Embedding rapid reviews in health policy and systems decision-making: Impacts and lessons learned from four low- and middle-income countries.

BACKGROUND: Demand for rapid evidence-based syntheses to inform health policy and systems decision-making has increased worldwide, including in low- and middle-income countries (LMICs). To promote use of rapid syntheses in LMICs, the WHO's Alliance for Health Policy and Systems Research (AHPSR) created the Embedding Rapid Reviews in Health Systems Decision-Making (ERA) Initiative. Following a call for proposals, four LMICs were selected (Georgia, India, Malaysia and Zimbabwe) and supported for 1 year to embed rapid response platforms within a public institution with a health policy or systems decision-making mandate. METHODS: While the selected platforms had experience in health policy and systems research and evidence syntheses, platforms were less confident conducting rapid evidence syntheses. A technical assistance centre (TAC) was created from the outset to develop and lead a capacity-strengthening program for rapid syntheses, tailored to the platforms based on their original proposals and needs as assessed in a baseline questionnaire. The program included training in rapid synthesis methods, as well as generating synthesis demand, engaging knowledge users and ensuring knowledge uptake. Modalities included live training webinars, in-country workshops and support through phone, email and an online platform. LMICs provided regular updates on policy-makers' requests and the rapid products provided, as well as barriers, facilitators and impacts. Post-initiative, platforms were surveyed. RESULTS: Platforms provided rapid syntheses across a range of AHPSR themes, and successfully engaged national- and state-level policy-makers. Examples of substantial policy impact were observed, including for COVID-19. Although the post-initiative survey response rate was low, three quarters of those responding felt confident in their ability to conduct a rapid evidence synthesis. Lessons learned coalesced around three themes - the importance of context-specific expertise in conducting reviews, facilitating cross-platform learning, and planning for platform sustainability. CONCLUSIONS: The ERA initiative successfully established rapid response platforms in four LMICs. The short timeframe limited the number of rapid products produced, but there were examples of substantial impact and growing demand. We emphasize that LMICs can and should be involved not only in identifying and articulating needs but as co-designers in their own capacity-strengthening programs. More time is required to assess whether these platforms will be sustained for the long-term.

Analysis of Using the Total White Blood Cell Count to Define Severe New-onset Ulcerative Colitis in Children.

OBJECTIVES: The aim of this study was to assess common laboratory tests in identifying severe ulcerative colitis in children at diagnosis. METHODS: A cohort of 427 children 4 to 17 years of age newly diagnosed with ulcerative colitis (UC) was prospectively enrolled. Boosted classification trees were used to characterize predictive ability of disease attributes based on clinical disease severity using Pediatric Ulcerative Colitis Activity Index (PUCAI), severe (65+) versus not severe (<65) and total Mayo score, severe (10-12) versus not severe (<10); mucosal disease by Mayo endoscopic subscore, severe (3) versus not severe (<3); and extensive disease versus not extensive (left-sided and proctosigmoiditis). RESULTS: Mean age was 12.7 years; 49.6% (n = 212) were girls, and 83% (n = 351) were Caucasian. Severe total Mayo score was present in 28% (n = 120), mean PUCAI score was 49.8 ±â€Š20.1, and 33% (n = 142) had severe mucosal disease with extensive involvement in 82% (n = 353). Classification and regression trees identified white blood cell count, erythrocyte sedimentation rate, and platelet count (PLT) as the set of 3 best blood laboratory tests to predict disease extent and severity. For mucosal severity, albumin (Alb) replaced PLT. Classification models for PUCAI and total Mayo provided sensitivity of at least 0.65 using standard clinical cut-points with misclassification rates of approximately 30%. CONCLUSIONS: A combination of the white blood cell count, erythrocyte sedimentation rate, and either PLT or albumin is the best predictive subset of standard laboratory tests to identify severe from nonsevere clinical or mucosal disease at diagnosis in relation to objective clinical scores.

Enhancing clarity of clinical trial safety reports for data monitoring committees.

A Data Monitoring Committee (DMC) evaluates patient safety in a clinical trial of an investigational intervention through periodic review of adverse events (AEs) and clinical safety assessments. Our aim was to construct DMC report displays to enhance the DMC safety review through use of graphics and clear identification and adjustment for missing data caused by early discontinuations and ongoing study participation. Suggested displays include a study snapshot graph, enhanced adverse event incidence tables including the incidence density and plotted incidence proportions, line graphs in place of by-patient listings, and trend plots in place of tables for continuous assessments.

Quality improvement strategies to prevent falls in older adults: a systematic review and network meta-analysis.

BACKGROUND: Falls are a common occurrence and the most effective quality improvement (QI) strategies remain unclear. METHODS: We conducted a systematic review and network meta-analysis (NMA) to elucidate effective quality improvement (QI) strategies for falls prevention. Multiple databases were searched (inception-April 2017). We included randomised controlled trials (RCTs) of falls prevention QI strategies for participants aged ≥65 years. Two investigators screened titles and abstracts, full-text articles, conducted data abstraction and appraised risk of bias independently. RESULTS: A total of 126 RCTs including 84,307 participants were included after screening 10,650 titles and abstracts and 1210 full-text articles. NMA including 29 RCTs and 26,326 patients found that team changes was statistically superior in reducing the risk of injurious falls relative to usual care (odds ratio [OR] 0.57 [0.33 to 0.99]; absolute risk difference [ARD] -0.11 [95% CI, -0.18 to -0.002]). NMA for the outcome of number of fallers including 61 RCTs and 40 128 patients found that combined case management, patient reminders and staff education (OR 0.18 [0.07 to 0.47]; ARD -0.27 [95% CI, -0.33 to -0.15]) and combined case management and patient reminders (OR, 0.36 [0.13 to 0.97]; ARD -0.19 [95% CI, -0.30 to -0.01]) were both statistically superior compared to usual care. CONCLUSIONS: Team changes may reduce risk of injurious falls and a combination of case management, patient reminders, and staff education, as well as case management and patient reminders may reduce risk of falls. Our results can be tailored to decision-maker preferences and availability of resources. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42013004151).

LIBERTI: A SMART study in plastic surgery.

BACKGROUND/AIMS: Laser treatment of burns scars is considered by some providers to be standard of care. However, there is little evidence-based research as to the true benefit. A number of factors hinder evaluation of the benefit of laser treatment. These include significant heterogeneity in patient response and possible delayed effects from the laser treatment. Moreover, laser treatments are often provided sequentially using different types of equipment and settings, so there are effectively a large number of overall treatment options that need to be compared. We propose a trial capable of coping with these issues and that also attempts to take advantage of the heterogeneous response in order to estimate optimal treatment plans personalized to each individual patient. It will be the first large-scale randomized trial to compare the effectiveness of laser treatments for burns scars and, to our knowledge, the very first example of the utility of a Sequential Multiple Assignment Randomized Trial in plastic surgery. METHODS: We propose using a Sequential Multiple Assignment Randomized Trial design to investigate the effect of various permutations of laser treatment on hypertrophic burn scars. We will compare and test hypotheses regarding laser treatment effects at a general population level. Simultaneously, we hope to use the data generated to discover possible beneficial personalized treatment plans, tailored to individual patient characteristics. RESULTS: We show that the proposed trial has good power to detect laser treatment effect at the overall population level, despite comparing a large number of treatment combinations. The trial will simultaneously provide high-quality data appropriate for estimating precision-medicine treatment rules. We detail population-level comparisons of interest and corresponding sample size calculations. We provide simulations to suggest the power of the trial to detect laser effect and also the possible benefits of personalization of laser treatment to individual characteristics. CONCLUSION: We propose, to our knowledge, the first use of a Sequential Multiple Assignment Randomized Trial in surgery. The trial is rigorously designed so that it is reasonably straightforward to implement and powered to answer general overall questions of interest. The trial is also designed to provide data that are suitable for the estimation of beneficial precision-medicine treatment rules that depend both on individual patient characteristics and on-going real-time patient response to treatment.

Comparisons of Interventions for Preventing Falls in Older Adults: A Systematic Review and Meta-analysis.

Importance: Falls result in substantial burden for patients and health care systems, and given the aging of the population worldwide, the incidence of falls continues to rise. Objective: To assess the potential effectiveness of interventions for preventing falls. Data Sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Ageline databases from inception until April 2017. Reference lists of included studies were scanned. Study Selection: Randomized clinical trials (RCTs) of fall-prevention interventions for participants aged 65 years and older. Data Extraction and Synthesis: Pairs of reviewers independently screened the studies, abstracted data, and appraised risk of bias. Pairwise meta-analysis and network meta-analysis were conducted. Main Outcomes and Measures: Injurious falls and fall-related hospitalizations. Results: A total of 283 RCTs (159 910 participants; mean age, 78.1 years; 74% women) were included after screening of 10 650 titles and abstracts and 1210 full-text articles. Network meta-analysis (including 54 RCTs, 41 596 participants, 39 interventions plus usual care) suggested that the following interventions, when compared with usual care, were associated with reductions in injurious falls: exercise (odds ratio [OR], 0.51 [95% CI, 0.33 to 0.79]; absolute risk difference [ARD], -0.67 [95% CI, -1.10 to -0.24]); combined exercise and vision assessment and treatment (OR, 0.17 [95% CI, 0.07 to 0.38]; ARD, -1.79 [95% CI, -2.63 to -0.96]); combined exercise, vision assessment and treatment, and environmental assessment and modification (OR, 0.30 [95% CI, 0.13 to 0.70]; ARD, -1.19 [95% CI, -2.04 to -0.35]); and combined clinic-level quality improvement strategies (eg, case management), multifactorial assessment and treatment (eg, comprehensive geriatric assessment), calcium supplementation, and vitamin D supplementation (OR, 0.12 [95% CI, 0.03 to 0.55]; ARD, -2.08 [95% CI, -3.56 to -0.60]). Pairwise meta-analyses for fall-related hospitalizations (2 RCTs; 516 participants) showed no significant association between combined clinic- and patient-level quality improvement strategies and multifactorial assessment and treatment relative to usual care (OR, 0.78 [95% CI, 0.33 to 1.81]). Conclusions and Relevance: Exercise alone and various combinations of interventions were associated with lower risk of injurious falls compared with usual care. Choice of fall-prevention intervention may depend on patient and caregiver values and preferences.

Patency rates of the arteriovenous fistula for hemodialysis: a systematic review and meta-analysis.

BACKGROUND: Advantages of the arteriovenous fistula (AVF), including long patency and few complications, were ascertained more than 2 decades ago and may not apply to the contemporary dialysis population. STUDY DESIGN: Systematic review and meta-analysis. Estimates were pooled using a random-effects model and sources of heterogeneity were explored using metaregression. SETTING & POPULATION: Patients treated with long-term hemodialysis using an AVF. SELECTION CRITERIA FOR STUDIES: English-language studies indexed in MEDLINE between 2000 and 2012 using prospectively collected data on 100 or more AVFs. PREDICTOR: Age, AVF location, and study location. OUTCOMES: Outcomes of interest were primary AVF failure and primary and secondary patency at 1 and 2 years. RESULTS: 7,011 citations were screened and 46 articles met eligibility criteria (62 unique cohorts; n = 12,383). The rate of primary failure was 23% (95% CI, 18%-28%; 37 cohorts; 7,393 AVFs). When primary failures were included, the primary patency rate was 60% (95% CI, 56%-64%; 13 studies; 21 cohorts; 4,111 AVFs) at 1 year and 51% (95% CI, 44%-58%; 7 studies; 12 cohorts; 2,694 AVFs) at 2 years. The secondary patency rate was 71% (95% CI, 64%-78%; 10 studies; 11 cohorts; 3,558 AVFs) at 1 year and 64% (95% CI, 56%-73%; 6 studies; 11 cohorts; 1,939 AVFs) at 2 years. In metaregression, there was a significant decrease in primary patency rate in studies that started recruitment in more recent years. LIMITATIONS: Low quality of studies, variable clinical settings, and variable definitions of primary AVF failure. CONCLUSIONS: In recent years, AVFs had a high rate of primary failure and low to moderate primary and secondary patency rates. Consideration of these outcomes is required when choosing a patient's preferred access type.

Risk of serious gastrointestinal bleeding in living kidney donors.

Individuals with moderate-to-severe reduced renal function have greater risk of gastrointestinal bleeding than those with normal renal function. We conducted a retrospective matched cohort study to assess whether living kidney donors share a similar risk. We reviewed pre-donation charts for living kidney donations from 1992 to 2009 in Ontario, Canada, and linked this information to healthcare databases. We selected healthy non-donors from the general population and matched ten non-donors to every donor. Of the 2009 donors and 20,090 matched non-donors, none had evidence of gastrointestinal bleeding prior to cohort entry. The cohort was followed for a median of 8.4 yr (maximum 19.7 yr; loss to follow-up <7%). There was no significant difference in the rate of hospitalization with gastrointestinal bleeding in donors compared to non-donors (18.5 vs. 14.9 events per 10,000 person-years; rate ratio 1.24; 95% confidence interval [CI] 0.85-1.81). Similar results were obtained when we assessed the time to first hospitalization with gastrointestinal bleeding (hazard ratio 1.25, 95% CI 0.87-1.79). In conclusion, we found living kidney donation was not associated with a higher risk of hospitalization with gastrointestinal bleeding. These results are reassuring for the safety of the practice.

Design of a Multicenter Randomized Controlled Trial comparing the effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for voluntary opioid tapering: The INSPIRE study protocol.

BACKGROUND: This paper describes the design and protocol of a pragmatic, randomized trial to evaluate the comparative effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for chronic pain for the voluntary tapering of opioid dose in adults with chronic noncancer pain. Integrated Services for Pain: Interventions to Reduce Pain Effectively (INSPIRE) is a multicenter, randomized trial conducted at three academic health centers in the southeastern United States. Participants are adults receiving long-term opioid therapy of at least 20 morphine milligram equivalents daily for chronic noncancer pain. METHODS: Participants were randomized to either the shared decision-making intervention or the motivational interviewing session and cognitive behavioral therapy for chronic pain intervention. All participants also received guideline-concordant care supporting opioid pharmacotherapy. The primary outcome was change from baseline in average daily prescribed opioid dose at 12 months, using prescribing data from electronic health records. Secondary outcomes were Patient-Reported Outcomes Measurement Information System Pain Interference and Physical Function at 12 months. CONCLUSION: This trial evaluates the comparative effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for chronic pain for the voluntary tapering of opioid dose in adults with chronic noncancer pain. Results from this study can guide clinicians, researchers, and policymakers as they seek to reduce opioid prescribing and improve management of chronic pain. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT03454555 (https://clinicaltrials.gov/ct2/show/record/NCT03454555). Participant enrollment began on June 26, 2019.

Implemented machine learning tools to inform decision-making for patient care in hospital settings: a scoping review.

OBJECTIVES: To identify ML tools in hospital settings and how they were implemented to inform decision-making for patient care through a scoping review. We investigated the following research questions: What ML interventions have been used to inform decision-making for patient care in hospital settings? What strategies have been used to implement these ML interventions? DESIGN: A scoping review was undertaken. MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) were searched from 2009 until June 2021. Two reviewers screened titles and abstracts, full-text articles, and charted data independently. Conflicts were resolved by another reviewer. Data were summarised descriptively using simple content analysis. SETTING: Hospital setting. PARTICIPANT: Any type of clinician caring for any type of patient. INTERVENTION: Machine learning tools used by clinicians to inform decision-making for patient care, such as AI-based computerised decision support systems or "'model-based'" decision support systems. PRIMARY AND SECONDARY OUTCOME MEASURES: Patient and study characteristics, as well as intervention characteristics including the type of machine learning tool, implementation strategies, target population. Equity issues were examined with PROGRESS-PLUS criteria. RESULTS: After screening 17 386 citations and 3474 full-text articles, 20 unique studies and 1 companion report were included. The included articles totalled 82 656 patients and 915 clinicians. Seven studies reported gender and four studies reported PROGRESS-PLUS criteria (race, health insurance, rural/urban). Common implementation strategies for the tools were clinician reminders that integrated ML predictions (44.4%), facilitated relay of clinical information (17.8%) and staff education (15.6%). Common barriers to successful implementation of ML tools were time (11.1%) and reliability (11.1%), and common facilitators were time/efficiency (13.6%) and perceived usefulness (13.6%). CONCLUSIONS: We found limited evidence related to the implementation of ML tools to assist clinicians with patient healthcare decisions in hospital settings. Future research should examine other approaches to integrating ML into hospital clinician decisions related to patient care, and report on PROGRESS-PLUS items. FUNDING: Canadian Institutes of Health Research (CIHR) Foundation grant awarded to SES and the CIHR Strategy for Patient Oriented-Research Initiative (GSR-154442). SCOPING REVIEW REGISTRATION: https://osf.io/e2mna.

Fracture risk in living kidney donors: a matched cohort study.

BACKGROUND: Chronic kidney disease increases the risk of bone fragility fractures (osteoporotic fractures). Living kidney donors lose 50% of their renal mass and show changes in calcium homeostasis. We studied whether living kidney donation increases the risk of fragility fracture. DESIGN: Retrospective matched-cohort study. SETTING & PARTICIPANTS: We reviewed the medical charts of all 2,015 adults in Ontario, Canada, who donated a kidney between 1992 and 2009 (surgeries performed across 5 transplant programs). We linked this information to health care databases and randomly selected 20,150 matched nondonors from the healthiest portion of the general population. Median age was 43 (95% CI, 24-50) years at study enrollment. Donors and nondonors were then followed up for a median of 6.6 years and a maximum of 17.7 years. PREDICTOR: Living donor nephrectomy. OUTCOMES: The primary outcome was lower- and upper-extremity fragility fractures. Individuals who reached 66 years or older in follow-up had bisphosphonate prescriptions recorded. RESULTS: The rate of fragility fracture was no higher in donors compared with nondonors (16.4 vs 18.7 events/10,000 person-years; rate ratio, 0.88; 95% CI, 0.58-1.32). Results were similar in multiple additional analyses. There was little difference in the proportion of older adults in follow-up who received a bisphosphonate prescription (17.1% vs 15.2%; P = 0.4). LIMITATIONS: These are interim results. Ongoing surveillance of this and other donor cohorts is warranted to be sure an association does not manifest with longer follow-up. CONCLUSIONS: To date, there is no evidence of increased fragility fracture risk in living kidney donors. Our results meet an information need and are reassuring for the safety of the practice.

Interventions for social isolation in older adults who have experienced a fall: a systematic review.

OBJECTIVES: The objective of our systematic review was to identify the effective interventions to prevent or mitigate social isolation and/or loneliness in older adults who experienced a fall. DESIGN: Systematic review. DATA SOURCES: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Ageline were searched (from inception to February 2020). METHODS: Studies were eligible if they described any intervention for social isolation in older adults living in a community setting who experienced a fall, and reported outcomes related to social isolation or loneliness.Two independent reviewers screened citations, abstracted data and appraised risk of bias using the Cochrane risk of bias tool. The results were summarised descriptively. RESULTS: After screening 4069 citations and 55 full-text articles, four studies were included. The four studies varied in study design, including a randomised controlled trial, non-randomised controlled trial, an uncontrolled before-after study and a quasiexperimental study. Interventions varied widely, and included singing in a choir, a patient-centred, interprofessional primary care team-based approach, a multifactorial assessment targeting fall risk, appropriate medication use, loneliness and frailty, and a community-based care model that included comprehensive assessments and multilevel care coordination. Outcome measures varied and included scales for loneliness, social isolation, social interaction, social networks and social satisfaction. Mixed results were found, with three studies reporting no differences in social isolation or loneliness after the intervention. Only the multifactorial assessment intervention demonstrated a small positive effect on loneliness compared with the control group after adjustment (B=-0.18, 95% CI -0.35 to -0.02). CONCLUSIONS: Few studies examined the interventions for social isolation or loneliness in older adults who experienced a fall. More research is warranted in this area. PROSPERO REGISTRATION NUMBER: CRD42020198487.

Global evidence on falls and subsequent social isolation in older adults: a scoping review.

BACKGROUND: Falls are a leading cause of injury-related hospitalizations among adults aged 65 years and older and may result in social isolation. OBJECTIVE: To summarise evidence on falls and subsequent social isolation and/or loneliness in older adults through a scoping review. ELIGIBILITY CRITERIA: Studies were eligible for inclusion if the population had a mean age of 60 years or older, they examined falls and subsequent social isolation, loneliness, fear of falling or risk factors and were primary studies (eg, experimental, quasi-experimental, observational and qualitative). SOURCES OF EVIDENCE: MEDLINE, CINAHL, Embase, Ageline and grey literature from inception until 11 January 2021. CHARTING METHODS: A screening and charting form was developed and pilot-tested. Subsequently, two reviewers screened citations and full-text articles, and charted the evidence. RESULTS: After screening 4993 citations and 304 full-text articles, 39 studies were included in this review. Participants had a history of falling (range: 11% to 100%). Most studies were conducted in Europe (44%) and North America (33%) and were of the cross-sectional study design (66.7%), in the community (79%). Studies utilised 15 different scales. Six studies examined risk factors for social isolation and activity restriction associated with fear of falling. Six studies reported mental health outcomes related to falls and subsequent social isolation. CONCLUSIONS: Consistency in outcome measurement is recommended, as multiple outcomes were used across the included studies. Further research is warranted in this area, given the ageing population and the importance of falls and social isolation to the health of older adults. SCOPING REVIEW REGISTRATION NUMBER: 10.17605/OSF.IO/2R8HM.

Text mining to support abstract screening for knowledge syntheses: a semi-automated workflow.

BACKGROUND: Current text mining tools supporting abstract screening in systematic reviews are not widely used, in part because they lack sensitivity and precision. We set out to develop an accessible, semi-automated "workflow" to conduct abstract screening for systematic reviews and other knowledge synthesis methods. METHODS: We adopt widely recommended text-mining and machine-learning methods to (1) process title-abstracts into numerical training data; and (2) train a classification model to predict eligible abstracts. The predicted abstracts are screened by human reviewers for ("true") eligibility, and the newly eligible abstracts are used to identify similar abstracts, using near-neighbor methods, which are also screened. These abstracts, as well as their eligibility results, are used to update the classification model, and the above steps are iterated until no new eligible abstracts are identified. The workflow was implemented in R and evaluated using a systematic review of insulin formulations for type-1 diabetes (14,314 abstracts) and a scoping review of knowledge-synthesis methods (17,200 abstracts). Workflow performance was evaluated against the recommended practice of screening abstracts by 2 reviewers, independently. Standard measures were examined: sensitivity (inclusion of all truly eligible abstracts), specificity (exclusion of all truly ineligible abstracts), precision (inclusion of all truly eligible abstracts among all abstracts screened as eligible), F1-score (harmonic average of sensitivity and precision), and accuracy (correctly predicted eligible or ineligible abstracts). Workload reduction was measured as the hours the workflow saved, given only a subset of abstracts needed human screening. RESULTS: With respect to the systematic and scoping reviews respectively, the workflow attained 88%/89% sensitivity, 99%/99% specificity, 71%/72% precision, an F1-score of 79%/79%, 98%/97% accuracy, 63%/55% workload reduction, with 12%/11% fewer abstracts for full-text retrieval and screening, and 0%/1.5% missed studies in the completed reviews. CONCLUSION: The workflow was a sensitive, precise, and efficient alternative to the recommended practice of screening abstracts with 2 reviewers. All eligible studies were identified in the first case, while 6 studies (1.5%) were missed in the second that would likely not impact the review's conclusions. We have described the workflow in language accessible to reviewers with limited exposure to natural language processing and machine learning, and have made the code available to reviewers.

Anti-vascular endothelial growth factor therapy for age-related macular degeneration: a systematic review and network meta-analysis.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42015022041.

Fall prevention interventions for older community-dwelling adults: systematic reviews on benefits, harms, and patient values and preferences.

BACKGROUND: An estimated 20-30% of community-dwelling Canadian adults aged 65 years or older experience one or more falls each year. Fall-related injuries are a leading cause of hospitalization and can lead to functional independence. Many fall prevention interventions, often based on modifiable risk factors, have been studied. Apart from the magnitude of the benefits and harms from different interventions, the preferences of older adults for different interventions as well as the relative importance they place on the different potential outcomes may influence recommendations by guideline panels. These reviews on benefits and harms of interventions, and on patient values and preferences, will inform the Canadian Task Force on Preventive Health Care to develop recommendations on fall prevention for primary care providers. METHODS: To review the benefits and harms of fall prevention interventions, we will update a previous systematic review of randomized controlled trials with adaptations to modify the classification of interventions and narrow the scope to community-dwelling older adults and primary-care relevant interventions. Four databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Ageline), reference lists, trial registries, and relevant websites will be searched, using limits for randomized trials and date (2016 onwards). We will classify interventions according to the Prevention of Falls Network Europe (ProFANE) Group's taxonomy. Outcomes include fallers, falls, injurious falls, fractures, hip fractures, institutionalization, health-related quality of life, functional status, and intervention-related adverse effects. For studies not included in the previous review, screening, study selection, data extraction on outcomes, and risk of bias assessments will be independently undertaken by two reviewers with consensus used for final decisions. Where quantitative analysis is suitable, network or pairwise meta-analysis will be conducted using a frequentist approach in Stata. Assessment of the transitivity and coherence of the network meta-analyses will be undertaken. For the reviews on patient preferences and outcome valuation (relative importance of outcomes), we will perform de novo reviews with searches in three databases (MEDLINE, PsycInfo, and CINAHL) and reference lists for cross-sectional, longitudinal quantitative, or qualitative studies published from 2000. Selection, data extraction, and risk of bias assessments suitable for each study design will be performed in duplicate. The analysis will be guided by a narrative synthesis approach, which may include meta-analysis for health-state utilities. We will use the CINeMa approach to a rate the certainty of the evidence for outcomes on intervention effects analyzed using network meta-analysis and the GRADE approach for all other outcomes. DISCUSSION: We will describe the flow of literature and characteristics of all studies and present results of all analyses and summary of finding tables. We will compare our findings to others and discuss the limitations of the reviews and the available literature. SYSTEMATIC REVIEW REGISTRATION: This protocol has not been registered.

Comparative effectiveness of exercise interventions for preventing falls in older adults: A secondary analysis of a systematic review with network meta-analysis.

BACKGROUND: Systematic reviews have established that exercise reduces falls in older adults, however the most effective types of exercise are not known. This secondary analysis determined the comparative effectiveness of fall prevention exercise approaches. METHOD: All fall prevention exercise interventions for older adults were identified from an existing search from inception until April 2017. Interventions were coded using a framework of 25 exercise types. Two reviewers independently screened studies, extracted data, and appraised risk of bias. Pairwise meta-analysis and network meta-analysis (NMA) were conducted. P-scores were used to rank exercise combinations. RESULTS: One hundred and sixty-nine studies were included. NMA was conducted on 73 studies (30,697 participants) for the outcome of number of fallers. The exercise combination ranked with the greatest likelihood of being most effective relative to no exercise was: anticipatory control, dynamic stability, functional stability limits, reactive control and flexibility (p-score = 0.95). This exercise combination also significantly reduced number of fallers compared to 16 other combinations. No exercise combination had a significantly greater effect on reducing number of fallers more than this combination. CONCLUSION: This analysis identified components of effective fall prevention exercise. The results can inform evidence-informed exercise recommendations and be used to design effective programs.

Feasibility of prehospital delivery of remote ischemic conditioning by emergency medical services in chest pain patients: protocol for a pilot study.

BACKGROUND: Remote ischemic conditioning (RIC) is a non-invasive procedure with hypothesized therapeutic benefits for patients experiencing an acute ST-elevation myocardial infarction (STEMI). Further study of emergency medical services (EMS) delivery of RIC in the prehospital setting is needed to inform the design and methods for future clinical trials of RIC in STEMI patients. The main objective of this pilot study is to assess the feasibility of prehospital delivery of RIC by EMS providers in the United States. METHODS: We will conduct a single-arm study of the standard RIC procedure (i.e., up to 4 cycles of alternating 5-min inflation and 5-min deflation of an upper arm cuff) administered by EMS paramedics in 50 patients experiencing acute onset chest pain. The investigational autoRIC® device (CellAegis Devices, Inc., Toronto, Ontario) will be initiated by paramedics during ground ambulance transport. Automated RIC cycles will continue through emergency department arrival and stay. The primary endpoint will be the completion of all 4 cycles of RIC without interruption. We will also examine study procedures and collect qualitative data from study participants and paramedics. DISCUSSION: To our knowledge, this will be the first study in the United States to assess the feasibility of completing the 40-min RIC procedure when initiated during ground ambulance transport. Findings from this pilot study will be used to optimize the design and methods for a future efficacy trial of RIC in acute STEMI patients. TRIAL REGISTRATION: NCT03400579 (ClinicalTrials.gov). Registered on 17 January 2018.

Few studies exist examining methods for selecting studies, abstracting data, and appraising quality in a systematic review.

OBJECTIVES: The aim of the article was to identify and summarize studies assessing methodologies for study selection, data abstraction, or quality appraisal in systematic reviews. STUDY DESIGN AND SETTING: A systematic review was conducted, searching MEDLINE, EMBASE, and the Cochrane Library from inception to September 1, 2016. Quality appraisal of included studies was undertaken using a modified Quality Assessment of Diagnostic Accuracy Studies 2, and key results on accuracy, reliability, efficiency of a methodology, or impact on results and conclusions were extracted. RESULTS: After screening 5,600 titles and abstracts and 245 full-text articles, 37 studies were included. For screening, studies supported the involvement of two independent experienced reviewers and the use of Google Translate when screening non-English articles. For data abstraction, studies supported involvement of experienced reviewers (especially for continuous outcomes) and two independent reviewers, use of dual monitors, graphical data extraction software, and contacting authors. For quality appraisal, studies supported intensive training, piloting quality assessment tools, providing decision rules for poorly reported studies, contacting authors, and using structured tools if different study designs are included. CONCLUSION: Few studies exist documenting common systematic review practices. Included studies support several systematic review practices. These results provide an updated evidence-base for current knowledge synthesis guidelines and methods requiring further research.