The relationship between preventive dental care and overall medical expenditures.

OBJECTIVES: To examine the relationship between preventive dental visits (PDVs) and medical expenditures while mitigating bias from unobserved confounding factors. STUDY DESIGN: Retrospective data analysis of Indiana Medicaid enrollment and claims data (2015-2018) and the Area Health Resources Files. METHODS: An instrumental variable (IV) approach was used to estimate the relationship between PDVs and medical and pharmacy expenditures among Medicaid enrollees. The instrument was defined as the number of adult enrollees with at least 1 nonpreventive dental claim per total Medicaid enrollees within a Census tract per year. RESULTS: In naive analyses, enrollees had on average greater medical expenditures if they had a prior-year PDV (ß = $397.21; 95% CI, $184.23-$610.18) and a PDV in the same year as expenditures were measured (ß = $344.81; 95% CI, $193.06-$496.56). No significant differences in pharmacy expenditures were observed in naive analyses. Using the IV approach, point estimates of overall medical expenditures for the marginal enrollee who had a prior-year PDV (ß = $325.17; 95% CI, -$708.03 to $1358.37) or same-year PDV (ß = $170.31; 95% CI, -$598.89 to $939.52) were similar to naive results, although not significant. Our IV approach indicated that PDV was not endogenous in some specifications. CONCLUSIONS: This is the first study to present estimates with causal inference from a quasi-experimental study of the effect of PDVs on overall medical expenditures. We observed that prior- or same-year PDVs were not related to overall medical or pharmacy expenditures.

The INGENIOUS trial: Impact of pharmacogenetic testing on adverse events in a pragmatic clinical trial.

Adverse drug events (ADEs) account for a significant mortality, morbidity, and cost burden. Pharmacogenetic testing has the potential to reduce ADEs and inefficacy. The objective of this INGENIOUS trial (NCT02297126) analysis was to determine whether conducting and reporting pharmacogenetic panel testing impacts ADE frequency. The trial was a pragmatic, randomized controlled clinical trial, adapted as a propensity matched analysis in individuals (N = 2612) receiving a new prescription for one or more of 26 pharmacogenetic-actionable drugs across a community safety-net and academic health system. The intervention was a pharmacogenetic testing panel for 26 drugs with dosage and selection recommendations returned to the health record. The primary outcome was occurrence of ADEs within 1 year, according to modified Common Terminology Criteria for Adverse Events (CTCAE). In the propensity-matched analysis, 16.1% of individuals experienced any ADE within 1-year. Serious ADEs (CTCAE level ≥ 3) occurred in 3.2% of individuals. When combining all 26 drugs, no significant difference was observed between the pharmacogenetic testing and control arms for any ADE (Odds ratio 0.96, 95% CI: 0.78-1.18), serious ADEs (OR: 0.91, 95% CI: 0.58-1.40), or mortality (OR: 0.60, 95% CI: 0.28-1.21). However, sub-group analyses revealed a reduction in serious ADEs and death in individuals who underwent pharmacogenotyping for aripiprazole and serotonin or serotonin-norepinephrine reuptake inhibitors (OR 0.34, 95% CI: 0.12-0.85). In conclusion, no change in overall ADEs was observed after pharmacogenetic testing. However, limitations incurred during INGENIOUS likely affected the results. Future studies may consider preemptive, rather than reactive, pharmacogenetic panel testing.

Does preventive dental care reduce nonpreventive dental visits and expenditures among Medicaid-enrolled adults?

OBJECTIVE: To determine whether preventive dental visits are associated with fewer subsequent nonpreventive dental visits and lower dental expenditures. DATA SOURCES: Indiana Medicaid enrollment and claims data (2015-2018) and the Area Health Resource File. STUDY DESIGN: A repeated measures design with individual and year fixed effects examining the relationship between preventive dental visits (PDVs) and nonpreventive dental visits (NPVs) and dental expenditures. DATA COLLECTION/EXTRACTION METHODS: Not applicable. PRINCIPAL FINDINGS: Of 28,152 adults (108,349 observation-years) meeting inclusion criteria, 36.0% had a dental visit, 27.8% a PDV, and 22.1% a NPV. Compared to no PDV in the prior year, at least one was associated with fewer NPVs (ß = -0.13; 95% CI -0.12, -0.11), lower NPV expenditures (ß = -$29.12.53; 95% CI -28.07, -21.05), and lower total dental expenditures (-$70.12; 95% -74.92, -65.31), as well as fewer PDVs (ß = -0.24; 95% CI -0.26, -0.23). CONCLUSIONS: Our findings suggest that prior year PDVs are associated with fewer subsequent NPVs and lower dental expenditures among Medicaid-enrolled adults. Thus, from a public insurance program standpoint, supporting preventive dental care use may translate into improved population oral health outcomes and lower dental costs among certain low-income adult populations, but barriers to consistent utilization of PDV prohibit definitive findings.

Prevalence of and factors associated with unmet dental need among the US adult population in 2016.

OBJECTIVES: Understanding and addressing contributing factors to unmet dental need is an important public health challenge. This study investigated the prevalence of, and factors associated with, self-reported unmet dental need using a nationally representative sample of US adults. METHODS: This was a cross-sectional study using the Medical Expenditures Panel Survey (MEPS) from 2016. The weighted prevalence of unmet dental need was estimated among individuals aged 18 years or older. Chi-squared and multivariate logit regression with marginal effects (ie absolute risk differences) were used to measure the association of unmet dental need with respondent characteristics. RESULTS: The prevalence of adults reporting unmet dental need was 6% (95% CI: 5.5 to 6.5). Adults with dental insurance were 1.7 percentage points (95% CI: -2.8 to -0.6) less likely to report unmet dental needs than adults without dental insurance. Those with middle income were 2.3 percentage points (95% CI: 1.2 to 3.4), those with low income were 3.3 percentage points (95% CI: 1.7 to 5.0), and those with poor/negative/near-poor income were 4.2 percentage points (95% CI: 2.7 to 5.7) more likely to report an unmet dental need than adults with high income. Both Hispanics (-1.7 percentage points [95% CI: -2.8 to -0.6]) and non-Hispanic Blacks (-1.1 percentage points [95% CI: -2.1 to -0.1]) were less likely to report an unmet dental need than whites. Smoking, education, general health status, chronic disease and marital status were also significantly associated with reporting an unmet dental need. CONCLUSIONS: Future policies should continue to address cost and coverage barriers to adult dental care, as these remain significant barriers to access, particularly for low-income adults. Future research should evaluate the reasons adults report unmet dental need and explore how adults' judgment of dental need compares to providers' clinical judgment. Additionally, research that explores how race and ethnicity affect perceptions of unmet dental need is warranted.

Correction: Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Enrollment of Diverse Populations in the INGENIOUS Pharmacogenetics Clinical Trial.

Recruitment of diverse populations and subjects living in Medically Underserved Areas and Populations (MUA/P's) into clinical trials is a considerable challenge. Likewise, representation of African-Americans in pharmacogenetic trials is often inadequate, but critical for identifying genetic variation within and between populations. To identify enrollment patterns and variables that predict enrollment in a diverse underserved population, we analyzed data from the INGENIOUS (Indiana GENomics Implementation and Opportunity for the UnderServed), pharmacogenomics implementation clinical trial conducted at a community hospital for underserved subjects (Safety net hospital), and a statewide healthcare system (Academic hospital). We used a logistic regression model to identify patient variables that predicted successful enrollment after subjects were contacted and evaluated the reasons that clinical trial eligible subjects refused enrollment. In both healthcare systems, African-Americans were less likely to refuse the study than non-Hispanic Whites (Safety net, OR = 0.68, and p < 0.002; Academic hospital, OR = 0.64, and p < 0.001). At the Safety net hospital, other minorities were more likely to refuse the study than non-Hispanic Whites (OR = 1.58, p < 0.04). The odds of refusing the study once contacted increased with patient age (Safety net hospital, OR = 1.02, p < 0.001, Academic hospital, OR = 1.02, and p < 0.001). At the Academic hospital, females were less likely to refuse the study than males (OR = 0.81, p = 0.01) and those not living in MUA/P's were less likely to refuse the study than those living in MUA/P's (OR = 0.81, p = 0.007). The most frequent barriers to enrollment included not being interested, being too busy, transportation, and illness. A lack of trust was reported less frequently. In conclusion, African-Americans can be readily recruited to pharmacogenetic clinical trials once contact has been successfully initiated. However, health care initiatives and increased recruitment efforts of subjects living in MUA/Ps are needed. Enrollment could be further enhanced by improving research awareness and knowledge of clinical trials, reducing time needed for participation, and compensating for travel.

Cost-effectiveness of CYP2C19-guided antiplatelet therapy in patients with acute coronary syndrome and percutaneous coronary intervention informed by real-world data.

Current guidelines recommend dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitors following percutaneous coronary intervention (PCI). CYP2C19 genotype can guide DAPT selection, prescribing ticagrelor or prasugrel for loss-of-function (LOF) allele carriers (genotype-guided escalation). Cost-effectiveness analyses (CEA) are traditionally grounded in clinical trial data. We conduct a CEA using real-world data using a 1-year decision-analytic model comparing primary strategies: universal empiric clopidogrel (base case), universal ticagrelor, and genotype-guided escalation. We also explore secondary strategies commonly implemented in practice, wherein all patients are prescribed ticagrelor for 30 days post PCI. After 30 days, all patients are switched to clopidogrel irrespective of genotype (nonguided de-escalation) or to clopidogrel only if patients do not harbor an LOF allele (genotype-guided de-escalation). Compared with universal clopidogrel, both universal ticagrelor and genotype-guided escalation were superior with improvement in quality-adjusted life years (QALY's). Only genotype-guided escalation was cost-effective ($42,365/QALY) and demonstrated the highest probability of being cost-effective across conventional willingness-to-pay thresholds. In the secondary analysis, compared with the nonguided de-escalation strategy, although genotype-guided de-escalation and universal ticagrelor were more effective, with ICER of $188,680/QALY and $678,215/QALY, respectively, they were not cost-effective. CYP2C19 genotype-guided antiplatelet prescribing is cost-effective compared with either universal clopidogrel or universal ticagrelor using real-world implementation data. The secondary analysis suggests genotype-guided and nonguided de-escalation may be viable strategies, needing further evaluation.

Effect on Health Care Expenditures During Nationwide Implementation of the Diabetes Prevention Program as a Health Insurance Benefit.

OBJECTIVE: Lifestyle interventions slow development of type 2 diabetes by half, but the impact of health payer reimbursement for delivery of intervention programs is not well known. We evaluated net commercial health payer expenditures when offering reimbursement for access to YMCA's Diabetes Prevention Program (YDPP) in 42 states. RESEARCH DESIGN AND METHODS: We used a nonequivalent comparison group design to evaluate net health care expenditures for adults with prediabetes who attended one or more YDPP visit between 1 July 2009 and 31 May 2013 ("YDPP users"). Rolling, 1:1 nearest neighbor propensity score (PS) matching was used to identify a comparison group of nonusers. Administrative data provided measures of YDPP attendance, body weight at YDPP visits, and health care expenditures. Random effects, difference-in-difference regression was used to estimate quarterly health care expenditures before and after participants' first visit to YDPP. RESULTS: Worksite screening identified 9.7% of the target population; 39.1% of those identified (19,933 participants through June 2015) became YDPP users. Mean weight loss for YDPP users enrolled before June 2013 (n = 1,725) was 7.5 lb (3.4%); 29% achieved ≥5% weight loss. Inclusive of added costs to offer YDPP, there were no statistically significant differences in mean per-person net health care expenditures between YDPP users and PS-matched nonusers over 2 years ($0.2 lower [95% CI $56 lower to $56 higher]). Mean reimbursement to the YMCA was $212 per YDPP user, with 92.8% of all expenditures made for those who attended at a high rate (≥9 completed YDPP visits). CONCLUSIONS: Worksite screening was inefficient for identifying the population with prediabetes, but those identified achieved modest YDPP attendance and clinically meaningful weight loss. Over 2 years, added costs to offer the intervention were modest, with neutral effects on net health care costs.

Drug-gene and drug-drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial.

Background: Tramadol and codeine are metabolized by CYP2D6 and are subject to drug-gene and drug-drug interactions. Methods: This interim analysis examined prescribing behavior and efficacy in 102 individuals prescribed tramadol or codeine while receiving pharmaco-genotyping as part of the INGENIOUS trial (NCT02297126). Results: Within 60 days of receiving tramadol or codeine, clinicians more frequently prescribed an alternative opioid in ultrarapid and poor metabolizers (odds ratio: 19.0; 95% CI: 2.8-160.4) as compared with normal or indeterminate metabolizers (p = 0.01). After adjusting the CYP2D6 activity score for drug-drug interactions, uncontrolled pain was reported more frequently in individuals with reduced CYP2D6 activity (odds ratio: 0.50; 95% CI: 0.25-0.94). Conclusion: Phenoconversion for drug-drug and drug-gene interactions is an important consideration in pharmacogenomic implementation; drug-drug interactions may obscure the potential benefits of genotyping.

Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network.

PURPOSE: While there is growing scientific evidence for and significant advances in the use of genomic technologies in medicine, there is a significant lag in the clinical adoption and sustainability of genomic medicine. Here we describe the findings from the National Human Genome Research Institute's (NHGRI) Implementing GeNomics In pracTicE (IGNITE) Network in identifying key constructs, opportunities, and challenges associated with driving sustainability of genomic medicine in clinical practice. METHODS: Network members and affiliates were surveyed to identify key drivers associated with implementing and sustaining a genomic medicine program. Tallied results were used to develop and weigh key constructs/drivers required to support sustainability of genomic medicine programs. RESULTS: The top three driver-stakeholder dyads were (1) genomic training for providers, (2) genomic clinical decision support (CDS) tools embedded in the electronic health record (EHR), and (3) third party reimbursement for genomic testing. CONCLUSION: Priorities may differ depending on healthcare systems when comparing the current state of key drivers versus projected needs for supporting genomic medicine sustainability. Thus we provide gap-filling guidance based on IGNITE members' experiences. Although results are limited to findings from the IGNITE network, their implementation, scientific, and clinical experience may be used as a road map by others considering implementing genomic medicine programs.

Graduation and Academic Placement of Underrepresented Racial/Ethnic Minority Doctoral Recipients in Public Health Disciplines, United States, 2003-2015.

OBJECTIVES: Given public health's emphasis on health disparities in underrepresented racial/ethnic minority communities, having a racially and ethnically diverse faculty is important to ensure adequate public health training. We examined trends in the number of underrepresented racial/ethnic minority (ie, non-Hispanic black, Hispanic, American Indian/Alaska Native, Native Hawaiian, and Pacific Islander) doctoral graduates from public health fields and determined the proportion of persons from underrepresented racial/ethnic minority groups who entered academia. METHODS: We analyzed repeated cross-sectional data from restricted files collected by the National Science Foundation on doctoral graduates from US institutions during 2003-2015. Our dependent variables were the number of all underrepresented racial/ethnic minority public health doctoral recipients and underrepresented racial/ethnic minority graduates who had accepted academic positions. Using logistic regression models and adjusted odds ratios (aORs), we examined correlates of these variables over time, controlling for all independent variables (eg, gender, age, relationship status, number of dependents). RESULTS: The percentage of underrepresented racial/ethnic minority doctoral graduates increased from 15.4% (91 of 592) in 2003 to 23.4% (296 of 1264) in 2015, with the largest increase occurring among black graduates (from 6.6% in 2003 to 14.1% in 2015). Black graduates (310 of 1241, 25.0%) were significantly less likely than white graduates (2258 of 5913, 38.2%) and, frequently, less likely than graduates from other underrepresented racial/ethnic minority groups to indicate having accepted an academic position (all P < .001). CONCLUSIONS: Stakeholders should consider targeted programs to increase the number of racial/ethnic minority faculty members in academic public health fields.

Correction: Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network.

The original version of this Article contained an error in the spelling of the author Geoffrey S. Ginsburg, which was incorrectly given as Geoffrey Ginsburg. This has now been corrected in both the PDF and HTML versions of the Article.

Employment Trends Among Public Health Doctoral Recipients, 2003-2015.

OBJECTIVES: To examine postgraduation employment trends among graduates of doctoral programs in public health from 2003 to 2015. METHODS: We analyzed pooled cross-sectional data from a census of graduates receiving a research doctorate from US accredited institutions. The outcome of interest was employment status. Covariates included public health discipline, sociodemographic characteristics, and institutional attributes. RESULTS: Of 11 771 graduates, nearly two thirds secured employment in either academic (34.8%) or nonacademic (31.4%) settings at the time of graduation. The proportion of those still seeking employment increased over time. Individuals who were White, younger, trained in either biostatistics or epidemiology, or from an institution with the highest level of research intensity were significantly more likely to secure employment. Academic employment was the most common setting for all 5 public health disciplines, but we observed differences in employment patterns (e.g., government, nonprofit, for-profit) across disciplines. CONCLUSIONS: Certain characteristics among public health doctoral recipients are correlated with postgraduation employment. More research is needed, but the observed increase in individuals still seeking employment may be attributable to increases in general public health graduates from for-profit institutions.

Interdisciplinary Dissertation Research Among Public Health Doctoral Trainees, 2003-2015.

OBJECTIVES: Given the call for more interdisciplinary research in public health, the objectives of this study were to (1) examine the correlates of interdisciplinary dissertation completion and (2) identify secondary fields most common among interdisciplinary public health graduates. METHODS: We analyzed pooled cross-sectional data from 11 120 doctoral graduates in the Survey of Earned Doctorates, 2003-2015. The primary outcome was interdisciplinary dissertation completion. Covariates included primary public health field, sociodemographic characteristics, and institutional attributes. RESULTS: From 2003 to 2015, a total of 4005 of 11 120 (36.0%) doctoral graduates in public health reported interdisciplinary dissertations, with significant increases observed in recent years. Compared with general public health graduates, graduates of environmental health (odds ratio [OR] = 1.74; P < .001) and health services administration (OR = 1.38; P < .001) doctoral programs were significantly more likely to report completing interdisciplinary dissertation work, whereas graduates from biostatistics (OR = 0.51; P < .001) and epidemiology (OR = 0.76; P < .001) were less likely to do so. Completing an interdisciplinary dissertation was associated with being male, a non-US citizen, a graduate of a private institution, and a graduate of an institution with high but not the highest level of research activity. Many secondary dissertation fields reported by interdisciplinary graduates included other public health fields. CONCLUSION: Although interdisciplinary dissertation research among doctoral graduates in public health has increased in recent years, such work is bounded in certain fields of public health and certain types of graduates and institutions. Academic administrators and other stakeholders may use these results to inform greater interdisciplinary activity during doctoral training and to evaluate current and future collaborations across departments or schools.

Medication Exposure Patterns in Primary Care Patients Prescribed Pharmacogenetically Actionable Opioids.

Current approaches to assessing medication exposure fail to capture the complexity of the phenomenon and the context in which it occurs. This study's purpose was to develop a typology of subgroups of patients who share common patterns of medication exposure. To create the typology, we used an exemplar sample of 30 patients in a large public healthcare system who had been prescribed the pharmacogenetically actionable opioids codeine or tramadol. Data related to medication exposure were drawn from large data repositories. Using a person-oriented qualitative approach, eight subgroups of patients who shared common patterns of medication exposure were identified. The subgroups had one of five opioid prescription patterns (i.e., singular, episodic, switching, sustained, multiplex), and one of three types of primary foci of medical care (i.e., pain, comorbidities, both). The findings reveal medication exposure patterns that are dynamic, multidimensional, and complex, and the typology offers an innovative approach to assessing medication exposure.

CYP2D6 drug-gene and drug-drug-gene interactions among patients prescribed pharmacogenetically actionable opioids.

PURPOSE: When codeine and tramadol are used for pain management, it is imperative that nurses are able to assess for potential drug-gene and drug-drug-gene interactions that could adversely impact drug metabolism and ultimately pain relief. Both drugs are metabolized through the CYP2D6 metabolic pathway which can be affected by medications as well the patient's own pharmacogenotype. The purpose of this brief report is to identify drug-gene and drug-drug-gene interactions in 30 adult patients prescribed codeine or tramadol for pain. METHODS: We used three data sources: (1) six months of electronic health record data on the number and types of medications prescribed to each patient; (2) each patient's CYP2D6 pharmacogenotype, and (3) published data on known CYP2D6 gene-drug and drug-drug-gene interactions. RESULTS: Ten patients (33%) had possible drug-gene or drug-drug-gene interactions. Five patients had CYP2D6 drug-gene interactions indicating they were not good candidates for codeine or tramadol. In addition, five patients had potential CYP2D6 drug-drug-gene interactions with either codeine or tramadol. CONCLUSION: Our findings from this exploratory study underscores the importance of assessing and accounting for drug-gene and drug-drug-gene interactions in patients prescribed codeine or tramadol.

Lessons Learned When Introducing Pharmacogenomic Panel Testing into Clinical Practice.

OBJECTIVES: Implementing new programs to support precision medicine in clinical settings is a complex endeavor. We describe challenges and potential solutions based on the Indiana GENomics Implementation: an Opportunity for the Underserved (INGenious) program at Eskenazi Health-one of six sites supported by the Implementing GeNomics In pracTicE network grant of the National Institutes of Health/National Human Genome Research Institute. INGenious is an implementation of a panel of genomic tests. METHODS: We conducted a descriptive case study of the implementation of this pharmacogenomics program, which has a wide scope (14 genes, 27 medications) and a diverse population (patients who often have multiple chronic illnesses, in a large urban safety-net hospital and its outpatient clinics). CHALLENGES: We placed the clinical pharmacogenomics implementation challenges into six categories: patient education and engagement in care decision making; clinician education and changes in standards of care; integration of technology into electronic health record systems; translational and implementation sciences in real-world clinical environments; regulatory and reimbursement considerations, and challenges in measuring outcomes. A cross-cutting theme was the need for careful attention to workflow. Our clinical setting, a safety-net health care system, presented some distinctive challenges. Patients often had multiple chronic illnesses and sometimes were taking more than one pharmacogenomics-relevant medication. Reaching patients for recruitment or follow-up was another challenge. CONCLUSIONS: New, large-scale endeavors in health care are challenging. A description of the challenges that we encountered and the approaches that we adopted to address them may provide insights for those who implement and study innovations in other health care systems.

Designing a natural experiment to evaluate a national health care-community partnership to prevent type 2 diabetes.

To address the growing incidence of type 2 diabetes in the United States, UnitedHealth Group, the YMCA of the USA, and the Centers for Disease Control and Prevention have partnered to bring a group-based adaptation of the Diabetes Prevention Program lifestyle intervention to a national scale. Researchers at Northwestern and Indiana universities are collaborating with these partners to design a robust evaluation of the reach, effectiveness, and costs of this natural experiment. We will employ a quasi-experimental, cluster-randomized study design and combine administrative, clinical, and programmatic data from existing sources to derive reliable, timely, and policy-relevant estimates of the program's impact and potential for sustainability. In this context, evaluation results will provide information about the unique role of a health care-community partnership to prevent type 2 diabetes.

Can lay health workers promote better medical self-management by persons living with HIV? An evaluation of the Positive Choices program.

OBJECTIVE: To evaluate Positive Choices (PC), a program that employed lay health workers to motivate antiretroviral adherence among persons living with HIV with coverage from Indiana's high-risk insurance pool. METHODS: Four hundred and forty nine participants living in the greater Indianapolis area were randomly allocated to treatment (n = 91) or control (n = 358) groups and followed for one year. RESULTS: Compared to control subjects, PC subjects were more likely to adhere to HIV medications (medication possession ratio adherence ≥ 0.95, OR = 1.83, p = 0.046), and to achieve undetectable viral load (<50 copies/mL, OR = 2.01, p = 0.011) in the 12 months following introduction of PC. There were no significant differences observed between groups in any of self-reported health status indicators. CONCLUSION: Estimates suggest that PC clients were 16% more likely to have undetectable viral loads than clients in standard care. The incremental program cost was approximately $10,000 for each additional person who achieved an undetectable viral load. PRACTICE IMPLICATIONS: As persons living with HIV experience greater longevity and healthcare reform expands coverage to these high-risk populations, greater demands will be placed on the HIV-care workforce. Results suggest lay health workers may serve as effective adjuncts to professional care providers.