Statin use and lung cancer risk in chronic obstructive pulmonary disease patients: a population-based cohort study.

BACKGROUND: Patients living with chronic obstructive pulmonary disease (COPD) are at an increased risk of lung cancer. A common comorbidity of COPD is cardiovascular disease; as such, COPD patients often receive statins. This study sought to understand the association between statin exposure and lung cancer risk in a population-based cohort of COPD patients. METHODS: We identified a population-based cohort of COPD patients based on having filled at least three prescriptions for an anticholinergic or short-acting beta-agonist (SABA). We used an array of methods of defining medication exposure including three conventional methods (ever statin exposure, cumulative duration of use, and cumulative dose) and two novel methods (recency-weighted cumulative duration of use and recency-weighted cumulative dose). To assess residual confounding, a negative control exposure was used to test the validity of our results. All exposure variables were time-dependent. RESULTS: The population-based cohort of COPD had 39,879 patients with mean age of 70.6 (SD: 11.2) years and, of which, 53.5% were female. There were 12,469 patients who received at least one statin prescription. Results from the reference case multivariable analysis indicated a reduced risk from statin exposure (HR: 0.85 (95% CI: 0.73-1.00) in COPD patients, but this result not statistically significant. Using the two recency-weighted modelling approaches, statin exposure was associated with a statistically significant reduction in lung cancer risk (recency-weighted cumulative dose, HR: 0.85 (95% CI: 0.77-0.93) and recency-weighted cumulative duration of use, HR: 0.97 (95% CI: 0.96-0.99). Multivariable analysis incorporating the negative control exposure was not statistically significant (HR: 0.89 (95% CI: 0.75-1.10). CONCLUSIONS: The results of this population-based analysis indicate that statin use in COPD patients may reduce the risk of lung cancer. While the effect was not statistically significantly across all exposure definitions, the overall results support the hypothesis that COPD patients might benefit from statin therapy.

Effects of long-term inhaled corticosteroid treatment on fragility fractures in older women: the Manitoba BMD registry study.

The effects of inhaled corticosteroids (ICS) on fracture risk in older women with chronic respiratory diseases are not well established. Our results indicate long-term ICS use in this population does not increase the risk of major osteoporotic fracture. This finding further elucidates the long-term safety of ICS in older women. INTRODUCTION: Inhaled corticosteroids (ICS) are frequently used in older women with chronic respiratory diseases. There is insufficient evidence regarding the association between long-term ICS use and the risk of fragility fractures in this population. METHODS: We used linked Manitoba health administrative databases and the provincial bone mineral density (BMD) registry (1996-2013) to identify women ≥ 40 years of age with asthma and/or chronic obstructive pulmonary disease (COPD) within 3 years preceding the baseline BMD test. We followed them until the first major osteoporotic fracture or end of study, whichever came first. ICS use, stratified by exposure tertiles, was measured within the 12-month period following the baseline BMD test (by total days and quantity, primary outcome), and over the entire follow-up period (by medication possession ratio (MPR) and average annual dose, secondary outcome). The hazard ratio of fracture with ICS use was estimated using a Cox proportional hazards model, controlling for baseline determinants of fracture. RESULTS: Of 6880 older women with asthma (38%) or COPD (62%), 810 (12%) experienced a major osteoporotic fracture over a mean follow-up of 7.7 years (SD = 3.9). ICS use at any tertile was not associated with an increased risk of fracture (dispensed days, p = 0.90; dispensed quantity, p = 0.67). Similarly, ICS use at any tertile during the entire follow-up period was not associated with an increased risk of fracture (MPR, p = 0.62; average annual dose, p = 0.58). CONCLUSION: Our findings do not support an increased risk of major osteoporotic fracture in older women with chronic respiratory diseases due to long-term ICS use.

Baseline characteristics and comorbidities in the CAnadian REgistry for Pulmonary Fibrosis.

BACKGROUND: The CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) is a multi-center, prospective registry designed to study the natural history of fibrotic interstitial lung disease (ILD) in adults. The aim of this cross-sectional sub-study was to describe the baseline characteristics, risk factors, and comorbidities of patients enrolled in CARE-PF to date. METHODS: Patients completed study questionnaires and clinical measurements at enrollment and each follow-up visit. Environmental exposures were assessed by patient self-report and comorbidities by the Charlson Comorbidity Index (CCI). Baseline characteristics, exposures, and comorbidities were described for the overall study population and for incident cases, and were compared across ILD subtypes. RESULTS: The full cohort included 1285 patients with ILD (961 incident cases (74.8%)). Diagnoses included connective tissue disease-associated ILD (33.3%), idiopathic pulmonary fibrosis (IPF) (24.7%), unclassifiable ILD (22.3%), chronic hypersensitivity pneumonitis (HP) (7.5%), sarcoidosis (3.2%), non-IPF idiopathic interstitial pneumonias (3.0%, including idiopathic nonspecific interstitial pneumonia (NSIP) in 0.9%), and other ILDs (6.0%). Patient-reported exposures were most frequent amongst chronic HP, but common across all ILD subtypes. The CCI was ≤2 in 81% of patients, with a narrow distribution and range of values. CONCLUSIONS: CTD-ILD, IPF, and unclassifiable ILD made up 80% of ILD diagnoses at ILD referral centers in Canada, while idiopathic NSIP was rare when adhering to recommended diagnostic criteria. CCI had a very narrow distribution across our cohort suggesting it may be a poor discriminator in assessing the impact of comorbidities on patients with ILD.

Incremental direct medical costs of systemic lupus erythematosus patients in the years preceding diagnosis: A general population-based study.

Objective We estimated the incremental (extra) direct medical costs of a population-based cohort of newly diagnosed systemic lupus erythematosus (SLE) for five years before and after diagnosis, and the impact of sex and socioeconomic status (SES) on pre-index costs for SLE. Methods We identified all adults newly diagnosed with SLE over 2001-2010 in British Columbia, Canada, and obtained a sample of non-SLE individuals from the general population, matched on sex, age, and calendar-year of study entry. We captured costs for all outpatient encounters, hospitalisations, and dispensed medications each year. Using generalised linear models, we estimated incremental costs of SLE each year before/after diagnosis (difference in costs between SLE and non-SLE, controlling for covariates). Similar models were used to examine the impact of sex and SES on costs within SLE. Results We included 3632 newly diagnosed SLE (86% female, mean age 49.6 ± 15.9) and 18,060 non-SLE individuals. Over the five years leading up to diagnosis, per-person healthcare costs for SLE patients increased year-over-year by 35%, on average, with the biggest increases in the final two years by 39% and 97%, respectively. Per-person all-cause medical costs for SLE the year after diagnosis (Year + 1) averaged C$12,019 (2013 Canadian) with 58% from hospitalisations, 24% outpatient, and 18% from prescription medications; Year + 1 costs for non-SLE averaged C$2412. Following adjustment for age, sex, urban/rural residence, socioeconomic status, and prior year's comorbidity score, SLE was associated with significantly greater hospitalisation, outpatient, and medication costs than non-SLE in each year of study. Altogether, adjusted incremental costs of SLE rose from C$1131 per person in Year -5 (fifth year before diagnosis) to C$2015 (Year -2), C$3473 (Year -1) and C$6474 (Year + 1). In Years -2, -1 and +1, SLE patients in the lowest SES group had significantly greater costs than the highest SES. Unlike the non-SLE cohort, male patients with SLE had higher costs than females. Annual incremental costs of SLE males (vs. SLE females) rose from C$540 per person in Year -2, to C$1385 in Year -1, and C$2288 in Year + 1. Conclusion Even years before diagnosis, SLE patients incur significantly elevated direct medical costs compared with the age- and sex-matched general population, for hospitalisations, outpatient care, and medications.

Ten-year trends in direct costs of asthma: a population-based study.

INTRODUCTION: There is little information on recent trends in the economic burden of asthma. Our objective was to estimate the excess costs of asthma and their trend in British Columbia, Canada, from 2002 to 2011. METHODS: A retrospective cohort of individuals aged 5-55 years was constructed from the provincial administrative health databases, consisting of patients with physician-diagnosed asthma and a propensity-score-matched comparison sample from the general population. Total direct medical costs were calculated as the sum of hospitalizations, outpatient visits and medication costs, adjusted to 2012 Canadian dollars ($). Excess costs were defined as the difference in costs between the asthma and comparison groups. RESULTS: A total of 341 457 individuals (mean age at entry 27.3, 54.1% female) were equally divided into the asthma and comparison groups. Excess costs in patients with asthma were $1028.0 (95% CI $982.7-$1073.4) per patient-year (PY). Medications contributed to the greatest share of excess costs ($471.7/PY), whereas hospitalization and outpatient costs were, respectively, $272.2/PY and $284.1/PY. Only $192.9/PY was attributable to asthma itself. There was a 2.9%/year increase in excess costs (P < 0.001), a combination of asthma-attributable costs declining by 0.8%/year while nonasthma excess costs increasing by 3.8%/year. The most dramatic trend was observed in asthma-related outpatient costs, which decreased by %6.6/year. CONCLUSIONS: A significant share of excess costs in asthma is not attributable to the disease itself. The pattern of costs changed significantly during the study period. The burden of comorbid conditions should be considered in developing evidence-based policies for management of patients with asthma.

Saving in medical costs by achieving guideline-based asthma symptom control: a population-based study.

BACKGROUND: Asthma control is increasingly used as an outcome measure in asthma trials. Economic evaluations of asthma interventions require converting the impact of interventions on control to impact on resource use. The purpose of this study was to estimate the savings in direct costs by achieving asthma symptom control as defined in the Global Initiative for Asthma (GINA) 2014 management strategy. METHODS: Adolescents and adults with asthma were recruited through random digit dialing. Asthma control per GINA and the use of healthcare resources were assessed at baseline and three-monthly visits up to 1 year. We used regression models to associate costs, measured in 2012 Canadian dollars ($), with symptom control, adjusting for potential confounding variables. RESULTS: The final sample included 517 individuals (average age 48.9, 65.8% female) with mostly mild-moderate asthma contributing 2033 follow-up visits. In 598 (29.4%), 809 (39.8%), and 626 (30.8%) of visits, asthma was symptomatically controlled, partially controlled, or uncontrolled, respectively. The average 3-month costs of asthma were $134.5. Of these, 20.5% were attributable to inpatient care, 47.8% to outpatient care, and 31.5% to medication. Compared to controlled asthma, partially controlled asthma was associated with a nonsignificant increase of $9.5 (95% CI -$13.6 - $32.6) in adjusted 3-month costs and uncontrolled asthma with a statistically significant increase of $81.7 (95% CI $48.5 - $114.9). CONCLUSION: A substantial fraction of this population-based sample of largely mild-moderate asthmatics was symptomatically uncontrolled. Achieving symptom control was associated with a reduction in direct costs. The adjusted values from this study can be used to inform cost-effectiveness analyses of asthma treatments.

The global economic burden of asthma and chronic obstructive pulmonary disease.

Non-communicable diseases are now the number one cause of disabilities and loss of life expectancy. Among them, chronic respiratory conditions constitute a major class. The burden of chronic respiratory diseases is generally increasing across the globe, and asthma and chronic obstructive pulmonary disease (COPD) are among the main causes of mortality and morbidity. However, the direct and indirect costs of these conditions vary across jurisdictions. This article reports on recent estimates of the costs of asthma and COPD, with a focus on comparing disease burden across different regions. Overall, there is tremendous variation in per capita annual costs of asthma and COPD. However, the methodology of the cost-of-illness studies is also vastly different, making it difficult to associate differences in reported costs to differences in the true burden of asthma and COPD. Suggestions are provided towards improving the validity and comparability of future studies.

Low-molecular-weight heparin versus unfractionated heparin for prophylaxis of venous thromboembolism in medicine patients--a pharmacoeconomic analysis.

BACKGROUND: Prevention of in-hospital venous thromboembolism (VTE) is identified internationally as a priority to improve patient safety. Advocated alternatives include low-dose unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Although LMWHs are as effective as UFH, less frequent administration and potentially safer adverse effect profile associated with LMWHs might off-set greater drug acquisition costs. The objective of this study was to determine the most cost-effective thromboprophylaxis strategy for hospitalized medicine patients and specific subgroups in Canada. METHODS: A decision-analytic model assessed costs and outcomes of LMWH compared to UFH for thromboprophylaxis in at-risk hospitalized medicine patients from an institutional perspective. The outcome of interest was the incremental cost-effectiveness ratio (ICER) for preventing deep vein thrombosis (DVT) and combined untoward events (pulmonary embolism [PE], major bleed, and death). The time horizon of the model was the hospital stay. RESULTS: In the base-case analysis, LMWH thromboprophylaxis resulted in higher costs ($7.40), but 3.6 and 1.1 fewer DVT and untoward events per 1000 patients, respectively, with associated ICERs of $2042 and $6832. Results remained predominantly stable when alternative assumptions were evaluated in the sensitivity analysis. Low-molecular-weight heparin had the most favorable economic profile in patients with a history of DVT. In the probabilistic sensitivity analysis, in 33% of simulations LMWH was less costly and more effective, whereas the reverse was true for UFH only in 13% of simulations. CONCLUSIONS: Low-molecular-weight heparin administration is a cost-effective alternative for thromboprophylaxis strategy in Canadian hospitalized medicine patients.

Secular decreases in fracture rates 1986-2006 for Manitoba, Canada: a population-based analysis.

SUMMARY: We examined trends in fracture rates over 20 years in the Province of Manitoba, Canada. Hip fractures, major low-trauma fractures, and high-trauma fractures declined significantly from 1986 to 2006. INTRODUCTION: Secular decreases in hip fracture rates have been reported in some countries. Whether this phenomenon applies to other fracture sites is not well described. METHODS: We used 20 years of data from the Population Health Research Data Repository for the Province of Manitoba, Canada. Age-adjusted fracture rates were calculated for men and women age 50 years and older 1986-2006 according to fracture site and mechanism (presence/absence of external injury codes). Generalized linear models with generalized estimating equations were used to derive adjusted annual rates and test for linear change in men and women. RESULTS: Major low-trauma fractures (hip, forearm, spine, and humerus) showed a significant annual linear decline in women (-1.2% [95% CI, -0.7% to -1.8%]) and in men (-0.4% [95% CI, -0.7% to -0.2%]). Hip fracture showed a significant annual decline for both sexes, while forearm and humerus fractures showed a significant decline only in women. The only fracture category that did not show a significant annual decline in either sex was the spine. The observed annual reduction in high-trauma fractures was even larger and did not show a sex difference (-1.8% [95% CI, -2.8% to -0.7%]). CONCLUSION: We observed a decrease in both low-trauma and high-trauma fracture rates over the study period. This decline was apparent in years prior to widespread osteoporosis testing or availability of modern pharmacotherapy.

Cost-effectiveness of a new interferon-based blood assay, QuantiFERON-TB Gold, in screening tuberculosis contacts.

BACKGROUND: Recent approval of interferon-gamma release assays that are more specific for Mycobacterium tuberculosis has given new options for the diagnosis of latent tuberculosis infection (LTBI). OBJECTIVE: To assess the cost-effectiveness of Quanti-FERON-TB Gold (QFT-G) vs. the tuberculin skin test (TST) in diagnosing LTBI in contacts of active TB cases using a decision analytic Markov model. METHODS: Three screening strategies--TST alone, QFT-G alone and sequential screening of TST then QFT-G--were evaluated. The model was further stratified according to ethnicity and bacille Calmette-Guérin (BCG) vaccination status. Data sources included published studies and empirical data. Results were reported in terms of the incremental net monetary benefit (INMB) of each strategy compared with the baseline strategy of TST-based screening in all contacts. RESULTS: The most economically attractive strategy was to administer QFT-G in BCG-vaccinated contacts, and to reserve TST for all others (INMB CA$3.70/contact). The least cost-effective strategy was QFT-G for all contacts, which resulted in an INMB of CA$-11.50 per contact. Assuming a higher prevalence of recent infection, faster conversion of QFT-G, a higher rate of TB reactivation, reduction in utility or greater adherence to preventive treatment resulted in QFT-G becoming cost-effective in more subgroups. CONCLUSIONS: Selected use of QFT-G appears to be cost-effective if used in a targeted fashion.

Cost effectiveness of therapy with combinations of long acting bronchodilators and inhaled steroids for treatment of COPD.

BACKGROUND: Little is known about the combination of different medications in chronic obstructive pulmonary disease (COPD). This study determined the cost effectiveness of adding salmeterol (S) or fluticasone/salmeterol (FS) to tiotropium (T) for COPD. METHODS: This concurrent, prospective, economic analysis was based on costs and health outcomes from a 52 week randomised study comparing: (1) T 18 microg once daily + placebo twice daily (TP group); (2) T 18 microg once daily + S 25 microg/puff, 2 puffs twice daily (TS group); and (3) T 18 microg once daily + FS 250/25 microg/puff, 2 puffs twice daily (TFS group). The incremental cost effectiveness ratios (ICERs) were defined as incremental cost per exacerbation avoided, and per additional quality adjusted life year (QALY) between treatments. A combination of imputation and bootstrapping was used to quantify uncertainty, and extensive sensitivity analyses were performed. RESULTS: The average patient in the TP group generated CAN$2678 in direct medical costs compared with $2801 (TS group) and $4042 (TFS group). The TS strategy was dominated by TP and TFS. Compared with TP, the TFS strategy resulted in ICERs of $6510 per exacerbation avoided, and $243,180 per QALY gained. In those with severe COPD, TS resulted in equal exacerbation rates and slightly lower costs compared with TP. CONCLUSIONS: TFS had significantly better quality of life and fewer hospitalisations than patients treated with TP but these improvements in health outcomes were associated with increased costs. Neither TFS nor TS are economically attractive alternatives compared with monotherapy with T.

Optimal decision criterion for detecting change in bone mineral density during serial monitoring: a Bayesian approach.

UNLABELLED: Interpretation of change in serial bone densitometry using least significant change (LSC) may not lead to optimal decision making. Using the principles of Bayesian statistics and decision sciences, we developed the Optimal Decision Criterion (ODC) which resulted in 11-12.5% higher rate of correct classification compared with the LSC method. INTRODUCTION: The interpretation of change in serial bone densitometry emphasizes using least significant change (LSC) to distinguish between true changes and measurement error. METHODS: Using the principles of Bayesian statistics and decision sciences, we developed the optimal decision criterion (ODC) based on maximizing a 'utility' function that rewards the correct and penalizes the incorrect classification of change. The relationship between LSC and ODC is demonstrated using a clinical sample from the Manitoba Bone Density Program. RESULTS: Under certain conditions, it can be shown that using LSC at the 95% confidence level implicitly equates the benefit of 39 true positive diagnoses with the harm of one false positive classification of BMD change. ODC resulted in an 11% higher rate of correct classification for lumbar spine BMD change and a 12.5% better performance for classifying total hip BMD change compared with LSC with this method. CONCLUSIONS: ODC has the same clinical interpretation as LSC but with two major advantages: it can incorporate prior knowledge of the likely values of the true change and it can be fine-tuned based on the relative value placed on the correct and incorrect classifications. Bayesian statistics and decision sciences could potentially increase the yield of a BMD monitoring program.

Validity and reliability of a new food frequency questionnaire compared to 24 h recalls and biochemical measurements: pilot phase of Golestan cohort study of esophageal cancer.

BACKGROUND: A pilot study was carried out to evaluate validity and reproducibility of a food frequency questionnaire (FFQ), which was designed to be used in a prospective cohort study in a population at high risk for esophageal cancer in northern Iran. METHODS: The FFQ was administered four times to 131 subjects, aged 35-65 years, of both sexes. Twelve 24-h dietary recalls for two consecutive days were administered monthly during 1 year and used as a reference method. The excretion of nitrogen was measured on four 24-h urine samples, and plasma levels of beta-carotene, retinol, vitamin C and alpha-tocopherol was measured from two time points. Relative validity of FFQ and 24-h diet recall was assessed by comparing nutrient intake derived from both methods with the urinary nitrogen and plasma levels of beta-carotene, retinol, vitamin C and alpha-tocopherol. RESULTS: Correlation coefficients comparing energy and nutrients intake based on the mean of the four FFQ and the mean of twelve 24-h diet recalls were 0.75 for total energy, 0.75 for carbohydrates, 0.76 for proteins and 0.65 for fat. Correlation coefficients between the FFQ-based intake and serum levels of beta-carotene, retinol, vitamin C and vitamin E/alpha-tocopherol were 0.37, 0.32, 0.35 and 0.06, respectively. Correlation coefficients between urinary nitrogen and FFQ-based protein intake ranged from 0.23 to 0.35. Intraclass correlation coefficients used to measure reproducibility of FFQ ranged from 0.66 to 0.89. CONCLUSION: We found that the FFQ provides valid and reliable measurements of habitual intake for energy and most of the nutrients studied.

Artificial neural networks in prediction of bone density among post-menopausal women.

Artificial neural networks (ANN) are promising tools in learning complex interplay of factors on a particular outcome. We performed this study to compare the predictive power of ANN and conventional methods in prediction of bone mineral density (BMD) in Iranian post-menopausal women. A database of 10 input variables from 2158 participants was randomly divided into training (1400), validation (150) and test (608) groups. Multivariate linear regression and ANN models were developed and validated on the training, and validation sets and outcomes (femoral neck and lumbar T-scores) were predicted and compared on the test group using different numbers of input variables. Results were evaluated by comparing the mean square of differences between predicted and reference values (non-central chi-square test) and by measuring area under the receiver operating characteristic curve (AUROC) around cut-off value of -2.5 for T-scores. For models with less than 3 input variables in femoral neck and 4 variables in spinal column, performance of regression and ANN models was almost the same. As more variables imported into models, ANN outperformed linear regression models. AUROC varied in 2 to 10 variable models as follows: for ANN in spine, from 0.709 to 0.774; linear models in spine, from 0.709 to 0.744; ANN in femoral neck, from 0.801 to 0.867; linear models in femoral neck, from 0.799 to 0.834. The ANN model performed better than five established patient selection tools in the test group. Superior performance of neural networks than linear models demonstrate their advantage especially in mass screening applications, when even a slight enhancement in performance results in significant decrease in number of misclassifications.