Mortality and Respiratory-Related Hospitalizations in Idiopathic Pulmonary Fibrosis Not Treated With Antifibrotics.

Background: Real-world data regarding outcomes of idiopathic pulmonary fibrosis (IPF) are scarce, outside of registries. The claims data from the French National Health System (SNDS) were used to describe outcomes in patients diagnosed with IPF in 2015-2016 but who did not receive antifibrotic therapies. Method: Patients aged <50 years were excluded, as were patients with pulmonary fibrosis other than IPF, patients who had previously received a lung transplant, and those who had received antifibrotic therapies at any time between 2010 and 2016. Patients were followed-up until their last health record, lung transplantation, initiation of antifibrotic therapies, death, or the end of the study period (31 December 2017), whichever occurred first. Results: A total of 5,360 patients (43.2%) not treated with antifibrotic therapies were included. The mean age was 75.5 years, and 57.9% were males. In the year before inclusion, 47.3% of patients had a Charlson score ≥5. During follow-up, 41.2% of patients died. The unadjusted incidence rate was 29.9 per 100 person-years (95%CI = [28.7-31.2]), and the cumulative incidence of death at 3 years was 50.2% (95% CI = [48.3-52.1%]). In the study population, 35.3% of patients experienced an acute respiratory-related hospitalization. The unadjusted incidence rate was 32.1 per 100 person-years (95%CI = [30.6-33.5]) and the cumulative incidence of the event at 3 years was 41.5% (95% CI = [39.7-43.2%]). Interpretation: This observational study showed that, if untreated with antifibrotics, IPF is associated with a 50% all-cause mortality at 3 years. These figures can serve as a historical control of the natural course of the disease.

Economic burden of impairment in children with severe or difficult-to-treat asthma.

BACKGROUND: The cost associated with asthma impairment in children with severe asthma has not been determined. OBJECTIVE: To assess the asthma cost burden in children with severe or difficult-to-treat asthma based on asthma impairment. METHODS: Children aged 6 to 12 years in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study with available data at baseline (n = 628), month 12 (n = 385), and month 24 (n = 280) corresponding to the National Heart, Lung, and Blood Institute asthma guidelines' impairment domain were included. Children were categorized as either very poorly controlled (VPC), not well controlled (NWC), or well controlled (WC) and assessed cross-sectionally and longitudinally. Mean total asthma costs based on direct (medication usage, unscheduled office visits, emergency department visits, hospitalizations) and indirect (school/work days lost) asthma costs were assessed. RESULTS: Mean annual total asthma costs were more than twice as high in the VPC group compared with NWC and WC groups (baseline: $7,846, $3,526, $3,766.44, respectively; month 12: $7,326, $2,959, $2,043, respectively; month 24: $8,879, $3,308, $1,861, respectively (all P < .001). Indirect costs accounted for approximately half the total asthma costs for VPC asthma patients at each time point. Significantly lower costs were observed for patients whose impairment status improved or temporarily improved from VPC after baseline. CONCLUSION: The economic burden of severe or difficult-to-treat asthma in children is associated with VPC asthma and improvement in asthma control and is associated with reducing cost. Further attention to patients with poorly controlled asthma, through better management strategies or more effective medications, may significantly reduce this burden of illness.

Asthma control, severity, and quality of life: quantifying the effect of uncontrolled disease.

BACKGROUND: Current practice guidelines emphasize the importance of attaining asthma control. We sought to quantify the degree of quality-of-life impairment associated with different levels of asthma control. METHODS: We analyzed prospective data for 987 adults in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. Asthma control was assessed by using the Asthma Therapy Assessment Questionnaire, a validated index of control problems ranging from 0 to 4. Disease-specific quality of life and preference-based health utilities were assessed after 12 months of follow-up by using the Mini-Asthma Quality of Life Questionnaire (AQLQ) and EuroQoL 5-D (EQ-5D). We used multiple linear regression to model the relationship between asthma control and the AQLQ and EQ-5D while controlling for severity classification and lung function. RESULTS: Asthma control varied widely, even within a population with predominantly moderate-to-severe disease. An inverse relationship was observed between the number of asthma control problems and quality of life. Specifically, poorer control at baseline predicted worse AQLQ and EQ-5D scores at follow-up. Asthma control remained an independent predictor of disease-specific quality of life and general health in multivariate models and was a better longitudinal predictor of health status than asthma severity at baseline. CONCLUSION: Poor asthma control is associated with a substantial degree of impairment and predicts quality of life at 12 months, even after taking baseline asthma severity into account. CLINICAL IMPLICATIONS: Self-assessed measures of asthma control might help to identify and manage those patients at greatest risk for future health impairment.

Evaluation of erlotinib in advanced non-small cell lung cancer: impact on the budget of a U.S. health insurance plan.

BACKGROUND: Lung cancer is the most common non-skin cancer and the leading cause of cancer death among men and women in North America. More than half of all patients diagnosed with lung cancer are diagnosed with advanced disease. Most cases of lung cancer are non-small cell lung cancer (NSCLC). Erlotinib monotherapy is indicated for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least 1 prior chemotherapy regimen. OBJECTIVE: To assess the budgetary impact, from the health plan perspective, of covering erlotinib for treating patients with NSCLC stage IIIb/IV who have failed at least 1 prior chemotherapy regimen. METHODS: An Excel-based model was developed to evaluate costs for U.S. Food and Drug Administration-approved and National Comprehensive Cancer Network guideline-recommended treatment options for second- and third-line NSCLC from the perspective of a U.S. health insurer. In particular, the model compares a formulary with erlotinib and a formulary without erlotinib, including the costs of treatment, drug administration, and adverse effects. The incidence of advanced NSCLC is based on the Surveillance, Epidemiology, and End Results Cancer Registry and adverse effects related to treatment (all agents) in published results of clinical trials. Drug and treatment costs were obtained from publicly available sources in 2005. RESULTS: The base case considers a health plan of 500,000 enrollees. Assuming that erlotinib comprises 30% of second-line treatments and 90% for third-line, total costs of treating stage IIIb/IV NSCLC patients over 1 year are Dollars 382,418 with erlotinib and Dollars 380,968 without erlotinib (difference: Dollars 1,450; 90% confidence interval, -Dollars 61,376 to Dollars 29,855), less than Dollars 0.01 per member per month (PMPM) in 2005. Erlotinib direct cost is offset by reductions in standard chemotherapy-related infusion costs and adverse events. CONCLUSIONS: Based on the analysis, the inclusion of erlotinib on a formulary appears to have a relatively small impact on the annual health care budget or PMPM expenditures if it is used consistent with the product label indications.

Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults.

BACKGROUND: Mortality resulting from coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in persons with diabetes and pre-existing CVD is high; however, these risks compared with those with metabolic syndrome (MetS) are unclear. We examined the impact of MetS on CHD, CVD, and overall mortality among US adults. METHODS AND RESULTS: In a prospective cohort study, 6255 subjects 30 to 75 years of age (54% female) (representative of 64 million adults in the United States) from the Second National Health and Nutrition Examination Survey were followed for a mean+/-SD of 13.3+/-3.8 years. MetS was defined by modified National Cholesterol Education Program criteria. From sample-weighted multivariable Cox proportional-hazards regression, compared with those with neither MetS nor prior CVD, age-, gender-, and risk factor-adjusted hazard ratios (HRs) for CHD mortality were 2.02 (95% CI, 1.42 to 2.89) for those with MetS and 4.19 (95% CI, 3.04 to 5.79) for those with pre-existing CVD. For CVD mortality, HRs were 1.82 (95% CI, 1.40 to 2.37) and 3.14 (95% CI, 2.49 to 3.96), respectively; for overall mortality, HRs were 1.40 (95% CI, 1.19 to 1.66) and 1.87 (95% CI, 1.60 to 2.17), respectively. In persons with MetS but without diabetes, risks of CHD and CVD mortality remained elevated. Diabetes predicted all mortality end points. Those with even 1 to 2 MetS risk factors were at increased risk for mortality from CHD and CVD. Moreover, MetS more strongly predicts CHD, CVD, and total mortality than its individual components. CONCLUSIONS: CHD, CVD, and total mortality are significantly higher in US adults with than in those without MetS.

Impact of guidelines on health care use for the management of dyslipidemia in two Canadian provinces, Alberta and Nova Scotia, from 1990 to 2001.

BACKGROUND: Guidelines for the treatment of hyperlipidemia aim at improving the management of people at a higher risk of developing cardiovascular disease. OBJECTIVES: To study the potential impact of hyperlipidemia guidelines on health care use in two Canadian provinces with different levels of hyperlipidemia. METHODS: Trends in physician billing were obtained from Alberta between 1990 and 2000 and from Nova Scotia between 1994 to 2001 using the 272 primary diagnostic code for hyperlipidemia. Record linkage between a 272 code and a prescription in the subsequent six months was made through the Pharmacare database (which automatically registers all individuals 65 years of age and over). Data were also linked between the 1995 Nova Scotia Health Survey and the Pharmacare data. RESULTS: Trends in hyperlipidemia codes were similar in Alberta and Nova Scotia by sex and age, with acceleration in the final years of the study. Approximately 5% of the adult population had a diagnosis of hyperlipidemia. Less than 60% of people aged 65 years and over with a 272 code filled an antilipemic prescription in the subsequent six months. Using the National Cholesterol Education Program Adult Treatment Panel III classification and the 1995 Nova Scotia Health Survey, less than 10% of the participants aged 65 years and over had a corresponding diagnostic code of 272, while more than half could be classified as having hyperlipidemia. In 1995, approximately one-half of people at high risk, with a 272 code in the subsequent five years, had a prescription for antilipemic drugs. CONCLUSIONS: Despite some limitations, these data show a discrepancy between guideline development and practice, leaving a high number of at-risk individuals undiagnosed and untreated. Mechanisms need to be put in place to ensure better classification and follow-up of people with hyperlipidemia at risk for cardiovascular disease.

Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome.

We estimated the coronary heart disease (CHD) events that are preventable by treatment of lipids and blood pressure in patients with metabolic syndrome (MetS), a contributor to coronary heart disease (CHD). Among patients aged 30 to 74 years (without diabetes or CHD) in the United States, MetS was defined by National Cholesterol Education Program criteria. CHD events over a period of 10 years were estimated by Framingham algorithms. Events that could be prevented by statistically "controlling" blood pressure, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol to either normal or optimal levels according to national guidelines were calculated. Of 7.5 million men and 9.0 million women aged 30 to 74 years with MetS, approximately 1.5 million men and 0.45 million women, if untreated, developed CHD events in 10 years. In men and women, blood pressure control to normal levels "prevented" 28.1% and 12.5% of CHD events, respectively (p <0.01); control to optimal levels resulted in preventing 28.2% and 45.2% of events, respectively (p <0.01). Control of HDL cholesterol to normal levels resulted in preventing 25.3% of events in men and 27.3% in women; optimal control prevented 51.2% and 50.6% of events, respectively. Control of LDL cholesterol to normal levels prevented 9.3% of events in men and 9.8% of events in women; control to optimal levels prevented 46.2% and 38.1% of events (p <0.05), respectively. Control of all 3 risk factors to normal levels resulted in preventing 51.3% of events for men and 42.6% for women; control to optimal levels resulted in preventing 80.5% and 82.1% of events, respectively. Thus, many CHD events in patients with MetS may be preventable by nominal or optimal control of lipids and/or blood pressure.