Todd A. Lee

International variation in the prevalence of COPD (The BOLD Study): a population-based prevalence study

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality worldwide, and accurate estimates of the prevalence of this disease are needed to anticipate the future burden of COPD, target key risk factors, and plan for providing COPD-related health services. We aimed to measure the prevalence of COPD and its risk factors and investigate variation across countries by age, sex, and smoking status. METHODS Participants from 12 sites (n=9425) completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. COPD prevalence estimates based on the Global Initiative for Chronic Obstructive Lung Disease staging criteria were adjusted for the target population. Logistic regression was used to estimate adjusted odds ratios (ORs) for COPD associated with 10-year age increments and 10-pack-year (defined as the number of cigarettes smoked per day divided by 20 and multiplied by the number of years that the participant smoked) increments. Meta-analyses provided pooled estimates for these risk factors. FINDINGS The prevalence of stage II or higher COPD was 10.1% (SE 4.8) overall, 11.8% (7.9) for men, and 8.5% (5.8) for women. The ORs for 10-year age increments were much the same across sites and for women and men. The overall pooled estimate was 1.94 (95% CI 1.80-2.10) per 10-year increment. Site-specific pack-year ORs varied significantly in women (pooled OR=1.28, 95% CI 1.15-1.42, p=0.012), but not in men (1.16, 1.12-1.21, p=0.743). INTERPRETATION This worldwide study showed higher levels and more advanced staging of spirometrically confirmed COPD than have typically been reported. However, although age and smoking are strong contributors to COPD, they do not fully explain variations in disease prevalence-other factors also seem to be important. Although smoking cessation is becoming an increasingly urgent objective for an ageing worldwide population, a better understanding of other factors that contribute to COPD is crucial to assist local public-health officials in developing the best possible primary and secondary prevention policies for their regions.

Multiple Chronic Conditions: Prevalence, Health Consequences, and Implications for Quality, Care Management, and Costs

Persons with multiple chronic conditions are a large and growing segment of the US population. However, little is known about how chronic conditions cluster, and the ramifications of having specific combinations of chronic conditions. Clinical guidelines and disease management programs focus on single conditions, and clinical research often excludes persons with multiple chronic conditions. Understanding how conditions in combination impact the burden of disease and the costs and quality of care received is critical to improving care for the 1 in 5 Americans with multiple chronic conditions. This Medline review of publications examining somatic chronic conditions co-occurring with 1 or more additional specific chronic illness between January 2000 and March 2007 summarizes the state of our understanding of the prevalence and health challenges of multiple chronic conditions and the implications for quality, care management, and costs.

Epidemiology and costs of chronic obstructive pulmonary disease

SERIES “THE GLOBAL BURDEN OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE” Edited by K.F. Rabe and J.B. Soriano Number 1 in this Series Chronic obstructive pulmonary disease (COPD) is a leading but under-recognised cause of morbidity and mortality worldwide 1. The prevalence of COPD in the general population is estimated to be ∼1% across all ages rising steeply to >10% amongst those aged ≥40 yrs. The prevalence climbs appreciably higher with age. The 30-yr projections for the global increase in COPD from 1990–2020 are startling. COPD is projected to move from the sixth to the third most common cause of death worldwide, whilst rising from fourth to third in terms of morbidity within the same time-frame 2. The cofactors responsible for this remarkable increase are the continued use of tobacco, coupled with the changing demographics of the world, such that many more people, especially those in developing countries, are living into the COPD age range. COPD is under-diagnosed not only in its early stages, but even when lung function is severely impaired. This is perhaps surprising, since simple and inexpensive spirometers that are suitable in clinical practice are now available, and lung function is a powerful predictor of all-cause mortality, regardless of smoking status. No other disease that is responsible for comparable morbidity, mortality and cost is neglected by healthcare providers as much as COPD. It may well be that the true burden of the disease is not fully appreciated, and the message that COPD is both preventable and treatable has yet to be fully understood by most healthcare providers. The hope is that highlighting these facts will help to raise the profile of COPD and begin to change long-held attitudes. Up to 2001, only 32 prevalence surveys of COPD had been reported 3. This is remarkable given the hundreds …

Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease

BackgroundStatins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Whether statins can benefit patients with dementia remains unclear because of conflicting results. We hypothesized that some of the confusion in the literature might arise from differences in efficacy of different statins. We used a large database to compare the action of several different statins to investigate whether some statins might be differentially associated with a reduction in the incidence of dementia and Parkinsons disease.MethodsWe analyzed data from the decision support system of the US Veterans Affairs database, which contains diagnostic, medication and demographic information on 4.5 million subjects. The association of lovastatin, simvastatin and atorvastatin with dementia was examined with Cox proportional hazard models for subjects taking statins compared with subjects taking cardiovascular medications other than statins, after adjusting for covariates associated with dementia or Parkinsons disease.ResultsWe observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects ≥65 years, using any of three models. The first model incorporated adjustment for age, the second model included adjusted for three known risk factors for dementia, hypertension, cardiovascular disease or diabetes, and the third model incorporated adjustment for the Charlson index, which is an index that provides a broad assessment of chronic disease. Data were obtained for over 700000 subjects taking simvastatin and over 50000 subjects taking atorvastatin who were aged >64 years. Using model 3, the hazard ratio for incident dementia for simvastatin and atorvastatin are 0.46 (CI 0.44–0.48, p < 0.0001) and 0.91 (CI 0.80–1.02, p = 0.11), respectively. Lovastatin was not associated with a reduction in the incidence of dementia. Simvastatin also exhibited a reduced hazard ratio for newly acquired Parkinsons disease (HR 0.51, CI 0.4–0.55, p < 0.0001).ConclusionSimvastatin is associated with a strong reduction in the incidence of dementia and Parkinsons disease, whereas atorvastatin is associated with a modest reduction in incident dementia and Parkinsons disease, which shows only a trend towards significance.

Pathogenic relevance of Lactobacillus: a retrospective review of over 200 cases.

Given that Lactobacillus has been reported to be the causative pathogen in many types of infection despite debate regarding the organism’s clinical significance, a literature review was conducted to investigate the treatments and outcomes of Lactobacillus infections reported to date. In this article, the characteristics of over 200 reported cases of Lactobacillus-associated infections are summarized. Lactobacillus was found to be frequently associated with endocarditis and bacteremia. Lactobacillus was also associated with a variety of other infections including, but not limited to, peritonitis, abscesses, and meningitis. The species casei and rhamnosus were the most common. The isolates tended to be most sensitive to erythromycin and clindamycin and most resistant to vancomycin. The species that was most sensitive to vancomycin was acidophilus. The overall mortality rate was nearly 30%. There was a significant association between mortality and polymicrobial infection (P=0.004). In the subset of patients with bacteremia, increased mortality was associated with inadequate treatment (P=0.001) and polymicrobial bacteremia (P=0.044).

The economic burden of allergic rhinitis: a critical evaluation of the literature.

AbstractAlthough a large number of economic analyses of allergic rhinitis have been published, there are relatively few empirically based studies, particularly outside the US. The majority of these analyses can be classified as burden-of-illness studies. Most estimates of the annual cost of allergic rhinitis range from

Risk for Death Associated with Medications for Recently Diagnosed Chronic Obstructive Pulmonary Disease

US2–5 billion (2003 values). The wide range of estimates can be attributed to differences in identifying patients with allergic rhinitis, differences in cost assignment, limitations associated with available data and difficulties in assigning indirect costs (associated with reduced productivity) of allergic rhinitis.Approximately one-third of burden-of-illness studies include direct and indirect costs of allergic rhinitis, about one-third focus on direct costs only, and the remaining one-third focus exclusively on indirect costs due to reduced productivity. Indirect costs attributable to allergic rhinitis were higher in studies only estimating indirect costs (

Performance of community pharmacy drug interaction software.

US5.5–9.7 billion) than in those estimating both direct and indirect costs (

The prevalence of clinically-relevant comorbid conditions in patients with physician-diagnosed COPD: a cross-sectional study using data from NHANES 1999–2008

US1.7–4.3 billion).Although there are many economic evaluations of allergic rhinitis treatments in the published medical literature, very few represent formal cost-effectiveness evaluations that compare the incremental costs and benefits of alternative treatment strategies. Those that are incremental cost-effectiveness analyses have several limitations, including small samples, short study periods and the lack of a standardized measure of effectiveness.To date, the medical literature is lacking a comprehensive economic evaluation of general treatment strategies for allergic rhinitis. In undertaking such an analysis, serious consideration must be given to the study population of interest, the choice of appropriate comparators, the perspective from which the analysis is conducted, the target audience, the changing healthcare marketplace and the selection of a measure of effectiveness that incorporates both positive and negative aspects of treatments for allergic rhinitis.Future work would benefit from the development of a consensus on a summary measure of effectiveness that could be used in cost-effectiveness analyses of therapies for allergic rhinitis as well as additional empirical work to measure the association between severity of disease and its impact on worker productivity.

Assessment of the emergence of Alzheimer's disease following coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty.

Context Many think we need more information about the safety of respiratory medications for chronic obstructive pulmonary disease (COPD). Contribution This large casecontrol study examined associations between medications and risk for death in veterans with newly diagnosed COPD. Inhaled corticosteroids were associated with decreased risk for death. Theophylline and ipratropium were associated with increased risk for respiratory and cardiovascular death, respectively. Caution Potential confounders, such as smoking status and disease severity, were not known. Associations may not reflect causal relationships. Implication Additional research about the safety of ipratropium, one of the most commonly prescribed medications for COPD, is needed. The Editors Chronic obstructive pulmonary disease (COPD) is associated with substantial burden in terms of prevalence of disease (1), death and disability risk (2, 3), and health care costs (4). Despite recent interest in examining long-term outcomes associated with medications in patients with COPD (5, 6), some issues are not easily addressed by using randomized clinical trials. From a pharmacovigilance perspective, relatively rare adverse eventssuch as death associated with medication usemay not be detected in the short term. The patients who receive a medication may not be similar to those participating in clinical trials (7, 8) and may be more vulnerable to such events. Thus, evidence of longer-term benefits and harms associated with medicationsparticularly in patients with COPD, who tend to be elderly and have multiple comorbid conditions (9)can be informed by research that relies on observational data. Potential safety concerns with medications used to manage COPD may be substantial. A recent meta-analysis (10) showed a nearly 2.5-fold increase in respiratory deaths among patients receiving long-acting -agonists compared with those receiving placebo. In the Lung Health Study (11), the group randomly assigned to ipratropium bromide had more than twice as many cardiovascular deaths as those receiving placebo. In addition, the U.S. Food and Drug Administration recently issued a notice regarding the potential for an increased risk for stroke associated with tiotropium use in patients with COPD (12). The extent to which these safety concerns exist and can be generalized to patients with COPD outside the context of clinical trials is unclear. Therefore, we sought to examine the association between medication use and risk for death, including respiratory and cardiovascular deaths, in a large population of patients with recently diagnosed COPD. Methods We conducted this nested casecontrol study in patients with recently diagnosed COPD by using national Veterans Affairs inpatient, outpatient, pharmacy, and mortality databases, supplemented with data from the Centers for Medicare & Medicaid Services. Our sample comprised U.S. veterans who used the U.S. Veterans Health Administration health care system. The Hines Veterans Affairs Hospital, Hines, Illinois, institutional review board approved our research. Cohort Patients were eligible for inclusion if they received a diagnosis of COPD (International Classification of Diseases, 9th Revision [ICD-9], codes 491.x, 492.x, or 496) between 1 October 1999 and 30 September 2003 at 2 or more outpatient visits within 12 months or were admitted to the hospital with a primary diagnosis of COPD. Patients had to be 45 years of age or older when they received their first eligible diagnosis, have used Veterans Health Administration health care services for at least 1 year before their first COPD diagnosis, and have received respiratory medications. We excluded patients with a diagnosis of asthma. We followed patients from the date of their second eligible outpatient visit or their inpatient visit until death or 30 September 2004. Case Patients We identified all deaths that occurred during follow-up by using the Veterans Affairs Vital Status database, a combination of Veterans Affairs, Medicare, and Social Security Administration mortality data that captures approximately 98% of veteran deaths (13). Of these, 40% was randomly sampled and we attempted to determine cause of death. This sample was estimated to provide more than 80% power to detect odds ratios of 0.85 or lower or 1.15 or higher for each medication class. We ascertained cause of death by using National Death Index Plus data from the National Center for Health Statistics. We defined 4 groups of case patients on the basis of cause of death: respiratory, cardiovascular, respiratory or cardiovascular, and all-cause mortality. We defined respiratory as death due to a respiratory system disease (ICD-10 codes J00 to J99) and cardiovascular as death due to ischemic heart disease (ICD-10 codes I20 to I25), cardiomyopathy, cardiac arrest, or arrhythmias (ICD-10 codes I42 to I51). The index date for case patients was their death date. Control Participants Selecting more than 5 control participants per case patient can yield limited gains in efficiency; however, because we were assessing several medications simultaneously, we selected up to 10 control participants per case patient (14). We randomly selected control participants for each case patient from eligible patients who were alive at the time of the case event (15, 16). We matched control participants to case patients individually on the basis of sex, age category (45 to 54 years, 55 to 64 years, 65 to 74 years, 75 to 84 years, and 85 years of age), region of the country, and year of diagnosis. We assigned control participants the same index date as their matched case patients. Exposure We defined exposure to respiratory medications as having received medications in the 180 days preceding each patients index date. We identified medication exposure to inhaled corticosteroids, ipratropium, long-acting -agonists, theophylline, and short-acting -agonists. We defined primary exposure as any exposure in the 180-day period before the index date. We created mutually exclusive medication regimens on the basis of medication exposure. Exposure to short-acting -agonists was not considered as part of the regimen but was included as a covariate in the analysis. Covariates We identified covariates by using data from the year before diagnosis date until the index date. We used pharmacy data to identify medication use, including exposure to systemic steroids, antihypertensives, lipid-lowering medications, antiarrhythmics, and diabetes medications. We used inpatient and outpatient diagnoses to identify comorbid conditions. We measured health care utilization as the annual number of hospitalizations and outpatient physician visits. We identified COPD exacerbations during follow-up and whether they were inpatient or outpatient by using a previously described algorithm (17). Statistical Analysis We performed separate analyses for respiratory-specific, cardiovascular-specific, and all-cause mortality. We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% CIs. We included the variables that we considered clinically important in each of the regression models. Specifically, we included measures of COPD-related severity in all of the models and included markers of cardiovascular disease in the models for cardiovascular and all-cause mortality. We included any remaining variables that changed OR estimates for respiratory medications by more than 10% in the final models (18). We assessed model fit by using the Bayesian information criterion and the Wald test of likelihood ratios and through examination of outlier effects with leverage and fit diagnostics (19). Adjusted odds ratios represented risk for events in patients receiving medication compared with those who had not received inhaled corticosteroids, ipratropium, long-acting -agonists, or theophylline in the previous 6 months. We performed all analyses with Stata/MP 10.0 for Windows (StataCorp, College Station, Texas). We conducted several sensitivity analyses to evaluate the robustness of our results. First, we restricted the comparison group to patients who were actively treated with a short-acting -agonist in the 180 days preceding the index date. Second, because veterans may use health care services outside the Veterans Health Administration system, we restricted the analysis to patients 65 years of age or older. We used Medicare health care utilization data on these patients to capture health care utilization outside of the Veterans Health Administration system. Third, we examined dose response by classifying those in the highest quartile of average daily dose into a high-dose group and the rest of those exposed into a low-dose group. Fourth, to observe the effects of ipratropium independent of short-acting -agonist exposure, we excluded patients who received a combination of ipratropium and short-acting -agonists in a single inhaler. Fifth, to address the imbalance in prevalence of chronic heart failure between case patients and control participants, we created analytic cohorts by matching on presence of chronic heart failure and repeated our analyses. Finally, we used the array approach to estimate the effect that unmeasured confounding could have had on point estimates of the association between medications and mortality (20). We varied the level of risk associated with the unmeasured confounder and the prevalence in the medication groups relative to the no-treatment groups to determine what level of differential exposure would change the conclusions from the primary analysis. We focused on current smoking rates and COPD severity because we considered these to be 2 of the most important and influential unmeasured confounders. We compared rates of smoking status and COPD severity across treatment groups by using data from a recently published study (21). Role of the Funding Source This research was funded by the U.S. Department of Veterans Affairs Health Services Research