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Despite the significant scientific advancement in deciphering the "deaths of despair" narrative, most relevant studies have focused on drug-, alcohol-, and suicide-related (DAS) deaths. This study directly investigated despair as a determinant of death and the temporal variation and racial heterogeneity among individuals. We used psychological distress (PD) as a proxy for despair and drew data from the US National Health Interview Survey-Linked Mortality Files 1997 to 2014, CDC (Centers for Disease Control and Prevention) Multiple Cause of Death database 1997 to 2014, CDC bridged-race population files 1997 to 2014, Current Population Survey 1997 to 1999, and the American Community Survey 2000 to 2014. We used Cox proportional hazards models to estimate mortality hazard ratios of PD and compared age-standardized PD- and DAS-related mortality rates by race/ethnicity and over time. We found that while Whites had a lower prevalence of PD than Blacks and Hispanics throughout the whole period, they underwent distinctive increases in PD-related death and have had a higher PD-related mortality rate than Blacks and Hispanics since the early 2000s. This was predominantly due to Whites' relatively high and increasing vulnerability to PD less the prevalence of PD. Furthermore, PD induced a more pervasive mortality consequence than DAS combined for Whites and Blacks. In addition, PD- and DAS-related deaths displayed a concordant trend among Whites but divergent patterns for Blacks and Hispanics. These findings suggest that 1) DAS-related deaths underestimated the mortality consequence of despair for Whites and Blacks but overestimated it for Hispanics; and 2) despair partially contributed to the DAS trend among Whites but probably not for Blacks and Hispanics.
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Morte , Etnicidade , Angústia Psicológica , Estresse Psicológico , Humanos , Etnicidade/psicologia , Etnicidade/estatística & dados numéricos , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Estados Unidos/epidemiologia , Brancos/psicologia , Brancos/estatística & dados numéricos , Estresse Psicológico/epidemiologia , Estresse Psicológico/etnologia , Estresse Psicológico/mortalidade , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricosRESUMO
This study aims to identify the timescale of suicidal thinking, leveraging real-time monitoring data and a number of different analytic approaches. Participants were 105 adults with past week suicidal thoughts who completed a 42-d real-time monitoring study (total number of observations = 20,255). Participants completed two forms of real-time assessments: traditional real-time assessments (spaced hours apart each day) and high-frequency assessments (spaced 10 min apart over 1 h). We found that suicidal thinking changes rapidly. Both descriptive statistics and Markov-switching models indicated that elevated states of suicidal thinking lasted on average 1 to 3 h. Individuals exhibited heterogeneity in how often and for how long they reported elevated suicidal thinking, and our analyses suggest that different aspects of suicidal thinking operated on different timescales. Continuous-time autoregressive models suggest that current suicidal intent is predictive of future intent levels for 2 to 3 h, while current suicidal desire is predictive of future suicidal desire levels for 20 h. Multiple models found that elevated suicidal intent has on average shorter duration than elevated suicidal desire. Finally, inferences about the within-person dynamics of suicidal thinking on the basis of statistical modeling were shown to depend on the frequency at which data was sampled. For example, traditional real-time assessments estimated the duration of severe suicidal states of suicidal desire as 9.5 h, whereas the high-frequency assessments shifted the estimated duration to 1.4 h.
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Modelos Estatísticos , Ideação Suicida , Adulto , Humanos , Fatores de Tempo , IntençãoRESUMO
In recent years, the United States has been experiencing historically high suicide rates. In the face of mental health care provider shortages that leave millions needing to travel longer to find providers with schedule openings, if any are available at all, the inaccessibility of mental health care has become increasingly central in explaining suicidality. To examine the relationship between access to care and suicide, we leverage a dataset mapping all licensed US psychiatrists and psychotherapists (N= 711,214), as of early 2020, and employ real-world transportation data to model patients' mobility barriers. We find a strong association between reduced mental health care provider spatial-social accessibility and heightened suicide risk. Using a machine learning approach to condition on a host of 22 contextual factors known to be implicated in suicide (e.g., race, education, divorce, gun shop prevalence), we find that in locales where individuals seeking care can access fewer mental health care providers, already more likely to be saturated by demand, suicide risk is increased (3.2% for each reduced SD of psychiatrist accessibility; 2.3% for psychotherapists). Additionally, we observe that local spatial-social accessibility inequalities are associated with further heightened risk of suicide, underscoring the need for research to account for the highly localized barriers preventing many Americans from accessing needed mental health services.
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Serviços de Saúde Mental , Suicídio , Humanos , Estados Unidos , Acessibilidade aos Serviços de Saúde , Saúde Mental , Ideação SuicidaRESUMO
Air pollution poses well-established risks to physical health, but little is known about its effects on mental health. We study the relationship between wildfire smoke exposure and suicide risk in the United States in 2007 to 2019 using data on all deaths by suicide and satellite-based measures of wildfire smoke and ambient fine particulate matter (PM2.5) concentrations. We identify the causal effects of wildfire smoke pollution on suicide by relating year-over-year fluctuations in county-level monthly smoke exposure to fluctuations in suicide rates and compare the effects across local areas and demographic groups that differ considerably in their baseline suicide risk. In rural counties, an additional day of smoke increases monthly mean PM2.5 by 0.41 µg/m3 and suicide deaths by 0.11 per million residents, such that a 1-µg/m3 (13%) increase in monthly wildfire-derived fine particulate matter leads to 0.27 additional suicide deaths per million residents (a 2.0% increase). These effects are concentrated among demographic groups with both high baseline suicide risk and high exposure to outdoor air: men, working-age adults, non-Hispanic Whites, and adults with no college education. By contrast, we find no evidence that smoke pollution increases suicide risk among any urban demographic group. This study provides large-scale evidence that air pollution elevates the risk of suicide, disproportionately so among rural populations.
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Poluição do Ar , Suicídio , Poluição por Fumaça de Tabaco , Incêndios Florestais , Adulto , Masculino , Humanos , Fumaça/efeitos adversos , População Rural , Poluição do Ar/efeitos adversos , Material Particulado/efeitos adversosRESUMO
The psychological safety of health care workers is an important but often overlooked aspect of the rising rates of burnout and workforce shortages. In addition, mental health conditions are prevalent among health care workers, but the associated stigma is a significant barrier to accessing adequate care. More efforts are therefore needed to foster health care work environments that are safe and supportive of self-care. The purpose of this brief document is to promote a culture of psychological safety in health care organizations. We review ways in which organizations can create a psychologically safe workplace, the benefits of a psychologically safe workplace, and strategies to promote mental health and reduce suicide risk.
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American Heart Association , Pessoal de Saúde , Saúde Mental , Humanos , Pessoal de Saúde/psicologia , Estados Unidos , Esgotamento Profissional/psicologia , Esgotamento Profissional/prevenção & controle , Esgotamento Profissional/epidemiologia , Local de Trabalho/psicologia , Saúde Ocupacional , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/psicologia , Segurança PsicológicaRESUMO
How to achieve a high-precision suicide attempt classifier based on the three-dimensional psychological pain model is a valuable issue in suicide research. The aim of the present study is to explore the importance of pain avoidance and its related neural features in suicide attempt classification models among patients with major depressive disorder. By recursive feature elimination with cross-validation and support-vector-machine algorithms, scores from the measurements and the task-based EEG signals were chosen to achieve a suicide attempt classification model. In the multimodal suicide attempt classifier with an accuracy of 83.91% and an area under the curve of 0.90, pain avoidance ranked as the top one in the optimal feature set. Theta (reward positive feedback minus neutral positive feedback) was the shared neural representation ranking as the top one of event-related potential features in pain avoidance and suicide attempt classifiers. In conclusion, the suicide attempt classifier based on pain avoidance and its related affective processing neural features has excellent accuracy among patients with major depressive disorder. Pain avoidance is a stable and strong indicator for identifying suicide risks in both traditional analyses and machine-learning approaches. A novel methodology is needed to clarify the relationship between cognitive and affective processing evoked by punishment stimuli and pain avoidance.
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Transtorno Depressivo Maior , Humanos , Tentativa de Suicídio , Dor , Potenciais Evocados , Aprendizado de MáquinaRESUMO
There are an increasing number of cell therapy approaches being studied and employed world-wide. An emerging area in this field is the use of human pluripotent stem cell (hPSC) products for the treatment of injuries/diseases that cannot be effectively managed through current approaches. However, as with any cell therapy, vast numbers of functional and safe cells are required. Bioreactors provide an attractive avenue to generate clinically relevant cell numbers with decreased labour and decreased batch to batch variation. Yet, current methods of performing quality control are not readily scalable to the cell densities produced during bioreactor scale-up. One potential solution is the application of inducible/controllable suicide genes that can trigger cell death in unwanted cell types. These types of approaches have been demonstrated to increase the quality and safety of the resultant cell products. In this review, we will provide background on these approaches and how they could be used together with bioreactor technology to create effective bioprocesses for the generation of high quality and safe hPSCs for use in regenerative medicine approaches.
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Técnicas de Cultura de Células , Células-Tronco Pluripotentes , Humanos , Técnicas de Cultura de Células/métodos , Reatores Biológicos , Controle de Qualidade , Terapia Baseada em Transplante de Células e Tecidos , Diferenciação Celular/genéticaRESUMO
Stress disorders impair sleep and quality of life; however, their pathomechanisms are unknown. Prolactin-releasing peptide (PrRP) is a stress mediator; we therefore hypothesized that PrRP may be involved in the development of stress disorders. PrRP is produced by the medullary A1/A2 noradrenaline (NA) cells, which transmit stress signals to forebrain centers, and by non-NA cells in the hypothalamic dorsomedial nucleus. We found in male rats that both PrRP and PrRP-NA cells innervate melanin-concentrating hormone (MCH) producing neurons in the dorsolateral hypothalamus (DLH). These cells serve as a key hub for regulating sleep and affective states. Ex vivo, PrRP hyperpolarized MCH neurons and further increased the hyperpolarization caused by NA. Following sleep deprivation, intracerebroventricular PrRP injection reduced the number of REM sleep-active MCH cells. PrRP expression in the dorsomedial nucleus was upregulated by sleep deprivation, while downregulated by REM sleep rebound. Both in learned helplessness paradigm and after peripheral inflammation, impaired coping with sustained stress was associated with (1) overactivation of PrRP cells, (2) PrRP protein and receptor depletion in the DLH, and (3) dysregulation of MCH expression. Exposure to stress in the PrRP-insensitive period led to increased passive coping with stress. Normal PrRP signaling, therefore, seems to protect animals against stress-related disorders. PrRP signaling in the DLH is an important component of the PrRP's action, which may be mediated by MCH neurons. Moreover, PrRP receptors were downregulated in the DLH of human suicidal victims. As stress-related mental disorders are the leading cause of suicide, our findings may have particular translational relevance.SIGNIFICANCE STATEMENT Treatment resistance to monoaminergic antidepressants is a major problem. Neuropeptides that modulate the central monoaminergic signaling are promising targets for developing alternative therapeutic strategies. We found that stress-responsive prolactin-releasing peptide (PrRP) cells innervated melanin-concentrating hormone (MCH) neurons that are crucial in the regulation of sleep and mood. PrRP inhibited MCH cell activity and enhanced the inhibitory effect evoked by noradrenaline, a classic monoamine, on MCH neurons. We observed that impaired PrRP signaling led to failure in coping with chronic/repeated stress and was associated with altered MCH expression. We found alterations of the PrRP system also in suicidal human subjects. PrRP dysfunction may underlie stress disorders, and fine-tuning MCH activity by PrRP may be an important part of the mechanism.
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Hormônios Hipotalâmicos , Privação do Sono , Ratos , Masculino , Humanos , Animais , Hormônio Liberador de Prolactina/farmacologia , Hormônio Liberador de Prolactina/metabolismo , Privação do Sono/metabolismo , Transtornos do Humor/etiologia , Qualidade de Vida , Ratos Wistar , Hormônios Hipotalâmicos/metabolismo , Sono/fisiologia , Neurônios/fisiologia , Norepinefrina/metabolismoRESUMO
Suicide remains a leading cause of death in the United States, and recent data suggests that suicide deaths involving opioids are increasing. Given unprecedented increases in drug poisoning deaths, suicidality, and suicide deaths in recent years, an updated examination of the trends in suicide deaths involving opioids is warranted. In this descriptive epidemiologic analysis, we leverage final and provisional mortality data from CDC WONDER to examine trends in suicide deaths involving opioid poisoning from 1999 - 2021 by biological sex. Results reveal complex changes over time: the number and age-adjusted rate of suicide deaths involving opioid poisoning among male and female residents tended to track together, and both increased through 2010, but then diverged with the number and rate of suicide deaths involving opioid poisoning among female residents outpacing that of male residents. However, the number and rate of suicide deaths involving opioid poisoning among male residents then began to stabilize, while that of female residents declined, closing the sex-based gap. Across all years of data, the proportion of suicide deaths that involved opioid poisoning was consistently higher among female decedents (5.8% - 11.0%) compared to male decedents (1.4% - 2.8%). Findings have implications for improved suicide prevention and harm reduction efforts.
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We aimed to compare rates and characteristics of suicide mortality in formerly incarcerated people with those of the general population in North Carolina. We conducted a retrospective cohort study of 266,400 people released from North Carolina state prisons between January 1, 2000, and March 1, 2020. Using direct and indirect standardization by age, sex, and calendar year, we calculated standardized suicide mortality rates and standardized mortality ratios comparing formerly incarcerated people with the North Carolina general population. We evaluated effect modification by race/ethnicity, sex, age, and firearm involvement. Formerly incarcerated people had approximately twice the overall suicide mortality of the general population for 3 years after release, with the highest rate of suicide mortality being observed in the 2-week period after release. In contrast to patterns in the general population, formerly incarcerated people had higher rates of non-firearm-involved suicide mortality than firearm-involved suicide mortality. Formerly incarcerated female, White and Hispanic/Latino, and emerging adult people had a greater elevation of suicide mortality than their general-population peers compared with other groups. These findings suggest a need for long-term support for formerly incarcerated people as they return to community living and a need to identify opportunities for interventions that reduce the harms of incarceration for especially vulnerable groups. This article is part of a Special Collection on Mental Health.
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Prisioneiros , Suicídio , Adulto , Humanos , Feminino , North Carolina/epidemiologia , Estudos Retrospectivos , Causas de MorteRESUMO
Suicide rates in the United States have increased over the past 15 years, with substantial geographic variation in these increases; yet there have been few attempts to cluster counties by the magnitude of suicide rate changes according to intercept and slope or to identify the economic precursors of increases. We used vital statistics data and growth mixture models to identify clusters of counties by their magnitude of suicide growth from 2008 to 2020 and examined associations with county economic and labor indices. Our models identified 5 clusters, each differentiated by intercept and slope magnitude, with the highest-rate cluster (4% of counties) being observed mainly in sparsely populated areas in the West and Alaska, starting the time series at 25.4 suicides per 100,000 population, and exhibiting the steepest increase in slope (0.69/100,000/year). There was no cluster for which the suicide rate was stable or declining. Counties in the highest-rate cluster were more likely to have agricultural and service economies and less likely to have urban professional economies. Given the increased burden of suicide, with no clusters of counties improving over time, additional policy and prevention efforts are needed, particularly targeted at rural areas in the West.
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Suicídio , Humanos , Estados Unidos/epidemiologia , População RuralRESUMO
In the article by Fitch et al. (Am J Epidemiol. 2024; 193(3):489-499) the authors highlight the concerning prevalence of suicide mortality among formerly incarcerated individuals in North Carolina. Their retrospective study reveals a doubled suicide risk post-release, with notable disparities among demographic groups. Urgent interventions are needed, including comprehensive re-entry programs and systemic reforms to address structural inequalities. I suggest tailored support services to mitigate suicide risks and promote successful community reintegration, advocating for equity, justice, and human dignity in post-release efforts.
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This article introduces bayesian spatial smoothing models for disease mapping-a specific application of small area estimation where the full universe of data is known-to a wider audience of public health professionals using firearm suicide as a motivating example. Besag, York, and Mollié (BYM) Poisson spatial and space-time smoothing models were fitted to firearm suicide counts for the years 2014-2018. County raw death rates in 2018 ranged from 0 to 24.81 deaths per 10 000 people. However, the highest mortality rate was highly unstable, based on only 2 deaths in a population of approximately 800, and 80.5% of contiguous US counties experienced fewer than 10 firearm suicide deaths and were thus suppressed. Spatially smoothed county firearm suicide mortality estimates ranged from 0.06 to 4.05 deaths per 10 000 people and could be reported for all counties. The space-time smoothing model produced similar estimates with narrower credible intervals as it allowed counties to gain precision from adjacent neighbors and their own counts in adjacent years. bayesian spatial smoothing methods are a useful tool for evaluating spatial health disparities in small geographies where small numbers can result in highly variable rate estimates, and new estimation techniques in R software have made fitting these models more accessible to researchers.
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Teorema de Bayes , Armas de Fogo , Suicídio , Humanos , Armas de Fogo/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Análise Espacial , Estados Unidos/epidemiologia , Modelos EstatísticosRESUMO
INTRODUCTION: Suicide rates are elevated after cancer diagnosis. Existential distress caused by awareness of one's impending death is well-described in patients with cancer. The authors hypothesized that suicide risk is associated with cancer prognosis, and the impact of prognosis on suicide risk is greatest for populations with higher baseline suicide risk. METHODS: The authors identified patients (≥16 years old) with newly diagnosed cancers from 2000 to 2019 in the Surveillance, Epidemiology, and End Results database, representing 27% of US cancers. Multiple primary-standardized mortality ratios (SMR) were used to estimate the relative risk of suicide within 6 months of diagnosis compared to the general US population, adjusted for age, sex, race, and year of follow-up. Suicide rates by 20 most common cancer sites were compared with respective 2-year overall survival rates (i.e., prognosis) using a weighted linear regression model. RESULTS: Among 6,754,704 persons diagnosed with cancer, there were 1610 suicide deaths within 6 months of diagnosis, three times higher than the general population (SMR = 3.1; 95% confidence interval, 3.0-3.3). Suicide risk by cancer site was closely associated with overall prognosis (9.5%/percent survival deficit, R2 = 0.88, p < .0001). The association of prognosis with suicide risk became attenuated over time. For men, the risk of suicide increased by 2.8 suicide deaths per 100,000 person-years (p < .0001) versus 0.3 in women (p < .0001). The risk was also higher for persons ≥60 old and for the White (vs. Black) race. CONCLUSIONS: Poorer prognosis was closely associated with suicide risk early after cancer diagnosis and had a greater effect on populations with higher baseline risks of suicide. This model highlights the need for enhanced psychiatric surveillance and continued research in this patient population.
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Neoplasias , Suicídio , Humanos , Masculino , Feminino , Adolescente , Suicídio/psicologia , Neoplasias/diagnóstico , Neoplasias/psicologia , Prognóstico , Risco , Fatores de RiscoRESUMO
This study aimed to investigate the behavioral responses and circadian rhythms of mice to both rapid and gradual increases in photoperiod, mimicking the transition from winter to summer, which is associated with a heightened prevalence of hospitalizations for mania and suicidal behavior. Behavioral tests were performed in C57BL/6 male mice exposed to a transitional photoperiod, from short to long durations. To determine if circadian rhythms are affected, we measured spontaneous locomotor activity and body temperature. Mice exhibited heightened exploratory and risk-taking behaviors compared with equatorial and static long (16:8 h of light-dark cycle for several days) groups. These behaviors were prevented by lithium. Spontaneous locomotor activity and body temperature rhythms persisted and were effectively synchronized; however, the relative amplitude of activity and interdaily stability were diminished. Additionally, the animals displayed increased activity during the light phase. Photoperiodic transition modulates behavior and circadian rhythms, mirroring certain features observed in bipolar disorder patients. This study introduces an animal model for investigating mania-like behavior induced by photoperiodic changes, offering potential insights for suicide prevention strategies and the management of mood disorders.
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For lethal means safety counseling interventions (LMSC) to reduce population-level suicide rates, interventions must be deployed across many settings and populations. We conducted a systematic search in six databases to review the current state of LMSC interventions across study designs, settings, messengers, populations, and injury prevention levels (e.g., universal). Eligibility criteria were: any individual or group receiving a LMSC intervention involving a human-to-human component aiming to influence adult behaviors related to lethal suicide methods, and outcome assessment of storage behaviors and/or suicidal self-directed violence (SDV). Risk of bias was assessed using the Effective Public Health Practice Project (EPHPP) quality assessment tool. A descriptive synthesis approach was used for analysis. Twenty-two studies were included that reported medication and/or firearm storage behaviors and/or SDV following LMSC. Fourteen of the 19 studies assessing behavioral change reported a significant improvement in safe storage behaviors, and all studies measuring acceptability reported that participants found the interventions favorable. Quality of evidence was limited. No studies were rated low risk of bias, and 77% were rated high risk of bias. There was substantial heterogeneity in the settings, populations, injury prevention levels, delivery methods, and intervention elements. Many included studies focused on caregivers of pediatric populations, and few studies assessed SDV outcomes. Higher quality trials conducted across a variety of settings, particularly those focusing on adults at risk of suicide, are needed. There was no funding for this review, and it was preregistered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42021230668).
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BACKGROUND: To prevent tobacco use in Korea, the national quitline number was added to tobacco packages in December 2012, tobacco prices were raised by 80% in January 2015, and graphic health warning labels were placed on tobacco packages in December 2016. This study evaluated the association of these tobacco packaging and pricing policies with suicide mortality in Korea. METHODS: Monthly mortality from suicide was obtained from Cause-of-Death Statistics in Korea from December 2007 to December 2019. Interrupted time-series analysis was performed using segmented Poisson regression models. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated adjusted for suicide prevention strategies. RESULTS: Suicide mortality was 20 per 1,000,000 in December 2007 and showed a downward trend over the study period. After the implementation of tobacco packaging and pricing policies, suicide mortality immediately declined by - 0.09 percent points (95% CI = - 0.19 to 0.01; P > 0.05) for the national quitline number, - 0.22 percent points (95% CI = - 0.35 to - 0.09; P < 0.01) for tobacco prices, and - 0.30 percent points (95% CI = - 0.49 to - 0.11; P < 0.01) for graphic health warning labels. The corresponding RRs for these post-implementation changes compared with the pre-implementation level were 0.91 (95% CI = 0.83 to 1.00), 0.80 (95% CI = 0.70 to 0.91), and 0.74 (95% CI = 0.61 to 0.90), respectively. Significant associations between tobacco control policies and suicide mortality were observed even when stratified by sex and region. CONCLUSIONS: The findings of this study provide new evidence for an association between tobacco control policies and deaths by suicide. An array of effective tobacco control policies should be considered for prevention programs targeting suicide.
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Análise de Séries Temporais Interrompida , Embalagem de Produtos , Suicídio , Produtos do Tabaco , Humanos , República da Coreia , Masculino , Suicídio/estatística & dados numéricos , Suicídio/economia , Feminino , Produtos do Tabaco/economia , Embalagem de Produtos/economia , Adulto , Pessoa de Meia-Idade , Prevenção do Suicídio , Adulto Jovem , Idoso , Custos e Análise de CustoRESUMO
BACKGROUND: Despite the importance of medication adherence in treatment effectiveness, little is known about the association between medication non-adherence and self-inflicted violence behaviors. We aimed to assess whether medication non-adherence increased the risk of self-inflicted violence behaviors among schizophrenics in communities (hypothesis 1) and whether the dose-response relationship existed (hypothesis 2). METHODS: This 12-year cohort study in western China recruited 292,667 community-dwelling schizophrenics. The proportion of regular medication (PRM) was calculated by dividing the time of "regular adherence" by the total time of antipsychotic treatment during follow-up period as an indicator of medication adherence. For hypothesis 1, medication adherence was designated as a binary variable with a threshold of 0.8 (PRM); for hypothesis 2, medication adherence was specified as five-category and continuous variables, respectively. Inverse probability weighting and mixed effects Cox proportional hazards models were conducted for confounders control and survival analyses. RESULTS: One hundred eighty-five thousand eight hundred participants were eligible for the final analyses, with a mean age of 47.49 years (SD 14.55 years), of whom 53.6% were female. For hypothesis 1, the medication non-adherence group (PRM < 0.8) had a lower risk of suicide (HR, 0.527, 95% CI, 0.447-0.620), an increased risk of NSSI (HR, 1.229, 95% CI, 1.088-1.388), and non-significant risk of attempted suicide compared with adherence group (PRM ≥ 0.8). For hypothesis 2, the lowest medication adherence (PRM < 0.2) was associated with increased risks of suicide attempt (HR, 1.614, 95% CI, 1.412-1.845), NSSI (HR, 1.873, 95% CI, 1.649-2.126), and a decreased risk of suicide (HR, 0.593, 95% CI, 0.490-0.719). The other non-adherence groups had lower risks for all three self-inflicted violence behaviors. The associations between medication adherence in continuous-variable and three outcomes were consistent with the categorical medication adherence results. CONCLUSIONS: Almost no medication taken as prescribed was associated with an increased risk of suicide attempt and NSSI. However, medication adherence did not appear to prevent completed suicide. Besides, patients with moderate adherence had a lower incidence of suicide attempt and NSSI. These findings highlight the need for a more detailed portrayal of medication adherence and the need to be vigilant for suicide intent in schizophrenics with good medication adherence who may be overlooked previously.
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Esquizofrenia , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos de Coortes , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Tentativa de Suicídio , Violência , Adesão à Medicação , Fatores de RiscoRESUMO
INTRODUCTION: Every year about 800,000 complete suicide events occur. The identification of biologic markers to identify subjects at risk would be helpful in targeting specific support treatments. AREA COVERED: A narrative review defines the meta-analytic level of current evidence about the biologic markers of suicide behavior (SB). The meta-analytic evidence gathered so far indicates that the hypothesis-driven research largely failed to identify the biologic markers of suicide. The most consistent and replicated result was reported for: 1) 5-HTR2A T102C, associated with SB in patients with schizophrenia (OR = 1.73 (1.11-2.69)) and 2) BDNF Val66Met (rs6265), with the Met-Val + Val-Val carriers found to be at risk for suicide in the Caucasian population (OR: 1.96 (1.58-2.43)), while Val-Val vs. Val-Met + Met carriers found to be at risk for suicide in the Asian populations (OR: 1.36 (1.04-1.78)). GWAS-based meta-analyses indicate some positive replicated findings regarding the DRD2, Neuroligin gene, estrogen-related genes, and genes involved in gene expression. EXPERT OPINION: Most consistent results were obtained when analyzing sub-samples of patients. Some promising results come from the implementation of the polygenic risk score. There is no current consensus about an implementable biomarker for SB.
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Polimorfismo de Nucleotídeo Único , Tentativa de Suicídio , Humanos , Fator Neurotrófico Derivado do Encéfalo/genética , BiomarcadoresRESUMO
Chemical-inducible gene expression systems are commonly used to regulate gene expression for functional genomics in various plant species. However, a convenient system that can tightly regulate transgene expression in Nicotiana benthamiana is still lacking. In this study, we developed a tightly regulated copper-inducible system that can control transgene expression and conduct cell death assays in N. benthamiana. We tested several chemical-inducible systems using Agrobacterium-mediated transient expression and found that the copper-inducible system exhibited the least concerns regarding leakiness in N. benthamiana. Although the copper-inducible system can control the expression of some tested reporters, it is not sufficiently tight to regulate certain tested hypersensitive cell death responses. Using the MoClo-based synthetic biology approach, we incorporated the suicide exon HyP5SM/OsL5 and Cre/LoxP as additional regulatory elements to enhance the tightness of the regulation. This new design allowed us to tightly control the hypersensitive cell death induced by several tested leucine-rich repeat-containing proteins and their matching avirulence factors, and it can be easily applied to regulate the expression of other transgenes in transient expression assays. Our findings offer new approaches for both fundamental and translational studies in plant functional genomics.