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.

Recommandations sur le dépistage pour la prévention primaire des fractures de fragilisation.

CONTEXTE: Les fractures de fragilisation sont un important problème de santé chez les adultes âgés et peuvent entraîner des incapacités, des hospitalisations et le placement en établissement de soins de longue durée, en plus de nuire à la qualité de vie. La présente ligne directrice du Groupe d'étude canadien sur les soins de santé préventifs (le Groupe d'étude) formule des recommandations fondées sur des données probantes au sujet du dépistage pour la prévention des fractures de fragilisation chez les personnes âgées de 40 ans et plus vivant dans la collectivité qui ne sont pas sous traitement pharmacologique préventif. MÉTHODES: Nous avons commandé des revues systématiques sur les bénéfices et les préjudices du dépistage, l'exactitude prédictive des outils d'évaluation du risque, les bénéfices du traitement, ainsi que l'acceptabilité de celui-ci par les patients. Nous avons analysé les préjudices des traitements au moyen d'un examen rapide de revues systématiques. Nous avons en outre analysé les valeurs et les préférences des patients par l'entremise de groupes de discussion et auprès d'intervenants mobilisés à certains moments clés, tout au long du projet. Nous avons utilisé l'approche méthodologique GRADE (Grading of Recommendations, Assessment, Development and Evaluation) afin de déterminer la certitude des données probantes pour chacune des issues cliniques ainsi que la force des recommandations, et nous avons appliqué les lignes directrices de l'instrument AGREE (Appraisal of Guidelines for Research and Evaluation), du Guidelines International Network (GIN) et du guide de rédaction Guidance for Reporting Involvement of Patients and the Public (GRIPP 2). RECOMMANDATIONS: Nous recommandons un dépistage débutant par une estimation du risque pour la prévention des fractures de fragilisation chez les femmes de 65 ans et plus. Le dépistage se fait d'abord au moyen de l'outil canadien FRAX, qui mesure le risque de fracture, sans densité minérale osseuse (DMO). Le score FRAX devrait guider la prise de décision partagée entourant les bénéfices et les préjudices potentiels de la pharmacothérapie préventive. Après cette discussion, si une pharmacothérapie préventive est envisagée, les médecins devraient demander une mesure de la DMO par absorptiométrie à rayons X biphotonique (DEXA) du col du fémur, puis réévaluer le risque de fracture en intégrant le score T de la DMO au score FRAX (recommandation conditionnelle, données de faible certitude). Nous ne recommandons pas le dépistage chez les femmes de 40­64 ans et les hommes de 40 ans et plus (recommandation forte, données de très faible certitude). Ces recommandations s'appliquent aux personnes vivant dans la collectivité qui ne sont pas sous pharmacothérapie pour la prévention des fractures de fragilisation. INTERPRÉTATION: Le dépistage débutant par une estimation du risque chez les femmes de 65 ans et plus facilite la prise de décision partagée et permet aux patientes d'envisager la pharmacothérapie préventive en fonction de leur propre risque (avant DMO). Le fait de ne pas recommander le dépistage chez les hommes et les femmes plus jeunes rappelle l'importance des bonnes pratiques cliniques, en vertu desquelles les médecins doivent demeurer à l'affût de tout changement de l'état de santé des personnes qui pourrait indiquer qu'elles ont subi une fracture de fragilisation ou pourraient y être plus sujettes.

Recommendations on screening for primary prevention of fragility fractures.

BACKGROUND: Fragility fractures are a major health concern for older adults and can result in disability, admission to hospital and long-term care, and reduced quality of life. This Canadian Task Force on Preventive Health Care (task force) guideline provides evidence-based recommendations on screening to prevent fragility fractures in community-dwelling individuals aged 40 years and older who are not currently on preventive pharmacotherapy. METHODS: We commissioned systematic reviews on benefits and harms of screening, predictive accuracy of risk assessment tools, patient acceptability and benefits of treatment. We analyzed treatment harms via a rapid overview of reviews. We further examined patient values and preferences via focus groups and engaged stakeholders at key points throughout the project. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to determine the certainty of evidence for each outcome and strength of recommendations, and adhered to Appraisal of Guidelines for Research and Evaluation (AGREE), Guidelines International Network and Guidance for Reporting Involvement of Patients and the Public (GRIPP-2) reporting guidance. RECOMMENDATIONS: We recommend "risk assessment-first" screening for prevention of fragility fractures in females aged 65 years and older, with initial application of the Canadian clinical Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD). The FRAX result should be used to facilitate shared decision-making about the possible benefits and harms of preventive pharmacotherapy. After this discussion, if preventive pharmacotherapy is being considered, clinicians should request BMD measurement using dual-energy x-ray absorptiometry (DXA) of the femoral neck, and re-estimate fracture risk by adding the BMD T-score into FRAX (conditional recommendation, low-certainty evidence). We recommend against screening females aged 40-64 years and males aged 40 years and older (strong recommendation, very low-certainty evidence). These recommendations apply to community-dwelling individuals who are not currently on pharmacotherapy to prevent fragility fractures. INTERPRETATION: Risk assessment-first screening for females aged 65 years and older facilitates shared decision-making and allows patients to consider preventive pharmacotherapy within their individual risk context (before BMD). Recommendations against screening males and younger females emphasize the importance of good clinical practice, where clinicians are alert to changes in health that may indicate the patient has experienced or is at higher risk of fragility fracture.

Interventions to address potentially inappropriate prescriptions and over-the-counter medication use among adults 65 years and older in primary care settings: protocol for a systematic review.

PURPOSE: To inform recommendations by the Canadian Task Force on Preventive Health Care on potentially inappropriate prescribing and over-the-counter (OTC) medication use among adults aged 65 years and older in primary care settings. This protocol outlines the planned scope and methods for a systematic review of the benefits and harms and acceptability of interventions to reduce potentially inappropriate prescriptions and OTC medication use. METHODS: De novo systematic reviews will be conducted to synthesize the available evidence on (a) the benefits and harms of interventions to reduce potentially inappropriate prescriptions and OTC medications compared to no intervention, usual care, or non- or minimally active intervention among adults aged 65 years and older and (b) the acceptability of these interventions or attributes among patients. Outcomes of interest for the benefits and harms review are all-cause mortality, hospitalization, non-serious adverse drug reactions, quality of life, emergency department visits, injurious falls, medical visits, and the number of medications (and number of pills). Outcomes for the acceptability review are the preference for and relative importance of different interventions or their attributes. For the benefits and harms review, we will search MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials. For the acceptability review, we will search MEDLINE, Embase, PsycInfo, Cochrane Central Register of Controlled Trials, and the NHS Economic Evaluation Database for experimental and observational studies with a comparator. Websites of relevant organizations, other grey literature sources, and reference lists of included studies and reviews will be searched. Title and abstract screening will be completed by two independent reviewers using the liberal accelerated approach. Full-text review, data extraction, risk of bias assessments, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers, with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE approach will be used to assess the certainty of the evidence for outcomes. DISCUSSION: The results of this systematic review will be used by the Canadian Task Force on Preventive Health Care to inform their recommendation on potentially inappropriate prescribing and OTC medication use among adults aged 65 years and older. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (KQ1: CRD42022302313; KQ2: CRD42022302324); Open Science Framework ( https://osf.io/urj4b/ ).

Family Experiences with Care for Children with Inherited Metabolic Diseases in Canada: A Cross-Sectional Survey.

BACKGROUND AND OBJECTIVE: Children with inherited metabolic diseases often require complex and highly specialized care. Patient and family-centered care can improve health outcomes that are important to families. This study aimed to examine experiences of family caregivers (parents/guardians) of children diagnosed with inherited metabolic diseases with healthcare to inform strategies to improve those experiences. METHODS: A cross-sectional mailed survey was conducted of family caregivers recruited from an ongoing cohort study. Participants rated their healthcare experiences during their child's visits to five types of healthcare settings common for inherited metabolic diseases: the metabolic clinic, the emergency department, hospital inpatient units, the blood laboratory, and the pharmacy. Participants provided narrative descriptions of any memorable negative or positive experiences. RESULTS: There were 248 respondents (response rate 49%). Caregivers were generally very or somewhat satisfied with the care provided at each care setting. Appropriate treatment, provider knowledge, provider communication, and care coordination were deemed essential aspects of satisfaction with care by the majority of participants across many settings. Memorable negative experiences were reported by 8-22% of participants, varying by setting. Among participants who reported memorable negative experiences, contributing factors included providers' demeanor, lack of communication, lack of involvement of the family, and disregard of an emergency protocol letter provided by the family. CONCLUSIONS: While caregivers' satisfaction with care for children with inherited metabolic diseases was high, we identified gaps in family-centered care and factors contributing to negative experiences that are important to consider in the future development of strategies to improve pediatric care for inherited metabolic diseases.

Core Outcome Sets for Medium-Chain Acyl-CoA Dehydrogenase Deficiency and Phenylketonuria.

BACKGROUND: Evidence to guide treatment of pediatric medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency and phenylketonuria (PKU) is fragmented because of large variability in outcome selection and measurement. Our goal was to develop core outcome sets (COSs) for these diseases to facilitate meaningful future evidence generation and enhance the capacity to compare and synthesize findings across studies. METHODS: Parents and/or caregivers, health professionals, and health policy advisors completed a Delphi survey and participated in a consensus workshop to select core outcomes from candidate lists of outcomes for MCAD deficiency and PKU. Delphi participants rated the importance of outcomes on a nine-point scale (1-3: not important, 4-6: important but not critical, 7-9: critical). Candidate outcomes were progressively narrowed down over 3 survey rounds. At the workshop, participants evaluated the remaining candidate outcomes using an adapted nominal technique, open discussion, and voting. After the workshop, we finalized the COSs and recommended measurement instruments for each outcome. RESULTS: There were 85, 61, and 53 participants across 3 Delphi rounds, respectively. The candidate core outcome lists were narrowed down to 20 outcomes per disease to be discussed at the consensus workshop. Voting by 18 workshop participants led to COSs composed of 8 and 9 outcomes for MCAD deficiency and PKU, respectively, with measurement recommendations. CONCLUSIONS: These are the first known pediatric COSs for MCAD deficiency and PKU. Adoption in future studies will help to ensure best use of limited research resources to ultimately improve care for children with these rare diseases.

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.