John R. Swiston

Economic burden of asthma: a systematic review

BackgroundAsthma is associated with enormous healthcare expenditures that include both direct and indirect costs. It is also associated with the loss of future potential earnings related to both morbidity and mortality. The objective of the study is to determine the burden of disease costs associated with asthma.MethodsWe performed a systematic search of MEDLINE, EMBASE, CINAHL, CDSR, OHE-HEED, and Web of Science Databases between 1966 and 2008.ResultsSixty-eight studies met the inclusion criteria. Hospitalization and medications were found to be the most important cost driver of direct costs. Work and school loss accounted for the greatest percentage of indirect costs. The cost of asthma was correlated with comorbidities, age, and disease severity.ConclusionDespite the availability of effective preventive therapy, costs associated with asthma are increasing. Strategies including education of patients and physicians, and regular follow-up are required to reduce the economic burden of asthma.

The effect of statins on mortality from severe infections and sepsis: a systematic review and meta-analysis.

PURPOSE The aim of this study was to systematically review the literature on the effect of statins on mortality in patients with infection and/or sepsis. MATERIALS AND METHODS MEDLINE, EMBASE, PapersFirst, and the Cochrane collaboration and the Cochrane Register of controlled trials were searched and were current as of December 2009. Randomized, double-blind or single-blind, placebo-controlled studies; observational cohort studies (retrospective and prospective); and case-controlled studies were included. Types of participants included adult and pediatric subjects with sepsis or various other types of infection. Exposure was defined as the use of a statin for any indication. The primary outcome chosen was mortality from any cause, and secondary outcomes included 30-day mortality, in-hospital mortality, mortality from pneumonia, mortality from bacteremia, mortality from sepsis, and mortality from mixed infection. RESULTS A total of 20 studies were included in the analysis, 18 being cohort studies (12 retrospective, 6 prospective), 1 matched cohort study with 2 case-control studies, and 1 randomized control trial. Meta-analysis for various infection-related outcomes revealed the following pooled odds ratios all in favor of statin use vs non: 0.61 (95% confidence interval [CI], 0.48-0.73) for 30-day mortality (n = 7), 0.38 (95% CI, 0.13-0.64) for in-hospital mortality (n = 7), 0.63 (95% CI, 0.55-0.71) for pneumonia-related mortality (n = 7), 0.33 (95% CI, 0.09-0.75) for bacteremia-related mortality (n = 4), 0.40 (95% CI, 0.23-0.57) for sepsis-related mortality (n = 4), and 0.50 (95% CI, 0.18-0.83) for mixed infection-related mortality (n = 4). CONCLUSIONS This meta-analysis demonstrated a protective effect for statins in patients with sepsis and/or other infections compared to placebo for various infection-related outcomes. However, our results are limited by the cohort design of the selected studies and the degree of heterogeneity among them, and as a result, further randomized trials are needed to validate the use of statins for sepsis and/or other infections.

Diagnostic accuracy of echocardiography for pulmonary hypertension: a systematic review and meta-analysis

Context Right heart catheterisation is the gold standard for the diagnosis of pulmonary hypertension. However, echocardiography is frequently used to screen for this disease and monitor progression over time because it is non-invasive, widely available and relatively inexpensive. Objective To perform a systematic review and quantitative meta-analysis to determine the correlation of pulmonary pressures obtained by echocardiography versus right heart catheterisation and to determine the diagnostic accuracy of echocardiography for pulmonary hypertension. Data sources MEDLINE, EMBASE, PapersFirst, the Cochrane collaboration and the Cochrane Register of controlled trials were searched and were inclusive as of February 2010. Study selection Studies were only included if a correlation coefficient or the absolute number of true-positive, false-negative, true-negative and false-positive observations was available, and the ‘reference standards’ were described clearly. Data extraction Two reviewers independently extracted the data from each study. Quality was assessed with the quality assessment for diagnostic accuracy studies. A random effects model was used to obtain a summary correlation coefficient and the bivariate model for diagnostic metaanalysis was used to obtain summary sensitivity and specificity values. Results 29 studies were included in the meta-analysis. The summary correlation coefficient between systolic pulmonary arterial pressure estimated from echocardiography versus measured by right heart catheterisation was 0.70 (95% CI 0.67 to 0.73; n=27). The summary sensitivity and specificity for echocardiography for diagnosing pulmonary hypertension was 83% (95% CI 73 to 90) and 72% (95% CI 53 to 85; n=12), respectively. The summary diagnostic OR was 13 (95% CI 5 to 31). Conclusions Echocardiography is a useful and noninvasive modality for initial measurement of pulmonary pressures but due to limitations, right heart catheterisation should be used for diagnosing and monitoring pulmonary hypertension.

Statins in COPD: A Systematic Review

BACKGROUND The 3-hydroxy 3-methylglutaryl coenzyme A reductase inhibitors (ie, statins) are widely used for the treatment of patients with hypercholesterolemia and cardiovascular disease. Emerging evidence suggests a beneficial effect of statins on the morbidity and mortality of patients with COPD. The objective of this study was to perform a systematic review of the literature evaluating the effect of statin therapy on outcomes in patients with COPD. METHODS Medline, Excerpta Medica Database, PapersFirst, and the Cochrane collaboration and Cochrane Register of controlled trials were searched. Randomized controlled trials (RCTs), observational cohort studies, case-control studies, and population-based analyses were considered for inclusion. RESULTS Nine studies were identified for review (four retrospective cohorts, one nested case-control study of a retrospective cohort, one retrospective cohort and case series, two population-based analyses, and one RCT). All studies showed a benefit from statin therapy for various outcomes in COPD patients, including the number of COPD exacerbations (n = 3), the number of and time to COPD-related intubations (n = 1), pulmonary function (eg, FEV(1) and FVC) [n = 1], exercise capacity (n = 1), mortality from COPD (n = 2), and all-cause mortality (n = 3). No studies describing a negative or neutral effect from statin therapy on outcomes in COPD patients were identified. CONCLUSIONS The current literature collectively suggests that statins may have a beneficial role in the treatment of COPD. However, the majority of published studies have inherent methodological limitations of retrospective studies and population-based analyses. There is a need for prospective interventional trials designed specifically to assess the impact of statins on clinically relevant outcomes in COPD.

Factors that prognosticate mortality in idiopathic pulmonary arterial hypertension: a systematic review of the literature.

RATIONALE There is a lack of consensus on factors that predict mortality in idiopathic pulmonary arterial hypertension (IPAH). Tests that can accurately predict prognosis are needed to guide treatment and counsel patients. METHODS We conducted a systematic review to identify factors that prognosticate mortality in IPAH. Study design, cohort size, comparison method, measured value, and statistical significance was extracted for eight pre-selected parameters [pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), mean right atrial pressure (mRAP), cardiac output, right ventricular end diastolic pressure, functional class, 6 min walk distance (6MWD), and diffusing capacity of carbon monoxide]. RESULTS 107 factors have been associated with mortality in IPAH. A reproducible predictive association with mortality was demonstrated for only 10 factors: functional class (14 studies), heart rate (10 studies), 6MWD (8 studies), pericardial effusion (5 studies), mPAP (10 studies), mRAP (17 studies), cardiac index (13 studies), stroke volume index (4 studies), PVR (10 studies), mixed venous PaO(2) or saturations (4 studies). Of the 8 factors chosen for detailed evaluation, there were at least half as many studies that evaluated the variable and did not find an association with mortality compared to those that did. CONCLUSIONS There is a large body of literature describing numerous factors that predict mortality in IPAH. Most factors have been assessed in very few studies. There are conflicting reports on the prognostic value of many factors. These discrepancies highlight the need to evaluate the literature in total when considering the utility of variables as prognostic factors in IPAH.

Pharmacotherapy in pulmonary arterial hypertension: a systematic review and meta-analysis

BackgroundPrevious meta-analyses of treatments for pulmonary arterial hypertension (PAH) have not shown mortality benefit from any individual class of medication.MethodsMEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through November 2009 for randomized trials that evaluated any pharmacotherapy in the treatment of PAH. Reference lists from included articles and recent review articles were also searched. Analysis included randomized placebo controlled trials of at least eight weeks duration and studies comparing intravenous medication to an unblinded control group.Results1541 unique studies were identified and twenty-four articles with 3758 patients were included in the meta-analysis. Studies were reviewed and data extracted regarding study characteristics and outcomes. Data was pooled for three classes of medication: prostanoids, endothelin-receptor antagonists (ERAs), and phosphodiesterase type 5 (PDE5) inhibitors. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for mortality, 6-minute walk distance, dyspnea scores, hemodynamic parameters, and adverse effects. Mortality in the control arms was a combined 4.2% over the mean study length of 14.9 weeks. There was significant mortality benefit with prostanoid treatment (RR 0.49, CI 0.29 to 0.82), particularly comparing intravenous agents to control (RR 0.30, CI 0.14 to 0.63). Mortality benefit was not observed for ERAs (RR 0.58, CI 0.21 to 1.60) or PDE5 inhibitors (RR 0.30, CI 0.08 to 1.08). All three classes of medication improved other clinical and hemodynamic endpoints. Adverse effects that were increased in treatment arms include jaw pain, diarrhea, peripheral edema, headache, and nausea in prostanoids; and visual disturbance, dyspepsia, flushing, headache, and limb pain in PDE5 inhibitors. No adverse events were significantly associated with ERA treatment.ConclusionsTreatment of PAH with prostanoids reduces mortality and improves multiple other clinical and hemodynamic outcomes. ERAs and PDE5 inhibitors improve clinical and hemodynamic outcomes, but have no proven effect on mortality. The long-term effects of all PAH treatment requires further study.

Risk factors and outcomes associated with chronic obstructive pulmonary disease exacerbations requiring hospitalization.

BACKGROUND Acute respiratory exacerbations are the most frequent cause of medical visits, hospitalization and death for chronic obstructive pulmonary disease (COPD) patients and, thus, exert a significant social and economic burden on society. OBJECTIVE To identify the risk factors associated with hospital readmission(s) for acute exacerbation(s) of COPD (AECOPD). METHODS A review of admission records from three large urban hospitals in Vancouver, British Columbia, identified 310 consecutive patients admitted for an AECOPD between April 1, 2001, and December 31, 2002. Logistic regression analysis was performed to identify risk factors for readmissions following an AECOPD. RESULTS During the study period, 38% of subjects were readmitted at least once. The mean (+/- SD) duration from the index admission to the first readmission was 5+/-4.08 months. Comparative analysis among the three hospitals identified a significant difference in readmission rates (54%, 36% and 18%, respectively). Logistic regression analysis revealed that preadmission home oxygen use (OR 2.55; 95%CI 1.45 to 4.42; P=0.001), history of a lung infection within the previous year (OR 1.73; 95% CI 1.01 to 2.97; P=0.048), other chronic respiratory disease (OR 1.78; 95% CI 1.06 to 2.99; P=0.03) and shorter length of hospital stay (OR 0.97; 95% CI 0.945 to 0.995; P=0.021) were independently associated with frequent readmissions for an AECOPD. CONCLUSIONS Hospital readmission rates for AECOPD were high. Only four clinical factors were found to be independently associated with COPD readmission. There was significant variability in the readmission rate among hospitals. This variability may be a result of differences in the patient populations that each hospital serves or may reflect variability in health care delivery at different institutions.

Intrapleural Fibrinolytic Therapy for Treatment of Adult Parapneumonic Effusions and Empyemas: A Systematic Review and Meta-analysis

BACKGROUND The purpose of our study was to conduct a systematic review and meta-analysis of all randomized controlled trials to date comparing fibrinolytics with placebo to clarify their current role in the management of parapneumonic effusions and empyemas. METHODS MEDLINE, EMBASE, PapersFirst, and the Cochrane Collaboration and the Cochrane Register of controlled trials were searched. All searches were inclusive as of October 2011. Two investigators independently reviewed articles and extracted data. Quality was assessed with the Cochrane concealment of allocation approach and the Jadad criteria. RESULTS Seven randomized controlled studies (total number of patients, 801) comparing fibrinolytic therapy with placebo were included in the meta-analysis. Fibrinolytic therapy was beneficial for the outcomes of treatment failure (surgical intervention or death) (risk ratio [RR], 0.50; 95% CI, 0.28-0.87) and surgical intervention alone (RR, 0.61; 95% CI, 0.45-0.82). There was no difference in mean duration of hospital stay (standard mean difference, -0.69; 95% CI, -1.54-0.16) or death (RR, 1.14; 95% CI, 0.74-1.74). CONCLUSIONS This meta-analysis does reveal that fibrinolytic therapy is potentially beneficial in the management of parapneumonic effusions and empyemas in the adult population. Although there is insufficient evidence to support the routine use of this therapy for all parapneumonic effusions/empyemas, fibrinolytic therapy may be considered in patients with loculated pleural effusions, because it may prevent the need for surgical intervention. Further randomized controlled trials with adequate power are needed to definitively address the effect of fibrinolytics and the combination of fibrinolytics and deoxyribonuclease on the clinical outcomes outlined in this analysis in patients with parapneumonic effusions/empyemas.

Original ResearchPulmonary ProceduresIntrapleural Fibrinolytic Therapy for Treatment of Adult Parapneumonic Effusions and Empyemas: A Systematic Review and Meta-analysis

BACKGROUND The purpose of our study was to conduct a systematic review and meta-analysis of all randomized controlled trials to date comparing fibrinolytics with placebo to clarify their current role in the management of parapneumonic effusions and empyemas. METHODS MEDLINE, EMBASE, PapersFirst, and the Cochrane Collaboration and the Cochrane Register of controlled trials were searched. All searches were inclusive as of October 2011. Two investigators independently reviewed articles and extracted data. Quality was assessed with the Cochrane concealment of allocation approach and the Jadad criteria. RESULTS Seven randomized controlled studies (total number of patients, 801) comparing fibrinolytic therapy with placebo were included in the meta-analysis. Fibrinolytic therapy was beneficial for the outcomes of treatment failure (surgical intervention or death) (risk ratio [RR], 0.50; 95% CI, 0.28-0.87) and surgical intervention alone (RR, 0.61; 95% CI, 0.45-0.82). There was no difference in mean duration of hospital stay (standard mean difference, -0.69; 95% CI, -1.54-0.16) or death (RR, 1.14; 95% CI, 0.74-1.74). CONCLUSIONS This meta-analysis does reveal that fibrinolytic therapy is potentially beneficial in the management of parapneumonic effusions and empyemas in the adult population. Although there is insufficient evidence to support the routine use of this therapy for all parapneumonic effusions/empyemas, fibrinolytic therapy may be considered in patients with loculated pleural effusions, because it may prevent the need for surgical intervention. Further randomized controlled trials with adequate power are needed to definitively address the effect of fibrinolytics and the combination of fibrinolytics and deoxyribonuclease on the clinical outcomes outlined in this analysis in patients with parapneumonic effusions/empyemas.

HIV and pulmonary arterial hypertension: a systematic review.

HIV‐related pulmonary arterial hypertension (PAH) is a rare entity but is associated with significant morbidity and mortality. The literature describing the outcomes of therapy for this disease is limited to case series and cohort studies. The objective of this study was to systematically review and synthesize the literature on HIV‐related PAH.