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Median Reduction (median + reduction)
Selected AbstractsEfficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2004S. T. Holgate Summary Background Patients with severe asthma are often inadequately controlled on existing anti-asthma therapy, constituting an unmet clinical need. Objective This randomized, double-blind, placebo-controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti-IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma. Methods After a run-in period when an optimized fluticasone dose (1000 ,g/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab [minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126] or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16-week add-on phase of treatment followed by a 16-week fluticasone-reduction phase. Short-/long-acting ,2 -agonists were allowed as needed. Results Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a 50% dose reduction (P=0.001). Fluticasone dose reduction to 500 ,g/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo-treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma-related quality of life compared to placebo. Conclusion Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use. [source] A blinded, crossover study of the efficacy of the ketogenic dietEPILEPSIA, Issue 2 2009John M. Freeman Summary Despite over 80 years of use, the ketogenic diet (KD) has never been tested in a blinded manner. Twenty children with intractable Lennox-Gastaut syndrome (LGS) were fasted 36 h and then randomized to receive the classic KD in conjunction with a solution containing either 60 g/day of glucose or saccharin. Parents and physicians were blinded to both the solution composition and level of ketosis. A crossover to the KD with the alternate solution occurred following the sixth day and a repeat fast. A 24-h electroencephalography (EEG) was obtained at baseline and after each arm. After administration of the solution, there was moderate evidence of a reduction in parent-reported seizures between the glucose and saccharin arms, with a median difference of 1.5 seizures per day (p = 0.07). There was no reduction in the number of EEG-identified events, with a median reduction of 7 events per day (p = 0.33). Ketosis was not completely eliminated in the glucose-added arm. [source] Medium-term results of oral tacrolimus treatment in refractory inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 2 2007Siew C. Ng MRCP Abstract Background: This study aimed to evaluate the efficacy of oral tacrolimus in patients with inflammatory bowel disease (IBD) refractory to conventional therapy, including azathioprine, 6-mercaptopurine, and infliximab. Methods: Retrospective review of all patients with IBD treated with oral tacrolimus was undertaken. Tacrolimus was administered at an initial dose of 0.05 mg/kg twice daily, aiming for serum trough levels of 5,10 ng/mL. We evaluated clinical response, a retrospective estimated Crohn's disease activity index (CDAI) for Crohn's disease (CD), modified Truelove-Witts index for ulcerative colitis (UC), and modified pouch disease activity index (mPDAI) for pouchitis. Patients had been monitored clinically for benefit and side effects and by whole blood tacrolimus level approximately every 4 weeks for the duration of treatment. Clinical remission was defined as an estimated CDAI <150 (CD), an inactive disease score on the Truelove-Witts index (UC), and mPDAI <5 (pouchitis). Results: Twelve patients with CD, six with UC, and one with pouchitis, all resistant to previous therapies, were treated for a median of 5 months. After 4 weeks 10 CD (83%), four UC (67%) patients, and one pouchitis patient had a clinical response. There was a median reduction of the estimated CDAI of 108 points (range 35,203; P = 0.002) and stool frequency of three per day at week 4. Remission was achieved in 42% (5/12) of CD and 50% (3/6) of UC patients at the end of follow-up. Side effects included temporary elevated creatinine (n = 1), tremor (n = 3), arthralgia (n = 1), insomnia (n = 1), and malaise (n = 1). Four patients discontinued treatment due to side effects. Conclusion: Oral tacrolimus is well tolerated and effective in patients with refractory IBD in the short- to medium-term. Further controlled, long-term evaluation is warranted. (Inflamm Bowel Dis 2007) [source] Masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid-dependent asthmaticsALLERGY, Issue 8 2009M. Humbert Background:, Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma. Objectives:, The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints. Methods:, A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management. Results:, At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of 78% and 57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 (P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema. Conclusions:, Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma (ClinicalTrials.gov Identifier: NCT00842270). [source] Diagnosis of vocal cord dysfunction in asthma with high resolution dynamic volume computerized tomography of the larynxRESPIROLOGY, Issue 8 2009Peter W. HOLMES ABSTRACT Background and objective: Vocal cord dysfunction (VCD) often masquerades as asthma and reports have suggested that up to 30% of patients with asthma may have coexistent VCD. Diagnosis of VCD is difficult, in part because it involves laryngoscopy which has practical constraints, and there is need for rapid non-invasive diagnosis. High speed 320-slice volume CT demonstrates laryngeal function during inspiration and expiration and may be useful in suspected VCD. Methods: Endoscopy and high resolution 320-slice dynamic volume CT were used to examine and compare laryngeal anatomy and movement in a case of subglottic stenosis and in a patient with confirmed VCD. Nine asthmatics with ongoing symptoms and suspected VCD also underwent 320-slice dynamic volume CT. Tracheal and laryngeal anatomy and movement were evaluated and luminal areas were measured. Reductions in vocal cord luminal area >40%, lasting for >70% duration of inspiration/expiration, were judged to be consistent with VCD. Results: Studies of subglottic tracheal stenosis validated anatomical similarities between endoscopy and CT images. Endoscopy and 320-slice volume CT also provided comparable dynamic images in a patient with confirmed VCD. A further nine patients with a history of severe asthma and suspected VCD were studied using CT. Four patients had evidence of VCD and the median reduction of luminal area during expiration was 78.2% (range 48.2,92.5%) compared with 10.4% (range 4.7,30%) in the five patients without VCD. Patients with VCD had no distinguishing clinical characteristics. Conclusions: Dynamic volume CT provided explicit images of the larynx, distinguished function of the vocal cords during the respiratory cycle and could identify putative VCD. The technique will potentially provide a simple, non-invasive investigation to identify laryngeal dysfunction, permitting improved management of asthma. [source] Point-of-care reversal treatment in phenprocoumon-related intracerebral hemorrhageANNALS OF NEUROLOGY, Issue 6 2010Timolaos Rizos MD Objective Rapid reversal of the anticoagulatory effect of vitamin K antagonists represents the primary emergency treatment for oral anticoagulant-related intracerebral hemorrhage (OAC-ICH). Predicting the amount of prothrombin complex concentrate (PCC) needed to reverse OAC in individual patients is difficult, and repeated international normalized ratio (INR) measurements in central laboratories (CLs) are time-consuming. Accuracy and effectiveness of point-of-care INR coagulometers (POCs) for INR reversal in OAC-ICH have not been evaluated. Methods In phase 1, the agreement of emergency POC and CL INR measurements was determined. In phase 2, stepwise OAC reversal was performed with PCC using a predetermined dosing schedule. Concordance of POC and CL INR measurements during reversal and time gain due to POC were determined. Results In phase 1 (n = 165), Bland-Altman analysis showed close agreement between POCs and CLs (mean INR deviation 0.04). In phase 2 (n = 26), POCs caused a median initial net time gain of 24 minutes for the start of treatment with PCC. Median time for POC-documented complete OAC reversal was 28 minutes, compared with 120 minutes for CLs. Bland-Altman analysis between POCs and CLs revealed a mean INR deviation of 0.13 during stepwise PCC administration. POCs tended to slightly overestimate the INR, especially at higher INR levels. Remarkably, POC-guided reversal led to a median reduction of 30.5% of PCC dose compared with the a priori dose calculation. Hematomas enlarged in 20% of patients. Interpretation POC INR monitoring is a fast, effective, and economic means of PCC dose-titration in OAC-ICH. Larger studies examining the clinical efficacy of this procedure are warranted. ANN NEUROL 2010;67:788,793 [source] Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS)ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010S. Dupont Dupont S, Striano S, Trinka E, Springub J, Giallonardo AT, Smith P, Ellis S, Yeates A, Baker G. Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS). Acta Neurol Scand: 2010: 121: 141,148. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, To assess the efficacy and tolerability of zonisamide in a study allowing flexible dosing in a more diverse and less refractory population than assessed in randomized controlled trials. Methods,,, This 19-week, non-comparative study of adjunctive zonisamide included 281 adults who had at least four partial-onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to zonisamide doses were allowed after titration, except during two fixed-dose periods (weeks 10,13 and 16,19). Results,,, At the end of the second fixed-dose period (median dose 300 mg/day), the median reduction in monthly seizure frequency was 33.3,41.1%; ,50% responder rate was 40.9,44.2%; and seizure freedom rate was 15.0,15.9%, depending on the analysis used. The most common adverse events were fatigue (16.7%) and somnolence (15.3%). Conclusions,,, Zonisamide demonstrated efficacy in a setting more reflective of clinical practice and was generally well tolerated. [source] Effects of intravenous dofetilide in patients with frequent premature ventricular contractions: A clinical trialCLINICAL CARDIOLOGY, Issue 6 2000Peter E. Pool M.D. Abstract Background: Although suppression of premature ventricular contractions (PVCs) is not a predictor of mortality over the long term, the extent of PVC suppression is an important characteristic of any antiarrhythmic drug. Hypothesis: This study was undertaken to determine whether intravenous (IV) dofetilide has the ability to suppress PVCs in patients who have frequent occurrences. Methods: Subjects were men and women, aged 18 to 75 years, with > 30 PVCs/h on two consecutive 24-h Holter recordings while drug free, and > 50 PVCs/h during a 2-hour telemetric electrocardiogram. The study was randomized, double-blind, and placebo controlled. Subjects received a single-blind, IV infusion of placebo and were randomized (3:1) to receive a double-blind second infusion of placebo or an infusion of dofetilide (a 15-min loading infusion of 4 g/kg followed by a 60-min maintenance infusion of 3.5 g/kg, for a total dose of 7.5 g/kg). Results: Dofetilide produced an 82.6% and placebo a 2.9% median reduction in PVCs. Drug responder rate, defined as 80% reduction in PVCs, was 50% in the dofetilide group and 0% in the placebo group. Conclusion: Intravenous dofetilide significantly reduced PVCs in patients who had > 30 PVCs/h at baseline, and it produced , 80% reduction in PVCs in 50% of all subjects. [source] | ||||||||||||||||||||||