Intersection of adverse childhood experiences, suicide and overdose prevention.

Adverse childhood experiences (ACEs), suicide and overdose are linked across the life course and across generations and share common individual-, interpersonal-, community- and societal-level risk factors. The purpose of this review is to summarise the shared aetiology of these public health issues, synthesise evidence regarding potential community- and societal-level prevention strategies and discuss future research and practice directions.Growing evidence shows the potential for community- and societal-level programmes and policies, including higher minimum wage; expanded Medicaid eligibility; increased earned income tax credits, child tax credits and temporary assistance for needy families benefits; Paid Family Leave; greater availability of affordable housing and rental assistance; and increased participation in the Supplemental Nutrition Assistance Program (SNAP), to contribute to ACEs, suicide and overdose prevention. Considerations for future prevention efforts include (1) expanding the evidence base through rigorous research and evaluation; (2) assessing the implications of prevention strategies for equity; (3) incorporating a relational health perspective; (4) enhancing community capacity to implement, scale and sustain evidenced-informed prevention strategies; and (5) acknowledging that community- and societal-level prevention strategies are longer-term strategies.

A unified metric of human immune health.

Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls. Despite the high penetrance of monogenic lesions, differences between individuals in diverse immune parameters tended to dominate over those attributable to disease conditions or medication use. Unsupervised or supervised machine learning independently identified a score that distinguished healthy participants from patients with monogenic diseases, thus suggesting a quantitative immune health metric (IHM). In ten independent datasets, the IHM discriminated healthy from polygenic autoimmune and inflammatory disease states, marked aging in clinically healthy individuals, tracked disease activities and treatment responses in both immunological and nonimmunological diseases, and predicted age-dependent antibody responses to immunizations with different vaccines. This discriminatory power goes beyond that of the classical inflammatory biomarkers C-reactive protein and interleukin-6. Thus, deviations from health in diverse conditions, including aging, have shared systemic immune consequences, and we provide a web platform for calculating the IHM for other datasets, which could empower precision medicine.

Economic Cost of U.S. Suicide and Nonfatal Self-harm.

INTRODUCTION: The U.S. age-adjusted suicide rate is 35% higher than two decades ago and the COVID-19 pandemic era highlighted the urgent need to address nonfatal self-harm, particularly among youth. This study aimed to report the estimated annual economic cost of U.S. suicide and nonfatal self-harm. METHODS: In 2023 CDC's WISQARS Cost of Injury provided the retrospective number of suicides and nonfatal self-harm injury emergency department (ED) visits from national surveillance sources by sex and age group, as well as the estimated annual economic cost of associated medical spending, lost work productivity, reduced quality of life from injury morbidity, and avoidable mortality based on the value of statistical life during 2015-2020. RESULTS: The economic cost of suicide and nonfatal self-harm averaged $510 billion (2020 USD) annually, the majority from life years lost to suicide. Working-aged adults (aged 25-64 years) comprised nearly 75% of the average annual economic cost of suicide ($356B of $484B) and children and younger adults (aged 10-44 years) comprised nearly 75% of the average annual economic cost of nonfatal self-harm injuries ($19B of $26B). CONCLUSIONS: Suicide and self-harm have substantial societal costs. Measuring the consequences in terms of comprehensive economic cost can inform investments in suicide prevention strategies.

CDC Guidance for Community Assessment and Investigation of Suspected Suicide Clusters, United States, 2024.

This report is the second of three reports in the MMWR supplement updating CDC's guidance for investigating and responding to suicide clusters. The first report, Background and Rationale - CDC Guidance for Assessing, Investigating, and Responding to Suicide Clusters, United States, 2024, describes an overview of suicide clusters, methods used to develop the supplement guidance, and intended use of the supplement reports. The final report, CDC Guidance for Community Response to Suicide Clusters, United States, 2024, describes how local public health and community leaders can develop a response plan for suicide clusters. This report provides updated guidance for the approach to assessing and investigating suspected suicide clusters. Specifically, this approach will guide lead agencies in determining whether a confirmed suicide cluster exists, what concerns are in the community, and what the specific characteristics are of the suspected or confirmed suicide cluster. The guidance in this report is intended to support and assist lead agencies and their community prepare for, assess, and investigate suicide clusters. The steps provided in this report can be adapted to the local context, culture, capacity, circumstances, and needs for each suspected suicide cluster.

CDC Guidance for Community Response to Suicide Clusters, United States, 2024.

This is the third of three reports in the MMWR supplement that updates and expands CDC's guidance for assessing, investigating, and responding to suicide clusters based on current science and public health practice. The first report, Background and Rationale - CDC Guidance for Communities Assessing, Investigating, and Responding to Suicide Clusters, United States, 2024, describes an overview of suicide clusters, methods used to develop the supplement guidance, and intended use of the supplement reports. The second report, CDC Guidance for Community Assessment and Investigation of Suspected Suicide Clusters, United States, 2024, describes the potential methods, data sources, and analysis that communities can use to identify and confirm suspected suicide clusters and better understand the relevant issues. This report describes how local public health and community leaders can develop a response plan for suicide clusters. Specifically, the steps for responding to a suicide cluster include preparation, direct response, and action for prevention. These steps are not intended to be explicitly adopted but rather adapted into the local context, culture, capacity, circumstances, and needs for each suicide cluster.

Background and Rationale - CDC Guidance for Communities Assessing, Investigating, and Responding to Suicide Clusters, United States, 2024.

To assist community leaders in public health, mental health, education, and other fields with developing a community response plan for suicide clusters or for situations that might develop into suicide clusters, in 1988, CDC published Recommendations for a Community Plan for the Prevention and Containment of Suicide Clusters (MMWR Suppl 1988;37[No. Suppl 6]:1-12). Since that time, the reporting and investigation of suicide cluster events has increased, and more is known about cluster risk factors, assessment, and identification. This supplement updates and expands CDC guidance for assessing, investigating, and responding to suicide clusters based on current science and public health practice. This report is the first of three in the MMWR supplement that describes an overview of suicide clusters, information about the other reports in this supplement, methods used to develop the supplement guidance, and the intended use of the supplement reports. The second report, CDC Guidance for Community Assessment and Investigation of Suspected Suicide Clusters - United States 2024, describes the potential methods, data sources and analysis that communities can use to identify and confirm suspected suicide clusters, and better understand the relevant issues. The final report, CDC Guidance for Community Response to Suicide Clusters - United States, 2024, describes how local public health and community leaders can develop a response plan for suicide clusters. The guidance in this supplement is intended as a conceptual framework that can be used by public health practitioners and state and local health departments to develop response plans for assessing and investigating suspected clusters that are tailored to the needs, resources, and cultural characteristics of their communities.

Interrupting an IFN-γ-dependent feedback loop in the syndrome of pyogenic arthritis with pyoderma gangrenosum and acne.

OBJECTIVES: To study the molecular pathogenesis of PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome, a debilitating hereditary autoinflammatory disease caused by dominant mutation in PSTPIP1. METHODS: Gene knock-out and knock-in mice were generated to develop an animal model. THP1 and retrovirally transduced U937 human myeloid leukaemia cell lines, peripheral blood mononuclear cells, small interfering RNA (siRNA) knock-down, site-directed mutagenesis, cytokine immunoassays, coimmunoprecipitation and immunoblotting were used to study inflammasome activation. Cytokine levels in the skin were evaluated by immunohistochemistry. Responsiveness to Janus kinase (JAK) inhibitors was evaluated ex vivo with peripheral blood mononuclear cells and in vivo in five treatment-refractory PAPA patients. RESULTS: The knock-in mouse model of PAPA did not recapitulate the human disease. In a human myeloid cell line model, PAPA-associated PSTPIP1 mutations activated the pyrin inflammasome, but not the NLRP3, NLRC4 or AIM2 inflammasomes. Pyrin inflammasome activation was independent of the canonical pathway of pyrin serine dephosphorylation and was blocked by the p.W232A PSTPIP1 mutation, which disrupts pyrin-PSTPIP1 interaction. IFN-γ priming of monocytes from PAPA patients led to IL-18 release in a pyrin-dependent manner. IFN-γ was abundant in the inflamed dermis of PAPA patients, but not patients with idiopathic pyoderma gangrenosum. Ex vivo JAK inhibitor treatment attenuated IFN-γ-mediated pyrin induction and IL-18 release. In 5/5 PAPA patients, the addition of JAK inhibitor therapy to IL-1 inhibition was associated with clinical improvement. CONCLUSION: PAPA-associated PSTPIP1 mutations trigger a pyrin-IL-18-IFN-γ positive feedback loop that drives PAPA disease activity and is a target for JAK inhibition.

Suicide Rates by Industry and Occupation - National Vital Statistics System, United States, 2021.

The suicide rate among the U.S. working-age population has increased approximately 33% during the last 2 decades. To guide suicide prevention strategies, CDC analyzed suicide deaths by industry and occupation in 49 states, using data from the 2021 National Vital Statistics System. Industry (the business activity of a person's employer or, if self-employed, their own business) and occupation (a person's job or the type of work they do) are distinct ways to categorize employment. The overall suicide rates by sex in the civilian noninstitutionalized working population were 32.0 per 100,000 among males and 8.0 per 100,000 among females. Major industry groups with the highest suicide rates included Mining (males = 72.0); Construction (males = 56.0; females = 10.4); Other Services (e.g., automotive repair; males = 50.6; females = 10.4); Arts, Entertainment, and Recreation (males = 47.9; females = 15.0); and Agriculture, Forestry, Fishing, and Hunting (males = 47.9). Major occupation groups with the highest suicide rates included Construction and Extraction (males = 65.6; females = 25.3); Farming, Fishing, and Forestry (e.g., agricultural workers; males = 49.9); Personal Care and Service (males = 47.1; females = 15.9); Installation, Maintenance, and Repair (males = 46.0; females = 26.6); and Arts, Design, Entertainment, Sports, and Media (males = 44.5; females = 14.1). By integrating recommended programs, practices, and training into existing policies, workplaces can be important settings for suicide prevention. CDC provides evidence-based suicide prevention strategies in its Suicide Prevention Resource for Action and Critical Steps Your Workplace Can Take Today to Prevent Suicide, NIOSH Science Blog.

Nonfatal suicidal behaviors among former active duty servicemembers-United States, 2013-2019.

Introduction: Examine characteristics associated with increased odds of nonfatal suicidal behaviors among former active-duty servicemembers (F-ADSM) using data from the 2013-2019 National Survey on Drug Use and Health (NSDUH). Methods: F-ADSM were respondents who reported being separated/retired from the military and previously serving on active-duty. For each outcome of interest (suicidal ideation, made a suicide plan, made a suicide attempt), we used multivariable logistic regression with backwards elimination to identify characteristics with statistically significant associations. Results: In the 12 months preceding the survey, 3.6% of F-ADSM reported suicidal ideation, 1.0% reported making a plan, and 0.3% reported making a suicide attempt. There were increased odds of self-reported suicide attempts among F-ADSM who were female; aged 18-49 years; non-Hispanic black; gay or bisexual; divorced/separated or widowed; not employed; in poverty; binged alcohol in the past month; or ever had a major depressive episode. Conclusions: Suicide can be prevented through a comprehensive, upstream approach addressing veteran's holistic needs to prevent them from becoming suicidal in the first place, and support veterans at increased risk.

Association of Recent Violence Encounters With Suicidal Ideation Among Adolescents With Depression.

Importance: Suicide prevention is an important component of depression management. Knowledge about depressed adolescents with increased risk for suicide can inform suicide prevention efforts. Objective: To describe the risk of documented suicidal ideation within a year following a diagnosis of depression and to examine how the risk of documented suicidal ideation differed by recent violence encounter status among adolescents with new depression diagnoses. Design, Setting, and Participants: Retrospective cohort study in clinical settings including outpatient facilities, emergency departments, and hospitals. Using IBM's Explorys database containing electronic health records from 26 US health care networks, this study observed a cohort of adolescents with new depression diagnoses from 2017 to 2018 for up to 1 year. Data were analyzed from July 2020 to July 2021. Exposures: Recent violence encounter was defined by a diagnosis of child maltreatment (physical, sexual, or psychological abuse or neglect) or physical assault within 1 year before depression diagnosis. Main Outcomes and Measures: The main outcome was diagnosis of suicidal ideation within 1 year following depression diagnosis. Multivariable adjusted risk ratios of suicidal ideation were calculated for overall recent violence encounters and for individual forms of violence. Results: Among a total of 24 047 adolescents with depression, 16 106 (67.0%) were female and 13 437 (55.9%) were White. A total of 378 had experienceda violence (hereafter, encounter group) and 23 669 had not (hereafter, nonencounter group). Following the diagnosis of depression, 104 adolescents with any past-year violence encounter (27.5%) documented suicidal ideation within 1 year. In contrast, 3185 adolescents in the nonencounter group (13.5%) experienced thoughts of suicide following the diagnosis of depression. In multivariable analyses, those with any violence encounter had 1.7 times (95% CI 1.4-2.0) higher risk of documented suicidal ideation compared with those in the nonencounter group (P < .001). Among different forms of violence, sexual abuse (risk ratio, 2.1; 95% CI, 1.6-2.8) and physical assault (risk ratio, 1.7; 95% CI, 1.3-2.2) were associated with significantly increased risk of suicidal ideation. Conclusions and Relevance: Among adolescents with depression, persons who experienced past-year violence encounters showed a higher rate of suicidal ideation than those who had not. These findings highlight the importance of identifying and accounting for past violence encounters when treating adolescents with depression to reduce risk of suicide. Public health approaches to prevent violence may help to avert morbidity associated with depression and suicidal ideation.

Multiomics integration of 22 immune-mediated monogenic diseases reveals an emergent axis of human immune health.

Monogenic diseases are often studied in isolation due to their rarity. Here we utilize multiomics to assess 22 monogenic immune-mediated conditions with age- and sex-matched healthy controls. Despite clearly detectable disease-specific and "pan-disease" signatures, individuals possess stable personal immune states over time. Temporally stable differences among subjects tend to dominate over differences attributable to disease conditions or medication use. Unsupervised principal variation analysis of personal immune states and machine learning classification distinguishing between healthy controls and patients converge to a metric of immune health (IHM). The IHM discriminates healthy from multiple polygenic autoimmune and inflammatory disease states in independent cohorts, marks healthy aging, and is a pre-vaccination predictor of antibody responses to influenza vaccination in the elderly. We identified easy-to-measure circulating protein biomarker surrogates of the IHM that capture immune health variations beyond age. Our work provides a conceptual framework and biomarkers for defining and measuring human immune health.

Case report: Novel variants in RELA associated with familial Behcet's-like disease.

RELA haploinsufficiency is a recently described autoinflammatory condition presenting with intermittent fevers and mucocutaneous ulcerations. The RELA gene encodes the p65 protein, one of five NF-κB family transcription factors. As RELA is an essential regulator of mucosal homeostasis, haploinsufficiency leads to decreased NF-κB signaling which promotes TNF-driven mucosal apoptosis with impaired epithelial recovery. Thus far, only eight cases have been reported in the literature. Here, we report four families with three novel and one previously described pathogenic variant in RELA. These four families included 23 affected individuals for which genetic testing was available in 16. Almost half of these patients had been previously diagnosed with more common rheumatologic entities (such as Behcet's Disease; BD) prior to the discovery of their pathogenic RELA variants. The most common clinical features were orogenital ulcers, rash, joint inflammation, and fever. The least common were conjunctivitis and recurrent infections. Clinical variability was remarkable even among familial cases, and incomplete penetrance was observed. Patients in our series were treated with a variety of medications, and benefit was observed with glucocorticoids, colchicine, and TNF inhibitors. Altogether, our work adds to the current literature and doubles the number of reported cases with RELA-Associated Inflammatory Disease (RAID). It reaffirms the central importance of the NF-κB pathway in immunity and inflammation, as well as the important regulatory role of RELA in mucosal homeostasis. RELA associated inflammatory disease should be considered in all patients with BD, particularly those with early onset and/or with a strong family history.

Social Determinants of Health Influence Early Outcomes Following Lumbar Spine Surgery.

Background: Disparities among social determinants of health (SDoH) can impact overall well-being and surgical outcomes. The purpose of this study was to identify SDoH for patients who underwent lumbar spine surgery and evaluate their relationship to the postoperative outcomes of length of stay (LOS), discharge disposition, and readmissions. Methods: We conducted a retrospective observational study of patients who underwent lumbar spine surgery from July 2017 to January 2021. We used a self-reported SDoH survey in conjunction with the electronic medical record to gather patient information. Multivariate analysis was used to evaluate the relationships between patient demographics, SDoH, and postoperative outcomes. Results: A total of 951 patients underwent lumbar spine surgery: 484 (50.9%) had decompressive laminectomy alone without fusion, and 467 (49.1%) had decompressive laminectomy with instrumented posterolateral fusion. When controlling for age, American Society of Anesthesiologists physical status classification, and surgery type, the SDoH of being currently married or having a life partner was associated with shorter LOS and decreased likelihood of discharge to a skilled nursing facility. Financial strain was associated with longer LOS, while attending church was associated with a decreased likelihood of 30-day emergency department (ED) return. Conclusion: This study identified various SDoH that may influence postoperative lumbar spine surgery outcomes of LOS, discharge disposition, 30-day ED return, and 30-day readmission. Patients at risk for suboptimal outcomes appear to be those with lower financial resources, less in-home support, and lower social connectivity. Routine screening of SDoH may enable care teams to effectively allocate resources for at-risk patients.

Suicides Among American Indian or Alaska Native Persons - National Violent Death Reporting System, United States, 2015-2020.

Compared with the general U.S. population, American Indian or Alaska Native (AI/AN) persons, particularly those who are not Hispanic or Latino (Hispanic) AI/AN, are disproportionately affected by suicide; rates among this group consistently surpass those among all other racial and ethnic groups (1). Suicide rates among non-Hispanic AI/AN persons increased nearly 20% from 2015 (20.0 per 100,000) to 2020 (23.9), compared with a <1% increase among the overall U.S. population (13.3 and 13.5, respectively) (1). Understanding characteristics of suicide among AI/AN persons is critical to developing and implementing effective prevention strategies. A 2018 report described suicides in 18 states among non-Hispanic AI/AN persons only (2). The current study used 2015-2020 National Violent Death Reporting System (NVDRS) data among 49 states, Puerto Rico, and the District of Columbia to examine differences in suicide characteristics and contributing circumstances among Hispanic and non-Hispanic AI/AN populations, including multiracial AI/AN. Results indicated higher odds across a range of circumstances, including 10 of 14 relationship problems (adjusted odds ratio [aOR] range = 1.2-3.8; 95% CI range = 1.0-5.3) and six of seven substance use problems (aOR range = 1.2-2.3; 95% CI range = 1.1-2.5), compared with non-AI/AN persons. Conversely, AI/AN decedents had reduced odds of having any current known mental health condition, any history of mental health or substance use treatment, and other common risk factors (aOR range = 0.6-0.8; 95% CI = 0.2-0.9). Suicide is preventable. Communities can implement a comprehensive public health approach to suicide prevention that addresses long-standing inequities affecting AI/AN populations (3).

Suicide Among Males Across the Lifespan: An Analysis of Differences by Known Mental Health Status.

INTRODUCTION: Suicide among males is a major public health challenge. In 2019, males accounted for nearly 80% of the suicide deaths in the U.S., and suicide was the eighth leading cause of death for males aged ≥10 years. Males who die by suicide are less likely to have known mental health conditions than females; therefore, it is important to identify prevention points outside of mental health systems. The purpose of this analysis was to compare suicide characteristics among males with and without known mental health conditions by age group to inform prevention. METHODS: Suicides among 4 age groups of males were examined using the 3 most recent years of data at the time of the analysis (2016-2018) from the Centers for Disease Control and Prevention's National Violent Death Reporting System. Decedents with and without known mental health conditions were compared within age groups. The analysis was conducted in August 2021. RESULTS: Most male suicide decedents had no known mental health conditions. More frequently, those without known mental health conditions died by firearm, and many tested positive for alcohol. Adolescents, young adults, and middle-aged males without known mental health conditions more often had relationship problems, arguments, and/or a crisis as a precipitating circumstance than those with known mental health conditions. CONCLUSIONS: Acute stressors more often precipitated suicides of males without known mental health conditions, and they more often involved firearms. These findings underscore the importance of mitigating acute situational stressors that could contribute to emotionally reactive/impulsive suicides. Suicide prevention initiatives targeting males might focus on age-specific precipitating circumstances in addition to standard psychiatric markers.

Vital Signs: Changes in Firearm Homicide and Suicide Rates - United States, 2019-2020.

INTRODUCTION: The majority of homicides (79%) and suicides (53%) in the United States involved a firearm in 2020. High firearm homicide and suicide rates and corresponding inequities by race and ethnicity and poverty level represent important public health concerns. This study examined changes in firearm homicide and firearm suicide rates coinciding with the emergence of the COVID-19 pandemic in 2020. METHODS: National vital statistics and population data were integrated with urbanization and poverty measures at the county level. Population-based firearm homicide and suicide rates were examined by age, sex, race and ethnicity, geographic area, level of urbanization, and level of poverty. RESULTS: From 2019 to 2020, the overall firearm homicide rate increased 34.6%, from 4.6 to 6.1 per 100,000 persons. The largest increases occurred among non-Hispanic Black or African American males aged 10-44 years and non-Hispanic American Indian or Alaska Native (AI/AN) males aged 25-44 years. Rates of firearm homicide were lowest and increased least at the lowest poverty level and were higher and showed larger increases at higher poverty levels. The overall firearm suicide rate remained relatively unchanged from 2019 to 2020 (7.9 to 8.1); however, in some populations, including AI/AN males aged 10-44 years, rates did increase. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: During the COVID-19 pandemic, the firearm homicide rate in the United States reached its highest level since 1994, with substantial increases among several population subgroups. These increases have widened disparities in rates by race and ethnicity and poverty level. Several increases in firearm suicide rates were also observed. Implementation of comprehensive strategies employing proven approaches that address underlying economic, physical, and social conditions contributing to the risks for violence and suicide is urgently needed to reduce these rates and disparities.

Rural-Urban Comparisons in the Rates of Self-Harm, U.S., 2018.

INTRODUCTION: This study compares rural and urban differences in the rates of nonfatal self-harm in the U.S. in 2018. METHODS: Nationwide Emergency Department Sample and Census data were analyzed to calculate the RR of emergency department visits for self-harm between rural and urban residents. The analyses were conducted in 2021. RESULTS: Among a weighted total of 488,000 emergency department visits for self-harm in the U.S., 80.5% were urban residents, and 18.3% were rural residents. In both settings, poisoning was the most common mechanism for self-harm, followed by cutting. Firearm-related self-harm and suffocation each accounted for <2% of total self-harm cases. Overall, the age-adjusted emergency department visit rate for self-harm was 252.3 per 100,000 for rural residents, which was 1.5 (95% CI=1.4, 1.6) times greater than the rate for urban residents (170.8 per 100,000 residents). The rates of self-harm among rural residents were higher than those of urban residents for both male and female residents, for all age groups except people aged ≥65 years, and by all mechanisms. CONCLUSIONS: Comprehensive suicide prevention strategies tailored to rural communities may mitigate the rural-urban disparity in morbidity from suicidal behavior.