Creating efficiencies in the extraction of data from randomized trials: a prospective evaluation of a machine learning and text mining tool.

BACKGROUND: Machine learning tools that semi-automate data extraction may create efficiencies in systematic review production. We evaluated a machine learning and text mining tool's ability to (a) automatically extract data elements from randomized trials, and (b) save time compared with manual extraction and verification. METHODS: For 75 randomized trials, we manually extracted and verified data for 21 data elements. We uploaded the randomized trials to an online machine learning and text mining tool, and quantified performance by evaluating its ability to identify the reporting of data elements (reported or not reported), and the relevance of the extracted sentences, fragments, and overall solutions. For each randomized trial, we measured the time to complete manual extraction and verification, and to review and amend the data extracted by the tool. We calculated the median (interquartile range [IQR]) time for manual and semi-automated data extraction, and overall time savings. RESULTS: The tool identified the reporting (reported or not reported) of data elements with median (IQR) 91% (75% to 99%) accuracy. Among the top five sentences for each data element at least one sentence was relevant in a median (IQR) 88% (83% to 99%) of cases. Among a median (IQR) 90% (86% to 97%) of relevant sentences, pertinent fragments had been highlighted by the tool; exact matches were unreliable (median (IQR) 52% [33% to 73%]). A median 48% of solutions were fully correct, but performance varied greatly across data elements (IQR 21% to 71%). Using ExaCT to assist the first reviewer resulted in a modest time savings compared with manual extraction by a single reviewer (17.9 vs. 21.6 h total extraction time across 75 randomized trials). CONCLUSIONS: Using ExaCT to assist with data extraction resulted in modest gains in efficiency compared with manual extraction. The tool was reliable for identifying the reporting of most data elements. The tool's ability to identify at least one relevant sentence and highlight pertinent fragments was generally good, but changes to sentence selection and/or highlighting were often required. PROTOCOL: https://doi.org/10.7939/DVN/RQPJKS.

Screening for Gestational Diabetes: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Gestational diabetes is associated with several poor health outcomes. Objective: To update the 2012 review on screening for gestational diabetes to inform the US Preventive Services Task Force. Data Sources: MEDLINE, EMBASE, and CINAHL (2010 to May 2020), ClinicalTrials.gov, reference lists; surveillance through June 2021. Study Selection: English-language intervention studies for screening and treatment; observational studies on screening; prospective studies on screening test accuracy. Data Extraction and Synthesis: Dual review of titles/abstracts, full-text articles, and study quality. Single-reviewer data abstraction with verification. Random-effects meta-analysis or bivariate analysis (accuracy). Main Outcomes and Measures: Pregnancy, fetal/neonatal, and long-term health outcomes; harms of screening; accuracy. Results: A total of 76 studies were included (18 randomized clinical trials [RCTs] [n = 31 241], 2 nonrandomized intervention studies [n = 190], 56 observational studies [n = 261 678]). Direct evidence on benefits of screening vs no screening was limited to 4 observational studies with inconsistent findings and methodological limitations. Screening was not significantly associated with serious or long-term harm. In 5 RCTs (n = 25 772), 1-step (International Association of Diabetes and Pregnancy Study Group) vs 2-step (Carpenter and Coustan) screening was significantly associated with increased likelihood of gestational diabetes (11.5% vs 4.9%) but no improved health outcomes. At or after 24 weeks of gestation, oral glucose challenge tests with 140- and 135-mg/dL cutoffs had sensitivities of 82% and 93%, respectively, and specificities of 82% and 79%, respectively, against Carpenter and Coustan criteria, and a test with a 140-mg/dL cutoff had sensitivity of 85% and specificity of 81% against the National Diabetes Group Data criteria. Fasting plasma glucose tests with cutoffs of 85 and 90 mg/dL had sensitivities of 88% and 81% and specificities of 73% and 82%, respectively, against Carpenter and Coustan criteria. Based on 8 RCTs and 1 nonrandomized study (n = 3982), treatment was significantly associated with decreased risk of primary cesarean deliveries (relative risk [RR], 0.70 [95% CI, 0.54-0.91]; absolute risk difference [ARD], 5.3%), shoulder dystocia (RR, 0.42 [95% CI, 0.23-0.77]; ARD, 1.3%), macrosomia (RR, 0.53 [95% CI, 0.41-0.68]; ARD, 8.9%), large for gestational age (RR, 0.56 [95% CI, 0.47-0.66]; ARD, 8.4%), birth injuries (odds ratio, 0.33 [95% CI, 0.11-0.99]; ARD, 0.2%), and neonatal intensive care unit admissions (RR, 0.73 [95% CI, 0.53-0.99]; ARD, 2.0%). The association with reduction in preterm deliveries was not significant (RR, 0.75 [95% CI, 0.56-1.01]). Conclusions and Relevance: Direct evidence on screening vs no screening remains limited. One- vs 2-step screening was not significantly associated with improved health outcomes. At or after 24 weeks of gestation, treatment of gestational diabetes was significantly associated with improved health outcomes.

Effectiveness and safety of interventions to manage childhood overweight and obesity: An Overview of Cochrane systematic reviews.

BACKGROUND: Childhood overweight and obesity are associated with adverse physical, social, and psychological outcomes. OBJECTIVES: We conducted an overview of Cochrane systematic reviews on the effectiveness and risks of interventions to treat overweight and obesity in children and adolescents. METHODS: In June 2019, we searched the Cochrane Database of Systematic Reviews for eligible reviews. The primary outcomes were change in adiposity (body mass and body mass index [BMI] z-score) and adverse events. Two reviewers screened studies and one reviewer extracted and another verified data. Two reviewers assessed methodological quality and reached consensus. Data were synthesized narratively. RESULTS: We included seven Cochrane reviews published between 2011 and 2017 containing evidence from 167 randomized controlled trials with 21,050 participants. Lifestyle and behavioural interventions more effectively reduced weight compared with no intervention, usual care, or another behavioural treatment (three reviews, low-to-moderate certainty). Parent-child lifestyle and behavioural interventions more effectively reduced BMI z-score compared with no intervention (one review, low certainty). Decision support tools for healthcare providers more effectively limited increases in BMI z-score compared with usual care (one review, moderate certainty). Pharmacologic treatments combined with behavioural modification more effectively reduced adiposity compared with placebo or usual care (one review, low certainty), but the risk of adverse events was greater than non-pharmacologic therapy. Surgical interventions (e.g., LAP-BAND) combined with behavioural modification more effectively reduced adiposity compared with behavioural modification alone (one review, low certainty). Those who underwent surgery reported a higher number of adverse events compared with those treated with lifestyle modification. CONCLUSIONS: There is low-certainty evidence that lifestyle and behavioural interventions, pharmacologic interventions, and surgical interventions are effective in weight management for children with overweight and obesity. Safety data remain lacking across all intervention modalities. Future research should focus on implementation strategies. Further, a focus on overall well-being may be more beneficial than weight management specifically.

How Perceptions Impact Recovery from Concussion in Childhood and Adolescence: a Systematic Review.

Perceptions about the causes and consequences of concussion, and individual representations and interpretations of these factors, can influence the post-concussive recovery process. The goal of this project was to synthesize evidence on perceptions related to concussions as experienced by children, adolescents, and parents, and to evaluate how these perceptions impact post-concussive recovery in physical, behavioural, cognitive, and psychological domains. We undertook a systematic review based on the Cochrane Handbook, conducting a comprehensive search of six databases and Google Scholar. Duplicate, independent screening was employed and the quality of studies was assessed using the Mixed Methods Appraisal Tool (MMAT). A total of 1552 unique records were identified, and six records (5 scientific articles and 1 thesis, published between 1990 and 2018; N = 26 to 412, age range from 2 to 18 years) were included. Perceptions about concussions were assessed differently between studies, with a range in types of measures and respondents. Some evidence suggested that perceptions could negatively impact concussion recovery, mostly post-concussive symptoms. However, results were not consistent between studies and the methodological quality was variable (and often low). There is limited evidence of the impact of perceptions of children, adolescents, and their parents on concussion recovery. Priorities for future research investigating concussion recovery should include recruiting representative samples, accounting for potential confounders, and measuring perceptions in children, adolescents and parents using validated measures. Higher quality studies are needed to better understand the role of perceptions in concussion recovery and to inform clinical care.

The semi-automation of title and abstract screening: a retrospective exploration of ways to leverage Abstrackr's relevance predictions in systematic and rapid reviews.

BACKGROUND: We investigated the feasibility of using a machine learning tool's relevance predictions to expedite title and abstract screening. METHODS: We subjected 11 systematic reviews and six rapid reviews to four retrospective screening simulations (automated and semi-automated approaches to single-reviewer and dual independent screening) in Abstrackr, a freely-available machine learning software. We calculated the proportion missed, workload savings, and time savings compared to single-reviewer and dual independent screening by human reviewers. We performed cited reference searches to determine if missed studies would be identified via reference list scanning. RESULTS: For systematic reviews, the semi-automated, dual independent screening approach provided the best balance of time savings (median (range) 20 (3-82) hours) and reliability (median (range) proportion missed records, 1 (0-14)%). The cited references search identified 59% (n = 10/17) of the records missed. For the rapid reviews, the fully and semi-automated approaches saved time (median (range) 9 (2-18) hours and 3 (1-10) hours, respectively), but less so than for the systematic reviews. The median (range) proportion missed records for both approaches was 6 (0-22)%. CONCLUSION: Using Abstrackr to assist one of two reviewers in systematic reviews saves time with little risk of missing relevant records. Many missed records would be identified via other means.

The Conduct and Reporting of Child Health Research: An Analysis of Randomized Controlled Trials Published in 2012 and Evaluation of Change over 5 Years.

OBJECTIVES: For child health randomized controlled trials (RCTs) published in 2012, we aimed to describe design and reporting characteristics and evaluate changes since 2007; assess the association between trial design and registration and risk of bias (RoB); and assess the association between RoB and effect size. STUDY DESIGN: For 300 RCTs, we extracted design and reporting characteristics and assessed RoB. We assessed 5-year changes in design and reporting (based on 300 RCTs we had previously analyzed) using the Fisher exact test. We tested for associations between design and reporting characteristics and overall RoB and registration using the Fisher exact, Cochran-Armitage, Kruskal-Wallis, and Jonckheere-Terpstra tests. We pooled effect sizes and tested for differences by RoB using the χ2 test for subgroups in meta-analysis. RESULTS: The 2012 and 2007 RCTs differed with respect to many design and reporting characteristics. From 2007 to 2012, RoB did not change for random sequence generation and improved for allocation concealment (P < .001). Fewer 2012 RCTs were rated high overall RoB and more were rated unclear (P = .03). Only 7.3% of 2012 RCTs were rated low overall RoB. Trial registration doubled from 2007 to 2012 (23% to 46%) (P < .001) and was associated with lower RoB (P = .009). Effect size did not differ by RoB (P = .43) CONCLUSIONS: Random sequence generation and allocation concealment were not often reported, and selective reporting was prevalent. Measures to increase trialists' awareness and application of existing reporting guidance, and the prospective registration of RCTs is needed to improve the trustworthiness of findings from this field.

Glucocorticoids for croup in children.

BACKGROUND: Glucocorticoids are commonly used for croup in children. This is an update of a Cochrane Review published in 1999 and previously updated in 2004 and 2011. OBJECTIVES: To examine the effects of glucocorticoids for the treatment of croup in children aged 0 to 18 years. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 2, 2018), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 3 April 2018), and Embase (Ovid) (1996 to 3 April 2018, week 14), and the trials registers ClinicalTrials.gov (3 April 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 3 April 2018). We scanned the reference lists of relevant systematic reviews and of the included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated children aged 0 to 18 years with croup and measured the effects of glucocorticoids, alone or in combination, compared to placebo or another pharmacologic treatment. The studies needed to report at least one of our primary or secondary outcomes: change in croup score; return visits, (re)admissions or both; length of stay; patient improvement; use of additional treatments; and adverse events. DATA COLLECTION AND ANALYSIS: One author extracted data from each study and another verified the extraction. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed risk of bias for each study using the Cochrane 'Risk of bias' tool and the certainty of the body of evidence for the primary outcomes using the GRADE approach. MAIN RESULTS: We added five new RCTs with 330 children. This review now includes 43 RCTs with a total of 4565 children. We assessed most (98%) studies as at high or unclear risk of bias. Compared to placebo, glucocorticoids improved symptoms of croup at two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs; 426 children; moderate-certainty evidence), and the effect lasted for at least 24 hours (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs; 351 children; low-certainty evidence). Compared to placebo, glucocorticoids reduced the rate of return visits or (re)admissions or both (risk ratio 0.52, 95% CI 0.36 to 0.75; 10 RCTs; 1679 children; moderate-certainty evidence). Glucocorticoid treatment reduced the length of stay in hospital by about 15 hours (mean difference -14.90, 95% CI -23.58 to -6.22; 8 RCTs; 476 children). Serious adverse events were infrequent. Publication bias was not evident. Uncertainty remains with regard to the optimal type, dose, and mode of administration of glucocorticoids for reducing croup symptoms in children. AUTHORS' CONCLUSIONS: Glucocorticoids reduced symptoms of croup at two hours, shortened hospital stays, and reduced the rate of return visits to care. Our conclusions have changed, as the previous version of this review reported that glucocorticoids reduced symptoms of croup within six hours.

Peer-led nutrition education programs for school-aged youth: a systematic review of the literature.

To date, the impacts of school-based, peer-led nutrition education initiatives have not been summarized or assessed collectively. This review presents the current evidence, identifies knowledge gaps, and provides recommendations for future research. PubMed, Scopus, ERIC and Google Scholar were searched for refereed Canadian and American primary studies published between January 2000 and November 2013, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seventeen articles (11 programs) from Canada (24%) and the United States (76%) were identified. The results were summarized in terms of the study population, program design and main outcomes. Common outcome measures included healthy eating knowledge (n = 5), self-efficacy or attitudes towards healthy eating (n = 13), dietary measures (n = 9) and body mass index (n = 4), all of which tended to improve as a result of the programs. More research is needed to ascertain the effect of improvements in knowledge, self-efficacy and attitudes towards healthy eating on food behaviors. When evaluated, programs were generally well received, while the long-term maintenance of positive impacts was a challenge. Studies of sustainability and feasibility to promote long-term impact are a logical next step.

Physical Activity and Fitness of First Nations Youth in a Remote and Isolated Northern Ontario Community: A Needs Assessment.

Among a group of First Nations youth, this research aimed to obtain objective measures of anthropometry, physical activity (PA) and fitness; to identify any group-level differences by sex, body mass index, waist circumference and body fat categories; to assess the barriers and supports to PA. Youth participated in anthropometric measures (BMI, waist circumference, body fat percentage), PA assessment (3 days of accelerometry) and fitness testing (guided by the Canadian Physical Activity, Fitness and Lifestyle Approach). Barriers and supports were assessed via environmental scan and focus groups. Descriptive statistics were compared to reference data. Group differences by sex, BMI status, waist circumference and body fat categories were tested using Mann-Whitney U and Chi square tests (p ≤ 0.05). Qualitative data were assembled into one file and coded manually for categories and themes. Seventy-two youth (12.1 ± 1.1 years, 61.1% male) participated in at least one measure; 36 completed the accelerometry. Sixty-three percent were overweight or obese, 51% were abdominally obese and 21% had excess body fat. Most (86.1%) met Canada's PA guidelines. Boys were more active than girls (p = 0.025) and had greater cardiorespiratory endurance (p = 0.003). Overweight, obese, or abdominally obese youth had lower cardiorespiratory endurance than normal weight youth (p < 0.001). Barriers and supports fell under the main themes: motivation, role models, personnel and facilities, environment and programs. Based on this assessment, youth in this community are active, but not sufficiently physically fit, especially among those affected by obesity and abdominal obesity. The findings, in addition to the numerous barriers to PA, support the community's desire for school-based PA programming.

Body weight perceptions and eating-related weight control behaviors of on-reserve First Nations youth from Ontario, Canada.

INTRODUCTION: Research investigating the body weight perceptions and eating-related weight control behaviors of First Nations (FN) youth living on reserve in Canada has been scarce. Knowledge of body weight perceptions may help to improve the relevance of initiatives promoting healthy weights. The purpose of this study was to examine the body weight perceptions and eating-related weight control behaviors of grade 6-8 on-reserve FN youth from seven Ontario communities. METHODS: Data were collected from December 2003 to June 2010 from a convenience sample of FN youth (aged 10-14 years) using the Waterloo Web-based Eating Behaviour Questionnaire (WEB-Q). Participants were categorized into body mass index (BMI) categories based on International Obesity Task Force (IOTF) cut points. Frequency statistics were computed in the comparison of measured BMI and weight perceptions and weight control behaviors. Differences by BMI category were tested using Pearson Χ2 tests. RESULTS: A total of 267 youth from seven Ontario FN communities participated in the study (48.6% male). Overall, 36.3% of youth were overweight and 21.3% were obese (combined total of 57.6%). Similar to non-Aboriginal youth, a greater proportion of FN girls who were at a normal weight were concerned that their weight was too high compared to boys. However, one-third of normal weight boys were currently trying to lose weight. A greater proportion of obese girls were trying to lose weight compared to boys. Overall, a large proportion of both overweight boys and girls were attempting to gain weight. CONCLUSIONS: The present study provides a unique investigation into the weight perceptions and weight control behaviors of on-reserve FN youth living in isolated communities in Ontario, Canada. Many of the perceptions elucidated in this study are similar to those observed in non-Aboriginal youth, while others differed. The knowledge of these perceptions and further research to investigate what factors influences them will help to customize health promoting initiatives that are relevant to the youth in the participating communities.

Intakes of milk and alternatives among on-reserve First Nations youth in northern and southern Ontario, Canada.

OBJECTIVE: To assess the adequacy of milk and alternatives, Ca and vitamin D intakes in First Nations (FN) youth in Ontario, Canada. Intakes were compared with the general population and dietary standards. Variation in intakes by community (proxy for remoteness) and BMI was examined. DESIGN: Data were collected by 24 h recall between November 2003 and June 2010. Intakes were analysed descriptively. Variation in intakes, by community and BMI category, was assessed using ANOVA. SETTING: Five remote FN communities of the Mushkegowuk Territory (northern Ontario, Canada) and two less-remote southern Ontario FN communities. SUBJECTS: Schoolchildren (n 457) in grades 6 to 12. RESULTS: Compared with Canada's Food Guide recommendations, 72.6 to 84.7% had an inadequate intake of milk and alternatives depending on age and sex group; 86.2% of individuals fell below the RDA for Ca; 96.4% fell below the RDA for vitamin D. Community variation in intakes was detected, although in all cases Fort Albany had higher intakes, even when it was the more northern (remote) community. A BMI × sex interaction was found for intake of milk and alternatives (P = 0.041): an inverse relationship between intake and BMI was seen in females; in males, those who were overweight had the highest intake, followed by normal-weight and obese youth. CONCLUSIONS: The nutritional inadequacies parallel the results of other Canadian studies of Aboriginal populations. Population health interventions to improve intakes are warranted. Moreover, community variation in intakes exists among FN youth in the present study (Fort Albany pairs only), but results were not as expected.

Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease.

Age-related disease, not aging per se, causes most morbidity in older humans. Here we report that skeletal muscle respiratory uncoupling due to UCP1 expression diminishes age-related disease in three mouse models. In a longevity study, median survival was increased in UCP mice (animals with skeletal muscle-specific UCP1 expression), and lymphoma was detected less frequently in UCP female mice. In apoE null mice, a vascular disease model, diet-induced atherosclerosis was decreased in UCP animals. In agouti yellow mice, a genetic obesity model, diabetes and hypertension were reversed by induction of UCP1 in skeletal muscle. Uncoupled mice had decreased adiposity, increased temperature and metabolic rate, elevated muscle SIRT and AMP kinase, and serum characterized by increased adiponectin and decreased IGF-1 and fibrinogen. Accelerating metabolism in skeletal muscle does not appear to impact aging but may delay age-related disease.

Reporting guideline for overviews of reviews of healthcare interventions: development of the PRIOR statement.

OBJECTIVE: To develop a reporting guideline for overviews of reviews of healthcare interventions. DESIGN: Development of the preferred reporting items for overviews of reviews (PRIOR) statement. PARTICIPANTS: Core team (seven individuals) led day-to-day operations, and an expert advisory group (three individuals) provided methodological advice. A panel of 100 experts (authors, editors, readers including members of the public or patients) was invited to participate in a modified Delphi exercise. 11 expert panellists (chosen on the basis of expertise, and representing relevant stakeholder groups) were invited to take part in a virtual face-to-face meeting to reach agreement (≥70%) on final checklist items. 21 authors of recently published overviews were invited to pilot test the checklist. SETTING: International consensus. INTERVENTION: Four stage process established by the EQUATOR Network for developing reporting guidelines in health research: project launch (establish a core team and expert advisory group, register intent), evidence reviews (systematic review of published overviews to describe reporting quality, scoping review of methodological guidance and author reported challenges related to undertaking overviews of reviews), modified Delphi exercise (two online Delphi surveys to reach agreement (≥70%) on relevant reporting items followed by a virtual face-to-face meeting), and development of the reporting guideline. RESULTS: From the evidence reviews, we drafted an initial list of 47 potentially relevant reporting items. An international group of 52 experts participated in the first Delphi survey (52% participation rate); agreement was reached for inclusion of 43 (91%) items. 44 experts (85% retention rate) completed the second Delphi survey, which included the four items lacking agreement from the first survey and five new items based on respondent comments. During the second round, agreement was not reached for the inclusion or exclusion of the nine remaining items. 19 individuals (6 core team and 3 expert advisory group members, and 10 expert panellists) attended the virtual face-to-face meeting. Among the nine items discussed, high agreement was reached for the inclusion of three and exclusion of six. Six authors participated in pilot testing, resulting in minor wording changes. The final checklist includes 27 main items (with 19 sub-items) across all stages of an overview of reviews. CONCLUSIONS: PRIOR fills an important gap in reporting guidance for overviews of reviews of healthcare interventions. The checklist, along with rationale and example for each item, provides guidance for authors that will facilitate complete and transparent reporting. This will allow readers to assess the methods used in overviews of reviews of healthcare interventions and understand the trustworthiness and applicability of their findings.

Vascular respiratory uncoupling increases blood pressure and atherosclerosis.

The observations that atherosclerosis often occurs in non-smokers without elevated levels of low-density lipoprotein cholesterol, and that most atherosclerosis loci so far identified in mice do not affect systemic risk factors associated with atherosclerosis, suggest that as-yet-unidentified mechanisms must contribute to vascular disease. Arterial walls undergo regional disturbances of metabolism that include the uncoupling of respiration and oxidative phosphorylation, a process that occurs to some extent in all cells and may be characteristic of blood vessels being predisposed to the development of atherosclerosis. To test the hypothesis that inefficient metabolism in blood vessels promotes vascular disease, we generated mice with doxycycline-inducible expression of uncoupling protein-1 (UCP1) in the artery wall. Here we show that UCP1 expression in aortic smooth muscle cells causes hypertension and increases dietary atherosclerosis without affecting cholesterol levels. UCP1 expression also increases superoxide production and decreases the availability of nitric oxide, evidence of oxidative stress. These results provide proof of principle that inefficient metabolism in blood vessels can cause vascular disease.

LOCATE: a prospective evaluation of the value of Leveraging Ongoing Citation Acquisition Techniques for living Evidence syntheses.

BACKGROUND: Living systematic reviews (LSRs) can expedite evidence synthesis by incorporating new evidence in real time. However, the methods needed to identify new studies in a timely manner are not well established. OBJECTIVES: To explore the value of complementary search approaches in terms of search performance, impact on results and conclusions, screening workload, and feasibility compared to the reference standard. METHODS: We developed three complementary search approaches for a systematic review on treatments for bronchiolitis: Automated Full Search, PubMed Similar Articles, and Scopus Citing References. These were automated to retrieve results monthly; pairs of reviewers screened the records and commented on feasibility. After 1 year, we conducted a full update search (reference standard). For each complementary approach, we compared search performance (proportion missed, number needed to read [NNR]) and reviewer workload (number of records screened, time required) to the reference standard. We investigated the impact of the new trials on the effect estimate and certainty of evidence for the primary outcomes. We summarized comments about feasibility. RESULTS: Via the reference standard, reviewers screened 505 titles/abstracts, 24 full texts, and identified four new trials (NNR 127; 12.4 h). Of the complementary approaches, only the Automated Full Search located all four trials; these were located 6 to 12 months sooner than via the reference standard but did not alter the results nor certainty in the evidence. The Automated Full Search was the most resource-intensive approach (816 records screened; NNR 204; 17.1 h). The PubMed Similar Articles and Scopus Citing References approaches located far fewer records (452 and 244, respectively), thereby requiring less screening time (9.4 and 5.2 h); however, each approach located only one of the four new trials. Reviewers found it feasible and convenient to conduct monthly screening for searches of this yield (median 15-65 records/month). CONCLUSIONS: The Automated Full Search was the most resource-intensive approach, but also the only to locate all of the newly published trials. Although the monthly screening time for the PubMed Similar Articles and Scopus Citing Articles was far less, most relevant records were missed. These approaches were feasible to integrate into reviewer work processes. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework. https://doi.org/10.17605/OSF.IO/6M28H .

Health inequities related to vaccination: An evidence map of potentially influential factors and systematic review of interventions.

INTRODUCTION: The National Advisory Committee on Immunization (NACI) makes recommendations for vaccines in Canada. To inform considerations for equity when making recommendations, the NACI Secretariat developed a matrix of factors that may influence vaccine equity. To inform the matrix we mapped the evidence for P2ROGRESS And Other factors potentially associated with unequal levels of illness or death from vaccine-preventable diseases (VPDs) and systematically reviewed the evidence for interventions aimed at reducing inequities. METHODS: In October 2019 we searched Medline, Embase, and CINAHL. Two reviewers agreed on the included studies. Our primary outcomes were VPD-related hospitalizations and deaths. Secondary outcomes were differential vaccine access, and exposure, susceptibility, severity, and consequences of VPDs. Two reviewers appraised the certainty of evidence. We mapped the evidence for P2ROGRESS And Other factors and summarized the findings descriptively. We summarized the interventions narratively. RESULTS: We identified 413 studies reporting on P2ROGRESS And Other factors. The most commonly investigated factors included age (n = 374, 89%), pre-existing conditions (n = 179, 42%), and gender identity or sex (n = 144, 34%). We identified 2 trials investigating the effects of interventions. One (n = 1249) provided very low certainty evidence that staff vaccination policies may reduce hospitalizations and deaths from influenza among private care home residents. The other (n not reported) provided very low certainty evidence that universal vaccination by nurses in clinics may reduce hospitalizations for rotavirus gastroenteritis compared with vaccination by physicians or no intervention. CONCLUSIONS: There is a large body of studies reporting on hospitalizations and deaths from VPDs stratified by P2ROGRESS And Other factors. We found only two trials examining the effects of interventions on hospitalization for or mortality from VPDs. This review has been helpful to NACI and will be helpful to similar organizations aiming to systematically identify and target health inequities through the development of vaccine program recommendations.

P value and Bayesian analysis in randomized-controlled trials in child health research published over 10 years, 2007 to 2017: a methodological review protocol.

BACKGROUND: There is an unresolved debate about the reliability of the interpretation of P value. Some investigators have suggested that an alternative Bayesian method is preferred in conducting health research. As randomized-controlled trials (RCTs) are important in generating research evidence, we decided to investigate the extent, if any, the inferential statistical framework in published RCTs in child health research have changed over 10 years. We aim to examine the change in P value and Bayesian analysis in RCTs in child health research papers published from 2007 to 2017. METHODS: We will search the Cochrane Central Register of Controlled Trials (Wiley) to identify relevant citations. We will leverage a pre-existing sample of child health RCTs published in 2007 (n=300) used in our previous study of reporting quality of pediatric RCTs. Using the same strategy and study selection methods, we will identify a comparable random sample of child health RCTs published in 2017 (n=300). Eligible studies will include RCTs in health research among individuals aged 21 years and below. One reviewer will select studies for inclusion and extract the data and another reviewer will verify these. Disagreements will be resolved by a discussion between reviewers or by involving another reviewer. We will perform a descriptive analysis of 2007 and 2017 samples and analyze the results using both the frequentist and Bayesian methods. We will present specific characteristics of the clinical trials from 2007 and 2017 in tabular and graphical forms. We will report the difference in the proportion of P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. Clustering around P values of significance, if observed, will be reported. DISCUSSION: This review will present the difference in the proportion of trials that reported on P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. The implications for future clinical research will be discussed and this research work will be published in a peer-reviewed journal. This review has the potential to help inform the need for a change in the methodological approach from the null hypothesis significance test to Bayesian methods. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework https://osf.io/aj2df.

Screening for the prevention and early detection of cervical cancer: protocol for systematic reviews to inform Canadian recommendations.

PURPOSE: To inform recommendations by the Canadian Task Force on Preventive Health Care on screening in primary care for the prevention and early detection of cervical cancer by systematically reviewing evidence of (a) effectiveness; (b) test accuracy; (c) individuals' values and preferences; and (d) strategies aimed at improving screening rates. METHODS: De novo reviews will be conducted to evaluate effectiveness and to assess values and preferences. For test accuracy and strategies to improve screening rates, we will integrate studies from existing systematic reviews with search updates to the present. Two Cochrane reviews will provide evidence of adverse pregnancy outcomes from the conservative management of cervical intraepithelial neoplasia. We will search Medline, Embase, and Cochrane Central (except for individuals' values and preferences, where Medline, Scopus, and EconLit will be searched) via peer-reviewed search strategies and the reference lists of included studies and reviews. We will search ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. Two reviewers will screen potentially eligible studies and agree on those to include. Data will be extracted by one reviewer with verification by another. Two reviewers will independently assess risk of bias and reach consensus. Where possible and suitable, we will pool studies via meta-analysis. We will compare accuracy data per outcome and per comparison using the Rutter and Gatsonis hierarchical summary receiver operating characteristic model and report relative sensitivities and specificities. Findings on values and preferences will be synthesized using a narrative synthesis approach and thematic analysis, depending on study designs. Two reviewers will appraise the certainty of evidence for all outcomes using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and come to consensus. DISCUSSION: The publication of guidance on screening in primary care for the prevention and early detection of cervical cancer by the Task Force in 2013 focused on cytology. Since 2013, new studies using human papillomavirus tests for cervical screening have been published that will improve our understanding of screening in primary care settings. This review will inform updated recommendations based on currently available studies and address key evidence gaps noted in our previous review.

A systematic review of factors that influence the acceptability of vaccines among Canadians.

BACKGROUND: Canada's National Advisory Committee on Immunization (NACI) provides guidance on the use of vaccines in Canada. To support the expansion of its mandate to include considerations for vaccine acceptability when making recommendations, the NACI Secretariat developed a matrix of factors that influence acceptability. To inform and validate the matrix, we systematically reviewed evidence for factors that influence vaccine acceptability, and for interventions aimed at improving acceptability. METHODS: On 10-11 October 2018 we searched four bibliographic databases, the Theses Canada Portal, and ClinicalTrials.gov. Two reviewers agreed on the included studies. From each study, we extracted information about the participants, intervention or exposure, comparator, and relevant outcomes. Due to heterogeneity in the reported factors and acceptability indicators we synthesized the findings narratively. We appraised the certainty of evidence using GRADE. For each vaccine-preventable disease we populated a matrix of factors for which there was evidence of an influence on acceptability. RESULTS: One hundred studies (>1 million participants) contributed data relevant to the public, 16 (6191 participants) to healthcare providers, and three (84 participants) to policymakers. There were 43 intervention studies (~2 million participants). Across vaccines, we identified low certainty evidence for 70 factors relevant to the general population, 56 to high-risk groups, and 30 to healthcare providers. The perceived safety and importance of the vaccine, vaccination history, and receiving a recommendation from a healthcare provider were common influential factors. We found low certainty evidence that reminders for childhood vaccines and policies or delivery models for rotavirus vaccines could improve uptake and coverage. Evidence for other interventions was of very low certainty. CONCLUSIONS: The NACI vaccine acceptability matrix is useful for categorizing acceptability factors for the general public. Reminder systems may improve the uptake of childhood vaccines. Policies that make the rotavirus vaccine universally available and easily accessible may improve coverage. FUNDING: This systematic review was completed under contract to the Public Health Agency of Canada, Contract #4600001536.