Intergenerational educational trajectories and premature mortality from chronic diseases: A registry population-based study.

The tracking of educational gradients in mortality across generations could create a long shadow of social inequality, but it remains understudied. We aimed to assess whether intergenerational educational trajectories shape inequalities in early premature mortality from chronic diseases. The study included 544 743 participants of the Swiss National Cohort, a registry population-based study. Individuals were born 1971-1980 and aged 10-19 at the start of the study (1990). Mortality follow-up was until 2018. Educational trajectories were High-High (reference), High-Low, Low-High, Low-Low, corresponding to the sequence of parental-individual attained education. Examined deaths were related to cardiovascular diseases (CVD), cancers, and substance use. Sex-specific inequalities in mortality were quantified via standardized cumulative risk differences/ratios between age 20 and 45. We triangulated findings with a negative outcome control. For women, inequalities were negligible. For men, while inequalities in cancers deaths were negligible, inequalities in CVD mortality were associated to low individual education regardless of parental education. Excess CVD deaths for Low-High were negligible while High-Low provided 234 (95% confidence intervals: 100 to 391) and Low-Low 185 (115 to 251) additional CVD deaths per 100 000 men compared to High-High. That corresponded to risk ratios of 2.7 (1.6 to 4.5) and 2.3 (1.6 to 3.4), respectively. Gradients in substance use mortality were observed only when education changed across parent-offspring. Excess substance use deaths for Low-Low were negligible while High-Low provided 225 (88 to 341) additional and Low-High 80 (23 to 151) fewer substance use deaths per 100 000 men compared to High-High. That corresponded to risk ratios of 1.8 (1.3 to 2.5) and 0.7 (0.5 to 0.9), respectively. Inequalities in premature mortality were driven by individual education and by parental education for some chronic diseases. This could justify the development of intergenerational prevention strategies.

SARS-CoV-2 infection among employees working from home and on site: An occupational study in Switzerland.

During the COVID-19 pandemic, many companies implemented working from home to mitigate the spread of the disease among their employees. Using data from Corona Immunitas Nestlé, a seroepidemiological study conducted among employees from two Nestlé sites in Switzerland, we aimed to investigate whether there was a difference in SARS-CoV-2 infection rates between employees working most of the time from home and employees mobilized in a workplace equipped with a specialized occupational safety unit and strict sanitary measures. We also investigated whether this association was modified by household size, living with children, vulnerability, worries about an infection, and worries about adverse health consequences if infected. Data were collected between 8 December 2020, and 11 February 2021. Previous SARS-CoV-2 infections were ascertained by the presence of anti-SARS-CoV-2 IgG antibodies in the blood. Of the 425 employees included (53% women; mean age 42 years ranging between 21 and 64 years), 37% worked most of the time from home in 2020 and 16% had been infected with SARS-CoV-2. Participants who worked most of the time from home in 2020 had slightly higher odds of being infected with SARS-CoV-2 compared to participants who never or only sometimes worked from home (adjusted OR 1.29, 95% CI 0.73-2.27). The association was stronger in participants living alone or with one other person (adjusted OR 2.62, 95% CI 1.13-6.25). Among participants living with two or more other persons (adjusted OR 0.66, 95% CI 0.30-1.39) and among vulnerable participants (adjusted OR 0.53, 95% CI 0.13-1.93), working from home tended to be associated with lower odds of infection. In conclusion, in a context of strict sanitary measures implemented in the workplace, employees working from home did not seem to be at lower risk of infection compared to those working on site, especially if living alone or with one other person.

Development and validation of a new prognostic index for mortality risk in multimorbid adults.

CONTEXT: Multimorbidity is highly prevalent among older adults and associated with a high mortality. Prediction of mortality in multimorbid people would be clinically useful but there is no mortality risk index designed for this population. Our objective was therefore to develop and internally validate a 1-year mortality prognostic index for older multimorbid adults. METHODS: We analysed data of the OPERAM cohort study in Bern, Switzerland, including 822 adults aged 70 years or more with multimorbidity (3 or more chronic medical conditions) and polypharmacy (use of 5 drugs or more for >30 days). Time to all-cause mortality was assessed up to 1 year of follow-up. We performed a parametric Weibull regression model with backward stepwise selection to identify mortality risk predictors. The model was internally validated and optimism corrected using bootstrapping techniques. We derived a point-based risk score from the regression coefficients. Calibration and discrimination were assessed by the calibration slope and C statistic. RESULTS: 805 participants were included in the analysis. During 1-year of follow-up, 158 participants (20%) had died. Age, Charlson-Comorbidity-Index, number of drugs, body mass index, number of hospitalizations, Barthel-Index (functional impairment), and nursing home residency were predictors of 1-year mortality in a multivariable model. Using these variables, the 1-year probability of dying could be predicted with an optimism-corrected C statistic of 0.70. The optimism-corrected calibration slope was 0.93. Based on the derived point-based risk score to predict mortality risk, 7% of the patients classified at low-risk of mortality, 19% at moderate-risk, and 37% at high-risk died after one year of follow-up. A simpler mortality score, without the Charlson-Comorbidity-Index and Barthel-Index, showed reduced discriminative power (optimism-corrected C statistic: 0.59) compared to the full score. CONCLUSION: We developed and internally validated a mortality risk index including for the first-time specific predictors for multimorbid adults. This new 1-year mortality prediction point-based score allowed to classify multimorbid older patients into three categories of increasing risk of mortality. Further validation of the score among various populations of multimorbid patients is needed before its implementation into practice.

Is living in a household with children associated with SARS-CoV-2 seropositivity in adults? Results from the Swiss national seroprevalence study Corona Immunitas.

BACKGROUND: We aimed to determine whether living in a household with children is associated with SARS-CoV-2 seropositivity in adults and investigated interacting factors that may influence this association. METHODS: SARS-CoV-2 serology testing was performed in randomly selected individuals from the general population between end of October 2020 and February 2021 in 11 cantons in Switzerland. Data on sociodemographic and household characteristics, employment status, and health-related history was collected using questionnaires. Multivariable logistic regression was used to examine the association of living with children <18 years of age (number, age group) and SARS-CoV-2 seropositivity. Further, we assessed the influence of reported non-household contacts, employment status, and gender. RESULTS: Of 2393 working age participants (18-64 years), 413 (17.2%) were seropositive. Our results suggest that living with children and SARS-CoV-2 seropositivity are likely to be associated (unadjusted odds ratio (OR) 1.22, 95% confidence interval [0.98-1.52], adjusted OR 1.25 [0.99-1.58]). A pattern of a positive association was also found for subgroups of children aged 0-11 years (OR 1.21 [0.90-1.60]) and 12-17 years (OR 1.14 [0.78-1.64]). Odds of seropositivity were higher with more children (OR 1.14 per additional child [1.02-1.27]). Men had higher risk of SARS-CoV-2 infection when living with children than women (interaction: OR 1.74 [1.10-2.76]). CONCLUSIONS: In adults from the general population living with children seems associated with SARS-CoV-2 seropositivity. However, child-related infection risk is not the same for every subgroup and depends on factors like gender. Further factors determining child-related infection risk need to be identified and causal links investigated. TRIAL REGISTRATION: https://www.isrctn.com/ISRCTN18181860 .

The Corona Immunitas Digital Follow-Up eCohort to Monitor Impacts of the SARS-CoV-2 Pandemic in Switzerland: Study Protocol and First Results.

Objectives: To describe the rationale, organization, and procedures of the Corona Immunitas Digital Follow-Up (CI-DFU) eCohort and to characterize participants at baseline. Methods: Participants of Corona Immunitas, a population-based nationwide SARS-CoV-2 seroprevalence study in Switzerland, were invited to join the CI-DFU eCohort in 11 study centres. Weekly online questonnaires cover health status changes, prevention measures adherence, and social impacts. Monthly questionnaires cover additional prevention adherence, contact tracing apps use, vaccination and vaccine hesitancy, and socio-economic changes. Results: We report data from the 5 centres that enrolled in the CI-DFU between June and October 2020 (covering Basel City/Land, Fribourg, Neuchâtel, Ticino, Zurich). As of February 2021, 4636 participants were enrolled and 85,693 weekly and 27,817 monthly questionnaires were collected. Design-based oversampling led to overrepresentation of individuals aged 65+ years. People with higher education and income were more likely to enroll and be retained. Conclusion: Broad enrolment and robust retention of participants enables scientifically sound monitoring of pandemic impacts, prevention, and vaccination progress. The CI-DFU eCohort demonstrates proof-of-principle for large-scale, federated eCohort study designs based on jointly agreed principles and transparent governance.

Interventions to Decrease Carotid-Intima Media Thickness in Children and Adolescents With Type 1 Diabetes: A Systematic Review and Meta-Analysis.

Introduction: Hyperglycemia is associated with a higher cardiovascular risk, as evidenced by increased carotid-intima media thickness (CIMT) in youth with diabetes. We conducted a systematic review and meta-analysis to assess the effect of pharmacological or non-pharmacological interventions on CIMT in children and adolescents with prediabetes or diabetes. Methods: We conducted systematic searches of MEDLINE, EMBASE, and CENTRAL, together with supplementary searches in trial registers and other sources for studies completed up to September 2019. Interventional studies assessing ultrasound CIMT in children and adolescents with prediabetes or diabetes were considered for inclusion. Where appropriate, data were pooled across studies using random-effect meta-analysis. Quality was assessed using The Cochrane Collaboration's risk-of-bias tool and a CIMT reliability tool. Results: Six studies involving 644 children with type 1 diabetes mellitus were included. No study involved children with prediabetes or type 2 diabetes. Three randomized controlled trials (RCTs) evaluated the effects of metformin, quinapril, and atorvastatin. Three non-randomized studies, with a before-and-after design, evaluated the effects of physical exercise and continuous subcutaneous insulin infusion (CSII). The mean CIMT at baseline ranged from 0.40 to 0.51 mm. The pooled difference in CIMT was -0.01 mm (95% CI: -0.04 to 0.01) for metformin compared to placebo (2 studies; 135 participants; I2: 0%). The difference in CIMT was -0.01 mm (95% CI: -0.03 to 0.01) for quinapril compared to placebo (1 study; 406 participants). The mean change from baseline in CIMT was -0.03 mm (95% CI: -0.14 to 0.08) after physical exercise (1 study; 7 participants). Inconsistent results were reported for CSII or for atorvastatin. CIMT measurement was rated at a higher quality on all reliability domains in 3 (50%) studies. The confidence in results is limited by the low number of RCTs and their small sample sizes, as well as the high risk of bias in before-and-after studies. Conclusions: Some pharmacological interventions may decrease CIMT in children with type 1 diabetes. However, there is great uncertainty with respect to their effects and no strong conclusions can be drawn. Further evidence from larger RCTs is required. Systematic Review Registration: PROSPERO, CRD42017075169.

How blood pressure predicts frailty transitions in older adults in a population-based cohort study: a multi-state transition model.

BACKGROUND: Low blood pressure (BP) is associated with frailty in older adults. Our aim was to explore how BP predicts transitions between frailty states. METHODS: We used data from the Lausanne cohort Lc65+, a population-based cohort of older adults randomly drawn from a population registry in Switzerland, in 2004, 2009 and 2014. BP was measured using a clinically validated oscillometric automated device and frailty was defined using Fried's phenotype, every 3 years. We used an illness-death discrete multi-state Markov model to estimate hazard ratios of forward and backward transitions between frailty states (outcome) in relation to BP categories (predictor of interest) with adjustment for sex, age and antihypertensive medication (other predictors). RESULTS: Among 4200 participants aged 65-70 years (58% female) at baseline, 70% were non-frail, 27% pre-frail and 2.0% frail. Over an average follow-up of 5.8 years, 2422 transitions were observed, with 1575 (65%) forward and 847 (35%) backward. Compared with systolic BP (SBP) <130 mmHg, the hazard ratio (95% confidence interval) of the transition from non-frail to pre-frail was 0.86 (0.74 to 1.00) for SBP 130-150 mmHg, and 0.89 (0.74 to 1.06) for SBP ≥150 mmHg. Compared with SBP <130 mmHg, the hazard ratio of the transition from pre-frail to frail was 0.71 (0.50 to 1.01) for SBP 130-150 mmHg, and 0.90 (0.62 to 1.32) for SBP ≥150 mmHg. Diastolic BP was a weaker predictor of forward transitions. CONCLUSIONS: BP categories had no strong relationship with either forward transitions or backward transitions in frailty states. If our findings are confirmed with greater precision and assuming a causal relationship, they would suggest that there is no well-defined optimal BP level to prevent frailty among older adults.

Development and validation of a life expectancy estimator for multimorbid older adults: a cohort study protocol.

BACKGROUND: Older multimorbid adults have a high risk of mortality and a short life expectancy (LE). Providing high-value care and avoiding care overuse, including of preventive care, is a serious challenge among multimorbid patients. While guidelines recommend to tailor preventive care according to the estimated LE, there is no tool to estimate LE in this specific population. Our objective is therefore to develop an LE estimator for older multimorbid adults by transforming a mortality prognostic index, which will be developed and internally validated in a prospective cohort. METHODS AND ANALYSIS: We will analyse data of the Optimising Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older People cohort study in Bern, Switzerland. 822 participants were included at hospitalisation with age of 70 years or older, multimorbidity (three or more chronic medical conditions) and polypharmacy (use of five drugs or more for >30 days). All-cause mortality will be assessed during 3 years of follow-up. We will apply a flexible parametric survival model with backward stepwise selection to identify the mortality risk predictors. The model will be internally validated using bootstrapping techniques. We will derive a point-based risk score from the regression coefficients. We will transform the 3-year mortality prognostic index into an LE estimator using the Gompertz survival function. We will perform a qualitative assessment of the clinical usability of the LE estimator and its application. We will conduct the development and validation of the mortality prognostic index following the Prognosis Research Strategy (PROGRESS) framework and report it following the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) statement. ETHICS AND DISSEMINATION: Written informed consent by patients themselves or, in the case of cognitive impairment, by a legal representative, was required before enrolment. The local ethics committee (Kantonale Ethikkommission Bern) has approved the study. We plan to publish the results in peer-reviewed journals and present them at national and international conferences.

Frailty to predict unplanned hospitalization, stroke, bleeding, and death in atrial fibrillation.

AIMS: Atrial fibrillation (AF) and frailty are common, and the prevalence is expected to rise further. We aimed to investigate the prevalence of frailty and the ability of a frailty index (FI) to predict unplanned hospitalizations, stroke, bleeding, and death in patients with AF. METHODS AND RESULTS: Patients with known AF were enrolled in a prospective cohort study in Switzerland. Information on medical history, lifestyle factors, and clinical measurements were obtained. The primary outcome was unplanned hospitalization; secondary outcomes were all-cause mortality, bleeding, and stroke. The FI was measured using a cumulative deficit approach, constructed according to previously published criteria and divided into three groups (non-frail, pre-frail, and frail). The association between frailty and outcomes was assessed using multivariable-adjusted Cox regression models. Of the 2369 included patients, prevalence of pre-frailty and frailty was 60.7% and 10.6%, respectively. Pre-frailty and frailty were associated with a higher risk of unplanned hospitalizations [adjusted hazard ratio (aHR) 1.82, 95% confidence interval (CI) 1.49-2.22; P < 0.001; and aHR 3.59, 95% CI 2.78-4.63, P < 0.001], all-cause mortality (aHR 5.07, 95% CI 2.43-10.59; P < 0.001; and aHR 16.72, 95% CI 7.75-36.05; P < 0.001), and bleeding (aHR 1.53, 95% CI 1.11-2.13; P = 0.01; and aHR 2.46, 95% CI 1.61-3.77; P < 0.001). Frailty, but not pre-frailty, was associated with a higher risk of stroke (aHR 3.29, 95% CI 1.2-8.39; P = 0.01). CONCLUSION: Over two-thirds of patients with AF are pre-frail or frail. These patients have a high risk for unplanned hospitalizations and other adverse events. These findings emphasize the need to carefully evaluate these patients. However, whether screening for pre-frailty and frailty and targeted prevention strategies improve outcomes needs to be shown in future studies. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier number: NCT02105844.

Blood pressure control and complex health conditions in older adults: impact of recent hypertension management guidelines.

The American College of Cardiology and the American Heart Association (ACC/AHA) 2017 guidelines for hypertension management lowered blood pressure (BP) thresholds to 130/80 mmHg to define hypertension while the European Society of Cardiology and the European Society of Hypertension (ESC/ESH) 2018 guidelines retained 140/90 mmHg. Both guidelines recommend adapting management for older patients with complex health conditions, without however clear indications on how to adapt. Our aims were to assess the impact of lowering BP thresholds on the prevalence of elevated BP and BP control, as well as the proportion of participants with a complex health condition across these BP categories. We used data from 3210 participants in the Lausanne cohort Lc65+ aged between 67 and 80 years. Hypertension diagnosis and antihypertensive medication use were self-reported. BP was measured three times at one visit. Some 51% of participants reported having hypertension and 44% reported taking antihypertensive medication. Compared with ESC/ESH thresholds, the prevalence of measured elevated BP was 24% percentage points higher and BP control was 24% percentage points lower using ACC/AHA thresholds. About one out of two participants with elevated BP and four out of five participants with uncontrolled BP had a complex health condition, i.e., frailty, multimorbidity, or polypharmacy. To comply with ACC/AHA guidelines, considerable effort would be required to reach BP control. This is a serious challenge because a large share of hypertensive older adults has complex health conditions, a type of patients for whom there is no strong evidence on how to manage hypertension.

Risk factors during first 1,000 days of life for carotid intima-media thickness in infants, children, and adolescents: A systematic review with meta-analyses.

BACKGROUND: The first 1,000 days of life, i.e., from conception to age 2 years, could be a critical period for cardiovascular health. Increased carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis. We performed a systematic review with meta-analyses to assess (1) the relationship between exposures or interventions in the first 1,000 days of life and CIMT in infants, children, and adolescents; and (2) the CIMT measurement methods. METHODS AND FINDINGS: Systematic searches of Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), and Cochrane Central Register of Controlled Trials (CENTRAL) were performed from inception to March 2019. Observational and interventional studies evaluating factors at the individual, familial, or environmental levels, for instance, size at birth, gestational age, breastfeeding, mode of conception, gestational diabetes, or smoking, were included. Quality was evaluated based on study methodological validity (adjusted Newcastle-Ottawa Scale if observational; Cochrane collaboration risk of bias tool if interventional) and CIMT measurement reliability. Estimates from bivariate or partial associations that were least adjusted for sex were used for pooling data across studies, when appropriate, using random-effects meta-analyses. The research protocol was published and registered on the International Prospective Register of Systematic Reviews (PROSPERO; CRD42017075169). Of 6,221 reports screened, 50 full-text articles from 36 studies (34 observational, 2 interventional) totaling 7,977 participants (0 to 18 years at CIMT assessment) were retained. Children born small for gestational age had increased CIMT (16 studies, 2,570 participants, pooled standardized mean difference (SMD): 0.40 (95% confidence interval (CI): 0.15 to 0.64, p: 0.001), I2: 83%). When restricted to studies of higher quality of CIMT measurement, this relationship was stronger (3 studies, 461 participants, pooled SMD: 0.64 (95% CI: 0.09 to 1.19, p: 0.024), I2: 86%). Only 1 study evaluating small size for gestational age was rated as high quality for all methodological domains. Children conceived through assisted reproductive technologies (ART) (3 studies, 323 participants, pooled SMD: 0.78 (95% CI: -0.20 to 1.75, p: 0.120), I2: 94%) or exposed to maternal smoking during pregnancy (3 studies, 909 participants, pooled SMD: 0.12 (95% CI: -0.06 to 0.30, p: 0.205), I2: 0%) had increased CIMT, but the imprecision around the estimates was high. None of the studies evaluating these 2 factors was rated as high quality for all methodological domains. Two studies evaluating the effect of nutritional interventions starting at birth did not show an effect on CIMT. Only 12 (33%) studies were at higher quality across all domains of CIMT reliability. The degree of confidence in results is limited by the low number of high-quality studies, the relatively small sample sizes, and the high between-study heterogeneity. CONCLUSIONS: In our meta-analyses, we found several risk factors in the first 1,000 days of life that may be associated with increased CIMT during childhood. Small size for gestational age had the most consistent relationship with increased CIMT. The associations with conception through ART or with smoking during pregnancy were not statistically significant, with a high imprecision around the estimates. Due to the large uncertainty in effect sizes and the limited quality of CIMT measurements, further high-quality studies are needed to justify intervention for primordial prevention of cardiovascular disease (CVD).

Corona Immunitas: study protocol of a nationwide program of SARS-CoV-2 seroprevalence and seroepidemiologic studies in Switzerland.

OBJECTIVES: Seroprevalence studies to assess the spread of SARS-CoV-2 infection in the general population and subgroups are key for evaluating mitigation and vaccination policies and for understanding the spread of the disease both on the national level and for comparison with the international community. METHODS: Corona Immunitas is a research program of coordinated, population-based, seroprevalence studies implemented by Swiss School of Public Health (SSPH+). Over 28,340 participants, randomly selected and age-stratified, with some regional specificities will be included. Additional studies in vulnerable and highly exposed subpopulations are also planned. The studies will assess population immunological status during the pandemic. RESULTS: Phase one (first wave of pandemic) estimates from Geneva showed a steady increase in seroprevalence up to 10.8% (95% CI 8.2-13.9, n = 775) by May 9, 2020. Since June, Zurich, Lausanne, Basel City/Land, Ticino, and Fribourg recruited a total of 5973 participants for phase two thus far. CONCLUSIONS: Corona Immunitas will generate reliable, comparable, and high-quality serological and epidemiological data with extensive coverage of Switzerland and of several subpopulations, informing health policies and decision making in both economic and societal sectors. ISRCTN Registry: https://www.isrctn.com/ISRCTN18181860 .

Blood pressure in relation to frailty in older adults: A population-based study.

In frail older adults, low blood pressure (BP) might be associated with worse health outcomes and hypertension management in this population is highly debated. Using data from a population-based study of older adults, we assessed the association between frailty and BP. We used data collected between 2014 and 2016 from 3157 participants aged between 67 and 80 years in the Lausanne cohort Lc65+. BP was measured three times at one visit, and frailty status was assessed based on Fried's phenotype model. We analyzed the cross-sectional association between BP and frailty by computing mean systolic and diastolic BP stratified by sex, age, and frailty and by fitting regression models. The average age of the participants was 73.3 (standard deviation [SD]: 4.1) years, and 59.1% were women. 34.1% were pre-frail, and 3.3% were frail. Mean BP was 135.1/76.3 mm Hg (SD 18.5/11.0). Age- and sex-adjusted systolic BP was on average lower by 2.8 mm Hg (95% confidence interval [CI]: 1.4-4.2) and 6.7 mm Hg (95% CI: 3.2-10.3) among pre-frail and frail compared to non-frail participants. Similar differences in mean diastolic BP across frailty status were found. Upon adjustment for antihypertensive treatment, the associations between frailty status and BP did not change substantially. Frail individuals had a substantially lower BP compared with non-frail older adults. Because low BP could be detrimental among frail older patients, our findings raise questions about hypertension management in this population and stress the need for additional evidence.

Screening and treatment of hypertension in older adults: less is more?

Screening and treatment of hypertension is a cornerstone of cardiovascular disease (CVD) prevention. Hypertension causes a large proportion of cases of stroke, coronary heart disease, heart failure, and associated disability and is highly prevalent especially among older adults. On the one hand, there is robust evidence that screening and treatment of hypertension prevents CVD and decreases mortality in the middle-aged population. On the other hand, among older adults, observational studies have shown either positive, negative, or no correlation between blood pressure (BP) and cardiovascular outcomes. Furthermore, there is a lack of high quality evidence for a favorable harm-benefit balance of antihypertensive treatment among older adults, especially among the oldest-old (i.e., above the age of 80 years), because very few trials have been conducted in this population. The optimal target BP may be higher among older treated hypertensive patients than among middle-aged. In addition, among frail or multimorbid older individuals, a relatively low BP may be associated with worse outcomes, and antihypertensive treatment may cause more harm than benefit. To guide hypertension screening and treatment recommendations among older patients, additional studies are needed to determine the most efficient screening strategies, to evaluate the effect of lowering BP on CVD risk and on mortality, to determine the optimal target BP, and to better understand the relationship between BP, frailty, multimorbidity, and health outcomes.