Alison Marquis

Electronic Medical Record Cancer Incidence over Six Years Comparing New Users of Glargine with New Users of NPH Insulin

Background Recent studies suggested that insulin glargine use could be associated with increased risk of cancer. We compared the incidence of cancer in new users of glargine versus new users of NPH in a longitudinal clinical cohort with diabetes for up to 6 years. Methods and Findings From all patients who had been regularly followed at Massachusetts General Hospital from 1/01/2005 to 12/31/2010, 3,680 patients who had a medication record for glargine or NPH usage were obtained from the electronic medical record (EMR). From those we selected 539 new glargine users (age: 60.1±13.6 years, BMI: 32.7±7.5 kg/m2) and 343 new NPH users (61.5±14.1 years, 32.7±8.3 kg/m2) who had no prevalent cancer during 19 months prior to glargine or NPH initiation. All incident cancer cases were ascertained from the EMR requiring at least 2 ICD-9 codes within a 2 month period. Insulin exposure time and cumulative dose were validated. The statistical analysis compared the rates of cancer in new glargine vs. new NPH users while on treatment, adjusted for the propensity to receive one or the other insulin. There were 26 and 28 new cancer cases in new glargine and new NPH users for 1559 and 1126 person-years follow-up, respectively. There were no differences in the propensity-adjusted clinical characteristics between groups. The adjusted hazard ratio for the cancer incidence comparing glargine vs. NPH use was 0.65 (95% CI: 0.36–1.19). Conclusions Insulin glargine is not associated with development of cancers when compared with NPH in this longitudinal and carefully retrieved EMR data.

Free and Bioavailable 25-Hydroxyvitamin D Concentrations are Associated With Disease Activity in Pediatric Patients With Newly Diagnosed Treatment Naïve Ulcerative Colitis

Background Vitamin D regulates intestinal epithelial and immune functions, and vitamin D receptor deficiency increases the severity of murine colitis. Bioavailable 25-hydroxyvitamin D (25(OH)D) is available to target tissues and may be a driver of immune function. The aim is to evaluate the relationship of bioavailable 25(OH)D to the clinical expression of treatment naive pediatric ulcerative colitis (UC). Methods The PROTECT (Predicting Response to Standardized Pediatric Colitis Therapy) study enrolled children ≤17 years newly diagnosed with UC. Free and total 25(OH)D were directly measured and 25(OH)D fractions were compared with disease activity measures. Results Data were available on 388 subjects, mean age 12.7 years, 49% female, 84% with extensive/pancolitis. The median (IQR) total 25(OH)D concentration was 28.5 (23.9, 34.8) ng/mL, and 57% of subjects demonstrated insufficient vitamin D status (25(OH)D < 30 ng/mL). We found no evidence of association between total 25(OH)D and disease activity. Regression models adjusted for age, sex, race, and ethnicity demonstrated that an increase from 25th to 75th percentile for bioavailable and free 25(OH)D were associated with a mean (95th CI) decrease in the Pediatric Ulcerative Colitis Activity Index (PUCAI) of -8.7 (-13.7, -3.6) and -3.1 (-5.0, -1.2), respectively. No associations were detected between 25(OH)D fractions and fecal calprotectin or Mayo endoscopy score. Conclusions Vitamin D insufficiency is highly prevalent in children with newly diagnosed UC. We found associations of free and bioavailable, but not total 25(OH)D, with PUCAI. Bioavailable vitamin D may contribute to UC pathophysiology and clinical activity.

Suboptimal Early Outcomes following Standardized Induction Therapy in Children Newly Diagnosed with Ulcerative Colitis: The Protect Study

Jeffrey S. Hyams , Sonia Davis, David R. Mack , Brendan Boyle, Anne M. Griffiths, Neal S. Leleiko, Cary G.Sauer, David J. Keljo, James Markowitz, Susan Baker, Joel Rosh, Robert N. Baldassano, Ashish Patel, Marian Pfefferkorn, Anthony Otley, Melvin Heyman, Joshua Noe, Maria OlivaHemker, Paul Rufo, Jennifer Strople, David Ziring, Stephen Guthery, Boris Sudel, Keith Benkov, Prateek Wali, Dedrick Moulton, Jonathan Evans, Michael Kappelman , Alison Marquis, Francisco A. Sylvester, Margaret H. Collins, Suresh Venkateswaran, Marla Dubinsky, Krista L. Spada, Ashley Britt, Bradley Saul, Nathan Gotman, Jose Serrano, Subra Kugathasan, Thomas Walters, Lee A. Denson