Dose-response Manner Research Articles

Association of longitudinal trajectories of general and abdominal adiposity during middle age with mental health and well-being in late life: A prospective analysis

Single measures of adiposity markers, such as body mass index (BMI) and waist circumference (WC), are associated with adverse mental health outcomes; however, long-term patterns of adiposity and their health effects remain unclear. The current study assessed adiposity trajectories during a 14-year span beyond middle age and their relevance to mental well-being in late life, and the contribution of genetic and lifestyle factors to the trajectories. Based on a nationally representative sample with longitudinal anthropometric measures, adiposity trajectories were identified by latent mixture modeling, and logistic regression model was used to estimate their associations with mental well-being, with adjustment for confounders. Of the 3491 eligible participants included (mean [SD] age, 69.5 [8.9] years), five discrete BMI and four WC trajectory patterns were identified over 14 years. Compared with the low-stable BMI group (range, 22.8 to 22.9 kg/m²; representing stable healthy body weight), the high-stable group (range, 34.3 to 35.4 kg/m²; stable obese) was associated with increased risk of depression (odds ratio [OR], 1.63; 95 % CI, 1.28–2.07) and low subjective well-being (OR, 1.35; 95 % CI, 1.02–1.79). Compared with the low-stable WC group (range, 75 to 79 cm healthy WC), the high-increasing group (range, 114 to 121 cm) was associated with increased risk of depression (odds ratio [OR], 1.64; 95 % CI, 1.19–2.25) and low well-being (OR, 1.48; 95 % CI, 1.01–2.16). The adiposity trajectories, especially the high-stable/increasing groups, were driven by genetic factors in a dose-response manner, whereas the high/moderate-increasing groups were also behaviorally related. This longitudinal cohort study reveals that stably high trajectory patterns of central and general adiposity during middle age were associated with higher risk of depression and low well-being in late life. The findings indicate the importance of weight management beyond middle age, such as adherence to a healthy lifestyle, in promoting mental health and well-being.

A novel body composition risk score (B-Score) and overall survival among patients with nonmetastatic breast cancer

Measurements (amount, distribution, and radiodensity) of muscle and adipose tissue were reported to be individually associated with overall survival in patients with breast cancer. However, they were not typically combined to develop an overall risk score, which can identify patients at high risk of death and prioritize patients in need of dietary and lifestyle interventions. Thus, we aimed to develop a novel composite body composition risk score (B-Score). We included 3105 patients with stage II or III breast cancer at Kaiser Permanente Northern California and Dana Farber Cancer Institute. From CT scans at diagnosis, we assessed areas and radiodensity of muscle and adipose tissue at the third lumber vertebrae. We considered skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI) and SAT radiodensity as they were independent prognostic factors for overall survival. Each measurement was dichotomized using optimal stratification, with low SMI (<40.1cm2/m2), high SATI (≥75.7cm2/m2), and high SAT radiodensity (≥-97.2HU) considered risk factors. We calculated B-Score as the sum of these factors and estimated its association with overall survival using Cox proportional hazards regression with adjustment for clinicopathologic factors. Mean (standard deviation) age was 53.9 (11.8) years, 70.3% were Non-Hispanic White, and 60.5% were stage II. Most patients (60.6%) had only one body composition risk factor (B-Score=1). Compared to those with no risk factors (B-Score=0), the risk of death increased with more body composition risk factors: the adjusted hazard ratios were 1.10 (95% CI: 0.85, 1.42), 1.47 (95% CI: 1.12, 1.92), and 2.11 (95% CI: 1.26, 3.53) for B-Scores of 1, 2, and 3, respectively (Ptrend < 0.001). More unfavorable body composition characteristics were associated with increased risks of overall mortality in a dose-response manner. Considering body composition measurements together as a composite score (B-Score) may improve risk stratification and inform dietary and lifestyle interventions following breast cancer diagnosis.

Association between person-centred care quality and advance care planning participation in haemodialysis

ObjectivePerson-centred care (PCC), which incorporates patients’ preferences and values for medical care and their life, has been proposed in decision-making for promoting advance care planning (ACP) among patients with kidney...

Greater Frequency of Cooking Dinner at Home and More Time Spent Cooking Are Inversely Associated With Ultra-Processed Food Consumption Among US Adults

BackgroundCooking at home has been promoted as a strategy to improve diet quality; however, the association between cooking behavior and ultra-processed food intake is unknown. ObjectiveThe objective of this study was to examine associations between frequency of cooking dinner at home and time spent cooking dinner with ultra-processed food intake. DesignCross-sectional, nationally representative data from the 2007-2010 National Health and Nutrition Examination Survey were analyzed. Participants/settingParticipants were 9,491 adults (20 years and older) in the United States. Main outcome measuresThe main outcome measure was the proportion of energy intake (averaged from two 24-hour dietary recalls) from the following 4 Nova food-processing groups: (1) unprocessed or minimally processed foods, (2) processed culinary ingredients, (3) processed foods, and (4) ultra-processed foods. Statistical analyses performedSeparate linear regression models examined associations between cooking frequency and time spent cooking dinner and proportion of energy intake from the 4 Nova food-processing groups, adjusting for sociodemographic characteristics and total energy intake. ResultsUltra-processed foods comprised >50% of energy consumed independent of cooking frequency or time spent cooking. Higher household frequency of cooking dinner and greater time spent cooking dinner were both associated with lower intake of ultra-processed foods (P trends < .001) and higher intake of unprocessed or minimally processed foods (P trends < .001) in a dose–response manner. Compared with cooking 0 to 2 times/wk, adults who cooked dinner 7 times/wk consumed a mean of 6.30% (95% CI –7.96% to –4.64%; P < .001) less energy from ultra-processed foods. Adults who spent more than 90 minutes cooking dinner consumed 4.28% less energy from ultra-processed foods (95% CI –6.08% to –2.49%; P < .001) compared with those who spent 0 to 45 minutes cooking dinner. ConclusionsCooking at home is associated with lower consumption of ultra-processed foods and higher consumption of unprocessed or minimally processed foods. However, ultra-processed food intake is high among US adults regardless of cooking frequency.

Personal and work-related burnout is associated with increased episodes of suicidal ideation or behavior among working adults in Chile

Burnout has been previously associated with suicidal risk factors and suicide itself, but these associations have only focused on work-related burnout among high-demand occupations. We aimed at examining the extent to which personal and/or work-related burnout are associated with suicidal ideation or behavior among working adults in Chile. We conducted a cross-sectional study among 1,970 working adults attending the Hospital del Trabajador in Santiago, Chile, between September 2015 and February 2018, using structured interviews. The Copenhagen Burnout Inventory (CBI) assessed levels of personal and work-related burnout (mild, moderate, and high-to-severe), and the Columbia Suicidal Rating Scale (C-SSRS) measured suicidal ideation or behavior. Multivariable logistic regression models were fit to estimate the magnitude of the association between burnout with suicidal ideation or behavior. After adjusting for putative confounders, moderate and high-to-severe personal burnout were associated with 5.07-fold (95% confidence interval (Al-Halabí et al.): 3.56–7.26) and 10.26-fold (95% CI: 5.75–18.50) increased odds of suicidal ideation or behavior, and high-to-severe work-related burnout associated with 2.47-fold increased odds (95% CI: 1.31–4.68). The dose-response pattern was shown in the association between both types of burnout and suicidal ideation or behavior (p for trend <0.05). Personal and work-related burnout were associated with increased odds of suicidal ideation or behavior in a dose-response manner. Focusing on alleviating burnout levels through mental health services or social support may effectively decrease the prevalence of suicidal ideation or behavior among working adults.

The NMDA receptor modulator zelquistinel durably relieves behavioral deficits in three mouse models of autism spectrum disorder

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by deficient social communication and interaction together with restricted, stereotyped behaviors. Currently approved treatments relieve comorbidities rather than core symptoms. Since excitation/inhibition balance and synaptic plasticity are disrupted in ASD, molecules targeting excitatory synaptic transmission appear as highly promising candidates to treat this pathology. Among glutamatergic receptors, the NMDA receptor has received particular attention through the last decade to develop novel allosteric modulators. Here, we show that positive NMDA receptor modulation by zelquistinel, a spirocyclic β-lactam platform chemical, relieves core symptoms in two genetic and one environmental mouse models of ASD. A single oral dose of zelquistinel rescued, in a dose-response manner, social deficits and stereotypic behavior in Shank3Δex13-16−/− mice while chronic intraperitoneal administration promoted a long-lasting relief of such autistic-like features in these mice. Subchronic oral mid-dose zelquistinel treatment demonstrated durable effects in Shank3Δex13-16−/−, Fmr1−/− and in utero valproate-exposed mice. Carry-over effects were best maintained in the Fmr1 null mouse model, with social parameters being still fully recovered two weeks after treatment withdrawal. Among recently developed NMDA receptor subunit modulators, zelquistinel displays a promising therapeutic potential to relieve core symptoms in ASD patients, with oral bioavailability and long-lasting effects boding well for clinical applications. Efficacy in three mouse models with different etiologies supports high translational value. Further, this compound represents an innovative pharmacological tool to investigate plasticity mechanisms underlying behavioral deficits in animal models of ASD.

The effect of caraway oil-loaded bio-nanoemulsions on the growth and performance of barnyard grass and maize

A proper formulation is crucial to improve the herbicidal effects of essential oils and their selectivity. In this study, we investigated the physicochemical properties of bio-based nanoemulsions (CNs) containing several concentrations of caraway (Carum carvi) essential oil stabilized with Eco Tween 80, as a surfactant, maintaining 1:1 proportions. Detailed physicochemical characteristics of the CNs revealed that their properties were most desired at 2% of the oil and surfactant, i.e., the smallest droplet size, polydispersity index, and viscosity. The CNs caused biochemical changes in maize and barnyard grass (Echinochloa crus-galli) seedlings, however, to a different extent. Barnyard grass has overall metabolism (measured as a thermal power) decreased by 39–82% when exposed to the CNs. The CNs triggered changes in the content and composition of carbohydrates in the endosperm of both species' seedlings in a dose–response manner. The foliar application of CNs caused significant damage to tissues of young maize and barnyard grass plants. The effective dose of the CN (ED50, causing a 50% damage) was 5% and 17.5% oil in CN for barnyard grass and maize tissues, respectively. Spraying CNs also decreased relative water content in leaves and affected the efficiency of photosynthesis by disturbing the electron transport chain. We found that barnyard grass was significantly more susceptible to the foliar application of CNs than maize, which could be used to selectively control this species in maize crops. However, further studies are needed to verify this hypothesis under field conditions.

Association of white matter hyperintensities with BMD, incident fractures, and falls in the UK Biobank cohort.

Osteoporosis is the most common metabolic bone disease globally, which increases the healthcare service burden. Recent studies have linked higher white matter hyperintensities (WMH) to reduced BMD, increasing the risk of fractures and falls in older adults. However, limited evidence exists regarding the dose-response relationship between WMH and bone health in a larger and younger population. Our study aimed to examine the association of WMH volume with BMD, incident fractures and falls, focusing on dose-response relationship with varying levels of WMH volume. We included 26 410 participants from the UK Biobank. The association between WMH volume and BMD was analyzed using multiple linear regression. Cox regression models were used to estimate the hazard ratios of incident fractures and falls. Restricted cubic spline (RCS) fitted for linear and Cox regression models were employed to explore potential non-linearity. Over a mean follow-up time of 3.8yr, we documented 59 hip fractures, 392 all fractures, and 375 fall incidents. When applying RCS, L-shaped relationships were identified between WMH volume and BMD across all 4 sites. Compared with those in the lowest fifth of WMH volume, individuals in the second to the highest fifths were associated with a reduction of 0.0102-0.0305g/cm2 in femur neck BMD, 0.0075-0.0273g/cm2 in femur troch BMD, 0.0173-0.0345g/cm2 in LS BMD, and 0.0141-0.0339g/cm2 in total body BMD. The association was more pronounced among women and younger participants under age 65 (Pinteraction < .05). Per 1 SD increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. Genetically determined WMH or apolipoprotein E genotypes did not modify these associations. We demonstrated that a greater WMH was associated with BMD in an L-shaped dose-response manner, especially in women and those under 65yr.

Cardiorespiratory fitness and risk of heart failure with preserved ejection fraction.

Preventive strategies for heart failure with preserved ejection fraction (HFpEF) include pharmacotherapies and lifestyle modifications. However, the association between cardiorespiratory fitness (CRF) assessed objectively by a standardized exercise treadmill test (ETT) and the risk of HFpEF has not been evaluated. Thus, we evaluated the association between CRF and HFpEF incidence. We assessed CRF in US Veterans (624 551 men; mean age 61.2 ± 9.7 years and 43 179 women; mean age 55.0 ± 8.9 years) by a standardized ETT performed between 1999 and 2020 across US Veterans Affairs Medical Centers. All had no evidence of heart failure or myocardial infarction prior to completion of the ETT. We assigned participants to one of five age- and gender-specific CRF categories (quintiles) based on peak metabolic equivalents (METs) achieved during the ETT and four categories based on CRF changes in those with two ETT evaluations (n = 139 434) ≥1.0 year apart. During a median follow-up of 10.1 years (interquartile range 6.0-14.3 years), providing 6 879 229 person-years, there were 16 493 HFpEF events with an average annual rate of 2.4 events per 1000 person-years. The adjusted risk of HFpEF decreased across CRF categories as CRF increased, independent of comorbidities. For fit individuals (≥10.5 METs) the hazard ratio (HR) was 0.48 (95% confidence interval [CI] 0.46-0.51) compared with least fit (≤4.9 METs; referent). Being unfit carried the highest risk (HR 2.88, 95% CI 2.67-3.11) of any other comorbidity. The risk of unfit individuals who became fit was 37% lower (HR 0.63, 95% CI 0.57-0.71), compared to those who remained unfit. Higher CRF levels are independently associated with lower HFpEF in a dose-response manner. Changes in CRF reflected proportional changes in HFpEF risk, suggesting that the HFpEF risk was modulated by CRF.

Association between alcohol consumption and latent fasting blood glucose trajectories among midlife women.

This investigation sought to elucidate the correlations between alcohol intake and trajectories of fasting blood glucose (FBG) among American women in midlife. Our analysis was rooted in the foundational data from the Study of Women's Health Across the Nation (SWAN), a comprehensive longitudinal study centered on US women during their midlife transition. We employed group-based trajectory modeling to chart the FBG trajectories spanning from 1996 to 2005. Employing logistic regression, we gauged the odds ratios (ORs) and 95% confidence intervals (CIs) to draw connections between initial alcohol consumption and FBG trajectory patterns, whilst controlling for predominant potential confounders. Our cohort comprised 2,578 women in midlife, ranging in age from 42 to 52, each having a minimum of three subsequent FPG assessments. We discerned two distinct FBG trajectories: a low-stable pattern (n = 2,467) and a high-decreasing pattern (n = 111). Contrasted with the low-stable group, our data showcased an inverse relationship between alcohol intake and the high-decreasing FBG trajectory in the fully adjusted model 3. The most pronounced reduction was evident in the highest tertile of daily servings of alcoholic beverages (OR: 0.23, 95% CI: 0.10-0.52, p < 0.001), percentage of kilocalories sourced from alcoholic beverages (OR: 0.30, 95% CI: 0.16-0.58, p < 0.001), and daily caloric intake from alcoholic beverages (OR: 0.31, 95% CI: 0.16-0.62, p < 0.001). Moderate alcohol consumption may protect against high FPG trajectories in middle-aged women in a dose-response manner. Further researches are needed to investigate this causality in midlife women.

P131 Therapeutic effects of KPG-818 in a trinitrobenzene sulfonic acid - induced mouse Crohn's/Ulcerative Colitis model

Abstract Background Immunomodulatory drugs have the potential therapeutic benefit not only in malignancy but also in diseases characterized by an inflammatory phenotype. In inflammatory bowel diseases (IBD), colonic inflammation results from dysregulation of the mucosal immune responses to intestinal flora together with genetic and environmental factors. Inflammatory cytokines are implicated in pathogenesis of IBD. Treatments for IBD that improve clinical outcomes and limit adverse effects are needed. KPG-818 is a novel generation of lenalidomide derivative and small molecule immunomodulatory drug. KPG-818 is currently under clinical development for therapy of multiple myeloma, lymphoma (phase 1), and systemic lupus erythematosus (SLE) (phase 2a). Remarkable immunomodulatory effects of KPG-818 are observed in SLE patients. In preclinical studies, KPG-818 significantly inhibits inflammatory cytokines interleukin-6 and TNF-α in human peripheral blood mononuclear cells, inhibits tumor growth in multiple myeloma and lymphoma xenograft tumor models. Here we report the significant therapeutic effects of KPG-818 in a chronic Crohn’s/ulcerative colitis mouse model. Methods Trinitrobenzene Sulfonic Acid (TNBS) was intra-colonially administered to induce Balb/c mouse Crohn’s/ulcerative colitis model at 50 mg/kg, once a week for 4 weeks. KPG-818 was orally administered at doses of 0.03, 0.12, 0.4, and 1.0 mg/kg, once a day for 6 consecutive weeks. Upadacitinib served as a positive control drug. Vehicle solution served as a negative control. To evaluate the therapeutic effects of the KPG-818, disease activity index (DAI) of ulcerative colitis, the degree of weight loss, fecal morphology, and rectal bleeding were scored once every other day for six consecutive weeks. At the end of the study, colonic samples were collected for gross observation and scoring of macroscopic damage, measurement of length and weight, and histopathological diagnosis and scoring. At the end of study, peripheral blood samples were also collected for analyses of immune cells and cytokines. Results Compared to the vehicle control, KPG-818 significantly improved the body weight loss, disease activity of ulcerative colitis, gross degree of colorectal injury, pathological lesions of colorectal tissue, inhibited the inflammatory cytokines in a dose-response manner. The effective dose was as low as 0.03 mg/kg. KPG-818 showed similar therapeutic effects to Upadacitinib. Conclusion In this mouse model of chronic Crohn’s/ulcerative colitis, KPG-818 showed remarkable therapeutic effects in a dose-dependent manner. These data encourage the clinical evaluation of KPG-818 in inflammatory bowel diseases.

Dose-response Associations of Physical Activity and Sitting Time With All-cause Mortality in Older Japanese Adults.

Although examining the dose-response curves of physical activity (PA) and sitting time with health-related outcomes is an important research agenda, the results for older Japanese adults are extremely limited. We examined the dose-response associations of PA and sitting time with all-cause mortality among older Japanese. Initially, 8,069 non-disabled residents (4,073 men; 3,996 women) aged 65-84 years of Ota City, Japan, were analyzed. Moderate-to-vigorous PA (MVPA) and sitting time were evaluated using the International Physical Activity Questionnaire-Short Form. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA and sitting time for all-cause mortality were calculated, and the dose-response curves were examined using restricted cubic splines (RCS). During 4.1 years of follow-up, 458 participants (5.7%; 331 men and 127 women) died. Compared with the low MVPA (<600 metabolic equivalents [METs]·minutes/week) group, HR for mortality gradually reduced in moderate (600-3,000 METs·minutes/week) and high (>3,000 METs·minutes/week) MVPA groups (moderate: HR 0.66; 95% CI, 0.54-0.82; high: HR 0.58; 95% CI, 0.45-0.75; P < 0.001 for trend). RCS showed that the HR for mortality reduced linearly up to approximately 2,000 METs·minutes/week of MVPA, and maximal risk reduction was seen at approximately 3,000-4,500 METs·minutes/week of MVPA. No significant dose-response association of sitting time with mortality was observed. Higher MVPA levels reduced all-cause mortality risk, in a significant inverse non-linear dose-response manner. Sitting time was not significantly associated with all-cause mortality. It is important to disseminate the significance of even a slight increase in the MVPA for reducing mortality risk.

Association of remnant cholesterol with decreased kidney function or albuminuria: a population-based study in the U.S.

BackgroundDyslipidemia is frequently exhibited in individuals with chronic kidney disease (CKD). Remnant cholesterol (RC), an emerging novel lipid marker, plays an elusive role in CKD progression. This study sought to investigate the association of RC with decreased kidney function or albuminuria in the general population of U.S.MethodData were retrieved from the continuous 2001 to 2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Individuals aged between 18 and 70 years were included. RC was divided into quartiles. Albuminuria was defined by albumin-to-creatinine ratio (ACR) ≥30 mg/g, while reduced kidney function was described as an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2. Using a multivariable regression model, the association of RC with decreased eGFR or albuminuria was examined. The dose‒response relationship between RC and eGFR or ACR was also investigated using a restricted cubic spline (RCS) model.ResultsA total of 1551 (10.98%) participants with impaired renal function or albuminuria were identified. After multivariate adjustment, RC was not significantly associated with kidney function decline or albuminuria (odds ratio (OR) 1.24, 95% confidence interval (95% CI): 0.95, 1.61). However, a significantly inverse correlation was observed between RC and eGFR in a dose‒response manner (β -2.12, 95% CI: -3.04, -1.21). This association remained consistent when stratifying data by gender, age, race, hypertension, diabetes and body mass index (BMI).ConclusionA higher RC was significantly correlated with a lower eGFR in the general population. The role of RC in predicting kidney outcomes needed further investigation in prospective studies.

Risk of Depression according to Cumulative Exposure to a Low-Household Income Status in Individuals with Type 2 Diabetes Mellitus: A Nationwide Population- Based Study.

We aimed to identify the risk of incident depression according to cumulative exposure to a low-household income status in individuals with type 2 diabetes mellitus (T2DM). For this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2002 to 2018. Risk of depression was assessed according to cumulative exposure to low-household income status (defined as Medical Aid registration) during the previous 5 years among adults (aged ≥20 years) with T2DM and without baseline depression who underwent health examinations from 2009 to 2012 (n=2,027,317). During an average 6.23 years of follow-up, 401,175 incident depression cases occurred. Advance in cumulative number of years registered for medical aid during the previous 5 years from baseline was associated with an increased risk of depression in a dose-dependent manner (hazard ratio [HR], 1.44 [95% confidence interval (CI), 1.38 to 1.50]; HR, 1.40 [95% CI, 1.35 to 1.46]; HR, 1.42, [95% CI, 1.37 to 1.48]; HR, 1.46, [95% CI, 1.40 to 1.53]; HR, 1.69, [95% CI, 1.63 to 1.74] in groups with 1 to 5 exposed years, respectively). Insulin users exposed for 5 years to a low-household income state had the highest risk of depression among groups categorized by insulin use and duration of low-household income status. Cumulative duration of low-household income status, defined as medical aid registration, was associated with an increased risk of depression in a dose-response manner in individuals with T2DM.

Dose-response associations of maternal prenatal noise exposure duration with antepartum depression status

BackgroundAntepartum depression has been reported to be associated with the intensity of maternal prenatal noise exposure; however, the association between noise exposure duration and the development of antepartum depression has not been established. This study aimed to determine the total and trimester-specific association of prenatal noise exposure duration with the development of antepartum depression.MethodsFrom May 2018 to June 2021, we recruited 2,166 pregnant women from Shengjing Hospital, northeast China. We used a standardized questionnaire to assess women’s prenatal noise exposure and used the Edinburgh Postnatal Depression Scale to assess pregnant women’s antepartum depression during the 1st -, 2nd -, and 3rd - trimesters. We calculated a cumulative noise exposure score ranging from 0 to 3, with a higher score reflecting higher frequency and longer duration of noise exposure during pregnancy.ResultsWomen who were exposed to noise for ≥ 15 min per day had an increased risk of antepartum depression compared with women who were not exposed to noise during pregnancy [odds ratio (OR) = 1.83, 95%CI:1.18, 2.83]. Noise exposure in a specific trimester was associated with higher risk of depression in the same trimester and subsequent trimesters. We observed increases in antepartum depression risk with increasing cumulative noise exposure scores (P for trend < 0.05 for all). Pregnant women with the highest scores had the highest risk of antepartum depression during the first (OR = 1.30, 95%CI:1.02, 1.65), second (OR = 1.75, 95%CI:1.23, 2.50) trimesters. Women with a cumulative noise exposure score of 2 had the highest risk of antepartum depression during the third trimester (OR = 1.79, 95%CI:1.14, 2.80), as well as during the whole pregnancy (OR = 1.94, 95%CI:1.14, 3.30).ConclusionsMaternal prenatal noise exposure duration was positively associated with antepartum depression risk in a dose-response manner. It is necessary to develop strategies by which pregnant women can avoid excessive exposure to noise to prevent antepartum depression.

Somatic disease burden and depression risk in late life: a community-based study.

Co-occurring somatic diseases exhibit complex clinical profiles, which can differentially impact the development of late-life depression. Within a community-based cohort, we aimed to explore the association between somatic disease burden, both in terms of the number of diseases and their patterns, and the incidence of depression in older people. We analysed longitudinal data of depression- and dementia-free individuals aged 60+years from the population-based Swedish National Study on Aging and Care in Kungsholmen. Depression diagnoses were clinically ascertained following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision over a 15-year follow-up. Somatic disease burden was assessed at baseline through a comprehensive list of chronic diseases obtained by combining information from clinical examinations, medication reviews and national registers and operationalized as (i) disease count and (ii) patterns of co-occurring diseases from latent class analysis. The association of somatic disease burden with depression incidence was investigated using Cox models, accounting for sociodemographic, lifestyle and clinical factors. The analytical sample comprised 2904 people (mean age, 73.2 [standard deviation (SD), 10.5]; female, 63.1%). Over the follow-up (mean length, 9.6years [SD, 4years]), 225 depression cases were detected. Each additional disease was associated with the occurrence of any depression in a dose-response manner (hazard ratio [HR], 1.16; 95% confidence interval [CI]: 1.08, 1.24). As for disease patterns, individuals presenting with sensory/anaemia (HR, 1.91; 95% CI: 1.03, 3.53), thyroid/musculoskeletal (HR, 1.90; 95% CI: 1.06, 3.39) and cardiometabolic (HR, 2.77; 95% CI: 1.40, 5.46) patterns exhibited with higher depression hazards, compared to those without 2+ diseases (multimorbidity). In the subsample of multimorbid individuals (85%), only the cardiometabolic pattern remained associated with a higher depression hazard compared to the unspecific pattern (HR, 1.71; 95% CI: 1.02, 2.84). Both number and patterns of co-occurring somatic diseases are associated with an increased risk of late-life depression. Mental health should be closely monitored among older adults with high somatic burden, especially if affected by cardiometabolic multimorbidity.

Air Pollutants and Risk of Parkinson's Disease among Women in the Sister Study.

Air pollutants may contribute to the development of Parkinson's disease (PD), but empirical evidence is limited and inconsistent. This study aimed to prospectively investigate the associations of PD with ambient exposures to fine particulate matter with aerodynamic diameter () and nitrogen dioxide (). We analyzed data from 47,108 US women from the Sister Study, enrolled from 2003-2009 (35-80 years of age) and followed through 2018. Exposures of interest included address-level ambient and in 2009 and their cumulative averages from 2009 to PD diagnosis with varying lag-years. The primary outcome was PD diagnosis between 2009 and 2018 (). We used multivariable Cox proportional hazards and time-varying Cox models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). exposure in 2009 was associated with PD risk in a dose-response manner. The HR and 95% CI were 1.22 (95% CI: 1.03, 1.46) for one interquartile [4.8 parts per billion (ppb)] increment in , adjusting for age, race and ethnicity, education, smoking status, alcohol drinking, caffeine intake, body mass index, physical activity, census region, residential area type, area deprivation index (ADI), and self-reported health status. The association was confirmed in secondary analyses with time-varying averaged cumulative exposures. For example, the multivariable adjusted HR for PD per increment in was 1.25 (95% CI: 1.05, 1.50) in the 2-year lag analysis using cumulative average exposure. Post hoc subgroup analyses overall confirmed the association. However, statistical interaction analyses found that the positive association of with PD risk was limited to women in urban, rural, and small town areas and women with percentile ADI but not among women from suburban areas or areas with percentile ADI. In contrast, exposure was not associated with PD risk with the possible exception for women from the Midwest region of the US (, 95% CI: 1.20, 5.14) but not in other census regions. In this nationwide cohort of US women, higher level exposure to ambient is associated with a greater risk of PD. This finding needs to be independently confirmed and the underlying mechanisms warrant further investigation. https://doi.org/10.1289/EHP13009.

Connection Between Depression, Sexual Frequency, and All-cause Mortality: Findings from a Nationally Representative Study

We used the 2005–2010 National Health and Nutrition Examination Survey (NHANES), constructed to evaluate health of adults in the United States using consolidated data from interviews and physical exams that were conducted to obtain data for this study. The analysis sample was representative of noninstitutionalized US adults aged 20–59 years. When considering sexual frequency, overall, only female participants with lower sexual frequency were at a higher risk of all-cause death in a dose-response manner with a hazard ratio (HR) of 1.70 (95% CI 1.38–2.10, p trend &lt; .001) during the follow-up period. This relationship was not significant in males. However, when sexual frequency was categorized (&lt;52 times/year vs. ≥52 times/year), the adjusted HR was elevated [2.97 (CI 1.20–7.32, p = .02)] among individuals who had depression and low sexual frequency, but it was close to 1.0 (1.75, CI 0.50–6.07, p = .36) among individuals who had depression and high sexual frequency after adjusting for medical (obesity) and demographic (age, gender, education, and ethnicity) risk factors, indicating a 197% increase in mortality among individuals with low sexual frequency and depression than depression alone. Sexual activity is important for overall cardiovascular health possibly due to reduction of heart rate variability and blood flow increase.

Dose of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding in older adults.

Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of upper gastrointestinal bleeding (UGIB) in older patients but little is known about the risk associated with individual SSRI drugs and doses. To quantify the risk of UGIB in relation to individual SSRI use in older adults. We conducted a nested case-control study within a cohort of 9565 patients aged ⩾65 years prescribed SSRIs from 2000 to 2013 using claims data of universal health insurance in Taiwan. Incident cases of UGIB during the follow-up period were identified and matched with three control subjects. Conditional logistic regression was used to estimate the odds ratio (OR) of UGIB associated with individual SSRI use and cumulative dose. UGIB risk increased with the increasing cumulative doses of SSRIs (adjusted OR: 1.28, 95% confidence interval (CI): 1.02-1.62 for the highest vs. the lowest tertile). Compared with users of other SSRIs, fluoxetine users were at an increased risk of UGIB (adjusted OR: 1.25, 95% CI: 1.03-1.50) with a dose-response manner, whereas paroxetine users had 29% decreased odds (95% CI: 0.56-0.91). The increased risk was only observed among current fluoxetine users. Fluoxetine therapy was associated with an increased risk of UGIB in a dose-response manner among older adults.

Time to pregnancy and life expectancy: a cohort study of 18 796 pregnant couples.

Is fecundity, measured as time to pregnancy (TTP), associated with mortality in parents? Prolonged TTP is associated with increased mortality in both mothers and fathers in a dose-response manner. Several studies have linked both male and female fecundity to mortality. In women, infertility has been linked to several diseases, but studies suggest that the underlying conditions, rather than infertility, increase mortality. A prospective cohort study was carried out on 18 796 pregnant couples, in which the pregnant women attended prophylactic antenatal care between 1973 and 1987 at a primary and tertiary care unit. The couples were followed in Danish mortality registers from their child's birth date until death or until 2018. The follow-up period was up to 47 years, and there was complete follow-up until death, emigration or end of study. At the first antenatal visit, the pregnant women were asked to report the time to the current pregnancy. Inclusion was restricted to the first pregnancy, and TTP was categorised into <12 months, ≥12 months, not planned, and not available. In sub-analyses, TTP ≥12 was further categorized into 12-35, 36-60, and >60 months. Information for parents was linked to several Danish nationwide health registries. Survival analysis was used to estimate the hazard ratios (HRs) with a 95% CI for survival and adjusted for age at the first attempt to become pregnant, year of birth, socioeconomic status, mother's smoking during pregnancy, and mother's BMI. Mothers and fathers with TTP >60 months survived, respectively, 3.5 (95% CI: 2.6-4.3) and 2.7 (95% CI: 1.8-3.7) years shorter than parents with a TTP <12 months. The mortality was higher for fathers (HR: 1.21, 95% CI: 1.09-1.34) and mothers (HR: 1.29, 95% CI: 1.12-1.49) with TTP ≥12 months compared to parents with TTP <12 months. The risk of all-cause mortality during the study period increased in a dose-response manner with the highest adjusted HR of 1.98 (95% CI: 1.62-2.41) for fathers and 2.03 (95% CI: 1.56-2.63) for mothers with TTP >60 months. Prolonged TTP was associated with several different causes of death in both fathers and mothers, indicating that the underlying causes of the relation between fecundity and survival may be multi-factorial. A limitation is that fecundity is measured using a pregnancy-based approach. Thus, the cohort is conditioned on fertility success and excludes sterile couples, unsuccessful attempts and spontaneous abortions. The question used to measure TTP when the pregnant woman was interviewed at her first attended prophylactic antenatal care: 'From the time you wanted a pregnancy until it occurred, how much time passed?' could potentially have led to serious misclassification if the woman did not answer on time starting unprotected intercourse but on the start of wishing to have a child. We found that TTP is a strong marker of survival, contributing to the still-emerging evidence that fecundity in men and women reflects their health and survival potential. The authors acknowledge an unrestricted grant from Ferring. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. M.L.E. is an advisor to Ro, VSeat, Doveras, and Next. N/A.