Direct oral anticoagulants in the treatment of acute venous thromboembolism in patients with obesity: A systematic review with meta-analysis.

BACKGROUND: Direct oral anticoagulants' (DOAC) pharmacokinetics are affected by obesity. Their efficacy and safety in obesity (BMI≥30 kg/m2) and morbid obesity (BMI≥40 kg/m2) are still unclear in the treatment of venous thromboembolism (VTE). OBJECTIVES: To compare the efficacy/safety of DOAC versus vitamin K antagonist (VKA)/low molecular weight heparin (LMWH) for the treatment of VTE in patients with obesity and morbid obesity. The primary efficacy/safety outcomes were VTE recurrence and major bleeding (MB). Clinically relevant non-MB and mortality were also evaluated. METHODS: A systematic literature search (MEDLINE, EMBASE, CENTRAL, Web of Science) identified studies evaluating DOAC in the treatment of VTE in patients with obesity and reporting one of the outcomes. Relative risks (RR) and 95 % confidence intervals (CI) were estimated using the Mantel-Haenszel method. RESULTS: We included 21 studies (50,360pts) of which 16,150 patients had a BMI≥30 kg/m2 and 6443 patients had a BMI≥40 kg/m2. VTE recurrence was similar with DOAC compared to VKA/LMWH in patients with obesity (RR 1.03;95 %CI 0.93-1.15;p = 0.55) and morbid obesity (RR 1.06;95 %CI 0.94-1.19;p = 0.35). DOAC were also associated with a reduction in MB (RR 0.57;95 %CI 0.34-0.94;p = 0.03 and RR 0.71;95 %CI 0.50-1.00;p = 0.05 in patients with obesity and morbid obesity, respectively). Subgroup analyses comparing randomized controlled trials to observational studies showed consistent results. No difference was observed in regards of clinically relevant non-MB and mortality. CONCLUSION: There is no signal for differences in VTE recurrence in patients with obesity and morbid obesity treated with DOAC compared to VKA/LMWH, while DOAC likely reduce the risk of MB compared to VKA/LMWH.

DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis.

Low molecular weight heparins (LMWH) are the standard of care for the treatment of cancer-associated venous thromboembolism (CA-VTE). We performed a systematic review and meta-analysis to compare the effects of direct oral anticoagulants (DOAC) versus LMWH for the treatment of CA-VTE. The primary efficacy and safety outcomes were VTE recurrence and major bleeding (MB). The secondary outcomes were clinically relevant non-MB (CRNMB), all-cause mortality and the net clinical benefit. We searched MEDLINE, EMBASE, CENTRAL and Web of Science (inception-December 2019) and abstracts of relevant conferences (2000-2019) to identify randomized controlled trials comparing DOAC and LMWH for the treatment of CA-VTE. Relative risks (RR) and 95% confidence intervals were estimated (Mantel-Haenszel method, random-effects models). A non-inferiority analysis with a margin of 1.3 for the upper boundary of the RR was conducted for the primary outcomes. From 637 references, we included four publications which encompass three trials (1756 patients). Compared to LMWH, DOAC were associated with a trend for decreased VTE recurrence (RR 0.51; 95%CI 0.25-1.03; p = 0.06; I2 = 51%), whereas MB (RR 1.64; 95%CI 1.00-2.69; p = 0.05; I2 = 0%) and CRNMB (RR 1.83; 95%CI 1.04-3.20; p = 0.03; I2 = 50%) were significantly more frequent with DOAC. Conversely, all-cause mortality (RR 1.06; 95%CI 0.83-1.35; p = 0.64; I2 = 36%) and net clinical benefit (RR 0.74; 95%CI 0.38-1.42; p = 0.36; I2 = 65%) were comparable. DOAC were non-inferior to LMWH in preventing CA-VTE recurrence, but were associated with an increased risk of MB and CRNMB. Further studies are required to confirm these results and inform on the risk/benefit ratio for specific populations.

Wait times for diagnosis and treatment of lung cancer: a single-centre experience.

BACKGROUND: Multiple clinical practice guidelines recommend rapid evaluation of patients with suspected lung cancer. It is uncertain whether delays in diagnosis and management have a negative effect on outcomes. METHODS: This retrospective study included 551 patients diagnosed with lung cancer through the diagnostic assessment program at the Institut universitaire de cardiologie et de pneumologie de Québec between September 2013 and March 2015. Median wait times between initial referral, diagnosis, and first treatment were calculated and compared with recommended targets. Analyses were performed to evaluate for specific factors associated with longer wait times and for the effect of delays on the outcomes of progression-free survival (pfs), relapse-free survival (rfs) after primary surgical resection, and overall survival (os). RESULTS: Most patients were investigated and treated within recommended targets. Of the entire cohort, 379 patients were treated at our institution. Of those 379 patients, 311 (82%) were treated within recommended targets. In comparing patients within and outside target times, the only statistically significant difference was found in the distribution of treatment modalities: patients meeting targets were more likely to be treated with surgery or chemotherapy rather than with radiation. The pfs on first treatment modality was influenced by clinical stage, but not by time to therapy [hazard ratio (hr): 1.10; p = 0.65]. The os for the entire cohort was also influenced by stage, but not by delays (hr: 1.04; p = 0.87). For the 209 patients treated by surgery with curative intent, a significant reduction in rfs was associated with male sex and TNM stage, but not with delays (hr: 1.11; p = 0.83). The os after primary surgical resection was also associated with TNM stage, but not with delays (hr: 1.82; p = 0.43). CONCLUSIONS: Recommended targets for wait times in the investigation and treatment of lung cancer can be achieved within a diagnostic assessment program. Compared with radiation treatment, treatment with surgery or chemotherapy is more likely to be completed within targets. Delays in investigation and treatment do not appear to negatively affect the clinical outcomes of os, rfs, and pfs. Prospective studies are needed to evaluate whether efficient work-up and treatment influence other important variables, such as quality of life, cost of care, and access to therapies while performance status is adequate.

Pericardiocentesis versus pericardiotomy for malignant pericardial effusion: a retrospective comparison.

BACKGROUND: Treatment of malignant pericardial effusion remains controversial, because no randomized controlled trials have been conducted to determine the best approach, and results of retrospective studies have been inconsistent. The objective of the present study was to compare pericardiocentesis and pericardiotomy with respect to efficacy for preventing recurrence, and to determine, for those two procedures, diagnostic yields, complication rates, and effects on survival. We also aimed to identify clinical and procedural factors that could predict effusion recurrence. METHODS: We retrospectively assessed 61 patients who underwent a procedure for treatment of a malignant pericardial effusion at the Institut universitaire de cardiologie et de pneumologie de Québec between February 2004 and September 2013. RESULTS: Pericardiocentesis was performed in 42 patients, and pericardiotomy, in 19 patients. The effusion recurrence rate was significantly higher in patients treated with pericardiocentesis than with pericardiotomy (31.0% vs. 5.3%, p = 0.046). The diagnostic yield of the procedures was not significantly different (92.9% vs. 86.7%, p = 0.6). The overall rate of complications was similar in the two groups, as was the median overall survival (2.4 months vs. 2.6 months, p = 0.5). In univariate analyses, the procedure type was the only predictor of recurrence that approached statistical significance. Age, sex, type of cancer, presence of effusion at the time of cancer diagnosis, prior chest irradiation, tamponade upon presentation, and total volume of fluid removed did not influence the recurrence rate. CONCLUSIONS: Compared with pericardiocentesis, pericardiotomy had higher success rate in preventing recurrence of malignant pericardial effusion, with similar diagnostic yields, complication rates, and overall survival.

Tiotropium improves walking endurance in COPD.

The primary objective of this study was to evaluate the effects of a 3-week treatment with tiotropium on walking capacity in chronic obstructive pulmonary disease (COPD). After familiarisation with study procedures, 36 patients were randomised to receive tiotropium 18 µg once daily or a matching placebo in a double-blind, parallel-group study. Pre- (trough) and 2-h post-dose pulmonary function was measured. An endurance shuttle walk was then completed. The same procedures were repeated after 3 weeks of treatment. Ventilatory parameters were monitored during exercise. At 3 weeks, tiotropium significantly improved walking endurance time in comparison with placebo, with a mean±sd between-group difference of 128±141 s (p=0.017). At 3 weeks, trough values for forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were significantly improved with tiotropium in comparison with placebo. The post-dose response to tiotropium was statistically superior to placebo after the first dose and after 3 weeks of treatment for FEV(1), FVC and inspiratory capacity. Ventilation and tidal volume at the end of walking were significantly improved with tiotropium. 3 weeks of tiotropium resulted in a greater walking endurance in patients with COPD. Improvements in FEV(1), maximal ventilation and tidal volume may contribute to this enhanced exercise capacity.

Natriuretic peptides and troponins in pulmonary embolism: a meta-analysis.

BACKGROUND: The role of biomarkers such as B-type natriuretic peptides (BNP and NT-proBNP) and troponins in risk stratification of acute pulmonary embolism (APE) is still debated. A meta-analysis was performed to assess the association between raised natriuretic peptide levels, alone or in conjunction with troponins, and all-cause and APE-related mortality, serious adverse events and echographic right ventricular dysfunction. METHODS: MEDLINE and EMBASE databases were searched and conference abstracts were hand searched up to February 2008. Studies were included if a 2x2 table could be constructed based on natriuretic peptide results and at least one of the outcomes. RESULTS: Twenty-three studies were included (1127 patients). Raised natriuretic peptide levels were significantly associated with all-cause mortality (odds ratio (OR) 6.2; 95% confidence interval (CI) 3.0 to 12.7), APE-related mortality (OR 5.0; 95% CI 2.2 to 11.5) and serious adverse events (OR 6.7; 95% CI 3.9 to 11.6), with homogeneity across studies. Among patients with raised natriuretic peptide levels, increased serum troponins were associated with a further increase in the risk of adverse outcomes. Analysis of the accuracy of natriuretic peptides in detecting right ventricular dysfunction was limited by heterogeneity across studies. BNP appeared to have better sensitivity and specificity than NT-proBNP in detecting right ventricular dysfunction. CONCLUSIONS: Raised levels of B-type natriuretic peptides identified a subset of patients with APE at higher risk of adverse outcomes. Among patients with raised natriuretic peptide levels, increased troponins were found to be an independent prognostic marker. The results of this meta-analysis may have important clinical implications in the management of APE.

Hypersensitivity pneumonitis.

The first few cases of hypersensitivity pneumonitis (HP) were described in the early 20th century in farmers exposed to moldy hay or straw. As then, HP has been ascribed to multiple inhaled antigens found in a large variety of environmental settings. Hypersensitivity pneumonitis results from an exaggerated immune response, which gives rise to acute infection-like symptoms or to progressive, sometimes irreversible lung damage. The diagnosis is based on a combination of clinical characteristics of the disease. Clinical diagnostic criteria have recently been published. The immune mechanisms leading to HP are still incompletely understood. Initially, believed to be a classes III and IV immune response, we now have a clearer understanding of the complex inflammatory events involved. These include the release of pro inflammatory cytokines and a decrease in the immune control mechanisms via surfactant, dendritic and T-regulatory cells. Despite the improved understanding, the treatment and outcome of HP have not changed. Oral corticosteroids remain the only effective drugs and contact withdrawal constitutes the ideal solution. If unchecked, HP can lead to irreversible lung damage in the form of fibrosis or emphysema, respiratory insufficiency and even death.

Assessing the impact of pulmonary rehabilitation on functional status in COPD.

BACKGROUND: The optimal way of assessing the impact of pulmonary rehabilitation on functional status in chronic obstructive pulmonary disease (COPD) is currently unknown. The minimal clinically important difference for the constant work rate cycling exercise test also needs to be investigated to facilitate its interpretation. A study was undertaken to evaluate the changes in the 6-min walking test and in the constant work rate cycle endurance test immediately following and 1 year after pulmonary rehabilitation, together with the importance of these changes in terms of health status in patients with COPD. METHODS: Patients with COPD of mean (SD) age 65 (8) years and mean (SD) forced expiratory volume in 1 s (FEV1) 45 (15)% predicted were recruited from a multicentre prospective cohort study and evaluated at baseline, immediately after a pulmonary rehabilitation programme (n = 157) and at 1 year (n = 106). The 6-min walking test and the cycle endurance test were performed at each evaluation. Health status was evaluated with the St George Respiratory Questionnaire. RESULTS: Following pulmonary rehabilitation, cycle endurance time increased (198 (352) s, p<0.001) and stayed over baseline values at 1 year (p<0.001). The 6-min walking distance also showed improvements following rehabilitation (25 (52) m, p<0.001) but returned to baseline values at the 1-year follow-up. Changes in cycle endurance time were more closely associated with changes in health status than with the 6-min walking test. An improvement of 100-200 s in the cycle endurance time was associated with clinically meaningful changes in the St George Respiratory Questionnaire scores. CONCLUSIONS: The cycle endurance test was more responsive than the 6-min walking test in detecting improvement in exercise tolerance following pulmonary rehabilitation, and was also better correlated with improvements in health status. An improvement in the cycle endurance time of 100-200 s appeared to be clinically meaningful.

Anxiety and depression in end-stage COPD.

Although feelings of anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), estimates of their prevalence vary considerably. This probably reflects the variety of scales and methods used to measure such symptoms. Regardless of whether anxiety and depression are considered separately or as a single construct, their impact on COPD patients is important. A heightened experience of dyspnoea is likely to be a contributing factor to anxiety. Feelings of depression may be precipitated by the loss and grief associated with the disability of COPD. Smoking has been associated with nicotine addiction, and the factors that contribute to smoking may also predispose to anxiety and depressive disorders. Randomised controlled trials indicate that exercise training and carefully selected pharmacological therapy are often effective in ameliorating anxiety and depression. Most medical illnesses are influenced by the psychological responses and coping mechanisms that patients use. However, anxiety and depression are associated with dyspnoea, fatigue and altered sleep, all of which also occur in COPD. An understanding of the psychological history and coping mechanisms of patients and the role of anxiety and depressive reactions to illness may enable clinicians to reduce these symptoms and improve quality of life among patients with chronic obstructive pulmonary disease.

Endurance shuttle walking test: responsiveness to salmeterol in COPD.

Few studies have shown that the endurance shuttle walking test (ESWT) is responsive to treatment in patients with chronic obstructive pulmonary disease (COPD). This exercise test needs to be further investigated because of its relevance for activity of daily living. The aim of the present study was to evaluate, in patients with COPD, the responsiveness of the ESWT in detecting improvement in walking performance after a single dose of salmeterol. In a randomised, double-blind, placebo-controlled crossover trial, 20 patients with COPD performed two ESWT at 80% of peak capacity 2.5 h after inhaling either a placebo or 50 microg of salmeterol. Cardiorespiratory parameters were monitored during each walking test. Inspiratory capacities and Borg ratings for dyspnoea were obtained every other minute throughout the tests. Compared with placebo, salmeterol produced a significant change in lung function and a significant improvement in walking performance (mean+/-sd difference in time: 117+/-20 s; difference in distance: 160+/-277 m). At isotime (the latest exercise time that was reached on both ESWT), a significant reduction in dyspnoea was observed after bronchodilation. Bronchodilation with salmeterol reduced dyspnoea during walking and improved walking capacity in patients with chronic obstructive pulmonary disease. These findings provide further support for the use of the endurance shuttle walking test as an evaluative tool in chronic obstructive pulmonary disease.

Outcomes following a negative computed tomography pulmonary angiography according to pulmonary embolism prevalence: a meta-analysis of the management outcome studies.

Essentials Computed tomographic pulmonary angiography (CTPA) is used to exclude pulmonary embolism. This meta-analysis explores the occurrence of venous thromboembolic events (VTE) after a CTPA. Occurrence of VTE after a negative CTPA is ˜8% in study subgroups with a prevalence of PE ≥ 40%. CTPA may be insufficient to safely rule out VTE as a stand-alone diagnostic test for this subgroup. SUMMARY: Background Outcome studies have reported the safety of computed tomographic pulmonary angiography (CTPA) as a stand-alone imaging technique to rule out pulmonary embolism (PE). Whether this can be applied to all clinical probabilities remains controversial. Objectives We performed a meta-analysis to determine the proportion of patients with venous thromboembolic events (VTE) despite a negative CTPA according to pretest PE prevalence. Methods We searched MEDLINE, EMBASE and the Cochrane Library (January 1990 to May 2017) for outcome studies recruiting patients with suspected PE using CTPA as a diagnostic strategy. The primary outcome was the cumulative occurrence of VTE at 3 months following a negative CTPA. Results Twenty-two different studies were identified. VTE was confirmed in 2.4% of patients (95% CI, 1.3-3.8%) either at the time of the index event or in the 3 months follow-up. Subgroup analyses suggested that the cumulative occurrence of VTE was related to pretest prevalence of PE, as VTE occurred in 1.8% (95% CI, 0.5-3.7%), 1.4% (95% CI, 0.7-2.3%), 1.0% (95% CI, 0.5-1.8%) and 8.1% (95% CI, 3.5-14.5%) of subgroups of patients with a PE prevalence < 20%, 20-29%, 30-39% and ≥ 40%, respectively. This was further confirmed using meta-regression analysis. Conclusions The negative predictive value of CTPA for VTE varies according to pretest prevalence of PE, and is likely to be insufficient to safely rule out VTE as a stand-alone diagnostic test amongst patients at the highest pretest probability of VTE. Prospective studies are required to validate the appropriate diagnostic algorithm for this subgroup of patients.

Oxygen therapy during exercise training in chronic obstructive pulmonary disease.

BACKGROUND: Exercise training within the context of pulmonary rehabilitation improves outcomes of exercise capacity, dyspnea and health-related quality of life in individuals with chronic obstructive pulmonary disease (COPD). Supplemental oxygen in comparison to placebo increases exercise capacity in patients performing single-assessment exercise tests. The addition of supplemental oxygen during exercise training may enable individuals with COPD to tolerate higher levels of activity with less exertional symptoms, ultimately improving quality of life. OBJECTIVES: To determine how supplemental oxygen in comparison to control (compressed air or room air) during the exercise-training component of a pulmonary rehabilitation program affects exercise capacity, dyspnea and health-related quality of life in individuals with COPD. SEARCH STRATEGY: All records in the Cochrane Airways Group Specialized Register of trials coded as 'COPD' were searched using the following terms: (oxygen* or O2*) AND (exercis* or train* or rehabilitat* or fitness* or physical* or activ* or endur* or exert* or walk* or cycle*). Searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE and CINAHL databases identified studies. The last search was carried out in June 2006. SELECTION CRITERIA: Only randomized controlled trials (RCTs) comparing oxygen-supplemented exercise training to non-supplemented exercise training (control group) were considered for inclusion. Participants were 18 years or older, diagnosed with COPD and did not meet criteria for long-term oxygen therapy. No studies with mixed populations (pulmonary fibrosis, cystic fibrosis, etc) were included. Exercise training was greater than or equal to three weeks in duration and included a minimum of two sessions a week. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion in the review and extracted data. Weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated using a random-effects model. Missing data were requested from authors of primary studies. MAIN RESULTS: Five RCTs met the inclusion criteria. The maximum number of studies compared in the meta-analysis was three (31 on oxygen versus 32 control participants), because all included studies did not measure the same outcomes. When two studies were pooled, statistically significant improvements of oxygen-supplemented exercise training were found in constant power exercise time, WMD 2.68 minutes (95% CI 0.07 to 5.28 minutes). Supplemental oxygen increased the average exercise time from 6 to 14 minutes; the control intervention increased average exercise time from 6 to 12 minutes. Constant power exercise end-of-test Borg score (on a scale from 1 to 10) also showed statistically significant improvements with oxygen-supplemented exercise training, WMD -1.22 units (95% CI -2.39 to -0.06). One study showed a significant improvement in the change of Borg score after the shuttle walk test, by -1.46 units (95% CI -2.72 to -0.19). There were no significant differences in maximal exercise outcomes, functional exercise outcomes (six-minute walk test), shuttle walk distance, health-related quality of life or oxygenation status. According to the GRADE system most outcomes were rated as low quality because they were limited by study quality. AUTHORS' CONCLUSIONS: This review provides little support for oxygen supplementation during exercise training for individuals with COPD, but the evidence is very limited. Studies with larger number of participants and strong design are required to permit strong conclusions, especially for functional outcomes such as symptom alleviation, health-related quality of life and ambulation.

Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. A Cochrane systematic review.

BACKGROUND: The widespread application of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function attributable to the programs. OBJECTIVES: To determine the impact of rehabilitation on health-related quality of life (QoL) and exercise capacity in patients with COPD. METHODS: We identified randomized controlled trials (RCTs) from the Cochrane Airways Group Specialised Register. We selected RCTs of rehabilitation in patients with COPD in which quality of life (QoL) and/or exercise capacity were measured. Rehabilitation was defined as exercise training for at least 4 weeks with or without education and/or psychological support. Control groups received conventional community care without rehabilitation. RESULTS: A total of 31 RCTs met the inclusion criteria. We found statistically significant improvements for all the outcomes. In 4 important domains of QoL (Chronic Respiratory Questionnaire scores for Dyspnea, Fatigue, Emotional function and Mastery), the effect was larger than the minimal clinically important difference. For exercise capacity, the effect was small and slightly below the threshold of clinical significance for the six-minute walking distance (WMD: 48 m; 95% CI: 32 to 65; n = 16 trials). CONCLUSIONS: Rehabilitation relieves dyspnea and fatigue, improves emotional function and enhances patients' control over their condition. These improvements are moderately large and clinically significant. Rehabilitation forms an important component of the management of COPD.

Evaluating the risk of pneumonia with inhaled corticosteroids in COPD: Retrospective database studies have their limitations SA.

An increased risk of non-fatal pneumonia has been documented in COPD patients treated with inhaled corticosteroids (ICS) in randomized clinical trials. Retrospective database analyses have been conducted to evaluate this signal in larger populations treated in the community. To understand how methodological choices may influence results in observational studies, we compared two recent Canadian studies which used health administrative databases from Quebec and Ontario and came to opposite conclusions on the risk of pneumonia in ICS treated COPD patients. Explanations for why the results of these studies diverged are explored. The Suissa analysis used RAMQ data from Quebec and showed an increased relative risk of serious pneumonia for current users of ICS compared to non users, RR = 1.69 (95% confidence interval, 1.63-1.75). The Gershon analysis used ODB data and showed no difference for pneumonia hospitalisation, RR = 1.01 (0.93-1.08). Reasons for differences in study findings include lack of validated definitions of COPD, poor selection of relevant exposure groups, channeling and confounding biases, and failure to perform on-treatment analyses for safety. CONCLUSION: Our study identifies methodological features that need consideration to increase robustness and minimize threats to internal validity of retrospective health administrative database studies.

An overview of obesity-specific quality of life questionnaires.

The measurement of quality of life in patients with obesity is useful to evaluate the effects of treatment (including bariatric surgery) and may influence the development of clinical pathways, service provision, healthcare expenditures and public health policy. Consequently, clinicians, researchers and policy makers must rely on valid measurement instruments. We reviewed 11 obesity-specific quality of life questionnaires and classified them according to their domain of interest and described their measurement properties (specifications, validity, reliability, responsiveness and interpretability). We found that (i) nine questionnaires were developed specifically to be used as evaluative instruments in clinical trials; (ii) only three targeted populations with morbid obesity (body mass index > 40 kg m(-2)); (iii) construct validity was properly studied in three questionnaires; (iv) demonstration of responsiveness from independent randomized controlled trials was available for two of the 11 questionnaires; (v) keys to interpretation of scores were provided for three questionnaires. Future research should include further validation and a better definition of the interpretability of existing instruments.

Pulmonary rehabilitation for chronic obstructive pulmonary disease.

BACKGROUND: The widespread application of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function attributable to the programs. This review updates that reported in 2001. OBJECTIVES: To determine the impact of rehabilitation on health-related quality of life (QoL) and exercise capacity in patients with COPD. SEARCH STRATEGY: We identified additional RCTs from the Cochrane Airways Group Specialised Register. Searches were current as of July 2004. SELECTION CRITERIA: We selected RCTs of rehabilitation in patients with COPD in which quality of life (QoL) and/or functional (FEC) or maximal (MEC) exercise capacity were measured. Rehabilitation was defined as exercise training for at least four weeks with or without education and/or psychological support. Control groups received conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS: We calculated weighted mean differences (WMD) using a random-effects model. We requested missing data from the authors of the primary study. MAIN RESULTS: We included the 23 randomized controlled trials (RCTs) in the 2001 Cochrane review. Eight additional RCTs (for a total of 31) met the inclusion criteria. We found statistically significant improvements for all the outcomes. In four important domains of QoL (Chronic Respiratory Questionnaire scores for Dyspnea, Fatigue, Emotional function and Mastery), the effect was larger than the minimal clinically important difference of 0.5 units (for example: Dyspnoea score: WMD 1.0 units; 95% confidence interval: 0.8 to 1.3 units; n = 12 trials). Statistically significant improvements were noted in two of the three domains of the St. Georges Respiratory Questionnaire. For FEC and MEC, the effect was small and slightly below the threshold of clinical significance for the six-minute walking distance (WMD: 48 meters; 95% CI: 32 to 65; n = 16 trials). AUTHORS' CONCLUSIONS: Rehabilitation relieves dyspnea and fatigue, improves emotional function and enhances patients' sense of control over their condition. These improvements are moderately large and clinically significant. Rehabilitation forms an important component of the management of COPD.

Efficacy of theophylline in people with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis.

OBJECTIVES: To determine the efficacy of oral theophylline compared with placebo in people with stable chronic obstructive pulmonary disease (COPD). METHODS: Systematic review of randomized-controlled trials comparing oral theophylline with placebo for a minimum of 7 days in people with stable COPD. RESULTS: Twenty randomized-controlled trials were included in this review. The following outcomes showed significant improvement with theophylline compared with placebo: FEV1 and FVC both improved with theophylline (weighted mean difference [WMD] 0.10 L; 95% confidence interval [95% CI] 0.04-0.16 and WMD 0.21 L; 95% CI 0.10-0.32, respectively). VO2 max also improved with theophylline (WMD 195.27mL/ min; 95% CI 112.71-277.83), as did PaO2 and PaCO2 (WMD 3.18 mmHg; 95% CI 1.23-5.13 and WMD -2.36mmHg; 95% CI -3.52 to -1.21, respectively). Patients preferred theophylline over placebo (relative risk 2.27; 95% CI 1.26-4.11). Theophylline increased the risk of nausea compared with placebo (RR 7.67; 95% CI 1.47-39.94). CONCLUSION: This review has shown that theophylline still has a role in the management of stable COPD, and is preferred by patients over placebo. However, the benefits of theophylline in stable COPD have to be weighed against the risk of adverse effects.

Nutritional supplementation for stable chronic obstructive pulmonary disease.

BACKGROUND: Low body weight in patients with chronic obstructive pulmonary disease (COPD) is associated with an impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity and higher mortality rate when compared to adequately nourished individuals with this disease. Nutritional support may therefore be a useful part of their comprehensive care. OBJECTIVES: To conduct a systematic review of randomised controlled trials (RCTs) to clarify whether nutritional supplementation (caloric supplementation for at least 2 weeks) improved anthropometric measures, pulmonary function, respiratory muscle strength and functional exercise capacity in patients with stable COPD. SEARCH STRATEGY: Randomized controlled trials (RCTs) were identified from the Cochrane Airways Group register of RCTs, a hand-search of abstracts presented at international meetings and consultation with experts. Searches are current as of March 2004. SELECTION CRITERIA: Two reviewers independently selected trials for inclusion, assessed quality and extracted the data. DATA COLLECTION AND ANALYSIS: Within each trial and for each outcome, we calculated an effect size. The effect sizes were then pooled by a random-effects model. Homogeneity among the effect sizes was also tested. MAIN RESULTS: Eleven studies recruiting 352 participants met the inclusion criteria. Eight papers were considered as high quality. Two studies were double-blinded. For each of the outcomes studied, the effect of nutritional support was small: the 95% confidence intervals around the pooled effect sizes all included zero. The effect of nutritional support was homogeneous across studies. AUTHORS' CONCLUSIONS: Nutritional support had no significant effect on anthropometric measures, lung function or exercise capacity in patients with stable COPD.

Critical appraisal of clinical practice guidelines targeting chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is so prevalent that the endorsement of management strategies by professional organizations issuing clinical practice guidelines (CPGs) will likely influence the clinical and financial resources allocated to this condition. OBJECTIVES: To examine the content of and to critically appraise the CPGs targeting COPD. METHODS: We identified, through a MEDLINE search (from January 1990 to May 1999) and contacts with experts and professional organizations, the CPGs for the overall management of COPD. We assessed the guidelines according to an index of quality measuring 3 dimensions: the rigor of development, the context and content, and the extent to which the dissemination and implementation have been addressed. The recommendations were also examined and compared. RESULTS: Of the 15 CPGs we included, none was based on a systematic review of the literature. Two were independently reviewed before their release, 1 included strategies for dissemination and implementation, and 1 estimated the economic implications associated with its recommendations. The recommendations were often difficult to interpret (reviewers' agreement: kappa median, 0.41). When unanimity existed regarding the benefits of a given management modality (such as respiratory rehabilitation), discrepancies were often identified in the application of the recommendation. CONCLUSIONS: The methodological quality of CPGs targeting COPD is limited, and there are disparities among many of their recommendations. Despite there being several CPGs worldwide, there is a need for an evidence-based summary of the literature to serve as a resource for those who provide health care to individuals with COPD.

Pharmacokinetic study of lorazepam overdosage.

The authors describe three patients who attempted to commit suicide by ingesting overdoses of lorazepam, an intermediate-acting benzodiazepine that, unlike diazepam, has no active metabolites. All three patients were clinically well within 24-30 hours of ingestion, although high lorazepam concentrations persisted. The authors point out that the elimination half-life of lorazepam after extremely high doses have been ingested is approximately the same as that found after ingestion of usual therapeutic doses.