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Selected AbstractsPost-prandial glucose excursions following four methods of bolus insulin administration in subjects with Type 1 diabetesDIABETIC MEDICINE, Issue 4 2002H. P. Chase Abstract Aims To determine if one method of short-acting insulin bolus administration is superior to other methods in managing a meal high in carbohydrates, calories and fat. Methods Nine subjects receiving continuous subcutaneous insulin infusion using insulin lispro (Humalog®) agreed to consume the same meal high in carbohydrates, calories and fat on four occasions 1 week apart. They received the same dose of bolus insulin on each of the four occasions randomly assigned and beginning 10 min prior to the meal as either a single bolus, two separate boluses of one-half the same total dose (the second after 90 min), the entire bolus given as a square-wave (over 2 h) or a dual-wave (70% as a bolus and 30% as a square-wave over 2 h). Blood glucose levels were measured at ,60 and ,30 min and at zero time, and then every half-hour for 6 h using the Hemacue® in the out-patient clinic. Results Changes in blood glucose values from fasting were the lowest after 90 and 120 min (P < 0.01) when the dual wave was administered. When the dual or square-wave methods of insulin administration were used, subjects had significantly lower glucose levels after 4 h in comparison with when the single or double boluses were used (P = 0.04). Conclusions We conclude that the dual wave provided the most effective method of insulin administration for this meal. The dual- and square-wave therapies resulted in lower glucose levels 4 h after the meal in comparison with the single and double-bolus treatments. [source] Latest news and product developmentsPRESCRIBER, Issue 8 2008Article first published online: 12 MAY 200 Glargine preferred to lispro as type 2 add-on Basal insulin glargine (Lantus) and insulin lispro (Humalog) at mealtimes improved glycaemic control equally well in patients with type 2 diabetes poorly controlled by oral agents, but patient satisfaction was greater with basal insulin (Lancet 2008;371:1073-84). The 44-week APOLLO trial, funded by Sanofi Aventis, was a nonblinded randomised comparison of basal and prandial insulin regimens added to oral treatment in 418 patients. It found similar reductions in HbA1C (,1.7 vs ,1.9 per cent respectively). Fasting and nocturnal glucose levels were lower with insulin glargine and postprandial levels were lower with insulin lispro. The basal regimen was associated with fewer hypoglycaemic events (5.2 vs 24 per patient per year), less weight gain (3.01 vs 3.54kg) and greater improvement in patient satisfaction scores. Treating hypertension cuts mortality in over-80s Treating hypertension in the over-80s reduces all-cause mortality by 21 per cent, the HYVET study has shown (N Engl J Med online: 31 March 2008; doi: 10.1056/NEJMoa 0801369). Compared with placebo, treatment with indapamide alone or with perindopril for an average of 1.8 years also reduced the incidence of fatal stroke by 39 per cent, cardiovascular death by 23 per cent and heart failure by 64 per cent. The incidence of stroke was reduced by 30 per cent but this was of borderline statistical significance. Fewer serious adverse events were reported with treatment than with placebo. New work for NICE The DoH has announced the 18th work programme for NICE. Seven public health interventions include preventing skin cancer, smoking by children and excess weight gain during pregnancy. Public health guidance will include the provision of contraceptive services for socially disadvantaged young people. Two new clinical guidelines are sedation in young people and management of fractured neck of femur. New technology appraisals may include eight therapies for cancer, two new monoclonal antibodies for psoriasis and rheumatoid arthritis, an oral retinoid for severe chronic hand eczema and methylnaltrexone for opioid-induced bowel dysfunction. Combinations no better against CV disease Taking ezetimibe and simvastatin (Inegy) does not appear to slow the progression of atherosclerosis more than high-dose simvastatin alone, say researchers from The Netherlands (N Engl J Med 2008;358: 1431-43). In patients with hypercholesterolaemia, there was no difference in regression or progression of atherosclerosis after two years' treatment with simvastatin 80mg per day alone or combined with ezetimibe 10mg per day. Adverse event rates were similar. In patients with vascular disease or high-risk diabetes, there was no difference between the ACE inhibitor ramipril 10mg per day or the ARB telmisartan (Micardis) 80mg per day as monotherapy, or their combination, in the risk of a composite outcome of cardiovascular death, MI, stroke and admission for heart failure (N Engl J Med 2008;358:1547-59). Combined treatment was associated with higher risks of hypotensive symptoms, syncope and renal dysfunction. Twice-daily celecoxib increases CV risk Taking celecoxib (Celebrex) twice daily carries a higher risk of cardiovascular events than the same total dose taken once daily, a metaanalysis suggests (Circulation 2008; doi: 10.1161/ CIRCULATIONAHA.108. 764530). The analysis of six placebo-controlled trials involving a total of 7950 patients taking celecoxib for indications other than rheumatoid arthritis found that the combined risk of cardiovascular death, myocardial infarction, stroke, heart failure or thromboembolic event increased with dose over the range 400-800mg per day. The risk was significantly greater with 200mg twice daily (HR 1.8) than 400mg once daily (HR 1.1). Patients at greatest baseline risk were at disproportionately increased risk from celecoxib. Long-term etanercept effective in AS An open-label study suggests that etanercept (Enbrel) remains effective in the treatment of ankylosing spondylitis in the long term (Ann Rheum Dis 2008;67:346-52). Of 257 patients who completed six months' treatment with etanercept and who entered the nonblinded extension study, 126 completed a total of 168-192 weeks' treatment. The commonest adverse events were injection-site reactions (22 per cent), headache (20 per cent) and diarrhoea (17.5 per cent). The annual rate of serious infections was 0.02 per person. Response and partial remission rates after 192 weeks were similar to those reported after 96 weeks. Metformin reduces risk Metformin reduces the risk of developing diabetes in individuals at increased risk, a meta-analysis suggests (Am J Med 2008;121:149-57.e2). The study included 31 mostly small, randomised, controlled trials involving a total of 4570 participants and lasting at least eight weeks (8267 patient-years of treatment). Metformin was associated with reductions in body mass (,5.3 per cent), fasting glucose (,4.5 per cent) and insulin resistance (,22.6 per cent); lipid profiles also improved. The odds of developing diabetes were reduced by 40 per cent,an absolute risk reduction of 6 per cent over 1.8 years. MHRA clarifies cough and colds advice Press reports mistakenly suggested that the MHRA had banned some cough and cold remedies when it issued new guidance on treating young children, the MHRA says. The Agency's advice followed a review of over-thecounter cough and cold medicines for children by the Commission on Human Medicines. Children under two are at increased risk of adverse reactions and should no longer be treated with products containing antihistamine (chlorphenamine, brompheniramine, diphenhydramine), antitussives (dextromethorphan, pholcodine), expectorants (guaifenesin, ipecacuanha) and decongestants (phenylephrine, pseudoephedrine, ephedrine, oxymetazoline and xylometazoline). The MHRA said these products, which are classified as general sale medicines, should be removed from open shelves until available in new packaging that complies with the advice. They may still be supplied by a pharmacist for the treatment of older children. Coughs and colds should be treated with paracetamol or ibuprofen for fever, a simple glycerol, honey or lemon syrup for cough, and vapour rubs and inhalant decongestants for stuffy nose. Saline drops can be used to thin and clear nasal secretions in young babies. Parents are being urged not to use more than one product at a time to avoid inadvertently administering the same constituent drug twice. Perindopril brand switch Servier Laboratories is replacing its current formulations of perindopril (Coversyl, Coversyl Plus) with a new product that is not bioequivalent. The current Coversyl brand contains perindopril erbumine (also known as tert -butylamine). The new formulation contains perindopril arginine; it will be distinguished by new brand names (Coversyl Arginine, Coversyl Arginine Plus) and new packaging. Coversyl 2, 4 and 8mg tablets are equivalent to Coversyl Arginine 2.5, 5 and 10mg. Servier says the change is part of the simplification and harmonisation of global manufacturing; the arginine salt is already used in other countries and offers greater stability and a longer shelf-life. Both Coversyl and Coversyl Arginine will be in the supply chain for the next few weeks. Generic perindopril will continue to be the erbumine salt and prescriptions for generic perindopril are not affected. New from NICE Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guidance No. 63, March 2008 This clinical guideline focuses on additional aspects of care for women with gestational diabetes (88 per cent of cases) or pre-existing diabetes (of which about 40 per cent is type 2 diabetes) and their babies. To date, insulin aspart (NovoRapid) is the only drug in the guideline specifically licensed for use in pregnancy and NICE advises obtaining informed consent to implement its recommendations for using other insulins and oral hypoglycaemic agents. As with other guidelines, NICE begins by stressing the importance of patient-centred care and involving women in decisions about their treatment. The guideline is divided into six sections, dealing with consecutive periods of pregnancy. Preconceptual planning should include empowering women to help them reduce risks, optimising glycaemic control (after retinal assessment) and increasing monitoring intensity, and providing information about the effects of pregnancy on diabetes. Metformin may be recommended as an adjunct or alternative to insulin, but other oral hypoglycaemic agents should be replaced with insulin, although glibenclamide is an option during pregnancy. Isophane insulin is the preferred long-acting insulin; lispro (Humalog) and aspart are considered safe to use. ACE inhibitors and angiotensin-II receptor blockers should be replaced with other antihypertensive agents and statins should be discontinued. Recommendations for screening and treatment of gestational diabetes build on previous guidance (CG62). Drug treatment will be needed by 10-20 per cent , this includes insulin (soluble, aspart or lispro) and/or metformin or glibenclamide, tailored to individual need. Antenatal care includes optimising glycaemic control. Insulin lispro or aspart should be considered in preference to soluble insulin. If glycaemic control cannot be achieved with insulin injections, an insulin pump may be indicated. The guideline includes a timetable for appointments and the care that should offered after each interval. Recommendations for intrapartum care, which supplement those in CG55, include frequent monitoring of blood glucose. Neonatal care includes recommendations for monitoring and screening the infant and the management of hypoglycaemia. Postnatal care (supplementing CG37) involves adjusting maternal treatment to avoid hypoglycaemia and recommendations for returning to community care. Metformin and glibenclamide are the only oral agents suitable for breastfeeding women. Women with gestational diabetes need advice about glycaemic control and planning for future pregnancies. Lifestyle advice and measurement of annual fasting plasma glucose should be offered. Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. Technology Appraisal No. 138, March 2008 The latest technology appraisal of asthma treatments covers inhaled steroids for adults and children over 12 with chronic asthma. It makes only two recommendations. First, the cheapest appropriate option is recommended. Second, when a steroid and a long-acting beta2-agonist are indicated, the decision to prescribe a combined inhaler or separate devices should take into account therapeutic need and likely adherence. Combined inhalers are currently less expensive than separate devices, though they may not remain so. When a combined inhaler is chosen it should be the cheapest. NICE concludes that, at equivalent doses, there is little difference in the effectiveness or adverse event profile of the available steroids or the fixed-dose combinations. According to specialist advice, choosing the best device for an individual remains the overriding concern. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. Technology Appraisal No. 139, March 2008 NICE recommends continuous positive airway pressure (CPAP) for adults with moderate or severe obstructive sleep apnoea, and for those with a milder disorder if quality of life and functioning are impaired and alternative strategies such as lifestyle change have failed. Diagnosis and treatment is the responsibility of a specialist team. A CPAP device costs £250-£550 and lasts for seven years. Copyright © 2008 Wiley Interface Ltd [source] ORIGINAL ARTICLE: Effects of Cyclic Versus Sustained Estrogen Administration on Peripheral Immune Functions in Ovariectomized MiceAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Jing Li Citation Li J, McMurray RW. Effects of cyclic versus sustained estrogen administration on peripheral immune functions in ovariectomized mice. Am J Reprod Immunol 2010; 63: 274,281 Problem, Estrogens have multiple influences on immune functions. We aimed to compare the effects of cyclic versus sustained estrogen treatments under the same accumulated dose on peripheral immune functions in ovariectomized mice. Method of study, Ovariectomized adult Balb/c mice were treated with estradiol (E2) by s.c. injection once every 4 days (total 44.8 ,g) or by pellet implantation (total 44.2 ,g). After 6 weeks of treatment, all animals were immunized with DNP-KLH. Peripheral immune functions were assessed 10 days later. Results, Both cyclic and sustained E2 treatments significantly reduced the percentage of splenic B220+sIgM+ cells, enhanced IFN-, production and suppressed IL-6 secretion from Con A-stimulated splenocytes, and increased serum anti-DNP antibody levels. No differences were found in the above responses or in uterine weight gain between the two regimens of E2 administration. Conclusion, There are no differential effects on peripheral immune functions between cyclic and sustained estrogen administration under the same total dose. [source] Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of torasemide in rabbitsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2004Yu C. Kim Abstract The pharmacokinetics and pharmacodynamics of torasemide were evaluated after intravenous administration of the same total dose of torasemide at a dose of 1mg/kg to rabbits with different infusion times, 1 min (treatment I), 30 min (treatment II) and 2 h (treatment III). The loss of water and electrolytes in urine induced by torasemide was immediately replaced with infusion of an equal volume of lactated Ringer's solution. All the pharmacokinetic parameters of torasemide, such as total area under the plasma concentration,time curve from time zero to time infinity (AUC), total body clearance (CL), apparent volume of distribution at steady state (Vss), terminal half-life and mean residence time (MRT), were independent of infusion times. However, the 8h urine output (235, 534 and 808 ml) and 8h urinary excretion of sodium (24.2, 80.1 and 89.2 mmol) and chloride (27.1, 89.2 and 94.0 mmol) were significantly greater in treatments II and III than those in treatment I, although the total 8 h urinary excretion of unchanged torasemide (1210, 1210 and 1310 µg) were not significantly different among the three treatments. This could be due to the higher diuretic efficiencies in treatments II and III. Copyright © 2004 John Wiley & Sons, Ltd. [source] |