Exploring robust methods for evaluating treatment and comparison groups in chronic care management programs.

Evaluation of chronic care management (CCM) programs is necessary to determine the behavioral, clinical, and financial value of the programs. Financial outcomes of members who are exposed to interventions (treatment group) typically are compared to those not exposed (comparison group) in a quasi-experimental study design. However, because member assignment is not randomized, outcomes reported from these designs may be biased or inefficient if study groups are not comparable or balanced prior to analysis. Two matching techniques used to achieve balanced groups are Propensity Score Matching (PSM) and Coarsened Exact Matching (CEM). Unlike PSM, CEM has been shown to yield estimates of causal (program) effects that are lowest in variance and bias for any given sample size. The objective of this case study was to provide a comprehensive comparison of these 2 matching methods within an evaluation of a CCM program administered to a large health plan during a 2-year time period. Descriptive and statistical methods were used to assess the level of balance between comparison and treatment members pre matching. Compared with PSM, CEM retained more members, achieved better balance between matched members, and resulted in a statistically insignificant Wald test statistic for group aggregation. In terms of program performance, the results showed an overall higher medical cost savings among treatment members matched using CEM compared with those matched using PSM (-$25.57 versus -$19.78, respectively). Collectively, the results suggest CEM is a viable alternative, if not the most appropriate matching method, to apply when evaluating CCM program performance.

The impact of proactive chronic care management on hospital admissions in a German senior population.

An increase in chronic disease prevalence is contributing to health care cost growth and decreased quality of life in industrialized nations worldwide. Inadequate management of chronic diseases is a leading cause of hospitalizations and, thus, avoidable expenditures. In this study, we evaluated the impact of nurse-delivered care calls, the primary intervention of a proactive chronic care management (CCM) program, in a population aged 65 and older in Germany. In this analysis, hospital admission rates were evaluated among program enrollees who were diagnosed with diabetes, heart failure, coronary heart disease, or chronic obstructive pulmonary disease. The Intervention group comprised those members who participated in care calls (n=13,486), whereas the Comparison group included enrollees who did not participate in these calls (n=4,582). Changes in admission rates were calculated between the year prior to and year after program commencement. Comparative analyses were adjusted for age, sex, region of residence, and disease severity (stratification of 3 [least severe] to 1 [most severe]). Overall, a 6.0% decrease in admissions was observed among Intervention group members compared with an 18.9% increase among Comparison group members (P ≤ 0.0001). This decrease in admissions was driven by participants with the highest levels of risk. In addition, a dose-response relationship was observed in which admissions decreased with an increased number of care calls (P=0.0001). These results indicate that proactive CCM interventions are effective in reducing hospital admission rates in a senior population with chronic disease.

Carcinogen-induced histone alteration in normal human mammary epithelial cells.

Little is known about early carcinogen-induced protein alterations in mammary epithelium. Detection of early alterations would enhance our understanding of early-stage carcinogenesis. Here, normal human mammary epithelial cells (HMECs) were exposed to dietary and environmental carcinogens [2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP), 4-aminobiphenyl (ABP), benzo[a]pyrene, 2,3,7,8-tetrachlorodibenzo-p-dioxin] individually or in combination. A phage display library of single-chain variable fragment antibodies was used to screen protein targets altered by the treatment. In combination with matrix-assisted laser desorption time of flight, we identified histone H3 as a target antigen. Although histone H3 total protein remained unchanged in control and treated HMEC, the methylation of lysine 4 was altered. A reduction in mono-methyl histone H3 (Lys 4) was observed in treated HMEC compared with control HMEC. This alteration was shown to be dependent on carcinogen concentration and specific for PhIP and ABP. To characterize potential histone demethylation mechanisms, localization and protein expression patterns of lysine-specific demethylase 1 (LSD1) were analyzed. In control HMEC, LSD1 was present at the nuclear periphery. However, following 72 h carcinogen treatment, LSD1 localized within the nucleus. Within 48 h after treatment, mono-methyl histone H3 (Lys 4) was restored and LSD1 localization was reversed. Protein expression levels of LSD1 were also increased in treated HMEC compared with control HMEC. Our data suggest that the induction of a single enzyme, LSD1, represents an early response to carcinogen exposure, which leads to the demethylation of histone H3 (Lys 4), which, in turn, may influence the expression of multiple genes critical in early-stage mammary carcinogenesis.