GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) is a 36-center unmasked, parallel treatment group, randomized controlled trial evaluating four diabetes medications added to metformin in people with type 2 diabetes (T2DM). We report baseline characteristics and compare GRADE participants to a National Health and Nutrition Examination Survey (NHANES) cohort. RESEARCH DESIGN AND METHODS Participants were age ‡30 years at the time of diagnosis, with duration of T2DM <10 years, HbA 1c 6.8-8.5% (51-69 mmol/mol), prescribed metformin monotherapy, and randomized to glimepiride, sitagliptin, liraglutide, or insulin glargine. RESULTS At baseline, GRADE's 5,047 randomized participants were 57.2 6 10.0 years of age, 63.6% male, with racial/ethnic breakdown of 65.7% white, 19.8% African American, 3.6% Asian, 2.7% Native American, 7.6% other or unknown, and 18.4% Hispanic/ Latino. Duration of diabetes was 4.2 6 2.8 years, with mean HbA 1c of 7.5 6 0.5% (58 6 5.3 mmol/mol), BMI of 34.3 6 6.8 kg/m 2 , and metformin dose of 1,944 6 204 mg/day. Among the cohort, 67% reported a history of hypertension, 72% a history of hyperlipidemia, and 6.5% a history of heart attack or stroke. Applying GRADE inclusion criteria to NHANES indicates enrollment of a representative cohort with T2DM on metformin monotherapy (NHANES cohort average age, 57.9 years; mean HbA 1c , 7.4% [57 mmol/mol]; BMI, 33.2 kg/m 2 ; duration, 4.2 6 2.5 years; and 7.2% with a history of cardiovascular disease). CONCLUSIONS The GRADE cohort represents patients with T2DM treated with metformin requiring a second diabetes medication. GRADE will inform decisions about the clinical effectiveness of the addition of four classes of diabetes medications to metformin. The optimal medication management of hyperglycemia in type 2 diabetes (T2DM) is not established. In addition to lifestyle intervention, metformin is the recommended initial medication in T2DM due to its glycemic effectiveness, lack of associated hypoglycemia or weight gain, low cost, and evidence of long-term benefit and safety

BackgroundHigher 25(OH)D3 levels are associated with lower HbA1c, but there are limited UK interventional trials assessing the effect of cholecalciferol on HbA1c.Aims(1) To assess the baseline 25(OH)D3 status in a Manchester cohort of children with type 1 diabetes (T1D). (2) To determine the effect of cholecalciferol administration on HbA1c.MethodsChildren with T1D attending routine clinic appointments over three months in late winter/early spring had blood samples taken with consent. Participants with a 25(OH)D3 level <50 nmol/L were treated with a one-off cholecalciferol dose of 100,000 (2–10 years) or 160,000 (>10 years) units. HbA1c levels before and after treatment were recorded.ResultsVitamin D levels were obtained from 51 children. 35 were Caucasian, 11 South Asian and 5 from other ethnic groups. 42 were vitamin D deficient, but 2 were excluded from the analysis. All South Asian children were vitamin D deficient, with mean 25(OH)D3 of 28 nmol/L. In Caucasians, there was a negative relationship between baseline 25(OH)D3 level and HbA1c (r = −0.484, P < 0.01). In treated participants, there was no significant difference in mean HbA1c at 3 months (t = 1.010, P = 0.328) or at 1 year (t = −1.173, P = 0.248) before and after treatment. One-way ANCOVA, controlling for age, gender, ethnicity, BMI and diabetes duration showed no difference in Δ HbA1c level.ConclusionWe report important findings at baseline, but in children treated with a stat dose of cholecalciferol, there was no effect on HbA1c. Further studies with larger sample sizes and using maintenance therapy are required.

Background: Despite availability of rapid fungal potassium hydroxide (KOH) tests, many care providers rely on visual assessment to determine the diagnosis of monilial diaper dermatitis (MDD). Purpose: To determine whether a KOH test, when MDD is suspected, would result in more accurate diagnoses, with decreased antifungal medication prescription and exposure. Methods: Quality improvement project from 2016 through 2017 with protocol implemented in 2017 for treatment of MDD after positive KOH testing. If monilial rash suspected, after 2 negative KOH tests, then antifungal ordered (considered false negative). χ2 testing and cost determination were performed. Sample: Neonates in 2 level III neonatal intensive care units. Outcome Variables: KOH test results, use of antifungal medication, and cost. Results: The patient census included 1051 and 1015 patients in the year before and after the protocol initiation. The medical orders for antifungal medication decreased from 143 to 36 (P < .001; 95% odds ratio confidence interval, 2.24-4.38). There was a 75% reduction in both use and cost, as charged, of antifungal agents. Overall charges, including KOH test costs, decreased by 12%. Three infants received multiple negative KOH tests, then a positive one. These met the definition of false-negative tests, per protocol. There were no cases of fungal sepsis. Implications for Practice: Use of a quality improvement protocol, in which the use of KOH testing is required, before antifungal agents are prescribed, results in decreased exposure and costs. Implications for Research: To test the feasibility of bedside “point-of-care” KOH testing, and whether KOH testing and reduced antifungal medication use affects antimicrobial resistance or invasive fungal sepsis.

BackgroundIntensive glycaemic control in type one diabetes (T1D) reduces progression of complications (DCCT and EDIC). In clinical practice, glycosylated haemoglobin (Hba1c) levels reflect control. Previous studies show that higher 25(OH)D3 levels are associated with lower Hba1c (US SEARCH study). However, there are limited interventional trials assessing the effect of cholecalciferol on Hba1c. Aims. 1. To assess the baseline 25(OH)D3 status in a paediatric cohort of patients with T1D. 2. To determine the effect of cholecalciferol administration on Hba1c.MethodsChildren with T1D attending routine clinic appointments from February to April 2011 had blood samples taken with consent, and patients with a 25(OH)D3 level <20ng/ml were treated with a one-off stat cholecalciferol dose of 100 000 (2–10 years) or 160 000 (>10 years) units. Hba1c levels from the year preceding treatment and the year after treatment were recorded.ResultsVitamin D levels were obtained from 51 patients (30 male, 21 female). 35 were Caucasian, 11 South Asian and 5 from other ethnic groups. 42 subjects were vitamin D deficient, but 2 were excluded from the analysis (one moved away, one was non-compliant). All South Asian patients were vitamin D deficient, with mean 25(OH)D3 of 11.2 ng/ml. In Caucasians, there was a negative relationship between baseline 25(OH)D3 level and HbA1C (r= –0.484, p < 0.01), but not in South Asians. In treated patients, paired t tests showed no significant difference in mean Hba1c at 3 months (t=1.010, p 0.328) or at 1 year (t=-1.173, p = 0.248) before and after treatment. One way ANCOVA, controlling for age, gender, ethnicity, BMI and diabetes duration showed no difference in change in Hba1c level between those treated and not treated, at 3m and at 1 year before and after treatment.ConclusionWe confirmed a high prevalence of vitamin D deficiency in this clinic cohort of children with T1D, and found a negative relationship between baseline 25(OH)D3 level and HbA1C in Caucasians. However, in patients treated with a stat dose of cholecalciferol there was no effect on Hba1c. Further studies with larger sample sizes, and using maintenance 25(OH)D3 therapy rather than stat therapy are required.