Safety and efficacy of rosiglitazone in the elderly diabetic patient

Diabetes is an important health condition for the aging population; at least 20% of patients over the age of 65 years have diabetes, and this number can be expected to grow rapidly in the coming decades. Rosiglitazone, a drug in the thiazolidinedione class which targets insulin resistance, was approved by drug regulatory bodies based on its ability to improve glycemic control nearly ten years ago. The greatest long-term risk in diabetes is cardiovascular disease with macrovascular disease being the cause of as much as 80% of mortality. More recently the cardiovascular safety of rosiglitazone was brought to center stage following several meta-analyses and the unplanned interim analysis of the RECORD trial. As opposed to pioglitazone, current evidence points to rosiglitazone having a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas. A thiazolidinedione class effect however seems apparent with respect to the increased risk for fractures and congestive heart failure. Clinical trial evidence on rosiglitazone therapy in the elderly is limited. The available evidence is mainly related to observational cohort studies. Most of the trial evidence relates to a younger population and therefore these data can not be directly extrapolated to an older population. The effects of the thiazolidinedione drug class remain incompletely understood

Safety and efficacy of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia

Statins form the cornerstone of pharmaceutical cardiovascular disease prevention. However, despite very effective statin intervention, the majority of events remain unpreventable. In some cases statin therapy alone is insufficient to achieve adequate lipid levels whereas other patients are unable to tolerate statins. This calls for additional treatment options. Niacin has a long history of success in reducing low-density lipoprotein cholesterol and triglycerides, and increasing high-density lipoprotein cholesterol. It was the first lipid-lowering drug to demonstrate a reduction in cardiovascular events, and remains the only one that has consistently shown benefits on surrogate outcomes when added to background therapies of other lipid-lowering drugs, including statins. Niacin’s uptake in clinical practice has been less successful due to its side-effect profile, most notable being flushing. The uncovering of the mechanism by which flushing is induced, together with the development of a prostaglandin D2 receptor inhibitor (laropiprant) which reduces this downstream flushing effect of niacin, has sparked new promise in therapeutic lipid management. It provides an additional treatment option into managing lipid abnormalities. The uptake in clinical practice of the niacin–laropiprant combination will depend on the relative improvements experienced by the patient in the side-effect profile compared to other treatment options, as well as on the the keenly-awaited outcome studies currently underway. Until these data become available guidelines and recommendations are unlikely to change and niacin’s position in therapeutic cardiovascular risk prevention will be determined by clinician opinion and experience, and patient preferences

A comparative study of blood endotoxin detection in haemodialysis patients

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wong et al Journal of Inflammation (2016) 13:24, the version of record is available online at doi: 10.1186/s12950-016-0132-5BACKGROUND: Endotoxemia is commonly reported in patients receiving haemodialysis and implicated in the pathogenesis of systemic inflammation. The Limulus Amoebocyte Lysate (LAL) assay is the most commonly used blood endotoxin detection assay. Two kinetic variations of the assay are commercially available - the turbidimetric and chromogenic assay, it is unknown which assay is superior for endotoxin detection in uremic patients. Selection of the optimum LAL technique for endotoxin detection in haemodialysis patients is important to further understanding of the sequela of endotoxemia and development of endotoxin-lowering strategies in this population. METHOD: A turbidimetric and chromogenic LAL assay from the same manufacturer were directly compared. We investigated the ability of both LAL assays to detect endotoxin in uremic plasma. Plasma samples from haemodialysis patients and healthy controls were spiked with endotoxin and percentage spike recovery for the chromogenic and turbidimetric assay was determined. Assay accuracy and precision were compared between both LAL assays. RESULTS: The turbidimetric assay had greater accuracy than the chromogenic assay. Spike recovery was 113.8 % vs. 53.8 % for the turbidimetric and chromogenic assay respectively. Assay bias was higher in the chromogenic assay (-0.384EU/mL vs. 0.011EU/mL). The turbidimetric assay demonstrated greater precision compared to the chromogenic assay. Coefficient of variation ranged from 4.5 to 24.1 % for the turbidimetric assay and 25.8-26.5 % for the chromogenic assay. CONCLUSION: The study findings suggest that the kinetic turbidimetric LAL assay has greater accuracy and precision than the chromogenic assay and is the optimum LAL technique for endotoxin detection in haemodialysis patients, though these findings should be verified using LAL reagents from other sources.Peer reviewe

SGLT2 Inhibitors in Type 2 Diabetes Management: Key Evidence and Implications for Clinical Practice

<p></p><p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s13300-018-0471-8">here<b>.</b></a> </p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p

State hospitals, academic medicine and the decline of health care in South Africa: A cry of support from those who have left for those who stay.

Recently a group of concerned South African doctors published a comment on the occupational-specific dispensation negotiations that have failed to address their concerns. As a group of South African trained physicians working out of South Africa we would like to add our voice in support of these concerned doctors. In particular, the South African public and government needs to acknowledge that poor working conditions and inadequate compensation play a large role in the loss of medical skill from South Africa

HEART UK Consensus Statement on Lipoprotein(a) - a call to action

Lipoprotein(a), Lp(a), is a modified atherogenic low-density lipoprotein particle that contains apolipoprotein(a). Its levels are highly heritable and variable in the population. This consensus statement by HEART UK is based on the evidence that Lp(a) is an independent cardiovascular disease (CVD) risk factor, provides recommendations for its measurement in clinical practice and reviews current and emerging therapeutic strategies to reduce CVD risk. Ten statements summarise the most salient points for practitioners and patients with high Lp(a). HEART UK recommends that Lp(a) is measured in adults as follows: 1)those with a personal or family history of premature atherosclerotic CVD; 2)those with first-degree relatives who have Lp(a)levels > 200nmol/l; 3) patients with familial hypercholesterolemia; 4) patients with calcific aortic valve stenosis and 5) those with borderline (but<15%) 10 year risk of a cardiovascular event. The management of patients with raised Lp(a) levels should include: 1) reducing overall atherosclerotic risk; 2)controlling dyslipidemia with a desirable nonHDL-cholesterol level of <100mg/d (2.5mmol/l) and 3) consideration of lipoprotein apheresis

Plasma Levels of Middle Molecules to Estimate Residual Kidney Function in Haemodialysis without Urine Collection

© 2015 Vilar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/Licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.BACKGROUND: Residual Kidney Function (RKF) is associated with survival benefits in haemodialysis (HD) but is difficult to measure without urine collection. Middle molecules such as Cystatin C and β2-microglobulin accumulate in renal disease and plasma levels have been used to estimate kidney function early in this condition. We investigated their use to estimate RKF in patients on HD. DESIGN: Cystatin C, β2-microglobulin, urea and creatinine levels were studied in patients on incremental high-flux HD or hemodiafiltration(HDF). Over sequential HD sessions, blood was sampled pre- and post-session 1 and pre-session 2, for estimation of these parameters. Urine was collected during the whole interdialytic interval, for estimation of residual GFR (GFRResidual = mean of urea and creatinine clearance). The relationships of plasma Cystatin C and β2-microglobulin levels to GFRResidual and urea clearance were determined. RESULTS: Of the 341 patients studied, 64% had urine output>100 ml/day, 32.6% were on high-flux HD and 67.4% on HDF. Parameters most closely correlated with GFRResidual were 1/β2-micoglobulin (r2 0.67) and 1/Cystatin C (r2 0.50). Both these relationships were weaker at low GFRResidual. The best regression model for GFRResidual, explaining 67% of the variation, was: GFRResidual = 160.3 · (1/β2m) - 4.2. Where β2m is the pre-dialysis β2 microglobulin concentration (mg/L). This model was validated in a separate cohort of 50 patients using Bland-Altman analysis. Areas under the curve in Receiver Operating Characteristic analysis aimed at identifying subjects with urea clearance≥2 ml/min/1.73 m2 was 0.91 for β2-microglobulin and 0.86 for Cystatin C. A plasma β2-microglobulin cut-off of ≤19.2 mg/L allowed identification of patients with urea clearance ≥2 ml/min/1.73 m2 with 90% specificity and 65% sensitivity. CONCLUSION: Plasma pre-dialysis β2-microglobulin levels can provide estimates of RKF which may have clinical utility and appear superior to cystatin C. Use of cut-off levels to identify patients with RKF may provide a simple way to individualise dialysis dose based on RKF.Peer reviewe

True or not: uncertainty of laboratory results

Complete and informative reporting and interpretation can only lead to better decisions in healthcar