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P Poole

Publications and source records attributed to P Poole.

At least 19 recordsLinked to original sources
PubMed2006

Long-acting beta2-agonists for poorly reversible chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by partially reversible airflow limitation. Many patients have little reversibility to short acting bronchodilators, but long acting bronchodilators are frequently advocated. OBJECTIVES: To determine the effectiveness of long acting beta-2 adrenoceptor agonists (LABAs) in COPD patients demonstrating poor reversibility to short-acting bronchodilators. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register was searched ('all years' to 2005) along with the reference lists from identified randomised controlled trials (RCTs). SELECTION CRITERIA: All RCTs comparing inhaled LABAs (salmeterol or formoterol) with placebo in the treatment of patients with stable, poorly reversible COPD. Studies were a minimum of four weeks in duration. DATA COLLECTION AND ANALYSIS: Two authors independently performed data extraction and study quality assessment. If we required additional data, we contacted authors and pharmaceutical companies sponsoring the identified RCTs. MAIN RESULTS: Twenty-three published and unpublished studies (6061 participants) were included in the review. There was a significant change in forced expiratory volume in 1 second (FEV1) in favour of salmeterol 50 mcg twice daily (BID) of 51 mls (95% confidence intervals (CI) 32 to 70), end of study morning peak expiratory flow (PEF) 14.89 L/min (95% CI 10.86 to 18.91). Supplemental short-acting bronchodilator usage was reduced by just under one puff per day. There were significant differences in the total, activity and impact domain scores of the St George's respiratory questionnaire in favour of salmeterol 50 mcg BID. Findings from other health status measurements and symptom scores were conflicting. There was no significant difference in exercise tolerance. The number of participants experiencing exacerbations was significantly reduced with salmeterol 50 mcg treatment compared with placebo (numbers needed to treat to benefit 21). AUTHORS' CONCLUSIONS: This review shows that the treatment of patients with COPD with salmeterol 50 mcg produces modest increases in lung function. There were varying effects for other important outcomes such as health related quality of life or reduction in symptoms. However, there was a consistent reduction in exacerbations which may help people with COPD who suffer frequent deterioration of symptoms prompting healthcare utilisation. The strength of evidence for the use of salmeterol 100 mcg, formoterol 12 mcg, 18 mcg, 24 mcg was insufficient to provide clear indications for practice.

Adrenergic beta-Agonists↗
PubMed2006

Ipratropium bromide versus long-acting beta-2 agonists for stable chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a condition associated with high morbidity, mortality and cost to the community. Patients often report symptomatic improvement with long acting beta-2 agonists (LABAs) and anticholinergic bronchodilator medications, both of which are recommended in COPD guidelines. These medications have different mechanisms of action and therefore theoretically could have an additive effect when combined. As these medications are prescribed in COPD as long term therapy, it is important to assemble reliable evidence on their relative and additive effects. OBJECTIVES: To compare the relative efficacy and safety of regular long term use (at least four weeks) of ipratropium bromide and LABA in patients with stable COPD. Comparisons were made between single agents and in combination versus LABAs alone. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of Trials (August 2005) and reference lists of articles. We also contacted drug companies for relevant trial data. SELECTION CRITERIA: All randomised controlled trials comparing treatment for at least four weeks with an anticholinergic agent (ipratropium bromide) alone or in combination with LABA versus LABA alone, delivered via metered dose inhaler or nebuliser, in non-asthmatic adult subjects with stable COPD. DATA COLLECTION AND ANALYSIS: Three review authors independently performed data extraction and study quality assessment. We contacted study authors and pharmaceutical companies for missing data. MAIN RESULTS: Seven studies met the inclusion criteria of the review (2652 participants). Monotherapy comparison (six studies): There was a significantly greater change in favour of salmeterol in morning PEF and FEV1. There were no significant differences in quality of life, exacerbations, or symptoms. Formoterol appeared to confer some benefits over ipratropium treatment in terms of morning peak flow. Combination comparison (three studies): There was a significant improvement in post-bronchodilator lung function, supplemental short-acting beta-agonist use and HRQL in favour of combination therapy compared with salmeterol alone. AUTHORS' CONCLUSIONS: The available data from the trials suggest that there is little difference between regular long term use of IpB alone and salmeterol if the aim is to improve COPD symptoms and exercise tolerance. However, salmeterol was more effective in improving lung function variables. In terms of post-bronchodilator lung function, combination therapy conferred modest benefits and a significant improvement in HRQL, and reduced supplemental short-acting beta-agonist requirement, although this effect was not consistent. Additional studies are needed to assess the relative effects of combining therapies, using validated subjective measurements, and should consider concordance and the convenience of people having to use different inhaler devices.

Adrenergic beta-Agonists↗
PubMed2006

Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a condition associated with high morbidity, mortality and cost to the community. Patients often report symptomatic improvement with short-acting beta-2 agonists (SABA) and anticholinergic bronchodilator medications, and both are recommended in COPD guidelines. These medications have different mechanisms of action and therefore could have an additive effect when combined. OBJECTIVES: To compare the relative efficacy and safety of regular long term use (at least four weeks) of ipratropium bromide and short- acting beta-2 agonist therapy in patients with stable COPD. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register of Trials was searched. Bibliographies were checked to identify relevant cross-references. Drug companies were contacted for relevant trial data. The searches are current to August 2005. SELECTION CRITERIA: All randomised controlled trials comparing at least 4 weeks of treatment with an anticholinergic agent (ipratropium bromide) alone or in combination with a beta-2 agonist (short acting) versus the beta-2 agonist alone, delivered via metered dose inhaler or nebuliser, in non-asthmatic adult subjects with stable COPD. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment was performed independently by three reviewers. Authors of studies and relevant manufacturers were contacted if data were missing. MAIN RESULTS: Eleven studies (3912 participants) met the inclusion criteria of the review. Small benefits of ipratropium over a short-acting beta-2 agonist were demonstrated on lung function outcomes. There were small benefits in favour of ipratropium on quality of life (HRQL), as well as a reduction in the requirement for oral steroids. Combination therapy with ipratropium plus a short-acting beta-2 agonist conferred benefits over a short-acting beta-2 agonist alone in terms of post-bronchodilator lung function. There was no significant benefit of combination therapy in subjective improvements in HRQL, but again there was a reduction in the requirement for oral steroids. AUTHORS' CONCLUSIONS: The available data from the trials included in this review suggest that the advantage of regular long term use of ipratropium alone or in combination with a short-acting beta-2 agonist or over a beta-2 agonist alone are small, if the aim is to improve lung function, symptoms and exercise tolerance. Until further data are available, the strategy of providing a short-acting beta-2 agonist on a PRN basis, and then either continuing with the short-acting beta-2 agonist regularly or conducting an "n of 1" trial of regular beta-2 agonist or regular anticholinergic to determine the treatment that gives the best relief of symptoms (and continuing with it), would seem cost effective. This strategy does need formal evaluation. Patient preference is also important, as is the relative importance of avoiding the use of systemic corticosteroids.

Adrenergic beta-Agonists↗
PubMed2006

Cautionary tales in the interpretation of systematic reviews of therapy trials.

This is the second in a series of articles emphasizing the cautions in the interpretation of health-care studies. Systematic reviews are presented as comprehensive, unbiased summaries of evidence and are often referred to by clinicians, guideline developers and health policy-makers. Their strengths and limitations, and how their results can be subject to bias and misinterpretation, are discussed.

Humans↗
PubMed2005

Preventing influenza: an overview of systematic reviews.

BACKGROUND: Many options are available for preventing people from getting infected by influenza virus, with vaccination being the most widely used. METHODS: We assessed the evidence available in Cochrane systematic reviews. We found nine reviews, five of them addressing influenza vaccination, and four addressing medication. RESULTS: Vaccination is effective in healthy adults and children, but the effect is modest in adults, and for young children few data are available. In patients with asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis, more evidence is needed to determine effectiveness. Vaccination does not result in exacerbation of asthma. Neuraminidase inhibitors may also have a place in limiting the spread of infection, at least in adults. Amantadine and rimantadine seem effective but have unfavourable adverse-effect profiles. The popularity of homoeopathic Oscillococcinum, especially in France, is not supported by current evidence. CONCLUSION: In many areas, more clinical trials are needed, as the current evidence is inconclusive. Furthermore, several other measures that may be helpful in preventing influenza that have not been addressed in Cochrane reviews.

Adult↗
PubMed2004

Combined corticosteroid and long acting beta-agonist in one inhaler for chronic obstructive pulmonary disease.

BACKGROUND: Long-acting beta-agonists and inhaled corticosteroids have both been recommended in guidelines for the treatment of chronic obstructive pulmonary disease. Their co-administration in a combined inhaler is intended to facilitate adherence to medication regimens, and to improve efficacy. OBJECTIVES: To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations, compared to placebo or the individual components, in the treatment of adults with chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group chronic obstructive pulmonary disease (COPD) trials register. Date of last search April 2004. SELECTION CRITERIA: Studies were included if they were randomised and double-blind. Studies could compare a combined inhaled corticosteroids and long-acting beta-agonist preparation with either component preparation or placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. The primary outcome was exacerbations. MAIN RESULTS: Six randomised trials with 4118 participants were included. Two different combination preparations (fluticasone/salmeterol and budesonide/formoterol) were used. Combination treatment was more effective than placebo for mean exacerbation rates, quality of life and lung function. No trials were found comparing the combination of drugs in a single inhaler with the same drugs both given in separate inhalers. Exacerbations: Fluticasone/salmeterol did not significantly reduce exacerbations compared with either of its component treatments in one large study. There was no significant difference when budesonide/formoterol was compared with budesonide. Budesonide/formoterol was more effective than formoterol in reducing exacerbations (Rate ratio: 0.78 [0.68 to 0.90], two studies). A pooled analysis of both combination therapies indicated that exacerbations were less frequent when compared with either placebo or long-acting beta-agonist (versus placebo Rate ratio: 0.76 [0.68, 0.84], three studies, versus beta-agonist, Rate ratio: 0.85 [0.77, 0.95], three studies), but not when compared with steroid. The clinical impact of this effect depends on the frequency of exacerbations experienced by patients. One full exacerbation was prevented for every two to four years of treatment in the type of patients included in the trials. Quality of Life: There were conflicting findings in quality of life and symptoms when fluticasone/salmeterol was compared with inhaled steroids alone (three studies). There was no significant difference between fluticasone/salmeterol and long-acting beta-agonist in quality of life scores (three studies). Budesonide/formoterol improved symptoms when compared with budesonide but not with formoterol. There were conflicting findings in quality of life scores when budesonide/formoterol was compared with component inhaled corticosteroid or beta-agonist. These may be accounted for by different study design. Lung Function: Treatment with either combination led to small, significant differences in lung function compared with component steroid medication. Fluticasone/salmeterol led to small improvements in FEV1 compared with salmeterol, but budesonide/formoterol treatment did not increase FEV1 significantly when compared with formoterol. REVIEWERS' CONCLUSIONS: Compared with placebo, combination therapy led to clinically meaningful differences in quality of life, symptoms and exacerbations. However, there were conflicting results when the different combination therapies were compared with the mono-components alone. In order to draw firmer conclusions about the effects of combination therapy in a single inhaler more data are necessary, including the assessment of the comparative effects with separate administration of the two drugs in double-dummy trials.

Adrenergic beta-Agonists↗
PubMed2004

Eletriptan for the acute treatment of migraine: results of bridging a Japanese study to Western clinical trials.

OBJECTIVE: To compare the efficacy, safety and tolerability of eletriptan (20, 40 and 80 mg) to placebo when given to Japanese and Western patients for the acute treatment of migraine. METHODS: A double-blind, randomized, parallel-group trial with the aforementioned therapeutic objectives was conducted in Japan (N = 321). By bridging analysis, data from this study were compared to two migraine trials previously conducted in the US (N = 1190) and Europe (N = 563). RESULTS: The 2-h post-dose headache response rates (i.e., the primary efficacy endpoint) of Japanese migraineurs to eletriptan 20, 40 and 80 mg were 64, 67 and 76%, respectively; European and American migraineurs showed similar trends and, in these studies, eletriptan was significantly superior to placebo (p < 0.05). Japanese patients did demonstrate a higher placebo response than Westerners, possibly due to differences in previous triptan exposure or expectation. Adverse events were generally mild to moderate, were comparable in all three studies, and showed a modest dose-response effect. CONCLUSION: The efficacy and tolerability of eletriptan for the acute treatment of migraine is comparable in Japan, Europe and the US.

Adolescent↗
PubMed2003

Combined corticosteroid and longacting beta-agonist in one inhaler for chronic obstructive pulmonary disease.

BACKGROUND: Long-acting beta-agonists and inhaled corticosteroids have been recommended in guidelines for the treatment of chronic obstructive pulmonary disease. However, they have only been available until recently via separate administration. They have been developed in order to facilitate adherence to medication regimens, and to improve efficacy. OBJECTIVES: To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations in the treatment of adults with chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group chronic obstructive pulmonary disease (COPD) trials register (March 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), LILACS (all years to March 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Studies were included if they were randomised, with adequate blinding procedures in place. Studies could compare a combined inhaled corticosteroids and long-acting beta-agonist preparation with either component preparation or placebo. Studies comparing different members of each class of combined therapies were included DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Four randomised trials with 2986 participants were included. Two different combination preparations (fluticasone/salmeterol and budesonide/formoterol) were studied in the trials. No meta-analysis on clinical outcomes was possible due to different outcome assessment across studies. All studies demonstrated a reduction in exacerbation rates versus placebo. Budesonide/formoterol was more effective than formoterol in reducing exacerbations in one study from 1.84 to 1.42 exacerbations per year. Fluticasone/salmeterol did not significantly reduce exacerbations compared with either of its component treatments. Fluticasone/salmeterol led to better quality of life compared with placebo (two studies), although there were conflicting results when compared with inhaled corticosteroid alone (two studies). There was no significant difference between fluticasone/salmeterol and long-acting beta-agonist (two studies). Budesonide/formoterol led to statistically significant differences in quality of life compared with placebo, but not when compared with component inhaled corticosteroid or beta-agonist (one study). REVIEWER'S CONCLUSIONS: For the primary outcome of exacerbations, budesonide/formoterol had a modest advantage over a component medication, formoterol, in a single trial, but fluticasone/salmeterol did not result in a significant reduction in exacerbations compared to either of its components. The combination of steroids and long-acting beta-agonist in one inhaler was effective in improving symptoms compared with placebo and on certain clinical outcomes compared with one of the individual components alone. In order to draw firmer conclusions about the effects of combination therapy in a single inhaler more data are necessary, including the assessment of the comparative effects with separate administration of the two drugs in double-dummy trials.

Adrenergic beta-Agonists↗
PubMed2003

Prophylactic antibiotic therapy for chronic bronchitis.

BACKGROUND: The use of prophylactic antibiotics to reduce the frequency and severity of acute exacerbations of chronic bronchitis is controversial. OBJECTIVES: To determine if prophylactic antibiotics reduce the frequency of exacerbations and/or days of disability in subjects with chronic bronchitis. SEARCH STRATEGY: We searched the Cochrane Airways Group Register of Clinical Trials and the bibliographies of relevant articles. SELECTION CRITERIA: Randomised controlled trials of prophylactic antibiotics in patients with chronic bronchitis and/or COPD were selected. DATA COLLECTION AND ANALYSIS: The eligibility of studies for inclusion was evaluated by three independent reviewers. MAIN RESULTS: Nine trials involving 1055 subjects were included in the analysis. All were performed before 1970. Concealment of allocation was assessed as clearly adequate in only 3 studies. The likelihood of having a exacerbation at any time during the course of the study was decreased with treatment (Relative Risk 0.91, 95% Confidence Intervals (CI) 0.84, 0.99). There was a small reduction in the number of exacerbations per patient per year with prophylactic antibiotics but this was not statistically significant ( Weighted Mean Difference (WMD) -0.15, 95%CI -0.34, 0.04 ). There was a modest but significant reduction of 22% in the number of days of disability per patient per month treated ( WMD -0.95, 95%CI -1.89 to - 0.01 ). A parallel reduction in the days of disability for each exacerbation (WMD -2.08, 95% CI -4.08 to -0.07) was seen. There was a small increase in adverse effects with antibiotics. REVIEWER'S CONCLUSIONS: Prophylactic antibiotics in chronic bronchitis / COPD have a small but statistically significant effect in reducing the days of illness due to exacerbations of chronic bronchitis. They do not have a place in routine treatment because of concerns about the development of antibiotic resistance and the possibility of adverse effects. The available data are over 30 years old, so the pattern of antibiotic sensitivity may have changed and there is a wider range of antibiotics in use.

Antibiotic Prophylaxis↗
PubMed2002

Cardioselective beta-blockers for chronic obstructive pulmonary disease.

BACKGROUND: Beta-blocker therapy has a proven mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To assess the effect of cardioselective beta-blockers on respiratory function of patients with COPD. SEARCH STRATEGY: A comprehensive search of EMBASE, MEDLINE and CINAHL was performed using the Cochrane Airways Group registry to identify randomised blinded controlled trials from 1966 to May 2001. The search was completed using the terms: asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* or obstructive airway disease*, and adrenergic antagonist*, sympatholytic* or adrenergic receptor block*. We did not exclude trials on the basis of language. SELECTION CRITERIA: Randomised, blinded, controlled trials of single dose or longer duration that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 second (FEV1) or symptoms in patients with COPD. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Two interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta2-agonist given after the study drug. MAIN RESULTS: Eleven studies of single-dose treatment and 8 of treatment for longer duration, ranging from 2 days to 12 weeks, met selection criteria. Cardioselective beta-blockers produced no statistically significant change in FEV1 or respiratory symptoms compared to placebo, given as a single dose (Weighted Mean Difference -2.05% [95% Confidence interval, -6.05 to 1.96%]) or for longer duration (WMD -2.55% [95% CI, -5.94 to 0.84]), and did not significantly affect the FEV1 treatment response to beta2-agonists. Exacerbations and hospitalizations were recorded in all trials, but none occurred during the periods of study, in either group. A subgroup analysis revealed no significant change in results for those participants with severe chronic airways obstruction or for those with a reversible obstructive component. REVIEWER'S CONCLUSIONS: The available evidence suggests that cardioselective beta-blockers, given to patients with COPD do not produce a significant short-term reduction in airway function or in the incidence of COPD exacerbations. However, the trials were small and of short duration. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should be considered for patients with COPD, but administered with careful monitoring since data concerning long term administration and their effects during exacerbations are not available.

Adrenergic beta-Antagonists↗
PubMed2001

Career and life experiences of New Zealand women medical graduates.

AIMS: To investigate the career and life experiences of a cohort of women graduating from a New Zealand medical school. METHODS: A questionnaire was mailed to 415 women who had graduated from the University of Auckland between 1973 and 1997. RESULTS: The response rate was 74%. Compared with a study undertaken in 1986, more women are entering clinical specialties and significantly fewer entering general practice. 60% had children (mean 2.3 children per participant). The majority of women had managed to work part-time in their careers. Income per hour was lower for those who chose specialties to fit in with family commitments. Job satisfaction was moderately high, but varied between specialties. Over half were undecided about their specialty at graduation. CONCLUSIONS: A higher proportion of women is moving into specialties other than general practice. As about half of all medical graduates are women, most of whom will want to have children, training agencies and employers should continue to develop their programmes and jobs to facilitate the combination of work and family life.

Adult↗
PubMed2001

Pantoprazole.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of pantoprazole are reviewed. Pantoprazole is a gastric hydrogen-potassium adenosine triphosphatase (H+/K(+)-ATPase) inhibitor. It shares the same core structure as other currently available proton-pump inhibitors (PPIs). The FDA-labeled indication is the short-term treatment of erosive esophagitis. PPIs act by selectively inhibiting H+/K(+)-ATPase in the secretory canaliculus of the stimulated parietal cell. Understanding the pharmacodynamics of PPIs is more relevant than knowing their pharmacokinetics, since the duration of action depends on the rate of de novo proton-pump regeneration, not the duration of drug circulation in the body. Pantoprazole is well absorbed, undergoes little first-pass metabolism, and has an absolute bioavailability of approximately 77%. Pantoprazole has been evaluated in more than 100 clinical trials involving more than 11,000 patients. It is effective in treating erosive esophagitis and duodenal and gastric ulcers. It is also effective as adjunctive treatment with antimicrobials in patients infected with Helicobacter pylori. Pantoprazole has been shown to control acid production in Zollinger-Ellison syndrome. Pantoprazole is well tolerated. The most commonly reported adverse effects are headache, diarrhea, and abdominal pain. The recommended oral dosage for erosive esophagitis is 40 mg once a day for up to eight weeks. The recommended i.v. dose is 40 mg given over 15 minutes once a day in patients with gastroesophageal reflux disease who are unable to take oral medication. Pantoprazole appears to be as safe and effective as other PPIs in acid-related disorders.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Long-acting beta2-agonists for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation which is only partially reversible. Long acting beta2-agonists, effective in the management of asthma,are also recommended for COPD management so it is important to establish whether these drugs are effective in reducing COPD symptoms in view of the potential side effect and cost burden. OBJECTIVES: To determine the effectiveness of long acting beta2-adrenoceptor agonists in improving lung function and quality of life and reducing dyspnoea in patients with COPD. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group register. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTs were contacted for other published and unpublished studies. In addition, unpublished studies were also obtained from the pharmaceutical companies that manufacture long acting beta2- adrenoceptor agonists. SELECTION CRITERIA: All randomised controlled trials over four weeks in duration comparing treatment with long-acting beta2-adrenoceptor agonists (salmeterol and formoterol) with placebo in patients with stable non-reversible COPD. Outcome measures included forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR), symptom scores, six minute walk distance, quality of life scores, Borg scores for dyspnoea and rescue bronchodilator use. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment was performed independently by two reviewers. Where further or missing data were required, authors of studies were contacted. MAIN RESULTS: Thirty three abstracts were identified as potentially relevant. Of these, four randomised controlled trials (RCTs) were included in this review. Two were parallel group studies of 16 week duration and two were cross-over studies with four week treatment arms. All four RCTs assessed the efficacy of salmeterol in COPD. In a 16 week study of salmeterol 50 mcg and 100 mcg twice daily treatment, a significant increase in FEV1 was seen in both treatment groups. The weighted mean difference (WMD) for the increase in FEV1 for the 50 mcg group was 0.10 litre (95% CI: 0.05;0. 15) and in the 100 mcg group the WMD was 0.12 litre (95% CI: 0.06; 0. 17 ). In the two cross-over studies of four weeks treatment, salmeterol 50 mcg twice daily treatment did not show significant increases in FEV1 (WMD = 0.04 litre, 95% CI: -0.06; 0.15). Similarly, morning and night time PEFR was not significantly improved with salmeterol treatment. In a 16 week study, disease-specific quality of life, measured using the St. George's Respiratory Questionnaire (SGRQ), showed a significant improvement after 50 mcg twice daily, but not after 100 mcg twice daily. This improvement exceeded the threshold for a clinically significant change with this questionnaire. General health status, as measured by the Medical Outcomes Short Form 36, did not improve in any of the eight components with either salmeterol dose. No significant difference was demonstrated in the mean change from baseline in the six minute walk distance (WMD = 1.9 metres, 95% CI: -15.4;19.3). Breathlessness was reduced in one study in patients receiving salmeterol 50 mcg twice daily group. Significantly more patients in this group had Borg scores for breathlessness less than three (a score of three indicating moderate dyspnoea) compared to the placebo treated group (Peto Odds Ratio = 0.60, 95% CI: 0.40; 0.88). Neither dose of salmeterol influenced the incidence of COPD exacerbations, (50 mcg: Peto Odds Ratio = 0.74, 95% CI: 0.47, 1.15) and (100 mcg: Peto Odds Ratio = 0.98, 95% CI: 0.64, 1.52). REVIEWER'S CONCLUSIONS: Treatment of patients with COPD with long acting beta2-agonists produces only small increases in FEV1. In one study, a dose of salmeterol 50 mcg twice daily produced a reduction in breathlessness and a clinically significant improvement in quality of life. (ABSTRACT TRUNCATED)

Adrenergic beta-Agonists↗
PubMed2000

Short-acting beta 2 agonists for stable chronic obstructive pulmonary disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterised by progressive airflow limitation that is at most partially reversible. Despite the lack of reversibility patients often report symptomatic improvement with short-acting beta 2 bronchodilator medications. They are used on either an "as required" or a "regular plus as required basis" and they may be used in conjunction with other bronchodilator medicines such as ipratropium and methylxanthines. These medicines are used in the management of both stable and acute exacerbations of COPD. This review examined the effect of short-acting beta 2 bronchodilators given by inhalation in stable COPD. OBJECTIVES: To determine the clinical effect and assess the adverse effects of inhaled short-acting beta 2 agonist bronchodilators compared with placebo in stable COPD. SEARCH STRATEGY: Only randomised controlled trials (RCTs) were considered. RCTs were identified using the Cochrane Airways Group database (CENTRAL). In addition, the reference lists of review articles and RCTs retrieved in full were searched for other potentially relevant citations. SELECTION CRITERIA: Only trials with adult patients with stable COPD, as defined by internationally accepted guidelines (ATS, ERS or BTS) were included in this review. All trials had a minimum duration of 7 days of regular treatment with short-acting beta 2 bronchodilators given by inhalation and compared with placebo. Data from trials where beta 2 agonists were used alone or in combination with other medicines (e.g. ipratropium bromide) were used only if there was a direct comparison between beta 2 bronchodilator alone and placebo. DATA COLLECTION AND ANALYSIS: Outcomes were analysed as continuous or dichotomous outcomes, using standard statistical techniques. For continuous outcomes, the weighted mean difference (WMD) and 95% confidence intervals were calculated and for dichotomous outcomes, the odds ratio was calculated with 95% confidence intervals by Peto's methods. Funnel plots were used to test for publication bias. MAIN RESULTS: Thirteen studies were included in this review. Most had small sample sizes and some of the sutides used very short-acting outdated compounds. All the studies used a cross-over design and were of high quality. Spirometry done at the end of study period was measured after administration of treatment (post-bronchodilator) which showed both FEV1 (0.150 L/min, 95%CI: 0. 02-0.28) and FVC (0.310 L, 95%CI: 0.00-0.62) to improve significanly but slightly when compared to placebo. A few studies measured FRC, airway resistance or conductance at the end of the study period. In all cases these measurements were done several hours after treatment, and no significant differences (p>0.05 in all cases) were found between the bronchodilator and placebo groups. Walking test Large increases in 6MW distance was observed in two studies, however one study did not show any positive improvements. There was a large increase in the 12MW distance as shown by one study. Due to the small number of studies reporting this outcome no significant differences were found in the walking distance between the bronchodilator and placebo groups. Peak Flow Rate Both morning (36. 04 L/min; 95%CI: 0.80-71.27) and evening (36.68 L/min; 95%CI: 2. 47-70.89) PEFR were significantly higher during active treatment than during placebo. Symptoms Breatlessness was measured on various scales therefore data that were presented in a suitable form were combined using standardized means for inclusion in the analysis. A significant improvement (-0.33; 95%CI: -0.58 to -0.07 with p=0.01) in the breathlessness score was observed during treatment with beta-2 agonist when compared to placebo. Cough was reported to improve significantly (data not usable) during treatment with beta2 agonist in one study but not in two others. A non-significant decrease in sputum production was reported by Wilson 1980, however four other studies reported no

Administration, Inhalation↗
PubMed2000

Carbon and nitrogen metabolism in Rhizobium.

One of the paradigms of symbiotic nitrogen fixation has been that bacteroids reduce N2 to ammonium and secrete it without assimilation into amino acids. This has recently been challenged by work with soybeans showing that only alanine is excreted in 15N2 labelling experiments. Work with peas shows that the bacteroid nitrogen secretion products during in vitro experiments depend on the experimental conditions. There is a mixed secretion of both ammonium and alanine depending critically on the concentration of bacteroids and ammonium concentration. The pathway of alanine synthesis has been shown to be via alanine dehydrogenase, and mutation of this enzyme indicates that in planta there is likely to be mixed secretion of ammonium and alanine. Alanine synthesis directly links carbon catabolism and nitrogen assimilation in the bacteroid. There is now overwhelming evidence that the principal carbon sources of bacteroids are the C4-dicarboxylic acids. This is based on labelling and bacteroid respiration data, and mutation of both the dicarboxylic acid transport system (dct) and malic enzyme. L-malate is at a key bifurcation point in bacteroid metabolism, being oxidized to oxaloacetate and oxidatively decarboxylated to pyruvate. Pyruvate can be aminated to alanine or converted to acetyl-CoA where it either enters the TCA cycle by condensation with oxaloacetate or forms polyhydroxybutyrate (PHB). Thus regulation of carbon and nitrogen metabolism are strongly connected. Efficient catabolism of C4-dicarboxylates requires the balanced input and removal of intermediates from the TCA cycle. The TCA cycle in bacteroids may be limited by the redox state of NADH/NAD+ at the 2-ketoglutarate dehydrogenase complex, and a number of pathways may be involved in bypassing this block. These pathways include PHB synthesis, glutamate synthesis, glycogen synthesis, GABA shunt and glutamine cycling. Their operation may be critical in maintaining the optimum redox poise and carbon balance of the TCA cycle. They can also be considered to be overflow pathways since they act to remove or add electrons and carbon into the TCA cycle. Optimum operation of the TCA cycle has a major impact on nitrogen fixation.

Alanine↗