Screening for lung cancer with computed tomography: protocol for systematic reviews for the Canadian Task Force on Preventive Health Care.

PURPOSE: Lung cancer is the leading cause of cancer deaths in Canada, and because early cancers are often asymptomatic screening aims to prevent mortality by detecting cancer earlier when treatment is more likely to be curative. These reviews will inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for lung cancer. METHODS: We will update the review on the benefits and harms of screening with CT conducted for the task force in 2015 and perform de novo reviews on the comparative effects between (i) trial-based selection criteria and use of risk prediction models and (ii) trial-based nodule classification and different nodule classification systems and on patients' values and preferences. We will search Medline, Embase, and Cochrane Central (for questions on benefits and harms from 2015; comparative effects from 2012) and Medline, Scopus, and EconLit (for values and preferences from 2012) via peer-reviewed search strategies, clinical trial registries, and the reference lists of included studies and reviews. Two reviewers will screen all citations (including those in the previous review) and base inclusion decisions on consensus or arbitration by another reviewer. For benefits (i.e., all-cause and cancer-specific mortality and health-related quality of life) and harms (i.e., overdiagnosis, false positives, incidental findings, psychosocial harms from screening, and major complications and mortality from invasive procedures as a result of screening), we will include studies of adults in whom lung cancer is not suspected. We will include randomized controlled trials comparing CT screening with no screening or alternative screening modalities (e.g., chest radiography) or strategies (e.g., CT using different screening intervals, classification systems, and/or patient selection via risk models or biomarkers); non-randomized studies, including modeling studies, will be included for the comparative effects between trial-based and other selection criteria or nodule classification methods. For harms (except overdiagnosis) we will also include non-randomized and uncontrolled studies. For values and preferences, the study design may be any quantitative design that either directly or indirectly measures outcome preferences on outcomes pertaining to lung cancer screening. We will only include studies conducted in Very High Human Development Countries and having full texts in English or French. Data will be extracted by one reviewer with verification by another, with the exception of result data on mortality and cancer incidence (for calculating overdiagnosis) where duplicate extraction will occur. If two or more studies report on the same comparison and it is deemed suitable, we will pool continuous data using a mean difference or standardized mean difference, as applicable, and binary data using relative risks and a DerSimonian and Laird model unless events are rare (< 1%) where we will pool odds ratios using Peto's method or (if zero events) the reciprocal of the opposite treatment arm size correction. For pooling proportions, we will apply suitable transformation (logit or arcsine) depending on the proportions of events. If meta-analysis is not undertaken we will synthesize the data descriptively, considering clinical and methodological differences. For each outcome, two reviewers will independently assess within- and across-study risk of bias and rate the certainty of the evidence using GRADE (Grading of Recommendations Assessment, Development, and Evaluation), and reach consensus. DISCUSSION: Since 2015, additional trials and longer follow-ups or additional data (e.g., harms, specific patient populations) from previously published trials have been published that will improve our understanding of the benefits and harms of screening. The systematic review of values and preferences will allow fulsome insights that will inform the balance of benefits and harms. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022378858.

Screening for hypertension in adults: protocol for evidence reviews to inform a Canadian Task Force on Preventive Health Care guideline update.

PURPOSE: To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening in a primary care setting for hypertension in adults aged 18 years and older. This protocol outlines the scope and methods for a series of systematic reviews and one overview of reviews. METHODS: To evaluate the benefits and harms of screening for hypertension, the Task Force will rely on the relevant key questions from the 2021 United States Preventive Services Task Force systematic review. In addition, a series of reviews will be conducted to identify, appraise, and synthesize the evidence on (1) the association of blood pressure measurement methods and future cardiovascular (CVD)-related outcomes, (2) thresholds for discussions of treatment initiation, and (3) patient acceptability of hypertension screening methods. For the review of blood pressure measurement methods and future CVD-related outcomes, we will perform a de novo review and search MEDLINE, Embase, CENTRAL, and APA PsycInfo for randomized controlled trials, prospective or retrospective cohort studies, nested case-control studies, and within-arm analyses of intervention studies. For the thresholds for discussions of treatment initiation review, we will perform an overview of reviews and update results from a relevant 2019 UK NICE review. We will search MEDLINE, Embase, APA PsycInfo, and Epistemonikos for systematic reviews. For the acceptability review, we will perform a de novo systematic review and search MEDLINE, Embase, and APA PsycInfo for randomized controlled trials, controlled clinical trials, and observational studies with comparison groups. Websites of relevant organizations, gray literature sources, and the reference lists of included studies and reviews will be hand-searched. Title and abstract screening will be completed by two independent reviewers. Full-text screening, data extraction, risk-of-bias assessment, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers. Results from included studies will be synthesized narratively and pooled via meta-analysis when appropriate. The GRADE approach will be used to assess the certainty of evidence for outcomes. DISCUSSION: The results of the evidence reviews will be used to inform Canadian recommendations on screening for hypertension in adults aged 18 years and older. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered on PROSPERO and is available on the Open Science Framework (osf.io/8w4tz).

Health equity considerations in guideline development: a rapid scoping review.

BACKGROUND: Systematic guidance for considering health equity in guidelines is lacking. This scoping review aims to synthesize current best practices for integrating health equity into guideline development and the benefits or drawbacks of these practices. METHODS: We searched Ovid MEDLINE ALL and Embase Classic+Embase on the Ovid platform, CINAHL on EBSCO, and Web of Science (Core Collection) from 2010 to 2022. We searched grey literature from 2015 to 2022, using the Canadian Agency for Drugs and Technologies in Health Grey Matters checklist and searches of potentially relevant websites. Articles were screened independently by 1 reviewer. Proposed best practices, advantages and disadvantages, and tools were extracted independently by 1 reviewer and qualitatively synthesized based on the relevant steps of a comprehensive checklist covering the stages of guideline development. RESULTS: We included 26 articles that proposed best practices for incorporating health equity within the guideline development process. These practices were organized under different stages of the development process, including guideline planning, evidence review, guideline development and dissemination. Included studies provided best practices from guideline producers, articles discussing health equity in current guidelines, articles addressing strategies to increase equity in the guideline implementation process, and literature reviews of promising health equity practices. INTERPRETATION: Our scoping review identified best practices to incorporate health equity considerations at each phase of guideline development. Identified practices may be used to inform equity-promoting strategies with the guideline development process; however, guideline producers should carefully consider the advantages and disadvantages of best practices when integrating health equity.

GRADE Guidance 34: update on rating imprecision using a minimally contextualized approach.

OBJECTIVES: The aim of this study is to provide updated guidance on when The Grading of Recommendations Assessment, Development and Evaluation (GRADE) users should consider rating down more than one level for imprecision using a minimally contextualized approach. STUDY DESIGN AND SETTING: Based on the first GRADE guidance addressing imprecision rating in 2011, a project group within the GRADE Working Group conducted iterative discussions and presentations at GRADE Working Group meetings to produce this guidance. RESULTS: GRADE suggests aligning imprecision criterion for systematic reviews and guidelines using the approach that relies on thresholds and confidence intervals (CI) of absolute effects as a primary criterion for imprecision rating (i.e., CI approach). Based on the CI approach, when a CI appreciably crosses the threshold(s) of interest, one should consider rating down two or three levels. When the CI does not cross the threshold(s) and the relative effect is large, one should implement the optimal information size (OIS) approach. If the sample size of the meta-analysis is far less than the OIS, one should consider rating down more than one level for imprecision. CONCLUSION: GRADE provides updated guidance for imprecision rating in a minimally contextualized approach, with a focus on the circumstances in which one should seriously consider rating down two or three levels for imprecision.

GRADE guidelines 32: GRADE offers guidance on choosing targets of GRADE certainty of evidence ratings.

OBJECTIVE: To provide practical principles and examples to help GRADE users make optimal choices regarding their ratings of certainty of evidence using a minimally or partially contextualized approach. STUDY DESIGN AND SETTING: Based on the GRADE clarification of certainty of evidence in 2017, a project group within the GRADE Working Group conducted iterative discussions and presentations at GRADE Working Group meetings to refine this construct and produce practical guidance. RESULTS: Systematic review and health technology assessment authors need to clarify what it is in which they are rating their certainty of evidence (i.e., the target of their certainty rating). The decision depends on the degree of contextualization (partially or minimally contextualized), thresholds (null, small, moderate or large effect threshold), and where the point estimate lies in relation to the chosen threshold(s). When the 95% confidence interval crosses multiple possible thresholds (i.e., including both large benefit and large harm), it is not worthwhile for authors to determine the target of certainty rating. CONCLUSION: GRADE provides practical principles to help systematic review and health technology assessment authors specify the target of their certainty of evidence rating.

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.

Developing trustworthy recommendations as part of an urgent response (1-2 weeks): a GRADE concept paper.

OBJECTIVES: The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 week) in the clinical, public health, and health systems fields. STUDY DESIGN AND SETTING: We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group. RESULTS: A request for developing recommendations within 2 week is the usual trigger for an urgent response. Although the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of the 4 potential approaches: adopt existing recommendations, adapt existing recommendations, develop new recommendations using existing adequate systematic review, or develop new recommendations using expert panel input; and (8) consider an updating plan. CONCLUSION: An urgent response for developing recommendations requires building a cohesive, skilled, and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise; adapting to shifting needs; complying with the principles of transparency; and properly managing conflicts of interest.

Effectiveness of stop smoking interventions among adults: protocol for an overview of systematic reviews and an updated systematic review.

BACKGROUND: Tobacco smoking is the leading cause of cancer, preventable death, and disability. Smoking cessation can increase life expectancy by nearly a decade if achieved in the third or fourth decades of life. Various stop smoking interventions are available including pharmacotherapies, electronic cigarettes, behavioural support, and alternative therapies. This protocol outlines an evidence review which will evaluate the benefits and harms of stop smoking interventions in adults. METHODS: The evidence review will consist of two stages. First, an overview of systematic reviews evaluating the benefits and harms of various stop smoking interventions delivered in or referred from the primary care setting will be conducted. The second stage will involve updating a systematic review on electronic cigarettes identified in the overview; randomized controlled trials will be considered for outcomes relating to benefits while randomized controlled trials, non-randomized controlled trials, and comparative observational studies will be considered for evaluating harms. Search strategies will be developed and peer-reviewed by medical information specialists. The search strategy for the updated review on e-cigarettes will be developed using that of the candidate systematic review. The MEDLINE®, PsycINFO, Embase, and the Cochrane Library electronic databases will be searched as of 2008 for the overview of reviews and from the last search date of the selected review for the updated review. Organizational websites and trial registries will be searched for unpublished or ongoing reviews/studies. Two reviewers will independently screen the title and abstracts of citations using the liberal accelerated method. Full-text screening will be performed independently by two reviewers. Extracted data will be verified by a second reviewer. Disagreements regarding full-text screening and data extraction will be resolved by consensus or third-party adjudication. The methodological quality of systematic reviews, risk of bias of randomized and non-randomized trials, and methodological quality of cohort studies will be evaluated using AMSTAR 2, the Cochrane risk of bias tool, and a modified version of the Scottish Intercollegiate Guidelines Network critical appraisal tool, respectively. The GRADE framework will be used to assess the quality of the evidence for outcomes. DISCUSSION: The evidence review will evaluate the benefits and harms of various stop smoking interventions for adults. Findings will be used to inform a national tobacco cessation guideline by the Canadian Task Force on Preventive Health Care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42018099691, CRD42018099692).

Risk of sexual transmission of human immunodeficiency virus with antiretroviral therapy, suppressed viral load and condom use: a systematic review.

BACKGROUND: The Public Health Agency of Canada reviewed sexual transmission of HIV between serodiscordant partners to support examination of the criminal justice system response to HIV nondisclosure by the Department of Justice of Canada. We sought to determine HIV transmission risk when an HIV-positive partner takes antiretroviral therapy, has a suppressed viral load or uses condoms. METHODS: We conducted an overview and systematic review update by searching MEDLINE and other databases (Jan. 1, 2007, to Mar. 13, 2017; and Nov. 1, 2012, to Apr. 27, 2017, respectively). We considered reviews and studies about absolute risk of sexual transmission of HIV between serodiscordant partners to be eligible for inclusion. We used A Measurement Tool to Assess Systematic Reviews (AMSTAR) for review quality, Quality in Prognosis Studies (QUIPS) instrument for study risk of bias and then the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence across studies. We calculated HIV incidence per 100 person-years with 95% confidence intervals (CIs). We assigned risk categories according to potential for and evidence of HIV transmission. RESULTS: We identified 12 reviews. We selected 1 review to estimate risk of HIV transmission for condom use without antiretroviral therapy (1.14 transmissions/100 person-years, 95% CI 0.56-2.04; low risk). We identified 11 studies with 23 transmissions over 10 511 person-years with antiretroviral therapy (0.22 transmissions/ 100 person-years, 95% CI 0.14-0.33; low risk). We found no transmissions with antiretroviral therapy and a viral load of less than 200 copies/mL across consecutive measurements 4 to 6 months apart (0.00 transmissions/100 person-years, 95% CI 0.00-0.28; negligible risk regardless of condom use). INTERPRETATION: Based on high-quality evidence, there is a negligible risk of sexual transmission of HIV when an HIV-positive sex partner adheres to antiretroviral therapy and maintains a suppressed viral load of less than 200 copies/mL measured every 4 to 6 months. Sexual transmissions of HIV have occurred when viral load was more than 200 copies/mL with antiretroviral therapy or condoms alone were used, although the risk remains low. These findings will help to support patient and clinician decision-making, affect public health case management and contact tracing, and inform justice system responses to HIV nondisclosure.

Associations between domains of physical literacy by weight status in 8- to 12-year-old Canadian children.

BACKGROUND: The Canadian Assessment of Physical Literacy (CAPL) is divided into four domains (Physical Competence, Daily Behaviour, Motivation and Confidence, and Knowledge and Understanding) and provides a robust and comprehensive assessment of physical literacy. As weight status is known to influence health-related behaviours such as physical fitness and activity, it is important to investigate whether the associations between the domains of physical literacy vary among children of different weight status. The aim of this study was to determine the associations among the four domains of physical literacy stratified by weight status. METHODS: Canadian children aged 8 to 12 years (n = 8343, 63.6% healthy-weight) completed the CAPL. Differences in domain scores and overall physical literacy score by weight status (children of healthy weight versus children with overweight/obese) were assessed using MANOVA (multivariate analysis of variance). Partial correlations between the four domains were calculated, adjusting for gender and age, and correlation coefficients of both weight status groups were compared using the Steiger test. RESULTS: For all four domains as well as overall physical literacy, healthy-weight children had higher scores than their overweight/obese peers (Cohen's d ranged from 0.05 to 0.44). Weak to moderate correlations were found between all of the domains for both groups. Correlation coefficients for Physical Competence and Daily Behaviour as well as for Physical Competence and Knowledge and Understanding were generally stronger in the healthy-weight children (r = 0.29 and 0.22, respectively) compared with the overweight/obese children (r = 0.23 and 0.17, respectively). CONCLUSIONS: All of the domains of the CAPL correlate positively with each other regardless of weight status, with a trend for these correlation coefficients to be slightly stronger in the healthy-weight children. The overall weak to moderate correlations between the domains in both groups suggest that the CAPL domains are not measuring the same constructs, thus providing support for CAPL's psychometric architecture in both healthy-weight and overweight/obese children.

Alcohol Consumption and Obesity: An Update.

Recreational alcohol intake is a widespread activity globally and alcohol energy (7 kcal/g) can be a contributing factor to weight gain if not compensated for. Given that both excessive alcohol intake and obesity are of public health interest, the present paper provides an update on the association between alcohol consumption and body weight. In general, recent prospective studies show that light-to-moderate alcohol intake is not associated with adiposity gain while heavy drinking is more consistently related to weight gain. Experimental evidence is also mixed and suggests that moderate intake of alcohol does not lead to weight gain over short follow-up periods. However, many factors can explain the conflicting findings and a better characterization of individuals more likely to gain weight as a result of alcohol consumption is needed. In particular, individuals who frequently drink moderate amounts of alcohol may enjoy a healthier lifestyle in general that may protect them from weight gain. In conclusion, despite the important limitations of current studies, it is reasonable to say that alcohol intake may be a risk factor for obesity in some individuals, likely based on a multitude of factors, some of which are discussed herein.