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BackgroundMaternal exposure to air pollution has been associated with birth outcomes; however, few studies examined biologically critical exposure windows shorter than trimesters or potential effect modifiers.ObjectivesTo examine associations of prenatal fine particulate matter (PM2.5), by trimester and in biologically critical windows, with birth outcomes and assess potential effect modifiers.MethodsThis study used two pregnancy cohorts (CANDLE and TIDES; N=2099) in the ECHO PATHWAYS Consortium. PM2.5 was estimated at the maternal residence using a fine-scale spatiotemporal model, averaged over pregnancy, trimesters, and critical windows (0-2 weeks, 10-12 weeks, and last month of pregnancy). Outcomes were preterm birth (PTB

Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM among children 6 to 59 months in Sierra Leone. EED was assessed at enrollment using the L:M test and 15 host fecal mRNA transcripts on 522 children. Recovery from MAM was defined as achieving mid-upper arm circumference ≥ 12.5 cm within 12 weeks of supplementation. Random forest classification models were used to examine prediction of presence and severity of EED by host fecal mRNA transcripts. Logistic regression was used to test for effect modification by L:M test variables including % lactulose excreted (%L). Eight host fecal mRNA transcripts (AQP9, REG3A, IFI30, DECR1, BIRC3, SELL, PIK3AP1, DEFA6) identified EED (%L ≥ 0.2) and severe EED (%L ≥ 0.45) with high sensitivity and specificity. The L:M test variables did not modify the effect of SNFs on recovery from MAM. In this study, we found host fecal mRNA transcripts that could be biomarkers of EED but did not find EED to modify the effect of SNFs on MAM treatment.

Qiuping Li, Xi Chen, Binru Han Department of Nursing, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Binru HanXuanwu Hospital, Capital Medical University, Chang Chun St.45, Xicheng District, Beijing, 100053, People’s Republic of ChinaTel +86 10-83198219Fax +86 10-83198258Email kinv246@126.comBackground: Hemoglobin concentration differs by sex, possibly affecting any association between hemoglobin and frailty. This study aimed to evaluate the potential interaction effect of hemoglobin and sex on frailty in Chinese older inpatients.Methods: A cross-sectional study was conducted between February 2015 and November 2017 in a tertiary hospital. Frailty was defined by the Fried phenotype. Hemoglobin concentration was measured with a standard procedure. Covariates included demographics, clinical characteristics, and serum biomarkers. Logistic regression was applied to examine the association between hemoglobin concentration and frailty. The relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) were used to evaluate the additive interaction.Results: A total of 619 older inpatients [mean age 69.26± 7.44 years; 334 men, 285 women] were included. The mean hemoglobin concentration was significantly lower in the elderly who were frail (11.9 g/L in frail versus 13.1g/L in non-frail; p< 0.001). In the multivariable regression models, lower hemoglobin in patients was significantly associated with frailty (adjusted odds ratio (OR) = 2.51, 95% CI:1.37, 4.60). The stratified analyses indicated that lower hemoglobin was associated with frailty among older inpatients with different characteristics. Female inpatients with lower hemoglobin had the highest risk of frailty (adjusted OR=6.43, 95%: 2.38, 17.3); there were interactions between hemoglobin and sex on the development of frailty (RERI=4.30, 95% CI=− 1.41, 10.01; AP=0.67, 95% CI=0.37, 0.97;SI=4.80, 95% CI=1.22, 18.84).Conclusions and Implications: Our study provided evidence that sex and lower hemoglobin have an interaction effect on frailty; it is suggested that clinicians may consider sex-specific strategies for the elderly to conform the concept of precision medicine.Keywords: hemoglobin concentration, frailty phenotype, older inpatient, interaction effect

Current knowledge of the link between dietary carbohydrate intake and insulin regulation in individuals after an attack of pancreatitis is limited. We aimed to investigate the associations between dietary carbohydrate intake and insulin traits in post-pancreatitis versus healthy individuals, taking into account intrapancreatic fat deposition (IPFD).All participants underwent magnetic resonance imaging (using the same protocol and 3T scanner) to quantify IPFD. Dietary carbohydrate intake was assessed using a validated 131-item food frequency questionnaire. Insulin, HOMA-IR, HOMA-β were determined in the fasted state. Linear regression and effect modification analyses were conducted in unadjusted and adjusted models (accounting for age, sex, body mass index, daily energy intake, use of anti-diabetic medications, and recurrence of acute pancreatitis).The study included 111 post-pancreatitis individuals (categorized into low IPFD (n = 33), moderate IPFD (n = 40), high IPFD (n = 38)) and 47 healthy controls. In the high IPFD group, starch intake was negatively associated with fasting insulin and HOMA-β in both the unadjusted (p 0.001 both) and fully adjusted models (p 0.001 both); and with HOMA-IR in the fully adjusted model (p 0.001) only. Total sugar intake was positively associated with fasting insulin (p = 0.015) and HOMA-β (p = 0.007) in the fully adjusted model but not associated with HOMA-IR. None of the above associations was statistically significant in the low IPFD, moderate IPFD, and healthy controls groups. The studied associations were more pronounced in the high IPFD group but not in the moderate IPFD or low IPFD groups (when compared with the healthy controls group).Dietary carbohydrate intake is differentially associated with insulin traits in individuals after an attack of pancreatitis and the associations are modified by IPFD. These findings will be helpful for the development of dietary guidelines specifically for individuals after an attack of pancreatitis.

Background and aims To elucidate the effect modification of general and central obesity by sex and age on the risk of cardiovascular events. Methods The analysis included 14,983 males and females aged 45–75 years from the Atherosclerosis Risk in Communities study. Obesity was defined with body mass index (BMI), waist-to-hip ratio (WHR) and body shape index (BSI) which categorized the participants as obese and non-obese. Targeted maximum likelihood estimation was used to estimate the risk ratio (RR) with the tmle package in R software. Results After adjustment, the strongest effect of BMI on CHD was in females (RR (95%CI): 1.26 (1.11, 1.42)) and in age>54 (RR (95%CI): 1.16 (1.06, 1.27)) and for HF it was in age>54 (RR (95%CI): 1.18 (1.10, 1.26)) and in females (RR (95%CI): 1.17 (1.08, 1.28)). Regarding central obesity, WHR (RR (95%CI): 1.19 (1.05, 1.34)) had the strongest effects on CHD for males and BSI (RR (95%CI): 1.140 (1.02, 1.26)) for age ≤ 54, and for HF the WHR (RR (95%CI): 1.22 (1.10, 1.36)) and BSI (RR (95%CI): 1.18 (1.07, 1.30)) had the strongest effects for age≤54, respectively. Conclusion Among males and age≤54, WHR index was associated with a higher risk of CHD and HF while BMI was so for females and age>54.

Introduction: The Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials aimed to compare the effects of hemodialysis (HD) given 6 versus 3 times per week. More frequent in-center HD significantly reduced left-ventricular mass (LVM), with more pronounced effects in patients with low urine volumes. In this study, we aimed to explore another potential effect modifier: the predialysis serum sodium (SNa) and related proxies of plasma tonicity. Methods: Using data from the FHN Daily and Nocturnal Trials, we compared the effects of frequent HD on LVM among patients stratified by SNa, dialysate-to-predialysis serum-sodium gradient (GNa), systolic and diastolic blood pressure, time-integrated sodium-adjusted fluid load (TIFL), and extracellular fluid volume estimated by bioelectrical impedance analysis. Results: In 197 enrolled subjects in the FHN Daily Trial, the treatment effect of frequent HD on ∆LVM was modified by SNa. When the FHN Daily Trial participants are divided into lower and higher predialysis SNa groups (less and greater than 138 mEq/L), the LVM reduction in the lower group was substantially higher (−28.0 [95% CI −40.5 to −15.4] g) than in the higher predialysis SNa group (−2.0 [95% CI −15.5 to 11.5] g). Accounting for GNa, TIFL also showed more pronounced effects among patients with higher GNa or higher TIFL. Results in the Nocturnal Trial were similar in direction and magnitude but did not reach statistical significance. Discussion/Conclusion: In the FHN Daily Trial, the favorable effects of frequent HD on left-ventricular hypertrophy were more pronounced among patients with lower predialysis SNa and higher GNa and TIFL. Whether these metrics can be used to identify patients most likely to benefit from frequent HD or other dialytic or nondialytic interventions remains to be determined. Prospective, adequately powered studies studying the effect of GNa reduction on mortality and hospitalization are needed.

Background Self-reported time spent standing has been associated with lower risk of mortality. No previous studies have examined this association using device-measured standing. Method This was a prospective cohort study of 5878 older (median age = 80 years), racial/ethnically diverse, community-dwelling women in the WHI Objective Physical Activity and Cardiovascular Health Study (OPACH). Women wore accelerometers for 1 week and were followed for mortality. The study applied previously validated machine learning algorithms to ActiGraph GT3X+ accelerometer data to separately measure time spent standing with and without ambulation. Cox proportional hazards models were used to estimate mortality risk adjusting for potential confounders. Effect modification by age, body mass index, moderate-to-vigorous physical activity, sedentary time, physical functioning, and race/ethnicity was evaluated. Results There were 691 deaths during 26 649 person-years of follow-up through March 31, 2018 (mean follow-up = 4.8 years). In fully adjusted models, all-cause mortality risk was lower among those with more standing without ambulation (quartile [Q] 4 vs Q1 HR = 0.63; 95% CI = 0.49–0.81, p-trend = .003) and more standing with ambulation (Q4 vs Q1 HR = 0.50; 95% CI = 0.35–0.71, p-trend < .001). Associations of standing with ambulation and mortality were stronger among women with above-median sedentary time (HR = 0.51; 95% CI = 0.38–0.68) compared to women with below-median sedentary time (HR = 0.80; 95% CI = 0.59–1.07; p-interaction = .02). Conclusions In this prospective study among older women, higher levels of accelerometer-measured standing were associated with lower risks of all-cause mortality. Standing is an achievable approach to interrupting prolonged sedentary time, and if not contraindicated, is a safe and feasible behavior that appears to benefit health in older ages.

PURPOSE Previous work has demonstrated that home care patients have an increased risk of visiting the emergency department after a home nursing visit on the same day. We investigated whether this association is modified by greater access to after-hours primary care. METHODS We conducted a population-based case-crossover study of home care patients in Ontario, Canada in 2014-2016. Emergency department visits after 5:00 pm were selected as case periods and matched, within the same patient, to control periods within the previous week. The association between home nursing visits and same-day emergency department visits was estimated with conditional logistic regression. Access to after-hours primary care, measured on the patient and practice level, was tested for effect modification using an interaction term approach. Analysis was performed separately for all emergency department visits and a less urgent subset not admitted to hospital. RESULTS A total of 11,840 patients contributed cases to the analysis. Patients with a history of after-hours primary care use had a smaller increased risk of a same-day after-hours emergency department visit (OR = 1.18; 95% CI, 1.06-1.30) compared with patients with no after-hours care (OR = 1.31; 95% CI, 1.25-1.39). The modifying effect was stronger among emergency department visits not admitted to hospital (OR = 1.11; 95% CI, 0.97-1.28 vs OR = 1.41; 95% CI, 1.31-1.51). CONCLUSION Greater access to after-hours primary care reduced the risk of less-urgent emergency department use associated with home nursing visits. These findings suggest increasing access to after-hours primary care could prevent some less-urgent emergency department visits.

International audience; The role of progesterone receptor (PR) status on the association between obesity and prognosis of estrogen receptor positive (ER+) breast cancer (BC) remains poorly understood. We aim to examine whether this association varies according to the tumor PR status. Data for 3,747 women diagnosed with nonmetastatic ER+ invasive BC between 1995 and 2010 were analyzed. Women were classified according to their body mass index (BMI) (

Background Food packages provided by the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) were revised in 2009 to better align them with the Dietary Guidelines for Americans. This study was conducted to evaluate whether the effect of the food package change on childhood obesity varied by the food environment in the neighborhoods where WIC-participating children live. Methods Administrative data from participating children in Los Angeles County, California (2003–2016) were merged with geocoded food vendor information by neighborhood of residence. Obesity risk at age 4 was compared between children receiving old (2003–2009) and new (2010–2016) WIC food packages using sex-stratified Poisson regression models, with interaction terms between WIC package and neighborhood density (number per square mile) of healthy and unhealthy food outlets. Results The new food package was associated with a significant decrease in obesity risk. Among boys, the new food package was associated with 8 to 18% lower obesity risk at all healthy and unhealthy food outlet densities, and the association was not modified by neighborhood food outlet density. Among girls, the association of the new food package with obesity risk was protective in neighborhoods with high healthy and low unhealthy food outlet densities, and adverse in neighborhoods with high unhealthy and low healthy food outlet densities. The effect of the new food package among girls was modified by unhealthy food outlet density, with significantly smaller (p-value = 0.004) decreases in obesity risk observed in neighborhoods with higher unhealthy food outlet density. Conclusions The impact of the food package change was modified by the neighborhood food environment among girls only. Future policy changes should incorporate consideration of ways to mitigate potentially inequitable geographic distribution of the health benefits of policy changes.

The majority of research within reproductive and gynecologic health, or investigating ART, is observational in design. One of the most critical challenges for observational studies is confounding, while one of the most important for discovery and inference is effect modification. In this commentary, we explain what confounding and effect modification are and why they matter. We present examples illustrating how failing to adjust for a confounder leads to invalid conclusions, as well as examples where adjusting for a factor that is not a confounder also leads to invalid or imprecise conclusions. Careful consideration of which factors may act as confounders or modifiers of the association of interest is critical to conducting sound research, particularly with complex observational studies in reproductive medicine.

This study aims to (1) assess the associations between sugar-sweetened beverages (SSB) consumption and C-reactive protein (CRP) levels, and (2) evaluate the modifying effect of body mass index (BMI) on the association between SSB consumption and CRP levels. A total of 6856 eligible adults were selected from the 2007–2010 National Health and Nutrition Examination Survey (NHANES). Average quantity of SSB consumption was calculated from 2-day 24-h dietary recalls. All data analyses were performed with appropriate sampling weights. Compared with non-SSB drinkers, a 0.26 mg/l higher CRP was observed in heavy SSB drinkers after adjusting for demographic characteristics, lifestyle patterns, and BMI. An effect modification of BMI on SSB intake and CRP levels was detected (P

Background Male infants have a higher incidence of invasive group B Streptococcus disease (iGBS) compared with female infants; however, data on sex differences in mortality and long-term outcomes after iGBS are lacking. We assessed whether a child’s sex influences the effects of iGBS on mortality and risk of neurodevelopmental impairments (NDIs). Methods We used Danish and Dutch registry data to conduct a nationwide cohort study of infants with a history of iGBS. A comparison cohort, children without a history of iGBS, was randomly selected and matched on relevant factors. Effect modification by sex was assessed on additive and multiplicative scales. Results Our analyses included data from children with a history of iGBS in Denmark (period 1997 -2017; n = 1432) and the Netherlands (2000 -2017; n = 697) and from 21 172 children without iGBS. There was no clear evidence of between-sex heterogeneity in iGBS-associated mortality. Boys had a higher risk of NDI, with evidence for effect modification on additive scale at the age of 5 years for any NDI (relative excess risk due to interaction = 1.28; 95% confidence interval [CI], -0.53 to 3.09 in Denmark and 1.14; 95% CI, -5.13 to 7.41 in the Netherlands). A similar pattern was observed for moderate/severe NDI at age 5 years in Denmark and age 10 years in the Netherlands. Conclusion Boys are at higher risk of NDI ; our results suggest this is disproportionally increased in those who develop iGBS. Future studies should investigate mechanisms of this effect modification by sex.

Objective: To evaluate the associations between 10 well-established ovarian cancer risk factors and risk of ovarian cancer among women with vs. without endometriosis. Design: Pooled analysis of 9 case-control studies in the Ovarian Cancer Association Consortium. Setting: Population-based. Patient(s): We included 8,500 women with ovarian cancer, 13,592 control women. Intervention(s): Ten well-established ovarian cancer risk factors. Main Outcome Measure(s): Risk of ovarian cancer for women with and without endometriosis. Result(s): Most risk factor-ovarian cancer associations were similar when comparing women with and without endometriosis, and no interactions were statistically significant. However, body mass index (BMI) 25–2 was associated with increased ovarian cancer risk among women with endometriosis (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.00–1.60), but not associated with the risk among women without endometriosis (OR = 0.97; 95% CI, 0.91–1.05) when compared with BMI 18.5–2; an increased risk was observed for a BMI ≥30 kg/m2, although there was little difference comparing women with endometriosis (OR = 1.21; 95% CI, 0.94–1.57) to women without (OR = 1.13; 95% CI, 1.04–1.22) (P-interaction = .51). Genital talcum powder use and long-term menopausal estrogen-only therapy use showed increased ovarian cancer risk, but risk appeared greater for those with endometriosis vs. those without (genital talcum powder: OR = 1.38; 95% CI, 1.04–1.84 vs. OR = 1.12; 95% CI, 1.01–1.25, respectively; ≥10 years of estrogen-only therapy: OR = 1.88; 95% CI, 1.09–3.24 vs. OR = 1.42; 95% CI, 1.14–1.76, respectively); neither of these interactions were statistically significant (P-interaction = .65 and P-interaction = .96, respectively). Conclusion(s): The associations between ovarian cancer and most risk factors were similar among women with and without endometriosis. However, there was some suggestion of differences by endometriosis status for BMI, menopausal hormone therapy use, and genital talcum powder use, highlighting the complexity of ovarian cancer etiology.

Background Telomere length (TL) shortens during aging, HIV seroconversion, and untreated chronic HIV infection. It is unknown whether early antiretroviral therapy (ART) start is associated with less TL shortening during primary HIV infection (PHI). Methods We measured TL in peripheral blood mononuclear cells by quantitative polymerase chain reaction in participants of the Zurich PHI Study with samples available for ≥6 years. We obtained univariable/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL. Results In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the first (shortest), second, and third (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (P for trend = .034), and longer TL over 6 years, but only with continuous ART (P Conclusions In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening.

Exposure to traffic-related air pollution is linked with acute alterations in blood pressure (BP). We examined the cumulative short-term effect of black carbon (BC) exposure on systolic (SBP) and diastolic (DBP) BP and assessed effect modification by participant characteristics. SBP and DBP were repeatedly measured on 152 traffic enforcers. Using a linear mixed-effects model with random intercepts, quadratic (QCDL) and cubic (CCDL) constrained distributed lag models were fitted to estimate the cumulative effect of BC concentration on SBP and DBP during the 10 hours (daily exposure) and 7 days (weekly exposure) before the BP measurement. Ambient BC was related to increased BP with QCDL models. An interquartile range change in BC cumulative during the 7 days before the BP measurement was associated with increased BP (1.2% change in mean SBP, 95% confidence interval (CI), 0.1 to 2.3, and 0.5% change in mean DBP, 95% CI, −0.8 to 1.7). Moreover, the association between the 10-h cumulative BC exposure and SBP was stronger for female (4.0% change, 95% CI: 2.1–5.9) versus male and for obese (2.9% change, 95% CI: 1.0–4.8) vs. non-obese traffic enforcers. Short-term cumulative exposure to ambient traffic-related BC could bring about cardiovascular diseases through mechanisms involving increased BP.

Studies have investigated the associations of coffee and tea with mammographic breast density (MBD) in premenopausal women with inconsistent results. We analyzed data from 375 premenopausal women who attended a screening mammogram at Washington University School of Medicine, St. Louis, MO in 2016, and stratified the analyses by race (non-Hispanic White (NHW) vs. Black/African American). Participants self-reported the number of servings of coffee, caffeinated tea, and decaffeinated tea they consumed. Volpara software was used to determine volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV). We used generalized linear regression models to quantify the associations of coffee and tea intake with MBD measures. Coffee: ≥1 time/day (β = 1.06, 95% CI = 0.93–1.21, p-trend = 0.61) and caffeinated tea: ≥1 time/day (β = 1.01, 95% CI = 0.88–1.17, p-trend = 0.61) were not associated with VPD. Decaffeinated tea (≥1 time/week) was positively associated with VPD in NHW women (β = 1.22, 95% CI = 1.06–1.39) but not in African American women (β = 0.93, 95% CI = 0.73–1.17, p-interaction = 0.02). Coffee (≥1 time/day) was positively associated with DV in African American women (β = 1.52, 95% CI = 1.11–2.07) but not in NHW women (β = 1.10, 95% CI = 0.95–1.29, p-interaction = 0.02). Our findings do not support associations of coffee and caffeinated tea intake with VPD in premenopausal women. Positive associations of decaffeinated tea with VPD, with suggestions of effect modification by race, require confirmation in larger studies with diverse study populations.

In randomized controlled trials, investigators often explore the possibility that the treatment effects differ between subgroups (eg, women vs men, old vs young, more versus less severe disease). Investigators often inappropriately claim subgroup effects (also called “effect modification” or “interaction”) when the likelihood of a true effect modification is low. Criteria for assessing the credibility of subgroup analyses, nicely summarized in a formal Instrument for Assessing the Credibility of Effect Modification Analyses (ICEMAN), include investigator postulation of a priori hypotheses with a specified direction; support from prior evidence; a low likelihood that chance explains the apparent subgroup effect; and only testing a small number of subgroup hypotheses. Patient summary Randomized clinical trials often use subgroup analyses to explore whether a treatment is more or less effective in a particular patient subgroup (eg, women vs men, old vs young). In this mini-review, we explore the common pitfalls of subgroup analyses.

Task sharing is a strategy with potential to increase access to effective modern contraceptive methods. This study examines whether community health extension workers (CHEWs) can insert contraceptive implants to the same safety and quality standards as nurse/midwives. We analyze data from 7,691 clients of CHEWs and nurse/midwives who participated in a noninferiority study conducted in Kaduna and Ondo States, Nigeria. Adverse events (AEs) following implant insertions were compared. On the day of insertion AEs were similar among CHEW and nurse/midwife clients-0.5 percent and 0.4 percent, adjusted odds ratio (aOR) 0.92 (95 percent CI 0.38-2.23)-but noninferiority could not be established. At follow-up 6.6 percent of CHEW clients and 2.1 percent of nurse/midwife clients experienced AEs. There was strong evidence of effect modification by State. In the final adjusted model, odds of AEs for CHEW clients in Kaduna was 3.34 (95 percent CI 1.53-7.33) compared to nurse/midwife clients, and 0.72 (95 percent CI 0.19-2.72]) in Ondo. Noninferiority could not be established in either State. Implant expulsions were higher among CHEW clients (142/2987) compared to nurse/midwives (40/3517). Results show the feasibility of training CHEWs to deliver implants in remote rural settings but attention must be given to provider selection, training, supervision, and follow-up to ensure safety and quality of provision.

OBJECTIVES In some studies, parents and toddlers verbalize less when engaging with a tablet versus a print book. More needs to be known regarding child contributions to specific parent verbalizations. We examined parent-toddler contingent interactions with tablet applications versus print books, as well as moderators of these associations. METHODS We conducted a laboratory-based, within-subjects counterbalanced study of 72 parent-toddler dyads engaging with a nursery rhyme application (with enhanced + autonarration [E+A] and enhanced formats) and print book. We coded parent verbalizations (eg, dialogic, nondialogic) and proportions of child responses to these in 5-second epochs. Poisson regressions were used to analyze within-subjects variance by tablet or print format. We tested effect modification by child emotion regulation and home media practices. RESULTS Children responded more to parent overall (print 0.38; E+A 0.31, P = .04; enhanced 0.11, P = .01), dialogic (print 0.21; E+A 0.13, P = .04; enhanced 0.1, P = .02), and nondialogic (print 0.45; E+A 0.27, P < .001; enhanced 0.32, P < .001) verbalizations during print book versus tablet. Stronger child emotion regulation, greater frequency of co-viewing, and instructive practices moderated associations such that differences between conditions were no longer significant for some parent verbalizations and child responses. CONCLUSIONS Parent-toddler reciprocal verbal interactions occurred less frequently with tablet versus print book use. Child emotion regulation and parent home media practices moderated some of these associations. Pediatricians may wish to promote co-viewing and instructive media practices but may also consider that child emotion regulation may determine response to interactive tablet design.

Background The treatment effects on hospitalization for heart failure (hHF) from sodium-glucose cotransporter 2 (SGLT2) inhibitors may vary among type 2 diabetes (T2D) patients depending on whether or not they have established atherosclerotic cardiovascular diseases (ASCVD). We aimed to examine differences in hHF outcomes after dapagliflozin or empagliflozin use between T2D patients with and without a history of established ASCVD. Methods We conducted a retrospective multi-institutional cohort study in Taiwan. We included T2D patients newly receiving dapagliflozin or empagliflozin during 2016–2019, and followed them up until December 31, 2020. We implemented 1:1 propensity score matching to create homogenous groups for comparisons. We generated Cox proportional hazard models to compare the risk of hHF between dapagliflozin and empagliflozin (reference group). We included interaction terms of SGLT2 inhibitor and ASCVD history in the regression models to examine effect modification by ASCVD. Results We included a total cohort of 9,586 dapagliflozin new users and 9,586 matched empagliflozin new users. The overall hHF risks were similar for dapagliflozin and empagliflozin (HR: 0.90, 95% CI 0.74–1.09). However, differential hHF risks between dapagliflozin and empagliflozin were observed only in the subgroup without ASCVD (HR: 0.67, 95% CI 0.49–0.90), while not in the subgroup with ASCVD (HR: 1.12, 95% 0.87–1.45), and the p-value for examining interaction was 0.0097. Conclusion In this study, history of established ASCVD was associated with different hHF risks among SGLT2 inhibitors. For T2D patients without ASCVD, dapagliflozin may offer a more favorable hHF reduction effect, compared to empagliflozin, in clinical practice. Future prospective studies should be conducted to validate our findings.

BACKGROUND: Preterm birth (PTB) disproportionately affects African-American compared to Caucasian women, although reasons for this disparity remain unclear. Some suggest that a differential effect of maternal age by race/ethnicity, especially at older maternal ages, may explain disparities. OBJECTIVE: To determine whether the relationship between maternal age and preterm birth varies by race/ethnicity among primiparae non-Hispanic blacks (NHB) and non-Hispanic whites (NHW). METHODS: A cross-sectional study of 367,081 singleton live-born first births to NHB and NHW women in California from 2008–2012 was conducted. Rate ratios (RR) were estimated for PTB and its subtypes – spontaneous and clinician-initiated – after adjusting for confounders through Poisson regression. Universal age/race reference groups (NHW, 25–29 years) and race-specific reference groups (NHW or NHB, 25–29 years) were used for comparisons. RESULTS: Among all women, RR of PTB was highest at the extremes of age (

Purpose - Few studies investigated roles of body mass index (BMI) on gastric cancer (GC) risk according to Helicobacter pylori infection status. This study was conducted to evaluate associations between BMI and GC risk with consideration of H. pylori infection information. Materials and Methods - We performed a case-cohort study (n=2,458) that consists of a subcohort, (n=2,193 including 67 GC incident cases) randomly selected from the Korean Multicenter Cancer Cohort (KMCC) and 265 incident GC cases outside of the subcohort. H. pylori infection was assessed using an immunoblot assay. GC risk according to BMI was evaluated by calculating hazard ratios (HRs) and their 95% confidence intervals (95% CIs) using weighted Cox hazard regression model. Results - Increased GC risk in lower BMI group (< 23 kg/m2) with marginal significance, (HR, 1.32; 95% CI, 0.98 to 1.77) compared to the reference group (BMI of 23-24.9 kg/m2) was observed. In the H. pylori non-infection, both lower (< 23 kg/m2) and higher BMI (≥ 25 kg/m2) showed non-significantly increased GC risk (HR, 10.82; 95% CI, 1.25 to 93.60 and HR, 11.33; 95% CI, 1.13 to 113.66, respectively). However, these U-shaped associations between BMI and GC risk were not observed in the group who had ever been infected by H. pylori. Conclusion - This study suggests the U-shaped associations between BMI and GC risk, especially in subjects who had never been infected by H. pylori.

Background Little is known about the role of social class in the association between adiposity measures and self-rated health, and several studies have evaluated its influence as a confounder. The aim of the study is to investigate whether social class is an effect modifier in the association between adiposity measures and self-rated health in participants in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Method Cross-sectional design, including 6453 men and 7686 women. Body mass index (kg/m2) and waist circumference (cms) were assessed. Self-rated health was categorized as good, fair and poor. Socio-occupational class was based on the participants’ occupation, education and per capita income. Multicovariate ordinal logistic model was used to evaluate the association between adiposity measures and self-rated health. Results For women, the low and medium socio-occupational class effects were higher for those with waist circumference between 80 and 88 cm or overweight. For men, the low and medium socio-occupational class effects were higher for those with adequate waist circumference or normal body mass index. Conclusions Social class is an effect modifier in the association between body mass index or waist circumference and self-rated health.

Urinary concentrations of several endocrine disrupting chemicals, including phthalate metabolites, bisphenol A (BPA), and benzophenone (BP)-type ultraviolet (UV) filters, have been associated with a longer time-to-pregnancy (TTP). Potential modification of these associations by couple’s age has not been studied. TTP was defined as the number of prospectively observed menstrual cycles a couple attempted pregnancy until the occurrence of a human chorionic gonadotropic-detected pregnancy. Urinary concentrations of two BP-type UV filters and three phthalate metabolites were measured at baseline. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated for each chemical adjusting for age, body mass index, serum cotinine, creatinine, and accounting for right censoring and left truncation. Models evaluated effect modification between EDC concentrations and TTP by partner’s age, dichotomized at 35 years. Separate models were run for male and female partners. No significant effect modification was observed for any EDC for either partner, but data were suggestive of a longer TTP among females aged ≥35 years, particularly for BP-2 (FOR = 0.61, 95% CI 0.36, 1.05) and 4-hydroxybenzophenone (FOR = 0.71, 95% CI: 0.46, 1.09) reflecting 39% and 29% reductions in fecundability, respectively. We saw no evidence of effect modification by couples’ age on associations between TTP and urinary phthalate or BPA metabolite concentrations. Across the EDCs we examined, we found little evidence that age modifies TTP-exposure associations.

BACKGROUND AND OBJECTIVES: Genome Wide Association Studies (GWAS) have identified genetic polymorphisms associated with bronchodilator response (BDR), but it is unknown how these associations change across life stages. We examined the impact of genetic variants on BDR from childhood to adulthood in asthmatics to uncover potential effect modification by age. METHODS: We searched the National Human Genome Research Institute (NHGRI) catalog of published GWAS to obtain a list of genetic associations with BDR, and tested them for effect modification by age in 604 subjects from the Childhood Asthma Management Program (CAMP), a clinical trial with longitudinal measures of BDR (age range 5 to 30 years). We performed longitudinal analyses using linear mixed models and visualized longitudinal changes in BDR using generalized additive models with repeated measures, adjusting for treatment group, sex, and main effects of age and additive genotype. RESULTS: Increasing age was associated with decreased BDR (−0.24 % per year). Polymorphisms rs295137 near SPATS2L and rs2626393 near ASB3 demonstrated their strongest associations with BDR in early childhood through adolescence, with a large decrease in their magnitude of effect from adolescence onward. The effect estimate for % BDR associated with rs295137 genotype (Beta=1.3; 95% CI 0.6 to 2.1) was diminished by age (interaction term=−0.06, p=0.004). The effect estimate for rs2626393 (Beta=−0.92 (95% CI −1.7 to −0.2) was also modified by age (interaction term= 0.05, p = 0.0004). CONCLUSIONS: Polymorphisms associated with BDR in childhood may not be relevant for predicting adolescent and adult BDR, which could reflect age-related changes in asthma phenotypes. TRIAL REGISTRATION: This work uses data from the previous clinical trial of asthma, the Childhood Asthma Management Program (CAMP), registered at ClinicalTrials.gov, #

Objective: To explore factors associated with social discrimination against users of health services regarding dental aesthetic conditions.Methods: Based on a Brazilian National Survey, multivariate Poisson regressions with robust variance were used to explore the association of outcome discrimination related to different motivations in health services and exposure to sociodemographic and dental variables. Effect modification by complete prosthesis wearing was assessed.Results: Among the 60,200 people interviewed, 11.5% reported being discriminated against in health services. For women, a higher prevalence of discrimination was found among those in the age group of 30–44 years. For both sexes, discrimination was associated with black and brown skin color. Regarding dental characteristics, the higher the tooth loss was, the higher the prevalence of discrimination; however, complete prosthesis wearing presented as a protective factor. Social discrimination was the major motivation for reported discrimination and presented higher prevalence in edentulous individuals who did not wear prosthesis.Conclusion: Dental loss may lead to self-reported discrimination in health care services. The prevalence of discrimination increases when tooth loss increases, and the major reason associated is social discrimination.

Background: Treatment with sacubitril-valsartan reduces mortality and heart failure (HF) events in HF with reduced ejection fraction and may reduce HF hospitalization in women with HF with preserved ejection fraction. Methods: EVALUATE-HF randomized 464 participants (109 women) with HF with reduced ejection fraction to sacubitril-valsartan or enalapril for 12 weeks. Documented left ventricular ejection fraction (LVEF) ≤0.40 within the prior 12 months was required, although core laboratory LVEF>0.40 was permitted. Assessments of aortic stiffness (pulse pressure and characteristic impedance, Z c ) were performed at baseline and at trough and 4 hours postdose at weeks 4 and 12. Results: In models of change from baseline adjusted for baseline value, treatment with sacubitril-valsartan produced greater overall reductions in mean arterial pressure (treatment group difference, −3.0±0.8 mm Hg, P P c were greater in the sacubitril-valsartan group (−16±6 dyne×second/cm 5 , P =0.012). Post hoc analyses found evidence of effect modification by LVEF (interaction P =0.036). With LVEFc were greater in the sacubitril-valsartan group (trough, −3±8 dyne×second/cm 5 versus post-dose, −17±8 dyne×second/cm 5 ; interaction P =0.024) with no sex difference (treatment×sex interaction, P =0.3). With LVEF≥0.40, treatment with sacubitril-valsartan was associated with greater overall reductions in Z c in women (women, −80±21 dyne×second/cm 5 versus men, −20±13 dyne×second/cm 5 ; interaction P =0.019). Conclusions: In prespecified analyses that include pre- and postdose assessments at 4 and 12 weeks, treatment with sacubitril-valsartan was associated with greater postdose reductions in aortic Z c . In a post hoc analysis, sacubitril-valsartan was associated with sustained reductions in Z c in women with LVEF≥0.40. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT02874794.

BACKGROUND Few studies have evaluated the quality of plant-based diets in relation to chronic diseases, and the potential role of BMI is not clearly explored. OBJECTIVES To study the associations between plant-based diet indices and type 2 diabetes (T2D) and hypertension risks, as well as the extent to which the associations were modified and/or mediated by BMI. METHODS The study included 74,522 women from the Etude Epidemiologique aupres de femmes de la Mutuelle Generale de l'Education Nationale prospective cohort [mean (SD): age, 52.94 (6.7) years; BMI, 22.970 (3.328) kg/m2]. Dietary data were collected at baseline (1993) via an FFQ. Overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) were developed. Multivariable Cox regression models were used to derive HRs and 95% CIs. Effect modification and mediation by BMI were explored. RESULTS There were 3292 (4.64%) incident cases of T2D and 12,504 (27.14%) incident cases of hypertension over ∼20 years of follow-up. In the multivariable model further adjusted for BMI, higher adherence to PDI and hPDI was associated with lower T2D and hypertension risks, with an HR per 1-SD increase (95% CI) of 0.88 (0.85, 0.91) and 0.96 (0.94, 0.98) for PDI and 0.88 (0.85, 0.92) and 0.94 (0.92, 0.95) for hPDI, respectively. uPDI was not associated with T2D [0.98 (0.94, 1.01)], whereas a positive association was observed with hypertension: 1.04 (1.02, 1.06). There was interaction between PDI and uPDI, as well as BMI, on T2D (P-interaction 0.05). In addition, BMI mediated 26-59% and 0.2-59% of diet-T2D and diet-hypertension associations, respectively. CONCLUSIONS Differential associations between plant-based diets and T2D and hypertension risks were observed among women in this large prospective study. Only healthier plant foods were associated with lower risks, partly through decreasing BMI. The protocol was registered at clinicaltrials.gov as NCT03285230.

Background In the context of ongoing climate change, temperature variability (TV) has been considered as an important trigger of death. However, evidence of association between mortality and hourly temperature variability (HTV) is scarce at the multi-city level, and the time window of health effects of HTV is lack of investigation. This study aims at quantifying the mortality risk and burden of HTV and exploring subpopulations susceptible to HTV from a large-scale multi-city perspective. Methods Data on daily number of deaths and meteorology were collected for 31 Chinese major cities during 2007–2013. HTV was calculated as the standard deviation of hourly temperature within a few days. The optimal exposure period of HTV was chosen according to multiple scientific criteria. A quasi-Poisson regression combined with distributed lag nonlinear model was used to assess the city-specific HTV-mortality associations. Then, meta-analysis was further applied to pool city-specific effect estimates. Finally, we calculated the fraction of mortality attributable to HTV. Stratification analyses were conducted by individual characteristics (i.e. age, sex, and educational attainment), season, and region. Results HTV calculated in a relatively long-time window like 18 d (HTV0–17) could capture the impact of HTV adequately. Per 1 °C raise of HTV0–17 associated with 1.38% (95%CI: 0.77, 1.99) increase of non-accidental mortality. During the study period, 5.47% (95%CI: 1.06, 9.64) of non-accidental mortality could be attributed to HTV. The females, the elderly, and individuals with low education level were more susceptible to HTV than their counterparts, respectively. Moreover, a stronger HTV-mortality association was observed in individuals who live in warmer season and temperature zone. Conclusion HTV is associated with a considerable mortality burden, which may be modified by season, geographic and individual-level factors. Our findings highlight the practical importance of establishing early warning systems and promoting health education to mitigate the impacts of temperature variability.

Objectives To determine the sex-specific associations of handgrip strength (HGS) and asymmetry with incident multimorbidity and examine whether these relationships differ by sex. Design Prospective cohort study. Setting and Participants Secondary analyses of data from the English Longitudinal Study of Ageing (ELSA, waves 2-8). The analytic sample included 3977 participants (51.4% female) aged ≥50 years who had data for HGS on both hands and were living without multimorbidity at baseline. Measures HGS was assessed with a handheld dynamometer. Individuals in the lowest tertile of sex-specific age-adjusted HGS were defined as having low HGS. The largest HGS readings from the nondominant and dominant hand were used to calculate HGS ratio [nondominant HGS (kg)/dominant HGS (kg)]. Those with HGS ratio 1.10 had any HGS asymmetry. Further, those with HGS ratio 1.10 had nondominant HGS asymmetry. Multimorbidity was defined as the coexistence of ≥2 chronic diseases. Cox proportional hazards regression models were conducted for analyses. Results Low HGS was associated with multimorbidity among older men [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.03-1.40] and women (HR 1.19, 95% CI 1.03-1.38). No significant effect modification by sex was observed (P-interaction = .71). HGS asymmetry increased the risk of multimorbidity in women only (HR 1.23, 95% CI 1.07-1.41). The relationship between HGS asymmetry and multimorbidity risk differed by sex (P-interaction = .01). Similarly, both dominant HGS asymmetry (HR 1.21, 95% CI 1.05-1.40) and nondominant HGS asymmetry (HR 1.32, 95% CI 1.03-1.68) were related to incident multimorbidity in women only. There was a significant interaction between dominant HGS asymmetry and sex (P-interaction = .02). Conclusions and Implications Examining HGS asymmetry in HGS test protocols can provide novel insights for the predictive power of HGS in the accumulation of diseases, particularly in women.

Background Excessive fluoride exposure is related to adverse health outcomes, but whether dopamine (DA) relative genes are involved in the health effect of low-moderate fluoride exposure on children’s intelligence remain unclear. Objectives We conducted a cross-sectional study to explore the role of DA relative genes in the health effect of low-moderate fluoride exposure in drinking water. Methods We recruited 567 resident children, aged 6–11 years old, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. Spot urine samples were tested for urinary fluoride concentration, combined Raven`s test was used for intelligence quotient test. Fasting venous blood were collected to analyze ANKK1 Taq1A (rs1800497), COMT Val158Met (rs4680), DAT1 40 bp VNTR and MAOA uVNTR. Multivariable linear regression models were used to assess associations between fluoride exposure and IQ scores. We applied multiplicative and additive models to appraise single gene-environment interaction. Generalized multifactor dimensionality reduction (GMDR) was used to evaluate high-dimensional interactions of gene-gene and gene-environment. Results In adjusted model, fluoride exposure was inversely associated with IQ scores (β = −5.957, 95% CI: −9.712, −2.202). The mean IQ scores of children with high-activity MAOA genotype was significantly lower than IQ scores of those with low-activity (P = 0.006) or female heterozygote (P = 0.016) genotype. We detected effect modification by four DA relative genes (ANKK1, COMT, DAT1 and MAOA) on the association between UF and IQ scores. We also found a high-dimensional gene-environment interaction among UF, ANKK1, COMT and MAOA on the effect of IQ (testing balanced accuracy = 0.5302, CV consistency: 10/10, P = 0.0107). Conclusions Our study suggests DA relative genes may modify the association between fluoride and intelligence, and a potential interaction among fluoride exposure and DA relative genes on IQ.

Background Although there are several human experimental studies on short-term effects of radiofrequency electromagnetic fields (RF-EMF) on sleep, the role of effect modification by sex or age in this context has not yet been considered. In an earlier study, we observed sex differences in RF-EMF effects in elderly subjects. The present study investigated possible RF-EMF effect modifications by age in men. Methods Data available for the present analysis come from three double-blind, randomized cross-over studies, in which effects of different RF-EMF exposure signals on sleep were investigated in young [sample 1: 25.3 (mean) ± 2.6 (SD) years; sample 2: 25.4 ± 2.6 years; n = 30, respectively] and older (69.1 ± 5.5 years; n = 30) healthy male volunteers. Studies comprised a screening/adaptation night followed by nine experimental nights at two-week intervals. RF-EMF exposure effect modifications by age were analysed for two different exposure signals (GSM900 at 2 W/kg, TETRA at 6 W/kg), each compared to a sham exposure. Polysomnography, during which the exposure signals were delivered by a head worn antenna, as well as sleep staging were performed according to the AASM standard. Four subjective and 30 objective sleep parameters were statistically analysed related to possible RF-EMF effects. Results Comparisons of sleep parameters observed under sham exposure revealed highly pronounced physiological differences between young and elderly men. A consistent exposure effect in both age groups was found for a shorter latency to persistent sleep under TETRA exposure reflecting a sleep-promoting effect. Exposure effect modifications by age were observed for two of the four self-reported sleep parameters following GSM900 exposure and for arousals during REM sleep under TETRA exposure. Conclusions As effects of a short-term all-night RF-EMF exposure on sleep occurred only sporadically in young and elderly men, it seems that age doesn't matter in this respect. However, as long as there are no corresponding data from young healthy women that would allow a comparison with the data from elderly women, this assumption cannot be conclusively verified. Nevertheless, the present results are not indicative of any adverse health effects.

Objectives This study investigated the modification of temperature effects on cardiovascular and respiratory mortality by air pollutants (particulate matter less than 2.5 and 10 µm in diameter [respectively], ozone, nitrogen dioxide, carbon monoxide, and sulfur dioxide). Methods Poisson additive models with a penalized distributed lag non-linear model were used to assess the association of air temperature with the daily number of deaths from cardiovascular and respiratory diseases in Ahvaz, Iran from March 21, 2014 to March 20, 2018, controlling for day of the week, holidays, relative humidity, wind speed, air pollutants, and seasonal and long-term trends. Subgroup analyses were conducted to evaluate the effect modification for sex and age group. To assess the modification of air pollutants on temperature effects, the level of each pollutant was categorized as either greater than the median value or less than/equal to the median value. Results We found no significant associations between temperature and cardiovascular and respiratory mortality. In the subgroup analyses, however, high temperatures were significantly associated with an increased risk of cardiovascular mortality among those 75 years old and older, with the strongest effect observed on day 0 relative to exposure. The results revealed a lack of interactive effects between temperature and air pollutants on cardiovascular and respiratory mortality. Conclusions A weak but significant association was found between high temperature and cardiovascular mortality, but only in elderly people. Air pollution did not significantly modify the effect of ambient temperature on cardiovascular and respiratory mortality.

Objectives This study determined the prospective relation between physical workload and long-term sickness absence (LTSA) and examined if work-unit social capital may buffer the effect of high physical workload on LTSA. Methods We included 28 925 participants from the Danish Well-being in HospitAL Employees (WHALE) cohort, and followed them for two years. Physical workload and social capital were self-reported and categorized into low, medium, and high. Physical workload was analyzed on the individual level, whereas social capital was analyzed on the work-unit level. LTSA data were obtained from the employers' payroll system. We performed two-level logistic regression analyses: joint-effect and stratified analyses adjusted for baseline covariates. Results High versus low physical workload was associated with a higher risk of LTSA [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.40-1.72]. There was a multiplicative interaction (P=0.007) and a tendency of sub-additive interaction [relative excess risk due to interaction (RERI) -0.49, 95% CI -1.03-0.06] between physical workload and social capital. Doubly exposed employees had the highest risk of LTSA (OR 2.45; 95% CI 2.02-2.98), but this effect was smaller than expected from the sum of their main effects. Conclusions We found a prospective relation between physical workload and LTSA but no evidence of high social capital buffering the effect of high physical workload. High physical workload was a risk factor for LTSA at all levels of social capital and employees exposed to both exposures had the highest risk of LTSA. Interventions should aim at both improving social capital and reducing physical workload in order to efficiently prevent LTSA.

Background Previous studies show a positive association between household wealth and overweight in sub-Saharan African (SSA) countries; however, the manner in which this relationship differs in the presence of educational attainment has not been well-established. This study examined the multiplicative effect modification of educational attainment on the association between middle-income and rich household wealth and overweight status among adult females in 22 SSA countries. We hypothesized that household wealth was associated with a greater likelihood of being overweight among middle income and rich women with lower levels of educational attainment compared to those with higher levels of educational attainment. Methods Demographic and Health Survey (DHS) data from 2006 to 2016 for women aged 18–49 years in SSA countries were used for the study. Overweight was defined as a body mass index (BMI) ≥ 25 kg/m2. Household wealth index tertile was the exposure and educational attainment, the effect modifier. Potential confounders included age, ethnicity, place of residence, and parity. Descriptive analysis was conducted, and separate logistic regression models were fitted for each of the 22 SSA countries to compute measures of effect modification and 95% confidence intervals. Analysis of credibility (AnCred) methods were applied to assess the intrinsic credibility of the study findings and guide statistical inference. Results The prevalence of overweight ranged from 12.6% in Chad to 56.6% in Swaziland. Eighteen of the 22 SSA countries had measures of effect modification below one in at least one wealth tertile. This included eight of the 12 low-income countries and all 10 middle income countries. This implied that the odds of overweight were greater among middle-income and rich women with lower levels of educational attainment than those with higher educational attainment. On the basis of the AnCred analysis, it was found that the majority of the study findings across the region provided some support for the study hypothesis. Conclusions Women in higher wealth strata and with lower levels of educational attainment appear to be more vulnerable to overweight compared to those in the same wealth strata but with higher levels of educational attainment in most low- and middle- income SSA countries.

Objectives Diurnal temperature range (DTR) is an important indicator of global climate change. Many epidemiological studies have reported the associations between high DTR and human health. This study investigated the association between DTR and hospitalisations for ischaemic stroke in Hefei, China. Study design This is an ecological study. Methods Data of daily hospital admissions for ischaemic stroke and meteorological variables from 1 January 2009 to 31 December 2017 were collected in Hefei, China. A generalised additive model combined with distributed lag non-linear model was used to quantify the effects of DTR on ischaemic stroke. The interactive effect between DTR and temperature was explored with a non-parametric bivariate response surface model. Results High DTR was associated with hospitalisations for ischaemic stroke. The adverse effect of extremely high DTR (99th percentile [17.1 °C]) occurred after 8 days (relative risk [RR] = 1.021, 95% confidence interval [CI] = 1.002, 1.041) and the maximum effect appeared after 12 days (RR = 1.029, 95% CI = 1.011, 1.046). The overall trend of the effect of DTR on ischaemic stroke was decreasing. In addition, there was a significant interactive effect of high DTR and low temperature on ischaemic stroke. Conclusions This study suggests that the impact of high DTR should be considered when formulating targeted measures to prevent ischaemic stroke, especially for those days with high DTR and low mean temperature.

IntroductionPrevious studies have identified a positive association between the inflammatory potential of the diet and hypertension. It is not known if BMI is an effect modifier for this association, nor if the association is dose-respondent. This study aimed to assess the association between the dietary inflammatory index (DII) and the risk of hypertension, and assess any effect modification from BMI.MethodsData from the E3N cohort study, a French prospective population-based study initiated in 1990 was used. From the women in the study, we included those who completed a detailed diet history questionnaire, and who did not have prevalent hypertension or cardiovascular disease at baseline, resulting in 46,652 women. The adapted DII was assessed with data from the dietary questionnaire. Hypertension cases were self-reported and verified through a drug-reimbursement database. Cox proportional hazard models were used to calculate hazard ratios. Spline regression was used to determine any dose-respondent relationship.ResultsDuring 884,267 person-years, 13,183 cases of incident hypertension were identified. The median DII in the population was slightly pro-inflammatory (DII = + 0.44). A highly pro-inflammatory diet (DII > 3.0) was associated with a slight increase in hypertension risk (HRQ1-Q5 = 1.07 [1.02, 1.13]). Evidence was observed for effect modification from BMI, with associations strongest amongst women in the 18.5–21.0 BMI range (HRQ1-Q5 = 1.17 [1.06, 1.29]). A weak dose-respondent relationship was observed.ConclusionEvidence for a weak association between DII and hypertension was observed. Associations were stronger amongst healthy-lean women.

Neighborhood demographic polarization, or the extent to which a privileged population group outnumbers a deprived group, can affect health by influencing social dynamics. While using birth records from 2001 to 2013 in Massachusetts (n = 629,675), we estimated the effect of two demographic indices, racial residential polarization (RRP) and economic residential polarization (ERP), on birth weight outcomes, which are established predictors of the newborn&rsquo, s future morbidity and mortality risk. Higher RRP and ERP was each associated with higher continuous birth weight and lower odds for low birth weight and small for gestational age, with evidence for effect modification by maternal race. On average, per interquartile range increase in RRP, the birth weight was 10.0 g (95% confidence interval: 8.0, 12.0) higher among babies born to white mothers versus 6.9 g (95% CI: 4.8, 9.0) higher among those born to black mothers. For ERP, it was 18.6 g (95% CI: 15.7, 21.5) higher among those that were born to white mothers versus 1.8 g (95% CI: &minus, 4.2, 7.8) higher among those born to black mothers. Racial and economic polarization towards more privileged groups was associated with healthier birth weight outcomes, with greater estimated effects in babies that were born to white mothers than those born to black mothers.