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Randomised Trials (randomised + trials)
Selected AbstractsWard reduction of gastroschisis in a single stage without general anaesthesia may increase the risk of short-term morbidities: Results of a retrospective auditJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 6 2009Shripada C Rao Background: Ward reduction of gastroschisis in a single stage without the need for general inhalational anaesthesia (ward reduction) has been reported by some authors to be effective and safe. We introduced this practice to our neonatal unit 2 years ago. Aim: To compare the short-term outcomes of this new practice with the standard procedure of reduction under general anaesthesia (GA). Methods: Retrospective case series of all infants with gastroschisis between January 2004 and January 2008. Results: Twenty-seven infants were managed with the traditional approach and 11 infants underwent ward reduction without GA. Infants in the ward reduction group had an increased frequency for all the three major adverse events (ischemic necrosis of bowel: 27.3% vs. 3.7%, odds ratio (OR) 10.72, 95% confidence interval (CI): 0.72, 159.6; need for total parenteral nutrition (TPN) more than 60 days: 18% vs. 3.7%, OR 4.13, 95% CI: 0.28, 61.55; and unplanned return to theatre: 27.3% vs. 7.4%, OR 3.88, 95% CI: 0.44, 34.08), although none of these events reached statistical significance. There were no significant differences between the groups for the outcomes of time to reach full feeds, duration of hospital stay and number of days on antibiotics. Conclusions: These results raise concerns over the role of ward reduction of gastroschisis in a single sitting without the use of GA. Randomised trials with appropriate design and sample size are needed before embracing this method as a standard practice. [source] Latest news and product developmentsPRESCRIBER, Issue 2 2008Article first published online: 11 FEB 200 NICE should evaluate all new medicines NICE should determine the cost effectiveness of all new medicines, the Health Select Committee has concluded in its second review of the Institute. The review, prompted by criticisms from patients, health professionals and the pharmaceutical industry, found that NICE is doing ,a vital job in difficult circumstances'. The Committee called for the costs to carers and society to be included in cost effectiveness estimates (this is currently prohibited) and for cost per QALY thresholds to be aligned with NHS affordability. NICE should publish brief appraisals at the time of a product launch , these could be used to negotiate prices. GPs responsible for unlicensed co-proxamol GPs who prescribe co-proxamol are now responsible for the consequences, the MHRA warns. The Agency agrees that the drug may be needed by ,a small group of patients who are likely to find it very difficult to change from co-proxamol or where alternatives appear not to be effective or suitable'. Following the withdrawal of product licences, stock that is currently in the supply chain may be dispensed but no new stock should be released by suppliers. The Drug Tariff price of co-proxamol has now increased from £2.79 to £20.36 per 100 tablets. Vitamin D deficiency on the increase Pregnant and breastfeeding women may need vitamin D supplements, the Department of Health has warned, and GPs are seeing increasing numbers of patients with vitamin D deficiency. Endogenous synthesis may be low in some ethnic groups and dark-skinned people, and north of Birmingham there is no light of the appropriate wavelength for the synthesis of vitamin D during the winter. The Department says free vitamin supplements are available for eligible patients through its Healthy Start Scheme (www.healthystart.nhs.uk) and may also be supplied at low cost by some PCTs. Innovation and good practice recognised Innovative practice and better outcomes for patients have been recognised through awards from the NHS Alliance and Improvement Foundation presented by the Secretary of State for Health, Rt Hon Alan Johnson, at the annual NHS Alliance conference held in Manchester. The Mountwood Surgery in Northwood, Middlesex, won the CHD QOF GP Practice Award sponsored by Schering Plough for their outstanding multidisciplinary approach to tackling CHD. In addition to having a highly organised in-house cardiology team, they have produced an interactive, patient-empowering booklet for CHD. Mountwood Surgery achieved blood pressure targets of 96.79 per cent in their CHD patients. North Tees PCT wins the CHD QOF PCO Award, also sponsored by Schering Plough, for their support and encouragement to GP practices to ,own' CHD care. They provide timely feedback of performance data using funnel plots and regular communication by the CHD LIT and Cardiac Network. Even though North Tees PCT has a high CHD prevalence, 4.2 per cent vs 3.6 per cent nationally, across the 27 practices 85 per cent of patients achieved cholesterol targets and 91 per cent reached the QOF blood pressure target. The St Benedict's Hospice Day Centre Project (for the Sunderland Teaching Primary Care Trust) won the Guy Rotherham Award for its excellent multidisciplinary team improvement of the palliative care provided. This team demonstrated a thorough understanding of the use of quality improvement methods to improve patient care, and carefully measured the individual improvements they made. Through the use of a referral ,decision tree', nonattenders were reduced by 300 per cent and average waiting times halved. The Extended Primary Care (EPC) Gynaecology Service (for the Practice Based Commissioning Consortium South Manchester Hub) was highly commended for its development of an effective and innovative service offering gynaecological treatment managed within a primary care setting, allowing patients improved access closer to home. The Salford Perinatal Mental Health Project was also highly commended for effectively challenging the high levels of maternal suicides. The awards were also supported by Prescriber, the British Cardiac Patients Association and the British Cardiac Society. Anastrozole superior to tamoxifen in long term A new analysis of the ATAC trial (Lancet Oncology 2008;9:45-53) shows that the advantages of the aromatase inhibitor anastrozole (Arimidex) over tamoxifen as adjuvant therapy for breast cancer persist for at least four years after the end of treatment. After primary treatment with surgery, chemotherapy or radiotherapy, postmenopausal women with localised invasive breast cancer were randomised to five years' treatment with anastrozole or tamoxifen. Among 5216 women who were hormone-receptor positive, anastrozole increased disease-free survival by 15 per cent after 100 months. Time to recurrence and distant recurrence were also increased, though overall survival was similar; the absolute difference in time to recurrence was greater at nine years (4.8 per cent) than at five years (2.8 per cent). Joint symptoms and fractures were more frequent with anastrozole during treatment but not thereafter. Use a steroid with a LABA , MHRA reminder The MHRA has reminded clinicians that patients treated with an inhaled long-acting beta-agonist (LABA) should also use an inhaled steroid. In the latest edition of Drug Safety Update (2008;1:No.6), the Agency reviews the implications of the SMART study (Chest 2006;129:15-26), which reported an increased risk of respiratory- and asthma-related deaths among patients using salmeterol (Serevent). This is contradicted by epidemiological data suggesting that asthma-related admissions have declined since LABAs were introduced. Randomised trials also do not support such a risk, probably because inhaled steroids are used more consistently in trial settings. The latest Update notes that product licences for carisoprodol (Carisoma) have been suspended due to concerns about the risk of abuse and psychomotor effects. It also includes a comprehensive summary of drug interactions with statins, a warning that methylene blue should not be prescribed for a patient taking a drug with serotonergic activity, and a reminder that only oral formulations of desmopressin are now licensed for primary nocturnal enuresis. This issue of Update is available at www.mhra.gov.uk. Copyright © 2008 Wiley Interface Ltd [source] Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trialsFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 1 2004Article first published online: 14 JUN 2010 [source] Warning about poorly designed randomised trialsFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 1 2004Article first published online: 14 JUN 2010 [source] Methods for incorporating covariate adjustment, subgroup analysis and between-centre differences into cost-effectiveness evaluationsHEALTH ECONOMICS, Issue 12 2005Richard M. Nixon Abstract Background: Overall assessments of cost,effectiveness are now commonplace in informing medical policy decision making. It is often important, however, also to investigate how cost,effectiveness varies between patient subgroups. Yet such analyses are rarely undertaken, because appropriate methods have not been sufficiently developed. Methods: We propose a coherent set of Bayesian methods to extend cost,effectiveness analyses to adjust for baseline covariates, to investigate differences between subgroups, and to allow for differences between centres in a multicentre study using a hierarchical model. These methods consider costs and effects jointly, and allow for the typically skewed distribution of cost data. The results are presented as inferences on the cost,effectiveness plane, and as cost,effectiveness acceptability curves. Results: In applying these methods to a randomised trial of case management of psychotic patients, we show that overall cost,effectiveness can be affected by ignoring the skewness of cost data, but that it may be difficult to gain substantial precision by adjusting for baseline covariates. While analyses of overall cost,effectiveness can mask important subgroup differences, crude differences between centres may provide an unrealistic indication of the true differences between them. Conclusions: The methods developed allow a flexible choice for the distributions used for cost data, and have a wide range of applicability , to both randomised trials and observational studies. Experience needs to be gained in applying these methods in practice, and using their results in decision making. Copyright © 2005 John Wiley & Sons, Ltd. [source] Fibromuscular dysplasia of cervical and intracranial arteriesINTERNATIONAL JOURNAL OF STROKE, Issue 4 2010Emmanuel Touzé Fibromuscular dysplasia is an uncommon, segmental, nonatherosclerotic arterial disease of unknown aetiology. The disease primarily affects women and involves intermediate-sized arteries in many areas of the body, including cervical and intracranial arteries. Although often asymptomatic, fibromuscular dysplasia can also be associated with spontaneous dissection, severe stenosis that compromises the distal circulation, or intracranial aneurysm, and is therefore responsible for cerebral ischaemia or subarachnoid haemorrhage. Fibromuscular dysplasia affects middle and distal portions of the internal carotid and vertebral arteries, and occasionally, intracranial arteries. Several pathological and angiographic patterns exist. The most frequent pathological type is medial fibromuscular dysplasia, which is associated with the ,string of beads' angiographic pattern. Unifocal lesions are less common and can be associated with several pathological subtypes. The pathophysiology of the disease is widely unknown. Fibromuscular dysplasia may in fact result from various causes and reflect a non-specific response to different insults. The poor knowledge of the natural history and the lack of randomised trials that compared the different treatment options do not allow any satisfactory judgement to be made regarding the need for or the efficacy of any treatment. [source] A systematic review of the effectiveness of cutaneous warming systems to prevent hypothermiaJOURNAL OF CLINICAL NURSING, Issue 5 2009Cristina M Galvćo Aims., To retrieve and critique recent randomised trials of cutaneous warming systems used to prevent hypothermia in surgical patients during the intraoperative period and to identify gaps in current evidence and make recommendations for future trials. Background., Hypothermia affects up to 70% of anaesthetised surgical patients and is associated with several significant negative health outcomes. Design., Systematic review using integrative methods. Methods., We searched CINAHL, EMBASE, Cochrane Register of Controlled Trials and Medline databases (January 2000,April 2007) for recent reports on randomised controlled trials of cutaneous warming systems used with elective patients during the intraoperative period. Inclusion criteria., We included randomised control trials examining the effects of cutaneous warming systems used intraoperatively on patients aged 18 years or older undergoing non-emergency surgery. Studies published in English, Spanish or Portuguese with a comparison group that consisted of either usual care or active cutaneous warming systems without prewarming were reviewed. Results., Of 193 papers initially identified, 14 studies met the inclusion criteria. There was moderate evidence to indicate that carbon-fibre blankets and forced-air warming systems are equally effective and that circulating-water garments are most effective for maintaining normothermia during the intraoperative period. Few trials reported costs. Conclusions., Carbon-fibre blankets and forced-air warming systems are effective and circulating-water garments may be preferable. Future research should measure the direct and indirect costs associated with competing systems. Relevance to clinical practice., Nurses can use this review to inform their selection of warming interventions in perioperative nursing practice. They can also assess other factors such as nursing workload, staff training and equipment maintenance, which should be incorporated into future research. [source] Heart rate variability , a therapeutic target?JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2002H. C. Routledge Reduced heart rate variability (HRV) is a powerful and independent predictor of an adverse prognosis in patients with heart disease and in the general population. The HRV is largely determined by vagally mediated beat to beat variability, conventionally known as respiratory sinus arrhythmia. Thus, HRV is primarily an indicator of cardiac vagal control. It is still unclear whether the relationship between measures of cardiac vagal control and mortality is causative or mere association. Possible mechanisms by which cardiac vagal activity might beneficially influence prognosis include a decrease in myocardial oxygen demand, a reduction in sympathetic activity and a decreased susceptibility of the ventricular myocardium to lethal arrhythmia. In animals, augmentation of cardiac vagal control by nerve stimulation or by drugs is associated with a reduction in sudden death in susceptible models. In humans a number of drugs which have been shown to reduce mortality and sudden death in large randomised trials can also be demonstrated to increase HRV. As a result of this evidence, it has been suggested that the effect of drugs or other therapeutic manoeuvres on HRV might be used to predict clinical efficacy. The use of HRV as a therapeutic target is discussed in this review. [source] A systematic review and meta-analysis of randomised controlled trials evaluating interventions in adult literacy and numeracyJOURNAL OF RESEARCH IN READING, Issue 3 2003Carole J. Torgerson This paper reports a systematic review of the trial literature in the field of adult literacy and numeracy. The review was undertaken to investigate the effectiveness of teaching strategies and pedagogies designed to increase adult literacy and numeracy. The objectives were to search for and locate, synthesise and quality appraise all the randomised controlled trials aiming to evaluate interventions in adult literacy and/or numeracy, published between 1980 and 2002. Fifty-nine papers were included in the descriptive map. Twelve papers were included that contained nine randomised controlled trials. All of the trials included in the review were of high quality in the sense that they had adopted an appropriate study design for assessing effectiveness. However, within that study design many of the studies had methodological problems, for example: small sample size and lack of justification of sample size calculation; unclear method of random allocation; high attrition rate and lack of ,intention to teach' analysis. There was evidence of publication bias. Pooling three studies that compared teaching against no teaching showed a strong, positive and statistically significant effect on outcome. Two other studies examined the use of computer-assisted instruction (CAI) on literacy among imprisoned adults. Pooling these two studies showed a modest but not statistically significant benefit. There is a dearth of rigorous RCTs in the field of adult literacy and numeracy. The evidence is suggestive of a benefit of adult literacy and numeracy interventions; however, because of the heterogeneity of studies, the precise role of any intervention is uncertain and this finding may be undermined by the presence of substantial publication bias. We recommend that a series of large, well-designed and well-conducted randomised trials should be undertaken in the field of adult literacy and numeracy. [source] The making of fetal surgeryPRENATAL DIAGNOSIS, Issue 7 2010Jan A. Deprest Abstract Fetal diagnosis prompts the question for fetal therapy in highly selected cases. Some conditions are suitable for in utero surgical intervention. This paper reviews historically important steps in the development of fetal surgery. The first invasive fetal intervention in 1963 was an intra-uterine blood transfusion. It took another 20 years to understand the pathophysiology of other candidate fetal conditions and to develop safe anaesthetic and surgical techniques before the team at the University of California at San Francisco performed its first urinary diversion through hysterotomy. This procedure would be abandoned as renal and pulmonary function could be just as effectively salvaged by ultrasound-guided insertion of a bladder shunt. Fetoscopy is another method for direct access to the feto-placental unit. It was historically used for fetal visualisation to guide biopsies or for vascular access but was also abandoned following the introduction of high-resolution ultrasound. Miniaturisation revived fetoscopy in the 1990s, since when it has been successfully used to operate on the placenta and umbilical cord. Today, it is also used in fetuses with congenital diaphragmatic hernia (CDH), in whom lung growth is triggered by percutaneous tracheal occlusion. It can also be used to diagnose and treat urinary obstruction. Many fetal interventions remain investigational but for a number of conditions randomised trials have established the role of in utero surgery, making fetal surgery a clinical reality in a number of fetal therapy programmes. The safety of fetal surgery is such that even non-lethal conditions, such as myelomeningocoele repair, are at this moment considered a potential indication. This, as well as fetal intervention for CDH, is currently being investigated in randomised trials. Copyright © 2010 John Wiley & Sons, Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 23-24 2007Article first published online: 8 JAN 200 Cervical cancer risk falls after COC use ends Combined oral contraceptives (COCs) are associated with a slight increase in the risk of cervical cancer but this diminishes with time after use ends, an international study has shown (Lancet 2007;370:1609,21). Analysis of data for 16 573 women with and 35 509 women without cervical cancer confirmed that using a COC for 10 years between the ages of 20 and 30 increases the incidence of invasive cervical cancer from 3.8 to 4.5 per 1000 by age 50. However, the excess risk disappears 10 years after cessation of use. , A new analysis of the US Nurses' Health Study suggests that protection against ovarian cancer does not persist beyond 20 years after cessation of COC use. This study also showed that tubal ligation is associated with reduced risk of ovarian cancer (Am J Epidemiol 2007; 166;894,901). Pharmaceutical services fund moves to PCTs The ,global sum' that provides central funding for NHS pharmaceutical services is being shifted to PCTs. The Government has included legislation for the change in the recent Health and Social Care Bill. The fund pays the fees and allowances for pharmacy contractors and appliance contractors. The Government says this is a ,natural progression and in keeping with moves to devolve NHS funds to the frontline' that will enable PCTs to manage pharmacy services better by ,encouraging best prescribing practice'. Fewer fluoroquinolones in the community Restricting prescribing of fluoroquinolone antibacterials does not increase hospital admissions for infection among older people, say Canadian researchers (Am J Med 2007;120:893,900). Their analysis of an Ontario medical database shows that, in a community where fluoroquinolones were the most widely prescribed antibacterials, a one-third reduction in prescribing was not followed by an increase in hospital admissions for infectious episodes in the over,65s. On the contrary, there was a 32 per cent reduction in admissions for gastrointestinal conditions. FDA reports increased TB risk with infliximab The US Food and Drug Administration has published an analysis of cases of TB associated with infliximab (Remicade) detected via its spontaneous adverse event reporting scheme (Ann Intern Med 2007;147: 699,702). In 2001 the FDA placed a warning about the risk of TB on product labelling for infliximab and advised testing for TB before initiating treatment. This analysis of 130 cases of TB since reported in patients treated with infliximab found that 45 per cent had developed extra-pulmonary disease; risk factors included use of immunosuppressants (including methotrexate), a history of TB and time spent in an endemic area. Of 67 cases in which treatment was initiated after the warning was issued, 34 with a negative tuberculin skin test developed TB after receiving infliximab. MHRA announces anticounterfeit strategy The UK is a transit point, distribution hub and end-user of counterfeit medicines, says the MHRA in its first anti-counterfeiting strategy (www.mhra.gov.uk). Counterfeits have been detected in the legitimate supply chain with increasing frequency since 2004, resulting in nine batch recalls and a further five incidents detected at wholesale level. The MHRA's proposed approach includes: communication to raise awareness of the risk and facilitate reporting, collaboration with the WHO, the industry and law enforcement agencies, and targeted surveillance, prosecution and regulation. Evidence lacking for choosing DMARD There is insufficient evidence to choose one DMARD or biological agent over another in patients with RA, US investigators say (www.annals.org/cgi/content/abstract/0000605,20080115000192v1). Their systematic review of meta-analyses and intervention and observational trials found no evidence of differences among DMARDs or anti-TNF agents. Mono-therapy with an anti-TNF agent was associated with superior radiographic but not clinical outcomes; methotrexate plus an anti-TNF agent was superior in clinical and functional terms to either drug given alone. Be alert to psychiatric ADRs with rimonabant Clinicians should remain alert for the development of anxiety, depression and an increased risk of suicide with rimonabant (Acomplia), say Danish investigators (Lancet 2007;370:1706,13). Their meta-analysis of four randomised trials involving a total of 4105 patients showed that rimonabant was associated with an increased risk of serious adverse events (odds ratio 1.4; number needed to harm, NNH, 59), including a 2.5,fold increased risk of depression (NNH 49) and a threefold increased risk of anxiety (NNH 166). Following a warning from the FDA of an increased risk of suicide with rimonabant, the authors say their findings indicate a need for ,increased alertness by physicians to these potentially severe psychiatric adverse reactions'. New strategy for NHS medicines information The UK Medicines Information Service (www.ukmi.nhs.uk) has published its new management strategy setting out how it will respond to recent developments in the NHS. Developments include greater access to information for patients, support for nontraditional prescribers and new commissioning arrangements. New antiretroviral Maraviroc (Celsentri) is the first CCR5 antagonist to be introduced for the treatment of HIV infection. CCR5 is one of two co-receptors to which the HIV virus must attach to achieve cell entry. Maraviroc is licensed for use by treatment-experienced patients in whom only CCR5-tropic HIV-1 is detectable. The recommended dose ranges from 150 to 600mg twice daily depending on interactions with concurrent medication. Dimeticone superior Dimeticone 4 per cent lotion (Hedrin) is superior to malathion 0.5 per cent in the eradication of head lice, a UK study in 58 children and 15 adults has shown (PLoS ONE 2007;2: e1127. doi:10.1371/journal.pone. 0001127). Two applications of dimeticone lotion one week apart cleared active infestation in 70 per cent of participants compared with 33 per cent in those who used a single application of malathion. Copyright © 2007 Wiley Interface Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 22 2007Article first published online: 28 DEC 200 Glitazones: benefits outweigh the risks Following a review of the safety of rosiglitazone and pioglitazone, the European Medicines Agency (EMEA) has concluded that their benefits outweigh their risks in the approved indications. The review was prompted by reports of an increased risk of fractures in women and, in patients taking rosiglitazone, ischaemic heart disease. The EMEA concluded that prescribing information for rosiglitazone should now include a warning that, in patients with ischaemic heart disease, it should only be used after careful evaluation of each patient's individual risk, and the combination of rosiglitazone and insulin should only be used in exceptional cases and under close supervision. No change was considered necessary to the prescribing information for pioglitazone. Modern dressings no better? A systematic review has found only weak evidence that modern dressings are better than saline gauze or paraffin gauze for healing acute and chronic wounds (Arch Dermatol 2007;143: 1297-304). The analysis, which included 99 studies, found that only hydrocolloids were demonstrably better than older dressings for healing chronic wounds, and alginates were superior to other modern dressings for debriding necrotic wounds. There was no evidence that modern dressings offered superior overall performance to the older alternatives. Hospital inflation twice primary care level The cost of drugs prescribed in secondary care but dispensed in the community increased by 6.4 per cent in 2006 - twice the rate of inflation in primary care - according to the latest statistics on hospital prescribing in England. The increase follows a reduction in costs in 2005 after the introduction of the new PPRS scheme. Data from The Information Centre (www.ic.nhs.uk) show that hospital medicines make up about 24 per cent of the NHS drugs budget. Secondary care has a consistently better record than primary care in prescribing lower-cost alternatives within therapeutic categories, eg simvastatin and pravastatin among the statins, omeprazole and lansoprazole among PPIs, and ACE inhibitors among drugs acting on the renin angiotensin system. The most expensive drug prescribed by hospital specialists and dispensed in the community is interferon beta. MHRA limits the use of fibrates The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that fibrates should now be reserved for the treatment of isolated severe hypertriglyceridaemia. They should be considered for hypercholesterolaemia only when a statin or other treatment is contraindicated or not tolerated. In the latest Drug Safety Update, the MHRA says there is insufficient evidence of long-term benefits from fibrates, and first-line use is no longer justified because the evidence for the benefits of statins is robust. The MHRA also warns that some breastfeeding infants have increased susceptibility to the adverse effects of codeine taken by their mother, and that St John's wort may affect the hepatic metabolism of any anticonvulsant. Annual zoledronic acid infusion cuts mortality after hip fracture Once-yearly infusion of zoledronic acid (Aclasta) after hip fracture reduces deaths over a two-year period by 28 per cent compared with placebo, US investigators say (N Engl J Med 2007;357:1799-809). The HORIZON Recurrent Fracture Trial randomised 2127 men and women (mean age 75) within 90 days of surgery for hip fracture to zoledronic acid 5mg yearly or placebo. Mortality over 1.9 years of follow-up was 9.6 per cent with zoledronic acid and 13.3 per cent with placebo. Zoledronic acid also significantly reduced the rate of any new clinical fractures (by 35 per cent) and new clinical vertebral fractures(by 45 per cent),but the lower rate of hip fracture (2.0 vs 3.5 per cent with placebo) was not statistically significant. Rivastigmine patch for mild to moderate AD Rivastigmine (Exelon) is now available as a transdermal patch for the treatment of mild to moderate Alzheimer's disease. Applied once daily, the patch delivers 9.5mg per 24 hours and, says manufacturer Novartis, is associated with a lower incidence of nausea and vomiting than a comparable oral dose. The patch is available in two strengths: 4.6mg per 24hr is equivalent to oral doses of 3 or 6mg per day, and the 9.5mg per 24hr patch is equivalent to 9 or 12mg per day orally. The recommended dose of the patch is 9.5mg per day; both strengths cost £83.84 for 30 patches. Women more aspirin resistant than men? The cardioprotective effect of low-dose aspirin may be lower in women than men, say Canadian investigators (BMC Medicine 2007;5:29 doi: 10.1186/1741-70155-29). Their meta-analysis of 23 randomised trials involving a total of 113 494 participants found that aspirin significantly reduced the risk of nonfatal but not fatal myocardial infarction (MI). About one-quarter of the variation in its effects on nonfatal MI was accounted for by the sex mix of the trial population. Separating the results by sex showed the reduction in risk with aspirin use was statistically significant in men (relative risk, RR, 0.62) but not in women (RR 0.87). Look after physical health of mentally ill GPs and other primary care workers should take more responsibility for the physical health of their mentally ill patients, say advocacy groups. Mind and Body: Preventing and Improving Physical Health Problems in Patients With Schizophrenia points out that the mental health needs of patients with schizophrenia are met in secondary care, but their physical health needs should be met in primary care. In particular, the metabolic effects of antipsychotics may lead to obesity, diabetes and cardiovascular disease, and weight gain in particular is a frequent reason for nonadherence to treatment. The Mind and Body Manifesto was developed by SANE, The Mental Health Nurses Association, The National Obesity Forum and The Disability Rights Commission and sponsored by Bristol-Myers Squibb Pharmaceuticals Limited and Otsuka Pharmaceuticals (UK) Ltd. Copies are available from elizabeth.green@ ogilvyhealthworld.com. Health eCard costs Some costs quoted in our article on the Health eCard (The Health eCard: the way ahead for medical records?,5 October issue, pages 28-9) have been revised: the card and initial download will cost patients £39.50, and GPs will be entitled to charge patients £10 per annum for subsequent downloads. NICE appraisals of cytokine inhibitors in RA NICE has endorsed the use of the anti-TNF agents adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade), normally in conjunction with methotrexate, for the treatment of active RA when methotrexate and another DMARD have failed (also see New from NICE below). NICE has provisionally concluded, subject to consultation, that abatacept (Orencia) should not be recommended for the treatment of RA. Boots and BMJ launch health advice site www.askbootshealth.com is a new website providing information about health and medicines for the public produced by Boots using information provided by the BMJ Publishing Group. The website covers many of the topics already available from NHSDirect, with perhaps more information about available treatments. Diabetes care shows small improvement The third National Diabetes Audit in England and Wales has found that more people with diabetes were achieving the targets set by NICE for cholesterol levels, glycaemic control and blood pressure in 2005/06 - but younger patients were doing less well. Overall, the HbA1C target of ,7.5 per cent was achieved in 60 per cent of people with diabetes compared with 58 per cent in 2004/05. However, HbA1C was >9.5 per cent in 30 per cent of children and young people, of whom 9 per cent experienced at least one episode of ketoacidosis. More topics for NICE New topics referred to NICE include clinical guidelines on ovarian cancer, coeliac disease and stable angina, public health guidance on preventing cardiovascular disease, and technology appraisals on insulin detemir (Levemir) for type 1 diabetes, several treatments for cancer and hepatic and haematological disorders, and biological therapies for juvenile arthritis. New from NICE NICE appraisal on anti-TNFs for RA Since NICE published its first appraisal of agents acting against tumour necrosis factor-alpha (anti-TNFs) for the treatment of RA in 2002, the product licences for etanercept (Enbrel) and infliximab (Remicade) have changed and a new agent, adalimumab (Humira), has been introduced. The anti-TNFs act in different ways. Infliximab is a chimeric monoclonal antibody that binds to TNF-alpha, neutralising its activity. Etanercept, a recombinant human TNF-alpha receptor fusion protein, and adalimumab, a human-sequence antibody, both bind to TNF-alpha and block its interaction with cell surface receptors. Adalimumab also modulates some biological responses induced or regulated by TNF-alpha. These agents are recommended for adults with severe active RA (defined as a disease activity score - DAS28 - greater than 5.1) who have already tried two disease-modifying drugs, including methotrexate (if not contraindicated). Prior treatment should have been of at least six months' duration, including two months at the standard dose (unless limited by toxicity). Anti-TNFs should normally be prescribed with methotrexate; when this is not appropriate, etanercept and adalimumab may be prescribed as monotherapy. Treatment with an anti-TNF should be continued beyond six months only if there is an adequate response (defined as an improvement in DAS28 of at least 1.2). Data from the British Rheumatology Society Biologics register show that, after six months, 67 per cent of patients met NICE criteria for an adequate response; this declined to 55 per cent at 18 months. The basic annual cost of treatment is £9295 for adalimumab 40mg on alternate weeks or etanercept 25mg twice weekly; infliximab costs £3777 for a loading dose, then £7553-£8812 depending on dose. Assuming no progression of disability, the incremental costs per QALY (compared with sequential DMARDs) were £30 200 for adalimumab, £24 600 for etanercept and £39 400 for infliximab. There are no direct comparative trials of the anti-TNFs, and their clinical trial findings are not directly comparable. Unless other factors determine treatment choice, NICE therefore recommends the least expensive. If the first anti-TNF is withdrawn within six months due to an adverse event, a second may be tried. [source] Latest news and product developmentsPRESCRIBER, Issue 17 2007Article first published online: 6 NOV 200 Drug information stilllacking for mentally ill Half of people with mental illness still have no say in the medication they are prescribed and one-third are not informed about side-effects, according to the latest report by the Healthcare Commission and the Commission for Social Care Inspection (www.health-carecommission.org.uk). The annual national review of adult mental health services found overall improvement among local intervention teams in 2005/06 compared with the preceding year, though all could improve further and the performance of 46 per cent were rated as only fair or weak. A survey of 7446 people with schizophrenia also showed that only 46 per cent had access to psychological treatments. More incentives for shift of care in Scotland Scotland has made good progress on shifting NHS care into the community but joined-up thinking, better information and incentives are needed to overcome barriers to better management of long-term conditions in adults, says Audit Scotland (www.audit-scotland.gov.uk). Reviewing progress on the 2005 strategy document Delivering for Health, Audit Scotland found good progress on asthma and diabetes services , partly due to the effects of the GMS contract. Better information about clinical activity, costs and effectiveness is needed to help redesign services. Patients with more than one long-term condition do not receive co-ordinated care and many want greater involvement in their care, the report concluded. Acorn, QOF and Guy Rotherham awards Entries are invited for the 2007 annual Acorn, QOF and Guy Rotherham Awards. The awards are run in association with the NHS Alliance, Improvement Foundation, British Cardiac Society, British Cardiac Patients Society and Prescriber. The CHD QOF Award, sponsored by Schering-Plough, recognises the achievement of an individual practice that gains maximum points in the CHD and heart failure QOF domains, and a second award is given to the primary care organisation (PCO) that achieves the best average scores across its practices. The entry form can be found at www.escriber.com. The closing date is 12 October. Entries are also invited for the Guy Rotherham Award from PCOs that can demonstrate they have delivered a high-impact change resulting in better outcomes and services for patients. For online entry go to www.improvementfoundation.org/guy rotherhamaward. Closing date is 5 October. Award winners will receive free entry for three to the NHS Alliance conference and the conference dinner. The winner of the Guy Rotherham Award will also receive £3000. NICE scores five out of six NICE acted unreasonably in relying solely on the Mini-Mental State Examination (MMSE) to define severity of Alzheimer's disease in its updated technology appraisals, with the effect of discriminating against people with learning or language difficulties, the High Court has ruled. The five other claims by Eisai that NICE acted unreasonably and irrationally were not upheld. This was the first court action against NICE in its eight-year history. It has now promised to publish revised appraisals on its website on 7 September and is consulting with Eisai, Shire Pharmaceuticals and the Alzheimer's Society on the best approach. PPRS reform follows Office of Fair Trading report The Government is to renegotiate the Pharmaceutical Price Regulation Scheme (PPRS) following the critical report by the Office of Fair Trading (OFT). In February, the OFT recommended renegotiation of the PPRS to reward innovation and obtain better value for patients. In particular, it called for a pricing scheme based on value for patients, ie effectiveness, rather than profit controls. The DoH, acknowledging the report's complexity, says it will take four principles into account in its negotiations during the forthcoming months: value for money, promoting innovation, assisting the uptake of new cost-effective medicines and promoting market stability. MHRA launches e-bulletin The MHRA (www.mhra.gov.uk) has next issue can be downloaded. The launched an electronic bulletin to August bulletin includes items on provide health professionals with antidepressants and suicide, updates about the safe use of medi-adverse effects of dopamine ago-cines. Users need to sign up to nists and information about smokreceive an e-mail alert when the ing cessation and isotretinoin. DURG call for abstracts The Drug Utilisation Research Group is calling for abstracts for its 19th annual meeting ,Target-driven medicine , is this the end of prescribing freedom?' to be held on 7 February 2008 at the Royal Society of Medicine, London. Abstracts are requested on any aspects of drug utilisation research. A bursary of £500 will be awarded for the best abstract received. The closing date for receipt of abstracts is 26 November. Further information about abstract submission is available at www.durg.org.uk. GP prescribing up by half Prescription volume and costs in England increased by approximately half over the decade to 2006, according to data published by the Information Centre for Health and Social Care (www.ic.nhs.uk). The number of items dispensed per year increased by 55 per cent and the cost by 60 per cent in real terms. The average number of items per head of population was 10.0 in 1996 and 14.8 in 2006; older people received 21.2 items per head in 1996 but 40.8 in 2006. MR morphines similar Modified-release preparations of morphine are equivalent in the treatment of severe pain, according to a new review by Bandolier (www.jr2.ox.ac.uk). The analysis of 54 randomised trials, which reviewed the release mechanisms and clinical data for four brands, showed these preparations provide effective analgesia for malignant and nonmalignant pain; about 4 per cent of patients were unable to tolerate the adverse effects of morphine. NSAIDs compared in OA Etoricoxib (Arcoxia) and naproxen are equally effective in the long-term treatment of osteoarthritis (Ann Rheum Dis 2007;66:945,51). Extension studies for two one-year trials showed that, after a total of 138 weeks, the two drugs had almost identical effects on pain and function assessments. All treatments were generally well tolerated, but serious cardiovascular effects were more common with etoricoxib and serious GI effects more common with naproxen. CPN nystatin allowed Community practitioner nurses (CPNs) may now prescribe oral nystatin (Nystan) to treat oral thrush in neonates, following a special amendment to the regulations limiting their prescribing to licensed indications. CPNs may now prescribe oral nystatin at the dose recommended in the BNF for Children provided they are sure of the diagnosis. In doing so, they accept clinical and medicolegal responsibility for their actions. There are no other exceptions to the prohibition of off-label prescribing. Copyright © 2007 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 5 2007Article first published online: 16 MAY 200 OFT wants PPRS reform The Office of Fair Trading (www.oft.gov.uk) says reform of the Pharmaceutical Price Regulatory Scheme (PPRS) would allow the NHS to re- invest £500 million in drugs it needs. Its investigation of the 50- year-old PPRS concludes that the scheme does not reflect the therapeutic value of drugs and, while providing a financial safety net for the industry, it mitigates against innovation. The OFT believes drugs should be priced according to their therapeutic value based on their cost effectiveness. Analyses would be fast- tracked for new drugs or, if there are insufficient data, a risk-sharing scheme should be adopted. The ABPI insists that its medicines offer the NHS value for money and believes the OFT's proposal for drug- by-drug pricing would delay access to new medicines. Switching saves money and is problem free Switching to cheaper alternatives within a drug class does not affect the quality of care and offers substantial savings, say UK researchers (Int J Clin Pract 2007;61:15-23). They switched selected patients from atorvastatin (Lipitor) to simvastatin and from losartan (Cozaar) to candesartan (Amias). Exclusion criteria included previous unsuccessful use, poor control of lipids or blood pressure, contraindications and potential drug interactions. In 70 patients switched to simvastatin, there was no change in mean total cholesterol after four months; one patient reverted to atorvastatin due to adverse effects. Of 115 switched to candesartan, seven reverted to losartan; in the remainder, blood pressure was slightly reduced after four months. The switch was not associated with adverse effects. Savings for the year 2005/06 were estimated at £12 716 for statins and £13 374 for antihypertensive drugs. Scotland gets donepezil for mild to moderate AD The Scottish Medicines Consortium (www.scottish medicines.org.uk) has approved the use of orodispersible donepezil (Aricept Evess) for the treatment of mild to moderate Alzheimer's disease in NHS Scotland. The decision conflicts with NICE advice that the drug is not appropriate for patients with mild disease. The SMC has not approved rimonabant (Acomplia) as adjunctive treatment for obese patients. Adherence threatens anticoagulation Patients find it difficult to adhere to anticoagulant treatment ,significantly impairing the quality of anticoagulation, US investigators have shown (Arch Intern Med 2007;167:229-35). Using electronic containers to monitor dose adherence over 32 weeks in 136 patients, they found that 92 per cent opened the container at least once too often or too little and one-third missed 20 per cent of scheduled openings. Patients with less than 20 per cent adherence were twice as likely to be undercoagulated compared with adherent patients. Those with overadherence were overcoagulated. Hypo risk greatest with glibenclamide Glibenclamide is associated with a significantly greater risk of hypoglycaemic events than other secretagogues, a new systematic review has concluded (Diabetes Care 2007;30:389-94). The review of 21 randomised trials found that the risk of experiencing at least one hypoglycaemic event was 52 per cent greater with glibenclamide compared with other secretagogues and 83 per cent greater than with other sulphonylureas. In three comparative trials with insulin, there was no significant difference in the risk of hypoglycaemia (though this could not be excluded) but only insulin was associated with weight gain. Glibenclamide was not associated with significantly increased risks of cardiovascular events, weight gain or death. Few major hypoglycaemic events were reported in these trials. Drug groups implicated in ADR admissions Four classes of drugs account for half of hospital admissions for adverse reactions, according to a new systematic review (Br J Clin Pharmacol 2007;63:136-47). Antiplatelet agents (16 per cent of admissions), diuretics (16 per cent), NSAIDs (11 per cent) and anticoagulants (8 per cent) were implicated in drug- related admissions according to a review of nine studies. Analysis of five studies also showed that adherence problems were associated with one-third of drug-related admissions. The authors suggest that focussing resources in these areas could substantially reduce admissions. Value of pharmacist MUR questioned Pharmacist medicines use review (MUR) for older patients does not reduce hospital readmission and is not cost effective by current standards, according to a study from Norfolk (Pharmacoeconomics 2007;25:171-80). A total of 872 patients aged over 80 who had been admitted as an emergency and discharged taking two or more drugs were randomised to MUR by a pharmacist or usual care. The pharmacist visited twice, providing education, removing out-of-date drugs and checking for adverse effects, interactions and the need for compliance aids. After six months, the admissions rate was not reduced among patients who received MUR and quality of life was not significantly improved. The estimated cost per QALY gained was £54 454 , above the conventional threshold for cost effectiveness of £30 000. MHRA review of LABAs The MHRA has clarified which aspects of long-acting beta-agonists (LABAs) are being addressed in its current review. This full review of salmeterol (Serevent) and formoterol, following advice issued in December last year, will consider recent research, whether the two agents differ significantly, dose-response relationships, the effect of concurrent treatment with inhaled steroid and how they are used in practice. Manufacturers have been asked to provide data by the end of March. Interventions for weight gain in schizophrenia There is not enough evidence to support the use of drugs to reduce weight gain associated with schizophrenia, a new Cochrane review has found (Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD005148. DOI: 10.1002/14651858. CD005148.pub2). Noting a lack of adequate trials, the review found that cognitive/behavioural interventions effectively prevented weight gain by a mean of 3.4kg and reduced established weight gain by a mean of 1.7kg. Drugs prevented weight gain by about 1.2kg. Switching anti-TNFs An analysis of a UK rheumatoid arthritis (RA) registry has shown that patients who stop treatment with their first anti-TNF agent should be switched to a second (Arthr Rheum 2007;56:13-20). Every UK patient with RA who receives an anti-TNF agent is included in the British Society for Rheumatology Biologics Register. Analysis of this database identified 6739 patients who started treatment, of whom 841 stopped within 15 months due to lack of efficacy and 1023 due to toxicity. Of these, 503 and 353 respectively were switched to another anti- TNF agent. Overall, 73 per cent of patients remained on their second drug by the end of follow-up, but patients were two to three times more likely to stop their second treatment for the same reason they discontinued their first. Copyright © 2007 Wiley Interface Ltd [source] A meta-analysis of the prospective randomised trials of coronary revascularisation before noncardiac vascular surgery with attention to the type of coronary revascularisation performedANAESTHESIA, Issue 10 2009B. M. Biccard Summary Prospective randomised trials of coronary revascularisation prior to noncardiac surgery have shown no survival benefit following noncardiac surgery. However, these studies have not differentiated the outcomes associated with coronary artery bypass grafting (CABG) and percutaneous coronary interventions. We performed a meta-analysis of the randomised controlled trials of pre-operative coronary revascularisation for noncardiac surgery, extracting data for 30 day and long term all-cause mortality and myocardial infarction (MI) following revascularisation, according to the type of revascularisation performed. Pre-operative percutaneous coronary intervention was associated with significantly increased 30 day MI and composite death and MI. Pre-operative CABG was associated with a significantly improved long term composite outcome of death and MI compared to percutaneous coronary interventions. The adverse effect of percutaneous coronary interventions on both short and long term outcomes in vascular surgical patients should be taken into consideration when interpreting these trials. CABG may improve long term outcomes in vascular surgical patients. The indications for and timing of CABG in vascular surgical patients needs further research. [source] Male breast cancer: Progress, prognosis and future pathwaysASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2008Kathryn M FIELD Abstract Breast cancer is one of the most commonly treated malignancies worldwide, but is rare in males. Less than one percent of all breast cancers occur in men, and breast cancer comprises less than one percent of all male malignancies. Thus, clinical experience in managing this condition is limited. In contrast to female breast cancer, much remains unknown about breast cancer in males. While there are similarities between the two, emerging data suggest that there are perhaps more differences than previously thought. Nevertheless, much of how males with breast cancer are managed continues to be extrapolated from randomised trials performed in females, due to lack of data in the male population alone. Another poorly understood aspect is the psychological impact experienced by male patients when diagnosed with what is generally thought of as a female malignancy. This review will discuss the known epidemiology, demographics, risk factors and genetic predispositions surrounding the development of breast cancer in males; as well as current surgical and radiotherapeutic interventional techniques. Histological profiles and subtypes as well as hormone receptor and HER-2 receptor status are also discussed, with an overview of chemotherapy and hormonal strategies in both the adjuvant and metastatic settings. [source] Innovations in Aged Care: Hip protectors: promising but no panaceaAUSTRALASIAN JOURNAL ON AGEING, Issue 1 2002I.D. Cameron Research indicates that almost all hip fractures occur after a fall onto the hip region and a number of hip protectors have been designed to reduce the force of the fall. Wearing of hip protectors has been shown to be effective in randomised trials in nursing homes with residents at high risk of hip fracture. However, adherence with use of hip protectors is incomplete and hip fracture can still occasionally occur while wearing hip protectors. No published studies have examined the effectiveness of hip protectors in people living in the community rather than in residential aged care facilities. [source] Efficacy of micronised vaginal progesterone versus oral dydrogestrone in the treatment of irregular dysfunctional uterine bleeding: A pilot randomised controlled trialAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2009Savas KARAKUS Background:, The vaginal route is more effective than the other drug delivery routes for some specific indications. Aim:, To compare the efficacy of a vaginal progesterone preparation with that of oral dydrogesterone. Methods:, A total of 69 women with irregular dysfunctional uterine bleeding were randomly assigned into one of two groups: oral dydrogesterone group (n = 35) and vaginal progesterone group (n = 34). At the end of a three-month treatment period, the women were re-evaluated. The endometrial histology findings and menstrual cycle characteristics were used as primary outcome measures. Pearson chi-square and Fisher's exact test were used for data analysis. Results:, Findings from 54 eligible women were evaluated. There was no statistically significant difference in both menstrual recordings and endometrial histology results between the groups. Conclusions:, Vaginal micronised progesterone could be an alternative to oral preparations in the treatment of dysfunctional uterine bleeding. This needs to be further evaluated in adequately controlled randomised trials against other effective treatments. [source] Gynaecological surgery from art and craft to science?AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2009Neil Philip JOHNSON Randomised controlled trials are applied more readily to medical than surgical interventions. There are even more barriers to randomised trials of surgical interventions than to other randomised trials. These include reluctance among surgeons to undertake trials (owing to concern over expressing equipoise, surgical training and surgical learning curve issues, restrictions of funding and time for research, even financial conflict of interest), reluctance of patients to participate in surgical trials owing to fears over ,experimental surgery', failure of randomised trials to detect rare surgical complications and the almost universal failure of those conducting surgical trials to examine important long-term outcomes. Rapid advances in surgical fields mean that new surgical techniques are rapidly superseded and clinical questions surrounding new techniques may linger only until the next new technique becomes available. Nonetheless randomised controlled trials remain the cornerstone of evaluating the effectiveness of surgical interventions. Genuine progress has been made in this field. However, large multicentre collaborative randomised trials that have been prospectively defined in trial registries will be required in the future to answer the important clinical questions regarding gynaecological surgical interventions. [source] Postoperative analgesic requirements , total laparoscopic hysterectomy versus vaginal hysterectomyAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2005Marcelo Carraro NASCIMENTO Abstract Background:, There is limited information available on the requirement for postoperative analgesic drugs in patients submitted to total laparoscopic hysterectomy (TLH) compared with patients undergoing vaginal hysterectomy (VH). Aim:, To compare the postoperative analgesic requirements in patients who underwent a TLH with patients who had a VH. Methods:, Chart review of 53 patients who had TLH and 47 who had VH and were seen postoperatively by an acute pain management service in order to assess postoperative analgesic requirements. Patient controlled analgesia (PCA) was part of the standard protocol for postoperative pain management. Analgesic requirement was recorded as the mean doses of morphine and number of days that patients used non-steroidal anti-inflammatory drugs (NSAIDs), oxycodone and tramadol. Results:, The requirement for total morphine was approximately half the dose in patients who had a TLH (10.8 ± 12.6 mg) compared with patients who had a VH (19.4 ± 21.9 mg) (P 0.017). The length of use of NSAIDs was significantly reduced in patients who had undergone a TLH (2.0 ± 0.95 days) as compared with patients who had a VH (2.85 ± 1.1 days) (P < 0.0001). Conclusions:, Patients submitted to TLH require less postoperative analgesic drugs when compared with patients who had VH. Prospective randomised trials are warranted to compare analgesic requirements between patients submitted to TLH and VH. [source] Meta-analysis using individual patient data from randomised trials to assess the effectiveness of laparoscopic uterosacral nerve ablation in the treatment of chronic pelvic pain: a proposed protocolBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2007T Xiong Background, Currently, there are a number of clinical trials, but no international collaboration for collating research on effectiveness of laparoscopic uterosacral nerve ablation (LUNA) for alleviating chronic pelvic pain. Objective, Meta-analysis was used by collecting individual patient data (IPD) from the existing trials, to provide a comprehensive assessment of the effectiveness of LUNA that will be generalisable in various clinical contexts. Methods, IPD will be sought and collected from all relevant (both already finished and continuing) randomised trials identified through previous systematic reviews. After obtaining raw data and cleaning the database, analysis will be of all patients ever randomised based on the intention-to-treat principle using endpoints measured at 12 months following randomisation. Proposal, We will update searches, contact all authors, obtain data in whatever form it can be provided, build a single database, produce results for individual studies, have them verified by original authors, explore of any heterogeneity and reasons behind it and finally pool all raw data in to a meta-analysis using appropriate statistical methods. The project will test the effectiveness of LUNA for women with chronic pelvic pain. It will also motivate collaborating primary investigators to undertake new primary studies to corroborate or improve upon the conclusions derived from the retrospective analysis. [source] Modelling the potential impact of population-wide periconceptional folate/multivitamin supplementation on multiple birthsBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 9 2001Judith Lumley Objective To develop a model of the impact of population-wide periconceptional folate supplementation on neural tube defects and twin births. Design A hypothetical cohort of 100,000 pregnancies ,20 weeks, plus terminations of pregnancy after prenatal diagnosis before 20 weeks. Methods Application of pooled data on the relative risks for neural tube defects and twins following periconceptional folate from meta-analysis of the randomised trials. Main outcome measures 1. Pregnancies with a neural tube defect (i.e. terminations of pregnancy, perinatal deaths, and surviving infants); 2. twin births (i.e. preterm births, perinatal deaths, postneonatal deaths, birth defects, cerebral palsy); 3. numbers needed to treat. Results The change in neural tube defects would be 75 fewer terminations (95% CI -47, -90), 30 fewer perinatal deaths (95% CI 18, -35), and 13 fewer surviving infants with a neural tube defect (95% CI ,8, -16). The change in twinning would be an additional 572 twin confinements (95% CI ,100, +1587), among whom there would be 63 very preterm twin confinements (95% CI ,11, +174), 54 perinatal and postneonatal deaths (95% CI ,9, +149), 48 surviving twins with a birth defect (95% CI ,8, +133), and nine with cerebral palsy (95% CI ,2, +26). The numbers needed to treat for the prevention of one pregnancy with a neural tube defect is 847, for the birth of one additional set of twins is 175, for the birth of one additional set of very preterm twins is 1587, and for the birth of an additional twin with any of the following outcomes (perinatal death, postneonatal death, survival with a birth defect, or survival with cerebral palsy) is 901. Conclusions Monitoring rates of neural tube defects and twinning is essential as supplementation or fortification with folate is implemented. [source] 92 Photoselective vaporisation of the prostate randomised against turp-preliminary resultsBJU INTERNATIONAL, Issue 2006D.M. BOUCHIER-HAYES Introduction:, Many technologies have attempted to supplant TURP as the surgical treatment of choice in the treatment of lower urinary tract symptoms, but have not undergone randomised trials. Photoselective vaporization of the prostate (PVP) using the Greenlight® laser system (Laserscope, San Jose, Ca.) gives an 80-watt laser ablation system and here is compared to TURP in the world's first randomised trial. Study Design:, One hundred and twenty patients are to be randomised to undergo TURP or PVP after evaluation which is repeated at 1, 3, 6 and 12 months. Irrigation use, length of catherisation time (LOC), length of hospital stay (LOS), blood loss and operative time are also assessed. All procedures were performed by fellows/registrars. Results:, To date 90 patients are randomised and 68 are evaluable and were similar at baseline. Both techniques produced equivalent significant improvement in flow rates and IPSSs, and significantly shorter length of time of catherisation (LOC) and length of stay (LOS) in the PVP group. Adverse events were less frequent in the PVP group, and the procedure was 22% cheaper than TURP. Conclusions:, This trial demonstrates with preliminary data that PVP may be an effective technique when compared to TURP, producing equivalent improvements in flow rates and IPSS scores with markedly reduced LOS, LOC and adverse events. [source] The Treatment of Cognitive Impairment Associated with Parkinson's DiseaseBRAIN PATHOLOGY, Issue 3 2010David J. Burn FRCP Abstract Cognitive impairment and dementia associated with Parkinson's disease (PD) are common and often have devastating effects upon the patient and their family. Early cognitive impairment in PD is frequent, and the functional impact may be underestimated. Optimal management will rely upon better identification of the predominant symptoms and greater knowledge of their pathophysiological basis. The management of dementia in PD (PD-D) also has to consider the significant neuropsychiatric burden that frequently accompanies the cognitive decline, as well as fluctuations in attention. Atypical anti-psychotics have a limited role at present in treating PD-D, although new drugs are under development. The mainstay of drug management for people with PD-D is cholinesterase inhibitors, although recent trials have suggested that the N-methyl-D aspartate antagonist memantine may also have some benefit. Disease modification remains the ultimate goal for preventing the inexorable decline in PD-D, although effective interventions are still some way off. Limited benefit may, however, be possible through exercise programmes and so-called "medical foods", although randomised trials are required to confirm largely anecdotal observations. [source] Electroconvulsive therapy versus transcranial magnetic stimulation for major depression: a review with recommendations for future researchACTA NEUROPSYCHIATRICA, Issue 6 2008Keith G. Rasmussen Objective:, To review the literature comparing electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) for major depression. Methods:, Data from the six randomised, prospective studies were agglutinated into one data set. Special attention was given to the methods of both TMS and ECT as well as data pertaining to differential outcomes in subgroups such as psychotic depressives and the elderly. Results:, There is a highly significant advantage for ECT in the prospective, randomised trials. The two non-randomised, retrospective comparative trials found the treatments to be equal in one study and superior for ECT in another. However, sample sizes are small in these studies, and both TMS and ECT may have been used suboptimally. Furthermore, the possibilities of differential efficacy of ECT or TMS for psychotic depressives or as a function of age have yet to be fully explored. Conclusions:, The data to date do not support the contention that TMS is equivalent in efficacy to ECT. It is recommended that a large-scale trial be undertaken using aggressive forms of both TMS and ECT with sample sizes sufficiently large to detect effects of moderating variables such as age and psychosis status. [source] Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studiesCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2009P. G. Gibson Prof. Summary Background Current asthma guidelines recommend treatment based on the assessment of asthma control using symptoms and lung function. Noninvasive markers are an attractive way to modify therapy since they offer improvedselection of active treatment(s) based on individual response, and improvedtitration of treatment using markers that are better related to treatment outcomes. Aims: To review the methodological and design features of noninvasive marker studies in asthma. Methods Systematic assessment of published randomized trials of asthma therapy guided by fraction of exhaled nitric oxide(FENO). Results FENO has appeal as a marker to adjust asthma therapy since it is readily measured, gives reproducible results, and is responsive to changes in inhaled corticosteroid doses. However, the five randomised trials of FENO guided therapy have had mixed results. This may be because there are specific design and methodological issues that need to be addressed in the conduct of ASthma TReatment ALgorithm(ASTRAL) studies. There needs to be a clear dose response relationship for the active drugs used and the outcomes measured. The algorithm decision points should be based on outcomes in the population of interest rather than the range of values in healthy people, and the algorithm used needs to provide a sufficiently different result to clinical decision making in order for there to be any discernible benefit. A new metric is required to assess the algorithm performance, and the discordance:concordance(DC) ratio can assist with this. Conclusion Incorporating these design features into future FENO studies should improve the study performance and aid in obtaining a better estimate of the value of FENO guided asthma therapy. [source] Survey of neonatal respiratory support strategiesACTA PAEDIATRICA, Issue 8 2007Atul Sharma Abstract Aim: To survey current practice regarding neonatal respiratory support strategies to determine whether it reflected evidence from randomised trials. Methods: A questionnaire (in Supplementary Material online) survey of all U.K. neonatal units was undertaken to determine what modes of ventilation, types of endotracheal tube, lung function monitoring and oxygen saturation levels were used. Results: There was an 80% response rate. Most (73%) units used in prematurely born infants (in the first 24 h) the intermittent positive pressure ventilation, and other respiratory modes included: CPAP (2%), triggered ventilation with or without volume guarantee (22%) and high frequency oscillation (2%). Only 15% of units used assist control mode for weaning; the preferred weaning mode was synchronous intermittent mandatory ventilation (73%). Few units used shouldered endotracheal tubes (3%) or lung function measurements (25%) to aid choice of ventilator settings. Oxygen saturation levels from 80% to 98% were used, levels greater or equal to 95% were used by 11% of units for infants with acute respiratory disease but by 34% of units for BPD infants (p < 0.001). Conclusion: Many practitioners do not base their choice of neonatal respiratory support strategies on the results of large randomised trials; more effective methods are required to ensure evidence-based practice. [source] | ||||||||||||||||||||||||||||