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The superiority of angiotensin receptor-neprilysin inhibitor (ARNI) over angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin receptor blocker (ARB) has not been reassessed after the publication of recent trials that did not find clinical benefits. Therefore, we performed an updated network meta-analysis comparing the efficacy and safety of ARNI, ACE-I, ARB, and placebo in heart failure with reduced ejection fraction. We included randomized clinical trials that compared ARNI, ARB, ACE-I, and placebo in heart failure with reduced ejection fraction. We extracted prespecified efficacy end points and produced network estimates, p scores, and surface under the cumulative ranking curve scores using frequentist and Bayesian network meta-analysis approaches. A total of 28 randomized controlled trials including 47,407 patients were included. ARNI was associated with lower risk of all-cause mortality (relative risk [RR] 0.81, 95% confidence interval [CI] 0.68 to 0.96), cardiac death (RR 0.79, 95% CI 0.64 to 0.99), and major adverse cardiac events (MACEs; RR 0.83, 95% CI 0.72 to 0.97) but higher risk of hypotension (RR 1.46, 95% CI 1.02 to 2.10) than ARB. ARNI was associated with lower risk of MACE (RR 0.85, 95% CI 0.74 to 0.97), but higher risk of hypotension (RR 1.69, 95% CI 1.27 to 2.24) compared with ACE-I. P scores and surface under the cumulative ranking curve scores demonstrated superiority of ARNI over ARB and ACE-I in all-cause mortality, cardiac death, MACE, and hospitalization for heart failure. In conclusion, ARNI was associated with improved clinical outcomes, except for higher risk of hypotension, compared with ARB and ACE-I.

Preemptive analgesia may improve postoperative pain management, but the optimal regimen is unclear. This study aimed to compare the effects and adverse events of preemptive analgesia on postoperative pain and opioid consumption.In this network meta-analysis, 19 preemptive analgesia regimens were compared. Two authors independently searched databases, selected studies, and extracted data. Primary outcomes were the intensity of postoperative pain and opioid consumption. Secondary outcomes included the time to first analgesia rescue and incidence of postoperative nausea or vomiting (PONV).In total, 188 studies were included (13 769 subjects). Ten of 19 regimens reduced postoperative pain intensity compared with placebo, with mean differences 100-point scale ranging from -4.79 (95% confidence interval [CI]: -8.61 to -0.96.) for gabapentin at 48 h to -21.99 (95% CI: -36.97 to -7.02) for lornoxicam at 6 h. Eight regimens reduced opioid consumption compared with placebo, with mean differences ranging from -0.48 mg (95% CI: -0.89 to -0.08) i.v. milligrams of morphine equivalents (IMME) for acetaminophen at 12 h to -2.27 IMME (95% CI: -3.07 to -1.46) for ibuprofen at 24 h. Five regimens delayed rescue analgesia from 1.75 (95% CI: 0.59-2.91) h for gabapentin to 7.35 (95% CI: 3.66-11.04) h for epidural analgesia. Five regimens had a lower incidence of PONV compared with placebo, ranging from an odds ratio of 0.22 (95% CI: 0.11-0.42) for ibuprofen to 0.59 (95% CI: 0.40-0.87) for pregabalin.Use of preemptive analgesia reduces postoperative pain, opioid consumption, and postoperative nausea or vomiting, and delays rescue analgesia.PROSPERO CRD42021232593.

To review the use of oral gonadotropin-releasing hormone (GnRH) antagonists and synthesize their efficacy and safety parameters for the treatment of endometriosis-associated pain.Systematic review and network meta-analysis.Not applicable.Premenopausal women with endometriosis who had experienced moderate or severe pain.The Web of Science, Embase, Scopus, and MEDLINE were searched until April 10, 2022. Only randomized controlled trials were included. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool 2. A Bayesian random-effects network meta-analysis was used to perform indirect comparisons. IEndometriosis-associated pain, dysmenorrhea, dyspareunia, and noncyclic pelvic pain reduction.(s): Five studies and 6 randomized controlled trials, including a total of 2,796 women and 10 different doses of oral GnRH antagonist treatments, were eligible for inclusion. All studies were considered to have a low risk of bias. Almost all efficacy- and safety-related outcomes showed a dose-response relationship. Regarding endometriosis-associated pain, the top 3 treatments were elagolix 400 mg, linzagolix 75 mg, and linzagolix 200 mg, with mean differences of -1.26 (95% credible interval [CrI], -1.70 to -0.79), -0.98 (95% CrI, -1.84 to -0.15), and -0.98 (95% CrI, -1.90 to -0.064), respectively. The top 3 treatments to decrease dysmenorrhea were relugolix 40 mg, elagolix 400 mg, and relugolix 20 mg, with mean differences of -1.60 (95% CrI, -2.07 to -1.14), -1.25 (95% CrI, -1.56 to -0.95), and -1.10 (95% CrI, -1.59 to -0.62), respectively. However, only high-dose treatments were significantly associated with most quality of life- and adverse effect-related outcomes. Relugolix 40 and 20 mg and elagolix 400 mg, with odds ratios of 6.88 (95% CrI, 2.18-24.58), 1.60 (95% CrI, 0.62-4.13), and 1.85 (95% CrI, 1.05-3.30), had a significantly increased incidence of adverse events.(s): Oral GnRH antagonists are effective for endometriosis-associated pain and dysmenorrhea and the patient global impression. The incidence of ovarian hypoestrogenic effects in a short-term duration was significant in a dose-effect response, particularly the highest dose.International Prospective Register of Systematic Reviews registration number CRD42022332904.

To assess exercise therapies that aim to enhance proprioception in individuals with chronic ankle instability (CAI).Five databases (PubMed, Embase, Cochrane Library, Web of Science, and EBSCO) were searched in October 2021.Randomized controlled trials involving exercise therapy conducted on individuals with CAI were included.Data were extracted by 2 independent reviewers using a standardized form. Methodological quality and risk of bias were assessed with the Physiotherapy Evidence Database scale.The end trial weighted mean difference and standard deviations were analyzed, and the synthetic value for the improvement in error scores of ankle joint position sense in multiple directions was evaluated.Eleven trials with 333 participants were eligible for inclusion in this systematic review and were included in the network meta-analysis. Foot and ankle muscle strengthening exercise showed the highest probability of being among the best treatments (surface under the cumulative ranking [SUCRA]=74.6%). The next 2 were static balance exercise only (SUCRA=67.9%) and corrective exercise (SUCRA=56.1%). The SUCRA values of proprioceptive exercise, dynamic balance exercise only, aquatic exercise, rehabilitation exercise with brace, mixed static/dynamic balance exercise, and control were at relatively low levels and scored at 49.6%, 48.8%, 47.8%, 47.7%, 44.0%, and 13.5%, respectively.Foot and ankle muscle strengthening exercise may have a good effect when used to improve joint position sense in individuals with CAI. The more complex balance exercise intervention becomes, the less effective the proprioceptive outcome.

Randomized controlled trials (RCTs) investigating the optimal screening strategy for atrial fibrillation (AF) have yielded conflicting results.To examine the comparative efficacy of different AF screening strategies in older adults.We searched MEDLINE, EMBASE and Cochrane without language restrictions through January 2022, for RCTs evaluating the outcomes of non-invasive AF screening approaches among adults ≥65 years. We conducted a pairwise meta-analysis comparing any AF screening approach versus no screening, and a network meta-analysis comparing systematic screening versus opportunistic screening versus no screening. The primary outcome was new AF detection.The final analysis included 9 RCTs with 85,209 patients. The weighted median follow-up was 12 months. The mean age was 73.4 years and men represented 45.6%. On pairwise meta-analysis, any AF screening (either systematic or opportunistic) was associated with higher AF detection (1.8% vs. 1.3%; risk ratio [RR] 2.10; 95% confidence interval [CI] 1.20-3.65) and initiation of oral anticoagulation (RR 3.26; 95%CI 1.15-9.23), compared with no screening. There was no significant difference between any AF screening versus no screening in all-cause mortality (RR 0.97; 95%CI 0.93-1.01) or acute cerebrovascular accident (CVA) (RR 0.92; 95%CI 0.84-1.01). On network meta-analysis, only systematic screening was associated with higher AF detection (RR 2.73; 95% CI 1.62-4.59) and initiation of oral anticoagulation (RR 5.67; 95% CI 2.68-11.99), but not with the opportunistic screening, compared with no screening.Systematic AF screening using non-invasive tools was associated with higher rate of new AF detection and initiation of OAC, but opportunistic screening was not associated with higher detection rates. There were no significant differences between the various AF screening approaches with respect to rates of all-cause mortality or CVA events. However, these analyses are likely underpowered and future RCTs are needed to examine the impact of systematic AF screening on mortality and CVA outcomes.None.

Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available evidence and provide estimates of comparative effectiveness and ranking of treatment effects.All randomized controlled trials studying patients (1 month of age) with benzodiazepine-resistant SE were included. Outcomes including seizure cessation within 60 min, seizure freedom for 24 h, death, respiratory depression warranting intubation and cardiovascular instability were studied. Conventional and network meta-analyses (NMA) were done.Seventeen studies were included (16 in NMA). Phenobarbital and high-dose levetiracetam were significantly superior to phenytoin with respect to seizure cessation within 60 min. Network ranking demonstrated that phenobarbital had the highest probability of being the best among the studied interventions followed by high-dose levetiracetam and high-dose valproate. Network meta-analysis was limited by predominant indirect evidence and high heterogeneity.On pairwise comparisons, phenobarbital was found to be associated with a higher risk of need for intubation and cardiovascular instability. Levetiracetam had a better safety profile than fosphenytoin.Based on low quality evidence, phenobarbital appears to be the most effective agent for seizure cessation within 60 min of administration in patients with benzodiazepine resistant status epilepticus. High-dose levetiracetam, high-dose valproate and fosphenytoin are probably equally effective. Choice of medication may be guided by effectiveness, safety concerns, availability, cost and systemic co-morbidities.

To assess the patterns and time trends in overall survival and progression-free survival treatment effects across randomized controlled trials (RCTs) in oncology.A PubMed search for oncology network meta-analyses (NMAs) was carried (to September 30, 2021). Relevant hazard ratios were extracted for systemic treatments from RCTs in the NMAs. After removing duplicate results, relationships between treatment effects, year of publication, trial design, and other features were explored.From 241 oncology NMAs, 2,109 unique eligible RCTs provided analyzable data. On average, there was a 12%-14% reduction in hazard for overall survival and 27%-30% reduction for progression-free survival, with substantial heterogeneity across different malignancies. Correlation between overall survival and progression-free survival treatment effects was modest (r = 0.60, 95% confidence interval, 0.56-0.64). Over time, there was a suggestive trend of increased progression-free survival treatment effect, although overall survival treatment effects remained steady. Only one in five trials met criteria for clinically meaningful improvements in overall survival. Among 300 randomly selected trials, mean absolute improvement was 1.6 months for median progression-free survival and 1.4 months for median overall survival.Broad patterns across the past 50 years of oncology research suggest continuous progress has been made, but few results meet clinically meaningful thresholds for overall survival improvement.

The aim of this systematic review and network meta-analysis was to comprehensively evaluate and compare the effectiveness of diverse therapies for disc displacement (DD) of the temporomandibular joint (TMJ). An electronic search of PubMed, Embase, the Cochrane Library, the China Academic Journals full-text database (CNKI), and Wanfang databases was performed to identify relevant studies available up to 31 July 2021. Study selection, data extraction, and quality assessment were performed for all included studies, while the outcomes of interest contained post-therapeutic maximum mouth opening and pain intensity. Interventions consisted of arthrocentesis, injections with diverse drugs, occlusal splints, or a combination of two to three of the above. Controls were regarded as oral analgesics, self-exercise, massage, or health instruction. Twenty-six studies appeared to meet the inclusion criteria and were subjected to further examination. Our data of the entire network showed that the most invasive therapies performed better than non-invasive therapies, while arthrocentesis + platelet-rich plasma injection and platelet-rich plasma injection in Grade I performed well in both mouth opening improvement and pain alleviation. Platelet-rich plasma injection is probably the best treatment overall for patients with DD owing to its anti-inflammatory, analgesic, and lubricating effects.

Specific treatments targeting Ebola virus are crucial in managing Ebola virus disease. To support the development of clinical practice guidelines on medications for Ebola virus disease, we aimed to evaluate the efficacy and safety of therapies for patients with Ebola virus disease.In this systematic review and network meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, Global Health, African Index Medicus, World Health Organization Global Index Medicus, the Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, Epistemonikos, bioRxiv, medRxiv, and SSRN without language restrictions for randomised controlled trials (RCTs) published between database inception and Jan 1, 2022, comparing at least one therapeutic agent for Ebola virus disease against standard care or another therapeutic agent for Ebola virus disease. Two reviewers assessed study eligibility and extracted summary data independently using a standardised form. Our outcomes of interest were mortality, adverse maternal outcomes, risk of onward transmission, duration of admission to a health-care facility, functional status after Ebola virus disease, serious adverse events from medication, adverse perinatal outcomes, time to symptom resolution, and time to viral clearance. We did frequentist network meta-analyses to estimate the effect of all interventions and applied the Grading of Recommendations Assessment, Development and Evaluation approach to rate the certainty of the evidence. We registered the protocol with PROSPERO, CRD42022296539.We identified 7840 records through database searches, of which two RCTs with a total of 753 patients proved eligible. Only data on mortality, the duration of admission, serious adverse events, and time to viral clearance were available for meta-analysis. Compared with standard care, REGN-EB3 (relative risk [RR] 0·40, 95% CI 0·18 to 0·89; moderate certainty) and mAb114 (0·42, 0·19 to 0·93; moderate certainty) probably reduce mortality. Whether ZMapp (0·60, 0·28 to 1·26; very low certainty) and remdesivir (0·64, 0·29 to 1·39; very low certainty) reduce mortality compared with standard care is uncertain. With high certainty, REGN-EB3 reduces mortality compared with ZMapp (0·67, 0·52 to 0·88) and remdesivir (0·63, 0·49 to 0·82). With high certainty, mAb114 also reduces mortality compared with ZMapp (0·71, 0·55 to 0·91) and remdesivir (0·66, 0·52 to 0·84). Compared with standard care, REGN-EB3, mAb114, ZMapp, and remdesivir might have little or no effect on the time to viral clearance (mean difference ranged from -0·25 days to -1·14 days; low certainty). ZMapp might reduce the duration of admission compared with standard care (mean difference -2·02 days, 95% CI -4·05 to 0·01; low certainty). Findings for all comparisons suggested that there might be little or no difference in the prevalence of serious adverse events, but certainty was low or very low in all comparisons but one.REGN-EB3 and mAb114 separately reduce mortality compared with ZMapp, remdesivir, or standard care in patients with Ebola virus disease. These findings suggest that health-care workers should prioritise the use of REGN-EB3 and mAb114 for patients with Ebola virus disease during future outbreaks.WHO.

To evaluate the effects of different interventions on Internet addiction (IA), a meta-analysis and network meta-analyses were performed.We searched PubMed, Cochrane, Embase, Web of Science, PsycINFO, ProQuest, CNKI, WanFang, VIP database, and CBM from their inception to August 2021 to identify randomized controlled trials (RCTs) where the effects of interventions on IA were assessed. The risk of bias was evaluated according to the Revised Cochrane risk-of-bias tool for randomized trials (RoB2). The R studio Software and Stata 14.0 were used to perform traditional meta-analysis and network meta-analyses.A total of 59 RCTs including 3832 participants were incorporated into meta-analysis. The results of the traditional meta-analysis of 24 studies showed that CBT, group counseling, sports intervention, and Internet-based intervention could significantly reduce IA levels (SMD = -1.90, 95%CI: -2.26 to -1.55, P 0.01, IMost interventions have significant effects on the treatment of IA. Compared with single interventions, combined interventions showed a more pronounced improvement in Internet addiction symptoms.

Virtual reality (VR) and computer-assisted cognitive rehabilitation (CACR) are two emerging rehabilitation therapies for stroke patients. The aim of this study was to compare the rehabilitation efficacy of these two treatments for patients with post-stroke cognitive impairment (PSCI).A network search of Embase, Web of Science, PubMed, Cochrane Library, VIP, WanFang Data, and CNKI databases was performed from their inception to February 2022 for screening randomized controlled trials related to VR and CACR in the treatment of PSCI. The quality of the included studies was assessed using the Cochrane risk bias assessment tool. The primary outcomes of the included studies contained at least one of the following clinical outcome measures: Mini-mental state examination (MMSE) or Montreal Cognitive Assessment (MoCA). After screening the literature, assessing the quality and extracting the data, a network meta-analysis was performed with STATA software.A total of 21 randomized controlled trials were included, including 1,047 patients. The results of network meta-analysis showed that under MMSE index, VR group (p = 0.067) and CACR group (p = 0.054) tended to be superior to CT group, but it was not significant. Both the VR (p = 0.024) and CACR (p 0.001) groups had significantly better outcomes compared to the conventional therapy group in terms of MoCA. The ranking results under both indicators showed that CACR had the best treatment effect, followed by VR.In general, VR and CACR have superior efficacy compared with conventional therapy, in which CACR may be the best treatment option.

This network meta-analysis aimed to compare the efficacy and safety of fluoroquinolone (FQ) monotherapy, β-lactam (BL) monotherapy and β-lactam/macrolide (BL-M) combination therapy in hospitalized patients with community-acquired pneumonia (CAP).Pubmed, Embase and the Cochrane Library were searched for randomized controlled trials (RCTs) comparing FQ monotherapy, BL monotherapy and BL-M combination therapy up to July 2021. The outcomes of interest included all-cause mortality, clinical success, microbiological success and drug-related adverse events. The summary relative risks (RRs) were estimated using pairwise and Bayesian network meta-analysis.A total of 12 RCTs involving 5009 patients were included. In pairwise meta-analysis, no significant differences were found among FQ monotherapy, BL monotherapy and BL-M dual therapy for all-cause mortality, clinical success or microbiological success. FQ monotherapy was associated with fewer adverse events compared with BL-M therapy (RR 0.80, 95% confidence interval [CI] 0.66-0.98). The network meta-analysis showed that there was no significant difference observed among FQ monotherapy, BL monotherapy and BL-M dual therapy regarding all the outcomes.FQ monotherapy, BL monotherapy and BL-M combination therapy demonstrated similar efficacy and safety for hospitalized patients with CAP in this network meta-analysis. Due to the limitations of quality and quantity of the included studies, it is difficult to make a definitive recommendation before more large-scale and high-quality RCTs are conducted.

A systematic review and network meta-analysis was performed to compare outcomes after living donor right hepatectomy via the following techniques: conventional open (Open), mini-laparotomy (Minilap), hybrid (Hybrid), totally laparoscopic (Lap), and robotic living donor right hepatectomy (Robotic).PubMed, EMBASE, Cochrane, and Scopus were searched from inception to August 2021 for comparative studies of patients who underwent living donor right hepatectomy.Nineteen studies comprising 2,261 patients were included. Operation time was longer in Lap versus Minilap and Open (mean difference 65.09 min, 95% confidence interval 3.40-126.78 and mean difference 34.81 minutes, 95% confidence interval 1.84-67.78), and in Robotic versus Hybrid, Lap, Minilap, and Open (mean difference 144.72 minutes, 95% confidence interval 89.84-199.59, mean difference 113.24 minutes, 95% confidence interval 53.28-173.20, mean difference 178.33 minutes, 95% confidence interval 105.58-251.08 and mean difference 148.05 minutes, 95% confidence interval 97.35-198.74, respectively). Minilap and Open were associated with higher blood loss compared to Lap (mean difference 258.67 mL, 95% confidence interval 107.00-410.33 and mean difference 314.11 mL, 95% confidence interval 143.84-484.37) and Robotic (mean difference 205.60 mL, 95% confidence interval 45.92-365.28 and mean difference 261.04 mL, 95% confidence interval 84.26-437.82). Open was associated with more overall complications compared to Minilap (odds ratio 2.60, 95% confidence interval 1.11-6.08). Recipient biliary complication rate was higher in Minilap and Open versus Hybrid (odds ratio 3.91, 95% confidence interval 1.13-13.55 and odds ratio 11.42, 95% confidence interval 2.27-57.49), and lower in Open versus Minilap (OR 0.07, 95% confidence interval 0.01-0.34).Minimally invasive donor right hepatectomy via the various techniques is safe and feasible when performed in high-volume centers, with no major differences in donor complication rates and comparable recipient outcomes once surgeons have mounted the learning curve.

BACKGROUND Although antipsychotic maintenance treatment is widely recommended to prevent relapse in chronic psychoses, evidence-based guidelines do not provide clear indications on different maintenance treatment strategies, including continuing the antipsychotic at standard doses, reducing the dose, switching to another antipsychotic, or even stopping the antipsychotic. We aimed to compare the effectiveness of these maintenance treatment strategies, hypothesising the superiority of all strategies over stopping, and of continuing at standard doses over both switching and reducing the dose. METHODS We did a systematic review and network meta-analysis of randomized controlled trials (RCTs) that investigated antipsychotics for relapse prevention in adults with schizophrenia-spectrum disorders who were clinically stable, and which compared four treatment strategies: continuing the current antipsychotic at standard doses recommended for acute treatment; reducing the current antipsychotic dose; switching to a different antipsychotic; and stopping the antipsychotic and replacing it with placebo. We excluded RCTs with fewer than 25 individuals, a prerandomisation washout period greater than 4 weeks, a follow-up shorter than 6 weeks, and those recruiting treatment-resistant individuals. We searched MEDLINE, EMBASE, PsycINFO, CINAHL, CENTRAL, and online trial registers for published and unpublished RCTs from inception to Sept 1, 2021, combining terms describing all available antipsychotics, and terms describing continuation, maintenance, or long-term treatment for schizophrenia-spectrum disorders. Relative risks (RRs) and standardised mean differences were pooled using random-effects pairwise and network meta-analyses. We assessed risk of bias of each RCT with the Cochrane Risk-of-Bias 2 tool, and confidence of pooled estimates with CINeMA. The primary outcome was relapse prevention. The study protocol was registered in advance in the Open Science Forum registry. FINDINGS Of 3936 records identified, 119 records, reporting on 101 RCTs, were eligible, 98 of which (including 13 988 individuals) provided data that could be meta-analysed for at least one outcome. The mean proportion of female participants per study was 38% (range 0-100; median 39%, IQR 29-50), whereas for male participants it was 62% (range 0-100; median 61%, IQR 50-71), and the overall mean age was 38·8 years (range 23·2-63·9; median 39·3, IQR 35·0-43·9). Of the 98 RCTs meta-analysed, 89·8% were done in high-income and upper-middle-income countries. The ethnic group White or so-called Caucasian was the most represented (mean 56% participants per study), although this information was relatively scarce. All continuation strategies were significantly more effective in preventing relapse than stopping antipsychotic treatment, with a large risk reduction for continuing at standard doses (RR 0·37, 95% CI 0·32-0·43; number-needed-to-treat [NNT] 3·17, 95% CI 2·94-3·51) and antipsychotic switching (RR 0·44, 0·37-0·53; NNT 3·57, 3·17-4·25), and moderate risk reduction for dose reduction (RR 0·68, 0·51-0·90; NNT 6·25, 4·08-20·00). Continuing and switching antipsychotics did not differ significantly (RR 0·84, 0·69-1·02; with lower values favouring continuing), whereas reducing antipsychotic dose was outperformed by both continuing (RR 0·55, 0·42-0·71; NNT 4·44, 3·45-6·90) and switching (RR 0·65, 0·47-0·89; NNT 5·17, 3·77-18·18). Results were supported by moderate confidence of evidence and confirmed by secondary analyses and by several sensitivity and subgroup analyses, including removing studies with abrupt antipsychotic discontinuation or fast tapering (≤4 weeks). No tolerability differences emerged between treatment strategies. According to the Cochrane Risk-of-Bias tool, version 2, 16·8% of included RCTs had an overall high risk of bias for the primary outcome. We found moderate heterogeneity (τ2=0·13; I2=61%) and no overall incoherence for the primary analysis. Results were supported by moderate confidence of evidence and confirmed by secondary analyses. INTERPRETATION Contrary to our original hypothesis, we found that continuing antipsychotic treatment at standard doses or switching to a different antipsychotic are similarly effective treatment strategies, whereas reducing antipsychotic doses below standard doses is associated with higher risk of relapse than the other two maintenance treatment strategies and should therefore be limited to selected cases. Despite limitations, including moderate heterogeneity and moderate certainty of evidence, these results are of pragmatic relevance for clinicians, and should support the update of evidence-based guidelines. FUNDING None.

To construct an algorithm to optimize clinical outcomes in subacromial impingement based on current, high-level evidence.A systematic review of all clinical trials on subacromial impingement published from 1999 to 2020 was performed. Demographic, clinical, range of motion (ROM), and patient-reported outcome measure (PROM) data were collected. Interventions were compared via arm-based Bayesian network meta-analysis in a random-effects model and treatments ranked via surface under the cumulative ranking curves with respect to 3 domains: pain, PROMs, and ROM.A total of 35 studies comprising 3,643 shoulders (42% female, age 50 ± 5 years) were included. Arthroscopic decompression with acromioplasty ranked much greater than arthroscopic decompression alone for pain relief and PROM improvement, but the difference in absolute PROMs was not statistically significant. Corticosteroid injection (CSI) alone demonstrated inferior outcomes across all 3 domains (pain, PROMs, and ROM) with low cumulative rankings. Physical therapy (PT) with CSI demonstrated moderate-to-excellent clinical improvement across all 3 domains whereas PT alone demonstrated excellent ROM and low-moderate outcomes in pain and PROM domains. PT with nonsteroidal anti-inflammatory drugs or alternative therapies ranked highly for PROM outcomes and moderate for pain and ROM domains. Finally, platelet-rich plasma injections demonstrated moderate outcomes for pain, forward flexion, and abduction with very low-ranking outcomes for PROMs and external rotation.Arthroscopic decompression with acromioplasty and PT demonstrated superior outcomes whereas CSI demonstrated poor outcomes in all 3 domains (pain, PROMs, and ROM). For patients with significant symptoms, the authors recommend PT with CSI as a first-line treatment, followed by acromioplasty and PT if conservative treatment fails. For patients with symptoms limited to 1 to 2 domains, the authors recommend a shared decision-making approach focusing on treatment rankings within domains pertinent to individual patient symptomatology.I, systematic review and network meta-analysis of Level I studies.

Cardioprotective therapies represent an important avenue to reduce treatment-limiting cardiotoxicities in patients receiving chemotherapy. However, the optimal duration, strategy and long-term efficacy of empiric cardio-protection remains unknown.Leveraging the MEDLINE/Pubmed, CENTRAL and clinicaltrials.gov databases, we identified all randomised controlled trials investigating cardioprotective therapies from inception to November 2021 (PROSPERO-ID:CRD42021265006). Cardioprotective classes included ACEIs, ARBs, Beta-blockers, dexrazoxane (DEX), statins and mineralocorticoid receptor antagonists. The primary end-point was new-onset heart failure (HF). Secondary outcomes were the mean difference in left ventricular ejection fraction (LVEF) change, hypotension and all-cause mortality. Network meta-analyses were used to assess the cardioprotective effects of each therapy to deduce the most effective therapies. Both analyses were performed using a Bayesian random effects model to estimate risk ratios (RR) and 95% credible intervals (95% CrI).Overall, from 726 articles, 39 trials evaluating 5931 participants (38.0 ± 19.1 years, 72.0% females) were identified. The use of any cardioprotective strategy associated with reduction in new-onset HF (RR:0.32; 95% CrI:0.19-0.55), improved LVEF (mean difference: 3.92%; 95% CrI:2.81-5.07), increased hypotension (RR:3.27; 95% CrI:1.38-9.87) and no difference in mortality. Based on control arms, the number-needed-to-treat for 'any' cardioprotective therapy to prevent one incident HF event was 45, including a number-needed-to-treat of 21 with ≥1 year of therapy. Dexrazoxane was most effective at HF prevention (Surface Under the Cumulative Ranking curve: 81.47%), and mineralocorticoid receptor antagonists were most effective at preserving LVEF (Surface Under the Cumulative Ranking curve: 99.22%).Cardiotoxicity remains a challenge for patients requiring anticancer therapies. The initiation of extended duration cardioprotection reduces incident HF. Additional head-to-head trials are needed.

To assess the short-term and long-term comparative efficacy and safety of ASMs for Lennox-Gastaut syndrome (LGS).Following a systematic literature search, randomized controlled trial (RCT) and open-label extension (OLE) studies on LGS comparing ASMs with placebo or other ASMs were included. ≥50% reduction in drop seizure frequency from baseline and occurrence of treatment-emergent adverse events (TEAEs) were the primary efficacy and safety outcomes. For short-term outcomes, a network meta-analysis (NMA) reporting odds ratio (OR) with 95% confidence intervals (CIs) and hierarchy of competing interventions [surface under the cumulative ranking curve(SUCRA)] was done. Long-term outcomes were reported as proportion with 95% CIs using the random-effects model.Fifteen studies including 1263 participants with LGS (aged 2-54years) receiving any of six ASMs [cannabidiol (CBD), clobazam (CLB), felbamate (FLB), lamotrigine (LTG), rufinamide (RFM), topiramate (TPM)] or placebo were included. High-dose CLB (1.0 mg/kg/day; CLB_H) [OR: 4.9; 95% CI: 2.3-10.8] was significantly associated with ≥50% reduction in drop seizure frequency as compared with placebo, and achieved the highest-ranking probability (0.89) based on SUCRA values (although there was an overlap between confidence intervals of effect sizes of CLB, RFM and CBD), while high-dose CBD (20 mg/kg/day; CBD_H) [OR: 3.8; 95% CI:1.6-9.0] had significantly higher odds for occurrence of any TEAEs and had the highest-ranking probability (0.85). Furthermore, the long-term treatment with CLB [78%; 95% CI: 70-85%] was associated with a significantly higher proportion of patients with reduction in drop-seizures, and long-term use of CBD [96%; 95% CI: 95-98%] was associated with a higher frequency of TEAEs.The study findings suggest that CLB_H, CBD and RFM are the most efficacious and safest in terms of both short and long-term outcomes with CLB_H probably leading the hierarchy. Future head-to-head trials comparing these ASMs are needed.

To evaluate various radiofrequency ablation (RFA) treatments for knee osteoarthritis (OA) and determine the best modality, target, number of electrodes, and image guidance for improving knee pain and function.Electronic databases were searched for randomized controlled trials (RCTs) comparing the efficacy of RFA treatments for knee OA from inception up to September 30, 2021. The primary outcome was the visual analog scale (VAS), and the secondary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Bayesian network meta-analysis was performed to synthesize the mean difference (MD) and rank the comparative effectiveness of treatments.A total of 21 eligible RCTs (from 2011 to 2021, involving 1,818 patients) with 8 RFA treatments, 6 intra-articular injections, NSAIDS, exercise, and placebo were assessed. Conventional bipolar genicular nerve RFA (GNRFA) had the greatest net benefit on the VAS at 6 months (MD, -5.5; 95% confidence interval [CI], -4.3 to -6.7; SUCRA, .98). And cooled monopolar GNRFA had the greatest net benefit on the WOMAC at 6 months (MD, -33; 95% CI, -37 to -29; SUCRA, .99). In conventional and pulsed modalities, bipolar RFA was associated with a significant decrease in VAS and WOMAC than monopolar RFA. Combining pulsed intra-articular RFA and platelet-rich plasma injection had no additional positive effects on VAS or WOMAC at 3 months.RFA is effective in improving both knee pain and function in patients with OA, at least in the short term (6 months). Patients respond better to the cooled modality than the conventional and pulsed modalities. Bipolar is more effective than monopolar for improving pain and function in conventional and pulsed modalities. Fluoroscopy and ultrasound guidance showed no differences in improving pain and function. The effectiveness of RFA in cooled modality using bipolar or in combination with various intra-articular injections remains to be compared.II, systematic review and meta-analysis of Level I and II studies.

We conducted an updated network meta-analysis to elucidate the best regimen for latent tuberculosis infection (LTBI).We searched the PubMed, Embase, and Cochrane Library databases on 16 August 2021 to perform an updated network meta-analysis. Only randomised controlled trials on populations with LTBI that reported the efficacy for preventing incident tuberculosis or the completion rates of treatment regimens were included. The Cochrane Collaboration tool was used to assess the risk of bias. We tested for possible global inconsistency with a χWe identified 27 studies that matched our inclusion criteria; the risk of bias was mostly low. Rifampicin for four months (RFMP-4) was the most likely to be effective (probability: 56.3%) and the second most likely treatment to be completed (probability: 22.4%). By applying a multidimensional scaling approach for ranking based on a scatterplot with the surface under the cumulative ranking values for efficacy and completion rates, RFMP-4 was deemed the best choice for treating LTBI. Similar results were demonstrated after sensitivity analysis.This updated network meta-analysis revealed RFMP-4 to be the best choice for treating LTBI, per simultaneous consideration of efficacy and completion rates.

Our study aims to evaluate the fracture nonunion rate and the functional score of plate and screw fixation, intramedullary nailing and non-surgical treatment in midshaft clavicle fractures patients using a network meta-analysis of data from clinical randomized controlled trials.The studies were abstracted from Medline, Embase, Web of Science, Google Scholar and the Cochrane Central Register of Controlled Trials. RCTs meeting the inclusion and exclusion criteria were selected. Statistical analyses were conducted using Stata software, version 14.0 (Stata Corporation, College Station, Texas, USA).24 randomized controlled trials involving 2161 participants were included. The studies were published between 2007 and 2019. A total of 3 treatment methods-plate and screw fixation, intramedullary nailing and non-surgical treatment- were included in the literature. The treatments were ranked based on the Surface Under the Cumulative Ranking Curve (SUCRA) probability. In terms of the constant score, the treatment methods were ranked as follows: intramedullary nailing, plate and screw fixation and non-surgical treatment. In terms of the DASH index, the treatment methods were ranked as follows: intramedullary nailing, plate and screw fixation and non-surgical treatment. In terms of the nonunion rate, the treatment methods were ranked as follows: intramedullary nailing, plate and screw fixation and non-surgical treatment.Non-surgical treatment has a high rate of nonunion for clavicular fractures with obvious displacement and notable comminution. Surgical treatment reduces the nonunion rate leads to better functional scores at long-term follow-up, although there may be no significant clinical differences. The fracture nonunion rate of plate screw fixation group and intramedullary nail group was low and the functional prognosis was similar. More RCTs focused on clavicular fractures are needed to further substantiate this conclusion.

Randomised controlled trials (RCTs) with systemic therapies for patients with pre-treated mesothelioma have reported equivocal efficacy results and generated a degree of clinical uncertainty about the choice of active treatment in this poor prognosis malignancy.To compare the effectiveness and safety and weigh the benefit of different systemic treatments in patients with pre-treated mesothelioma by systematic review, meta-analysis and network meta-analysis of RCTs. Full-text articles and abstracts were searched on PubMed, EMBASE, Cochrane Library and oncology conferences proceedings from 2005 through November 2021 for phase 2 and 3 RCTs. The protocol was submitted to the PROSPERO registry. Reporting followed the PRISMA guideline. Outcomes of interest were overall survival (OS) and progression-free (PFS), grade ≥3 treatment-related (Tr) adverse events (AEs), Tr-deaths and Tr-AEs leading to treatment discontinuation.Nine trials at low risk of bias by Cochrane Collaboration's methodology were included, encompassing 2789 patients. Five studies showed PFS benefit in the experimental treatment. In two studies, OS was prolonged by immunotherapy (versus placebo) or by adding an antiangiogenic agent to chemotherapy. Reported Tr-AE were lower with single-agent anti-PD1 compared with chemotherapy or placebo. The meta-analysis revealed a beneficial global effect on OS and PFS from experimental treatments (HR 0.86, 95% CI 0.77-0.96, p = 0.0083 and HR 0.79, 95% CI 0.72-0.86, p 0.001), that for the PFS significantly favoured the comparison with non-active treatments (HR 0.73, 95% CI 0.66-0.81, p 0.001). Younger patients (i.e. 65-70 years) appeared to benefit the most in OS (HR 0.71, 95% CI 0.55-0.92, p = 0.04). The risk of serious Tr-AEs and Tr-deaths was not significantly increased by experimental treatments (RR 1.38, 95% CI 0.81-2.35, p = 0.24 and RR 2.07, 95% CI 0.69-6.24, p = 0.19, respectively) that instead increased TrAEs leading to treatment discontinuation (RR 2.9, 95% CI 1.44-6.08, p = 0.003). The network meta-analysis did not identify any superior treatment in PFS.For patients with pre-treated MPM, single-agent anti-PD1 or chemotherapy ± the antiangiogenic agent can be considered active and safe systemic therapeutic options, particularly for younger patients.

This study aimed to determine the comparative effectiveness of interventions in treatment of sarcopenia. The primary outcome was the measure of treatment effect on muscle mass, and secondary outcomes were the treatment effect on muscle strength and physical performance.Systematic review and network meta-analysis (NMA).Participants with sarcopenia receiving interventions targeting sarcopenia in any setting.Data sources: Relevant RCTs were identified by a systematic search of several electronic databases, including CINAHL, Embase, MEDLINE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) from January 1995 to July 2019. Duplicate title and abstract and full-text screening, data extraction, and risk of bias assessment were performed.All RCTs examining sarcopenia interventions [mixed exercise (combined aerobic and resistance exercise), aerobic exercise, resistance exercise, balance exercise, physical activity and protein or nutrition supplementation, acupuncture, whole-body vibration, protein supplement or interventions to increase protein intake, any nutritional intervention other than protein, and pharmacotherapy] were included. Comparators were standard care, placebo, or another intervention.We performed Bayesian NMA; continuous outcome data were pooled using the standardized mean difference effect size. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) for each outcome.A total of 59 RCTs were included after screening of 4315 citations and 313 full-text articles. Network meta-analysis of muscle mass outcome (including 46 RCTs, 3649 participants, 11 interventions) suggested that mixed exercise were the most effective intervention (SUCRA = 93.94%) to increase muscle mass. Physical activity and protein or nutrition supplementation, and aerobic exercise were the most effective interventions to improve muscle strength and physical performance, respectively. Overall, mixed exercise is the most effective intervention in increasing muscle mass and was one of the 3 most effective interventions in increasing muscle strength and physical performance.Mixed exercise and physical activity with nutritional supplementation are the most effective sarcopenia interventions. Most of the included studies have a high risk of bias. More robust RCTs are needed to increase the confidence of our NMA results and the quality of evidence.

Cirrhosis is the 11th leading cause of death worldwide. Because of the limitations of liver transplantation, cell- and granulocyte colony-stimulating factor (G-CSF)-based therapies are considered potential treatment methods. This work analyzes the effectiveness of cell- and G-CSF-based therapies by network meta-analysis.A literature search was performed in four databases from inception to September 10, 2021. Registered randomized controlled trials (RCTs) evaluating cell-based therapies and/or G-CSF-based therapies for cirrhosis patients were included. Traditional and network meta-analyses were analyzed in terms of survival, model for end-stage liver disease (MELD) score, Child-Turcotte-Pugh (CTP) score, alanine aminotransferase levels and aspartate aminotransferase levels.Twenty-four studies were included in this analysis. The results showed that G-CSF-based therapies (odds ratio [OR], 2.38, 95% confidence interval [CI], 1.49-3.79, P0.01) and cell-based therapies (OR, 1.54, 95% CI, 1.00-2.40, P = 0.048) improved the transplantation-free survival rate compared with standard medical treatment. Network analysis results showed that G-CSF combined with erythropoietin (EPO) and growth hormone (GH) had a therapeutic advantage, and cell-based therapy with mononuclear cell (MNC) hepatic artery injection and intravenous mesenchymal stem cells (MSCs) combined with G-CSF also had a relative advantage in terms of survival outcome. For the MELD score, G-CSF plus GH and MSC portal vein injection had relative advantages. G-CSF plus GH and G-CSF plus EPO had advantages in terms of CTP scores. The included strategies demonstrated no obvious improvement in liver injury indicators.Cell-based therapy has potential therapeutic effects for liver cirrhosis. Among cell-based therapies, intravenous MSCs and hepatic artery injection of MNCs have advantageous therapeutic effects. The use of G-CSF was also noted in regimens that improved survival outcomes. However, more well-designed, large-scale RCTs are needed to confirm this conclusion.

Objectives To assess the cost-effectiveness of systemic treatments for metastatic castration-sensitive prostate cancer from the US healthcare sector perspective with a lifetime horizon. Methods We built a partitioned survival model based on a network meta-analysis of 7 clinical trials with 7287 patients aged 36 to 94 years between 2004 and 2018 to predict patient health trajectories by treatment. We tested parameter uncertainties with probabilistic sensitivity analyses. We estimated drug acquisition costs using the Federal Supply Schedule and adopted generic drug prices when available. We measured cost-effectiveness by an incremental cost-effectiveness ratio (ICER). Results The mean costs were approximately $392 000 with androgen deprivation therapy (ADT) alone and approximately $415 000, $464 000, $597 000, and $959 000 with docetaxel, abiraterone acetate, enzalutamide, and apalutamide, added to ADT, respectively. The mean quality-adjusted life-years (QALYs) were 3.38 with ADT alone and 3.92, 4.76, 3.92, and 5.01 with docetaxel, abiraterone acetate, enzalutamide, and apalutamide, added to ADT, respectively. As add-on therapy to ADT, docetaxel had an ICER of $42 069 per QALY over ADT alone; abiraterone acetate had an ICER of $58 814 per QALY over docetaxel; apalutamide had an ICER of $1 979 676 per QALY over abiraterone acetate; enzalutamide was dominated. At a willingness to pay below $50 000 per QALY, docetaxel plus ADT is likely the most cost-effective treatment; at any willingness to pay between $50 000 and $200 000 per QALY, abiraterone acetate plus ADT is likely the most cost-effective treatment. Conclusions These findings underscore the value of abiraterone acetate plus ADT given its relative cost-effectiveness to other systemic treatments for metastatic castration-sensitive prostate cancer.

Contains fulltext : 247522.pdf (Publisher’s version ) (Open Access) Background: We evaluated the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD), and ranked the relative efficacy of different stimulation protocols. Methods: We performed a search for randomised, sham-controlled trials of rTMS for OCD. The primary analysis included both a pairwise meta-analysis and a series of frequentist network meta-analyses (NMA) of OCD symptom severity. Secondary analyses were carried out on relevant clinical factors and safety. Results: 21 studies involving 662 patients were included. The pairwise meta-analysis showed that rTMS for OCD is efficacious across all protocols (Hedges' g=-0.502 [95%CI= -0.708, -0.296]). The first NMA, with stimulation protocols clustered only by anatomical location, showed that both dorsolateral prefrontal cortex (dlPFC) stimulation and medial frontal cortex stimulation were efficacious. In the second NMA, considering each unique combination of frequency and location separately, low frequency (LF) pre-supplementary motor area (preSMA) stimulation, high frequency (HF) bilateral dlPFC stimulation, and LF right dlPFC stimulation were all efficacious. LF right dlPFC was ranked highest in terms of efficacy, although the corresponding confidence intervals overlapped with the other two protocols. Limitations Evidence base included mostly small studies, with only a few studies using similar protocols, giving a sparse network. Studies were heterogeneous, and a risk of publication bias was found. Conclusions: rTMS for OCD was efficacious compared with sham stimulation. LF right dlPFC, HF bilateral dlPFC and LF preSMA stimulation were all efficacious protocols with significant and comparable clinical improvements. Future studies should further investigate the relative merits of these three protocols. 11 p.

High grade gliomas (HGGs) are aggressive brain tumors associated with poor prognosis despite advances in surgical treatment and therapy. Navigated tumor resection has yielded improved outcomes for patients. We compare 5-ALA, fluorescein sodium (FS), and intraoperative MRI (IMRI) with no image guidance to determine the best intraoperative navigation method to maximize rates of gross total resection (GTR) and outcomes. A frequentist network meta-analysis was performed following standard PRISMA guidelines (PROSPERO registration CRD42021268659). Surface-under-the-cumulative ranking (SUCRA) analysis was executed to hierarchically rank modalities by the outcomes of interest. Heterogeneity was measured by the I

Background: Studies have shown that pharmacological and psychological treatments are effective for children and adolescents with obsessive-compulsive disorder (OCD). However, few network meta-analyses have examined whether pharmacological or psychological treatments on their own, or combined, are most effective. Methods: We conducted a database search and selected randomized controlled trials of pharmacological or psychological treatments, alone or in combination, for children and adolescents with OCD. The primary outcome was change in symptom severity as a result of treatment, as assessed using the Yale-Brown Obsessive Compulsive Scale (BOCS) or Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) . Findings: We included 18 studies with 1353 participants and 12 kinds of treatments. In terms of efficacy, all pharmacological and psychotherapy treatments were more effective than placebo. Among the 12 treatments, the efficacy of pharmacological treatment combined with cognitive behavioral therapy (CBT) was better than pharmacological treatment alone. When pharmacological treatment was used alone, escitalopram was significantly better than clomipramine(CY-BOCS average change 3.42; 95% CI 2.11, 4.65), fluvoxamine(CY-BOCS average change 3.59; 95% CI 1.09, 6.20), paroxetine(CY-BOCS average change 2 .80; 95% CI 0.01, 5.64) and sertraline(CY-BOCS average change 3.49; 95% CI 1.53, 5.64). Interpretation: The available evidence suggests that the combination of pharmacological and psychological treatment is likely to be most effective for children and adolescents with OCD. Funding: The National Nature Science Foundation of China (81801357, 81801350), the Science and Technology Education Program of the Sichuan Province (2020JDKP0013), the Key R&D Projects of the Science and Technology Department of Sichuan Province(2020YFS0259 ), and the Chengdu Key Technology R&D Program (2019-YF05– 00284-SN). Declaration of Interest: None to declare.

The aim of this study was to determine the severe bleeding safety of direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE).PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched up to 6 January 2021. The incidence of severe bleeding (major, gastrointestinal [GI], intracranial, and fatal) was investigated. Using frequentist network meta-analysis, interventions that were not compared directly could be compared indirectly by the 95% confidence interval (CI), making the search results more intuitive. Based on surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.Thirty-one randomised controlled trials (76 641 patients) were included. For the treatment of VTE, the risk of major bleeding with apixaban was significantly lower than dabigatran (odds ratio [OR] 2.10, 95% CI 1.07 - 4.12) and edoxaban (OR 2.64, 95% CI 1.36 - 5.15). The safety of the drugs was ranked from highest to lowest as follows: major bleeding: apixaban (SUCRA 98.0), rivaroxaban (SUCRA 69.6), dabigatran (SUCRA 50.7), edoxaban (SUCRA 26.5), and vitamin K antagonists (VKAs; SUCRA 5.1); GI bleeding: apixaban (SUCRA 80.7), rivaroxaban (SUCRA 66.8), edoxaban (SUCRA 62.3), VKAs (SUCRA 34.4), and dabigatran (SUCRA 5.8); intracranial bleeding: rivaroxaban (SUCRA 74.4), edoxaban (SUCRA 70.4), dabigatran (SUCRA 58.2), apixaban (SUCRA 44.4), and VKAs (SUCRA 5.6); fatal bleeding: edoxaban (SUCRA 82.7), rivaroxaban (SUCRA 59.2), dabigatran (SUCRA 48.6), apixaban (SUCRA 43.0), and VKAs (SUCRA 16.3). For the prevention of VTE, the risk of major bleeding with apixaban was significantly lower than rivaroxaban (OR 2.14, 95% CI 1.02 - 4.52). Among the four types of bleeding, apixaban had the lowest bleeding risk among DOACs (major bleeding: SUCRA 81.6; GI bleeding: SUCRA 75.4; intracranial bleeding: SUCRA 64.1; fatal bleeding: SUCRA 73.6).For the treatment of VTE, in terms of major bleeding and GI bleeding, apixaban had the lowest bleeding risk; in terms of intracranial bleeding, rivaroxaban had the lowest bleeding risk; in terms of fatal bleeding, edoxaban had the lowest bleeding risk. For the prevention of VTE, apixaban had the lowest bleeding risk.

To perform a systematic review and network meta-analysis to provide comparative evidence and quantitative hierarchies of the effectiveness of positive airway pressure (PAP) treatment on obesity hypoventilation syndrome (OHS).We searched PubMed, Embase, and Cochrane Library databases for relevant articles about the treatment of OHS published from the time of database creation to February 2021. Two independent reviewers performed the study search and screening, quality assessment and data extraction. The network meta-analysis within the frequentist framework was performed using Stata 15.0. The outcomes included changes in arterial blood gases, sleep quality, and polysomnography parameters.Ten articles were included in the study. The results of the network meta-analysis showed that PAP treatment could decrease the partial pressure of carbon dioxide, bicarbonate level, apnea-hypopnea index, Epworth sleepiness scale score, and percentage of light sleep, and increase the partial pressure of oxygen, oxygen saturation, and percentage of rapid eye movement sleep and deep sleep when compared with control group in OHS patients. In addition, the results of the derived hierarchy showed that BPAP-AVAPS and BPAP-ST were the first two modes of PAP treatment that reduced the partial pressure of carbon dioxide and percentage of light sleep and improved the percentage of rapid eye movement sleep and deep sleep. However, there was no difference in the quality of life, total sleep time, and sleep efficiency between any mode of PAP treatment and the control group.PAP treatment is beneficial for OHS patients, and the modes of BPAP-AVAPS and BPAP-ST demonstrated the largest improvement in hypercapnia and objective sleep structure.

Background Exercise is a promising nonpharmacological therapy for cognitive dysfunction, but it is unclear which type of exercise is most effective. The objective of this study was to compare and rank the effectiveness of various exercise interventions on cognitive function in patients with mild cognitive impairment (MCI) or dementia and to examine the effects of exercise on the symptoms relevant to cognitive impairment. Methods We searched PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, SPORTDiscus, and PsycInfo through September 2019 and included randomized controlled trials that examined the effectiveness of exercise interventions in patients with MCI or dementia. Primary outcomes included global cognition, executive cognition, and memory cognition. Secondary outcomes included activities of daily living, neuropsychiatric symptoms, and quality of life. Pairwise analyses and network meta-analyses were performed using a random effects model. Results A total of 73 articles from 71 trials with 5606 participants were included. All types of exercise were effective in increasing or maintaining global cognition, and resistance exercise had the highest probability of being the most effective intervention in slowing the decrease in global cognition: (standard mean difference (SMD) = 1.05, 95% confidence interval (95%CI): 0.56−1.54), executive function (SMD = 0.85, 95%CI: 0.21−1.49), and memory function (SMD = 0.32, 95%CI: 0.01−0.63) in patients with cognitive dysfunction. Subgroup analyses for patients with MCI revealed different effects, and multicomponent exercise was most likely to be the optimal exercise therapy for preventing the decline of global cognition (SMD = 0.99, 95%CI: 0.44−1.54) and executive function (SMD = 0.72, 95%CI: 0.06−1.38). However, only resistance exercise showed significant effects on memory function for patients with MCI (SMD = 0.35, 95%CI: 0.01−0.69). Exercise interventions also showed various effects on the secondary outcomes. Conclusion Resistance exercise had the highest probability of being the optimal exercise type for slowing cognitive decline in patients with cognitive dysfunction, especially in patients with dementia. Multicomponent exercise tended to be most effective in protecting global cognition and executive function in patients with MCI.

Background There is limited evidence about which composite feature of asthma self-management strategies is the best and should be adopted into practice. Objective To compare the efficacy of different strategies to support self-management, based on the newly developed framework, in patients with asthma. Methods We searched PubMed, EMBASE, CENTRAL, CINAHL, and PsycInfo from 1993 to December 2019. We identified randomized controlled trials that explored effects of strategies to support self-management in adult patients with asthma. We conducted network meta-analyses using a random effects model with usual care as the common comparator. Surface under the cumulative ranking curve methods were used to rank different support strategies. Results Thirty-five trials (5195 patients) were included and classified on the basis of our newly created TIP framework: Theme, Intensity, and Provider/Platform. We identified 6 features from the included trials, each represented by 1 element of the TIP framework: (1) behavioral support more than once a month by e-Health; (2) behavioral support more than once a month by health care personnel (HCP); (3) behavioral support less often than or equal to once a month by HCP; (4) education support less often than or equal to once a month by e-Health; (5) education support less often than or equal to once a month by HCP; and (6) psychosocial support less often than or equal to once a month by HCP. Behavioral support more than once a month by e-Health showed significant improvement in asthma control when compared with the other 2 support strategies, which was confirmed by the highest surface under the cumulative ranking of 97.6%. However, the surface under the cumulative ranking for behavioral support less often than or equal to once a month by HCP suggested that it has the potential to be the best intervention to reduce the risk of hospitalization (89.1%) and emergency department visit (84.2%). Conclusions Different features of asthma self-management support strategies work best on unique outcomes.

In the present study, we evaluated the efficacy and safety of different stem cell types for spinal cord injury (SCI) therapy to determine the superior treatment of SCI.A systematic literature search was performed using PubMed, Embase, the Cochrane Library, Web of Science, VIP, Chinese National Knowledge Infrastructure, and Wan Fang databases from initiation to January 30, 2021. A Bayesian network meta-analysis was performed using ADDIS (Aggregate Data Drug Information System) software. The PROSPERO registration number was CRD42020129635.We included 12 studies with 642 patients in the present study. A network meta-analysis revealed that bone mesenchymal stem cells (BMSCs) combined with rehabilitation training were significantly more effective than rehabilitation training alone in improving the American Spinal Injury Association (ASIA) impairment scale grade (odds ratio, 94.25; 95% confidence interval [CI], 6.71-9321.95), ASIA motor score (weighted mean difference [WMD], 6.67; 95% CI, 0.83-12.73), ASIA sensory functional score (WMD, 12.41; 95% CI, 3.42-21.72), and Barthel index (WMD, 7.24; 95% CI, 0.21-14.30). However, no statistically significant differences were observed between bone marrow mononuclear cells (MNCs) combined with rehabilitation training, umbilical cord-derived mesenchymal stem cells (UCMSCs) combined with rehabilitation training, or UCMSCs alone and rehabilitation alone for all indicators. In terms of safety, there were no serious and permanent adverse effects after transplantation of BMSCs, MNCs, or UCMSCs.BMSCs plus rehabilitation might be superior to other stem cell treatments of SCI in improving the ASIA impairment scale grade, ASIA motor score, ASIA sensory functional score, and Barthel index. The therapeutic effects of UCMSCs and MNCs remain to be confirmed.

Background This network meta-analysis was performed to determine the optimal surgical approach for pancreatoduodenectomy by comparing outcomes after laparoscopic pancreatoduodenectomy, robotic pancreatoduodenectomy and open pancreatoduodenectomy. Methods A systematic search of the PubMed, EMBASE, Scopus, and Web of Science databases was conducted to identify eligible randomized controlled trials and propensity-score matched studies. Results Four randomized controlled trials and 23 propensity-score matched studies comprising a total of 4,945 patients were included for analysis. Operation time for open pancreatoduodenectomy was shorter than both laparoscopic pancreatoduodenectomy (mean difference –57.35, 95% CI 26.25–88.46 minutes) and robotic pancreatoduodenectomy (mean difference –91.08, 95% CI 48.61–133.56 minutes), blood loss for robotic pancreatoduodenectomy was significantly less than both laparoscopic pancreatoduodenectomy (mean difference –112.58, 95% CI 36.95–118.20 mL) and open pancreatoduodenectomy (mean difference –209.87, 95% CI 140.39–279.36 mL), both robotic pancreatoduodenectomy and laparoscopic pancreatoduodenectomy were associated with reduced rates of delayed gastric emptying compared with open pancreatoduodenectomy (odds ratio 0.59, 95% CI 0.39–0.90 and odds ratio 0.69, 95% CI 0.50–0.95, respectively), robotic pancreatoduodenectomy was associated with fewer wound infections compared with open pancreatoduodenectomy (odds ratio 0.35, 95% CI 0.18–0.71), and laparoscopic pancreatoduodenectomy patients enjoyed significantly shorter length of stay compared with open pancreatoduodenectomy (odds ratio 0.43, 95% CI 0.28–0.95). There were no differences in other outcomes. Conclusion This network meta-analysis of high-quality studies suggests that when laparoscopic pancreatoduodenectomy and robotic pancreatoduodenectomy are performed in high-volume centers, short-term perioperative and oncologic outcomes are largely comparable, if not slightly improved, compared with traditional open pancreatoduodenectomy. These findings should be corroborated in further prospective randomized studies.

OBJECTIVES This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction. BACKGROUND The estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized. METHODS We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor-neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]). RESULTS We identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses. CONCLUSIONS In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i. (J Am Coll Cardiol HF 2022;10:73-84) (c) 2022 by the American College of Cardiology Foundation.

To investigate the outcomes of treatment strategies for proximal and iliofemoral deep vein thrombosis (DVT).Randomised controlled trials (RCTs) investigating outcomes of catheter directed thrombolysis (CDT), ultrasound assisted CDT (USCDT), percutaneous aspiration thrombectomy (PAT), and best medical therapy (BMT) for proximal DVT from 2000 onwards were considered. MEDLINE, EMBASE, and CINAHL were searched using the Healthcare Databases Advanced Search interface developed by the National Institute for Health and Care Excellence. The primary outcome was the rate of post-thrombotic syndrome (PTS), which was defined using the Villalta scoring system (score of ≥5). Secondary outcomes included vessel patency, recurrence, bleeding, and mortality. The network of evidence was summarised using network plots, and random effects network meta-analyses were performed. The certainty of evidence was assessed using the Certainty In Network Meta-Analysis (CINeMA) approach.Seven RCTs meeting the inclusion criteria were identified. There were direct comparisons between medical therapy, CDT, and USCDT across outcomes, except for patency. There were no direct comparisons between medical therapy and PAT (except for patency), and USCDT and PAT. There was no significant difference observed in PTS between the treatment modalities for proximal and iliofemoral DVT (low certainty). There was a significant difference in patency rates between medical therapy and USCDT (odds ratio [OR] 9.46, 95% confidence interval [CI] 3.05 - 29.35; low certainty) and CDT (OR 2.03, 95% CI 1.46 - 2.80; low certainty) in favour of USCDT and CDT, respectively, for proximal DVT. USCDT significantly improved patency rates compared with CDT (OR 4.67, 95% CI 1.58 - 13.81; very low certainty) for proximal DVT. There was no significant difference in DVT recurrence, bleeding, or mortality between treatment groups for proximal and iliofemoral DVT (low to moderate certainty for most comparisons).USCDT may improve patency rates compared with BMT and the other interventional treatment modalities used for the management of proximal DVT. However, no treatment modality showed superiority with regard to a reduction in PTS, and overall, the quality of available evidence is poor.

Antioxidant micronutrients (AxMs) have been administered to critically ill adults attempting to counteract the oxidative stress imposed during critical illness. However, results are conflicting and relative effectiveness of AxMs regimens is unknown. We conducted a Bayesian multi-treatment comparison (MTC) meta-analysis to identify the best AxM treatment regimen that will improve clinical outcomes.PubMed, EMBASE, Web of Science and Cochrane databases were searched from the inception of databases through August 2020. Randomized controlled trials (RCT) comparing AxMs supplementations with placebo among critically ill adults were included. Two authors assessed trial quality using Cochrane risk of bias tool and assessed certainty of evidence (CoE). A random effect model, non-informative priors Bayesian MTC meta-analysis using gemtc package in R version 3.6.2 was performed. AxMs treatment effect on clinical outcomes (mortality, infection rates, intensive care unit (ICU) and hospital stays and ventilator days) were represented by absolute risk differences (ARD) for dichotomous outcomes and mean differences (MD) for continuous outcomes. Prior to final analysis, we repeated the search through January 2021.37 RCT (4905 patients) were included with 16 direct comparisons. With respect to mortality, the ARD for "vitamin E" compared with placebo was centred at -0.19 [95%CrI: -0.54,0.16; very low CoE] and was ranked the best treatment for mortality reduction as per surface under the cumulative ranking curve (SUCRA 0.71, 95%CrI: 0.07,1.00). A combination of "selenium, zinc and copper" was ranked the best for lowest ICU stay [-9.40, 95% CrI: -20.0,1.50; low CoE]. A combination of "selenium, zinc, copper and vitamin E" was ranked the best treatment for infection risk reduction [-0.22, 95% CrI: -0.61,0.17; very low CoE]. Ventilator days were least with a combination of "selenium, zinc and manganese" [2.80, 95% CrI: -6.30,0.89; low CoE]. Hospital stay was the lowest using a combination of "selenium, zinc and copper" [-13.00, 95% CrI: -38.00,13.00; very low CoE]. There is substantial uncertainty present in the rankings due to wide and overlapping 95% CrIs of SUCRA scores for the treatments.Studies on critically ill adult patients have suggested a possible beneficial effects of certain AxM supplementations over and above the recommended dietary allowance. However, evidence does not support their use in clinical practice due to the low confidence in the estimates. Current studies evaluating specific AxMs or their combinations are limited with small sample sizes.PROSPERO, CRD42020210199.Evidence suggesting a potential benefit of AxMs use more than recommended doses in critically ill adults is weak, indicating that there is no justification for this practice.

To maintain living, interactive evidence (LIvE) on the benefits and harms of different treatment options in adults with cancer-associated thrombosis (CAT).We have used a novel LIvE synthesis framework to maintain this living, interactive systematic review since September 19, 2018. Randomized controlled trials evaluating the efficacy and safety of direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin for CAT are included in this analysis. Details of LIvE synthesis framework are available at the website https://cat.network-meta-analysis.com.The results are constantly updated as new information becomes available (https://cat.network-meta-analysis.com/CAT.html). The living, interactive systematic review currently includes 4 randomized controlled trials (N=2894). Direct comparisons show that DOACs significantly decrease recurrent venous thromboembolism (VTE) events compared with dalteparin (odds ratio [OR], 0.59; 95% CI, 0.41 to 0.86; IDOACs should be considered a standard of care for the treatment of CAT except in patients with a high risk of bleeding. Current evidence favors the use of apixaban for the treatment of CAT among other DOACs.Open Science Framework (https://osf.io/dth86).

Objective Type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD) are closely related, and antidiabetic medications have been shown to be potential therapeutics in NAFLD. Using a network meta-analysis, we sought to examine the effectiveness of antidiabetic agents for the treatment of NAFLD in patients with type 2 diabetes mellitus. Methods Medline and Embase were searched for randomized controlled trials relating to the use of antidiabetic agents, including sodium-glucose transport protein 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor gamma (PPARγ) agonists, biguanides, sulfonylureas and insulin, on NAFLD in patients with diabetes. The p-score was used as a surrogate marker of effectiveness. Results A total of 14 articles were included in the analysis. PPARγ agonists were ranked as the best treatment in steatosis reduction, resulting in the greatest reduction of steatosis. There was statistical significance between PPARγ agonists [mean difference (MD): −6.02%, confidence interval (CI): −10.37% to −1.67%] and SGLT2 inhibitors (MD: −2.60%, CI: −4.87% to −0.33%) compared with standard of care for steatosis reduction. Compared with PPARγ agonists, SGLT2 inhibitors resulted in a statistical significant reduction in fibrosis (MD: −0.06, CI: −0.10 to −0.02). Body mass index reduction was highest in SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists. Additionally, SGLT2 inhibitors were ranked as the best treatment for increasing high-density lipoprotein and reducing low-density lipoprotein. Conclusion Glucagon-like peptide-1 receptor agonists and SGLT2 inhibitors were suitable alternatives for the treatment of NAFLD in those with type 2 diabetes mellitus with a reduction in body mass index, fibrosis, and steatosis. SGLT2 inhibitors also have the added benefit of lipid modulation.

Patients with atrial fibrillation (AF) who take direct oral anticoagulants (DOACs) face the risk of intracranial hemorrhage (ICH), which can be serious and even life threatening, but the risk of ICH of anticoagulants is still controversial. In this meta-analysis, we compared the risk of ICH between vitamin K antagonists (VKAs) and DOACs. Furthermore, we also compared the risk of ICH in different DOACs. PubMed, Embase, Web of Science, and the Cochrane Library were searched for relevant randomized controlled trials. The outcome was ICH, shown as the odds ratio (OR) with a 95% confidence interval (CI). DOACs were ranked by calculating the surface under the cumulative ranking curve (SUCRA). We included a total of 82,404 patients with AF. DOACs reduced the ICH risk by nearly half compared with VKAs (OR 0.47, 95% CI 0.40 to 0.54, p0.001). VKAs were the least safe among all oral anticoagulants (SUCRA 1.7). Dabigatran 110 mg was the safest DOAC (SUCRA 87.3) for ICH risk, whereas rivaroxaban 20 mg was a relatively unsafe DOAC (SUCRA 27.5). Compared with rivaroxaban 20 mg, dabigatran 110 mg presented 53% (OR 0.47, 95% CI 0.27 to 0.82) lower relative risk for ICH. In conclusion, DOACs present less ICH risk than VKAs in patients with AF. For patients with AF who are at high risk of ICH, dabigatran 110 mg may be the safest choice among the DOACs.

The efficacy comparison of osteoporosis treatments can be hindered by the absence of head-to-head trials; instead, network meta-analyses (NMAs) have been used to determine comparative effectiveness. This study was the first to investigate the impact of time point-specific NMAs of osteoporosis treatments on variability in treatments' onset of action caused by their different mechanisms of actions and trial designs.A systematic literature review was conducted to identify randomized controlled trials (RCTs) of treatments for postmenopausal women with osteoporosis, including romosozumab (ROMO), teriparatide (TPTD), abaloparatide (ABL), alendronate (ALN), risedronate (RIS), ibandronate (IB), zoledronic acid/zoledronate (ZOL), denosumab (DEN), and raloxifene (RLX), on at least 1 fracture or bone mineral density (BMD) outcome. Of 100 RCTs identified in 5 databases, 27 RCTs were included for NMAs of new vertebral, nonvertebral, and hip fracture outcomes at 12, 24, and 36 months, and 47 RCTs were included for NMAs of BMD outcomes at lumbar spine, total hip, and femoral neck to compare the relative efficacy of osteoporosis treatments. Quality of included studies was assessed using the Cochrane Risk of Bias tool.For vertebral fractures, TPTD (83.63%), ABL (69.11%), and ROMO/ALN (78.70%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO/ALN had the highest probability (54.4%, 64.69%, and 90.29%, respectively) to be the most effective treatment for nonvertebral fractures at 12, 24, and 36 months. For hip fractures, ROMO/ALN (46.31%), ABL (61.1%), and DEN (55.21%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO had the highest probability (76.06%, 44.19%, and 51.78%, respectively) to be the most effective treatment for BMD outcomes at lumbar spine, total hip, and femoral neck.The importance of indirectly comparing available osteoporosis treatments using time point-specific NMAs was confirmed because indirect comparison results differed substantially across time points.

Abstact Objective Microscopic identification of monosodium urate (MSU) crystals is the gold standard for gout diagnosis. However, joint aspiration is not always practical, and imaging is increasingly used in clinical practice. This study aimed to assess the diagnostic accuracy of imaging features for gout compared with microscopy, using network meta-analysis methodology. Methods MEDLINE, EMBASE, PubMed and Cochrane databases were searched for studies reporting on the use of imaging modalities to diagnose gout in patients with an unclear diagnosis or suspected gout, which was later confirmed by microscopy. A combination of direct and indirect comparisons were performed by network meta-analysis to evaluate the combined odds ratios for sensitivity, specificity, and accuracy. To assist interpretation, the surface under the cumulative ranking curve (SUCRA) scores were calculated to provide a ranking of the imaging features. Results Fifteen eligible studies were included. Compared to the gold standard microscopic identification of MSU crystals, dual energy computed tomography (DECT) MSU crystal deposition and ultrasound double contour had greater sensitivity than ultrasound tophus. DECT, ultrasound double contour sign and ultrasound tophus all had greater specificity than ultrasound aggregates. The SUCRA scores ranked DECT as highest for overall accuracy, followed by ultrasound double contour, aggregates, and tophus, while ultrasound snowstorm was ranked the lowest. However, there were no significant differences in the odds ratios for overall accuracy between these imaging features. Conclusion DECT and ultrasound are both useful modalities for the detection of imaging features of MSU crystal deposition, and have a similar overall diagnostic accuracy for gout diagnoses.

Background Vaccination and single-dose rifampin are the main proven effective intervention types for preventing leprosy among contacts of Mycobacterium leprae endemic areas. Currently, no high-quality evidence is available regarding the best prophylactic intervention. Objectives Our primary study aim is to detect the most effective prophylactic intervention for the prevention of leprosy. Methods In May 2019, 12 databases were searched systematically. Updated search terms were developed in March 2020 to complete an updated search. All randomized controlled trials (RCTs) comparing the different types of chemoprophylactic and immunoprophylactic interventions in leprosy prevention were included. Our participants were contacts of patients with leprosy or people residing in leprosy endemic communities. We searched for different types of chemoprophylactic and immunoprophylactic interventions used in leprosy prevention. We used network meta-analysis and meta-analysis. Quality assessment was performed using Cochrane Risk of Bias for included RCTs, in which all included RCTs were rated to be low to moderate risk. We registered our protocol in Prospero with ID CRD42019143207. Results Among 11 included studies (326 264 patients) from original and updated search terms, eight were eligible for network meta-analysis (NMA) while four were eligible for MA. Findings suggest that Bacillus Calmette–Guerin (BCG) vaccination was the most effective intervention compared to placebo (risk ratios (RRs) 0.49 (0.30, 0.80), p 0.77), followed by combined BCG vaccination and single-dose rifampicin (SDR) with similarly low values (RR 48%, p 0.77). BCG revaccination was the least effective intervention compared to placebo (RR 1.08 (0.36, 3.22), p 0.26). Conclusion Compared to placebo, the BCG vaccine was the most effective prophylactic intervention. The combination of BCG vaccination + SDR had nearly the same efficacy as BCG vaccination alone, while BCG revaccination was the least effective. Thus, vaccination proved to be a more effective treatment than SDR alone. A well-designed multicenter RCT is warranted to evaluate the safety of these vaccines.

Summary Background Different catheter lock solutions (CLSs) are used to reduce catheter-related bloodstream infection (CRBSI) for paediatric patients with central venous catheters (CVCs), but the most effective CLS is unknown. Aim To compare the effectiveness of different CLSs for the prevention of CRBSI in paediatric patients. Methods Potential studies were searched and selected through the PubMed, Embase, Web of Science and Cochrane Library up to May 2021. Randomized controlled trials that assessed the effects of CLSs for preventing CRBSI in paediatric patients were included. We performed a random-effects network meta-analysis to estimate risk ratio (RR) with 95% confidence interval (CI). Findings Thirteen studies comprising 1335 patients were included in the network meta-analysis. Taurolidine + heparin was effective in the prevention of CRBSI compared with heparin in paediatric patients (RR: 0.21, 95% CI: 0.09–0.51). No significant difference was found between the other CLSs (such as vancomycin, ethanol, fusidic acid, amikacin, and amikacin and vancomycin) and heparin or between different intervention lock solutions for CRBSI prevention. Based on the surface under the cumulative ranking curve, taurolidine + heparin (85.3%) appeared to be the most effective solution for effectiveness on CRBSI prevention, followed by fusidic acid + heparin (77.0%) and amikacin + heparin (65.7%). There was no statistical global inconsistency among the included studies after design by treatment test (χ2 = 2.22, P=0.137). Conclusion The study showed that taurolidine lock solution seemed to be the most effective for the prevention of CRBSI in paediatric patients. Well-designed randomized trials in paediatric patients are needed to provide more reliable evidence in the effectiveness of different CLSs.

Purpose Leukocyte- and platelet-rich fibrin (L-PRF) and advanced-platelet-rich fibrin (A-PRF) that are derivatives of PRF (platelet-rich fibrin) accelerate wound healing and reduce postoperative sequelae after tooth extraction. This network meta-analysis aimed to investigate the effectiveness of L-PRF and A-PRF in mandibular third molar extraction and provide suggestions for alleviating postoperative symptoms and signs. Methods A comprehensive search of the literature was conducted in PubMed, Embase, Web of Science, and SinoMed databases up to Oct 9, 2020. Three types of randomized controlled trials were included to investigate the effects of PRF derivatives after extracting mandibular third molars: A-PRF and L-PRF groups; A-PRF and control groups; L-PRF and control groups. Their relative effectiveness and ranking were assessed using network meta-analysis and the surface under the cumulative ranking curve (SUCRA) with STATA 16.0 and Revman 5.3, respectively. Results Ten randomized controlled trials were included, with 307 mandibular third molar extraction patients involved. The results showed that A-PRF had the best effect among the 3 groups in improving postoperative pain on the third (SUCRA = 98.2%) and seventh (SUCRA = 88.4%) days; L-PRF promoted soft tissue healing (MD = -0.90, 95% CI [-1.40, -0.40], P = .0004) on the seventh day compared with the control. However, other comparisons showed no significant differences (P > .05). Conclusion The limited results confirmed that PRF derivatives only reduced some postoperative symptoms and did not prevent them all. Application of A-PRF after third molar extraction reduced postoperative pain, and L-PRF improved the degree of soft tissue healing.

Summary Aim To test the null hypothesis that there was no difference in treatment efficiency between therapies undertaken with conventional (CBs), passive self-ligating (PSLBs) or active self-ligating (ASLBs) brackets. Materials and methods An electronic search was performed in 3 data bases (Pubmed, Web of Science, Cochrane Library) from their origin up to January 2019. Additional references were hand searched. Search was strictly restricted to randomized controlled trials (RCTs) and split-mouth design studies (SMDs). RCTs and SMDs were initially processed separately and subsequently combined in a network meta-analysis. The following variables were evaluated: treatment duration, number of visits, occlusal outcomes, alignment rate, transverse arch dimensional changes, incisor position modification, rate of space closure, anchorage loss, bond failure, root resorption, perception of discomfort during the initial phase of alignment, time to ligate in or to untie an archwire, periodontal variables, quality of life. Results On 229 papers, 30 RCTs and 9 SMDs were finally included in this study. Out of 85 comparisons, 16 only revealed statistically significant differences. It was quicker to untie and ligate an 0.014 NiTi arch from/in 6 ASLBs anterior ceramic brackets compared to 6 ceramic CBs. It was also more painful to insert and remove an 0.019 × 0.025 SS wire in/from PSLB's brackets compared to CB's attachments. Compared to conventional brackets, there was less maxillary incisor proclination with PSLBs in non-extraction cases. Moreover, there was less bleeding on probing 4-5 weeks after bonding with PSLBs compared to CBs brackets. The only significant difference between ASLBs and PSLBs was that alignment was 10 days faster with active self-ligating braces compared with passive self-ligating braces even if treatment duration between ASLBs and PSLBs was not significantly different. The network meta-analysis revealed that IMPA was greater in extractions cases with CBs compared with both ASLBs (+2,5°) and PSLBs (+1,6°). Conclusions The vast majority of the studied variables did not show any significant differences between the three types of brackets. The most significant findings were that it was quicker to insert and remove archwires from ASLBs compared to CBs, and it was more painful to insert and remove an 0.019 × 0.025” stainless steel wire in/from PSLBs compared to CBs. The major difference between ASLBs and PSLBs was that alignment was 10 days faster with active self-ligating braces compared with passive self-ligating braces even if treatment duration between ASLBs and PSLBs was not significantly different. Most of the claims put forward by the suppliers were not substantiated by our network meta-analysis.

Context Identifying the most effective first-line treatment for metastatic renal cell carcinoma (mRCC) is challenging as rapidly evolving data quickly outdate the existing body of evidence, and current approaches to presenting the evidence in user-friendly formats are fraught with limitations. Objective To maintain living evidence for contemporary first-line treatment for previously untreated mRCC. Evidence acquisition We have created a living, interactive systematic review (LISR) and network meta-analysis for first-line treatment of mRCC using data from randomized controlled trials comparing contemporary treatment options with single-agent tyrosine kinase inhibitors. We applied an advanced programming and artificial intelligence–assisted framework for evidence synthesis to create a living search strategy, facilitate screening and data extraction using a graphical user interface, automate the frequentist network meta-analysis, and display results in an interactive manner. Evidence synthesis As of October 22, 2020, the LISR includes data from 14 clinical trials. Baseline characteristics are summarized in an interactive table. The cabozantinib + nivolumab combination (CaboNivo) is ranked the highest for the overall response rate, progression-free survival, and overall survival, whereas ipilimumab + nivolumab (NivoIpi) is ranked the highest for achieving a complete response (CR). NivoIpi, and atezolizumab + bevacizumab (AteBev) were ranked highest (lowest toxicity) and CaboNivo ranked lowest for treatment-related adverse events (AEs). Network meta-analysis results are summarized as interactive tables and plots, GRADE summary-of-findings tables, and evidence maps. Conclusions This innovative living and interactive review provides the best current evidence on the comparative effectiveness of multiple treatment options for patients with untreated mRCC. Trial-level comparisons suggest that CaboNivo is likely to cause more AEs but is ranked best for all efficacy outcomes, except NivoIpi offers the best chance of CR. Pembrolizumab + axitinib and NivoIpi are acceptable alternatives, except NivoIpi may not be preferred for patients with favorable risk. Although network meta-analysis provides rankings with statistical adjustments, there are inherent biases in cross-trial comparisons with sparse direct evidence that does not replace randomized comparisons. Patient summary It is challenging to decide the best option among the several treatment combinations of immunotherapy and targeted treatments for newly diagnosed metastatic kidney cancer. We have created interactive evidence summaries of multiple treatment options that present the benefits and harms and evidence certainty for patient-important outcomes. This evidence is updated as soon as new studies are published.

Background Anti-epileptic drugs have different effects on neonatal seizures, and new agents have been widely used in recent years. Meanwhile, significant differences still exist in the treatment for neonatal seizures, whether in choice of drug or in duration of treatment. And with the increase in options for treatment, the best choice of second-line treatment has not been recommended. Methods The MEDLINE, the Cochrane Library, Web of Science, Embase and clinicaltrials.gov databases were searched (January 1, 1960 to October 20, 2020). Randomized controlled trials (RCTs) or observational investigations studying anti-epileptic drugs for neonatal seizures were selected. And then we conducted a network meta-analysis and examined comparative efficacy of the first-line and second-line anti-epileptic drugs for neonatal seizures. Results Data were extracted from 11 included studies by 2 independent investigators. Random effects models were used to estimate odds ratios (ORs). We performed direct meta-analyses with a random effects model and network meta-analyses for first-line and second-line drugs. Five published RCTs and 6 observational investigations with 1333 patients and 6 interventions contributed to the analysis. Conclusion We recommend phenobarbital as the first-line drug for neonatal seizures. In addition, there is a tendency for levetiracetam to be an effective second-line treatment for neonatal seizures after failure of first-line drugs.

To evaluate the most effective endovascular treatment modalities for de novo femoropopliteal lesions in intermittent claudication (IC) in terms of technical success, primary patency, target lesion revascularization (TLR) and all-cause mortality through network meta-analysis of randomized controlled trials.Medical databases were searched on December 3, 2020. 16 studies (3265 patients) and 7 treatments were selected. Outcomes were technical success, primary patency, TLR and mortality at 6 and/or 12 months.Regarding 6-month primary patency, drug-eluting stents (DES) was better than balloon angioplasty (BA; odds ratio [OR], 23.27; 95% confidence interval [CI], 12.57-43.06), drug-coated balloons (DCB; OR, 5.63; 95% CI, 2.26-14.03) and directional atherectomy (DA; OR, 31.52; 95% CI, 7.81-127.28), and bare nitinol stents (BNS) was better than BA (OR, 17.91; 95% CI, 7.22-44.48), DCB (OR, 4.33; 95% CI, 1.40-13.45) and DA (OR, 24.27; 95% CI, 5.16-114.11). Regarding 12-month primary patency, DES was better than BA (OR, 10.05; 95% CI, 4.56-22.16), DCB (OR, 3.70; 95% CI, 1.54-8.89) and DA (OR, 29.54; 95% CI, 7.26-120.26). DCB and combination of balloon and atherectomy were the most effective treatment regarding 12-month TLR and technical success (residual stenosis30%), respectively. DES, BNS and DA with DCB (DA-DCB) were included in the best cluster in the clustered ranking plot combining 12-month primary patency and TLR.Balloon and atherectomy may confer advantages over other treatments for technical success; DCB may for TLR. Stent technologies confer substantial advantages regarding primary patency. Stent technologies and DA-DCB should be given priority in treating femoropopliteal lesions in IC.

Postoperative pain management after total shoulder arthroplasty (TSA) can be challenging. Given the variety of pain management options available, the purpose of this investigation was to systematically review the literature for randomized controlled trials reporting on pain control after shoulder arthroplasty. We sought to determine which modalities are most effective in managing postoperative pain and reducing postoperative opioid use.A systematic review was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched for Level I-II randomized controlled trials that compared interventions for postoperative pain control after TSA. Pain control measures included nerve blocks and nerve block adjuncts, local injections, patient-controlled analgesia, oral medications, and other modalities. The 2 primary outcome measures were pain level measured on a 0-10 visual analog scale and opioid use. The risk of study bias and methodologic quality were analyzed using The Cochrane Collaboration's Risk of Bias 2 (RoB 2) tool. Network meta-analyses were performed for visual analog scale pain scores at postsurgical time points and opioid use using a frequentist approach and random-effects model, with heterogeneity quantified using the IThe initial search yielded 2391 articles (695 duplicates, 1696 screened, 53 undergoing full-text review). Eighteen articles (1358 shoulders; 51% female patients; mean age range, 65-73.7 years; 4 studies with low risk of bias, 12 with some risk, and 2 with high risk) were included and analyzed. At 4 and 8 hours postoperatively, patients receiving local liposomal bupivacaine (LB) injection (P.001 for 4 and 8 hours) or local ropivacaine injection (P.001 for 4 hours and P = .019 for 8 hours) had significantly more pain compared with patients who received either a continuous interscalene block (cISB) or single-shot interscalene block (ssISB). No differences in opioid use (at P.05) were detected between modalities. The P scores of treatments demonstrated that ssISBs were most favorable at time points24 hours, whereas pain at 24 and 48 hours after surgery was best managed with cISBs or a combination of an ssISB with a local LB injection.Interscalene blocks are superior to local injections alone at managing pain after TSA. Single-shot interscalene blocks are optimal for reducing early postoperative pain (24 hours), whereas pain at 24-48 hours after surgery may be best managed with cISBs or a combination of an ssISB with a local LB injection.