• The Association of Antiretroviral Treatment and Early Menopause in Women Aging with the Human Immunodeficiency Virus

      Bozzi, Laura; dosReis, Susan; 0000-0001-5326-6521 (2021)
      Women living with HIV (WLWH) have irregular menses with several periods of prolonged amenorrhea but their risk of early menopause, clinically defined as before age 45 years, is unknown. This is largely because there is no gold standard method to confirm menopause. Antimullerian hormone (AMH) is a biomarker indicative of ovarian reserve; however, no prior study has used this to confirm menopause. This study aimed to 1) confirm menopause using AMH; 2) determine if WLWH are at an increased risk of early menopause compared to at-risk, uninfected women; and 3) evaluate the relationship between time-varying ART use with early menopause in WLWH. Data were derived from the Women’s Interagency HIV Study, which had four enrollment waves from 1994 through 2016 across 11 US clinic sites. Women were followed prospectively from their baseline visit until menopause confirmation, loss to follow up, or end of study (12/31/2018), whichever came first. The study cohort was women ages 18 or older with no history of: menopause; hysterectomy/uterine cancer/double oophorectomy; any type of cancer, except skin cancer. Women were censored if they experienced any aforementioned events in follow-up. The study measures confirm menopause were at least 12 months of amenorrhea without resumption of menses and an undetectable AMH (<0.10ng/mL). Age at menopause was determined upon confirmation of final menstrual period. A Cox Proportional Hazards model determined the risk of early menopause among WLWH relative to at-risk uninfected women. Marginal Structural Cox Proportional Hazards models with stabilized weights estimated the effect of >75% adherence to ART, modeled as a time-varying covariate, on the risk of early menopause. Age at confirmed menopause with undetectable AMH was 48.6±4.3 years as compared to 41.2±5.6 years for women with amenorrhea without menses resumption and detectable AMH. WLWH reached menopause at significantly earlier ages and had a two-fold increased risk of experiencing early menopause than at-risk, uninfected women. There was a non-significant protective effect of ≥75% ART adherence on early menopause. AMH can improve the precision in determining age of menopause, which is an integral part of understanding the risk for early menopausal and future planning for postmenopausal care in WLWH.
    • Early Symptom Improvement as a Predictor of Antidepressant Response in Children and Adolescents Diagnosed with Depression: Translating Evidence from Randomized Controlled Trials to Community Practice

      Spence, O'Mareen; dosReis, Susan (2020)
      Statement of the Problem: A common problem among children and adolescents diagnosed with depression who receive care in community settings is that antidepressant regimen changes such as psychotropic augmentation may occur soon after starting treatment. This raises the question as to whether such changes are implemented among youth who would otherwise respond to the antidepressant. Thus, the overarching objectives of this dissertation were to 1) distinguish early in treatment children and adolescents who are likely to respond, and 2) empirically evaluate the association between predicted response and psychotropic augmentation or switching in real world settings. Summary of Methods: Using randomized clinical trial (RCT) data, this research applied a Bayesian approach to predict the likelihood of initial (12 week) and sustained (18 week) response to treatment as a function of early changes in depressive symptoms (i.e. mood, somatic, subjective and behavioral) and other demographic and clinical factors. An innovative application of combined sample multiple imputations (CSMI) was used to estimate the 12-week predicted probability of response among commercially insured adolescents who received care in real-world settings. Each adolescent received a probability of treatment response, which was then used to compare the odds of psychotropic augmentation or switch. Results: Early changes in mood and somatic symptoms within the first six weeks of treatment are primary predictors of initial (at 12 weeks) and sustained (at 18 weeks) response to an antidepressant. Baseline depression severity is an important prognostic factor for initial response, and additional, though minimal improvement, in somatic symptoms from weeks 6 to 12 is indicative of sustained response. In a highly selected cohort of adolescents receiving care in community settings, an augmentation or switch occurred similarly among adolescents with a high versus low likelihood of responding to fluoxetine. Conclusion: The results suggest that other factors beyond expected antidepressant response (or lack thereof) might influence current treatment practices. Our findings have clinical and public health implications that support measurement-based care in pediatric depression. Our application of CSMI highlights several key areas of consideration for future pharmacoepidemiologic research aimed at translating RCT evidence to real world data to better understand clinical practices patterns.
    • The Impact of Maryland Care Management Entity on Quality of Antipsychotic Medication Use and Clinical Outcomes

      Tai, Ming-Hui; dosReis, Susan; 0000-0002-3540-5425 (2016)
      Background: Care Management Entity (CME) using the wraparound practice is a type of care delivery model for youth with severe mental/behavioral disorders. The CME provides coordinated, child-centered services that aim to improve youth's clinical and functional outcomes. The impact of this care management on the quality of psychotropic medication treatment and outcomes following discharge is unknown. The goals of this dissertation are to examine the quality of antipsychotic use and mental health-related outcomes between CME-enrolled and non-CME youth. Methods: Data comprised Medicaid claims linked with the CME administrative records anytime from December 2009 through December 2013. A difference-in-difference design was used to estimate the odds ratio (OR) and the average marginal effect (AME) of antipsychotic use, concomitant antipsychotic use, higher-than-recommended antipsychotic dose, and metabolic monitoring among inverse probability of treatment weighting-adjusted CME and non-CME youth. To avoid loss of the sample due to missing information on length of stay (LOS) in CME services, methods for imputing LOS in CME care were conducted and cross-validated. Building on the data imputation, two-part models were used to examine the mental health-related emergency department (ED) visits, hospitalizations, and outpatient visits within one-year post discharge between CME and non-CME youth. Results: Among the 3,493 IPTW-adjusted cohort (679 CME and 2,814 non-CME youth), the CME-served youth had a significant decrease in any concomitant antipsychotic use relative to non-CME youth (AME= -3.28%, 95% CI= -4.19% to -2.38%). However, there was no difference in antipsychotic dosing or metabolic monitoring between the two groups. In the methodological study, the multiple imputation was preferred over single imputation because it produced smaller errors and similar LOS distribution. In the outcome analyses, the CME care model resulted in a lower likelihood of receiving any mental health-related service (mental health-related ED visits: OR=0.65, 95%CI=0.46 to 0.93; hospitalizations: OR=0.60, 95%CI=0.40 to 0.89; outpatient visits OR=0.46, 95%CI= 0.32 to 0.66) post discharge. Conclusions: Future optimization of this care model may benefit from 1) greater attention to improving antipsychotic monitoring, 2) stronger prescriber engagement in the wraparound practice, and 3) further research to identify potential risk factors that associated with mental health services utilization among youth in public health insurance programs.
    • Impact of Undertreatment of Depression on Suicide and Suicide Attempt among Children and Adolescents: A Simulation Study with Microsimulation and Agent-Based Models

      Zhang, Chengchen; dosReis, Susan; 0000-0003-3349-8725 (2022)
      Background: Depression is a strong risk factor for suicide, but undertreatment of depression is common among children and adolescents. The impact of undertreatment of depression on suicidal behaviors in this population is largely unknown due to the limitations of conventional data sources and methods. This dissertation research aims to overcome these challenges by using simulation models to answer two questions: 1) Is undertreatment of depression associated with increased risk of suicidal behaviors? 2) Do interventions that reduce undertreatment of depression lower the risk of suicidal behaviors? Methods: A microsimulation model simulated the 1-year suicide rate and suicide attempt risk with 12-, 36-, 52-week antidepressant treatment and no treatment in children and adolescents with depression. Modified Poisson regression estimated the suicide rate ratios and suicide attempt risk ratios for 12-, 36- and 52-week treatment compared with no treatment. An agent-based model simulated the potential impact of the following interventions in preventing suicide and suicide attempt in a synthetic population of children and adolescents: 1) depression screening (i.e. reducing untreated depression); 2) reducing attrition during depression treatment (i.e., increasing the proportion who complete the first 12 weeks of treatment); 3) suicide intervention (i.e., screen and treat individuals who need suicide care) among depressed individuals; 4) universal suicide intervention in medical settings. Results: Compared with no treatment, 12-, 36- and 52-week antidepressant treatment was significantly associated with decreased suicide rate and risk of suicide attempt. Depression screening could reduce the risk of suicide attempt (-0.64% (95% Credible Interval (CI): -1.13%, -0.11%)) only when 80% untreated depression was reduced. Universal suicide intervention showed a significant decrease in the risk of suicide attempt, which increased with the screened proportion (20%: -0.68% (95% CI: -0.87%, -0.55%), 50%: -1.47% (95% CI: -1.61%, -1.77%), 80%: -2.89% (95% CI: -4.57%, -2.31%). The other interventions did not show a significant effect in reducing the risk of suicide attempt in the population. Conclusion: Antidepressant treatment for at least 12 weeks may reduce risk of suicidal behaviors. Universal suicide intervention in medical care settings may be more effective in reducing suicidal behaviors compared with interventions that reduce undertreatment of depression.
    • Measuring Priorities for Nonmedical Use of Stimulants among College Students to Optimize Prevention

      Ross, Melissa Mary; dosReis, Susan (2017)
      Background: According to recent estimates, approximately one third of college students have engaged in nonmedical use of prescription stimulants (NPS) which is both dangerous and illegal, yet most universities do not have programs in place to address this growing public health concern. Methods: This mixed-methods study used in-depth interviews (n=8), four focus groups (n=17), and cognitive interviews (n=5) to elicit, refine, and vet attributes for the development of two preference elicitation instruments (Phase 1) that were used in an online survey (Phase 2). The preference elicitation instruments included a best-worst scaling (BWS) instrument that assessed college students' priorities around perceived benefits and risks of NPS and a discrete-choice experiment (DCE) that measured students' preferences for components of a college-sponsored NPS reduction program. Results: Thirty and 259 college students participated in Phase 1 and Phase 2, respectively. All participants were 18-25 years old, enrolled at a public university in Maryland, and a self-reported past-year NPS user. The majority were upperclassman (71%), female (57%), and white (66%). Phase 1 yielded 12 attributes related to students' perceived academic, punitive, health, and social benefits and risks of NPS and four three-level attributes related to components of an NPS reduction program: setting, leader, discussion topics, and additional resources. In Phase 2, for the BWS, participants prioritized the benefits and risks of NPS. Better grades and meeting deadlines, followed by college expulsion and limited future career opportunities, were most important concerns when engaging in NPS. A latent class analysis (LCA) yielded four segments with different priorities for NPS. For the DCE, program setting and leader most influenced participants' preferences for a college-sponsored NPS reduction program. A LCA generated three segments with heterogeneous preferences for components of a program. Conclusions: This dissertation is the first to apply advanced preference elicitation methods to the field of substance use. We identified college students' modifiable expectancies that most influence on NPS and their preferences for the delivery of an NPS reduction program in which they would be willing to engage. These findings can inform the delivery of personalized NPS reduction programs to maximize engagement.
    • Patterns of psychopharmacologic treatment for attention deficit hyperactivity disorder

      dosReis, Susan; Zito, Julie Magno (1999)
      Outpatient office visits and stimulant medication treatments for attention deficit hyperactivity disorder (ADHD), the most common childhood psychiatric disorder, show sizeable increases in the US from 1990-1995. Current research findings do not fully explain the increases in diagnostic and treatment prevalence. Descriptive information of ADHD treatments across different youth populations would inform how clinical, demographic, and cultural factors influence treatment practices. This study examines child characteristics, parental perceptions, and health care system factors associated with ADHD medication treatment to understand their role in clinical decision-making. The specific aims of the study are to: compare ADHD treatment patterns for health maintenance organization (HMO) child members with Medicaid child members in the same geographic region; describe ADHD treatment referral patterns among a sample of school-aged children in an HMO; and survey parents' knowledge, attitude, and satisfaction with their child's ADHD treatment. Data were obtained from HMO and Medicaid computerized medical and prescription databases and a self-administered Attitude, Satisfaction, Knowledge and Medication Experiences (ASK-ME) survey for parents of children with ADHD. Findings from the computerized data show that HMO youths receiving care from a non-mental health provider were 4 times more likely to be diagnosed with ADHD than Medicaid youths. The survey study findings revealed that Caucasian parents had significantly greater knowledge of and more positive attitudes towards ADHD medication treatment. A larger proportion of non-Caucasian than Caucasian parents preferred counseling over medication and believed that stimulant medication led to substance abuse. Parents in both groups had false expectations about the medication's ability to improve the child's academic performance and behavior later in life. Parents were less satisfied with the medication's ability to enhance their child's self-esteem and social relations at home and at school. This study identified health care system, clinical, economic, and racial differences in perceptions of and treatments for ADHD among HMO and Medicaid youths. Additional research that includes a broader range of racial, cultural, and economic characteristics is needed to corroborate these findings. This work is important for the advancement of scientific knowledge of pediatric psychopharmacologic practices and for improvement in the clinical management of children with ADHD.
    • Race and Age Differences in HAART Discontinuation and Treatment Outcomes Among Individuals with HIV/AIDS and a Comorbid Serious Mental Illness

      Wagner, Lauren Dianne; dosReis, Susan (2014)
      An important but understudied public health problem in HIV/AIDS research is disparities in highly active antiretroviral therapy (HAART) discontinuation among those with a comorbid serious mental illness (SMI). Despite evidence that Blacks are more likely to discontinue HAART than Whites, few studies have investigated disparities in HAART use and health outcomes among individuals with HIV/AIDS and a comorbid SMI. This study aimed to 1) assess the relationship of race and age on HAART discontinuation; 2) assess whether mental health visits mediate the relationship of race and age on HAART discontinuation; and 3) determine if HAART discontinuation is associated with hospitalizations for all-cause and immunocompromised conditions, and if this differs by race and age. HIV Research Network data from 2000-2010 were used for this study. The cohort was selected among individuals aged 18 or older, diagnosed with HIV/AIDS and a comorbid SMI, in care for HIV/AIDS, and initiated HAART between 2001-2007. The cohort was followed for four years to assess HAART discontinuity and treatment outcomes. Logistic regression was used to analyze the proposed relationships between race and age on HAART discontinuation, mental health visits, and hospitalizations for all-cause and immunocompromised conditions. HAART discontinuation was not statistically significantly different between Black and White individuals, but Hispanics had 32% lower odds than Whites of discontinuing HAART. Younger age was associated with a 28%-74% greater odds of HAART discontinuation compared to those aged 50 and older. Mental health visits did not differ significantly between Blacks and Whites, but Hispanics were more likely to have mental health visits than Whites. Ten or more mental health visits was a partial mediator between younger age and HAART discontinuation, with adults aged 18-29 and 30-39 years less likely to have 10 or more mental health visits and more likely to discontinue HAART. Compared to Whites, Blacks were more likely to be hospitalized in year four for all-cause and immunocompromised conditions. Individuals who discontinued HAART were less likely to have a year four all-cause hospitalization than those who continued HAART. This research deepens our understanding of disparities in HAART continuity and the impact on health outcomes for a vulnerable population.
    • Systemic Lupus Erythematosus Patients' Benefit-Risks Preferences for Corticosteroid Use

      Ng, Xinyi; dosReis, Susan (2017)
      Introduction: Striking a balance between maximizing the effectiveness of corticosteroids while minimizing its adverse effects in Systemic Lupus Erythematosus (SLE) treatment requires careful consideration of how SLE patients value improvements in their disease versus risks of treatment adverse effects. Hence, this study aimed to elicit SLE patients' benefit-risks preferences for corticosteroid use, and to examine variation in preferences. Methods: SLE patients with current/past experience with using corticosteroids were recruited from the Johns Hopkins Lupus Center, the University of Maryland Medical Center and PatientsLikeMe. Study participants completed a web-based survey that comprised three sections: 1) sociodemographic characteristics, 2) a discrete choice experiment (DCE) measuring benefit-risks preferences, and 3) self-rated disease severity using the Systemic Lupus Activity Questionnaire (SLAQ). The DCE assessed two attributes of treatment benefit (time between flares and activities limitations), and four attributes of treatment risks relating to corticosteroids (heart-related damage, bone fractures, weight gain, and unusual mood swings/irritability). Preference weights were estimated using a conditional logit model and used to calculate the relative importance scores for each attribute and maximum acceptable risk that patients would tolerate. We also evaluated variations in preferences using a latent class analysis, and a stratified analysis based on SLAQ scores. Results: When making trade-offs between the risks and benefits of corticosteroid use, our 141 study participants (95% Female, 61% White) viewed weight gain as the most important, followed by heart-related damage and activities limitations. SLE patients were willing to tolerate higher risks for improvements in activities limitations (4.5% risk of heart damage) compared to improvements in time between flares (3.1% risk of heart damage). Our latent class analysis demonstrated the relative importance of three key attributes varied significantly across patient segments: activities limitations, weight gain, and heart damage. Individuals with SLAQ score ≤ 21 (N=75) were more willing to accept treatment risks in exchange for improvements in activity limitations compared to individuals with SLAQ score > 21 (N=66). Conclusions: Our study sheds light on SLE patients' benefit-risk trade-offs for corticosteroid use. This information can be used to guide corticosteroid therapy in this population.