Extrapancreatic insulin effect of glibenclamide

In eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The rise in serum insulin levels persisted longer after glibenclamide. The initial rise in serum insulin was of the same magnitude in both situations, as was the rise in serum C-peptide levels during the entire 5 h study. It is concluded that glibenclamide is able to maintain a more protonged increase in serum insulin levels by inhibiting the degradation of insulin in the vascular endothelial cells of the liver. The inhibition contributes to the blood glucose lowering effect of glibenclamide

Markers of inflammation and coagulation indicate a prothrombotic state in HIV-infected patients with long-term use of antiretroviral therapy with or without abacavir

Background: Abacavir (ABC) treatment has been associated with an increased incidence of myocardial infarction. The pathophysiological mechanism is unknown. In this study markers of inflammation and coagulation in HIV-infected patients using antiretroviral therapy with or without ABC were examined to pinpoint a pathogenic mechanism. Given the important role of high sensitivity C-reactive protein (hsCRP) levels in predicting cardiovascular risk, patient groups were also analyzed according to hsCRP levels.Method

HALON-hysterectomy by transabdominal laparoscopy or natural orifice transluminal endoscopic surgery : a randomised controlled trial (study protocol)

Acknowledgments The authors acknowledge the NOTES Investigators' team for taking care of the study participants; and Amanda McPhail for language correction and editing of the manuscript.Peer reviewedPublisher PD

A metabolomics based molecular pathway analysis for how the SGLT2-inhibitor dapagliflozin may slow kidney function decline in patients with diabetes

Aim: To investigate which metabolic pathways are targeted by the sodium-glucose co-transporter-2 inhibitor dapagliflozin to explore the molecular processes involved in its renal protective effects. Methods: An unbiased mass spectrometry plasma metabolomics assay was performed on baseline and follow-up (week 12) samples from the EFFECT II trial in patients with type 2 diabetes with non-alcoholic fatty liver disease receiving dapagliflozin 10 mg/day (n = 19) or placebo (n = 6). Transcriptomic signatures from tubular compartments were identified from kidney biopsies collected from patients with diabetic kidney disease (DKD) (n = 17) and healthy controls (n = 30) from the European Renal cDNA Biobank. Serum metabolites that significantly changed after 12 weeks of dapagliflozin were mapped to a metabolite-protein interaction network. These proteins were then linked with intra-renal transcripts that were associated with DKD or estimated glomerular filtration rate (eGFR). The impacted metabolites and their protein-coding transcripts were analysed for enriched pathways. Results: Of all measured (n = 812) metabolites, 108 changed (P &lt; 0.05) during dapagliflozin treatment and 74 could be linked to 367 unique proteins/genes. Intra-renal mRNA expression analysis of the genes encoding the metabolite-associated proteins using kidney biopsies resulted in 105 genes that were significantly associated with eGFR in patients with DKD, and 135 genes that were differentially expressed between patients with DKD and controls. The combination of metabolites and transcripts identified four enriched pathways that were affected by dapagliflozin and associated with eGFR: glycine degradation (mitochondrial function), TCA cycle II (energy metabolism), L-carnitine biosynthesis (energy metabolism) and superpathway of citrulline metabolism (nitric oxide synthase and endothelial function). Conclusion: The observed molecular pathways targeted by dapagliflozin and associated with DKD suggest that modifying molecular processes related to energy metabolism, mitochondrial function and endothelial function may contribute to its renal protective effect.</p

Fidelity and Clinical Competence in Providing Illness Management and Recovery:An Explorative Study

Illness Management and Recovery (IMR) is a psychosocial intervention supporting people with serious mental illnesses. In this study, 15 IMR groups were assessed for fidelity and clinician competency to establish the implementation level of all IMR elements and explore complementarity of the IMR Treatment Integrity Scale (IT-IS) to the standard IMR Fidelity Scale. Use of the IT-IS was adapted, similar to the IMR Fidelity Scale. Descriptive statistics were applied. Implementation success of IMR elements varied widely on the IMR Fidelity Scale and IT-IS (M = 3.94, SD = 1.13, and M = 3.29, SD = 1.05, respectively). Twelve IMR elements (60%) were well-implemented, whereas eight (40%) were implemented insufficiently, including some critical cognitive-behavioral techniques (e.g., role-playing). The scales appeared largely complementary, though strongly correlated (r (13) = 0.74, p = 0.002). Providing all IMR elements adequately requires a variety of clinical skills. Specific additional training and supervision may be necessary

Effects of illness management and recovery:A multicenter randomized controlled trial

There have been inconsistent findings in the literature with respect to the efficacy of Illness Management and Recovery (IMR) in the psychosocial treatment of people with schizophrenia or other severe mental illnesses. This study aimed to comprehensively investigate the effectiveness of IMR, including the impact of completion and fidelity. In this randomized controlled trial (RCT), 187 outpatients received either IMR plus care as usual (CAU) or only CAU. Multilevel modeling was implemented to investigate group differences over an 18-month period, comprising 12 months of treatment and six months of follow-up. The primary outcome was overall illness management, which was assessed using the client version of the IMR scale. Secondary outcomes included measures regarding illness management, clinical, personal, and functional recovery, and hospitalizations. The interviewers were blinded to group allocation. This clinical trial was registered with the Netherlands Trial Register (NL4931, NTR5033). Patients who received IMR showed statistically significant improvement in self-reported overall illness management (the primary outcome). Moreover, they showed an improvement in self-esteem, which is a component of personal recovery. There were no effects within the other questionnaires. There were also no statistically significant between-group differences in terms of hospitalizations. Patients in both groups showed statistically significant improvement in clinician-rated overall illness management, social support, clinical and functional recovery, and self-stigma over time. IMR completion was associated with stronger effects. High IMR fidelity was associated with self-esteem. This study confirms the efficacy of IMR in overall illness self-management. To our knowledge, this is the first RCT on IMR to explore the impact of fidelity on treatment efficacy. Future studies should further establish efficacy in personal recovery. To improve efficacy, it appears important to promote IMR completion and fidelity

Time to improve statin prescription guidelines in low-risk patients?

Background The challenge of the primary prevention of cardiovascular disease (CVD) is to identify patients who would benefit from treatment with statins. Statins are currently prescribed to many patients, even those at a low 10-year risk of CVD. These latter patients may not be eligible for statins according to current guidelines. Design This study investigated the prescription of guideline-consistent (according to guidelines) and guideline-inconsistent (not according to guidelines) lipid-lowering treatment in primary prevention in a large contemporary Dutch cohort study (Lifelines). Methods Lifelines is a large cohort study from the Netherlands. Participants were recruited between 2006 and 2013. They completed questionnaires and underwent a physical examination. Participants with previous CVD were excluded. Statins and ezetimibe were grouped as statin treatment. The Dutch guideline on cardiovascular management was used to assess eligibility for statins. Results Of 147,785 participants, 7092 (4.8%) reported statin treatment. In 4667 (66%) participants, statin treatment was inconsistent with the Dutch guideline. A total of 78% of these participants had a low 10-year predicted CVD risk. Multivariable logistic regression analysis showed that female sex and smoking were strongly associated with guideline-inconsistent treatment. Interestingly, 65% of the these participants had low-density lipoprotein cholesterol levels above the 95(th) percentile, adjusted for age and sex, two or more major risk factors of CVD or a positive family history of premature CVD. Therefore treatment might be reasonable. Conclusions There is a large inconsistency between guideline recommendations and the prescription of statins in clinical practice in the Netherlands. This is especially true for patients with low CVD risk. Many of these patients probably had risk-increasing circumstances justifying treatment

Adnexectomy by vaginal Natural Orifice Transluminal Endoscopic Surgery versus laparoscopy : results of a first randomised controlled trial (NOTABLE trial)

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