Sex differences in suicide mortality among Vietnam War-era veterans 1979–2019: a cohort study

Despite growing awareness of the burden of cardiovascular disease (CVD) in women over the past 2 decades, reports of disparities in the delivery of health care for these diseases have persisted over time.1 Under-treatment of women as compared with men has been described for primary prevention, stable coronary artery disease (CAD) and suspected or diagnosed acute coronary syndromes in both observational studies and controlled experiments.2–6 However, because men and women are nonidentical in many ways that might be relevant for treatment decisions, a critical question for policy makers and clinicians is whether these gender-based variations in treatment correspond to lower quality care. A demonstration of clinical inequity (unequal treatment despite equal clinical need) rather than strict inequality (unequal treatment regardless of need or condition) has been proposed as a framework to identify inappropriate variations in healthcare utilization.7 Following this model, it is important to consider whether observed gender differences correspond to inequities or may reflect appropriate variations explained by differences in treatment indications and contraindications or patient preferences.7 In a well-known study published over a decade ago, investigators devised a clever experiment to address just this question of identifying inappropriate healthcare variations.8 Using actors posing as patients with chest pain, primary care physicians were less likely to refer women for cardiac catheterization than men. Because these patients were carefully designed to be identical in age, cardiac risk factors, and symptoms, followed a script standardizing patient communication, and only differed by gender (and race), it seemed obvious that biased decision-making must account for treatment differences. In this commentary, we illustrate why analyses that attempt to control for all known cardiac risk factors that affect treatment decisions might still yield misleading findings about the presence, magnitude, and causes of gender disparities. This residual bias occurs …

People with bipolar disorder have an elevated risk of mortality. This study evaluated associations between the use of mood stabilizers and the risks of all-cause mortality, suicide, and natural mortality in a national cohort of people with bipolar disorder. In this nationwide cohort study, we used data from January 1, 2000, to December 31, 2016, collected from Taiwan's National Health Insurance Research Database and included 25,787 patients with bipolar disorder. Of these patients, 4000 died during the study period (including 760 and 2947 from suicide and natural causes, respectively). Each standardized mortality ratio (SMR) was calculated as the ratio of observed mortality in the bipolar cohort to the number of expected deaths in the general population. Multivariable Cox proportional hazards regression with a time-dependent model was performed to estimate the hazard ratio (HR) of each mood stabilizer with each mortality outcome. The SMRs of all-cause mortality, suicide, and natural mortality in the bipolar disorder cohort were 5.26, 26.02, and 4.68, respectively. The use of mood stabilizers was significantly associated with decreased risks of all-cause mortality (adjusted HR [aHR]=0.58, p< 0.001), suicide (aHR=0.60, p < 0.001), and natural mortality (aHR=0.55, p < 0.001) within a 5-year follow-up period after index admission. Among the individual mood stabilizers, lithium was associated with the lowest risks of all-cause mortality (aHR=0.38, p < 0.001), suicide (aHR=0.39, p < 0.001), and natural mortality (aHR=0.37, p < 0.001). In addition to having protective effects against suicide and all-cause mortality, mood stabilizers also exert a substantial protective effect against natural mortality, with lithium associated with the lowest risk of mortality.

In Lewis Carroll’s Alice’s Adventures in Wonderland, the eponymous heroine falls down a rabbit hole and finds a flask labeled “Drink Me” (1). Following this instruction, Alice shrinks to a size small enough to fit through the door to the mysterious world of Wonderland (Figure 1). Let us imagine another, less fanciful Alice: a woman of less-thanaverage height, who if she is both sensible and lucky is a neversmoker, drinks alcohol only in moderation, and is able to maintain a healthy weight through diet and exercise. We do not fully understand why, but the good news for our Alice is that as a shorter woman with a healthy lifestyle she has a lower risk of cancer than most of her taller and/or male peers. In this issue of the Journal, Walter and colleagues (2) bring together these two mysteries of cancer epidemiology: a greater incidence among men than women of cancer at shared anatomic sites, and the association of greater height with increased risks for many cancer sites in both sexes. Some of the reasons why Alice and other women have a lower incidence of cancer than men are already understood. Leaving aside cancers that are sex-specific due to anatomical differences between women and men, known environmental risk factors including alcohol intake, smoking, and occupational exposures to carcinogens are likely to contribute to sex differences in cancer risk at several shared sites (3). For example, in most populations the prevalence of smoking has been lower in women than men, and therefore women have had a lower rate of smoking-related cancers such as lung cancer. As smoking patterns of men and women have become more similar in developed countries, the disparity between the sexes in lung cancer risk has largely disappeared (3–5). However, cancer incidence at several other sites is greater among men than women by 50% or more, a finding that is consistent across countries at different stages of economic development but which cannot easily be explained by known risk factors (3). Even less is known about why our Alice’s height should be associated with her risk of cancer. Overall cancer risk increases by 10% to 15% per 10 cm (4 in) of height in both men and women, again consistent across different countries (6). Adult height can be measured accurately in middle age, but it is a marker of developmental processes and exposures that occur in early life and has been linked to a very large number of genetic (7) and environmental (8) factors. It is unknown whether a relatively small number of early-life factors might be conspiring to produce the height–cancer association through multiple mechanisms, or if instead the large number of genetic and environmental determinants of height might influence cancer risk through a single, intermediate mechanism. For example, there has been considerable interest in insulin-like growth factor 1 (IGF-1), a correlate of growth in childhood and of risk for some cancers (9). But taller people may simply have more cells, or it may be that many determinants of growth during normal development (perhaps including IGF-1) also have general effects on tumor growth (8). Given the obvious relationship between height and sex, it is surprising that height and sex differences in cancer risk seem not to have been investigated together before. Walter et al. looked at whether height could statistically account for sex differences in cancer risk in the Vitamins and Lifestyle (VITAL) Study, a cohort of approximately 33 000 women and 32 000 men (2). They found that differences in height might account for a third to a half of the excess risk in men of cancers at shared anatomic sites. As with most previous studies, power was limited for specific cancer sites, but the cancers for which height accounted for a large proportion of the sex differences in risk (kidney cancer, melanoma, and hematological malignancies) have previously been found to be associated with height (6).

There is evidence of increased rates of suicide among veterans when compared to those without history of military service. However, empirical studies of the associations between military service and risk for suicide have reported confl icting results. Results from studies of mortality among Vietnam veterans have suggested that rates of suicide may be elevated following service in a combat area. 1 However, not all studies have reported statistically signifi cant increases in suicide mortality among veterans from the Vietnam War. 2‐4 Assessments of postservice mortality among veterans of the Persian Gulf War similarly failed to identify a statistically signifi cant increase in risk for suicide. 5,6 A more recent study of suicide risk among more than 490,000 veterans of Iraq and Afghanistan did report a statistically signifi cant increase in suicide risk among veterans who had been on active duty (standardized mortality ratio 1.33) and among those who had been diagnosed with a mental disorder and had received services from the Veterans Health Administration (VHA) (standardized mortality ratio 1.77). 7 Analyses of existing survey data, when linked with information on the participant’s manner of death, can be used to identify risk for suicide when veteran status is included in the original data fi le. A recent analysis of more than 300,000 male participants in the National Health Interview Survey series (1986‐ 1997) reported a twofold increase in risk for suicide among veterans when compared to those without self-reported history of military service. 8 Somewhat paradoxically, another prospective study of mortality among more than 500,000 male participants in a large cancer survey using similar methodology failed to identify an increased risk for suicide among veterans. 9 Contradictory fi ndings exist in prior work partially because, while national-level mortality data provide an important surveillance tool for understanding changes in overall and groupspecifi c U.S. rates of suicide, veteran-specifi c data are limited. The National Center for Health Statistics (Centers for Disease Control and Prevention) does not currently upload veteran identifi ers as part of their routine death reporting protocol from states that collect this information. Rates of suicide for the entire U.S. veteran population are therefore not routinely attainable. The consequence of current gaps in data availability has been a general reliance on convenience data (such as state-level mortality records) or other existing data sources (including a veteran identifi er) that are linked with information from the National Death Index. In either case, veteran status is often obtained through self- or proxy-report and the sampling procedures employed by existing studies are unlikely to ensure representation of high-risk subpopulations. Questions surrounding the reliability or validity of much existing data remain largely unanswered. Despite challenges associated with ascertainment of veteran status and the relative lack of data for the identifi cation of clinical and behavioral characteristics associated with increased risk for suicide, our understanding of suicide risk among some veteran groups is improving. By linking administrative data obtained from the VHA with national level cause of death data obtained from the National Death Index, researchers from the VA-funded Serious Mental Illness Treatment Research and Evaluation Center (SMITREC) were able to identify 1,613 suicides among veterans who had received inpatient or outpatient VHA services during the 2000 and 2001 fi scal years. 10 When compared to suicide rates for the general U.S. population, the authors identifi ed a statistically signifi cant increase in the relative risk for suicide for both male (standardized mortality ratio 1.66) and female (standardized mortality ratio 1.87) veterans. 10 Comparisons of rates of suicide for veterans and similarly aged groups from the U.S. general population are useful, yet may lack suffi cient information to identify potential differences in clinical or behavioral characteristics among veterans and nonveterans or between veterans who do and do not receive VHA services, effectively limiting our ability to identify those characteristics associated with increased risk. The introduction and limited expansion of the National Violent Death Reporting System (NVDRS) has provided data that can be used to compare the prevalence and characteristics of suicide among veterans and nonveterans in a small number of states. In 2006, there were 1,594 veteran suicides identifi ed in the 16 states participating in NVDRS and 5,966 suicides among those who were not identifi ed as veterans of military service (approximately 21% of all suicides in these areas). However, results from comparisons of NVDRS data should be interpreted with caution. To date, NVDRS has only been implemented in a limited number of states and the

Sex differences in the risk of hospitalization among patients presenting to US emergency departments with asthma exacerbation, 2010-2012

BackgroundThere has been concern about the risk of suicide among veterans returning from deployment to Afghanistan and Iraq as part of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND). This study assessed suicide risk among OEF/OIF/OND veterans by gender and unit component. Firearm related suicide was also briefly examined.FindingsThe study cohort was identified from records of the US Department of Defense. Vital status and cause of death through 2016 was obtained from the Mortality Data Repository, which obtains data from the National Death Index. Suicide risk was first assessed using standardized mortality ratios (SMR)s, comparing the rate of suicide among all veterans, both collectively and separately by gender and unit component (active vs. reserve/National Guard) to the expected based on the US population adjusted for age, race, sex, and calendar year. Risk of suicide among active duty compared to reserve/National Guard veterans and male compared to female veterans was assessed with hazard ratios (HR) s, generated by Cox proportional hazards models, that included the covariates race, age, marital status, rank, and branch of service. There was an increased risk of suicide when all OEF/OIF/OND Veterans were compared to the US population, (SMR = 1.42; 95%, C.I., 1.38,1.46). Both male and female veterans had an increased risk of suicide when compared to their gender specific non-veteran counterparts, (SMR = 1.40; 95%, C.I., 1.36,1.45 and SMR = 1.85; 95%, C.I., 1.60,2.13), respectively. Active duty veterans had an increased risk of suicide compared to reserve/National Guard veterans, (HR = 1.22; 95%, C.I., 1.14,1.30). Male veterans had an almost 3-fold increased risk compared to female veterans, (HR = 2.85; 95%, C.I., 2.47,3.29). Among all veteran suicides 68.3% involved a firearm, including 68.7% among males and 59.5% among females.ConclusionsAll OEF/OIF/OND veterans have an increased risk of suicide compared to non-veterans. Veterans will benefit from enhanced access to mental health services and initiatives to promote suicide prevention. Strategies that emphasize lethal means safety, an evidence based suicide prevention strategy which includes increasing safe storage practices (i.e., storing firearms unloaded and locked) can help address this increased risk of veteran suicide.

There are marked variations in the risk of hormone-dependent cancers between males and females, and these are likely to reflect sex differences in endogenous hormone profiles. The authors examined sex differences in the risk of hormone-dependent cancers of sex-shared sites by using data from the England and Wales national cancer registry for 1962-1984. Both breast and thyroid cancers showed marked excesses in risk for women, but the female: male ratio peaked around menopause for breast cancer and a puberty for thyroid cancer, suggesting that although female sex hormones may influence the risk of these two cancers, the mechanisms involved are probably different. In the descending colon, the risk of cancer was greater in females than in males at ages under 60 years, but greatest in males at ages above this, whereas in the ascending colon there were no age-specific differences in risk between the sexes. This is consistent with the hypothesis that female reproductive events may decrease a woman's risk of cancer in the descending but not in the ascending colon. Sex differences in bone cancer risk at puberty, particularly for osteosarcomas and Ewing's sarcomas, paralleled known sex differences in skeletal growth; there was a peak in age-specific rates earlier and lower in girls than in boys. Rhabdomyosarcoma, a soft tissue cancer, also showed a rise in risk at puberty with age differences between boys and girls that correlated with sex differences in muscle growth patterns; this suggests that its etiology may be hormonally related as well.

Suicide is a serious public health concern. An increased risk of suicide ideation previously has been reported among survivors of childhood cancer. Suicide mortality was assessed for all potentially eligible survivors (those aged ≥18 years who were ≥5 years after their cancer diagnosis; 7312 survivors). Risk factors for acute suicidal ideation were assessed among clinically evaluated survivors (3096 survivors) and the prevalence of acute ideation was compared with that of community controls (429 individuals). The prevalence of 12-month suicidality was assessed among survivors who could be compared with population data (1255 survivors). Standardized mortality ratios compared rates of suicide mortality among survivors with those of the general population. Risk ratios (RRs) and 95% confidence intervals (95% CIs) derived from generalized linear models identified risk factors associated with acute suicidal ideation. Standardized incidence ratios (SIRs) compared the prevalence of 12-month suicidality among survivors with that of a matched sample from the general population. Survivors reported a similar 12-month prevalence of ideation compared with the general population (SIR, 0.68; 95% CI, 0.35-1.01) and a lower prevalence of suicidal behaviors (planning: SIR, 0.17 [95% CI, 0.07-0.27]; attempts: SIR, 0.07 [95% CI, 0.00-0.15]) and mortality (standardized mortality ratio, 0.60; 95% CI, 0.34-0.86). Among survivors, depression (RR, 12.30; 95% CI, 7.89-19.11), anxiety (RR, 2.19; 95% CI, 1.40-3.40), and financial stress (RR, 1.47; 95% CI, 1.00-2.15) were found to be associated with a higher prevalence of acute suicidal ideation. Survivors of childhood cancer were found to be at a lower risk of suicidal behaviors and mortality, yet endorsed a prevalence of ideation similar to that of the general population. These results are in contrast to previous findings of suicidal ideation among survivors and support the need for further research to inform screening strategies and interventions. The purpose of the current study was to compare the risk of suicidal ideation, behaviors, and mortality in adult survivors of childhood cancer with those of the general population. Risk factors associated with suicidal ideation among survivors of childhood cancer also were examined. Survivors of childhood cancer reported a similar risk of ideation compared with the general population, but a lower risk of suicidal behaviors and mortality. Psychological health and financial stressors were found to be risk factors associated with suicidal ideation. Although adult survivors of childhood cancer did not report a greater risk of suicidality compared with the general population, psychosocial care in survivorship remains essential.

Accelerating the Growth of Evidence-Based Care for Women and Men Veterans.

This study sought to determine if women are more likely than men to experience an episode of major depression in response to stressful life events. Sex differences in event-related risk for depression were examined by means of secondary analyses employing data from the Americans' Changing Lives study. The occurrence and time of occurrence of depression onset and instances of stressful life events within a 12-month period preceding a structured interview were documented in a community-based sample of 1024 men and 1800 women. Survival analytical techniques were used to examine sex differences in risk for depression associated with generic and specific stressful life events. Women were approximately three times more likely than men to experience major depression in response to any stressful life event. Women and men did not differ in risk for depression associated with the death of a spouse or child, events affecting their relationship to a spouse/partner (divorce and marital/love problems) or events corresponding to acute financial or legal difficulties. Women were at elevated risk for depression associated with more distant interpersonal losses (death of a close friend or relative) and other types of events (change of residence, physical attack, or life-threatening illness/injury). Stressful life events overall, with some exceptions among specific event types, pose a greater risk for depression among women compared to men.

ABSTRACTBackground:Living with multiple sclerosis (MS) means facing significant obstacles in managing the unpredictable nature of this lifelong condition. Studies highlight a concerning connection between the disease and an elevated risk of suicide. In this study, we assessed the prevalence of suicide and suicide mortality risk in people with MS (PwMS).Methods:A comprehensive and systematic search of Medline, EMBASE, Scopus, and Web of Science databases was conducted. Studies of any design were included if they reported at least one of the following outcomes: (1) the prevalence of suicide ideation, suicide attempts, suicide deaths, and the proportion of suicide deaths among total deaths in MS populations (2) the risk of suicide mortality in PwMS compared to healthy controls.Results:The systematic review and meta‐analysis included 64 studies across 19 countries, predominantly from Europe and North America, encompassing over 200,000 PwMS. The pooled prevalence of suicide ideation was 22.6% (95% CI: 16.9–28.3). Suicide attempts were reported at 3.4% (95% CI: 1.6–5.2), while suicide mortality was 0.5% (95% CI: 0.3–0.7), accounting for 2.1% (95% CI: 1.5–2.7) of total mortality in PwMS. PwMS had a significantly higher suicide mortality risk compared to healthy controls (standardized mortality ratio [SMR] = 1.49, 95% CI: 1.08–2.05).Conclusion:This study highlights the elevated suicide mortality risk among PwMS, underscoring the urgent need for integrated mental health care in MS management. Future research should explore the impact of disease‐modifying therapies, protective factors, and standardized risk assessment tools to improve early intervention and reduce suicidal behavior in this vulnerable population.

Sex differences have been reported for diseases of the musculoskeletal system (MSK) as well as the risk for injuries to tissues of the MSK system. For females, some of these occur prior to the onset of puberty, following the onset of puberty, and following the onset of menopause. Therefore, they can occur across the lifespan. While some conditions are related to immune dysfunction, others are associated with specific tissues of the MSK more directly. Based on this life spectrum of sex differences in both risk for injury and onset of diseases, a role for sex hormones in the initiation and progression of this risk is somewhat variable. Sex hormone receptor expression and functioning can also vary with life events such as the menstrual cycle in females, with different tissues being affected. Furthermore, some sex hormone receptors can affect gene expression independent of sex hormones and some transitional events such as puberty are accompanied by epigenetic alterations that can further lead to sex differences in MSK gene regulation. Some of the sex differences in injury risk and the post-menopausal disease risk may be “imprinted” in the genomes of females and males during development and sex hormones and their consequences only modulators of such risks later in life as the sex hormone milieu changes. The purpose of this review is to discuss some of the relevant conditions associated with sex differences in risks for loss of MSK tissue integrity across the lifespan, and further discuss several of the implications of their variable relationship with sex hormones, their receptors and life events.

PurposeThere are notable geographic variations in incidence rates of suicide both in Japan and globally. Previous studies have found that rurality/urbanity shapes intra-regional differences in suicide mortality, and suicide risk associated with rurality can vary significantly by gender and age. This study aimed to examine spatial patterning of and rural–urban differences in suicide mortality by gender and age group across 1887 municipalities in Japan between 2009 and 2017.MethodsSuicide data were obtained from suicide statistics of the Ministry of Health, Labour and Welfare in Japan. We estimated smoothed standardized mortality ratios for suicide for each of the municipalities and investigated associations with level of rurality/urbanity using Bayesian hierarchical models before and after adjusting for socioeconomic characteristics.ResultsThe results of the multivariate analyses showed that, for males aged 0–39 and 40–59 years, rural residents tended to have a higher suicide risk compared to urban ones. For males aged 60+ years, a distinct rural–urban gradient in suicide risk was not observed. For females aged 0–39 years, a significant association between suicide risk and rurality was not observed, while for females aged 40–59 years and females aged 60 years or above, the association was a U-shaped curve.ConclusionOur results showed that geographical distribution of and rural–urban differences in suicide mortality in Japan differed substantially by gender and age. These findings suggest that it is important to take demographic factors into consideration when municipalities allocate resources for suicide prevention.

Objectives: to measure sex differences in the risk of receiving potentially inappropriate prescription drugs and to examine what are the factors that contribute to these differences.Design: a retrospective cohort study.Setting: community setting of British Columbia, Canada.Participants: residents of British Columbia aged 65 and older (n = 660,679).Measurements: we measured 2013 period prevalence of prescription dispensations satisfying the American Geriatrics Society's 2012 version of the Beers Criteria for potentially inappropriate medication use in older adults. We used logistic regressions to test for associations between this outcome and a number of clinical and socioeconomic factors.Results: a larger share of women (31%) than of men (26%) filled one or more potentially inappropriate prescription in the community. The odds of receiving potentially inappropriate prescriptions are associated with several clinical and socioeconomic factors. After controlling for those factors, community-dwelling women were at 16% higher odds of receiving a potentially inappropriate prescription than men (adjusted odds ratio = 1.16, 95% confidence interval = 1.12–1.21). Much of this sex difference stemmed from women's increased odds of receiving potentially inappropriate prescriptions for benzodiazepines and other hypnotics, for tertiary tricyclic antidepressants and for non-selective NSAIDs.Conclusion: there are significant sex differences in older adults' risk of receiving a potentially inappropriate prescription as a result of complex intersections between gender and other social constructs. Appropriate responses will therefore require changes in the information, norms and expectations of both prescribers and patients.

OBJECTIVE—In participants of the Diabetes Prevention Program (DPP) randomized to intensive lifestyle modification (ILS), meeting ILS goals strongly correlated with prevention of diabetes in the group as a whole. Men met significantly more ILS goals than women but had a similar incidence of diabetes. Therefore, we explored sex differences in risk factors for diabetes and the effect of ILS on risk factors.RESEARCH DESIGN AND METHODS—Baseline risk factors for diabetes and percent change in risk factors over the first year in men versus women were compared using Wilcoxon's rank-sum tests.RESULTS—At baseline, men were older and had a larger waist circumference; higher fasting plasma glucose concentration, caloric intake, and blood pressure; and lower HDL cholesterol and corrected insulin response than women, who were less physically active and had a higher BMI (P < 0.01 for all comparisons). Over the first year of the DPP, no sex difference in risk factors for diabetes was observed for those who lost <3% body weight. Weight loss of 3–7% body weight yielded greater decreases in 2-h glucose (P < 0.01), insulin concentration (P < 0.04), and insulin resistance (P < 0.03) in men than in women. Weight loss of >7% body weight resulted in greater decreases in 2-h glucose (P < 0.01), triglyceride level (P < 0.01), and A1C (P < 0.03) in men than in women.CONCLUSIONS—Weight loss >3% body weight yielded greater reduction in risk factors for diabetes in men than in women. Despite the more favorable effects of ILS in men, baseline risk factors were more numerous in men and likely obscured any sex difference in incident diabetes.