OBJECTIVE -Neonatal diabetes can result from mutations in the Kir6.2 or sulfonylurea receptor 1 (SUR1) subunits of the ATP-sensitive K ϩ channel. Transfer from insulin to oral sulfonylureas in patients with neonatal diabetes due to Kir6.2 mutations is well described, but less is known about changing therapy in patients with SUR1 mutations. We aimed to describe the response to sulfonylurea therapy in patients with SUR1 mutations and to compare it with Kir6.2 mutations.RESEARCH DESIGN AND METHODS -We followed 27 patients with SUR1 mutations for at least 2 months after attempted transfer to sulfonylureas. Information was collected on clinical features, treatment before and after transfer, and the transfer protocol used. We compared successful and unsuccessful transfer patients, glycemic control before and after transfer, and treatment requirements in patients with SUR1 and Kir6.2 mutations. RESULTS -Twenty-three patients (85%) successfully transferred onto sulfonylureas without significant side effects or increased hypoglycemia and did not need insulin injections. In these patients, median A1C fell from 7.2% (interquartile range 6.6 -8.2%) on insulin to 5.5% (5.3-6.2%) on sulfonylureas (P ϭ 0.01). When compared with Kir6.2 patients, SUR1 patients needed lower doses of both insulin before transfer (0.4 vs. 0.7 units ⅐ kg Ϫ1 ⅐ day Ϫ1 ; P ϭ 0.002) and sulfonylureas after transfer (0.26 vs. 0.45 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ; P ϭ 0.005).CONCLUSIONS -Oral sulfonylurea therapy is safe and effective in the short term in most patients with diabetes due to SUR1 mutations and may successfully replace treatment with insulin injections. A different treatment protocol needs to be developed for this group because they require lower doses of sulfonylureas than required by Kir6.2 patients.

BackgroundSerum phosphate is a known risk factor for cardiovascular events and mortality in people with chronic kidney disease (CKD), however data on the association of these outcomes with serum phosphate in the general population are scarce. We investigate this relationship in people with and without CKD in a large community-based population.MethodsThree groups from an adult cohort of the Quality Improvement in Chronic Kidney Disease (QICKD) cluster randomised trial (ISRCTN56023731) were followed over a period of 2.5 years: people with normal renal function (N = 24,184), people with CKD stages 1–2 (N = 20,356), and people with CKD stages 3–5 (N = 13,292). We used a multilevel logistic regression model to determine the association between serum phosphate, in these groups, and a composite outcome of all-cause mortality, cardiovascular events, and advanced coronary artery disease. We adjusted for known cardiovascular risk factors.FindingsHigher phosphate levels were found to correlate with increased cardiovascular risk. In people with normal renal function and CKD stages 1–2, Phosphate levels between 1.25 and 1.50 mmol/l were associated with increased cardiovascular events; odds ratio (OR) 1.36 (95% CI 1.06–1.74; p = 0.016) in people with normal renal function and OR 1.40 (95% CI 1.09–1.81; p = 0.010) in people with CKD stages 1–2. Hypophosphatemia (<0.75 mmol/l) was associated with fewer cardiovascular events in people with normal renal function; OR 0.59 (95% CI 0.36–0.97; p = 0.049). In people with CKD stages 3–5, hyperphosphatemia (>1.50 mmol/l) was associated with increased cardiovascular risk; OR 2.34 (95% CI 1.64–3.32; p<0.001). Other phosphate ranges were not found to have a significant impact on cardiovascular events in people with CKD stages 3–5.ConclusionsSerum phosphate is associated with cardiovascular events in people with and without CKD. Further research is required to determine the mechanisms underlying these associations.

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Background It has been proposed that changes in healthcare use before cancer diagnosis could signal opportunities for quicker detection, but systematic appreciation of such evidence is lacking. We reviewed studies examining pre-diagnostic changes in healthcare utilisation (e.g. rates of GP or hospital consultations, prescriptions or diagnostic tests) among patients subsequently diagnosed with cancer. Methods We identified studies through Pubmed searches complemented by expert elicitation. We extracted information on the earliest time point when diagnosis could have been possible for at least some cancers, together with variation in the length of such ‘diagnostic windows’ by tumour and patient characteristics. Results Across twenty-eight studies, changes in healthcare use were observable at least six months pre-diagnosis for many common cancers, and potentially even earlier for colorectal cancer, multiple myeloma and brain tumours. Early changes were also identified for brain and colon cancer sub-sites. Conclusion Changing healthcare utilisation patterns before diagnosis indicate that future improvements in diagnostic technologies or services could help to shorten diagnostic intervals for cancer. There is greatest potential for quicker diagnosis for certain cancer types and patient groups, which can inform priorities for the development of decision support tools.

Risk of Hodgkin's Lymphoma in allergic disease Hodgkin's Lymphoma Immune suppression Corticosteroids Eczema Asthma Allergic rhinitis 1.4 x 95%CI(1.2-1.6) p<0.001 6.1 x 95%CI(3.0-12.3) p<0.001 1.9 x 95%CI(1.3-2.7) P<0.001 1.1 x 95%CI(0.9-1.3) P=0.56 1.2 x 95%CI(1.0-1.5) P=0.016 1.4 x 95%CI(1.2-1.7) p<0.001 Infectious mononucleosis Background: Immunodeficiency syndromes (acquired/ congenital/iatrogenic) are known to increase Hodgkin lymphoma (HL) risk, but the effects of allergic immune dysregulation and corticosteroids are poorly understood. Objective: We sought to assess the risk of HL associated with allergic disease (asthma, eczema, and allergic rhinitis) and corticosteroid use. Methods: We conducted a case-control study using the United Kingdom Clinical Practice Research Datalink (CPRD) linked to hospital data. Multivariable logistic regression investigated associations between allergic diseases and HL after adjusting for established risk factors. Potential confounding or effect modification by steroid treatment were examined. Results: One thousand two hundred thirty-six patients with HL were matched to 7416 control subjects. Immunosuppression was associated with 6-fold greater odds of HL (adjusted odds ratio [aOR], 6.18; 95% CI, 3.04-12.57), with minimal change after adjusting for steroids. Any prior allergic disease or eczema alone was associated with 1.4-fold increased odds of HL (aOR, 1.