Jean P. O’Malley

Angiotensin-Converting Enzyme DD Genotype and Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia

BACKGROUND Controversy exists as to whether the deletion/deletion genotype (DD) of the ACE gene polymorphism increases the risk of myocardial infarction (MI). Studies have suggested that the ACE DD genotype is associated with increased plaque instability. We hypothesized that the ACE DD genotype may increase the risk of myocardial infarction and coronary heart disease (CHD) in patients with heterozygous familial hypercholesterolemia (FH) or familial defective apolipoprotein B-100 (FDB) who, as a group, are at high risk of having lipid-rich plaques in their coronary arteries. METHODS AND RESULTS We determined the ACE genotypes and incidence of MI or surgical intervention for CHD in 213 adult patients with heterozygous FH or FDB. The incidence of MI in 35 male patients who carried the ACE DD genotype was 2.5 times that observed in male patients with the II or DI genotypes, and the incidence of CHD in male patients with the DD genotype was 2.2 times higher than in those who had ACE DI+II. The potential effects of ACE genotype on CHD could not be directly compared in female patients because of a disparity in the smoking history of the genotypic groups. From logistic regression analysis, the estimated odds ratio associated with the ACE DD genotype was 2.57 for MI and 2.21 for CHD adjusted for age, sex, and smoking history. CONCLUSIONS The ACE DD genotype is associated with an increased risk of MI and CHD in patients with heterozygous FH or FDB. Determination of the ACE genotype in asymptomatic FH and FDB patients provides an additional means to identify those patients at greatest risk for the premature development of CHD.

Thoracic Aortic Aneurysm Frequency and Dissection are Associated with Fibrillin-1 Fragment Concentrations in Circulation

Rationale: Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome. Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA. Objective: Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated with TAA and dissection. Methods and Results: Plasma samples were obtained from 1265 patients with aortic aneurysm or dissection and from 125 control subjects. Concentrations of fibrillin-1, fibrillin-2, and fibulin-4 were measured with novel immunoassays. One hundred and seventy-four patients (13%) had aneurysms with only abdominal aortic involvement (abdominal aortic aneurysm), and 1091 (86%) had TAA. Of those with TAA, 300 patients (27%) had chronic dissection and 109 (10%) had acute or subacute dissection. Associations of fragment concentrations with TAA (versus abdominal aortic aneurysm) or with dissection (versus no dissection) were estimated with odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, sex, and smoking. Compared with controls, significantly higher percentages of aneurysm patients had detectable levels of fibrillin fragments. TAA was significantly more common (than abdominal aortic aneurysm) in the highest compared with lowest quartile of fibrillin-1 concentration (OR=2.9; 95% CI, 1.6–5.0). Relative to TAA without dissection, acute or subacute dissection (OR=2.9; 95% CI, 1.6–5.3), but not chronic dissection, was more frequent in the highest compared with lowest quartile of fibrillin-1 concentration. Neither TAA nor dissection was associated with fibrillin-2 or fibulin-4. Conclusions: Circulating fibrillin-1 fragments represent a new potential biomarker for TAA and acute aortic dissection.

An analysis of electronically monitored adherence to antiretroviral medications.

Medication adherence studies increasingly collect data electronically, often using Medication Event Monitoring System (MEMS) caps. Analyses typically focus on summary adherence measures, although more complete analyses are possible using adaptive statistical methods. These methods were used to describe individual-subject adherence patterns for MEMS data from a clinical trial. Subjects were adaptively clustered into groups with similar adherence patterns and clusters were compared on a variety of subject characteristics. There were seven different adherence clusters: consistently high, consistently moderately high, consistently moderate, consistently moderately low, consistently low, deteriorating starting early, and deteriorating late. Compared to other subjects, subjects with consistently high and consistently moderately high adherence were more likely to be male, White, and older and to maintain during study participation a CD4 cell count over 500 and an HIV viral load of at most 400 copies/ml. These results demonstrate the effectiveness of adaptive methods for comprehensive analysis of MEMS data.

Community Health Center Use After Oregon’s Randomized Medicaid Experiment

PURPOSE There is debate about whether community health centers (CHCs) will experience increased demand from patients gaining coverage through Affordable Care Act Medicaid expansions. To better understand the effect of new Medicaid coverage on CHC use over time, we studied Oregon’s 2008 randomized Medicaid expansion (the “Oregon Experiment”). METHODS We probabilistically matched demographic data from adults (aged 19–64 years) participating in the Oregon Experiment to electronic health record data from 108 Oregon CHCs within the OCHIN community health information network (originally the Oregon Community Health Information Network) (N = 34,849). We performed intent-to-treat analyses using zero-inflated Poisson regression models to compare 36-month (2008–2011) usage rates among those selected to apply for Medicaid vs not selected, and instrumental variable analyses to estimate the effect of gaining Medicaid coverage on use. Use outcomes included primary care visits, behavioral/mental health visits, laboratory tests, referrals, immunizations, and imaging. RESULTS The intent-to-treat analyses revealed statistically significant differences in rates of behavioral/mental health visits, referrals, and imaging between patients randomly selected to apply for Medicaid vs those not selected. In instrumental variable analyses, gaining Medicaid coverage significantly increased the rate of primary care visits, laboratory tests, referrals, and imaging; rate ratios ranged from 1.27 (95% CI, 1.05–1.55) for laboratory tests to 1.58 (95% CI, 1.10–2.28) for referrals. CONCLUSIONS Our results suggest that use of many different types of CHC services will increase as patients gain Medicaid through Affordable Care Act expansions. To maximize access to critical health services, it will be important to ensure that the health care system can support increasing demands by providing more resources to CHCs and other primary care settings.

Receipt of Diabetes Preventive Services Differs by Insurance Status at Visit

BACKGROUND Lack of insurance is associated with suboptimal receipt of diabetes preventive care. One known reason for this is an access barrier to obtaining healthcare visits; however, little is known about whether insurance status is associated with differential rates of receipt of diabetes care during visits. PURPOSE To examine the association between health insurance and receipt of diabetes preventive care during an office visit. METHODS This retrospective cohort study used electronic health record and Medicaid data from 38 Oregon community health centers. Logistic regression was used to test the association between insurance and receipt of four diabetes services during an office visit among patients who were continuously uninsured (n=1,117); continuously insured (n=1,466); and discontinuously insured (n=336) in 2006-2007. Generalized estimating equations were used to account for within-patient correlation. Data were analyzed in 2013. RESULTS Overall, continuously uninsured patients had lower odds of receiving services at visits when due, compared to those who were continuously insured (AOR=0.73, 95% CI=0.66, 0.80). Among the discontinuously insured, being uninsured at a visit was associated with lower odds of receipt of services due at that visit (AOR=0.77, 95% CI=0.64, 0.92) than being insured at a visit. CONCLUSIONS Lack of insurance is associated with a lower probability of receiving recommended services that are due during a clinic visit. Thus, the association between being uninsured and receiving fewer preventive services may not be completely mediated by access to clinic visits.

Health Care Utilization Rates After Oregon's 2008 Medicaid Expansion: Within-Group and Between-Group Differences Over Time Among New, Returning, and Continuously Insured Enrollees.

Background:Although past research demonstrated that Medicaid expansions were associated with increased emergency department (ED) and primary care (PC) utilization, little is known about how long this increased utilization persists or whether postcoverage utilization is affected by prior insurance status. Objectives:(1) To assess changes in ED, PC, mental and behavioral health care, and specialist care visit rates among individuals gaining Medicaid over 24 months postinsurance gain; and (2) to evaluate the association of previous insurance with utilization. Methods:Using claims data, we conducted a retrospective cohort analysis of adults insured for 24 months following Oregon’s 2008 Medicaid expansion. Utilization rates among 1124 new and 1587 returning enrollees were compared with those among 5126 enrollees with continuous Medicaid coverage (≥1 y preexpansion). Visit rates were adjusted for propensity score classes and geographic region. Results:PC visit rates in both newly and returning insured individuals significantly exceeded those in the continuously insured in months 4 through 12, but were not significantly elevated in the second year. In contrast, ED utilization rates were significantly higher in returning insured compared with newly or continuously insured individuals and remained elevated over time. New visits to PC and specialist care were higher among those who gained Medicaid compared with the continuously insured throughout the study period. Conclusions:Predicting the effect of insurance expansion on health care utilization should account for the prior coverage history of new enrollees. In addition, utilization of outpatient services changes with time after insurance, so expansion evaluations should allow for rate stabilization.

Supporting health insurance expansion: do electronic health records have valid insurance verification and enrollment data?

OBJECTIVE To validate electronic health record (EHR) insurance information for low-income pediatric patients at Oregon community health centers (CHCs), compared to reimbursement data and Medicaid coverage data. MATERIALS AND METHODS Subjects Children visiting any of 96 CHCs (N = 69 189) from 2011 to 2012. Analysis The authors measured correspondence (whether or not the visit was covered by Medicaid) between EHR coverage data and (i) reimbursement data and (ii) coverage data from Medicaid. RESULTS Compared to reimbursement data and Medicaid coverage data, EHR coverage data had high agreement (87% and 95%, respectively), sensitivity (0.97 and 0.96), positive predictive value (0.88 and 0.98), but lower kappa statistics (0.32 and 0.49), specificity (0.27 and 0.60), and negative predictive value (0.66 and 0.45). These varied among clinics. DISCUSSION/CONCLUSIONS EHR coverage data for children had a high overall correspondence with Medicaid data and reimbursement data, suggesting that in some systems EHR data could be utilized to promote insurance stability in their patients. Future work should attempt to replicate these analyses in other settings.

The Association Between Medicaid Coverage for Children and Parents Persists: 2002-2010

To assess the association between a child’s and their parent’s public health insurance status during a time when children had access to coverage independent of policies that impacted adults’ access. Secondary data from the Oregon Health Plan (OHP) [Oregon’s Medicaid and Children’s Health Insurance Programs] for families with at least one parent and one child with OHP coverage at any time during the study period (2002–2010). We linked children to their parents in the OHP data set and examined longitudinal associations between the coverage patterns for children and their parents, controlling for several demographic and economic confounders. We tested for differences in the strength of associations in monthly coverage status in five time periods throughout the nine-year study period. The odds of a child being insured by the OHP in months in which at least one parent had OHP coverage were significantly higher than among children whose parents were not enrolled at that time. Children with at least one parent who maintained or gained OHP coverage in a given month had a much higher probability of being enrolled in the OHP in that month, compared to children who had no covered parents in the given month or the month prior. Despite implementation of policies that differentially affected eligibility requirements for children and adults, strong associations persisted between coverage continuity for parents and children enrolled in Oregon public health insurance programs.

Oregon Medicaid Expenditures After the 2014 Affordable Care Act Medicaid Expansion: Over-time Differences Among New, Returning, and Continuously Insured Enrollees

Background: There is interest in assessing health care utilization and expenditures among new Medicaid enrollees after the 2014 Medicaid expansion. Recent studies have not differentiated between newly enrolled individuals and those returning after coverage gaps. Objectives: To assess health care expenditures among Medicaid enrollees in the 24 months after Oregon’s 2014 Medicaid expansions and examine whether expenditure patterns were different among the newly, returning, and continuously insured (CI). Research Design: Retrospective cohort study using inverse-propensity weights to adjust for differences between groups. Subjects: Oregon adult Medicaid beneficiaries insured continuously from 2014 to 2015 who were either newly, returning, or CI. Measures: Monthly expenditures for inpatient care, prescription drugs, total outpatient care, and subdivisions of outpatient care: emergency department, dental, mental and behavioral health, primary care, and specialist care. Results: After initial increases, newly and returning insured (RI) outpatient expenditures dropped below CI. Expenditures for emergency department and dental services among the RI remained higher than among the newly insured. Newly insured mental and behavioral health, primary care, and specialist expenditures plateaued higher than RI. Prescription drug expenditures increased over time for all groups, with CI highest and RI lowest. All groups had similar inpatient expenditures over 24 months post-Medicaid expansion. Conclusions: Our findings reveal that outpatient expenditures for new nonpregnant, non–dual-eligible Oregon Medicaid recipients stabilized over time after meeting pent-up demand, and prior insurance history affected the mix of services that individuals received. Policy evaluations should consider expenditures over at least 24 months and should account for enrollees’ prior insurance histories.

Electronic health record tools to assist with children’s insurance coverage: a mixed methods study

BackgroundChildren with health insurance have increased access to healthcare and receive higher quality care. However, despite recent initiatives expanding children’s coverage, many remain uninsured. New technologies present opportunities for helping clinics provide enrollment support for patients. We developed and tested electronic health record (EHR)-based tools to help clinics provide children’s insurance assistance.MethodsWe used mixed methods to understand tool adoption, and to assess impact of tool use on insurance coverage, healthcare utilization, and receipt of recommended care. We conducted intent-to-treat (ITT) analyses comparing pediatric patients in 4 intervention clinics (n = 15,024) to those at 4 matched control clinics (n = 12,227). We conducted effect-of-treatment-on-the-treated (ETOT) analyses comparing intervention clinic patients with tool use (n = 2240) to intervention clinic patients without tool use (n = 12,784).ResultsTools were used for only 15% of eligible patients. Qualitative data indicated that tool adoption was limited by: (1) concurrent initiatives that duplicated the work associated with the tools, and (2) inability to obtain accurate insurance coverage data and end dates. The ITT analyses showed that intervention clinic patients had higher odds of gaining insurance coverage (adjusted odds ratio [aOR] = 1.32, 95% confidence interval [95%CI] 1.14–1.51) and lower odds of losing coverage (aOR = 0.77, 95%CI 0.68–0.88), compared to control clinic patients. Similarly, ETOT findings showed that intervention clinic patients with tool use had higher odds of gaining insurance (aOR = 1.83, 95%CI 1.64–2.04) and lower odds of losing coverage (aOR = 0.70, 95%CI 0.53–0.91), compared to patients without tool use. The ETOT analyses also showed higher rates of receipt of return visits, well-child visits, and several immunizations among patients for whom the tools were used.ConclusionsThis pragmatic trial, the first to evaluate EHR-based insurance assistance tools, suggests that it is feasible to create and implement tools that help clinics provide insurance enrollment support to pediatric patients. While ITT findings were limited by low rates of tool use, ITT and ETOT findings suggest tool use was associated with better odds of gaining and keeping coverage. Further, ETOT findings suggest that use of such tools may positively impact healthcare utilization and quality of pediatric care.Trial registrationClinicalTrials.gov, NCT02298361; retrospectively registered on November 5, 2014.