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PURPOSE: Health disparities in transgender and gender diverse (TGD) veterans compared with cisgender veterans have been documented. However, there is a paucity of literature focused on older TGD veterans. We assessed health conditions and social stressors in older TGD veterans compared with matched cisgender veterans. METHODS: Using gender identity disorder diagnosis codes, we identified 1244 TGD veterans (65+ years of age) receiving care in the Veterans Health Administration (VHA) from 2006 to 2018. These TGD veterans were then matched to 3732 cisgender veterans based on age, VHA site, and date of care in VHA. RESULTS: In adjusted models, TGD veterans compared with cisgender veterans were less likely to have alcohol use disorder (adjusted odds ratio [AOR; 95% confidence interval]: [0.70; 0.58–0.85]), drug use disorder (0.59; 0.47–0.74), tobacco use (0.75; 0.65–0.86), and anxiety (0.74; 0.62–0.90). However, compared with cisgender veterans, TGD veterans were more likely to experience depression (1.63; 1.39–1.93), Alzheimer's disease (8.95; 4.25–18.83), cancer (1.83; 1.56–2.14), violence (1.82; 1.14–2.91), social/familial problems (2.45; 1.99–3.02), lack of access to care/transportation (2.23; 1.48–3.37), and military sexual trauma (2.59; 1.93–3.46). Furthermore, compared with cisgender veterans, TGD veterans were more likely to have documentation of a higher count of social stressors: 1 or more stressors (1.64; 1.38–1.95) and 2 or more stressors (1.22; 1.01–1.49). CONCLUSION: Despite significant disparities in social stressors and health conditions compared with cisgender veterans, TGD veterans had a lower likelihood of substance use and anxiety. Interventions are needed to mitigate social stressors and improve health among the older TGD veteran population.

The present study sought to understand the antecedents to COVID-19 vaccination among those reporting a change in vaccine intention in order to improve COVID-19 vaccine uptake in the United States. We employed semi-structured interviews and one focus group discussion with vaccinated and unvaccinated Veterans Health Administration (VHA) employees and Veterans at three Veterans' Affairs medical centers between January and June 2021. A subset of these participants (n=21) self-reported a change in COVID-19 vaccine intention and were selected for additional analysis. We combined thematic analysis using the 5C scale (confidence, collective responsibility, complacency, calculation, constraints) as our theoretical framework with a constant comparative method from codes based on the SAGE Working Group on Vaccine Hesitancy. We generated 13 themes distributed across the 5C constructs that appeared to be associated with a change in COVID-19 vaccine intention. Themes included a trusted family member, friend or colleague in a healthcare field, a trusted healthcare professional, distrust of government or politics (confidence); duty to family and protection of others (collective responsibility); perceived health status and normative beliefs (complacency); perceived vaccine safety, perceived risk-benefit, and orientation towards deliberation (calculation); and ease of process (constraints). Key factors in promoting vaccine uptake included a desire to protect family; and conversations with as key factors in promoting vaccine uptake. Constructs from the 5C scale are useful in understanding intrapersonal changes in vaccine intentions over time, which may help public health practitioners improve future vaccine uptake.In this study of the Veteran and VA employee population, we aimed to understand what factors led to a decision to receive a COVID-19 vaccine. As part of a quality improvement project, we interviewed individuals at three Veterans’ Affairs sites in the first six months of 2021. We then used a smaller sample of 21 participants who reported a change in their intentions to receive a COVID-19 vaccine to analyze for this study. This analysis utilizes constructs from the 5C scale, which was developed to understand the conditions required for an individual to decide to receive a vaccine (confidence, collective responsibility, complacency, calculation, constraints). The coding process revealed a number of recurring themes across the interviews falling under each of the five constructs, but concepts relating to vaccine confidence (i.e., level of trust in those developing and disseminating the vaccine) were most common, and constraints (i.e., psychological and structural barriers that stand in the way of vaccination) appeared least frequently in our interviews. We found that significant motivators to receive the vaccine included a desire to protect family and conversations with trusted clinicians, particularly mental healthcare providers. Our study was unique in using the 5Cs to understand changes in vaccine changes over time. Findings show that change in vaccine attitudes is possible even in the presence of concerns and shed light on approaches that public health providers could use to improve vaccine and booster rates.

PURPOSE: Transgender (TG) individuals are a historically understudied and underserved patient population. Although clinical guidelines for the care of TG patients exist, quality measures (QMs) specific to this population are lacking. The goal of this study was to obtain expert input on aspects of care for which quality measurement may be appropriate and describe feedback on candidate QMs. METHODS: We convened a virtual technical expert panel in September 2020 with six experts in TG medical care. Experts participated in a guided discussion and provided numeric ratings on dimensions of measure suitability (importance, validity/reliability, feasibility, and ease of understanding) for eight candidate QMs spanning multiple care domains (e.g., laboratory testing/monitoring, cancer screening, and sexually transmitted infection screening). RESULTS: Panelists acknowledged high importance and potential to improve care for some candidate QMs, particularly those related to laboratory testing before initiating and during hormone therapy. Numeric ratings of QMs varied but tended to be higher for testing-focused QMs. Experts raised concerns about overly prescriptive language for some QMs and emphasized the importance of considering more flexible specifications to accommodate diverse care scenarios—including care provided to nonbinary individuals—and align with the individualized nature of gender-affirming care. CONCLUSION: These preliminary findings support a potential role for QMs in improving quality of care for TG patients. Measures related to laboratory testing/monitoring for patients who receive or plan to initiate hormone therapy may be feasible and promising to explore in the future. Additional larger-scale efforts are needed to develop and test QMs for the care of TG individuals.

Background The effect of gender affirming hormone therapy (GAHT) on clinical laboratory parameters, including levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), is an area of uncertainty in transgender health. Aim We sought to estimate the distribution parameters of liver enzyme levels among transmasculine (TM) and transfeminine (TF) persons receiving GAHT relative to the corresponding measures in cisgender reference groups, and to evaluate longitudinal changes in these laboratory measures following GAHT initiation. Methods The data for this longitudinal study included 624 TF and 438 transmasculine (TM) people as well as 4,090 cisgender males and 4,797 cisgender females enrolled in 3 integrated health systems. Time under observation was divided into 2 intervals: from the first blood test to the date of the first filled GAHT prescription and from GAHT initiation to the most recent ALT or AST measurement. Linear mixed models were used to compare changes in log-transformed ALT and AST values among transgender cohort members before and after GAHT initiation, and relative to the reference groups. The results were expressed as relative differences (in %) and the ratios of these differences (ratios-of-ratios) along with the 95% confidence intervals (CIs). Outcomes Changes in ALT and AST levels among transgender people over time and relative to the corresponding changes in cisgender referents. RESULTS Among TM study participants, the post GAHT ratios-of-ratios for AST were 1.61 (95% CI: 1.13, 2.31) and 1.57 (95% CI: 1.06, 2.31) relative to cisgender males and females respectively. For ALT, the corresponding comparisons yielded the ratios-of-ratios (95% CIs) of 2.06 (1.67, 2.54) and 1.90 (1.50, 2.40). No statistically significant changes were observed among TF participants. Other factors associated with higher liver enzyme levels included alcohol use/abuse and obesity. Clinical Implications TM persons may experience modest increases in ALT and AST concentrations following testosterone initiation; however, clinical significance of the observed association remains unclear and requires further investigation. By contrast, feminizing GAHT is unlikely to induce appreciable changes in liver enzyme levels. Strength and Limitations The strengths of this study are the longitudinal design and the ability to assemble an unselected cohort nested within large health systems. The main limitations include the lack of information on hormone levels and the inability to take into account GAHT doses and routes of administration. CONCLUSION The influence of long-term GAHT on ALT and AST levels appears modest and not likely to reflect clinically meaningful changes in liver function.

We examined patient attitudes and beliefs and provider perspectives on patients' attitudes and beliefs towards testosterone therapy in Veterans Affairs (VA).We used a thematic analysis approach to understand variation in patient attitudes and beliefs towards testosterone at six VA sites with high and low levels of testosterone prescribing in VA. Semi-structured phone interviews with 18 patients and 22 providers at these sites were transcribed and coded using a priori theoretical constructs and emergent themes. A cross-case matrix of coded data was used to evaluate themes related to patient-level factors.Patients' beliefs toward testosterone did not differ across sites. Patients, not providers, generally initiated conversations about testosterone. We identified five key domains related to patient beliefs and provider perceived patient beliefs towards testosterone: reasons for initiating testosterone, patient information sources and expectations about testosterone, receptivity towards discontinuation of testosterone, patient/provider engagement in information sharing, and self-advocacy by the patients in decision-making.Patient factors play an important role in testosterone prescribing decisions.By considering these patient factors, providers can potentially help create a partnership with patients and foster shared decision-making for testosterone and other, similar medications.

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 m...

BACKGROUND Compared with non-Veterans, Veterans are at higher risk of experiencing homelessness, which is associated with opioid overdose. OBJECTIVE To understand how homelessness and Veteran status are related to risks of nonfatal and fatal opioid overdose in Massachusetts. DESIGN A cross-sectional study. PARTICIPANTS All residents aged 18 years and older during 2011-2015 in the Massachusetts Department of Public Health's Data Warehouse (Veterans: n=144,263; non-Veterans: n=6,112,340). A total of 40,036 individuals had a record of homelessness, including 1307 Veterans and 38,729 non-Veterans. MAIN MEASURES The main independent variables were homelessness and Veteran status. Outcomes included nonfatal and fatal opioid overdose. RESULTS A higher proportion of Veterans with a record of homelessness were older than 45 years (77% vs. 48%), male (80% vs. 62%), or receiving high-dose opioid therapy (23% vs. 15%) compared with non-Veterans. The rates of nonfatal and fatal opioid overdose in Massachusetts were 85 and 16 per 100,000 residents, respectively. Among individuals with a record of homelessness, these rates increased 31-fold to 2609 and 19-fold to 300 per 100,000 residents. Homelessness and Veteran status were independently associated with higher odds of nonfatal and fatal opioid overdose. There was a significant interaction between homelessness and Veteran status in their effects on risk of fatal overdose. CONCLUSIONS Both homelessness and Veteran status were associated with a higher risk of fatal opioid overdoses. An understanding of health care utilization patterns can help identify treatment access points to improve patient safety among vulnerable individuals both in the Veteran population and among those experiencing homelessness.

Background Among midlife and older women, menopause symptoms and menopausal hormone therapy have been linked to mental health disorders and other comorbidities related to suicide. However, the role of hormone therapy as a prognostic factor of suicide risk is largely unknown. Objectives To examine associations between menopausal hormone therapy, suicide attempts, and suicide among midlife and older women Veterans. Research design In this longitudinal analysis of national Veterans Health Administration data from women Veterans aged 50 years and above, we used Fine-Gray proportional hazards models to examine associations between menopausal hormone therapy (prescribed in 2012-2013) and incident suicide attempts and suicide (index date-2016). Measures Menopausal hormone therapy and psychoactive medications from pharmacy records; suicide attempts and suicide from national suicide data repositories; demographic variables, medical and psychiatric diagnoses, and substance use disorders from electronic medical record data and International Classification Diagnoses-9-CM codes. Results In this national sample of 291,709 women Veterans (mean age 60.47, SD 9.81), 6% were prescribed menopausal hormone therapy at baseline. Over an average of 4.5 years, 2673 had an incident suicide attempt (93%) or death by suicide (7%). Adjusting for age, race, and medical diagnoses, menopausal hormone therapy was associated with increased risk of suicide attempt (hazard ratio 1.41; 95% confidence interval, 1.22-1.64) and over 2-fold increased risk of death by suicide (hazard ratio 2.47; 95% confidence interval, 1.58-3.87). Associations with death by suicide remained significant after accounting for psychiatric comorbidity and psychoactive medications. Conclusions Menopausal hormone therapy may be an important indicator of suicide risk among midlife and older women.

Utilizing data from the Million Veteran Program (MVP), we investigated the genetic determinants underlying total testosterone levels via a multi-ancestral analysis of 124,593 individuals of European (n=88,385), African (n=25,235) and Hispanic (n=10,973) ancestry. We identified 46 trans-ancestry variants and 17 ancestry-specific variants, of which 14 trans-ancestry variants and 15 ancestry-specific variants are novel associations with testosterone. Results implicate genes regulating testosterone shared across ancestral groups, which include SHBG, JMJD1C, FXR2, SENP3, TNFSF12-TNFSF13 while implicating genes such as MSN, DMD, VSIG4, CHEK2, TKTL1 that may underlie ancestry-group differences in testosterone regulation. We also linked testosterone variants on the X chromosome with differential risk of chronic kidney disease and hereditary hemolytic anemias in African and Hispanic ancestry groups, respectively. Lastly, we constructed a polygenic score from our 46 trans-ancestry variants and associated it with testicular dysfunction, hyperlipidemia, gout and prostate cancer with stronger prostate cancer associations in Hispanic and African ancestry groups compared to the European ancestry group. These findings provide insight into ancestry-specific androgen regulation and identify novel variants for disease risk stratification in patients.

Although COVID-19 vaccines have been available to many U.S. Veterans Affairs (VA) healthcare system employees and Veteran patients since early 2021, vaccine receipt data indicates some groups are not receiving them. Our objective was to conduct a rapid qualitative assessment of Veterans' and VA employees' views on COVID-19 vaccination to inform clinical leaders' ongoing efforts to increase vaccine uptake across the VA. We employed semi-structured interviews and a focus group involving employees and Veterans as part of a quality improvement project between January and June 2021 at three VA medical centers. Thirty-one employees and 27 Veterans participated in semi-structured interviews; 5 Veterans from a national stakeholder organization participated in a focus group. Data were analyzed using directed content analysis, involving an a priori coding framework comprised of four domains with subcodes under each: contextual influences, barriers and facilitators, vaccine-specific issues, and VA/military experiences. We then classified initial codes into five categories of hesitancy: vaccine deliberation, dissent, distrust, indifference and skepticism. A subset of Veterans (n = 14) and employees (n = 8) identified as vaccine hesitant. Vaccine hesitancy categories were represented by subcodes of religion, culture, gender or socio-economic factors, perceptions of politics and policies, role of healthcare providers, and historical influences; (contextual influences); knowledge or awareness of vaccines, perceived susceptibility to COVID-19, and beliefs and attitudes about health and illness (barriers and facilitators); vaccine development process (vaccine-specific issues) and military experiences (VA/military factors). Facilitators involved talking with trusted others, ease of vaccine access, and perceptions of family and societal benefits of vaccines. Vaccine hesitancy is multi-faceted and likely requires multiple strategies for engaging in conversations to address Veteran and VA employee concerns. Messages should involve patient-centered communication strategies delivered by trusted healthcare providers and peers and should focus on addressing expected benefits for family, friends, and society.

Importance: Early detection of prostate cancer to reduce mortality remains controversial because there is often also overdiagnosis of low-risk disease and unnecessary treatment. Genetic scores may provide an objective measure of a man9s risk of dying from prostate cancer and thus inform screening decisions, especially in men of African ancestry, who have a higher average risk of prostate cancer death but are often treated as a homogeneous group. Objective: Determine whether a polygenic hazard score based on 290 genetic variants (PHS290) is associated with risk of metastatic or fatal prostate cancer in a racially and ethnically diverse population. Design: Million Veteran Program (MVP) cohort study, 2011-2021. Setting: Nation-wide study of United States military veterans. Participants: Population-based volunteer sample of male participants. Exposure(s): Genotype data were used to calculate the genetic score, PHS290. Family history of prostate cancer and ancestry group (harmonized genetic ancestry and self-reported race/ethnicity: European, African, Hispanic, or Asian) were also studied. Main Outcome(s) and Measure(s): Study designed after MVP data collected. Primary outcome: age at death from prostate cancer. Key secondary outcome: age at diagnosis of prostate cancer metastases. Hypothesis: A germline genetic score (PHS290) is associated with risk of fatal (or metastatic) prostate cancer. Results: 513,997 MVP participants were included. Median age at last follow-up: 69 years. PHS290 was associated with age at death from prostate cancer in the full cohort and for each ancestry group (p

Background Rates of suicide and unintended overdose death are high among midlife and older women, yet there is paucity of data identifying women at greatest risk. Psychoactive medications, commonly prescribed and co-prescribed in this population, may serve as salient indicators of risk for these outcomes. Objective To determine whether long-term psychoactive medications and psychoactive polypharmacy predict risk of suicide and unintended overdose death among midlife and older women Veterans above and beyond other recognized factors. Design Longitudinal cohort study Participants Women Veterans aged ≥ 50 with at least one Veterans Health Administration (VHA) clinical encounter in FY2012–2013. Main Measures Long-term psychoactive medications (opioids, benzodiazepines, sedative-hypnotics, antidepressants, antipsychotics, and antiepileptics, prescribed for ≥ 90/180 days) and psychoactive polypharmacy (overlapping for ≥ 1 day) from VHA pharmacy records; suicide and unintended overdose death through December 31, 2018. Key Results In this national sample of 154,558 midlife and older women Veterans (mean age 63.4, SD 9.3 years), 130 died by suicide and 175 died from unintentional overdose over an average of 5.6 years. In fully adjusted models, long-term opioids (hazard ratio (HR) 2.01, 95% CI 1.21–3.35) and benzodiazepines (HR 2.99, 95% CI 1.82–4.91) were associated with death by suicide; opioids (HR 3.62, 95% CI 2.46–5.34), benzodiazepines (HR 2.77, 95% CI 1.73–4.42), sedative-hypnotics (HR 1.87, 95% CI 1.06–3.29), antidepressants (HR 1.47, 95% CI 1.03–2.12), antipsychotics (HR 1.81, 95% CI 1.02–3.22), and antiepileptics (HR 2.17, 95% CI 1.48–3.19) were associated with unintended overdose death. Women who were co-prescribed ≥ 3 psychoactive medications had over 2-fold increased risk of suicide (HR 2.83, 95% CI 1.65–4.84) and unintended overdose death (HR 2.60, 95% CI 1.72–3.94). Conclusions Long-term psychoactive medications and psychoactive medication polypharmacy were important indicators of risk for death by suicide and death by unintended overdose among midlife and older women Veterans, even after accounting for psychiatric and substance use disorders.

BACKGROUND: Inappropriate testosterone use and variations in testosterone prescribing patterns exist in the Veterans Health Administration (VHA) despite the presence of clinical guidelines. OBJECTIVE: We examined system and clinician factors that contribute to patterns of potentially inappropriate testosterone prescribing in VHA. DESIGN: Qualitative study using a positive deviance approach to understand practice variation in high- and low-testosterone prescribing sites. PARTICIPANTS: Twenty-two interview participants included primary care and specialty clinicians, key opinion leaders, and pharmacists at 3 high- and 3 low-testosterone prescribing sites. APPROACH: Semi-structured phone interviews were conducted, transcribed, and coded using a priori theoretical constructs and emergent themes. Case studies were developed for each site and a cross-case matrix was created to evaluate variation across high- and low-prescribing sites. KEY RESULTS: We identified four system-level domains related to variation in testosterone prescribing: organizational structures and processes specific to testosterone prescribing, availability of local guidance on testosterone prescribing, well-defined dissemination process for local testosterone polices, and engagement in best practices related to testosterone prescribing. Two clinician-level domains were also identified, specifically, structured initial testosterone prescribing process and specified follow-up testosterone prescribing process. High- and low-testosterone prescribing sites systematically varied in the four system-level domains, while the clinician-level domains looked similar across all sites. The third high-prescribing site was unusual in that it exhibited the four domains similar to the 3 low-prescribing sites at the time of our visit. This site had greatly reduced its prescribing of testosterone in the interim. CONCLUSIONS: Findings suggest that local organizational factors play an important role in influencing prescribing. Sites have the potential to transform their utilization patterns by providing access to specialty care expertise, an electronic health record-based system to facilitate guideline-concordant prescribing, well-defined dissemination processes for information, guidance from multiple sources, and clarity regarding best practices for prescribing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-019-05270-6) contains supplementary material, which is available to authorized users.

We sought to operationalize and validate data-driven approaches for identifying transgender individuals in the Veterans Health Administration (VHA) of the US Department of Veterans Affairs (VA) through a retrospective analysis using VA administrative data from 2006–2018. Besides diagnoses of gender identity disorder (GID), a combination of non-GID data elements was used to identify potentially transgender veterans, including 1) an International Classification of Diseases (Ninth or Tenth Revision) code of endocrine disorder, unspecified or not otherwise specified; 2) receipt of sex hormones not associated with the sex documented in the veteran’s records (gender-affirming hormone therapy); and 3) a change in the veteran’s administratively recorded sex. Both GID and non-GID data elements were applied to a sample of 13,233,529 veterans utilizing the VHA of the VA between January 2006 and December 2018. We identified 10,769 potentially transgender veterans. Based on a high positive predictive value for GID-coded veterans (83%, 95% confidence interval: 77, 89) versus non–GID-coded veterans (2%, 95% confidence interval: 1, 11) from chart review validation, the final analytical sample comprised only veterans with a GID diagnosis code (n = 9,608). In the absence of self-identified gender identity, findings suggest that relying entirely on GID diagnosis codes is the most reliable approach for identifying transgender individuals in the VHA of the VA.

We sought to operationalize and validate data-driven approaches to identify transgender individuals in the U.S. Department of Veteran Affairs (VA) health care system through a retrospective analysis using VA administrative data from 2006 to 2018. Besides gender identity disorder (GID) diagnoses, a combination of non-GID data elements were used to identify potential transgender veterans, including: 1) endocrine disorder, unspecified or not otherwise specified codes, 2) receipt of sex hormones not associated with the sex documented in the veteran's records (gender-affirming hormone therapy), and 3) change in the administratively recorded sex. Both GID and non-GID data elements were applied to a sample of 13,233,529 veterans utilizing the VA healthcare system between January 2006 and December 2018. We identified 10,769 potential transgender veterans. Based on a high positive predictive value of GID (83%, 95% Confidence Interval (CI)=77-89%) versus non-GID-coded veterans (2%, 95% CI=1-11%) from chart review validation, the final analytical sample comprised of only veterans with a GID diagnosis code (n=9,608). In the absence of self-identified gender identity, findings suggest that relying entirely on GID diagnosis codes are the most reliable approach to identify transgender individuals in the VA.

Background Valid and reliable quality measures can help catalyze improvements in health care. The care of transgender patients is ripe for quality measurement, as there is increasing awareness of the increasing prevalence of this population and the urgency of improving the health care they receive. While best practices may not exist for some aspects of transgender health care, other aspects are characterized by well-developed and highly evidence-based recommendations. Our objective was to create a list of potential quality measures for transgender care. Methods and results In consultation with our advisory panel, which consisted of clinical and academic experts in transgender medicine, we selected eight prominent clinical practice guidelines of transgender health care for review. Our four team investigators carefully reviewed all eight clinical practice guidelines. Through the course of multiple consensus-building meetings, we iteratively refined items until we had agreed upon a list of forty potential quality measures, all of which met the criteria for quality measures set forth in the Center for Medicare and Medicaid Services Blueprint for developing quality measures. Conclusions This manuscript explains the origin of the quality measures we developed, and also provides a useful roadmap to any group hoping to develop quality measures for a field that has not previously had any.

Background Large administrative databases often do not capture gender identity data, limiting researchers' ability to identify transgender people and complicating the study of this population. Objective The objective of this study was to develop methods for identifying transgender people in a large, national dataset for insured adults. Research design This was a retrospective analysis of administrative claims data. After using gender identity disorder (GID) diagnoses codes, the current method for identifying transgender people in administrative data, we used the following 2 strategies to improve the accuracy of identifying transgender people that involved: (1) Endocrine Disorder Not Otherwise Specified (Endo NOS) codes and a transgender-related procedure code; or (2) Receipt of sex hormones not associated with the sex recorded in the patient's chart (sex-discordant hormone therapy) and an Endo NOS code or transgender-related procedure code. Subjects Seventy-four million adults 18 years and above enrolled at some point in commercial or Medicare Advantage plans from 2006 through 2017. Results We identified 27,227 unique transgender people overall; 18,785 (69%) were identified using GID codes alone. Using Endo NOS with a transgender-related procedure code, and sex-discordant hormone therapy with either Endo NOS or transgender-related procedure code, we added 4391 (16%) and 4051 (15%) transgender people, respectively. Of the 27,227 transgender people in our cohort, 8694 (32%) were transmasculine, 3959 (15%) were transfeminine, and 14,574 (54%) could not be classified. Conclusion In the absence of gender identity data, additional data elements beyond GID codes improves the identification of transgender people in large, administrative claims databases.

This cohort study analyzes the association between testosterone and opioid use and improved health outcomes among male US military veterans with opioid-induced androgen deficiency., Key Points Question What are the health outcomes among long-term opioid users who receive testosterone treatment compared with opioid users who do not? Findings In this cohort study of 21 272 male long-term opioid users with testosterone deficiency, those who received opioids plus testosterone therapy had significantly lower all-cause mortality and lower incidence of major adverse cardiovascular events, anemia, and femoral or hip fractures than their counterparts who received opioids only in covariate-adjusted and propensity score–matched models. Meaning This study’s findings suggest that receiving opioids plus testosterone treatment is associated with lower all-cause mortality and a lower incidence of other adverse health outcomes among men with opioid-induced androgen deficiency., Importance Androgen deficiency is common among male opioid users, and opioid use has emerged as a common antecedent of testosterone treatment. The long-term health outcomes associated with testosterone therapy remain unknown, however. Objective To compare health outcomes between long-term opioid users with testosterone deficiency who filled testosterone prescriptions and those with the same condition but who did not receive testosterone treatment. Design, Setting, and Participants This cohort study focused on men in the care of the Veterans Health Administration (VHA) facilities throughout the United States from October 1, 2008, to September 30, 2014. It included male veterans who were long-term opioid users, had low testosterone levels (

Medications are often prescribed suboptimally; some effective medications are underused, some ineffective medications are overused, and some medications that should be received by a few are instead given to many. The underlying causes of suboptimal prescribing likely differ for each medication, and therefore must be understood anew, although previous studies can help generate hypotheses. This perspective sets forth a 3-step research agenda, which has worked well for us in several recently completed and ongoing projects. The three steps are to 1) demonstrate variation in suboptimal prescribing for the targeted medication; 2a) use mixed methods to understand the patient-, provider-, and system-level causes of suboptimal prescribing for this medication; 2b) develop a justification for improving the use of this medication, often involving a business case analysis; and 3) develop and implement interventions to improve prescribing of the targeted medication, informed by what has been learned in Steps 1 and 2 and relying on the principles of implementation science. Previous efforts have focused disproportionately on Step 1, or documenting gaps in practice, and Step 3, or deploying and evaluating efforts to improve practice. Our contention is that addressing all three steps sequentially, while effort-intensive, will maximize the chances of deploying a more effective intervention that will impact population health. We commend this three-step approach to health services researchers who wish to maximize impact by basing their research on a natural progression from documenting problems, to understanding their causes, to formulating and deploying a solution.

Key Points Question What are veterans’ attitudes and intentions associated with COVID-19 vaccination? Findings In this survey study of 1178 US veterans in March 2021, 71% of veterans reported being vaccinated against COVID-19. Fears about side effects and worry about the newness of vaccines were the primary reasons given for not getting vaccinated, reflecting vaccine skepticism and deliberation. Meaning These findings suggest that targeting veterans’ concerns around the adverse effects and safety of COVID-19 vaccines through conversations with trusted Veterans Health Administration health care practitioners is key to increasing vaccine acceptance., This survey study assesses veterans’ attitudes toward and intentions to receive COVID-19 vaccines., Importance Compared with the general population, veterans are at high risk for COVID-19 and have a complex relationship with the government. This potentially affects their attitudes toward receiving COVID-19 vaccines. Objective To assess veterans’ attitudes toward and intentions to receive COVID-19 vaccines. Design, Setting, and Participants This cross-sectional web-based survey study used data from the Department of Veterans Affairs (VA) Survey of Healthcare Experiences of Patients’ Veterans Insight Panel, fielded between March 12 and 28, 2021. Of 3420 veterans who were sent a link to complete a 58-item web-based survey, 1178 veterans (34%) completed the survey. Data were analyzed from April 1 to August 25, 2021. Exposures Veterans eligible for COVID-19 vaccines. Main Outcomes and Measures The outcomes of interest were veterans’ experiences with COVID-19, vaccination status and intention groups, reasons for receiving or not receiving a vaccine, self-reported health status, and trusted and preferred sources of information about COVID-19 vaccines. Reasons for not getting vaccinated were classified into categories of vaccine deliberation, dissent, distrust, indifference, skepticism, and policy and processes. Results Among 1178 respondents, 974 (83%) were men, 130 (11%) were women, and 141 (12%) were transgender or nonbinary; 58 respondents (5%) were Black, 54 veterans (5%) were Hispanic or Latino, and 987 veterans (84%) were non-Hispanic White. The mean (SD) age of respondents was 66.7 (10.1) years. A total of 817 respondents (71%) self-reported being vaccinated against COVID-19. Of 339 respondents (29%) who were not vaccinated, those unsure of getting vaccinated were more likely to report fair or poor overall health (32 respondents [43%]) and mental health (33 respondents [44%]) than other nonvaccinated groups (overall health: range, 20%-32%; mental health: range, 18%-40%). Top reasons for not being vaccinated were skepticism (120 respondents [36%] were concerned about side effects; 65 respondents [20%] preferred using few medications; 63 respondents [19%] preferred gaining natural immunity), deliberation (74 respondents [22%] preferred to wait because vaccine is new), and distrust (61 respondents [18%] did not trust the health care system). Among respondents who were vaccinated, preventing oneself from getting sick (462 respondents [57%]) and contributing to the end of the COVID-19 pandemic (453 respondents [56%]) were top reasons for getting vaccinated. All veterans reported the VA as 1 of their top trusted sources of information. The proportion of respondents trusting their VA health care practitioner as a source of vaccine information was higher among those unsure about vaccination compared with those who indicated they would definitely not or probably not get vaccinated (18 respondents [26%] vs 15 respondents [15%]). There were no significant associations between vaccine intention groups and age (χ24 = 5.90; P = .21) or gender (χ22 = 3.99; P = .14). Conclusions and Relevance These findings provide information needed to develop trusted messages used in conversations between VA health care practitioners and veterans addressing specific vaccine hesitancy reasons, as well as those in worse health. Conversations need to emphasize societal reasons for getting vaccinated and benefits to one’s own health.

Background: Many transgender patients experience gender dysphoria as a result of an incongruence between their gender identity and sex assigned at birth. Gender-affirming hormone therapy improves the quality of life for transgender patients seeking to increase alignment of their secondary sex characteristics and gender identity. However, little is known about the patient factors that are associated with receipt of this therapy which is critical to identifying areas for improvement in care for transgender patients. Objective: To evaluate patient characteristics associated with transgender patients’ receipt of hormone therapy from the Veterans Health Administration (VHA). Methods: Inpatient and outpatient data were reviewed for transgender patients, identified through ICD-9/ICD-10 diagnosis codes for gender identity disorder (GID), receiving VHA health care from January 2006 to December 2018. We evaluated receipt of hormone therapy (testosterone or estrogen +/- spironolactone) from the VHA, socio-demographics, comorbidities, social stressors, military sexual trauma, and documented suicide attempts. Adjusted Odds Ratios (aOR) and 95% Confidence Intervals (CI) were obtained from a multivariable logistic regression model used to ascertain the relationship between patient characteristics and hormone therapy. Results: Of 9,406 patients with documented GID, 5,487 (58.3%) received hormone therapy from the VHA. Compared to patients not receiving hormone therapy, a higher proportion of patients receiving hormone therapy were younger (21-29 years: 18.1% vs. 11.6%; 30-39 years: 20.0% vs. 14.6%; 40-49 years: 16.2% vs. 13.6%), had documentation of a positive military sexual trauma screening (22.2% vs. 16.2%; p

Use of nonbenzodiazepine sedative hypnotics, especially zolpidem, has grown substantially, raising concerns about safety. Here, we evaluated prescribing patterns of zolpidem in the Veterans Health Administration.A cross-sectional study of veterans receiving zolpidem in the outpatient setting from October 1, 2011, to September 30, 2016.The study population consisted of 500,332 zolpidem users (58,598 women and 441,734 men) and a random 10% sample (n = 631,449) of nonusers. We examined 2 outcomes related to inappropriate prescribing: high-dose zolpidem prescribing and overlap with benzodiazepines. We generated interrupted time series and logistic regression models to analyze these outcomes in men and women separately.In 2016, 29.7% of female veterans received an inappropriately high guideline-discordant dosage compared with 0.1% of male veterans (P.001 for all reported comparisons). Furthermore, more women than men had overlapping benzodiazepine and zolpidem prescriptions (18.8% vs 14.3%). In fully adjusted models, inappropriately high doses were more commonly received by younger women (adjusted odds ratios [AORs]: 2.75 for 21-39 years and 2.97 for 40-49 years compared with ≥80 years) and women with substance use disorder (AOR, 1.48). In the second inappropriateness outcome models, women with anxiety (AOR, 2.28) or schizophrenia (AOR, 2.05) and men with cancer (AOR, 1.42), anxiety (AOR, 2.66), or schizophrenia (AOR, 2.46) were more likely to receive an overlapping prescription of zolpidem and benzodiazepines.We found evidence of inappropriate zolpidem prescribing among veterans, particularly women. Greater understanding of the drivers of this inappropriate prescribing is necessary to develop interventions to promote safer, more guideline-concordant prescribing.

The aim of this study was to evaluate whether veterans in Massachusetts receiving opioids and/or benzodiazepines from both Veterans Health Administration (VHA) and non-VHA pharmacies are at higher risk of adverse events compared with those receiving opioids at VHA pharmacies only.A cohort study of veterans who filled a prescription for any Schedule II through V substance at a Massachusetts VHA pharmacy. Prescriptions were recorded in the Massachusetts Department of Public Health Chapter 55 data set.The study sample included 16,866 veterans residing in Massachusetts, of whom 9238 (54.8%) received controlled substances from VHA pharmacies only and 7628 (45.2%) had filled prescriptions at both VHA and non-VHA pharmacies ("dual care users") between October 1, 2013, and December 31, 2015. Our primary outcomes were nonfatal opioid overdose, fatal opioid overdose, and all-cause mortality.Compared with VHA-only users, more dual care users resided in rural areas (12.6% vs 10.6%), received high-dose opioid therapy (26.3% vs 7.3%), had concurrent prescriptions of opioids and benzodiazepines (34.8% vs 8.2%), and had opioid use disorder (6.8% vs 1.6%) (P.0001 for all). In adjusted models, dual care users had higher odds of nonfatal opioid overdose (odds ratio [OR], 1.29; 95% CI, 0.98-1.71) and all-cause mortality (OR, 1.66; 95% CI, 1.43-1.93) compared with VHA-only users. Dual care use was not associated with fatal opioid overdoses.Among veterans in Massachusetts, receipt of opioids from multiple sources was associated with worse outcomes, specifically nonfatal opioid overdose and mortality. Better information sharing between VHA and non-VHA pharmacies and prescribers has the potential to improve patient safety.

Importance Substance use disorders are a major source of morbidity and mortality in the United States. National data comparing the prevalence of substance use disorder diagnoses (SUDDs) among transgender and cisgender individuals are lacking in the United States. Objectives To investigate the prevalence of SUDDs among transgender and cisgender adults and to identify within-group and between-group differences by age, gender, and geographic location. Design, Setting, and Participants This cross-sectional study used the OptumLabs Data Warehouse to analyze deidentified claims from approximately 74 million adults aged 18 years or older enrolled in commercial or Medicare Advantage insurance plans in 2017. A total of 15 637 transgender adults were identified based on a previously developed algorithm using a combination ofInternational Classification of Diseases, Tenth Revision (ICD-10) transgender-related diagnosis and procedure codes and sex-discordant hormone prescriptions. A cohort of 46 911 cisgender adults was matched to the transgender cohort in a 3:1 ratio based on age and geographic location. Main Outcomes and Measures SUDDs, based onICD-10codes, were assessed overall and compared between transgender and cisgender cohorts and by geographic region (ie, Northeast, Midwest, South, and West); age groups (eg, 18-25, 26-30, 31-35 years), and gender (ie, transfeminine [TF; assigned male sex at birth, identify along feminine gender spectrum], transmasculine [TM; assigned female sex at birth, identify along masculine gender spectrum], male, and female). Results In this study of 15 637 transgender adults (4955 [31.7%] TM) and 46 911 cisgender adults (23 664 [50.4%] female), most (8627 transgender adults [55.2%]; 25 882 cisgender adults [55.2%]) were aged between 18 and 40 years, and 6482 transgender adults (41.5%) and 19 446 cisgender adults (41.5%) lived in the South. Comparing transgender to cisgender groups, significant differences were found in the prevalence of a nicotine (2594 [16.6%] vs 2551 [5.4%];P Conclusions and Relevance In this study, the prevalence of SUDDs was significantly elevated among transgender adults relative to their cisgender peers. These findings underscore the need for culturally tailored clinical interventions to treat substance use disorder in transgender populations.

RESEARCH OBJECTIVE: Inappropriate testosterone use and variations in testosterone prescribing patterns exist in the Veterans Health Administration (VHA) despite the presence of clinical guidelines. Understanding the context within which testosterone prescribing occurs is key to planning successful interventions to improve guideline‐concordant prescribing. We examined system‐ and clinician‐level factors that contribute to patterns of potentially inappropriate testosterone prescribing in VHA. STUDY DESIGN: We conducted a qualitative study using a positive deviance approach to understand practice variation in high‐ and low‐testosterone prescribing sites. Semi‐structured phone interviews were conducted, transcribed, and coded using a priori theoretical constructs and emergent themes. Case studies were developed for each site and a cross‐case matrix was created to evaluate variation across high‐ and low‐prescribing sites. POPULATION STUDIED: Twenty‐two interview participants included primary care and specialty clinicians, key opinion leaders, and pharmacists at 3 high‐ and 3 low‐testosterone prescribing sites. These high‐ and low‐testosterone‐prescribing sites were located in six states and all four regions of the United States. PRINCIPAL FINDINGS: We identified four system‐level domains related to variation in testosterone prescribing: organizational structures and processes specific to testosterone prescribing, availability of local guidance on testosterone prescribing, well‐defined dissemination process for local testosterone polices, and engagement in best practices related to testosterone prescribing. Two clinician‐level domains were also identified: structured initial testosterone prescribing process and well‐specified follow‐up protocols following testosterone prescription. The four system‐level domains were related systematically to level of testosterone prescribing whereas the clinician level domains were similar across all sites. At all sites, most testosterone prescriptions were initiated by patient request and clinicians varied in their adherence to guideline‐concordant prescribing. The third high‐prescribing site was unusual in that, at the time of our visit, it exhibited system‐level domain characteristics similar to the 3 low‐prescribing sites. This outlier had recognized its status as a high‐prescribing site and implemented several improvement strategies in the year between selection and interviews, resulting in greatly reduced rates of testosterone prescribing. CONCLUSIONS: In this study, we found that low‐prescribing sites shared some common features, including easier access to specialty care expertise, existence of an electronic health record‐based system to facilitate guideline‐concordant prescribing, well‐defined dissemination processes for information, availability of guidance from multiple sources, and clarity regarding what constitutes best practices for prescribing. Findings suggest that local organizational factors play an important role in influencing prescribing. Sites have the potential to transform their utilization patterns by providing access to specialty care expertise, an electronic health record‐based system to facilitate guideline‐concordant prescribing, well‐defined dissemination processes for information, guidance from multiple sources, and clarity regarding best practices for prescribing. IMPLICATIONS FOR POLICY OR PRACTICE: The use of these system‐level factors to change medication prescribing can also be extrapolated to improving other prescribing behavior, including safer prescribing of high‐risk drugs and facilitating deprescribing of unnecessary and/or harmful medications. Lessons learned from this study will serve as an exemplar for any site aiming to improve its testosterone‐prescribing practices and prescribing in general beyond testosterone. PRIMARY FUNDING SOURCE: Department of Veterans Affairs.

Use of nonbenzodiazepine sedative hypnotics, especially zolpidem, has grown substantially, raising concerns about safety. Gender‐specific guidelines have been recommended for appropriate zolpidem prescribing to address patient safety concerns. In line with an FDA recommendation in 2013, the Veterans Health Administration (VHA) issued a similar directive to lower the doses of zolpidem in women in 2013. However, little is known about zolpidem prescribing patterns in the VHA in general. Therefore, the goal of this study was to examine utilization trends and inappropriate prescribing of zolpidem in accordance with VHA guidelines in male and female veterans in the VHA. A cross‐sectional study of veterans receiving zolpidem in the outpatient setting from October 1, 2011, to September 30, 2016. We examined 2 outcomes related to inappropriate zolpidem prescribing: high‐dose and overlap with benzodiazepines. The study population consisted of 500 332 zolpidem users (58 598 women and 441 734 men) and a random 10% sample (n = 631 449) of nonusers. Across the VHA, 7.1% of men and 10.0% of women received zolpidem at least once during the study period. In 2016, 29.7% of female veterans received an inappropriately high guideline‐discordant dosage compared with 0.1% of male veterans (P

Testosterone supplementation has been widely used in those infected with human immunodeficiency virus (HIV) for hypogonadism, and wasting. But with effective antiretroviral therapy and increasing recognition of atherosclerotic disease and adults infected with HIV, the risks of inappropriate testosterone use in HIV-infected patients are far better recognized than previously. Testosterone use has expanded among U.S. males, but few studies have examined prescribing in those infected with HIV. In a national cohort of males with at least one outpatient prescription in the Veterans Health Administration (VHA), we examined 9475 HIV-infected males, including 2484 who had received testosterone and a randomly selected 6991 who had not. For comparison, we identified 1,387,241 uninfected males (189,369 had received testosterone and a randomly selected 1,197,872 had not). We determined rates of new and prevalent testosterone use, and also examined the adequacy of the diagnostic evaluation that had preceded testosterone initiation among our HIV-infected and uninfected testosterone groups. Our main results were as follows. HIV-infected men had higher rates of initiation (0.8% vs. 0.4% in FY09; p 0.001) and prevalence of testosterone use (2.2% vs. 0.8% in FY08; p 0.001) compared to the uninfected men across the entire period. Trends of prescribing for both groups followed a similar pattern, rising from FY08, reaching a peak in FY13, and then dipping in FY 14. Only 1.1% of HIV-infected patients had a fully guideline-concordant workup before starting testosterone therapy, compared to 3.5% of uninfected patients (p 0.001). In conclusion, testosterone use among HIV-infected patients in the VHA system rose to a peak in FY13 and has decreased somewhat since. Only a small minority of HIV-infected patients who receive testosterone therapy from VHA have undergone an appropriate workup before starting therapy, suggesting an opportunity for improvement.

SummaryAmong patients receiving oral anticoagulation for atrial fibrillation (AF), heart failure (HF) is associated with poor anticoagulation control. However, it is not known which patients with heart failure are at greatest risk of adverse outcomes. We evaluated 62,156 Veterans Health Administration (VA) patients receiving warfarin for AF between 10/1/06–9/30/08 using merged VA-Medicare dataset. We predicted time in therapeutic range (TTR) and rates of adverse events by categorising patients into those with 0, 1, 2, or 3+ of five putative markers of HF severity such as aspartate aminotransferase (AST)> 80 U/l, alkaline phosphatase> 150 U/l, serum sodium< 130 mEq/l, any receipt of metolazone, and any inpatient admission for HF exacerbation. These risk categories predicted TTR: patients without HF (referent) had a mean TTR of 65.0 %, while HF patients with 0, 1, 2, 3 or more markers had mean TTRs of 62.2 %, 57.2 %, 53.5 %, and 50.7 %, respectively (p< 0.001). These categories also discriminated for major haemorrhage well; compared to patients without HF, HF patients with increasing severity had hazard ratios of 1.84, 3.06, 3.52 and 5.14 respectively (p< 0.001). However, although patients with HF had an elevated hazard for bleeding compared to those without HF, these categories did not effectively discriminate risk of ischaemic stroke across HF. In conclusion, we developed a HF severity model using easily available clinical characteristics that performed well to risk-stratify patients with HF who are receiving anticoagulation for AF with regard to major haemorrhage.

Context Testosterone prescribing rates have increased substantially in the past decade. However, little is known about the context within which such prescriptions occur. Objective We evaluated provider- and site-level determinants of receipt of testosterone and of guideline-concordant testosterone prescribing. Design This study was cross-sectional in design. Setting This study was conducted at the Veterans Health Administration (VA). Participants Study participants were a national cohort of male patients who had received at least one outpatient prescription within the VA during fiscal year (FY) 2008 to FY 2012. A total of 38,648 providers and 130 stations were associated with these patients. Main Outcome Measure This study measured receipt of testosterone and guideline-concordant testosterone prescribing. Results Providers ranging in age from 31 to 60 years, with less experience in the VA [all adjusted odds ratio (AOR)

There has been an increase in the prescribing of testosterone therapy in the past decade. There is concern that at least part of this increase is driven by advertising rather than sound medical practice. The purpose of this review is to summarize the recent trends in testosterone prescribing, and to examine whether testosterone is being appropriately prescribed as per guidelines.Both global and U.S. data reflect an overall increase in the use of testosterone in the last decade, although there are early signs of a decline in testosterone sales since 2014. This increased prescribing has been accompanied with an overall increase in testing for testosterone levels, prescription of testosterone without the appropriate diagnostic evaluation recommended by clinical practice guidelines, and apparent use of this therapy for unproven medical conditions.Research to date suggests that there is room to improve our prescribing of testosterone. Greater understanding of the potential provider-level and system-level factors that contribute to the current prescribing practices may help accomplish such improvement.

Background— Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin. Methods and Results— Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases -Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases -Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P P P =0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P Conclusions— Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes.

Warfarin is effective in preventing thromboembolic events, but concerns exist regarding its use in patients with substance abuse.Identify which patients with substance abuse who receive warfarin are at risk for poor outcomes.Retrospective cohort study. Diagnostic codes, lab values, and other factors were examined to identify risk of adverse outcomes.Veterans AffaiRs Study to Improve Anticoagulation (VARIA) database of 103,897 patients receiving warfarin across 100 sites.Outcomes included percent time in therapeutic range (TTR), a measure of anticoagulation control, and major hemorrhagic events by ICD-9 codes.Nonusers had a higher mean TTR (62 %) than those abusing alcohol (53 %), drugs (50 %), or both (44 %, p 0.001). Among alcohol abusers, an increasing ratio of the serum hepatic transaminases aspartate aminotransferase/alanine aminotransferase (AST:ALT) correlated with inferior anticoagulation control; normal AST:ALT ≤ 1.5 predicted relatively modest decline in TTR (54 %, p 0.001), while elevated ratios (AST:ALT 1.50-2.0 and2.0) predicted progressively poorer anticoagulation control (49 % and 44 %, p 0.001 compared to nonusers). Age-adjusted hazard ratio for major hemorrhage was 1.93 in drug and 1.37 in alcohol abuse (p 0.001 compared to nonusers), and remained significant after also controlling for anticoagulation control and other bleeding risk factors (1.69 p 0.001 and 1.22 p = 0.003). Among alcohol abusers, elevated AST:ALT2.0 corresponded to more than three times the hemorrhages (HR 3.02, p 0.001 compared to nonusers), while a normal ratio AST:ALT ≤ 1.5 predicted a rate similar to nonusers (HR 1.19, p 0.05).Anticoagulation control is particularly poor in patients with substance abuse. Major hemorrhages are more common in both alcohol and drug users. Among alcohol abusers, the ratio of AST/ALT holds promise for identifying those at highest risk for adverse events.

Introduction Identifying major bleeding is fundamental to assessing the outcomes of anticoagulation therapy. This drives the need for a credible implementation in automated data for the International Society of Thrombosis and Haemostasis (ISTH) definition of major bleeding. Materials and Methods We studied 102,395 patients who received 158,511 person-years of warfarin treatment from the Veterans Health Administration (VA) between 10/1/06-9/30/08. We constructed a list of ICD-9-CM codes of "candidate" bleeding events. Each candidate event was identified as a major hemorrhage if it fulfilled one of four criteria: 1) associated with death within 30days; 2) bleeding in a critical anatomic site; 3) associated with a transfusion; or 4) was coded as the event that precipitated or was responsible for the majority of an inpatient hospitalization. Results This definition classified 11,240 (15.8%) of 71, 338 candidate events as major hemorrhage. Typically, events more likely to be severe were retained at higher rates than those less likely to be severe. For example, Diverticula of Colon with Hemorrhage (562.12) and Hematuria (599.7) were retained 46% and 4% of the time, respectively. Major, intracranial, and fatal hemorrhage were identified at rates comparable to those found in randomized clinical trials however, higher than those reported in observational studies: 4.73, 1.29, and 0.41 per 100 patient years, respectively. Conclusions We describe here a workable definition for identifying major hemorrhagic events from large automated datasets. This method of identifying major bleeding may have applications for quality measurement, quality improvement, and comparative effectiveness research.

Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men.TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study.In a reference sample of 456 men, mean (sd), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes.Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.

The effect of diet quality on weight change, relative to other body weight determinants, is insufficiently understood. Furthermore, research on long-term weight change in U.S. adults is limited. We evaluated prospectively patterns and predictors of weight change in Framingham Offspring/Spouse (FOS) women and men (n = 1515) aged > or =30 y with BMI > or = 18.5 kg/m2 and without cardiovascular disease, diabetes, and cancer at baseline over a 16-y period. Diet quality was assessed using the validated Framingham Nutritional Risk Score. In women, older age (P < 0.0001) and physical activity (P < 0.05) were associated with lower weight gain. Diet quality interacted with former smoking status (P-interaction = 0.02); former smokers with lower diet quality gained an additional 5.2 kg compared with those with higher diet quality (multivariable-adjusted P-trend = 0.06). Among men, older age (P < 0.0001) and current smoking (P < 0.01) were associated with lower weight gain, and weight fluctuation (P < 0.01) and former smoking status (P < 0.0001) were associated with greater weight gain. Age was the strongest predictor of weight change in both women (partial R(2) = 11%) and men (partial R(2) = 8.6%). Normal- and overweight women gained more than obese women (P < 0.05) and younger adults gained more weight than older adults (P < 0.0001). Patterns and predictors of weight change differ by sex. Age in both sexes and physical activity among women as well as weight fluctuation and smoking status in men were stronger predictors of weight change than diet quality among FOS adults. Women who stopped smoking over follow-up and had poor diet quality gained the most weight. Preventive interventions need to be sex-specific and consider lifestyle factors.

The study examined the simultaneous longitudinal relationships of cigarette use in adolescence to continuing cigarette use, psychological distress, physical activity, subjective rating of health in emerging adulthood and, finally, to body mass index (BMI) in early adulthood. The study utilized data (N=414) from a drug abuse prevention trial, Midwestern Prevention Project, with subjects participating from ages 11-34 years. Structural equation modeling showed that cigarette use in early adolescence had direct paths to distress in the beginning of emerging adulthood, which in turn had significant relationships to cigarette use, physical activity, and subjective rating of health in mid-emerging adulthood. Finally, both cigarette use and physical activity had significant negative relationships to BMI in early adulthood. Results suggest that prevention programs that have been previously applied to either cigarette use or distress prevention might be re-examined for their potential to also affect obesity risk in adulthood.

Background Self-rated health is a commonly used global indicator of health status. Few studies have examined the association of self-rated health and mobility with estrone and estradiol in men. Accordingly, we determined the cross-sectional, incident, and mediating relations between circulating estrone and estradiol levels with self-rated health, mobility limitation, and physical performance in community-dwelling men. Methods The cross-sectional sample included 1,148 men, who attended Framingham Offspring Study Examinations 7 and 8. Estrone and estradiol levels were measured using liquid chromatography tandem mass spectrometry at Examination 7. Self-reported mobility limitation and self-rated health were assessed at Examinations 7 and 8. Additionally, short physical performance battery, usual walking speed, and grip strength were assessed at Examination 7. Results In incident analysis, estradiol levels at Examination 7 were associated with increased odds of fair or poor self-rated health at Examination 8, after adjusting for age, body mass index, comorbidities, and testosterone levels; in an individual with 50% greater estradiol than other, the odds of reporting "fair or poor" self-rated health increased by 1.78 (95% confidence interval: 1.25-2.55; p = .001). Neither estrone nor estradiol levels were associated with any physical performance measure at baseline. Conclusions Higher circulating levels of estradiol are associated with increased risk of incident fair/poor self-rated health in community-dwelling men. The mechanisms by which circulating levels of estradiol are related to self-rated health in men need further investigation.

Prescribing of exogenous testosterone is increasing. Because of the risks associated with testosterone, it is important to follow evidence-based procedures when initiating therapy.We evaluated whether dispensing of testosterone was preceded by appropriate ascertainment of androgen deficiency, and consideration of potential contraindications, in accordance with practice guidelines.A cross-sectional study.All outpatient clinics within Veterans Affairs (VA) during fiscal years 2009-2012 (FY09-FY12).A total of 111,631 men who had not previously received testosterone from VA, and received at least 1 testosterone dispensing during the study period. A 1-year "look-back" period was used to check for diagnostic tests that occurred before the first fill.Proportion who underwent appropriate diagnostic evaluation of androgen deficiency and ascertainment of contraindications for testosterone therapy during the year before receiving their first testosterone dispensing.New testosterone dispensing in VA increased from 20,437 in FY09 to 36,394 in FY12. Only 3.1% of men who received testosterone had 2 or more low (total or free) testosterone levels in the morning, LH and/or FSH level measured, and no contraindications to testosterone therapy. A total of 16.5% did not have their testosterone level checked at all. Among those prescribed therapy, 1.4% had prostate cancer, 7.6% had obstructive sleep apnea, and 3.5% had elevated hematocrit at baseline.Only a small proportion of men receiving testosterone in VA underwent appropriate testing, and some received this therapy despite important contraindications. Promoting a more uniform application of clinical guidelines may facilitate appropriate use of testosterone.