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Selected AbstractsSafety and efficacy of nabumetone in osteoarthritis: emphasis on gastrointestinal safetyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2000Scott To compare the efficacy and gastrointestinal (GI) safety of nabumetone with two comparator non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac SR and piroxicam. Methods: Two randomized, double-blind, multicentre, parallel group trials were carried out in patients with moderate to severe osteoarthritis of the hip or knee. During the 6 month treatment phase, the safety and efficacy of nabumetone (1500,2000 mg/day) was compared to diclofenac SR (100 mg/day) or piroxicam (20,30 mg/day). GI safety was evaluated by reviewing all adverse events reported during the trials and presenting all cases of ulcers (complicated and uncomplicated), as well as other bleeding events that may have been associated with NSAID administration. Results: Most of the efficacy parameters showed no significant differences between the NSAIDs, although diclofenac SR was significantly better than nabumetone in one of 18 efficacy parameters. Nabumetone-treated patients experienced significantly fewer ulcer and bleeding events compared to patients treated with the comparator NSAIDs [1.1% (4/348) vs. 4.3% (15/346), P= 0.01]. Bleeding events, including outright upper or lower GI bleeding or a significant decline in haemoglobin, occurred in significantly fewer patients treated with nabumetone than with the comparator NSAIDs [1.1% (4/348) vs. 3.5% (12/346), P < 0.05]. More importantly, complications associated with either ulcers (perforation) or bleeding (leading to hospitalization or withdrawal) occurred in significantly fewer patients receiving nabumetone [0% (0/348)] than with comparator NSAIDs [1.4% (5/346), (P < 0.05)]. Conclusion: The results suggest that nabumetone was similar in efficacy by most criteria to diclofenac SR and piroxicam in relieving the symptoms of osteoarthritis; however, nabumetone's GI safety profile was generally superior to that of both comparator NSAIDs. In the pooled analysis, nabumetone was associated with a significantly lower total incidence of ulcers and bleeding events, and a significantly lower incidence of complications associated with these events. [source] Centella asiatica extract selectively decreases amyloid , levels in hippocampus of Alzheimer's disease animal modelPHYTOTHERAPY RESEARCH, Issue 1 2009Muralikrishnan Dhanasekaran Abstract PSAPP mice expressing the ,Swedish' amyloid precursor protein and the M146L presenilin 1 mutations are a well-characterized model for spontaneous amyloid , plaque formation. Centella asiatica has a long history of use in India as a memory enhancing drug in Ayurvedic literature. The study investigated whether Centella asiatica extract (CaE) can alter the amyloid pathology in PSAPP mice by administering CaE (2.5 or 5.0 g/kg/day) starting at 2 months of age prior to the onset of detectable amyloid deposition and continued for either 2 months or 8 months. A significant decrease in amyloid , 1,40 and 1,42 was detectable by ELISA following an 8 month treatment with 2.5 mg/kg of CaE. A reduction in Congo Red stained fibrillar amyloid plaques was detected with the 5.0 mg/kg CaE dose and long-term treatment regimen. It was also confirmed that CaE functions as an antioxidant in vitro, scavenging free radicals, reducing lipid peroxidation and protecting against DNA damage. The data indicate that CaE can impact the amyloid cascade altering amyloid , pathology in the brains of PSAPP mice and modulating components of the oxidative stress response that has been implicated in the neurodegenerative changes that occur with Alzheimer's disease. Copyright © 2008 John Wiley & Sons, Ltd. [source] Treatment of Nonparaphilic Hypersexuality in Men with a Long-Acting Analog of Gonadotropin-Releasing HormoneTHE JOURNAL OF SEXUAL MEDICINE, Issue 4 2009Mohammad R. Safarinejad MD ABSTRACT Introduction., Hypersexuality is one of the most embarrassing behaviors for both patients and their families and there are no effective drug treatments for this sexual inappropriateness. Aim., To evaluate the efficacy and safety of a long-acting analog of gonadotropin-releasing hormone (triptorelin) in men with nonparaphilic hypersexuality (NPH). Main Outcome Measures., Primary outcome measure was the frequency of intercourse. The designated secondary outcome measures were the changes in International Index of Erectile Function (IIEF) questionnaire and responses to the questions from the IIEF in the preceding month: question 11, "How often have you felt sexual desire?" and question 12, "How would you rate your level of sexual desire"? Methods., Seventy-six men (mean age 44.4 years) with NPH were treated with monthly intramuscular injections of 3.75 mg of triptorelin for an indefinite period. During treatment, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone (T), and free testosterone (fT), were measured monthly, and bone mineral density every 6 months. Results., The mean sexual attempts decreased from 7.6 ± 1.4 per day at baseline to 4.2 ± 1.2 (P = 0.001), 1.2 ± 0.4 (P = 0.001), and <1 per week (P = 0.0001), after 6-, 12-, and 24-month treatment, respectively. The mean scores for questions 11 and 12, improved from 6.8 ± 1.1, and 6.6 ± 1.2, at baseline to 0.7 ± 0.4 (P = 0.0001), and 0.7 ± 0.5 (P = 0.0001), at 24-month treatment, respectively. Positive response to triptorelin was significantly associated with severity of baseline hypersexuality (r = ,0.62, P = 0.01), and treatment duration (r = 0.78, P = 0.001). These beneficial effects persisted 6 months in all men who were treated for at least 24 months. The serum LH and FSH concentrations begun to decrease after two doses of triptorelin. After 3 months, serum T, and fT levels decreased by 50% in 65 (85.5%) of patients (P = 0.01). Conclusions., Triptorelin was very effective and well tolerated in men with NPH. Further studies are needed to replicate our results. Safarinejad MR. Treatment of nonparaphilic hypersexuality in men with a long-acting analog of gonadotropin-releasing hormone. J Sex Med **;**:**,**. [source] Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2009Zheng Jiao WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT? , Sirolimus is an immunosuppressive agent used for the prophylaxis of renal allograft rejection. , Several conventional pharmacokinetic and population pharmacokinetic studies have been conducted to assess the pharmacokinetic characteristics of sirolimus in White or African-American recipients. WHAT THIS STUDY ADDS? , The population pharmacokinetics of sirolimus in Chinese adult renal transplant recipients was characterized for the first time. , New drug,drug interactions between herbal medicines and sirolimus were identified as the covariates on sirolimus clearance. AIMS This study was aimed at determining the population pharmacokinetics of sirolimus and identifying factors that explain pharmacokinetic variability in de novo Chinese adult renal transplant patients. METHODS Data were retrospectively extracted from a formal multicentre clinical trial, which was originally designed to evaluate the safety and efficacy of ciclosporin dose reduction and ciclosporin elimination in patients receiving sirolimus. All patients received 12-month treatment, i.e. induction therapy with ciclosporin, sirolimus and corticosteroids during the first 3 months followed by either ciclosporin dose reduction or ciclosporin discontinuation thereafter. Eight-hundred and four sirolimus trough blood concentrations (C0) from 112 patients were used to develop a population pharmacokinetic model using the nonmem program. A one-compartment model with first-order absorption and elimination was selected as the base model. The influence of demographic characteristics, biochemical and haematological indices, ciclosporin daily dose, ciclosporin C0 as well as other commonly used co-medications were explored. RESULTS The typical values with interindividual variability for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 10.1 l h,1 (23.8%) and 3670 l (56.7%), respectively. The residual variability was 29.9%. CL/F decreased significantly with silymarin or glycyrrhizin co-therapy in hepatically impaired patients, and with increasing total cholesterol levels or ciclosporin C0. Moreover, CL/F increased nonlinearly with increasing sirolimus daily dose. The median parameter estimates from a nonparametric bootstrap procedure were comparable and within 5% of the estimates from nonmem. CONCLUSIONS These results provide important information for clinicians to optimize sirolimus regimens in Chinese renal transplant patients. [source] Latest news and product developmentsPRESCRIBER, Issue 21 2008Article first published online: 2 DEC 200 Osteoporosis guideline A new guideline on the management of osteoporosis in men over 50 and post-menopausal women has been published by the National Osteoporosis Guideline Group (www.shef.ac.uk/NOGG), a group of organisations representing health professionals and patients, with funding from several pharmaceutical companies. The guideline recommends using the FRAX tool (www.shef.ac.uk/FRAX) to assess the 10-year fracture risk in individuals with risk factors to facilitate targeting DXA scans to measure bone mineral density. Patients who have already sustained a fragility fracture should be treated without risk assessment. Treatment recommendations are similar to those published in draft NICE guidance on primary and secondary prevention, selecting alendronate as the drug of first choice for most patients. Efalizumab efficacy A multicentred postapproval trial has demonstrated long-term efficacy and a favourable safety profile for efalizumab (Raptiva) in moderate to severe chronic plaque psoriasis. The CONTROL II study, presented in September at the 17th EADV congress in Paris, was conducted at 170 sites in 18 European countries and involved 1255 patients who had failed to respond to traditional systemic therapies. In this non-blinded study, 68 per cent of participants achieved the primary efficacy end-point and showed improvement within the first 12 weeks; control was maintained in responding patients who continued treatment. Adverse effects were graded as mild or moderate and similar to those reported in earlier studies. There was no evidence of an increase in malignancies or infections. New oral anticoagulant Rivaroxaban (Xarelto), an oral factor Xa inhibitor, has been introduced for the prevention of venous thrombo-embolism in patients undergoing elective hip or knee replacement surgery. Compared with the low molecular weight heparin enoxaparin (Clexane), rivaroxaban has been shown to reduce the risk of venous thrombosis by 70 per cent after hip replacement and by 49 per cent after knee replacement; the risk of bleeding was similar. At the recommended dose of 10mg once daily, prophylaxis after hip surgery lasts five weeks and costs £157; prophylaxis after knee surgery lasts two weeks and costs £63. New products UCB Pharma has introduced lacosamide (Vimpat) as adjunctive treatment of partial-onset epilepsy with or without secondary generalisation in patients aged 16 and over. A month's treatment at the recommended maintenance dose of 100-200mg twice daily costs approximately £73-£140. A new non-nucleoside reverse transcriptase inhibitor (NNRI) is available for the treatment of HIV-1 infection in combination with a boosted protease inhibitor (PI) and other antiretrovirals in treatment-experienced adults. Etravirine (Intelence) costs approximately £320 for one month's treatment at the recommended dose of 200mg twice daily. Voltarol Pain-Eze (diclofenac) 12.5mg tablets are now available without prescription; a pack of 18 tablets costs £5.99. Atypicals and EPS risk Atypical antipsychotics are not associated with a significantly lower risk of extra-pyramidal symptoms than first-generation agents such as perphenazine (Fentazin), a new analysis of the CATIE study has shown (Br J Psychiatry 2008;193:279,88). CATIE was a large trial comparing the efficacy and safety of antipsychotics in the treatment of schizophrenia in which perphenazine was a representative first-generation agent (Am J Psychiatry 2006;163:611,22). This analysis found no differences in the risk of parkinsonism, dystonia, akathisia or tardive dyskinesia between perphenazine and the newer antipsychotics; use of antiparkinsonian medication was higher with risperidone and lower with quetiapine (Seroquel). Mental health website A new website offering information about mental illnesses and drug treatment has been launched by the United Kingdom Psychiatric Pharmacy Group (UKPPG), the College of Mental Health Pharmacists (CMHP), the Pharmaceutical Schizo-phrenia Initiative (PSI) and the National Institute for Mental Health in England (NIMHE). www.choiceandmedication.org.uk includes information about 17 mental illnesses and a large number of drug treatments. It offers links to other sites offering information and downloadable leaflets, help to identify the local mental health trust and downloadable charts comparing treatments for each indication. [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] Latest news and product developmentsPRESCRIBER, Issue 7 2008Article first published online: 28 APR 200 Referrals from Boots The majority of people requesting Boots' erectile dysfunction or weight management programmes are referred to their GP(Pharm J 2008;280:297). The programmes are run under patient group directions and exclude people with elevated blood pressure, blood glucose or cholesterol. Over 80 per cent of customers screened for the erectile dysfunction programme in Manchester and two-thirds of those screened for the national obesity programme were referred. Vildagliptin: new DPP-4 inhibitor for diabetes Novartis has introduced the DPP-4 inhibitor vildagliptin for the treatment of type 2 diabetes. Two formulations are available: Galvus (vildagliptin 50mg) is licensed for use with metformin, a sulphonylurea or a thiazolidinedione when these agents do not achieve glycaemic control alone, and Eucreas (vildagliptin 50mg plus metformin 850 or 1000mg) is licensed for patients requiring combined therapy with vildagliptin and metformin. Inhibition of DPP-4 blocks the breakdown of the incretin hormones GIP and GLP-1, reducing fasting plasma glucose and postprandial hyperglycaemia. Vildagliptin is the second DPP-4 inhibitor to be introduced; the first was sitagliptin (Januvia), which has similar licensed indications. The third available drug acting on the incretin system is the incretinmimetic exenatide (Byetta); administered by injection, this is licensed for use with metformin and/or a sulphonylurea and is the only agent in this class to be approved for triple therapy. No comparative trials of these agents have been published. A month's treatment with twice-daily vildagliptin 50mg or either strength of vildagliptin plus metformin costs £31.76. Sitagliptin 100mg once daily costs £33.26. Sinusitis symptoms don't guide treatment The severity and duration of symptoms do not help to identify which patients with sinusitis will be helped by antibiotics, a new meta-analysis suggests (Lancet 2008;371: 908-14). The analysis of patient-level data from nine trials involving a total of 2547 adults showed that the number needed to treat (NNT) to cure one patient with rhinosinusitis was 15. Cure took longer to achieve in older patients and in those reporting symptoms for longer or with more severe symptoms. The authors comment that treatment is not justified given the risk of resistance and adverse effects and cost of antibiotics. Draft guidance from the National Institute for Health and Clinical Excellence (NICE) on the management of respiratory infections states that no antibiotic therapy or a delayed antibiotic prescribing strategy should be negotiated for patients with acute sinusitis. Taking cod liver oil leads to fewer NSAIDs Cod liver oil could help some patients with rheumatoid arthritis to reduce their NSAID consumption, according to a study from Dundee (Rheumatology online: 24 March 2008; doi: 10.1093/rheumatology/ ken024). A total of 97 patients were randomised to nine months' treatment with cod liver oil 10g per day or placebo. After 12 weeks, patients attempted to reduce or stop their use of NSAIDs. Significantly more of those taking cod liver oil achieved at least a 30 per cent reduction in NSAID use compared with placebo (39 vs 10 per cent). There were no differences in adverse effects or disease activity. Welsh prescriptions up The reduction in the prescription charge in Wales in 2004 was followed by an increase in prescribing of nonsedating antihistamines in wealthier areas, a study suggests (Health Policy online: 5 March 2008; doi:10.1016/j. healthpol.2008.01.006). In the two years preceding the cut, prescriptions for nonsedating antihistamines increased by about 7 per cent; in the two years after the cut, the increase was nearly 14 per cent. By contrast, there was no change in the rate of increase in the south-east of England (4,5 per cent in both periods). The increased growth in prescribing was statistically significant in the five least deprived but not in the five most deprived health boards in Wales. Aspirin linked with reduced asthma risk Low-dose aspirin is associated with a reduced risk of developing asthma, a new analysis of the Women's Health Study has shown (Thorax online: 13 March 2008; doi:10.1136/ thx.2007.091447). The analysis included 37 270 women with no asthma at baseline who were randomised to take placebo or aspirin 100mg every other day. After 10 years, 872 cases of asthma occurred in women taking aspirin and 963 with placebo, a 10 per cent reduction in risk. However, risk was not reduced in obese women. The mechanism by which aspirin may affect the risk of asthma is unknown. The latest evidence is consistent with findings published by the same investigators after analysis of two other large observational studies, the Physicians' Health Study and the Nurses Health Study. Anastrozole bone loss Long-term follow-up of the ATAC (Anastrozole, Tamoxifen, Alone or in Combination) trial has confirmed that adjuvant therapy with anastrozole (Arimidex) is associated with greater loss of bone mineral density (BMD) than tamoxifen in postmenopausal women with invasive primary breast cancer (J Clin Oncol 2008;26: 1051,7). After five years, median BMD was reduced by 6 and 7 per cent in the lumbar spine and hip with anastrozole compared with approximately 3 and 1 per cent respectively for tamoxifen, though no patients developed osteoporosis. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 10 2007Article first published online: 13 SEP 200 Sitagliptin: novel drug for type 2 diabetes Sitagliptin (Januvia), the first dipeptidyl peptidase-4 (DPP-4) inhibitor, has been introduced for the treatment of type 2 diabetes in combination with metformin or a glitazone when either agent plus exercise and diet fail to control blood glucose. Inhibition of DPP-4 prevents the breakdown of incretin hormones that promote insulin release from pancreatic beta cells. In trials lasting up to 24 weeks, adding sitagliptin to established therapy reduced HbA1C by 0.67-0.90 per cent. It is contraindicated in patients with moderate or more severe renal impairment. At the recommended dose of 100mg per day, a month's treatment with sitagliptin costs £33.36. Guide to treating mentalillness in primary care A new guide from the Centre for Clinical and Academic Workforce Innovation aims to help health professionals and others treating people with mental illness. A Complete Guide to Primary Care Mental Health, a toolkit presented as a reference book and CD, covers aspects of treatment, the law and working with the voluntary sector and includes training materials compatible with evidence-based guidance. Copies are available from amazon.co.uk. Follow-up improves statin adherence Patients may take long holidays from statin treatment but a visit to the doctor is among the most effective ways to improve adherence, a US study shows (Arch Intern Med 2007;167:847,52). Observation of 239 911 patients who began statin treatment during a seven-year period showed that 54 per cent stopped their treatment for at least 90 days. Of these, 48 per cent restarted within one year and 60 per cent within two years. Factors associated with restarting treatment were a visit to the doctor who prescribed the statin (odds ratio, OR, 6.1) or a visit to a different doctor (OR 2.9). A cholesterol test and hospital admission for a cardiovascular event were also significant factors. Pharmacist MUR does not reduce heart failure deaths Medication review by trained community pharmacists does not reduce admissions or deaths among patients with heart failure, according to a study from East Anglia (BMJ online: 23 April 2007; doi:10.1136/bmj.39164.568183.AE). Patients admitted as emergencies with heart failure were randomised to usual care or two home visits by a community pharmacist within two and eight weeks after discharge. Pharmacists reviewed medication and advised on self-management of symptoms and lifestyle. There were no significant differences in hospital admissions over the next six months (rate ratio 1.15 for pharmacist vs control) or deaths (rate ratio 1.18); quality of life scores were similar in the two groups. The authors speculate that the interventions may have been too brief or too late (lifestyle changes having been made already), or disadvantaged by not adjusting beta-blocker doses. A Cardiff study of pharmacist medication reviews for elderly patients (BMJ online: 20 April 2007; doi:10.1136/bmj.39171. 577106.55), found that their advice had the potential to undermine patients' ,confidence, integrity and self-governanc'. The study found that pharmacists gave advice unnecessarily and uninvited. CHD targets met early The national programme to tackle heart disease has made substantial progress towards it targets, the Department of Health says in a 10-year report, and a 40 per cent cut in mortality will be achieved ahead of the deadline of 2010. Coronary Heart Disease Ten Years On: Improving Heart Care, a report by Professor Roger Boyle, National Director for Heart Disease and Stroke, states that 7 per cent of the population is now taking statins, resulting in 9700 deaths avoided annually. The prevalence of untreated hypertension fell from 32 to 24 per cent between 1998 and 2003. The report also summarises changes in service delivery, nutrition and smoking cessation. HRT: ovarian cancer risk The MHRA has not altered its advice on the use of HRT following news that five years' use increases ovarian cancer risk in women over 50. The Million Women Study revealed an approximately 20 per cent increased risk of ovarian cancer or death among women still using HRT after five or more years. There was no difference in risk between oestrogen-only and combined formulations. The MHRA says HRT is still indicated for relieving symptoms of the menopause for short-term use; as an alternative for women over 50 who cannot take other treatments to prevent osteoporosis, or when such options fail; and in women under 50 who experience a premature menopause. Poor angina treatment Over half of patients with angina continue to experience attacks despite treatment, according to a survey by the British Cardiac Patients Association. The survey of 600 patients with angina also found that twot-hirds of respondents reported that angina had a moderate to severe impact on their lives. Half said that the adverse effects of their treatment negatively affected their work, two-thirds reported an adverse impact on sex, and almost three-quarters of patients taking beta-blockers reported fatigue. A second survey of 2000 adults revealed widespread ignorance about the prevalence and symptoms of angina. The surveys were sponsored by Servier Laboratories Limited and conducted in collaboration with Research Quorum. Cabergoline restriction Indications for the dopamine agonist cabergoline (Cabaser) are being restricted to match those of pergolide (Celance), the MHRA has announced. Pergolide was recently withdrawn in the United States and its use in the EU is limited because of the risk of cardiac valvular damage. Similar toxicity has been reported with cabergolide, which is now restricted to second-line use when a nonergot treatment for Parkinson's disease has failed. It is contraindicated in patients with valvular damage or a history of fibrotic disorders and requires patient monitoring. Sodium reduction cuts CV events Long-term reduction in dietary sodium may reduce cardiovascular events by 25 per cent, US epidemiologists say (BMJ online: 20 April 2007; doi:10.1136/bmj.39147.604896.55). Participants in the two Trials of Hypertension Prevention (TOHP I and II) reduced their sodium intake by 44 and 33mmol per 24hr. After 10,15 years' follow-up of 2415 participants, the adjusted relative risk of cardiovascular events was 0.75 compared with controls. There was a nonsignificant 20 per cent reduction in mortality. Copyright © 2007 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 8 2007Article first published online: 23 JUL 200 Lamotrigine for partial, valproate for generalised A large UK trial has shown that lamotrigine is the most effective choice in the treatment of partial epilepsy (Lancet 2007;369: 1000-15). The SANAD trial, commissioned by the National Institute for Health Research's Health Technology Assessment programme, randomised 1721 patients (for whom carbamazepine monotherapy would have been the treatment of choice) to treatment with carbamazepine, gabapentin, lamotrigine, oxcarbazepine (Trileptal) or topiramate (Topamax). Lamotrigine was associated with a longer time to treatment failure, though time to 12-month remission favoured carbamazepine. Over four years' follow-up, lamotrigine was numerically but not significantly superior. The authors concluded lamotrigine is clinically superior to carbamazepine for partial epilepsy A second arm of the trial, yet to be published, evaluated the treatment of generalised epilepsy and found valproate to be clinically most effective, though topiramate was cost effective for some patients. Chronic pain common in nursing homes Most residents in nursing homes say they have long- term pain but only one in seven say a health professional has ever discussed its treatment with them, according to a report by the Patients' Association (www.patients-association.org.uk). Pain in Older People ,A Hidden Problem was a qualitative study of 77 older residents in care homes in England. Most were frail and suffered long-term illness. The study found that 85 per cent of residents said they were often troubled by aches or pains and these lasted over a year in 74 per cent. Most described their pain as moderate (33 per cent) or severe (38 per cent) but 8 per cent said it was excruciating. Many reported limitations on mobility and social activities despite a high level of stoicism. All but one were taking medication to relive pain; one-third experienced adverse effects but 78 per cent believed drugs offered the most effective treatment. One-quarter said a doctor or nurse had discussed how to stop their pain worsening, and 15 per cent said they had discussed how to treat their pain. Visits from GPs appeared to be uncommon. Atherothrombotic events despite treatment Between one in five and one in seven of high-risk patients experience atherothrombotic events despite evidence-based treatment, the REACH study has shown (J Am Med Assoc 2007;297:1197-1206). REACH (REduction of Atherothrombosis for Continued Health) is an international observational study involving 68 236 patients with atherothrombotic disease or at least three risk factors. Most were taking conventional evidence-based medication. After one year, the incidence of the combined endpoint of cardiovascular death, myocardial infarction, stroke or hospitalisation for atherothrombotic events was approximately 15 per cent for patients with coronary artery disease or cardiovascular disease, and 21 per cent in patients with peripheral artery disease and established coronary disease. Event rates increased with the number of vascular beds affected, rising to 26 per cent in patients with three symptomatic arterial disease locations. Extended CD prescribing by nurses and pharmacists The Medicines and Healthcare products Regulatory Agency (MHRA) is consulting on expanding the prescribing of controlled drugs (CDs) by nonmedical prescribers. Currently, nurse independent prescribers can prescribe 12 CDs, including diamorphine and morphine, but pharmacist independent prescribers may not prescribe any CDs. The proposal is to allow both professions to prescribe any CDs within their competence, with the exception of cocaine, diamorphine or dipipanone for the management of addiction. The closing date for consultation is 15 June. Consultation is also underway on expanding the range of CDs nurses and pharmacists can prescribe under a patient group direction (PGD), and their use for pain relief. The closing date for consultation is 20 April. Intrinsa: transdermal testosterone for women A transdermal formulation of testosterone has been introduced for the treatment of low sexual desire associated with distress in women who have experienced an early menopause following hysterectomy involving a bilateral oophorectomy and are receiving concomitant oestrogen therapy. Manufacturer Procter & Gamble says that Intrinsa, a twice-weekly patch, delivers testosterone 300µg every 24 hours, achieving premenopausal serum testosterone levels. Clinical trials showed that Intrinsa reduced distress in 65-68 per cent and increased satisfying sexual activity in 51-74 per cent of women. A month's treatment (eight patches) costs £28.00. Fish oil for secondary ,not primary ,prevention of CHD Supplementing statin therapy with eicosapentaenoic acid (EPA) reduces the risk of major coronary events in patients with coronary heart disease (CHD) ,but not in patients with no history of CHD Lancet 2007;369:1090-8). The five-year study in 18 645 patients with total cholesterol levels of 6.5mmol per litre or greater found that the incidence of sudden cardiac death, fatal and nonfatal myocardial infarction in CHD patients treated with EPA plus a statin was 8.7 per cent compared with 10.7 per cent with a statin alone (relative risk reduction 19 per cent). A similar relative risk reduction in patients with no CHD was not statistically significant. There was no difference in mortality between the groups but EPA did reduce unstable angina and nonfatal coronary events. Department pilots information prescriptions The Department of Health has announced 20 sites to pilot information prescriptions prior to a nationwide roll-out in 2008. The prescriptions will guide people with long-term conditions such as diabetes and cancer to sources of support and information about their condition. The Department hopes the project will increase patients' understanding of their discussions with health professionals, empower them to locate the information they need, and provide long-term support. NPSA guidelines for safer prescribing The National Patient Safety Agency (www.npsa.nhs.uk) has published five guidelines to improve medication safety in the NHS. Targeting ,high-risk issues', the guidance covers anticoagulant prescribing, liquid medicines for oral or enteral administration, injectable medicines, epidural injections and infusions, and paediatric intravenous infusions. The implementation of each guide is supported by additional tools and resources. Better adherence not matched to outcomes A systematic review has found that interventions can increase adherence to prescribed medication but there is no evidence that clinical outcomes also improve (Arch Intern Med 2007;167:540-9). The review of 37 trials identified 20 reporting increased adherence. The most effective interventions were behavioural changes to reduce dose demands and those involving monitoring and feedback. Improvements in clinical outcomes were variable and did not correspond to changes in adherence. Antidepressant plus mood stabiliser no better US investigators have found that combining a mood stabiliser with an antidepressant is no more effective than a mood stabiliser alone in preventing mood changes (N Engl J Med 2007; published online 28 March, doi.10.1056/NEJMoa064135). The study found durable recovery occurred in 23.5 per cent of patients treated with a mood stabiliser and adjunctive antidepressant therapy for six months compared with 27.3 per cent of those taking a mood stabiliser plus placebo. [source] Latest news and product developmentsPRESCRIBER, Issue 7 2007Article first published online: 11 JUL 200 Poor asthma control with off-licence prescribing Children who are prescribed off-licence medications are more likely to have poor asthma control, according to an analysis from Dundee (Br J Gen Practice 2007;57:220-2). The review of 17 163 consultations identified 1050 (6.1 per cent) who received a prescription for an unlicensed use (defined as not licensed for children or the particular age group, or dose not licensed). High doses (4.5 per cent) were more frequent than unlicensed indications (1.9 per cent). Children who received off-label prescriptions reported statistically significantly more symptoms in the day or night, symptoms during activity, and increased use of daily short-acting beta2-agonists. The authors note that off-label prescribing appears to be increasing. Atkins diet most effective over one year? The ultra low-carbohydrate, high-protein Atkins diet achieved greater weight loss than other popular diets in overweight women over one year, say US investigators (J Am Med Assoc 2007;297:969-77). The study compared the Atkins diet with three diets designed as low- or very high-carbohydrate, or based on USA nutritional guidance, in 311 women with body mass index 27-40. After one year, mean weight loss was 4.7kg with the Atkins diet , significantly greater than with the low- carbohydrate diet (1.6kg) but not compared with very high-carbohydrate (2.2kg) or the nutrition-based diet (2.6kg). Metabolic endpoints were comparable or more favourable in women using the Atkins diet. Androgen therapy linked to gum disease The majority of men treated with androgen deprivation therapy for prostate cancer are more likely to have periodontal disease (J Urol 2007;177:921-4). After controlling for risk factors, the prevalence of periodontal disease was 80.5 per cent among treated men compared with 3.7 per cent in matched controls not receiving treatment. There was no difference in bone mineral density between the groups but plaque scores were significantly higher among treated men. Food Commission rebuts MHRA on additives An independent watchdog has not accepted the MHRA's justification for including certain additives in medicines for children. The Food Commission (www.foodcomm.org.uk) found that most medicines for children contained additives, some of which , including azo dyes and benzoates , are not permitted in food. The Commission called on the pharmaceutical industry to stop using ,questionable additives'. The MHRA stated that the licensing process takes into account the likely exposure to excipients that are considered essential to make medicines palatable to children. Colouring helps children to identify the correct medicine, and preservatives ensure a reasonable shelf-life. A list of additives is included in the product's summary of product characteristics and patient information leaflet. In response, the Commission states: , , it is quite possible to flavour medicines with natural oils or extracts, and natural colourings such as beetroot and beta-carotene can be used instead of azo dyes. If parents were advised to give these medicinal products at mealtimes the manufacturers could also add a little sugar to sweeten their products, rather than relying on artificial sweeteners.' All triptans the same? There is no economic case for choosing one triptan over another and no evidence for preferring a particular triptan for adults, a systematic review has concluded. The Canadian Agency for Drugs and Technologies in Health (www.cadth.ca) found that published trials had compared most triptans with sumatriptan but not with one another, and most economic evaluations were flawed. New drug for HIV Janssen-Cilag has introduced darunavir (Prezista), a new protease inhibitor for the treatment of HIV infection. Licensed for highly pre- treated patients in whom more than one other pro- tease inhibitor regimen has failed, darunavir must be co-administered with ritonavir (Norvir). A month's treatment at the recommended dose of 600mg twice daily costs £446.70. Variation in liquid captopril for children The NHS uses a wide range of liquid formulations of captopril to treat children with heart failure , with no assurance of their bioequivalence (Arch Dis Child 2007; published online 15 March. doi: 10.1136/adc.2006.109389). Specialists in Leicester surveyed 13 tertiary paediatric cardiac centres and 13 hospitals that referred patients to them. Only three tertiary centres supplied the same liquid for-mulation of captopril as their referring hospitals. Four hospitals supplied tablets for crushing and dissolving in water; the other hospitals and centres used a total of nine different formulations. The authors say the formulations had widely varying shelf-lives, determined empirically in all but one case, and were used interchangeably despite a lack of quality control data to establish their bioequivalence. QOF CVD targets not good enough for GPs Two-thirds of GPs want Quality Outcome Framework (QOF) targets for cardiovascular disease brought into line with those of the Joint British Societies latest guidance (JBS2), according to a survey by doctor.net.uk. The survey of 1000 GPs showed that 88 per cent were aware of the JBS2 guidelines and most were already implementing the targets for lipids, blood pressure and blood glucose in some form; however, only 55 per cent were implementing the JBS2 obesity target and 14 per cent were implementing screening for the over-40s. The JBS2 target for lipids in at-risk patients is <4mmol per litre total cholesterol and <2 mmol per litre LDL-cholesterol, compared with <5 and <3mmol per litre respectively in QOF and the NSF. The survey was commissioned by Merck Sharp & Dohme and Schering- Plough. Fracture warning Following warnings in the US that rosiglitazone (Avandia) is associated with an increased risk of fractures in women, Takeda has advised prescribers that pioglitazone (Actos) carries a similar risk. An analysis of the company's clinical trials database has revealed an excess risk of fractures of bones below the elbow and knee. The incidence was similar to the excess risk associated with rosiglitazone and also confined to women. Scottish approvals The Scottish Medicines Consortium (www.scottish medicines.org.uk) has approved for use within NHS Scotland the sublingual tablet formulation buprenorphine/naloxone (Suboxone) for the treatment of opioid dependence. It has also approved the combined formulation of valsartan and amlodipine (Exforge) and the restricted use of the If inhibitor ivabradine (Procoralan). [source] Latest news and product developmentsPRESCRIBER, Issue 6 2007Article first published online: 8 JUN 200 Initial macrolide better for pneumonia? An observational study has suggested that initial treatment with a macrolide antibiotic (such as erythromycin) may be more effective than a fluoroquinolone (like ciprofloxacin) or tetracycline as initial treatment for community acquired pneumonia and bacteraemia (Chest 2007;131:466-73). The US review of 2209 hospital episodes found that macrolide therapy was associated with a 40 per cent lower risk of death during hospital stay or within 30 days and of hospital readmission within 30 days of discharge. By contrast, no such benefit was apparent with fluoroquinolones or tetracycline. Two-year safety data for inhaled insulin Compared with sc insulin, inhaled insulin (Exubera) is associated with a small early decrease in lung function in the first three months of therapy but no further difference for up to two years (Diabetes Care 2007;30: 579-85). The comparative trial found that FEV1 declined at a mean rate of 0.051 litres per year with inhaled insulin and 0.034 litres per year with sc insulin, but there was no significant difference in the rates of decline after three months. Inhaled insulin was associated with a higher incidence of cough (37.6 vs 13.1 per cent) but a lower incidence of severe hypoglycaemic events (2.8 vs 4.1 events per 100 subject- months) and mean weight gain was 1.25kg less. Fracture risk warning with rosiglitazone GlaxoSmithKline has warned US prescribers that rosiglitazone may be associated with an increased risk of fractures. The company says information for prescribers in Europe will follow shortly. The warning comes from the ADOPT study (N Engl J Med 2006;355:2427-43), which found a significantly higher incidence of fractures of the humerus, hand and foot among women taking rosiglitazone (9.3 per cent) than with metformin (5.1 per cent) or glibenclamide (3.5 per cent). There was no difference in fracture incidence among men. The company recommends that fracture risk should be considered for women taking or about to take rosiglitazone. Oral treatment for grass pollen allergy A new treatment for allergic rhinitis due to grass pollen allergy has been introduced by ALK-Abelló. Grazax is a sublingual tablet containing a stan-dardised dose of allergen from the pollen of timothy grass. Treatment should be initiated by a specialist four months before the onset of the allergy season and continued throughout the season. Adverse effects include oral and ear pruritus, nasopharyngitis and mouth oedema. A month's treatment at the recommended dose of one tablet daily costs £67.50. Frequent analgesics linked with hypertension Men who take analgesics regularly have an increased frequency of hypertension, a US study has shown (Arch Intern Med 2007;167:394-9). The US Health Professionals Follow-Up study evaluated the use of NSAIDs, paracetamol and aspirin in 16 031 men with normal blood pressure and followed them up for four years. Compared with those who did not report analgesic use, the risk of hypertension was increased by 38 per cent for NSAID use, 34 per cent for paracetamol and 26 per cent for aspirin, all for for six or seven days a week. Similar risks were found when anal- gesic use was determined according to the number of tablets taken. The authors acknowledge the increased risk is modest, but point out that the implications may nonetheless be important because analgesics are widely used. Multiples do most pharmacist MURs Uptake of medicines use reviews (MURs) by pharmacists was modest in 2005 and most reviews were carried out by pharmacy chains rather than independent contractors, a new study has shown (Pharm J 2007;278:218-23). The survey of PCTs and SHAs in England and Wales found that, although 38 per cent of community pharmacies claimed payments for the service, 84 per cent of MURs were carried out by pharmacy chains. Uptake was low, amounting to only 7 per cent of the maximum possible number of MURs. Patients see information needs differently There is a mismatch in the perceptions of patients and health professionals about the purpose of written information about medicines, a systematic review has concluded (Health Technol Assess 2007;11:1-178). Some health professionals believe the main purpose of information is to promote compliance, whereas patients want information to help them make decisions about their treatment, including not taking it. In particular, patients want information on adverse effects, but health professionals have reservations about providing it. Aspirin for all women over 65? All women over 65 should take low-dose aspirin if the benefits are likely to outweigh the risk of adverse effects, according to new guidelines from the American Heart Association on preventing cardiovascular disease in women (published online 19 Feb 2007;doi: 10.1161/circulationaha.107.181546). The guidelines have moved away from the long-established Framingham model of risk assessment to categorising three levels of risk: high (heart disease or other relevant disease present), at risk (at least one risk factor) and optimal (healthy lifestyle, no risk factors). Low-dose aspirin is recommended for all women at high risk, for women aged 65 or over when reducing the risk of MI or ischaemic stroke outweighs the risk of adverse effects, and for younger women when reducing the risk of ischaemic stroke outweighs that of toxicity. Combination inhaler therapy Combining an inhaled long-acting bronchodilator with a steroid reduces COPD exacerbations but not all-cause mortality, a three-year trial has shown (N Engl J Med 2007;356:775-89). However, inhaled steroids appear to increase the risk of pneumonia. The TORCH trial randomised 6112 patients (FEV1<60 per cent predicted) to treatment with salmeterol 50µg plus fluticasone 500µg (Seretide) twice daily, salmeterol (Serevent) or fluticasone (Flixotide) as monotherapy, or placebo. All-cause mortality rates were 12.6, 13.5, 16.0 and 15.2 per cent respectively; the risk of death was 17 per cent lower with combined therapy, but the difference did not reach statistical significance. The combination reduced the incidence of exacerbations by 25 per cent and improved health status and FEV1. Use of fluticasone was not associated with more ocular or bone disorders, but there was an increased incidence of pneumonia among users (19.6 per cent with combined therapy and 18.3 per cent with fluticasone vs 12.3 per cent with placebo). Seretide is currently licensed in the UK for use in patients with FEV1 <50 per cent predicted. Tamoxifen long- term benefits Women with breast cancer who take tamoxifen for five to eight years continue to have a lower risk of recurrence for 10-20 years, long-term follow-up of two blinded trials has shown (J Nat Cancer Inst 2007; 99:258-60, 272-90). The frequency of adverse effects was markedly reduced when treatment ended, changing the balance of risk and benefit. Copyright © 2007 Wiley Interface Ltd [source] An increase in insulin sensitivity and basal beta-cell function in diabetic subjects treated with pioglitazone in a placebo-controlled randomized studyDIABETIC MEDICINE, Issue 6 2004T. M. Wallace Abstract Aims To investigate the effect of treatment with pioglitazone on beta-cell function and insulin sensitivity in Type 2 diabetes. Methods Thirty subjects with diet-controlled Type 2 diabetes were randomized to 3 months treatment with pioglitazone (n = 19) or placebo (n = 11). All subjects underwent basal sampling for homeostatic model assessment (HOMA), followed by an intravenous glucose tolerance test and hyperglycaemic clamp, followed by an euglycaemic hyperinsulinaemic clamp; at baseline and after treatment. Results All results are expressed as mean (sem). Pioglitazone increased basal insulin sensitivity by 24.7% (7.8) HOMA-%S vs. 2.1% (5.9) in the placebo group (P = 0.02). Stimulated insulin sensitivity, M/I, increased in the pioglitazone group compared with placebo: +15.1 (2.8) l kg,1 min,1 vs. +3.2 (2.9) l kg,1 min,1, respectively (P = 0.009). Pioglitazone increased adiponectin by 39.3 (6.3), ng/ml compared with a decrease of 0.8 (1.3) ng/ml with placebo (P = 0.00004). HOMA-%B increased with pioglitazone, +11.5% (4.8) vs. ,2.0% (4.8) with placebo (P = 0.049), but there was no change in stimulated beta-cell function as determined by hyperglycaemic clamps. There was a significant reduction in the proinsulin/insulin ratio in the pioglitazone group, ,0.057 (0.02) compared with placebo, +0.004 (0.02) (P = 0.03). There was a significant reduction in HbA1c of 0.6% (0.1) in the pioglitazone group compared with placebo (P = 0.003). There was no significant weight gain associated with pioglitazone therapy: +0.7 (sem 0.6) kg vs. +1.1 (sem 0.5) kg in placebo group (P = NS). Conclusions Basal beta-cell function and insulin sensitivity improved following pioglitazone therapy. The improvement in proinsulin to insulin ratio suggests that beta-cells are under less stress. [source] Combined therapy of silymarin and desferrioxamine in patients with ,-thalassemia major: a randomized double-blind clinical trialFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2009Marjan Gharagozloo Abstract Silymarin, a flavonolignan complex isolated from Silybum marianum, has a strong antioxidant, hepatoprotective, and iron chelating activities. The present study was designed to investigate the therapeutic activity of orally administered silymarin in patients with thalassemia major under conventional iron chelation therapy. A 3-month randomized, double-blind, clinical trial was conducted in 59 ,-thalassemia major patients in two well-matched groups. Patients were randomized to receive a silymarin tablet (140 mg) three times a day plus conventional desferrioxamine therapy. The second group received the same therapy but a placebo tablet instead of silymarin. Clinical laboratory tests were assessed at the beginning and the end of the trial, except for serum ferritin level that was assessed at the middle of the trial as well. Results of this study revealed that the combined therapy was well tolerated and more effective than desferrioxamine in reducing serum ferritin level. Significant improvement in liver alkaline phosphatase and glutathione levels of red blood cells was also observed in silymarin-treated ,-thalassemia patients. However, no significant difference in serum ferritin levels was detected between silymarin and placebo groups after 1.5 and 3 months treatment, probably because of insufficient sample size to detect subtle changes in ferritin levels between groups. This is the first report showing the beneficial effects of silymarin in thalassemia patients and suggests that silymarin in combination with desferrioxamine can be safely and effectively used in the treatment of iron-loaded patients. [source] The effect of oral folic acid upon plasma homocysteine, endothelial function and oxidative stress in patients with type 1 diabetes and microalbuminuriaINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2008F. Wotherspoon Summary Aims:, The purpose of this study was to investigate the effect of oral folic acid supplementation upon plasma homocysteine (HCY), endothelial function and oxidative stress on patients with type 1 diabetes and microalbuminuria to test the hypothesis that oral folic acid would lower plasma HCY and thereby improve endothelial function and reduce oxidant stress in this high-risk group of patients. Methods:, We measured plasma HCY, forearm blood flow, total antioxidant status and whole blood glutathione at baseline and after 2 months treatment with oral folic acid or placebo in 16 patients with type 1 diabetes and microalbuminuria. Results:, Plasma HCY fell by 25% in the folic acid group but there was no difference in endothelial function or markers of oxidant stress in the treatment group. Conclusions:, Oral folic acid supplementation successfully lowered plasma HCY levels in patients with type 1 diabetes and microalbuminuria, however this was not associated with improvements in endothelial function or markers of oxidant stress. [source] Hypertension, white matter change and response to cholinesterase inhibitors in Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 7 2005Peter J. Connelly Abstract Background Cholinesterase inhibitors are used to treat mild to moderate Alzheimer's disease. Their role in patients with concurrent cerebrovascular disease has been less well studied, and the influence of vascular risk factors on response to treatment is uncertain. We investigated the effect of hypertension and white matter lesions (WML) on response. Methods A retrospective sample of 160 consecutive out-patients who had blood pressure measured and the presence or absence of WML recorded at baseline and who completed six months treatment with a cholinesterase inhibitor was studied. Subjects scored either zero or one on the Modified Hachinski Ischaemic Scale. Subjects were assessed using the Mini-Mental State Examination (MMSE), the Digit Symbol Substitution test (DSST) and both the Instrumental Activities of Daily Living (IADL) and Social Behaviour (SB) sub-scales of the Nurses Observation Scale for Geriatric Patients (NOSGER). Results 43.9% of the total study population were classified as good responders using our criteria. Neither the presence of hypertension nor the presence of WML alone influenced outcome. However, there was a statistically significant interaction between blood pressure and WML on outcome variables on multiple analysis of variance (MANOVA) (F(4,,139),=,5.60, p,<,0.0005). Subjects with both hypertension and WML deteriorate to a significantly greater extent in IADL and SB scores than any other group (p,<,0.05 in each case). This effect could not be explained by age or by smoking status. Conclusion Our results support the hypothesis that there is an interaction between hypertension and WML that adversely influences functional change during cholinesterase inhibitor treatment. Our results are a contrast to suggestions that subjects with vascular disease show a better response to cholinesterase inhibitors. We recommend careful exploration of factors that may influence outcome. Copyright © 2005 John Wiley & Sons, Ltd. [source] Excellent response of refractory life-threatening thrombotic thrombocytopenic purpura to cyclosporine treatmentINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2004M. Itälä Summary The introduction of plasma exchange has significantly improved the outcome of thrombotic thrombocytopenic purpura (TTP), and survival has increased from 10 to 80,90%. TTP refractory to plasma exchange therapy, however, is still a therapeutic challenge. We describe here a patient who partially responded to plasma exchange therapy, but remained totally dependent on plasma infusions. Several attempts to discontinue plasma therapy repeatedly lead to relapses. TTP did not response to vincristine, either. After 3 months treatment with plasma therapy, cyclosporine was started. Plasma therapy could be discontinued after 3 weeks on cyclosporine, and serum LDH and blood platelet count were gradually normalized during 2 months. Cyclosporine was tapered off after 6 months treatment, and the patient has stayed in remission ever since. We conclude that cyclosporine is a worthwhile treatment option in patients with refractory TTP. [source] Can sildenafil treat primary premature ejaculation?INTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2007A prospective clinical study Background: Recently, sildenafil has been demonstrated to be effective in treating premature ejaculation (PE). However, these studies ignored female factors and could not exclude the probability of drug interaction when combined with paroxetine. Therefore, the aim of this study was to evaluate the efficacy and safety of sildenafil alone in the treatment of primary PE, taking female factors into consideration. Methods: One hundred and eighty potent men with primary PE were randomly divided into three groups and followed up for 6 months. Group A were treated with 50 mg sildenafil as needed, group B with 20 mg paroxetine daily and group C with squeeze technique daily. Intravaginal ejaculatory latency time (IELT), PE grade, intercourse satisfactory score (ISS), frequency of intercourse, and adverse effects of drugs were recorded before treatment, and 3 and 6 months after treatment. Results: Compared with pretreatment, the three groups had significant differences in all the parameters after 3 or 6 months treatment, except the frequency of intercourse in Group C (all P = 0.00). However, there were no significant differences between 3 and 6 months. Compared with paroxetine and squeeze technique, after 3 or 6 months, sildenafil had significant differences in all the parameters (all P = 0.00). After 6 months, 1.7%, 18.3% and 36.7% patients in groups A, B and C, respectively, withdrew from the study and 86.7%, 60.0% and 45.0% patients, respectively, wanted to be treated further with the original administration, and this was statistically significant (both P = 0.00). Conclusion: Sildenafil is very effective and safe to treat PE, and has much higher efficacy than paroxetine and squeeze technique. [source] Treatment of chronic liver diseases with traditional Chinese medicineJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2000Bao-En Wang Traditional Chinese medicine is still being extensively used for treatment of liver disease in China. The anti-viral herbs, Phyllanthus amarus, P. niruri and P. urninaria, and Oxymatrine extracted from Sophora flavecientis and S. subprostratae, have been shown to have a remarkable HBV suppressing effect with a serum conversion rate for HBeAg and HBV DNA around 45%, similar to that of IFN-,. The anti-inflammatory compound, Stronger NeoMinophagen C (SNMC), is a Japanese preparation of glycerrhizin, extracted from Glyceriza glabra, which has shown an effective rate of ALT and AST normalization and reduction to < 60 U/L in 65.6% and 73.5% of patients. Compound 861, made of 10 herbs with Salvia miltiorrhiza as its chief component, has been shown experimentally to be effective in suppressing fibrogenesis, enhancing collagen degradation, and inhibiting TIMP expression. Clinically, an open trial of 2000 patients showed improvement of symptoms in 83% and normalization of serum ALT in 82%. In a controlled study of 107 patients with HBV-related diseases, double liver biopsies showed that the fibrosis reversal rate after 6 months treatment with Cpd 861 was 78% in S2, 82% in S3 (precirrhotic stage) and 75% in S4 (early cirrhosis), as assessed by Scheuer's and Chevallier's criterion. In conclusion, traditional Chinese medicine has great potential in the treatment of chronic hepatitis B. [source] A United States compassionate use study of lamivudine treatment in nontransplantation candidates with decompensated hepatitis B virus,related cirrhosisLIVER TRANSPLANTATION, Issue 1 2003Hie-Won L. Hann MD Patients with hepatitis B,related decompensated cirrhosis have limited treatment options. This prospective, multicenter study assessed lamivudine in 75 patients with decompensated cirrhosis, the majority of whom (93%) were not candidates for liver transplantation. At baseline, all 75 patients tested positive for hepatitis B surface antigen [HBsAg (+)] and 62% tested positive for hepatitis B e antigen [HBeAg (+)]. Hepatitis B virus (HBV) DNA levels were detectable in 64% of patients by the branched chain DNA (bDNA) assay. Patients received lamivudine 100 mg once daily (median duration, 12.7 months; range, 0.5 to 33 months). In patients with detectable HBV DNA pretreatment, the virus became undetectable by the bDNA assay in 69% of patients with , 6 months treatment and in 64% overall. Alanine aminotransferase (ALT) level improved in 90% and normalized in 55% of patients with , 6 months treatment and in 48% overall. Improvements in bilirubin and albumin levels occurred throughout treatment. The median Child-Pugh score improved from a baseline of 10 to 8 at last visit, with 31% (23/75) having an improved score of , 2 points, 57% (43/75) unchanged (< 2 points), and 12% (9/75) worsened (, 2 points). A virologic breakthrough developed in eight of 41 patients (18%) after a median of 13.1 months of treatment. Tyrosine-methionine-aspartate-aspartate (YMDD) variant HBV was detected in three of four patients tested. Nevertheless, at last visit, ALT, albumin, and bilirubin levels were similar for patients with and without breakthrough. Lamivudine treatment can lead to significant improvements in liver disease severity in nontransplantation candidates with advanced disease. Additional studies of lamivudine in combination with other antivirals are indicated for the large population of patients worldwide with advanced HBV-related cirrhosis and inadequate access to liver transplantation. [source] Modest increase in plasma homocysteine follows levodopa initiation in Parkinson's diseaseMOVEMENT DISORDERS, Issue 12 2004Padraig E. O'Suilleabhain MB Abstract Levodopa, typically ingested chronically at high daily doses, is predictably methylated by means of a series of reactions using B vitamins, which convert methionine to homocysteine. Elevated total plasma homocysteine (tHcy), a risk factor for dementia, has been found in PD patients using levodopa. We prospectively measured the effects on plasma tHcy and B vitamins of levodopa initiation, and measured the effects of dose changes and of treatment with dopamine agonists and entacapone. We collected paired plasma samples, at baseline and again after several months treatment, from patients initiating levodopa (n = 30), from patients whose levodopa dose was doubled (n = 15), halved or stopped (n = 14), from patients starting or stopping entacapone (n = 15) and from patients initiating or doubling dopamine agonist monotherapy (n = 16). Vitamin B12, folate, and tHcy concentrations were measured. Baseline tHcy concentration of 8.7 (2.8) ,mol/L increased to 10.1 (3.1) ,mol/L (P = 0.004) an average of 94 (range 36 to 200) days after initiation of 604 (240 to 1050) mg/day of L -dopa. Average concentration of vitamin B12 fell from 380 to 291 pmol/ L (P = 0.01). Patients who doubled their daily levodopa dose experienced tHcy elevations from 9.5 to 11.1 ,mol/L (P = 0.05). Levodopa reduction, agonist treatment, and entacapone treatment did not have significant effects. Levodopa elevates tHcy and lowers vitamin B12 concentration to modest degrees. The clinical implications, if any, have not yet been determined. © 2004 Movement Disorder Society [source] Sexuality and Management of Benign Prostatic Hyperplasia with Alfuzosin: SAMBA ThailandTHE JOURNAL OF SEXUAL MEDICINE, Issue 9 2010Somboon Leungwattanakij MD ABSTRACT Introduction., Benign prostatic hyperplasia (BPH) is a common condition among elderly men. The aim of therapy is to improve lower urinary tract symptoms (LUTS) and quality of life (QoL) and to prevent complications. Aim., The primary objective was to assess the effect on ejaculatory dysfunction (EjD) of 6 months treatment with alfuzosin (XATRAL) 10 mg once daily (OD) in men with LUTS suggestive of BPH in Thailand. Secondary objectives were to evaluate the efficacy of alfuzosin on LUTS, bother score (International Prostate Symptom Score [IPSS] 8th question), erectile dysfunction (ED), onset of action, and tolerability. Methods., Overall, 99 men with moderate to severe LUTS suggestive of BPH (mean IPSS 18.9, bother score 4.3) were enrolled in an open-label study. Sexual function was evaluated at baseline and after 6 months treatment, using the International Index of Erectile Function-5 and the Male Sexual Health Questionnaire (MSHQ) ejaculation score, a new validated questionnaire assessing seven EjD symptoms. Main Outcome Measure., The main outcome measure is mean change from baseline to the end of treatment in the MSHQ Ejaculation score. Results., MHSQ ejaculation score significantly improved from 23.09 at baseline to 21.54 at 6 months (P = 0.022). Overall, 70% of patients perceived an improvement in LUTS within 1 week (36.3% within 3 days). IPSS total score significantly improved from 18.93 at baseline to 9.59 at 6 months (P < 0.001). IPSS voiding and irritative subscores also significantly improved. The percentage of patients with moderate or severe ED decreased from 35.3% at baseline to 21.8% at 6 months. Most adverse events were dizziness (3%) and orthostatic hypotension (1%) with minor intensity. No significant change in blood pressure and heart rate was observed. Conclusions., Alfuzosin 10 mg OD administered for 6 months provides a marked and rapid (within 1 week) improvement in LUTS and bother score while improving both ED and EjD. Leungwattanakij S, Watanachote D, Noppakulsatit P, Petchpaibuol T, Choeypunt N, Tongbai T, Wanamkang T, Lojanapiwat B, Permpongkosol S, Tantiwong A, Pripatnanont C, Akarasakul D, Kongwiwatanakul S, and Chotikawanich E. Sexuality and management of benign prostatic hyperplasia with alfuzosin: SAMBA Thailand. J Sex Med 2010;7:3115,3126. [source] Drug-related pemphigus and angiotensin converting enzyme inhibitorsAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2000Colin S Ong SUMMARY A 105-year-old woman developed pemphigus foliaceus. She had been on fosinopril, an angiotensin-converting enzyme inhibitor (ACE inhibitor) for 4 years. Anti-intercellular cement substance antibodies were positive with titre > 160. She died during admission of an unrelated illness. A 57-year-old man developed pemphigus vulgaris after 11 months treatment with quinapril. At 14 months after developing pemphigus, this man continues on prednisone and azathioprine. We speculate that these are cases of ACE-inhibitor-related pemphigus and we review ACE-inhibitor-related pemphigus. [source] Effect Of Anti-Oxidant Treatment And Cholesterol Lowering On Resting Arterial Tone, Metabolic Vasodilation And Endothelial Function In The Human Forearm: A Randomized, Placebo-Controlled StudyCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2001Stephen J Duffy SUMMARY 1. The aim of the present study was to determine whether anti-oxidant therapy with vitamin E and/or cholesterol-lowering therapy with simvastatin would augment resting forearm blood flow (FBF) and metabolic vasodilation in response to exercise and improve endothelial function in young patients with hypercholesterolaemia. 2. Endothelium-dependent and -independent, nitric oxide (NO)-mediated vasodilation have been shown to be impaired in young, otherwise healthy subjects with hypercholesterolaemia. Recent experimental and clinical studies suggest that vascular function may be improved with anti-oxidant or cholesterol- lowering therapy, although these treatments may be synergistic. 3. We compared FBF at rest, in response to isotonic exercise, the endothelium-dependent vasodilator acetylcholine (ACh), the endothelium-independent vasodilator sodium nitroprusside (SNP) and the NO synthase inhibitor NG -monomethyl- L -arginine (L -NMMA) in 26 young, otherwise healthy volunteers (mean (±SD) age 29±7 years; 14 female, 12 male) with hypercholesterolaemia, before and after 6 months treatment with vitamin E, simvastatin and/or placebo. Treatment was randomized, double-blinded in a 2 × 2 factorial design. Forearm blood flow was measured using venous occlusion plethysmography. 4. Vitamin E therapy increased plasma ,-tocopherol from 39.5±9.6 to 75.7±33.8 ,mol/L (P < 0.001). Simvastatin reduced total cholesterol from 6.9±1.7 to 4.9±0.8 mmol/L and low- density lipoprotein (LDL) from 4.8±1.7 to 3.0±0.7 mmol/L (both P < 0.001), although total and LDL,cholesterol also decreased slightly in the placebo group. Vitamin E increased resting FBF from 2.1±0.3 to 2.4±0.3 mL/100 mL per min (P = 0.04) and decreased resting forearm vascular resistance from 42.1±4.2 to 36.1±3.4 units (P = 0.01), but the reduction in resting FBF with L -NMMA was not affected. Vasodilation in response to isotonic exercise, ACh and SNP was similar before and after treatment in the placebo, vitamin E, simvastatin and in the combined vitamin E,simvastatin groups. NG -Monomethyl- L -arginine infusion reduced resting FBF and functional hyperaemia in response to exercise and these responses were not altered by treatment. 5. These data suggest that while vitamin E therapy augments resting FBF and reduces forearm vascular resistance in young hypercholesterolaemic subjects, these effects may not be via NO-dependent pathways. Metabolic vasodilation and responses to the NO-mediated vasodilators ACh and SNP were not favourably affected by anti-oxidant or cholesterol-lowering therapy, either alone or in combination. [source] Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesityCLINICAL ENDOCRINOLOGY, Issue 3 2009M. Mraz Summary Objective, Fibroblast growth factor-21 (FGF21) is a novel endocrine and paracrine regulator of metabolic homeostasis. The aim of our study was to measure its serum concentrations in patients with obesity, obesity and type 2 diabetes mellitus (T2DM) and healthy subjects (C), and to assess the changes of its circulating levels and mRNA expression after dietary and pharmacological interventions. Design, We measured biochemical parameters, serum FGF21, adiponectin, leptin and insulin levels by commercial ELISA and RIA kits, and mRNA expression in the liver, subcutaneous and visceral fat by RT PCR in 26 obese patients, 11 T2DM patients and 32 control subjects. The interventions were acute hyperinsulinaemia during isoglycaemic,hyperinsulinaemic clamp, very low calorie diet (VLCD) and 3 months treatment with PPAR-, agonist fenofibrate. Results, Baseline serum FGF21 levels were significantly higher in both obese and T2DM patients relative to healthy controls. FGF21 levels in obesity did not significantly differ from T2DM group. Both 3 weeks of VLCD and 3 months of fenofibrate treatment significantly increased FGF21 levels. FGF21 mRNA expression in visceral fat was twofold higher in obesity relative to C group, while it did not differ in subcutaneous fat. VLCD significantly increased FGF21 mRNA expression in subcutaneous fat of obesity. 3-h hyperinsulinaemia during the clamp increased FGF21 levels in T2DM but not in C group. Conclusion, An increase in FGF21 levels after VLCD and fenofibrate treatment may contribute to positive metabolic effect of these interventions and suggests the possibility of direct positive metabolic effects of FGF21 in humans. [source] Long-term desmopressin response in primary nocturnal enuresis: open-label, multinational studyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2009H. Lottmann Summary Background:, Primary nocturnal enuresis (PNE) is a distressing condition, particularly in severe cases (, 3 wet nights/week). A prevalent pathophysiological mechanism, especially in monosymptomatic PNE (PMNE), is commonly believed to be an insufficient increase in night-time release of antidiuretic hormone. Desmopressin, a synthetic analogue of antidiuretic hormone, has been shown to reduce the number of wet nights experienced by PMNE patients in several controlled trials. Aim: This study was performed to evaluate desmopressin treatment in the real-life clinical setting and was a large-scale, 6-month investigation of efficacy and safety in patients with severe PNE. Predictive factors for desmopressin response were also evaluated. A total of 744 children aged 5 years and above from four countries were involved in the study. Results: At baseline, patients had a median of 6 wet nights/week; at 6 months, 41% of patients had experienced , 50% reduction in the mean number of wet nights. Long-term desmopressin treatment was consistently well-tolerated across all ages, with 5% of patients experiencing any treatment-related adverse events. The strength of treatment response was associated with nocturnal diuresis (p < 0.0001) and age (p = 0.0167) in logistic regression analyses. Compliance and dosage were also associated with response and more patients experienced , 50% reduction in wet nights after 6 months' treatment than earlier in the study, suggesting the value of persistent treatment. Conclusion: This study shows that long-term desmopressin treatment in the clinical setting is effective and well-tolerated in PNE patients of 5 years and upwards. Early improvements in bedwetting of any appreciable magnitude may be rewarding, may facilitate compliance and enable good long-term response. [source] Effectiveness of a lifestyle modification programme in weight maintenance in obese subjects after cessation of treatment with OrlistatJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 6 2007Jean Woo MD Abstract Objective, To examine the efficacy of a lifestyle modification programme in weight maintenance for obese subjects after cessation of treatment with Orlistat. Methods, Fifty-five subjects with and without diabetes mellitus were randomized to a lifestyle modification programme or to usual care at the end of 6 months' treatment with Orlistat. The intervention programme was nutritionist led, consisting of components of dietary management, physical activity, peer group support and discussion using techniques of self-monitoring, stimulus control and cognitive restructuring. Anthropometric indices, body composition, basal metabolic rate, blood pressure, fasting glucose, glycosylated haemoglobin, lipid profile, 24-hour urinary albumin excretion, dietary intake, physical activity level, and quality of life were assessed before and after the intervention period. Results, Subjects in the intervention group maintained their weight loss and favourable anthropometric, metabolic, dietary intake, physical activity and quality of life profiles, while most parameters deteriorated in the usual care group, being more marked in subjects with diabetes. The magnitude of weight gain was comparable to that lost during Orlistat treatment. Conclusion, A specially designed nutritionist-led lifestyle modification programme for obese subjects is effective in weight maintenance after treatment with Orlistat, in the absence of which the benefits of drug treatment were lost. The magnitude of the effect of lifestyle modification is comparable to that observed with Orlistat. [source] Topical 3.0% diclofenac in 2.5% hyaluronic acid gel induces regression of cancerous transformation in actinic keratosesJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2010T Dirschka Abstract Background, Actinic keratoses (AKs) are frequently diagnosed in dermatological patients. As they represent in situ carcinomas, effective treatment is required. Objectives, We investigated the effect of topical 3.0% diclofenac in 2.5% hyaluronic acid gel on AK. Methods, Sixty-five patients with AKs were clinically evaluated before and after 3 months' treatment with topical 3.0% diclofenac in 2.5% hyaluronic gel. Biopsy specimens were taken and stained with haematoxylin-eosin and immunohistological markers. Specimens were evaluated for histological type of AKs using the AK classification scheme suggested by Röwert-Huber et al. [(early) in situ squamous cell carcinoma type AK Grade I,III], number of mitoses per high-power field and expression of immunohistological markers. Results, Complete clinical resolution was observed in 11 patients (16.9%). A significant (P < 0.001) downgrading of AK grade was observed. Complete histological resolution was achieved in 15 patients (23.1%). The number of mitoses per high-power field was reduced significantly (P < 0.001). The expression of anti-p53-antibody decreased significantly (P = 0.009), as did the expression of anti-MiB-1 antibody (P = 0.021). Conclusions, 3.0% diclofenac in 2.5% hyaluronic acid gel causes regression of signs of cancerous transformation after 3 months' therapy. [source] Clinical trial: ulcerative colitis maintenance treatment with 5-ASA: a 1-year, randomized multicentre study comparing MMX® with Asacol®ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009C. PRANTERA Summary Background, 5-ASA-MMX® (1.2 g/tablet) is a 5-aminosalicylic acid formulation, designed for once-daily dosing in the treatment of ulcerative colitis. Aim, To evaluate the efficacy and safety of 5-ASA-MMX (2.4 g/day, once daily), compared with Asacol® (2.4 g/day, twice daily) in the maintenance of left-sided UC, through a double-blind, double-dummy, parallel-group, randomized, comparator study. Methods, In all, 331 patients with UC were randomized to receive either 5-ASA-MMX 2.4 g/day, once daily, or Asacol 2.4 g/day, twice daily, for 12 months. All patients were in remission for ,1 month prior to the trial, with ,1 documented relapse in the previous year. The co-primary endpoints of this study were the proportion of patients in clinical, and clinical and endoscopic remission following 12 months' treatment. Results, In the intent-to-treat population, excluding those with major protocol deviations, 68.0 and 65.9% patients in the 5-ASA-MMX and Asacol groups, respectively, were in clinical remission (P = 0.69), and 60.9 and 61.7% of patients, respectively, were in clinical and endoscopic remission (P = 0.89). Diary card data revealed statistically significant treatment differences favouring 5-ASA-MMX. Both treatments were similarly tolerated. Conclusions, Once-daily 5-ASA-MMX is similarly effective with a comparable safety profile to Asacol administered twice daily, for the maintenance treatment of ulcerative colitis. [source] Increased plasma fibrin gel porosity in patients with Type I diabetes during continuous subcutaneous insulin infusionJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2003G. Jörneskog Summary.,Background:,Patients with Type 1 diabetes have a tighter plasma fibrin gel structure, to which impaired glycemic control might contribute. Improved glycemic control can be achieved with continuous subcutaneous insulin infusion (CSII). Objectives:,The aim of the present study was to investigate the effect of CSII on plasma fibrin gel properties and circulating markers of inflammatory activity in patients with Type 1 diabetes. Patients and methods:,Twenty-eight patients were investigated before and after 4,6 months' treatment with CSII. Fibrin gel structure formed in vitro from plasma samples was investigated by liquid permeation of hydrated fibrin gel networks. P-fibrinogen was analyzed by a syneresis method. Comparisons were made between patients with improved (> 0.5%) and unchanged (< 0.5%) glucosylated hemoglobin (HbA1c) during CSII. Results:,Eighteen patients showed improved and 10 patients unchanged HbA1c during CSII. P-fibrinogen, high sensitive C-reactive protein and serum amyloid A-antigen were not significantly changed, while fibrin gel permeability (Ks) and fiber mass,length ratio (µ) increased in both groups (P < 0.02). P-insulin and triglycerides decreased (P < 0.05) in both groups, while reductions of total cholesterol and intercellular adhesion molecule-1 were seen only in patients with improved HbA1c (P < 0.05). Absolute changes in Ks were inversely correlated to changes in plasma fibrinogen (r = 0.50; P < 0.01) and in LDL-cholesterol (r = 0.46; P < 0.05). Conclusions:,Treatment with CSII in patients with Type 1 diabetes is associated with increased plasma fibrin gel porosity. Slight attenuation of the inflammatory activity was also observed. The changes in fibrin gel porosity seem to be mainly mediated by changes in plasma fibrinogen and blood lipids, and are probably secondary to improved insulin sensitivity. [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] | |||||||||||||||||||||||||