Associations of combined accelerated biological aging and genetic susceptibility with incident dementia: a prospective study in the UK Biobank.

BACKGROUND: Accelerated biological aging has been verified to be a critical risk factor for a number of age-related diseases, but its role in dementia remained unclear. Whether it modified the effects of genetic factors was also unknown. This study evaluated the associations between accelerated biological aging and dementia and the moderating role of accelerated biological aging in the genetic susceptibility to the disease. METHODS: We included 200,731 participants in the UK biobank. Nine clinical blood biomarkers and chronological age were used to calculate Phenotypic age acceleration (PhenoAgeAccel), which is a novel indicator for accelerated biological aging. The associations of PhenoAgeAccel with dementia, both young-onset and late-onset dementia, were assessed by Cox proportional hazard models. Apolipoprotein E (APOE) alleles and polygenic risk scores (PRS) were used to evaluate the genetic risk of dementia. The interactions between genetic susceptibility and biological aging were tested on both multiplicative and additive scales. RESULTS: These findings showed individuals who were in the highest quartile of PhenoAgeAccel had a higher risk with incidence of dementia compared to individuals in the lowest quartile of PhenoAgeAccel (HR: 1.145 (95% CI: 1.050, 1.249)). Individuals with biologically older had a higher risk of dementia than individuals with biologically younger (HR: 1.069 (95% CI: 1.004, 1.138)). Furthermore, compared to individuals with biologically younger and low APOE ε4-related genetic risk, individuals with biologically younger and high APOE ε4-related genetic risk (HR:3.048 (95% CI: 2.811, 3.305)) had a higher risk of dementia than individuals with biologically older and high APOE ε4-related genetic risk (HR: 2.765 (95% CI: 2.523, 3.029)). Meanwhile, referring to low dementia PRS and biologically younger, the risk of dementia increased by 72.7% (HR: 1.727 (95% CI: 1.538, 1.939) in the biologically younger and high PRS group and 58.7% (HR: 1.587 (95% CI: 1.404, 1.793) in the biologically older and high PRS group, respectively. The negative interactions between PhenoAgeAccel with APOE ε4 and PRS were also tested on the additive scale. CONCLUSIONS: Accelerated biological aging could bring the extra risk of dementia but attenuate the effects of genetic risk on dementia. These findings provide insights for precise prevention and intervention of dementia.

L'impatto dell'esposizione occupazionale ad amianto sul tumore del polmone in Italia.

OBJECTIVES: to perform a meta-analysis of cohort studies on lung cancer mortality in occupational sectors exposed to asbestos, particularly in the construction sector, and to use data from Italian cohorts exposed to asbestos to estimate the number of lung cancer cases attributable to asbestos in Italy. METHODS: systematic literature review and estimation of lung cancer deaths and cases attributable to asbestos in Italian cohorts and from the Italian National Register of Malignant Mesothelioma (ReNaM). SETTING AND PARTICIPANTS: the literature search was conducted in Medline and Embase (Ovid), including papers published from 1999 to May 2019. The following sectors were considered most exposed to asbestos: asbestos-cement, rolling-stock, shipyards, dockyards, glass workers, insulators, asphalt roll production workers, industrial ovens, miners. Moreover, the construction sector was included. MAIN OUTCOME MEASURES: the standardized mortality ratio (SMR) was estimated from the meta-analysis of the literature review. The ratio lung cancer to mesothelioma attributable cases was estimated by occupational sector from the Italian cohorts. For the construction sector, the ratio lung cancer to mesothelioma cases was estimated within the exposed workers estimated by CAREX (1990-1993). The ratios were applied to the mesothelioma cases registered at the ReNaM for the 2010-2015 period, to obtain a national estimate of lung cancer cases attributable to occupational exposure to asbestos. RESULTS: the meta-analytical SMR for lung cancer in men varied between 1.05 (asphalt roll) and 2.36 (insulation). The mean risk for all sectors was 1.37 in men and 1.60 in women. It increased in cohorts with latency higher than 20 years. Significant risks were observed in asbestos-cement (both genders), construction, and mining sectors. There was a mean of 1.1, 2.7, and 2.8 lung cancer deaths per mesothelioma death in the cement-asbestos, harbour, and construction sectors, respectively. The impact in terms of lung cancer cases estimated at the national level was equal to 3,814 cases between 2010 and 2015. CONCLUSIONS: to provide an overall assessment of the impact of the occupational asbestos exposure, it is important to consider lung cancer cases, in addition to malignant mesotheliomas. This study was able to estimate the impact of asbestos on lung cancer in Italy 25 years after the ban of this occupational carcinogen, with the largest contribution in terms of attributable cases coming from the construction sector. It is urgent to implement adequate information and prevention strategies, health surveillance of workers, and the appropriate legal framework for insurance purposes.

Disparities at the intersection of marginalized groups.

PURPOSE: Mental health disparities exist across several dimensions of social inequality, including race/ethnicity, socioeconomic status and gender. Most investigations of health disparities focus on one dimension. Recent calls by researchers argue for studying persons who are marginalized in multiple ways, often from the perspective of intersectionality, a theoretical framework applied to qualitative studies in law, sociology, and psychology. Quantitative adaptations are emerging but there is little guidance as to what measures or methods are helpful. METHODS: Here, we consider the concept of a joint disparity and its composition, show that this approach can illuminate how outcomes are patterned for social groups that are marginalized across multiple axes of social inequality, and compare the insights gained with that of other measures of additive interaction. We apply these methods to a cohort of young men from the National Longitudinal Survey of Youth, examining disparities for black men with low early life SES vs. white men with high early life SES across several outcomes that predict mental health, including unemployment, wages, and incarceration. RESULTS AND CONCLUSIONS: We report striking disparities in each outcome, but show that the contribution of race, SES, and their intersection varies.

Combined effects of sleep quality and depression on quality of life in patients with type 2 diabetes.

BACKGROUND: Poor sleep quality and depression negatively impact the health-related quality of life of patients with type 2 diabetes, but the combined effect of the two factors is unknown. This study aimed to assess the interactive effects of poor sleep quality and depression on the quality of life in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes (n = 944) completed the Diabetes Specificity Quality of Life scale (DSQL) and questionnaires on sleep quality and depression. The products of poor sleep quality and depression were added to the logistic regression model to evaluate their multiplicative interactions, which were expressed as the relative excess risk of interaction (RERI), the attributable proportion (AP) of interaction, and the synergy index (S). RESULTS: Poor sleep quality and depressive symptoms both increased DSQL scores. The co-presence of poor sleep quality and depressive symptoms significantly reduced DSQL scores by a factor of 3.96 on biological interaction measures. The relative excess risk of interaction was 1.08. The combined effect of poor sleep quality and depressive symptoms was observed only in women. CONCLUSIONS: Patients with both depressive symptoms and poor sleep quality are at an increased risk of reduction in diabetes-related quality of life, and this risk is particularly high for women due to the interaction effect. Clinicians should screen for and treat sleep difficulties and depressive symptoms in patients with type 2 diabetes.

Prevalence of prolonged otitis media with effusion among 2 to 3 years old Cameroonian children in the era of 13-valent pneumococcal conjugate vaccines.

Objectives: There is data scarcity on the overall effects of pneumococcal conjugate vaccines (PCVs) on otitis media (OM) in low- and middle-income countries. The impact of the 13-valent PCV (PCV13) program on OM was evaluated in Cameroon where infant vaccination was implemented in July 2011 using a 3-dose primary series at 6, 10 and 14 weeks of age. Methods: Through community-based surveillance, we used a retrospective cohort study design to assess OM prevalence among PCV13-vaccinated children aged 24 to 36 months in 2015. This was compared with a 2013 age-matched cohort of PCV13-unvaccinated children. OM was diagnosed by clinical inspection for chronic suppurative OM (CSOM) and tympanometry for OM with effusion (OME). CSOM was defined as draining of the middle ear with duration of more than 2 weeks and prolonged OME was defined as a flat 'type B' tympanogram. PCV13-vaccinated and PCV13-unvaccinated cohorts were compared by calculating prevalence odds ratios for OM and baseline characteristics. Results: Altogether, 111 OM cases were identified; 42/433 (9.7%) in the PCV13-unvaccinated in 2013 and 69/413 (16.7%) in the PCV13-vaccinated cohort in 2015. In the 2013 baseline survey, 3/433 (0.7%) children were identified with unilateral CSOM compared to 9/413 (2.2%) in the PCV13-vaccinated cohort in 2015. Bilateral prolonged OME was diagnosed in 7/433 (1.6%) PCV13-unvaccinated children and in 12/413 (2.9%) in PCV13-vaccinated children. Proportions of children with unilateral prolonged OME were 31/433 (7.2%) in the PCV13-unvaccinated group compared with 48/413 (11.6%) in the PCV13-vaccinated group. Multivariate logistic regression analysis showed evidence that PCV13-vaccinated children in 2015 had 40% less risk of contracting OM compared to PCV13-unvaccinated children in 2013 (adjusted prevalence odds ratios = 0.60 [95% confidence interval: 0.38 to 0.94], P = 0.025). Additionally, attributable proportion estimates show that, 58% of OM infections among the PCV13-vaccinated group would still have occurred despite PCV13 vaccination. Conclusion: Our findings provide significant evidence on the effect of PCV13 in decreasing OM or OME among children in this age group. It also supports justification for government's continuation of PCV13 immunization program in the absence of GAVI's funding. Further research is needed to assess the long-term impact of the PCV13 program on in OM Cameroon.

Interaction analysis of subgroup effects in randomized trials: the essential methodological points.

Subgroup analysis aims to identify subgroups (usually defined by baseline/demographic characteristics), who would (or not) benefit from an intervention under specific conditions. Often performed post hoc (not pre-specified in the protocol), subgroup analyses are prone to elevated type I error due to multiple testing, inadequate power, and inappropriate statistical interpretation. Aside from the well-known Bonferroni correction, subgroup treatment interaction tests can provide useful information to support the hypothesis. Using data from a previously published randomized trial where a p value of 0.015 was found for the comparison between standard and Hemopatch® groups in (the subgroup of) 135 patients who had hand-sewn pancreatic stump closure we first sought to determine whether there was interaction between the number and proportion of the dependent event of interest (POPF) among the subgroup population (patients with hand-sewn stump closure and use of Hemopatch®), Next, we calculated the relative excess risk due to interaction (RERI) and the "attributable proportion" (AP). The p value of the interaction was p = 0.034, the RERI was - 0.77 (p = 0.0204) (the probability of POPF was 0.77 because of the interaction), the RERI was 13% (patients are 13% less likely to sustain POPF because of the interaction), and the AP was - 0.616 (61.6% of patients who did not develop POPF did so because of the interaction). Although no causality can be implied, Hemopatch® may potentially decrease the POPF after distal pancreatectomy when the stump is closed hand-sewn. The hypothesis generated by our subgroup analysis requires confirmation by a specific, randomized trial, including only patients undergoing hand-sewn closure of the pancreatic stump after distal pancreatectomy.Trial registration: INS-621000-0760.

Synergistic effects of family history of hepatocellular carcinoma and hepatitis B virus infection on risk for incident hepatocellular carcinoma.

BACKGROUND & AIMS: Little is known about the effects of family history of hepatocellular carcinoma (HCC) on hepatitis B progression or risk of HCC. We examined how family HCC history and presence or stage of hepatitis B virus (HBV) infection affect risk for HCC. METHODS: We performed a population-based cohort study of 22,472 participants from 7 townships in Taiwan who underwent evaluation for liver disease from 1991 through 1992. Those who received a first diagnosis of HCC from January 1, 1991, to December 31, 2008, were identified from the Taiwanese cancer registry. RESULTS: There were 374 cases of incident HCC over 362,268 person-years of follow-up evaluation. The cumulative risk of HCC in hepatitis B surface antigen (HBsAg)-seronegative patients without a family history of HCC was 0.62%, in those with a family history of HCC the cumulative risk was 0.65%, in HBsAg-seropositive patients without a family history of HCC the cumulative risk was 7.5%, and in HBsAg-seropositive patients with a family history of HCC the cumulative risk was 15.8% (P < .001). The multivariate-adjusted hazard ratio for HBsAg-seropositive individuals with family history, compared with HBsAg-seronegative individuals without a family history of HCC, was 32.33 (95% confidence interval, 20.8-50.3; P < .001). The relative excess risk owing to interaction was 19, the attributable proportion was 0.59, and the synergy index value was 2.54. These findings indicate synergy between family HCC history and HBsAg serostatus. The synergy between these factors remained significant in stratification analyses by HBeAg serostatus and serum level of HBV DNA. CONCLUSIONS: Family history of HCC multiplies the risk of HCC at each stage of HBV infection. Patients with a family history of HCC require more intensive management of HBV infection and surveillance for liver cancer.

Cardiovascular disease, mortality and exposure to particulate matter (PM): a systematic review and meta-analysis.

One of the main factors that causes health effects in humans such as hospital admissions for cardiovascular disease (HACVD), respiratory disease (RD), lung function, cardiovascular mortality (MCVD), lung cancer, and increased mortality is air pollution especially particulate matter (PM). This a systematic review and meta-analysis aims to investigate the effects of particulate matter on the occurrence of cardiovascular disease and mortality. A systematic review and meta-analysis of the literature was done from 2011 to 2021 based on various databases. Based on the result of this study, subgroup analysis based on temperature conditions showed a different estimation in cold cities (6.24, UR (4.36-8.12)), moderate cities (4.86, UR (3.57-6.15)) and warm cities (8.96, UR (7.06-10.86)). Test of group differences showed a significant difference (Q=12.22, p-value<0.001). There was publication bias among the studies (the Egger's test; (Z=14.18, p<0.001)). According result study pooled estimation of AP% for MCVD from the random-effect meta-analysis based on DerSimonian-Laird model, overall is 5.04, UR (3.65-6.43) (Figure 4). Subgroup analysis based on temperature conditions showed the estimation in cold cities (5.47, UR (3.97-6.97)) and moderate cities (4.65, UR (0.54-8.77)). Test of group differences showed a non-significant difference (Q=0.13, p-value=0.71). There was no publication bias among the studies (the Egger's test; (Z=0.82, p=0.376)). Exposed to air pollutants and particulate matter can be increase the risk of cardiovascular disease, respiratory disease, and cardiovascular mortality.

Outpatient antibiotic use attributable to viral acute lower respiratory tract infections during the cold season in France, 2010-2017.

Antibiotic stewardship requires clear insight into antibiotic overuse and the syndromes that lead to prescription. The aim of this study was to estimate the proportion of antibiotic prescriptions attributable to acute lower respiratory tract infections (LRTIs) during the cold season. Using individual data from the French National Health Insurance (NHI) database, weekly time series were constructed of outpatient antibiotic (beta-lactams and macrolides) prescriptions between January 2010 and December 2017. Time series were also constructed of tenth edition of the International Classification of Diseases (ICD-10) discharge diagnoses from a national network of emergency departments (EDs), stratified by specific syndromes (pneumonia, bronchitis, bronchiolitis and influenza-like illness). The number of outpatient antibiotic prescriptions attributable to these syndromes during the cold season in France was modeled and estimated for the entire population, young children (≤5 years) and the elderly (≥75 years). LRTIs accounted for 40% (95% confidence interval [95% CI]: 29, 52) of outpatient antibiotic use during the cold season for the entire population, including 23% (95% CI: 13, 33) and 17% (95% CI: 13, 22) for bacterial and viral infections, respectively. In children and the elderly, viral LRTIs were the reason for 38% (95% CI: 31, 46) and 20% (95% CI: 16, 25) of outpatient antibiotic use, respectively (with bronchiolitis accountable for half of use in young children). In the entire population and in children, respectively, outpatient antibiotic overuse attributable to viral LRTIs was estimated to be 289 (95% CI: 221, 374) and 1588 (95% CI: 1295, 1922) prescriptions per 100 000 inhabitants per week. These results highlight the major role of viral infections in driving antibiotic prescriptions, particularly in young children.

Synergistic Effect of History of Cardiovascular Disease and Mental Distress on Post-Traumatic Stress Disorder after the Great East Japan Earthquake: The Fukushima Health Management Survey.

Cardiovascular disease (CVD) and mental distress have been suggested to be associated with post-traumatic stress disorder (PTSD), but the effect of their combination on PTSD is unknown. We reviewed the synergistic effects of the history of CVD and mental distress on the possibility of PTSD among residents in Fukushima after the Great East Japan Earthquake. This cross-sectional study was conducted among 38,392 participants aged 40-74 years in the evacuation area who applied for the Fukushima Health Management Study in Fiscal Year 2011. Relative excess risk due to interaction (RERI), attributable proportion (AP), odds ratio (OR), and 95% confidence interval (CI) were calculated to investigate the combined effect of history of CVD and mental distress on PTSD. We identified 8104 probable cases of PTSD (21.1%). History of CVD, mental distress, and their combination were positively associated with probable PTSD: the multivariable ORs (95% CIs) were 1.44 (1.04, 2.01), 20.08 (18.14, 22.22), and 26.60 (23.07, 30.67), respectively. There was a significant increase in RERI: the corresponding RERI (95% CI) and AP were 6.08 (3.16, 9.00) and 22.9%. Gender-specific analyses showed similar associations. Thus, we found a supra-additive association of history of CVD and mental distress with probable PTSD after the disaster.

Tobacco and alcohol as risk factors for oesophageal cancer in a high incidence area in South Africa.

BACKGROUND: The Eastern Cape Province of South Africa, which includes the former Transkei has high rates of squamous cell oesophageal cancer (OC), thought to be caused mainly by nutritional deficiencies and fungal contamination of staple maize. A hospital-based case-control study was conducted at three of the major referral hospitals in this region to measure, among other suspected risk factors, the relative importance of tobacco smoking and alcohol consumption for the disease in this population. METHODS: Incident cases (n=670) of OC and controls (n=1188) were interviewed using a structured questionnaire which included questions on tobacco and alcohol-related consumption. Odds ratios (ORs) with 95% confidence intervals for each of the risk factors were calculated using unconditional multiple logistic regression models. RESULTS: A monotonic dose-response was observed across the categories of each tobacco-related variable in both sexes. Males and females currently smoking a total of >14g of tobacco per day were observed to have over 4-times the odds of developing OC (males OR=4.36, 95% CI 2.24-8.48; females OR=4.56, 95% CI 1.46-14.30), with pipe smoking showing the strongest effect. Similar trends were observed for the alcohol-related variables. The quantity of ethanol consumed was the most important factor in OC development rather than any individual type of alcoholic beverage, especially in smokers. Males and females consuming >53g of ethanol per day had approximately 5-times greater odds in comparison to non-drinkers (males OR=4.72, 95% CI 2.64-8.41; females OR=5.24, 95% CI 3.34-8.23) and 8.5 greater odds in those who smoked >14g tobacco daily. The attributable fractions for smoking and alcohol consumption were 58% and 48% respectively, 64% for both factors combined. CONCLUSION: Tobacco and alcohol use are major risk factors for OC development in this region. IMPACT: This study provides evidence for further reinforcement of cessation of smoking and alcohol consumption to curb OC development.