Individual and county-level factors associated with use of multiple prescribers and multiple pharmacies to obtain opioid prescriptions in California.

Use of multiple prescribers and pharmacies is a means by which some individuals misuse opioids. Community characteristics may be important determinants of the likelihood of this phenomenon independent of individual-level factors. This was a retrospective cohort study with individual-level data derived from Californias statewide prescription drug monitoring program (PDMP) and county-level socioeconomic status (SES) data derived from the United States Census. Zero-truncated negative binomial (ZTNB) regression was used to model the association of individual factors (age, gender, drug schedule and drug dose type) and county SES factors (ethnicity, adult educational attainment, median household income, and physician availability) with the number of prescribers and the number of pharmacies that an individual used during a single year (2006). The incidence rates of new prescriber use and new pharmacy use for opioid prescriptions declined across increasing age groups. Males had a lower incidence rate of new prescriber use and new pharmacy use than females. The total number of licensed physicians and surgeons in a county was positively, linearly, and independently associated with the number of prescribers and pharmacies that individuals used for prescription opioids. In summary, younger age, female gender, and living in counties with more licensed physicians and surgeons were associated with use of more prescribers and/or more pharmacies for obtaining prescription opioids

A Spline-Based Lack-of-Fit Test for Independent Variable Effect

In regression analysis of count data, independent variables are often modeled by their linear effects under the assumption of log-linearity. In reality, the validity of such an assumption is rarely tested, and its use is at times unjustifiable. A lack-of-fit test is proposed for the adequacy of a postulated functional form of an independent variable within the framework of semiparametric Poisson regression models based on penalized splines. It offers added flexibility in accommodating the potentially non-loglinear effect of the independent variable. A likelihood ratio test is constructed for the adequacy of the postulated parametric form, for example log-linearity, of the independent variable effect. Simulations indicate that the proposed model performs well, and misspecified parametric model has much reduced power. An example is given

A Linear \u3cem\u3eB\u3c/em\u3e-Spline Threshold Dose-Response Model with Dose-Specific Response Variation Applied to Developmental Toxicity Studies

A linear B-spline function was modified to model dose-specific response variation in developmental toxicity studies. In this new model, response variation is assumed to differ across dose groups. The model was applied to a developmental toxicity study and proved to be significant over the previous model of singular response variation

Topical clobetasol for the treatment of toxic epidermal necrolysis: study protocol for a randomized controlled trial.

BackgroundToxic epidermal necrolysis (TEN) is a rare systemic allergic drug eruption with high patient mortality. Currently, no established treatments have been shown to be effective for TEN beyond supportive care. Prior studies of systemic corticosteroids have yielded conflicting data, with some showing a possible benefit and others reporting in increased mortality. However, topical steroids have shown promise for treatment of ocular sequelae of TEN, such as scarring and vision loss. We have designed a randomized controlled trial to evaluate topical clobetasol for treatment of the epidermal manifestations of TEN. In addition, we propose genetic studies to characterize the TEN transcriptome and alterations in cutaneous gene expression that might occur following topical steroid treatment.Methods/designThis split-body randomized, double-blind, placebo-controlled Phase IIa proof-of-concept trial will evaluate the safety and efficacy of once-daily topical clobetasol applied to the skin of patients with TEN. This multicenter trial will recruit a total of 15 patients between the ages of 12 and 85 from the University of California Davis Medical Center and Shriners Hospital for Children inpatient burn units. Designated treatment areas on opposite sides of the body will be treated with blinded clobetasol 0.05% ointment or control petrolatum ointment daily for 14 days. On day 3 of therapy, a biopsy will be taken from the treated area for genetic studies. The primary study aims will be to establish the safety of topical clobetasol treatment and determine the time to cessation of skin detachment for the control and clobetasol-treated areas. Secondary endpoints will evaluate efficacy using parameters such as time to 90% re-epithelialization and percentage of affected skin at 0, 3, 6, 9, 12 and 15 days. Genomic DNA and RNA will be obtained from biopsy samples, to characterize the TEN transcriptome and identify changes in gene expression after topical steroid treatment.DiscussionTopical steroids have shown promise for treating ocular complications of TEN, but to date have not been evaluated for cutaneous manifestations of the disease. This trial will investigate clinical and molecular outcomes of topical clobetasol application and hopefully provide insight into the disease pathophysiology.Trial registrationClinicalTrials.gov NCT02319616. https://clinicaltrials.gov/ct2/show/NCT02351037