A Cost-Effectiveness Analysis of Azithromycin for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Rationale: Daily oral azithromycin therapy can reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (COPD). However, given its adverse events and additional costs, it is not known whether adding long-term azithromycin as an adjunct therapy to inhaled pharmacotherapy is cost effective. Objectives: The objective of this study was to evaluate the cost-effectiveness of add-on azithromycin therapy in COPD as recommended by contemporary COPD management guidelines. Methods: We extended a previously validated Canadian COPD policy model to include azithromycin-related inputs and outcomes. The cost-effectiveness of azithromycin was evaluated over a 20-year time horizon in patients who continue to exacerbate despite receiving maximal inhaled therapies. The benefit of azithromycin was modeled as a reduction in exacerbation rates. Adverse events included cardiovascular death, hearing loss, gastrointestinal symptoms, and antimicrobial resistance. The incremental cost-effectiveness ratio (ICER) was calculated with costs in 2020 Canadian dollars ($) and quality-adjusted life-years (QALYs) discounted at 1.5% per year. The analysis was stratified among patient subgroups based on exacerbation histories. Results: In patients with a positive exacerbation history (one or more events in the previous 12 mo), azithromycin was associated with $49,732 costs, 7.65 QALYs, and 10.95 exacerbations per patient over 20 years. The corresponding values were $48,436, 7.62, and 11.86 for the reference group, resulting in an ICER of $43,200 per QALY gained. In patients defined as frequent exacerbators (two or more moderate or one or more severe events in the past 12 mo), the ICER was reduced to $8,862 per QALY gained. In patients with no history of exacerbation, azithromycin had lower QALYs and higher costs than the reference group. Conclusions: Add-on azithromycin is cost effective in patients with a recent history of exacerbations at commonly accepted willingness-to-pay thresholds of $50,000-$100,000/QALY. Guidelines should consider recommending add-on azithromycin for patients who had at least one moderate or severe exacerbation in the past year, albeit more information about treatment efficacy would strengthen this recommendation.

IMplementing Predictive Analytics towards efficient COPD Treatments (IMPACT): protocol for a stepped-wedge cluster randomized impact study.

INTRODUCTION: Personalized disease management informed by quantitative risk prediction has the potential to improve patient care and outcomes. The integration of risk prediction into clinical workflow should be informed by the experiences and preferences of stakeholders, and the impact of such integration should be evaluated in prospective comparative studies. The objectives of the IMplementing Predictive Analytics towards efficient chronic obstructive pulmonary disease (COPD) treatments (IMPACT) study are to integrate an exacerbation risk prediction tool into routine care and to determine its impact on prescription appropriateness (primary outcome), medication adherence, quality of life, exacerbation rates, and sex and gender disparities in COPD care (secondary outcomes). METHODS: IMPACT will be conducted in two phases. Phase 1 will include the systematic and user-centered development of two decision support tools: (1) a decision tool for pulmonologists called the ACCEPT decision intervention (ADI), which combines risk prediction from the previously developed Acute COPD Exacerbation Prediction Tool with treatment algorithms recommended by the Canadian Thoracic Society's COPD pharmacotherapy guidelines, and (2) an information pamphlet for COPD patients (patient tool), tailored to their prescribed medication, clinical needs, and lung function. In phase 2, we will conduct a stepped-wedge cluster randomized controlled trial in two outpatient respiratory clinics to evaluate the impact of the decision support tools on quality of care and patient outcomes. Clusters will be practicing pulmonologists (n ≥ 24), who will progressively switch to the intervention over 18 months. At the end of the study, a qualitative process evaluation will be carried out to determine the barriers and enablers of uptake of the tools. DISCUSSION: The IMPACT study coincides with a planned harmonization of electronic health record systems across tertiary care centers in British Columbia, Canada. The harmonization of these systems combined with IMPACT's implementation-oriented design and partnership with stakeholders will facilitate integration of the tools into routine care, if the results of the proposed study reveal positive association with improvement in the process and outcomes of clinical care. The process evaluation at the end of the trial will inform subsequent design iterations before largescale implementation. TRIAL REGISTRATION: NCT05309356.

Cost Effectiveness of Case Detection Strategies for the Early Detection of COPD.

OBJECTIVES: The value of early detection and treatment of chronic obstructive pulmonary disease (COPD) is currently unknown. We assessed the cost effectiveness of primary care-based case detection strategies for COPD. METHODS: A previously validated discrete event simulation model of the general population of COPD patients in Canada was used to assess the cost effectiveness of 16 case detection strategies. In these strategies, eligible patients (based on age, smoking history, or symptoms) received the COPD Diagnostic Questionnaire (CDQ) or screening spirometry, at 3- or 5-year intervals, during routine visits to a primary care physician. Newly diagnosed patients received treatment for smoking cessation and guideline-based inhaler pharmacotherapy. Analyses were conducted over a 20-year time horizon from the healthcare payer perspective. Costs are in 2019 Canadian dollars ($). Key treatment parameters were varied in one-way sensitivity analysis. RESULTS: Compared to no case detection, all 16 case detection scenarios had an incremental cost-effectiveness ratio (ICER) below $50,000/QALY gained. In the most efficient scenario, all patients aged ≥ 40 years received the CDQ at 3-year intervals. This scenario was associated with an incremental cost of $287 and incremental effectiveness of 0.015 QALYs per eligible patient over the 20-year time horizon, resulting in an ICER of $19,632/QALY compared to no case detection. Results were most sensitive to the impact of treatment on the symptoms of newly diagnosed patients. CONCLUSIONS: Primary care-based case detection programs for COPD are likely to be cost effective if there is adherence to best-practice recommendations for treatment, which can alleviate symptoms in newly diagnosed patients.

Trends in prescriptions and costs of inhaled medications in chronic obstructive pulmonary disease: a 19-year population-based study from Canada.

Background: The patterns of medication use in chronic obstructive pulmonary disease (COPD) may change over time due to the availability of new medications, updates in guideline-based recommendations, and changes in patient and care provider preferences. Objectives: To document population-level trends of filled prescriptions and costs for major classes of inhaled COPD therapies. Method: We used administrative health databases of the province of British Columbia, Canada, from 1997 to 2015, to create a retrospective cohort of COPD patients. We documented the percentage of patients receiving major inhaled COPD-related medications, including short-acting beta-2 adrenoreceptor agonists (SABA), long-acting beta-2 adrenoreceptor agonists (LABA), inhaled corticosteroids (ICS), short-acting muscarinic receptor antagonists (SAMA), and long-acting muscarinic receptor antagonists (LAMA). We quantified the average, and relative annual change in, dispensed quantities and costs (in 2015 Canadian dollars [$]) of medications. Combination therapy was assessed as the proportion of time covered by two or more long-acting medications of different classes. Results: A total of 176,338 patients were included in the final cohort (mean age at entry 68.7, 48.5% female). In 2015, the most common medication was ICS (45.7% of the patients), followed by LABA (36.5%). LAMA was the least used medication (18.9%). The number of filled prescriptions per patient per year for LAMA (+7.8% per year) and LABA (+4.9%) increased, while they decreased for SAMA (-6.3%) and SABA (-3.8%), and remained relatively constant for ICS. The average annual per-patient costs of inhaled medications were $570.8 in 2015, which was double the costs from 1997. Single-inhaler ICS/LABA had the highest rate of increase (11.6% per year), and comprised 53.7% of the total costs of inhalers in 2015. In 2015, 28.5% of the patient time was on combination therapies, with 7.1% on triple ICS/LABA/LAMA therapy. Conclusion: Utilization of inhaled therapies for COPD has changed significantly over time. The low utilization of LAMA and high utilization of combination therapies (particularly those containing ICS) do not seem to be aligned with COPD treatment guidelines.

Economic burden of multimorbidity in patients with severe asthma: a 20-year population-based study.

BACKGROUND: The economic impact of multimorbidity in severe or difficult-to-treat asthma has not been comprehensively investigated. AIMS: To estimate the incremental healthcare costs of coexisting chronic conditions (comorbidities) in patients with severe asthma, compared with non-severe asthma and no asthma. METHODS: Using health administrative data in British Columbia, Canada (1996-2016), we identified, based on the intensity of drug use and occurrence of exacerbations, individuals who experienced severe asthma in an incident year. We also constructed matched cohorts of individuals without an asthma diagnosis and those who had mild/dormant or moderate asthma (non-severe asthma) throughout their follow-up. Health service use records during follow-up were categorised into 16 major disease categories based on the International Classification of Diseases. Incremental costs (in 2016 Canadian Dollars, CAD$1=US$0.75=£0.56=€0.68) were estimated as the adjusted difference in healthcare costs between individuals with severe asthma compared with those with non-severe asthma and non-asthma. RESULTS: Relative to no asthma, incremental costs of severe asthma were $2779 per person-year (95% CI 2514 to 3045), with 54% ($1508) being attributed to comorbidities. Relative to non-severe asthma, severe asthma was associated with incremental costs of $1922 per person-year (95% CI 1670 to 2174), with 52% ($1003) being attributed to comorbidities. In both cases, the most costly comorbidity was respiratory conditions other than asthma ($468 (17%) and $451 (23%), respectively). CONCLUSIONS: Comorbidities accounted for more than half of the incremental medical costs in patients with severe asthma. This highlights the importance of considering the burden of multimorbidity in evidence-informed decision making for patients with severe asthma.

The Impact of Care Specialty on Survival-Adjusted Medical Costs of COPD Patients After a Hospitalization: a longitudinal analysis.

BACKGROUND: Little is known about the impact of care provider's specialty on the medical costs of COPD patients over time. OBJECTIVE: To compare the long-term medical costs between newly hospitalized COPD patients whose post-discharge care was initiated by a pulmonary specialist versus by a general practitioner. DESIGN: Retrospective matched cohort study. PARTICIPANTS: We identified patients with an incident COPD-related hospitalization from the administrative health database (January 1, 1996, to December 31, 2012) of British Columbia, Canada. MAIN MEASURES: Patients were categorized as receiving specialist care or primary care within the first 90 days after discharge from an incident COPD-related hospitalization. Using propensity scores, we matched each patient who initially received specialist care to a patient who received primary care based on demographics, COPD severity, comorbidity, and admission time. A survival-adjusted, multi-part generalized linear model was used to estimate direct medical costs (in 2015 Canadian dollars, [$], including inpatient, outpatient, pharmacy, and community care costs) as overall and as COPD-specific and comorbidity-related costs over the following 5 years. KEY RESULTS: The sample included 7710 patients under each group. The initial specialist-care recipients had a modestly higher 5-year survival than the generalist-care recipients (0.564 [95% CI 0.535, 0.634] vs 0.555 [95% CI 0.525, 0.625]; P < .001). Meanwhile, the former incurred $2809 higher all-cause medical costs over 5 years compared to the latter (95% CI $2343, $2913; P < .001), mainly driven by higher medication costs (difference $1782 [95% CI $1658, $1830]; P < .001) particularly related to COPD medications ($1170 [95% CI $1043, $1225]; P < .001). Specialist care recipients also incurred higher costs of COPD-related hospitalization ($1144 [95% CI $650, $1221]; P < .001). CONCLUSIONS: Compared to generalist care, specialist care following COPD hospitalization is slightly more expensive, mainly driven by medication costs especially COPD-specific medications. Future studies should compare differences in health-related quality of life and COPD functional status.

Characterizing undiagnosed chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: A significant proportion of patients with chronic obstructive pulmonary disease (COPD) remain undiagnosed. Characterizing these patients can increase our understanding of the 'hidden' burden of COPD and the effectiveness of case detection interventions. METHODS: We conducted a systematic review and meta-analysis to compare patient and disease factors between patients with undiagnosed persistent airflow limitation and those with diagnosed COPD. We searched MEDLINE and EMBASE for observational studies of adult patients meeting accepted spirometric definitions of COPD. We extracted and pooled summary data on the proportion or mean of each risk factor among diagnosed and undiagnosed patients (unadjusted analysis), and coefficients for the adjusted association between risk factors and diagnosis status (adjusted analysis). RESULTS: Two thousand eighty-three records were identified through database searching and 16 articles were used in the meta-analyses. Diagnosed patients were less likely to have mild (v. moderate to very severe) COPD (odds ratio [OR] 0.30, 95%CI 0.24-0.37, 6 studies) in unadjusted analysis. This association remained significant but its strength was attenuated in the adjusted analysis (OR 0.72, 95%CI 0.58-0.89, 2 studies). Diagnosed patients were more likely to report respiratory symptoms such as wheezing (OR 3.51, 95%CI 2.19-5.63, 3 studies) and phlegm (OR 2.16, 95% CI 1.38-3.38, 3 studies), had more severe dyspnea (mean difference in modified Medical Research Council scale 0.52, 95%CI 0.40-0.64, 3 studies), and slightly greater smoking history than undiagnosed patients. Patient age, sex, current smoking status, and the presence of coughing were not associated with a previous diagnosis. CONCLUSIONS: Undiagnosed patients had less severe airflow obstruction and fewer respiratory symptoms than diagnosed patients. The lower disease burden in undiagnosed patients may significantly delay the diagnosis of COPD.

Excess economic burden of comorbidities in COPD: a 15-year population-based study.

A better understanding of the true burden of chronic obstructive pulmonary disease (COPD) needs to consider the implications of comorbidities. This study comprehensively examined the impact of comorbidities on excess direct medical costs in COPD patients.From health administrative data in British Columbia, Canada (1996-2012), we created a propensity-score-matched cohort of incident COPD patients and individuals without COPD. Health services use records were compiled into 16 major disease categories based on International Classification of Diseases codes. Excess costs (in 2015 Canadian dollars and converted to 2015 Euros; CAD1.000=EUR 0.706) were estimated as the adjusted difference in direct medical costs between the two groups.The sample included 128 424 subjects in each group. COPD patients generated excess costs of CAD5196/EUR3668 per person-year (95% CI CAD3540-8529), of which 26% was attributable to COPD itself and 51% was attributable to comorbidities (the remaining 23% could not be attributed to any specific condition). The major cost driver was excess hospitalisation costs. The largest components of comorbidity costs were circulatory diseases, other respiratory disorders, digestive disorders and psychological disorders (CAD696/EUR491, CAD312/EUR220, CAD274/EUR193 and CAD249/EUR176 per person-year, respectively).These findings suggest that the prevention and appropriate management of comorbidities in COPD patients may effectively reduce the overall burden of COPD.

The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency.

INTRODUCTION: Lung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited. METHODS: Participants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk-selected in Canada. A comparison of high-risk screening versus standard care was made with a decision-analytic model using data from the NLST with Canadian cost data from screening and treatment in the PanCan study. Probabilistic and deterministic sensitivity analyses were undertaken to assess uncertainty and identify drivers of program efficiency. RESULTS: Use of the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with a threshold set at 2% over 6 years would have reduced the number of individuals who needed to be screened in the NLST by 81%. High-risk screening participants in the NLST had more adverse demographic characteristics than their counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015 Canadian dollars) per quality-adjusted life-year gained and would be considered cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars per quality-adjusted life-year gained with a probability of 0.62. Cost-effectiveness was driven primarily by non-lung cancer outcomes. Higher noncurative drug costs or current costs for immunotherapy and targeted therapies in the United States would render lung cancer screening a cost-saving intervention. CONCLUSIONS: Non-lung cancer outcomes drive screening efficiency in diverse, tobacco-exposed populations. Use of risk selection can reduce the budget impact, and screening may even offer cost savings if noncurative treatment costs continue to rise.

A Systematic Review of Health Economics Simulation Models of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Many decision-analytic models with varying structures have been developed to inform resource allocation in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To review COPD models for their adherence to the best practice modeling recommendations and their assumptions regarding important aspects of the natural history of COPD. METHODS: A systematic search of English articles reporting on the development or application of a decision-analytic model in COPD was performed in MEDLINE, Embase, and citations within reviewed articles. Studies were summarized and evaluated on the basis of their adherence to the Consolidated Health Economic Evaluation Reporting Standards. They were also evaluated for the underlying assumptions about disease progression, heterogeneity, comorbidity, and treatment effects. RESULTS: Forty-nine models of COPD were included. Decision trees and Markov models were the most popular techniques (43 studies). Quality of reporting and adherence to the guidelines were generally high, especially in more recent publications. Disease progression was modeled through clinical staging in most studies. Although most studies (n = 43) had incorporated some aspects of COPD heterogeneity, only 8 reported the results across subgroups. Only 2 evaluations explicitly considered the impact of comorbidities. Treatment effect had been mostly modeled (20) as both reduction in exacerbation rate and improvement in lung function. CONCLUSIONS: Many COPD models have been developed, generally with similar structural elements. COPD is highly heterogeneous, and comorbid conditions play an important role in its burden. These important aspects, however, have not been adequately addressed in most of the published models.

Biomarker Development in COPD: Moving From P Values to Products to Impact Patient Care.

There is a great interest in developing biomarkers to enable precision medicine and improve health outcomes of patients with COPD. However, biomarker development is extremely challenging and expensive, and translation of research endeavors to date has been largely unsuccessful. In most cases, biomarkers fail because of poor replication of initial promising results in independent cohorts and/or inability to transfer the biomarker from a discovery platform to a clinical assay. Ultimately, new biomarker assays must address 5 questions for optimal clinical translation. They include the following: is the biomarker likely to be (1) superior (will the test outperform current standards?); (2) actionable (will the test change patient management?); (3) valuable (will the test improve patient outcomes?); (4) economical (will the implementation of the biomarker in the target population be cost-saving or cost-effective?); and (5) clinically deployable (is there a pathway for the biomarker and analytical technology to be implemented in a clinical laboratory?)? In this article we review some of the major barriers to biomarker development in COPD and provide possible solutions to overcome these limitations, enabling translation of promising biomarkers from discovery experiments to clinical implementation.

Ten-Year Trends in Direct Costs of COPD: A Population-Based Study.

BACKGROUND: Up-to-date estimates of burden of diseases are required for evidence-based decision-making. The objectives of this study were to determine the excess costs of COPD and its trend from 2001 to 2010 in British Columbia, Canada. METHODS: We used British Columbia's administrative health data to construct a cohort of patients with COPD and a matched comparison cohort of subjects without COPD. We followed each patient from the time of first COPD-related health-care event (or equivalent time for the comparison cohort). Direct medical costs (in 2010 Canadian dollars [$]) were calculated based on billing records pertaining to hospital admissions, outpatient services use, medication dispensations, and community care services. We determined the excess medical costs of COPD by calculating the difference in overall medical costs between the COPD and the comparison cohorts. RESULTS: The COPD and comparison cohorts comprised 153,570 and 246,801 people, respectively (for both cohorts, mean age at entry was 66.9 years; 47.2% female patients). The excess costs of COPD during the study period were $5,452 per patient-year. Inpatient, outpatient, medication, and community care costs were responsible for 57%, 16%, 22%, and 5% of the excess costs, respectively. Excess costs increased by $296/person-y (P < .01), with hospital costs demonstrating the largest increase over time ($258/person-y; P < .01). CONCLUSIONS: The direct economic burden of COPD is high and has increased significantly between 2001 and 2010 over and above the increase in the health-care costs of the general population. Further investigation is required to elucidate the underlying reasons for the temporal increase in COPD direct costs.

Qualitative and quantitative assessment of smoking-related lung disease: effect of iterative reconstruction on low-dose computed tomographic examinations.

PURPOSE: The purpose of this research is to examine the role that differing levels of adaptive statistical iterative reconstruction (ASIR) have on the qualitative and quantitative assessment of smoking-related lung disease. MATERIALS AND METHODS: Institutional board review approval was obtained. A total of 52 patients undergoing clinically indicated low-dose computed tomographic (CT) examinations of the chest (100 kVp, 65 mAs, mean radiation dose 1.0±0.12 mSv), with reconstruction of data with different levels of blended ASIR (0%, 40%, and 100%), were consented. Qualitative assessment of CT data sets was performed by 2 trained thoracic radiologists blinded to clinical history, spirometry, and quantitative data for the presence of emphysema (%/lung zone) and the degree of respiratory bronchiolitis. Quantitative analysis was performed (Apollo Image analysis, VIDA Diagnostics) to assess emphysema and airway measures of chronic obstructive pulmonary disease. RESULTS: The application of ASIR results in alterations in both qualitative and quantitative assessment of smoking-related lung disease. As levels of ASIR increased, both readers scored more respiratory bronchiolitis (P<0.05). At increased levels of ASIR (ie, 100% vs. 0%), the amount of emphysema measured (% below -950 HU) decreased, the number of airways measured diminished, and the airway thickness (Pi10mm) increased (P<0.001). CONCLUSIONS: The use of ASIR alters both the qualitative and quantitative assessment of smoking-related lung disease. Although a powerful tool to allow dose reduction, caution must be exercised when iterative reconstruction techniques are utilized when evaluating CT examinations for findings of chronic obstructive pulmonary disease.

Resource utilization and costs during the initial years of lung cancer screening with computed tomography in Canada.

BACKGROUND: It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs. METHODS: Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer's perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study. RESULTS: The average per-person cost for screening individuals with LDCT was $453 (95% confidence interval [CI], $400-$505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was $33,344 (95% CI, $31,553-$34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, ($47,792; 95% CI, $43,254-$52,200; p = 0.061). CONCLUSION: In the Pan-Canadian study, the average cost to screen individuals with a high risk for developing lung cancer using LDCT and the average initial cost of curative intent treatment were lower than the average per-person cost of treating advanced stage lung cancer which infrequently results in a cure.

The determinants of poor respiratory health status in adults living with human immunodeficiency virus infection.

The increased longevity afforded by combination antiretroviral therapy in developed countries has led to an increased concern regarding senescence-related diseases in patients with human immunodeficiency virus (HIV) infection. Previous epidemiologic analyses have demonstrated an increased risk of chronic obstructive pulmonary disease, as well as a significant burden of respiratory symptoms in HIV-infected patients. We performed the St. George's Respiratory Questionnaire (SGRQ) in 199 HIV-positive men, and determined the predominant factors contributing to poor respiratory-related health status. In univariate analyses, worse SGRQ scores were associated with respiratory-related variables such as greater smoking pack-year history (p=0.028), lower forced expiratory volume in 1 second (FEV1) (p<0.001), and worse emphysema severity as quantified by computed tomographic imaging (p=0.017). In addition, HIV-specific variables, such as a history of plasma viral load >100,000 copies/mL (p=0.043), lower nadir CD4 cell count (p=0.040), and current CD4 cell count ≤350 cells/µL (p=0.005), as well as elevated levels of inflammatory markers, specifically plasma interleukin (IL)-6 (p=0.002) and alpha-1 antitrypsin (p=0.005) were also associated with worse SGRQ scores. In a multiple regression model, FEV1, current CD4 count ≤350 cells/µL, and IL-6 levels remained significant contributors to reduced respiratory-related health status. HIV disease activity as measured by HIV-related immunosuppression in conjunction with the triggering of key inflammatory pathways may be important determinants of worse respiratory health status among HIV-infected individuals. Limitations of this analysis include the absence of available echocardiograms, diffusion capacity and lung volume testing, and an all-male cohort due to the demographics of the clinic population.

What to do when a smoker's CT scan is "normal"?: Implications for lung cancer screening.

Lung cancer is the leading cause of cancer-related mortality in the United States and around the world. There are > 90 million current and ex-smokers in the United States who are at increased risk of lung cancer. The published data from the National Lung Screening Trial (NLST) suggest that yearly screening with low-dose thoracic CT scan in heavy smokers can reduce lung cancer mortality by 20% and all-cause mortality by 7%. However, to implement this program nationwide using the NLST inclusion and exclusion criteria would be extremely expensive, with CT scan costs alone > $2 billion per annum. In this article, we offer a possible low-cost strategy to risk-stratify smokers on the basis of spirometry measurements and emphysema scoring by radiologists on CT scans.

Integrative approach to quality assessment of medical journals using impact factor, eigenfactor, and article influence scores.

BACKGROUND: Impact factor (IF) is a commonly used surrogate for assessing the scientific quality of journals and articles. There is growing discontent in the medical community with the use of this quality assessment tool because of its many inherent limitations. To help address such concerns, Eigenfactor (ES) and Article Influence scores (AIS) have been devised to assess scientific impact of journals. The principal aim was to compare the temporal trends in IF, ES, and AIS on the rank order of leading medical journals over time. METHODS: The 2001 to 2008 IF, ES, AIS, and number of citable items (CI) of 35 leading medical journals were collected from the Institute of Scientific Information (ISI) and the http://www.eigenfactor.org databases. The journals were ranked based on the published 2008 ES, AIS, and IF scores. Temporal score trends and variations were analyzed. RESULTS: In general, the AIS and IF values provided similar rank orders. Using ES values resulted in large changes in the rank orders with higher ranking being assigned to journals that publish a large volume of articles. Since 2001, the IF and AIS of most journals increased significantly; however the ES increased in only 51% of the journals in the analysis. Conversely, 26% of journals experienced a downward trend in their ES, while the rest experienced no significant changes (23%). This discordance between temporal trends in IF and ES was largely driven by temporal changes in the number of CI published by the journals. CONCLUSION: The rank order of medical journals changes depending on whether IF, AIS or ES is used. All of these metrics are sensitive to the number of citable items published by journals. Consumers should thus consider all of these metrics rather than just IF alone in assessing the influence and importance of medical journals in their respective disciplines.

Corticosteroids and adrenoceptor agonists: the compliments for combination therapy in chronic airways diseases.

The combination of inhaled corticosteroids and long-acting beta2-adrenoceptor agonists is increasingly used as maintenance therapy in patients with moderate to severe asthma or chronic obstructive pulmonary disease (COPD). The main effect of inhaled corticosteroids is thought to be mediated through suppression of airway inflammation, while long-acting beta2-adrenoceptor agonists are thought to work by inducing bronchodilation. However, there is emerging data to indicate that these two classes of drugs interact positively with each other, leading to added or perhaps synergistic benefits for patients. Corticosteroids enhance the expression of beta2-adrenoceptor, thus providing protection against desensitization and development of tolerance to beta2-adrenoceptor agonists, which may occur with prolonged use of these medications. Long-acting beta2-adrenoceptor agonists, on the other hand, may amplify the anti-inflammatory effects of corticosteroids by accelerating nuclear translocation of the glucocorticoid receptor complex, and enhancing transcription and expression of steroid-inducible genes in pro-inflammatory cells. In clinical trials, corticosteroids in combination with long-acting beta2-adrenoceptor agonists reduce exacerbation rates, and improve lung function and health status of patients with moderate to severe asthma or COPD beyond that achieved by individual component therapy. Their effects on mortality are unknown. There is a large clinical trial currently underway, which will provide mortality data by the year 2006. On balance, clinical evidence supports the use of combination therapy in moderate to severe asthma and COPD.