A randomized comparison of caspofungin versus antifungal prophylaxis according to investigator policy in acute leukaemia patients undergoing induction chemotherapy (PROFIL-C study).

BACKGROUND: Invasive fungal infections (IFIs) are considered a major problem among patients undergoing acute leukaemia (AL) induction treatment. PROphylaxis of Fungal invasive Infections in Leukaemia-Caspofungin (PROFIL-C) is a multicentre study aiming to assess the comparative yield of using caspofungin versus standard policy (SP) regimens and the overall impact of IFI in routine clinical care conditions. METHODS: All AL patients receiving IFI prophylaxis according to local SP were prospectively included in the study by Northern Italy Leukaemia Group (NILG) centres. To allow the comparison of caspofungin versus SP regimens as prophylaxis strategies, caspofungin treatment was assigned via a centralized randomized procedure. The study was registered at http://www.clinicaltrial.gov (NCT00501098). RESULTS: Over a 2 year period, 175 patients were included. The overall incidence of IFI was 32/175 (18.3%) [10/175 (5.7%) probable/proven and 22/175 (12.6%) possible], with no statistically significant differences between caspofungin-based versus SP-based regimens [overall: 15/93 (16.1%) versus 17/82 (20.7%), relative risk (RR) 0.78, 95% confidence interval (CI) 0.42-1.46; probable/proven: 7/93 (7.5%) versus 3/82 (3.7%), RR 2.06, 95% CI 0.55-7.7; possible: 8/93 (8.6%) versus 14/82 (17.1%), RR 0.5, 95% CI 0.22-1.14]. Only one IFI-related death was recorded (10%). CONCLUSIONS: The incidence and mortality of IFI were lower than expected in this strictly sequential cohort representative of the routine care in the NILG network. The efficacy and safety of caspofungin were similar to other prophylactic regimens.

Antidepressants and cardiovascular outcomes in patients without known cardiovascular risk.

PURPOSE: To identify a cohort of subjects without treatment for any cardiovascular risk and analyze the potential causative role of treatment for depression on the development of major cardiovascular outcomes during 2 years of follow-up. METHODS: We carried out a record-linkage analysis of hospital discharge records, prescription databases and vital statistics for all consecutive patients aged 30 years or older in one Italian region during a 4-year period. Depression was defined in terms of exposure to at least three prescriptions of antidepressant drugs within 1 year. Patients had no history of treatment with cardiovascular or antidiabetic agents and had not been hospitalized with a diagnosis of any cardiovascular condition in the preceding year. Follow-up was extended up to 2 years or to time to occurrence of major outcomes defined as either all-cause mortality, hospitalization for any cardiovascular cause or chronic exposure to cardiovascular drugs (antihypertensive, statins, antidiabetics). The results are expressed hazard ratios (HRs) and 95% confidence intervals (CIs) within age categories (30-49, 50-59, > or = 60 years). RESULTS: A total of 105,573 persons without treated cardiovascular risk at baseline were identified, among whom 1,129 (1.1%) had been chronically exposed to antidepressant treatment. Treated depression determined an increased risk of all cause-mortality (HR 1.88, 95% CI 1.33-2.66, p < 0.001) and of subsequent treatment with antidiabetic agents (HR 0.89, 95% CI 1.34-2.66, p < 0.001), statins (HR 1.87, 95% CI 1.53-2.29, p < 0.001) and antihypertensive drugs (HR 1.25, 95% CI 1.07-1.47, p = 0.006). CONCLUSION: Among the general population without treated cardiovascular risk, pharmacologic treatment for depression was associated with an increase in all-cause mortality and major cardiovascular outcomes.

Anemia and chronic heart failure: from pathophysiologic mechanisms to clinical trial designs.

In patients with heart failure, anemia is highly prevalent and associated with impaired outcomes. These clinical observations necessitate the realization of pharmacologic interventions to mitigate the effects of anemia and a number of available agents are being tested in large, randomized clinical trials. However, from the pathophysiologic point of view, anemia is multifactorial and difficult to attribute to a single mechanism. Moreover, classic indicators for the identification of etiology and pathways have been found to be less accurate than expected. For these reasons future clinical trials must be designed to be able to elucidate the complexity of mechanisms and the implications for treatment strategies.

Depression worsens outcomes in elderly patients with heart failure: an analysis of 48,117 patients in a community setting.

AIMS: To assess the relationship between depression and clinical outcomes among elderly patients with heart failure (HF) in a community setting. METHODS AND RESULTS: To identify patients with HF and depression we used record linkage analysis of hospital discharge records, prescription databases and vital statistics. All consecutive patients aged>or=60 years in 6 Local Health Authorities in Italy were included. HF was defined as either: 1) hospital discharge with HF diagnosis (ICD-9: 428) and/or 2) chronic treatment for HF identified as concomitant (within 45 days) prescription of any combination of ACE inhibitors, digoxin, furosemide, bisoprolol, carvedilol, spironolactone, ARB-blockers. Depression was identified from exposure to psychotropic drugs before HF diagnosis. Cox proportional hazards models adjusted for major confounders were used. To adjust for potential residual known confounders, a propensity score analysis was performed. Sensitivity and subgroup analysis were used to demonstrate the consistency or robustness of the results. 48,117 patients with HF were identified. Of these, 3328 (6.9%) were treated for depression. Among patients with HF, those with depression were significantly older, and more likely to be women with a previous stroke. Depression significantly worsened major outcomes including all cause mortality [HR (95%CI); 1.20 (1.08-1.33)] and the composite of stroke/TIA/AMI [1.23 (1.13-1.34)]. Patients with depression had no increased risk of rehospitalisation for HF. Propensity scores and subgroup analysis confirmed these findings. CONCLUSION: Among elderly patients with HF, depression was independently associated with poor clinical outcomes mostly due to an increase in vascular events.

Omega-3 fatty acid supplementation reduces one-year risk of atrial fibrillation in patients hospitalized with myocardial infarction.

PURPOSE: Current strategies for avoiding atrial fibrillation (AF) are of limited value. We aim to assess the relationship between omega-3 fatty acids (n-3 PUFA) and AF occurrence in post-myocardial infarction (MI) patients. METHODS: A population study, linking hospital discharge records, prescription databases, and vital statistics, was conducted and included all consecutive patients with MI (ICD-9: 410) in six Italian local health authorities over a 3-year period. A propensity score (PS)-based, 5-to-1, greedy 1:1 matching algorithm was used to check consistency of results. Sensitivity analysis was performed to assess the robustness of findings. RESULTS: N-3 PUFA reduced the relative risk of the hospitalization for AF [hazard ratio (HR) 0.19, 95% CI 0.07-0.51] and was associated with a further and complementary reduction in all-cause mortality (HR 0.15, 95% CI 0.05-0.46). PS-based matched analysis and sensitivity analysis confirmed the main results. CONCLUSION: n-3 PUFA reduced both all-cause mortality and incidence of 1-year AF in patients hospitalized with MI.

The prognostic influence of chronic obstructive pulmonary disease in patients hospitalised for chronic heart failure.

AIMS: To investigate the prevalence and the prognostic impact of chronic obstructive pulmonary disease (COPD), in patients hospitalised with chronic heart failure (CHF). METHODS AND RESULTS: In an observational study based on longitudinal information from administrative registers, 1020 patients aged >or=60 years, who were chronically treated for and hospitalised with CHF were identified and followed-up for major events up to 1 year. Median age was 80 years, half of the patients were female and 241 patients (23.6%) had concomitant COPD. There were no differences in the prevalence of cardiovascular and non-cardiovascular comorbidities between CHF patients with or without COPD. However, COPD patients were more often male (60.6% vs. 46.3%), more frequently treated with diuretics (95.9% vs. 91.5%) but less often exposed to beta-blockers (16.2% vs. 22.0%). Significantly higher adjusted in-hospital (HR 1.50 [95%CI 1.00-2.26]) and out-of-hospital (1.42 [1.09-1.86]) mortality rates were found in CHF patients with concomitant COPD. A higher occurrence of non-fatal AMI/stroke/rehospitalisation for CHF (1.26 [1.01-1.58]) as well as hospitalisation for CHF (1.35 [1.00-1.82]) was associated with COPD. CONCLUSIONS: COPD is a frequent concomitant disease in patients with heart failure and it is an independent short-term prognostic indicator of mortality and cardiovascular comorbidity in patients who have been admitted to hospital for heart failure.

Antithrombotic treatment is strongly underused despite reducing overall mortality among high-risk elderly patients hospitalized with atrial fibrillation.

AIMS: To assess the use of antithrombotic treatment (ATT) after hospitalization with atrial fibrillation (AF) and the attributable effectiveness of ATT during follow-up. METHODS AND RESULTS: On the basis of record linkage of administrative registers, 1812 patients discharged with AF were identified and followed-up for major clinical events up to 1 year. Mean age was 79 years. After hospitalization, 56% of the patients received ATT: 29% anticoagulants, 22% antiplatelets (APs), and 5% both agents. Among patients without comorbidities, 63.0% were exposed to ATT. Several factors significantly influence the use of antithrombotic agents, including increasing age [odds ratio (OR) 0.93 (95% confidence interval (CI), 0.92-0.95)], chronic obstructive pulmonary disease [0.77 (0.59-1.00)], malignancy [0.57 (0.39-0.82)], and previous use of ATT [4.56 (3.67-5.67)]. A significantly lower mortality was observed in patients exposed to ATT [hazard ratio (HR) 0.36 (95% CI, 0.28-0.47)], both to anticoagulants [0.23 (0.15-0.35)] and to APs [0.66 (0.50-0.86)]. ATT was associated with the reduction of thrombo-embolic events [0.52 (0.25-1.07)]. Major bleeding did not contribute to increased morbidity. Subgroups analysis, propensity score (PS), and sensitivity analysis confirmed these results. CONCLUSION: Our data demonstrated that ATT was underused, also in patients without comorbidities. Exposure to ATT is associated with improved survival among elderly high-risk community patients hospitalized with AF.

[Administrative databases as a basic tool for the epidemiology of cardiovascular diseases]. / Database amministrativi come risorsa accessibile e strumento efficiente per l'epidemiologia cardiovascolare. Metodologia generale e scenari di applicazione ai modelli della cronicità e dello scompenso.

The broader availability of administrative databases, characterized by increasing data reliability, related to the various steps of the healthcare process, has became also in Italy an important resource for epidemiological studies. Specifically, the methodological developments in the handling and analysis of drug prescription files can be seen as the original and highly informative backbone of a comprehensive monitoring of healthcare delivery processes. The area of chronic cardiovascular treatments occupies a privileged space in these developments, which are illustrated in the paper, with a synthetic presentation of the methodology supported by a model analysis of the epidemiology of heart failure in a healthcare district and by a reference list which has been conceived to provide to the reader a comprehensive perspective on an area so far largely unexplored.