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.

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.

Screening for prostate cancer: protocol for updating multiple systematic 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 for prostate cancer in adults aged 18 years and older in primary care. This protocol outlines the planned scope and methods for a series of systematic reviews. METHODS: Updates of two systematic reviews and a de novo review will be conducted to synthesize the evidence on the benefits and harms of screening for prostate cancer with a prostate-specific antigen (PSA) and/or digital rectal examination (DRE) (with or without additional information) and patient values and preferences. Outcomes for the benefits of screening include reduced prostate cancer mortality, all-cause mortality, and incidence of metastatic prostate cancer. Outcomes for the harms of screening include false-positive screening tests, overdiagnosis, complications due to biopsy, and complications of treatment including incontinence (urinary or bowel), and erectile dysfunction. The quality of life or functioning (overall and disease-specific) and psychological effects outcomes are considered as a possible benefit or harm. Outcomes for the values and preferences review include quantitative or qualitative information regarding the choice to screen or intention to undergo screening. For the reviews on benefits or harms, we will search for randomized controlled trials, quasi-randomized, and controlled studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. For the review on values and preferences, we will search for experimental or observational studies in MEDLINE, Embase, and PsycInfo. For all reviews, we will also search websites of relevant organizations, gray literature, and reference lists of included studies. Title and abstract screening, full-text review, data extraction, and risk of bias assessments will be completed independently by pairs of reviewers with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of the evidence for each outcome. DISCUSSION: The series of systematic reviews will be used by the Canadian Task Force on Preventive Health Care to update their 2014 guideline on screening for prostate cancer in adults aged 18 years and older. Systematic review registration This review has been registered with PROSPERO (CRD42022314407) and is available on the Open Science Framework (osf.io/dm32k).

PROTOCOL: Conflict of interest issues when engaging stakeholders in health and healthcare guideline development: a systematic review.

This is the protocol for a Campbell systematic review. The overall objective of this study is to gather and summarize the existing literature on conflict of interest issues when engaging stakeholders in guideline development.

PROTOCOL: Barriers and facilitators to stakeholder engagement in health guideline development: A qualitative evidence synthesis.

Background: There is a need for the development of comprehensive, global, evidence-based guidance for stakeholder engagement in guideline development. Stakeholders are any individual or group who is responsible for or affected by health- and healthcare-related decisions. This includes patients, the public, providers of health care and policymakers for example. As part of the guidance development process, Multi-Stakeholder Engagement (MuSE) Consortium set out to conduct four concurrent systematic reviews to summarise the evidence on: (1) existing guidance for stakeholder engagement in guideline development, (2) barriers and facilitators to stakeholder engagement in guideline development, (3) managing conflicts of interest in stakeholder engagement in guideline development and (4) measuring the impact of stakeholder engagement in guideline development. This protocol addresses the second systematic review in the series. Objectives: The objective of this review is to identify and synthesise the existing evidence on barriers and facilitators to stakeholder engagement in health guideline development. We will address this objective through two research questions: (1) What are the barriers to multi-stakeholder engagement in health guideline development across any of the 18 steps of the GIN-McMaster checklist? (2) What are the facilitators to multi-stakeholder engagement in health guideline development across any of the 18 steps of the GIN-McMaster checklist? Search Methods: A comprehensive search strategy will be developed and peer-reviewed in consultation with a medical librarian. We will search the following databases: MEDLINE, Cumulative Index to Nursing & Allied Health Literature (CINAHL), EMBASE, PsycInfo, Scopus, and Sociological Abstracts. To identify grey literature, we will search the websites of agencies who actively engage stakeholder groups such as the AHRQ, Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR), INVOLVE, the National Institute for Health and Care Excellence (NICE) and the PCORI. We will also search the websites of guideline-producing agencies, such as the American Academy of Pediatrics, Australia's National Health Medical Research Council (NHMRC) and the WHO. We will invite members of the team to suggest grey literature sources and we plan to broaden the search by soliciting suggestions via social media, such as Twitter. Selection Criteria: We will include empirical qualitative and mixed-method primary research studies which qualitatively report on the barriers or facilitators to stakeholder engagement in health guideline development. The population of interest is stakeholders in health guideline development. Building on previous work, we have identified 13 types of stakeholders whose input can enhance the relevance and uptake of guidelines: Patients, caregivers and patient advocates; Public; Providers of health care; Payers of health services; Payers of research; Policy makers; Program managers; Product makers; Purchasers; Principal investigators and their research teams; and Peer-review editors/publishers. Eligible studies must describe stakeholder engagement at any of the following steps of the GIN-McMaster Checklist for Guideline Development. Data Collection and Analysis: All identified citations from electronic databases will be imported into Covidence software for screening and selection. Documents identified through our grey literature search will be managed and screened using an Excel spreadsheet. A two-part study selection process will be used for all identified citations: (1) a title and abstract review and (2) full-text review. At each stage, teams of two review authors will independently assess all potential studies in duplicate using a priori inclusion and exclusion criteria. Data will be extracted by two review authors independently and in duplicate according to a standardised data extraction form. Main Results: The results of this review will be used to inform the development of guidance for multi-stakeholder engagement in guideline development and implementation. This guidance will be official GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group guidance. The GRADE system is internationally recognised as a standard for guideline development. The findings of this review will assist organisations who develop healthcare, public health and health policy guidelines, such as the World Health Organization, to involve multiple stakeholders in the guideline development process to ensure the development of relevant, high quality and transparent guidelines.

Screening to prevent fragility fractures among adults 40 years and older in primary care: protocol for a systematic review.

PURPOSE: To inform recommendations by the Canadian Task Force on Preventive Health Care by systematically reviewing direct evidence on the effectiveness and acceptability of screening adults 40 years and older in primary care to reduce fragility fractures and related mortality and morbidity, and indirect evidence on the accuracy of fracture risk prediction tools. Evidence on the benefits and harms of pharmacological treatment will be reviewed, if needed to meaningfully influence the Task Force's decision-making. METHODS: A modified update of an existing systematic review will evaluate screening effectiveness, the accuracy of screening tools, and treatment benefits. For treatment harms, we will integrate studies from existing systematic reviews. A de novo review on acceptability will be conducted. Peer-reviewed searches (Medline, Embase, Cochrane Library, PsycINFO [acceptability only]), grey literature, and hand searches of reviews and included studies will update the literature. Based on pre-specified criteria, we will screen studies for inclusion following a liberal-accelerated approach. Final inclusion will be based on consensus. Data extraction for study results will be performed independently by two reviewers while other data will be verified by a second reviewer; there may be some reliance on extracted data from the existing reviews. The risk of bias assessments reported in the existing reviews will be verified and for new studies will be performed independently. When appropriate, results will be pooled using either pairwise random effects meta-analysis (screening and treatment) or restricted maximum likelihood estimation with Hartun-Knapp-Sidnick-Jonkman correction (risk prediction model calibration). Subgroups of interest to explain heterogeneity are age, sex, and menopausal status. Two independent reviewers will rate the certainty of evidence using the GRADE approach, with consensus reached for each outcome rated as critical or important by the Task Force. DISCUSSION: Since the publication of other guidance in Canada, new trials have been published that are likely to improve understanding of screening in primary care settings to prevent fragility fractures. A systematic review is required to inform updated recommendations that align with the current evidence base.

Relative incidence of common cancers in people with severe mental illness. Cohort study in the United Kingdom THIN primary care database.

BACKGROUND: A recent United Kingdom (UK) report found that breast and colorectal cancers were more common in people with severe mental illness (SMI) and recommended targeted screening. Epidemiological evidence is however inconsistent. OBJECTIVES: To estimate relative incidence rates for colorectal, breast and lung cancer, and the overall incidence of the commonest other UK cancers, in people with SMI compared with people without SMI. METHOD: Cohort study in the UK using The Health Improvement Network (THIN) primary care database between 1990 and June 2008. Poisson regression was used to obtain adjusted incidence rate ratios (IRRs) for cancer, comparing two cohorts of people over 18; with and without a diagnosis of SMI. RESULTS: We identified 20,632 people with SMI and 116,152 people without, with median follow up of over 6years. No significant associations were observed between SMI and cancers of the breast (adjusted IRR 1.17; 95% confidence interval 0.95-1.45), colon (0.70; 0.46-1.05), rectum (1.05; 0.65-1.69) or lung (0.84; 0.65-1.10). The adjusted IRR for an aggregate cancer outcome in SMI was 0.95; 0.85-1.06. Results were similar for schizophrenia and bipolar disorder. CONCLUSIONS: In a cohort analysis within a large UK primary care database, the incidence of colo-rectal, breast and lung cancer, and of all common cancers, did not differ significantly in people with SMI, including schizophrenia, compared with people without SMI. Our results do not support enhanced screening procedures for cancer in people with SMI.

Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism: influence on prostate cancer risk and interactions.

PURPOSE: Folate is essential to DNA methylation and synthesis and may have a complex dualistic role in prostate cancer. Alcohol use may increase risk and epigenetic factors may interact with lifestyle exposures. We aimed to characterize the independent and joint effects of folate intake, alcohol consumption, and the MTHFR C677T gene polymorphism on prostate cancer risk, while accounting for intakes of vitamins B(2), B(6), B(12), methionine, total energy, and confounders. METHODS: A case-control study was conducted at Kingston General Hospital of 80 incident primary prostate cancer cases and 334 urology clinic controls, all with normal age-specific PSA levels (to exclude latent prostate cancers). Participants completed a questionnaire on folate and alcohol intakes and potential confounders prior to knowledge of diagnosis, eliminating recall bias, and blood was drawn for MTHFR genotyping. Joint effects of exposures were assessed using unconditional logistic regression and significance of multiplicative and additive interactions using general linear models. RESULTS: Folate, vitamins B(2), B(6), B(12), methionine, and the CT and TT genotypes were not associated with prostate cancer risk. The highest tertile of lifetime alcohol consumption was associated with increased risk (OR = 2.08; 95% CI: 1.12-3.86). Consumption of >5 alcoholic drinks per week was associated with increased prostate cancer risk among men with low folate intake (OR = 2.38; 95% CI: 1.01-5.57), and higher risk among those with the CC MTHFR genotype (OR = 4.43; 95% CI: 1.15-17.05). Increased risk was also apparent for average weekly alcohol consumption when accounting for the multiplicative interaction between folate intake and MTHFR C677T genotype (OR = 3.22; 95% CI: 1.36-7.59). CONCLUSION: Alcohol consumption is associated with increased prostate cancer risk, and this association is stronger among men with low folate intake, with the CC MTHFR genotype, and when accounting for the joint effect of folate intake and MTHFR C677T genotype.

Inequalities in the provision of cardiovascular screening to people with severe mental illnesses in primary care: cohort study in the United Kingdom THIN Primary Care Database 2000-2007.

BACKGROUND: People with severe mental illnesses (SMI), including schizophrenia, are at increased risk of cardiovascular disease (CVD). Guidelines recommend regular CVD screening and in the United Kingdom, since 2004, General Practitioners are remunerated for annual reviews. OBJECTIVES: To compare annual rates of CVD screening provision in people with and without SMI between 2000 and 2008. METHOD: We identified 18,696 people with SMI and 95,512 people without SMI in the UK The Health Improvement Network (THIN) primary care database. We compared the rates of measurement of blood pressure (BP), glucose, cholesterol and body mass index (BMI). RESULTS: Prior to 2004, all people with SMI, were significantly less likely to receive each measurement, (including people above and below 60 years of age). In 2003; adjusted incidence rate ratios (95% CI) for screening in people with SMI under 60 years compared to people without SMI were: BMI: 0.62 (0.58-0.65); BP: 0.59 (0.56-0.62); glucose: 0.66 (0.61-0.70) and cholesterol: 0.54 (0.49-0.59). By 2007 people with SMI under 60 were equally likely receive a measurement of BMI: 1.00 (0.96-1.04), glucose: 1.00 (0.96-1.05) and cholesterol: 0.95 (0.90-1.0); the gap in screening for BP had narrowed 0.87 (0.83-0.90). However people with SMI over 60 years of age remained significantly less likely to be screened. There was little difference in screening according to social deprivation. CONCLUSIONS: In UK primary care, people with SMI over 60 years of age remain less likely than the general population to receive annual CVD screening despite higher risk of developing CVD.

Impact of childhood cancer on parental employment and sources of income: a Canadian pilot study.

BACKGROUND: Loss of income and out of pocket expenses related to childhood cancer care can account for over 25% of a family's total disposable income, adding to the stress of facing a life-threatening disease. The objective of this pilot study was to assess the impact of childhood cancer on employment and sources of income within families. PROCEDURE: A retrospective postal-administered questionnaire was used to collect information from parents of children diagnosed with cancer before 20 years of age between 1990 and 1996 in the province of British Columbia (n = 111). RESULTS: Among full or part-time employed parents, 64% of mothers and 16% of fathers left their job after their child's diagnosis. The large majority of parents who left their jobs were away for less than 1 year (65% of mothers; 78% of fathers) and nearly all were able to return to the same job if they chose to do so (80% of mothers; 89% of fathers). Parents with children <10 years of age at diagnosis and those with leukemia were most likely to take leave from their jobs. There was considerable change in sources of income between the time of diagnosis and survey with more families relying on employment insurance, social assistance or other financial support at diagnosis. Reliance on sources of income other than salary decreased with time since diagnosis. CONCLUSIONS: It appears that the diagnosis of childhood cancer may cause an important but short-term impact on the employment and income sources of affected families.