Home About us Contact
|
Home About us Contact | ||
|
|
||
Oral Agents (oral + agent)
Selected AbstractsPX-478, an inhibitor of hypoxia-inducible factor-1,, enhances radiosensitivity of prostate carcinoma cells,INTERNATIONAL JOURNAL OF CANCER, Issue 10 2008Sanjeewani T. Palayoor Abstract Overexpression of hypoxia-inducible factor-1, (HIF-1,) in human tumors is associated with poor prognosis and poor outcome to radiation therapy. Inhibition of HIF-1, is considered as a promising approach in cancer therapy. The purpose of this study was to test the efficacy of a novel HIF-1, inhibitor PX-478 as a radiosensitizer under normoxic and hypoxic conditions in vitro. PC3 and DU 145 prostate carcinoma cells were treated with PX-478 for 20 hr, and HIF-1, protein level and clonogenic cell survival were determined under normoxia and hypoxia. Effects of PX-478 on cell cycle distribution and phosphorylation of H2AX histone were evaluated. PX-478 decreased HIF-1, protein in PC3 and DU 145 cells. PX-478 produced cytotoxicity in both cell lines with enhanced toxicity under hypoxia for DU-145. PX-478 (20 ,mol/L) enhanced the radiosensitivity of PC3 cells irradiated under normoxic and hypoxic condition with enhancement factor (EF) 1.4 and 1.56, respectively. The drug was less effective in inhibiting HIF-1, and enhancing radiosensitivity of DU 145 cells compared to PC3 cells with EF 1.13 (normoxia) and 1.25 (hypoxia) at 50 ,mol/L concentration. PX-478 induced S/G2M arrest in PC3 but not in DU 145 cells. Treatment of PC3 and DU 145 cells with the drug resulted in phosphorylation of H2AX histone and prolongation of ,H2AX expression in the irradiated cells. PX-478 is now undergoing Phase I clinical trials as an oral agent. Although the precise mechanism of enhancement of radiosensitivity remains to be identified, this study suggests a potential role for PX-478 as a clinical radiation enhancer. Published 2008 Wiley-Liss, Inc. [source] Prospective evaluation of the management of moderate to severe cellulitis with parenteral antibiotics at a paediatric day treatment centreJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 4 2008Serge Gouin Aim: To assess the clinical outcome of patients with moderate to severe cellulitis managed at a paediatric day treatment centre (DTC). Methods: Prospective observational study of all patients (3 months to 18 years) with a presumed diagnosis of moderate to severe cellulitis made in a university-affiliated paediatric emergency department (ED) (September 2003 to September 2005). Patients treated at the DTC were given ceftriaxone or clindamycin. Results: During the study period, a presumed diagnosis of moderate to severe cellulitis was made in 224 patients in the ED. Ninety-two patients were treated at the DTC (41%). The cellulitis had a median width of 7.0 cm (range: 1.0,50.0 cm) and a median length of 6.5 cm (range: 1.0,40.0 cm). Blood cultures were performed in 95.7%; one was positive for Staphylococcus aureus. After a mean of 2.5 days of intravenous therapy (first injection in the ED and a mean of 1.5 days at the DTC), 73 patients (79.3%) were successfully discharged from the DTC and switched to an oral agent. For these patients no relapse occurred. Nineteen patients (20.7%) required inpatient admission for further therapy. No patient was diagnosed with necrotizing fasciitis in the course of therapy. Seventy-eight satisfaction questionnaires were handed in and revealed very good to excellent parental satisfaction with treatment at the DTC in 94.8%. Conclusion: Treatment with parenteral antibiotic at a DTC is a viable alternative to hospitalisation for moderate to severe cellulitis in children. [source] Review article: current antiviral therapy of chronic hepatitis BALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2008W. S. AYOUB Summary Background, The long-term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of cirrhosis and hepatocellular carcinoma. Aim, To review the current treatment of chronic hepatitis B, with a focus on diagnosis and management of resistance and active management of suboptimal responses. Methods, A systematic review of the literature, with a focus on recent guidelines, was undertaken. Results, Among the six drugs licensed for the treatment of chronic hepatitis B in the US, the preferred agents in 2008 will include entecavir, peginterferon alfa-2a, possibly telbivudine, and tenofovir following licensure. When using an oral agent, a major focus of management is on the selection of a drug with high potency and low rate of resistance, and active on-treatment management to optimize therapy. Preventing the sequelae of antiviral drug resistance and appropriate management when resistance is initially detected are also the major focus of current management. The addition of an antiviral agent that is not cross-resistant is critical to restore suppression of viral replication. Conclusions, Newer agents and modified treatment strategies, especially using combination therapy, hold promise to optimize the management of patients with chronic hepatitis B by achieving the high potency and the lowest rate of resistance. [source] Exenatide: a review from pharmacology to clinical practiceDIABETES OBESITY & METABOLISM, Issue 6 2009R. Gentilella Background:, Exenatide is an incretin mimetic that activates glucagon-like-peptide-1 receptors. It blunts the postprandial rise of plasma glucose by increasing glucose-dependent insulin secretion, suppressing inappropriately high glucagon secretion and delaying gastric emptying. Methods:, In seven clinical trials performed in 2845 adult patients with type 2 diabetes mellitus who were inadequately controlled by a sulphonylurea and/or metformin (glycosylated haemoglobin, HbA1c ,11%), or by thiazolidinediones (with or without metformin) and treated for periods from 16 weeks to 3 years, exenatide (5 ,g b.i.d. s.c. for the first 4 weeks of treatment and 10 ,g b.i.d. s.c. thereafter) reduced HbA1c, fasting and postprandial glucose, and body weight dose dependently, and was similar to insulin glargine and biphasic insulin aspart in reducing HbA1c. Body weight diminished with exenatide, whereas it increased with both insulin preparations. Positive effects on the lipid profile and a reduction in C-reactive protein were also recorded with exenatide. Treatment extensions up to 3 years showed that benefits were maintained in the long term. Adverse events were usually mild to moderate in intensity, and generally the frequency decreased with continued therapy. The most common was nausea (whose incidence may be reduced by gradual dose escalation from 5 ,g b.i.d. to 10 ,g b.i.d.), vomiting, diarrhoea, headache and hypoglycaemia (almost exclusively in patients treated with a sulphonylurea). Results and conclusions:, Exenatide is a new, promising therapeutic option for type 2 diabetic patients inadequately controlled by oral agents, before insulin therapy, offering the added benefits of body weight reduction and tight postprandial glucose control. [source] Insulin therapy in type 2 diabetes patients failing oral agents: cost-effectiveness of biphasic insulin aspart 70/30 vs. insulin glargine in the US,DIABETES OBESITY & METABOLISM, Issue 1 2007J. A. Ray Objectives:, To project the long-term clinical and economic outcomes of treatment with biphasic insulin aspart 30 (BIAsp 70/30, 30% soluble and 70% protaminated insulin aspart) vs. insulin glargine in insulin-naïve type 2 diabetes patients failing to achieve glycemic control with oral antidiabetic agents alone (OADs). Methods:, Baseline patient characteristics and treatment effect data from the recent ,INITIATE' clinical trial served as input to a peer-reviewed, validated Markov/Monte-Carlo simulation model. INITIATE demonstrated improvements in HbA1c favouring BIAsp 70/30 vs. glargine (,0.43%; p < 0.005) and greater efficacy in reaching glycaemic targets among patients poorly controlled on OAD therapy. Effects on life expectancy (LE), quality-adjusted life expectancy (QALE), cumulative incidence of diabetes-related complications and direct medical costs (2004 USD) were projected over 35 years. Clinical outcomes and costs were discounted at a rate of 3.0% per annum. Sensitivity analyses were performed. Results:, Improvements in glycaemic control were projected to lead to gains in LE (0.19 ± 0.24 years) and QALE (0.19 ± 0.17 years) favouring BIAsp 70/30 vs. glargine. Treatment with BIAsp 70/30 was also associated with reductions in the cumulative incidences of diabetes-related complications, notably in renal and retinal conditions. The incremental cost-effectiveness ratio was $46 533 per quality-adjusted life year gained with BIAsp 70/30 vs. glargine (for patients with baseline HbA1c , 8.5%, it was $34 916). Total lifetime costs were compared to efficacy rates in both arms as a ratio, which revealed that the lifetime cost per patient treated successfully to target HbA1c levels of <7.0% and , 6.5% were $80 523 and $93 242 lower with BIAsp 70/30 than with glargine, respectively. Conclusions:, Long-term treatment with BIAsp 70/30 was projected to be cost-effective for patients with type 2 diabetes insufficiently controlled on OADs alone compared to glargine. Treatment with BIAsp 70/30 was estimated to represent an appropriate investment of healthcare dollars in the management of type 2 diabetes. [source] Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof-of-concept studyDIABETES OBESITY & METABOLISM, Issue 5 2006M. Hausmann Aim:, This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes. Methods:, Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 ± 6.6 years, body mass index 32.7 ± 4.2 kg/m2, glycosylated haemoglobin (HbA1c) 8.4 ± 0.8% (mean ± s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets. Results:, INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (,2.7 vs. ,3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (,1.23 vs. ,1.05%), body weight (,1.9 vs. ,2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (,1.15 ,mol/l; p < 0.001) but not with GLA [,0.52 ,mol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation. Conclusions:, In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies. [source] Unlocking the opportunity of tight glycaemic controlDIABETES OBESITY & METABOLISM, Issue 2005Inhaled insulin: clinical efficacy Numerous attempts have been made to develop novel routes of insulin delivery that are both effective and tolerable. Of all the potential non-invasive delivery options, pulmonary delivery is the most clinically viable. Early studies demonstrate that the inhaled insulin is rapidly absorbed and is closer to biological insulin than standard subcutaneous insulin (SC). To date, inhaled insulin (Exubera®) has been clinically assessed in more than 3500 patients with type 1 or type 2 diabetes, some treated for more than 7 years. Several phase 3 studies of 24-week duration have demonstrated comparable glycosylated haemoglobin (HbA1c) control in patients with type 1 diabetes treated with Exubera® vs. SC insulin. Similar results have also been recorded in patients with type 2 diabetes. Furthermore, Exubera® has shown clinical superiority to oral agent regimens in patients with type 2 diabetes who failed to achieve their target HbA1c using lifestyle modification and oral agents. Exubera® was well tolerated and treatment satisfaction was high, with Exubera® being the preferred insulin therapy in all studies. The results of these trials, and others, suggest that Exubera® may be a valuable tool to help a wide variety of patients with type 1 or type 2 diabetes reach their recommended goals for glycaemic control, irrespective of their current therapy. [source] Differential effects of short and long duration insulinotropic agents on meal-related glucose excursionsDIABETES OBESITY & METABOLISM, Issue 2 2001C. J. De Souza SUMMARY Aim Abnormal ,-cell function, characterized as the inability of the ,-cell to mount a rapid secretory response to glucose, is a well-established pathology of type 2 diabetes mellitus. These studies were designed to demonstrate the importance of early insulin release on the control of meal-induced glucose excursions by capitalizing on the significant pharmacodynamic differences between several oral insulin secreting agents. Methods Male Sprague Dawley fitted with indwelling jugular cannulas were used to compare the pharmacodynamic profiles of nateglinide (Nateg), glipizide (Glip) and repaglinide (Repag) through frequent blood samples following the administration of these compounds via oral gavage. In similar animals which were pretrained to consume their daily food intake in two discrete 45-min meals, the effects of compound induced changes in pre-meal, meal and post-meal insulin profiles on glycaemic control were assessed through frequent blood sampling following the administration of these compounds 10 min prior to a 30-min meal. Results There were significant pharmacodynamics differences between the three oral agents tested and the time to elicit peak insulin secretory responses increased from Nateg (4 min) to Repag (10 min) to Glip (45 min). During the meal tolerance test, glibenclamide did not increase pre-meal insulin levels and glucose excursions paralleled those in the control. Conversely, the other three agents, at doses that produced hypoglycaemic responses of similar magnitude, all increased early insulin release (,AUC(-15 to 3 min) = 0.5 ± 0.01, 1.6 ± 0.4, 3.6 ± 0.0, 1.2 ± 0.1 and 1.73 ± 0.4 nmol/min, for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively) and curbed glucose excursions during the meal at varying rates and degrees (,AUC(0,30 min) = 39 ± 6, 8 ± 7, 5 ± 7, ,,1 ± 8 and ,,3 ± 8 mmol/min for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively). However, unlike Nateg, the longer duration of action of Repag and Glip elicited sustained post-meal relative hypoglycaemia. Conclusion These data support the impact of early and rapid insulin release in the control of prandial and post-meal glycaemia and demonstrate that a short anticipatory burst of insulin, restricted to the beginning of a meal, provides a clear metabolic advantage and prevents post-meal hypoglycaemic episodes when compared to a greater but reactive insulin exposure that follows a meal-induced increase in glucose excursion. [source] ,-cell preservation: a potential role for thiazolidinediones to improve clinical care in Type 2 diabetesDIABETIC MEDICINE, Issue 8 2005L. A. Leiter Abstract Type 2 diabetes is caused by progressively increasing insulin resistance coupled with deteriorating ,-cell function, and there is a growing body of evidence to suggest that both of these defects precede hyperglycaemia by many years. Several studies have demonstrated the importance of maintaining ,-cell function in patients with Type 2 diabetes. This review explores parameters used to indicate ,-cell dysfunction, in Type 2 diabetes and in individuals with a predisposition to the disease. A genetic element undoubtedly underlies ,-cell dysfunction; however, a number of modifiable components are also associated with ,-cell deterioration, such as chronic hyperglycaemia and elevated free fatty acids. There is also evidence for a link between pro-inflammatory cytokines and impairment of insulin-signalling pathways in the ,-cell, and the potential role of islet amyloid deposition in ,-cell deterioration continues to be a subject for debate. The thiazolidinediones are a class of agents that have demonstrated clinical improvements in indices of ,-cell dysfunction and have the potential to improve ,-cell function. Data are accumulating to show that this therapeutic group offers a number of advantages over traditionally employed oral agents, and these data demonstrate the growing importance of thiazolidinediones in Type 2 diabetes management. [source] The backbone of oral glucose-lowering therapy: time for a paradigm shift?FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2009Jochen Seufert Abstract The complex array of metabolic abnormalities associated with type 2 diabetes provides a number of new targets for therapeutic intervention. Although the established oral glucose-lowering therapies, metformin and the sulfonylureas, continue to provide the backbone of therapeutic approaches, the thiazolidinediones (TZDs) also play an important role. Further, a new class of oral agents, the dipeptidyl peptidase-IV (DPP-IV) inhibitors, has recently become available with apparent utility in decreasing postprandial glucose excursions. This review examines how the TZDs and the DPP-IV inhibitors might integrate into current treatment strategies, considering not only glycemic goals, but also longer-term benefits such as durability of glycemic control, effect on metabolic parameters and cardiovascular outcomes. A practical approach is taken, reflecting potential clinical situations in which therapeutic intervention is required. [source] Liraglutide: can it make a difference in the treatment of type 2 diabetes?INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2010J. Unger Summary Despite advances in the management of type 2 diabetes, glycaemic control remains suboptimal for many patients because of the complexities of disease progression and the need to balance improved glycaemic control against adverse treatment effects, particularly weight gain and hypoglycaemia. Thus, the development of new antidiabetes therapies continues in earnest. Incretin hormones have been the recent focus of research, as they account for up to 70% of the insulin response following a meal. There is also a high concordance between the physiological actions of one hormone, glucagon-like peptide-1 (GLP-1), and the therapeutic needs of patients. As native human GLP-1 has a half life of only approximately 2 min, researchers have developed molecules that act as GLP-1 receptor agonists or inhibit the enzyme responsible for GLP-1 degradation (dipeptidyl peptidase-4). Liraglutide, a human GLP-1 analogue sharing 97% of its amino acid sequence identity with native GLP-1, has been approved for use as monotherapy (not in Europe) and in combination with selected oral agents. In this supplement, we summarise key liraglutide data, offer practical insight into what we might expect of liraglutide in clinical use and examine selected case studies. For reasons of the safety and efficacy of GLP-1 receptor agonists, many thought leaders believe that these will become background therapy for majority of patients in the coming years. This supplement will serve as a resource from which readers can extract information concerning the potential benefits for patients who are overweight, losing pancreatic beta-cell function and drifting towards the ravaging effects of chronic hyperglycaemia. [source] Ionic Basis of Pharmacological Therapy in Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2007MANLIO F. MÁRQUEZ M.D. An implantable cardioverter-defibrillator is considered the only effective therapy to terminate ventricular arrhythmias in symptomatic patients with Brugada syndrome. However, it does not prevent future arrhythmic episodes. Only antiarrhythmic drug therapy can prevent them. There have been several reports of a beneficial effect of oral quinidine in both asymptomatic and symptomatic patients. Other possible beneficial oral agents could be Ito blockers. Intravenous isoproterenol has been reported to be especially useful in abolishing arrhythmic storms in emergency situations. Also, isolated case reports on the usefulness of cilostazol, sotalol, and mexiletine have been described. The present article reviews the mechanisms by which these drugs may act and their possible role in the pharmacotherapy of this disease. [source] Topical antifungal drugs for the treatment of onychomycosis: an overview of current strategies for monotherapy and combination therapyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2005R Baran ABSTRACT Background, Onychomycosis is a relatively common disease accounting for up to 50% of all nail disorders and its prevalence rises with age. As onychomycosis is an important medical disorder affecting both patient's health and quality of life, it requires prompt and effective treatment. Objective, Topical antifungal nail lacquers have been formulated to provide efficient delivery to the nail unit. As both amorolfine and ciclopirox have proved useful as monotherapy for onychomycosis that does not involve the nail matrix area, the purpose of this article is to check if, when combined with oral agents, the effectiveness and scope of treatment can be improved further. Methods, Combining data for mycological cure with clinical success (nail morphology) provides a more exacting efficacy measure. Results, Clinical investigations have shown that the combination of oral therapies with antifungal nail lacquer can confer considerable advantage over monotherapy with either drug type. Conclusion, The improved effectiveness and economic advantages of combined topical/oral therapies benefit both patients and health providers; these treatment regimens therefore have an important role to play in the modern management of onychomycosis. [source] Review article: pharmacological therapy for hepatocellular carcinoma with sorafenib and other oral agentsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2008M. CHAPARRO Summary Background, Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Unresectable disease patients have median survival of few months. There is a substantial need for novel treatments for patients with advanced HCC. Aim, To provide an update review of mechanism of hepatocarcinigenesis and systemic therapies for HCC and the relevant role of Sorafenib in patients with advanced disease. Methods, A Medline search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated. Results, Systemic chemotherapy for HCC has been quite ineffective. Preclinical studies demonstrated that Raf/MAPK-ERK kinase (MEK)/Extracellular signal regulated kinase (ERK) pathway has a role in HCC. HCC tumours are highly vascularized and vascular endothelial growth factor (VEGF) augments HCC development and metastasis. Sorafenib blocks tumour cell proliferation by targeting Raf/MEK/ERK signalling and exerts an antiangiogenic effect by targeting VEGF receptors-2/3 and platelet derived growth factor receptor , tyrosine kinases. Conclusions, Currently available therapies are not effective for patients with advanced HCC. Sorafenib has demonstrated for the first time to prolong survival in patients with advanced HCC, and it is the new reference standard for systemic treatment in these patients. [source] Liraglutide: new GLP-1 analogue for uncontrolled type 2 diabetesPRESCRIBER, Issue 23-24 2009MRPharmS, Steve Chaplin MSc Liraglutide (Victoza) is a new GLP-1 analogue given by once-daily injection for the treatment of type 2 diabetes not controlled by mono- or dual therapy with oral agents. In our New products review, Steve Chaplin presents the clinical data relating to its efficacy and adverse effects, and Dr Aftab Ahmad considers its potential place in therapy. Copyright © 2009 Wiley Interface Ltd [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] Teleconferenced educational detailing: Diabetes education for primary care physiciansTHE JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS, Issue 2 2005FACPM, Stewart B. Harris MD Abstract Introduction: Formal didactic continuing medical education (CME) is relatively ineffective for changing physician behaviur. Diabetes mellitus is an increasingly prevalent disease, and interventions to improve adherence to clinical practice guidelines (CPGs) are needed. Methods: A stratified, cluster-randomized, controlled trial design was used to evaluate the effects of a teleconferenced educational detailing (TED) CME on glycemic control (hemoglobin [Hb] A1c) and family physician adherence to national diabetes guidelines. TED employed sequential, small-group, case-based education using CPGs delivered by a diabetes specialist. Medical record audit data from baseline through the end of a 12-month postintervention period were compared for the control and intervention groups. Satisfaction with the intervention was evaluated. Results: Sixty-one physicians provided 660 medical records. The intervention did not affect mean Hb A1c levels but did significantly (p = .04) alter the distribution of patients by category of glycemic control, with fewer in the intervention group in inadequate control (15.8% versus 23.9%). More patients took insulin (alone or with oral agents) in the intervention group (21.2% versus 12.0%, p = .03), and more took oral agents only in the control group (89.0% versus 82.9%, p = .005). More patients in the intervention group had documentation of body mass index (7.8% versus 1.9%, p < .02), eye exam (12.1% versus 5.1%, p = .02), and treatment plan (43.5% versus 23.6%, p = .01) and used a flow sheet (14.6% versus 7.7%, p < .03). Although there was general satisfaction with the teleconferencing format, specialist educators found the format more challenging than the family physicians. Discussion: CME delivered by teleconference was feasible, well attended, well received by participants, and improved some key diabetes management practices and outcomes. [source] A randomized, single-blind comparison of topical clindamycin + benzoyl peroxide and adapalene in the treatment of mild to moderate facial acne vulgarisBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2008A. Langner Summary Background, Antibiotics are often combined with other agents to provide topical acne treatments that are effective against both inflammatory and noninflammatory lesions and minimize the development of antibiotic resistance. Retinoids and associated treatments also have anti-inflammatory activity and decrease microcomedo formation. To date, few direct comparisons of these different acne treatments have been conducted. Objectives, To compare the clinical effectiveness of two treatments for facial acne: a ready-mixed once-daily gel containing clindamycin phosphate 10 mg mL,1 + benzoyl peroxide 50 mg mL,1 (CDP + BPO; Duac®; Stiefel, High Wycombe, U.K.) and a once-daily gel containing adapalene 0·1% (ADA; Differin®; Galderma, Watford, U.K.). Methods, In this assessor-blind, randomized study; 65 patients were treated with CDP + BPO once daily and 65 patients with ADA once daily. The treatment period was 12 weeks and lesion counts, acne grade and global improvement were assessed at weeks 1, 2, 4, 8 and 12. Results, CDP + BPO showed an earlier onset of action with a faster significant reduction in inflammatory and total lesion counts than ADA. A between-group comparison of the percentage change from baseline showed that CDP + BPO was statistically significantly superior to ADA from week 1 onwards both for inflammatory lesions (P , 0·001) and for total lesions (P , 0·004). While 76% of inflammatory lesions remained at week 2 for patients using ADA, in contrast, only 55% of inflammatory lesions remained at week 2 in the CDP + BPO group, resulting in a treatment effect of 1·38. Thus CDP + BPO removed 38% more inflammatory lesions than ADA at this timepoint. The trend in favour of CDP + BPO, although less marked, continued to the end of the study. CDP + BPO was better tolerated than ADA, with a greater proportion of ADA-treated patients experiencing treatment-related adverse events. Adjunctive topical or oral agents and their impact on acne were not studied in this trial. Due to product differences, this study could not be double blinded but was only single (assessor) blinded. Conclusions, CDP + BPO and ADA are both effective treatments for acne, but CDP + BPO has a significantly earlier onset of action, is significantly more effective against inflamed and total lesions and is better tolerated, which should improve patient compliance. [source] | ||||||||||||||||||||||