Cardiovascular Outcomes in Trials of New Antidiabetic Drug Classes

Type 2 diabetes is among the most prevalent chronic diseases worldwide and the prevention of associated cardiovascular complications is an important treatment goal. Sodium–glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are second-line options after metformin, while cardiovascular outcome trials have been conducted to establish the cardiovascular safety of these antidiabetic drug classes. SGLT2 inhibitors have been shown to have the best overall mortality, renal and cardiovascular outcomes. Reduction in hospitalisation for heart failure is particularly consistent. GLP-1 receptor agonists have also showed some benefits, especially in stroke prevention. DPP-4 inhibitors showed neutral effects on cardiovascular outcomes, but may increase the incidence of heart failure. Favourable outcomes observed in trials of SGLT2 inhibitors mean that these should be the preferred second-line option. DPP-4 inhibitors are useful for patients with diabetes at low cardiovascular risk

Detection of microalbuminuria in non-insulin dependent diabetes mellitus (NIDDM) patients without overt proteinuria by a semiquantitative albumin-creatinine urine strips

AbstractMicroalbuminuria is the hallmark of the reversible stage of incipient diabetic nephropathy. A cost- effective and convenient bedside screening test is essential to detect this phase. We used Clinitek 50® which is a semiquantitative strip test to check spot urine sample from 81 patients with albustix one plus or less. The incidence of Clinitek 50® microalbuminuria was 17%, 18.2% and 75% in 47, 22 and 12 patients with albustix negative, trace or one plus respectively. Nineteen and 13 of the 21 Clinitek 50® positive patients were checked for spot urine DCA 2000® and two 12-hour urine collection for immunoassay respectively. Around 60% of these samples fell into the microalbuminuria range and 40% into the overt albuminuria range by either technique. There was no false positive of Clinitek 50®. The lowest range of microalbuminuria detected by Clinitek 50® was 27 μg/minute (38 mg/day). We concluded that Clinitek 50® is a useful screening test as it is nonexpensive, easily operated and has a sensitivity close to the lower range of microalbuminuria

Pegylated derivatives of recombinant human arginase (rhArg1) for sustained in vivo activity in cancer therapy: preparation, characterization and analysis of their pharmacodynamics in vivo and in vitro and action upon hepatocellular carcinoma cell (HCC)

<p>Abstract</p> <p>Background</p> <p>Protein used in medicine, e.g. interferon, are immunogenic and quickly broken down by the body. Pegylation is a recognized way of preserving their integrity and reducing immune reactions, and works well with enzymes used to degrade amino acids, a recent focus of attention in controlling cancer growth. Of the two arginine-degrading enzymes being explored clinically, arginine deiminase is a decidedly foreign mycoplasm-derived enzyme, whereas human arginase 1 is a native liver enzyme. Both have been pegylated, the former with adjuncts of 20 kD, the latter with 5 kD PEG. Pegylation is done by several different methods, not all of which are satisfactory or desirable.</p> <p>Methods</p> <p>The preparation of novel polyethylene glycol (PEG) derivatives for modifying proteins is described, but directed specifically at pegylation of recombinant human arginase 1 (rhArg1). rhArg1 expressed in <it>Escherichia coli </it>was purified and coupled in various ways with 5 different PEG molecules to compare their protective properties and the residual enzyme activity, using hepatocellular cell lines both in vitro and in vivo.</p> <p>Results</p> <p>Methoxypolyethylene glycol-succinimidyl propionate (mPEG-SPA 5,000) coupled with very high affinity under mild conditions. The resulting pegylated enzyme (rhArg1-peg_{5,000 mw}) had up to 6 PEG chains of 5K length which not only protected it from degradation and any residual immunogenicity, but most importantly let it retain >90% of its native catalytic activity. It remained efficacious in depleting arginine in rats after a single ip injection of 1,500 U of the conjugate as the native enzyme, plasma arginine falling to >0.05 μM from ~170 μM within 20 min and lasting 6 days. The conjugate had almost the same efficacy as unpegylated rhArg1 on 2 cultured human liver cancer (HCC) cell lines. It was considerably more effective than 4 other pegylated conjugates prepared.</p> <p>Conclusion</p> <p>Valuable data on the optimization of the pegylation procedure and choice of ligand that best stabilizes the enzyme arginase 1 are presented, a protocol that should equally fit many other enzymes and proteins. It is a long lasting arginine-depleting enzyme in vivo which will greatly improve its use in anti-cancer therapy.</p

Developing a ‘defamilisation framework’ to examine the strategies for promoting the adult worker model and women’s welfare in eight European countries

This article is intended to explore the link between the study of defamilisation and that of the adult worker model. To meet this purpose, a defamilisation framework for studying issues concerning the adult worker model and defamilisation is developed. To show the empirical significance of these issues, evidence is drawn from a childcare gap typology covering eight European countries. Conducting these analytical tasks provides insights into the development of social work practices for enhancing women’s welfare

Government strategies for supporting the adult worker model in European countries: mixed implications for defamilisation

Purpose – This article explores the link between defamilisation studies and studies of the adult worker model and discusses the mixed implications that government strategies for supporting the adult worker model have for defamilisation. The adult worker model emphasizes that all adult men and women ought to engage in formal employment; defamilisation studies stress the importance of enhancing women’s chances of choosing (not) to perform important family roles such as the receiver of financial support and the care provider. Design/methodology/approach – Two new strategies (‘condition building’ and ‘rewarding/penalizing’) for promoting the adult worker model are identified based on literature review; their empirical significance is explored through an examination of comparative data concerning early childhood education and care policies (ECEC) and reforms in pension age in fourteen countries. Findings – The evidence shows that promoting the adult worker model does not necessarily benefit all women. While the fourteen countries provide ECEC to varying extents, the increase in pension age in most countries shows that governments adopt a ‘rewarding/penalizing’ strategy for promoting the adult worker model by allocating major welfare based on people’s labour force participation. These pension reforms may generate a negative impact on women’s chances of attaining financial autonomy. Originality/value – This study presents two new strategies for promoting the adult worker model and shows the empirical significance of these strategies based on comparative data. It also highlights the importance of searching for alternative concepts, namely economic defamilisation, for guiding pension reforms

Mindfulness-based cognitive therapy v. group psychoeducation for people with generalised anxiety disorder: randomised controlled trial

Background: Research suggests that an 8-week mindfulness-based cognitive therapy (MBCT) course may be effective for generalised anxiety disorder (GAD). Aims: To compare changes in anxiety levels among participants with GAD randomly assigned to MBCT, cognitive–behavioural therapy-based psychoeducation and usual care. Method: In total, 182 participants with GAD were recruited (trial registration number: CUHK_CCT00267) and assigned to the three groups and followed for 5 months after baseline assessment with the two intervention groups followed for an additional 6 months. Primary outcomes were anxiety and worry levels. Results: Linear mixed models demonstrated significant group × time interaction (F(4,148) = 5.10, P = 0.001) effects for decreased anxiety for both the intervention groups relative to usual care. Significant group × time interaction effects were observed for worry and depressive symptoms and mental health-related quality of life for the psychoeducation group only. Conclusions: These results suggest that both of the interventions appear to be superior to usual care for the reduction of anxiety symptoms