The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis.

BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT4 based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT4, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT4, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT4 with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L [IQR 11·2-13·9]) to 40th percentiles (median 14·8 pmol/L [12·3-15·0]) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT4 in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT4 greater than the 85th percentile (median 17·6 pmol/L [IQR 15·0-18·3]), and men with FT4 greater than the 75th percentile (16·7 pmol/L [14·0-17·4]). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L [IQR 1·68-2·25]) to 80th percentiles (2·90 mIU/L [2·41-3·32]) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality. INTERPRETATION: There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes. FUNDING: None.

Association of statin use and lipid levels with cerebral microbleeds and intracranial hemorrhage in patients with atrial fibrillation: A prospective cohort study.

BACKGROUND: An increased risk of intracranial hemorrhage (ICH) associated with statins has been reported, but data on the relationship between statin use and cerebral microbleeds (CMBs) in patients with atrial fibrillation (AF), a population at high bleeding and cardiovascular risk, are lacking. AIMS: To explore the association between statin use and blood lipid levels with the prevalence and progression of CMBs in patients with AF with a particular focus on anticoagulated patients. METHODS: Data of Swiss-AF, a prospective cohort of patients with established AF, were analyzed. Statin use was assessed during baseline and throughout follow-up. Lipid values were measured at baseline. CMBs were assessed using magnetic resonance imagining (MRI) at baseline and at 2 years follow-up. Imaging data were centrally assessed by blinded investigators. Associations of statin use and low-density lipoprotein (LDL) levels with CMB prevalence at baseline or CMB progression (at least one additional or new CMB on follow-up MRI at 2 years compared with baseline) were assessed using logistic regression models; the association with ICH was assessed using flexible parametric survival models. Models were adjusted for hypertension, smoking, body mass index, diabetes, stroke/transient ischemic attack, coronary heart disease, antiplatelet use, anticoagulant use, and education. RESULTS: Of the 1693 patients with CMB data at baseline MRI (mean ± SD age 72.5 ± 8.4 years, 27.6% women, 90.1% on oral anticoagulants), 802 patients (47.4%) were statin users. The multivariable adjusted odds ratio (adjOR) for CMBs prevalence at baseline for statin users was 1.10 (95% CI = 0.83-1.45). AdjOR for 1 unit increase in LDL levels was 0.95 (95% CI = 0.82-1.10). At 2 years, 1188 patients had follow-up MRI. CMBs progression was observed in 44 (8.0%) statin users and 47 (7.4%) non-statin users. Of these patients, 64 (70.3%) developed a single new CMB, 14 (15.4%) developed 2 CMBs, and 13 developed more than 3 CMBs. The multivariable adjOR for statin users was 1.09 (95% CI = 0.66-1.80). There was no association between LDL levels and CMB progression (adjOR 1.02, 95% CI = 0.79-1.32). At follow-up 14 (1.2%) statin users had ICH versus 16 (1.3%) non-users. The age and sex adjusted hazard ratio (adjHR) was 0.75 (95% CI = 0.36-1.55). The results remained robust in sensitivity analyses excluding participants without anticoagulants. CONCLUSIONS: In this prospective cohort of patients with AF, a population at increased hemorrhagic risk due to anticoagulation, the use of statins was not associated with an increased risk of CMBs.

Cardiovascular disease and type 2 diabetes in older adults: a combined protocol for an individual participant data analysis for risk prediction and a network meta-analysis of novel anti-diabetic drugs.

Introduction: Older and multimorbid adults with type 2 diabetes (T2D) are at high risk of cardiovascular disease (CVD) and chronic kidney disease (CKD). Estimating risk and preventing CVD is a challenge in this population notably because it is underrepresented in clinical trials. Our study aims to (1) assess if T2D and haemoglobin A1c (HbA1c) are associated with the risk of CVD events and mortality in older adults, (2) develop a risk score for CVD events and mortality for older adults with T2D, (3) evaluate the comparative efficacy and safety of novel antidiabetics. Methods and analysis: For Aim 1, we will analyse individual participant data on individuals aged ≥65 years from five cohort studies: the Optimising Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older People study; the Cohorte Lausannoise study; the Health, Aging and Body Composition study; the Health and Retirement Study; and the Survey of Health, Ageing and Retirement in Europe. We will fit flexible parametric survival models (FPSM) to assess the association of T2D and HbA1c with CVD events and mortality. For Aim 2, we will use data on individuals aged ≥65 years with T2D from the same cohorts to develop risk prediction models for CVD events and mortality using FPSM. We will assess model performance, perform internal-external cross validation, and derive a point-based risk score. For Aim 3, we will systematically search randomized controlled trials of novel antidiabetics. Network meta-analysis will be used to determine comparative efficacy in terms of CVD, CKD, and retinopathy outcomes, and safety of these drugs. Confidence in results will be judged using the CINeMA tool. Ethics and dissemination: Aims 1 and 2 were approved by the local ethics committee (Kantonale Ethikkommission Bern); no approval is required for Aim 3. Results will be published in peer-reviewed journals and presented in scientific conferences.

Association of clinical and genetic risk factors with management of dyslipidaemia: analysis of repeated cross-sectional studies in the general population of Lausanne, Switzerland.

OBJECTIVES: To assess the importance of clinical and genetic factors in management of dyslipidaemia in the general population. DESIGN: Repeated cross-sectional studies (2003-2006; 2009-2012 and 2014-2017) from a population-based cohort. SETTING: Single centre in Lausanne, Switzerland. PARTICIPANTS: 617 (42.6% women, mean±SD: 61.6±8.5 years), 844 (48.5% women, 64.5±8.8 years) and 798 (50.3% women, 68.1±9.2) participants of the baseline, first and second follow-ups receiving any type of lipid-lowering drug. Participants were excluded if they had missing information regarding lipid levels, covariates or genetic data. PRIMARY AND SECONDARY OUTCOME MEASURES: Management of dyslipidaemia was assessed according to European or Swiss guidelines. Genetic risk scores (GRSs) for lipid levels were computed based on the existing literature. RESULTS: Prevalence of adequately controlled dyslipidaemia was 52%, 45% and 46% at baseline, first and second follow-ups, respectively. On multivariable analysis, when compared with intermediate or low-risk individuals, participants at very high cardiovascular risk had an OR for dyslipidaemia control of 0.11 (95% CI: 0.06 to 0.18), 0.12 (0.08 to 0.19) and 0.38 (0.25 to 0.59) at baseline, first and second follow-ups, respectively. Use of newer generation or higher potency statins was associated with better control: OR of 1.90 (1.18 to 3.05) and 3.62 (1.65 to 7.92) for second and third generations compared with first in the first follow-up, with the corresponding values in the second follow-up being 1.90 (1.08 to 3.36) and 2.18 (1.05 to 4.51). No differences in GRSs were found between controlled and inadequately controlled subjects. Similar findings were obtained using Swiss guidelines. CONCLUSION: Management of dyslipidaemia is suboptimal in Switzerland. The effectiveness of high potency statins is hampered by low posology. The use of GRSs in the management of dyslipidaemia is not recommended.

Major malformations risk following early pregnancy exposure to metformin: a systematic review and meta-analysis.

Metformin is considered as first-line treatment for type 2 diabetes and an effective treatment for polycystic ovary syndrome (PCOS). However, evidence regarding its safety in pregnancy is limited. We conducted a systematic review and meta-analysis of major congenital malformations (MCMs) risk after first-trimester exposure to metformin in women with PCOS and pregestational diabetes mellitus (PGDM). Randomized controlled trials (RCTs) and observational cohort studies with a control group investigating risk of MCM after first-trimester pregnancy exposure to metformin were searched until December 2021. ORs and 95% CIs were calculated separately according to indications and study type using Mantel-Haenszel method; outcome data were combined using random-effects model. Eleven studies (two RCTs; nine observational cohorts) met the inclusion criteria: four included pregnant women with PCOS, four included those with PGDM and three evaluated both indications separately and were considered in both indication groups. In PCOS group, there were two RCTs (57 exposed, 52 control infants) and five observational studies (472 exposed, 1892 control infants); point estimates for MCM rates in RCTs and observational studies were OR 0.93 (95% CI 0.09 to 9.21) (I2=0%; Q test=0.31; p value=0.58) and OR 1.35 (95% CI 0.37 to 4.90) (I2=65%; Q test=9.43; p value=0.05), respectively. In PGDM group, all seven studies were observational (1122 exposed, 1851 control infants); the point estimate for MCM rates was OR 1.05 (95% CI 0.50 to 2.18) (I2=59%; Q test=16.34; p value=0.01). Metformin use in first-trimester pregnancy in women with PCOS or PGDM do not meaningfully increase the MCM risk overall. However, further studies are needed to characterize residual safety concerns.

Slowness as a Predictor of Functional Decline in Older Adults: Comparison of Moberg Picking-Up Test and Walking Speed.

OBJECTIVES: Slowness, generally assessed by walking speed (WS), is an estimator of frailty and its outcomes. Because of potential difficulties in assessing WS, the Moberg picking-up test (MPUT) might be an alternative. This study investigated the capacity of slowness measurements (WS and MPUT) to predict nonfatal adverse consequences of frailty: primarily, decline in basic activities of daily living (BADL); and secondarily, decline in instrumental activities of daily living (IADL), fall, hospitalization, and incident disease. DESIGN: Observational (prospective longitudinal study). SETTING AND PARTICIPANTS: This study used data from the population-based Lausanne cohort 65+. At baseline, 1887 individuals (aged 72-77 years) completed both WS (time to walk 20 m at usual pace) and MPUT (time to pick up 12 objects) assessments. METHODS: All outcomes, assessed at 1- and 4-year follow-ups, were entered in separate logistic regression models with adjustment for age, sex, and respective values at baseline. The prediction of all outcomes by either WS or MPUT was assessed using area under the receiver operating characteristic curve and compared by χ2 tests. RESULTS: There were positive associations between slowness either assessed by WS [relative risk (RR) = 2.48; P < .001] or MPUT (RR = 1.91; P < .001) and decline in BADL at 1-year follow-up. These associations remained significant at 4-year follow-up for both WS (RR = 2.28; P < .001) and MPUT (RR = 1.95; P < .001). There was no significant difference between predictive values of slow WS and MPUT for decline in BADL at 1-year (P = .328) and 4-year follow-ups (P = .413). The prediction was not significantly different for secondary outcomes, except for decline in IADL for which the prediction was slightly better for WS. CONCLUSIONS AND IMPLICATIONS: MPUT may be an alternative measurement of slowness with predictive value of functional decline. No significant difference in predictive capabilities of MPUT and WS for specific adverse consequences of frailty is promising in favor of using MPUT for measuring slowness.

Thyroid antibodies and levothyroxine effects in subclinical hypothyroidism: A pooled analysis of two randomized controlled trials.

BACKGROUND: Antithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4). OBJECTIVE: To determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies. METHODS: We pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti-thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. RESULTS: Among 660 participants (54% women) ≥65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of -2.07 (95% confidence interval: -6.04 to 1.90) for positive antibodies versus 0.89 (-1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores-adjusted between-group difference 1.75 (-3.60 to 7.09) for positive antibodies versus 1.14 (-1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment. CONCLUSIONS: Among older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4.

Real-world gait speed estimation, frailty and handgrip strength: a cohort-based study.

Gait speed is a reliable outcome measure across multiple diagnoses, recognized as the 6th vital sign. The focus of the present study was on assessment of gait speed in long-term real-life settings with the aim to: (1) demonstrate feasibility in large cohort studies, using data recorded with a wrist-worn accelerometer device; (2) investigate whether the walking speed assessed in the real-world is consistent with expected trends, and associated with clinical scores such as frailty/handgrip strength. This cross-sectional study included n = 2809 participants (1508 women, 1301 men, [45-75] years old), monitored with a wrist-worn device for 13 consecutive days. Validated algorithms were used to detect the gait bouts and estimate speed. A set of metrics were derived from the statistical distribution of speed of gait bouts categorized by duration (short, medium, long). The estimated usual gait speed (1-1.6 m/s) appears consistent with normative values and expected trends with age, gender, BMI and physical activity levels. Speed metrics significantly improved detection of frailty: AUC increase from 0.763 (no speed metrics) to 0.798, 0.800 and 0.793 for the 95th percentile of individual's gait speed for bout durations < 30, 30-120 and > 120 s, respectively (all p < 0.001). Similarly, speed metrics also improved the prediction of handgrip strength: AUC increase from 0.669 (no speed metrics) to 0.696, 0.696 and 0.691 for the 95th percentile of individual's gait speed for bout durations < 30, 30-120 and > 120 s, respectively (all p < 0.001). Forward stepwise regression showed that the 95th percentile speed of gait bouts with medium duration (30-120 s) to be the best predictor for both conditions. The study provides evidence that real-world gait speed can be estimated using a wrist-worn wearable system, and can be used as reliable indicator of age-related functional decline.

Polypill eligibility and equivalent intake in a Swiss population-based study.

The polypill has been advocated for cardiovascular disease (CVD) management. The fraction of the population who could benefit from the polypill in Switzerland is unknown. Assess (1) the prevalence of subjects (a) eligible for the polypill and (b) already taking a polypill equivalent; and (2) the determinants of polypill intake in the first (2009-2012) and second follow-ups (2014-2017) of a population-based prospective study conducted in Lausanne, Switzerland. The first and the second follow-ups included 5038 and 4596 participants aged 40-80 years, respectively. Polypill eligibility was defined as having a high CVD risk as assessed by an absolute CVD risk ≥ 5% with the SCORE equation for Switzerland and/or presenting with CVD. Four polypill equivalents were defined: statin + any antihypertensive with (A) or without (B) aspirin; statin + calcium channel blocker (CCB) (C); and statin + CCB + angiotensin-converting enzyme inhibitor (D). The prevalence of polypill eligibility was 20.6% (95% CI 19.5-21.8) and 27.7% (26.5-29.1) in the first and second follow-up, respectively. However, only around one-third of the eligible 29.5% (95% CI 26.7-32.3) and 30.4% (27.9-33.0) respectively, already took the polypill equivalents. All polypill equivalents were more prevalent among men, elderly and in presence of CVD. After multivariable adjustment, in both periods, male gender was associated with taking polypill equivalent A (OR: 1.93; 95% CI 1.45-2.55 and OR: 1.67; 95% CI 1.27-2.19, respectively) and polypill equivalent B (OR: 1.52; 95% CI 1.17-1.96 and OR: 1.41; 95% CI 1.07-1.85, respectively). Similarly, in both periods, age over 70 years, compared to middle-age, was associated with taking polypill equivalent A (OR: 11.71; CI 6.74-20.33 and OR: 9.56; CI 4.13-22.13, respectively) and equivalent B (OR: 13.22; CI 7.27-24.07 and OR: 20.63; CI 6.51-56.36, respectively). Former or current smoking was also associated with a higher likelihood of taking polypill equivalent A in both periods. A large fraction of the population is eligible for the polypill, but only one-third of them actually benefits from an equivalent, and this proportion did not change over time.

Trends and Determinants of Polypharmacy and Potential Drug-Drug Interactions at Discharge From Hospital Between 2009-2015.

BACKGROUND: Polypharmacy (PP) and excessive polypharmacy (EPP) are increasingly common and associated with risk of drug-drug interactions (DDIs). We aimed to measure the trends and determinants of PP and DDIs among patients discharged from the Department of Internal Medicine of the Lausanne University Hospital. METHODS: The retrospective study included 17,742 adult patients discharged between 2009 and 2015. Polypharmacy and EPP were defined as the concomitant prescription of five or more and ten or more drugs, respectively. Drug-drug interactions were defined as any combination of a drug metabolized by a cytochrome P450 or P-glycoprotein, and a drug considered as strong inductor or inhibitor of the corresponding enzyme was defined as a potential interaction. RESULTS: Three most commonly classes of drugs prescribed were "alimentary tract and metabolism (including insulins)," "nervous system," and "blood and blood forming organs." Polypharmacy decreased from 45% in 2009 to 41% in 2015, whereas EPP increased from 40% to 46%. In 2015, 13% of patients received 15 or more drugs. Age, coming from other health care settings, higher Charlson Index, number of comorbidities, and quartiles of length of stay were significantly and independently associated with PP and EPP. The risk of having at least one DDI decreased from 67.0% (95% confidence interval = 64.8-69.0) in 2009 to 59.3% (57.6-62.0) in 2015 (P < 0.001). Multivariate analysis showed number of drugs (odds ratio and 95% confidence interval = 3.68 [3.3-4.1], 9.39 [8.3-10.6], and 20.5 [17.3-28.4] for [5-9], [10-14], and 15+ drugs, respectively), gastrointestinal disease (3.13 [2.73-3.58]), and cancer (1.37 [1.18-1.58]) to be positively associated, and lung (0.82 [0.74-0.90]) and endocrinological (0.62 [0.52-0.74]) diseases to be negatively associated with risk of DDI. CONCLUSIONS: The pattern of drug prescription has changed and most prescribed groups increased during the study period. Excessive polypharmacy is increasing among hospital patients. The decrease in the overall risk of DDI could be due to an improved management of multidrug therapy.

Ten-Year Trend in Polypharmacy in the Lausanne Population.

BACKGROUND: Aging and associated morbidities place individuals at higher risk of polypharmacy and drug-drug interactions (DDIs). How polypharmacy and DDIs change with aging is important for public health management. OBJECTIVES: The aim of the study was to assess the 10-year trends in prevalence of polypharmacy and potential DDIs in a population-based sample. METHODS: Baseline (2003-2006) and follow-up (2014-2016) data were obtained from a sample of 4512 participants (baseline age range = 35-75 y, 55.1% women) from the population of Lausanne, Switzerland. Polypharmacy and polyactive drug use were defined by the regular use of five or more medications and five or more pharmacologically active substances, respectively. Drug-drug interactions were defined according to the criteria of the Geneva University Hospital. RESULTS: The percentage of participants taking at least one drug increased from 56.1% to 79.5% (P < 0.001). Among participants taking drugs, number of medications increased from 2.6 ± 1.9 (mean ± standard deviation) to 3.8 ± 2.9 after 10.9-year follow-up (P < 0.001); the corresponding values for active substances were 2.7 ± 2.0 and 4.0 ± 3.0 (P < 0.001). The prevalence of polypharmacy and polyactive substance use increased from 7.7% to 25.0% and from 8.8% to 27.1%, respectively (P < 0.001). The presence of at least one potential DDI increased from less than 1% to almost one sixth of all participants. CONCLUSIONS: In a community-dwelling sample, the prevalence of polypharmacy and polyactive substance use tripled during a 10.9-year follow-up, with an even greater increase in the prevalence of potential DDIs. Increasing rates of polypharmacy and DDIS warns the importance of preventing potential DDIs throughout healthcare system through various interventions.

Impact of urine and mixed incontinence on long-term care preference: a vignette-survey study of community-dwelling older adults.

BACKGROUND: In view of population aging, a better knowledge of factors influencing the type of long-term care (LTC) among older adults is necessary. Previous studies reported a close relationship between incontinence and institutionalization, but little is known on opinions of older citizens regarding the most appropriate place of care. This study aimed at evaluating the impact of urine and/or fecal incontinence on preferences of community-dwelling older citizens. METHODS: We derived data from the Lausanne cohort 65+, a population-based study of individuals aged from 68 to 82 years. A total of 2974 community-dwelling persons were interviewed in 2017 on the most appropriate place of LTC delivery for three vignettes displaying a fixed level of disability with varying degrees of incontinence (none, urinary, urinary and fecal). Multinomial logistic regression analyses explored the effect of respondents' characteristics on their opinion according to Andersen's model. RESULTS: The level of incontinence described in vignettes strongly determined the likelihood of considering institutional care as most appropriate. Respondents' characteristics such as age, gender, educational level, being a caregiver, knowledge of shelter housing or feeling supported by family influenced LTC choices. Self-reported incontinence and other indicators of respondents' need, however, had no significant independent effect. CONCLUSION: Among older community-dwelling citizens, urinary and fecal incontinence play a decisive role in the perception of a need for institutionalization. Prevention and early initiation of support for sufferers may be a key to prevent this need and ensure familiar surrounding as long as possible.

Ten-year trend in sleeping pills use in Switzerland: the CoLaus study.

OBJECTIVE: The aim of this study was to assess the trends and determinants of sleeping pill consumption in the general population. METHODS: This was a prospective study that included 4329 participants (2379 women, 51.9 ± 10.4 years) living in the city of Lausanne, Switzerland, followed up for an average of 10.9 years. Benzodiazepines and benzodiazepine receptor agonists were considered as sleeping pills. RESULTS: The prevalence (95% confidence interval [CI]) of sleeping pills use was 8.0% (7.2-8.9) at baseline and 8.4 (7.6-9.3) after 10.9 years. Overall, sleeping pills use was higher among women, elderly individuals, and individuals reporting a history of anxiety and depression. During the 10.9-year follow-up, 85.8% of participants never used sleeping pills, 2.7% used the sleeping pills at all assessments, and 11.5% shifted from using to quitting (and vice versa). On multivariate analysis, the factors associated with "always" sleeping pills use were as follows: female gender (relative risk ratio and [95% CI] = 1.80 [1.14-2.85]); older age (7.05 [3.56-14.0] for 65 + vs < 45 years); lower educational level (2.06 [1.06-3.99] for mandatory vs university); anxiety (5.61 [3.61-8.71] for yes/no); and depression (3.75 [2.47-5.69] for yes/no). The same factors were also associated with occasional sleeping pills use (ie, shifters): relative risk ratios and 95% CI = 1.56 (1.26-1.94), 2.37 (1.72-3.26), 1.35 (0.98-1.87), 3.40 (2.59-4.45), and 2.50 (1.99-3.15) for female gender, older age, lower educational level, and anxiety and depression, respectively. CONCLUSION: During a 10.9-year follow-up, one out of seven participants (14.2%) used sleeping pills at least once during the study period. Sleeping pills use is more frequent among individuals with anxiety or depression, elderly individuals, and women.

Readiness to accept health information and communication technologies: A population-based survey of community-dwelling older adults.

INTRODUCTION: The development of health information and communication technologies (HICTs) could modify the quality and cost of healthcare services delivered to an aging population. However, the acceptance of HICTs - a prerequisite for users to benefit from them - remains a challenge. This population-based study aimed to 1) explore the acceptance of HICTs by community-dwelling older adults as well as the factors associated to the overall acceptance/refusal of HICTs; 2) identify the factors associated with confidentiality (i.e., access to data allowed to physicians only versus to all caregivers) in the subgroup of older adults willing to accept HICTs. METHODS: A total of 3195 community-dwelling 69-83 year-old members of the Lausanne cohort 65+ were included. In 2017, participants filled out a 9-item questionnaire to assess their acceptance of HICTs ("yes without reluctance"; "yes but with reluctance"; "no"). A bivariate analysis was conducted to examine gender and age differences in the acceptance of HICTs. A multivariable logistic regression was performed to model 1) accepting all or rejecting all HICTs items; 2) willing to share HICTs items with physicians only versus all caregivers. RESULTS: The answer "acceptance without reluctance" ranged from 26.4% to 70.4% across HICTs and was the most frequent answer to six out of nine HICT items. For every HICT item, the acceptance rate decreased across age categories in women. Overall, 20.2% accepted all the HICTs without reluctance and 9.9% rejected them all. Older age and a lower level of education were significantly associated with both accepting all HICTs without reluctance (OR = 0.78 and OR = 0.65, respectively) and rejecting all HICTs (OR = 1.54 and OR = 2.89, respectively). Women and participants with health vulnerability (depressive symptoms, difficulty in activities of daily living (ADLs)) were less likely to accept data accessibility to non-physicians. CONCLUSION: Acceptance of HICTs was relatively high. To deploy HICTs in the older population, demographic, socioeconomic and health profiles, alongside confidentiality concerns, should be considered.

Gender differences regarding opinions on long-term care arrangements: A study of community-dwelling older adults.

BACKGROUND: Numerous studies have attempted to identify predictors of institutionalization in the general population. Gender studies have led to inconsistent results. Some authors argued that older women were more likely than older men to use long-term care services, while others failed to highlight a specific gender effect on the use of long-term care services. The aim of this study was to assess the effects of gender on the preferences of older citizens for long-term care using a panel of disability situations. METHODS: We used a set of ten vignettes displaying disability situations with or without an able-bodied spouse present and used a population-based survey to inquire about appropriate long-term care. Participants were 3102 community-dwelling persons aged 68-83 years included in the representative Lausanne cohort 65+ study in January 2017. Multinomial logistic regression analyses were used to explore the effect of gender on long-term care choices by older men and women, controlling for the respondent's age and living arrangement. RESULTS: The respondents' choices shifted toward institutionalization when the disorder severity increased in vignettes and when there was no spouse able to help. Men were more likely to choose a home setting with caregiving only by spouse even when the level of disability increased. Women chose help from professionals, sheltered homes, or institutionalization more quickly than men. CONCLUSIONS: Exploring gender preferences for long-term care arrangements is critical for improving and planning long-term care services.

Quality of life profile in three cohorts of community-dwelling Swiss older people.

BACKGROUND: Quality of life (QoL) is a subjective and dynamic concept resulting from an interplay between importance of and satisfaction with different aspects of life. However, it is unclear whether social contexts experienced by individuals born at specific times in history (cohort effects) may influence QoL in old age. This study aimed to compare among older persons born before, during, and at the end of World War II: a) satisfaction with QoL, overall and per domains; b) importance of QoL domains. METHODS: This repeated cross-sectional study included representative samples of community-dwelling adults born in 1934-1938 (pre-war), 1939-1943 (war), and 1944-1948 (baby-boom) from the Lausanne cohort 65+. QoL was assessed overall, and in seven domains in 2011 and 2016. Two-by-two cohort comparisons were performed at ages 68-72 (war versus baby-boom) and 73-77 years (pre-war versus war). RESULTS: Overall satisfaction with QoL did not differ between cohorts despite increased education level across cohorts and a shift between pre-war and war cohorts towards lower morbidity and higher proportion living alone. However, "Feeling of safety" consistently showed significant improvements from earlier to later-born cohorts. Furthermore, the war cohort reported higher satisfaction than pre-war cohort in "Autonomy". Conversely, no significant difference was observed between cohorts in importance of QoL domains, except increased importance given to "Health and mobility" in the war compared to pre-war cohort. CONCLUSIONS: Societal changes reflected in the profile of successive elders' cohorts did not appear to modify the overall satisfaction with QoL.

Change in quality of life among community-dwelling older adults: population-based longitudinal study.

PURPOSE: This population-based study aimed to determine 5-year change in multidimensional QoL among community-dwelling older people, and to identify predictors of QoL change among demographic, socioeconomic, and health characteristics. METHODS: Data of the 2011 and 2016 annual assessments of 1845 older men and women (age range 68-77 years) from the Lc65 + cohort study were used. QoL was assessed using a 28-item instrument yielding a QoL overall score and seven domain-specific QoL subscores. Additional ratings of QoL included a single item (excellent; very good; good; fair; poor), expected QoL in 1 year (better; worse; same as today), and retrospective assessment of QoL 5-year change (better; worse; same as 5 years ago). The predictors of 5-year change in the QoL score were assessed using linear regression, controlling for baseline QoL score. RESULTS: All prospective and retrospective indicators of QoL converged towards a slight deterioration over 5 years. QoL subscores significantly decreased in domains "Close entourage" (P = 0.004), "Social and cultural life" (P < 0.001), "Esteem and recognition" (P = 0.001), "Health and mobility" (P < 0.001), and "Autonomy" (P < 0.001), whereas "Material resources" (P = 0.345) and "Feeling of safety" (P = 0.380) remained stable. A stronger decrease in QoL was observed in the most vulnerable profiles at baseline in terms of demographic, socioeconomic, and health characteristics. Changes in depressive symptoms and in disability-either worsening or improving-predicted QoL change in the expected direction. CONCLUSIONS: Age-related decline in QoL may be limited through the prevention of disability and depressive symptoms, and more generally by devoting special attention to vulnerable profiles.

Temporal changes in importance of quality of life domains: a longitudinal study in community-dwelling Swiss older people.

PURPOSE: Population aging is a global phenomenon requiring interventions to improve quality of life (QoL), a subjective and dynamic concept. Such interventions should be based on QoL domains considered as important from older people's viewpoint. It is unclear whether and how much these domains may vary over time as people age. This study aims to assess the importance of QoL domains, their pattern and determinants of change among the non-institutionalized older population over a 5-year period. METHODS: This longitudinal study included community-dwelling older adults (N = 1947, aged 68-77 years at baseline) from the Lausanne cohort 65+. In 2011 and 2016, participants rated the importance of 28 QoL items in seven domains. The difference between scores (0-100) of importance attributed to each QoL domain between two assessments was calculated and used as a dependent variable to assess the associations with covariates in multivariable analysis for each domain. RESULTS: Importance scores slightly but significantly decreased in five of the seven QoL domains. Despite the majority of participants did not modify their ranking of importance for each QoL domain between the two time points, the proportion of change was still substantial. Bivariate and multivariable analyses showed that education and to a lesser extent age, living arrangement and morbidity, were associated with decrease in the importance of specific QoL domains; characteristics indicating vulnerability (e.g., low education or morbidity) were associated with a decline in the importance. CONCLUSION: Although aging individuals modified the importance they give to the seven QoL domains, at population level, changes in opposite directions overall resulted in only small decline; importance seems less stable over time among individuals with vulnerable sociodemographic and health profiles.

Polypharmacy, defined as taking five or more drugs, is inadequate in the cardiovascular setting.

BACKGROUND: By how much polypharmacy (defined by number of drugs) differs from polyactive ingredient use (defined by the number of pharmacologically active ingredients) has not been assessed. OBJECTIVES: To compare the extent of polypharmacy vs. polyactive ingredients among patients taking cardiovascular (CV) medicines. METHODS: Prospective, 10-year follow-up study conducted among 880 participants of the CoLaus study taking CV drugs at baseline. Polypharmacy was defined as the use of five or more CV medicines; polyactive ingredient use was defined as the use of five or more pharmacologically active CV ingredients. RESULTS: The prevalence of polypharmacy increased from 1.4% (0.7-2.4) (prevalence rate [95% confidence interval]) at baseline to 11.9% (9.9-14.3) at follow-up, and the prevalence of polyactive ingredients increased from 2.4% (1.5-3.6) at baseline to almost 17.6% (15.2-20.3) at follow-up. The prevalence of combination drugs increased from 15.7% (13.3-18.3) at baseline to 25.9% (23-28.9) at follow-up, and the prevalence of three-component combination use increased from 0.1% (0.0-0.6) at baseline to 2.3% (1.4-3.5) at follow-up. At baseline, nine of 21 participants on polyactive ingredients were not considered as being on polypharmacy; at follow-up, the rate was 50 of 155 participants. CONCLUSION: Among individuals taking CV drugs, polypharmacy as defined by the number of drugs underestimates the prevalence of individuals taking five or more pharmacologically active drugs. Polypharmacy should no longer be based on the number of drugs but on the number of pharmacologically active drugs.

Assessment of Orthographic Similarity of Drugs Names between Iran and Overseas Using the Solar Model.

BACKGROUND: The recognition of patient safety is now occupying a prominent place on the health policy agenda since medical errors can result in adverse events. The existence of confusing drug names is one of the most common causes of medication errors. In Iran, the General Office of Trademarks Registry (GOTR), for four years (2010-2014) was responsible for approving drug proprietary names. This study aimed to investigate the performance of the GOTR in terms of drug names orthographic similarity using the SOLAR model. METHODS: First, 100 names were randomly selected from the GOTR's database. Then, each name was searched through pharmaceutical websites including Martindale (the Complete Drug Reference published by Pharmaceutical Press), Drugs.com and Medicines Complete. Pair of drugs whose names look orthographically similar with different indications were identified. Then, the SOLAR model was utilized to determine orthographic similarity between all pair of drug names. RESULTS: The mean of match values of these 100 pairs of drug was 77% indicating the high risk of similarity. The match value for most of the reviewed pairs (92%) was high (≥66%). This value was medium (≥ 33% and <66%) just for 8% of the pairs of drug. These results indicate high risk of confusion due to similarity of drug names. CONCLUSION: The stewardship of the GOTR in patient safety considerations is fundamentally problematic. Thus, as a best practice, we recommend that proprietary names of drugs be evaluated by an entity within the health system. While an entity within the health system should address patient safety considerations, the GOTR is responsible for intellectual property rights.