Publications

Failure of the right ventricle (RV) is a serious disease with a poor prognosis and limited treatment options. Signaling by α-adrenergic receptors (α-ARs), in particular the α-subtype, mediate cardioprotective effects in multiple heart failure models. Recent studies have shown that chronic treatment with the α-subtype agonist A61603 improves function and survival in a model of left ventricular failure. The goal of the present study was to determine if chronic A61603 treatment is beneficial in a RV failure model. We used tracheal instillation of the fibrogenic antibiotic bleomycin in mice to induce pulmonary fibrosis, pulmonary hypertension, and RV failure within 2 wk. Some mice were chronically treated with a low dose of A61603 (10 ng·kg·day). In the bleomycin model of RV failure, chronic A61603 treatment was associated with improved RV fractional shortening and greater in vitro force development by RV muscle preparations. Cell injury markers were reduced with A61603 treatment (serum cardiac troponin I, RV fibrosis, and expression of matrix metalloproteinase-2). RV oxidative stress was reduced (using the probes dihydroethidium and 4-hydroxynonenal). Consistent with lowered RV oxidative stress, A61603 was associated with an increased level of the cellular antioxidant superoxide dismutase 1 and a lower level of the prooxidant NAD(P)H oxidase isoform NOX4. In summary, in the bleomycin model of RV failure, chronic A61603 treatment reduced RV oxidative stress, RV myocyte necrosis, and RV fibrosis and increased both RV function and in vitro force development. These findings suggest that in the context of pulmonary fibrosis, the α-subtype is a potential therapeutic target to treat the failing RV. Right ventricular (RV) failure is a serious disease with a poor prognosis and no effective treatments. In the mouse bleomycin model of RV failure, we tested the efficacy of a treatment using the α-adrenergic receptor subtype agonist A61603. Chronic A61603 treatment improved RV contraction and reduced multiple indexes of RV injury, suggesting that the α-subtype is a therapeutic target to treat RV failure.

OBJECTIVE

To contribute to decision analysis by estimating utility, defined as an individual's valuation of specific health states, for different pregnancy contexts.

STUDY DESIGN

Cross-sectional analysis of data from pregnant women recruited at pregnancy testing clinics during June 2014-June 2015. Utility was measured using the visual analog scale (VAS), PROMIS GSF-derived utility, standard gamble (SG), and time-trade-off (TTO) approaches. Six dimensions of pregnancy context were assessed including: intention, desirability, planning, timing, wantedness, and happiness. Multivariable regression modeling was used to examine the associations between pregnancy context and utility while controlling for women's sociodemographic and health characteristics.

RESULTS

Among 123 participants with diverse characteristics, aged 27±6 years, with mean gestation of 7.5±3 weeks, few reported optimal pregnancy contexts. Mean utility of the pregnancy state varied across contexts, whether measured with VAS (0.28-0.91), PROMIS GSF-derived utility (0.66-0.75), SG (0.985-1.00) or TTO (0.9990-0.99999). The VAS-derived mean utility score for unintended pregnancy was 0.68 (95% CI 0.59, 0.77). Multivariable regression analysis demonstrated significant disutility of unintended pregnancy, as well as all other unfavorable pregnancy contexts, when measured by VAS. In contrast, PROMIS GSF-derived utility only detected a significant reduction in utility among ambivalent compared to wanted pregnancy, while SG and TTO did not show meaningful differences in utility across pregnancy contexts.

CONCLUSIONS

Unintended pregnancy is associated with significant patient-reported disutility, as is pregnancy occurring in other unfavorable contexts. VAS-based measurements provide the most nuanced measures of the utility for pregnancy in varying contexts.

IMPLICATIONS

Decision analyses, including assessments of the cost-effectiveness of pregnancy related interventions, should incorporate measures of the utility of pregnancy in various contexts.

BACKGROUND

Management of patients with chronic conditions relies on accurate measurement. It is unknown how transition to the ICD-10 coding system affected reporting of chronic condition rates over time. We measured chronic condition rates 2 years before and 1 year after the transition to ICD-10 to examine changes in prevalence rates and potential measurement issues in the Veterans Affairs (VA) health care system.

METHODS

We developed definitions for 34 chronic conditions using ICD-9 and ICD-10 codes and compared the prevalence rates of these conditions from FY2014 to 2016 in a 20% random sample (1.0 million) of all VA patients. In each year we estimated the total number of patients diagnosed with the conditions. We regressed each condition on an indicator of ICD-10 (versus ICD-9) measurement to obtain the odds ratio associated with ICD-10.

RESULTS

Condition prevalence estimates were similar for most conditions before and after ICD-10 transition. We found significant changes in a few exceptions. Alzheimer's disease and spinal cord injury had more than twice the odds of being measured with ICD-10 compared to ICD-9. HIV/AIDS had one-third the odds, and arthritis had half the odds of being measured with ICD-10. Alcohol dependence and tobacco/nicotine dependence had half the odds of being measured in ICD-10.

CONCLUSION

Many chronic condition rates were consistent from FY14-16, and there did not appear to be widespread undercoding of conditions after ICD-10 transition. It is unknown whether increased sensitivity or undercoding led to decreases in mental health conditions.