Biochemical and Radiological Changes in Liver Steatosis Following Mifepristone Treatment in Patients With Hypercortisolism.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western industrialized countries and may progress to liver injury. Cortisol is thought to play a role in the pathogenesis of NAFLD, and cortisol modulation has shown efficacy in preclinical models. However, published reports on the clinical effects of glucocorticoid receptor antagonism in these patients are limited. CASE REPORT: Two women (aged 66 and 60 years) with endogenous hypercortisolism presented with a history of hepatic steatosis, hypertension, type 2 diabetes mellitus, and dyslipidemia. Both patients declined adrenalectomy or pituitary tumor surgery, and treatment with mifepristone 300 mg daily was initiated. During mifepristone treatment (follow up durations ranging from 10 months to 5 years), improvements in hypercortisolism-related cardiometabolic abnormalities were observed, including the normalization of lipid levels and improvement of hyperglycemia. In both cases, findings on follow-up imaging revealed resolution of fatty liver, which was supported by a decrease in liver enzymes on liver function tests. No adverse events were reported. DISCUSSION: NAFLD is frequently observed in patients with endogenous hypercortisolism. Improvement in liver function tests has previously been demonstrated in patients with hypercortisolism treated with mifepristone. The present cases showed, for the first time, radiological improvement of liver steatosis following mifepristone use in patients with hypercortisolism and NAFLD. CONCLUSION: This case series demonstrated improvements in biochemical and imaging parameters of NAFLD in patients with hypercortisolism treated with mifepristone. Further research is needed to investigate the effects of glucocorticoid receptor modulation in fatty liver disease.

Infrared Spectroscopic Analysis of the Adsorption of Pyridine Carboxylic Acids on Colloidal Ceria.

Surface adsorption of a homologous series of pyridine carboxylic acids on a hydrated colloidal cerium dioxide (ceria) film is characterized using the combination of experimental and computationally determined infrared (IR) spectra. Experimental analyses employ attenuated total reflectance (ATR) IR spectroscopy of deposited colloidal ceria thin films equilibrated with three pyridine carboxylic acids at pH 3.0, 5.5, and 8.5. The corresponding computational IR spectra for the energy-minimized intermediate and base forms of the pyridine carboxylic acids use density functional theory calculations at the B3LYP/6-311++G** level of theory. Solvent effects are modeled using both the COSMO implicit solvation model and the inclusion of explicit water molecules. Experimental IR spectra show that the adsorptive interactions between the pyridine carboxylic acids and ceria surface are due to the outer-sphere coordination of cerium ions in the films. Vibrational assignments based on combined experimental and computational results indicate that both pyridyl ring nitrogen and carboxylate functional groups account for the interaction of pyridine carboxylic acids at ceria surfaces. Experimentally determined Langmuir constants point to the intermediate form of picolinic acid (pyridine-2-carboxylic acid) as having the strongest adsorption to ceria compared to the other pyridine carboxylic acids investigated. The enhanced adsorption of picolinic acid is attributed to the adjacency of the protonated pyridyl nitrogen and the carboxylate group relative to nicotinic acid (pyridine-3-carboxylic acid) and isonicotinic acid (pyridine-4-carboxylic acid).

Value-based insurance design program in north Carolina increased medication adherence but was not cost neutral.

Value-based insurance design (VBID) has shown promise for improving medication adherence by lowering or eliminating patients' payments for some medications. Yet the business case for VBID remains unclear. VBID is based on the premise that higher medication and administrative expenses incurred by insurers will be offset by lower nonmedication expenditures that result from better disease control. This article examines Blue Cross Blue Shield of North Carolina's VBID program, which began in 2008. The program eliminated copayments for generic medications and reduced copays for brand-name medications. Patient adherence improved 2.7-3.4 percent during the two-year study period. Hospital admissions decreased modestly, but there were no significant changes in emergency department use or total health expenditures. The insurer incurred $6.4 million in higher medication expenditures; total nonmedication expenditures for the study population decreased $5.7 million. Our results provide limited support for the idea that VBID can be cost-neutral in specific subpopulations. The business case for VBID may be more compelling over the long term and in high risk subgroups for whose members cost is an important barrier to improved medication adherence.

Medication adherence changes following value-based insurance design.

OBJECTIVES: To determine whether participation in a value-based insurance design (VBID) program was associated with improved medication adherence in 8 drug classes 2 years after implementation and to examine whether adherence changes varied by baseline adherence. STUDY DESIGN: We used a pre-post quasi-experimental study design with a retrospective cohort of 74,748 enrollees using 8 different therapeutic classes of medications to treat diabetes, hypertension, hyperlipidemia, or congestive heart failure. METHODS: Brand-name medication copayments were lowered (from tier 3 to tier 2) for all enrollees, while generic copayments were waived only for employers who opted into the VBID program. Medication adherence of VBID program participants and nonparticipants 12 months before and 12 and 24 months after program implementation were estimated on 8 propensity-matched cohorts using generalized estimating equations, as well as on subgroups stratified by baseline adherence. Adherence was measured using the medication possession ratio (MPR) from medication refill records. RESULTS: VBID was associated with improved medication adherence ranging from 1.4% to 3.2% at 1 year, which increased to 2.1% to 5.2% 2 years following VBID adoption. Adherence changes were most notable among patients who were nonadherent (MPR <.50) before VBID implementation. CONCLUSIONS: Population-based implementation of VBID can improve adherence to medications to treat cardiometabolic conditions, particularly for previously nonadherent patients. VBID guidelines being developed in response to healthcare reform should account for the heterogeneity in patient response to VBID programs.

Micropapillary thyroid carcinoma and concomitant ectopic thyroid tissue in the adrenal gland: metastasis or metaplasia?

BACKGROUND: Ectopic thyroid tissue is a rare finding but has been reported in many thoracic and abdominal locations. It is usually an incidental pathologic finding after an unrelated surgical intervention. When thyroid tissue is found outside the thyroid bed, it is important to rule out thyroid cancer metastasis. PATIENT FINDINGS: We present a case of a 61-year-old African American woman who was incidentally found to have concomitant ectopic thyroid tissue in the adrenal gland and a papillary thyroid microcarcinoma (PTMC) in the right lobe of the thyroid. SUMMARY: The concurrent finding of ectopic thyroid tissue and PTMC posed the diagnostic dilemma of whether the extrathyroidal tissue was metastasis or metaplasia, with very different treatment implications. Although many of these incidental micropapillary cancers are indolent, some patients do experience local or distant metastasis. Therefore, it is important to delineate which of these microtumors are likely to metastasize. Some tumor markers and gene mutations have been proposed to help differentiate the more benign tumors from the more aggressive tumors, but there is currently no standard method for determination of metastatic potential. CONCLUSIONS: Here we present the seventh known case of ectopic thyroid tissue in the adrenal gland and the first case of concomitant incidental PTMC in the setting of this ectopic tissue finding. Using this case, we discuss the diagnostic and therapeutic challenges faced and propose the use of biomarkers to help determine the metastatic potential of these tumors.

Risk factors for pathological gambling.

To better understand pathological gambling, potential risk factors were assessed within three domains--gambling behaviors, substance abuse and other problem behaviors, and sociodemographic factors. A random-digit-dial telephone survey was conducted in 1999-2000 with a representative sample of the U.S. population aged 18 or older. The current analyses uses data from the 2168 respondents who gambled in the year before the interview. Gambling measures included the Diagnostic Interview Schedule (DIS)-IV for pathological gambling, frequency of 15 types of gambling, and size of win or loss on the last occasion. Other measures included the quantity and frequency of alcohol consumption, frequency of illicit drug use and criminal offending, and the DIS-IV for alcohol and drug abuse and dependence. Results showed that casino gambling is associated with a high risk of gambling pathology. Lottery, cards, and bingo are associated with a moderately high risk of gambling pathology. Participation in a greater number of types of gambling is strongly predictive of gambling pathology, even after frequency of gambling and size of win or loss are taken into account. Alcohol abuse is strongly predictive of gambling pathology, even with gambling behaviors held constant. Minority and low socioeconomic status (SES) group members have higher levels of gambling pathology than other groups after all other factors are considered.

Ancillary services in the health care industry: is Six Sigma reasonable?

Within the naval medical center construct, the disparate disciplines encompassed within ancillary services lend themselves to formal quality analysis and process improvement. This analysis uses the Six Sigma approach. Error rates were investigated and calculated for various processes within ancillary services at Naval Medical Center, San Diego. These were translated into the common metric of defects per million opportunities (DPMO). DPMO rates vary between 21.5 and 420,000. These correspond to Sigma values from 1.7 to approaching 6. Rates vary with biological complexity of the system and the degree of automation available. Some ancillary services translate well into a Six Sigma schema. Systems with high potential patient risk if performed poorly and those amenable to second checking and computer oversight may be candidates for such optimization. This should be undertaken in a local environment conducive to individual error reporting, and in a corporate environment with the will and funding to support the transition.