Enrollment of underrepresented racial and ethnic groups in the Rare and Atypical Diabetes Network (RADIANT).

Introduction: Diabetes mellitus in underrepresented racial and ethnic groups (URG) is rapidly increasing in incidence and has worse outcomes than diabetes in non-Hispanic White individuals. Rare and Atypical Diabetes Network (RADIANT) established recruitment targets based on the racial and ethnic distribution of the USA to enroll a diverse study population. We examined participation of URG across RADIANT study stages and described strategies to enhance recruitment and retention of URG. Materials and Methods: RADIANT is a multicenter NIH-funded study of people with uncharacterized forms of atypical diabetes. RADIANT participants consent online and progress through three sequential study stages, as eligible. Results: We enrolled 601 participants with mean age 44 ± 16.8 years, 64.4% female. At Stage 1, 80.6% were White, 7.2% African American (AA), 12.2% other/more than one race, and 8.4% Hispanic. Enrollment of URG was significantly below preset targets across most stages. Referral sources differed by race (p < 0.001) but not ethnicity (p = 0.15). Most AA participants were referred by RADIANT investigators (58.5% vs. 24.5% in Whites), whereas flyers, news, social media, and family or friends were more frequent referral sources for White individuals (26.4% vs. 12.2% in AA). Ongoing initiatives to increase enrollment of URG in RADIANT include engaging with clinics/hospitals serving URG, screening electronic medical records, and providing culturally competent study coordination and targeted advertisement. Conclusions: There is low participation of URG in RADIANT, potentially limiting the generalizability of its discoveries. Investigations into barriers and facilitators for recruitment and retention of URG in RADIANT, with implications for other studies, are ongoing.

Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders.

Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism.

Acute porphyrias in the USA: features of 108 subjects from porphyrias consortium.

BACKGROUND: Recent descriptions of the clinical and laboratory features of subjects with acute porphyrias in the US are lacking. Our aim was to describe clinical, biochemical, and genetic features of 108 subjects. METHODS: Between September 2010 and December 2012, 108 subjects with acute porphyrias (90 acute intermittent porphyrias, 9 hereditary coproporphyrias, 9 variegate porphyrias) were enrolled into an observational study. Genetic testing was performed at a central genetic testing laboratory and clinical information entered into a central database. Selected features were compared with data for adults in the US. RESULTS: Most subjects (88/108, 81%) were female, with self-reported onset of symptoms in the second through fourth decades of life. The most common symptom was abdominal pain. Appendectomies and cholecystectomies were common before a diagnosis of porphyria. The diagnosis was delayed by a mean of 15 years. Anxiety and depression were common, and 18% complained of chronic symptoms, especially neuropathic and other pains. The incidences of systemic arterial hypertension, chronic kidney disease, seizure disorders, and psychiatric conditions were markedly increased. Mutations of the known causative genes were found in 102/105 of those tested, with novel mutations being found in 37, including in 7/8 subjects with hereditary coproporphyria. Therapy with intravenous hematin was the most effective therapy both for treatment of acute attacks and for prevention of recurrent attacks. CONCLUSIONS: Acute porphyrias often remain undiagnosed for more than a decade after first symptoms develop. Intravenous hematin is the treatment of choice, both for treatment of acute attacks and for prevention of recurrent attacks.

Trends in the golden state: small-group premiums rise sharply while actuarial values for individual coverage plummet.

Using multiple databases, this paper examines recent trends in the affordability and comprehensiveness of small-group and individual health insurance markets in California. Both became less affordable over the study period. In 2006, a single person age 32-52 earning the median income who purchased individual insurance spent on average 16 percent of income on premiums and out-of-pocket medical expenses. For individual insurance, the share of medical expenses paid by insurance as opposed to patients declined from 2002 to 2006. In the small-group market, premiums rose more than 50 percent from 2003 to 2006, but the proportion of claims paid by insurers for a standardized population remained constant.

Financial protection afforded by employer-sponsored health insurance: current plan designs and high-deductible health plans.

This article provides the first national estimates of actuarial values and out-of-pocket spending from the era of nonrestrictive managed care that began in the late 1990s. Employer plans paid about 84 percent of total medical expense for those with employer-sponsored coverage in 2004, about 1 percent less than in 2000, and high users faced potential out of pocket spending in the thousands of dollars when they received a portion of their care out of network. Since 2004, more employers have offered plans with higher deductibles coupled with employer-funded personal accounts. These arrangements can result in low out of pocket costs for many employees, but high users will face substantially higher costs. Many employers adopting high-deductible plans are not contributing to personal accounts. Those who are concerned about higher out-of-pockets might consider income-related cost sharing, educational efforts to communicate the savings that can result from using in-network providers, and continued availability of managed care options that limit out-of-pocket spending.

Generosity and adjusted premiums in job-based insurance: Hawaii is up, Wyoming is down.

This paper reports national and state findings on the generosity or actuarial value of U.S. employer-based plans and adjusted premiums in 2002. The basis for our calculations is simulated bill paying for a large standardized population. After adjusting for the quality of benefits, we find from regression analysis that adjusted premiums are 18 percent higher in the nation's smallest firms than in firms with 1,000 or more workers. They are 25 percent higher in indemnity plans and 18 percent higher in preferred provider organizations than in health maintenance organizations. The generosity of coverage increased from 1997 to 2002.