A scoping review of triage approaches for the referral of patients with suspected inflammatory arthritis, from primary to rheumatology care.

We aimed to (1) identify existing triage approaches for referral of patients with suspected inflammatory arthritis (IA) from primary care physicians (PCP) to rheumatologists, (2) describe their characteristics and methodologies for clinical use, and (3) report their level of validation for use in a publicly funded healthcare system. The comprehensive search strategy of multiple databases up to October 2023 identified relevant literature and focussed on approaches applied at the PCP-Rheumatologist referral stage. Primary, quantitative studies, reported in English were included. Triage approaches were grouped into patient conditions as defined by the authors of the reports, including IA, its subtypes and combinations. 13952 records were identified, 425 full text reviewed and 55 reports of 53 unique studies were included. Heterogeneity in disease nomenclature and study sample pretest probability was found. The number of published studies rapidly increased after 2012. Studies were mostly from Europe and North America, in IA and Axial Spondyloarthritis (AxSpa). We found tools ranging the continuum of development with those best performing, indicated by the area under the receiver operating curve (AUC) >0.8), requiring only patient-reported questions. There were AUCs for some tools reported from multiple studies, these were in the outstanding to excellent range for the Early IA Questionnaire (EIAQ) (0.88 to 0.92), acceptable for the Case Finding AxSpa (CaFaSpa) (0.70 to 0.75), and poor to outstanding for the Psoriasis Epidemiology Screening Tool (PEST) (0.61 to 0.91). Given the clinical urgency to improve rheumatology referrals and considering the good.

Risk prediction models for lung cancer in people who have never smoked: a protocol of a systematic review.

BACKGROUND: Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related death worldwide. Although smoking is the primary cause of the cancer, lung cancer is also commonly diagnosed in people who have never smoked. Currently, the proportion of people who have never smoked diagnosed with lung cancer is increasing. Despite this alarming trend, this population is ineligible for lung screening. With the increasing proportion of people who have never smoked among lung cancer cases, there is a pressing need to develop prediction models to identify high-risk people who have never smoked and include them in lung cancer screening programs. Thus, our systematic review is intended to provide a comprehensive summary of the evidence on existing risk prediction models for lung cancer in people who have never smoked. METHODS: Electronic searches will be conducted in MEDLINE (Ovid), Embase (Ovid), Web of Science Core Collection (Clarivate Analytics), Scopus, and Europe PMC and Open-Access Theses and Dissertations databases. Two reviewers will independently perform title and abstract screening, full-text review, and data extraction using the Covidence review platform. Data extraction will be performed based on the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS). The risk of bias will be evaluated independently by two reviewers using the Prediction model Risk-of-Bias Assessment Tool (PROBAST) tool. If a sufficient number of studies are identified to have externally validated the same prediction model, we will combine model performance measures to evaluate the model's average predictive accuracy (e.g., calibration, discrimination) across diverse settings and populations and explore sources of heterogeneity. DISCUSSION: The results of the review will identify risk prediction models for lung cancer in people who have never smoked. These will be useful for researchers planning to develop novel prediction models, and for clinical practitioners and policy makers seeking guidance for clinical decision-making and the formulation of future lung cancer screening strategies for people who have never smoked. SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered in PROSPERO under the registration number CRD42023483824.

First-line diuretics versus other classes of antihypertensive drugs for hypertension.

BACKGROUND: Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity outcomes, and lowering blood pressure. First-line low-dose thiazide diuretics have been previously shown to have the best mortality and morbidity evidence when compared with placebo or no treatment. Head-to-head comparisons of thiazides with other blood pressure-lowering drug classes would demonstrate whether there are important differences. OBJECTIVES: To compare the effects of first-line diuretic drugs with other individual first-line classes of antihypertensive drugs on mortality, morbidity, and withdrawals due to adverse effects in patients with hypertension. Secondary objectives included assessments of the need for added drugs, drug switching, and blood pressure-lowering. SEARCH METHODS: Cochrane Hypertension's Information Specialist searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, and trials registers to March 2021. We also checked references and contacted study authors to identify additional studies. A top-up search of the Specialized Register was carried out in June 2022. SELECTION CRITERIA: Randomized active comparator trials of at least one year's duration were included. Trials had a clearly defined intervention arm of a first-line diuretic (thiazide, thiazide-like, or loop diuretic) compared to another first-line drug class: beta-blockers, calcium channel blockers, alpha adrenergic blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, direct renin inhibitors, or other antihypertensive drug classes. Studies had to include clearly defined mortality and morbidity outcomes (serious adverse events, total cardiovascular events, stroke, coronary heart disease (CHD), congestive heart failure, and withdrawals due to adverse effects). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: We included 20 trials with 26 comparator arms randomizing over 90,000 participants. The findings are relevant to first-line use of drug classes in older male and female hypertensive patients (aged 50 to 75) with multiple co-morbidities, including type 2 diabetes. First-line thiazide and thiazide-like diuretics were compared with beta-blockers (six trials), calcium channel blockers (eight trials), ACE inhibitors (five trials), and alpha-adrenergic blockers (three trials); other comparators included angiotensin II receptor blockers, aliskiren (a direct renin inhibitor), and clonidine (a centrally acting drug). Only three studies reported data for total serious adverse events: two studies compared diuretics with calcium channel blockers and one with a direct renin inhibitor. Compared to first-line beta-blockers, first-line thiazides probably result in little to no difference in total mortality (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.84 to 1.10; 5 trials, 18,241 participants; moderate-certainty), probably reduce total cardiovascular events (5.4% versus 4.8%; RR 0.88, 95% CI 0.78 to 1.00; 4 trials, 18,135 participants; absolute risk reduction (ARR) 0.6%, moderate-certainty), may result in little to no difference in stroke (RR 0.85, 95% CI 0.66 to 1.09; 4 trials, 18,135 participants; low-certainty), CHD (RR 0.91, 95% CI 0.78 to 1.07; 4 trials, 18,135 participants; low-certainty), or heart failure (RR 0.69, 95% CI 0.40 to 1.19; 1 trial, 6569 participants; low-certainty), and probably reduce withdrawals due to adverse effects (10.1% versus 7.9%; RR 0.78, 95% CI 0.71 to 0.85; 5 trials, 18,501 participants; ARR 2.2%; moderate-certainty). Compared to first-line calcium channel blockers, first-line thiazides probably result in little to no difference in total mortality (RR 1.02, 95% CI 0.96 to 1.08; 7 trials, 35,417 participants; moderate-certainty), may result in little to no difference in serious adverse events (RR 1.09, 95% CI 0.97 to 1.24; 2 trials, 7204 participants; low-certainty), probably reduce total cardiovascular events (14.3% versus 13.3%; RR 0.93, 95% CI 0.89 to 0.98; 6 trials, 35,217 participants; ARR 1.0%; moderate-certainty), probably result in little to no difference in stroke (RR 1.06, 95% CI 0.95 to 1.18; 6 trials, 35,217 participants; moderate-certainty) or CHD (RR 1.00, 95% CI 0.93 to 1.08; 6 trials, 35,217 participants; moderate-certainty), probably reduce heart failure (4.4% versus 3.2%; RR 0.74, 95% CI 0.66 to 0.82; 6 trials, 35,217 participants; ARR 1.2%; moderate-certainty), and may reduce withdrawals due to adverse effects (7.6% versus 6.2%; RR 0.81, 95% CI 0.75 to 0.88; 7 trials, 33,908 participants; ARR 1.4%; low-certainty). Compared to first-line ACE inhibitors, first-line thiazides probably result in little to no difference in total mortality (RR 1.00, 95% CI 0.95 to 1.07; 3 trials, 30,961 participants; moderate-certainty), may result in little to no difference in total cardiovascular events (RR 0.97, 95% CI 0.92 to 1.02; 3 trials, 30,900 participants; low-certainty), probably reduce stroke slightly (4.7% versus 4.1%; RR 0.89, 95% CI 0.80 to 0.99; 3 trials, 30,900 participants; ARR 0.6%; moderate-certainty), probably result in little to no difference in CHD (RR 1.03, 95% CI 0.96 to 1.12; 3 trials, 30,900 participants; moderate-certainty) or heart failure (RR 0.94, 95% CI 0.84 to 1.04; 2 trials, 30,392 participants; moderate-certainty), and probably reduce withdrawals due to adverse effects (3.9% versus 2.9%; RR 0.73, 95% CI 0.64 to 0.84; 3 trials, 25,254 participants; ARR 1.0%; moderate-certainty). Compared to first-line alpha-blockers, first-line thiazides probably result in little to no difference in total mortality (RR 0.98, 95% CI 0.88 to 1.09; 1 trial, 24,316 participants; moderate-certainty), probably reduce total cardiovascular events (12.1% versus 9.0%; RR 0.74, 95% CI 0.69 to 0.80; 2 trials, 24,396 participants; ARR 3.1%; moderate-certainty) and stroke (2.7% versus 2.3%; RR 0.86, 95% CI 0.73 to 1.01; 2 trials, 24,396 participants; ARR 0.4%; moderate-certainty), may result in little to no difference in CHD (RR 0.98, 95% CI 0.86 to 1.11; 2 trials, 24,396 participants; low-certainty), probably reduce heart failure (5.4% versus 2.8%; RR 0.51, 95% CI 0.45 to 0.58; 1 trial, 24,316 participants; ARR 2.6%; moderate-certainty), and may reduce withdrawals due to adverse effects (1.3% versus 0.9%; RR 0.70, 95% CI 0.54 to 0.89; 3 trials, 24,772 participants; ARR 0.4%; low-certainty). For the other drug classes, data were insufficient. No antihypertensive drug class demonstrated any clinically important advantages over first-line thiazides. AUTHORS' CONCLUSIONS: When used as first-line agents for the treatment of hypertension, thiazides and thiazide-like drugs likely do not change total mortality and likely decrease some morbidity outcomes such as cardiovascular events and withdrawals due to adverse effects, when compared to beta-blockers, calcium channel blockers, ACE inhibitors, and alpha-blockers.

Hydroxyzine Initiation Following Drug Safety Advisories on Cardiac Arrhythmias in the UK and Canada: A Longitudinal Cohort Study.

INTRODUCTION: Regulatory advisories on hydroxyzine and risk of QT prolongation and Torsade de pointes (TdP) were issued in the UK in April 2015 and Canada in June 2016. We hypothesized patients with risk factors for QT prolongation and TdP, compared with those without risk factors, would be less likely to initiate hydroxyzine in the UK and in British Columbia (BC), Canada, following advisories. METHODS: We conducted a longitudinal study with repeated measures, and evaluated hydroxyzine initiation in a UK cohort and a concurrent BC control cohort (April 2013-March 2016) as well as in a BC advisory cohort (June 2014-May 2017). RESULTS: This study included 247,665 patients in the UK cohort, 297,147 patients in the BC control cohort, and 303,653 patients in the BC advisory cohort. Over a 12-month post-advisory period, hydroxyzine initiation decreased by 21% in the UK (rate ratio 0.79, 95% confidence interval 0.66-0.96) relative to the expected level of initiation based on the pre-advisory trend. Hydroxyzine initiation did not change in the BC control cohort or following the Canadian advisory in the BC advisory cohort. The decrease in hydroxyzine initiation in the UK in the 12 months after the advisories was not significantly different for patients with risk factors compared with those without risk factors. CONCLUSION: Hydroxyzine initiation decreased in the UK, but not in BC, in the 12 months following safety advisories. The decrease in hydroxyzine initiation in the UK was not significantly different for patients with versus without risk factors for QT prolongation and TdP.

Influence of drug safety advisories on drug utilisation: an international interrupted time series and meta-analysis.

OBJECTIVE: To evaluate the association between regulatory drug safety advisories and changes in drug utilisation. DESIGN: We conducted controlled, interrupted times series analyses with administrative prescription claims data to estimate changes in drug utilisation following advisories. We used random-effects meta-analysis with inverse-variance weighting to estimate the average postadvisory change in drug utilisation across advisories. STUDY POPULATION: We included advisories issued in Canada, Denmark, the UK and the USA during 2009-2015, mainly concerning drugs in common use in primary care. We excluded advisories related to over-the-counter drugs, drug-drug interactions, vaccines, drugs used primarily in hospital and advisories with co-interventions within ±6 months. MAIN OUTCOME MEASURES: Change in drug utilisation, defined as actual versus predicted percentage change in the number of prescriptions (for advisories without dose-related advice), or in the number of defined daily doses (for dose-related advisories), per 100 000 population. RESULTS: Among advisories without dose-related advice (n=20), the average change in drug utilisation was -5.83% (95% CI -10.93 to -0.73; p=0.03). Advisories with dose-related advice (n=4) were not associated with a statistically significant change in drug utilisation (-1.93%; 95% CI -17.10 to 13.23; p=0.80). In a post hoc subgroup analysis of advisories without dose-related advice, we observed no statistically significant difference between the change in drug utilisation following advisories with explicit prescribing advice, such as a recommendation to consider the risk of a drug when prescribing, and the change in drug utilisation following advisories without such advice. CONCLUSIONS: Among safety advisories issued on a wide range of drugs during 2009-2015 in 4 countries (Canada, Denmark, the UK and the USA), the association of advisories with changes in drug utilisation was variable, and the average association was modest.

Over half of clinical practice guidelines use non-systematic methods to inform recommendations: A methods study.

INTRODUCTION: Assessing the process used to synthesize the evidence in clinical practice guidelines enables users to determine the trustworthiness of the recommendations. Clinicians are increasingly dependent on guidelines to keep up with vast quantities of medical literature, and guidelines are followed to avoid malpractice suits. We aimed to assess whether systematic methods were used when synthesizing the evidence for guidelines; and to determine the type of review cited in support of recommendations. METHODS: Guidelines published in 2017 and 2018 were retrieved from the TRIP and Epistemonikos databases. We randomly sorted and sequentially screened clinical guidelines on all topics to select the first 50 that met our inclusion criteria. Our primary outcomes were the number of guidelines using either a systematic or non-systematic process to gather, assess, and synthesise evidence; and the numbers of recommendations within guidelines based on different types of evidence synthesis (systematic or non-systematic reviews). If a review was cited, we looked for evidence that it was critically appraised, and recorded which quality assessment tool was used. Finally, we examined the relation between the use of the GRADE approach, systematic review process, and type of funder. RESULTS: Of the 50 guidelines, 17 (34%) systematically synthesised the evidence to inform recommendations. These 17 guidelines clearly reported their objectives and eligibility criteria, conducted comprehensive search strategies, and assessed the quality of the studies. Of the 29/50 guidelines that included reviews, 6 (21%) assessed the risk of bias of the review. The quality of primary studies was reported in 30/50 (60%) guidelines. CONCLUSIONS: High quality, systematic review products provide the best available evidence to inform guideline recommendations. Using non-systematic methods compromises the validity and reliability of the evidence used to inform guideline recommendations, leading to potentially misleading and untrustworthy results.

Do Intervention Studies to Promote Physical Activity and Reduce Sedentary Behavior in Children and Adolescents Take Sex/Gender Into Account? A Systematic Review.

BACKGROUND: Physical inactivity is often reported in youth and differs among boys and girls. The aim of this study is to assess sex/gender considerations in intervention studies promoting physical activity and reducing sedentary behavior in youth using a sex/gender checklist. METHODS: A systematic search was conducted in August 2018 to identify all relevant controlled trials. Studies screened must have reported a quantified measure of physical activity and/or sedentary behavior, and identified participants by sex/gender at baseline. For evaluation of the sex/gender consideration, the authors used a sex/gender checklist developed by expert consensus. RESULTS: The authors reviewed sex/gender considerations in all aspects of intervention development, implementation, and evaluation in 217 studies. Sex/gender aspects were only rudimentarily taken into account, most frequently during statistical analyses, such as stratification or interaction analysis. CONCLUSIONS: Sex/gender effects are not sufficiently reported. To develop guidelines that are more inclusive of all girls and boys, future interventions need to document sex/gender differences and similarities, and explore whether sex/gender influences different phases of intervention programs. The newly developed sex/gender checklist can hereby be used as a tool and guidance to adequately consider sex/gender in the several steps of intervention planning, implementation, and evaluation.

A sex/gender perspective on interventions to promote children's and adolescents' overall physical activity: results from genEffects systematic review.

BACKGROUND: To evaluate the effects of interventions on children's and adolescents' overall physical activity (PA) for boys and girls separately and to appraise the extent to which the studies haven taken sex/gender into account. METHODS: Systematic review and semi-quantitative analysis. Eleven electronic databases were searched to identify all relevant randomized and non-randomized controlled trials. Studies had to report overall PA as the main outcome to be eligible for inclusion in the review. The main outcomes of the studies is a quantified measure of overall PA. Additionally, all studies had to report sex/gender disaggregated overall PA at baseline and/or follow up and/or explain how they dealt with sex/gender during outcome analysis (i.e., sex/gender adjusted analyses) and/or report that there were no differences in the outcome when looking at sex/gender. PRISMA guidelines were followed. Two authors independently screened studies for eligibility and assessed the risk of bias. Semi-quantitative analyses were conducted to evaluate intervention effects, taking into account the extent to which studies have considered sex/gender aspects. To evaluate sex/gender considerations in primary studies, a newly developed sex/gender checklist was used. The study was registered previously (registration number CRD42018109528). RESULTS: In total, 97 articles reporting 94 unique studies with 164 outcomes for overall PA were included in the present review. Average sample size was 829 participants, ranging from five to 9839. Participants' ages ranged from three to 19 years. Our review shows that overall 35% of PA outcomes had significant effects in increasing overall PA of children and adolescents. Not including single sex/gender studies, 105 out of 120 PA outcomes resulted in same intervention effects for boys and girls. The interventions reported to have similar effects on PA outcomes for boys and girls showed higher quality of reporting sex/gender aspects of measurement instruments, participant flow and intervention content and materials than PA outcomes with effects only in boys or only in girls. Overall, consideration of sex/gender aspects in intervention studies is low. CONCLUSIONS: There is still a need to address sufficient consideration of sex/gender aspects in developing and implementing interventions in the context of PA.

A descriptive analysis of medicines safety advisories issued by national medicines regulators in Australia, Canada, the United Kingdom and the United States - 2007 to 2016.

PURPOSE: To determine the frequency and characteristics of safety advisories issued by medicines regulatory agencies in Australia, Canada, United Kingdom (UK) and the United States (US). METHODS: This retrospective analysis examines medicines safety warnings issued by the US Food and Drug Administration (FDA), Health Canada (HC), the Australian Therapeutic Goods Administration (TGA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) from January 1, 2007 until December 31, 2016. A database of warnings obtained from regulators' websites was developed and warnings were classified by communication type, drug, or therapeutic class focus, and the risk discussed. Advisories identifying the same drug or therapeutic class and risk were combined into groups termed "drug-risk issues" for comparisons between regulators. RESULTS: Over this 10-year period, 1441 advisories were identified, with the MHRA issuing the most advisories (MHRA = 469, FDA = 382, HC = 370 TGA = 220). Seventy two percent focussed on single drugs (1034/1441) and 58.7% were alerts (846/1441) posted on the regulators' websites. Diabetes drugs, smoking cessation drugs and immunomodulatory agents were the individual drug types most often subject to safety advisories, while antidepressants, antipsychotics, and proton-pump inhibitors were the top three therapeutic classes. Of 680 identified drug-risk issues, 3.8% (26/680) described a risk of death. By body system, cardiac effects were the most frequent: 10.4% (71/680). CONCLUSION: We found considerable differences in the use of advisories including frequency, communication type, and focus. Disparities in communication about emergent evidence on risks may mean that clinicians and patients in some countries are less well informed about medicine safety concerns than others.

Media coverage of drug regulatory agencies' safety advisories: A case study of citalopram and denosumab.

AIMS: Drug regulators issue safety advisories to warn clinicians and the public about new evidence of harmful effects of medicines. It is unclear how often these messages are covered by the media. Our aim was to analyse the extent of media coverage of two medicines that were subject to safety advisories from 2007 to 2016 in Australia, Canada, the United Kingdom and the United States. METHODS: Two medicines widely used to treat mental health or physical conditions were selected: citalopram and denosumab. Media reports were identified by searching LexisNexis and Factiva. Reports were included if they stated at least one health benefit or harm. A content analysis of the reports was conducted. RESULTS: In total, 195 media reports on citalopram and 239 on denosumab were included. For citalopram, 43.1% (84/195) of the reports mentioned benefits, 85.6% (167/195) mentioned harms and 9.7% (19/195) mentioned the harm described in the advisories (cardiac arrhythmia). For denosumab, 94.1% (225/239) of the reports mentioned benefits and 39.7% (95/239) mentioned harms. The harms described in the advisories were rarely mentioned: 10.9% (26/239) of the reports mentioned osteonecrosis and ≤5% mentioned any of the other harms (atypical fractures, hypocalcaemia, serious infections and dermatologic reactions). CONCLUSIONS: We found limited media coverage of the harms highlighted in safety advisories. Almost two-thirds of the media stories on denosumab did not include any information about harms, despite the many advisories during this time frame. Citalopram coverage covered harms more often but rarely mentioned cardiac arrhythmias. These findings raise questions about how to better ensure that regulatory risk communications reach the general public.

Impact and use of reviews and 'overviews of reviews' to inform clinical practice guideline recommendations: protocol for a methods study.

INTRODUCTION: Guidelines are systematically developed recommendations to assist practitioner and patient decisions about treatments for clinical conditions. High quality and comprehensive systematic reviews and 'overviews of systematic reviews' (overviews) represent the best available evidence. Many guideline developers, such as the WHO and the Australian National Health and Medical Research Council, recommend the use of these research syntheses to underpin guideline recommendations. We aim to evaluate the impact and use of systematic reviews with and without pairwise meta-analysis or network meta-analyses (NMAs) and overviews in clinical practice guideline (CPG) recommendations. METHODS AND ANALYSIS: CPGs will be retrieved from Turning Research Into Practice and Epistemonikos (2017-2018). The retrieved citations will be sorted randomly and then screened sequentially by two independent reviewers until 50 CPGs have been identified. We will include CPGs that provide at least two explicit recommendations for the management of any clinical condition. We will assess whether reviews or overviews were cited in a recommendation as part of the development process for guidelines. Data extraction will be done independently by two authors and compared. We will assess the risk of bias by examining how each guideline developed clinical recommendations. We will calculate the number and frequency of citations of reviews with or without pairwise meta-analysis, reviews with NMAs and overviews, and whether they were systematically or non-systematically developed. Results will be described, tabulated and categorised based on review type (reviews or overviews). CPGs reporting the use of the Grading of Recommendations, Assessment, Development and Evaluation approach will be compared with those using a different system, and pharmacological versus non-pharmacological CPGs will be compared. ETHICS AND DISSEMINATION: No ethics approval is required. We will present at the Cochrane Colloquium and the Guidelines International Network conference.

Validation of five search filters for retrieval of clinical practice guidelines produced low precision.

OBJECTIVES: The aim of the study was to validate search filters for retrieval of clinical practice guidelines (CPGs) in MEDLINE, Embase, and PubMed. STUDY DESIGN AND SETTING: A search for filters for identifying CPGs was conducted in Google and the InterTASC Information Specialists Sub-Group Search Filter Resource. To retrieve a random sample of CPGs to test sensitivity and precision of the filters, we used the TRIP and Epistemonikos databases. The citations were screened independently by two researchers. The sensitivity and precision were calculated. RESULTS: Five search filters were retrieved: two from the Canadian Agency for Drugs and Technologies in Health (CADTH), two from the University of Texas, and one from the MD Anderson Cancer Center Library. A total of 478 records were screened to identify 109 CPGs, which comprised the sample for testing sensitivity and precision. The sensitivity ranged from 87% to 98% for the five search filters and very low precision (<1%) across all databases. CONCLUSION: Knowledge users who are interested in retrieving all relevant CPGs can use the CADTH broad filter with the highest sensitivity. However, our analysis shows that it remains difficult to efficiently identify CPGs because of low precision of five search filters. We recommend searching guideline-specific resources as a more time-efficient approach than searching bibliographic databases.

Pharmacotherapy for hypertension in adults 60 years or older.

BACKGROUND: This is the second substantive update of this review. It was originally published in 1998 and was previously updated in 2009. Elevated blood pressure (known as 'hypertension') increases with age - most rapidly over age 60. Systolic hypertension is more strongly associated with cardiovascular disease than is diastolic hypertension, and it occurs more commonly in older people. It is important to know the benefits and harms of antihypertensive treatment for hypertension in this age group, as well as separately for people 60 to 79 years old and people 80 years or older. OBJECTIVES: Primary objective• To quantify the effects of antihypertensive drug treatment as compared with placebo or no treatment on all-cause mortality in people 60 years and older with mild to moderate systolic or diastolic hypertensionSecondary objectives• To quantify the effects of antihypertensive drug treatment as compared with placebo or no treatment on cardiovascular-specific morbidity and mortality in people 60 years and older with mild to moderate systolic or diastolic hypertension• To quantify the rate of withdrawal due to adverse effects of antihypertensive drug treatment as compared with placebo or no treatment in people 60 years and older with mild to moderate systolic or diastolic hypertension SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to 24 November 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work. SELECTION CRITERIA: Randomised controlled trials of at least one year's duration comparing antihypertensive drug therapy versus placebo or no treatment and providing morbidity and mortality data for adult patients (≥ 60 years old) with hypertension defined as blood pressure greater than 140/90 mmHg. DATA COLLECTION AND ANALYSIS: Outcomes assessed were all-cause mortality; cardiovascular morbidity and mortality; cerebrovascular morbidity and mortality; coronary heart disease morbidity and mortality; and withdrawal due to adverse effects. We modified the definition of cardiovascular mortality and morbidity to exclude transient ischaemic attacks when possible. MAIN RESULTS: This update includes one additional trial (MRC-TMH 1985). Sixteen trials (N = 26,795) in healthy ambulatory adults 60 years or older (mean age 73.4 years) from western industrialised countries with moderate to severe systolic and/or diastolic hypertension (average 182/95 mmHg) met the inclusion criteria. Most of these trials evaluated first-line thiazide diuretic therapy for a mean treatment duration of 3.8 years.Antihypertensive drug treatment reduced all-cause mortality (high-certainty evidence; 11% with control vs 10.0% with treatment; risk ratio (RR) 0.91, 95% confidence interval (CI) 0.85 to 0.97; cardiovascular morbidity and mortality (moderate-certainty evidence; 13.6% with control vs 9.8% with treatment; RR 0.72, 95% CI 0.68 to 0.77; cerebrovascular mortality and morbidity (moderate-certainty evidence; 5.2% with control vs 3.4% with treatment; RR 0.66, 95% CI 0.59 to 0.74; and coronary heart disease mortality and morbidity (moderate-certainty evidence; 4.8% with control vs 3.7% with treatment; RR 0.78, 95% CI 0.69 to 0.88. Withdrawals due to adverse effects were increased with treatment (low-certainty evidence; 5.4% with control vs 15.7% with treatment; RR 2.91, 95% CI 2.56 to 3.30. In the three trials restricted to persons with isolated systolic hypertension, reported benefits were similar.This comprehensive systematic review provides additional evidence that the reduction in mortality observed was due mostly to reduction in the 60- to 79-year-old patient subgroup (high-certainty evidence; RR 0.86, 95% CI 0.79 to 0.95). Although cardiovascular mortality and morbidity was significantly reduced in both subgroups 60 to 79 years old (moderate-certainty evidence; RR 0.71, 95% CI 0.65 to 0.77) and 80 years or older (moderate-certainty evidence; RR 0.75, 95% CI 0.65 to 0.87), the magnitude of absolute risk reduction was probably higher among 60- to 79-year-old patients (3.8% vs 2.9%). The reduction in cardiovascular mortality and morbidity was primarily due to a reduction in cerebrovascular mortality and morbidity. AUTHORS' CONCLUSIONS: Treating healthy adults 60 years or older with moderate to severe systolic and/or diastolic hypertension with antihypertensive drug therapy reduced all-cause mortality, cardiovascular mortality and morbidity, cerebrovascular mortality and morbidity, and coronary heart disease mortality and morbidity. Most evidence of benefit pertains to a primary prevention population using a thiazide as first-line treatment.

Interventions on children's and adolescents' physical activity and sedentary behaviour: protocol for a systematic review from a sex/gender perspective.

BACKGROUND: Low levels of physical activity (PA) and high levels of sedentary behaviour (SB) have been observed in young people. Both behaviours are detrimental for health with patterns tending to continue into adulthood. There is sustained value in establishing health habits in early years. Even though levels of SB and participation in PA differ among boys and girls, and the effectiveness of interventions to promote PA and/or prevent sedentary behaviours varies by sex/gender to date, sex/gender in systematic reviews is not yet widely considered. Additionally, while tools have been proposed, there is no consensus on the criteria to assess sex/gender in systematic reviews in the context of health promotion. The main objectives of this systematic review are to evaluate the effects of interventions on girls' and boys' PA and SB and to appraise the extent to which the studies have taken sex/gender into account. METHODS: Eleven electronic databases will be searched to identify all relevant (randomized) controlled trials. Two independent reviewers will screen studies, extract data and appraise the quality of studies. The main outcome of the studies will be a quantified measure of PA and/or SB. Risk of bias of individual studies will be assessed using the Cochrane Risk of Bias Tool for RCTs. Meta-analyses will be conducted when possible among studies with sufficient homogeneity. To evaluate sex/gender considerations in primary studies, we will use a sex/gender checklist that builds on existing tools and was developed during a 2-day, iterative process among a multidisciplinary panel of 16 experts. The GRADE framework will be used to evaluate evidence across studies for each main efficacy outcome. DISCUSSION: To our knowledge, our systematic review will be the first to analyse how sex/gender is considered in interventions promoting PA and/or reducing SB in children and adolescents in detail. The review will provide information on how sex/gender aspects have been considered in recent research and the extent to which sex/gender might impact study outcomes. Our findings will be of interest to stakeholders, health promoters, researchers and policy makers who wish to support more equal outcomes from interventions promoting PA and/or reducing SB. TRIAL REGISTRATION: PROSPERO CRD42018109528 .

Pharmacotherapy for hypertension in adults aged 18 to 59 years.

BACKGROUND: Hypertension is an important risk factor for adverse cardiovascular events including stroke, myocardial infarction, heart failure and renal failure. The main goal of treatment is to reduce these events. Systematic reviews have shown proven benefit of antihypertensive drug therapy in reducing cardiovascular morbidity and mortality but most of the evidence is in people 60 years of age and older. We wanted to know what the effects of therapy are in people 18 to 59 years of age. OBJECTIVES: To quantify antihypertensive drug effects on all-cause mortality in adults aged 18 to 59 years with mild to moderate primary hypertension. To quantify effects on cardiovascular mortality plus morbidity (including cerebrovascular and coronary heart disease mortality plus morbidity), withdrawal due adverse events and estimate magnitude of systolic blood pressure (SBP) and diastolic blood pressure (DBP) lowering at one year. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to January 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work. SELECTION CRITERIA: Randomized trials of at least one year' duration comparing antihypertensive pharmacotherapy with a placebo or no treatment in adults aged 18 to 59 years with mild to moderate primary hypertension defined as SBP 140 mmHg or greater or DBP 90 mmHg or greater at baseline, or both. DATA COLLECTION AND ANALYSIS: The outcomes assessed were all-cause mortality, total cardiovascular (CVS) mortality plus morbidity, withdrawals due to adverse events, and decrease in SBP and DBP. For dichotomous outcomes, we used risk ratio (RR) with 95% confidence interval (CI) and a fixed-effect model to combine outcomes across trials. For continuous outcomes, we used mean difference (MD) with 95% CI and a random-effects model as there was significant heterogeneity. MAIN RESULTS: The population in the seven included studies (17,327 participants) were predominantly healthy adults with mild to moderate primary hypertension. The Medical Research Council Trial of Mild Hypertension contributed 14,541 (84%) of total randomized participants, with mean age of 50 years and mean baseline blood pressure of 160/98 mmHg and a mean duration of follow-up of five years. Treatments used in this study were bendrofluazide 10 mg daily or propranolol 80 mg to 240 mg daily with addition of methyldopa if required. The risk of bias in the studies was high or unclear for a number of domains and led us to downgrade the quality of evidence for all outcomes.Based on five studies, antihypertensive drug therapy as compared to placebo or untreated control may have little or no effect on all-cause mortality (2.4% with control vs 2.3% with treatment; low quality evidence; RR 0.94, 95% CI 0.77 to 1.13). Based on 4 studies, the effects on coronary heart disease were uncertain due to low quality evidence (RR 0.99, 95% CI 0.82 to 1.19). Low quality evidence from six studies showed that drug therapy may reduce total cardiovascular mortality and morbidity from 4.1% to 3.2% over five years (RR 0.78, 95% CI 0.67 to 0.91) due to reduction in cerebrovascular mortality and morbidity (1.3% with control vs 0.6% with treatment; RR 0.46, 95% CI 0.34 to 0.64). Very low quality evidence from three studies showed that withdrawals due to adverse events were higher with drug therapy from 0.7% to 3.0% (RR 4.82, 95% CI 1.67 to 13.92). The effects on blood pressure varied between the studies and we are uncertain as to how much of a difference treatment makes on average. AUTHORS' CONCLUSIONS: Antihypertensive drugs used to treat predominantly healthy adults aged 18 to 59 years with mild to moderate primary hypertension have a small absolute effect to reduce cardiovascular mortality and morbidity primarily due to reduction in cerebrovascular mortality and morbidity. All-cause mortality and coronary heart disease were not reduced. There is lack of good evidence on withdrawal due to adverse events. Future trials in this age group should be at least 10 years in duration and should compare different first-line drug classes and strategies.

Development and evaluation of 'briefing notes' as a novel knowledge translation tool to aid the implementation of sex/gender analysis in systematic reviews: a pilot study.

BACKGROUND: There is increasing recognition of sex/gender differences in health and the importance of identifying differential effects of interventions for men and women. Yet, to whom the research evidence does or does not apply, with regard to sex/gender, is often insufficiently answered. This is also true for systematic reviews which synthesize results of primary studies. A lack of analysis and reporting of evidence on sex/gender raises concerns about the applicability of systematic reviews. To bridge this gap, this pilot study aimed to translate knowledge about sex/gender analysis (SGA) into a user-friendly 'briefing note' format and evaluate its potential in aiding the implementation of SGA in systematic reviews. METHODS: Our Sex/Gender Methods Group used an interactive process to translate knowledge about sex/gender into briefing notes, a concise communication tool used by policy and decision makers. The briefing notes were developed in collaboration with three Cochrane Collaboration review groups (HIV/AIDS, Hypertension, and Musculoskeletal) who were also the target knowledge users of the briefing notes. Briefing note development was informed by existing systematic review checklists, literature on sex/gender, in-person and virtual meetings, and consultation with topic experts. Finally, we held a workshop for potential users to evaluate the notes. RESULTS: Each briefing note provides tailored guidance on considering sex/gender to reviewers who are planning or conducting systematic reviews and includes the rationale for considering sex/gender, with examples specific to each review group's focus. Review authors found that the briefing notes provided welcome guidance on implementing SGA that was clear and concise, but also identified conceptual and implementation challenges. CONCLUSIONS: Sex/gender briefing notes are a promising knowledge translation tool. By encouraging sex/gender analysis and equity considerations in systematic reviews, the briefing notes can assist systematic reviewers in ensuring the applicability of research evidence, with the goal of improved health outcomes for diverse populations.

Failure of psychological interventions to lower blood pressure: a randomized controlled trial.

BACKGROUND: Previous studies have suggested that psychological interventions may be effective in reducing blood pressure. Using rigorous methodology and 24-hour monitoring of ambulatory blood pressure, we compared 2 psychological interventions with treatment using a first-line antihypertensive drug in terms of their efficacy in lowering blood pressure in patients with mild primary hypertension. METHODS: In this prospective, open-label randomized controlled trial (RCT), 65 adult patients with mild, uncomplicated hypertension were randomly assigned to receive one of the following interventions for 12 weeks: (1) pharmacotherapy with hydrochlorothiazide 12.5 titrated to 25 mg/d ; (2) individualized behavioural psychotherapy, consisting of ten 1-hour sessions of stress reduction training with a psychologist; or (3) self-help psychotherapy, consisting of a 1.5-hour session with a psychologist and then daily sessions that involved reading a self-help manual and listening to an audiotape. The primary outcome measure was mean change in ambulatory blood pressure from baseline to week 12. Resting blood pressure readings were taken in the clinic, and adverse events were recorded. RESULTS: Monitoring of ambulatory blood pressure over 24 hours showed that hydrochlorothiazide therapy significantly reduced both systolic and diastolic blood pressure relative to baseline, and that this reduction was significantly greater than that achieved with either individualized behavioural psychotherapy or self-help psychotherapy (mean reduction [standard error; SE] -11.03 [2.53] / -6.06 [1.56] mm Hg v. -0.08 [2.38] / 0.29 [1.47] mm Hg v. -1.23 [2.83] / -0.71 [1.75] mm Hg, respectively; p = 0.01). Neither form of psychological therapy significantly lowered 24-hour ambulatory blood pressure relative to baseline. CONCLUSION: For patients with primary elevated blood pressure, 2 psychological interventions did not lower 24-hour ambulatory blood pressure, whereas hydrochlorothiazide reduced blood pressure, as expected. The findings of this RCT represent an important addition to the evidence for health care practitioners and for patients seeking psychological interventions to reduce blood pressure.

Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health.

The objective of this evidence review was to synthesize the literature on the effectiveness and safety of nutritional and ultraviolet radiation sources of vitamin D with respect to bone health outcomes at all stages of life. The goals were to identify knowledge gaps for the research community and to highlight areas that required further research. We completed an extensive literature search of multiple databases and a multilevel selection process with synthesis of results from 167 included studies. We included a variety of outcomes (eg, falls, bone mineral density, fractures, and adverse events). This report provides an overview of the methods and a summary of the key findings. In addition, we discuss areas where the evidence is inconclusive, as well as methodologic issues that we encountered. We found inconsistent evidence of an association between serum 25-hydroxyvitamin D [25(OH)D] concentration and bone mineral content in infants and fair evidence of an association with bone mineral content or density in older children and older adults. The evidence of an association between serum 25(OH)D concentration and some clinical outcomes (fractures, performance measures) in postmenopausal women and older men was inconsistent, and the evidence of an association with falls was fair. We found good evidence of a positive effect of consuming vitamin D-fortified foods on 25(OH)D concentrations. The evidence for a benefit of vitamin D on falls and fractures varied. We found fair evidence that adults tolerated vitamin D at doses above current dietary reference intake levels, but we had no data on the association between long-term harms and higher doses of vitamin D.