Smoking cessation treatment and outcomes patterns simulation: a new framework for evaluating the potential health and economic impact of smoking cessation interventions.

BACKGROUND: Most existing models of smoking cessation treatments have considered a single quit attempt when modelling long-term outcomes. OBJECTIVE: To develop a model to simulate smokers over their lifetimes accounting for multiple quit attempts and relapses which will allow for prediction of the long-term health and economic impact of smoking cessation strategies. METHODS: A discrete event simulation (DES) that models individuals' life course of smoking behaviours, attempts to quit, and the cumulative impact on health and economic outcomes was developed. Each individual is assigned one of the available strategies used to support each quit attempt; the outcome of each attempt, time to relapses if abstinence is achieved, and time between quit attempts is tracked. Based on each individual's smoking or abstinence patterns, the risk of developing diseases associated with smoking (chronic obstructive pulmonary disease, lung cancer, myocardial infarction and stroke) is determined and the corresponding costs, changes to mortality, and quality of life assigned. Direct costs are assessed from the perspective of a comprehensive US healthcare payer ($US, 2012 values). Quit attempt strategies that can be evaluated in the current simulation include unassisted quit attempts, brief counselling, behavioural modification therapy, nicotine replacement therapy, bupropion, and varenicline, with the selection of strategies and time between quit attempts based on equations derived from survey data. Equations predicting the success of quit attempts as well as the short-term probability of relapse were derived from five varenicline clinical trials. RESULTS: Concordance between the five trials and predictions from the simulation on abstinence at 12 months was high, indicating that the equations predicting success and relapse in the first year following a quit attempt were reliable. Predictions allowing for only a single quit attempt versus unrestricted attempts demonstrate important differences, with the single quit attempt simulation predicting 19 % more smoking-related diseases and 10 % higher costs associated with smoking-related diseases. Differences are most prominent in predictions of the time that individuals abstain from smoking: 13.2 years on average over a lifetime allowing for multiple quit attempts, versus only 1.2 years with single quit attempts. Differences in abstinence time estimates become substantial only 5 years into the simulation. In the multiple quit attempt simulations, younger individuals survived longer, yet had lower lifetime smoking-related disease and total costs, while the opposite was true for those with high levels of nicotine dependence. CONCLUSION: By allowing for multiple quit attempts over the course of individuals' lives, the simulation can provide more reliable estimates on the health and economic impact of interventions designed to increase abstinence from smoking. Furthermore, the individual nature of the simulation allows for evaluation of outcomes in populations with different baseline profiles. DES provides a framework for comprehensive and appropriate predictions when applied to smoking cessation over smoker lifetimes.

Prevalence of renal and hepatobiliary disease, laboratory abnormalities, and potentially toxic medication exposures among persons with COPD.

BACKGROUND: The purpose of this study was to describe the prevalence of renal and hepatic disease, related laboratory abnormalities, and potentially hepatotoxic and nephrotoxic medication use in a population-based cohort of persons with chronic obstructive pulmonary disease (COPD). METHODS: This was a retrospective case-control cohort analysis of COPD patients enrolled in one regional health system for at least 12 months during a 36-month study period (n = 2284). Each COPD patient was matched by age and gender to up to three persons not diagnosed with COPD (n = 5959). RESULTS: The mean age for cases and controls was 70.3 years, and 52.5% were women. The COPD cohort had significantly higher prevalences (cases/100) of acute, chronic, and unspecified renal failure as compared with controls (1.40 versus 0.59, 2.89 versus 0.79, and 1.09 versus 0.44, respectively). Among the cases, 31.3% had at least one renal or urinary tract diagnosis during the study period, as compared with 21.1% of controls. COPD cases also had more gallbladder disease (2.76 versus 1.63) and pancreatic disease (1.40 versus 0.60), but not hepatic disease. COPD patients were more likely to have at least one serum creatinine level (5.1 versus 2.1) or liver aspartate aminotransferase level (4.5 versus 2.7) that was more than twice the upper limit of normal. COPD patients had prescription fills for an average of 17.6 potentially nephrotoxic and 27.4 hepatotoxic drugs during the study period, as compared with 13.6 and 19.9 for the controls (P value for all comparisons < 0.01). CONCLUSION: COPD patients have a substantially increased prevalence of renal, gallbladder, and pancreatic diseases, as well as abnormal renal and hepatic laboratory values, but not diagnosed liver disease. COPD patients are also more likely to be prescribed medications with potentially toxic renal or hepatic side effects.

Lost productivity due to premature mortality in developed and emerging countries: an application to smoking cessation.

BACKGROUND: Researchers and policy makers have determined that accounting for productivity costs, or "indirect costs," may be as important as including direct medical expenditures when evaluating the societal value of health interventions. These costs are also important when estimating the global burden of disease. The estimation of indirect costs is commonly done on a country-specific basis. However, there are few studies that evaluate indirect costs across countries using a consistent methodology. METHODS: Using the human capital approach, we developed a model that estimates productivity costs as the present value of lifetime earnings (PVLE) lost due to premature mortality. Applying this methodology, the model estimates productivity costs for 29 selected countries, both developed and emerging. We also provide an illustration of how the inclusion of productivity costs contributes to an analysis of the societal burden of smoking. A sensitivity analysis is undertaken to assess productivity costs on the basis of the friction cost approach. RESULTS: PVLE estimates were higher for certain subpopulations, such as men, younger people, and people in developed countries. In the case study, productivity cost estimates from our model showed that productivity loss was a substantial share of the total cost burden of premature mortality due to smoking, accounting for over 75 % of total lifetime costs in the United States and 67 % of total lifetime costs in Brazil. Productivity costs were much lower using the friction cost approach among those of working age. CONCLUSIONS: Our PVLE model is a novel tool allowing researchers to incorporate the value of lost productivity due to premature mortality into economic analyses of treatments for diseases or health interventions. We provide PVLE estimates for a number of emerging and developed countries. Including productivity costs in a health economics study allows for a more comprehensive analysis, and, as demonstrated by our illustration, can have important effects on the results and conclusions.

Undertreatment of COPD: a retrospective analysis of US managed care and Medicare patients.

BACKGROUND: We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy. METHODS: Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US. Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD. As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes. RESULTS: A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified. Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively. In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting ß2-agonist only). In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting ß2-agonist only). A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy. Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination. CONCLUSION: This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination.

A discrete-event simulation of smoking-cessation strategies based on varenicline pivotal trial data.

BACKGROUND: Smoking is the leading cause of preventable death in the US. While one in five individuals smoke, and 70% of these indicate a desire to quit, <5% of unaided quit attempts succeed. Cessation aids can double or triple the odds of successfully quitting. Models of smoking-cessation behaviour can elucidate the implications of individual abstinence patterns to allow better tailoring of quit attempts to an individual's characteristics. OBJECTIVE: The objectives of this study were to develop and validate a discrete-event simulation (DES) to evaluate the benefits of smoking abstinence using data from the pooled pivotal clinical trials of varenicline versus bupropion or placebo for smoking cessation and to provide a foundation for the development of a lifetime smoking-cessation model. METHODS: The DES model simulated the outcome of a single smoking-cessation attempt over 1 year, in accordance with the clinical trial timeframes. Pharmaceutical costs were assessed from the perspective of a healthcare payer. The model randomly sampled patient profiles from the pooled varenicline clinical trials. All patients were physically and mentally healthy adult smokers who were motivated to quit abruptly. The model allowed for comparisons of up to five distinct treatment approaches for smoking cessation. In the current analyses, three interventions corresponding to the clinical trials were evaluated, which included brief counselling plus varenicline 1.0 mg twice daily (bid) or bupropion SR 150 mg bid versus placebo (i.e. brief counselling only). The treatment periods in the clinical trials were 12 weeks (target quit date: day 8), with a 40-week non-treatment follow-up, and counselling continuing over the entire 52-week period in all treatment groups. The main outcome modelled was the continuous abstinence rate (CAR; defined as complete abstinence from smoking and confirmed by exhaled carbon monoxide ≤ 10 ppm) at end of treatment (weeks 9-12) and long-term follow-up (weeks 9-52), and total time abstinent from smoking over the course of 52 weeks. The model also evaluated costs and cost-effectiveness outcomes. RESULTS: For the varenicline, bupropion and placebo cohorts, respectively, the model predicted CARs for weeks 9-12 of 44.3%, 30.4% and 18.6% compared with observed rates of 44.0%, 29.7% and 17.7%; over weeks 9-52, predicted CARs in the model compared with observed rates in the pooled clinical studies were 22.9%, 16.4% and 9.4% versus 22.4%, 15.4% and 9.3%, respectively. Total mean abstinence times accrued in the model varenicline, bupropion and placebo groups, respectively, were 3.6, 2.6 and 1.5 months and total pharmaceutical treatment costs were $US261, $US442 and $US0 (year 2008 values) over the 1-year model period. Using cost per abstinent-month achieved as a measure of cost effectiveness, varenicline dominated bupropion and yielded an incremental cost-effectiveness ratio of $US124 compared with placebo. CONCLUSION: The model accurately replicated abstinence patterns observed in the clinical trial data using individualized predictions and indicated that varenicline was more effective and may be less costly than bupropion. This simulation incorporated individual predictions of abstinence and relapse, and provides a framework for lifetime modelling that considers multiple quit attempts over time in diverse patient populations using a variety of quit attempt strategies.

The analysis of Lupinus albus root proteome revealed cytoskeleton altered features due to long-term boron deficiency.

Boron (B) deficiency greatly limits plants' growth and development. Since the root is the organ that first senses the deficiency, we have analyzed the adaptive responses of Lupinus albus roots to long-term B deficiency. Large morphological differences were observed between plants grown with or without B, and 265 polypeptides were found to be responsive to B deficiency out of a total of 406 polypeptides detected by two-dimensional electrophoresis in the L. albus root proteome. By using mass spectrometry techniques we were able to securely identify 128 of the responsive polypeptides that are related to cell wall metabolism, cell structure, defense, energy pathways and protein metabolism. The detection of multiple peptide isoforms is striking, suggesting that protein modification may have an important contribution during the plant response to long-term B deficiency. Furthermore, detected changes in cytoskeletal associated proteins indicate altered cytoskeletal biosynthesis and suggest that B may have an important contribution in this process.

Identifying and characterizing COPD patients in US managed care. A retrospective, cross-sectional analysis of administrative claims data.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among US adults and is projected to be the third by 2020. In anticipation of the increasing burden imposed on healthcare systems and payers by patients with COPD, a means of identifying COPD patients who incur higher healthcare utilization and costs is needed. METHODS: This retrospective, cross-sectional analysis of US managed care administrative claims data describes a practical way to identify COPD patients. We analyze 7.79 million members for potential inclusion in the COPD cohort, who were continuously eligible during a 1-year study period. A younger commercial population (7.7 million) is compared with an older Medicare population (0.115 million). We outline a novel approach to stratifying COPD patients using "complexity" of illness, based on occurrence of claims for given comorbid conditions. Additionally, a unique algorithm was developed to identify and stratify COPD exacerbations using claims data. RESULTS: A total of 42,565 commercial (median age 56 years; 51.4% female) and 8507 Medicare patients (median 75 years; 53.1% female) were identified as having COPD. Important differences were observed in comorbidities between the younger commercial versus the older Medicare population. Stratifying by complexity, 45.0%, 33.6%, and 21.4% of commercial patients and 36.6%, 35.8%, and 27.6% of older patients were low, moderate, and high, respectively. A higher proportion of patients with high complexity disease experienced multiple (≥2) exacerbations (61.7% commercial; 49.0% Medicare) than patients with moderate- (56.9%; 41.6%), or low-complexity disease (33.4%; 20.5%). Utilization of healthcare services also increased with an increase in complexity. CONCLUSION: In patients with COPD identified from Medicare or commercial claims data, there is a relationship between complexity as determined by pulmonary and non-pulmonary comorbid conditions and the prevalence of exacerbations and utilization of healthcare services. Identification of COPD patients at highest risk of exacerbations using complexity stratification may facilitate improved disease management by targeting those most in need of treatment.

A new method for examining the cost savings of reducing COPD exacerbations.

BACKGROUND: Some treatments for chronic obstructive pulmonary disease (COPD) can reduce exacerbations, and thus could have a favourable impact on overall healthcare costs. OBJECTIVE: To evaluate a new method for assessing the potential cost savings of COPD controller medications based on the incidence of exacerbations and their related resource utilization in the general population. METHODS: Patients with COPD (n = 1074) enrolled in a regional managed care system in the US were identified using administrative data and divided by their medication use into three groups (salbutamol, ipratropium and salmeterol). Exacerbations were captured using International Classification of Diseases, Ninth Edition (ICD-9) and current procedural terminology (CPT) codes, then logistic regression models were created that described the risk of exacerbations for each comparator group and exacerbation type over a 6-month period. A Monte Carlo simulation was then applied 1000 times to provide the range of potential exacerbation reductions and cost consequences in response to a range of hypothetical examples of COPD controller medications. RESULTS: Exacerbation events for each group could be modelled such that the events predicted by the Monte Carlo estimates were very close to the actual prevalences. The estimated cost per exacerbation avoided depended on the incidence of exacerbation in the various subpopulations, the assumed relative risk reduction, the projected daily cost for new therapy, and the costs of exacerbation treatment. CONCLUSIONS: COPD exacerbation events can be accurately modelled from the healthcare utilization data of a defined cohort with sufficient accuracy for cost-effectiveness analysis. Treatments that reduce the risk or severity of exacerbations are likely to be cost effective among those patients who have frequent exacerbations and hospitalizations.

Can outpatient pharmacy data identify persons with undiagnosed COPD?

OBJECTIVE: To develop and validate a method for identifying persons with undiagnosed chronic obstructive pulmonary disease (COPD) using outpatient pharmacy data. STUDY DESIGN: Case-control analysis of managed care administrative data with clinical validation by spirometry and standardized questionnaires. METHODS: Patients with a new diagnosis of COPD were matched to 3 control subjects by age and sex. Outpatient pharmacy utilization for the 2 years prior to the initial diagnosis was captured. Drugs associated with an eventual diagnosis of COPD were identified using conditional logistic regression, and then entered into a predictive algorithm using discriminant function analysis. The algorithm was tested in a second population from the same health plan and externally validated using 2 large multicenter databases. This system was clinically validated by testing 100 individuals identified by the algorithm with spirometry plus health status and respiratory symptoms questionnaires. RESULTS: COPD patients used significantly more antibiotics, cardiac medications, and respiratory drugs than their matched controls. The final algorithm identified COPD patients with a sensitivity of 60% and specificity of 70%, without the benefit of knowing any patient's smoking history. Of the first 100 persons identified by the algorithm as being at risk and recruited for testing, 25 were proven to have previously undiagnosed COPD. CONCLUSIONS: Pharmacy utilization increases in the years prior to initial COPD diagnosis. Algorithms based on pharmacy utilization can efficiently identify persons at risk for undiagnosed COPD.

The cost-effectiveness of an extended course (12+12 weeks) of varenicline compared with other available smoking cessation strategies in the United States: an extension and update to the BENESCO model.

OBJECTIVES: This study aimed to estimate the cost-effectiveness of an extended (12+12 weeks) course of varenicline using the (Benefits of Smoking Cessation on Outcomes) BENESCO smoking cessation model. METHODS: Data on the efficacy of 12+12 weeks varenicline therapy in aiding smoking cessation were analyzed in conjunction with the efficacy data for 12 weeks of varenicline, bupropion, and placebo previously included in the BENESCO model, by using a mixed treatment comparison. This analysis provided updated efficacy estimates for all the interventions, and these were used to update the model to estimate the relative cost-effectiveness of all smoking cessation interventions considered, now including 12+12 weeks of varenicline. RESULTS: The updated 1-year abstinence estimates derived from the mixed treatment comparison were, for 12+12 weeks of varenicline, 12 weeks of varenicline, 12 weeks of bupropion, and 12 weeks of placebo, respectively: 27.7%, 22.9%, 15.9%, and 9.3%. The average cost of the course of 12+12 weeks of varenicline was estimated at $603.89, based on a 12-week course followed by a further 12 weeks for successful quitters. Over all subjects' lifetimes, 12+12 weeks of varenicline is less costly and more effective than (dominates) all other strategies compared in the updated BENESCO model, with the exception of 12 weeks of varenicline. In this comparison, 12+12 weeks of varenicline is a very cost-effective alternative to the 12-week course, with an incremental cost of less than $1000 per quality-adjusted life year (QALY) gained. CONCLUSIONS: A total of 12 weeks of varenicline followed by a further 12-week course for successful quitters is a highly cost-effective alternative compared with currently available smoking cessation options.

Inpatient treatment patterns, outcomes, and costs of skin and skin structure infections because of Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus (SA) is a common bacterial pathogen in skin and skin structure infections (SSSIs). Limited data exist on hospital treatment patterns and costs for SA-SSSIs. METHODS: This retrospective analysis examined the lengths of stay, treatment patterns, and costs of hospitalized patients with an SA-SSSI diagnosis using a nationally representative inpatient database. Patients were selected if they had an ICD-9-CM diagnosis of an SSSI with SA noted between January 2005 and June 2006, received a study antibiotic (ie, intravenous [IV] vancomycin, IV or oral linezolid, and IV daptomycin), and were not in the intensive care unit before receiving a study antibiotic. Generalized linear models assessed predictors of length of stay and costs. Costs are expressed in 2005 US dollars. RESULTS: Thirteen thousand four hundred thirty-three patients met the selection criteria and mean (+/-SD) age was 48.2 (+/-18.3) years. Forty percent of patients received a nonstudy antibiotic before receiving their first study antibiotic. Ninety-five percent were prescribed vancomycin as their first study antibiotic. Study antibiotics were administered for an average of 4.3 days, and 8% of patients switched study antibiotics. Nineteen percent of patients receiving IV linezolid stepped down to oral linezolid. Mean (+/-SD) lengths of hospital stay and costs were 6.1 (+/-6.0) days and $6830 (+/-$7100). In-hospital mortality, switching antibiotics, and diagnoses of selected complications or comorbidities were associated with increased lengths of stay and costs. Younger age, location outside the Northeast, and use of oral linezolid were associated with lower lengths of stay and costs. CONCLUSION: The costs of treating inpatient SA-SSSIs are substantial and vary by patient demographics and treatment characteristics.

Costs of skin and skin structure infections due to Staphylococcus aureus: an analysis of managed-care claims.

OBJECTIVES: The incidence of skin and skin structure infections (SSSIs) due to Staphylococcus aureus (SA) is increasing. The objective of this study was to assess the costs of a treatment episode for SA-SSSIs. METHODS: This retrospective analysis used a managed-care claims database to assess the duration and costs of incident SA-SSSI episodes treated with selected antibiotics (i.v. vancomycin, oral linezolid, and daptomycin, termed 'study antibiotics'). Patients were included if they had an ICD-9-CM diagnosis of an SSSI and SA between January 1, 2002 and December 31, 2005. Treatment episodes began on the date of the first antibiotic and ended when the patient had fourteen consecutive days without a study antibiotic or SSSI hospitalization. Costs, represented by health plan payments for SSSIs and overall, were updated to 2005 US dollars. A generalized linear model (GLM) assessed predictors of costs. RESULTS: A total of 1997 patients met the selection criteria. Mean (+/- SD) age was 46.3 (+/- 12.6) years and 55.9% of patients were male. Average episode length was 24 days, and over 95% of patients received i.v. vancomycin or oral linezolid as their initial study antibiotic. Patients remained on study antibiotics for an average of 16.4 days, and only 5% of patients were switched to another study antibiotic. Mean (+/- SD) overall episode costs were $8865 (+/- $20,003), primarily composed of inpatient and outpatient medical services. Treatment failure (i.e., study antibiotic switching or hospitalization), younger age, a diagnosis of bacteremia, osteomyelitis, or multiple complications during the episode, treatment with daptomycin, and greater Charlson co-morbidity score were significant positive predictors of overall costs. Alternatively, treatment with oral linezolid and hospitalization before the start of the outpatient treatment episode were significant negative predictors of overall costs. Mean (+/- SD) SSSI-related costs were $4551 (+/- $11,058). LIMITATIONS: Medical charts and laboratory test results were not available to confirm SSSI and SA diagnoses, and no information was available regarding antibiotics received in the inpatient setting. CONCLUSIONS: The costs of treating SA-SSSIs are substantial and vary by failure rates, co-morbidities, and type of antibiotic therapy.

A retrospective analysis of disability and its related costs among employees with chronic obstructive pulmonary disease.

OBJECTIVE: The objective of this study was to examine the frequency and cost of disability among actively employed individuals with chronic obstructive pulmonary disease (COPD). METHODS: The authors conducted a retrospective analysis of disability and claims data. Employees 40 to 63 years old with a diagnosis of COPD between January 1, 2001, and March 31, 2004, were identified, and controls were matched 2:1 to these subjects. Likelihood and cost of disability were compared between cohorts. RESULTS: A total of 2696 controls were matched to 1349 COPD subjects. Mean age was 52 years, and cohorts were approximately 50% male. A significantly (P < 0.0001) greater proportion of COPD subjects used short-term (21.8% vs 7.0%), long-term (2.4% vs 0.4%), or any disability (22.8% vs 7.3%). Associated costs were also higher among COPD subjects (8559 dollars vs 5443 dollars; P = 0.07). CONCLUSIONS: Within a population of actively employed individuals 40 to 63 years old, COPD was found to have a substantial impact on the frequency and cost of disability.

An algorithm for the identification of undiagnosed COPD cases using administrative claims data.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of death in the United States, but most persons who have airflow obstruction have never been diagnosed with lung disease. This undiagnosed COPD negatively affects health status, and COPD patients may have increased health care utilization several years before the initial diagnosis of COPD is made. OBJECTIVE: To investigate whether utilization patterns derived from analysis of administrative claims data using a discriminant function algorithm could be used to identify undiagnosed COPD patients. METHODS: Each patient who had a new diagnosis of COPD during the study period (N = 2,129) was matched to as many as 3 control subjects by age and gender. Controls were assigned an index date that was identical to that of the corresponding case, and then all health care utilization for cases and controls for the 24 months prior to the initial COPD diagnosis was compared using logistic regression models. Factors that were significantly associated with COPD were then entered into a discriminant function algorithm. This algorithm was then validated using a separate patient population. RESULTS: In the main model, 19 utilization characteristics were significantly associated with preclinical COPD, although most of the power of the discriminant function algorithm was concentrated in a few of these factors. The main model was able to identify COPD patients in the validation population of adult subjects aged 40 years and older (N = 41,428), with a sensitivity of 60.5% and specificity of 82.1%, even without having information on the history of tobacco use for the majority of the group. Models developed and tested on only 12 months of utilization data performed similarly. CONCLUSION: Discriminant function algorithms based on health care utilization data can be developed that have sufficient positive predictive value to be used as screening tools to identify individuals at risk for having undiagnosed COPD.

Assessing the costs of chronic obstructive pulmonary disease: the state medicaid perspective.

BACKGROUND: State Medicaid programs provide insurance coverage to over 40 million Americans. However, estimates of the annual cost of chronic obstructive pulmonary disease (COPD) from the Medicaid perspective are lacking. METHODS: This retrospective cohort study used Medicaid administrative claims data from California and Florida to estimate COPD expenditures using two alternative methods: (1) excess costs (comparing a COPD cohort to a matched comparison cohort); and (2) attributable costs (COPD-related expenditures within a COPD cohort, inclusive of respiratory medications). The COPD cohort in each state included Medicaid recipients not dually eligible for Medicare who were 40+ years of age with at least one medical claim for COPD during 2001. The comparison cohort consisted of patients with medical claims during 2001 for conditions other than chronic respiratory disease, matched by age, sex, and race to the COPD cohort. RESULTS: A total of 6,738 Medicaid recipients in California and 18,017 in Florida were included in the COPD cohort, with mean ages of 56 and 60 years, respectively. Comorbidities, especially congestive heart failure and vascular disease, were more common in the COPD cohort than among matched controls. The mean excess cost of COPD per-patient was estimated to be approximately 6,500 US dollars in California Medicaid and 5,200 US dollars in Florida Medicaid. Mean attributable costs of COPD were similar in the two Medicaid programs (approximately 2,200 US dollars and 2,300 US dollars per patient, respectively). CONCLUSIONS: COPD places a substantial financial burden on State Medicaid programs. These findings may be of interest to clinicians and policy-makers involved in preventing or managing this chronic disease.

Assessment of the economic burden of COPD in the U.S.: a review and synthesis of the literature.

The costs of chronic obstructive pulmonary disease (COPD) pose a major economic burden to the United States. Studies evaluating COPD costs have generated widely variable estimates; we summarized and critically compared recent estimates of the annual national and per-patient costs of COPD in the U.S. Thirteen articles reporting comprehensive estimates of the direct costs of COPD (costs related to the provision of medical goods and services) were identified from searches of relevant primary literature published since 1995. Few papers reported indirect costs of COPD (lost work and productivity). The National Heart, Lung, and Blood Institute (NHLBI) provides the single current estimate of the total (direct plus indirect) annual cost of COPD to the U.S., $38.8 billion in 2005 dollars. More than half of this cost ($21.8 billion) was direct, aligning with the $20-26 billion range reported by two other recent analyses of large national datasets. For per-patient direct costs (in $US 2005), studies using recent data yield attributable cost estimates (costs deemed to be related to COPD) in the range of $2,700-$5,900 annually, and excess cost estimates (total costs incurred by COPD patients minus total costs incurred by non-COPD patients) in the range of $6,100-$6,600 annually. Studies of both national and per-patient costs that use data approximately 8-10 years old or older have produced estimates that tend to deviate from these ranges. Cost-of-illness studies using recent data underscore the substantial current cost burden of COPD in the U.S.

Excess mortality, length of stay, and costs associated with serious fungal infections among elderly cancer patients: findings from linked SEER-Medicare data.

OBJECTIVE: To calculate the excess mortality, length of stay, and costs attributable to serious fungal infections in hospitalized elderly patients with selected cancers. METHODS: This study involved a retrospective cohort analysis using linked data from the Surveillance, Epidemiology and End Results Program of the National Cancer Institute (SEER) and Medicare claims data. Study cohorts included patients aged 65 years and older who newly received a diagnosis of a selected cancer (acute myeloid leukemia [AML] or squamous cell carcinoma of the head and neck [SCCHN]) in a SEER registry between 1991 and 1996 and who had a subsequent diagnosis of a serious fungal infection during an inpatient hospitalization, and hospitalized controls without a fungal infection matched 1:1 by age, geographic region, receipt of recent chemotherapy, concomitant bacterial infection, timing of the index hospitalization, and cancer stage at diagnosis (for SCCHN patients only). RESULTS: Eighty AML patients and 52 SCCHN patients experienced a serious fungal infection involving hospitalization. Relative to matched controls, SCCHN patients with fungal infections had significantly higher all-cause mortality (40% vs. 14%, P = 0.002), while mortality rates did not differ between AML cohorts. Patients with fungal infections had significantly longer index hospitalizations regardless of cancer type (mean: 30 days vs. 19 days for AML patients; 20 days vs. 9 days for SCCHN patients), and correspondingly higher Medicare payments (mean +/- SD: 34,268 dollars +/- 31,811 dollars vs. 21,416 dollars +/- 22,449 dollars among AML patients, P < 0.0001; 25,942 dollars +/- 29,122 dollars vs. 10,131 dollars +/- 10,686 dollars among SCCHN patients, P < 0.0001). CONCLUSIONS: Efforts to prevent these infections and/or initiate early treatment may yield both clinical and economic benefits.

Direct costs of COPD in the U.S.: an analysis of Medical Expenditure Panel Survey (MEPS) data.

Chronic obstructive pulmonary disease (COPD) is a costly cause of morbidity and mortality in the U.S. The objective of this study was to use contemporary national data-specifically, those from the 2000 Medical Expenditure Panel Survey (MEPS)-to estimate direct costs of COPD in the U.S. from an all-payer perspective. Due to constraints of MEPS data, indirect costs were excluded from our analyses, as were costs of long-term oxygen therapy and costs from nursing homes and long-term care facilities. Two methods of cost estimation were employed. First, we estimated resources used and expenditures incurred by individuals with COPD that were directly attributable to the disease (attributable cost approach). Second, we compared overall medical expenditures of patients with COPD to those of the non-COPD population; the resulting difference represented excess costs of COPD. Approximately 1.7% (n = 144) of the nearly 8,300 persons in the analysis data set aged > or = 45 years used medical resources and incurred expenditures related to treatment of COPD. Mean attributable costs per patient were estimated at dollar 2,507, with more than one-half of these costs (dollar 1,365) associated with hospitalization. Mean excess costs of COPD, after adjustment for sociodemographic factors and smoking status, were substantially higher, at dollar 4,932 per patient. Results of our study indicate that COPD-associated healthcare utilization and expenditures are considerable, and that annual per-patient costs of COPD are comparable to those of other chronic diseases of the middle-aged and elderly.

Structural characterization of two aquaporins isolated from native spinach leaf plasma membranes.

Two members of the aquaporin family, PM28A and a new one, PM28C, were isolated and shown to be the major constituents of spinach leaf plasma membranes. These two isoforms were identified and characterized by matrix-assisted laser desorption ionization-mass spectrometry. Edman degradation yielded the amino acid sequence of two domains belonging to the new isoform. PM28B, a previously described isoform, was not found in our preparations. Scanning transmission electron microscopy mass analysis revealed both PM28 isoforms to be tetrameric. Two types of particles, a larger and a smaller one, were found by transmission electron microscopy of negatively stained solubilized proteins and by atomic force microscopy of PM28 two-dimensional crystals. The ratio of larger to smaller particles observed by transmission electron microscopy and single particle analysis correlated with the ratio of PM28A to PM28C determined by matrix-assisted laser desorption ionization-mass spectrometry. The absence of PM28B and the ratio of PM28A to PM28C indicate that these plasma membrane intrinsic proteins are differentially expressed in spinach leaves. These findings suggest that differential expression of the various aquaporin isoforms may regulate the water flux across the plasma membrane, in addition to the known mechanism of regulation by phosphorylation.

The transcriptional activator Cat8p provides a major contribution to the reprogramming of carbon metabolism during the diauxic shift in Saccharomyces cerevisiae.

In yeast, the transition between the fermentative and the oxidative metabolism, called the diauxic shift, is associated with major changes in gene expression and protein synthesis. The zinc cluster protein Cat8p is required for the derepression of nine genes under nonfermentative growth conditions (ACS1, FBP1, ICL1, IDP2, JEN1, MLS1, PCK1, SFC1, and SIP4). To investigate whether the transcriptional control mediated by Cat8p can be extended to other genes and whether this control is the main control for the changes in the synthesis of the respective proteins during the adaptation to growth on ethanol, we analyzed the transcriptome and the proteome of a cat8 Delta strain during the diauxic shift. In this report, we demonstrate that, in addition to the nine genes known as Cat8p-dependent, there are 25 other genes or open reading frames whose expression at the diauxic shift is altered in the absence of Cat8p. For all of the genes characterized here, the Cat8p-dependent control results in a parallel alteration in mRNA and protein synthesis. It appears that the biochemical functions of the proteins encoded by Cat8p-dependent genes are essentially related to the first steps of ethanol utilization, the glyoxylate cycle, and gluconeogenesis. Interestingly, no function involved in the tricarboxylic cycle and the oxidative phosphorylation seems to be controlled by Cat8p.