Quality of life improvement in older patients with heart failure initiated on ivabradine: Results from the UK multi-centre LIVE:LIFE prospective cohort study.

AIMS: LIVE:LIFE is a multi-centre, open-label, prospective observational cohort study assessing health-related quality of life (HRQoL) in older patients with chronic heart failure (CHF) following initiation of ivabradine. The primary endpoint is change in Minnesota Living with Heart Failure Questionnaire (MLWHFQ) total score after 6months. METHODS AND RESULTS: Consenting patients aged ≥70years with CHF, in whom ivabradine was initiated within its licensed indication, were enrolled. Demographic, clinical and HRQoL (MLWHFQ, SF-12) data were collected at baseline (V1), 2 (V2) and 6months (V3). Over 14months, 240 patients were recruited from 44 UK centres. Ninety-nine (41%) were female and 28% aged ≥80years. Aetiology was ischaemic in 152 (63%) and 59% had been diagnosed with CHF for ≤2yrs. 52% of patients were New York Heart Association (NYHA) Class III and 57% had left ventricular ejection fraction <35%. 57% received beta-blockers. Patients had multiple comorbidities (144 (60%) hypertension, 105 (44%) asthma/COPD, 80 (33%) diabetes) and were prescribed a mean of 9±3 daily medications. Resting heart rate was 83bpm at baseline and fell 13bpm by V3. In patients completing both visits (n=187), comparing V3 to baseline: MLWHFQ total score improved by 9 points (p<0.0001, 95% CI: 7-12); 30% of patients improved ≥1 NYHA class and global assessment improved from patient (59%) and physician (60%) perspectives. 88% of patients completing V3 were still taking ivabradine. CONCLUSIONS: These contemporary prospective UK data demonstrate improvements in HRQoL and functional status with ivabradine therapy in typical older CHF patients. Despite comorbidities and polypharmacy, ivabradine was well tolerated.

Increasing the use of anti-inflammatory agents for acute asthma in the emergency department: experience with an asthma care map.

PURPOSE: Acute asthma is a common emergency department (ED) presentation and variation in its management is well recognized. The present study examined the use of an asthma care map (ACM) in one Canadian ED to improve adherence to acute asthma guidelines, emphasizing the use of systemic corticosteroids (SCSs) and inhaled corticosteroids (ICSs). METHODS: Three time periods were studied: the 15 months before ACM introduction (PRE), the 15 months following a three-month introduction of the ACM (POST(1)) and the 18 months after POST(1) (POST(2)). Randomly selected patient charts from each period were included from patients who were 18 to 60 years of age and presented with a primary diagnosis of acute asthma. A priori criteria were established to determine the degree of completion and success of the ACM. Primary outcomes included documentation, use of SCSs in the ED, and prescription of SCSs and ICSs at ED discharge. RESULTS: A total of 387 patient charts were included (PRE, n=150; POST(1), n=150; POST(2), n=87). Patient characteristics in the three groups were similar; however, patients in POST(1) and POST(2) showed higher use of newer agents than those in the PRE group. Overall, more women (n=209; 54%) than men were seen; the mean age was 32.4 years. The care map was used in 67% of cases during POST(1) and 70% during POST(2). The use of peak expiratory flow (PEF) was high during the PRE, POST(1) and POST(2) periods (91%, 89% and 91%, respectively); however, documentation of other markers of severity increased in the POST periods. Use of SCSs occurred earlier (P<0.01) and more often (57% PRE, 68% POST(1) and 75% POST(2); P<0.01) in the POST(1,2) periods than the PRE period. There was a significant increase in use of SCSs on discharge (55% PRE, 66% POST(1) and 69% POST(2); P<0.05), and prescription of ICSs significantly increased (24% PRE, 45% POST(1) and 61% POST(2); P<0.001) in the POST(1,2) periods. Discharge without any corticosteroids decreased over the three periods (32% PRE, 21% POST(1) and 17% POST(2); P<0.05). The length of stay in the ED increased over the study periods (181 min PRE, 209 min POST(1) and 265 min POST(2); P<0.01) and admissions were infrequent (9% PRE, 13% POST(1) and 6% POST(2); P=0.50). CONCLUSIONS: The present study provides evidence that the standardized ED ACM was widely accepted, improved chart documentation, improved some aspects of ED care and increased prescribing of discharge preventive medications.

Corticosteroids for preventing relapse following acute exacerbations of asthma.

BACKGROUND: Acute asthma is responsible for many emergency department (ED) visits annually. Between 12 to 16% will relapse to require additional interventions within two weeks of ED discharge. Treatment of acute asthma is based on rapid reversal of bronchospasm and reducing airway inflammation. OBJECTIVES: To determine the benefit of corticosteroids (oral, intramuscular, or intravenous) for the treatment of asthmatic patients discharged from an acute care setting (i.e. usually the emergency department) after assessment and treatment of an acute asthmatic exacerbation. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register and reference lists of articles. In addition, authors of all included studies were contacted to locate unpublished studies. The most recent search was run in October 2006. SELECTION CRITERIA: Randomized controlled trials comparing two types of corticosteroids (oral, intra-muscular, or inhaled) with placebo for outpatient treatment of asthmatic exacerbations in adults or children. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Six trials involving 374 people were included. One study used intramuscular corticosteroids, five studies used oral corticosteroids. The review was split into two reviews and although the latest search yielded no additional placebo controlled trials an additional IM study was included. Significantly fewer patients in the corticosteroid group relapsed to receive additional care in the first week (Relative risk (RR) 0.38; 95% confidence interval (CI) 0.2 to 0.74). This favourable effect was maintained over the first 21 days (RR 0.47; 95% CI 0.25 to 0.89) and there were fewer subsequent hospitalizations (RR 0.35; 95% CI 0.13 to 0.95). Patients receiving corticosteroids had less need for beta(2)-agonists (mean difference (MD) -3.3 activations/day; 95% CI -5.6 to -1.0). Changes in pulmonary function tests (SMD 0.045; 95% CI -0.47 to 0.56) and side effects (SMD 0.03; 95% CI -0.38 to 0.44) in the first 7 to 10 days, while rarely reported, showed no significant differences between the treatment groups. Statistically significant heterogeneity was identified for the side effect results; all other outcomes were homogeneous. From these results, as few as ten patients need to be treated to prevent relapse to additional care after an exacerbation of asthma. AUTHORS' CONCLUSIONS: A short course of corticosteroids following assessment for an asthma exacerbation significantly reduces the number of relapses to additional care, hospitalizations and use of short-acting beta(2)-agonist without an apparent increase in side effects. Intramuscular and oral corticosteroids are both effective.

New-onset temporal lobe epilepsy in children: lesion on MRI predicts poor seizure outcome.

OBJECTIVE: To determine factors predictive of long-term seizure outcome in children with new-onset temporal lobe epilepsy (TLE). METHODS: A community-based cohort of 77 children with new-onset TLE, including 14 with possible TLE, were followed prospectively with formal review 7 and 14 years following seizure onset. Diagnoses were re-evaluated at each review, and changed when new clinical, EEG, or imaging data were compelling. RESULTS: Sixty-four patients sustained the diagnosis of TLE over time; two were lost to follow-up. Age at follow-up was 12 to 29 years (median 20 years). Median follow-up was 13.7 years, 95% being followed for greater than 10 years. Nineteen patients were seizure free (SF) and off treatment, having not had seizures for 5 to 15 years. Duration of active TLE in the SF group was 1 to 8 years, the children being treated with 0 to 3 antiepileptic drugs (AEDs). Forty-three patients were not seizure free (NSF) and had ongoing seizures or had undergone epilepsy surgery. These children were treated with 1 to 10 AEDs. Fifteen NSF patients experienced 22 nonterminal seizure remissions of 1 to 7 years duration. Seventeen children had a significant antecedent to TLE. Lesions were identified on neuroimaging in 28 and included hippocampal sclerosis (HS) in 10, tumor in 8, and dysplasia in 7. All children with lesions on MRI were NSF (p < 0.001). Focal slowing on EEG was also associated with persistent seizures (p = 0.05), although this was correlated with a lesion on MRI. Infantile onset of epilepsy, family history of seizures, initial seizure frequency, antecedents, and early seizure remissions were not predictive of seizure outcome. CONCLUSION: Seizures spontaneously remit in approximately one third of children with new-onset TLE. A lesion on MRI predicts intractable seizures in TLE and the potential need for epilepsy surgery.

Corticosteroid therapy for acute asthma.

Asthma is a chronic inflammatory disease, which is characterised by reversible airflow obstruction in response to a variety of stimuli. Exacerbations in response to airway irritants are part of the natural history of asthma, but often they also represent a failure in chronic treatment. Presentations to emergency departments and other acute care settings are common and frequently lead to hospitalisation and other complications. After treatment, however, most patients are discharged to the care of their primary care physician for further management. This review highlights the role of systemic and inhaled corticosteroids as mainstays of treatment in the acute and sub-acute phase of an exacerbation. These agents form the basis of most current clinical practice guidelines, yet their use is not universal. We will review the evidence for the use of these agents that arises from the Cochrane Collaboration of Systematic Reviews contained in the Cochrane Library.

Continuous versus intermittent beta-agonists in the treatment of acute asthma.

BACKGROUND: Patients with acute asthma treated in the emergency department are frequently treated with intermittent inhaled beta-agonists delivered by nebulisation. The use of continuous beta-agonist (CBA) via nebulisation in the emergency setting may offer additional benefits in acute asthma. OBJECTIVES: To determine the efficacy (e.g., reductions in admission, improvement in pulmonary functions) and risks (e.g., adverse events, effects on vital signs) of continuous versus intermittent inhaled beta-agonists for the treatment of patients with acute asthma managed in the emergency department. SEARCH STRATEGY: Randomised controlled trials were identified from the Cochrane Airways Review Group "Asthma and WHEEZ*" Register which is a compilation of systematic searches of CINAHL, EMBASE, MEDLINE and CENTRAL and hand searching of 20 respiratory journals. In addition, primary authors and content experts were contacted to identify eligible studies. Bibliographies from included studies, known reviews and texts were also searched. The search is considered updated to June 2003. SELECTION CRITERIA: Only randomised controlled trials (RCTs) were eligible for inclusion. Studies were included if patients presented with acute asthma and were treated with either continuous or intermittent inhaled beta-agonists early in the ED treatment. "Continuous" nebulisation was defined as truly continuous aerosol delivery of beta-agonist medication (e.g., using a commercially available large-volume nebuliser, or a small-volume nebuliser with infusion pump) or sufficiently frequent nebulisations that medication delivery was effectively continuous (i.e., 1 nebulisation every 15 minutes or > 4 nebulisations per hour). Studies also needed to report either pulmonary function or admission results. Two reviewers independently selected potentially relevant articles and two additional reviewers independently selected articles for inclusion. Methodological quality was independently assessed by two reviewers. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers if the authors were unable to verify the validity of information. Missing data were obtained from authors or calculated from other data presented in the paper. The data were analysed using the Cochrane Review Manager (Version 4.1). Relative risks (RR), weighted mean differences (WMD) and standardized mean differences (SMD) are reported with corresponding 95% confidence intervals (CI); both peak expiratory flow rates (PEFR) and forced expiratory volume in one second (FEV-1) data are reported. MAIN RESULTS: 165 trials were reviewed and eight were included; a total of 461 patients have been studied (229 with CBA; 232 with intermittent beta-agonists). Overall, admission to hospital was reduced with CBA compared to intermittent beta-agonists (RR: 0.68; 95% CI: 0.5 to 0.9); patients with severe airway obstruction at presentation appeared to benefit most from this intervention (RR: 0.64; 95% CI: 0.5 to 0.9). Patients receiving CBA demonstrated small but statistically significant improvements in pulmonary function tests when all studies were pooled. Patients receiving CBA had greater improvements in % predicted FEV-1 (SMD: 0.3; 95% CI: 0.03 to 0.5) and PEFR (SMD: 0.33; 95% CI: 0.1 to 0.5); this effect was observed by 2-3 hours. Continuous treatment was generally well tolerated, with no clinically important differences observed in pulse rate (WMD: -2.87; 95% CI: -6.0 to 0.3) or blood pressure (WMD: -1.75; 95% CI: -5.6 to 2.1) between the treatment groups. Tremor was equally common in both groups (OR: 0.81; 95% CI: 0.5 to 1.3) and potassium concentration was unchanged (WMD: 0.02; 95% CI: -0.2 to 0.2). REVIEWER'S CONCLUSIONS: Current evidence supports the use of CBA in patients with severe acute asthma who present to the emergency department to increase their pulmonary functions and reduce hospitalisation. Moreover, CBA treatment appears to be safe and well tolerated in patients who receive it.

Mast-cell stabilising agents to prevent exercise-induced bronchoconstriction.

BACKGROUND: Exercise-induced bronchoconstriction (or asthma) following strenuous physical exertion is common and can cause sub-optimal performance, symptoms such as cough, dyspnea, wheeze, chest tightness, and can lead people to avoid physical activity. Management focuses on prevention with pre-exercise treatment using various pharmacologic agents. Mast cell stabilizing agents are effective in attenuating exercise-induced bronchoconstriction but their effectiveness compared to bronchodilator agents is unclear. OBJECTIVES: To quantitatively compare the effects of inhaling a single dose of either mast cell stabiliser - nedocromil sodium or sodium cromoglycate - to a single dose of short acting beta-agonists or anti-cholinergic agents - atropine or ipratropium bromide - prior to a strenuous exercise challenge in participants with asthma who are at least 6 years of age and suffer from reproducible exercise-induced bronchoconstriction. The review also compares the effects between a short acting beta-agonist alone to a combination of a short acting beta-agonist + mast cell stabiliser. SEARCH STRATEGY: We searched the Cochrane Airways Group ASTHMA and WHEEZ* trials register, Cochrane CENTRAL, Current Contents, review articles, textbooks and reference lists of articles. We also contacted the drug manufacturer and primary authors for additional citations. SELECTION CRITERIA: Randomised trials comparing a single prophylactic dose of a mast cell stabiliser to a short acting beta-agonist, anti-cholinergic agent, or a short acting beta-agonist alone to a combination of short acting beta-agonist plus a mast cell stabiliser to prevent exercise-induced bronchoconstriction in asthmatics over six years old. The exercise challenge had to conform to acceptable standards and pulmonary function (PFT) reported as percent decrease from baseline of FEV1 or peak flow. Complete protection (maximum % fall PFT <15% post-exercise) and clinical protection (50% improvement over placebo effect) measures were included. DATA COLLECTION AND ANALYSIS: Trial inclusion and quality assessments were conducted independently by two reviewers using standardised forms. A second reviewer confirmed data extraction and calculations. Attempts were made to contact study authors. The pooled estimate involving continuous pulmonary function measures are reported as a weighted mean difference (WMD), dichotomous data as an odds ratio (OR), both with 95% confidence intervals (95%CI) using a random effects model. Heterogeneity tests for pooled results were performed. MAIN RESULTS: Twenty-four trials (518 participants) conducted in 13 countries between 1976 and 1998 were included. All drugs were effective at attenuating the exercise-induced bronchoconstriction response but to varying degrees even within the same individual. Compared to anti-cholinergic agents, mast cell stabilisers were somewhat more effective at attenuating bronchoconstriction. On average the maximum fall on MCS was reduced to 7.1% compared to 13.8% on AC ( WMD = 6.7%; 95% CI: 3.3 to 10.0), provided more individuals with complete protection (73% vs 56%; OR = 2.2; 95% CI: 1.3 to 3.7) and clinical protection (73% vs 52%; OR = 2.7; 95% CI: 1.1 to 6.4). There were no subgroup differences based on age, severity, or study quality, and no adverse effects were reported for either agent group. When compared to short acting beta-agonists mast cell stabilisers were not as effective at preventing deterioration. On average the maximum fall on MCS was 11.2% compared to 4.3% on beta agonists ( WMD = 6.8%; 95% CI: 4.5 to 9.2). MCS provided fewer individuals with complete protection (66% vs 85%; OR = 0.3; 95% CI: 0.2 to 0.5) or clinical protection (55% vs 77%; OR = 0.4; 95% CI: 0.2 to 0.8). There were no significant subgroup differences based on age, severity, drug, delivery, or study quality. A non-significant difference in side effects was demonstrated with 11% of short acting beta-agonist patients experiencing side effects compared to 3% of those receiving mast cell stabilisers (OR = 0.2; 95% CI: 0.0 to 8.2). Combining masta-agonist patients experiencing side effects compared to 3% of those receiving mast cell stabilisers (OR = 0.2; 95% CI: 0.0 to 8.2). Combining mast cell stabilisers with a short acting beta-agonist did not produce significant advantages to pulmonary function over short acting beta-agonists alone. On average the maximum fall on SABA only was reduced to 5.3% compared to 3.5% on the combination ( WMD = 1.8%; 95% CI: -1.1 to 4.6). Beta-agonists alone provided fewer individuals with complete protection (68% vs 80%; OR = 0.5; 95% CI: 0.2 to 1.4) or clinical protection (70% vs 86%; OR=0.4; 95% CI: 0.1 to 1.2) but the difference did not reach significance (p=0.17). There were no subgroup differences. REVIEWER'S CONCLUSIONS: In a population of stable asthmatics short acting beta-agonists, mast cell stabilisers, or anticholinergics will provide a significant protective effect against exercise-induced bronchoconstriction with few adverse effects. On average, SABAs resulted in more effective attenuation than mast cell stabilisers, while mast cell stabilisers were more effective than anti-cholinergic agents. Combining SABA and mast cell stabilisers may be appropriate in selected cases. The variability in the individual degree of response to these drugs in multi arm trials suggests clinicians and patients work together to identify the most effective prophylactic therapy.

Nedocromil sodium for preventing exercise-induced bronchoconstriction.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) following strenuous physical exertion afflicts many people. It can be the cause of sub-optimal performance, symptoms such as cough, dyspnea, wheeze and chest tightness, and can lead people to avoid physical activity. Management of EIB focuses on prevention through pharmaco-therapy and alternate strategies. Single use, pre-exercise, beta-agonists and non-steroidal antiinflammatory agents are recommended. OBJECTIVES: Bronchodilator medications have been commonly used to prevent narrowing of airways after exercise, but anti-inflammatory drugs such as nedocromil sodium have also been used. The objective of this review was to assess the effects of a single dose of nedocromil sodium to prevent exercise-induced bronchoconstriction. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register, the Cochrane Controlled Trials Register, Current Contents, review articles, textbooks and reference lists of articles. We also contacted the drug manufacturer and primary authors for additional citations. SELECTION CRITERIA: Randomised trials comparing a single dose of nedocromil sodium with placebo to prevent exercise-induced bronchoconstriction in patients with EIB over six years of age. DATA COLLECTION AND ANALYSIS: Trial quality assessment and data extraction were conducted independently by two reviewers. Study authors were contacted for confirmation of data. MAIN RESULTS: The combined results from 20 randomised controlled trials involving 280 participants, show that 4 mg, of nedocromil sodium inhaled 15 to 60 minutes prior to exercise significantly reduce the severity and duration of EIB in both adults and children, when compared to placebo. The maximum percentage fall in FEV1 was improved significantly compared to placebo (weighted mean difference 15.5 %; 95% confidence interval:13.2 to 18.1). For the maximum percentage fall in peak expiratory flow rate (PEFR) the improvement was similar: WMD 15.0%, (95% CI 8.3 to 21.6). Nedocromil shortened the time to recover lung normal function from more than 30 minutes with placebo to less than 10 minutes with the drug. It had a greater effect on those patients with more severe exercise-induced bronchoconstriction (defined as an exercise-induced fall in lung function > 30% from baseline). There were no significant adverse effects reported with the short term use of nedocromil. A further search conducted in September 2001 did not yield any further studies. REVIEWER'S CONCLUSIONS: Nedocromil sodium used before exercise reduces the severity and duration of exercise-induced bronchoconstriction. This effect appears to be more pronounced in people with severe exercise-induced bronchoconstriction.

Evidence-based treatments for acute asthma.

Asthma is an important health care problem; over 12 million people in the United States suffer from asthma, the majority of whom are young patients. Presentations of acute asthma to emergency departments are common. In the United States, acute asthma presentations account for close to 2 million emergency department visits annually, and these patients often exhibit acute and chronic markers of severe asthma; so controlling asthma is important from many perspectives. We review the evidence for various acute asthma therapies, using the highest levels of evidence, employing systematic reviews (especially those from the Cochrane Collaboration) and evidence from randomized controlled trials to guide therapy decisions. beta agonists and systemic corticosteroids are the cornerstones of initial treatment. Delivery of beta agonists via nebulizer or metered-dose inhaler with spacer device appear to be similarly efficacious. However, recent evidence from studies involving children and adults indicate that addition of ipratropium bromide to early beta agonist treatments may reduce airway obstruction and reduce hospital admissions, especially for more severe asthma. Evidence from systematic reviews indicates that intravenous magnesium sulfate may provide similar benefits in severe asthma. Antibiotics, intravenous beta agonists, and intravenous aminophylline have been shown to add little and may increase adverse effects. Treatment for discharged patients should include systemic corticosteroids for 5-7 days, for all but the mildest asthma. Addition of inhaled corticosteroids should be considered for most patients, since evidence suggests that inhaled corticosteroids may reduce relapses and improve quality of life. Alternative treatments such as long-acting beta agonists and leukotriene antagonists remain unproven in this setting. Linking a discharge plan to close follow-up and asthma education (especially an action plan) needs to be encouraged. Acute asthma is a common problem and treatment has improved dramatically over the past 10 years. Employing the evidence-based practice outlined above should reduce the burden of acute asthma on patients and the health care system.

Outcomes of a comprehensive treatment program for adolescents with a substance-use disorder.

Outcomes of a multimodal residential treatment program for adolescents were compared with usual care. The quasiexperimental design included pretest, 3-month posttest, and 6-month follow-up of program referrals (mean age 16; 53% male). The intervention group (IG) comprised referrals who entered the program (n=61) and the comparison group (CG) comprised referrals who did not enter the program (n=60). The six outcomes (substance use, criminal behavior, social functioning, psychological distress, physical health, and HIV risk-taking behavior) were assessed using the Opiate Treatment Index and the Symptom Checklist-90-Revised. The study groups demonstrated equivalent improvement on all six outcomes. Multiple factors are likely to have influenced these results, including inadequate program implementation and differential drop-out. There was, however, a higher prevalence of multiple improvements among the IG than the CG. It is concluded that adolescents with a PSUD can improve, however, a superior means of achieving this improvement has yet to be demonstrated.

Corticosteroids for preventing relapse following acute exacerbations of asthma.

BACKGROUND: Acute asthma is responsible for many emergency department visits annually. Between 12-16% will relapse to require additional interventions within two weeks of ED discharge. Treatment of acute asthma is based on rapid reversal of bronchospasm and reducing airway inflammation and this review examines the evidence for using systemic corticosteroids to improve outcomes after discharge from the ED. OBJECTIVES: To determine the benefit of corticosteroids (oral, intramuscular, or intravenous) for the treatment of asthmatic patients discharged from an acute care setting (i.e. usually the emergency department) after assessment and treatment of an acute asthmatic exacerbation. SEARCH STRATEGY: The Cochrane Airways Group "Asthma and Wheez* RCT" register was searched using the terms: a) Asthma OR Wheez* b) Glucocorticoid OR Steroid* AND c) Exacerbat* OR Relapse* OR Emerg*. In addition, authors of all included studies were contacted to determine if unpublished studies which met the inclusion criteria were available. Bibliographies from included studies, known reviews and texts were also searched for additional citations. SELECTION CRITERIA: Only randomized controlled trials were eligible for selection. Studies were included in this review if they dealt with the outpatient treatment of asthmatic exacerbations using glucocorticoids at discharge and reported either relapse rate or PFTs. Two independent reviewers first identified potentially relevant studies and then selected articles for inclusion. Methodological quality was assessed independently by two reviewers. Agreement was assessed using kappa (k) statistics. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers; authors were contacted to verify the extracted data and clarify missing information. When author contact was unsuccessful, missing data were estimated from graphs where possible. Sensitivity, sub-group and overall analyses were performed using the Cochrane Review Manager. MAIN RESULTS: A search that yielded 229 references identified 169 (73%) original publications. Reviewers identified 8 studies for potential inclusion (k =0.76); 18 references were added by searching publication reference lists and contact with authors. Of these 26 articles, a total of 7 were included in the overview. Two studies used intramuscular corticosteroids, five studies used oral corticosteroids. Significantly fewer patients in the corticosteroid group relapsed to receive additional care in the first week (odds ratio (OR) 0.35; 95% confidence interval (CI): 0.17, 0.73). This favourable effect was maintained over the first 21 days (OR 0.33; 95% CI: 0.13, 0.82). Patients receiving corticosteroids had less need for beta-agonists (weighted mean difference (WMD) -3.3 activations/day; 95% CI: -5.5, -1.0). Changes in pulmonary function tests (SMD 0.045; 95% CI: -0.47, 0.56) and side effects (SMD 0.03; 95% CI : -0.38, 0.44) in the first 7-10 days, while rarely reported, showed no differences between the treatment groups. Statistically significant heterogeneity was identified for the side effect results; all other outcomes were homogeneous. It appears that IM corticosteroids are similarly efficacious to a 7-10 day tapering course of oral agents. From these results, as few as 13 patients need to be treated to prevent relapse to additional care after an exacerbation of asthma. REVIEWER'S CONCLUSIONS: A short course of corticosteroids following assessment for an acute exacerbation of asthma significantly reduces the number of relapses to additional care and decreases beta-agonist use without an apparent increase in side effects. Intramuscular corticosteroids appear as effective as oral agents.

Early emergency department treatment of acute asthma with systemic corticosteroids.

BACKGROUND: The airway edema and secretions associated with acute asthma are most effectively treated with anti-inflammatories such as corticosteroids delivered by inhaled, oral, intravenous or intra-muscular routes. There is an unresolved debate about the use of systemic corticorticoids in the early treatment of acute asthma for emergency department patients. OBJECTIVES: To determine the benefit of treating patients with acute asthma with systemic corticosteroids within an hour of presenting to the emergency department (ED). SEARCH STRATEGY: Randomised controlled trials were identified from the Cochrane Airways Group Asthma Register. Primary authors and content experts were contacted to identify eligible studies. Bibliographies from included studies and known reviews were searched. SELECTION CRITERIA: Only randomised controlled trials (RCTs) or quasi-randomised trials were eligible for inclusion. Studies were included if patients presenting to the ED with acute asthma were treated with IV/IM or oral corticosteroids (CS) vs. placebo within 1 hour of arrival and either admission rate or pulmonary function results were reported. DATA COLLECTION AND ANALYSIS: Trial selection, data extraction and quality assessment were carried out independently by two reviewers, and confirmed with corresponding authors. MAIN RESULTS: Twelve studies involving 863 patients (435 corticosteroids; 428 placebo) were included. Early use of CS for acute asthma in the ED significantly reduced admission rates (N = 11; pooled OR: 0.40, 95% CI: 0.21 to 0.78). This would correspond with a number needed to treat of 8 (95% CI: 5 to 21). This benefit was more pronounced for those not receiving systemic CS prior to ED presentation (N = 7; OR: 0.37, 95% CI: 0.19 to 0.70) and those with more severe asthma (N = 7; OR: 0.35, 95% CI: 0.21 to 0.59). Oral CS therapy in children was particularly effective (N = 3; OR: 0.24, 95% CI: 0.11 to 0.53); no trials in adults used the oral route. Side effects were not significantly different between corticosteroid treatments and placebo. A further search was conducted in September 2000 which did not yield any further trials. REVIEWER'S CONCLUSIONS: Use of corticosteroids within 1 hour of presentation to an ED significantly reduces the need for hospital admission in patients with acute asthma. Benefits appear greatest in patients with more severe asthma, and those not currently receiving steroids. Children appear to respond well to oral steroids.

Nedocromil sodium versus sodium cromoglycate in treatment of exercise-induced bronchoconstriction: a systematic review.

The objective of this review was to compare the effects of prophylactic doses of nedocromil sodium (NCS) and sodium cromoglycate (SCG) on postexercise lung function, in persons diagnosed with exercise-induced bronchoconstriction. Randomized controlled trials were identified from the Cochrane Airways Review Group Asthma Register, plus hand searching for trials in journals, bibliographies of relevant studies and review articles. Randomized controlled trials comparing NCS to SCG in prophylactic treatment of exercise-induced bronchoconstriction were eligible. Studies were pooled using odds ratios (OR) for dichotomous outcomes or weighted mean differences (WMD) with 95% confidence intervals (95% CI) for continuous outcomes. No significant differences were noted between NCS and SCG with respect to the maximum per cent decrease in forced expiratory volume in one second (WMD=-0.88; 95% CI -4.50-2.74), complete protection (OR=0.95; 95% CI 0.50-1.81), clinical protection (OR=0.71; 95% CI 0.36-1.39), unpleasant taste (OR=6.85; 95% CI 0.77-60.73), or sore throat (OR=3.46; 95% CI 0.32-37.48). Subgroup analyses based on age, dosages of medications and timing of exercise postinhalation were consistent with the overall pooled analyses. No significant differences were evident between the effects of nedocromil sodium and sodium cromoglycate during the immediate postexercise period in adults and children with exercise-induced bronchoconstriction, with regards to maximum per cent decrease in forced expiratory volume in one second, complete protection, or clinical protection. Side-effect profiles were similar.

A study of the patterns and correlates of substance use among adolescents applying for drug treatment.

OBJECTIVE: To inform planners by providing a psychosocial and drug-use profile of adolescents who have applied for a drug-treatment program. METHOD: The setting was a residential drug-treatment program in Sydney for adolescents from NSW and the ACT. The design was a descriptive study of consecutive program applicants over 18 months. Study participants were 14-18 years, 53% were male. Most assessments were telephone interviews. The instrument incorporated the Opiate Treatment Index, Adolescent Drug Abuse Diagnosis, Severity of Dependence Scale and Symptom Checklist 90-Revised (SCL-90-R). RESULTS: Study participants tended to be poly-substance users, mostly using cannabis, heroin and/or alcohol. Heavy use in terms of frequency and amounts of use were reported, e.g. 50% of the sample used heroin daily and the mean number of standard drinks consumed on the last day of drinking was 18. High levels of problems in the areas of social functioning, criminal activity, psychological distress, physical health, HIV risk and substance dependence were reported. For example, most participants were unemployed and 88% had committed a crime in the previous month. Higher rates of some problems were identified among females, heroin users and benzodiazepine users. CONCLUSIONS: The sample reported a high level of involvement in substance use and associated problems. The profile suggested that improvements might be difficult to achieve and to maintain. IMPLICATIONS: A comprehensive, intensive, longer-term drug-treatment program to address the number and extent of substance-related problems for such adolescents is recommended.

Penicillamine for treating rheumatoid arthritis.

OBJECTIVES: To estimate the short-term effects of D-penicillamine for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register (issue 3, 2000) and Medline up to and including August 2000 and Embase from 1988-2000. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials and controlled clinical trials comparing D-penicillamine against placebo in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed independently by two reviewers (CS, EB) and checked by a third (MS) using a validated quality assessment tool (Jadad 1996). Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint and stratified according to D-penicillamine dosages: low (<500mg/day), moderate (500 to <1000mg/day) and high (1000 mg/day or greater). Data was abstracted by one reviewer and checked by a second (CS, MS). The pooled analysis was performed using the standardized mean difference for joint counts, pain and global assessments. The weighted mean difference was used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout, since no statistical heterogeneity was found. MAIN RESULTS: Six trials were identified, with 425 patients randomized to D-penacillamine and 258 to placebo. A statistically significant benefit was observed for D-penicillamine when compared to placebo for all three-dose ranges and for most outcome measures including: tender joint counts, pain, physician's global assessments and ESR. The standardized weighted mean differences between treatment and placebo in moderate doses were -0.51 [95% CI -0.88, -0.14] for tender joint counts, -0.56 (95% CI -0.87, -0.26) for pain and -0.97 (95% CI -1.25, -0.70) for global assessment. The difference for ESR was -10.6 mm/hr. Similar results were observed for the higher dose group. Total withdrawals were significantly higher in the moderate and high dosage D-penicillamine groups (OR=1.63 and 2.13 respectively), mostly due to increased adverse reactions (OR = 2.60 and 4.95 respectively), including renal and hematological abnormalities. REVIEWER'S CONCLUSIONS: D-penicillamine appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. Its efficacy appears to be similar to that of other disease modifying anti-rheumatic drugs (DMARDs), but with a significantly higher toxicity. Its effects on long-term functional status and radiological progression are not clear from this review.

Azathioprine for treating rheumatoid arthritis.

OBJECTIVES: To assess the short-term effects of azathioprine for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register (issue 3, 2000), Medline up to and including August 2000 and Embase from 1988 to August 2000. We also conducted a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials and controlled clinical trials comparing azathioprine against placebo in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Data was extracted independently by two reviewers (CS, EB); disagreements were resolved by discussion or third party adjudication (MS). The same reviewers (CS, EB) assessed the methodological quality of the trials using a validated quality assessment tool. Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and functional status assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and for adverse reactions. The 95% confidence intervals (95% CI) are presented. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout, since no statistical heterogeneity was found. MAIN RESULTS: Three trials with a total of 81 patients were included in the analysis. Forty patients were randomized to azathioprine and forty-one to placebo. A pooled estimate was calculated for two outcomes. A statistically significant benefit was observed for azathioprine when compared to placebo for tender joint scores. The standardized weighted mean difference between treatment and placebo was -0.98 (95% CI -1.45, -0.50). Withdrawals from adverse reactions were significantly higher in the azathioprine group OR=4.56 (95% CI 1.16, 17.85). REVIEWER'S CONCLUSIONS: Azathioprine appears to have a statistically significant benefit on the disease activity in joints of patients with RA. This evidence however is based on a small number of patients, included in older trials. Its effects on long-term functional status and radiological progression were not assessed due to lack of data. Toxicity is shown to be higher and more serious than that observed with other disease-modifying anti-rheumatic drugs (DMARDs). Given this high risk to benefit ratio, there is no evidence to recommend the use of azathioprine over other DMARDs.

Nedocromil sodium vs. sodium cromoglycate for preventing exercise-induced bronchoconstriction in asthmatics.

BACKGROUND: Nedocromil sodium and sodium cromoglycate inhaled shortly before exercise appear to reduce the severity of exercise-induced bronchoconstriction. There is some debate over which drug may be more effective. OBJECTIVES: The objective of this review was to compare the effects on post-exercise lung function between prophylactic doses of nedocromil sodium (NSG) and sodium cromoglycate (SCG) in persons diagnosed with exercise-induced bronchoconstriction. SEARCH STRATEGY: Randomized controlled trials were identified from the Cochrane Airways Review Group Asthma Register which compiles searches of CINAHL, EMBASE, MEDLINE and CENTRAL, plus hand searches for trials in 20 journals. Bibliographies of relevant studies and review articles were searched and primary authors, content experts and manufacturers of drugs were contacted for additional relevant studies. No language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials comparing NCS to SCG in prophylactic treatment of exercise-induced bronchoconstriction were eligible. Studies were included if: the participants, aged 6 or over, had a confirmed diagnosis of asthma with exercise-induced bronchoconstriction, were subjected to an exercise challenge sufficient to trigger bronchoconstriction, and the measures of lung function were reported as either changes in forced expiratory volume in one second or peak expiratory flow rate. DATA COLLECTION AND ANALYSIS: Data extraction and methodological quality assessments were conducted independently by two reviewers using standard forms and validated assessment criteria. In some cases results were extrapolated from graphs. Results from similar studies were pooled and reported as the weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CI) using the random effects model. MAIN RESULTS: Of the 92 citations retrieved from the original search, a total of 8 studies were included in this review (117 participants). No significant difference was noted between NCS and SCG with respect to the maximum percent decrease in FEV1 (WMD = -0.88; 95% CI: -4.50, 2.74), complete protection (i.e. maximum % fall FEV1 still =>10%); OR = 0.95; 95% CI: 0.50 to 1.8, clinical protection (i.e. < 50% improvement over placebo); OR = 0.71; 95% CI: 0.36 to 1.39; unpleasant taste (OR = 6.85; 95% CI: 0.77, 60.73), or sore throat (OR = 3.46; 95% CI: 0.32, 37.48). For these pooled comparisons, no statistically significant heterogeneity was identified. Subgroup analyses based on age, dosage of medications and timing of exercise post-inhalation were consistent with the overall pooled analyses. REVIEWER'S CONCLUSIONS: No significant differences were evident between the effect of NCS and SCG during the immediate post-exercise period in adults and children with EIB with regards to pulmonary function - specifically maximum percent decrease in FEV1, complete protection, clinical protection, or side effects.

Edmonton Quality Assessment Tool for Drug Utilization Reviews: EQUATDUR-2: the development of a scale to assess the methodological quality of a drug utilization review.

OBJECTIVE: The objective of this study was to develop an instrument that will assist in evaluating the methodological quality of drug utilization reviews (DURs) and studies of prescribing appropriateness. DESIGN: An expert committee followed accepted steps for developing and testing new instruments. Consultations on content, face validity, and scoring of items were solicited from external experts. Seven raters tested an initial version; subsequently, a refined instrument was designed. The Edmonton Quality Assessment Tool for Drug Utilization Reviews (EQUATDUR-2) evaluates 3 domains: sample selection (1 item), data collection (1 item), and data analysis (3 items). Sixteen raters tested EQUATDUR-2 on a random sample of DURs. MEASURES: The study measures were reliability-using random effects interclass correlation coefficients for ratings by individual raters (ICC2,1) and the mean of ratings (ICC2,k)-and variability between DUR quality levels and rater groups. RESULTS: There were significant differences in methodological quality (P <0.001) and in mean scores comparing low-, moderate-, and high-quality DURs. Nonmethodologists' ratings exhibited significant variability (P = 0.03) and tended to be higher. Agreement varied for individual items (ICC2,1, 0.22 to 0.44; ICC2,k, 0.81 to 0.91) and for mean summary ratings (ICC2,1, 0.42 [95% CI, 0.28 to 0.61]; ICC2,k, 0.92 [95% CI, 0.86 to 0.96]). The average time to rate each DUR was 10.0 minutes (95% CI, 9.2 to 10.9). CONCLUSIONS: EQUATDUR-2 is a succinct, self-administered instrument with evidence of validity and reliability. We recommend that > or =2 raters independently assess each DUR and resolve disagreements by consensus. EQUATDUR-2 will help clinicians and decision makers to evaluate the quality of DUR studies and provide a framework for enhancing rigor in the design, conduct, and reporting of DURs.