Use and effectiveness of dapagliflozin in routine clinical practice. An Italian multicenter retrospective study

In randomized controlled trials (RCTs), sodium-glucose co-transporter-2 (SGLT2) inhibitors have been shown to confer glycaemic and extra-glycaemic benefits. The DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) study was a multicentre retrospective study designed to evaluate the baseline characteristics of patients receiving dapagliflozin vs those receiving selected comparators (dipeptidyl peptidase-4 inhibitors, gliclazide, or glucagon-like peptide-1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281 217, the analysis included 17 285 patients initiating dapagliflozin or comparator glucose-lowering medications (GLMs), 6751 of whom had a follow-up examination. At baseline, participants starting dapagliflozin were younger, had a longer disease duration, higher glycated haemoglobin (HbA1c) concentration, and a more complex history of previous GLM use, but the clinical profile of patients receiving dapagliflozin changed during the study period. Dapagliflozin reduced HbA1c by 0.7%, body weight by 2.7 kg, and systolic blood pressure by 3.0 mm Hg. Effects of comparator GLMs were also within the expected range, based on RCTs. This real-world study shows an initial channelling of dapagliflozin to difficult-to-treat patients. Nonetheless, dapagliflozin provided significant benefits with regard to glucose control, body weight and blood pressure that were in line with findings from RCTs

An overall strategy based on regression models to estimate relative survival and model the effects of prognostic factors in cancer survival studies.

Relative survival provides a measure of the proportion of patients dying from the disease under study without requiring the knowledge of the cause of death. We propose an overall strategy based on regression models to estimate the relative survival and model the effects of potential prognostic factors. The baseline hazard was modelled until 10 years follow-up using parametric continuous functions. Six models including cubic regression splines were considered and the Akaike Information Criterion was used to select the final model. This approach yielded smooth and reliable estimates of mortality hazard and allowed us to deal with sparse data taking into account all the available information. Splines were also used to model simultaneously non-linear effects of continuous covariates and time-dependent hazard ratios. This led to a graphical representation of the hazard ratio that can be useful for clinical interpretation. Estimates of these models were obtained by likelihood maximization. We showed that these estimates could be also obtained using standard algorithms for Poisson regression

Is low fertility really a problem? Population aging, dependency, and consumption.

Copyright 2014 by the American Association for the Advancement of Science; all rights reserved.Longer lives and fertility far below the replacement level of 2.1 births per woman are leading to rapid population aging in many countries. Many observers are concerned that aging will adversely affect public finances and standards of living. Analysis of newly available National Transfer Accounts data for 40 countries shows that fertility well above replacement would typically be most beneficial for government budgets. However, fertility near replacement would be most beneficial for standards of living when the analysis includes the effects of age structure on families as well as governments. And fertility below replacement would maximize per capita consumption when the cost of providing capital for a growing labor force is taken into account. Although low fertility will indeed challenge government programs and very low fertility undermines living standards, we find that moderately low fertility and population decline favor the broader material standard of living

Longitudinal assessment of high blood pressure in children with nonalcoholic fatty liver disease.

ObjectiveNonalcoholic fatty liver disease (NAFLD) affects 9.6% of children and may put these children at elevated risk of high blood pressure and subsequent cardiovascular morbidity and mortality. Therefore, we sought to determine the prevalence of and risk factors for high blood pressure in children with NAFLD.MethodsCohort study performed by the NIDDK NASH Clinical Research Network. There were 484 children with NAFLD ages 2 to 17 at enrollment; 382 children were assessed both at enrollment and 48 weeks afterwards. The main outcomes were high blood pressure at baseline and persistent high blood pressure at both baseline and 48 weeks.ResultsPrevalence of high blood pressure at baseline was 35.8% and prevalence of persistent high blood pressure was 21.4%. Children with high blood pressure were significantly more likely to have worse steatosis than children without high blood pressure (mild 19.8% vs. 34.2%, moderate 35.0% vs. 30.7%, severe 45.2% vs. 35.1%; P = 0.003). Higher body mass index, low-density lipoprotein, and uric acid were independent risk factors for high blood pressure (Odds Ratios: 1.10 per kg/m2, 1.09 per 10 mg/dL, 1.25 per mg/dL, respectively). Compared to boys, girls with NAFLD were significantly more likely to have persistent high blood pressure (28.4% vs.18.9%; P = 0.05).ConclusionsIn conclusion, NAFLD is a common clinical problem that places children at substantial risk for high blood pressure, which may often go undiagnosed. Thus blood pressure evaluation, control, and monitoring should be an integral component of the clinical management of children with NAFLD

Decrease in antibiotic resistance of Streptococcus pneumoniae between 2003 and 2009 in France and changes in serotype distribution: Ongoing survey of the French Pneumococcus Surveillance Network

Background: The French regional pneumococcal observatories (ORP) network was created in 1995, it participates to the close monitoring of the trends in antimicrobial resistance and serotype distribution with the National Reference Centre for Pneumococci (NRCP) and the Institut de Veille Sanitaire (InVS). The aim of this survey was to assess the antibiotic resistance and the distribution of vaccine and non-vaccine serotypes in invasive pneumococcal disease (IPD) in adults and children as well in otitis in children in France in 2009. Methods: Antimicrobial susceptibility testing was performed on 5,194 isolates of S. pneumoniae recovered from cerebrospinal fluid (CSF), blood, middle ear fluid (MEF) and pleural fluid during the year 2009 by the 23 ORP. MICs of penicillin (P), amoxicillin (AMX) and cefotaxime (CTX) were determined by the agar dilution method and interpreted according to the Antibiotics Comity of the French Society of Microbiology breakpoints. Serotyping was performed at the NRCP with serotype-specific antisera, by latex agglutination test. Results: Results of susceptibility between 2003 and 2009 to P are presented in Table 1. The pneumococci with decreased susceptibility to penicillin G (PDSP) decreased significantly in all types of samples except for MEF’s isolates in children between 2007 and 2009. In the global population, the percentage of I+R (2003 vs 2009) decreased significantly for AMX (30.3% versus 9.6%) and for CTX (18.2% versus 10.5%). Strains highly resistant (MIC > 2 mg/L) remained rare: 0.4%, 1.1% and 0.2% for P, AMX and CTX respectively. The most frequent capsular types in CSF were 3, 7F, 19A, 6C, 23B for adults and 7F, 19A, 3, 33F and 15B for children. Serotypes included in the PCV-7 and PCV-13 vaccine accounted in children for 4% and 51% respectively and in adults for 12% and 48% respectively. By contrast, the serotype 19A remained highly predominant (80%) among MEF isolates. Conclusions: We observed a significant decrease of PDSP between 2003 and 2009 (50.2 to 33.0%). The decrease coincided with the introduction of PCV7 and with a general reduction in levels of antibiotic consumption in France. This continuous survey is necessary to underline modification in serotype distribution in France after PVC13 introduction (June 2010)

Effect of consanguinity on birth weight for gestational age in a developing country.

Consanguinity, the marriage between relatives, has been associated with adverse child health outcomes because it increases homozygosity of recessive alleles. The objective of this study was to assess the effect of consanguinity on the birth weight of newborns in Greater Beirut, Lebanon. Cross-sectional data were collected on 10,289 consecutive liveborn singleton newborns admitted to eight hospitals belonging to the National Collaborative Perinatal Neonatal Network during the years 2000 and 2001. Birth weight was modeled by use of the fetal growth ratio, defined as the ratio of the observed birth weight to the median birth weight for gestational age. A mixed-effect multiple linear regression model was used to predict the net effect of first- and second-cousin marriage on the birth weight for gestational age, accounting for within-hospital clustering of data. After controlling for medical and sociodemographic covariates, the authors found a statistically significant negative association between consanguinity and birth weight at each gestational age. No significant difference was observed in the decrease in birth weight between the first- and second-cousin marriages. Overall, consanguinity was associated with a decrease in birth weight for gestational age by 1.8% (beta = -0.018, 95% confidence interval: -0.027, -0.008). The largest effects on fetal growth were seen with lower parity and smoking during pregnancy