C. Fornari

The clinical and economic impact of exacerbations of chronic obstructive pulmonary disease: a cohort of hospitalized patients.

Background Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences. This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs. Methods This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy. The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006. Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period. Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status. Results 15857 patients were enrolled –9911 males, mean age: 76 years (SD 10). Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%. A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD. On average, the healthcare system spent 6725€ per year per person (95%CI 6590–6863). Occurrence and type of exacerbations drove the direct healthcare cost. Less than one quarter of patients presented claims for pulmonary function tests. Conclusions COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes. A more tailored approach to the management of COPD patients is required.

Design and evaluation of a semantic approach for the homogeneous identification of events in eight patient databases: a contribution to the European EU-ADR project

The overall objective of the EU-ADR project is the design, development, and validation of a computerised system that exploits data from electronic health records and biomedical databases for the early detection of adverse drug reactions. Eight different databases, containing health records of more than 30 million European citizens, are involved in the project. Unique queries cannot be performed across different databases because of their heterogeneity: Medical record and Claims databases, four different terminologies for coding diagnoses, and two languages for the information described in free text. The aim of our study was to provide database owners with a common basis for the construction of their queries. Using the UMLS, we provided a list of medical concepts, with their corresponding terms and codes in the four terminologies, which should be considered to retrieve the relevant information for the events of interest from the databases.

Burden of Diabetes Mellitus Estimated with a Longitudinal Population-Based Study Using Administrative Databases

Objective To assess the epidemiologic and economic burden of diabetes mellitus (DM) from a longitudinal population-based study. Research Design and Methods Lombardy Region includes 9.9 million individuals. Its DM population was identified through a data warehouse (DENALI), which matches with a probabilistic linkage demographic, clinical and economic data of different Healthcare Administrative databases. All individuals, who, during the year 2000 had an hospital discharge with a IDC-9 CM code 250.XX, and/or two consecutive prescriptions of drugs for diabetes (ATC code A10XXXX) within one year, and/or an exemption from co-payment healthcare costs specific for DM, were selected and followed up to 9 years. We calculated prevalence, mortality and healthcare costs (hospitalizations, drugs and outpatient examinations/visits) from the National Health Service’s perspective. Results We identified 312,223 eligible subjects. The study population (51% male) had a mean age of 66 (from 0.03 to 105.12) years at the index date. Prevalence ranged from 0.4% among subjects aged ≤45 years to 10.1% among those >85 years old. Overall 43.4 deaths per 1,000 patients per year were estimated, significantly (p<0.001) higher in men than women. Overall, 3,315€/patient-year were spent on average: hospitalizations were the cost driver (54.2% of total cost). Drugs contributed to 31.5%, outpatient claims represented 14.3% of total costs. Thirty-five percent of hospital costs were attributable to cerebro−/cardiovascular reasons, 6% to other complications of DM, and 4% to DM as a main diagnosis. Cardiovascular drugs contributed to 33.5% of total drug costs, 21.8% was attributable to class A (16.7% to class A10) and 4.3% to class B (2.4% to class B01) drugs. Conclusions Merging different administrative databases can provide with many data from large populations observed for long time periods. DENALI shows to be an efficient instrument to obtain accurate estimates of burden of diseases such as diabetes mellitus.

Social status and cardiovascular disease: a Mediterranean case. Results from the Italian Progetto CUORE cohort study.

BackgroundSocial factors could offer useful information for planning prevention strategy for cardiovascular diseases. This analysis aims to explore the relationship between education, marital status and major cardiovascular risk factors and to evaluate the role of social status indicators in predicting cardiovascular events and deaths in several Italian cohorts.MethodsThe population is representative of Italy, where the incidence of the disease is low. Data from the Progetto CUORE, a prospective study of cohorts enrolled between 1983-1997, were used; 7520 men and 13127 women aged 35-69 years free of previous cardiovascular events and followed for an average of 11 years. Educational level and marital status were used as the main indicators of social status.ResultsAbout 70% of the studied population had a low or medium level of education (less than high school) and more than 80% was married or cohabitating. There was an inverse relationship between educational level and major cardiovascular risk factors in both genders. Significantly higher major cardiovascular risk factors were detected in married or cohabitating women, with the exception of smoking. Cardiovascular risk score was lower in married or cohabitating men. No relationship between incidence of cardiac events and the two social status indicators was observed. Cardiovascular case-fatality was significantly higher in men who were not married and not cohabitating (HR 3.20, 95%CI: 2.21-4.64). The higher cardiovascular risk observed in those with a low level of education deserves careful attention even if during the follow-up it did not seem to determine an increase of cardiac events.ConclusionsPreventive interventions on cardiovascular risk should be addressed mostly to people with less education. Cardiovascular risk score and case-fatality resulted higher in men living alone while cardiovascular factors were higher in women married or cohabitating. Such gender differences seem peculiar of our population and require further research on unexpected cultural and behavioural influences.

Using real-world healthcare data for pharmacovigilance signal detection – the experience of the EU-ADR project

A prospective pharmacovigilance signal detection study, comparing the real-world healthcare data (EU-ADR) and two spontaneous reporting system (SRS) databases, US FDA’s Adverse Event Reporting System and WHOs Vigibase is reported. The study compared drug safety signals found in the EU-ADR and SRS databases. The potential for signal detection in the EU-ADR system was found to be dependent on frequency of the event and utilization of drugs in the general population. The EU-ADR system may have a greater potential for detecting signals for events occurring at higher frequency in general population and those that are commonly not considered as potentially a drug-induced event. Factors influencing various differences between the datasets are discussed along with potential limitations and applications to pharmacovigilance practice.

Administrative databases as a tool for identifying healthcare demand and costs in an over-one million population

Background: the aim of this study was to assess healthcare demand of specific groups of population and their costs borne by Italian Health System, using healthcare administrative databases. Methods: demographic, clinical and economic data were obtained from datasets available at the Regional Health System, combined into a data warehouse (DENALI), using a probabilistic record linkage to optimize the data matching process. The study population consisted of more than 1 million people registered in 2005 at one Local Healthcare Unit of Lombardy. Eight different segments were identified. Costs occurring in 2005 for hospital admissions, drug prescriptions, outpatient medical specialist visits were quantified in each segment. Results: healthy people accounted for 53% of the population and cost € 180 per-capita. Subjects with only one chronic disease made up 16% of the population and cost € 916 per-capita, those affected by several chronic diseases accounted for 13% and cost € 3 457 per-capita. Hospitalizations were the cost driver in five segments, ranging from 42% to 89% of total expenditures. Outpatient visits were the cost driver among healthy subjects (54%) and those with a possible chronic disease (42%), while drug costs ranged between 4% (“acute event”) and 32% (“one chronic disease”). Overall, healthcare cost was € 809 per-capita. Conclusions: healthcare costs were mainly determined by people affected by chronic conditions, even if “healthy people” ranked third for total expenditure. These costs need an appropriate identification of healthcare demand, that could be efficiently monitored through the use of administrative databases.

Cardiorespiratory treatments as modifiers of the relationship between particulate matter and health: a case-only analysis on hospitalized patients in Italy.

BACKGROUND A few panel and toxicological studies suggest that health effects of particulate matter (PM) might be modified by medication intake, but whether this modification is confirmed in the general population or for more serious outcomes is still unknown. OBJECTIVES We carried out a population-based pilot study in order to assess how pre-hospitalization medical treatments modify the relationship between PM<10 μm in aerodynamic diameter (PM10) and the risk of cardiorespiratory admission. METHODS We gathered information on hospitalizations for cardiorespiratory causes, together with pre-admission pharmacological treatments, that occurred during 2005 in seven cities located in Lombardy (Northern Italy). City-specific PM10 concentrations were measured at fixed monitoring stations. Each treatment of interest was analyzed separately through a case-only approach, using generalized additive models accounting for sex, age, comorbidities, temperature and simultaneous intake of other drugs. Analyses were stratified by season and, if useful, by age and sex. RESULTS Our results showed a higher effect size for PM10 on respiratory admissions in subjects treated with theophylline (Odds Ratio (OR) of treatment for an increment of 10 μg/m(3) in PM10 concentration: 1.119; 95% Confidence Interval (CI): 1.013-1.237), while for cardiovascular admissions treatment with cardiac therapy (OR: 0.967, 95% CI: 0.940-0.995) and lipid modifying agents (OR: 0.962, 95% CI: 0.931-0.995) emerged as a protective factor, especially during the warm season. Evidence of a protective effect against the pollutant was found for glucocorticoids and respiratory admissions. CONCLUSIONS Our study showed that the treatment with cardiac therapy and lipid modifying agents might mitigate the effect of PM10 on cardiovascular health, while the use of theophylline seems to enhance the effect of the pollutant, possibly due to confounding by indication. It is desirable to extend the analyses to a larger population.

Amplitude Spectrum Area to Guide Defibrillation: A Validation on 1617 Ventricular Fibrillation Patients

Background— This study sought to validate the ability of amplitude spectrum area (AMSA) to predict defibrillation success and long-term survival in a large population of out-of-hospital cardiac arrests. Methods and Results— ECGs recorded by automated external defibrillators from different manufacturers were obtained from patients with cardiac arrests occurring in 8 city areas. A database, including 2447 defibrillations from 1050 patients, was used as the derivation group, and an additional database, including 1381 defibrillations from 567 patients, served as validation. A 2-second ECG window before defibrillation was analyzed, and AMSA was calculated. Univariable and multivariable regression analyses and area under the receiver operating characteristic curve were used for associations between AMSA and study end points: defibrillation success, sustained return of spontaneous circulation, and long-term survival. Among the 2447 defibrillations of the derivation database, 26.2% were successful. AMSA was significantly higher before a successful defibrillation than a failing one (13±5 versus 6.8±3.5 mV-Hz) and was an independent predictor of defibrillation success (odds ratio, 1.33; 95% confidence interval, 1.20–1.37) and sustained return of spontaneous circulation (odds ratio, 1.22; 95% confidence interval, 1.17–1.26). Area under the receiver operating characteristic curve for defibrillation success prediction was 0.86 (95% confidence interval, 0.85–0.88). AMSA was also significantly associated with long-term survival. The following AMSA thresholds were identified: 15.5 mV-Hz for defibrillation success and 6.5 mV-Hz for defibrillation failure. In the validation database, AMSA ≥15.5 mV-Hz had a positive predictive value of 84%, whereas AMSA ⩽6.5 mV-Hz had a negative predictive value of 98%. Conclusions— In this large derivation-validation study, AMSA was validated as an accurate predictor of defibrillation success. AMSA also appeared as a predictor of long-term survival.Background— This study sought to validate the ability of amplitude spectrum area (AMSA) to predict defibrillation success and long-term survival in a large population of out-of-hospital cardiac arrests. Methods and Results— ECGs recorded by automated external defibrillators from different manufacturers were obtained from patients with cardiac arrests occurring in 8 city areas. A database, including 2447 defibrillations from 1050 patients, was used as the derivation group, and an additional database, including 1381 defibrillations from 567 patients, served as validation. A 2-second ECG window before defibrillation was analyzed, and AMSA was calculated. Univariable and multivariable regression analyses and area under the receiver operating characteristic curve were used for associations between AMSA and study end points: defibrillation success, sustained return of spontaneous circulation, and long-term survival. Among the 2447 defibrillations of the derivation database, 26.2% were successful. AMSA was significantly higher before a successful defibrillation than a failing one (13±5 versus 6.8±3.5 mV-Hz) and was an independent predictor of defibrillation success (odds ratio, 1.33; 95% confidence interval, 1.20–1.37) and sustained return of spontaneous circulation (odds ratio, 1.22; 95% confidence interval, 1.17–1.26). Area under the receiver operating characteristic curve for defibrillation success prediction was 0.86 (95% confidence interval, 0.85–0.88). AMSA was also significantly associated with long-term survival. The following AMSA thresholds were identified: 15.5 mV-Hz for defibrillation success and 6.5 mV-Hz for defibrillation failure. In the validation database, AMSA ≥15.5 mV-Hz had a positive predictive value of 84%, whereas AMSA ≤6.5 mV-Hz had a negative predictive value of 98%. Conclusions— In this large derivation-validation study, AMSA was validated as an accurate predictor of defibrillation success. AMSA also appeared as a predictor of long-term survival. # CLINICAL PERSPECTIVE {#article-title-40}

The short-term effect of particulate matter on cardiorespiratory drug prescription, as a proxy of mild adverse events

Introduction and aims The association between particulate matter < 10 &mgr;m in aerodynamic diameter (PM10) and mild disease episodes, not leading to hospitalization or death, has been rarely investigated. We studied the short‐term effect of PM10 on purchases of specific cardiorespiratory medications, as proxies of mild episodes, in 7 small‐ and medium‐sized cities of Northern Italy, during 2005–2006. Materials and methods We extracted information on purchased prescriptions from healthcare administrative databases, and we obtained daily PM10 concentrations from fixed monitoring stations. We applied a time‐stratified case‐crossover design, using the time‐series of antidiabetic drugs purchases to control for confounding due to irregularities in daily purchase frequencies. Results During the warm season, we estimated a delayed (lags 2–6) increased risk of buying glucocorticoid (4.53%, 95% Confidence Interval (CI): 2.62, 6.48) and adrenergic inhalants (1.66%, 95% CI: 0.10, 3.24), following an increment (10 &mgr;g/m3) in PM10 concentration. During the cold season, we observed an immediate (lags 0–1) increased risk of purchasing antiarrhythmics (0.76%; 95% CI: 0.16, 1.36) and vasodilators (0.72%; 95% CI: 0.30, 1.13), followed by a risk reduction (lags 2–6), probably due to harvesting. Conclusions Focusing on drug purchases, we reached sufficient statistical power to study PM10 effect outside large urban areas and conclude that short‐term increments in PM10 concentrations might cause mild cardiorespiratory disease episodes. HighlightsCardiorespiratory prescriptions are stored in administrative databases.Such prescriptions can be used as tracers of mild disease episodes.We studied the relationship between PM10 and such prescriptions outside urban areas.PM10 is associated with a short‐term increase in cardiorespiratory drugs consumption.