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

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

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

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

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. Keywords: SARS-CoV-2; digital follow-up; eCohort; population-based study; prevention; public health surveillanc

A year in heart failure : an update of recent findings

Major changes have occurred in these last years in heart failure (HF) management. Landmark trials and the 2021 European Society of Cardiology guidelines for the diagnosis and treatment of HF have established four classes of drugs for treatment of HF with reduced ejection fraction: angiotensin‐converting enzyme inhibitors or an angiotensin receptor‐neprilysin inhibitor, beta‐blockers, mineralocorticoid receptor antagonists, and sodium‐glucose co‐transporter 2 inhibitors, namely, dapagliflozin or empagliflozin. These drugs consistently showed benefits on mortality, HF hospitalizations, and quality of life. Correction of iron deficiency is indicated to improve symptoms and reduce HF hospitalizations. AFFIRM‐AHF showed 26% reduction in total HF hospitalizations with ferric carboxymaltose vs. placebo in patients hospitalized for acute HF (P = 0.013). The guanylate cyclase activator vericiguat and the myosin activator omecamtiv mecarbil improved outcomes in randomized placebo‐controlled trials, and vericiguat is now approved for clinical practice. Treatment of HF with preserved ejection fraction (HFpEF) was a major unmet clinical need until this year when the results of EMPEROR‐Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic HFpEF) were issued. Compared with placebo, empagliflozin reduced by 21% (hazard ratio, 0.79; 95% confidence interval, 0.69 to 0.90; P < 0.001), the primary outcome of cardiovascular death or HF hospitalization. Advances in the treatment of specific phenotypes of HF, including atrial fibrillation, valvular heart disease, cardiomyopathies, cardiac amyloidosis, and cancer‐related HF, also occurred. Coronavirus disease 2019 (COVID‐19) pandemic still plays a major role in HF epidemiology and management. All these aspects are highlighted in this review

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

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

Sodium–glucose co‐transporter 2 inhibitors as an early, first‐line therapy in patients with heart failure and reduced ejection fraction

Sodium–glucose co‐transporter 2 (SGLT2) inhibitors have recently been recommended as a foundational therapy for patients with heart failure (HF) and reduced ejection fraction (HFrEF) because of their favourable effects on mortality, clinical events and quality of life. While clinical practice guidelines have recommended dapagliflozin or empagliflozin in all patients with HFrEF, or sotagliflozin in those with HFrEF and concomitant diabetes, the timing and practical integration of these drugs in clinical practice is less well defined. We propose that these drugs are candidates for early, upfront administration to patients with newly diagnosed HFrEF and for patients hospitalized with HF. Growing evidence has established early benefits, with clinically meaningful reductions in clinical events that reach statistical significance within days to weeks, following dapagliflozin, empagliflozin or, in diabetic patients, sotagliflozin initiation. Secondly, although major clinical trials have tested these drugs in patients already receiving background HF therapy, secondary analyses showed that their efficacy is independent of that. Third, SGLT2 inhibitors are generally safe and well tolerated, with clinical trial data reporting minimal effects on blood pressure, glycaemia‐related adverse events, and no excess in acute kidney injury. Rather, they exert renal protective effects and reduce risk of hyperkalaemia, properties that favour initiation, tolerance and persistence of renin–angiotensin system inhibitors and mineralocorticoid receptor antagonists. This review supports the early initiation of dapagliflozin and empagliflozin (or sotagliflozin limited to patients with diabetes) to rapidly improve clinical outcome and quality of life of HFrEF patients

mTORC1 is essential for early steps during Schwann cell differentiation of amniotic fluid stem cells and regulates lipogenic gene expression.

Schwann cell development is hallmarked by the induction of a lipogenic profile. Here we used amniotic fluid stem (AFS) cells and focused on the mechanisms occurring during early steps of differentiation along the Schwann cell lineage. Therefore, we initiated Schwann cell differentiation in AFS cells and monitored as well as modulated the activity of the mechanistic target of rapamycin (mTOR) pathway, the major regulator of anabolic processes. Our results show that mTOR complex 1 (mTORC1) activity is essential for glial marker expression and expression of Sterol Regulatory Element-Binding Protein (SREBP) target genes. Moreover, SREBP target gene activation by statin treatment promoted lipogenic gene expression, induced mTORC1 activation and stimulated Schwann cell differentiation. To investigate mTORC1 downstream signaling we expressed a mutant S6K1, which subsequently induced the expression of the Schwann cell marker S100b, but did not affect lipogenic gene expression. This suggests that S6K1 dependent and independent pathways downstream of mTORC1 drive AFS cells to early Schwann cell differentiation and lipogenic gene expression. In conclusion our results propose that future strategies for peripheral nervous system regeneration will depend on ways to efficiently induce the mTORC1 pathway