Biomedical subjects

K Rickard

Publications and source records attributed to K Rickard.

At least 19 recordsLinked to original sources

PubMed2001

Low-dose fluticasone propionate compared with montelukast for first-line treatment of persistent asthma: a randomized clinical trial.

BACKGROUND: Both inhaled corticosteroids and leukotriene modifiers are used in the maintenance treatment of persistent asthma. OBJECTIVE: The goal was to compare the efficacy and safety of low-dose fluticasone propionate (FP) and montelukast as first-line maintenance therapy in symptomatic patients by using short-acting beta2-agonists alone to treat persistent asthma. METHODS: In this multicenter, randomized, double-blind, double-dummy, parallel-group study, 533 patients (>15 years old) with persistent asthma who remained symptomatic while taking short-acting beta2-agonists alone were treated with FP (88 microg [2 puffs of 44 microg] twice daily) or montelukast (10 mg once daily) for 24 weeks. RESULTS: Compared with treatment with montelukast, treatment with FP resulted in significantly greater improvements at endpoint in morning predose FEV(1) (22.9% vs 14.5%, P <.001), forced midexpiratory flow (0.66 vs 0.41 L/sec, P <.001), forced vital capacity (0.42 vs 0.29 L, P =.002), morning peak expiratory flow (PEF) (68.5 vs 34.1 L/min, P <.001), and evening PEF (53.9 vs 28.7 L/min, P <.001). Similar improvements in PEF were observed in patients with milder asthma (>70%-80% predicted FEV(1)). At endpoint, FP was more effective than montelukast at decreasing rescue albuterol use (3.1 puffs/day vs 2.3 puffs/day, P <.001), asthma symptom scores (-0.85 [48.6% decrease] vs -0.60 [30.5%], P <.001), and nighttime awakenings due to asthma (-0.64 awakenings/night [62% decrease] vs -0.48 awakenings/night [47.5%], P =.023), and FP increased the percentage of symptom-free days (32.0% vs 18.4% of days, P <.001) compared with montelukast. The adverse event and asthma exacerbation profiles for FP and montelukast were similar. CONCLUSIONS: Low-dose FP is more effective than montelukast as first-line maintenance therapy for patients with persistent asthma who are undertreated and remain symptomatic while taking short-acting beta2-agonists alone.

Acetates↗

PubMed2001

Addition of salmeterol to low-dose fluticasone versus higher-dose fluticasone: an analysis of asthma exacerbations.

BACKGROUND: Adding salmeterol to low-dose fluticasone propionate (FP) produces greater improvements in pulmonary function and symptom control than increasing the dose of FP in patients who remain symptomatic with low-dose FP. OBJECTIVE: We sought to compare the rates and characteristics of asthma exacerbations in patients after adding salmeterol to low-dose FP with the rates and characteristics of exacerbations in patients receiving higher dose FP. METHODS: In 2 multicenter, double-blind studies, 925 patients 12 years of age and older receiving 88 microg twice daily FP randomly received either 42 microg of salmeterol and 88 microg of FP or an increased dose of FP (220 microg) twice daily for 24 weeks. Exacerbation rates and clinical measures of asthma worsening were assessed for all patients who experienced an asthma exacerbation. RESULTS: The addition of salmeterol resulted in a significantly lower rate and number of exacerbations compared with higher dose FP. A total of 41 (8.8%) patients experienced 47 exacerbations with the addition of salmeterol compared with 63 (13.8%) patients with 75 exacerbations in the group receiving increased-dose FP (P =.017). Salmeterol plus low-dose FP was significantly more protective than increased-dose FP in preventing asthma exacerbations, as assessed by the time to first exacerbation (P <.05). In both groups clinical indicators of worsening asthma showed parallel changes before asthma exacerbation, and greater improvements were observed after exacerbation with salmeterol compared with higher dose FP. CONCLUSION: Salmeterol plus low-dose FP was more effective than higher dose FP alone in reducing asthma exacerbations in patients with persistent asthma. The ability to detect deteriorating asthma and the severity of exacerbation was similar between groups.

Acute Disease↗

PubMed2001

Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a condition in which continuous bronchodilation may have clinical advantages. This study evaluated salmeterol, a beta-agonist bronchodilator with a duration of action substantially longer than that of short-acting beta-agonists, compared with ipratropium, an anticholinergic bronchodilator, and placebo in patients with COPD. Four hundred and five patients with COPD received either salmeterol 42 microg twice daily, ipratropium bromide 36 microg four times daily, or placebo for 12 wk in this randomized, double-blind, parallel-group study. Patients were stratified on the basis of bronchodilator response to albuterol (> 12% and > 200-ml improvement) and were randomized within each stratum. Bronchodilator response was measured over 12 h four times during the treatment period. Salmeterol provided similar maximal bronchodilatation to ipratropium but had a longer duration of action and a more constant bronchodilatory effect with no evidence of bronchodilator tolerance. Both active treatments were well tolerated. Salmeterol was an effective bronchodilator with a consistent effect over this 12-wk study in patients with COPD, including those "unresponsive" to albuterol. The long duration of action of salmeterol offers the advantage of twice daily dosing compared with the required four times a day dosing with ipratropium.

Adrenergic beta-Agonists↗

PubMed2001

Salmeterol plus theophylline combination therapy in the treatment of COPD.

BACKGROUND: Patients with COPD often require multiple therapies to improve lung function and decrease symptoms and exacerbations. Salmeterol and theophylline are indicated for the treatment of COPD, but the use of these agents in combination has not been extensively studied. OBJECTIVES: To compare the efficacy and safety of salmeterol plus theophylline vs either agent alone in COPD. METHODS: Randomized, double-blind, double-dummy, parallel-group trial in 943 patients with COPD. After an open-label theophylline titration period (serum levels, 10 to 20 microg/mL), patients were randomly assigned to receive salmeterol (42 microg bid) plus theophylline, salmeterol (42 microg bid), or theophylline for 12 weeks. Serial pulmonary function tests were completed on day 1 and treatment week 12. Patients kept diary cards and noted their peak flow rates, symptom scores, and albuterol use, and periodically completed quality-of-life and dyspnea questionnaires. RESULTS: All three groups significantly improved compared with baseline. Combination treatment with salmeterol plus theophylline provided significantly (p < or = 0.045) greater improvements in pulmonary function; significantly (p < or = 0.048) greater decreases in symptoms, dyspnea, and albuterol use; and significantly fewer COPD exacerbations (p = 0.023 vs theophylline). In general, treatment with salmeterol provided greater improvement in lung function and satisfaction with treatment compared with theophylline. Salmeterol treatment was also associated with significantly fewer drug-related adverse events (p < or = 0.042) than either treatment that included theophylline. The safety profile (adverse events, vital signs, and ECG findings) of the two treatments that included theophylline were similar. CONCLUSION: Patients with COPD may benefit from combination treatment with salmeterol plus theophylline, without a resulting increase in adverse events or other adverse sequelae.

Adrenergic beta-Agonists↗

PubMed2001

Cost-efficacy analysis of fluticasone propionate versus zafirlukast in patients with persistent asthma.

OBJECTIVE: To compare the relative value of an inhaled corticosteroid, fluticasone propionate 88 microg twice daily, versus an oral leukotriene receptor antagonist, zafirlukast 20 mg twice daily, in patients with persistent asthma currently receiving short acting beta2-agonists alone. STUDY DESIGN: A cost-efficacy analysis using resource utilisation and clinical data obtained prospectively from a multicentre, randomised, double-blind, double-dummy, placebo-controlled 12-week clinical trial conducted in the US. PERSPECTIVE: Third-party payor. PATIENTS AND METHODS: A total of 451 corticosteroid-naive patients with persistent asthma were treated with either fluticasone propionate 88 microg twice daily or zafirlukast 20 mg twice daily. All patients were given salbutamol (albuterol) to be used as rescue medication. Data were examined using intent-to-treat analysis. RESULTS: Mean daily per person cost-efficacy ratios using improvement in forced expiratory volume in 1 second (FEV1) [> or = 12% increase from baseline] were $US 3.47 for fluticasone propionate compared with $US 7.81 for zafirlukast (1999 values). The mean daily per person cost-efficacy ratios for symptom-free days obtained were $US 5.51 for fluticasone propionate compared with $US 14.98 for zafirlukast. These cost-efficacy ratios remained in favour of fluticasone propionate after a robust sensitivity analysis. CONCLUSIONS: Treatment with fluticasone propionate 88 kg twice daily was the most cost effective treatment compared with zafirlukast 20 mg twice daily in this 12-week clinical trial. This analysis supports the use of fluticasone propionate 88 microg twice daily as first-line treatment in patients with persistent asthma previously treated with short-acting beta2-agonist alone.

Adult↗

PubMed2001

Fluticasone propionate compared with zafirlukast in controlling persistent asthma: a randomized double-blind, placebo-controlled trial.

OBJECTIVE: The objective of our study was to compare the efficacy and safety of fluticasone propionate (an inhaled corticosteroid) with zafirlukast (a leukotriene modifier) for persistent asthma. STUDY DESIGN: In this randomized placebo-controlled, parallel-group, double-blind, double-dummy trial, patients underwent an 8- to 14-day run-in period followed by 12 weeks of treatment with inhaled fluticasone propionate (88 mg twice daily by metered-dose inhaler), oral zafirlukast (20 mg twice daily), or placebo. POPULATION: We included a total of 338 persistent asthma patients, 12 years of age or older, using short-acting b2-agonists alone. OUTCOMES: measured Efficacy outcomes included changes in pulmonary function, asthma symptoms, rescue albuterol use, nighttime awakenings due to asthma, and quality of life. Safety outcomes included asthma exacerbations, adverse events, and clinically significant laboratory test results. RESULTS: After 12 weeks of treatment, patients taking fluticasone propionate experienced significantly greater improvements in all clinical parameters (symptom scores, percentages of symptom-free and albuterol-free days, albuterol use, and nighttime awakenings) compared with patients taking zafirlukast (P <.05) or placebo (P <.05). Treatment with fluticasone propionate resulted in significantly greater improvements in pulmonary function compared with zafirlukast (P <.05) or placebo (P <.05). Fewer fluticasone propionate patients (4%) had an exacerbation requiring oral corticosteroids compared with those taking zafirlukast (12%) or placebo (10%). CONCLUSIONS: Inhaled fluticasone propionate is more effective than zafirlukast in controlling asthma symptoms, improving pulmonary function, and improving quality of life for patients who are symptomatic with the use of short-acting b2-agonists alone.

Administration, Inhalation↗

PubMed2001

Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study.

AIM: To compare clinical outcomes in a randomised comparison of treatment with danaparoid sodium (a heparinoid), or dextran 70, for heparin-induced thrombocytopaenia (HIT) plus thrombosis. METHODS: Forty-two patients with recent thrombosis and a clinical diagnosis of probable HIT who presented at ten Australian hospitals during a study period of six and one half years were randomly assigned to open-label treatment with intravenous danaparoid or dextran 70, each combined with oral warfarin. Thirty-four patients (83%) had a positive platelet aggregation or 14C-serotonin release test for HIT antibody. Twenty-five received danaparoid as a bolus injection of 2400 anti-Xa units followed by 400 units per hour for 2 h, 300 units per hour for 2 h, and then 200 units per hour for five days. Seventeen received 1000 mL dextran 70 on day one and then 500 mL on days 2-5. Patients were reviewed daily for clinical evidence of thrombus progression or resolution, fresh thrombosis or embolism, bleeding or other complications. The primary trial endpoint was the proportion of thromboembolic events with complete clinical resolution by the time of discharge from hospital. RESULTS: With danaparoid, there was complete clinical recovery from 56% of thromboembolic events compared to 14% after dextran 70 (Odds Ratio 10.53, 95% Confidence Interval 1.6-71.4; p = 0.02). Clinical recovery with danaparoid was complete or partial in 86% of thromboembolic events compared with 53% after dextran 70 (Odds Ratio 4.55, 95% Confidence Interval 1.2-16.7; p = 0.03). Overall clinical effectiveness of danaparoid was rated as high or moderate in 88% of patients compared with 47% for dextran 70 (p = 0.01). One patient given danaparoid died of thrombosis compared with three patients given dextran 70. The platelet count returned to normal after a mean of 6.7 days with danaparoid and 7.3 days with dextran 70. There was no major bleeding with either treatment. CONCLUSION: danaparoid plus warfarin treatment for HIT with thrombosis is effective, safe, and superior to dextran 70 plus warfarin.

Aged↗

PubMed2000

Fluticasone propionate versus zafirlukast: effect in patients previously receiving inhaled corticosteroid therapy.

BACKGROUND: The use of inhaled corticosteroids compared with leukotriene modifying drugs in the treatment of persistent asthma has not been extensively studied. OBJECTIVE: To compare the efficacy and safety of a low dose of fluticasone propionate (FP) and zafirlukast in patients previously maintained on inhaled corticosteroids. METHODS: Patients (> or = 12 years old; FEV1 = 60% to 85% of predicted) with persistent asthma who were previously treated with low doses of triamcinolone acetonide (TAA) 400 to 800 microg/day or beclomethasone dipropionate (BDP) 168 to 336 microg/day were randomized to treatment with FP aerosol 88 microg BID (FP, n = 221) or zafirlukast 20 mg BID (n = 216) over 6 weeks. RESULTS: Treatment with FP significantly increased the mean change at endpoint (the last post-baseline observation) in FEV1 (0.22 L versus 0.03 L, P < .001), morning PEF (17.8 versus 3.1 L/min, P = .004), evening PEF (16.7 versus 2.6 L/min, P = .002), the percentage of symptom-free days (16.2 versus 7.1%, P = .007), and the percentage of rescue-free days (23.4 versus 9.3%, P < .001), and significantly decreased rescue albuterol use (-0.66 puffs/day versus an increase of 0.27 puffs/day, P < .001) and combined symptom scores (-0.13 versus an increase of 0.08, P < .001) compared with zafirlukast. Treatment with FP maintained the percentage of awakening-free nights (-1.0 +/- 1.0); in contrast, treatment with zafirlukast reduced the percentage of awakening-free nights (-9.0 +/- 1.6, P < .001). A clinically meaningful difference (change of > or = 0.5; P < .001) was observed between FP and zafirlukast in the Asthma Quality of Life Questionnaire (AQLQ) global score and for each domain score except activity limitation (change of 0.3, P < .001). Significantly more patients in the zafirlukast group experienced an asthma exacerbation (n = 14) compared with FP-treated patients (n = 5, P = .035). Patients in the zafirlukast group were significantly more likely to be withdrawn due to lack of efficacy (P < .001). CONCLUSION: Switching patients from low doses of inhaled corticosteroids to a lower total microgram dose of FP improves pulmonary function, asthma symptoms, and quality of life, while switching to the leukotriene receptor antagonist zafirlukast may result in worsening of asthma control. This was indicated by the significant number of zafirlukast-treated patients who were dropped from the study due to lack of efficacy within 6 weeks of discontinuing inhaled corticosteroids.

Administration, Inhalation↗

PubMed2000

Cardiac surgery and catheterization in patients with haemophilia.

The present study summarizes the results of 12 cardiac surgical procedures performed in a carrier of Haemophilia B and in six patients with Haemophilia A at a single centre from 1979 to 1998. The median age of the patients at the time of intervention was 56 years ranging from 18 years to 73 years. The six patients with Haemophilia A ranged in severity from moderately to mildly affected. Three patients were hepatitis C antibody positive. No patients were HIV antibody or hepatitis B surface antigen positive. The cardiac procedures included cardiac catheterization (n=4), coronary artery bypass surgery (n=2), percutaneous transluminal coronary angioplasty (n=1), cardiac valve replacement (AVR n=1 and AVR/MVR n=2), and closure of an atrial septal defect and subsequent drainage of a pericardial effusion (n=1). No patients had demonstrable inhibitors at the time of surgery. Haemostasis was achieved with AHF in 10/11 procedures and high purity factor IX (Immunine) in one procedure. The initial procedures involved intermittent bolus factor therapy while more recently, AHF was administered by continuous intravenous infusion. All patients demonstrated excellent intra- and post-operative haemostasis. These results, although from a small and varied group of patients, demonstrate that cardiac surgical procedures can be performed safely in patients with Haemophilia.

Adolescent↗

PubMed2000

Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast.

BACKGROUND: Asthma is a disease of chronic inflammation and bronchoconstriction. Inhaled corticosteroids (ICSs) provide important anti-inflammatory treatment but may not provide optimal control of asthma when taken alone. Two therapeutic alternatives for enhanced asthma control are to substitute the combination of fluticasone propionate (FP) and salmeterol (FP/Salm Combo) through the Diskus inhaler or to add montelukast to existing ICS therapy. OBJECTIVE: We compared the efficacy and safety of FP/Salm Combo through the Diskus inhaler versus montelukast added to FP (FP + montelukast) in patients whose symptoms were suboptimally controlled with ICS therapy. METHODS: We performed a multicenter, double-blind, double-dummy, parallel-group, 12-week study in 447 patients with asthma who were symptomatic at baseline while receiving low-dose FP. Patients were treated for 12 weeks with one of the following: (1) combination of FP 100 microg plus salmeterol 50 microg twice daily through the Diskus inhaler, or (2) FP 100 microg twice daily through the Diskus inhaler plus oral montelukast 10 mg once daily. RESULTS: FP/Salm Combo treatment provided better overall asthma control than FP + montelukast with significantly greater improvements in morning peak expiratory flow (+24.9 L/min vs +13.0 L/min, P <.001), evening peak expiratory flow (+18.9 L/min vs +9.6 L/min, P <.001), and forced expiratory volume in 1 second (+0.34 L vs +0.20 L, P <.001), as well as a change in the percentage of days with no albuterol use (+26.3% vs +19.1%, P =.032) and the shortness of breath symptom score (-0.56 vs -0.40, P =.017). The groups had comparable improvements in chest tightness, wheeze, and overall symptom scores. Asthma exacerbation rates were significantly lower (P =.031) in the FP/Salm Combo group (4 patients, 2%) than in the FP + montelukast group (13 patients, 6%). Adverse event profiles were comparable. CONCLUSION: Symptomatic patients on low-dose ICS therapy had significantly greater improvement in asthma control when switched to the FP/Salm Combo than when montelukast was added to ICS therapy.

Acetates↗

PubMed1999

A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma.

BACKGROUND: Inhaled corticosteroids are recommended for the treatment of persistent asthma. Comparative clinical studies evaluating 2 or more doses of these agents are few. OBJECTIVE: We sought to compare the efficacy and safety of 2 doses of fluticasone propionate (88 micrograms twice daily and 220 micrograms twice daily) with 2 doses of beclomethasone dipropionate (168 micrograms twice daily and 336 micrograms twice daily) in subjects with persistent asthma. METHODS: Three hundred ninety-nine subjects participated in this randomized, double-blind, parallel-group clinical trial. Eligible subjects were using daily inhaled corticosteroids and had an FEV1 of 45% to 80% of predicted value. Clinic visits, including spirometry, were conducted every 1 to 2 weeks. Subjects recorded symptoms, use of albuterol, and peak expiratory flows on daily diary cards. RESULTS: Fluticasone propionate treatment resulted in significantly (P </=.034) greater improvements in objective pulmonary function parameters than did beclomethasone dipropionate treatment and significantly greater reductions in daily albuterol use (P </=.010) and asthma symptoms (P </=.027). Both low-dose (88 micrograms twice daily) and medium-dose (220 micrograms twice daily) fluticasone propionate significantly increased FEV1 compared with higher doses of beclomethasone dipropionate (P =. 006). Low-dose and medium-dose fluticasone propionate improved FEV1 by 0.31 L (14%) and 0.36 L (15%), respectively, compared with improvements of 0.18 L (8%) and 0.21 L (9%) with low-dose and medium-dose beclomethasone dipropionate. The adverse event profiles were similar for both medications. CONCLUSION: Fluticasone propionate provides greater asthma control at roughly half the dose of beclomethasone dipropionate, with a comparable adverse event profile.

Adolescent↗

PubMed1999

The addition of salmeterol to fluticasone propionate versus increasing the dose of fluticasone propionate in patients with persistent asthma. Salmeterol Study Group.

BACKGROUND: Current treatment guidelines define inhaled corticosteroids such as fluticasone propionate (FP) as the cornerstone of anti-inflammatory therapy for asthma. OBJECTIVE: The objective was to evaluate the efficacy and safety of adding salmeterol therapy to patients who remain symptomatic while receiving FP as compared with increasing the dose of FP. METHODS: In a multicenter, double-blind study conducted over 24-weeks, 437 patients aged 12 years and older and receiving FP 88 microg twice daily for 2 to 4 weeks were randomly assigned to receive either salmeterol (42 microg twice daily) or FP 220 microg twice daily. The primary efficacy endpoint was morning peak expiratory flow. Secondary measures included FEV1, symptom scores, nighttime awakenings, and supplemental albuterol use. Safety was assessed by reported adverse events and asthma exacerbations. RESULTS: The addition of salmeterol resulted in significantly greater improvements in lung function and symptom control as compared with increasing the dose of FP. Over weeks 1 to 24, morning peak expiratory flow was increased by 47 L/min from baseline with salmeterol treatment as compared with 24 L/min with FP 220 microg twice daily (P < .001) while the percent of symptom-free days increased from baseline by 26% of days as compared with 10% of days (P < .001). The adverse event profiles were similar between groups and fewer exacerbations were reported with salmeterol treatment. CONCLUSIONS: The addition of salmeterol therapy to patients who remain symptomatic while using a low dose of FP was clinically and statistically superior to increasing the dose of FP.

Adolescent↗

PubMed1999

Colonic epithelial cell activation and the paradoxical effects of butyrate.

Butyrate may have paradoxical effects on epithelial cells of similar origin. This study aimed to examine the hypothesis that one mechanism that dictates a cell's response to butyrate is its state of activation. First, the responses to 24 h exposure to butyrate (1-2 mM) of normal and neoplastic human colonic epithelial cells activated by their isolation and primary culture, and of colon cancer cell lines, LIM1215 and Caco-2, were examined. In primary cultures of normal and cancer cells, butyrate had no effect on alkaline phosphatase activities but significantly suppressed urokinase receptor expression by a mean +/- SEM of 30 +/- 12% and 36 +/- 9%, respectively. Interleukin-8 secretion was suppressed by 44 +/- 7% in normal cells (P < 0.05) but was unchanged in cancer cells. In contrast, the cell lines significantly increased alkaline phosphatase activities by >50%, urokinase receptor expression >2-fold and interleukin-8 secretion >3-fold in response to butyrate. Secondly, the effect of butyrate on Caco-2 cells was examined with or without prior exposure to a specific activating stimulus [tumour necrosis factor alpha (TNF alpha)]. Interleukin-8 secretion increased by 145 +/- 23% and 132 +/- 17% on 24 h exposure to 2 mM butyrate or 0.1 microM TNF alpha alone, respectively. However, in cells pre-treated with TNF alpha, butyrate significantly inhibited secretion by 34 +/- 7% below unstimulated levels. The response to butyrate of urokinase receptor, whose expression was not stimulated by TNF alpha, was unchanged. These effects were mimicked by trichostatin A, an inhibitor of histone deacetylase, suggesting that butyrate's paradoxical effects may have been operating by the same mechanism. In conclusion, some of the paradoxical effects of butyrate do not appear to represent inherent differences between normal and transformed cells. Rather, the response may be determined by the state of activation of the cells.

Adult↗

PubMed1999

Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes.

OBJECTIVE: To evaluate the effect of salmeterol on asthma-specific quality of life in patients experiencing significant nocturnal symptoms. DESIGN: Randomized, double-blind, placebo-controlled, multicenter clinical trial. SETTING: Allergy/respiratory care clinics. PATIENTS: Nonsmokers > or = 12 years of age with nocturnal asthma symptoms on at least 6 of 14 days during screening and > or = 15% decrease in peak expiratory flow (PEF) from baseline on nocturnal awakening at least once during screening. INTERVENTIONS: Salmeterol, 42 microg, or placebo twice daily. Patients were allowed to continue theophylline, inhaled corticosteroids, and "as-needed" albuterol. MEASUREMENTS AND RESULTS: Outcome measures included Asthma Quality of Life Questionnaire (AQLQ) global and individual domain scores, FEV1, PEF, nighttime awakenings, asthma symptoms, and supplemental albuterol use. Mean change from baseline for the global and domain AQLQ scores was significantly greater (p < or = 0.005) with salmeterol compared with placebo. At week 12, salmeterol significantly (p < 0.001 compared with placebo) increased mean change from baseline in FEV1, morning and evening PEF, percentage of symptom-free days, percentage of nights with no awakenings due to asthma, and the percentage of days and nights with no supplemental albuterol use. Significant improvements in PEF were observed after treatment with salmeterol regardless of concomitant treatment with theophylline (p < 0.05). CONCLUSIONS: These results provide evidence that validates the role of salmeterol in improving quality of life in patients with moderate persistent asthma who exhibited nocturnal asthma symptoms and supports the efficacy of salmeterol compared with that of placebo (ie, "as-needed" albuterol).

Adolescent↗

PubMed1998

Salmeterol improves quality of life in patients with asthma requiring inhaled corticosteroids. Salmeterol Quality of Life Study Group.

BACKGROUND: Traditional clinical outcomes have demonstrated that salmeterol improves pulmonary function and reduces asthma symptoms. However, they do not evaluate how patients perceive the effect of therapeutic intervention on day-to-day functioning and well-being. OBJECTIVE: We sought to evaluate the impact of salmeterol on disease-specific quality of life with the Asthma Quality-of-Life Questionnaire, as well as the efficacy and safety of salmeterol in patients with stable asthma who were symptomatic despite daily use of inhaled corticosteroids. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group study of 506 patients. Patients were treated with 42 microg salmeterol or placebo twice daily for 12 weeks delivered through a metered dose inhaler. RESULTS: Mean change from baseline in asthma quality-of-life scores was significantly greater (p < or = 0.006) after 12 weeks of treatment with salmeterol compared with placebo ("as-needed" albuterol) in global scores (1.08 vs 0.61) and individual domains (activity limitations, 0.91 vs 0.54; asthma symptoms, 1.28 vs 0.71; emotional function, 1.17 vs 0.65; and environmental exposure, 0.84 vs 0.47). Patients treated with salmeterol experienced significantly greater improvements from baseline to week 12 compared with placebo in FEV1 (0.42 L vs 0.15 L, p < 0.001), morning peak expiratory flow (47 L/min vs 14 L/min, p < 0.001), evening peak expiratory flow (29 L/min vs 11 L/min, p < 0.001), and asthma symptom scores (daytime scores reduced by 0.55 vs 0.30, p < 0.001). Patients treated with salmeterol used significantly less supplemental albuterol (reduced by 3 puffs/day vs 1 puff/day, p < 0.001). CONCLUSION: Salmeterol provided significantly greater improvement in quality-of-life outcomes in patients whose asthma symptoms are not well controlled with inhaled corticosteroids. These results demonstrate that the benefits of salmeterol are not limited to conventional clinical measures of efficacy.

Administration, Inhalation↗

PubMed1998

Efficacy, safety, and effects on quality of life of salmeterol versus albuterol in patients with mild to moderate persistent asthma.

BACKGROUND: Salmeterol xinafoate is a long-acting, highly selective, beta2-adrenergic agonist that produces bronchodilation and clinically significant improvement in pulmonary function for up to 12 hours in patients with asthma. OBJECTIVE: To evaluate the impact on asthma-specific quality of life, efficacy, and safety of salmeterol versus albuterol in adult patients with mild-to-moderate persistent asthma. METHODS: A randomized, double-blind, double-dummy, parallel-group, multicenter study was conducted in 539 adult asthma patients over 12 weeks. Patients were randomized to receive either salmeterol 42 microg via metered-dose inhaler twice daily or albuterol 180 microg four times daily. Upon entry into the study, 46% of patients were being treated with an inhaled corticosteroid and were allowed to continue treatment throughout the study. Pulmonary function and asthma symptoms were monitored daily, and patients completed the Asthma Quality of Life Questionnaire (AQLQ) at baseline and after 4, 8, and 12 weeks of treatment. RESULTS: Treatment with salmeterol twice daily produced significantly greater improvements from baseline in all quality of life domain ("Activity Limitation," "Asthma Symptoms," "Emotional Function," "Environmental Exposure") scores and in the global AQLQ score at 12 weeks (P < or = .038) compared with albuterol treatment four times daily. Pulmonary function and asthma symptoms were also significantly improved with salmeterol compared with albuterol. CONCLUSIONS: Salmeterol 42 microg administered twice daily is significantly more effective than albuterol 180 microg four times daily for improving asthma-specific quality of life, controlling asthma symptoms, and improving pulmonary function in patients with mild-to-moderate persistent asthma. Furthermore, those improvements were maintained over a 12-week period.

Adolescent↗

PubMed1998

Efficacy, safety, and impact on quality of life of salmeterol in patients with moderate persistent asthma.

OBJECTIVE: To evaluate the efficacy, safety, and impact on asthma-specific quality of life of salmeterol, a highly selective, long-acting beta 2-agonist, compared with that of placebo (i.e., "as-needed" albuterol). STUDY DESIGN: Randomized, double-blind, placebo-controlled, parallel-group, multicenter study. PATIENTS AND METHODS: Five hundred thirty-eight nonsmoking symptomatic patients 12 years of age and older meeting American Thoracic Society asthma criteria were enrolled at 55 outpatient clinics; 443 patients completed the study. Patients were randomly assigned to treatment with either salmeterol aerosol 42 micrograms twice daily or placebo (as-needed albuterol) for 12 weeks. We assessed changes in quality of life using the Asthma Quality of Life Questionnaire (AQLQ). Efficacy measurements included daily peak expiratory flow (PEF) rate, daytime and nighttime asthma symptoms, results of pulmonary function tests, and supplemental albuterol use. Patients recorded their PEF rate, supplemental albuterol use, and asthma-related symptoms daily. Pulmonary function tests and AQLQ assessments were performed at baseline and after 4, 8, and 12 weeks of treatment. Safety measurements included vital signs, physical examination, and reports of clinical adverse events at baseline and after 4, 8, and 12 weeks of treatment. RESULTS: Mean changes from baseline in AQLQ global and domain scores were significantly greater in the salmeterol group compared with the placebo group (P < 0.001). Patients treated with salmeterol also had significant improvements in mean PEF rates, supplemental albuterol use, asthma symptom scores, and forced expiratory volume in 1 second compared with those given placebo. Both salmeterol and placebo were well tolerated and were not associated with any clinically significant changes in vital signs or physical examination findings. CONCLUSIONS: Salmeterol 42 micrograms twice daily resulted in significantly greater improvements in asthma-specific quality of life, pulmonary function, and asthma symptoms compared with placebo (as-needed albuterol) in patients with moderate persistent asthma.

Adolescent↗

PubMed1997

Hepatitis C virus genotypes in a cohort of Australian blood donors and haemophiliac and liver transplant patients.

The aim of the present study was to characterize hepatitis C virus (HCV) genotypes using the INNO-LiPA HCV line probe assay and direct sequencing from three different HCV-RNA-positive (serum) groups: (i) blood donors (n = 59); (ii) haemophiliacs (n = 43); and (iii) patients undergoing liver transplantation (n = 26). Of 128 HCV-RNA-positive samples, 74 (58%) were genotype 1. Of these, 41 were genotype 1a, 32 were genotype 1b and one was genotype 1 indeterminate. Of the remaining 54 samples, seven (5%) were genotype 2a, two (2%) were genotype 2b, 26 (20%) were genotype 3a, three (2%) were genotype 4a, while 16 (12.5%) were of a mixed genotype. There was no significant difference between the three groups with regard to the prevalence of any specific genotype. However, in blood donors and haemophiliac patients there was a statistically significant difference in the occurrence of genotype 3a in patients with elevated alanine aminotransferase (ALT) levels (30.3%) compared with those patients with persistently normal ALT levels (5.6%; P = 0.004; chi 2). Genotype 3a was also uncommon in liver transplant patients (one of 14) with "sporadic' HCV infection. Genotype 4a was detected only in liver transplant patients. These patients had originated from Egypt (n = 1), Italy (n = 1) and Romania (n = 1).

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