Aetna's Compassionate Care Program: Sustained Value for Our Members with Advanced Illness.

Background: In 2004, Aetna, a national health insurer, launched the Aetna Compassionate Care Program (ACCP) targeting members diagnosed with an advanced illness with a view to increase access to palliative care and hospice services. Objective: The objective of this study is to evaluate the impact of ACCP on health care utilization and hospice enrollment among enrolled members. Methods: This was a retrospective cohort study comparing participants in ACCP to a matched control group using a propensity score method. The study group consisted of Aetna Medicare Advantage members who participated in the ACCP between January 2014 and June 2015. Potential control group members were those who were not identified by the predictive model nor were referred to the ACCP program through other means. The primary outcomes of interest were hospice use measured as percent of members electing hospice and median number of days in hospice; health care utilization and medical costs measured as rates and medical costs associated with acute inpatient admissions, emergency room, primary care, and specialty visits in the 30 and 90 days before death. Results: Participants in the ACCP program were 36% more likely to enroll in hospice (79% vs. 58%, p < 0.0001) and had reduced acute inpatient medical costs ($4169 vs. $5863, p < 0.0001) driven primarily by fewer inpatient admissions (860 vs. 1017, p < 0.0001) in the last 90 days of life. Conclusions: Advanced illness case management programs such as ACCP can improve access to hospice and improve patient outcomes while reducing unnecessary admissions in the last 90 days of life.

Drug-induced eosinophilia.

BACKGROUND: Drug reactions have been associated with increased blood eosinophil levels. OBJECTIVE: To review clinical characteristics, the diagnosis, and the management of drug-induced eosinophilia. METHODS: Pertinent articles were selected and reviewed in relation to a case presentation of drug-induced eosinophilia. RESULTS: A case of asymptomatic eosinophilia in the setting of acetylsalicylic acid (aspirin) use was presented, followed by discussion of the clinical characteristics, diagnosis, and management of drug-induced eosinophilia. Clinical pearls and pitfalls were reviewed for the practicing allergist, clinical immunologist, and fellow-in-training. CONCLUSION: Drug-induced eosinophilia is a diagnosis of exclusion. Although most cases of drug-induced eosinophilia are asymptomatic, one study showed an increased rate of hypersensitivity reactions in patients with higher eosinophil counts and earlier onset of eosinophilia.

Assessing the Impact of Medication Adherence on Long-Term Cardiovascular Outcomes.

BACKGROUND: Although guideline-recommended therapies reduce major adverse cardiovascular events (MACE) in patients after myocardial infarction (MI) or those with atherosclerotic disease (ATH), adherence is poor. OBJECTIVES: The goal of this study was to determine the association between medication adherence levels and long-term MACE in these patients. METHODS: We queried the claims database of a large health insurer for patients hospitalized for MI or with ATH. The primary outcome measure was a composite of all-cause death, MI, stroke, or coronary revascularization. Using proportion of days covered for statins and angiotensin-converting enzyme inhibitors, patients were stratified as fully adherent (≥80%), partially adherent (≥40% to ≤79%), or nonadherent (<40%). Per-patient annual direct medical (ADM) costs were estimated by using unit costs from 2 national files. RESULTS: Data were analyzed for 4,015 post-MI patients and 12,976 patients with ATH. In the post-MI cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (18.9% vs. 26.3%; hazard ratio [HR]: 0.73; p = 0.0004) and partially adherent (18.9% vs. 24.7%; HR: 0.81; p = 0.02) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $369 and $440 compared with the partially adherent and nonadherent groups, respectively. In the ATH cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (8.42% vs. 17.17%; HR: 0.56; p < 0.0001) and the partially adherent (8.42% vs. 12.18%; HR: 0.76; p < 0.0001) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $371 and $907 compared with the partially adherent and nonadherent groups. CONCLUSIONS: Full adherence to guideline-recommended therapies was associated with a lower rate of MACE and cost savings, with a threshold effect at >80% adherence in the post-MI population; at least a 40% level of long-term adherence needs to be maintained to continue to accrue benefit. Novel approaches to improve adherence may significantly reduce cardiovascular events.

Abortive placode formation in the feather tract of the scaleless chicken embryo.

The featherless phenotype of the scaleless mutant provides a model for delineating the process of feather follicle formation. Initial studies established that the mutation affects the epidermis and suggested that epidermis is unable to respond to signals from underlying dermis, or propagate a reciprocal signal. The work presented here demonstrates that scaleless epidermis does indeed respond to the initial inductive signals from dermis, as indicated by the localization of nuclear beta-catenin and transient focal expression of genes expressed in the placode of wild-type feather rudiments. In the sporadic "escaper" feathers that form in scaleless, expression of many genes associated with the progression of feather development is comparable to that in wild-type embryos. An exception is the ectodysplasin receptor gene Edar, which is expressed at lower levels in mutant feather buds. These observations suggest that the scaleless mutation impairs the locally augmented expression of Edar required to stabilize the placodal fate and sustain feather development.

Challenges in improving the quality of osteoporosis care for long-term glucocorticoid users: a prospective randomized trial.

BACKGROUND: In light of widespread undertreatment for glucocorticoid-induced osteoporosis (GIOP), we designed a group randomized controlled trial to increase bone mineral density (BMD) testing and osteoporosis medication prescribing among patients receiving long-term glucocorticoid therapy. METHODS: Using administrative databases of a large US health plan, we identified physicians who prescribed long-term glucocorticoid therapy to at least 3 patients. One hundred fifty-three participating physicians were randomized to receive a 3-module Web-based GIOP intervention or control course. Intervention modules focused on GIOP management and incorporated case-based continuing medical education and personalized audit and feedback of GIOP management compared with that of the top 10% of study physicians. In the year following the intervention, we compared rates of BMD testing and osteoporosis medication prescribing between intervention and control physicians. RESULTS: Following the intervention, intent-to-treat analyses showed that 78 intervention physicians (472 patients) vs 75 control physicians (477 patients) had similar rates of BMD testing (19% vs 21%, P = .48; rate difference, -2%; 95% confidence interval [CI], -8% to 4%) and osteoporosis medication prescribing (32% vs 29%, P = .34; rate difference, 3%; 95% CI, -3% to 9%). Among 45 physicians completing all modules (343 patients), intervention physicians had numerically but not significantly higher rates of BMD testing (26% vs 16%, P =.04; rate difference, 10%; 95% CI, 1%-20%) and bisphosphonate prescribing (24% vs 17%, P =.09; rate difference, 7%; 95% CI, -1% to 16%) or met a combined end point of BMD testing or osteoporosis medication prescribing (54% vs 44%, P =.07; rate difference, 10%; 95% CI, -1% to 21%) compared with control physicians. CONCLUSIONS: In the main analysis, a Web-based intervention incorporating performance audit and feedback and case-based continuing medical education had no significant effect on the quality of osteoporosis care. However, dose-response trends showed that physicians with greater exposure to the intervention had higher rates of GIOP management. New cost-effective modalities are needed to improve the quality of osteoporosis care.

Population-based assessment of adverse events associated with long-term glucocorticoid use.

OBJECTIVE: The frequency of many adverse events (AEs) associated with low-dose glucocorticoid use is unclear. We sought to determine the prevalence of glucocorticoid-associated AEs in a large US managed care population. METHODS: Using linked administrative and pharmacy claims, adults receiving >or=60 days of glucocorticoids were identified. These individuals were surveyed about glucocorticoid use and symptoms of 8 AEs commonly attributed to glucocorticoid use. RESULTS: Of the 6,517 eligible glucocorticoid users identified, 2,446 (38%) returned the mailed survey. Respondents were 29% men with a mean +/- SD age of 53 +/- 14 years; 79% were white and 13% were African American. Respondents had a mean +/- SD of 7 +/- 3 comorbid conditions and were prescribed a mean +/- SD prednisone-equivalent dosage of 16 +/- 14 mg/day. More than 90% of individuals reported at least 1 AE associated with glucocorticoid use; 55% reported that at least 1 AE was very bothersome. Weight gain was the most common self-reported AE (70% of the individuals), cataracts (15%) and fractures (12%) were among the most serious. After multivariable adjustment, all AEs demonstrated a strong dose-dependent association with cumulative glucocorticoid use. Among users of low-dose therapy (

Agreement and validity of pharmacy data versus self-report for use of osteoporosis medications among chronic glucocorticoid users.

PURPOSE: Pharmacy and linked claims databases are commonly used to determine medication receipt as a measure of quality of care. However, these data sources have not been previously compared with self-reported data for receipt of medications used for glucocorticoid-induced osteoporosis (GIOP). METHODS: Using databases from a national managed care organization (MCO), we identified 6282 chronic glucocorticoid users (60+ days in 18 months). We compared self-reported current use of alendronate, risedronate, calcitonin, and raloxifene (reference standard) to different intervals of preceding pharmacy data to determine agreement, sensitivity, specificity, and positive and negative predictive values of the pharmacy data. RESULTS: Survey respondents (n = 2363) were mean +/- SD age 53 +/- 14 years old, 70% women, and 78% Caucasian. Agreement between self-reported and pharmacy data ranged from Kappa = 0.64 (95%CI 0.53-0.75) (calcitonin) to 0.80 (0.76-0.84) (alendronate). The positive predictive value of a filled prescription in the pharmacy database in the prior 6 months exceeded 90% compared to the reference standard of self-reported current bisphosphonate use. However, the 6-month interval of pharmacy data failed to capture >25% of self-reported current bisphosphonate users. The optimal interval of pharmacy data to distinguish between current and past bisphosphonate users was 120-180 days. CONCLUSIONS: Among chronic glucocorticoid users enrolled in managed care, underreporting of current osteoporosis medication use was uncommon, and agreement between self-report and pharmacy data was high. Use of pharmacy data alone is unlikely to underestimate quality of osteoporosis care, but different intervals of pharmacy data have important implications on the ability to identify current users of osteoporosis medications.

Longitudinal patterns in the prevention of osteoporosis in glucocorticoid-treated patients.

OBJECTIVE: To evaluate patient and physician factors associated with prevention of glucocorticoid-induced osteoporosis and to describe temporal trends in screening and prevention of glucocorticoid-induced osteoporosis. METHODS: Using databases from a national managed care organization, enrollees who had been prescribed glucocorticoids (taken for at least 60 days) during an 18-month period were identified. Administrative data from January 2001 through June 2003 and linked survey data from October 2003 were examined for measurement of bone mass, prescription of antiresorptive medication, and use of over-the-counter calcium and/or vitamin D treatment. Factors associated with screening and bone-protective therapies were identified using multivariable logistic regression, focusing on physician specialty and survey respondent ethnicity. Trends in glucocorticoid-induced osteoporosis prevention were assessed using administrative data from 2001-2003 versus 1995-1998. RESULTS: We identified 6,281 patients who were prescribed glucocorticoids in 2001-2003 (mean +/- SD prescribed prednisone-equivalent dosage 16 +/- 14 mg/day). Forty-two percent underwent bone mass measurement and/or were prescribed bone-protective medication; rates were lowest for men (25%). Compared with patients of internists, the odds of bone mass measurement were lowest among patients prescribed glucocorticoids by family physicians (odds ratio [OR] 0.56 [95% confidence interval] [95% CI] 0.30-1.04) and highest among patients prescribed glucocorticoids by rheumatologists (OR 1.48 [95% CI 1.06-2.08]). Patients prescribed glucocorticoids by gastroenterologists were less likely to be treated with antiresorptive agents (OR 0.49 [95% CI 0.28-0.86]). African American patients were less likely than white patients to be screened (OR 0.55 [95% CI 0.40-0.75]) or treated (OR 0.71 [95% CI 0.51-0.98]). The frequency of bone mass measurement among glucocorticoid-treated patients in 2001-2003 increased 3-fold compared with 1995-1998, and the use of prescription antiresorptive medication increased approximately 2-fold. CONCLUSION: Despite significant temporal increases in the frequency of screening for and treatment of glucocorticoid-induced osteoporosis, absolute rates remain low, especially among men, African Americans, and patients of certain physician specialties.

Expression and regulation of Groucho-related genes in the embryonic chicken feather bud.

The groucho-related gene (Grg) products modulate the transcriptional response to several extracellular signals, including the Wnts. In an effort to define the roles of Grgs in the morphogenesis of the feather bud, cDNAs encoding members of the Grg family were cloned from embryonic chick skin. In situ hybridization was used to localize transcripts for cGrg2, Grg3, Grg4, and Grg5 in embryos from day 6 through day 9. Expression of cGrg2, 3, and 5 is detected throughout the initial epidermal placode. As the buds mature, expression becomes limited to the posterior halves and eventually to the distal tip of the outgrowing bud. This pattern and the effects of forced activation of the bone morphogenetic protein and beta-catenin signal transduction pathways on Grg gene expression suggest that these genes act downstream of the early activation of the beta-catenin pathway that initiates placode formation. Induction of Grg genes by beta-catenin may serve as a negative feedback to modulate pathway activation while also altering the activity of other transduction pathways involved in bud patterning.