Suicide, Homicide, and All-Cause Mortality Among Transgender and Cisgender Patients in the Veterans Health Administration.

Purpose: This study examines the differences in suicide, homicide, and all-cause mortality between transgender and cisgender Veterans Health Administration (VHA) patients. Methods: VHA electronic medical record data from October 1, 1999 to December 31, 2016 were used to create a sample of transgender and cisgender patients (n = 32,441). Cox proportional hazard regression was used to evaluate differences in survival time (date of birth to death date/study end). Death data were from the National Death Index. Results: Transgender patients had more than twofold greater hazard of suicide than cisgender patients (adjusted hazard ratio [aHR] = 2.77, 95% confidence interval [CI] = 1.88-4.09), especially among younger (18-39 years) (aHR = 3.35, 95% CI = 1.30-8.60) and older (≥65 years) patients (aHR = 9.48, 95% CI = 3.88-23.19). Alternatively, transgender patients had an overall lower hazard of all-cause mortality (aHR = 0.90, 95% CI = 0.84-0.97) compared with cisgender patients, which was driven by patients 40-64 years old (aHR = 0.78, 95% CI = 0.72-0.86) and reversed by those 65 years and older (aHR = 1.17, 95% CI = 1.03-1.33). Conclusion: Transgender patients' hazard of suicide mortality was significantly greater than that of cisgender VHA patients.

Differences in Methods of Suicide Death Among Transgender and Nontransgender Patients in the Veterans Health Administration, 1999-2016.

BACKGROUND: Limited research suggests that rates of suicide death among transgender people may be higher than their nontransgender peers. OBJECTIVE: The objective of this study was to compare rates of suicide deaths by different means between transgender and nontransgender patients. RESEARCH DESIGN: This secondary analysis used VHA administrative and electronic health record (EHR) data from October 1, 1999 through December 31, 2016. SUBJECTS: Transgender patients (n=8981) were categorized as such based on a set of International Classification of Disease codes, and a comparison sample was selected by randomly choosing 3 nontransgender patients (n=26,924). MEASURES AND ANALYSES: Cause and date of death data are from the National Death Index. Because of low frequencies amid different methods of suicide death, we combined categories into self-poisoning; hanging, strangulation and suffocation; discharge of firearms; and self-harm by all other and unspecified means. We conducted Cox regression analyses to model time-to-event for each method of suicide, adjusted for age, sex based on EHR, race, ethnicity, marital status, and whether patients had ever been diagnosed with depression. RESULTS: Among transgender patients, 73 died by suicide (22 female EHR-based sex, 51 male EHR-based sex), and among nontransgender patients, 71 died by suicide (4 female EHR-based sex, 67 male EHR-based sex). In adjusted models, transgender patients had significantly greater hazards of death by self-poisoning and firearms than their nontransgender peers. CONCLUSIONS: Differences in methods of suicide death suggest that firearms and self-poisoning may be specific areas of concern for transgender individuals experiencing suicidal crisis, which underscore needs for examining effective delivery of evidence-based care.

Using clinician text notes in electronic medical record data to validate transgender-related diagnosis codes.

Objective: Transgender individuals are vulnerable to negative health risks and outcomes, but research remains limited because data sources, such as electronic medical records (EMRs), lack standardized collection of gender identity information. Most EMR do not include the gold standard of self-identified gender identity, but International Classification of Diseases (ICDs) includes diagnostic codes indicating transgender-related clinical services. However, it is unclear if these codes can indicate transgender status. The objective of this study was to determine the extent to which patients' clinician notes in EMR contained transgender-related terms that could corroborate ICD-coded transgender identity. Methods: Data are from the US Department of Veterans Affairs Corporate Data Warehouse. Transgender patients were defined by the presence of ICD9 and ICD10 codes associated with transgender-related clinical services, and a 3:1 comparison group of nontransgender patients was drawn. Patients' clinician text notes were extracted and searched for transgender-related words and phrases. Results: Among 7560 patients defined as transgender based on ICD codes, the search algorithm identified 6753 (89.3%) with transgender-related terms. Among 22 072 patients defined as nontransgender without ICD codes, 246 (1.1%) had transgender-related terms; after review, 11 patients were identified as transgender, suggesting a 0.05% false negative rate. Conclusions: Using ICD-defined transgender status can facilitate health services research when self-identified gender identity data are not available in EMR.

Exploring Rural Disparities in Medical Diagnoses Among Veterans With Transgender-related Diagnoses Utilizing Veterans Health Administration Care.

OBJECTIVES: Research shows transgender individuals experience pronounced health disparities compared with their nontransgender peers. Yet, there remains insufficient research about health differences within transgender populations. This study seeks to fill this gap by exploring how current urban/rural status is associated with lifetime diagnosis of mood disorder, alcohol dependence disorder, illicit drug abuse disorder, tobacco use, posttraumatic stress disorder, human immunodeficiency virus, and suicidal ideation or attempt among veterans with transgender-related diagnoses. METHODS: This study used a retrospective review of The Department of Veterans Affairs (VA) administrative data for transgender patients who received VA care from 1997 through 2014. Transgender patients were defined as individuals that had a lifetime diagnosis of any of 4 International Classification of Diseases-9 diagnosis codes associated with transgender status. Independent multivariable logistic regression models were used to explore associations of rural status with medical conditions. RESULTS: Veterans with transgender-related diagnoses residing in small/isolated rural towns had increased odds of tobacco use disorder (adjusted odds ratio=1.39; 95% confidence intervals, 1.09-1.78) and posttraumatic stress disorder (adjusted odds ratio=1.33; 95% confidence intervals, 1.03-1.71) compared with their urban transgender peers. Urban/rural status was not significantly associated with other medical conditions of interest. CONCLUSIONS: This study contributes the first empirical investigations of how place of residence is associated with medical diagnoses among veterans with transgender-related diagnoses. The importance of place as a determinant of health is increasingly clear, but for veterans with transgender-related diagnoses this line of research is currently limited. The addition of self-reported sex identity data within VA electronic health records is one way to advance this line of research.

Impact of Social Determinants of Health on Medical Conditions Among Transgender Veterans.

INTRODUCTION: Transgender individuals experience pronounced disparities in health (e.g., mood disorders, suicide risk) and in the prevalence of social determinants of housing instability, financial strain, and violence. The objectives of this study were to understand the prevalence of social determinants among transgender veterans and assess their associations with medical conditions. METHODS: This project was a records review using administrative data from the U.S. Department of Veterans Affairs databases for 1997-2014. Transgender veterans (N=6,308) were defined as patients with any of four ICD-9 diagnosis codes associated with transgender status. Social determinants were operationalized using ICD-9 codes and Department of Veterans Affairs clinical screens indicating violence, housing instability, or financial strain. Multiple logistic regression was used to assess the associations of social determinants with medical conditions: mood disorder, post-traumatic stress disorder, alcohol abuse disorder, illicit drug abuse disorder, tobacco use disorder, suicidal risk, HIV, and hepatitis C. RESULTS: After adjusting for sociodemographic variables, housing instability and financial strain were significantly associated with all medical conditions except for HIV, and violence was significantly associated with all medical conditions except for tobacco use disorder and HIV. There was a dose response-like relationship between the increasing number of forms of social determinants being associated with increasing odds for medical conditions. CONCLUSIONS: Social determinants are prevalent factors in transgender patients' lives, exhibiting strong associations with medical conditions. Documenting social determinants in electronic health records can help providers to identify and address these factors in treatment goals.

Advancing methods for US transgender health research.

PURPOSE OF REVIEW: This article describes methodological challenges, gaps, and opportunities in US transgender health research. RECENT FINDINGS: Lack of large prospective observational studies and intervention trials, limited data on risks and benefits of sex affirmation (e.g., hormones and surgical interventions), and inconsistent use of definitions across studies hinder evidence-based care for transgender people. Systematic high-quality observational and intervention-testing studies may be carried out using several approaches, including general population-based, health systems-based, clinic-based, venue-based, and hybrid designs. Each of these approaches has its strength and limitations; however, harmonization of research efforts is needed. Ongoing development of evidence-based clinical recommendations will benefit from a series of observational and intervention studies aimed at identification, recruitment, and follow-up of transgender people of different ages, from different racial, ethnic, and socioeconomic backgrounds and with diverse gender identities. SUMMARY: Transgender health research faces challenges that include standardization of lexicon, agreed upon population definitions, study design, sampling, measurement, outcome ascertainment, and sample size. Application of existing and new methods is needed to fill existing gaps, increase the scientific rigor and reach of transgender health research, and inform evidence-based prevention and care for this underserved population.

Mental Health of Transgender Veterans in US States With and Without Discrimination and Hate Crime Legal Protection.

OBJECTIVES: To examine whether indicators of community- and state-level lesbian, gay, bisexual, and transgender equality are associated with transgender veterans' mental health. METHODS: We extracted Veterans Administration data for patients who were diagnosed with gender identity disorder, had at least 1 visit in 2013, and lived in a zip code with a Municipality Equality Index score (n = 1640). We examined the associations of whether a state included transgender status in employment nondiscrimination laws and in hate crimes laws with mood disorders; alcohol, illicit drug, and tobacco use disorders; posttraumatic stress disorder; and suicidal ideation or attempt. RESULTS: Nearly half (47.3%) of the sample lived in states with employment discrimination protection, and 44.8% lived in states with hate crimes protection. Employment nondiscrimination protection was associated with 26% decreased odds of mood disorders (adjusted odds ratio [AOR] = 0.74; 95% confidence interval [CI] = 0.59, 0.93) and 43% decreased odds of self-directed violence (AOR = 0.57; 95% CI = 0.34, 0.95). CONCLUSIONS: Understanding lesbian, gay, bisexual, and transgender social stressors can inform treatment and care coordination for transgender populations.

Priorities for transgender medical and healthcare research.

PURPOSE OF REVIEW: Transgender individuals experience unique health disparities but are the subject of little focused health research. This manuscript reviews current literature on transgender medical and mental health outcomes and proposes research priorities to address knowledge gaps. RECENT FINDINGS: Published research in transgender healthcare consists primarily of case reports, retrospective and cross-sectional studies, involving largely European settings. Challenges to US-based transgender health research include a diverse population where no single center has sufficient patient base to conduct clinical research with statistical rigor. Treatment regimens are heterogeneous and warrant study for best practices. Current research suggests increased mortality and depression in transgender individuals not receiving optimal care, and possibly a modest increase in cardiovascular risk related to hormone therapy. Current evidence does not support concerns for hormone-related malignancy risk. SUMMARY: The priorities for transgender medical outcomes research should be to determine health disparities and comorbid health conditions over the life span, along with the effects of mental health, medical, and surgical interventions on morbidity and mortality. Specific outcomes of interest based on frequency in the literature, potential severity of outcome, and patient-centered interest, include affective disorders, cardiovascular disease, malignancies, fertility, and time dose-related responses of specific interventions.

Mental Health and Medical Health Disparities in 5135 Transgender Veterans Receiving Healthcare in the Veterans Health Administration: A Case-Control Study.

PURPOSE: There are no large controlled studies of health disparities in transgender (TG) or gender dysphoric patients. The Veterans Health Administration (VHA) is the largest healthcare system in the United States and was an early adopter of electronic health records. We sought to determine whether medical and/or mental health disparities exist in VHA for clinically diagnosed TG veterans compared to matched veterans without a clinical diagnosis consistent with TG status. METHODS: Using four ICD-9-CM codes consistent with TG identification, a cohort of 5135 TG veterans treated in VHA between 1996 and 2013 was identified. Veterans without one of these diagnoses were matched 1:3 in a case-control design to determine if medical and/or mental health disparities exist in the TG veteran population. RESULTS: In 2013, the prevalence of TG veterans with a qualifying clinical diagnosis was 58/100,000 patients. Statistically significant disparities were present in the TG cohort for all 10 mental health conditions examined, including depression, suicidality, serious mental illnesses, and post-traumatic stress disorder. TG Veterans were more likely to have been homeless, to have reported sexual trauma while on active duty, and to have been incarcerated. Significant disparities in the prevalence of medical diagnoses for TG veterans were also detected for 16/17 diagnoses examined, with HIV disease representing the largest disparity between groups. CONCLUSION: This is the first study to examine a large cohort of clinically diagnosed TG patients for psychiatric and medical health outcome disparities using longitudinal, retrospective medical chart data with a matched control group. TG veterans were found to have global disparities in psychiatric and medical diagnoses compared to matched non-TG veterans. These findings have significant implications for policy, healthcare screening, and service delivery in VHA and potentially other healthcare systems.

Health Correlates of Criminal Justice Involvement in 4,793 Transgender Veterans.

PURPOSE: Transgender (TG) persons are overrepresented in prison settings and in the U.S. veteran population. Health disparities studies of large populations of transgender people involved with the criminal justice system have not been published to date. METHODS: We studied a large cohort of TG veterans who received care in Veterans Health Administration (VHA) facilities during 2007-2013 (n = 4,793) and a 3:1 matched control group of veterans without known TG identification (n = 13,625). Three hundred twenty six (n = 138 TG, 188 non-TG) had received VHA services in programs designed to address the needs of justice involved (JI) veterans. We linked patients in each of the three groups to their medical and administrative data. RESULTS: TG veterans were more likely to be justice involved than controls (2.88% vs. 1.38%; P < .0001). Compared to non-TG JI veterans, TG JI veterans were more likely to have a history of homelessness (80% vs. 67%; P < .05) and to have reported sexual trauma while serving in the military (23% vs. 12%; P < .01). Significant health disparities were noted for TG JI veterans for depression, hypertension, obesity, posttraumatic stress disorder, serious mental illness, and suicidal ideation/attempts. CONCLUSION: These data suggest that TG veterans experience a number of health risks compared to non-TG veterans, including an increased likelihood of justice involvement. TG veterans involved with the criminal justice system are a particularly vulnerable group and services designed to address the health care needs of this population, both while incarcerated and when in the community, should take these findings into account in the development of health screenings and treatment plans.

Incidence of breast cancer in a cohort of 5,135 transgender veterans.

Transgender (TG) persons often receive, or self-treat, with cross-sex hormone (CSH) treatments as part of their treatment plans, with little known about their incidence of breast cancer. This information gap can lead to disparities in the provision of transgender health care. The purpose of the study was to examine the incidence of breast cancer in the largest North American sample of TG patients studied to date to determine their exposure to CSH, incidence of breast cancer, and to compare results with European studies in transsexual populations. We used Veterans Health Administration (VHA) data from 5,135 TG veterans in the United States from 1996 to 2013 to determine the incidence of breast cancer in this population. Chart reviews were completed on all patients who developed breast cancer. Age-standardized incidences of breast cancer from the general population were used for comparison. Person-years of exposure to known CSH treatment were calculated. Ten breast cancer cases were confirmed. Seven were in female-to-male patients, two in male-to-female patients, and one in a natal male with transvestic fetishism. Average age at diagnosis was 63.8 (SD = 8.2). 52 % received >1 dose of CSH treatment from VHA clinicians. All three males presented with late-stage disease were proved fatal. The overall incidence rate was 20.0/100,000 patient-years of VHA treatment (95 % CI 9.6-36.8), irrespective of VA CSH treatment. This rate did not differ from the expected rate in an age-standardized national sample, but exceeded that reported for smaller European studies of transsexual patients that were longer in duration. Although definitive conclusions cannot be made regarding breast cancer incidence in TG veterans who did or did not receive VA CSH due to the sample size and duration of observation, it appears that TG veterans do not display an increase in breast cancer incidence. This is consistent with European studies of longer duration that conclude that CSH treatment in gender dysphoric patients of either birth sex does not result in a greater incidence than the general population.

Breast Cancer in Transgender Veterans: A Ten-Case Series.

All known cases of breast cancer in patients with a diagnosis consistent with transgender identification were identified in the Veterans Health Administration (1996-2013). Ten cases were confirmed: seven birth sex females and three birth sex males. Of the three birth sex males, two identified as gender dysphoric male-to-female and one identified as transgender with transvestic fetishism. The birth sex males all presented with late-stage disease that proved fatal, whereas most of the birth sex female transgender veterans presented with earlier stage disease that could be treated. These cases support the importance of screening for breast cancer using standard guidelines in birth sex males and females. Family history of breast cancer should be obtained from transgender people as part of routine care. This report expands the known cases of breast cancer in transgender persons from 5 to 12 (female-to-male) and from 10 to 13 (male-to-female).

Access to care for transgender veterans in the Veterans Health Administration: 2006-2013.

A 2011 Veterans Health Administration directive mandated medically necessary care for transgender veterans. Internal education efforts informed staff of the directive and promoted greater access to care. For fiscal years 2006 through 2013, we identified 2662 unique individuals with International Classification of Diseases, Ninth Revision diagnoses related to transgender status in Veterans Health Administration medical records, with 40% of new cases in the 2 years following the directive. A bottom-up push for services by veterans and top-down education likely worked synergistically to speed implementation of the new policy and increase access to care.

Qualitative analysis of transgender inmates' correspondence: implications for departments of correction.

Claims of inadequate health care and safety afforded to transgender inmates have become the subject of litigation. This article reviews 129 unsolicited letters from transgender inmates writing from 24 states and the Federal Bureau of Prisons to identify their concerns. Among the letters reviewed were reports from 10 inmates who had filed lawsuits naming departments of correction (DOCs) as defendants, claiming inadequate access to transgender health care. Five of these lawsuits have gone to trial. In all of those cases, the defendant settled the matter or was found liable as of the time of this report. Claims of inadequate care for transgendered patients that have sufficient merit to be fully litigated in U.S. courts appear likely to produce verdicts in favor of plaintiff inmates. The information gleaned from reviewing letters from transgendered inmates may alert staffs of DOCs to concerns worth addressing proactively to avoid the costs associated with transgender-related lawsuits.

Mortality Among Veterans with Transgender-Related Diagnoses in the Veterans Health Administration, FY2000-2009.

PURPOSE: The aims of this project were to document all-cause and suicide mortality among Veteran Healthcare Administration (VHA) utilizers with The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis consistent with transgender status. METHODS: The study population consisted of VHA patients identified as having any one of four diagnosis codes indicating transgender status (n=5,117) gathered from the VA National Patient Care Database. Mortality data were gathered from the National Death Index from 2000-2009 for 1,277 veterans with transgender-related ICD-9-CM diagnoses. The remaining 3,840 were not searched because they had VHA utilization after 2009 (indicating they were alive). Person-time at risk (person-years) for crude rates were calculated based on the time from an individual's index diagnosis to either death or the end of FY 2009. Causes of death were categorized using ICD-10 code groups. RESULTS: Approximately 9.3% (n=309) veterans with transgender-related ICD-9-CM diagnoses died across the study period. Although diseases of the circulatory system and neoplasms were the first and second leading causes of death, respectively, the other ranked causes of mortality differed somewhat from patterns for the US during the same time span. The crude suicide rate among veterans with transgender-related ICD-9-CM diagnoses across the 10-year period was approximately 82/100,000 person-years, which approximated the crude suicide death rates for other serious mental illness in VHA (e.g., depression, schizophrenia). The average age of suicide decedents was 49.4 years. CONCLUSION: The crude suicide rate among veterans with transgender-related ICD-9-CM diagnoses is higher than in the general population, and they may be dying by suicide at younger ages than their veteran peers without transgender-related ICD-9-CM diagnoses. Future research, such as age-adjusted rates or accounting for psychiatric co-morbidities, will help to better clarify if the all-cause and suicide mortality rates are elevated for veterans with transgender-related ICD-9-CM diagnoses.

Prevalence of gender identity disorder and suicide risk among transgender veterans utilizing veterans health administration care.

OBJECTIVES: We estimated the prevalence and incidence of gender identity disorder (GID) diagnoses among veterans in the Veterans Health Administration (VHA) health care system and examined suicide risk among veterans with a GID diagnosis. METHODS: We examined VHA electronic medical records from 2000 through 2011 for 2 official ICD-9 diagnosis codes that indicate transgender status. We generated annual period prevalence estimates and calculated incidence using the prevalence of GID at 2000 as the baseline year. We cross-referenced GID cases with available data (2009-2011) of suicide-related events among all VHA users to examine suicide risk. RESULTS: GID prevalence in the VHA is higher (22.9/100 000 persons) than are previous estimates of GID in the general US population (4.3/100 000 persons). The rate of suicide-related events among GID-diagnosed VHA veterans was more than 20 times higher than were rates for the general VHA population. CONCLUSIONS: The prevalence of GID diagnosis nearly doubled over 10 years among VHA veterans. Research is needed to examine suicide risk among transgender veterans and how their VHA utilization may be enhanced by new VA initiatives on transgender care.

Health care policies addressing transgender inmates in prison systems in the United States.

Inmates with gender identity disorders (GID) pose special challenges to policy makers in U.S. prison systems. Transgender persons are likely overrepresented in prisons; a reasonable estimate is that at least 750 transgender prisoners were in custody in 2007. Using the Freedom of Information Act, requests were mailed to each state, the District of Columbia, and the Federal Bureau of Prisons in 2007. The requests were for copies of policies, directives, memos, or other documents concerning placement and health care access of transgender inmates. By April 2008, 46 responses were received; 6 states did not reply. Information was qualitatively analyzed and summarized. There was substantial disparity in transgender health care for inmates with GID or related conditions. Most systems allowed for diagnostic evaluations. There was wide variability in access to cross-sex hormones, with some allowing for continuation of treatment and others allowing for both continuation and de novo initiation of treatment. There was uniformity in denial of surgical treatments for GID.

Impact of childhood abuse on the course of bipolar disorder: a replication study in U.S. veterans.

BACKGROUND: The association between early childhood abuse and the course of illness, including psychiatric comorbidities, in adults with bipolar disorder has not been examined in a predominantly male or veteran population. METHODS: As part of the VA Cooperative Study 430, "Reducing the Efficacy-Effectiveness Gap in Bipolar Disorder," 330 veterans (91% male) with bipolar I or II disorder who were enrolled in a 3-year prospective study were examined for baseline data obtained at study entry. Diagnoses were determined by the use of the SCID. A semistructured interview designed to elicit data about exposure to childhood physical, sexual, or combined abuse was conducted as part of baseline demographic and clinical information. Other reports from this data set have not addressed the issues of childhood adversity. RESULTS: Childhood abuse was reported by 48.3% of the subjects (47.3% of men). Any abuse (AA) was reported by 48.3%; sexual abuse without physical abuse (SA) was reported by 8%, physical abuse without sexual abuse (PA) by 20.7%, and both types of abuse (combined abuse, CA) by 18.7% of the male subjects. Female veterans reported more SA (27%) and less PA (6.7%). AA subjects were more likely to have current PTSD and lifetime diagnoses of panic disorder and alcohol use disorders. CA was associated with lower SF-36 Mental scores, higher likelihood of current PTSD and lifetime diagnoses of alcohol use disorders, as well as more lifetime episodes of major depression and higher likelihood of at least one suicide attempt. Younger age at study entry was associated with AA and PA. LIMITATIONS: Potential limitations include generalizability beyond the male, veteran population of patients with bipolar disorder and the methodology used to elicit abuse histories. CONCLUSIONS: Similar to studies of predominantly female nonveteran samples, this study extends the finding that a history of childhood abuse acts as a disease course modifier in male veterans with bipolar disorder. Clinicians should routinely seek information regarding abuse and be aware that these patients may be more difficult to treat than bipolar patients who have no abuse histories.

A novel series of p38 MAP kinase inhibitors for the potential treatment of rheumatoid arthritis.

A novel p38 MAP kinase inhibitor structural class was discovered through selectivity screening. The rational analogue design, synthesis and structure-activity relationship of this series of bis-amide inhibitors is reported. The inhibition in vitro of human p38alpha enzyme activity and lipopolysaccharide-induced tumour necrosis factor-alpha release is described for the series. The activity in vivo and pharmacokinetic properties are exemplified for the more potent analogues.