Comparing Continuous and Binary Group-based Trajectory Modeling Using Statin Medication Adherence Data.

BACKGROUND: Of 58 medication adherence group-based trajectory modeling (GBTM) published studies, 74% used binary and 26% used continuous GBTM. Few studies provided a rationale for this choice. No medication adherence studies have compared continuous and binary GBTM. OBJECTIVE: The objective of this study was to assess whether continuous versus binary GBTM: (1) impacts adherence trajectory shapes; and (2) results in the differential classification of patients into adherence groups. METHODS: Patients were prevalent statin users with myocardial infarction hospitalization, 66+ years old, and continuously enrolled in fee-for-service Medicare. Statin medication adherence was measured 6 months prehospitalization using administrative claims. Final GBTM specifications beyond default settings were selected using a previously defined standardized procedure and applied separately to continuous and binary (proportion of days covered ≥0.80) medication adherence measures. Assignment to adherence groups was compared between continuous and binary models using percent agreement of patient classification and the κ coefficient. RESULTS: Among 113,296 prevalent statin users, 4 adherence groups were identified in both models. Three groups were consistent: persistently adherent, progressively nonadherent, and persistently nonadherent. The fourth continuous group was moderately adherent (progressively adherent in the binary model). When comparing patient assignment into adherence groups between continuous and binary trajectory models, only 78.4% of patients were categorized into comparable groups (κ=0.641; 95% confidence interval: 0.638-0.645). The agreement was highest in the persistently adherent group (∼94%). CONCLUSIONS: Continuous and binary trajectory models are conceptually different measures of medication adherence. The choice between these approaches should be guided by study objectives and the role of medication adherence within the study-exposure, outcome, or confounder.

Opening the black box of the group-based trajectory modeling process to analyze medication adherence patterns: An example using real-world statin adherence data.

PURPOSE: The rationale for choosing a final group-based trajectory modeling (GBTM) specification and evaluations of patient adherence patterns within groups are often omitted in the GBTM medication adherence literature. We aimed to (1) reveal the complexity of GBTM and (2) assess model discrimination of patient medication adherence patterns. METHODS: Medicare administrative claims were used to measure statin medication adherence as a continuous value in the 6 months before an acute myocardial infarction (AMI) hospitalization. Different GBTM specifications beyond default settings were constructed and compared with the Bayesian information criterion. Spaghetti plots were used to compare individual adherence patterns with group averages. RESULTS: Overall, 113,296 prevalent statin users met eligibility criteria. Four adherence groups were identified: persistently adherent, moderately adherent, progressively nonadherent, and persistently nonadherent. Spaghetti plots showed the persistently adherent and persistently nonadherent groups had relatively homogeneous adherence patterns that matched predicted trajectories well. Spaghetti plots also showed that, while adherence patterns in the progressively nonadherent group were not as homogeneous, most patients in this group appeared to be discontinuing statin therapy pre-AMI. CONCLUSIONS: Subjective decisions are necessary to identify a final trajectory model. Greater transparency and disclosure of these decisions in the medication adherence literature are needed. Individual patient adherence patterns from spaghetti plots provided additional diagnostic information about trajectory models beyond standard model-fit assessments to determine if group-average adherence estimates represent homogeneous patterns of medication adherence.

It's Not Too Late to Improve Statin Adherence: Association Between Changes in Statin Adherence from Before to After Acute Myocardial Infarction and All-Cause Mortality.

Background Many older patients have a change in statin adherence-either an increase or a decrease-from before to after an acute myocardial infarction ( AMI ), but its association with mortality is unknown. Methods and Results Using Medicare administrative claims, a cohort of patients ≥66 years old with an AMI hospitalization from 2008 to 2010 was assembled. Statin adherence was measured for 180 days pre- AMI and 180 days post- AMI and categorized as severely nonadherent, moderately nonadherent, or adherent. Categorical change in statin adherence from pre- to post- AMI was assessed. Patients were then followed for up to 18 months for all-cause mortality. A Cox proportional hazards model was applied to estimate the effects of statin adherence change on all-cause mortality, adjusted for patient baseline characteristics. Of 101 011 eligible patients, 20% had a categorical increase in adherence, 16% decreased, and 14% remained nonadherent both pre- and post- AMI . Compared with patients who were always severely nonadherent (both pre- and post- AMI ), patients whose adherence increased from severely nonadherent to adherent (hazard ratio=0.83; 95% CI : 0.75-0.92) and patients who were always adherent (hazard ratio=0.88; 95% CI : 0.82-0.94) were less likely to die; patients whose adherence decreased from moderately nonadherent to severely nonadherent were more likely to die (hazard ratio=1.11; 95% CI : 1.01-1.22). Conclusions After an AMI , patients with decreased statin adherence had the worst mortality outcomes. However, patients with increased statin adherence had a similar risk of mortality compared with continuously adherent patients, suggesting that, even after an AMI , it is not too late to improve statin adherence.

Changes in Statin Adherence Following an Acute Myocardial Infarction Among Older Adults: Patient Predictors and the Association With Follow-Up With Primary Care Providers and/or Cardiologists.

BACKGROUND: Hospitalizations for acute myocardial infarctions (AMIs) are associated with changes in statin adherence. It is unclear to what extent adherence changes, which patients are likely to change, and how post-discharge follow-up is associated with statin adherence change. METHODS AND RESULTS: This retrospective study used Medicare data for all fee-for-service beneficiaries 66 years and older with an AMI hospitalization in 2008-2010 and statin use before their index AMI. Multivariable multinomial logistic regression models (odds ratio [OR] and 99% confidence interval [CI]) were applied to assess associations between both patient characteristics and follow-up with a primary care provider and/or cardiologist with the outcome of statin adherence change (increase or decrease) from the 6-month pre- to 6-month post-AMI periods. Of 113 296 patients, 64.0% had no change in adherence, while 19.7% had increased and 16.3% had decreased adherence after AMI hospitalization. Black and Hispanic patients were more likely to have either increased or decreased adherence than white patients. Patients who required coronary artery bypass graft surgery (OR, 1.34; 99% CI, 1.21-1.49) or percutaneous transluminal coronary angioplasty/stent procedure (OR, 1.25; 99% CI, 1.17-1.32) during their index hospitalization were more likely to have increased adherence. Follow-up with a primary care provider was only mildly associated with increased adherence (OR, 1.08; 99% CI, 1.00-1.16), while follow-up with a cardiologist (OR, 1.15; 99% CI, 1.05-1.25) or both provider types (OR, 1.21; 99% CI, 1.12-1.30) had stronger associations with increased adherence. CONCLUSIONS: Post-AMI changes in statin adherence varied by patient characteristics, and improved adherence was associated with post-discharge follow-up care, particularly with a cardiologist or both a primary care provider and a cardiologist.

Depression, Stressful Life Events, and the Impact of Variation in the Serotonin Transporter: Findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health).

BACKGROUND: The low transcriptionally efficient short-allele of the 5HTTLPR serotonin transporter polymorphism has been implicated to moderate the relationship between the experience of stressful life events (SLEs) and depression. Despite numerous attempts at replicating this observation, results remain inconclusive. METHODS: We examined this relationship in young-adult Non-Hispanic white males and females between the ages of 22 and 26 (n = 4724) participating in the National Longitudinal Study of Adolescent to Adult Health (Add Health) with follow-up information every six years since 1995. RESULTS: Linear and logistic regression models, corrected for multiple testing, indicated that carriers of one or more of the S-alleles were more sensitive to stress than those with two L-alleles and at a higher risk for depression. This relationship behaved in a dose-response manner such that the risk for depression was greatest among those who reported experiencing higher numbers of SLEs. In post-hoc analyses we were not able to replicate an interaction effect for suicide ideation but did find suggestive evidence that the effects of SLEs and 5HTTLPR on suicide ideation differed for males and females. There were no effects of childhood maltreatment. DISCUSSION: Our results provide partial support for the original hypothesis that 5-HTTLPR genotype interacts with the experience of stressful life events in the etiology of depression during young adulthood. However, even with this large sample, and a carefully constructed a priori analysis plan, the results were still not definitive. For the purposes of replication, characterizing the 5HTTLPR in other large data sets with extensive environmental and depression measures is needed.

Pneumococcal Carriage and Vaccine Coverage in Retirement Community Residents.

OBJECTIVES: To evaluate pneumococcal immunization in older adults living in retirement communities and to measure nasopharyngeal carriage of Streptococcus pneumoniae to better assess the potential for herd protection from the 13-valent pneumococcal conjugate vaccine (PCV-13) in these settings. DESIGN: Cross-sectional observational study of adults aged 65 and older living in retirement communities to determine coverage with 23-valent pneumococcal vaccine (PPSV-23), coverage with PCV-13 in immuncompromised individuals according to 2012 Advisory Committee on Immunization Practices (ACIP) guidelines, and nasopharyngeal carriage of S. pneumoniae. SETTING: Two retirement communities in North Carolina. PARTICIPANTS: Older adults recruited between December 2013 and April 2014 (N = 21, 64.8% female, mean age 81.4). MEASUREMENTS: A survey was used to assess chronic illnesses, immunization history, and potential risk factors for pneumococcal carriage; a chart review was used to confirm immunization history and abstract chronic conditions; and a nasopharyngeal swab was collected and cultured for S. pneumoniae. RESULTS: Eighty-seven percent of participants reported receiving PPSV-23 since age 65. Of the 16.2% of participants with an immunocompromising condition, only one had received PCV-13. Nasopharyngeal carriage with S. pneumoniae was detected in 1.9% (95% confidence interval = 0.0-3.8%) of participants. CONCLUSION: In this select sample, PPSV-23 coverage was high, but adherence to the ACIP recommendation for PCV-13 in immunocompromised groups was low. Nasopharyngeal carriage of S. pneumoniae was present, although infrequent, suggesting that immunization with PCV-13 could provide an individual benefit and a small degree of herd protection.

Blood spot-based measures of glucose homeostasis and diabetes prevalence in a nationally representative population of young US adults.

PURPOSE: We investigated understudied biomarker-based diabetes among young US adults, traditionally characterized by low cardiovascular disease risk. METHODS: We examined 15,701 participants aged 24 to 32 years at Wave IV of the National Longitudinal Study of Adolescent Health (Add Health, 2008). The study used innovative and relatively noninvasive methods to collect capillary whole blood via finger prick at in-home examinations in all 50 states. RESULTS: Assays of dried blood spots produced reliable and accurate values of HbA1c. Reliability was lower for fasting glucose and lowest for random glucose. Mean (SD) HbA1c was 5.6% (0.8%). More than a quarter (27.4%) had HbA1c-defined prediabetes. HbA1c was highest in the black, non-Hispanic race/ethnic group, inversely associated with education, and more common among the overweight/obese and physically inactive. The prevalence of diabetes defined by previous diagnosis or use of antidiabetic medication was 2.9%. Further incorporating HbA1c and glucose values, the prevalence increased to 6.8%, and among these participants, 38.9% had a previous diagnosis of diabetes (i.e., aware). Among those aware, 37.6% were treated and 64.0% were controlled (i.e., HbA1c < 7%). CONCLUSIONS: A contemporary cohort of young adults faces a historically high risk of diabetes but there is ample opportunity for early detection and intervention.

Simple sequence repeats in the national longitudinal study of adolescent health: an ethnically diverse resource for genetic analysis of health and behavior.

Simple sequence repeats (SSRs) are one of the earliest available forms of genetic variation available for analysis and have been utilized in studies of neurological, behavioral, and health phenotypes. Although findings from these studies have been suggestive, their interpretation has been complicated by a variety of factors including, among others, limited power due to small sample sizes. The current report details the availability, diversity, and allele and genotype frequencies of six commonly examined SSRs in the ethnically diverse, population-based National Longitudinal Study of Adolescent Health. A total of 106,743 genotypes were generated across 15,140 participants that included four microsatellites and two di-nucleotide repeats in three dopamine genes (DAT1, DRD4, DRD5), the serotonin transporter, and monoamine oxidase A. Allele and genotype frequencies showed a complex pattern and differed significantly between populations. For both di-nucleotide repeats we observed a greater allelic diversity than previously reported. The availability of these six SSRs in a large, ethnically diverse sample with extensive environmental measures assessed longitudinally offers a unique resource for researchers interested in health and behavior.

MAOA genotype, childhood maltreatment, and their interaction in the etiology of adult antisocial behaviors.

BACKGROUND: Maltreatment by an adult or caregiver during childhood is a prevalent and important predictor of antisocial behaviors in adulthood. A functional promoter polymorphism in the monoamine oxidase A (MAOA) gene has been implicated as a moderating factor in the relationship between childhood maltreatment and antisocial behaviors. Although there have been numerous attempts at replicating this observation, results remain inconclusive. METHODS: We examined this gene-environment interaction hypothesis in a sample of 3356 white and 960 black men (aged 24-34) participating in the National Longitudinal Study of Adolescent Health. RESULTS: Primary analysis indicated that childhood maltreatment was a significant risk factor for later behaviors that violate rules and the rights of others (p < .05), there were no main effects of MAOA genotype, and MAOA genotype was not a significant moderator of the relationship between maltreatment and antisocial behaviors in our white sample. Post hoc analyses identified a similar pattern of results among our black sample in which maltreatment was not a significant predictor of antisocial behavior. Post hoc analyses also revealed a main effect of MAOA genotype on having a disposition toward violence in both samples and for violent convictions among our black sample. None of these post hoc findings, however, survived correction for multiple testing (p > .05). Power analyses indicated that these results were not due to insufficient statistical power. CONCLUSIONS: We could not confirm the hypothesis that MAOA genotype moderates the relationship between childhood maltreatment and adult antisocial behaviors.

Effect of genetic testing for risk of type 2 diabetes mellitus on health behaviors and outcomes: study rationale, development and design.

BACKGROUND: Type 2 diabetes is a prevalent chronic condition globally that results in extensive morbidity, decreased quality of life, and increased health services utilization. Lifestyle changes can prevent the development of diabetes, but require patient engagement. Genetic risk testing might represent a new tool to increase patients' motivation for lifestyle changes. Here we describe the rationale, development, and design of a randomized controlled trial (RCT) assessing the clinical and personal utility of incorporating type 2 diabetes genetic risk testing into comprehensive diabetes risk assessments performed in a primary care setting. METHODS/DESIGN: Patients are recruited in the laboratory waiting areas of two primary care clinics and enrolled into one of three study arms. Those interested in genetic risk testing are randomized to receive either a standard risk assessment (SRA) for type 2 diabetes incorporating conventional risk factors plus upfront disclosure of the results of genetic risk testing ("SRA+G" arm), or the SRA alone ("SRA" arm). Participants not interested in genetic risk testing will not receive the test, but will receive SRA (forming a third, "no-test" arm). Risk counseling is provided by clinic staff (not study staff external to the clinic). Fasting plasma glucose, insulin levels, body mass index (BMI), and waist circumference are measured at baseline and 12 months, as are patients' self-reported behavioral and emotional responses to diabetes risk information. Primary outcomes are changes in insulin resistance and BMI after 12 months; secondary outcomes include changes in diet patterns, physical activity, waist circumference, and perceived risk of developing diabetes. DISCUSSION: The utility, feasibility, and efficacy of providing patients with genetic risk information for common chronic diseases in primary care remain unknown. The study described here will help to establish whether providing type 2 diabetes genetic risk information in a primary care setting can help improve patients' clinical outcomes, risk perceptions, and/or their engagement in healthy behavior change. In addition, study design features such as the use of existing clinic personnel for risk counseling could inform the future development and implementation of care models for the use of individual genetic risk information in primary care. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00849563.

Genomic risk profiling: attitudes and use in personal and clinical care of primary care physicians who offer risk profiling.

BACKGROUND: Genomic risk profiling involves the analysis of genetic variations linked through statistical associations to a range of disease states. There is considerable controversy as to how, and even whether, to incorporate these tests into routine medical care. OBJECTIVE: To assess physician attitudes and uptake of genomic risk profiling among an 'early adopter' practice group. DESIGN: We surveyed members of MDVIP, a national group of primary care physicians (PCPs), currently offering genomic risk profiling as part of their practice. POPULATION: All physicians in the MDVIP network (N = 356) RESULTS: We obtained a 44% response rate. One third of respondents had ordered a test for themselves and 42% for a patient. The odds of having ordered personal testing were 10.51-fold higher for those who felt well-informed about genomic risk testing (p < 0.0001). Of those who had not ordered a test for themselves, 60% expressed concerns for patients regarding discrimination by life and long-term/disability insurers, 61% about test cost, and 62% about clinical utility. The odds of ordering testing for their patients was 8.29-fold higher among respondents who had ordered testing for themselves (p < 0.0001). Of those who had ordered testing for patients, concerns about insurance coverage (p = 0.014) and uncertain clinical utility (p = 0.034) were associated with a lower relative frequency of intention to order testing again in the future. CONCLUSIONS: Our findings demonstrate that respondent familiarity was a key predictor of physician ordering behavior and clinical utility was a primary concern for genomic risk profiling. Educational and interpretive support may enhance uptake of genomic risk profiling.

Early adolescents' social standing in peer groups: behavioral correlates of stability and change.

Sociometric nominations, social cognitive maps, and self-report questionnaires were completed in consecutive years by 327 students (56% girls) followed longitudinally from grade 7 to grade 8 to examine the stability of social standing in peer groups and correlates of changes in social standing. Social preference, perceived popularity, network centrality, and leadership were moderately stable from grade 7 to grade 8. Alcohol use and relational aggression in grade 7 predicted changes in social preference and centrality, respectively, between grade 7 and grade 8, but these effects were moderated by gender and ethnicity. Changes in social standing from grade 7 to grade 8 were unrelated to grade 8 physical aggression, relational aggression, and alcohol use after controlling for the grade 7 corollaries of these behaviors. Results are discussed in terms of their implications for understanding links between social standing and problem behaviors during adolescence.

Early Adolescent Romantic Partner Status, Peer Standing, and Problem Behaviors.

This study examined associations among early adolescent romantic relationships, peer standing, problem behaviors, and gender as a moderator of these associations, in a sample of 320 seventh-grade students. Popular and controversial status youth were more likely to have a romantic partner, whereas neglected status youth were less likely to have a romantic partner. Similarly, youth perceived as conventional and unconventional leaders were also more likely to have a romantic partner than were non-leaders. Youth who had a romantic partner drank more alcohol and were more aggressive than were youth who did not have a romantic partner. Among those youth who had romantic partners, those who reported having more deviance-prone partners were themselves more likely to use alcohol and to be more aggressive, and those who engaged in deviant behavior with their partners used more alcohol. However, these associations varied somewhat by gender. These findings underscore the salience of early romantic partner relationships in the adjustment of early adolescents.

Peer standing and substance use in early-adolescent grade-level networks: a short-term longitudinal study.

Two competing hypotheses were tested concerning the associations between current alcohol and cigarette use and measures of individual, group and network peer standing in an ethnically-diverse sample of 156 male and female adolescents sampled at two time points in the seventh grade. Findings lent greater support to the person hypothesis, with early regular substance users enjoying elevated standing amongst their peers and maintaining this standing regardless of their maintenance of or desistance from current use later in the school year. In the fall semester, users (n=20, 13%) had greater social impact, were described by their peers as more popular, and were more central to the peer network than abstainers (i.e., those who did not report current use).Conversely, in the spring semester, there were no differences between users (n=22, 13%) and abstainers in peer ratings of popularity or social impact. Notably, the spring semester users group retained fewer than half of the users from the fall semester. Further, students who had reported current use in the fall, as a group, retained their positions of elevated peer standing in the spring, compared to all other students, and continued to be rated by their peers as more popular and as having greater social impact. We discuss the findings in terms of the benefit of employing simultaneous systemic and individual measures of peer standing or group prominence, which in the case of peer-based prevention programs, can help clarify the truly influential from the "pretenders" in the case of diffusion of risk-related behaviors.

Norm-Narrowing and Self- and Other-Perceived Aggression in Early-Adolescent Same-Sex and Mixed-Sex Cliques.

We examined the relations between group context and self- and other-perceptions of aggressive behavior in an ethnically-diverse sample of 168 male and female grade 7 adolescents. We used self- and peer-reports of aggression in high- and average-aggressive mixed-sex and same-sex cliques to examine whether group members would assimilate their self-report of aggression to the aggression report of their peers by way of perceived homophily or, conversely, engage in contrast and see their level of aggression as comparatively low in the face of high-aggression peers. Among boys in mixed-sex groups, comparison with highly-aggressive others resulted in a self-perception of lower levels of aggression than those perceived by their peers. Conversely, girls in mixed-sex groups reported their own levels of aggression to be higher than those perceived by their peers. We interpret these findings in terms of the notion of "norm narrowing": rather than being set by the larger social environment, such as the school, norms are more narrowly determined within one's immediate peer group.

Substance abuse prevention infrastructure: a survey-based study of the organizational structure and function of the D.A.R.E. program.

BACKGROUND: The only national drug abuse prevention delivery system that supports the rapid diffusion of new prevention strategies and includes uniform training and credentialing of instructors who are monitored for quality implementation of prevention programming is the Drug Abuse Resistance Education network (D.A.R.E.) linking community law enforcement to schools. Analysis of the organizational structure and function of D.A.R.E. provides an understanding of the essential parameters of this successful delivery system that can be used in the development of other types of national infrastructures for community-based prevention services. Information regarding organizational structure and function around funding issues, training, quality control and community relationships was gathered through telephone surveys with 50 state D.A.R.E. coordinators (including two major cities), focus groups with local D.A.R.E. officers and mentors, and interviews with national D.A.R.E. office staff. RESULTS: The surveys helped identify several strengths inherent in the D.A.R.E. program necessary for building a prevention infrastructure, including a well-defined organizational focus (D.A.R.E. America), uniform training and means for rapid dissemination (through its organized training structure), continuing education mechanisms (through the state and national conference and website), mechanisms for program monitoring and fidelity of implementation (formal and informal), branding and, for several states, predictable and consistent financing. Weaknesses of the program as currently structured include unstable funding and the failure to incorporate components for the continual upgrading of curricula reflecting research evidence and "principles of prevention". CONCLUSION: The D.A.R.E. organization and service delivery network provides a framework for the rapid dissemination of evidence-based prevention strategies. The major strength of D.A.R.E. is its natural affiliation to local law enforcement agencies through state coordinators. Through these affiliations, it has been possible for D.A.R.E. to become established nationally within a few years and internationally within a decade. Understanding how this structure developed and currently functions provides insights into how other such delivery systems could be developed.

Understanding differences in marijuana use among urban Black and suburban White high school students from two U.S. community samples.

To examine community/racial differences in adolescent marijuana use and the variations in factors underlying the observed differences, a questionnaire survey study was conducted with 9th to 12th graders (n = 1,936) from two communities in New Jersey. Marijuana use was significantly higher among suburban (mostly White) students than among their urban (mostly Black) counterparts. Significant differences in marijuana use between the two community sub-samples were explained by differences in type of risk factors, mean number of risk factors, and the strength of the association (slopes) between risk factors and marijuana use. Social-environmental factors (including positive after-school activities and negative peer influences) and, to a lesser degree, family factors (including family income, parental and sibling drug use), accounted for most community/racial differences in marijuana use.

Prevalence and co-occurrence of psychiatric symptom clusters in the U.S. adolescent population using DISC predictive scales.

OBJECTIVE: To estimate 12-month prevalence and co-occurrence of symptoms of specific mental problems among US adolescents (12-17 years) by age, sex and racial/ethnic subgroups. METHOD: Data from the 2000 National Household Survey of Drug Abuse (NHSDA) adolescent sample are used to estimate prevalence and co-occurrence rates using the DISC predictive scales. Multiple logistic regressions were used to derive significant correlates of each domain of DPS-derived symptom cluster indicators of psychiatric problems and of severe comorbidity, with control of demographics and environmental factors. SETTING: The National Household Survey on Drug Abuse (NHSDA), a national household probability sample, includes a nationally representative sample of 12-17 year-old adolescents (N = 19,430), through in-home surveys. RESULTS: Three out of five adolescents screened positive for at least one DPS symptom cluster with estimates for specific symptom cluster ranging over 9.7% (substance use disorder), 13.4% (affective), 36.3% (disruptive-behavior), and 40.1% (anxiety). Co-occurrence was high with almost one-third of any DPS symptom cluster reporting multiple positive screens of four or more clusters. Blacks and younger females were most likely to report mental health problems and co-occurrence. CONCLUSION: Mental health problems among U.S. youth may be far more common than previously believed, although these symptoms have not yet reached the point of clinical impairment. The data speak to important patterns of age, gender and racial/ethnic differences in mental health problems deserving of further study.