a systematic review and network meta-analysis.

Numerous studies have demonstrated the efficiency of tacrolimus + rituximab and rituximab in idiopathic membranous nephropathy (IMN). But optimal dosages of rituximab for IMN are still controversial. This network meta-analysis (NMA) was conducted to compare the efficacy of different rituximab dosages and other main treatments in IMN treatment. Randomized controlled trials (RCTs) and observational studies analyzing nine therapeuticregimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR) and relapse rate. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions. Twelve RCTs and 12 observational studies involving 1724 patients were pooled for comparison of 9 interventions. This NMA demonstrated steroids + tacrolimus was ranked first in the aspect of total remission at 6months (92%) and 12months (81.3%). The total remission rate associated with tacrolimus + rituximab increased rapidly between the sixth (SUCRA 22.5%) and the twelfth month (SUCRA 63.9%). Tacrolimus and cyclosporine A were associated with higher total remission at 6months (78.8% and 65.4%, separately) and decreased at 12months (58.1 and 34.9%, separately). Steroids + cyclophosphamide, rituximab (Heavy dose) and rituximab (Low dose) had stable remission rates at 6 (63.7%, 46.6%, and 19.4%) and 12months (SUCRA 66.9%, 39.6%, and 28.8%). Tacrolimus and cyclosporine A were associated with a significantly higher risk of relapse than that with steroids + cyclophosphamide, rituximab (Heavy dose), and rituximab (Low dose). For IMN in adults, steroids + tacrolimus was ranked first in the aspect of total remission, followed by steroids + cyclophosphamide and steroids + cyclosporine A. The TR associated with rituximab (Heavy and Low dosage) at 12months was higher than that at 6months. And rituximab (Heavy dose) achieves a higher rate of total remission than that of rituximab (Low dose).

Determining the Optimal (Neo)Adjuvant Regimen for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Regarding Survival Outcome: A Network Meta-Analysis.

BackgroundThe optimal (neo)adjuvant regimen for human epidermal growth factor receptor-2 (HER2)-positive breast cancer regarding survival outcomes remains unclear.MethodsWe searched Web of Science, PubMed, and the Cochrane Central Register of Controlled Trials systematically to find out randomized controlled studies, up to January 2022, that compared different anti-HER2 regimens in the (neo)adjuvant setting. The primary endpoint was disease-free survival (DFS). We used a Bayesian statistical model to combine direct and indirect comparisons and used odds ratios (ORs) to pool effect sizes and performed the surface under the cumulative ranking area (SUCRA) curves to estimate the ranking probabilities of various regimens. For survival outcomes, we performed two parallel analyses, one based on data from both neoadjuvant and adjuvant studies and the other specific to adjuvant studies. All statistics were two-sided.ResultsFifteen studies were finally enrolled. Regarding DFS, the overall analysis indicated that the top two regimens for HER2-positive breast cancer were chemotherapy plus trastuzumab with lapatinib, and chemotherapy plus trastuzumab with pertuzumab (SUCAR of 81% and 79%, respectively), with the OR of 0.99 [95% confidence interval (CI), 0.59 to 1.54]; the parallel analysis specific to adjuvant trials indicated that the top two regimens were chemotherapy plus trastuzumab with sequential neratinib, and chemotherapy plus trastuzumab with pertuzumab (SUCRA of 80% and 76%, respectively), with the OR of 1.04 (95% CI, 0.63 to 1.73). The dual-target therapy that combines trastuzumab and pertuzumab showed the highest risk of inducing cardiac events, with an SUCRA of 92%.ConclusionsChemotherapy plus trastuzumab and pertuzumab might be the optimal regimen for HER2-positive breast cancer in improving the survival rate. However, the cardiotoxicity of this dual-target therapy should be taken care of.

Treatment of Idiopathic Membranous Nephropathy for Moderate or Severe Proteinuria: A Systematic Review and Network Meta-Analysis.

Objective Numerous studies have demonstrated that the efficacy of drugs differs in idiopathic membranous nephropathy (IMN) patients with moderate or high proteinuria. However, there is no systematic comparison confirming it. This network meta-analysis (NMA) was performed to respectively compare the efficacy of ten IMN treatments in patients with moderate and high proteinuria and compare the risk of adverse events with 10 IMN regimens. Methods Randomized controlled trials (RCTs) and observational studies analyzing the main therapeutic regimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR), bone marrow suppression, and gastrointestinal symptoms. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions. Results Seventeen RCTs and eight observational studies involving 1778 patients were pooled for comparison of ten interventions. Steroid + tacrolimus (TAC) showed the highest probabilities of TR whether patients had severe proteinuria or not (SUCRA 89.5% and 88.9%, separately). Rituximab (RTX) was more beneficial for TR on patients with proteinuria <8 g/d (SUCRA 66.0%) and was associated with a lower risk of bone marrow suppression and gastrointestinal symptoms (SUCRA 21.7% and 21.4%, separately). TAC + RTX and steroids + cyclophosphamide induced the highest rates of bone marrow suppression (SUCRA 90.6% and 88.3%, separately) and gastrointestinal symptoms (SUCRA 86.0% and 72.1%, separately). Conclusions Steroids + TAC showed significant efficacy in patients with all degrees of proteinuria, while RTX was more effective in patients with moderate proteinuria and was safer in bone marrow suppression and gastrointestinal symptoms.

Effect of exercise on bone mineral density among patients with osteoporosis and osteopenia: A systematic review and network meta-analysis.

To systematically review and compare the efficacy of different exercise interventions on bone mineral density (BMD, g/cm2 ) in patients with osteoporosis and osteopenia. It is vitally important to prevent and treat bone loss in patients with osteoporosis and osteopenia. Exercise can effectively increase bone density and slow down bone loss in middle-aged and older people. However, it is still unclear which type of exercise intervention is the most effective on bone mineral density. Systematic review and network meta-analysis (NMA) according to PRISMA. Randomised controlled trials of different exercise treatments for osteopenia and primary osteoporosis were included. A Frequentist network meta-analysis was conducted to appraise the efficacy of different types of exercise. The outcome was bone mineral density of different parts of the body. Ninety-seven studies were included. The network meta-analysis showed that combined exercise, resistance exercise, aerobic exercise and mind-body exercise had a significant effect in improving the bone density of lumbar spine. The surface under the cumulative ranking area (SUCRA) values for mind-body exercise was 0.99 and ranked first. For BMD of the femoral neck, all kinds of exercise interventions increased the bone density significantly compared with no exercise and the optimal type was mind-body exercise (SUCRA=0.99). In terms of the total hip bone mineral density, aerobic exercise and resistance exercise could improve hip bone density, with the resistance exercise (SUCRA=0.95) ranking as first. This NMA demonstrated the mind-body exercise might be the optimal exercise type to increase the BMD of the lumbar spine and femoral neck and resistance exercise is the most promising type for total hip BMD.

A pairwise and network meta-analysis comparing the efficacy and safety of progestogens in threatened abortion.

Progesterone is widely used to prevent threatened miscarriage. To determine the efficacy and safety of progestogens in the treatment of threatened miscarriage. PubMed, Cochrane Library, EMBASE, CNKI, CBM, and WanFang databases were searched for randomized controlled trials (RCTs) published from the date of inception of the database to August 2020. The search terms included "abortion, threatened," "progesterone," and "progestogens." A network meta-analysis was conducted of all the RCTs on threatened abortion so far to compare the efficacy and safety of different progestogens in the treatment of threatened abortion. Odds ratios for dichotomous data with 95% confidence intervals were calculated and the data were pooled using a random-effects model. The surface under the cumulative ranking area (SUCRA) was calculated for efficacy and safety with different interventions. A total of 59 RCTs with 10 424 participants were included. Oral dydrogesterone (DYD) had the lowest risk of miscarriage (SUCRA 100.0%), followed by vaginal progesterone (SUCRA 67.9%). Oral micronized progesterone had the highest risk of miscarriage (SUCRA 15.7%). Oral DYD is effective in the treatment of threatened miscarriage. The results of the present study can help patients make informed decisions about treatment options for threatened miscarriage.

Different pedagogies for acquisition of knowledge and skill: a systematic review and network meta-analysis

BackgroundThis network meta-analysis aimed to assess the efficacy of different educational methods for healthcare professionals.MethodsA systematic literature search was conducted to identify relevant randomised controlled trials. The standardised mean difference...

Efficacy and cost of different treatment in patients with idiopathic membranous nephropathy: A network meta-analysis and cost-effectiveness analysis

BackgroundIdiopathic membranous nephropathy (IMN) is the most common pathological type of adult nephrotic syndrome. However, the treatments for IMN patients had not been compared from the perspectives of therapeutic effect and pharmacoeconomics. Therefore, a network meta-analysis and a cost-effectiveness analysis were conducted to find the optimum treatment for IMN patients. MethodsRandomized controlled trials (RCTs) which compared the treatments including cyclophosphamide (CTX), mycophenolate mofetil (MMF), cyclosporine (CsA), tacrolimus (TAC), leflunomide (LEF), chlorambucil (CLB) and rituximab (RTX) for patients with IMN were reviewed. The complete and partial remission rates were extracted and then compared by network meta-analysis. The surface under the cumulative ranking area (SUCRA) was calculated to rank the remission rate for all treatments. Then, the cost-effectiveness analysis was performed to compared the incremental cost-effectiveness ratio (ICER) of different treatments. ResultsA total of 75 articles with 4806 participants were included according to the inclusion and exclusion criteria. Compared with the glucocorticoids (GC) group, CTX + GC (95%RR 1.02,1.76), CsA + GC (95%RR 1.11,2.13) and TAC + GC (95%RR 1.44,2.59) were associated with a significantly higher rate of complete remission. TAC + GC were most likely to be ranked the best (SUCRA of 92.1%). From the perspective of the cost-effectiveness analysis in China, the ICER of LEF + GC to CTX + GC was $30616.336 per unit utility, and that of TAC + GC to CTX + GC was $670475.210 per unit utility. And the ICER of CTX + GC to LEF + GC in the UK was $-65680.879 per unit utility. ConclusionsCTX + GC was the cheapest treatment with obvious curative effect in China, while LEF + GC was a cost-effective alternative to CTX + GC. The remission rate of TAC + GC was highest despite the high single-dose cost.

Comparative efficacy between monoclonal antibodies and conventional drugs in postmenopausal women with osteoporosis: a network meta-analysis.

To evaluate the efficacy of different pharmacological interventions, with emphasis on monoclonal antibodies (McAbs) for the treatment of postmenopausal osteoporotic women. A search of PubMed, Google Scholar, Embase, and the Cochrane Library, as well as China National Knowledge Infrastructure (CNKI) was performed. Data were collected and pooled using Bayesian network meta-analysis (NMA), which conducts both direct and indirect comparisons. The primary outcome was the percentage change in bone mineral density (BMD) in the lumbar spine from baseline to 1 year of treatment. All drugs were ranked based on the surface under the cumulative ranking area (SUCRA). Furthermore, the heterogeneity, consistency, and publication bias of the enrolled literature were assessed. There were 14 randomized controlled trials (RCTs) consisting of 4,881 participants included to compare 11 interventions. Compared with that of a placebo, all the 10 selected therapies showed significant efficacy through changes in BMD ranging from 6.0% to 19.0% (all P<0.01). As the SUCRA values indicated, the therapeutic performance of antibody drugs was better than that of the conventional chemical agents, and blosozumab was the best choice (SUCRA 99.2%) to improve lumbar spine BMD. Novel McAb treatments achieved better therapeutic effects in the treatment of postmenopausal osteoporosis (PMO), especially blosozumab. Further trials are needed to investigate and optimize the delivery strategy of McAbs.

Comparative Efficacy and Safety of Anti-PD-1/PD-L1 Immune Checkpoint Inhibitors for Refractory or Relapsed Advanced Non-Small-Cell Lung Cancer-A Systematic Review and Network Meta-Analysis.

Simple SummaryImproving treatment strategies for refractory or relapsed advanced non-small-cell lung cancer (NSCLC) remains a challenge. Efficacy and safety of the immune checkpoint inhibitors (ICIs), nivolumab (Niv) plus atezolizumab (Atz), were compared with those of ramucirumab (Ram) plus docetaxel (Doc), and the efficacy and safety of these two ICIs were compared with each other, using patient groups without programmed cell death ligand-1 (PD-L1) constraint. Additionally, efficacy and safety of, Niv, Atz, and pembrolizumab (Pem) were compared using a PD-L1 positive (≥1%) subgroup with refractory or relapsed advanced NSCLC. Niv or Atz was found to be more effective and safer than Ram plus Doc in groups without PD-L1 constraint. In the PD-L1 positive subgroup, Pem (10 mg/kg) showed the highest efficacy for ensuring overall survival, followed by Niv, Pem (2 mg/kg), Atz, and Doc. These results may help clinicians select and evaluate treatment options for relapsed or refractory advanced NSCLC.The efficacy and safety of immune checkpoint inhibitors (ICIs) in refractory or relapsed advanced non-small-cell lung cancer (NSCLC) have not yet been compared with those of ramucirumab (Ram) plus docetaxel (Doc). Furthermore, comprehensive comparisons between ICIs have not been conducted to date. In the current study, a Bayesian network meta-analysis of related phase III clinical trials was performed to compare the efficacy and safety of Ram+Doc, Niv, Atz, and Doc treatments in patient groups lacking the PD-L1 constraint. Surface under the cumulative ranking area (SUCRA) revealed that the overall survival (OS) of patients treated with Niv was the highest, followed by Atz, Ram+Doc, and Doc. Regarding grades 3–5 treatment-related adverse events (G3–5AEs), the use of Niv was ranked the safest, followed by Atz, Doc, and Ram+Doc. Significant differences in OS were observed between Niv and Ram+Doc, while significant differences in G3–5AEs were observed between Ram+Doc and Niv or Atz. In the PD-L1 positive (≥1%) patient subgroup, Pem (10 mg/kg) ranked the highest in efficacy for OS, followed by Niv, Pem (2 mg/kg), Atz, and Doc. These findings may expectedly provide oncologists with useful insights into therapeutic selection for refractory or relapsed advanced NSCLC.

HER2-targeted regimens after prior trastuzumab for patients with HER2-positive unresectable, locally advanced or metastatic breast cancer: a network meta-analysis of randomized controlled trials.

BackgroundSeveral human epidermal growth factor receptor 2 (HER2)-targeted regimens (anti-HER2 target agent combined chemotherapy) have been introduced for the treatment of HER2-positive locally advanced or metastatic breast cancer progressed after trastuzumab. We therefore conducted a network meta-analysis to compare and rank HER2-targeted regimens in this population after trastuzumab therapy.MethodsThe electronic databases of PubMed, EmBase, Cochrane Central Register of Controlled Trials, and the websites of http://clinicaltrials.gov/ (US NIH) were systematically searched for published and unpublished randomized controlled trials (RCTs) from their inception to October, 2020. Nine treatment regimens were eligible to be included in this analysis. The primary outcomes were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS), while the secondary outcomes were grade ≥3 adverse events.ResultsA total of 2,104 citations were identified and 12 RCTs comprising 3,769 patients were selected for final analysis. For HER2 positive unresectable, locally advanced or metastatic patients progressed after trastuzumab therapy pyrotinib plus capecitabine ranked the highest surface under the cumulative ranking area (SUCRA) in PFS, ORR and its SUCRA in OS was higher than Trastuzumab emtansine (T-DM1). T-DM1 plus atezolizumab, pyrotinib plus capecitabine, and pertuzumab plus trastuzumab plus capecitabine had comparable SUCRA in OS (76.1% vs. 74.5% vs. 71.2%). Six of included studies reported any grade ≥3 adverse events, the prevalence of any grade ≥3 adverse events in lapatinib plus capecitabine (353/683), T-DM1 (213/558), trastuzumab plus capecitabine (130/218), pertuzumab plus trastuzumab plus capecitabine (118/228), pyrotinib plus capecitabine (220/384), T-DM1 plus atezolizumab (43/132) and capecitabine (24/94) were 51.7%, 38.2%, 59.6%, 51.8%, 57.3%, 32.6% and 25.5%, respectively. Specific adverse event characteristics related to different HER2-targeted regimens need to be well known ahead and managed during the therapy.ConclusionsThe results indicated that for HER2 positive breast cancer with previous trastuzumab therapy pyrotinib plus capecitabine was probably more efficacious in PFS and ORR. T-DM1 plus atezolizumab, pyrotinib plus capecitabine and pertuzumab plus trastuzumab plus capecitabine have comparable effect on OS improvement and all of them were likely better than T-DM1. The risk of grade ≥3 adverse events for specific treatment regimens were also provided.

Comparative Efficacy of Acalabrutinib in Frontline Treatment of Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-analysis

PurposeThe goal of this study was to estimate the relative efficacy of acalabrutinib (monotherapy and in combination with obinutuzumab) compared with standard frontline treatments for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, through a network meta-analysis (NMA). MethodsThe efficacy of acalabrutinib from ELEVATE-TN (study of Obinutuzumab + Chlorambucil, Acalabrutinib [ACP-196] + Obinutuzumab, and Acalabrutinib in Subjects With Previously Untreated CLL) was compared to bendamustine + rituximab, chlorambucil-based therapy, alemtuzumab, ibrutinib mono/combination therapy and venetoclax + obinutuzumab using data from eight randomized controlled trials (RCTs). Relevant RCTs were identified using a systematic literature review. Two evidence networks were constructed: Network A, composed solely of RCTs that met the inclusion criteria; and Network B, composed of 7 RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil + obinutuzumab from iLLUMINATE. Bayesian NMAs were conducted on progression-free survival (PFS) and overall survival (OS) endpoints; results were reported by using hazard ratios (HRs) and 95% credible intervals (CrIs). HRs were considered significant if their CrIs did not cross 1. Treatments were ranked by using the surface under the cumulative ranking area (SUCRA) values. Expert opinion from 2 hematologists was sought to validate results. FindingsBoth networks showed a significant improvement in PFS for acalabrutinib + obinutuzumab over all comparators. Both networks also showed a significant improvement in PFS for acalabrutinib monotherapy versus most comparators, with a significant difference to ibrutinib monotherapy found in Network A but not Network B. Conversely, a significant difference in PFS was observed for acalabrutinib monotherapy versus venetoclax + obinutuzumab in Network B but not Network A. Although OS HRs all favored acalabrutinib, most were not significant and were characterized by wide CrIs, indicating a high level of uncertainty. Acalabrutinib + obinutuzumab ranked highest in terms of PFS improvement (SUCRA values, 98% and 100%) and OS improvement (SUCRA values, 92% and 94%), followed by acalabrutinib monotherapy (SUCRA values for PFS, 88% and 90%; OS, 83% and 87%) in Networks A and B, respectively. ImplicationsAcalabrutinib was associated with favorable PFS and OS compared with frontline CLL therapies and ranked highest in treatment efficacy over the other comparators. The NMA was limited by heterogeneity in patient baseline characteristics across trials, variable treatment regimens, and short study follow-up times. Despite these limitations, the NMA provides insights into the relative efficacy of acalabrutinib compared with frontline CLL therapies in the absence of head-to-head clinical trials.

The Inhibition of Complement System in Formal and Emerging Indications: Results from Parallel One-Stage Pairwise and Network Meta-Analyses of Clinical Trials and Real-Life Data Studies

This manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common “off-label” (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484): Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA < 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs.