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Background and Purpose: The international Consensus on Therapeutic Exercise aNd Training (i-CONTENT) tool is a new instrument developed to evaluate the therapeutic quality of exercise interventions. Home-based exercise has been shown to improve physical fitness in older adults, but its effects may be influenced by therapeutic quality. The purpose of this systematic review was to describe the therapeutic quality of home-based exercise interventions for community-dwelling older adults and examine the relationship between therapeutic quality and changes in physical fitness. Methods: Six electronic databases and 2 clinical trial registries were searched for randomized controlled trials investigating the effects of home-based exercise on physical fitness in community- dwelling older adults (≥60 years). Therapeutic quality was evaluated using the i-CONTENT tool for items of patient selection, type of exercise, safety, type/timing of outcomes, exercise dose, and adherence. International Consensus on Therapeutic Exercise aNd Training items were used to explain heterogeneity in meta-regression analyses. Risk of bias, certainty of evidence and credibility of analyses were assessed. Results: Thirty-six trials (n = 6157 participants) were identified. Most studies (≥66.7%) had high or probably high therapeutic quality for i-CONTENT items, except exercise dose (47.2%) and adherence (16.7%). Interventions improved upper- (N = 20 trials; standardized mean difference [SMD] = 0.39; 95% CI, 0.13-0.64; low certainty of evidence) and lower-body strength (N = 28; SMD = 0.42; 95% CI, 0.08-0.77; very low certainty), and aerobic fitness (N = 8; SMD = 0.42; 95% CI, 0.08-0.77; very low certainty). For exercise dose, low- or probably low-quality studies negatively influenced effects on upper- (estimated β = -.48; P = .049; moderate credibility) and lower-body strength (estimated β = -.77; P = .048; moderate credibility). For adherence, low- or probably low-quality studies negatively influenced effects on aerobic fitness (estimated β = -.97; P = .02; low credibility). Conclusions: Home-based exercise may improve upper- and lower-body strength, as well as aerobic fitness in older adults. However, the effectiveness of interventions is affected by inadequate dosing of exercise programs and adherence issues. Physical therapists should have the best available evidence to support their clinical decision making, especially when designing and monitoring home programs. [ABSTRACT FROM AUTHOR]

Purpose: Retinal non‐perfusion (RNP) is fundamental to disease onset and progression in diabetic retinopathy (DR). Whether anti‐vascular endothelial growth factor (anti‐VEGF) therapy can modify RNP progression is unclear. This investigation quantified the impact of anti‐VEGF therapy on RNP progression compared with laser or sham at 12 months. Methods: A systematic review and meta‐analysis of randomised controlled trials (RCTs) were performed; Ovid MEDLINE, EMBASE and CENTRAL were searched from inception to 4th March 2022. The change in any continuous measure of RNP at 12 months and 24 months was the primary and secondary outcomes, respectively. Outcomes were reported utilising standardised mean differences (SMD). The Cochrane Risk of Bias Tool version‐2 and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines informed risk of bias and certainty of evidence assessments. Results: Six RCTs (1296 eyes) and three RCTs (1131 eyes) were included at 12 and 24 months, respectively. Meta‐analysis demonstrated that RNP progression may be slowed with anti‐VEGF therapy compared with laser/sham at 12 months (SMD: −0.17; 95% confidence interval [CI]: −0.29, −0.06; p = 0.003; I2 = 0; GRADE rating: LOW) and 24‐months (SMD: −0.21; 95% CI: −0.37, −0.05; p = 0.009; I2 = 28%; GRADE rating: LOW). The certainty of evidence was downgraded due to indirectness and due to imprecision. Conclusion: Anti‐VEGF treatment may slightly impact the pathophysiologic process of progressive RNP in DR. The dosing regimen and the absence of diabetic macular edema may impact this potential effect. Future trials are needed to increase the precision of the effect and inform the association between RNP progression and clinically important events. PROSPERO Registration: CRD42022314418. [ABSTRACT FROM AUTHOR]

Background: Subgroup analyses are widely used to evaluate the heterogeneity of treatment effects in randomized clinical trials. However, there is a limited investigation of the quality of prespecified and reported subgroup analyses in stroke trials. This study evaluated the credibility of subgroup analyses in stroke trials. Methods and analysis: We searched Medline/PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science from inception to 24 March 2021. Three reviewers screened, extracted, and analyzed the data from the publications. Primary publications of stroke trials that reported at least one subgroup effect and had published corresponding study protocols were included. The Instrument for Assessing the Credibility of Effect Modification Analyses (ICEMAN) was used to examine the quality of the subgroup effects reported, with each subgroup effect assigned a credibility rating ranging from very low to high. Subgroup effects with two or more "definitely no" responses received a low credibility rating. The risk of bias was assessed using the Cochrane Risk-of-Bias tool for randomized trials version 2. Results: Seventy-four articles met the inclusion criteria and reported a combined total of 647 subgroup effects. The median sample size was 1264 (interquartile range (IQR): 380–3876), and the median number of subgroups prespecified in the protocol was 6 (IQR: 2–10). Sixty-one (82%) studies used the univariate test of interaction. Of the total 647 subgroup effects reported in these studies, 319 (49%) were reported in acute stroke trials, while 423 (65%) had low credibility. Conclusion: The quality of subgroup analysis reporting in stroke trials remains poor. More effort is needed to train trialists on the best methods for designing and performing subgroup analyses, and how to report the results. Trial registration number: We prospectively registered the review with International Prospective Register for Systematic Reviews (registration number: CRD42020223133) [ABSTRACT FROM AUTHOR]

Introduction Cannabis is a widely used substance in pregnancy, yet there is a paucity of literature addressing the neuro-behavioural consequences for prenatally exposed children. Our systematic review synthesizes currently available data for the impact of prenatal cannabis use on offspring intelligence and cognitive functioning. Methods MEDLINE, EMBASE, PsychINFO, CINAHL, and Clinicaltrials.gov were searched. Observational studies comparing prenatal cannabis use to controls were included. Offspring neuro-behavioural outcomes were grouped in prespecified domains of (1) intelligence and (2) cognitive functioning. Random-effect models were performed for meta-analyses when at least three studies reported the same outcome. All others were summarized qualitatively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework was used to assess evidence certainty. Results Of the 1982 reviewed studies (n = 523,107 patients), 28 were included. Significant heterogeneity and cohort redundancy limited meta-analysis. Very low-quality evidence from pooled analyses showed no significant associations between prenatal cannabis exposure and attention [standardized mean difference = −0.27 (95% CI = −0.60 to 0.07)], global intelligence quotient [−0.16 (−0.42 to 0.10)], reading [−0.05 (−0.29 to 0.20)], written comprehension [−0.09 (−0.40 to 0.22)], spelling [−0.04 (−0.26 to 0.17)], and mathematics [−0.01 (−0.15 to 0.13)]. No significant associations were found between prenatal cannabis exposure for all other outcomes. Individual studies reported significant differences between the heavy use groups and non-exposed, although this did not prove to be significant when outcomes were pooled. Conclusions The current review did not find a clear association between prenatal cannabis use and offspring neuro-behavioural outcomes. However, evidence was low quality and heterogenous. Further prospective investigation is needed to elucidate any potential association between prenatal cannabis use and long-term neuro-developmental outcomes. [ABSTRACT FROM AUTHOR]

Objective: To investigate treat‐and‐extend (T&E) regimens of anti‐vascular endothelial growth factor (anti‐VEGF) therapy for the treatment of macular oedema secondary to retinal vein occlusions (RVOs). Methods: Ovid MEDLINE, Ovid EMBASE and CENTRAL were searched on 25 February 2021. Randomized controlled trials, cohort studies, case–control studies and case series were included. The primary outcome was the change in Early Treatment Diabetic Retinopathy Score (ETDRS) letters from baseline. Conversions from Snellen to ETDRS letters were performed utilizing a published protocol. Secondary outcomes included improvement in retinal thickness from baseline, number of anti‐VEGF injections and frequency of adverse events. Outcomes were examined at 12 and 24 months. Certainty of evidence was assessed utilizing GRADE (Grading of Recommendations Assessments, Development and Evaluations) guidelines. Results: Seven hundred eighty‐six eyes from 16 studies were included. Meta‐analysis demonstrated a mean improvement of 15.7 (95% CI: 13.3–18.0) ETDRS letters at 12 months. Central retinal thickness improved 269.7 μm (95% CI: 233.64–305.90) at 12 months. Injections were performed 8.1 (95% CI: 7.4–8.7) and 13.1 (95% CI: 9.4–16.8) times at 12 and 24 months respectively. Adverse events were infrequent across all studies. Grading of Recommendations Assessments, Development and Evaluations (GRADE) certainty of evidence was very low across all outcomes. Conclusions: The results support the viability of T&E regimens for the treatment of macular oedema secondary to RVOs. [ABSTRACT FROM AUTHOR]

Background dance is a mind–body activity that stimulates neuroplasticity. We explored the effect of dance on cognitive function in older adults. Methods we searched MEDLINE, EMBASE, CENTRAL and PsycInfo databases from inception to August 2020 (PROSPERO:CRD42017057138). Inclusion criteria were (i) randomised controlled trials (ii) older adults (aged ≥ 55 years), (iii) intervention—dance and (iv) outcome—cognitive function. Cognitive domains were classified with the Diagnostic and Statistical Manual of Mental Disorders-5 Neurocognitive Framework. Meta-analyses were performed in RevMan5.3 and certainty of evidence with GradePro. Results we reviewed 3,997 records and included 11 studies (N  = 1,412 participants). Seven studies included only healthy older adults and four included those with mild cognitive impairment (MCI). Dance interventions varied in frequency (1–3×/week), time (35–60 minutes), duration (3–12 months) and type. We found a mean difference (MD) = 1.58 (95% confidence interval [CI) = 0.21–2.95) on the Mini Mental State Examination for global cognitive function (moderate-certainty evidence), and the Wechsler Memory Test for learning and memory had an MD = 3.02 (95% CI = 1.38–4.65; low-certainty evidence). On the Trail Making Test-A for complex attention, MD = 3.07 (95% CI = −0.81 to 6.95; high-certainty evidence) and on the Trail Making Test-B for executive function, MD = −4.12 (95% CI = −21.28 to 13.03; moderate-certainty evidence). Subgroup analyses did not suggest consistently greater effects in older adults with MCI. Evidence is uncertain for language, and no studies evaluated social cognition or perceptual–motor function. Conclusions dance probably improves global cognitive function and executive function. However, there is little difference in complex attention, and evidence also suggests little effect on learning and memory. Future research is needed to determine the optimal dose and if dance results in greater cognitive benefits than other types of physical activity and exercise. [ABSTRACT FROM AUTHOR]

Objective: Prescription opioid misuse has led to a new cohort of opioid use disorder (OUD) patients who were introduced to opioids through a legitimate prescription. This change has caused a shift in the demographic profile of OUD patients from predominantly young men to middle age and older people. The management of OUD includes medication-assisted treatment (MAT), which produces varying rates of treatment response. In this study, we will examine whether the source of first opioid use has an effect on treatment outcomes in OUD. Using a systematic review of the literature, we will investigate the association between source of first opioid introduction and treatment outcomes defined as continuing illicit opioid use and poly-substance use while in MAT. Methods: Medline, EMBASE, CINHAL, and PsycInfo were searched from inception to December 31st, 2019 inclusive using a comprehensive search strategy. Five pairs of reviewers conducted screening and data extraction independently in duplicate. The review is conducted and reported according to the PRISMA guidelines. A random-effects model was used for meta analyses assuming heterogeneity among the included studies. Results: The initial search results in 27,345 articles that were screened, and five observational studies were included in the qualitative and quantitative analyses. Our results found that those who were introduced to opioids through a legitimate prescription were significantly less likely to have illicit opioid use (0.70, 95% CI 0.50, 0.99) while on MAT. They were also less likely to use cannabis (0.54, 95% CI 0.32, 0.89), alcohol (0.75, 95% CI 0.59, 0.95), cocaine (0.50, 95% CI 0.29, 0.85), and injection drug use (0.25, 95% CI 0.14, 0.43) than those introduced to opioids through recreational means. Conclusion: This study shows that the first exposure to opioids, whether through a prescription or recreationally, influences prognosis and treatment outcomes of opioid use disorder. Although the increased pattern of prescribing opioids may have led to increased OUD in a new cohort of patients, these patients are less likely to continue to use illicit drugs and have a different prognostic and clinical profile that requires a tailored approach to treatment. Systematic Review Registration: PROSPERO CRD42017058143. [ABSTRACT FROM AUTHOR]

Background: The standard of care in management of hypothyroidism is treatment with levothyroxine (L-T4). Sometimes patients are dissatisfied with L-T4 and the combination of levo-triiodothyronine (L-T3) with L-T4 is considered. Methods: We performed a systematic review and meta-analysis of blinded randomized controlled trials (RCTs), reporting how often hypothyroid patients prefer combination L-T3/L-T4 treatment to L-T4 alone. We also explored for explanatory factors for combination therapy preference in sensitivity analyses examining trial, patient, and disease characteristics. Potential dose-response relationships were explored using meta-regression analyses. We searched 9 electronic databases (from inception until February, 2019), supplemented with a hand-search. Two reviewers independently screened abstracts and citations and reviewed full-text papers, with consensus achieved on the included studies. Two reviewers independently critically appraised the quality of included studies and abstracted the data. Random effects meta-analyses were reported for the percentage of patients preferring combination L-T3/T-T4 therapy over L-T4 alone. A binomial distribution of choices (i.e., preference of combination therapy or no preference for combination therapy) was assumed. Results: We included 7 blinded RCTs including 348 hypothyroid individuals in the primary meta-analysis. The pooled prevalence rate for preference of combination therapy over L-T4 was 46.2% (95% confidence interval 40.2%, 52.4%) (p = 0.231 for the difference from chance). There was no significant statistical heterogeneity among study results (Q = 7.32, degrees of freedom = 6, p = 0.293, I 2 = 18.0%). In sensitivity analyses, combination treatment preference was explained in part by treatment effects on TSH concentration, mood and symptoms, but not quality of life nor body weight. In a secondary dose-response meta-regression analyses, a statistically significant association of treatment preference was identified for total daily L-T3 dose, but not L-T3:L-T4 dose ratio. Conclusions: In conclusion, in RCTs in which patients and investigators were blinded to treatment allocation, approximately half of participants reported preferring combination L-T3 and L-T4 therapy compared to L-T4 alone; this finding was not distinguishable from chance. An observed potential positive L-T3 dose effect on treatment preference deserves further study, with careful consideration of thyroid biochemical indices and patient reported outcomes. [ABSTRACT FROM AUTHOR]

Background: The potential risk of subsequent malignant neoplasms (SMNs) after radioactive iodine (RAI) treatment of thyroid cancer (TC) is an important concern. Methods: A systematic review was updated comparing the risk of SMNs in TC patients treated with RAI to TC patients without RAI. Six electronic databases were searched (up to March, 2018), supplemented with a hand search. Two reviewers independently screened citations, reviewed full-text papers, and critically appraised/abstracted data. Random-effects meta-analyses were conducted using crude data and data statistically adjusted for confounders. The outcomes were any SMN and specific SMNs for which sufficient data were available. Results: In total, 3506 unique electronic search citations and 93 full-text papers were examined, including 17 studies (3 systematic reviews and 14 original studies). Published knowledge syntheses were limited by inclusion of small numbers of studies, with two systematic reviews suggesting an increased risk of any SMN and one meta-analysis suggesting a reduced risk of breast SMN after RAI treatment. In a meta-analysis of crude data, the risk ratio of any SMN in RAI-treated TC patients was 0.98 ([confidence interval (CI) 0.76–1.27]; n = 10 studies of 65,539 individuals, heterogeneity Q = 64.26, degrees of freedom [df] = 9, p < 0.001, I2 = 85.99). The pooled risk ratio for any SMN, adjusted for confounders, was 1.16 ([CI 0.97–1.39]; n = 6 studies, data from at least 11,241 TC patients, Q = 10.86, df = 5, p = 0.054, I2 = 53.96). In secondary analyses examining specific SMNs, although relatively rare, the risk of subsequent leukemia was increased, but the risk of multiple myeloma was reduced in RAI-treated TC patients. There was no significant increased relative risk of breast cancer, salivary cancer, or combined hematologic malignancies according to RAI treatment status. Conclusions: The body of evidence on whether 131I treatment of thyroid cancer is associated with the primary outcome of any SMN is highly heterogeneous and complex. More research examining the long-term risk of specific SMNs after 131I treatment is needed. [ABSTRACT FROM AUTHOR]

Background: The pragmatic-explanatory continuum indicator summary version 2 (PRECIS-2) tool has recently been developed to classify randomized clinical trials (RCTs) as pragmatic or explanatory based on their design characteristics. Given that treatment effects in explanatory trials may be greater than those obtained in pragmatic trials, conventional meta-analytic approaches may not accurately account for the heterogeneity among the studies and may result in biased treatment effect estimates. This study investigates if the incorporation of PRECIS-2 classification of published trials can improve the estimation of overall intervention effects in meta-analysis. Methods: Using data from 31 published trials of intervention aimed at reducing obesity in children, we evaluated the utility of incorporating PRECIS-2 ratings of published trials into meta-analysis of intervention effects in clinical trials. Specifically, we compared random-effects meta-analysis, stratified meta-analysis, random-effects meta-regression, and mixture random-effects meta-regression methods for estimating overall pooled intervention effects. Results: Our analyses revealed that mixture meta-regression models that incorporate PRECIS-2 classification as covariate resulted in a larger pooled effect size (ES) estimate (ES = - 1.01, 95%CI = [- 1.52, - 0.43]) than conventional random-effects meta-analysis (ES = - 0.15, 95%CI = [- 0.23, - 0.08]). Conclusions: In addition to the original intent of PRECIS-2 tool of aiding researchers in their choice of trial design, PRECIS-2 tool is useful for explaining between study variations in systematic review and meta-analysis of published trials. We recommend that researchers adopt mixture meta-regression methods when synthesizing evidence from explanatory and pragmatic trials. [ABSTRACT FROM AUTHOR]

Background: Acute low back pain (ALBP) is the top cause of global disability, demonstrating a significant impact on individuals and society and demanding the need for appropriate management. There is a trend towards an increasing number of opioid prescriptions for ALBP despite the lack of investigation for its various short- and long-term outcomes. The objective of this review is to examine adverse outcomes associated with opioid use for ALBP. Methods/design: Using a search strategy, the search will be conducted using the following electronic databases: PubMed/MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Cochrane Library, the National Institutes for Health Clinical Trials Registry and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). We will include randomized clinical trials and observational studies investigating the impact of opioid use in ALBP in the adult population. All phases of screening, data extraction and assessment of methodological quality will be performed by two independent reviewers. We will perform quality and risk of bias assessment for the included articles and compare high and low risk of bias with a sensitivity analysis. We will conduct random- and fixed-effects meta-analyses with heterogeneity calculated using the I2 statistic and evaluate publication bias. Discussion: There are current guidelines published to alert clinicians in prescribing opioids for ALBP due to its likelihood of misuse, yet there is little change in prescribing patterns. To date, there is an absence of systematic information about the outcomes of prescription opioid in patients with ALBP. We will address this gap by providing evidence that will be useful for clinical practice. [ABSTRACT FROM AUTHOR]

Background: Frailty is a common syndrome affecting 5-17% of community-dwelling older adults. Various interventions are used to prevent or treat frailty. Given the diversity of singular and multi-faceted frailty interventions, not all of them have been compared in head-to-head studies. Network meta-analyses provide an approach to simultaneous consideration of the relative effectiveness of multiple treatment alternatives. This systematic review and network meta-analysis of RCTs aims to determine the comparative effect of interventions targeting the prevention or treatment of frailty. Method: We will identify relevant RCTs, in any language and publication date, by a systematic search of databases including MEDLINE, EMBASE, CINAHL, AMED, the Cochrane Central Registry of Controlled Trials (CENTRAL), HealthSTAR, DARE, PsychINFO, PEDro, SCOPUS, and Scielo. Duplicate title and abstract and full-text screening will be performed. Authors will extract data and assess risk of bias (using the Cochrane Risk of Bias tool) of eligible studies. The review interventions will include (1) physical activity only, (2) physical activity with protein supplementation or other nutritional supplementation, (3) psychosocial intervention, (4) medication management, (5) pharmacotherapy, and (6) multi-faceted intervention (defined as an intervention that combine physical activity and/or nutrition with any of the following: (1) psychosocial intervention, (2) medication management, and (3) pharmacotherapy). Our primary outcome is difference in change of physical frailty from baseline measured by a reliable and valid frailty measure. Secondary outcomes and the assessments are (1) cognition, (2) short physical performance battery, (3) any other physical performance measure, (4) treatment cost, (5) quality of life, and (6) any adverse outcome. We will conduct a network meta-analysis using a Bayesian hierarchical model. We will also estimate the ranking probabilities for all treatments at each possible rank for each intervention and will assess the certainty of the estimates of effect using GRADE approach. Discussion: To the best of our knowledge, this will be the first systematic review and network meta-analysis considering the direct and indirect effect of interventions targeting frailty prevention or treatment. Given the established high prevalence and socio-economic burden of frailty, there is an urgent need for a high-quality systematic review to inform evidence-based management of frailty. [ABSTRACT FROM AUTHOR]

Background: With the non-medical use of prescription opioids increasingly becoming a method of abuse in Canada, the number of patients requiring methadone maintenance treatment (MMT) for opioid use disorder has increased dramatically. The rate of cannabis use in this population is disproportionately high (~50 %). Because its use is generally perceived as harmless, cannabis use is often not monitored during MMT. Current literature regarding the effects of cannabis use on MMT is conflicting, and the presence and nature of an association has not been clearly established. The primary objective of this review will be to conduct a systematic review of the literature and, if appropriate, a meta-analysis to determine whether there is an association between cannabis use and MMT outcomes. A secondary objective will be to perform subgroup analyses (by age, sex, method of cannabis measurement, and country) to determine whether cannabis use differentially influences MMT outcomes within these subgroups. Methods/design: The search will be conducted on the following electronic databases using a predefined search strategy: MEDLINE, EMBASE, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Two authors (LZ and MB) will independently screen articles using predetermined inclusion/exclusion criteria and will extract data from included articles using a pilot-tested data extraction form. Disagreements at all stages of the screening process will be settled through discussion, and when consensus cannot be reached, a third author (ZS) will be consulted. An assessment of quality and risk of bias will be conducted on all included articles, and a sensitivity analysis will be used to compare results of studies with high and low risk of bias. We will perform random- and fixed-effects meta-analyses, if appropriate, with heterogeneity calculated using the I² statistic and formal evaluation of publication bias. Discussion: Results of this systematic review will elucidate the association between cannabis use and methadone maintenance treatment outcomes. We will provide evidence that will be useful to clinicians regarding whether monitoring cannabis use during MMT is advantageous for optimizing MMT outcomes. [ABSTRACT FROM AUTHOR]

Background: Mesothelin is a membrane-bound glycoprotein. Although the biologic function of mesothelin is not very clear, researchers have found that it plays a role in the survival, proliferation, and migration of tumor cells. Identified as a tumor-associated biomarker, mesothelin is more often overexpressed in triple-negative breast cancer (TNBC) than in common luminal breast tumor subtype or normal tissues. The objective of this review is to determine the association between the expression of mesothelin and overall survival in patients with TNBC. Methods/design: We will search the following electronic databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Web of Science with no time or language restriction. Prospective or retrospective longitudinal studies that investigate mesothelin expression in TNBC or the prognosis of TNBC with mesothelin baseline measurement will be selected. Two reviewers will independently assess every abstract or full text for inclusion. Data on clinical outcomes, as well as on study design, research setting, study population, demographic characteristics of the participants, and methodological quality, will be extracted using a structured codebook developed by the authors. A pooled measure of associations will be assessed through meta-analyses if appropriate. Heterogeneity across the included studies will be evaluated using the I2 statistics. Findings will be reported according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The quality of evidence and risk of bias of the studies will be evaluated. Discussion: The aim of this systematic review is to synthesize the evidence regarding the association between the expression of mesothelin and the survival outcomes of patients with TNBC. A better understanding of the expression frequency and prognostic value of mesothelin in TNBC will be essential to identifying a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Stepped wedge design (SWD) is a cluster randomized controlled trial (RCT) design that sequentially rolls out intervention to all clusters at varying time points. Being a relatively new design method, reporting quality has yet to be explored, and this review will seek to fill this gap in knowledge. Objectives: The objectives of this review are: 1) to assess the quality of SWD trial reports based on the CONSORT guidelines or CONSORT extension to cluster RCTs; 2) to assess the completeness of reporting of SWD trial abstracts using the CONSORT extension for abstracts; 3) to assess the reporting of sample size details in SWD trial reports or protocols; 4) to assess the completeness of reporting of SWD trial protocols according to SPIRIT guidelines; 5) to assess the consistency between the trial registration information and final SWD trial reports; and 6) to assess the consistency of what is reported in the abstracts and main text of the SWD trial reports. We will also explore factors that are associated with the completeness of reporting. Methods: We will search MEDLINE, EMBASE, Web of Science, CINAHL, and PsycINFO for all randomized controlled trials utilizing SWD. Details from eligible papers will be extracted in duplicate. Demographic statistics obtained from the data extraction will be analyzed to answer the primary objectives pertaining to the reporting quality of several aspects of a published paper, as well as to explore possible temporal trends and consistency between abstracts, trial registration information, and final published articles. Discussion: Findings from this review will establish the reporting quality of SWD trials and inform academics and clinicians on their completeness and consistency. Results of this review will influence future trials and improve the overall quality and reporting of SWD trials. [ABSTRACT FROM AUTHOR]

The article argues about association of asthma with different fecal bacterial patterns that includes examination of gastro-intestinal tract (GIT) fecal bacteria involvement in asthma pathogenesis, utilization of high-resolution methods for investigation and assessment of airway micro biome impact.

Background: Pediatric brain tumors are the most common solid tumors in children. Advances in understanding the hallmarks of cancer biology and novel therapies have led to an increasing number of survivors of childhood brain tumors (SCBT). However, these survivors are at an increased risk of obesity and cardiometabolic disorders that affect their quality of life and lifespan. It is important to define effective strategies to treat and prevent obesity in this population. This systematic review aims to investigate the effectiveness of lifestyle interventions, pharmacotherapy, and bariatric surgery on treating obesity in SCBT. Methods: Searches will be conducted in PubMed, MEDLINE, EMBASE, PsycINFO, SPORTDiscus, CINAHL, Cochrane Database of Systematic Review, Cochrane Central Register of Controlled Trials (CENTRAL), and Database of Abstracts of Reviews of Effect (DARE). In addition, ClinicalTrials.gov and ProQuest Dissertations and Theses A&I will be searched to identify relevant gray literature. The reference lists of eligible articles will be searched for additional studies. All screening, quality assessment, and data abstraction will be done independently by two reviewers. We will perform meta-analysis if there are sufficient studies. Discussion: This review will summarize evidence for the effectiveness of interventions used to reduce obesity risk in SCBT. This has significant implications for SCBT, as it can identify gaps in knowledge and provide insights into the development of new interventions to manage obesity in survivors, which may improve their outcomes. [ABSTRACT FROM AUTHOR]

Background: Steroids are often combined with local anesthetic (LA) and injected to reduce pain associated with various chronic non-cancer pain (CNCP) complaints. The biological rationale behind injection of a steroid solution is unclear, and it is uncertain whether the addition of steroids offers any additional benefits over injection of LA alone. We propose to conduct a systematic review and meta-analysis to summarize the evidence for using steroids and LA vs. LA alone in the treatment of CNCP. Methods: An experienced librarian will perform a comprehensive search of EMBASE, MEDLINE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) databases with search terms for clinical indications, LA, and steroid agents. We will review bibliographies of all relevant published reviews in the last 5 years for additional studies. Eligible trials will be published in English and randomly allocate patients with CNCP to treatment with steroid and LA injection therapy or injection with LA alone. We will use the guidelines published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes that we collect and present. Teams of reviewers will independently and in duplicate assess trial eligibility, abstract data, and assess risk of bias among eligible trials. We will prioritize intention to treat analysis and, when possible, pool outcomes across trials using random effects models. We will report our findings as risk differences, weighted mean differences, or standardized mean differences for individual outcomes. Further, to ensure interpretability of our results, we will present risk differences and measures of relative effect for pain reduction based on anchor-based minimally important clinical differences. We will conduct a priori defined subgroup analyses and use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to evaluate the certainty of the evidence on an outcome-by-outcome basis. Discussion: Our review will evaluate both the effectiveness and the adverse events associated with steroid plus LA vs. LA alone for CNCP, evaluate the quality of the evidence using the GRADE approach, and prioritize patientimportant outcomes guided by IMMPACT recommendations. Our results will facilitate evidence-based management of patients with chronic non-cancer pain and identify key areas for future research. [ABSTRACT FROM AUTHOR]

Background: Up to 90% of people with scleroderma have gastrointestinal (GI) problems such as constipation, bloating, diarrhea, and malabsorption. These problems significantly impair quality of life. Our objective was to determine the risk factors for gastrointestinal issues in people with scleroderma. Methods: We conducted a systematic review of observational studies that report GI problems in patients with scleroderma along with the associated risk factors. We were interested in any GI problem and any risk factor as long as the study included patients diagnosed with scleroderma according to the 1980 or 2013 American College of Rheumatology guideline. We searched the following databases: CINAHL, EMBASE, LILACS, MEDLINE, and Web of Science for relevant articles from June 1884 to May 2014. Two authors independently screened citations and full text articles and extracted data. Discrepancies were resolved by consensus or by consulting a third author. Methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Results: After removing duplicates, 645 unique citations were identified. A total of three studies, three crosssectional (n = 64, n = 42, n = 606), were included in this systematic review. Collectively, these three studies explored Helicobacter pylori and smoking status as risk factors. We found conflicting evidence on the role of H. pylori with two studies showing opposite yet statistically significant results. One moderate quality study showed smoking as a risk factor. Key limitations include the small sample sizes of two studies and poor study designs to draw causal links. Conclusions: There is insufficient evidence to describe the risk factors for GI problems in patients with scleroderma. Longitudinal observational studies are warranted in patients with scleroderma. [ABSTRACT FROM AUTHOR]

Background: STRATIFY is a prediction tool developed for use in for hospital inpatients, using a 0-5 score to predict patients who will fall. It has been widely used as part of hospital fall prevention plans, but it is not clear how good its operational utility is in a variety of settings. Objectives: (i) to describe the predictive validity of STRATIFY for identifying hospital inpatients who will fall via systematic review and descriptive analysis, based on its use in several prospective cohort studies of hospital inpatients; (ii) to describe the predictive validity of STRATIFY among inpatients in geriatric rehabilitation via meta-analysis and (iii) in turn, to help practitioners and institutions wishing to implement interventions to prevent in-hospital falls. Methods: a systematic literature review of prospective validation studies of STRATIFY for falls prediction in hospital inpatients. For inclusion, studies must report prospective validation cohorts, with sufficient data for calculation of sensitivity (SENS), specificity (SPEC), negative and positive predictive value (NPV and PPV), total predictive accuracy (TPA) and 95% confidence intervals (Cl). We performed meta-analysis using precision-weighted fixed- and random-effects models using studies that evaluated STRATIFY among geriatric rehabilitation inpatients. Measurements: key features of the patient population, setting, study design and numbers of falls/fallers were abstracted. SENS, SPEC, PPV, NPV, TPA and 95% CI were reported for each cohort. Pooled values and cu-squared test for homogeneity were reported for a meta-analysis of studies conducted in geriatric rehabilitation settings. Results: forty-one papers were identified by the search, with eight ultimately eligible for inclusion in the systematic review and four for inclusion in the meta-analysis. The predictive validity of STRATIFY, using a random-effects model, for the four studies involving geriatric patients was as follows: SENS 67.2 (95% CI 60.8, 73.6), SPEC 51.2 (95% CI 43.0, 59.3), PPV 23.1 (95% CI 14.9, 31.2), NPV 86.5 (95% CI 78.4, 94.6). The Q(3) test for homogeneity was not significant for SENS at P = 0.36, but it was significant at P < 0.01 for SPEC, PPV and NPV. TPA across all four studies varied from 43.2 to 60.0. Conclusion: the current study reveals a relatively high NPV and low PPV and TPA for the STRATIFY instrument, suggesting that it may not be optimal for identifying high-risk individuals for fall prevention. Further, the study demonstrates that population and setting affect STRATIFY performance. [ABSTRACT FROM AUTHOR]

Immunoglobulin A nephropathy (IgAN) is a primary glomerulonephritis which may lead to end-stage renal disease. This article aims to provide the latest evidence with respect to the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of IgAN. We systematically searched PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database (VIP), and WanFang databases for randomized controlled trials from inception until 31 December, 2020. The quality of the included studies was evaluated using the Cochrane Reviewers' Handbook 5.3 and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). In total, 47 eligible studies with 3523 patients were included. Three were multicenter, double-blind studies which included a placebo, 13 studies used a patented TCM, 28 studies used TCM decoctions, and 6 studies used granules. The results indicated that, compared with routine treatment alone, a combination of TCM with routine treatment improved 24-h urine protein levels (mean difference [MD] = −0.36, 95% confidence interval [CI] = −0.44 to −0.29, P < 0.001; GRADE rating: moderate), serum creatinine levels (MD = −8.68, 95% CI = −10.72 to −6.64, P < 0.001; GRADE rating: moderate), the estimated glomerular filtration rate (MD = 4.15, 95% CI = 1.01 to 7.28, P = 0.01; GRADE rating: low), and the urine red blood cell count (MD = −7.58, 95% CI = −10.79 to −4.37, P < 0.001; GRADE rating: low), and reduced the incidence of adverse events (risk ratio = 0.54, 95% CI = 0.41 to 0.72, P < 0.001). Sensitivity analysis showed the results were robust, and there was no significant publication bias. Evidence from this meta-analysis suggests that the combination of routine treatment and TCM treatment was more effective in treating IgAN than routine treatment alone but heterogeneity is high due the different TCMs assessed. Safety remains unclear due to insufficient reporting. Before widespread use more long-term, multicenter, randomized, double-blind, and placebo controlled clinical trials are necessary. [ABSTRACT FROM AUTHOR]

Background: Most systematic reviews of opioids for chronic pain have pooled treatment effects across individual opioids under the assumption they provide similar benefits and harms. We examined the comparative effects of individual opioids for chronic non-cancer pain through a network meta-analysis of randomised controlled trials.Methods: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials to March 2021 for studies that enrolled patients with chronic non-cancer pain, randomised them to receive different opioids, or opioids vs placebo, and followed them for at least 4 weeks. Certainty of evidence was evaluated using the GRADE approach.Results: We identified 82 eligible trials (22 619 participants) that evaluated 14 opioids. Compared with placebo, several opioids showed superiority to others for analgesia and improvement in physical function; however, when restricted to pooled-effect estimates supported by moderate certainty evidence, no differences between opioids were evident. Among opioids with moderate certainty evidence, all increased the risk of gastrointestinal adverse events compared with placebo, although no opioids were more harmful than others. Low to very low certainty evidence suggests that extended-release vs immediate-release opioids may provide similar benefits for pain relief and physical functioning, and gastrointestinal harms.Conclusions: Our findings support the pooling of effect estimates across different types and formulations of opioids to inform effectiveness for chronic non-cancer pain. [ABSTRACT FROM AUTHOR]

Oral anticoagulant (OAC) intervention trials have typically included clinical event outcomes. However, there is no standard list of outcomes to be used in OAC research. This study aimed to describe and classify the outcomes used in recent prospective clinical studies involving OACs. We searched MEDLINE, EMBASE, and CINAHL databases from January 2009 to July 2019 for prospective studies with an intervention or control group that included one or more oral anticoagulants. We abstracted details about each included study and the outcomes used from the study report and its accompanying protocol. Using the Core Outcome Measures in Effectiveness Trials (COMET) Initiative recommendations, we categorised each outcome into one of five domains (mortality/survival, physiological/clinical, life impact, resource use, and adverse events). Our primary outcome was the prevalence of use of an outcome domain across studies. We included 70 prospective studies, including 52 randomized controlled trials and 18 prospective cohort studies. A total of 121 different outcomes were reported. The COMET domains were represented in the 70 studies as follows: mortality (63/70, 90.0%); physiological/clinical domain (70/70, 100%), life impact domain (43/70, 61.4%), resource use domain (26/70, 37.1%), and adverse events domain (55/70, 78.6%). Outcome reporting in prospective studies of OACs more frequently concentrates on mortality, physiological/clinical domains, and adverse events compared to life impact and resource utilization domains, the latter uncommonly used. A priority for future research includes developing a core outcome set (COS) for OAC research that represents all domains. • No standard list of outcomes to be used in oral anticoagulants research • Most papers having mortality, physiological/clinical, and adverse events domains • Fewer outcomes measured in the life impact and resource use domains • Provide information useful for developing COS for oral anticoagulants research [ABSTRACT FROM AUTHOR]

Background: Despite common use, the benefit of adding steroids to local anaesthetics (SLA) for chronic non-cancer pain (CNCP) injections is uncertain. We performed a systematic review and meta-analysis of English-language RCTs to assess the benefit and safety of adding steroids to local anaesthetics (LA) for CNCP.Methods: We searched MEDLINE, EMBASE, and CENTRAL databases from inception to May 2019. Trial selection and data extraction were performed in duplicate. Outcomes were guided by the Initiative in Methods, Measurements, and Pain Assessment in Clinical Trials (IMMPACT) statement with pain improvement as the primary outcome and pooled using random effects model and reported as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CIs).Results: Among 5097 abstracts, 73 trials were eligible. Although SLA increased the rate of success (42 trials, 3592 patients; RR=1.14; 95% CI, 1.03-1.25; number needed to treat [NNT], 13), the effect size decreased by nearly 50% (NNT, 22) with the removal of two intrathecal injection studies. The differences in pain scores with SLA were not clinically meaningful (54 trials, 4416 patients, MD=0.44 units; 95% CI, 0.24-0.65). No differences were observed in other outcomes or adverse events. No subgroup effects were detected based on clinical categories. Meta-regression showed no significant association with steroid dose or length of follow-up and pain relief.Conclusions: Addition of cortico steroids to local anaesthetic has only small benefits and a potential for harm. Injection of local anaesthetic alone could be therapeutic, beyond being diagnostic. A shared decision based on patient preferences should be considered. If used, one must avoid high doses and series of steroid injections.Clinical Trial Registration: PROSPERO #: CRD42015020614. [ABSTRACT FROM AUTHOR]

PROBLEM IDENTIFICATION: The comparative effectiveness of available management options for cancer-related secondary lymphedema is unknown. LITERATURE SEARCH: CINAHL®, Embase®, and MEDLINE® were searched for randomized trials comparing conservative treatment strategies. DATA EVALUATION: A network meta-analysis was conducted for lymphedema volume, along with pairwise meta-analyses for remaining outcomes. Evidence certainty was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. SYNTHESIS: Overall, 36 studies with a total of 1,651 participants were included. Compared to standard care, conservative treatments did not significantly reduce lymphedema volume. There was low to very low certainty evidence of benefit for several treatments on secondary outcomes. IMPLICATIONS FOR PRACTICE: There is insufficient evidence to suggest important differences between standard care and conservative treatment strategies for reducing lymphedema volume and improving lymphedema-related symptoms. [ABSTRACT FROM AUTHOR]