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Large Trials (large + trials)
Selected AbstractsTreatment of CML in pediatric patients: Should imatinib mesylate (STI-571, Gleevec) or allogeneic hematopoietic cell transplant be front-line therapy?PEDIATRIC BLOOD & CANCER, Issue 5 2004Michael A. Pulsipher MD Abstract Background Long-term survival of pediatric patients with chronic myelogenous leukemia (CML) receiving myeloablative hematopoietic stem cell transplantation from fully-matched related and unrelated donors has been reported between 60 and 75%, but is associated with significant morbidity. Imatinib mesylate (STI-571, Gleevec) and reduced intensity conditioning stem cell transplantation (RIC) are two promising new tools that offer potential for decreasing therapy associated morbidity for patients with CML. Results Large trials have shown significant responses in chronic phase patients treated with imatinib and reasonable but short-lived responses in advanced phase CML. Data from adult studies is beginning to define populations likely to progress or have prolonged responses to imatinib, and some adult treatment paradigms are moving toward reserving transplantation until patients are at risk of failure with imatinib. Early trials of RIC transplantation in CML show decreased transplant related morbidity with efficacy similar to conventional transplantation, but the approach has yet to be verified in phase III studies. Data in pediatric patients with imatinib and RIC transplantation is limited. Conclusions Studies with imatinib are underway in pediatrics, but whether pediatric dosing schemes will lead to outcomes similar to adults is unknown. Because HLA-matched myeloablative transplantation offers a high rate of cure in the pediatric population, clinical studies assessing the role of imatinib mesylate and RIC transplantation should be planned carefully in order to avoid sub-optimal outcomes. © 2004 Wiley-Liss, Inc. [source] Cutting through the statistical fog: understanding and evaluating non-inferiority trialsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2010W. S. Weintraub Summary Every year, results from many important randomised, controlled trials are published. Knowing the elements of trial design and having the skills to critically read and incorporate results are important to medical practitioners. The goal of this article is to help physicians determine the validity of trial conclusions to improve patient care through more informed medical decision making. This article includes a review of 162 randomised, controlled non-inferiority (n = 116) and equivalence (n = 46) hypothesis studies as well as the larger Stroke Prevention using Oral Thrombin Inhibitor in atrial Fibrillation V study and the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial. Evaluation of data from small and large trials uncovers significant flaws in design and models employed and uncertainty about calculations of statistical measures. As one example of questionable study design, discussion includes a large (n = 3922), double-blind, randomised, multicentre trial comparing the efficacy of ximelagatran with warfarin for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and additional stroke risk factors. Investigators concluded that ximelagatran was effective compared with well-controlled warfarin for prevention of thromboembolism. However, deficiencies in design, as well as concerns about liver toxicity, resulted in the rejection of the drug by the US Food and Drug Administration. Many trials fail to follow good design principles, resulting in conclusions of questionable validity. Well-designed non-inferiority trials can provide valuable data and demonstrate efficacy for beneficial new therapies. Objectives and primary end-points must be clearly stated and rigorous standards met for sample size, establishing the margin, patient characteristics and adherence to protocol. [source] Stent-protected angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy: SPACE2 , a three-arm randomised-controlled clinical trialINTERNATIONAL JOURNAL OF STROKE, Issue 4 2009T. Reiff Moderate to severe (,70%) asymptomatic stenosis of the extracranial carotid artery leads to an increased rate of stroke of approximately 11% in 5 years. Patients with asymptomatic carotid stenosis, however, are also at a higher risk of nonstroke vascular events. The estimated annual risks of such events in patients with asymptomatic stenosis are 7% for a coronary ischaemic event and 4,7% for overall mortality. The superiority of carotid endarterectomy compared with medical treatment in symptomatic carotid disease is established, provided that the surgical procedure can be performed with a perioperative morbidity and mortality of <6%. The advantage of carotid endarterectomy for asymptomatic patients is less established. An alternative treatment, carotid artery stenting, has been developed. This treatment is used frequently in both symptomatic and asymptomatic patients. In the last decade, major advantages in medical primary prevention of cerebrovascular and cardiovascular disease have been accomplished. The control groups in the large trials for asymptomatic carotid artery disease (ACAS and ACST) originate from more than a decade ago and, for the most part, have not received a medical primary prevention strategy that would now be considered the standard according to current national and international guidelines. For this reason, a three-arm trial (SPACE2; http://www.space-2.de) with a hierarchical design and a recruitment target of 3640 patients is chosen. Firstly, a superior trial of intervention (carotid artery stenting or carotid endarterectomy) vs. state-of-the-art conservative treatment is designed. In case of superiority of the interventions, a noninferiority end-point will be tested between carotid artery stenting and carotid endarterectomy. This trial is registered at Current Controlled Trials ISRCTN 78592017. [source] Medical management of patients with aneurysmal subarachnoid haemorrhageINTERNATIONAL JOURNAL OF STROKE, Issue 3 2008Gabriel J. E. Rinkel Abstract Treating patients with aneurysmal subarachnoid haemorrhage is taking care of acutely ill patients, and should be performed in centres where a multidisciplinary team is available 24 hours a day 7 days a week, and where enough patients are managed to maintain and improve standards of care. There is no medical management that improves outcome by reducing the risk of rebleeding, therefore occlusion of the aneurysm, nowadays preferably by means of coiling, remains an important goal in treating patients with aneurysms. Because the poor outcome after subarachnoid haemorrhage is caused to a large extent by complications other than rebleeding, proper medical management to prevent and treat these complications is therefore essential. On basis of the available evidence, oral (not intravenous) nimodipine should be standard care in patients with subarachnoid haemorrhage. It is rational to refrain from treating hypertension unless cardiac failure develops and to aim for normovolaemia, even in case of hyponatraemia. There is no evidence for prophylactic hypervolaemia, and the strategy of hypervolaemia and hypertension in patients with secondary cerebral ischaemia is based on case reports and uncontrolled observational series of patients. Magnesium sulphate and statins are promising therapies, and large trials on effectiveness in improving clinical outcome are underway. There is no evidence for prophylactic use of anti epileptic drugs, and routine use of corticosteroids should be avoided. [source] Evidence-based medicine: Review of guidelines and trials in the prevention of secondary stroke,JOURNAL OF HOSPITAL MEDICINE, Issue S4 2008David J. Likosky MD Abstract Transient ischemic attack (TIA) carries a substantial short-term risk for stroke, which is a leading cause of disability and death in the United States. Despite the existing evidence-based guidelines for secondary prevention of stroke, variability in the assessment, diagnostic testing, and treatment of patients with TIA in actual clinical practice remains. Identification of stroke etiology via radiological examination is of paramount importance for the appropriate treatment of patients after TIA or stroke. Management of ischemic stroke or TIA includes lifestyle modifications, reduction of modifiable risk factors (eg, hypertension, diabetes, and elevated cholesterol), and appropriate therapeutic treatments. Antiplatelet therapy is the cornerstone of secondary prevention of stroke; guidelines for its use for noncardioembolic cases have been developed from a solid evidence base. Additional therapeutic approaches include HMG-CoA reductase inhibitors (statins), antihypertensives, and anticoagulants. The results of ongoing large trials will further clarify the role of specific antiplatelet agents for the secondary prevention of stroke in patients with noncardioembolic ischemic stroke or TIA. Journal of Hospital Medicine 2008;3(4 Suppl):S6,S19. © 2008 Society of Hospital Medicine. [source] A systematic review of multivitamin and multimineral supplementation for infectionJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 3 2006A. I. Stephen Abstract Background, Infections are major causes of morbidity and mortality worldwide. Micronutrients have important functions in the body's immune system. This systematic review examined the evidence from randomized controlled trials (RCTs) on whether multivitamin and multimineral supplementation is effective in reducing infection. Methods, Electronic databases searched: Cochrane Controlled Trials Register, EMBASE, MEDLINE, BIOSIS, CAB abstracts. Hand searching of nutrition journals and reference lists was carried out. RCTs and quasi-randomized trials of supplementation of adults with at least two vitamins or minerals or a combination were selected. Study results were combined in meta-analysis plots where appropriate. Results, Twenty studies were included in the review. Small numbers were available for each meta-analysis. Results are presented here without the Chandra group studies. No significant difference was found in the number of episodes of infection in older people (,65 years) between those supplemented and those not supplemented; (WMD) 0.06 [95% confidence interval (CI) ,0.04, 0.16], P = 0.25. In other adults groups, there were significantly less episodes of infection in those supplemented; (WMD) ,1.20 (95% CI ,2.08, ,0.32), P = 0.008. There was no significant difference between those older people supplemented and those not supplemented in the number with at least one infection; relative risk (RR) 0.98 (95% CI 0.86, 1.11), P = 0.77. Similarly, there was no significant difference in the numbers in other adult groups who had at least one episode of infection between those supplemented and those taking placebo; (RR) 0.81 (95% CI 0.65, 1.00), P = 0.06. Subgroup analyses suggested that supplemented people aged 65 years or over may benefit more if they are undernourished and supplemented for over 6 months, WMD ,0.67 infections (95% CI ,1.24, ,0.10), P = 0.02. Conclusion, Further large trials are needed, particularly in undernourished older people. Trials of supplementation periods of over 6 months are recommended. [source] Is the placebo powerless?JOURNAL OF INTERNAL MEDICINE, Issue 2 2004Update of a systematic review with 52 new randomized trials comparing placebo with no treatment Abstract. Background., It is widely believed that placebo interventions induce powerful effects. We could not confirm this in a systematic review of 114 randomized trials that compared placebo-treated with untreated patients. Aim., To study whether a new sample of trials would reproduce our earlier findings, and to update the review. Methods., Systematic review of trials that were published since our last search (or not previously identified), and of all available trials. Results., Data was available in 42 out of 52 new trials (3212 patients). The results were similar to our previous findings. The updated review summarizes data from 156 trials (11 737 patients). We found no statistically significant pooled effect in 38 trials with binary outcomes, relative risk 0.95 (95% confidence interval 0.89,1.01). The effect on continuous outcomes decreased with increasing sample size, and there was considerable variation in effect also between large trials; the effect estimates should therefore be interpreted cautiously. If this bias is disregarded, the pooled standardized mean difference in 118 trials with continuous outcomes was ,0.24 (,0.31 to ,0.17). For trials with patient-reported outcomes the effect was ,0.30 (,0.38 to ,0.21), but only ,0.10 (,0.20 to 0.01) for trials with observer-reported outcomes. Of 10 clinical conditions investigated in three trials or more, placebo had a statistically significant pooled effect only on pain or phobia on continuous scales. Conclusion., We found no evidence of a generally large effect of placebo interventions. A possible small effect on patient-reported continuous outcomes, especially pain, could not be clearly distinguished from bias. [source] Critical role of ribavirin for the achievement of early virological response to HCV therapy in HCV/HIV-coinfected patientsJOURNAL OF VIRAL HEPATITIS, Issue 6 2007B. Ramos Summary., The response to hepatitis C virus (HCV) therapy seems to be lower in HCV/HIV-coinfected patients than in HCV-monoinfected individuals. Given that most pivotal trials conducted in coinfected patients have used the combination of pegylated interferon (pegIFN) along with fixed low doses (800 mg/day) of ribavirin (RBV), it is unclear whether HIV itself and/or suboptimal RBV exposure could explain this poorer outcome. Two well-defined end points of early virological response were evaluated in Peginterferon Ribavirina España Coinfección (PRESCO), a multicentre trial in which the combination of pegIFN plus RBV (1000 mg if body weight <75 kg and 1200 mg if >75 kg) was prescribed to coinfected patients. For comparisons, we used unpublished data from early kinetics in two other large trials, one performed in HIV-negative patients [Pegasys International Study Group (PISG)] in which RBV 1000,1200 mg/day was used and another [AIDS Pegasys Ribavirin Coinfection Trial (APRICOT)] in which HIV-positive patients received fixed low RBV doses (800 mg/day). A total of 348 HCV/HIV-coinfected patients from the PRESCO trial were analysed as well as all patients treated with pegIFN plus RBV, who completed 12 weeks of therapy in the comparative studies (435 in PISG and 268 in APRICOT). Negative serum HCV-RNA at week 4 (which has the highest positive predictive value of sustained virological response, SVR) was attained in 33.3%, 31.2% and 13% of treated patients with HCV genotype 1, respectively, in PRESCO, PISG and APRICOT. For HCV genotypes 2/3, responses were 83.7%, 84.2% and 37%, respectively. A decline lower than 2 log10 at week 12 (which has the highest negative predictive value of SVR) was seen in 25.5%, 19.5% and 37% of HCV genotype-1-infected patients, and in 2.1%, 2.9% and 12% of genotypes-2/3-infected patients, respectively. Prescription of high RBV doses enhances the early virological response to HCV therapy in HCV/HIV-coinfected patients, with results approaching those seen in HCV-monoinfected patients. [source] Glycemic Targets for Patients with Type 2 Diabetes MellitusMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2009Ole-Petter R. Hamnvik MB Abstract Cardiovascular disease is the predominant cause of death in diabetic patients, and reducing the risk of cardiovascular disease in diabetics has recently been the focus of several highly publicized large trials, including ACCORD (Action To Control Cardiovascular Risk in Diabetes), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), and VADT (Veterans Affairs Diabetes Trial). These studies randomized high-risk diabetic patients into either intensive treatment or standard treatment. The glycemic control arm of ACCORD was terminated 17 months before the planned end of the study because of a finding of significantly increased all-cause and cardiovascular mortality in the intensive treatment group. These findings were not duplicated in either ADVANCE or VADT. Multiple possible explanations have been brought forward, including a higher incidence of death from unrecognized hypoglycemia, effects due to increased exposure to particular antidiabetic medications, adverse effects of rapid correction of hyperglycemia, weight gain, and differences in baseline characteristics. None of these were validated in post hoc analyses of the trial data, and the cause of the increased mortality remains elusive. Subgroup analyses suggest that those who start off with better control of their diabetes or without preexisting cardiovascular disease may have the most to gain from tight glycemic control. Reducing the risk of macrovascular disease and death in diabetic patients requires not only attention to glucose control but also meticulous attention to control of nonglycemic risk factors, including hypertension, hyperlipidemia, smoking, lack of exercise, and unhealthy diet as well as timely prescription of medications with proven preventative benefits, such as aspirin and statins. Mt Sinai J Med 76:227,233, 2009. © 2009 Mount Sinai School of Medicine [source] Ventilator treatment in the Nordic countries.ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2002A multicenter survey Background: A 1-day point prevalence study was performed in the Nordic countries to identify ventilator-treatment strategies in the region. Material and methods: On 30 May 30 2001 all mechanically ventilated patients in 27 intensive care units (ICUs) were registered via the internet. The results are shown as medians (25th, 75th percentile). Results: ,One hundred and eight patients were included (69% male) with new simplified acute physiology score (SAPS) 48 (37,57) and 4.5 d (2,11) of ventilator treatment. The most frequent indication for ventilator treatment was acute respiratory failure (73%). Airway management was by endotracheal tube (64%), tracheostomy (32%) and facial mask (4%). Pressure regulated ventilator modes were used in 86% of the patients and spontaneous triggering was allowed in 75%. The tidal volume was 7 ml/kg (6,9), peak inspiratory pressure 22 cmH2O (18,26) and positive end-expiratory pressure (PEEP) 6 cmH2O (6,9). FiO2 was 40% (35,50), SaO2 97% (95,98), PaO2 11 kPa (10,13), PaCO2 5.4 kPa (4.7,6.3), pH 7.43 (7.38,7.47) and BE 2.0 mmol/l (, 0.5,5). The PaO2/FiO2 ratio was 220 mmHg (166,283). The peak inspiratory pressure (r=0.37), mean airway pressure (r=0.36), PEEP (r=0.33), tidal volume (r=0.22) and SAPS score (r=0.19) were identified as independent variables in relation to the PaO2/FiO2 ratio. Conclusion: The vast majority of patients were ventilated with pressure-regulated modes. Tidal volume was well below what has been considered conventional in recent large trials. Correlations between the parameters of gas exchange, respiratory mechanics, ventilator settings and physiological status of the patients was poor. It appears that blood gas values are the main tool used to steer ventilator treatment. These results may help to design future interventional studies of ventilator treatment. [source] Efficacy of weight loss drugs on obesity and cardiovascular risk factors in obese adolescents: a meta-analysis of randomized controlled trialsOBESITY REVIEWS, Issue 2 2010S. Czernichow Summary Weight loss drugs have been developed to reduce the comorbidities associated with excess weight. We conducted a meta-analysis of the efficacy of orlistat and sibutramine on weight, body mass index, waist circumference and cardiovascular risk factors in overweight adolescents. MEDLINE and the Cochrane Library were searched for relevant articles using MESH terms and keywords. Studies were included if they had reported quantitative estimates and standard deviations of the association between each weight loss drug and weight, with information on at least one cardiovascular risk factor. A total of eight trials (three orlistat and five sibutramine) with information on 1391 individuals was included in the present analysis. The mean decrease in weight between the intervention and control groups was 5.25 kg (95% confidence interval: 3.03,7.48) after a minimum follow-up of 6 months. There was evidence of statistical heterogeneity between the studies (I2 = 76%) that was no longer apparent after exclusion of trials of orlistat (mean weight decrease = 5.32 kg; I2 = 38%). There was little evidence that treatment was associated with adverse effects on cardiovascular risk factors but this requires verification from future large trials with longer study follow-up. [source] Approach to eradication of initial Pseudomonas aeruginosa infection in children with cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 9 2007Miriam M. Treggiari MD Abstract The primary cause of morbidity and mortality in children with cystic fibrosis (CF) is the progression of obstructive lung disease secondary to chronic endobronchial infection, mainly caused by Pseudomonas aeruginosa (Pa). Initial Pa isolates are typically non-mucoid, usually susceptible to most anti-pseudomonal antibiotics, and potentially amenable to eradication. Preliminary studies of early intervention suggest a "window of opportunity" with anti-pseudomonal antibiotics to eradicate Pa from upper and lower airways. Several large trials in young children with CF are currently ongoing with the goals of (1) investigating if early intervention at the time of initial Pa acquisition is effective and safe and (2) identifying the least invasive and safest treatment regimen to achieve both microbiologic and clinical benefits. Pediatr Pulmonol. 2007; 42:751,756. © 2007 Wiley-Liss, Inc. [source] Latest news and product developmentsPRESCRIBER, Issue 19 2008Article first published online: 16 OCT 200 ARBs less effective than ACE inhibitors? The efficacy of angiotensin-II receptor blockers (ARBs) in preventing cardiovascular events in high-risk patients has been challenged by the findings of a large randomised trial (Lancet 2008 published online; doi 10.1016/ S0140-6736(08)61242-8). In the TRANSCEND trial, 5926 patients with cardiovascular disease or diabetes with end-organ damage who could not tolerate ACE inhibitor therapy were randomised to placebo or telmisartan (Micardis) 80mg per day in addition to standard therapies. After 56 months, mean blood pressure was lower with telmisartan (by 4.0/2.2mmHg) but there were no significant differences between telmisartan and placebo in the risk of cardiovascular events , a composite of cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure. Hospitalisation for cardiovascular reasons were slightly but significantly reduced by telmisartan (33 vs 30 per cent). MHRA: fentanyl patch errors potentially fatal Errors in dosing, accidental exposure and enhanced absorption from heat exposure have resulted in life-threatening and fatal incidents with transdermal fentanyl, warns the MHRA in its latest Drug Safety Update (September 2008). There is also evidence that fentanyl patches are being prescribed for nonlicensed indications, including treatment of opioid-naive patients. Other topics in this issue include managing adverse reactions to HPV vaccine and an update on new cases of progressive multifocal leucoencephalopathy associated with natalizumab (Tysabri). Call for DURG research The Drug Utilisation Research Group is inviting abstracts for oral and poster presentations at its 20th annual meeting on 5 February 2009. The theme of the morning session is ,Whose prescribing budget is it anyway?'. Abstracts will be accepted on any drug utilisation research studies and will be published in the Journal of Pharmacoepidemiology and Drug Safety. Information is available at www.durg.org.uk the deadline for submissions is 1 December. Early bromocriptine no benefit in Parkinson's Initiating treatment of Parkinson's disease with the dopamine agonist bromocriptine offers no long-term benefit compared with levodopa, the UK Parkinson's Disease Research Group trial has shown (Neurology 2008;71:474-80). After 14 years' follow-up of 166 patients, there were no differences in the prevalence of motor complications, dementia or mortality, but levodopa was associated with superior scores of disability and physical functioning. The authors say the belief that early dopamine agonist treatment is neuroprotective in Parkinson's disease should be abandoned. Ezetimibe with statin cancer risk ,not credible' Analysis of data pooled from two large trials provides ,no credible evidence' that ezetimibe (Ezetrol) is associated with an increased risk of cancer when added to statin therapy (N Engl J Med 2008 published online; doi 10.1056/NEJMsa0806603). A possible link with increased risk of cancer with ezetimibe plus simvastatin was suggested by the SEAS trial (N Engl J Med 2008 published online; doi 10.1056/NEJMoa 0804602). This hypothesis was tested in two trials involving more than 20 500 patients over 1.0-2.7 years. There was no excess of cancer overall or at particular sites; cancer deaths were more numerically but not significantly higher with ezetimibe and there was no evidence of increased risk with duration of treatment. Telmisartan provides no advantage after stroke Adding telmisartan (Micardis) to standard treatment after ischaemic stroke does not reduce morbidity, US investigators report (N Engl J Med 2008 published online; doi 10.1056/NEJMoa 0804593). A total of 20 332 patients with recent ischaemic stroke were randomised to placebo or telmisartan 80mg per day in addition to antiplatelet therapy and antihypertensive agents. After 2.5 years, blood pressure was 3.8/2.0mmHg lower in patients taking telmisartan but there were no significant differences from placebo in the risks of recurrent stroke, cardiovascular events or new-onset diabetes. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 13-14 2008Article first published online: 29 JUL 200 NSAIDs stroke risk NSAIDs have been linked with an increased risk of stroke in an epidemiological study from The Netherlands (Arch Intern Med 2008;168: 1219-24). Nine years' follow-up of 7636 older persons (mean age 70) identified 807 strokes. The risk of stroke was significantly increased for current use of nonselective NSAIDs (hazard ratio 1.72 for all strokes) and COX-2 selective NSAIDs (HR 2.75 for all strokes; HR 4.54 for ischaemic stroke). Increased risk was found for several individual NSAIDs but was statistically significant only for naproxen (HR 2.63) and the withdrawn rofecoxib (HR 3.38). HPV vaccine chosen The DoH has chosen GlaxoSmithKline's Cervarix HPV vaccine for the national immunisation campaign beginning in September. Cervarix is a bivalent vaccine conferring immunity against HPV16 and 18, which account for 70 per cent of cervical cancers worldwide. Its competitor, Gardasil, is a quadrivalent vaccine additionally protecting against HPV6 and 11, which cause 90 per cent of genital warts. The procurement process assessed the vaccines against ,a wide range of criteria such as their scientific qualities and cost effectiveness'. The DoH has not revealed what it will pay for Cervarix. Melatonin for insomnia Lundbeck has introduced melatonin (Circadin) as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over. The dose is 2mg once daily two hours before bed-time and after food for three weeks. A course costs £10.77. Fesoterodine launched Pfizer has introduced feso-terodine (Toviaz), a prodrug for tolterodine (Detrusitol), for the treatment of symptoms of overactive bladder. Treatment is initiated at a dose of 4mg per day and increased to 8mg per day according to response. The full therapeutic effect may not occur until after two to eight weeks; treatment should be re-evaluated after eight weeks. A month's treatment at either dose costs £29.03, the same as sustained-release tolterodine (Detrusitol XL). Intensive glycaemic control for T2D? Two large trials of intensive glycaemic control in patients with type 2 diabetes have conflicting implications for clinical practice. The ACCORD study (N Engl J Med 2008;358:2545-9) found that treating patients at high CVD risk to a target HbA1c of <6.0 per cent was associated with a 22 per cent increased risk of death and no reduction in macrovascular end-points compared with a target of 7.0-7.9 per cent. The ADVANCE study compared treating to a standard (HbA1c 7.3 per cent) or low (HBA1c 6.5 per cent) target. More intensive glycaemic control significantly reduced microvascular end-points, primarily due to a reduction in nephropathy. There was no difference in the risk of retinopathy or macrovascular end-points. Nicorandil as ulcer cause The potassium-channel activator nicorandil (Ikorel) may be associated with gastro-intestinal ulceration but is frequently overlooked as a possible cause, warns the MHRA in its latest Drug Safety Update (2008;1:Issue 11). Ulceration may affect any portion of the gastro-intestinal tract from the mouth to the perianal area, and it is frequently severe and may cause perforation. Ulcers due to nicorandil are refractory to treatment and only resolve on withdrawal of the drug. Withdrawal should be carried out under the supervision of a cardiologist. , This issue of Drug Safety Update also includes an overview of safety issues with natalizumab (Tysabri) for multiple sclerosis. Atypical antipsychotics diabetes risk ,small' The excess risk of diabetes due to treatment with an atypical antipsychotic is small compared with older anti-psychotics, say UK researchers (Br J Psychiatry 2008;192:406-11). Their meta-analysis of 11 studies found that, compared with the use of first-generation antipsychotics in patients with schizophrenia, the over-all increased risk of diabetes with atypicals was 32 per cent. Risperidone was associated with lowest excess risk (16 per cent), followed by quetiapine (Seroquel) and olanzapine (Zyprexa; 28 per cent) then clozapine (39 per cent). Most studies had method-ological limitations. Copyright © 2008 Wiley Interface Ltd [source] Pathophysiology and treatment of arterial dissection and strokePROGRESS IN NEUROLOGY AND PSYCHIATRY, Issue 6 2007Kunal Khanna Arterial dissection is the commonest cause of stroke in younger people; however, the mechanisms involved and how it is treated remain controversial. In this article, the authors outline the possible pathophysiology of arterial dissection causing stroke, how it is currently diagnosed and treated and how further large trials are required to improve the prognosis of this condition. Copyright © 2007 Wiley Interface Ltd [source] Utilization of catheterization and revascularization procedures in patients with non-ST segment elevation acute coronary syndrome over the last decadeCATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 2 2005Glenn N. Levine MD Abstract The degree to which catheterization and revascularization procedures are utilized in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) during hospitalization has broad implications with respect to initial pharmacotherapeutic decisions (upfront therapies), treatment and hospital transfer protocols, guideline recommendations, and allocation of training, material, and financial resources. Analysis of data from multiple trials and registries of patients with NSTE-ACS has the potential to assess more broadly utilization of invasive and revascularization procedures and provide a wide angle or bird's-eye view of the management of such patients, complementing the data obtained from any one trial or registry. We therefore undertook a systematic overview of all large trials and registries of patients with NSTE-ACS conducted over the last decade that were deemed appropriate to provide information on catheterization and revascularization procedures. Although not unexpectedly the percentage of patients with NSTE-ACS managed with cardiac catheterization, percutaneous coronary intervention (PCI), and coronary artery bypass grafting varies in different clinical trials and registries, general findings and trends were still discernable from these studies. During the initial treatment period, the majority of patients were ultimately treated with medical therapy alone (e.g., without revascularization). The percentage of those NSTE-ACS patients undergoing diagnostic cardiac catheterization who were then managed with PCI increased over the last decade and now stands at approximately 50%. Of NSTE-ACS patients who undergo revascularization, the percentage of those patients who are revascularized via PCI similarly increased, and PCI is currently the revascularization procedure utilized in approximately three-fourths of patients undergoing revascularization. The percentages of patients undergoing invasive and revascularization procedures were consistently higher in the U.S. cohorts of study subjects when compared to non-U.S. cohorts of study subjects. © 2005 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||