Risk Due To Interaction Research Articles

The independent and joint contribution of objective and subjective socioeconomic status on oral health indicators.

The understanding of how subjective socioeconomic status (SSS) relates to objective socioeconomic status (OSS), and how both conditions act together in oral health outcomes is still unclear. This study aims to test the independent and joint association between OSS and SSS with oral health, to assess the role of socioeconomic status discrepancies, and to evaluate the role of SSS in the association between OSS and oral health. Data from 1140 adults from a population-based study in Southern Brazil were used. We applied diagonal reference models DRM to disentangle the effects of OSS (education) and SSS (MacArthur Scale) to oral health outcomes. The outcomes were functional dentition clinically evaluated (FD ≥20 teeth) and self-reported oral health SROH. We also examined the discrepancy between OSS and SSS to oral health indicators and the effect measure modification (EMM) of SSS on the association between OSS and oral health. Subjective socioeconomic status and OSS contributed equally to SROH, while OSS explained a substantially higher amount of FD than SSS (0.85 vs 0.15). An EMM of SSS was found on the association between OSS and fair/poor SROH, with a relative excess risk due to interaction (RERI) of 1.08. Less evidence of EMM was found for FD (RERI=0.14). Individuals with lower SSS and OSS had four times the risk of the outcomes than the reference group. Adults with concordant lower SSS and OSS have a worse oral health than those with concordant higher status. There was evidence that the association between OSS and SROH is modified by SSS.

Associations of solid fuel use and ambient air pollution with estimated 10-year atherosclerotic cardiovascular disease risk.

Although exposure to ambient air pollution (AAP) increases the risk for arteriosclerotic cardiovascular disease (ASCVD), evidence on the association of solid fuel use with ASCVD and its association modified by ambient air pollution remains limited. A total of 16,779 adults were derived from the Henan Rural Cohort Study. Concentrations of ambient air pollutants (PM1, PM2.5, PM10, and NO2) were estimated by a spatiotemporal model based on satellites data. Solid fuel use was assessed by a self-reported questionnaire. The associations of solid fuel use with high 10-year ASCVD risk and the modified association by exposure to air pollutants were explored using logistic regression models. There were positive associations of AAP exposure with high 10-year ASCVD risk among individuals with self-cooking. The joint associations between high AAP exposures and solid fuel use with high 10-year ASCVD risk were found. Compared to clean fuel user with low PM2.5 exposure, the odds ratios (ORs) and 95% confidence intervals (CIs) of high 10-year ASCVD risk was 1.25 (1.09, 1.42) for solid fuel user with low PM2.5 exposure, 1.93 (1.75, 2.12) for clean fuel user with high PM2.5 exposure, and 3.08 (2.67, 3.54) for solid fuel user with high PM2.5 exposure, respectively. Their additive effect on high 10-year ASCVD risk was observed (relative excess risk due to interaction (RERI): 0.90 (95%CI: 0.50, 1.30), attributable proportion due to interaction (AP): 0.29 (95%CI: 0.19, 0.40), and synergy index (SI): 1.77 (95%CI: 1.38, 2.26)). This study showed a synergistic effect of AAP and household air pollution reflected by solid fuel use on high 10-year ASCVD risk, suggesting that reducing solid cooking fuels and controlling air pollution may have a joint effect on public health improvement.

Circulating cystatin‐C is associated with dementia in a racial and ethnically diverse cohort: An interaction decomposition analysis

AbstractBackgroundCystatin‐C has an important role in the pathogenesis of dementia, as evidenced by expression in the brain and co‐localization with beta‐amyloid deposits. Circulating Cystatin‐C may be directly implicated in neurodegeneration, or the result of a compensatory mechanism of neuroprotection. Our study aims to understand the relationship between circulating Cystatin‐C and dementia, and to test the interaction between Cystatin‐C and race/ethnicity.MethodsWe performed a cross‐sectional analysis of serum Cystatin‐C levels with dementia and cognitive impairment non‐dementia (CIND) in two waves (2006 and 2008) of the Health and Retirement Study (n=9,984). We used Poisson regression with robust variance to estimate the interactive effect of race/ethnicity and Cystatin‐C >75th on dementia. We calculated three measures of interaction in the additive scale: the excess risk due to interaction (RERI), the attributable proportion, and the synergy index (SI). We decomposed the interaction to calculate the percentage of the excess risk attributable to the effects of race/ethnicity and Cystatin‐C alone.ResultsAfrican Americans and Hispanics had higher levels of Cystatin‐C at every decade of life except for the 80s with respect to Whites (see Figure 1). The prevalence ratio for dementia among African Americans with levels of Cystatin‐C >75th was 7.33 (95%CI: 5.43, 9.89) times of White Americans with Cystatin‐C <75th. A RERI of 1.89 (95%CI: ‐0.17, 3.95) indicates more than an additive interaction; and attributable proportion of 0.26 (95%CI: 0.02, 0.50) suggests than roughly a quarter of the excess risk was due to the interaction of both race and Cystatin‐C; and a synergy index of 1.43 (95%CI: 0.97, 2.10) provided evidence of synergism between the two exposures. We found 26% (95%CI: 2%, 50%) of the excess risk among the doubly exposed group (i.e., African Americans with levels of Cystatin‐C >75th) was attributable to the interaction between Cystatin‐C and race. Similar patterns were observed for Hispanics in relation to Whites.ConclusionElevated levels of circulating Cystatin‐C are implicated in impaired cognition, and the association between Cystatin‐C and cognition varies dramatically by race/ethnicity.

Inequality in Social Support Associated With Mild Cognitive Impairment: A Cross-Sectional Study of Older (≥60 Years) Residents in Shanghai, China.

Objective: Social support plays a critical role in the detection and management of mild cognitive impairment (MCI). However, socioeconomic inequalities exist in both social support and health care services. Our study aimed to compare the level of social support received by MCI patients in comparison with those without MCI and to determine its link with income.Methods: Secondary data analyses were performed. Social support was measured using the Duke Social Support Index (DSSI) and satisfaction ratings. Multivariate logistic regression models were constructed to determine the associations of personal income and MCI with social support after adjustment for variations in the sociodemographic and health characteristics of the respondents. The multiplicative and additive interaction effects of income and MCI were further examined through introducing the MCI*Income variable to the regression models and using the relative excess risk due to interaction (RERI) analysis, respectively.Results: The logistic regression models showed that the respondents with MCI had significantly lower social support as measured by the DSSI scores (AOR = 33.03, p < 0.001) and satisfaction ratings (AOR = 7.48, p < 0.001) compared with those without MCI. Similarly, social support decreased with lower personal income (p < 0.001). There existed a significant multiplicative interaction effect between personal income and MCI on social support (AOR = 0.30–0.32, p < 0.01). The gap in social support between those with and without MCI was higher in the higher income group compared with the lower income group (p < 0.001). No significant additive interaction effects on social support were found between MCI and income.Conclusions: There are significant disparities in social support between people living with and without MCI. Such a gap is more profound in people with higher income. The inequality in social support associated with MCI may present a significant challenge to the successful implementation of community MCI detection and management.

The Independent, Joint, and Additive Associations of Physical Activity and Self-Compassion on Depression Symptoms Among Chinese College Students.

BackgroundPhysical activity and self-compassion are closely related to individuals’ mental health (eg, depression). However, most studies only examined their independent roles in mental health without considering the potential interaction between the two variables. The present study aimed to investigate the independent and joint associations between physical activity (PA) and self-compassion (SC) on depression symptoms and examine the additive interaction between PA and SC.MethodsA cross-sectional design was utilized in the present descriptive study. By recruiting participants via social media platforms, 1846 Chinese college students completed International Physical Activity Questionnaire Short Form, the Self-Compassion Scale-Short Form, the 9-item Patient Health Questionnaire, and items regarding socio-demographic information. Independent and joint roles of low-level PA (LPA) and low-level SC (LSC) on depression symptoms were examined by logistic regression models. Additive interaction between LPA and LSC on depression symptoms was examined by the following indices: relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S). Socio-demographic variables were included in the models as covariates.ResultsBoth LPA (OR = 1.47 [1.16, 1.86]) and LSC (OR = 5.74 [3.89, 8.45]) were independently associated with higher probability of depression symptoms. Combining LPA and LSC led to an additive interaction and greatly increased the odds of depression symptoms (OR = 9.62 [5.38, 17.22]; RERI = 2.47 [0.19, 4.75], AP = 0.25 [0.05, 0.44], S = 1.38 [1.02, 1.87]).ConclusionBoth LPA and LSC were associated with an increased risk of depression symptoms. Moreover, combining LPA and LSC may develop an additive risk for depression symptoms. Future research and clinical intervention could integrate PA and SC to find a better way to resist depression symptoms.

Joint effect of urinary arsenic species and serum one-carbon metabolism nutrients on gestational diabetes mellitus: A cross-sectional study of Chinese pregnant women.

Growing evidence indicates that arsenic (As) exposure can increase the risk of gestational diabetes mellitus (GDM). However, little is known about As species and GDM and the combined effect of As and one-carbon metabolism (OCM) on GDM. We aimed to examine the associations between As species and GDM and evaluate the potential interactions of folate, vitamin B12, and homocysteine (Hcy) with As species on GDM prevalence. We measured levels of arsenite (As3+), arsenate (As5+), dimethylarsinic acid (DMA), and arsenobetaine (AsB) species in urine and folate, vitamin B12, and Hcy in serum from 396 pregnant women in Tianjin, China. The diagnosis of GDM was based on an oral glucose tolerance test. Associations of As species in urine with GDM were evaluated using generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR). Additive interactions of As and OCM with GDM were estimated by determining the relative excess risk due to interaction (RERI). Of the 396 pregnant women, 89 were diagnosed with GDM. Continuous increases in urinary inorganic As were associated with GDM in the GLMs, with adjusted odds ratios of 2.12 (95% CI: 0.96, 4.71) for As3+, and 0.27 (95% CI: 0.07, 0.98) for As5+. The BKMR in estimating the exposure-response functions showed that As3+ and AsB were positively associated with GDM. However, As5+ showed a negative relationship with GDM. Although the additive interactions between As exposure and OCM indicators were not significant, we found that pregnant women with higher urinary As3+ and total As accompanied by lower serum vitamin B12 were more likely to have higher odds of GDM (3.12, 95% CI: 1.32, 7.38 and 3.10, 95% CI: 1.30, 7.38, respectively). Our data suggest a positive relation between As3+ and GDM but a negative relation between As5+ and GDM. Potential additive interaction of As and OCM with GDM requires further investigation.

The influence of probable rapid eye movement sleep behavior disorder and sleep insufficiency on fall risk in a community-dwelling elderly population

BackgroundThe objective was to investigate the individual effect and potential interactions of probable rapid eye movement sleep behavior disorder (pRBD) and sleep insufficiency on fall risk among a Chinese elderly population.MethodsCommunity-dwelling population aged 55 years or above were recruited from the Beijing Longitudinal Study on Aging II cohort from 2010 to 2011. Odds ratio (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression models. Multiplicative and additive interactions between pRBD and sleep insufficiency were examined using likelihood ratio tests and relative excess risk due to interaction (RERI), respectively.ResultsAmong 6891 included participants, 479 experienced at least once fall. pRBD and sleep insufficiency were both independently associated with elevated fall risk. Compared to the elderly without pRBD or sleep insufficiency, pRBD and sleep insufficiency was each associated with a 2.57-fold (OR = 2.57, 95%CI: 1.46–4.31) and 1.45-fold (OR = 1.45, 95%CI: 1.11–1.88) risk of falls individually, while their coexistence was associated with a less-than-additive 17% (OR = 1.17, 95%CI: 0.43–2.63) increased risk of falls. The combination of these two factors demonstrated evidence of a negative interaction on both multiplicative (ratio of ORs = 0.31, 95%CI: 0.10, 0.86) and additive (RERI = − 1.85, 95%CI: − 3.61, − 0.09) scale.ConclusionsOur study has provided robust evidence for the adverse effect of pRBD and sleep insufficiency, as well as their negative interaction on increasing fall risk in a Chinese elderly population.

Does allostatic load predict incidental coronary events differently among sexes?

BackgroundOne measure to quantify the degree of dysregulation is allostatic load (AL). Typically, AL incorporates information on diverse biomarkers and is associated with health outcomes such as cardiovascular diseases or the incidence of coronary events (C-E). AimsThis study investigates the predictive performance of different AL scoring methods on the incidence of coronary events (C-E). This study also elaborates sex differences in the baseline risks of C-E and the AL associated risks of C-E. DesignLongitudinal data analysis of the Heinz Nixdorf Recall Study (Risk Factors, Evaluation of Coronary Calcification, and Lifestyle) of 4327 participants free of C-E at study baseline aged 45–75. The data contains over 13 biomarkers measuring AL. MethodsAfter conducting multiple imputations on missing values on AL for 826 participants, the analysis sample consisted of N = 4327 participants. We applied the two most commonly used methods of AL scoring AL (count-based and Z-score) and a recently developed logistic regression weighting method (LRM) approach. Cox regression was used to predict the incidence of C-E for each AL score. Results were estimated without (M0) and with (M1) covariate adjustment, and in a final model (M2), with an interaction between AL and sex. ResultsWe found no violation of the proportional hazard assumption and significant differences in the survival curves between the sexes for C-E (Log-rank test: prob. > Chi2 = 0.000). In M0, all AL-scoring methods predicted C-E significantly, with the LRM based AL-score having the best performance (hazard ratio = 3.133; CI: [2.630, 3.732]; Somer's D = 0.717). After covariate inclusion, differences between the scoring methods levelled, though the count-based method and LRM performed better than the Z-scoring method. The interaction analysis in M2 showed a significant multiplicative interaction for the count-based method (1.254; [1.066, 1.475]) and for the LRM (1.746; [1.132, 2.692]). The additive relative excess risk due to interaction (RERI) measure was negative for the count-based method (RERI = −1.967; [-3.778; −0.156]) and the LRM (RERI = −1.909 [-3.910; 0.091]), indicating subadditivity. ConclusionAL scores are suitable for predicting C-E. Differences between the AL-scoring algorithms were only present after including interactions. We value the count-based method as suitable for clinical practice since its calculation is relatively simple, and performance was among the best. Interaction analysis revealed that despite strong sex differences in baseline C-E, the effect of AL is more pronounced for females at high levels of AL; thus, females could benefit more from a potential intervention on AL. We suggest further investigation of sex differences concerning the mediation by physiological and psychological intermediates.

A multicenter case\u2013control study of the effect of e-nos VNTR polymorphism on upper gastrointestinal hemorrhage in NSAID users

Bleeding in non-steroidal anti-inflammatory drug (NSAID) users limited their prescription. This first multicenter full case–control study (325 cases and 744 controls), explored the association of e-NOS intron 4 variable number tandem repeat (VNTR) polymorphism with upper gastrointestinal hemorrhage (UGIH) in NSAID exposed and unexposed populations and assessed any interaction between this polymorphism and NSAIDs. NSAID users carrying e-NOS intron 4 wild type genotype or VNTR polymorphism have higher odds of UGIH than those unexposed to NSAIDs [Odds Ratio (OR): 6.62 (95% Confidence Interval (CI): 4.24, 10.36) and OR: 5.41 (95% CI 2.62, 11.51), respectively], with no effect modification from VNTR polymorphism-NSAIDs interaction [Relative Excess Risk due to Interaction (RERI): −1.35 (95% CI −5.73, 3.03); Synergism Index (S): 0.77 (95% CI 0.31, 1.94)]. Similar findings were obtained for aspirin exposure. Non-aspirin NSAID users who carry e-NOS intron 4 VNTR polymorphism have lower odds of UGIH [OR: 4.02 (95% CI 1.85, 8.75) than those users with wild type genotype [OR: 6.52 (95% CI 4.09, 10.38)]; though the interaction estimates are not statistically significant [RERI: −2.68 (95% CI −6.67, 1.31); S: 0.53 (95% CI 0.18, 1.55)]. This exploratory study suggests that the odds of UGIH in NSAID or aspirin users does not modify according to patient´s e-NOS intron 4 genotype.

Do overweight/obesity and low levels of leisure-time vigorous physical activity moderate the effect of occupational physical activity on self-rated health of construction workers?

PurposeTo investigate the combined effects of occupational physical activity (OPA) and either overweight/obesity or low levels of leisure-time vigorous physical activity (LTVPA) on self-rated health.MethodsA longitudinal study was performed among 29,987 construction workers with complete data on 2 Workers’ Health Surveillance Programs during 2010–2018. Self-reported OPA involved strenuous work postures and manual material handling. Low level of LTVPA was defined as self-reported vigorous activity for less than three times per week lasting at least 20 min per session. Overweight and obesity were based on Body Mass Index (BMI) (25.0 ≤ BMI < 30.0 kg/m2 and BMI ≥ 30.0 kg/m2, respectively) using measured body height and weight. Self-rated health was measured using a single item question. Logistic regression analysis was used to investigate the associations between the separate risk factors at baseline and self-rated health at follow-up. The combined effects of demanding OPA and either overweight/obesity or low level of LTVPA on self-rated health were analyzed using the relative excess risk due to interaction (RERI).ResultsMean follow-up duration was 31.7 (SD = 14.9) months. Construction workers with strenuous work postures (OR 1.35 95% CI 1.25–1.46), manual material handling (OR 1.29 95% CI 1.19–1.40), obesity (OR 1.31 95% CI 1.17–1.47) and low LTVPA (OR 1.13 95% CI 1.01–1.25) were more likely to report poor self-rated health at follow-up. No statistically significant interaction effects were found for OPA and obesity or low LTVPA.ConclusionsOPA, obesity and low level of LTVPA were separate risk factors for poor self-rated health, but did not appear to have a synergistic effect.

Assessment of Cardiovascular Risk Factors and Their Interactions in the Risk of Coronary Heart Disease in Patients with Type 2 Diabetes with Different Weight Levels, 2013-2018.

PurposeIn addition to hyperglycemia and hyperlipidemia, obesity and hypertension are important cardiovascular risk factors for coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). This study aims to explore the interaction of these risk factors.Patients and MethodsData of hospitalized patients with T2DM from 2013 to 2018 were collected. A multivariate logistic regression model was established. Patients with normal weight and blood pressure were recruited as controls. The interaction on the risk of CHD was evaluated by relative excess risk due to interaction (RERI).ResultsAmong the 30,693 patients with T2DM, 7202 (23.5%) had CHD. In the low weight group, the prevalence of CHD in patients with hypertension was nearly four times higher than that in patients without hypertension (42.7% vs 11.3%, P < 0.01). The OR value of hypertension alone on CHD increased from 1.29 (95% CI 1.06–1.56) in the body mass index (BMI) 30.0–34.9 kg/m2 group to 1.35 (95% CI 1.11–1.62) in the BMI ≤ 18.5 kg/m2 group. Additive interaction was observed between hypertension and BMI in CHD risk, especially in the low weight group (RERI:2.2, 95% CI 0.9–3.5). BMI and CHD risk showed a smile curve relationship. The attributive proportion in the low weight group was higher than that in the severe obesity group, that is, 0.52 (95% CI 0.35–0.69) vs 0.18 (95% CI −0.59 to 0.95).ConclusionMaintaining normal weight and avoiding low weight are particularly important for patients with co-occurring diabetes and hypertension to prevent the risk of CHD.

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.

Life dissatisfaction in Canadians aged 40 and above with cancer and mental health disorders: A cross‐sectional study using the Canadian Community Health Survey

BackgroundLife dissatisfaction varies with different factors––particularly in the presence of chronic conditions, such as cancer. The combination of cancer and mental health disorders may increase life dissatisfaction due to lowered resilience against stress. We sought to determine if life dissatisfaction is higher in Canadians aged 40 and above with cancer compared to the cancer‐free population and if there is a synergistic effect between cancer and mental health disorder on life dissatisfaction.MethodsWe conducted a cross‐sectional study using the 2015–2016 Canadian Community Health Survey. We included 67,294 subjects aged 40+, and evaluated the association between cancer, mental health disorders, and life dissatisfaction using logistic regression and odds ratios (ORs) while adjusting for age, sex, marital status, education level, and chronic conditions. Relative excess risk due to interaction (RERI), attributional proportion due to interaction (AP), and Synergy index (S‐index), were calculated to determine the significance of additive interaction.ResultsCompared to the cancer‐free population, life dissatisfaction was higher in patients with cancer (OR 2.44, 95% CI: 1.88–3.16) and mental health disorders (OR 5.17, 95% CI: 4.56–5.85). The adjusted ORs for life dissatisfaction were 2.45 (95% CI: 1.74–3.43) and 5.17 (95% CI: 4.55–5.87) for cancer and mental health disorders, respectively, but when both conditions were present, the OR increased to 12.50 (95% CI: 8.40–18.62). The results suggested a synergistic interaction (RERI: 5.89 [95% CI: 0.91–10.87]; AP: 0.47 [95% CI: 0.25–0.69]; and S‐index: 2.05 [95% CI: 1.30–3.23]).ConclusionThis study showed higher life dissatisfaction in cancer and mental health disorder patients. A synergistic effect was detected between cancer and mental health disorder on life dissatisfaction. These results suggest cancer patients with mental health disorders require additional support and psychological resources to improve their quality of life.

Synergistic associations of visual and self-reported hearing acuity with low handgrip strength in older adults: a population-based cross-sectional study

BackgroundIt is unclear whether visual and hearing acuity are independently or synergistically associated with muscle strength. We aimed to examine the associations of visual and self-reported hearing acuity with low handgrip strength and the additive interaction between visual and hearing acuity on low handgrip strength in people over 60 years.MethodData of 3,075 individuals aged over 60 years from the 2017 and 2018 Korea National Health and Nutrition Examination Survey were used for this cross-sectional study. Low handgrip strength was defined based on the 20th percentile of the study population (< 30.4 kg for male and < 17.7 kg for female). Visual and self-reported hearing acuity were each divided into three categories: good, moderate, and impaired. Multiple logistic regression and relative excess risk due to interaction (RERI) were performed.ResultsOf the 3,075 participants, 993 (32.3 %) demonstrated low handgrip strength. Low handgrip strength was more prevalent in participants with moderate (adjusted odds ratio [AOR] = 1.54, 95 % confidence interval [CI] = 1.12–2.12) and impaired visual acuity (AOR = 2.00, 95 % CI = 1.34–2.96). Both moderate and impaired self-reported hearing acuity were significantly associated with low handgrip strength (moderate: AOR = 1.25, 95 % CI = 1.01–1.55; impaired: AOR = 1.66, 95 % CI = 1.15–2.38). The more severe the sensory function decline, the higher the association with muscle weakness. Moreover, combined sensory impairments were associated with deteriorating low handgrip strength (AOR = 8.38), with significantly strong additive interactions (RERI = 2.61, 95 % CI = 2.52–2.70).ConclusionsAwareness is needed regarding the risk of reduced muscle strength in individuals with moderate and impaired sensory function. Older people with sensory function decline in clinical settings may benefit from programs such as exercise prescription to prevent muscle weakness.

Emotional demands at work and risk of long-term sickness absence in 1·5 million employees in Denmark: a prospective cohort study on effect modifiers

High emotional demands at work can affect employees' health and there is a need to understand whether such an association might be modified by other working conditions. We aimed to examine emotional demands at work as a risk factor for long-term sickness absence and analyse whether influence, possibilities for development, role conflicts, and physical demands at work might modify this risk. We did a nationwide, population-based, prospective cohort study in Denmark and included employed individuals who were residing in Denmark in 2000, aged 30-59 years, who had complete data on age, sex, and migration background, with information on emotional demands and possible effect modifiers from job exposure matrices, and covariates and outcome (sickness absence) from population registers. Individuals with long-term sickness absence (≥6 weeks of consecutive sickness absence) between Jan 1, 1998, and Dec 31, 2000, and self-employed individuals were excluded. We assessed long-term sickness absence during a 10-year period from Jan 1, 2001, to Dec 31, 2010. Using Cox regression, we estimated hazard ratios (HRs) and 95% CIs and tested interaction as departure from additivity, estimating relative excess risk due to interaction (RERI). Multivariable adjusted models included sex, age, cohabitation, migration background, and income. 1 521 352 employed individuals were included and contributed data between Jan 1, 2000, and Dec 31, 2010. During 11 919 021 person-years (mean follow-up 7·8 years), we identified 480 685 new cases of long-term sickness absence. High emotional demands were associated with increased risk of long-term sickness absence compared with low emotional demands, after adjusting for age, sex, cohabitation, migration background, income, and the four possible effect modifiers (adjusted HR 1·55 [95% CI 1·53-1·56]). The association between high emotional demands and risk of long-term sickness absence was stronger in a synergistic way when individuals were also exposed to low possibilities for development (RERI 0·35 [95% CI 0·22-0·47]; 28·9 additional cases per 1000 person-years) and high role conflicts (0·13 [0·11-0·15]; 22·0 additional cases per 1000 person-years). No synergy was observed for influence and physical demands at work. People in occupations with high emotional demands were at increased risk of long-term sickness absence. Our findings on synergistic interactions suggest that, in emotionally demanding occupations, increasing possibilities for development and reducing work-related role conflicts might reduce long-term sickness absence. Further interventional studies are needed to confirm or refute this hypothesis. Danish Work Environment Research Fund, NordForsk.

Bacillus of Calmette and Guérin (BCG) and the risk of leprosy in Ciudad del Este, Paraguay, 2016-2017.

OBJECTIVESParaguay has experienced a 35% reduction in the detected incidence of leprosy during the last ten years, as the vaccination coverage against tuberculosis (Bacillus of Calmette and Guérin [BCG] vaccine) reached ≥95% among infants. The objective of this case-control study was to evaluate the protective effect of BCG on the risk of leprosy.METHODSWe used a population-based case-control study of 20 leprosy confirmed cases reported among residents of Ciudad del Este, Paraguay, diagnosed in 2016–2017. Three controls were selected from a random sample of households from the city. We assessed vaccine effectiveness using 1- odds ratio [OR], and confounding for age, gender, education, occupation, and marital status using stratified and exact logistic regression, and explored if there was effect modification calculating the synergy factor (SF) and relative excess risk due to interaction (RERI).RESULTSAfter controlling for age, gender, education, occupation and marital status, the OR of BCG scar on the risk of leprosy was 0.10 (95% confidence interval [CI], 0.02 to 0.45), for an estimate of vaccine effectiveness of 89.5% reduced risk of leprosy (95% CI, 55.2 to 98.1). There was evidence of heterogeneity by which the effectiveness of BCG seemed stronger among younger persons (Breslow-Day and Z-test of the SF had a p<0.05), and both the RERI and SF indicated a less then multiplicative and additive interaction of BCG and younger age.CONCLUSIONSBCG vaccination was associated with a decreased risk of leprosy in the study population, particularly in persons born after 1980.

Maternal obesity, pregnancy weight gain, and birth weight and risk of colorectal cancer

ObjectiveColorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Obesity is a well-established risk factor for CRC, and fetal or developmental origins of obesity may underlie its effect...

Prenatal Air Pollution, Maternal Immune Activation, and Autism Spectrum Disorders

BACKGROUND AND AIM: Early-life causes of autism spectrum disorders (ASD) are multifactorial, including prenatal air pollution and gestational conditions with maternal immune activation (MIA) which may share common biological mechanisms. This study examined the potential synergistic effects of prenatal air pollution and MIA on ASD risk. METHODS: This retrospective cohort study included 311,617 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals in 2001-2014. Children were followed through electronic medical records (EMR) until ASD diagnosis, non-KPSC membership, death, or December 31, 2019, whichever came first. The presence of five broad categories of MIA during pregnancy (asthma, infections, any hypertension, allergies, and autoimmune diseases) were identified by International Classification of Diseases, Ninth Revision (ICD-9). Pregnancy average PM2.5, NO2, and O3 exposures were estimated using high spatio-temporal resolution models based on maternal residential address history during pregnancy. Hazard ratios of ASD associated with air pollution and MIA were estimated using Cox regression models adjusted for birth year, KPSC medical center, child sex, and maternal sociodemographic characteristics. Multiplicative interactions were assessed in Cox models using interaction terms; additive interactions were assessed using relative excess risk due to interaction (RERI). RESULTS:The prevalence of maternal asthma, infection, hypertension, allergy, and autoimmune diseases was 7.17%, 48.6%, 9.6%, 13.7%, and 11.2%, respectively. During follow-up 6,291 children were diagnosed with ASD. Higher levels of average pregnancy PM2.5, and each of the five categories of MIA exposures was associated with ASD risk (p-value0.05). However, no statistically significant interactions were found between the five categories of MIA and any of the three air pollutants on either multiplicative or the additive scales. CONCLUSIONS:This study found little evidence that MIA and prenatal air pollution have synergistic effects on ASD. MIA and prenatal air pollution may contribute independently to ASD risk. KEYWORDS: Air pollution, Neurodevelopmental outcomes, Pregnancy outcomes

The multimorbidity of hypertension and osteoarthritis and relation with sleep quality and hyperlipemia/hyperglycemia in China\u2019s rural population

Hypertension (HTN) and osteoarthritis (OA) are frequent in middle-aged and elderly people, and the co-occurrence of these two diseases is common. However, the pathogenesis of the multimorbidity of both diseases and the relation with sleep quality, hyperlipemia, and hyperglycemia is unclear. We conducted a cross-sectional study to make sense of the multimorbidity of HTN and OA and the relation with sleep quality, hyperlipemia, and hyperglycemia. The relation between sleep quality and OA and its joint effect with hyperlipemia or hyperglycemia was evaluated with logistic regression models. The additive interaction was assessed with the relative excess risk due to interaction (REEI), the attributable proportion (AP), and the synergy index (S). According to this research in a remote rural area, approximately 34.2% of HTN patients are accompanied with OA and 49.1% are suffering poor sleep. Both hyperlipemia/hyperglycemia and sleep quality were related to OA prevalence with crude ORs of 1.43 (95% CI 1.014–2.029) and 1.89 (95% CI 1.411–2.519, P < 0.001) respectively. An observed additive effect was found greater than the sum of the effects of sleep quality and hyperlipemia/hyperglycemia posed on OA prevalence alone. This additive interaction was observed in females (OR = 3.19, 95% CI 1.945–5.237) as well as males ≥ 65 years old (OR = 2.78, 95% CI 1.693–4.557), with RERI, AP, and S significant. Therefore, poor sleep and hyperlipemia/hyperglycemia are associated with OA, and further studies on the additive interaction among females and males ≥ 65 are warranted.

Interaction of Alzheimer's Disease-Associated Genetic Risk with Indicators of Socioeconomic Position on Mild Cognitive Impairment in the Heinz Nixdorf Recall Study.

Background:The apolipoprotein E (APOE) ɛ4 allele is reported to be a strong genetic risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Additional genetic loci have been detected that influence the risk for late-onset AD. As socioeconomic position (SEP) is also strongly related to cognitive decline, SEP has been suggested to be a possible modifier of the genetic effect on MCI.Objective:To investigate whether APOE ɛ4 and a genetic sum score of AD-associated risk alleles (GRSAD) interact with SEP indicators to affect MCI in a population-based cohort.Methods:Using data of 3,834 participants of the Heinz Nixdorf Recall Study, APOE ɛ4 and GRSAD by SEP interactions were assessed using logistic regression models, as well as SEP-stratified genetic association analysis. Interaction on additive scale was calculated using the relative excess risk due to interaction (RERI). All analysis were additionally stratified by sex.Results:Indication for interaction on the additive scale was found between APOE ɛ4 and low education on MCI (RERI: 0.52 [95% confidence interval (CI): 0.01; 1.03]). The strongest genetic effects of the APOE ɛ4 genotype on MCI were observed in groups of low education (Odds ratio (OR): 1.46 [95% CI: 0.79; 2.63] for≤10 years of education versus OR: 1.00 [95% CI: 0.43; 2.14] for≥18 years of education). Sex stratified results showed stronger effects in women. No indication for interaction between the GRSAD and SEP indicators on MCI was observed.Conclusion:Results indicate that low education may have an impact on APOE ɛ4 expression on MCI, especially among women.