SGLT inhibitors in management of diabetes

The two main sodium-glucose cotransporters (SGLTs), SGLT1 and SGLT2, provide new therapeutic targets to reduce hyperglycaemia in patients with diabetes. SGLT1 enables the small intestine to absorb glucose and contributes to the reabsorption of glucose filtered by the kidney. SGLT2 is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors with varying specificities for these transporters (eg, dapagliflozin, canagliflozin, and empagliflozin) can slow the rate of intestinal glucose absorption and increase the renal elimination of glucose into the urine. Results of randomised clinical trials have shown the blood glucose-lowering efficacy of SGLT inhibitors in type 2 diabetes when administered as monotherapy or in addition to other glucose-lowering therapies including insulin. Increased renal glucose elimination also assists weight loss and could help to reduce blood pressure. Effective SGLT2 inhibition needs adequate glomerular filtration and might increase risk of urinary tract and genital infection, and excessive inhibition of SGLT1 can cause gastro-intestinal symptoms. However, the insulin-independent mechanism of action of SGLT inhibitors seems to offer durable glucose-lowering efficacy with low risk of clinically significant hypoglycaemia at any stage in the natural history of type 2 diabetes. SGLT inhibition might also be considered in conjunction with insulin therapy in type 1 diabetes. © 2013 Elsevier Ltd.

Increased risk of diabetes mellitus among persons with psychotic symptoms:results from the WHO World Health Survey

OBJECTIVE: To analyze with a symptom-based approach the relationship between psychosis and diabetes mellitus in the general population. METHOD: Nationally representative samples from the World Health Organization (WHO) World Health Survey, totaling 224,743 randomly selected adults 18 years and older from 52 countries worldwide, were interviewed to establish the presence of psychotic symptoms and diabetes mellitus. Presence of psychotic symptoms was established using questions pertaining to positive symptoms from the psychosis screening module of the Composite International Diagnostic Interview. Presence of diabetes was established with a response of "yes" to the question, "Have you ever been diagnosed with diabetes (high blood sugar)?" The World Health Survey was conducted between 2002 and 2004. RESULTS: An increasing number of psychotic symptoms was related to increasing likelihood of diabetes mellitus (OR = 1.27; 95% CI, 1.24-1.30). As compared to no symptoms, at least 1 psychotic symptom substantially elevated the risk (OR = 1.71; 95% CI, 1.61-1.81). In people with a lifetime diagnosis of schizophrenia or psychosis, the prevalence of diabetes was higher in those with current psychotic symptoms (7.3% vs 5.2%; OR = 1.65; 95% CI, 1.21-2.26), suggesting that the persistence of symptoms over time could play a central role. After controlling for different potential confounders, there was a clear increase in the probability of having diabetes as the number of psychotic symptoms increased. The relationship between psychotic symptoms and diabetes was tested with multiple mediation models and path analyses for categorical outcomes. Only body mass index appeared as a relevant mediator in a model with a good fit (ie, χ21 = 3.2, P = .0742; comparative fit index = 0.999). CONCLUSIONS: Psychotic symptoms are related to increased rates of diabetes mellitus in nonclinical samples, independent of several potential confounders-including a clinical diagnosis of psychosis or schizophrenia, previous antipsychotic treatment, depression, lifestyle, and individual or country socioeconomic status. The findings highlight the worldwide relevance of the problem and the importance of identifying the specific paths of this association.

The epidemiology of prostate cancer among multiethnic men

The research goal was to document differences in the epidemiology of prostate cancer among multicultural men [non-Hispanic White (NHW), Hispanic (H), non-Hispanic Black (NHB)], and Black subgroups, particularly among NHB subgroups [US-born (USB) and Caribbean-born (CBB)]. Study findings will be useful in supporting further research into Black subgroups. Aim 1 explored changes over time in reported prostate cancer prevalence, by race/ethnicity and by birthplace (within the Black subgroups). Aim 2 investigated relationships between observed and latent variables. The analytical approaches included confirmatory factor analysis (CFA for measurement models) and structural equation modeling (SEM for regression models). National Center for Health Statistics, National Health Interview Survey (NHIS) data from 1999–2008 were used. The study sample included men aged 18 and older, grouped by race/ethnicity. Among the CBB group, survey respondents were limited to the English-speaking Caribbean. Prostate cancer prevalence, by race showed a higher trend among NHB men than NHW men overall, however differences over time were not significant. CBB men reported a higher proportion of prostate cancer among cancers diagnosed than USB men overall. Due to small sample sizes, stable prostate cancer prevalence trends could not be assessed over time nor could trends in the receipt of a PSA exam among NHB men when stratified by birthplace. USB and CBB men differ significantly in their screening behavior. The effect of SES on PSA screening adjusted for risk factors was statistically significant while latent variable lifestyle was not. Among risk factors, family history of cancer exhibited a consistent positive effect on PSA screening for both USB and CBB men. Among the CBB men, the number of years lived in the US did not significantly affect PSA screening behavior. When NHB men are stratified by birthplace, CBB men had a higher overall prevalence of prostate cancer diagnoses than USB men although not statistically significant. USB men were 2 to 3 times more likely to have had a PSA exam compared to CBB men, but among CBB men birthplace did not make a significant difference in screening behavior. Latent variable SES, but not lifestyle, significantly affected the likelihood of a PSA exam.

Epidemiology of medication discrepancies upon hospital admission in children - a systematic review

Objectives: NICE/NPSA excluded children under 16 from their guidance concerning medicines reconciliation (MR) upon admission.1 Our aims and objectives of conducting the literature review was to identify the epidemiology of medication discrepancies upon admission, transfer and discharge in children, and if they require MR. Method: Six bibliographical databases (Medline, Embase, CINAHL, International Pharmaceutical Abstracts, Web of Science and Biosis Previews) and selected key words were used to find epidemiological studies on medication discrepancies in children upon hospital admission, transfer and discharge (key words included ‘medication discrepancy’; ‘medication reconciliation’; ‘hospital admission’; ‘hospital discharge’; ‘hospital transfer’); studies where the data for children could be extracted were included. Results: From the 1239 articles found (in May 2011), eight of the articles had extractable paediatric information, (five from Canada, two from USA, one from UK). Five of the studies involved discrepancies on admission, one involved discrepancies on admission and transfer, one involved discrepancies at transfer and one considered discharge. The reference point used to compare against the admission, transfer and the discharge order differed in each of the studies. Four studies used a rating scale to assess the clinical significance of the discrepancies to demonstrate the potential adverse clinical outcome of patients in the absence of clinical intervention. Two studies2 3 used a rating scale that was used in adults.4 A study of paediatric neurosurgical patients found that initial hospital prescriptions for children differed from the preadmission prescriptions in 39% of occasions and 50% of all prescribing variations had the potential to cause moderate or severe discomfort or clinical deterioration.2 A study by Coffey et al in general paediatric admissions in Canada showed 22% of patients experienced at least one discrepancy and 29% of the discrepancies had the potential to cause moderate or severe discomfort or clinical deterioration.3 By comparison an epidemiological study in discrepancies in adults on admission had 38.6% of the discrepancies identified with a potential to cause moderate or severe discomfort or clinical deterioration.4 All the studies involved small samples or specific patient groups such as medically complex patients. However all of the studies demonstrated that discrepancies occurred among paediatric populations during transitions in care settings and mentioned MR as an intervention. Conclusion: The results have shown that discrepancies of medication upon hospital admission, transfer and discharge occur regularly in children. With only one published study in the UK looking at hospital admission in children, and no published articles on the incidence and epidemiology of medication discrepancies upon hospital transfer or discharge further research is required in a wider paediatric population. Further work is also required to define the required interventions to improve practice.

Molecular epidemiology of sexually transmitted human papillomavirus in a self referred group of women in Ireland

Background: Human papillomavirus (HPV) causes cervical cancer and external genital warts. The purpose of this study is to document the genotype distribution of HPV in females aged between 18 and 34 who self-referred to an STI clinic with visible external genital warts (EGW). Scrapings were taken from visible external genital warts (EGW). These scrapings were analysed by PCR for the presence of HPV DNA. Positive samples were then genotyped by means of a commercially available assay (LiPA). A comparison of genotyping results determined by the LiPA assay and direct amplicon DNA sequencing was also performed. Results: Ninety-two patients out of 105 samples (88%) had detectable levels of HPV DNA. The majority of individuals with EGW (66%) showed the presence of two or more genotypes. The most common HPV genotypes present in the study population were HPV-6, HPV-11, HPV-16, HPV-18, HPV-33 and HPV-53. Potential effects of vaccination on HPV molecular epidemiology indicate that 40% of the patients could have been protected from the high risk genotypes HPV-16 and HPV-18.Conclusion: This is the first report of the molecular epidemiology of external genital warts in women aged between 18 and 34 from Ireland based on results from a LiPA assay. The study shows that most individuals are infected with multiple genotypes including those with high oncogenic potential and that the newly available HPV vaccines could have a significant impact on prevalence of the most common HPV genotypes in this study population.

Influence of diabetes on natriuretic peptide thresholds in screening for Stage B heart failure

CONTEXT: Natriuretic peptide (NP) has been shown to be an effective screening tool to identify patients with Stage B heart failure and to have clinical value in preventing heart failure progression. The impact of associated metabolic confounders on the screening utility of NP needs clarification.

OBJECTIVE: To assess the impact of diabetes mellitus (DM) on NP screening for asymptomatic Stage B heart failure.

MATERIALS AND METHODS: The study population consisted of 1368 asymptomatic patients with cardiovascular risk factors recruited from general practice as part of the STOP-HF trial. B-type NP (BNP) was quantified at point-of-care.

RESULTS: BNP was found to be as accurate for detecting Stage B heart failure in DM patients compared to non-DM patients (AUC 0.75 [0.71,0.78] and 0.77 [0.72,0.82], respectively). However, different BNP thresholds are required to achieve the same level of diagnostic sensitivity in DM compared with non-DM patients. To achieve 80% sensitivity a difference of 5-ng/L lower is required for patients with DM.

CONCLUSION: Although a significantly different BNP threshold is detected for patients with DM, the BNP concentration difference is small and unlikely to warrant a clinically different diagnostic threshold.

The changing epidemiology of Ebstein's anomaly and its relationship with maternal mental health conditions: a European registry-based study

OBJECTIVES: The aim of this study was to describe the epidemiology of Ebstein's anomaly in Europe and its association with maternal health and medication exposure during pregnancy.

DESIGN: We carried out a descriptive epidemiological analysis of population-based data.

SETTING: We included data from 15 European Surveillance of Congenital Anomalies Congenital Anomaly Registries in 12 European countries, with a population of 5.6 million births during 1982-2011. Participants Cases included live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. Main outcome measures We estimated total prevalence per 10,000 births. Odds ratios for exposure to maternal illnesses/medications in the first trimester of pregnancy were calculated by comparing Ebstein's anomaly cases with cardiac and non-cardiac malformed controls, excluding cases with genetic syndromes and adjusting for time period and country.

RESULTS: In total, 264 Ebstein's anomaly cases were recorded; 81% were live births, 2% of which were diagnosed after the 1st year of life; 54% of cases with Ebstein's anomaly or a co-existing congenital anomaly were prenatally diagnosed. Total prevalence rose over time from 0.29 (95% confidence interval (CI) 0.20-0.41) to 0.48 (95% CI 0.40-0.57) (p<0.01). In all, nine cases were exposed to maternal mental health conditions/medications (adjusted odds ratio (adjOR) 2.64, 95% CI 1.33-5.21) compared with cardiac controls. Cases were more likely to be exposed to maternal β-thalassemia (adjOR 10.5, 95% CI 3.13-35.3, n=3) and haemorrhage in early pregnancy (adjOR 1.77, 95% CI 0.93-3.38, n=11) compared with cardiac controls.

CONCLUSIONS: The increasing prevalence of Ebstein's anomaly may be related to better and earlier diagnosis. Our data suggest that Ebstein's anomaly is associated with maternal mental health problems generally rather than lithium or benzodiazepines specifically; therefore, changing or stopping medications may not be preventative. We found new associations requiring confirmation.

The political economy of co-ordination challenges in the National Health Service: a postpositivist evaluation of diabetes policy and governance

The present PhD thesis develops and applies an evaluative methodology suited to the evaluation of policy and governance in complex policy areas. While extensive literatures exist on the topic of policy evaluation, governance evaluation has received less attention. At the level of governance, policymakers confront choices between different policy tools and governance arrangements in their attempts to solve policy problems, including variants of hierarchy, networks and markets. There is a need for theoretically-informed empirical research to inform decision-making at this level. To that end, the PhD develops an approach to evaluation by combining postpositivist policy analysis with heterodox political economy. Postpositivist policy analysis recognises that policy problems are often contested, that choices between policy options can involve significant trade-offs and that knowledge of policy options is itself dispersed and fragmented. Similarly, heterodox economics combines a concept of incommensurable values with an appreciation of the strengths and weaknesses of different institutional arrangements to realise them. A central concept of the field is coordination, which orientates policy analysis to the interactions of stakeholders in policy processes. The challenge of governance is to select the appropriate policy tools and arrangements which facilitate coordination. Via a postpositivist exploration of stakeholder ‘frames’, it is possible to ascertain whether coordination is occurring and to identify problems if it is not. Evaluative claims of governance can be made where arrangements can be shown to frustrate the realisation of shared values and objectives. The research makes a contribution to knowledge in a number of ways a) a distinctive evaluative approach that could be applied to other areas of health and public policy b) greater appreciation of the strengths and weaknesses of different forms of evidence in public policy and in particular health policy and c) concrete policy proposals for the governance and organisation of diabetes services, with implications for the NHS more broadly.

Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes

INTRODUCTION: Invasive aspergillosis (IA) is a fungal infection that particularly affects immunocompromised hosts. Recently, several studies have indicated a high incidence of IA in intensive care unit (ICU) patients. However, few data are available on the epidemiology and outcome of patients with IA in this setting.

Epidemiology of injuries in female high school soccer players.

Background: Sport is a compulsory activity in schools in South Africa. Female learners participating in soccer are more vulnerable to injuries than males. Objective: This study determined the epidemiology of injuries in female high school soccer players. Methods: A cross sectional survey captured the epidemiology of injuries in the players. The population included 200 players from 27 high schools in one district between the ages of 14 to 19 years. A self-administered questionnaire was used to collect data. Results: Only 85 scholars from 8 schools participated. From the 85 respondents, 31 (36.5%) sustained injuries. Only 61 injuries were reported by the injured players. The injury prevalence for the season was 36.5%. The rate of injury was 90 per 1000 athlete exposure hours during the season. The defenders and midfielders sustained the most injuries. Most injuries reported were contact in nature. More injuries occurred during training than during matches. The lower extremity (77.8%) was injured more than the upper extremity (22.2%). The knee (22.2%) and ankle (15.9%) were the most frequently injured body parts. Muscle injury was the most commonly reported followed by bruising. Conclusion: Prevalence of injuries was high with the lower limb, specifically the knee and ankle being commonly injured.

The Prevalence of Diabetes and Prediabetes Among Elementary School Children in Birjand

Background: Diabetes is associated with increased cardiovascular disease, mortality and morbidity. Objectives: The present study aimed at assessing fasting blood sugar (FBS) in elementary school students in Birjand, 2012. Materials and Methods: This cross-sectional and descriptive study was done on 1530 elementary school students who had been selected through multiple cluster sampling. FBS of these students was tested applying the enzymatic process. The obtained data was analyzed by means of SPSS software (v15) and statistical tests t and X2. Results: In this study, 833 girls and 697 boys were evaluated. Mean FBS of the whole study population was 86.9 ± 8.8 mg/dL; FBS was higher in boys compared to girls. FBS of 1453 (95%) children was < 100 mg/dL, the mean being 85.8 ± 6.8 mg/dL. FBS of 698 (45.6%) students of the above population was 86-99 mg/dl. It was 100-125 mg/dL in 72 (4.7%) individuals. Five (0.3%) students had FBS >126 mg/dL. Mean FBS increased in proportion to age, which was statistically significant. Conclusions: Although the prevalence of diabetes is not considerable; however, based on the relatively high portion of those children with high degree of blood glucose in the range in which the risk of diabetes and prediabetes in the following years rises dramatically, the need for further care of health authorities, an extensive screening activity, and undertaking intervening measures to prevent the epidemic of diabetes and consequently cardiovascular disease is emphasized.

Natural antioxidant vitamins: A review of their beneficial roles in management of diabetes mellitus and its complications

Diabetes mellitus is a complex and progressive metabolic disease which is associated with multiple complications. Chronic hyperglycaemia is the defining characteristic of diabetes mellitus. Hyperglycaemia leads to generation of free radicals and induces oxidative stress, which has become the chief factor that leads to diabetic complications. This review supports the use of antioxidant vitamins as therapeutic agents in the management of diabetes mellitus and its complications, and also provides an insight into the potential pharmacological effects of natural antioxidant vitamins in diabetic conditions. These antioxidant vitamins can be used as safe supplements to manage the occurrence and complications of the disease. Selected studies have reported on the beneficial effects of antioxidant vitamins in experimental models. The involvement of oxidative stress in diabetes and its complications has made the use of natural antioxidant vitamins (free radical scavengers) from plants inevitable as they may be very effective and safer in the management of diabetes.