The Autism - Tics, AD/HD and other Comorbidities inventory (A-TAC): further validation of a telephone interview for epidemiological research

<p>Abstract</p> <p>Background</p> <p>Reliable, valid, and easy-to-administer instruments to identify possible caseness and to provide proxies for clinical diagnoses are needed in epidemiological research on child and adolescent mental health.</p> <p>The aim of this study is to provide further validity data for a parent telephone interview focused on Autism - Tics, Attention-deficit/hyperactivity disorder (AD/HD), and other Comorbidities (A-TAC), for which reliability and preliminary validation data have been previously reported.</p> <p>Methods</p> <p>Parents of 91 children clinically diagnosed at a specialized Child Neuropsychiatric Clinic, 366 control children and 319 children for whom clinical diagnoses had been previously assigned were interviewed by the A-TAC over the phone. Interviewers were blind to clinical information. Different scores from the A-TAC were compared to the diagnostic outcome.</p> <p>Results</p> <p>Areas under ROC curves for interview scores as predictors of clinical diagnoses were around 0.95 for most disorders, including autism spectrum disorders (ASDs), attention deficit/hyperactivity disorder (AD/HD), tic disorders, developmental coordination disorders (DCD) and learning disorders, indicating excellent screening properties. Screening cut-off scores with sensitivities above 0.90 (0.95 for ASD and AD/HD) were established for most conditions, as well as cut-off scores to identify proxies to clinical diagnoses with specificities above 0.90 (0.95 for ASD and AD/HD).</p> <p>Conclusions</p> <p>The previously reported validity of the A-TAC was supported by this larger replication study using broader scales from the A-TAC-items and a larger number of diagnostic categories. Short versions of algorithms worked as well as larger. Different cut-off levels for screening versus identifying proxies for clinical diagnoses are warranted. Data on the validity for mood problems and oppositional defiant/conduct problems are still lacking. Although the A-TAC is principally intended for epidemiological research and general investigations, the instrument may be useful as a tool to collect information in clinical practice as well.</p

Geography of non-melanoma skin cancer and ecological associations with environmental risk factors in England.

This is the author's peer reviewed version of the article. Please cite the published, final version which is available via the DOI link in this record.This study investigates the geography of non-melanoma skin cancer (NMSC) in England, and ecological associations with three widespread environmental hazards: radon, arsenic and ultraviolet radiation from the sun.European Regional Development FundEuropean Social Fund Convergence Programme for Cornwall and the Isles of Scill

Convergence Without Hard Criteria: Does EU Soft Law Affect Domestic Unemployment Protection Schemes?

(VLID)177126

Skin Cancer:Epidemiology, Disease Burden, Pathophysiology, Diagnosis, and Therapeutic Approaches

Skin cancer, including both melanoma and non-melanoma, is the most common type of malignancy in the Caucasian population. Firstly, we review the evidence for the observed increase in the incidence of skin cancer over recent decades, and investigate whether this is a true increase or an artefact of greater screening and over-diagnosis. Prevention strategies are also discussed. Secondly, we discuss the complexities and challenges encountered when diagnosing and developing treatment strategies for skin cancer. Key case studies are presented that highlight the practic challenges of choosing the most appropriate treatment for patients with skin cancer. Thirdly, we consider the potential risks and benefits of increased sun exposure. However, this is discussed in terms of the possibility that the avoidance of sun exposure in order to reduce the risk of skin cancer may be less important than the reduction in all-cause mortality as a result of the potential benefits of increased exposure to the sun. Finally, we consider common questions on human papillomavirus infection

Upregulation of Cellular Bcl-2 by the KSHV Encoded RTA Promotes Virion Production

Apoptosis of virus infected cells can restrict or dampen full blown virus propagation and this can serve as a protective mechanism against virus infection. Consequently, viruses can also delay programmed cell death by enhancing the expression of anti-apoptotic proteins. Human Bcl-2 is expressed on the surface of the mitochondrial membrane and functions as the regulator of the delicate balance between cell survival and apoptosis. In this report, we showed that the replication and transcription activator (RTA) encoded by KSHV ORF 50, a key regulator for KSHV reactivation from latent to lytic infection, upregulates the mRNA and protein levels of Bcl-2 in 293 cells, and TPA-induced KSHV-infected cells. Further analysis revealed that upregulation of the cellular Bcl-2 promoter by RTA is dose-dependent and acts through targeting of the CCN9GG motifs within the Bcl-2 promoter. The Bcl-2 P2 but not the P1 promoter is primarily responsive to RTA. The results of ChIP confirmed the direct interaction of RTA protein with the CCN9GG motifs. Knockdown of cellular Bcl-2 by lentivirus-delivered small hairpin RNA (shRNA) resulted in increased cell apoptosis and decreased virion production in KSHV-infected cells. These findings provide an insight into another mechanism by which KSHV utilizes the intrinsic apoptosis signaling pathways for prolonging the survival of lytically infected host cells to allow for maximum production of virus progeny

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Low glycaemic index diet and disposition index in type 2 diabetes (the Canadian trial of carbohydrates in diabetes): a randomised controlled trial

AIMS/HYPOTHESIS: We recently found that oral glucose tolerance over 1 year in type 2 diabetic patients declined to a significantly lesser degree on a low-glycaemic-index than on a reduced-carbohydrate diet. Here, we examined whether that finding was associated with an improvement in disposition index, an index of beta cell function defined as the product of insulin sensitivity and insulin secretion. Since this is a report of secondary analysis on a previously published trial, the results should be considered as hypothesis-generating. METHODS: Type 2 diabetic patients treated by diet alone (n = 162) were randomised by computer to high-carbohydrate/high-glycaemic index (High-GI, n = 52), high-carbohydrate/low-glycaemic index (Low-GI, n = 56) or low-carbohydrate/high-monounsaturated-fat (Low-CHO, n = 54) diets for 1 year in a multi-centre, parallel-design clinical trial conducted at University teaching hospitals. At baseline and at 3, 6 and 12 months participants underwent 75 g OGTTs; 27 participants dropped out or were excluded. Indices of insulin sensitivity, insulin secretion and disposition index, derived from the OGTT, were compared among diets. Those assessing the outcomes were blinded to group assignment. RESULTS: Neither muscle insulin sensitivity index nor insulinogenic index differed significantly among diets. However, a significant time x diet interaction existed for disposition index (muscle insulin sensitivity index x insulinogenic index) (p = 0.036). After 3 months, disposition index tended to be higher on Low-CHO than on Low-GI diets, namely by 0.07 h(-1) (95% CI -0.04, 0.18). However, by 12 months this reversed and disposition index became higher on Low-GI than on Low-CHO, namely by 0.12 h(-1) (0.01, 0.23; p < 0.05, baseline disposition index 0.23 h(-1)). There were no important adverse effects associated with the treatments. CONCLUSIONS/INTERPRETATION: These results suggest that, in patients with type 2 diabetes on diet alone, a Low-GI diet for 1 year increases disposition index, an index of beta cell function, compared with a Low-CHO diet.Clinical Research: Long term effect of altering the source and amount of dietary carbohydrate in type 2 diabetesCIHRMCT-4420

The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low-glycemic-index dietary carbohydrate in type 2 diabetes: no effect on glycated hemoglobin but reduction in C-reactive protein

BACKGROUND: The optimal source and amount of dietary carbohydrate for managing type 2 diabetes (T2DM) are unknown. OBJECTIVE: We aimed to compare the effects of altering the glycemic index or the amount of carbohydrate on glycated hemoglobin (HbA1c), plasma glucose, lipids, and C-reactive protein (CRP) in T2DM patients. DESIGN: Subjects with T2DM managed by diet alone (n=162) were randomly assigned to receive high-carbohydrate, high-glycemic-index (high-GI), high-carbohydrate, low-glycemic-index (low-GI), or low-carbohydrate, high-monounsaturated-fat (low-CHO) diets for 1 y. RESULTS: The high-GI, low-GI, and low-CHO diets contained, respectively, 47%, 52%, and 39% of energy as carbohydrate and 31%, 27%, and 40% of energy as fat; they had GIs of 63, 55, and 59, respectively. Body weight and HbA1c did not differ significantly between diets. Fasting glucose was higher (P=0.041), but 2-h postload glucose was lower (P=0.010) after 12 mo of the low-GI diet. With the low-GI diet, overall mean triacylglycerol was 12% higher and HDL cholesterol 4% lower than with the low-CHO diet (P<0.05), but the difference in the ratio of total to HDL cholesterol disappeared by 6 mo (time x diet interaction, P=0.044). Overall mean CRP with the low-GI diet, 1.95 mg/L, was 30% less than that with the high-GI diet, 2.75 mg/L (P=0.0078); the concentration with the low-CHO diet, 2.35 mg/L, was intermediate. CONCLUSIONS: In subjects with T2DM managed by diet alone with optimal glycemic control, long-term HbA1c was not affected by altering the GI or the amount of dietary carbohydrate. Differences in total:HDL cholesterol among diets had disappeared by 6 mo. However, because of sustained reductions in postprandial glucose and CRP, a low-GI diet may be preferred for the dietary management of T2DM.Clinical Study: Long term effect of altering the source and amount od dietary carohydrate in type 2 diabetesCIHRMCT-4420