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

Effects of starting hemodialysis with an arteriovenous fistula or central venous catheter compared with peritoneal dialysis: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Although several studies have demonstrated early survival advantages with peritoneal dialysis (PD) over hemodialysis (HD), the reason for the excess mortality observed among incident HD patients remains to be established, to our knowledge. This study explores the relationship between mortality and dialysis modality, focusing on the role of HD vascular access type at the time of dialysis initiation.</p> <p>Methods</p> <p>A retrospective cohort study was performed among local adult chronic kidney disease patients who consecutively initiated PD and HD with a tunneled cuffed venous catheter (HD-TCC) or a functional arteriovenous fistula (HD-AVF) in our institution in the year 2008. A total of 152 patients were included in the final analysis (HD-AVF, n = 59; HD-TCC, n = 51; PD, n = 42). All cause and dialysis access-related morbidity/mortality were evaluated at one year. Univariate and multivariate analysis were used to compare the survival of PD patients with those who initiated HD with an AVF or with a TCC.</p> <p>Results</p> <p>Compared with PD patients, both HD-AVF and HD-TCC patients were more likely to be older (<it>p</it><0.001) and to have a higher frequency of diabetes mellitus (<it>p</it> = 0.017) and cardiovascular disease (<it>p</it> = 0.020). Overall, HD-TCC patients were more likely to have clinical visits (<it>p</it> = 0.069), emergency room visits (<it>p</it><0.001) and hospital admissions (<it>p</it><0.001). At the end of follow-up, HD-TCC patients had a higher rate of dialysis access-related complications (1.53 <it>vs.</it> 0.93 <it>vs.</it> 0.64, per patient-year; <it>p</it><0.001) and hospitalizations (0.47 <it>vs.</it> 0.07 <it>vs.</it> 0.14, per patient-year; <it>p</it> = 0.034) than HD-AVF and PD patients, respectively. The survival rates at one year were 96.6%, 74.5% and 97.6% for HD-AVF, HD-TCC and PD groups, respectively (<it>p</it><0.001). In multivariate analysis, HD-TCC use at the time of dialysis initiation was the important factor associated with death (HR 16.128, 95%CI [1.431-181.778], <it>p</it> = 0.024).</p> <p>Conclusion</p> <p>Our results suggest that HD vascular access type at the time of renal replacement therapy initiation is an important modifier of the relationship between dialysis modality and survival among incident dialysis patients.</p

Regional distribution of blood volume within the preterm infant thorax during synchronised mechanical ventilation

Perfusion in healthy adults is gravity-dependent. Little is known about lung perfusion in the preterm infant. The aim of this study was to describe the regional distribution of blood volume within the thorax in preterm infants receiving synchronised volume-targeted mechanical ventilation (SIPPV + TTV) and to compare this to regional distribution of tidal ventilation using electrical impedance tomography (EIT)