Risk of incident gout following exposure to recombinant zoster vaccine in US adults aged ≥50 years.

OBJECTIVE: To assess whether recombinant zoster vaccine (RZV) is associated with an increased risk of new-onset gout among US adults aged ≥50 years. METHODS: We conducted a real-world, retrospective safety study with a self-controlled risk interval (SCRI) design using administrative claims data. We included health plan members aged ≥50 years with RZV exposure, followed by incident gout within 60 days. Days 1-30 following RZV exposure were considered the risk window (RW), and days 31-60 were considered the control window (CW). We estimated the risk ratio (RR) of gout in the RW versus CW, using a conditional Poisson model. The primary analysis estimated the risk of incident gout following any RZV dose. Sensitivity analyses evaluated dose 1- and dose 2-specific risks, risk among patients compliant with recommended dose spacing of 60-183 days, adjustment for seasonality, and restriction to the pre-COVID-19 era (before December 1, 2019). RESULTS: A total of 461,323 individuals received ≥1 RZV dose; we included 302 individuals (mean age 72.5 years; 66 % male) with evidence of new-onset gout within 60 days in SCRI analyses. A total of 153 (50.7 %) individuals had gout events in the RW and 149 (49.3 %) in the CW (RR 1.03; 95 % confidence interval 0.81, 1.29). All sensitivity analyses had consistent results, with no association of RZV with incident gout. CONCLUSION: In a population of US adults aged ≥50 years, there was no statistically significant increase in the risk of gout during the 30 days immediately after RZV exposure, compared with a subsequent 30-day CW.

Comparative safety of conjugated estrogens/bazedoxifene versus estrogen/progestin combination hormone therapy among women in the United States: a multidatabase cohort study.

OBJECTIVE: To assess the risk of select safety outcomes including endometrial cancer, endometrial hyperplasia, and breast cancer among women using conjugated estrogens/bazedoxifene (CE/BZA) as compared with estrogen/progestin combination hormone therapy (EP). METHODS: We conducted a new-user cohort study in five US healthcare claims databases representing more than 92 million women. We included CE/BZA or EP new users from May 1, 2014, to August 30, 2019. EP users were propensity score (PS) matched to users of CE/BZA. Incidence of endometrial cancer, endometrial hyperplasia, breast cancer, and eight additional cancer and cardiovascular outcomes were ascertained using claims-based algorithms. Rate ratios (RR) and differences pooled across databases were estimated using random-effects models. RESULTS: The study population included 10,596 CE/BZA and 33,818 PS-matched EP new users. Rates of endometrial cancer and endometrial hyperplasia were slightly higher among CE/BZA users (1.6 and 0.4 additional cases per 10,000 person-years), although precision was limited because of small numbers of cases (endometrial cancer: RR, 1.50 [95% confidence interval {CI}, 0.79-2.88]; endometrial hyperplasia: RR, 1.69 [95% CI, 0.51-5.61]). Breast cancer incidence was lower in CE/BZA users (9.1 fewer cases per 10,000 person-years; RR, 0.79; 95% CI, 0.58-1.05). Rates of other outcomes were slightly higher among CE/BZA users, but with confidence intervals compatible with a wider range of possible associations. CONCLUSIONS: CE/BZA users might experience slightly higher rates of endometrial cancer and endometrial hyperplasia, and a lower rate of breast cancer, than EP users in the first years of use.

Weight-based discrimination and disordered eating behaviors in a cohort of U.S. sexual minority young adults.

OBJECTIVE: Though prevalent, weight-based discrimination is understudied and has been linked to disordered eating behaviors (DEB) among adolescents and adults. Sexual minority populations experience elevated risk of DEB, but little is known about the role of weight discrimination in this elevated risk. METHODS: Participants were 1257 sexual minority women and men (ages 18-31 years) in the US Growing Up Today Study cohort. We examined cross-sectional associations between weight discrimination victimization and three DEB in the past year: unhealthy weight control behaviors, overeating, and binge eating. Generalized estimating equations, adjusted for potential confounders, were used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS: Three in 10 participants (31%) reported weight-based discrimination victimization. Sexual minority young adults who reported weight-based discrimination had greater relative prevalence of unhealthy weight control behaviors (PR [95% CI]: 1.92 [1.35, 2.74]), overeating (3.15 [2.24, 4.44]), and binge eating (3.92 [2.51, 6.13]), compared with those who reported no weight-based discrimination. Associations with overeating and binge eating remained significant after adjusting for BMI. DISCUSSION: The role of weight-based discrimination, and its intersections with other forms of stressors for sexual minority young adults, must be included in efforts to advance eating disorder prevention for this underserved population. PUBLIC SIGNIFICANCE: Three in 10 sexual minority young adults in this study had experienced weight-based discrimination, a common but understudied form of discrimination. Sexual minority young adults who experienced weight-based discrimination were at greater risk of disordered eating behaviors than those who had not experienced weight-based discrimination. These findings suggest that weight-based discrimination may be an important-and preventable-risk factor for disordered eating behaviors among sexual minority young adults.

Sexual Orientation and Age at Menarche in Three U.S. Longitudinal Cohorts.

PURPOSE: The aim of this study is to examine age at menarche across sexual orientation groups. METHODS: Data were obtained from 131,090 female participants, born 1947-2001, in 3 longitudinal studies-the Growing Up Today Study and Nurses' Health Study 2 and 3. We estimated the association between sexual orientation and age at menarche using regression models adjusted for age, race/ethnicity, birthweight, height, and body mass index. RESULTS: Compared to heterosexual participants, sexual minorities were younger at menarche. Sexual minorities were more likely to have early menarche (≤11 years) and less likely to have late menarche (≥14 years) compared to heterosexual girls. As an example of this pattern, Nurses' Health Study 3 bisexual participants were >30% more likely than heterosexuals to have early versus average menarche (odds ratio 1.37, 95% confidence interval 1.09-1.72). CONCLUSION: Sexual minority girls have a younger age at menarche than heterosexual girls and may benefit from screening for adverse outcomes associated with early menarche.

Risk of Thyroid Cancer Associated with Use of Liraglutide and Other Antidiabetic Drugs in a US Commercially Insured Population.

BACKGROUND: Quantify association between the glucagon-like peptide-1 receptor agonist liraglutide and risk of thyroid cancer (TC) compared to other antidiabetics. PATIENTS AND METHODS: Initiators of liraglutide, exenatide, metformin, pioglitazone or groups of dipeptidyl peptidase-4 inhibitors or sulfonylureas were identified in a US health plan (2010-2014) and followed for a median of 17 months. Thyroid cancer cases during follow-up were identified via a validated algorithm. Incidence rates of TC among liraglutide and comparators were assessed using relative risks estimated within propensity score-matched cohorts using intention to treat (ITT) and time on drug analyses. Latency effects and potential surveillance bias were evaluated. RESULTS: Relative risks from ITT analyses ranged from 1.00 (95% confidence interval (CI) 0.56-1.79) versus metformin to 1.70 (95% CI 1.03-2.81) versus all comparators excluding exenatide. Effect estimates from latency analyses were slightly attenuated. Time on drug analyses suggested no increased risk for either longer duration or higher cumulative dose of liraglutide. Medical record review found 85% were papillary or a follicular variant of papillary or both; 46% were microcarcinomas (≤10 millimeters), which were more prevalent in the liraglutide cohort (67% versus 43% in all comparators). CONCLUSION: Relative risks were elevated for several comparisons, which should be interpreted cautiously because of potential residual confounding and surveillance bias. Liraglutide cases had smaller thyroid nodules and shorter time-to-diagnosis, suggesting increased surveillance for TC among liraglutide initiators, especially shortly after the drug´s approval. After adjusting the primary analyses (ITT) for latency, no significant elevated risk of TC was observed among liraglutide initiators.

Post-approval Safety Surveillance Study of Golimumab in the Treatment of Rheumatic Disease Using a United States Healthcare Claims Database.

BACKGROUND AND OBJECTIVE: Golimumab is a fully human anti-tumor necrosis factor monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This study estimated rates of prespecified outcomes in patients with RA, PsA or AS initiating golimumab versus matched patients initiating non-biologic systemic (NBS) medications. METHODS: Patients enrolled in a US health plan with rheumatic disease who initiated a study medication were accrued between April 2009 and November 2014. Golimumab initiators were matched by propensity score to NBS initiators in a 1:4 ratio. Outcomes were identified through September 2015. As-treated, as-matched, and nested case-control (NCC) analyses were conducted in the matched cohorts. Sensitivity analyses evaluated the impact of residual confounding and nondifferential misclassification of exposure and outcomes. RESULTS: Risks of outcomes were similar between golimumab and NBS initiators. In the as-treated analysis, the rate ratio (RR) for depression was elevated during current golimumab use versus golimumab non-use in the NBS cohort [RR 1.45, 95% confidence interval (CI) 1.31-1.61]. This finding was not replicated in as-matched (RR 1.08, 95% CI 0.97-1.19) or NCC (odds ratio 1.01, 95% CI 0.78-1.31) analyses, which focused on incident cases. Sensitivity analyses suggest that depression was sensitive to misclassification, and the RR changed from greater than to less than one across a plausible range of specificity. CONCLUSIONS: This study suggests that there is no association between exposure to golimumab and an increased risk of prespecified outcomes. Increased depression risk in the as-treated analysis was not replicated in other analyses and may be associated with residual imbalance in baseline history or severity of depression.

Indoor Ultraviolet Tanning Among U.S. Adolescents and Young Adults: Results From a Prospective Study of Early Onset and Persistence.

PURPOSE: The purpose of the study was to test whether those who initiate tanning during adolescence are more likely to continue tanning in young adulthood, potentially increasing their risk for melanoma. METHODS: The study included prospective data from the Growing Up Today Study, a cohort study started in 1996 (N = 5,882). RESULTS: Among men and women who ever indoor UV tanned, those who indoor UV tan by age 17 years consistently indoor tanned at least twice the prevalence as those who did not indoor UV tan by age 17 years. Indoor tanning prevalence at age 27 years was nearly 4 times as high (18.8% vs. 4.8%) among men who started indoor tanning by age 17 years than those who did not indoor tan by age 17 years. These differences persisted through age 27 years and are more pronounced in men (18.8% vs. 4.8%) than in women (30.5% vs. 13.0%). CONCLUSION: Adolescents who indoor UV tan by age 17 years are more likely to continue to indoor tan through young adulthood than those who begin indoor UV tanning at age 18 years or older. Our findings suggest that interventions to prevent indoor UV tanning among minors may substantially reduce years of exposure to this carcinogenic behavior in young adults.

Liraglutide use and evaluation of pancreatic outcomes in a US commercially insured population.

AIMS: Both acute pancreatitis (AP) and pancreatic cancer (PC) have been areas of focus for studies of incretin drugs. This 5-year prospective cohort study aimed to quantify possible associations between liraglutide and risk of AP and PC as compared to other antidiabetic drugs (ADs). MATERIALS AND METHODS: Patients initiating liraglutide or other ADs who were enrolled in a US health plan (2010-2014) were included. Comparisons of AP and PC incidence rates were made between matched cohorts of liraglutide initiators and initiators of other ADs. Adjudicated AP cases and algorithm-based PC cases were identified. Propensity score-matched intention-to-treat (ITT) and time-on-drug (TOD) analyses were completed using Poisson regression. A latency analysis was performed for PC. RESULTS: Median follow-up was 405 days for AP cohorts (9995 liraglutide, 1:1 matched to all comparators) and 503 days for PC cohorts (35 163 liraglutide, 1:1 matched to all comparators). In the primary AP analysis, "current" use of liraglutide was not significantly associated with elevated risk across comparators (all comparators relative risk [RR] = 1.2; 95% confidence interval [CI], 0.6-2.3). ITT results were similar where, in the primary analysis, no RRs were significantly associated with PC (all comparators RR = 0.7; 95% CI, 0.3-1.4); latency and TOD analyses did not alter findings. There was no evidence of a dose-response effect. CONCLUSIONS: Liraglutide was not associated with an increased risk of AP or PC, although risk estimates were more variable for AP, and numbers of cases for both outcomes were limited because of the rarity of outcomes.

Stigma and Health-Related Quality of Life in Sexual Minorities.

INTRODUCTION: Stigma against sexual minorities is well documented, but its long-term consequences for health-related quality of life (HRQL) are unknown. This study examined stigma-related predictors of sexual orientation disparities in HRQL and their contribution to young adult HRQL disparities. METHODS: In 2013, participants (N=7,304, aged 18-31 years) reported sexual orientation (completely heterosexual [CH], mostly heterosexual, bisexual, and lesbian/gay). The EQ5D-5L, preference weighted for the U.S. population, was used to assess HRQL (range, -0.109 [worse than dead] to 1 [full health]). In prior waves conducted during adolescence, participants reported past-year bullying victimization (range, 1 [never] to 5 [several times/week]) and subjective social status (SSS) in their school (range, 1 [top] to 10 [bottom]). Analyses conducted in 2016 used longitudinal, multivariable linear and logistic regression to assess the contribution of bullying victimization and SSS in adolescence to sexual orientation disparities in HRQL in young adulthood, controlling for confounders and stratified by gender. RESULTS: Compared with CHs, both female and male sexual minorities reported more bullying victimization and lower SSS in adolescence and lower HRQL in young adulthood (HRQL score among women: mostly heterosexual, 0.878; bisexual, 0.839; lesbian, 0.848; CH, 0.913; HRQL score among men: mostly heterosexual, 0.877; bisexual, 0.882; gay, 0.890; CH, 0.925; all p-values <0.05). When bullying and SSS were added into multivariable models, orientation group effect estimates were attenuated substantially, suggesting bullying and lower SSS in adolescence partly explained HRQL disparities in young adulthood. CONCLUSIONS: Stigma-related experiences in adolescence may have lasting adverse effects on sexual minority health in adulthood.

Gender expression associated with BMI in a prospective cohort study of US adolescents.

OBJECTIVE: To examine the relationship between gender expression (GE) and BMI in adolescence. METHODS: Repeated measures of weight-related behaviors and BMI were collected from 1996 to 2011 via annual/biennial self-report surveys from youth aged 10 to 23 years (6,693 females, 2,978 males) in the longitudinal Growing Up Today Study. GE (very conforming [referent], mostly conforming, nonconforming) was assessed in 2010/11. Sex-stratified, multivariable linear models estimated GE group differences in BMI and the contribution of sexual orientation and weight-related exposures to group differences. Models for males included interaction terms for GE with age. RESULTS: In females, mostly conforming youth had 0.53 kg m(-2) and nonconforming had 1.23 kg m(-2) higher BMI; when adding adjustment for sexual orientation and weight-related exposures, GE group estimates were attenuated up to 8% and remained statistically significant. In males, mostly conforming youth had -0.67 kg m(-2) and nonconforming had -1.99 kg m(-2) lower BMI (age [in years]) interactions were between -0.09 and -0.14 kg m(-2) ; when adding adjustment for sexual orientation and weight-related exposures, GE group estimates were attenuated up to 11% and remained statistically significant. CONCLUSIONS: GE is a strong independent predictor of BMI in adolescence. Obesity prevention and treatment interventions with youth must address ways that gender norms may reinforce or undermine healthful behaviors.

Screening high school students for eating disorders: validity of brief behavioral and attitudinal measures.

BACKGROUND: Early identification can greatly impact the trajectory of eating disorders, and school-based screening is 1 avenue for identifying those at risk. To be feasible in a school setting, a screening program must use a brief, valid screening tool. The aim of this study was to assess how well brief attitudinal and behavioral survey items identify adolescents at risk in a large sample of high school students from across the United States. METHODS: Data were drawn from the National Eating Disorder Screening Program, the first-ever national eating disorders screening initiative for US high schools. A 2-stage, clustered sampling method was used to randomly select a subset of student screening forms (n = 5740), which included the Eating Attitudes Test (EAT-26), behavioral questions assessing the frequency of vomiting and binge eating in the past 3 months, and an attitudinal item that assessed preoccupation with thinness. RESULTS: Nearly 12% of females and 3% of males reported vomiting to control their weight and 17% of females and 10% of males reported binge eating 1 or more times per month. Approximately 24% of females and 8% of males report being preoccupied with being thinner. We found that the attitudinal measure yielded high sensitivity and specificity. Combined screening measures that used both the attitudinal and behavioral items yielded slightly higher sensitivity values than those found with the attitudinal measure alone. CONCLUSION: High school administrators should include items that assess both preoccupation with thinness as well as behavioral items that deal with eating disorders on student health surveys.

Sexual orientation disparities in purging and binge eating from early to late adolescence.

PURPOSE: To describe patterns of purging and binge eating from early through late adolescence in female and male youth across a range of sexual orientations. METHODS: Using data from the prospective Growing Up Today Study, a large cohort of U.S. youth, we investigated trends in past-year self-reports of purging (ever vomit or use laxatives for weight control) and binge eating at least monthly. The analytic sample included 57,668 observations from repeated measures gathered from 13,795 youth aged 12-23 years providing information collected by self-administered questionnaires from six waves of data collection. We used multivariable logistic regression models to examine sexual orientation group (heterosexual, "mostly heterosexual," bisexual, and lesbian/gay) differences in purging and binge eating throughout adolescence, with same-gender heterosexuals as the referent group and controlling for age and race/ethnicity. RESULTS: Throughout adolescence, in most cases, sexual orientation group differences were evident at the youngest ages and persisted through adolescence. Among females and compared with heterosexuals, "mostly heterosexuals," bisexuals, and lesbians were more likely to report binge eating, but only "mostly heterosexuals" and bisexuals were also more likely to report purging. Among males, all three sexual orientation subgroups were more likely than heterosexual males to report both binge eating and purging. Within each orientation subgroup, females generally reported higher prevalence of purging and binge eating than did males. CONCLUSIONS: Clinicians need to be alert to the risk of eating disordered behaviors in lesbian, gay, bisexual, and "mostly heterosexual" adolescents of both genders to better evaluate these youth and refer them for treatment.

Sexual orientation disparities in weight status in adolescence: findings from a prospective study.

A growing number of studies among adult women have documented disparities in overweight adversely affecting lesbian and bisexual women, but few studies have examined sexual orientation-related patterns in weight status among men or adolescents. We examined sexual orientation group trends in BMI (kg/m(2)), BMI Z-scores, and overweight using 56,990 observations from 13,785 adolescent females and males in the Growing Up Today Study (GUTS), a large prospective cohort of US youth. Participants provided self-reported information from six waves of questionnaire data collection from 1998 to 2005. Gender-stratified linear regression models were used to estimate BMI and BMI Z-scores and modified Poisson regression models to estimate risk ratios for overweight, controlling for age and race/ethnicity, with heterosexuals as the referent group. Among females, we observed fairly consistently elevated BMI in all sexual orientation minority groups relative to heterosexual peers. In contrast, among males we documented a sexual-orientation-by-age interaction indicating steeper increases in BMI with age from early-to-late adolescence in heterosexuals relative to sexual orientation minorities. Additional prospective research is needed to understand the determinants of observed sexual orientation disparities and to inform appropriate preventive and treatment interventions. The long-term health consequences of overweight are well-documented and over time are likely to exact a high toll on populations with elevated rates.

Screening high school students for eating disorders: results of a national initiative.

INTRODUCTION: Early identification and treatment of disordered eating and weight control behaviors may prevent progression and reduce the risk of chronic health consequences. METHODS: The National Eating Disorders Screening Program coordinated the first-ever nationwide eating disorders screening initiative for high schools in the United States in 2000. Students completed a self-report screening questionnaire that included the Eating Attitudes Test (EAT-26) and items on vomiting or exercising to control weight, binge eating, and history of treatment for eating disorders. Multivariate regression analyses examined sex and racial/ethnic differences. RESULTS: Almost 15% of girls and 4% of boys scored at or above the threshold of 20 on the EAT-26, which indicated a possible eating disorder. Among girls, we observed few significant differences between ethnic groups in eating disorder symptoms, whereas among boys, more African American, American Indian, Asian/Pacific Islander, and Latino boys reported symptoms than did white boys. Overall, 25% of girls and 11% of boys reported disordered eating and weight control symptoms severe enough to warrant clinical evaluation. Of these symptomatic students, few reported that they had ever received treatment. CONCLUSION: Population screening for eating disorders in high schools may identify at-risk students who would benefit from early intervention, which could prevent acute and long-term complications of disordered eating and weight control behaviors.

Irregular menses linked to vomiting in a nonclinical sample: findings from the National Eating Disorders Screening Program in high schools.

PURPOSE: Using data from an eating disorders screening initiative conducted in high schools across the United States, we examined the relationship between vomiting frequency and irregular menses in a nonclinical sample of adolescent females. METHODS: A self-report questionnaire was administered to students from U.S. high schools participating in the National Eating Disorders Screening Program in 2000. The questionnaire included items on frequency of vomiting for weight control in the past 3 months, other eating disorder symptoms, frequency of menses, height, and weight. Multivariable regression analyses were conducted using data from 2791 girls to estimate the risk of irregular menses (defined as menses less often than monthly) associated with vomiting frequency, adjusting for other eating disorder symptoms, weight status, age, race/ethnicity, and school clusters. RESULTS: Girls who vomited to control their weight one to three times per month were one and a half times more likely (risk ratio [RR] = 1.6; 95% confidence interval [CI] = 1.2-2.2), and girls who vomited once per week or more often were more than three times more likely (RR = 3.2; 95% CI = 2.3-4.4), to experience irregular menses than were girls who did not report vomiting for weight control. Vomiting for weight control remained a strong predictor of irregular menses even when overweight and underweight participants were excluded. CONCLUSIONS: Our study adds to the evidence that vomiting may have a direct effect on hormonal function in adolescent girls, and that vomiting for weight control may be a particularly deleterious component of eating disorders.

Sexual orientation, gender, and alcohol use in a cohort study of U.S. adolescent girls and boys.

BACKGROUND: Sexual minority youth may be at elevated risk for alcohol use relative to heterosexual youth, but the reasons underlying higher rates and whether there may be gender differences in risk are not known. METHODS: Cross-sectional survey data from 9731 early and middle adolescent girls and boys in the Growing Up Today Study in 1999 were examined to assess sexual orientation and gender patterns in alcohol use. Multivariable regression models estimated associations between sexual orientation and alcohol-related behaviors, such as binge drinking and drinking before age 12 years. Models controlled for sociodemographic and psychosocial factors, with heterosexuals as the reference. RESULTS: Girls who described themselves as "mostly heterosexual" and lesbian/bisexual girls were at elevated risk compared to heterosexual girls on almost all alcohol-related behaviors and exposures. "Mostly heterosexual" boys were also at elevated risk. No significant differences in alcohol-related behaviors were observed between gay/bisexual and heterosexual boys. Gender-by-sexual orientation interactions were statistically significant for LGB but not other orientations, indicating that lesbian/bisexual girls experienced elevated risk above and beyond that of gay/bisexual boys relative to same-gender heterosexual peers. CONCLUSIONS: In early and middle adolescence, sexual minority girls and "mostly heterosexual" boys experienced consistent patterns of elevated risk for alcohol use.