Early drug use of dapagliflozin prescribed by general practitioners and diabetologists in Germany.

OBJECTIVES: Dapagliflozin is an inhibitor of the human sodium-glucose co-transporter 2 (SGLT2) that has been shown to improve glycaemic control in patients with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the characteristics and treatment patterns of dapagliflozin users in comparison to users of other anti-diabetic (AD) treatments in Germany. METHODS: Data from patients with T2DM initiating at least one prescription for dapagliflozin or other AD therapy between November 2012 and April 2014 were collected from the IMS German Disease Analyzer database. RESULTS: The use of dapagliflozin combination therapy (n=1034; 74%) was more common than monotherapy (n=371; 26%). In comparison with other AD therapy users, a higher percentage of dapagliflozin users were ⩽64years of age (62.3% vs. 36.4%), and a higher proportion were male (59.1% vs. 53.6%). The average duration of diabetes was comparable between dapagliflozin patients and other AD therapy users (5.7yearsvs. 5.5years), however higher levels of HbA1c were found in dapagliflozin users (8.2% (66mmol/mol) vs. 7.5% (58mmol/mol). For the vast majority (71.5% of 10mg dapagliflozin users and 88.9% of 5mg users), dapagliflozin was prescribed in combination with other AD therapy. CONCLUSIONS: Patients starting on dapagliflozin differed in several demographic and health-related respects to patients starting another AD therapy during the same period. Dapagliflozin was predominantly used as a component of combination therapy, adding on to existing therapy. After initiation, switching to other AD treatments or adding to therapy was comparatively rare during the first year

Comparison of Early and Late Mortality in Men and Women After Isolated Coronary Artery Bypass Graft Surgery in Stockholm, Sweden, 1980 to 1989

AbstractObjectives. We sought to analyze early and late mortality after coronary artery bypass graft surgery (CABG) in relation to gender.Background. Early mortality after CABG is generally higher in women than in men, but the causes are controversial. Few studies have investigated long-term mortality after CABG in relation to gender.Methods. In all, 3,326 men and 607 women underwent isolated CABG in Stockholm from 1980 to 1989. Mortality for these patients was followed by means of the National Cause of Death Register, from the time of operation until the end of 1990. Survival was evaluated by life-table methods and by proportional hazards regression.Results. Early mortality (within 30 days) was 3% in women and 1.7% in men, corresponding to a relative risk of 1.8 (95% confidence interval [CI] 1.0 to 3.0) in women compared with men. When age and body surface area were taken into account, the relative risk was 1.0 (95% CI 0.5 to 2.0), which was not markedly different but multivariate analyses that included hypertension, diabetes mellitus, previous myocardial infarction, left ventricular function and number of diseased vessels. Only small gender differences in mortality were observed for 5 years after the operation among those who survived for 30 days.Conclusions. The results suggest that men and women run similar risks of early and late mortality after CABG when patient characteristics are taken into account.(J Am Coll Cardiol 1997;29:659–64

Low noise 874 GHz receivers for the international submillimetre airborne radiometer (ISMAR)

We report on the development of two 874 GHz receiver channels with orthogonal polarizations for the international submillimetre airborne radiometer. A spline horn antenna and dielectric lens, a Schottky diode mixer circuit, and an intermediate frequency (IF) low noise amplifier circuit were integrated in the same metallic split block housing. This resulted in a receiver mean double sideband (DSB) noise temperature of 3300 K (minimum 2770 K, maximum 3400 K), achieved at an operation temperature of 40 C and across a 10 GHz wide IF band. A minimum DSB noise temperature of 2260 K at 20 C was measured without the lens. Three different dielectric lens materials were tested and compared with respect to the radiation pattern and noise temperature. All three lenses were compliant in terms of radiation pattern, but one of the materials leads to a reduction in a noise temperature of approximately 200 K compared to the others. The loss in this lens was estimated to be 0.42 dB. The local oscillator chains have a power consumption of 24W and consist of custom-designed Schottky diode quadruplers (5% power efficiency in operation, 8%-9% peak), commercial heterostructure barrier varactor (HBV) triplers, and power amplifiers that are pumped by using a common dielectric resonator oscillator at 36.43 GHz. Measurements of the radiation pattern showed a symmetric main beam lobe with full width half maximum <5 and side lobe levels below 20 dB. The return loss of a prototype of the spline horn and lens was measured using a network analyzer and frequency extenders to be 750-1100 GHz. Time-domain analysis of the reflection coefficients shows that the reflections are below 25 dB and are dominated by the external waveguide interface

Circulating gamma-glutamyl transferase and development of specific breast cancer subtypes:Findings from the Apolipoprotein Mortality Risk (AMORIS) cohort

BACKGROUND: Different etiological pathways may precede development of specific breast cancer subtypes and impact prevention or treatment strategies. We investigated the association between gamma-glutamyl transferase (GGT) and development of specific breast cancer subtypes based on oestrogen receptor (ER), progesterone receptor (PR) and HER2 status. METHODS: We included 231,283 cancer-free women in a Swedish cohort. Associations between GGT and breast cancer subtypes were investigated with nested case–control and case–case analyses. We used logistic regression models to assess serum GGT in relation to breast cancer subtype, based on individual and combined receptor status. RESULTS: Positive associations were found between serum GGT and development of ER+, ER− and PR+ breast cancers compared to controls (odds ratio (OR) 1.14 (95% confidence interval (CI) 1.08–1.19), 1.11 (1.01–1.23) and 1.18 (1.12–1.24), respectively) and of ER+/PR+ tumours. We found inverse associations between GGT levels and PR− breast cancers compared to PR+ (OR 0.87 (0.80–0.95)), between ER+/PR− tumours compared to ER+/PR+ tumours and between ER−/PR−/HER+ compared to ER+/HER2 or PR+/HER2 tumours (OR 0.55 (95% CI 0.34–0.90). CONCLUSION: The observed associations between pre-diagnostic serum GGT and different breast cancer subtypes may indicate distinct underlying pathways and require further investigations to tease out their clinical implications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-017-0816-7) contains supplementary material, which is available to authorized users

Mortality from circulatory diseases by specific country of birth across six European countries: test of concept

Background: Important differences in cardiovascular disease (CVD) mortality by country of birth have been shown within European countries. We now focus on CVD mortality by specific country of birth across European countries. Methods: For Denmark, England and Wales, France, The Netherlands, Scotland and Sweden mortality information on circulatory disease, and the subcategories of ischaemic heart disease, and cerebrovascular disease, was analysed by country of birth. Information on population was obtained from census data or population registers. Directly age-standardized rates per 100 000 were estimated by sex for each country of birth group using the WHO World Standard population 2000-25 structure. For differences in the results, at least one of the two 95% confidence intervals did not overlap. Results: Circulatory mortality was similar across countries for men born in India (355.7 in England and Wales, 372.8 in Scotland and 244.5 in Sweden). For other country of birth groups-China, Pakistan, Poland, Turkey and Yugoslavia-there were substantial between-country differences. For example, men born in Poland had a rate of 630.0 in Denmark and 499.3 in England and Wales and 153.5 in France; and men born in Turkey had a rate of 439.4 in Denmark and 231.4 in The Netherlands. A similar pattern was seen in women, e.g. Poland born women had a rate of 264.9 in Denmark, 126.4 in England and Wales and 54.4 in France. The patterns were similar for ischaemic heart disease mortality and cerebrovascular disease mortality. Conclusion: Cross-country comparisons are feasible and the resulting findings are interesting. They merit public health consideratio

Prevalence and progression of chronic kidney disease among patients with type 2 diabetes:Insights from the DISCOVER study

We report the prevalence and change in severity of chronic kidney disease (CKD) in DISCOVER, a global, 3-year, prospective, observational study of patients with type 2 diabetes (T2D) initiating second-line glucose-lowering therapy. CKD stages were defined according to estimated glomerular filtration rate (eGFR). Overall, 7843 patients from 35 countries had a baseline serum creatinine measurement. Of these (56.7% male; mean age: 58.1 years; mean eGFR: 87.5 mL/min/1.73 m2), baseline prevalence estimates for stage 0-1, 2, 3 and 4-5 CKD were 51.4%, 37.7%, 9.4% and 1.4%, respectively. A total of 5819 patients (74.2%) also had at least one follow-up serum creatinine measurement (median time between measurements: 2.9 years, interquartile range: 1.9-3.0 years). Mean eGFR decreased slightly to 85.7 mL/min/1.73 m2 over follow-up. CKD progression (increase of ≥1 stage) occurred in 15.7% of patients, and regression (decrease of ≥1 stage) in 12.0%. In summary, a substantial proportion of patients with T2D developed CKD or had CKD progression after the initiation of second-line therapy. Renal function should be regularly monitored in these patients, to ensure early CKD diagnosis and treatment

A Dynamic Aspartate-to-Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease

The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.Peer reviewe

Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering DrugsClinical Perspective: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)

Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) empagliflozin in patients with type 2 diabetes mellitus who have atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose-lowering drugs in 6 countries to determine if these benefits are seen in real-world practice and across SGLT-2i class