To evaluate the efficacy of various pharmacological treatments for olfactory disorders in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).

PubMed, Embase, Cochrane Library, and Web of Science.

We searched the related literature in PubMed, Embase, Cochrane Library, and Web of Science up to Aug 2024 to appraise the effects of pharmacotherapy on olfactory sensation. After that, two reviewers independently screened the retrieved articles, extracted the pertinent data, and assessed the risk of bias in the included studies. Then we used Stata 14.2 to perform a network meta-analysis.

Ninteen randomized controlled trials (RCTs) and 2354 participants were included. Compared with placebo, biologics demonstrated the most significant improvement in subjective olfactory dysfunction (OD) [standardized mean difference (SMD) = -0.75, 95% confidence intervals (CI) (-1.08, -0.41)]. In terms of objective olfactory function improvement, biologics also exhibited the greatest effect (SMD = 0.93, 95% CI [0.56, 1.31]). Among various biologics, dupilumab was the most effective in alleviating both subjective OD (SMD = -1.30, 95% CI [-1.51, -1.09]) and objective OD (mean difference [MD] = 11.13, 95% CI [9.91, 12.35]).

Our research results indicated that biologics might show better performance in terms of improving the olfactory sensation of patients with CRSwNP, particularly dupilumab. However, given the limitations of this study, future research should employ more standardized olfactory assessment methods and conduct more large-scale RCTs, ultimately guiding clinicians and patients in making informed and optimal treatment choices.

NA.

Network meta-analysis has emerged as a method for analysing clinical trials, with a large increase in the number of publications over the past decade. Network meta-analysis offers advantages over traditional pairwise meta-analysis, including increased power, the ability to compare treatments not compared in the original trials, and the ability to rank treatments. However, network meta-analyses are inherently more complex than pairwise meta-analyses, requiring additional statistical expertise and assumptions. Many factors can affect the certainty of evidence from pairwise meta-analysis and can often lead to unreliable results. Network meta-analysis is prone to all these issues, although it has the additional assumption of transitivity. Here we review network meta-analyses, problems with their conduct and reporting, and methodological strategies that can be used by those conducting reviews to help improve the reliability of their findings. We provide evidence that violation of the assumption of transitivity is relatively common and inadequately considered in published network meta-analyses. We explain key concepts with clinically relevant examples for those unfamiliar with network meta-analysis to facilitate their appraisal and application of their results to clinical practice.

Several surgical techniques have been used to treat cervical dystonia (CD), however, to date, the optimal surgical technique for CD remains controversial. We therefore conducted the first network meta-analysis to compare different surgical strategies for CD to inform clinical practice.

Electronic databases were searched for surgical strategies for treating CD. The primary outcome was improvement in total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score. Subgroup analysis was performed to compare short-term (< 1 year) and long-term (≥ 1 year) outcomes. Safety outcomes included surgery-related adverse events (AEs).

A total of 55 trials with 2032 patients employing five surgical strategies were identified, including globus pallidus internus (GPi)/subthalamic nucleus (STN)-deep brain stimulation (DBS), selective peripheral denervation (SPD), microvascular decompression (MVD) and pallidotomy. All strategies led to significant improvement in total TWSTRS score (mean improvement range 18.65-28.22). GPi-DBS showed significantly greater enhancement than SPD for the whole dataset (mean difference [MD] 7.03, 95% credible interval [Crl] 1.53-12.56), while both GPi-DBS (MD 8.05, 95% Crl 2.35-13.80) and STN-DBS (MD 10.71, 95% Crl 2.22-19.20) exhibited more long-term improvement than SPD. Regarding safety outcomes, GPi/STN-DBS and MVD were associated with fewer surgery-related AEs than SPD (ln odds ratio range -1.68 to -1.41).

We conclude that DBS should be the preferred surgical option for CD, and the STN is a promising alternative target choice due to its comparable efficacy with the GPi. However, more direct evidence is still required.

The optimal duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) remains under debate.

To analyze the efficacy and safety of DAPT strategies in patients with ACS using a bayesian network meta-analysis.

MEDLINE, Embase, Cochrane, and LILACS databases were searched from inception to April 8, 2024.

Randomized clinical trials (RCTs) comparing DAPT duration strategies in patients with ACS undergoing PCI were selected. Short-term strategies (1 month of DAPT followed by P2Y12 inhibitors, 3 months of DAPT followed by P2Y12 inhibitors, 3 months of DAPT followed by aspirin, and 6 months of DAPT followed by aspirin) were compared with conventional 12 months of DAPT.

This systematic review and network meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The risk ratio (RR) with a 95% credible interval (CrI) was calculated within a bayesian random-effects network meta-analysis. Treatments were ranked using surface under the cumulative ranking (SUCRA).

The primary efficacy end point was major adverse cardiac and cerebrovascular events (MACCE); the primary safety end point was major bleeding.

A total of 15 RCTs randomizing 35 326 patients (mean [SD] age, 63.1 [11.1] years; 26 954 male [76.3%]; 11 339 STEMI [32.1%]) with ACS were included. A total of 24 797 patients (70.2%) received potent P2Y12 inhibitors (ticagrelor or prasugrel). Compared with 12 months of DAPT, 1 month of DAPT followed by P2Y12 inhibitors reduced major bleeding (RR, 0.47; 95% CrI, 0.26-0.74) with no difference in MACCE (RR, 1.00; 95% CrI, 0.70-1.41). No significant differences were observed in MACCE incidence between strategies, although CrIs were wide. SUCRA ranked 1 month of DAPT followed by P2Y12 inhibitors as the best for reducing major bleeding and 3 months of DAPT followed by P2Y12 inhibitors as optimal for reducing MACCE (RR, 0.85; 95% CrI, 0.56-1.21).

Results of this systematic review and network meta-analysis reveal that, in patients with ACS undergoing PCI with DES, 1 month of DAPT followed by potent P2Y12 inhibitor monotherapy was associated with a reduction in major bleeding without increasing MACCE when compared with 12 months of DAPT. However, an increased risk of MACCE cannot be excluded, and 3 months of DAPT followed by potent P2Y12 inhibitor monotherapy was ranked as the best option to reduce MACCE. Because most patients receiving P2Y12 inhibitor monotherapy were taking ticagrelor, the safety of stopping aspirin in those taking clopidogrel remains unclear.

Network Meta-analysis (NMA) is an advanced statistical method that combines direct evidence (ie, from head-to-head comparisons) and indirect evidence (ie, estimated from the direct available evidence) to obtain network estimates. NMAs are helpful to determine the comparative effectiveness of interventions that have not been directly compared and may provide more precise estimates for those comparisons that have been directly compared. NMA provides hierarchies which can be helpful for decision-making, much more in scenarios when multiple interventions exist for the same indication. In this article we provide a summary of the key concepts that users, namely, clinicians and methodologists need to consider when using an NMA to inform decision making.

Paediatric patients undergoing surgery for congenital heart disease (CHD) are at risk for postoperative low cardiac output syndrome (LCOS) and mortality. LCOS affects up to 25% of children after heart surgery. It consists of reduced myocardial function and increases postoperative morbidity, prolongs mechanical ventilation, and lengthens the duration of intensive care unit (ICU) stay. Pharmacological prophylaxis involves inotropes, including catecholamines, phosphodiesterase III inhibitors, or calcium sensitisers, to enhance myocardial contractility. It is unclear whether they are effective in preventing LCOS or death in this vulnerable population.

1. To evaluate the relative benefits and harms of inotropes for the prevention of LCOS and mortality in paediatric patients undergoing surgery for CHD. 2. To generate a clinically useful ranking of prophylactic inotropes for the prevention of LCOS and mortality in paediatric patients undergoing surgery for CHD according to benefits and harms.

We searched CENTRAL, MEDLINE, Embase, Web of Science, and clinical trial registries, most recently in December 2023 and April 2024. We also checked reference lists from identified studies and review articles. We did not apply any language restrictions.

We included randomised controlled trials comparing inotropes from one drug class (catecholamines, phosphodiesterase type III inhibitors, calcium sensitisers) to another (either alone or in combination) or placebo, in paediatric patients (birth to 18 years of age) undergoing surgery for CHD.

Two review authors independently selected studies, extracted data, assessed risk of bias, and rated the certainty of evidence using the CINeMA framework. We performed random-effects network and pairwise meta-analyses comparing the relative effects of each possible pair of medications with each other or placebo. Where meta-analysis was not possible, we provided a narrative description of the results. We ranked the prophylactic medications according to their effects relative to each other. The primary outcomes were all-cause mortality within 30 days, time to death, and LCOS incidence; secondary outcomes were length of ICU stay, length of hospital stay, duration of mechanical ventilation, inotrope score, mechanical circulatory support, and adverse events.

We included 13 studies with 937 participants. All except two multicentre studies were conducted at single tertiary care hospitals. Participants comprised children from birth to 14 years of age undergoing surgery for different types of CHD on cardiopulmonary bypass. Five studies compared levosimendan versus milrinone; two compared levosimendan versus placebo; two compared milrinone versus placebo (one comparing two different doses); one compared levosimendan versus dobutamine, another milrinone versus dobutamine. Two studies used combinations of inotropes. Study duration was between less than one year and 5.3 years, with follow-up mostly during ICU or hospital stay. Funding sources included governmental bodies and hospital departments, but also drug manufacturers. We downgraded the certainty of evidence for high risk of bias at study level, or imprecision at comparison level. Primary outcomes Compared to placebo, levosimendan likely results in a large reduction in mortality (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.15 to 2.13) and milrinone likely results in no difference (RR 0.97, 95% CI 0.11 to 8.49), whereas for dobutamine, no effect was estimable; all moderate-certainty evidence (9 studies, 557 participants, 14 events). LCOS was largely reduced with levosimendan (RR 0.45, 95% CI 0.24 to 0.83; high-certainty evidence), likely largely reduced with milrinone (RR 0.46, 95% CI 0.24 to 0.89; moderate-certainty evidence), and may be reduced with low-dose milrinone (RR 0.7, 95% CI 0.39 to 1.28; low-certainty evidence), compared with placebo (5 studies, 513 participants, 85 events). Secondary outcomes The length of ICU stay may be no different with levosimendan (ratio of means (ROM) 1.12, 95% CI 0.77 to 1.63; low-certainty evidence), and is likely no different with milrinone (ROM 1.13, 95% CI 0.75 to 1.69) or with dobutamine (ROM 1.11, 95% CI 0.66 to 1.86), compared with placebo (9 studies, 577 participants); both moderate-certainty evidence. The length of hospital stay, compared with placebo, is likely no different with levosimendan (ROM 1.03, 95% CI 0.84 to 1.27) or with milrinone (ROM 1, 95% CI 0.78 to 1.3), but is likely reduced with dobutamine (ROM 0.68, 95% CI 0.37 to 1.26); all moderate-certainty evidence (7 studies, 297 participants). The duration of mechanical ventilation, compared with placebo, is likely increased with levosimendan (ROM 1.17, 95% CI 0.65 to 2.12) or with milrinone (ROM 1.25, 5% CI 0.67 to 2.36) and is likely no different with dobutamine (ROM 1.04, 95% CI 0.45 to 2.38); all moderate-certainty evidence (9 studies, 577 participants). There is moderate-certainty evidence that adverse events are likely increased with levosimendan (incidence rate ratio (IRR) 1.23, 95% CI 0.78 to 1.96) or dobutamine (IRR 1.24, 95% CI 0.75 to 2.03) and low-certainty evidence that they may be increased with milrinone (IRR 1.31, 95% CI 0.96 to 1.79) and decreased with low-dose milrinone (IRR 0.84, 95% CI 0.47 to 1.5), compared with placebo (8 studies, 706 participants, 380 events).

Levosimendan likely results in a large reduction in mortality compared to placebo in paediatric patients undergoing surgery for congenital heart disease, whereas milrinone likely results in no difference, and the effect of dobutamine is unknown. Low cardiac output syndrome (LCOS) is largely reduced with levosimendan, likely largely reduced with milrinone, and may be reduced with low-dose milrinone, compared to placebo. The length of ICU stay may be no different with levosimendan and is likely no different with milrinone or with dobutamine, compared to placebo. The length of hospital stay is likely no different with levosimendan or with milrinone, but is likely reduced with dobutamine, compared to placebo. The duration of mechanical ventilation is likely increased with levosimendan or with milrinone and is likely no different with dobutamine, compared to placebo. Adverse events are likely increased with levosimendan or dobutamine, and may be increased with milrinone and decreased with low-dose milrinone, compared to placebo. The evidence is based on few, heterogeneous studies, with small numbers of patients and short follow-up periods. Future research should include large numbers of patients, consistently report all co-interventions, and ensure the longest possible follow-up.

Network meta-analysis is a powerful tool to synthesize evidence from independent studies and compare multiple treatments simultaneously. A critical task of performing a network meta-analysis is to offer ranks of all available treatment options for a specific disease outcome. Frequently, the estimated treatment rankings are accompanied by a large amount of uncertainty, suffer from multiplicity issues, and rarely permit possible ties of treatments with similar performance. These issues make interpreting rankings problematic as they are often treated as absolute metrics. To address these shortcomings, we formulate a ranking strategy that adapts to scenarios with high-order uncertainty by producing more conservative results. This improves the interpretability while simultaneously accounting for multiple comparisons. To admit ties between treatment effects in cases where differences between treatment effects are negligible, we also develop a Bayesian non-parametric approach for network meta-analysis. The approach capitalizes on the induced clustering mechanism of Bayesian non-parametric methods, producing a positive probability that two treatment effects are equal. We demonstrate the utility of the procedure through numerical experiments and a network meta-analysis designed to study antidepressant treatments.

Cognitive behavioral therapy (CBT) is effective for headache disorders. However, it is unclear whether the emerging digital CBT is noninferior to face-to-face CBT. An indirect treatment comparison (ITC) meta-analysis was conducted to assess the relative effects between them using standard mean differences (SMDs). Effective sample size (ESS) and required sample size (RSS) were calculated to demonstrate the robustness of the results. Our study found that digital CBT had a similar effect on headache frequency reduction (SMD, 0.12; 95%CI, -2.45 to 2.63) compared with face-to-face CBT. The ESS had 84 participants, while the RSS had 466 participants to achieve the same power as a non-inferior head-to-head trial. Digital CBT is as effective as face-to-face CBT in preventing headache disorders. Due to the heterogeneity (I2 = 94.5%, τ2 = 1.83) and the fact that most of the included studies were on migraine prevention, further head-to-head trials are warranted.

Noise and lighting are prime factors of poor sleep quality in critically ill patients, which impair recovery and increase the risk of delirium or complications.

To identify and rank the effectiveness of sound and darkness interventions on the sleep quality of critically ill patients.

This systematic review and component network meta-analysis was based on the Preferred Reporting Items for Systematic Reviews incorporating the Network Meta-Analyses (PRISMA-NMA) Statement. The Embase, MEDLINE, Cochrane CENTRAL, CINAHL, Airiti Library, and Google Scholar databases were searched from inception to August 10, 2021, for randomized controlled trials (RCTs) on sound and darkness interventions targeting critically ill patients' sleep quality. We applied standard and component NMA to determine the effects of interventions. The certainty of evidence was evaluated using the Cochrane risk-of-bias tool (V.2.0) and the online Confidence in Network Meta-Analysis (CINeMA) application.

Twenty-four RCTs with 1507 participants who used combined interventions constituting seven competing interventions were included in the standard NMA. The combination of earplugs, eye masks, and music; eye masks alone; earplugs combined with eye masks; and music alone had beneficial intervention effects. The combination of earplugs, eye masks, and music was the best intervention, and these components had no interaction effect. An eye mask had the best relative effect, followed by music, quiet time, and earplugs.

This study provides clinical evidence of the effectiveness of using eye masks, music, and earplugs to improve sleep quality in critically ill patients. We also recommend future research using bedtime music, nocturnal eye masks, and quiet time, which had the best relative effects on sleep quality.

This study provides recommendations for interventions that nurses can use to improve critically ill patients' sleep quality.

The increase in the number of patients with uncontrolled type 2 diabetes mellitus (T2DM) is in need of effective management interventions. However, research to date has been limited to the evaluation of the outcomes of community pharmacists alone. Therefore, the aim of the study protocol is to compare the effects of clinical pharmacist-led intervention strategies for the management of T2DM in the outpatient settings.

The study will collect and analyse data applying standard Cochrane methodological procedures. A search for eligible studies and ongoing trials will be conducted using PubMed, Embase, Medline (via Ovid), EBSCO (via Ovid), Lippincott Williams & Wilkins (LWW) Journals (via Ovid), ProQuest Health and Medical Complete, and ClinicalTrials.gov (clinicaltrials.gov) from database inception to December 2023. Clinical and health outcomes will be measured using both glycaemic control related indicators (eg, glycated haemoglobin, fasting blood glucose, postprandial glucose) and general indicators (eg, adherence, disease management and health-related quality of life). The meta-analysis will conduct pairwise meta-analysis using random effects models and network meta-analysis (NMA) employing the Bayesian hierarchical model. The visualisation and statistical analysis will be carried out using RevMan, R Studio and ADDIS. Additionally, we will evaluate the certainty of the evidence by using Grading of Recommendations Assessment, Development and Evaluation system.

There will be no primary data collection from NMA participants, and there is no requirement for formal ethical review. Our aim is to present the results of this NMA in a peer-reviewed scientific journal, at conferences, and in the mainstream media.

CRD42022355368.

The current comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP) are not entirely understood.

To evaluate comparative efficacy, safety, and acceptability of AAPs in patients with PDP.

We conducted a systematic review and a network meta-analysis to compare the efficacy, safety, and acceptability of pimavanserin, quetiapine, olanzapine, clozapine, ziprasidone, and risperidone. We estimated relative standardized mean differences (SMDs) for continuous outcomes and odds ratios (OR) for binary outcomes, with their respective 95% confidence intervals (CIs).

We included 19 unique studies evaluating AAPs in a total of 1,242 persons with PDP. Based on Clinical Global Impression Scale for Severity, pimavanserin (SMD, -4.81; 95% CI, -5.39, -4.24) and clozapine (SMD, -4.25; 95% CI, -5.24, -3.26) significantly improved symptoms compared with placebo. Also, compared to placebo, pimavanserin (OR, 1.16; 95% CI, 1.07, 1.24) significantly improved psychotic symptoms based on Scale for Assessment of Positive Symptoms for Parkinson's Disease Psychosis/Hallucinations and Delusions scores. In comparison to placebo, clozapine (SMD, -0.69; 95% CI, -1.35, -0.02), pimavanserin (SMD, -0.01; 95% CI, -0.56, 0.53), and quetiapine (SMD, 0.00; 95% CI, -0.68, 0.69) did not impair motor function per Unified Parkinson's Disease Rating scale. Based on Mini-Mental State Examination scale, quetiapine (SMD, 0.60; 95% CI, 0.07, 1.14) significantly impaired cognition compared to placebo.

In patients with PDP, pimavanserin and clozapine demonstrated significant improvement in psychosis without affecting motor function. With quetiapine being associated with a significant decline in cognition and despite not impairing motor function, our findings suggest that it should be avoided in patients with PDP and reduced cognitive abilities.

To evaluate and compare the efficacy of different mind-body therapies (MBTs) for sleep disturbance in patients with early-stage cancer.

Randomised controlled trials that included patients (aged ≥18 years) with early stage cancer who underwent MBTs (mindfulness, hypnosis, relaxation, yoga, and qigong) were searched in the CINAHL via the EBSCO Host, Cochrane Library, Embase, MEDLINE, PsycINFO, PubMed, and Scopus databases, from the date of database inception to October 2022. The outcomes were subjective sleep disturbance and objective sleep efficiency. Network meta-analysis (NMA) and comparative effects ranking were performed using STATA (v14.0; STATACorp, College Station, TX, USA).

Forty-seven studies investigating five MBTs were included in the NMA. For cancer patients receiving active treatment, mindfulness demonstrated the largest effect size in reducing subjective sleep disturbance (standardised mean difference [SMD]: 0.85; 95% confidence intervals [CI]: 0.20-1.50; Grading of Recommendations Assessment, Development, and Evaluation assessment: moderate), and had the highest cumulative probability compared to usual care or waitlist. For cancer patients who had completed active treatment, qigong demonstrated the largest effect size in reducing subjective sleep disturbance (SMD: 0.99; 95% CI: 0.35-1.63; GRADE: low), followed by hypnosis (SMD: 0.87; 95% CI: 0.32-1.42; GRADE: moderate), and mindfulness (SMD: 0.42; 95% CI: 0.24-0.59; GRADE: moderate). Qigong also demonstrated the largest effect size in improving objective sleep efficiency (weighted mean differences: 10.76; 95% CI: 2.01-19.50; GRADE: low); however, the effect of qigong was tested in only one study in this NMA. Among the eight different treatment conditions, cognitive behavioral therapy (CBT) showed the highest cumulative probability (surface under the cumulative ranking curve: 96.3%) in reducing subjective sleep disturbance and the second highest cumulative probability (SUCRA: 83.3%) in improving objective sleep efficiency.

There is no evidence supporting the use of MBTs to replace or be comparable to CBT. Mindfulness can be recommended as an optional treatment for reducing sleep disturbance in patients with early-stage cancer. Some support was observed for qigong and hypnosis in reducing sleep disturbances in patients with early-stage cancer who had completed active treatment. More rigorous trials are warranted to confirm whether different forms of MBTs have different effects on sleep in patients with cancer.

Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.

To compare the benefits and harms of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their benefits and harms.

For this update of the living systematic review, we updated our searches of the following databases monthly to October 2022: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase.

Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation).

We conducted duplicate study selection, data extraction, risk of bias assessment, and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety).

This update includes an additional 12 studies, taking the total number of included studies to 179, and randomised participants to 62,339, 67.1% men, mainly recruited from hospitals. Average age was 44.6 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (56%). We assessed a total of 20 treatments. Most (152) trials were multicentric (two to 231 centres). One-third of the studies (65/179) had high risk of bias, 24 unclear risk, and most (90) low risk. Most studies (138/179) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 49.16, 95% CI 20.49 to 117.95), bimekizumab (RR 27.86, 95% CI 23.56 to 32.94), ixekizumab (RR 27.35, 95% CI 23.15 to 32.29), risankizumab (RR 26.16, 95% CI 22.03 to 31.07). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab and ixekizumab were significantly more likely to reach PASI 90 than secukinumab. Bimekizumab, ixekizumab, and risankizumab were significantly more likely to reach PASI 90 than brodalumab and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab, and brodalumab), and anti-IL23 drugs except tildrakizumab were significantly more likely to reach PASI 90 than ustekinumab, three anti-TNF alpha agents, and deucravacitinib. Ustekinumab was superior to certolizumab. Adalimumab, tildrakizumab, and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with very low- to moderate-certainty evidence for all the comparisons. The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.

Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.6 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was very low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Our objective was to conduct a systematic review and meta-analysis of adverse effects on sleep in patients with schizophrenia receiving antipsychotic treatment.

A systematic search was performed in PubMed, Cochrane Central, Embase, Toxline, Ebsco, Virtual Health Library, Web of Science, SpringerLink, and in Database of abstracts of Reviews of Effects of Randomized Clinical Trials to identify eligible studies published from January 1990 to October 2021. The methodological quality of the studies was evaluated using the CONSORT list, and the Cochrane bias tool. Network meta-analysis was performed using the Bayesian random-effects model, with multivariate meta-regression to assess the association of interest.

87 randomized clinical trials were identified that met the inclusion criteria, and 70 articles were included in the network meta-analysis. Regarding the methodological quality of the studies, 47 had a low or moderate bias risk. The most common adverse effects on sleep reported in the studies were insomnia, somnolence, and sedation. The results of the network meta-analysis showed that ziprasidone was associated with an increased risk of insomnia (OR, 1.56; 95% credible interval CrI, 1.18-2.06). Several of the included antipsychotics were associated with a significantly increased risk of somnolence; haloperidol (OR, 1.90; 95% CrI, 1.12-3.22), lurasidone (OR, 2.25; 95% CrI, 1.28-3.97) and ziprasidone (OR, 1.79; 95% CrI, 1.06-3.02) had the narrowest confidence intervals. In addition, perphenazine (OR, 5.33; 95% CrI, 1.92-14.83), haloperidol (OR, 2.61; 95% CrI, 1.14-5.99), and risperidone (OR, 2.41; 95% CrI, 1.21-4.80) were associated with an increased risk of sedation compared with placebo, and other antipsychotics did not differ. According to the SUCRAs for insomnia, chlorpromazine was ranked as the lowest risk of insomnia (57%), followed by clozapine (20%), while flupentixol (26 %) and perospirone (22.5%) were associated with a lower risk of somnolence. On the other hand, amisulpride (89.9%) was the safest option to reduce the risk of sedation.

Insomnia, sedation, and somnolence were the most frequent adverse effects on sleep among the different antipsychotics administered. The evidence shows that chlorpromazine, clozapine, flupentixol, perospirone, and amisulpride had favorable safety profiles. In contrast, ziprasidone, perphenazine, haloperidol, and risperidone were the least safe for sleep.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017078052, identifier: PROSPERO 2017 CRD42017078052.

Network meta-analysis (NMA) is becoming a popular statistical tool for analyzing a network of evidence comparing more than two interventions. A particular advantage of NMA over pairwise meta-analysis is its ability to simultaneously compare multiple interventions including comparisons not previously trialed together, permitting intervention hierarchies to be created. Our aim was to develop a novel graphical display to aid interpretation of NMA to clinicians and decision-makers that incorporates ranking of interventions.

Current literature was searched, scrutinized, and provided direction for developing the novel graphical display. Ranking results were often found to be misinterpreted when presented alone and, to aid interpretation and effective communication to inform optimal decision-making, need to be displayed alongside other important aspects of the analysis including the evidence networks and relative intervention effect estimates.

Two new ranking visualizations were developed-the 'Litmus Rank-O-Gram' and the 'Radial SUCRA' plot-and embedded within a novel multipanel graphical display programmed within the MetaInsight application, with user feedback gained.

This display was designed to improve the reporting, and facilitate a holistic understanding, of NMA results. We believe uptake of the display would lead to better understanding of complex results and improve future decision-making.

The objective of the study was to examine differences in nutrient intake between consumers and non-consumers of red meat and to assess nutritional adequacy of consumers relative to Recommended Daily Allowance (RDA) in Canada. Matching estimators were used to identify differences in nutrient intake between the two groups. Statistically significant differences were observed in nutrient intake between red meat consumers and non-consumers, including lower daily intake of protein, riboflavin, niacin, vitamin D, and zinc and a higher daily intake of dietary fiber, folate, and magnesium among Canadians who did not consume red meat. Further, red meat consumers and non-consumers had nutrient intakes below RDA for dietary energy, fiber, and calcium. While individuals who did not consume red meat were at increased risk of calcium, vitamin D, energy, and potassium inadequacy, those who consumed red meat were at increased risk of dietary fiber, vitamin A, and magnesium inadequacy.

Indirect comparisons (including network meta-analyses [NMAs]) allow us to compare benefits and risks of multiple interventions for the same clinical condition when head-to-head comparisons are not feasible.

To provide guidance to the clinical community on better understanding indirect comparison methods to help them to interpret their results by applying two quality standards to published indirect comparisons of systemic biologics for moderate to severe psoriasis.

A systematic literature review (SLR) of published indirect comparisons of biologics for the treatment of moderate to severe psoriasis in adults was conducted. Data extraction was performed using a predefined subset of NICE TSD7 (National Institute for Health and Care Excellence Technical Support Document 7) checklist questions and methods used to perform each analysis were descriptively compared. Methodological quality of the SLR underlying each indirect comparison was assessed using AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews version 2).

Twenty-two NMAs and four adjusted indirect comparisons (AICs) were identified. Although there were some similarities, for example, application of Bayesian random-effects models, several important methodological aspects varied considerably across NMAs identified, for example, classes of drugs, number of treatments and studies included, reporting and handling of different doses, and reporting of both checks for and investigations of inconsistency. Methodological comparisons across AICs were limited by the small number. The quality of most underlying SLRs described, assessed as overall level of confidence in the results, was 'critically low'.

Understanding that there are different methodologies employed to answer differing research questions is key to helping clinicians to interpret the indirect evidence currently available in psoriasis.

It can be challenging for dermatologists to keep abreast of the growing evidence from published indirect comparisons (ICs) of treatments for psoriasis. The objective of this analysis was to summarise comparative clinical efficacy and safety findings from ICs of systemic biologics for the treatment of moderate-to-severe psoriasis and to identify factors potentially affecting efficacy outcomes and their possible implications for clinical decision making.

An umbrella review of short- and long-term efficacy and safety findings from 26 ICs visually compared 90% improvement in Psoriasis Area Severity Index (PASI90) treatment rankings and three safety outcome rankings side by side. Pearson's correlation coefficients measured the strength of the association between each pair of ICs on the basis of identified factors that could potentially affect efficacy findings.

Some consistency in short-term PASI90 efficacy rankings was observed for certain drugs, although rankings for most drugs varied by IC. Factors potentially affecting efficacy outcomes included the use of different methodologies for head-to-head comparison and statistical analyses, and variation in drugs and classes included treatment dosing and duration, outcome definitions and effect measures reported between ICs. Considerable variation in these factors was found across all 26 ICs. Comparative safety information of value to physicians was limited.

Substantial differences were identified between ICs in factors that could potentially affect efficacy outcomes. Treatment rankings must be interpreted alongside actual differences in IC outcomes to allow conclusions on clinical relevance. Drugs within a class cannot be considered of equal efficacy: therapies should be considered individually rather than by class.

Network meta-analysis (NMA) is a central tool for evidence synthesis in clinical research. The results of an NMA depend critically on the quality of evidence being pooled. In assessing the validity of an NMA, it is therefore important to know the proportion contributions of each direct treatment comparison to each network treatment effect. The construction of proportion contributions is based on the observation that each row of the hat matrix represents a so-called "evidence flow network" for each treatment comparison. However, the existing algorithm used to calculate these values is associated with ambiguity according to the selection of paths. In this article, we present a novel analogy between NMA and random walks. We use this analogy to derive closed-form expressions for the proportion contributions. A random walk on a graph is a stochastic process that describes a succession of random "hops" between vertices which are connected by an edge. The weight of an edge relates to the probability that the walker moves along that edge. We use the graph representation of NMA to construct the transition matrix for a random walk on the network of evidence. We show that the net number of times a walker crosses each edge of the network is related to the evidence flow network. By then defining a random walk on the directed evidence flow network, we derive analytically the matrix of proportion contributions. The random-walk approach has none of the associated ambiguity of the existing algorithm.

Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.

To compare the efficacy and safety of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their efficacy and safety.

For this update of the living systematic review, we updated our searches of the following databases monthly to October 2021: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase.

Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation).

We conducted duplicate study selection, data extraction, risk of bias assessment and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety).

This update includes an additional 19 studies, taking the total number of included studies to 167, and randomised participants to 58,912, 67.2% men, mainly recruited from hospitals. Average age was 44.5 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (57%). We assessed a total of 20 treatments. Most (140) trials were multicentric (two to 231 centres). One-third of the studies (57/167) had high risk of bias; 23 unclear risk, and most (87) low risk. Most studies (127/167) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions, except anti-IL23. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23 and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 50.19, 95% CI 20.92 to 120.45), bimekizumab (RR 30.27, 95% CI 25.45 to 36.01), ixekizumab (RR 30.19, 95% CI 25.38 to 35.93), risankizumab (RR 28.75, 95% CI 24.03 to 34.39). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab, ixekizumab and risankizumab showed a higher proportion of patients reaching PASI 90 than other anti-IL17 drugs (secukinumab and brodalumab) and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab and brodalumab) and anti-IL23 drugs (risankizumab and guselkumab) except tildrakizumab showed a higher proportion of patients reaching PASI 90 than ustekinumab and three anti-TNF alpha agents (adalimumab, certolizumab and etanercept). Ustekinumab was superior to certolizumab; adalimumab and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with low- to moderate-certainty for all the comparisons (except methotrexate versus placebo, which was high-certainty). The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.

Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.5 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies and postmarketing reports from regulatory agencies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Dementia-related psychosis (DRP) is characterized by hallucinations and delusions, which may increase the debilitating effects of underlying dementia. This network meta-analysis (NMA) evaluated the comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) commonly used off label to treat DRP.

We included 22 eligible studies from a systematic literature review of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) used off label to treat DRP. Study outcomes were: (1) efficacy-neuropsychiatric inventory-nursing home (NPI-NH psychosis subscale), (2) safety-mortality, cerebrovascular events (CVAEs), and others (somnolence, falls, fractures, injuries, etc.), and (3) acceptability-discontinuations due to all causes, lack of efficacy, and adverse events (AEs). We used random-effects modeling to estimate pooled standardized mean differences (SMDs) for NPI-NH psychosis subscale scores and odds ratios (OR) for other dichotomous outcomes, with their respective 95% confidence intervals (CIs).

Compared with placebo, aripiprazole (SMD - 0.12; 95% CI - 0.31, 0.06), and olanzapine (SMD - 0.17; 95% CI - 0.04; 0.02) demonstrated small, non-significant numerical improvements in NPI-NH psychosis scores (5 studies; n = 1891), while quetiapine (SMD 0.04; 95% CI - 0.23, 0.32) did not improve symptoms. The odds of mortality (15 studies, n = 4989) were higher for aripiprazole (OR 1.58; 95% CI 0.62, 4.04), brexpiprazole (OR 2.22; 95% CI 0.30, 16.56), olanzapine (OR 2.21; 95% CI 0.84, 5.85), quetiapine (OR 1.68; 95% CI 0.70, 4.03), and risperidone (OR 1.63; 95% CI 0.93, 2.85) than for placebo. Risperidone (OR 3.68; 95% CI 1.68, 8.95) and olanzapine (OR 4.47; 95% CI 1.36, 14.69) demonstrated significantly greater odds of CVAEs compared to placebo. Compared with placebo, odds of all-cause discontinuation were significantly lower for aripiprazole (OR 0.71; 95% CI 0.51, 0.98; 20 studies; 5744 patients) and higher for other AAPs. Aripiprazole (OR 0.5; 95% CI 0.31, 0.82) and olanzapine (OR 0.48; 95% CI 0.31, 0.74) had significantly lower odds of discontinuation due to lack of efficacy (OR 12 studies; n = 4382) compared to placebo, while results for quetiapine and risperidone were not significant. Compared with placebo, the odds of discontinuation due to AEs (19 studies, n = 5445) were higher for olanzapine (OR 2.62; 95% CI 1.75, 3.92), brexpiprazole (OR 1.80; 95% CI 0.80, 4.07), quetiapine (OR 1.25; 95% CI 0.82, 1.91), aripiprazole (OR 1.38; 95% CI 0.90, 2.13), and risperidone (OR 1.41; 95% CI 1.02, 1.94).

Overall results demonstrate that, compared with placebo, quetiapine is not associated with improvement in psychosis in patients with dementia, while olanzapine and aripiprazole have non-significant small numerical improvements. These off-label AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) are associated with greater odds of mortality, CVAEs, and discontinuations due to AEs than placebo. These results underscore the ongoing unmet need for newer pharmacological options with a more favorable benefit-risk profile for the treatment of DRP.

Comparative effectiveness research using network meta-analysis can present a hierarchy of competing treatments, from the most to the least preferable option. However, in published reviews, the research question associated with the hierarchy of multiple interventions is typically not clearly defined. Here we introduce the novel notion of a treatment hierarchy question that describes the criterion for choosing a specific treatment over one or more competing alternatives. For example, stakeholders might ask which treatment is most likely to improve mean survival by at least 2 years, or which treatment is associated with the longest mean survival. We discuss the most commonly used ranking metrics (quantities that compare the estimated treatment-specific effects), how the ranking metrics produce a treatment hierarchy, and the type of treatment hierarchy question that each ranking metric can answer. We show that the ranking metrics encompass the uncertainty in the estimation of the treatment effects in different ways, which results in different treatment hierarchies. When using network meta-analyses that aim to rank treatments, investigators should state the treatment hierarchy question they aim to address and employ the appropriate ranking metric to answer it. Following this new proposal will avoid some controversies that have arisen in comparative effectiveness research.

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.

Evidence for perioperative methods to prevent persistent postsurgical pain (PPP) is uncertain, in part because few treatments have been directly compared. Here we have used component network meta-analysis (cNMA) to incorporate both direct and indirect evidence in the evaluation of the efficacy and tolerability of pharmacological and neural block treatments.

We searched the Cochrane Central Registry of Controlled Trials, Embase, MEDLINE, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry up to January 2021, for randomized, double-masked, controlled trials that reported the prevalence of PPP. We assessed trial quality with the Cochrane risk of bias tool (RoB 2.0). We analyzed the results with frequentist cNMA models. The primary outcome was the relative risk (RR) of PPP. We assessed efficacy in relation to a clinically important effect size of RR = 0.9, which is a 10% improvement with treatment.

The analysis included 107 trials (13,553 participants) of 13 treatments. The effects of complex interventions were the multiplicative effects of their components. Compared with placebo, serotonin-norepinephrine reuptake inhibitors (SNRIs), neural block alone, or in combination with NMDA receptor blockers or gabapentanoids were effective. Treatments with benefit in the immediate post-operative period predicted a reduced risk of PPP.

Several treatments and treatment combinations effectively reduce PPP prevalence. Pain outcomes in the immediate postoperative period are an important mediator of PPP. Multimodal interventions can be analyzed using cNMA.

The comparative safety and efficacy between anti-vascular endothelial growth factor agents (anti-VEGFs) and between combined therapies for patients with neovascular age-related macular degeneration (nAMD) is unclear. We conducted a systematic review to examine the comparative safety and efficacy anti-VEGFs for adults with nAMD.

Studies were identified through MEDLINE, EMBASE, and Cochrane CENTRAL (inception to June 3, 2019), grey literature, and scanning reference lists. Two reviewers independently screened citations and full-text articles to identify randomized controlled trials (RCTs), extracted data, and appraised risk of bias. Pairwise random-effects meta-analysis and Bayesian network meta-analysis (NMA) were conducted. The primary outcomes were the proportion of patients experiencing moderate vision gain (≥ 15 letters on the Early Treatment Diabetic Retinopathy Study chart) and the proportion of patients experiencing moderate vision loss (≤ 15 letters).

After screening 3647 citations and 485 potentially relevant full-text articles, 92 RCTs with 24,717 patients were included. NMA (34 RCTs, 8809 patients, 12 treatments) showed small differences among anti-VEGFs in improving the proportion of patients with moderate vision gain, with the largest for conbercept versus broluczumab (OR 0.15, 95% CrI: 0.05-0.56), conbercept versus ranibizumab (OR 0.17, 95% CrI: 0.05-0.59), conbercept versus aflibercept (OR 0.19, 95% CrI: 0.06-0.65), and conbercept versus bevacizumab (OR 0.2, 95% CrI: 0.06-0.69). In NMA (36 RCTs, 9081 patients, 13 treatments) for the proportion of patients with moderate vision loss, small differences were observed among anti-VEGFs, with the largest being for conbercept versus aflibercept (OR 0.24, 95% CrI: 0-4.29), conbercept versus brolucizumab (OR 0.24, 95% CrI: 0-4.71), conbercept versus bevacizumab (OR 0.26, 95% CrI: 0-4.65), and conbercept versus ranibizumab (OR 0.27, 95% CrI: 0-4.67).

The only observed differences were that ranibizumab, bevacizumab, aflibercept, and brolucizumab were statistically superior to conbercept in terms of the proportion of patients with nAMD who experienced moderate vision gain. However, this finding is based on indirect evidence through one small trial comparing conbercept with placebo. This does not account for drug-specific differences when assessing anatomic and functional treatment efficacy in variable dosing regimens.

PROSPERO registration number CRD42015022041.

Network meta-analysis (NMA) is a widely used tool to compare multiple treatments by synthesizing different sources of evidence. Measures such as the surface under the cumulative ranking curve (SUCRA) and the P-score are increasingly used to quantify treatment ranking. They provide summary scores of treatments among the existing studies in an NMA. Clinicians are frequently interested in applying such evidence from the NMA to decision-making in the future. This prediction process needs to account for the heterogeneity between the existing studies in the NMA and a future study.

This article introduces the predictive P-score for informing treatment ranking in a future study via Bayesian models. Two NMAs were used to illustrate the proposed measure; the first assessed 4 treatment strategies for smoking cessation, and the second assessed treatments for all-grade treatment-related adverse events. For all treatments in both NMAs, we obtained their conventional frequentist P-scores, Bayesian P-scores, and predictive P-scores.

In the two examples, the Bayesian P-scores were nearly identical to the corresponding frequentist P-scores for most treatments, while noticeable differences existed for some treatments, likely owing to the different assumptions made by the frequentist and Bayesian NMA models. Compared with the P-scores, the predictive P-scores generally had a trend to converge toward a common value of 0.5 due to the heterogeneity. The predictive P-scores' numerical estimates and the associated plots of posterior distributions provided an intuitive way for clinicians to appraise treatments for new patients in a future study.

The proposed approach adapts the existing frequentist P-score to the Bayesian framework. The predictive P-score can help inform medical decision-making in future studies.

In the past years, network meta-analysis (NMA) has been widely used among clinicians, guideline makers, and health technology assessment agencies and has played an important role in clinical decision-making and guideline development. To inform further development of NMAs, we conducted a bibliometric analysis to assess the current status of published NMA methodological studies, summarized the methodological progress of seven types of NMAs, and discussed the current challenges of NMAs.

Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer-related deaths. Metastatic bone disease occurs in 20% to 40% of patients with lung cancer, and these patients often present with pain or skeletal-related events (SREs) that are associated with decreased survival. Bone-modifying agents such as denosumab or bisphosphonates are routinely used; however, to our knowledge, there has been no quantitative synthesis of randomized controlled trial data to determine the most effective pharmacologic treatment of metastatic bone disease because of lung cancer.

We aimed to perform a network meta-analysis of randomized trials to identify the bone-modifying agent that is associated with the (1) highest overall survival, (2) longest time to SRE, (3) lowest SRE incidence, and (4) greatest likelihood of pain resolution.

We conducted our study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and pre-registered the analysis on PROSPERO (ID: CRD42019124364). We performed a librarian-assisted search of MEDLINE, PubMed, EMBASE, Cochrane Library, and Chinese databases including China National Knowledge Infrastructure and Wanfang Data. We included randomized controlled trials reporting outcomes specifically for patients with lung cancer treated with a bisphosphonate or denosumab. SREs included pathologic fractures, spinal cord compression, hypercalcemia of malignancy, or pain resulting in surgical intervention or radiation therapy. We excluded trials exclusively reporting surrogate outcomes such as changes in bone turnover markers. Screening, data extraction, risk of bias evaluation, and Grading of Recommendations Assessment, Development, and Evaluation evaluations were performed in duplicate. We included 131 randomized controlled trials that evaluated 11,105 patients with skeletal metastases from lung cancer. The network meta-analysis was performed using a frequentist model and the R statistical software. Results are reported as relative risks or mean differences, and the I2 value is reported for heterogeneity. The P-score, a measure of ranking certainty that accounts for standard error, is reported for each outcome. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for the incidence of SRE, and low for pain resolution.

For overall survival, denosumab was ranked above zoledronic acid and estimated to confer a mean of 3.3 months (95% CI 0.3-6.3) of increased overall survival compared with untreated patients (P-score = 89%). For the time to SRE, denosumab was ranked first with a mean of 9.1 additional SRE-free months (95% CI 6.7-11.5) compared with untreated patients (P-score = 99%), while zoledronic acid conferred an additional 4.8 SRE-free months (95% CI 3.6-6.1). Reduction in the incidence of SREs was not different between patients treated with denosumab (relative risk 0.54; 95% CI 0.33-0.87) and those treated with zoledronic acid (relative risk 0.56; 95% CI 0.46-0.67). Patients treated with the combination of ibandronate and systemic therapy were more likely to experience successful pain resolution than untreated patients (relative risk 2.4; 95% CI 1.8-3.2).

In this comprehensive synthesis of all available randomized controlled trial evidence guiding the pharmacologic treatment of bone metastases from lung cancer, denosumab was ranked above zoledronic acid for overall survival and time to SRE and was not different for reducing the incidence of SRE. Both were superior to no treatment for each of these outcomes. Given this, we encourage physicians to consider the use of denosumab or zoledronic acid in treating this patient population. The combination of ibandronate and systemic therapy was the most effective at reducing pain because of metastases. No cost-effectiveness analysis has yet been performed for denosumab and zoledronic acid on patients with metastatic lung cancer, and this represents an avenue for future research.

Level I, therapeutic study.

Ranking of treatments offers a straightforward interpretation of results derived from network meta-analysis. However, some published network meta-analyses have overemphasized treatment ranking without paying attention to its uncertainty. According to a review of 91 network meta-analyses, 52 reported treatment ranking, but 43 of them did not report the uncertainty of ranking. Without reporting the uncertainty, small differences in the ranking of treatments may be overinterpreted. Rankograms, cumulative rankograms, the credible/confidence interval of mean rank, the surface under the cumulative ranking curve (SUCRA), and the interquartile range of median rank have been used to show the uncertainty of rankings. However, it is not always straightforward to compare the differences in the distribution of probabilities by inspecting rankograms or to compare the intervals or ranges of treatment ranks. We therefore proposed normalized entropy, which transforms the distribution of ranking probabilities into a single quantitative measure, to facilitate a refined interpretation of uncertainty of treatment ranking. We used 4 real examples to demonstrate the uncertainty of ranking quantified by ranking probabilities, 95% confidence interval of SUCRA, and normalized entropy. We showed that as normalized entropy ranges from 0 to 1 and is independent of the number of treatments, it can be used to compare the uncertainty of treatment ranking within a network meta-analysis (NMA) and between different NMAs. Normalized entropy is an alternative tool for measuring the uncertainty of treatment ranking by improving the translation of results from NMAs to clinical practice and avoiding naïve interpretation of treatment ranking. We therefore recommend normalized entropy to be included in the presentation and interpretation of results from NMAs.

A variety of minimally invasive treatments are available as an alternative to transurethral resection of the prostate (TURP) for management of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). However, it is unclear which treatments provide better results.

Our primary objective was to assess the comparative effectiveness of minimally invasive treatments for lower urinary tract symptoms in men with BPH through a network meta-analysis. Our secondary objective was to obtain an estimate of relative ranking of these minimally invasive treatments, according to their effects.

We performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase, Scopus, Web of Science and LILACS), trials registries, other sources of grey literature, and conference proceedings, up to 24 February 2021. We had no restrictions on language of publication or publication status.

We included parallel-group randomized controlled trials assessing the effects of the following minimally invasive treatments, compared to TURP or sham treatment, on men with moderate to severe LUTS due to BPH: convective radiofrequency water vapor therapy (CRFWVT); prostatic arterial embolization (PAE); prostatic urethral lift (PUL); temporary implantable nitinol device (TIND); and transurethral microwave thermotherapy (TUMT).

Two review authors independently screened the literature, extracted data, and assessed risk of bias. We performed statistical analyses using a random-effects model for pair-wise comparisons and a frequentist network meta-analysis for combined estimates. We interpreted them according to Cochrane methods. We planned subgroup analyses by age, prostate volume, and severity of baseline symptoms. We used risk ratios (RRs) with 95% confidence intervals (CIs) to express dichotomous data and mean differences (MDs) with 95% CIs to express continuous data. We used the GRADE approach to rate the certainty of evidence.

We included 27 trials involving 3017 men, mostly over age 50, with severe LUTS due to BPH. The overall certainty of evidence was low to very low due to concerns regarding bias, imprecision, inconsistency (heterogeneity), and incoherence. Based on the network meta-analysis, results for our main outcomes were as follows. Urologic symptoms (19 studies, 1847 participants): PUL and PAE may result in little to no difference in urologic symptoms scores (MD of International Prostate Symptoms Score [IPSS]) compared to TURP (3 to 12 months; MD range 0 to 35; higher scores indicate worse symptoms; PUL: 1.47, 95% CI -4.00 to 6.93; PAE: 1.55, 95% CI -1.23 to 4.33; low-certainty evidence). CRFWVT, TUMT, and TIND may result in worse urologic symptoms scores compared to TURP at short-term follow-up, but the CIs include little to no difference (CRFWVT: 3.6, 95% CI -4.25 to 11.46; TUMT: 3.98, 95% CI 0.85 to 7.10; TIND: 7.5, 95% CI -0.68 to 15.69; low-certainty evidence). Quality of life (QoL) (13 studies, 1459 participants): All interventions may result in little to no difference in the QoL scores, compared to TURP (3 to 12 months; MD of IPSS-QoL score; MD range 0 to 6; higher scores indicate worse symptoms; PUL: 0.06, 95% CI -1.17 to 1.30; PAE: 0.09, 95% CI -0.57 to 0.75; CRFWVT: 0.37, 95% CI -1.45 to 2.20; TUMT: 0.65, 95% CI -0.48 to 1.78; TIND: 0.87, 95% CI -1.04 to 2.79; low-certainty evidence). Major adverse events (15 studies, 1573 participants): TUMT probably results in a large reduction of major adverse events compared to TURP (RR 0.20, 95% CI 0.09 to 0.43; moderate-certainty evidence). PUL, CRFWVT, TIND and PAE may also result in a large reduction in major adverse events, but CIs include substantial benefits and harms at three months to 36 months; PUL: RR 0.30, 95% CI 0.04 to 2.22; CRFWVT: RR 0.37, 95% CI 0.01 to 18.62; TIND: RR 0.52, 95% CI 0.01 to 24.46; PAE: RR 0.65, 95% CI 0.25 to 1.68; low-certainty evidence). Retreatment (10 studies, 799 participants): We are uncertain about the effects of PAE and PUL on retreatment compared to TURP (12 to 60 months; PUL: RR 2.39, 95% CI 0.51 to 11.1; PAE: RR 4.39, 95% CI 1.25 to 15.44; very low-certainty evidence). TUMT may result in higher retreatment rates (RR 9.71, 95% CI 2.35 to 40.13; low-certainty evidence). Erectile function (six studies, 640 participants): We are very uncertain of the effects of minimally invasive treatments on erectile function (MD of International Index of Erectile Function [IIEF-5]; range 5 to 25; higher scores indicates better function; CRFWVT: 6.49, 95% CI -8.13 to 21.12; TIND: 5.19, 95% CI -9.36 to 19.74; PUL: 3.00, 95% CI -5.45 to 11.44; PAE: -0.03, 95% CI -6.38, 6.32; very low-certainty evidence). Ejaculatory dysfunction (eight studies, 461 participants): We are uncertain of the effects of PUL, PAE and TUMT on ejaculatory dysfunction compared to TURP (3 to 12 months; PUL: RR 0.05, 95 % CI 0.00 to 1.06; PAE: RR 0.35, 95% CI 0.13 to 0.92; TUMT: RR 0.34, 95% CI 0.17 to 0.68; low-certainty evidence). TURP is the reference treatment with the highest likelihood of being the most efficacious for urinary symptoms, QoL and retreatment, but the least favorable in terms of major adverse events, erectile function and ejaculatory function. Among minimally invasive procedures, PUL and PAE have the highest likelihood of being the most efficacious for urinary symptoms and QoL, TUMT for major adverse events, PUL for retreatment, CRFWVT and TIND for erectile function and PUL for ejaculatory function.

Minimally invasive treatments may result in similar or worse effects concerning urinary symptoms and QoL compared to TURP at short-term follow-up. They may result in fewer major adverse events, especially in the case of PUL and PAE; resulting in better rankings for symptoms scores. PUL may result in fewer retreatments compared to other interventions, especially TUMT, which had the highest retreatment rates at long-term follow-up. We are very uncertain about the effects of these interventions on erectile function. There was limited long-term data, especially for CRFWVT and TIND. Future high-quality studies with more extended follow-up, comparing different, active treatment modalities, and adequately reporting critical outcomes relevant to patients, including those related to sexual function, could provide more information on the relative effectiveness of these interventions.

We determined the relative efficacy of non-surgical monotherapies for hidradenitis suppurativa (HS).

Network meta-analyses were conducted to determine treatments' surface under the cumulative ranking curve (SUCRA) value (i.e., an estimate that ranks efficacy); pairwise comparisons were conducted.

Ten trials were eligible for quantitative analyses; however, all did not have a common endpoint. Outcomes corresponded to pain severity, clinical response, quality of life and abscess count. For pain reduction, infliximab was ranked most efficacious (SUCRA =94%) compared to bermekimab, anakinra and placebo; infliximab reduced pain more significantly (p < 0.05) than anakinra and than placebo. For occurrence of clinical response, bimekizumab had the highest SUCRA (67%) relative to adalimumab, anakinra and placebo; bimekizumab was more efficacious than placebo (p < 0.05). For quality of life in mild HS, Botox had the highest SUCRA (94%) compared to adalimumab and placebo; Botox was more efficacious than placebo (p < 0.05). For reduction in abscess count, oral tetracycline had the highest SUCRA (48%) compared to topical clindamycin and vehicle. Our work-being the first NMA study on non-surgical HS monotherapies-contributes to the comparative effectiveness literature for this condition.

Background No network meta-analysis has considered the relative efficacy of cilostazol, home exercise therapy, supervised exercise therapy (SET), endovascular revascularization (ER), and ER plus SET (ER+SET) in improving maximum walking distance (MWD) over short- (<1 year), moderate- (1 to <2 years), and long-term (≥2 years) follow-up in people with intermittent claudication. Methods and Results A systematic literature search was performed to identify randomized controlled trials testing 1 or more of these 5 treatments according to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The primary outcome was improvement in MWD assessed by a standardized treadmill test. Secondary outcomes were adverse events and health-related quality of life. Network meta-analysis was performed using the gemtc R statistical package. The Cochrane collaborative tool was used to assess risk of bias. Forty-six trials involving 4256 patients were included. At short-term follow-up, home exercise therapy (mean difference [MD], 89.4 m; 95% credible interval [CrI], 20.9-157.7), SET (MD, 186.8 m; 95% CrI, 136.4-237.6), and ER+SET (MD, 326.3 m; 95% CrI, 222.6-430.6), but not ER (MD, 82.5 m; 95% CrI, -2.4 to 168.2) and cilostazol (MD, 71.1 m; 95% CrI, -24.6 to 167.9), significantly improved MWD (in meters) compared with controls. At moderate-term follow-up, SET (MD, 201.1; 95% CrI, 89.8-318.3) and ER+SET (MD, 368.5; 95% CrI, 195.3-546.9), but not home exercise therapy (MD, 99.4; 95% CrI, -174.0 to 374.9) or ER (MD, 84.2; 95% CrI, -35.3 to 206.4), significantly improved MWD (in meters) compared to controls. At long-term follow-up, none of the tested treatments significantly improved MWD compared to controls. Adverse events and quality of life were reported inconsistently and could not be meta-analyzed. Risk of bias was low, moderate, and high in 4, 24, and 18 trials respectively. Conclusions This network meta-analysis suggested that SET and ER+SET are effective at improving MWD over the moderate term (<2 year) but not beyond this. Durable treatments for intermittent claudication are needed.

Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.

To compare the efficacy and safety of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their efficacy and safety.

For this living systematic review we updated our searches of the following databases monthly to September 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched two trials registers to the same date. We checked the reference lists of included studies and relevant systematic reviews for further references to eligible RCTs.

Randomised controlled trials (RCTs) of systemic treatments in adults (over 18 years of age) with moderate-to-severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate-to-severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. The primary outcomes of this review were: the proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90 at induction phase (from 8 to 24 weeks after the randomisation), and the proportion of participants with serious adverse events (SAEs) at induction phase. We did not evaluate differences in specific adverse events.

Several groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the PASI 90 score) and acceptability (the inverse of serious adverse events). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes and all comparisons, according to CINeMA, as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer on treatment hierarchy: 0% (treatment is the worst for effectiveness or safety) to 100% (treatment is the best for effectiveness or safety).

We included 158 studies (18 new studies for the update) in our review (57,831 randomised participants, 67.2% men, mainly recruited from hospitals). The overall average age was 45 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo-controlled (58%), 30% were head-to-head studies, and 11% were multi-armed studies with both an active comparator and a placebo. We have assessed a total of 20 treatments. In all, 133 trials were multicentric (two to 231 centres). All but two of the outcomes included in this review were limited to the induction phase (assessment from 8 to 24 weeks after randomisation). We assessed many studies (53/158) as being at high risk of bias; 25 were at an unclear risk, and 80 at low risk. Most studies (123/158) declared funding by a pharmaceutical company, and 22 studies did not report their source of funding. Network meta-analysis at class level showed that all of the interventions (non-biological systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in reaching PASI 90. At class level, in reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the non-biological systemic agents. At drug level, infliximab, ixekizumab, secukinumab, brodalumab, risankizumab and guselkumab were significantly more effective in reaching PASI 90 than ustekinumab and three anti-TNF alpha agents: adalimumab, certolizumab, and etanercept. Ustekinumab and adalimumab were significantly more effective in reaching PASI 90 than etanercept; ustekinumab was more effective than certolizumab, and the clinical effectiveness of ustekinumab and adalimumab was similar. There was no significant difference between tofacitinib or apremilast and three non-biological drugs: fumaric acid esters (FAEs), ciclosporin and methotrexate. Network meta-analysis also showed that infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab, and brodalumab outperformed other drugs when compared to placebo in reaching PASI 90. The clinical effectiveness of these drugs was similar, except for ixekizumab which had a better chance of reaching PASI 90 compared with secukinumab, guselkumab and brodalumab. The clinical effectiveness of these seven drugs was: infliximab (versus placebo): risk ratio (RR) 50.29, 95% confidence interval (CI) 20.96 to 120.67, SUCRA = 93.6; high-certainty evidence; ixekizumab (versus placebo): RR 32.48, 95% CI 27.13 to 38.87; SUCRA = 90.5; high-certainty evidence; risankizumab (versus placebo): RR 28.76, 95% CI 23.96 to 34.54; SUCRA = 84.6; high-certainty evidence; bimekizumab (versus placebo): RR 58.64, 95% CI 3.72 to 923.86; SUCRA = 81.4; high-certainty evidence; secukinumab (versus placebo): RR 25.79, 95% CI 21.61 to 30.78; SUCRA = 76.2; high-certainty evidence; guselkumab (versus placebo): RR 25.52, 95% CI 21.25 to 30.64; SUCRA = 75; high-certainty evidence; and brodalumab (versus placebo): RR 23.55, 95% CI 19.48 to 28.48; SUCRA = 68.4; moderate-certainty evidence. Conservative interpretation is warranted for the results for bimekizumab (as well as mirikizumab, tyrosine kinase 2 inhibitor, acitretin, ciclosporin, fumaric acid esters, and methotrexate), as these drugs, in the NMA, have been evaluated in few trials. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. Nevertheless, the SAE analyses were based on a very low number of events with low to moderate certainty for all the comparisons. Thus, the results have to be viewed with caution and we cannot be sure of the ranking. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1) the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.

Our review shows that compared to placebo, the biologics infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab and brodalumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of moderate- to high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes were measured from 8 to 24 weeks after randomisation) and is not sufficient for evaluation of longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean age of 45 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice. Another major concern is that short-term trials provide scanty and sometimes poorly-reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the evidence for all the interventions was of low to moderate quality. In order to provide long-term information on the safety of the treatments included in this review, it will also be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies. In terms of future research, randomised trials directly comparing active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between non-biological systemic agents and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve participants, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Network meta-analysis (NMA) produces complex outputs as many comparisons between interventions are of interest. The estimated relative treatment effects are usually displayed in a forest plot or in a league table and several ranking metrics are calculated and presented.

In this article, we estimate relative treatment effects of each competing treatment against a fictional treatment of average performance using the "deviation from the means" coding that has been used to parametrize categorical covariates in regression models. We then use this alternative parametrization of the NMA model to present a ranking metric (PreTA: Preferable Than Average) interpreted as the probability that a treatment is better than a fictional treatment of average performance.

We illustrate the alternative parametrization of the NMA model using two networks of interventions, a network of 18 antidepressants for acute depression and a network of four interventions for heavy menstrual bleeding. We also use these two networks to highlight differences among PreTA and existing ranking metrics. We further examine the agreement between PreTA and existing ranking metrics in 232 networks of interventions and conclude that their agreement depends on the precision with which relative effects are estimated.

A forest plot with NMA relative treatment effects using "deviation from means" coding could complement presentation of NMA results in large networks and in absence of an obvious reference treatment. PreTA is a viable alternative to existing probabilistic ranking metrics that naturally incorporates uncertainty.

More than one-half of pregnant women experience pregnancy-related low back pain (LBP). Pregnancy-related LBP greatly affects activities of daily life, and although many interventions have been proposed, the optimal treatment for pregnancy-related LBP remains unclear. The purpose of this study was to compare conservative care strategies on their efficacy and safety for women with pregnancy-related LBP through systematic review with pairwise meta-analysis and network meta-analysis.

MEDLINE, Embase, the Cochrane Library, AMED, CINAHL, PEDro, PsycINFO, and ClinicalTrials.gov were searched from inception to November 2019. Randomized controlled trials and observational controlled studies were included without restriction to language, sample size, or duration of follow-up. Two independent investigators extracted the data and assessed the risk of bias. The quality of evidence was evaluated through Grading of Recommendations Assessment, Development and Evaluation.

Twenty-three studies were included in the qualitative synthesis (18 randomized controlled trials were included in the network meta-analysis). For women with LBP during pregnancy, progressive muscle relaxation therapy (mean difference = -3.96; 95% CI = -7.19 to -0.74; moderate-quality evidence) and Kinesio Taping (mean difference = -3.71; 95% CI = -6.55 to -0.87; low-quality evidence) reduced pain intensity (Visual Analog Scale, range = 0 to 10) compared with placebo. Moderate-quality evidence suggested that transcutaneous electrical nerve stimulation improved physical function (mean difference = -6.33; 95% CI = -10.61 to -2.05; Roland Morris Disability Questionnaire, range = 0-24) compared with placebo.

For patients with LBP during pregnancy, progressive muscle relaxation therapy and Kinesio Taping may help to decrease pain, and transcutaneous electrical nerve stimulation may improve physical function.

This review helps fill the gap in evidence regarding optimal treatment for pregnancy-related LBP.

If you have LBP during pregnancy, your physical therapist has evidence to support the use of progressive muscle relaxation therapy and Kinesio Taping to help decrease pain and the use of transcutaneous electrical nerve stimulation to help improve physical function.

This study aimed to evaluate the comparative clinical effectiveness and safety of dexamethasone vs betamethasone for preterm birth.

The sources searched were MEDLINE, EMBASE, Cochrane Library, LILACS, ClinicalTrials.gov, and International Clinical Trials Registry Platform without language restrictions until October 2019 in addition to the reference lists of included studies. Field experts were also contacted.

Randomized or quasi-randomized controlled trials comparing any corticosteroids against each other or against placebo at any dose for preterm birth were included in the study.

Three researchers independently selected and extracted data and assessed the risk of bias of the included studies by using Early Review Organizing Software and Covidence software. Random-effects pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcomes were chorioamnionitis, endometritis or puerperal sepsis, neonatal death, respiratory distress syndrome, and neurodevelopmental disability.

A total of 45 trials (11,227 women and 11,878 infants) were included in the study. No clinical or statistical difference was found between dexamethasone and betamethasone in neonatal death (odds ratio, 1.05; 95% confidence interval, 0.62-1.84; moderate-certainty evidence), neurodevelopmental disability (odds ratio, 1.03; 95% confidence interval, 0.80-1.33; moderate-certainty evidence), intraventricular hemorrhage (odds ratio, 1.04; 95% confidence interval, 0.56-1.78); low-certainty evidence), or birthweight (+5.29 g; 95% confidence interval, -49.79 to 58.97; high-certainty evidence). There was no statistically significant difference, but a potentially clinically important effect was found between dexamethasone and betamethasone in chorioamnionitis (odds ratio, 0.70; 95% confidence interval, 0.45-1.06; moderate-certainty evidence), fetal death (odds ratio, 0.81; 95% confidence interval, 0.24-2.41; low-certainty evidence), puerperal sepsis (odds ratio, 2.04; 95% confidence interval, 0.72-6.06; low-certainty evidence), and respiratory distress syndrome (odds ratio, 1.34; 95% confidence interval, 0.96-2.11; moderate-certainty evidence). Meta-regression, subgroup, and sensitivity analyses did not reveal important changes regarding the main analysis.

Corticosteroids have proven effective for most neonatal and child-relevant outcomes compared with placebo or no treatment for women at risk of preterm birth. No important difference was found on neonatal death, neurodevelopmental disability, intraventricular hemorrhage, and birthweight between corticosteroids, and there was no statistically significant difference, but a potentially important difference was found in chorioamnionitis, fetal death, endometritis or puerperal sepsis, and respiratory distress syndrome. Further research is warranted to improve the certainty of evidence and inform health policies.

To analyze and determine the comparative effectiveness of interventions targeting frailty prevention or treatment on frailty as a primary outcome and quality of life, cognition, depression, and adverse events as secondary outcomes.

Systematic review and network meta-analysis (NMA).

Data sources-Relevant randomized controlled trials (RCTs) were identified by a systematic search of several electronic databases including MEDLINE, EMBASE, CINAHL, and AMED. Duplicate title and abstract and full-text screening, data extraction, and risk of bias assessment were performed. Data extraction-All RCTs examining frailty interventions aimed to decrease frailty were included. Comparators were standard care, placebo, or another intervention. Data synthesis-We performed both standard pairwise meta-analysis and Bayesian NMA. Dichotomous outcome data were pooled using the odds ratio effect size, whereas continuous outcome data were pooled using the standardized mean difference (SMD) effect size. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) for each outcome. The quality of evidence was evaluated using the GRADE approach.

A total of 66 RCTs were included after screening of 7090 citations and 749 full-text articles. NMA of frailty outcome (including 21 RCTs, 5262 participants, and 8 interventions) suggested that the physical activity intervention, when compared to placebo and standard care, was associated with reductions in frailty (SMD -0.92, 95% confidence interval -1.55, -0.29). According to SUCRA, physical activity intervention and physical activity plus nutritional supplementation were probably the most effective intervention (100% and 71% likelihood, respectively) to reduce frailty. Physical activity was probably the most effective or the second most effective interventions for all included outcomes.

Physical activity is one of the most effective frailty interventions. The quality of evidence of the current review is low and very low. More robust RCTs are needed to increase the confidence of our NMA results and the quality of evidence.