No abstract

No abstract

Background Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. Methods We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid stimulating hormone (TSH) 0.45–4.49mIU/l, and subclinical hypothyroidism as TSH 4.5–19.9mIU/l with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. Results Of 30,085 participants from 11 cohorts (278,955 person-years of follow-up), 1,958 (6.5%) had subclinical hypothyroidism, and 2,574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio=1.45; 95% confidence interval, 1.26–1.66, for the highest quartile vs the lowest quartile of fT4, p for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. Conclusion In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.

Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.

Objective To examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital. Design Cluster randomised controlled trial. Setting 110 clusters of inpatient wards within university based hospitals in four European countries (Switzerland, Netherlands, Belgium, and Republic of Ireland) defined by attending hospital doctors. Participants 2008 older adults (≥70 years) with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 drugs used long term). Intervention Clinical staff clusters were randomised to usual care or a structured pharmacotherapy optimisation intervention performed at the individual level jointly by a doctor and a pharmacist, with the support of a clinical decision software system deploying the screening tool of older person’s prescriptions and screening tool to alert to the right treatment (STOPP/START) criteria to identify potentially inappropriate prescribing. Main outcome measure Primary outcome was first drug related hospital admission within 12 months. Results 2008 older adults (median nine drugs) were randomised and enrolled in 54 intervention clusters (963 participants) and 56 control clusters (1045 participants) receiving usual care. In the intervention arm, 86.1% of participants (n=789) had inappropriate prescribing, with a mean of 2.75 (SD 2.24) STOPP/START recommendations for each participant. 62.2% (n=491) had ≥1 recommendation successfully implemented at two months, predominantly discontinuation of potentially inappropriate drugs. In the intervention group, 211 participants (21.9%) experienced a first drug related hospital admission compared with 234 (22.4%) in the control group. In the intention-to-treat analysis censored for death as competing event (n=375, 18.7%), the hazard ratio for first drug related hospital admission was 0.95 (95% confidence interval 0.77 to 1.17). In the per protocol analysis, the hazard ratio for a drug related hospital admission was 0.91 (0.69 to 1.19). The hazard ratio for first fall was 0.96 (0.79 to 1.15; 237 v 263 first falls) and for death was 0.90 (0.71 to 1.13; 172 v 203 deaths). Conclusions Inappropriate prescribing was common in older adults with multimorbidity and polypharmacy admitted to hospital and was reduced through an intervention to optimise pharmacotherapy, but without effect on drug related hospital admissions. Additional efforts are needed to identify pharmacotherapy optimisation interventions that reduce inappropriate prescribing and improve patient outcomes. Trial registration ClinicalTrials.gov NCT02986425 .

Context: While both overt hyper-and hypothyroidism are known to lead to cognitive impairment, data on the association between subclinical thyroid dysfunction and cognitive function are conflicting. Objective: To determine the risk of dementia and cognitive decline associated with subclinical thyroid dysfunction among prospective cohorts. Data Sources: Search in MEDLINE, EMBASE until November 2014. Study Selection: Two physicians identified prospective cohorts that assessed thyroid function and cognitive outcomes (dementia; Mini-Mental State Examination, MMSE). Data Extraction: Data were extracted by one reviewer following standardized protocols and verified by a second reviewer. The primary outcome was dementia and decline in cognitive function was the secondary outcome. Data Synthesis: Eleven prospective cohorts followed 16,805 participants during a median follow-up of 44.4 months. Five studies analyzed the risk of dementia in subclinical hyperthyroidism (n=6410), six in subclinical hypothyroidism (n=7401). Five studies analyzed MMSE decline in subclinical hyperthyroidism (n=7895), seven in subclinical hypothyroidism (n=8960). In random-effects models, the pooled adjusted RR for dementia in subclinical hyperthyroidism was 1.67 (95% confidence interval [CI] 1.04-2.69) and 1.14 (95%CI 0.84-1.55) in subclinical hypothyroidism versus euthyroidism, both without evidence of significant heterogeneity (I 2 =0.0%). The pooled mean MMSE decline from baseline to follow-up (mean 32 months) did not significantly differ between subclinical hyper-or hypothyroidism versus euthyroidism. Conclusions: Subclinical hyperthyroidism might be associated with an elevated risk for dementia, while subclinical hypothyroidism is not, and both conditions are not associated with faster decline in MMSE over time. Available data are limited, and additional large, high-quality studies are needed. * Unadjusted additional data has been used for this meta-analysis. The original study adjusted for age, sex, education, serum cholesterol, Geriatric Depression Scale Score, BMI, hypertension, diabetes mellitus, history of cardiovascular disease, plasma total homocysteine. ** No adjustment for age because of same aged cohort.

Background: Fecal immunochemical testing is the most commonly used method for colorectal cancer screening worldwide. However, its effectiveness is frequently undermined by failure to obtain follow-up colonoscopy after positive test results. Purpose: To evaluate interventions to improve rates of follow-up colonoscopy for adults after a positive result on a fecal test (guaiac or immunochemical). Data Sources: English-language studies from the Cochrane Central Register of Controlled Trials, PubMed, and Embase from database inception through June 2017. Study Selection: Randomized and nonrandomized studies reporting an intervention for colonoscopy follow-up of asymptomatic adults with positive fecal test results. Data Extraction: Two reviewers independently extracted data and ranked study quality; 3 rated overall strength of evidence for each category of study type. Data Synthesis: Twenty-three studies were eligible for analysis, including 7 randomized and 16 nonrandomized studies. Three were at low risk of bias. Eleven studies described patient-level interventions (changes to invitation, provision of results or follow-up appointments, and patient navigators), 5 provider-level interventions (reminders or performance data), and 7 system-level interventions (automated referral, precolonoscopy telephone calls, patient registries, and quality improvement efforts). Moderate evidence supported patient navigators and provider reminders or performance data. Evidence for system-level interventions was low. Seventeen studies reported the proportion of test-positive patients who completed colonoscopy compared with a control population, with absolute differences of −7.4 percentage points (95% CI, −19 to 4.3 percentage points) to 25 percentage points (CI, 14 to 35 percentage points). Limitation: More than half of studies were at high or very high risk of bias; heterogeneous study designs and characteristics precluded meta-analysis. Conclusion: Patient navigators and the provision to providers of reminders or performance data may help improve colonoscopy rates of asymptomatic adults with positive fecal blood test results. Current evidence about useful system-level interventions is scant and insufficient.

Subclinical hypothyroidism, which is defined as elevated thyroid-stimulating hormone (TSH) levels with free thyroxine concentrations within the reference range, is a common disorder that increases with age and affects up to 18% of the elderly, with a higher prevalence in women compared to men. Prospective data have shown an increased risk of coronary heart disease events, heart failure, and cardiovascular mortality among affected adults. Conflicting results have been found on the association between subclinical hypothyroidism and cognitive impairment, depression and the risk of fractures. Management strategies including screening and treatment of subclinical hypothyroidism are still controversial, while the ongoing European randomised controlled trial "TRUST" targets to solve these uncertainties. This narrative review aims to assess current evidence on the clinical aspects, as well as screening and treatment recommendations in adults with subclinical hypothyroidism.