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Event Profile (event + profile)

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Medical Sciences100%

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  • adverse event profile
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    Selected Abstracts

    Relationship between adverse effects of antiepileptic drugs, number of coprescribed drugs, and drug load in a large cohort of consecutive patients with drug-refractory epilepsy

    EPILEPSIA, Issue 5 2010
    Maria Paola Canevini
    Summary Purpose:, To evaluate the adverse effects (AEs) of antiepileptic drugs (AEDs) in adults with refractory epilepsy and their relationship with number of coprescribed AEDs and AED load. Methods:, Patients with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers. AEs were assessed through unstructured interview and the Adverse Event Profile (AEP) questionnaire. AED loads were calculated as the sum of prescribed daily dose (PDD)/defined daily dose (DDD) ratios for each coprescribed AED. Results:, Of 809 patients enrolled, 709 had localization-related epilepsy and 627 were on polytherapy. AED loads increased with increasing number of AEDs in the treatment regimen, from 1.2 ± 0.5 for patients on monotherapy to 2.5 ± 1, 3.7 ± 1.1, and 4.7 ± 1.1 for those on two, three, and ,4 AEDs, respectively. The number of spontaneously reported AEs correlated with the number of AEs identified by the AEP (r = 0.27, p < 0.0001). AEP scores did not differ between patients with monotherapy and patients with polytherapy (42.8 ± 11.7 vs. 42.6 ± 11.2), and there was no correlation between AEP scores and AED load (r = ,0.05, p = 0.16). Conclusions:, AEs did not differ between monotherapy and polytherapy patients, and did not correlate with AED load, possibly as a result of physicians' intervention in individualizing treatment regimens. Taking into account the limitations of a cross-sectional survey, these findings are consistent with the hypothesis that AEs are determined more by individual susceptibility, type of AEDs used, and physicians' skills, than number of coprescribed AEDs and AED load. [source]

    Review article: Efficacy and safety of methoxyflurane analgesia in the emergency department and prehospital setting

    EMERGENCY MEDICINE AUSTRALASIA, Issue 1 2009
    Joanne Grindlay
    Abstract This article reviews the evidence for the analgesic efficacy of methoxyflurane in both prehospital and ED settings, as well as the adverse event profile associated with methoxyflurane use. Although there are no published controlled trials of methoxyflurane in sub-anaesthetic doses, available data indicate that it is an efficacious analgesic. There is inadequate evidence regarding its use as an agent for procedural pain. Despite the potential for renal impairment evident when it was used in anaesthetic doses, no significant adverse effects have been reported in the literature, neither in patients nor occupationally, when the dose used is limited to that currently recommended. [source]

    Characteristics of Migraine Attacks and Responses to Almotriptan Treatment: A Comparison of Menstrually Related and Nonmenstrually Related Migraines

    HEADACHE, Issue 2 2008
    Merle L. Diamond MD
    Objectives., To compare the clinical characteristics of menstrually related migraines (MRMs) and nonmenstrually related migraines (nonMRMs) and to investigate the efficacy of almotriptan in the treatment of these migraine subtypes. Design/Methods., These are post hoc analyses of data from the AXERT® Early miGraine Intervention Study (AEGIS), a multicenter, double-blind, parallel-group trial that evaluated adults with IHS-defined migraine with and without aura. Patients were randomized 1 : 1 to treat 3 consecutive headaches with almotriptan 12.5 mg or matching placebo at the first sign of headache typical of their usual migraine, at any level of pain intensity but within 1 hour of onset. MRMs were defined as those occurring ±2 days of the first day of menstrual flow. Post hoc analyses to describe headache characteristics pooled all migraine attacks experienced by patients who reported ,1 menses during the study regardless of assigned treatment group. The post hoc efficacy analyses included outcomes of almotriptan treatment compared with placebo treatment for all migraines in patients with a menstrual record. Results., Of the 275 women in the AEGIS intent-to-treat population, 190 (69.1%; 97 almotriptan, 93 placebo; aged 18-54 years) reported ,1 menses during the trial. Of the 506 migraines reported by these patients, 95 (18.8%) occurred ±2 days of the first day of menstrual flow and were defined as MRM. Aura was associated with 11.7% of MRM and 15.0% of nonMRM. Allodynia-associated symptoms were present with 62.8% of MRM and 57.0% of nonMRM. Prior to treatment, 19.1% of MRM were associated with normal functional ability, 68.1% with disturbed functional ability, and 12.8% required bed rest compared with 18.9%, 68.8%, and 12.3%, respectively, of nonMRM. Pretreatment pain intensity was mild in 40.0%, moderate in 47.4%, and severe in 12.6% of MRM compared with 43.6%, 47.2%, and 9.2%, respectively, of nonMRM. Almotriptan treatment efficacy outcomes for MRM vs nonMRM, respectively, were: 2-hour pain relief, 77.4% vs 68.3%; 2-hour pain free, 35.4% vs 35.9%; and sustained pain free, 22.9% vs 23.8%. Almotriptan was similarly effective in relieving migraine-associated symptoms and improving functional disability associated with both MRM and nonMRM. Conclusions., Prior to treatment, the presence of migraine-associated characteristics including aura, allodynia-associated symptoms, photophobia, phonophobia, and nausea were similar for both MRM and nonMRM attacks. The pretreatment levels of pain intensity and functional disability were likewise similar across the migraine subtypes. Almotriptan was equally effective in the treatment of both MRM and nonMRM attacks and was associated with an adverse event profile that was similar to placebo treatment. [source]

    Effect of Teriparatide {rhPTH(1-34)} on BMD When Given to Postmenopausal Women Receiving Hormone Replacement Therapy

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2006
    Louis G Ste-Marie
    Abstract The effects of teriparatide when given in combination with HRT were studied in postmenopausal women with low bone mass or osteoporosis. The data provide evidence that the adverse event profile for combination therapy with teriparatide + HRT together is consistent with that expected for each treatment alone and that the BMD response is greater than for HRT alone. Introduction: Teriparatide {rhPTH(1-34)}, given as a once-daily injection, activates new bone formation in patients with osteoporosis. Hormone replacement therapy (HRT) prevents osteoporosis by reducing bone resorption and formation. Combination therapy with these two compounds, in small clinical trials, increased BMD and reduced vertebral fracture burden. The purpose of this study was to determine whether teriparatide provided additional effect on BMD when given in combination with HRT. Materials and Methods: A randomized, double-blind, placebo-controlled study was conducted in postmenopausal women with either low bone mass or osteoporosis. Patients were randomized to placebo subcutaneous plus HRT (n = 125) or teriparatide 40 ,g/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a median treatment exposure of 13.8 months. Approximately one-half of the patients in each group were pretreated with HRT for at least 12 months before randomization. Patients received 1000 mg calcium and 400,1200 IU of vitamin D daily as oral supplementation. BMD was measured by DXA. Results: Compared with HRT alone, TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD (14% versus 3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%) at study endpoint. BMD, in whole body and ultradistal radius, was higher, and in the one-third distal radius was lower, in the combination therapy but not in the HRT group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr were increased significantly (p < 0.01) in the women receiving TPTD40 + HRT compared with HRT. A similar profile of BMD and bone markers was evident in both randomized patients as well as in subgroups of patients not pretreated or pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg cramps were more frequently reported in the TPTD40 + HRT group. Conclusions: Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent, provides additional increases in BMD beyond that provided by HRT alone. The adverse effects of teriparatide when added to HRT were similar to the adverse effects described for teriparatide administered alone. Whether teriparatide was initiated at the same time as HRT or after at least 1 year on HRT, the incremental increases over HRT alone were similar. [source]

    Anticholinergics and Ketamine Sedation in Children: A Secondary Analysis of Atropine Versus Glycopyrrolate

    ACADEMIC EMERGENCY MEDICINE, Issue 2 2010
    Steven M. Green MD
    Abstract Objectives:, Adjunctive anticholinergics are commonly administered during emergency department (ED) ketamine sedation in children under the presumption that drying oral secretions should decrease the likelihood of airway and respiratory adverse events. Pharmacologic considerations suggest that glycopyrrolate might exhibit a superior adverse effect profile to atropine. The authors contrasted the adverse events noted with use of each of these anticholinergics in a large multicenter observational database of ketamine sedations. Methods:, This was a secondary analysis of an observational database of 8,282 ED ketamine sedations assembled from 32 prior series. The authors compared the relative incidence of six adverse events (airway and respiratory adverse events, laryngospasm, apnea, emesis, recovery agitation, and clinically important recovery agitation) between children who received coadministered atropine, glycopyrrolate, or no anticholinergic. Multivariable analysis using the specific anticholinergic as a covariate was performed, while controlling for other known predictors. Results:, Atropine was associated with less vomiting (5.3%) than either glycopyrrolate (10.7%) or no anticholinergic (11.4%) in both unadjusted and multivariable analyses. Glycopyrrolate was associated with significantly more airway and respiratory adverse events (6.4%) than either atropine (3.3%) or no anticholinergic (3.0%) and similarly more clinically important recovery agitation (2.1% vs. 1.2 and 1.3%). There were, however, no differences noted in odds of laryngospasm and apnea. Conclusions:, This secondary analysis unexpectedly found that the coadministered anticholinergic atropine exhibited a superior adverse event profile to glycopyrrolate during ketamine sedation. Any such advantage requires confirmation in a separate trial; however, our data cast doubt on the traditional premise that glycopyrrolate might be superior. Further, neither anticholinergic showed efficacy in decreasing airway and respiratory adverse events. ACADEMIC EMERGENCY MEDICINE 2010; 17:157,162 © 2010 by the Society for Academic Emergency Medicine [source]

    A Prospective Case Series of Pediatric Procedural Sedation and Analgesia in the Emergency Department Using Single-syringe Ketamine,Propofol Combination (Ketofol)

    ACADEMIC EMERGENCY MEDICINE, Issue 2 2010
    Gary Andolfatto MD
    Abstract Objectives:, This study evaluated the effectiveness, recovery time, and adverse event profile of intravenous (IV) ketofol (mixed 1:1 ketamine,propofol) for emergency department (ED) procedural sedation and analgesia (PSA) in children. Methods:, Prospective data were collected on all PSA events in a trauma-receiving, community teaching hospital over a 3.5-year period, from which data on all patients under 21 years of age were studied. Patients receiving a single-syringe 1:1 mixture of 10 mg/mL ketamine and 10 mg/mL propofol (ketofol) were analyzed. Patients received ketofol in titrated aliquots at the discretion of the treating physician. Effectiveness, recovery time, caregiver and patient satisfaction, drug doses, physiologic data, and adverse events were recorded. Results:, Ketofol PSA was performed in 219 patients with a median age of 13 years (range = 1 to 20 years; interquartile range [IQR] = 8 to 16 years) for primarily orthopedic procedures. The median dose of medication administered was 0.8 mg/kg each of ketamine and propofol (range = 0.2 to 3.0 mg/kg; IQR = 0.7 to 1.0 mg/kg). Sedation was effective in all patients. Three patients (1.4%; 95% confidence interval [CI] = 0.0% to 3.0%) had airway events requiring intervention, of which one (0.4%; 95% CI = 0.0% to 1.2%) required positive pressure ventilation. Two patients (0.9%; 95% CI = 0.0% to 2.2%) had unpleasant emergence requiring treatment. All other adverse events were minor. Median recovery time was 14 minutes (range = 3 to 41 minutes; IQR = 11 to 18 minutes). Median staff satisfaction was 10 on a 1-to-10 scale. Conclusions:, Pediatric PSA using ketofol is highly effective. Recovery times were short; adverse events were few; and patients, caregivers, and staff were highly satisfied. ACADEMIC EMERGENCY MEDICINE 2010; 17:194,201 © 2010 by the Society for Academic Emergency Medicine [source]

    Disappointing results and low tolerability of photodynamic therapy with topical 5-aminolaevulinic acid in psoriasis.

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 7 2006
    A randomized, double-blind phase I/II study
    Abstract Background, Based on good results in the treatment of superficial skin tumours, since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA PDT) has been used for disseminated, inflammatory dermatoses including psoriasis. However, there is still a lack of well-documented trials. Objective, A prospective randomized, double-blind phase I/II intrapatient comparison study was conducted in 12 patients to investigate whether topical ALA PDT is an effective treatment for chronic plaque-type psoriasis. Methods, In each patient three psoriatic plaques were randomly treated with a light dose of 20 J/cm2 and 0.1%, 1% and 5% ALA, respectively. Treatment was conducted twice a week until complete clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed by weekly determination of the psoriasis severity index (PSI). Results, The mean percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA-treated groups, respectively. Irradiation had to be interrupted several times because of severe burning and pain sensation. Conclusion, Topical ALA PDT did not prove to be an appropriate treatment option for plaque-type psoriasis due to disappointing clinical efficacy, the time-consuming treatment procedure and its unfavourable adverse event profile. [source]

    Rupatadine in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled multicentre study

    ALLERGY, Issue 5 2007
    A. Gimenez-Arnau
    Background:, Chronic urticaria is one of the most common and disturbing cutaneous condition. The treatment of chronic idiopathic urticaria (CIU) is still a challenge. Antihistamines are recommended as first-line treatment. Rupatadine is a new potent nonsedative anti-H1. Objective:, To study rupatadine efficacy and safety for moderate to severe CIU treatment. Methods:, This randomized, double-blind, placebo-controlled, parallel-group, multicentre, study was designed to assess primarily mean pruritus score (MPS) reduction with rupatadine, 10 and 20 mg, administered once daily for 4 weeks. Three hundred and thirty-three patients with active episodes of moderate-to-severe CIU were included. Results:, A 57.5% (P < 0.005) and 63.3% (P = 0.0001) significative MPS reduction from baseline, was observed at week 4 with 10 and 20 mg rupatadine, respectively, compared with placebo (44.9%). Both doses of rupatadine were not significantly different at any time point, with respect to their effects on pruritus severity, number of wheals and total symptoms scores. Rupatadine 10 mg had an overall better adverse event profile. Conclusion:, Rupatadine 10 mg is a fast, long-acting, efficacious and safe treatment option for the management of patients with moderate-to-severe CIU. [source]

    Open retropubic colposuspension for urinary incontinence in women: A short version cochrane review,,

    NEUROUROLOGY AND URODYNAMICS, Issue 6 2009
    Marie Carmela M. Lapitan
    Abstract Background Urinary incontinence is a common and potentially debilitating problem. Open retropubic colposuspension is a surgical treatment which involves lifting the tissues near the bladder neck and proximal urethra in the area behind the anterior pubic bones to correct deficient urethral closure. Objectives To assess the effects of open retropubic colposuspension for the treatment of urinary incontinence. Search Strategy We searched the Cochrane Incontinence Group Specialized Register (searched June 30, 2008) and reference lists of relevant articles. We contacted investigators to locate extra studies. Selection Criteria Randomized or quasi-randomized controlled trials in women with symptoms or urodynamic diagnoses of stress or mixed urinary incontinence that included open retropubic colposuspension surgery in at least one trial group. Data Collection and Analysis Studies were evaluated for methodological quality/susceptibility to bias and appropriateness for inclusion and data extracted by two of the reviewers. Trial data were analyzed by intervention. Where appropriate, a summary statistic was calculated. Main Results This review included 46 trials involving a total of 4,738 women. Overall cure rates were 68.9,88.0% for open retropubic colposuspension. Two small studies suggest lower failure rates after open retropubic colposuspension compared with conservative treatment. Similarly, one trial suggests lower failure rates after open retropubic colposuspension compared to anticholinergic treatment. Evidence from six trials showed a lower failure rate for subjective cure after open retropubic colposuspension than after anterior colporrhaphy. Such benefit was maintained over time (RR of failure 0.51; 95% CI 0.34,0.76 before the first year, RR 0.43; 95% CI 0.32,0.57 at 1,5 years, RR 0.49; 95% CI 0.32,0.75 in periods beyond 5 years). In comparison with needle suspensions there was a lower failure rate after colposuspension in the first year after surgery (RR 0.66; 95% CI 0.42,1.03), after the first year (RR 0.48; 95% CI 0.33,0.71), and beyond 5 years (RR 0.32; 95% CI 15,0.71). Evidence from 12 trials in comparison with suburethral slings found no significant difference in failure rates in all time periods assessed. Patient-reported failure rates in short, medium and long-term follow-up showed no significant difference between open and laparoscopic retropubic colposuspension, but with wide confidence intervals. In two trials failure was less common after Burch (RR 0.38 95% CI 0.18,0.76) than after the Marshall-Marchetti-Krantz procedure at 1,5-year follow-up. There were few data at any other follow-up time. In general, the evidence available does not show a higher morbidity or complication rate with open retropubic colposuspension, compared to the other open surgical techniques, although pelvic organ prolapse is more common than after anterior colporrhaphy and sling procedures. Authors' Conclusions The evidence available indicates that open retropubic colposuspension is an effective treatment modality for stress urinary incontinence especially in the long term. Within the first year of treatment, the overall continence rate is approximately 85,90%. After 5 years, approximately 70% of patients can expect to be dry. Newer minimal access procedures such as tension free vaginal tape look promising in comparison with open colposuspension but their long-term performance is not known and closer monitoring of their adverse event profile must be carried out. Laparoscopic colposuspension should allow speedier recovery but its relative safety and effectiveness is not known yet. Neurourol. Urodyn. 28:472,480, 2009. © 2009 Wiley-Liss, Inc. [source]

    Latest news and product developments

    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]

    Latest news and product developments

    PRESCRIBER, Issue 6 2008
    Article first published online: 24 APR 200
    Government responds to NICE report The Government has published its response to the Health Select Committee's report into NICE, broadly arguing that the Committee's recommendations are either already being dealt with or are not appropriate. The Committee recommended appraisals for all new drugs, shorter, rapid appraisals to coincide with their launch, and improved mechanisms for setting drug prices. The Government says its negotiations on the PPRS preclude a detailed response but suggests a rapid system may not be transparent or legally robust. It is exploring how high-cost drugs can be brought within the payment-by-results tariff. While defending NICE's reliance on QALYs, the Government accepts the need to explore how wider economic factors can be considered. As for the threshold cost per QALY by which NICE defines cost effectiveness, it says this is being validated scientifically and NICE will continue to determine the threshold. More topically, the Committee criticised the quality of clinical trial data available to NICE. The Government sees no need to compel pharmaceutical companies to disclose information and says NICE is already becoming more involved with research programmes. All clinical trials must be registered (confidentially) with the EU and the Government believes mandatory registration in the UK would be ineffective and illegal. Prescription charge up again from April The Government has raised the prescription charge by 25p to £7.10 per item with effect from 1 April. Prescription prepayment certificates will cost £27.85 for three months and £102.50 for 12 months. The increase, below the annual rate of inflation for the 10th successive year, will be levied on the 12 per cent of prescriptions that are liable for the charge: 5 per cent via prepayment certificates and 7 per cent from other prescriptions. The charge will generate £435 million in England in 2008/09; this excludes money from prescriptions written by dispensing doctors, which is retained by the PCT. Following criticism of the charge by the Health Select Committee, the Government says it has reviewed the charge and is now consulting on ,cost-neutral' options. MHRA safety update The MHRA warns of possible dose errors associated with Boots Medisure Domiciliary Dosage System in its latest issue of Drug Safety Update (2008;1:issue 8). One case has been reported in which incomplete sealing allowed tablets to mix between compartments. No other cases are known and the MHRA says no harm was reported but the risk is serious. The system should be carefully sealed and inspected visually and physically. The MHRA reaffirms its plans to reclassify all pseudoephedrine and ephedrine products to prescription-only status in 2009 if the new restrictions on sales do not reduce misuse. Other topics in this month's Update include revised indications for oral ketoconazole (Nizoral), restricting its use to selected conditions unresponsive to topical therapy; reformulation of the injectable antibiotic Tazocin (piperacillin plus tazobactum); the risk of peripheral neuropathy associated with pegylated interferon and telbivudine (Sebivo) in the treatment of hepatitis B; and serious adverse events associated with modafinil (Provigil). First oral anticoagulant since warfarin In January this year the EMEA issued a positive opinion to recommend marketing authorisation of the oral, fixed-dose, direct thrombin inhibitor dabigatran etexilate (Pradaxa) for the primary prevention of venous thromboembolism (VTE) in adult patients that have undergone elective knee or hip replacement surgery. Marketing authorisation for the EU (including the UK) is expected from the European Commission in the next few weeks, making dabigatran the first oral anticoagulant since warfarin was introduced in 1954. Dabigatran etexilate has been shown to be as safe and effective as enoxaparin (Clexane) with a similar adverse event profile in the noninferiority phase III RENOVATE (Lancet 2007;370: 949-56) and RE-MODEL (J Throm Haemost 2007;5:217885) trials, which investigated the efficacy and safety of dabigatran compared to enoxaparin in reducing the risk of VTE after total hip and knee surgery respectively. Dabigatran has the practical advantage over low-molecular-weight heparin of oral postoperative administration and no risk of heparin-induced thrombocytopenia and, unlike warfarin, does not require monitoring or dose titration. Risk scale predicts anticholinergic effects US investigators have developed a scale for predicting the risk of anticholinergic side-effects from older patients' medicines (Arch Intern Med 2008;168: 508-13). The scale assigns a score from 1 (low) to 3 (high) for the risk of anticholinergic effects such as dry mouth, constipation and dizziness associated with commonly prescribed medicines. Checking the scale retrospectively in older patients in residential care, a higher score was associated with a 30 per cent increased risk of side-effects after adjustment for age and number of medicines. When this was repeated prospectively in a primary-care cohort, the increased risk was 90 per cent. HRT cancer risk persists The latest analysis of the Women's Health Initiative (WHI) trial of HRT shows that the small increase in the risk of cancer persists for up to three years after stopping treatment (J Am Med Assoc 2008;299:1036-45). WHI was stopped after 5.6 years' follow-up when it became clear the risks of HRT outweighed its benefits. This follow-up after a further three years (mean 2.4) involved 15 730 women. The annual risk of cardiovascular events was similar for HRT (1.97 per cent) and placebo (1.91 per cent). Cancers were more common among women who had taken HRT (1.56 vs 1.26 per cent), in particular breast cancer (0.42 vs 0.33 per cent). All-cause mortality was higher, but not statistically significantly so, with HRT (1.20 vs 1.06 per cent). Tight glycaemic control may increase falls Maintaining HbA1C at or below 6 per cent with insulin is associated with an increased risk of falls, a US study suggests (Diabetes Care 2008;31:391-6). The Health, Aging and Composition study involved 446 older people with type 2 diabetes (mean age 74) followed up for approximately five years. The incidence of falls ranged from 22 to 30 per cent annually. Comparing subgroups with HbA1C of ,6 per cent and >8 per cent, an increased risk of falls was associated with insulin use (odds ratio 4.4) but not oral hypoglycaemic drugs. Copyright © 2008 Wiley Interface Ltd [source]

    A Randomized, Double-Blind, Pharmacokinetic Study of Oral Maribavir with Tacrolimus in Stable Renal Transplant Recipients

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009
    M. D. Pescovitz
    Maribavir is being developed as a novel agent for the prevention or treatment of cytomegalovirus infections after stem cell and organ transplantation. This was a randomized, double-blind, placebo-controlled study designed to evaluate the potential pharmacokinetic interaction of concomitant administration of maribavir and tacrolimus. Twenty-five adult renal transplant recipients with stable renal function and stable dosing regimens of tacrolimus were randomized (20 maribavir 400 mg p.o. q12 h: 5 placebo). Tacrolimus whole blood concentration profiles were determined before and after 7 days of co-administration with maribavir. When co-administered with maribavir, tacrolimus mean Cmax increased 38%, tacrolimus trough concentrations (12 h post-dose) increased 57% and tacrolimus AUC(0-,) increased 51%. Apparent oral clearance of tacrolimus decreased 34% and Tmax was delayed by 0.5 h. There were no serious adverse events and no subject prematurely discontinued treatment. Because of the limited 7-day dosing course, the adverse event profile could not be adequately assessed. However, as seen with other maribavir studies, dysgeusia was common (90% of maribavir subjects and 20% of placebo subjects). In conclusion, co-administration of maribavir 400 mg twice daily increases exposure to tacrolimus. Routine therapeutic drug monitoring of tacrolimus blood concentrations should be included both at initiation and completion of maribavir treatment. [source]

    Combination therapy using metformin or thiazolidinediones and insulin in the treatment of diabetes mellitus

    DIABETES OBESITY & METABOLISM, Issue 6 2005
    Suzanne M. Strowig
    The biguanide, metformin, sensitizes the liver to the effect of insulin, suppressing hepatic glucose output. Thiazolidinediones such as rosiglitazone and pioglitazone enhance insulin-mediated glucose disposal, leading to reduced plasma insulin concentrations. These classes of drugs may also have varying beneficial effects on features of insulin resistance such as lipid levels, blood pressure and body weight. Metformin in combination with insulin has been shown to significantly improve blood glucose levels while lowering total daily insulin dose and body weight. The thiazolidinediones in combination with insulin have also been effective in lowering blood glucose levels and total daily insulin dose. Triple combination therapy using insulin, metformin and a thiazolidinedione improves glycaemic control to a greater degree than dual therapy using insulin and metformin or insulin and a thiazolidinedione. There is insufficient evidence to recommend the use of metformin or thiazolidinediones in type 1 diabetic patients. Although these agents are largely well tolerated, some subjects experience significant gastrointestinal problems while using metformin. Metformin is associated with a low risk of lactic acidosis, but should not be used in patients with elevated serum creatinine or those being treated for congestive heart failure. The thiazolidinediones are associated with an increase in body weight, although this can be avoided with careful lifestyle management. Thiazolidinediones may also lead to oedema and are associated with a low incidence of hepatocellular injury. Thiazolidinediones are contraindicated in patients with underlying heart disease who are at risk of congestive heart failure and in patients who have abnormal hepatic function. The desired blood glucose-lowering effect and adverse event profiles of these agents should be considered when recommending these agents to diabetic patients. The potential for metformin or the thiazolidinediones to impact long-term cardiovascular outcomes remains under investigation. [source]

    Efficacy of a standardized echinacea preparation (EchinilinTM) for the treatment of the common cold: a randomized, double-blind, placebo-controlled trial

    JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2004
    V. Goel PhD
    Summary Background:, Recently, echinacea has regained popularity as one of the treatments chosen most commonly by consumers with the expectation that it will reduce the severity and duration of the common cold. However, the results from a limited number of clinical trials for this application have thus far been inconclusive. This incongruity may be the result of investigators utilizing poorly standardized echinacea products, likely devoid of sufficient quantities of active constituents necessary to exert a definitive clinical effect. Therefore, a formulation containing alkamides, cichoric acid, and polysaccharides at concentrations of 0·25, 2·5, and 25 mg/mL, respectively, was prepared from freshly harvested Echinacea purpurea plants (commercially available as Echinilin, Natural Factors Nutritional Products, Inc., Vancouver, BC, Canada). The objective of this study was to test the efficacy of this highly standardized formulation in reducing the severity and duration of symptoms of a naturally acquired common cold. Methods:, In a randomized, double-blind, placebo-controlled trial, 282 subjects aged 18,65 years with a history of two or more colds in the previous year, but otherwise in good health, were recruited. The subjects were randomized to receive either echinacea or placebo. They were instructed to start the echinacea or placebo at the onset of the first symptom related to a cold, consuming 10 doses the first day and four doses per day on subsequent days for 7 days. Severity of symptoms (10-point scale: 0, minimum; 9, maximum) and dosing were recorded daily. A nurse examined the subjects on the mornings of days 3 and 8 of their cold. Results:, A total of 128 subjects contracted a common cold (59 echinacea, 69 placebo). The total daily symptom scores were found to be 23·1% lower in the echinacea group than in placebo in those who followed all elements of the study protocol (P < 0·01). Throughout the treatment period, the response rate to treatments was greater in the echinacea group. A few adverse event profiles were observed in both groups. Conclusions:, Early intervention with a standardized formulation of echinacea resulted in reduced symptom severity in subjects with naturally acquired upper respiratory tract infection. Further studies with larger patient populations appear to be warranted. [source]

    Darbepoetin alfa 300 or 500 ,g once every 3 weeks with or without intravenous Iron in patients with chemotherapy-induced anemia,

    AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010
    Michael Auerbach
    This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks (Q3W) at fixed doses of 300 or 500 ,g with or without intravenous (IV) iron in treating anemia in patients receiving multicycle chemotherapy. This Phase 2, double-blind, 2 × 2 factorial study randomized patients to one of four treatment arms; darbepoetin alfa 300 ,g (n = 62), darbepoetin alfa 300 ,g plus IV iron (n = 60), darbepoetin alfa 500 ,g (n = 60), or darbepoetin alfa 500 ,g plus IV iron (n = 60). Patients had nonmyeloid malignancies, hemoglobin levels ,10 g dL,1, and no iron deficiency. Primary endpoint was achievement of target hemoglobin (,11 g dL,1). Secondary endpoints included incidence of transfusions and change in Functional Assessment of Cancer Therapy Fatigue (FACT-F) score from baseline to end of study. Safety was evaluated by incidence of adverse events. No evidence of a statistically significant interaction between darbepoetin alfa dose received and IV iron usage was observed, therefore, results are provided separately comparing darbepoetin alfa doses and comparing IV iron usage groups. Similar proportions of patients receiving darbepoetin alfa 300 or 500 ,g achieved target hemoglobin (75 and 78%, respectively); Kaplan,Meier median time to target hemoglobin was 10 and 8 weeks, respectively. More patients receiving IV iron (82%) than not receiving IV iron (72%) achieved hemoglobin target. Adverse events profiles were similar for darbepoetin alfa treatment groups. Transient anaphylactoid reactions were reported in two patients receiving IV iron. Darbepoetin alfa at 300 ,g Q3W and 500 ,g Q3W showed similar benefit, while added IV iron improved treatment response in these patients. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source]