Dynamic path analysis for exploring treatment effect mediation processes in clinical trials with time-to-event endpoints.

Why does a beneficial treatment effect on a longitudinal biomarker not translate into overall treatment benefit on survival, when the biomarker is in fact a prognostic factor of survival? In a recent exploratory data analysis in oncology, we were faced with this seemingly paradoxical result. To address this problem, we applied a theoretically principled methodology called dynamic path analysis, which allows us to perform mediation analysis with a longitudinal mediator and survival outcome. The aim of the analysis is to decompose the total treatment effect into a direct treatment effect and an indirect treatment effect mediated through a carefully constructed mediation path. The dynamic nature of the underlying methodology enables us to describe how these effects evolve over time, which can add to the mechanistic understanding of the underlying processes. In this paper, we present a detailed description of the dynamic path analysis framework and illustrate its application to survival mediation analysis using simulated and real data. The use case analysis provides clarity on the specific exploratory question of interest while the methodology generalizes to a wide range of applications in drug development where time-to-event is the primary clinical outcome of interest.

Suicide rates among physicians compared with the general population in studies from 20 countries: gender stratified systematic review and meta-analysis.

OBJECTIVES: To estimate age standardised suicide rate ratios in male and female physicians compared with the general population, and to examine heterogeneity across study results. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Studies published between 1960 and 31 March 2024 were retrieved from Embase, Medline, and PsycINFO. There were no language restrictions. Forward and backwards reference screening was performed for selected studies using Google Scholar. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies with directly or indirectly age standardised mortality ratios for physician deaths by suicide, or suicide rates per 100 000 person years of physicians and a reference group similar to the general population, or extractable data on physician deaths by suicide suitable for the calculation of ratios. Two independent reviewers extracted data and assessed the risk of bias using an adapted version of the Joanna Briggs Institute checklist for prevalence studies. Mean effect estimates for male and female physicians were calculated based on random effects models, with subgroup analyses for geographical region and a secondary analysis of deaths by suicide in physicians compared with other professions. RESULTS: Among 39 included studies, 38 studies for male physicians and 26 for female physicians were eligible for analyses, with a total of 3303 suicides in male physicians and 587 in female physicians (observation periods 1935-2020 and 1960-2020, respectively). Across all studies, the suicide rate ratio for male physicians was 1.05 (95% confidence interval 0.90 to 1.22). For female physicians, the rate ratio was significantly higher at 1.76 (1.40 to 2.21). Heterogeneity was high for both analyses. Meta-regression revealed a significant effect of the midpoint of study observation period, indicating decreasing effect sizes over time. The suicide rate ratio for male physicians compared with other professions was 1.81 (1.55 to 2.12). CONCLUSION: Standardised suicide rate ratios for male and female physicians decreased over time. However, the rates remained increased for female physicians. The findings of this meta-analysis are limited by a scarcity of studies from regions outside of Europe, the United States, and Australasia. These results call for continued efforts in research and prevention of physician deaths by suicide, particularly among female physicians and at risk subgroups. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019118956.

The Relationship between Big Five Personality Traits and Depression in the German-Speaking D-A-CH Region Including an Investigation of Potential Moderators and Mediators.

Considerable evidence links the "Big Five" personality traits (neuroticism, extroversion, conscientiousness, agreeableness, and openness) with depression. However, potential mediating and moderating factors are less well understood. We utilized data from a cross-sectional survey of 3065 German-speaking adults from the D-A-CH region to estimate multivariable-adjusted odds ratios and 95% confidence intervalsbetween personality traits and lifetime prevalence of depression (overall and stratified by sex and age). We further explored proportions mediated by psychosocial factors optimism, empathy, perspective-taking, work-life balance, and interpersonal trust. High levels of neuroticism were associated with more than two-fold higher odds of depression, whereas higher levels of conscientiousness were associated with approximately 30% lower odds of depression. The association with neuroticism persisted in all investigated subgroups; apparently, stronger associations for females and participants aged ≥60 years did not correspond to statistically significant interactions. Overall and across all strata, the association of neuroticism with depression appeared to be mediated in part by the considered psychosocial factors; optimism explained the largest proportion of the association. Our results provide empirical evidence for the dynamic predisposition model. Further investigations of these relationships are warranted in longitudinal data with more precise outcome assessments.

Pet Attachment and Anxiety and Depression in Middle-Aged and Older Women.

Importance: Understanding how attachment to pets can alleviate depression and anxiety offers valuable insights for developing preventive and therapeutic strategies, particularly for those with insecure attachment styles from childhood trauma. Objective: To determine if a close bond with a pet is associated with reduced depression and anxiety, especially among women who experienced childhood abuse. Design, Setting, and Participants: This cross-sectional study involved women who voluntarily enrolled in the Mind Body Study (MBS), a substudy of the Nurses' Health Study II (NHS2) focusing on psychosocial factors. Women reporting childhood abuse were oversampled to capture their psychosocial distress in adulthood. MBS participants were invited to complete comprehensive online questionnaires, which were administered twice (March 2013 and February 2014). Exposure: Pet attachment measured by Lexington Attachment to Pets Scale (LAPS). Main Outcomes and Measures: Levels of depression and anxiety (10-item Centre for Epidemiologic Studies Depression Scale [CESD-10]; Kessler Psychological Distress Scale [K6]; 7-item Generalized Anxiety Disorder scale [GAD-7]; Crown Crisp Experiential Index phobic anxiety subscale [CCI]), considered individually and combined into an overall z-score measure of anxiety and depression symptoms. Results: A total of 214 women (mean [SD] age, 60.8 [3.9] years) were included; 156 women (72.6%) reported a history of childhood abuse. Of 688 invited MBS participants in 2013, 293 (42.6%) expressed interest; there were 228 completed questionnaires (response rate, 77.8%) in 2013 and 208 questionnaires (response rate, 71.0%) in 2014. LAPS scores were provided by 140 participants (65.4%), 78 (55.7%) for dogs and 46 (32.9%) for cats. Overall higher pet attachment on the LAPS score was significantly associated with lower GAD-7 scores (ß = -0.17; 95% CI, -0.29 to -0.06), but there was no association for phobic anxiety or depression. There were no statistically significant associations between cat attachment and depression or anxiety. Higher dog attachment was associated with significantly lower scores in depression (CESD-10: ß, -0.47; 95% CI, -0.68 to -0.26; K6: ß = -0.42; 95% CI, -0.54 to -0.31), generalized anxiety (GAD-7: ß = -0.47; 95% CI, -0.65 to -0.3), and the overall measure of anxiety and depression (z score: ß = -0.12; 95% CI, -0.17 to -0.08), but there was no association between dog attachment and phobic anxiety (CCI: ß = -0.08; 95% CI, -0.24 to 0.09). All effect sizes for associations were higher when analyses were restricted to women with a history of childhood abuse. Conclusions and relevance: In this explorative cross-sectional study, strong attachment to pets, especially dogs, was associated with lower anxiety and depression symptoms. The favorable association was particularly apparent in women with a history of childhood abuse.

Mortality of working-age physicians compared to other high-skilled occupations in Austria from 1998 to 2020.

OBJECTIVES: Physicians have been shown to have lower mortality compared to the general population, particularly regarding lifestyle-associated causes of death. Prior literature is divided on whether this is due to higher socioeconomic position (SEP), healthier lifestyle, or other specific occupational characteristics. This study analyzed the mortality of Austrian physicians compared to the general population and other (health) professionals with a similar SEP, and investigated patterns of lifestyle-associated mortality among physicians. METHODS: Data from professional associations and cause-of-death statistics were collated to determine causes of death for all occupational groups. Gender-specific age-standardized mortality rates (ASMR) and standardized rate ratios (SRR) were calculated to compare main causes of death [cancer, cardiovascular disease (CVD), external causes] among physicians to other (health) professionals and the general population. Standardized mortality ratios (SMR) were calculated for more detailed causes of death in physicians compared to the general population. RESULTS: Physicians had lower all-cause mortality than the general population [SRR 0.45, 95% confidence interval (CI) 0.41-0.49 for males and SRR 0.60, 95% CI 0.54-0.66 for females] and health professionals (SRR 0.72, 95% CI 0.60-0.88 for males and SRR 0.77, 95% CI 0.63-0.93 for females), mostly due to low CVD and cancer mortality. SMR for detailed causes of death among physicians exhibited a pattern of particularly low mortality in lifestyle-associated causes of death and an increased SMR for suicide among female physicians (SMR 1.58, 95% CI 1.22-2.02). CONCLUSIONS: This study confirmed lower mortality among physicians compared to the general population and compared to other (health) professionals. Low physician mortality can be primarily explained by lifestyle-associated causes of death.

Maternal One-Carbon Nutrient Intake and Risk of Being Overweight or Obese in Their Offspring-A Transgenerational Prospective Cohort Study.

We aimed to investigate the associations between maternal intake of folate, vitamin B12, B6, B2, methionine, choline, phosphatidylcholine and betaine during the period surrounding pregnancy and offspring weight outcomes from birth to early adulthood. These associations were examined among 2454 mother-child pairs from the Nurses' Health Study II and Growing Up Today Study. Maternal energy-adjusted nutrient intakes were derived from food frequency questionnaires. Birth weight, body size at age 5 and repeated BMI measurements were considered. Overweight/obesity was defined according to the International Obesity Task Force (<18 years) and World Health Organization guidelines (18+ years). Among other estimands, we report relative risks (RRs) for offspring ever being overweight with corresponding 95% confidence intervals across quintiles of dietary factors, with the lowest quintile as the reference. In multivariate-adjusted models, higher maternal intakes of phosphatidylcholine were associated with a higher risk of offspring ever being overweight (RRQ5vsQ1 = 1.16 [1.01-1.33] p-trend: 0.003). The association was stronger among offspring born to mothers with high red meat intake (high red meat RRQ5vsQ1 = 1.50 [1.14-1.98], p-trend: 0.001; low red meat RRQ5vsQ1 = 1.05 [0.87-1.27], p-trend: 0.46; p-interaction = 0.13). Future studies confirming the association between a higher maternal phosphatidylcholine intake during pregnancy and offspring risk of being overweight or obese are needed.

Bleb vessel density as a predictive factor for surgical revisions after Preserflo Microshunt implantation.

PURPOSE: Bleb failure is a common complication after glaucoma filtration surgery. Different bleb classification schemes incorporating filtration bleb vascularization have been proposed, but the reported correlation with intraocular pressure (IOP) has been variable, possibly because of subjective vascularization grading. The purpose of the present study was to evaluate bleb vascularization after Preserflo Microshunt (PM) implantation using anterior segment OCT-angiography (AS-OCTA) as a biomarker for bleb failure. METHODS: Twenty-three eyes of twenty-three patients underwent PM implantation. Up to 12 months after surgery PM scleral passage-centred AS-OCTA measurements (PLEX Elite 9000) for bleb-vessel density (BVD) determination were performed and IOP as well as necessity for surgical revisions (needling and open revision) were documented. After multi-step image analysis (region of interest definition, artefact removal, binarization, BVD calculation), the predictive value of early postoperative BVD for surgical revisions was assessed using logistic regression modelling. RESULTS: Baseline IOP (23.57 ± 7.75 mmHg) decreased significantly to 8.30 ± 2.12, 9.17 ± 2.33 and 11.70 ± 4.40 mmHg after 1, 2 and 4 week(s), and 13.48 ± 5.83, 11.87 ± 4.49, 12.30 ± 6.65, 11.87 ± 3.11 and 13.05 ± 4.12 mmHg after 2, 3, 6, 9 and 12 month(s), respectively (p < 0.001). Nine patients (39%) needed surgical revisions after a median time of 2 months. Bleb vessel densities at 2 and 4 weeks were significantly associated with future surgical revisions upon logistic regression analysis (2 W/4 W likelihood-ratio test p-value: 0.0244/0.0098; 2 W/4 W area under the receiver operating characteristics curve: 0.796/0.909). CONCLUSION: Filtration bleb vessel density can be determined using AS-OCTA in the early postoperative period and is predictive for bleb failure after PM implantation.

Timing and duration of dog walking and dog owner's chronotype in relation to incident depression risk among middle to older-aged female nurses.

BACKGROUND: We examined associations between dog ownership, morning dog walking and its timing and duration, and depression risk in female nurses, exploring effect modification by chronotype. We hypothesized that dog ownership and morning walking with the dog are associated with lower odds of depression, and that the latter is particularly beneficial for evening chronotypes by helping them to synchronize their biological clock with the solar system. METHODS: 26,169 depression-free US women aged 53-72 from the Nurses' Health Study 2 (NHS2) were prospectively followed from 2017-2019. We used age- and multivariable-adjusted logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for depression according to dog ownership, and morning dog walking, duration, and timing. RESULTS: Overall, there was no association between owning a dog (ORvs_no_pets = 1.12, 95%CI = 0.91-1.37), morning dog walking (ORvs_not = 0.87, 95%CI = 0.64-1.18), or the duration (OR>30min vs. ≤15mins = 0.68, 95%CI = 0.35-1.29) or timing of morning dog walks (ORafter9am vs. before7am = 1.06, 95%CI = 0.54-2.05) and depression. Chronotype of dog owners appeared to modify these associations. Compared to women of the same chronotype but without pets, dog owners with evening chronotypes had a significantly increased odds of depression (OR = 1.60, 95%CI = 1.12-2.29), whereas morning chronotypes did not (OR = 0.94, 95%CI = 0.71-1.23). Further, our data suggested that evening chronotypes benefited more from walking their dog themselves in the morning (OR = 0.75, 95%CI = 0.46-1.23, Pintx = 0.064;) than morning chronotypes. CONCLUSIONS: Overall, dog ownership was not associated with depression risk though it was increased among evening chronotypes. Walking their dog in the morning might help evening chronotypes to lower their odds of depression, though more data are needed to confirm this finding.

The history of circadian rhythm research in Austria.

In view of the recent revival of interest in circadian biology and circadian epidemiology at the Medical University of Vienna, it seems appropriate to highlight the rich and pioneering history of circadian research in Austria. Among the forefathers of circadian research in Vienna are Otto Marburg (1874-1948), who discovered important elements of the pineal gland physiology, Robert Hofstätter (1883-1970), who used pineal gland extract in obstetrics/gynecology, and Paul Engel (1907-1997), who discovered that the pineal gland was controlled by light. More recently, Vera Lapin (1920-2007) showed that surgical removal of the pineal gland increased tumor growth, while Franz Waldhauser (*1946) investigated melatonin in conjunction with night work. Michael Kundi (*1950) and his team conducted among the first studies demonstrating differences in rhythms of night workers and early evidence for health impairments among them. Furthermore, Vienna-born Erhard Haus (1926-2013) pioneered the discovery of the role and importance of melatonin in relation to numerous diseases. This rich pioneering contribution of scientists in Vienna or with roots in Vienna is continued today by a new generation of chronobiologists, epidemiologists and clinicians in Vienna whose new insights contribute to the rapidly developing field of circadian rhythms research. Current topics and contributions relate to the impact of circadian rhythm disruption on health, and the application of chronotherapeutic approaches in clinical and preventive settings.

Rotating Night Shift Work, Sleep, and Thyroid Cancer Risk in the Nurses' Health Study 2.

Night shift work has been associated with breast, prostate, and colorectal cancer, but evidence on other types of cancer is limited. We prospectively evaluated the association of rotating night shift work, sleep duration, and sleep difficulty with thyroid cancer risk in the Nurses' Health Study 2 (NHS2). We assessed rotating night shift work duration (years) at baseline and throughout follow-up (1989-2015) and sleep characteristics in 2001. Cox proportional hazard models, adjusted for potential confounders, were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for (a) shift work duration, (b) sleep duration, and (c) difficulty falling or staying asleep. We stratified the analyses of night shift work by sleep duration and sleep difficulty. Over 26 years of follow-up, 588 incident cases were identified among 114,534 women in the NHS2 cohort. We observed no association between night shift work and the risk of thyroid cancer. Difficulty falling or staying asleep was suggestively associated with a higher incidence of thyroid cancer when reported sometimes (HR 1.26, 95% CI 0.95, 1.66) and all or most of the time (HR 1.35, 95% CI 1.00, 1.81). Night shift workers (10+ years) with sleep difficulty all or most of the time (HR 1.47; 0.58-3.73) or with >7 h of sleep duration (HR 2.17; 95% CI, 1.21-3.92) had a higher risk of thyroid cancer. We found modest evidence for an increased risk of thyroid cancer in relation to sleep difficulty, which was more pronounced among night shift workers.

Eeny, meeny, miny, moe-Summer time and out are you? The working population in the EU would likely benefit from elimination of daylight saving time.

Daylight (saving) time (DST) is an over one century old practice to maximize the overlap between natural day light and individual active time (i.e., non-sleep time). Whether to abandon the practice is subject to an ongoing, twice a year intensifying debate. A request to abandon the practice is based on the lack of benefits in terms of energy savings and potential negative health effects. We present a tool that captures one key aspect of importance to the circadian system: maximizing the overlap of natural day light with human active time, focusing on early morning light exposure as the primary stimulus for our circadian system. Based on publicly available data we incorporated an approximation of the 27 European Union (EU) countries' spatial population distribution into a calculation of average exposure to morning sunlight under DST or no DST conditions for each EU27 country and the entire region. An online app offers visualization of these differences on the country level alongside a population-weighted average for the EU27. Our findings support that the majority of the EU's working population would likely benefit from the elimination of daylight saving time if maximizing an adequate morning stimulus is the primary goal and adjusting actual time zones or biennially changing the clock is not an option.

Lack of Correlation Between Segmental Trabecular Meshwork Pigmentation and Angiographically Determined Outflow in Ex-Vivo Human Eyes.

PRECIS: Trabecular meshwork pigmentation is not correlated with angiographically determined aqueous humor outflow in an ex-vivo perfusion model using human eyes. PURPOSE: To evaluate whether segmental trabecular meshwork (TM) pigmentation is correlated to segmental aqueous humor outflow (AHO) in human eyes. METHODS: Post-mortem human eyes were acquired, and anterior segments were dissected. TM pigmentation was photographed 360-degrees around the eye. The anterior segments were then mounted onto a perfusion apparatus and perfused with DPBS until a stabile baseline outflow facility was achieved. Aqueous angiography (AHO angiography) was performed using fluorescein (2%), and segmental AHO was documented around the limbus using an angiographic camera (Spectralis HRA+OCT). Circumferential and nasal TM pigmentation were compared to respective angiographic outflow imaging using a Pearson's correlation analysis. RESULTS: Segmental TM pigment distribution and segmental AHO were seen. TM pigment was statistically greatest in the inferior quadrant. AHO angiographic outflow was numerically greatest in the nasal quadrant, but this was not statistically significant. No statistically significant correlation was observed (r=-0.083, P=0.06) between segmental TM pigmentation and segmental AHO angiographic signal. Analyzing just the nasal quadrant, a significant weak negative correlation was found (r=-0.296, P=0.001). DISCUSSION: Segmental TM pigmentation circumferentially around the eye is not a good proxy for segmental AHO circumferentially around the eye and should not be used to guide trabecular minimally invasive glaucoma surgeries.

Sleeping Difficulties, Sleep Duration, and Risk of Hypertension in Women.

BACKGROUND: Rates of poor sleep and hypertension are alarming worldwide. In this study, we investigate the association between sleeping difficulties and sleep duration with hypertension risk in women. METHODS: Sixty-six thousand one hundred twenty-two participants of the Nurses' Health Study 2, who were free of hypertension at baseline (2001), were followed prospectively for 16 years and incident hypertension assessed every 2 years. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for hypertension incidence associated with sleeping difficulties and sleep duration. RESULTS: During follow-up, we documented 25 987 incident cases of hypertension. After controlling for demographic and lifestyle risk factors, compared with women who slept 7 to 8 hours, women with shorter sleep duration had a significantly higher risk of hypertension (≤5 hours: HR, 1.10 [95% CI, 1.05-1.16]; 6 hours: HR, 1.07 [95% CI, 1.03-1.10]), whereas the risk for women with longer sleep duration was not statistically significant (9 hours: HR, 1.03 [95% CI, 0.97-1.10]; >9 hours: HR, 1.08 [95% CI, 0.94-1.23]). Compared with women rarely having difficulty falling or staying asleep, women sometimes or usually having these sleep difficulties had significantly higher risk of developing hypertension (HR, 1.14 [95% CI, 1.11-1.17] and 1.28 [95% CI, 1.22-1.35]; Ptrend<0.001). Early morning awakening was not associated with hypertension risk (Ptrend=0.722). There was no effect modification by night work or chronotype. CONCLUSIONS: Difficulty falling or staying asleep and short sleep duration were associated with higher risk of hypertension among women in our study. Screening for poor sleep could be useful in identifying people at higher risk for hypertension.

Time Spent Outdoors and Associations with Sleep, Optimism, Happiness and Health before and during the COVID-19 Pandemic in Austria.

Social restriction measures (SRM) implemented during the COVID-19 pandemic led to a reduction in time spent outdoors (TSO). The aim of this study was to describe TSO and evaluate its association with sleep outcomes, optimism, happiness and health-status before and during SRM. Two online surveys were conducted in 2017 (N = 1004) and 2020, during SRM (N = 1010), in samples representative of the age, sex and region of the Austrian population. Information on the duration of TSO, sleep, optimism, happiness and health-status was collected. Multivariable-adjusted logistic regression models were used to study the association of TSO with chronic insomnia, short sleep, late chronotype, optimism, happiness and self-rated health-status. The mean TSO was 3.6 h (SD: 2.18) in 2017 and 2.6 h (SD: 1.87) during times of SRM. Men and participants who were older, married or in a partnership and lived in a rural area reported longer TSO. Participants who spent less time outdoors were more likely to report short sleep or a late chronotype in both surveys and, in 2020, also chronic insomnia. Less TSO was associated with lower happiness and optimism levels and poor health-status. Our findings suggest that TSO may be a protective factor for sleep, mood and health, particularly during stressful and uncertain times.

Sex differences in the survival benefit of kidney transplantation: a retrospective cohort study using target trial emulation.

BACKGROUND: Kidney transplantation is the preferred treatment for eligible patients with kidney failure who need renal replacement therapy. However, it remains unclear whether the anticipated survival benefit from kidney transplantation is different for women and men. METHODS: We included all dialysis patients recorded in the Austrian Dialysis and Transplant Registry who were waitlisted for their first kidney transplant between 2000 and 2018. In order to estimate the causal effect of kidney transplantation on 10-year restricted mean survival time, we mimicked a series of controlled clinical trials and applied inverse probability of treatment and censoring weighted sequential Cox models. RESULTS: This study included 4408 patients (33% female) with a mean age of 52 years. Glomerulonephritis was the most common primary renal disease both in women (27%) and men (28%). Kidney transplantation led to a gain of 2.22 years (95% CI 1.88 to 2.49) compared with dialysis over a 10-year follow-up. The effect was smaller in women (1.95 years, 95% CI 1.38 to 2.41) than in men (2.35 years, 95% CI 1.92 to 2.70) due to a better survival on dialysis. Across ages the survival benefit of transplantation over a follow-up of 10 years was smaller in younger women and men and increased with age, showing a peak for both women and men aged about 60 years. CONCLUSIONS: There were few differences in survival benefit by transplantation between females and males. Females had better survival than males on the waitlist receiving dialysis and similar survival to males after transplantation.

The association between night shift work and breast cancer risk in the Finnish twins cohort.

Breast cancer is highly prevalent yet a more complete understanding of the interplay between genes and probable environmental risk factors, such as night work, remains lagging. Using a discordant twin pair design, we examined the association between night shift work and breast cancer risk, controlling for familial confounding. Shift work pattern was prospectively assessed by mailed questionnaires among 5,781 female twins from the Older Finnish Twin Cohort. Over the study period (1990-2018), 407 incident breast cancer cases were recorded using the Finnish Cancer Registry. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for potential confounders. Within-pair co-twin analyses were employed in 57 pairs to account for potential familial confounding. Compared to women who worked days only, women with shift work that included night shifts had a 1.58-fold higher risk of breast cancer (HR = 1.58; 95%CI, 1.16-2.15, highest among the youngest women i.e. born 1950-1957, HR = 2.08; 95%CI, 1.32-3.28), whereas 2-shift workers not including night shifts, did not (HR = 0.84; 95%CI, 0.59-1.21). Women with longer sleep (average sleep duration > 8 h/night) appeared at greatest risk of breast cancer if they worked night shifts (HR = 2.91; 95%CI, 1.55-5.46; Pintx=0.32). Results did not vary by chronotype (Pintx=0.74). Co-twin analyses, though with limited power, suggested that night work may be associated with breast cancer risk independent of early environmental and genetic factors. These results confirm a previously described association between night shift work and breast cancer risk. Genetic influences only partially explain these associations.

Suicide mortality among physicians, dentists, veterinarians, and pharmacists as well as other high-skilled occupations in Austria from 1986 through 2020.

Some evidence puts health professionals at increased risk of suicide, especially females, whereas other research suggests a lower risk in high-skilled occupations. This study investigated the suicide risk of four health professions (physicians, dentists, veterinarians, pharmacists) and three other high-skilled occupations (notaries, lawyers, tax advisors/public accountants) in Austria compared to the general population, and analyzed suicide methods across occupations. Data was collected from professional associations and Austrian cause-of-death statistics to determine suicide cases. Gender-specific standardized mortality ratios (SMRs), crude and age-adjusted suicide rates and frequencies for suicide methods were calculated for each profession (maximum time span 1986-2020). Among males, only veterinarians had a significantly elevated suicide risk compared to the general population. Physicians and tax advisors/public accountants had a significantly lower suicide risk. Among females, the veterinarians, physicians, and pharmacists had a significantly elevated suicide risk; for dentists, it was also elevated, though non-significantly. Age-adjusted suicide rates showed a smaller gap between men and women in all professions compared to the general population. Poisoning was the predominant suicide method among health professions, except dentists. These findings are consistent with some of the prior literature and call for specific suicide prevention efforts in health professions, focusing on women.

Rotating Night Shift Work and Bladder Cancer Risk in Women: Results of Two Prospective Cohort Studies.

Bladder cancer is the sixth most common cancer in the United States. Night shift work has previously been linked with cancer risk. Whether there is an association between rotating night shift work and bladder cancer in women has not been studied previously. Eligible participants in the Nurses' Health Study (NHS, n = 82,147, 1988-2016) and Nurses' Health Study II (NHSII, n = 113,630, 1989-2015) were prospectively followed and a total of 620 and 122 incident bladder cancer cases were documented during the follow-up of NHS and NHSII, respectively. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for bladder cancer incidence. We observed a significantly increased risk of bladder cancer among women with >5 years of night shift work history compared with women who never worked rotating night shifts in NHS (HR = 1.24; 95%CI = 1.01-1.54, p for trend = 0.06), but not in the pooled NHS and NHS II (HR = 1.18; 95%CI = 0.97-1.43, p for trend = 0.08). Secondary analyses stratified by smoking status showed no significant interaction (p = 0.89) between the duration of rotating night shift work and smoking status. In conclusion, our results did not provide strong evidence for an association between rotating night shift work and bladder cancer risk.

Maternal adherence to healthy lifestyle and risk of depressive symptoms in the offspring: mediation by offspring lifestyle.

BACKGROUND: Adherence to healthy lifestyles can be beneficial for depression among adults, but the intergenerational impact of maternal healthy lifestyles on offspring depressive symptoms is unknown. METHODS: In total, 10 368 mothers in Nurses' Health Study II and 13 478 offspring in the Growing Up Today Study were paired. Maternal and offspring healthy lifestyles were defined as a composite score including a healthy diet, normal body mass index (BMI), never-smoking, light-to-moderate consumption of alcohol, and regular moderate-to-vigorous physical activity. Maternal lifestyles were assessed during their offspring's childhood. Offspring depressive symptoms were repeatedly assessed five times using the Center for Epidemiological Studies Depression Scale-10 (CESD-10); the offspring were between the ages of 14 and 30 when the first CESD-10 was assessed. Covariates included maternal variables (age at baseline, race/ethnicity, antidepressant use, pregnancy complications, etc.) and offspring age and sex. RESULTS: Children of mothers with the healthiest lifestyle had significantly fewer depressive symptoms (a 0.30 lower CESD-10 score, 95% confidence interval (CI) 0.09-0.50) in comparison with children of mothers with the least healthy lifestyle. The association was only found significant in female offspring but not in males. For individual maternal lifestyle factors, a normal BMI, never-smoking, and adherence to regular physical activity were independently associated with fewer depressive symptoms among the offspring. The association between maternal healthy lifestyles and offspring depressive symptoms was mediated by offspring's healthy lifestyles (mediation effect: 53.2%, 95% CI 15.8-87.3). CONCLUSIONS: Our finding indicates the potential mechanism of intergenerational transmission of healthy lifestyles to reduce the risk of depressive symptoms in offspring.

Relationship between pet ownership and risk of high depressive symptoms in adolescence and young adulthood.

BACKGROUND: Only few longitudinal studies with high risk of bias have examined relationship between pets and adolescents' mental health. METHODS: Our prospective cohort study followed depression-free US adolescents aged 12-18, enrolled in the Growing Up Today Study from pet ownership assessment in 1999 to possible occurrence of high depressive symptoms defined based on the McKnight Risk Factor Survey between 2001 and 2003. Propensity-score-adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using generalized estimating equation models. RESULTS: Among 9631 adolescents [42.4 % male, mean age 14.9 years (SD 1.6)], we found no association between pet ownership and risk of high depressive symptoms (ORany_pet = 1.14; 95%CI, 0.95-1.38). Stratified analyses revealed no evidence of effect modification by sex, but effect modification by maternal history of depression (depressed mothers ORany_pet = 0.83; 95 % CI: 0.58-1.19, non-depressed mothers ORany_pet = 1.27; 95 % CI: 1.02-1.58; Pintx = 0.03), which differed further by children's sex. Effects were more pronounced among children with a history of childhood abuse (ORany_pet = 0.41 (0.14-1.15); Pintx ≤0.03). No major differences by type of pet owned were observed in any of these analyses. LIMITATIONS: Our sample is predominantly white and all are offspring of nurses with a similar academic background which could affect generalizability. CONCLUSIONS: Overall, we found no association between pet ownership and depression during adolescence, however subgroup analyses indicated some individuals may benefit from a pet. Future longitudinal studies with more detailed exposure assessments, including pet attachment are needed to further explore the potential of human-animal interaction on mental health.