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Inhaled Steroids (inhaled + steroid)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Allergy & Clinical Immunology	18%
Pediatrics	15%
Respiratory Medicine	12%

Selected Abstracts

Airway Selectivity: An Update of Pharmacokinetic Factors Affecting Local and Systemic Disposition of Inhaled Steroids

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2006
Staffan Edsbäcker
The antiinflammatory properties of these products, combined with the targeting of formulations and optimization of the intrinsic pharmacokinetic features of the newer corticosteroid molecules has resulted in substantially improved airway selectivity. This review sets out to summarize the pharmacokinetic properties of inhaled corticosteroids that are important for the achievement of high levels of airway selectivity, with additional focus on the use of prodrugs/softdrugs relative to those of conventional corticosteroid molecules, mechanisms (such as esterification) by which retention at the target site is achieved while minimizing systemic exposure, and the role of plasma protein binding. [source]

Inhaled drugs for the prevention and treatment of bronchopulmonary dysplasia

PEDIATRIC PULMONOLOGY, Issue 8 2006
T. Pantalitschka MD
Abstract Bronchopulmonary dysplasia (BPD) is one of the most common long-term complications and treatment challenges in preterm infants. Theoretically, inhaled corticosteroids may suppress pulmonary inflammation without causing systemic side-effects, while bronchodilators will improve airway resistance and thereby work of breathing. This article reviews current data on these drugs in BPD prevention or treatment. Trials published to date have not demonstrated that regular bronchodilator administration influences the incidence of BPD or improves long-term outcome. Inhaled steroids started before 2 weeks of age may improve rates of successful extubation and reduce the need for rescue systemic glucocorticoids, but have not been shown to reduce the incidence of BPD. Thus, their use cannot be generally recommended. The data currently available are not sufficient to give any clearer recommendation on the use of these drugs in infants at high risk of, or established, BPD. Pediatr Pulmonol. 2006; 41: 703,708. © 2006 Wiley-Liss, Inc. [source]

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PRESCRIBER, Issue 18 2008
Article first published online: 3 OCT 200
Inhaled steroids for all children with asthma? Some children with mild well-controlled asthma may not need a daily inhaled steroid, a Scandinavian study suggests (Arch Dis Child 2008;93:654-9). A total of 176 children aged 5-10 years were randomised to treatment with cromoglicate (Intal) or budesonide. Initially high doses of budesonide (400,g twice daily) were reduced after one month to 200,g twice daily for four months; subsequent treatment for a further year was 100,g twice daily as required for exacerbations or 100,g twice daily regularly. Budesonide was associated with greater improvement in lung function and fewer exacerbations compared with cromoglicate, but after 18 months lung function improvements did not differ. Regular budesonide was associated with fewer exacerbations than as-required administration (0.97 vs 1.69 per patient in months 7-18) but no difference in asthma-free days or use of rescue medication. Growth suppression was slightly greater with continuous budesonide. Interventions to reduce atypicals weight gain A systematic review has found that techniques such as cognitive behaviour therapy and nutritional counselling can reduce weight gain associated with atypical antipsychotics (Br J Psychiatry 2008;193:101-7). Analysis of 10 randomised trials lasting eight weeks to six months found that nonpharmacological intervention increased mean weight loss by about 2.5kg compared with usual care. Check flu vaccine delivery Production of flu vaccine is proceeding according to plan, the Director of Immunisation has told GPs. Practices should now contact their suppliers to confirm a delivery schedule so that clinics can be arranged. New BNF for Children The fourth BNF for Children has been published, containing new sections on HPV vaccination, contraception, treatment of pelvic inflammatory disease and the use of continuous iv infusions in neonates. BNFC 2008 is available online at bnfc.org/bnfc. MMR catch-up ,urgent' The DoH has called for urgent action to reduce the risk of a measles epidemic. Following years of relatively low uptake of MMR vaccine, the pool of unprotected children is now large enough to raise the prospect of 30 000-100 000 measles cases in England. A catch-up campaign will now target children and young people who have never been vaccinated, followed by those who have not completed their course of immunisation. Resource materials are available at www.immunisation.nhs.uk. , A new brand of MMR vaccine is now available. Sanofi Pasteur MSD has replaced MMRII with a new formulation and presentation, MMRvaxPro. The new vaccine is equivalent to its predecessor and interchangeable with Priorix. Early primary prevention with low-dose aspirin? GPs should consider prescribing low-dose aspirin for primary prevention for men aged 48 and women aged 57, say UK researchers (Heart 2008; published online 15 August 2008. doi:10.1136/hrt.2008.150698). Using data from the THIN network of electronic patient records, they modelled the age at which 10-year coronary risk changed from <10 per cent to >10 per cent in men and women without diabetes, not taking lipid-lowering therapy and with no history of cardiovascular disease. Does COPD therapy slow progression? Treatment with an inhaled steroid and long-acting beta-agonist may slow progression of COPD, according to a new analysis of the TORCH study (Am J Respir Crit Care Med 2008;178:332-8). TORCH was designed to determine the effects of COPD treatment on mortality; the primary analysis found no significant difference between fluticasone/salmeterol (Seretide) and placebo (N Engl J Med 2007;356:775-89). This analysis found that the rate of decline in FEV1 (a marker of disease progression) was significantly greater with placebo (55ml per year) than with salmeterol or fluticasone monotherapy (both 42ml per year) or their combination (39ml per year). Faster decline in FEV1 was associated with current smoking, lower BMI and more frequent exacerbations. Copyright © 2008 Wiley Interface Ltd [source]

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PRESCRIBER, Issue 21 2007
Article first published online: 3 DEC 200
NSAIDs and SSRIs increase GI bleeding Taking an NSAID and an SSRI increases the risk of GI bleeding more than six-fold compared with taking neither drug, a meta-analysis shows (Aliment Pharmacol Ther online: 5 Oct 2007; doi:10.1111/j.1365-2036.20 07.03541.x). The analysis included four observational studies involving a total of 153 000 patients, and 101 cases reported in postmarketing surveillance. Compared with nonuse, the odds ratio for upper GI haemorrhage in patients taking an SSRI alone was 2.36; the number needed to harm (NNH) was 411 for one year's treatment in patients aged over 50 with no risk factors. For those taking an SSRI and an NSAID, it was 6.33 (NNH 106). Of 22 cases where treatment duration was known, the median time to onset of bleeding was 25 weeks and five occurred within one month. The MHRA warns of this interaction in its latest issue of Drug Safety Update, noting: ,corticosteroids, antiplatelet agents, and SSRIs may increase the risk of GI ulceration or bleeding. NSAIDs may enhance the effects of anticoagulants, such as warfarin'. MHRA warning on NSAID safety The MHRA reminds prescribers of new restrictions on prescribing piroxicam and the risks associated with ketorolac and ketoprofen in its latest Drug Safety Update (2007;1:Issue 3). Treatment with piroxicam should now only be initiated by a specialist as a second-line drug; patients currently taking it should be reviewed at the next routine appointment. Piroxicam is no longer indicated for any acute indications. These restrictions do not apply to topical piroxicam (Feldene gel). Ketorolac and ketoprofen are associated with a higher risk of adverse GI effects than other NSAIDs. The MHRA advises prescribers to adhere to the licensed indications that limit oral ketorolac therapy to seven days (two days for continuous iv or im use) and the maximum dose of ketoprofen to 100-200mg. Inhaled steroids may increase the risk of pneumonia in patients with COPD. In the TORCH study (N Engl J Med 2007;356:775-89), fluticasone (Flixotide) and fluticasone plus salmeterol (Seretide) were associated with a significantly increased risk compared with salmeterol alone. The MHRA recommends vigilance for signs of pneumonia or bronchitis in patients with COPD who are treated with inhaled steroids; affected patients should have their treatment reconsidered. Other issues reviewed in Drug Safety Update include: a more intense reaction after revaccination with the pneumococcal vaccine, Pneumovax II; exacerbation of osteonecrosis of the jaw by dental surgery in patients taking a bisphosphonate; a lower maximum dose for lorazepam (4mg for severe anxiety, 2mg for severe insomnia) rare reactions with botulinum toxin; and the cardiovascular safety and risk of fractures with the glitazones. Antibiotic resistance GPs who reduce their antibiotic prescribing achieve a significant reduction in bacterial resistance, a study from Wales has shown (Br J Gen Pract 2007;57:785-92). The analysis of 164 225 coliform isolates from urine samples submitted from 240 general practices found a 5.2 per cent decrease in ampicillin resistance in practices with the greatest reductions in total antibiotic prescribing. Overall, ampicillin resistance decreased by 1 per cent for every reduction of 50 amoxicillin prescriptions per 1000 patients. Trimethoprim resistance showed a similar trend. Mortality risk with discontinuing statins Patients who discontinue statin therapy after acute stroke are almost three times more likely to die than those who do not, an Italian study shows (Stroke 2007;38:2652-7). Follow-up of 631 patients discharged after acute stroke revealed that 39 per cent discontinued statin therapy. The hazard ratio for all-cause mortality in the first 12 months was 2.78 compared with those who continued treatment; this compared with a hazard ratio of 1.81 for stopping antiplatelet therapy. The authors argue that patient care should be improved during the transition from hospital to outpatient primary care. ACEI ± ARB = ADRs Combining an ACE inhibitor and an angiotensin-II receptor blocker increases the risk of adverse effects in patients with symptomatic left ventricular dysfunction, according to a US study (Arch Intern Med 2007;167:1930-6). Meta-analysis of four trials involving a total of 17 337 patients followed up for about two years showed that, compared with therapy including an ACE inhibitor, combined treatment increased the risk of stopping treatment due to adverse events by 38 per cent in patients with heart failure and by 17 per cent in patients with MI. The authors estimate that, for every 1,000 patients treated, 25 will discontinue treatment due to adverse effects and 17 will develop renal dysfunction. WOSCOPS: statin protection continues Pravastatin reduces the risk of death years after treatment has stopped, according to a follow-up of the WOSCOPS study (N Engl J Med 2007;357:1477-86). The West of Scotland Coronary Prevention Study originally randomised men with hypercholesterolaemia but no history of myocardial infarction (MI) to treatment with pravastatin or placebo. After five years, the combined incidence of death from CHD or nonfatal MI was reduced from 7.9 to 5.5 per cent in the treatment group. During the 10 years after completion of the trial, the incidence of the combined end-point was 8.6 per cent in those originally assigned to pravastatin and 10.3 per cent in the placebo group. All- cause mortality was also reduced over the entire 15-year period. The proportions of patients still taking a statin in the middle of this period, ie five years after the trial ended, were 39 per cent of the placebo group. Prescribing policies on HRT need reappraisal Health authorities should reconsider their policy on prescribing HRT, the International Menopause Society (IMS) says. In an open letter, the IMS says current safety concerns over HRT use are founded, but have been misinterpreted in observational studies, such as the Women's Health Initiative, that led to changes in guidelines. The IMS says HRT is the most effective treatment for vasomotor and urogenital symptoms and the risk:benefit profile is favourable until age 60. Low-dose oestrogen or the transdermal route of administration may lead to a more favourable risk profile. Flu vaccine does cut morbidity and mortality Following The Lancet's commentary doubting the effectiveness of flu vaccination (Lancet Infectious Diseases 2007;7:658-66), a US cohort study has found that it does reduce morbidity and mortality (N Engl J Med 2007;357:1373-81). The observational study included 713 872 person-seasons in older people living in the community over a 10year period from 1990 to 2000. Vaccination was associated with a 48 per cent reduction in the risk of death and a 27 per cent reduction in admission for pneumonia or flu. These benefits changed little in subgroups or with age. Copyright © 2007 Wiley Interface Ltd [source]

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PRESCRIBER, Issue 11 2006
Article first published online: 14 SEP 2010
NSAIDs linked to erectile dysfunction Use of NSAIDs may double the risk of erectile dysfunction, according to an observational study from Finland (J Urol 2006;175:1812-6). A survey of 1683 men aged 50-70 showed that, over a five-year period, the incidence of erectile dysfunction was 93 per 1000 person-years of NSAID use compared with 35 per 1000 person-years in nonusers. After controlling for risk factors and compared with nonusers of NSAIDs who did not have arthritis, the relative risk was greater in NSAID users whether they had arthritis (1.9, 95% CI 1.2-3.1) or not (2.0, 95% CI 1.2-3.5). The risk was somewhat higher in nonusers with arthritis (1.3, 95% CI 0.9-1.8). Inhaled steroids do not modify asthma course Fluticasone does not ameliorate the course of asthma in young children, say US investigators (N Engl J Med 2006;354:1985-97). Fluticasone 88,g twice daily controlled symptoms for two years in 285 children aged two to three. However, in the following treatment-free year there were no differences from placebo in asthma-free days, lung function or exacerbation frequency. Fluticasone was associated with a 1.1cm reduction in growth during treatment, though this decreased to 0.7cm after a year without treatment. A second study (N Engl J Med 2006;354:1998-2005) found that introducing an inhaled steroid after a three-day episode of wheezing in one-month-old infants did not prevent the development of persistent wheezing in the first three years of life. Prescribing for fracture prevention increases Prescribing of medicines to reduce fracture risk in post-menopausal women has tripled in the last five years, according to a PPA prescribing review (www.ppa.org.uk/news/pact-052006.htm). The change predates NICE guidance on secondary prevention, published in 2005. Approximately 480 000 women in the UK receive treatment. Alendronic acid accounts for almost a third of prescriptions and half of the £45 million spent in the last quarter of 2005. There was a two-fold variation in prescribing costs between strategic health authorities. Pharmacist prescribing for hypertension A survey of patients attending a pharmacist-led clinic for hypertension has found overwhelming support for pharmacist prescribing (Pharm J 2006;276:567-9). All 127 patients offered an appointment at a hypertension clinic run by pharmacist supplementary prescribers were surveyed; the response rate was 87 per cent. Eighteen respondents chose not to attend, of whom five preferred their usual medical care. Responses from 88 patients revealed that 57 per cent believed the standard of care was better than previously, and 86 per cent said they now understood more about their condition, felt more involved in treatment decisions and were able to make an appointment easily. Ninety-two per cent considered pharmacist supplementary prescribing a good idea. Anti-TNFs linked to malignancy/infections The anti-TNF monoclonals infliximab (Remicade) and adalimumab (Humira) are associated with an increased risk of cancer and serious infections in patients with rheumatoid arthritis (JAMA 2006;295:2275-85). A meta-analysis of nine randomised trials involving 3493 treated patients showed that, compared with placebo, these agents were associated with an odds ratio (OR) of 3.3 (95% CI 1.2-9.1) for malignancy, and there was evidence of a dose-response effect. The number needed to harm (NNH) for one additional malignancy in 6-12 months' treatment was 154. There was also an increased risk of serious infection (OR 2.0; 95% CI 1.3-3.1), for which the NNH was 59 for one case in 3-12 months' treatment. The authors say that the findings were based on low numbers of events and should be interpreted cautiously. Travelling abroad with CDs Aintree Hospitals NHS Trust has published a guide to help patients who travel abroad while taking controlled drugs (www.aintree hospitals.nhs.uk/publications/file.aspx?int_version_id=912). The leaflet explains the need for a licence and provides contact details for relevant organisations. New PCTs announced The government has announced the long-awaited reorganisation of PCTs in England (www.dh.gov.uk/PublicationsAndStatistics/PressReleases/PressReleases Notices/fs/en?CONTENT_ID=4135001&chk=j12UcL). The current total will be reduced from 303 to 152 from 1 October. More than 70 per cent will be co-terminous with local authorities in the hope that services will be delivered more efficiently. The changes will reduce administrative costs, with anticipated savings of £250 million in the next two years. The reorganisation of PCTs follows a restructuring of strategic health authorities and was the subject of a major public consultation exercise in 2005/06. There will also be a reorganisation of ambulance trusts, reducing the number from 29 to 12. Regional maps of the new PCT boundaries are available atwww.dh.gov.uk/ NewsHome/NewsArticle/fs/en?CONTENT_ID=4135088&chk=oJufTo. New and updated guides New medicines guides for GI disease have been published by the Medicines Information Project at http://medguides.medicines.org.uk. PRODIGY has issued 11 updated and five new full guides and has also updated five of its quick reference guides (www.prodigy.nhs.uk). [source]

Risk factors for allergic rhinitis in Costa Rican children with asthma

ALLERGY, Issue 2 2010
S. Bunyavanich
To cite this article: Bunyavanich S, Soto-Quiros ME, Avila L, Laskey D, Senter JM, Celedón JC. Risk factors for allergic rhinitis in Costa Rican children with asthma. Allergy 2010; 65; 256,263 DOI: 10.1111/j.1398-9995.2009.02159.x. Abstract Background:, Risk factors for allergic rhinitis (AR) in asthmatics are likely distinct from those for AR or asthma alone. We sought to identify clinical and environmental risk factors for AR in children with asthma. Methods:, We performed a cross-sectional study of 616 Costa Rican children aged 6,14 years with asthma. Candidate risk factors were drawn from questionnaire data, spirometry, methacholine challenge testing, skin testing, and serology. Two outcome measures, skin test reaction (STR)-positive AR and physician-diagnosed AR, were examined by logistic regression. Results:, STR-positive AR had high prevalence (80%) in Costa Rican children with asthma, and its independent risk factors were nasal symptoms after exposure to dust or mold, parental history of AR, older age at asthma onset, oral steroid use in the past year, eosinophilia, and positive IgEs to dust mite and cockroach. Physician-diagnosed AR had lower prevalence (27%), and its independent risk factors were nasal symptoms after pollen exposure, STR to tree pollens, a parental history of AR, inhaled steroid and short-acting ,2 agonist use in the past year, household mold/mildew, and fewer older siblings. A physician's diagnosis was only 29.5% sensitive for STR-positive AR. Conclusions:, Risk factors for AR in children with asthma depend on the definition of AR. Indoor allergens drive risk for STR-positive AR. Outdoor allergens and home environmental conditions are risk factors for physician-diagnosed AR. We propose that children with asthma in Costa Rica and other Latin American nations undergo limited skin testing or specific IgE measurements to reduce the current under-diagnosis of AR. [source]

Assessment of right ventricular diastolic filling parameters by Doppler echocardiography

PEDIATRICS INTERNATIONAL, Issue 3 2003
Ayten Pamukcu Uyan
AbstractBackground: Right ventricular diastolic function has been evaluated in various diseases by the pulsed Doppler technique. Right ventricular diastolic filling parameters show changes with age, heart rate and respiration. Evidences of diastolic left and right ventricular dysfunctions have been reported by echocardiographic studies in asthmatic patients. In the present study, before and after treatment of asthma the right ventricular diastolic filling parameters were compared in children with moderate asthma by Doppler echocardiography (a non-invasive technique). Methods: The study group consisted of 20 children (eight girls, 12 boys) with asthma. During the present study these patients were treated with inhaled steroid and beta-2 agonist daily. Before treatment all patients were evaluated by Doppler echocardiography. At 4,6 weeks after treatment 15 patients that had shown improvement in their symptoms according to the symptom score were also evaluated by Doppler echocardiography. Results: The mean age was 8.6 ± 2.69 years and mean period of symptoms were 56.4 ± 35.8 months. When compared with results of echocardiography before and after treatment, the right ventricular diastolic filling parameters (acceleration time: P < 0.01, deceleration time: P < 0.01 and isovolumetric relaxation time: P < 0.05) were found to be significantly different. Conclusions: We observed significant improvement of right ventricular diastolic filling parameters by Doppler echocardiography after treatment in children with asthma. [source]

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PRESCRIBER, Issue 12 2008
Article first published online: 14 JUL 200
Patients want to stop ,Z' drugs more than benzos A study from Lincolnshire has revealed that patients prescribed a ,Z' drug - zaleplon (Sonata), zolpidem or zopiclone - for insomnia are more likely to want to stop treatment than those prescribed a benzodiazepine (Br J Gen Pract 2008;58:417-22). The cross-sectional survey of 705 patients prescribed a hypnotic for insomnia found that more patients taking a Z drug wanted to stop (23 vs 12 per cent prescribed a benzodiazepine) and tried to stop treatment (52 vs 41 per cent). New NICE guidance NICE has published an updated clinical guideline for the management of type 2 diabetes, covering: the control of blood glucose with lifestyle modification, oral hypoglycaemic drugs and insulin; reducing blood pressure and lipids, antithrombotic therapy and estimating cardiovascular risk; and screening and treatment for long-term complications. There is also a new clinical guideline on cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. New technology appraisals include the use of erythropoietin analogues for cancer-associated anaemia, and adalimumab (Humira) and etanercept (Enbrel) for ankylosing spondylitis; infliximab (Remicade) is not recommended. See New from NICE (pages 13-14) for further details. Prescriber consultant editor wins award Professor Tony Avery, professor of primary care at Nottingham University and consultant editor for Prescriber, has won the John Fry Award for his work in promoting the discipline of general practice through research and publishing as a practising GP. The citation acknowledges Professor Avery as ,quite simply one of the best researchers we have had in general practice,' describing his output of original work and research as impressive. The award commemorates the work of the late Dr John Fry, perhaps the most prominent GP of his generation involved in research. Antihypertensive dose ignores adherence Clinicians take no account of poor adherence when they increase the dose of antihypertensive therapy due to apparent lack of effect, US researchers say (Circulation 2008; published online May 27; doi 10.1161/CIRCULATIONAHA.107.724104). Their retrospective analysis included reimbursement records for 38 327 patients with hypertension who presented with elevated BP (140-200/>90mmHg) in one year (mean 1.8 events per patient). After adjusting for potential confounders, they found that antihypertensive medications were added or the dose of medication increased in about one-third of patients regardless of the degree of nonadherence in the previous year. LABAs improve COPD Inhaled long-acting beta2-agonists (LABAs) improve COPD and do not increase the risk of death, a new safety review has concluded (Chest 2008;133:1079-87). The meta-analysis of 27 RCTs in patients with moderate to severe stable COPD found that LABAs reduced exacerbations by 22 per cent, improved lung function, reduced use of rescue medication and improved quality of life. There was no effect on respiratory deaths, though a combination of a LABA with an inhaled steroid reduced the risk by two-thirds compared with LABA monotherapy. Tiotropium (Spiriva) was associated with a 50 per cent lower risk of exacerbations than LABAs. These findings follow the MHRA's review of LABAs in the treatment of asthma, which found no increase in mortality provided they are used with an inhaled steroid (Drug Safety Update 2008;1:9). Naproxen as effective in acute gouty arthritis Naproxen is as effective as prednisolone in the treatment of acute gouty arthritis, say researchers from The Netherlands (Lancet 2008;371:1854-60). Their study in 118 primary care patients showed that five days' treatment with naproxen 500mg twice daily or prednisolone 35mg daily reduced pain scores to a similar extent with a comparable incidence of adverse effects. Copyright © 2008 Wiley Interface Ltd [source]

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PRESCRIBER, Issue 2 2008
Article 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]

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PRESCRIBER, Issue 5 2007
Article 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]

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Changes in malondialdehyde levels in bronchoalveolar fluid and serum by the treatment of asthma with inhaled steroid and beta2 -agonist

RESPIROLOGY, Issue 3 2000
Resat Ozaras
Objective: Oxidative stress plays an important role in the pathogenesis of asthma. Recent data suggest that clinical indices of the patients with asthma may not correlate with the underlying inflammatory process. We aimed to measure the level of malondialdehyde (MDA), which is a marker of lipid peroxidation, a free radical-mediated process, before and after a well-accepted treatment of asthma. Methodology: Nine non-smoking females and five non-smoking males with mild,moderate asthma were included. Twenty-four age- and sex-matched, non-smoking healthy people (17 females and seven males, mean age 32.1 years, range 20,59) were included for control. After initial evaluation, spirometry, broncoscopy with bronchoalveolar lavage (BAL), and blood sample were maintained. The patients were treated with twice-daily salmeterol inhaler (100 ,g/d) and fluticasone propionate inhaler (500 ,g/d). One month later the investigations were repeated. Serum MDA levels before treatment were compared with both the levels after treatment and levels of controls. Malondialdehyde levels of BAL were compared before and after treatment. Results: Serum MDA level of the patient before treatment was 6.7 ± 0.8 nmol/mL, significantly higher than that of healthy controls; 3.8 ± 0.4, P < 0.001. One month after the treatment, serum MDA level decreased to 5.3 ± 0.7 nmol/mL (P < 0.001). However, this level is still significantly higher than healthy controls (P < 0.0001). Forced expiratory volume in 1 s level of the patients increased from 2.43 ± 0.79 L to 3.50 ± 1.21 L after the treatment (P < 0.001). Conclusion: Although treatment with beta2 -agonist and corticosteroid inhalers for the duration of 1 month reduced lipid peroxidation significantly, it was still at a level significantly higher than healthy controls. The treatment may need a longer duration to improve lipid peroxidation or an alternative regimen which is more effective in controlling inflammation may be warranted. [source]

Impact of quality circles for improvement of asthma care: results of a randomized controlled trial

JOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 2 2008
Antonius Schneider MD
Abstract Rationale and aims, Quality circles (QCs) are well established as a means of aiding doctors. New quality improvement strategies include benchmarking activities. The aim of this paper was to evaluate the efficacy of QCs for asthma care working either with general feedback or with an open benchmark. Methods, Twelve QCs, involving 96 general practitioners, were organized in a randomized controlled trial. Six worked with traditional anonymous feedback and six with an open benchmark; both had guided discussion from a trained moderator. Forty-three primary care practices agreed to give out questionnaires to patients to evaluate the efficacy of QCs. Results, A total of 256 patients participated in the survey, of whom 185 (72.3%) responded to the follow-up 1 year later. Use of inhaled steroids at baseline was high (69%) and self-management low (asthma education 27%, individual emergency plan 8%, and peak flow meter at home 21%). Guideline adherence in drug treatment increased (P = 0.19), and asthma steps improved (P = 0.02). Delivery of individual emergency plans increased (P = 0.008), and unscheduled emergency visits decreased (P = 0.064). There was no change in asthma education and peak flow meter usage. High medication guideline adherence was associated with reduced emergency visits (OR 0.24; 95% CI 0.07,0.89). Use of theophylline was associated with hospitalization (OR 7.1; 95% CI 1.5,34.3) and emergency visits (OR 4.9; 95% CI 1.6,14.7). There was no difference between traditional and benchmarking QCs. Conclusions, Quality circles working with individualized feedback are effective at improving asthma care. The trial may have been underpowered to detect specific benchmarking effects. Further research is necessary to evaluate strategies for improving the self-management of asthma patients. [source]

Asthma patients with low perceived burden of illness: a challenge for guideline adherence

JOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 6 2007
Antonius Schneider MD
Abstract Rationale and aims, The reason why many patients seem to tolerate suffering from sub-optimal treated asthma remains unclear. The aim was to evaluate the guideline adherence combined with quality of life of patients with moderate to severe asthma. Methods, 256 asthma patients from 43 primary care practices in Saxony-Anhalt filled in a questionnaire including the Asthma Quality of Life Questionnaire (AQLQ), the Patient Health Questionnaire (PHQ-D) and questions evaluating the asthma severity, medication and self-management. Results, 43.4% suffered from moderate to severe asthma. Drug treatment accorded with guidelines in 36.9%, drug dosage of inhaled steroids was too low in 34.3%, and 21.5% were not treated according to guidelines. A total of 7.3% of the patients received end-of-dose therapy. AQLQ declined and depression rose with asthma severity and guideline non-adherence (P < 0.001). Only 29.1% received asthma education. However, 64.5% of the patients without education did not want to receive education. They had a higher quality of life, lower depression (P < 0.001) and lower use of steroids (P = 0.016). Higher depression scores where related with hospital admission (OR 3.29; 95% CI 1.57,6.87 for each quartile of PHQ-D) and unscheduled home visits or ambulatory care (OR 1.58; 1.07,2.33). Conclusion, There is a large variation of asthma severity which can partly be explained by the guideline adherence of medication and deficits of patients' management. The perceived burden of illness plays a more important role for education and self-management than the real severity of disease. Therefore, target-oriented interventions are needed to identify and motivate patients at risk. [source]

Neutrophilic airway inflammation is a main feature of induced sputum in nonatopic asthmatic children

ALLERGY, Issue 11 2009
A. C. Drews
Background:, Asthma phenotypes are well described among children. However, there are few studies comparing airway inflammation in different clinical presentations of pediatric asthma. We tested the hypothesis that nonatopic asthma is associated with a predominant noneosinophilic inflammation in the airways, as assessed by induced sputum. The objective of this study was to evaluate the cytological characteristics of induced sputum (IS) in atopic (AA), nonatopic asthmatics (NAA) and nonatopic nonasthmatic children (NANA). Methods:, Of 90 selected children, 77 met eligibility criteria for performing IS and were classified as: AA, n = 28, NAA, n = 29 and NANA, n = 19. Subjects answered to a set of ISAAC-based questions and were skin-tested for common aeroallergens. A defined series of exclusion criteria was applied. Results:, Induced sputum was obtained from 54 (70.1%) subjects (21 AA, 20 NAA and 13 NANA). Demographic data and mean FEV1 were similar in the three groups. The proportion of eosinophils [median, inter quartile range (IQR)] was significantly higher in the sputum of AA [(6.0.)12)] compared with NAAs [0 (2)] and NANAs [0 (1)], P < 0.001. The proportion of children with sputum eosinophilia (eos > 3%) was also significantly higher in AA (71.4%) when compared with NAA (28.6%); none of the NANA had sputum eosinophilia. Nonatopic asthmatic children had significantly higher proportions and absolute number of neutrophils than AA and controls. Conclusions:, The results suggest that nonatopic children present IS with a cell pattern that is predominantly neutrophilic while eosinophilia is the hallmark of airway inflammation in the majority of atopic wheezing children not treated with inhaled steroids. [source]

Monitoring adherence to beclomethasone in asthmatic children and adolescents through four different methods

ALLERGY, Issue 10 2009
N. S. Jentzsch
Background:, Suboptimal adherence to inhaled steroids is a known problem in children and adolescents, even when medications are administered under parental supervision. This study aimed to verify the adherence rate to beclomethasone dipropionate (BDP) by four currently available methods. Methods:, In this concurrent cohort study, 102 randomly selected asthmatic children and adolescents aged 3,14 years were followed for 12 months. Adherence rate was assessed every 2 months by self and/or parent report, pharmacy dispensing data, electronic device (Doser®; Meditrack Products, Hudson, MA, USA) monitor, and canister weight. Results:, Mean adherence rates to BDP by self and/or parent report, pharmacy records, Doser, and canister weight were 97.9% (95% CI 88.0,98.6), 70.0% (95% CI 67.6,72.4), 51.5% (95% CI 48.3,54.6), and 46.3% (95% CI 44.1,48.4), respectively. Agreement analysis between (Doser) and canister weight revealed a weighted kappa equal to 0.76 (95% CI 0.65,0.87). Conclusions:, Adherence was a dynamic event and rates decreased progressively for all methods over the 12-month follow-up. Canister weight and electronic monitoring measures were more accurate than self/parent reports and pharmacy records. Rates obtained by these two methods were very close and statistical analysis also showed a substantial agreement between them. As measurements by canister weight are less costly compared with currently available electronic devices, it should be considered as an alternative method to assess adherence in both clinical research and practice. [source]

Adherence rate to inhaled corticosteroids and their impact on asthma control

ALLERGY, Issue 5 2009
L. Lasmar
Background:, Poor asthma control is associated to high morbidity. The objective of this study was to assess the association between adherence rates to beclomethasone dipropionate (BDP) and the degree of asthma control. Methods:, A cohort concurrent study was carried out for 12 months with 122 asthmatic patients, aged 3,12 years, randomly selected in a pediatric pulmonology outpatient clinic, who received BDP free of charge. Adherence rates were verified by pharmacy records. Clinical control was assessed through a scoring system comprised four variables (nocturnal and morning symptoms, limitation of physical activities and exacerbations). Total score was 16 points. Patients whose score was below or equal to two were considered controlled (group 1), and patients whose score was above or equal to three were considered uncontrolled (group 2). For patients able to perform spirometry, we considered as controlled the patients with forced expiratory volume in 1 s (FEV1) equal to or above 80% of the predicted value, and as uncontrolled the patients with FEV1 below 80%. Results:, Fewer than half (40.3% maximum) of the 122 patients maintained asthma control. Median adherence rate of groups 1 and 2 were 85.5% and 33.8%, (P < 0.001) in the 4th month, 90.0% and 48.0% (P < 0.001) in the 8th month and 84.4% and 47.0% in the 12th month (P < 0.001), respectively. Conclusion:, In all periods, there were statistically significant differences in adherence rates for maintaining or not maintaining the asthma control. Optimal asthma control entailed adherence rate higher than 80%. Strategies for reducing asthma morbidity should include a regular monitoring of adherence to inhaled steroids. [source]

Corticosteroids for acute chest syndrome in children with sickle cell disease: Variation in use and association with length of stay and readmission,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010
Amy Sobota
Acute chest syndrome (ACS) causes significant morbidity and mortality in sickle cell disease. The role of corticosteroids is unclear. The objectives of our study were to examine the variation between hospitals in their use of corticosteroids for ACS, describe characteristics associated with corticosteroids, and investigate the association between corticosteroids, length of stay, and readmission. We performed a retrospective examination of 5,247 hospitalizations for ACS between January 1, 2004, and June 30, 2008, at 32 hospitals in the Pediatric Health Information System database. We used multivariate regression to examine the variability in the use of corticosteroids adjusting for hospital case mix, identify factors associated with corticosteroid use, and evaluate the association of corticosteroids with length of stay and 3-day readmission rates controlling for propensity score. Corticosteroid use varied greatly by hospital (10,86% among all patients, 18,92% in patients with asthma). Treatment with corticosteroids was associated with comorbid asthma (OR 3.9, 95% CI: 3.2,4.8), inhaled steroids (OR 1.4, 95% CI: 1.1,1.7), bronchodilators (OR 3.2, 95% CI: 2.5,4.2), nitric oxide (OR 2.4, 95% CI: 1.2,5.0), oxygen (OR 2.3, 95% CI: 1.8,2.9), ICU (OR 1.7, 95% CI: 1.3,2.3), ventilation (OR 2.0, 95% CI: 1.4,2.8), APR-DRG severity level (OR 1.4, 95% CI: 1.2,1.6), and discharge year (OR 0.86, 95% CI: 0.80,0.92). Corticosteroids were associated with an increased length of stay (25%, 95% CI: 14,38%) and a higher 3-day readmission rate (OR 2.3, 95% CI: 1.6,3.4), adjusted for confounding. Hospitals vary greatly in the use of corticosteroids for ACS, even in patients with asthma. Clear evidence of the efficacy and toxicity of corticosteroid treatment in ACS may reduce variation in care. Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc. [source]

Effect of montelukast on exhaled NO in asthmatic children exposed to relevant allergens

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2 2002
Giorgio L. Piacentini
The level of exhaled nitric oxide (FENO) is increased in house dust mite (HDM)-sensitized asthmatic children after exposure to HDM antigen, and inhaled steroids can prevent this increase. The aim of this study was to evaluate whether montelukast could prevent an increase in FENO levels in allergic asthmatic children after a brief period of exposure to relevant allergens. Sixteen children were evaluated at the residential house ,Istituto Pio XII' (Misurina, Bellunio, Italy) in the Italian Alps, a dust mite-free environment. FENO levels were evaluated before (t0) and immediately after (t1) the children were exposed to HDM allergens for 2 weeks in their homes at sea level. No significant difference in FENO was observed in the fluticasone-treated group of children after 2 weeks at sea level. In the group treated with montelukast, an increase in FENO was observed between t0 and t1, which failed to reach statistical significance. These preliminary data suggest that oral montelukast could be effective in preventing the relapse in airway inflammation in allergic asthmatic children who are occasionally exposed to relevant allergens for a short period of time. [source]

How pediatricians manage asthma in Thailand

PEDIATRIC PULMONOLOGY, Issue 2 2001
Pakit Vichyanond MD
Abstract Currently, there is no existing information regarding prescribing practices for the management of childhood asthma among pediatricians in Thailand. In order to evaluate the management standards for childhood asthma in Thailand, 400 self-administered questionnaires were randomly mailed to nonacademic pediatricians throughout Thailand, asking questions about their preferences in the treatment of childhood asthma. One hundred and seventy-four of these 400 questionnaires were returned (a response rate of 43.5%). Data were analyzed using the descriptive module of the Epi-info 6 program. For acute asthma, 17% of the respondents used objective measures such as peak flow meters in assessing asthma severity and severity of acute asthma attacks. The drug of first choice for treating acute attacks was a nebulized beta-agonist q 20 min (81.8%). Although 93% indicated that they had used theophylline for treating acute attacks, most would reserve the drug for patients with severe symptoms. Corticosteroids were reserved for those with severe attacks (91.7% both for clinic and for in-hospital settings). Hydrocortisone was the most preferred corticosteroid preparation (59.8%). Ninety-seven percent used antibiotics in treating acute asthma, but only with appropriate indications. For chronic asthma, a strong preference was observed for oral beta-agonists as the bronchodilator of choice (88%). For moderately severe asthmatics, theophylline was still preferred by 41% of the responders. Among prophylactic agents, ketotifen was the most favored drug (90.4%), whereas inhaled steroids and cromolyn were chosen by 9.6% and 2.4%, respectively. Eighty-five percent indicated that they would prescribe prophylactic agents for 1 year or less. Forty-two percent never considered allergy evaluation as a part of a workup for childhood asthma. Certain prescribing practices of childhood asthma management in Thailand were observed among pediatricians, i.e., 1) low frequency of using objective measures in assessing asthma severity among pediatricians; 2) frequent use of theophylline and antibiotics in the treatment of acute asthma; 3) late introduction of corticosteroids in treating acute asthma; 4) preference for oral bronchodilators; and 5) preference of ketotifen as the prophylactic drug of choice. This survey provides baseline data and will aid in the evaluation of management guidelines for childhood asthma in Thailand. Pediatr Pulmonol. 2001; 32:109,114. © 2001 Wiley-Liss, Inc. [source]

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PRESCRIBER, Issue 8 2008
Article 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]

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PRESCRIBER, Issue 6 2007
Article 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]

Airway hyperresponsiveness: the usefulness of airway hyperresponsiveness testing in epidemiology, in diagnosing asthma and in the assessment of asthma severity

THE CLINICAL RESPIRATORY JOURNAL, Issue 1 2007
Celeste Porsbjerg MD
Abstract The present PhD thesis was conducted at the Respiratory Research Unit at the Pulmonary Department L in Bispebjerg Hospital, Copenhagen, Denmark and describes airway hyperresponsiveness in asthma patients in four studies. The first study concerned risk factors for the development of asthma in young adults in a 12-year prospective follow-up study of a random population sample of 291 children and adolescents from Copenhagen, who were followed up from the age of 7,17 years (1986) until the age of 19,29 years (1998). During follow-up, 16.1% developed asthma, and in these subjects, the most important predictor of asthma development was airway hyperresponsiveness to histamine at baseline. Airway hyperresponsiveness is associated with more severe asthma and a poorer prognosis in terms of more exacerbations and less chance of remission of the disease. The second study described the relation between airway hyper-responsiveness to methacholine and the quality of life in 691 asthma patients: In asthma patients with airway hyperresponsiveness to methacholine, the quality of life measured with a validated questionnaire (Junipers Asthma Quality of Life Questionnaire) was significantly reduced compared to asthma patients who did not respond to bronchial provocation with methacholine. Airway hyperresponsiveness is not uncommonly observed in non-asthmatics, and the response to bronchial provocation with methacholine is therefore relatively non-specific. The mannitol test is a relatively new bronchial provocation test that acts indirectly on the smooth airway muscle cells through the release of mediators from inflammatory cells in the airways; the mannitol could consequently be a more specific test compared with methacholine. The third study showed that out of 16 non-asthmatics with airway hyperresponsiveness to methacholine, 15 did not respond to bronchial provocation with mannitol Because of the mechanism of action of mannitol, it seems plausible that the response to mannitol is more closely correlated to airway inflammation in asthma compared with the response to methacholine. The fourth study showed that in 53 adult asthma patients, who did not receive treatment with inhaled steroids, there was a positive correlation between the degree of airway inflammation and the degree of airway responsiveness to mannitol as well as to methacholine. The mannitol does, however, have the advantage of being a faster and simpler test to perform, requiring no additional equipment apart from a spirometer. Conclusions:, Airway hyperresponsiveness in children and in adolescents without asthma predicts asthma development in adulthood. Asthma patients with airway hyperresponsiveness to methacholine have a poorer quality of life as well as more severe disease and a poorer prognosis compared with asthma patients without airway hyperresponsiveness. Bronchial provocation with mannitol as well as with methacholine were useful for evaluating the severity of asthma and the degree of airway inflammation, and accordingly for determining the need for steroid statement. The mannitol test does, however, have practical advantages over the methacholine test that make it preferable for clinical use. [source]

Drug prescribing by Italian family paediatricians: an exception?

ACTA PAEDIATRICA, Issue 5 2010
A Clavenna
Abstract Aims:, To identify which drugs are considered ,essential' by Italian family paediatricians based on their prescriptions. Methods:, Prescriptions reimbursed by the National Health System, involving 923 177 children < 14 years old, and dispensed during 2005 by the retail pharmacies of 15 local health units (LHUs) in the Lombardy Region, were analysed. The percentage of family paediatricians prescribing each single drug was calculated. A percentage ,75% was considered as a high degree of agreement. Results:, In all, 746 different drugs were prescribed to 486 405 children (52.7%). The median number of drugs prescribed by each paediatrician was 60 (interquartile range 51,71). A total of 22 drugs were prescribed by at least 75% of paediatricians and six were prescribed by all the paediatricians. In all, 95% of the paediatricians prescribed four or more cephalosporins and 92% prescribed four inhaled steroids. Only eight of the 22 most frequent drugs are included in the World Health Organization Essential Medicines for children list. Conclusion:, Despite the huge number of drugs prescribed, only for 22 there was a concordance between family paediatricians. Initiatives to evaluate and promote a more rational use of drugs in Italian children are necessary. [source]

Identifying problematic severe asthma in the individual child , does lung function matter?,

ACTA PAEDIATRICA, Issue 3 2010
AM Lang
Abstract Aim:, Measures of lung function (usually FEV1 <80% predicted) are used to classify asthma severity in both adults and children, despite evidence that lung function impairment is less pronounced in the paediatric asthma population. The present study assesses the relevance of lung function measurements as discriminators of severe childhood asthma. Methods:, Fifty-one school-aged children with problematic severe asthma, 37 mild-to-moderate asthmatics and 29 healthy controls underwent a comprehensive clinical work-up. Problematic severe asthma was defined in patients exhibiting poor asthma control despite high-dose inhaled corticosteroid treatment and at least one other asthma controller drug. Mild-to-moderate asthmatic children used low-dose inhaled steroids and reported minimal asthma symptoms. Results:, Baseline FEV1 values were significantly reduced in children with problematic severe asthma, yet FEV1 <80% predicted showed a low sensitivity (41%) for discriminating severe vs. mild-to-moderate asthma. Receiver-operated characteristic analysis estimated the optimal cut-off of FEV1 to be 90% predicted in this population (sensitivity 61%, specificity 83%). Baseline FEV1/FVC and FEF25,75 values were not superior to FEV1 in discriminating problematic severe asthma, and neither exhaled nitric oxide levels nor bronchial hyperresponsiveness differentiated between the two asthmatic study populations. Conclusion:, Spirometric measurements are insensitive discriminators of problematic severe asthma in childhood. [source]

Repeatability of the low-dose ACTH test in asthmatic children on inhaled corticosteroids

ACTA PAEDIATRICA, Issue 12 2009
Atul Gupta
Abstract Aim:, To assess the repeatability of low-dose Synacthen test (LDST) in asthmatic children receiving high-dose fluticasone propionate (FP). Methods:, Low-dose Synacthen test was performed on 18 children with stable chronic asthma treated with FP at a constant daily dose of ,500 ,g and repeated 1 month later. Repeatability was assessed using the Kappa statistic for categorical variables. Results:, Fifteen patients had consistent results (either two normal or two abnormal responses) and three patients had inconsistent results (one normal and one abnormal response). The Kappa statistic was 0.56 indicating fair to good agreement between the tests. Conclusion:, The results of adrenal function testing in patients on inhaled steroids can have major implications for patient management, making it important to use a test with excellent repeatability. The LDST conducted using our protocol does not fulfil this criterion. [source]

Montelukast does not prevent reactive airway disease in young children hospitalized for RSV bronchiolitis

ACTA PAEDIATRICA, Issue 11 2009
M Proesmans
Abstract Aim:, To evaluate the long-term effect of montelukast on symptoms of cough and wheeze following RSV bronchiolitis. Methods:, Fifty eight patients (aged , 24 months) hospitalized with a first episode of RSV bronchiolitis were enrolled in this double blind prospective randomized trial comparing montelukast (n = 31) vs placebo (n = 27). Results:, During the 3-month treatment period, there were no statistical significant differences between the two groups for symptom-free days and nights (48.5 [interquartile range 33.0.0,66.0] for montelukast vs 57.0 [29.0,71.0] for placebo p = 0.415) nor disease-free days and nights (44.5 days [26.0,54.0] vs 53.0 [22.3,71.0]; p = 0.266). During the 1 year follow-up, there were 41 exacerbations in the montelukast group vs 54 exacerbations in the placebo group (p = 0.57). Time to first exacerbation was not different. Number of unscheduled visits and need to start inhaled steroids were comparable in the two groups. Conclusion:, Treatment with montelukast after hospital admission for RSV bronchiolitis in children younger than 2 years of age did not reduce symptoms of cough and wheeze. We cannot exclude that a subgroup of children may, however, benefit from this treatment. [source]