Risk-adapted treatment of acute promyelocytic leukemia: results from the International Consortium for Childhood APL.

Pediatric acute promyelocytic leukemia (APL) can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials have employed high cumulative doses of anthracyclines. Here, we report the outcome of newly diagnosed APL patients enrolled in the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically proven APL. Patients were stratified into standard-risk (SR) and high-risk (HR) groups according to baseline white blood cell counts (<10 × 109/L or ≥10 × 109/L); both groups received identical induction treatment with ATRA and 3 doses of idarubicin. Two or 3 blocks of consolidation therapy were administered to SR and HR patients, respectively, while maintenance therapy with low-dose chemotherapy and ATRA cycles was given to all patients for 2 years. The cumulative dose of daunorubicin equivalent anthracyclines in SR and HR patients was lower than that of previous studies (355 mg/m2 and 405 mg/m2, respectively). Hematologic remission was obtained in 97% of patients; 8 children died of intracranial hemorrhage in the first 2 weeks following diagnosis. Five-year overall and event-free survival for the whole cohort were 94.6% and 79.9%, respectively; they were 98.4% and 89.4% in SR patients and 84.3% and 74.2% in HR patients (P = .002 and P = .043, respectively). These data demonstrate that extended use of ATRA coupled to a risk-adapted consolidation can achieve high cure rates in childhood APL and limit anthracycline exposure. The trial was registered at www.clinicaltrials.gov as EudractCT 2008-002311-40.

[The contribution of the Italian Association of paediatric haematology and oncology (AIEOP)]. / Il contributo dell'Associazione italiana di ematologia e oncologia pediatrica (AIEOP).

Since 1972, children affected by cancer took advantage from multi-centric diagnostic and therapeutic protocols produced by the Italian Association of paediatric haematology and oncology (AIEOP). At the beginning, these protocols were used in few well-trained centres, later in almost all Italian haemato-oncological centres. The need of a careful monitoring of his own activity induced AIEOP to achieve, in 1989, an Italian hospital- based registry (database Mod.1.01) of malignant tumours diagnosed and treated in the participating centres, with the aim to quantify the number of cases diagnosed and treated in the different centres, the agreement (or not) to official diagnostic- therapeutic protocols, and the extraregional migration. The database Mod.1.01, which is available via web to the current 55 AIEOP centres since 2000, recruits annually about 1,400 children (0-14 years) and 200 adolescents (15-19 years). While the first accounts for over 90% of expected subjects, the latter are only 25%. Leukaemias (30% of cases) are the most frequent childhood cancers, followed by central nervous system (CNS) tumours and lymphomas, 18% of cases both. In children, leukaemias (34%) are prevalent, mostly acute lymphoblastic leukaemia (26%), followed by CNS tumours (18%); in adolescents, lymphomas (30%) are prevalent, mostly Hodgkin lymphomas (22%), followed by bone sarcomas (16%). The recruitment of registered cases in AIEOP protocols is overall good both for children (70%) and for adolescents (60%), achieving outstanding results in leukaemia protocols. Extraregional migration of patients for diagnosis and therapy is decreasing over time, being currently about 20%, higher in adolescents, in solid tumours, and in residents in South Italy and in the islands. On the contrary, an increase of subjects born and resident abroad who are hospitalised in AIEOP centres for diagnosis and treatment, accounting at present for 5% of all cases, was observed. The results confirm that the database Mod.1.01 can be a valid tool able to contribute to epidemiologic research on childhood cancer in Italy.

Outcomes, health costs and use of antiplatelet agents in 7,082 patients admitted for an acute coronary syndrome occurring in a large community setting.

PURPOSE: To assess the outcomes of patients admitted for ACS and the prescription pattern of antiplatelets of patients discharged alive. METHODS: From the ARNO Observatory database, we performed a record linkage analysis of hospital discharge and prescription databases, which included 2,758,872 subjects of 7 Italian Local Health Authorities. The accrual period lasted from January 1 to December 31, 2008. Discharge records and prescription patterns were analyzed for 1 year before and after the accrual period. RESULTS: Of 2,758,872 subjects, 7,082 (2.6‰) were hospitalized for ACS. Mean age was 72±13 years, females and diabetics accounted for 36% and 25% of the cases. Of the 7,082 patients, in-hospital death occurred in 6.9%. Of the survivors, 64.5% was treated medically, 35.5% with PCI. Of the patients discharged alive, 65.8% were treated with an antiplatelet, 21.9% aspirin alone, 33.1% aspirin plus a thienopyridine (mostly clopidogrel), 10.5% a thienopyridine alone. Dual antiplatelet treatment was prescribed more frequently in patients treated with PCI than in those treated medically (57.3% vs 19.7%, p<0.0001). At least one re-hospitalization occurred in 58.6% (18.5% for a recurrent episode of ACS, 24.8% for other CV reasons, 15.3% for non CV reasons). Prescription continuity to antiplatelets was observed in 68.0% and 60.3% of the patients, respectively at 6 and 12 months after discharge. CONCLUSION: In a large community setting, the prescription rate of antiplatelets after ACS seems to be far from the guidelines recommendation. Rates of 1 year re-hospitalizations after ACS remain high, recurrence of ACS accounted for just one third of the cases.

Antidepressant drug prescription and risk of abnormal bleeding: a case-control study.

This study assessed the risk of any bleeding abnormalities, including the risk of gastrointestinal bleeding, associated with antidepressant exposure. We used a case-control methodology. Case patients were individuals admitted with a diagnosis of abnormal bleeding. Control subjects were individuals admitted on the same date without evidence of abnormal bleeding. During the study period, 11,025 case patients were admitted for bleeding abnormalities (matched with 21,846 eligible control subjects), and 1008 were admitted for gastrointestinal bleeding (matched with 1990 eligible control subjects). With respect to any bleeding abnormalities, antidepressants as a group were not associated with an increased risk (adjusted odds ratio [OR], 0.99; 95% confidence interval [CI], 0.90-1.08). Similarly, selective serotonin reuptake inhibitors as a group, the group of tricyclic and related antidepressants, and the group of other antidepressants were not associated with an increased risk of bleeding. With respect to gastrointestinal bleeding abnormalities, antidepressants as a group were associated with a modestly increased risk (adjusted OR, 1.34; 95% CI, 1.01-1.80). Whereas the group of tricyclic and related antidepressants was not associated with an increased risk of bleeding, the group of selective serotonin reuptake inhibitors was associated with a nonsignificant trend toward an increased risk of bleeding (adjusted OR, 1.31; 95% CI, 0.91-1.88) and the group of other antidepressants with a statistically significant increase in the risk of bleeding (adjusted OR, 1.74; 95% CI, 1.04-2.93). In a population with a low baseline risk of bleeding, we detected a significant increase in the risk of gastrointestinal bleeding only.

Drug utilisation profile in the Italian paediatric population.

OBJECTIVE: In order to evaluate the prescribing pattern in the Italian paediatric population, prescriptions involving 923,353 children under 14 years old and dispensed during 2006 by the retail pharmacies of 22 Italian local health units were analysed. MATERIALS AND METHODS: A total of 561,237 children (61%) received at least one drug prescription. The prescription prevalence rate was highest in children 3 years of age (78%), decreased with increasing age and was higher in boys than in girls (chi(2)=655; p<<0.001). Each treated child received an average of 3.2 prescriptions and 4.8 boxes. RESULTS: Antibiotics and anti-asthmatics were the more prescribed therapeutic classes and represented 80% of prescriptions. Amoxicillin+clavulanic acid was the most prescribed drug (24% of the overall population; 17% of all boxes), followed by inhaled beclometasone and amoxicillin. A total of 620 different drugs were prescribed and the ten leading drugs represented 64% of the prescribed boxes. Six of the ten most prescribed drugs were the same in all age groups. Wide differences were found in the prevalence rate between the different local health units; these ranged between 50.1 and 68.4% (p<<0.001). The prescription prevalence increased in the 2000-2002 period (from 62.2 to 68.3%) and slightly decreased afterwards. CONCLUSION: Despite some limitations, the systematic monitoring of prescriptions is a valuable tool for evaluating the appropriateness of the care.

Survival of children with cancer in Italy, 1989-98. A report from the hospital based registry of the Italian Association of Paediatric Haematology and Oncology (AIEOP).

We describe the survival patterns of 10,791 Italian children (age 0-14) diagnosed with cancer during 1989-1998 and who were included in the hospital-based registry of the Italian Association of Paediatric Haematology and Oncology. Five-year cumulative survival percentages were 76% for lymphoproliferative disorders and 68% for solid tumours. Survival rates in 1994-1998 significantly improved for acute lymphocytic leukaemia (ALL), acute non-lymphocytic leukaemia, Hodgkin's lymphoma and Wilms' tumour. Gender and age were determinants of survival for some specific types of cancer. Girls with ALL and neuroblastoma exhibited a significant advantage (hazard ratio HR 0.72, 0.62-0.83) and disadvantage (HR 0.73, 0.59-0.90) over boys, respectively. Children with a Wilms' tumour diagnosed above age 3 had a worse prognosis than younger children (HR 2.3, 1.4-4.1). The persisting gender-related difference in survival rate for ALL requires understanding as to whether it is attributable to delays in the adoption of more recent therapeutic protocols, while the corresponding findings for Wilms' tumour and neuroblastoma deserve further biological interpretation.

The 'Survivorship Passport' for childhood cancer survivors.

BACKGROUND: Currently, there are between 300,000 and 500,000 childhood cancer survivors (CCSs) in Europe. A significant proportion is at high risk, and at least 60% of them develop adverse health-related outcomes that can appear several years after treatment completion. Many survivors are unaware of their personal risk, and there seems to be a general lack of information among healthcare providers about pathophysiology and natural history of treatment-related complications. This can generate incorrect or delayed diagnosis and treatments. METHOD: The Survivorship Passport (SurPass) consists of electronic documents, which summarise the clinical history of the childhood or adolescent cancer survivor. It was developed by paediatric oncologists of the PanCare and SIOPE networks and IT experts of Cineca, together with parents, patients, and survivors' organisations within the European Union-funded European Network for Cancer research in Children and Adolescents. It consists of a template of a web-based, simply written document, translatable in all European languages, to be given to each CCS. The SurPass provides a summary of each survivor's clinical history, with detailed information about the original cancer and of treatments received, together with personalised follow-up and screening recommendations based on guidelines published by the International Guidelines Harmonization Group and PanCareSurFup. RESULTS: The SurPass data schema contains a maximum of 168 variables and uses internationally approved nomenclature, except for radiotherapy fields, where a new classification was defined by radiotherapy experts. The survivor-specific screening recommendations are mainly based on treatment received and are automatically suggested, thanks to built-in algorithms. These may be adapted and further individualised by the treating physician in case of special disease and survivor circumstances. The SurPass was tested at the Istituto Giannina Gaslini, Italy, and received positive feedback. It is now being integrated at the institutional, regional and national level. CONCLUSIONS: The SurPass is potentially an essential tool for improved and more harmonised follow-up of CCS. It also has the potential to be a useful tool for empowering CCSs to be responsible for their own well-being and preventing adverse events whenever possible. With sufficient commitment on the European level, this solution should increase the capacity to respond more effectively to the needs of European CCS.

Massive pulmonary embolism.

BACKGROUND: Acute massive pulmonary embolism (PE) carries an exceptionally high mortality rate. We explored how often adjunctive therapies, particularly thrombolysis and inferior vena caval (IVC) filter placement, were performed and how these therapies affected the clinical outcome of patients with massive PE. METHODS AND RESULTS: Among 2392 patients with acute PE and known systolic arterial blood pressure at presentation, from the International Cooperative Pulmonary Embolism Registry (ICOPER), 108 (4.5%) had massive PE, defined as a systolic arterial pressure <90 mm Hg, and 2284 (95.5%) had non-massive PE with a systolic arterial pressure > or =90 mm Hg. PE was first diagnosed at autopsy in 16 patients (15%) with massive PE and in 29 patients (1%) with non-massive PE (P<0.001). The 90-day mortality rates were 52.4% (95% CI, 43.3% to 62.1%) and 14.7% (95% CI, 13.3% to 16.2%), respectively. In-hospital bleeding complications occurred in 17.6% versus 9.7% and recurrent PE within 90 days in 12.6% and 7.6%, respectively (P<0.001). In patients with massive PE, thrombolysis, surgical embolectomy, or catheter embolectomy were withheld in 73 (68%). Thrombolysis was performed in 33 patients, surgical embolectomy in 3, and catheter embolectomy in 1. Thrombolytic therapy did not reduce 90-day mortality (thrombolysis, 46.3%; 95% CI, 31.0% to 64.8%; no thrombolysis, 55.1%; 95% CI, 44.3% to 66.7%; hazard ratio, 0.79; 95% CI, 0.44 to 1.43). Recurrent PE rates at 90 days were similar in patients with and without thrombolytic therapy (12% for both; P=0.99). None of the 11 patients who received an IVC filter developed recurrent PE within 90 days, and 10 (90.9%) survived at least 90 days. IVC filters were associated with a reduction in 90-day mortality (hazard ratio, 0.12; 95% CI, 0.02 to 0.85). CONCLUSIONS: In ICOPER, two thirds of the patients with massive PE did not receive thrombolysis or embolectomy. Counterintuitively, thrombolysis did not reduce mortality or recurrent PE at 90 days. The observed reduction in mortality from IVC filters requires further investigation.

Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher.

BACKGROUND: The prognostic role of echocardiographic right ventricular (RV) dysfunction for predicting mortality in patients with acute pulmonary embolism and a preserved systemic arterial pressure remains controversial. METHODS: We evaluated 1035 patients with pulmonary embolism from the International Cooperative Pulmonary Embolism Registry who (1) presented with systolic systemic arterial pressure of 90 mm Hg or higher and (2) who underwent echocardiography within 24 hours of a diagnosis of pulmonary embolism, showing presence (n = 405) or absence (n = 630) of RV hypokinesis. The main outcome measure was the cumulative survival rate through 30 days in patients with and without RV hypokinesis. RESULTS: In patients with RV hypokinesis, the initial systolic systemic pressure was lower (125 +/- 22 mm Hg vs 131 +/- 22 mm Hg; P<.001), and the initial heart rate was higher (104 +/- 21 beats per minute vs 99 +/- 22 beats per minute; P<.001) than in patients without RV hypokinesis. Cancer was less often present (14.1% vs 22.5%, P = .001). The 30-day survival rates in patients with and without RV hypokinesis were 83.7% (95% confidence interval [CI], 79.3%-87.0%) and 90.6% (95% CI, 88.0%-92.6%), respectively (log-rank P value <.001). The univariate hazard ratio of RV hypokinesis for predicting 30-day mortality was 2.11 (95% CI, 1.41-3.16; P<.001). Right ventricular hypokinesis remained an independent predictor of 30-day mortality (hazard ratio, 1.94; 95% CI, 1.23-3.06) after adjusting for univariately significant predictors, including cancer, congestive heart failure, chronic lung disease, age older than 70 years, systolic arterial pressure of 100 mm Hg or lower, administration of thrombolytic therapy, and heart rate greater than 100 beats per minutes. CONCLUSION: Among patients with pulmonary embolism who present with a systolic arterial pressure greater than or equal to 90 mm Hg, echocardiographic RV hypokinesis is an independent predictor of early death.

Gefitinib in pretreated non-small-cell lung cancer (NSCLC): analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC.

PURPOSE: To evaluate the correlation between HER2 expression and gefitinib (ZD 1839, Iressa; AstraZeneca, London, United Kingdom) efficacy in terms of response rate, time to progression (TTP), and overall survival (OS) time. PATIENTS AND METHODS: Patients with pretreated advanced non-small-cell lung cancer (NSCLC) received gefitinib at a daily dose of 250 mg until disease progression. Tumor tissue specimens obtained at the time of primary diagnosis were collected to determine HER2/epidermal growth factor receptor (EGFR) status by immunohistochemistry. RESULTS: From February 2001 to June 2002, 63 consecutive patients were enrolled onto the study. The overall disease control rate was 58.7% (partial response [PR], 15.9%; stable disease [SD], 42.8%), median TTP was 3.3 months, and median OS was 4.1 months. Among the 43 patients in whom EGFR/HER2 status was determined, we observed six PRs (14%) and 18 SDs (42%). Disease control, including PR and SD, was 40% in the 15 patients overexpressing HER2 and 64.3% in the 28 patients not overexpressing HER2 (P =.126). No difference was found between the two groups in terms of TTP (3.5 v 3.7 months, respectively) and OS (5.7 v 6.8 months, respectively). In addition, we did not find any difference in TTP, OS, toxicity, and symptom outcome in the group of patients overexpressing both HER2 and EGFR compared with patients who had no overexpression of HER2 CONCLUSION: According to these data, efficacy, toxicity, and symptom outcome in patients with NSCLC treated with gefitinib do not seem to be related to HER2 expression.

Right heart thrombi in pulmonary embolism: results from the International Cooperative Pulmonary Embolism Registry.

OBJECTIVES: This study was designed to investigate the prevalence and prognostic significance of right heart thrombi (RHTh) in pulmonary embolism. BACKGROUND: Most reports about patients with RHTh are small case series. We analyzed data referring to RHTh among 2,454 consecutive pulmonary embolism patients enrolled in the International Cooperative Pulmonary Embolism Registry. METHODS: Of the 2,454 patients, 1,113 had results available from baseline echocardiography. We compared the 42 patients with RHTh versus 1,071 without RHTh. RESULTS: Patients with RHTh had shorter duration of symptoms (2.2 +/- 2.9 days vs. 4.3 +/- 6.0 days, p = 0.013), lower systolic blood pressure (BP) (116.0 +/- 28.8 vs. 125.7 +/- 25.0 mm Hg, p = 0.008), and more frequent right ventricular hypokinesis (64% vs. 40%, p = 0.002) and congestive heart failure (26% vs. 13%, p = 0.024); but they had similar age (62.9 vs. 62.5 years), arterial oxygen pressure (71.3 +/- 26.0 vs. 69.5 +/- 30.5 mm Hg), and prevalence of cancer (14% vs. 19%). The overall mortality rate at 14 days and at three months was higher in patients with RHTh (21% vs. 11%, p = 0.032, and 29% vs. 16%, p = 0.036). The difference in early mortality was observed almost entirely within the subgroup of patients treated with heparin alone (23.5% vs. 8%, p = 0.02), despite similar clinical severity at presentation (systolic BP 122.2 +/- 24.2 vs. 127.8 +/- 24.1 mm Hg, hypotension in 5.9% vs. 3.4% patients). CONCLUSIONS: Among patients with acute pulmonary embolism, RHTh is usually found in those more hemodynamically compromised but is also a marker of worse prognosis in initially apparently stable patients treated with heparin alone.

Overt hepatic encephalopathy in Italy: clinical outcomes and healthcare costs.

PURPOSE: Hepatic encephalopathy (HE) is a recurrent severe complication of progressive hepatic cirrhosis. The aim of this study is to evaluate the average annual direct healthcare costs for the treatment of patients with overt HE in Italy. PATIENTS AND METHODS: This retrospective, observational study analyzed information from the database of ARNO Observatory. Patients with at least one hospitalization due to overt HE in the period from January 1, 2011 to December 31, 2011, were selected and observed during the year following the hospitalization. Costs for drugs, diagnostic and therapeutic procedures, and hospitalizations were estimated from the Italian National Health Service perspective. RESULTS: Out of a population of 2,678,462 subjects, 381 patients were identified, of whom, 21.5% died during the first hospitalization and 5.8% during the follow-up; the survival rate was 72.7% at the end of the observation period. The direct healthcare costs per patient amounted to €13,393/year (15,295 USD) (88% for hospitalizations, 8% for drugs, and 4% for diagnostic procedures). During the follow-up, 42.5% of patients had at least one rehospitalization due to HE. Patients readmitted for HE had an average annual cost of €21,272 (24,293 USD), almost doubled if compared to patients without readmissions (€12,098 [13,816 USD]). CONCLUSION: This analysis showed that patients with HE had relevant direct healthcare costs, in which hospitalizations were the most important cost drivers.

Use and misuse of statins after ACS: analysis of a prescription database of a community setting of 2,042,968 subjects.

AIMS: To assess in a community setting how patients discharged alive after an acute coronary syndrome (ACS) are treated with statins. Specifically, the rate of prescription, the dosages, and 1-year adherence have been evaluated. METHODS AND RESULTS: From the ARNO Observatory, we carried out a record linkage analysis of discharge records for ACS and prescription databases, which included 2,042,968 subjects of seven local health authorities from northern to southern Italy. The accrual period lasted from 1 January to 30 June 2007. Logistic regression analysis was performed to identify the independent predictors of prescription continuity. Of the 2,042,968 subjects, 1.5‰ were hospitalised for ACS over the 6 months, 58% of patients were aged more than 70 years, and females accounted for 33% of the cases. In-hospital all-cause death was 7.4%. Of the patients discharged alive, 80.7% received a statin treatment. High dosage of statins were used only in a minority of cases. After 1-year follow up, adherence to treatment was observed in 67.2% of patients. Older age and the presence of comorbidities were independently associated with a better prescription continuity, while presence of cancer or depression was associated with a poor prescription continuity. CONCLUSION: In a community setting, the rate of prescription of statins seems to be satisfactory. However, the dosages of statins suggest that the recommendation to use intensive statin treatment seems to be not adequately followed. Further, prescription continuity over time was suboptimal. There is still a relevant gap between evidence-based recommendations and what actually happens in routine clinical practice.

Direct healthcare costs and resource consumption after acute coronary syndrome: a real-life analysis of an Italian subpopulation.

BACKGROUND: Acute coronary syndrome (ACS) is the most common cause of morbidity and mortality in Italy and worldwide. Aim of this study was to evaluate the average annual direct healthcare costs for the treatment of patients with a recent hospitalization for ACS. DESIGN AND METHODS: The direct medical costs of patients with a first ACS hospitalization (index event) in the period from 1 January 2008 to 31 December 2008 were estimated for a 1-year follow-up period. The resource consumption was measured in terms of: reimbursed drugs, diagnostic procedures, outpatient visits, and hospitalizations. The analysis was performed from the Italian National Health Service perspective. RESULTS: A total of 2,758,872 subjects were observed, 7082 (35.8% women) of whom being hospitalized for ACS during the accrual period (2.6 ‰). Among patients with ACS, 60% were medically treated, 33.1% were treated with percutaneous coronary intervention (PCI), and 6.9% died during the index hospitalization. Dual antiplatelet treatment (ASA plus clopidogrel) was prescribed in 25.9% of the medically treated ACS patients and in 70.1% of the ACS patients treated with PCI. The average yearly cost per patient for the total ACS population was 11,464€/year (drugs 1,304€; hospitalizations 9,655€; diagnostic and outpatient visits 505€). The average annual cost was 10,862€ for medically treated patients and 14,111€ for patients treated with PCI. Patients who died of cardiovascular events during follow up had an average cost of 16,231€/patient. CONCLUSIONS: Patients with ACS had higher direct healthcare costs, their management and rehospitalizations being the main cost drivers.

Antidiabetic therapy in real practice: indicators for adherence and treatment cost.

BACKGROUND: Type 2 diabetes has become a disease with a high economic and social impact. The ARNO Observatory is a clinical data warehouse consisting of a network of local health care units (ASL) scattered throughout the Italian territory which collects data on health care consumption for about 10.5 million people. The purpose of this study was to evaluate the use of antidiabetic drugs with particular reference to type of treatment. The analyses were carried out on a sample of 169,375 patients treated with oral blood glucose-lowering drugs in 2008 from a total population of 4,040,624 health care beneficiaries at 12 local health care units in the ARNO Observatory. METHODS: Patients were considered "on treatment with oral blood glucose-lowering drugs" if they had received at least one prescription of an antidiabetic drug (Anatomical Therapeutic Chemical code A10B) during 2008. The patients were divided into three treatment groups, ie, monotherapy, fixed-combination drugs, and dual therapy. The following indicators were assessed: number of patients treated with an oral antidiabetic drug, mean number of hospitalizations, mean number of specialist examinations, and mean expenditure per treated patient. Adherence was assessed using the medication possession ratio indicator (MPR). RESULTS: Patients treated with oral blood glucose-lowering drugs comprised 4.2% of the investigated population, and had an average age of 68.9 years. The mean annual number of hospitalizations was lower in the dual therapy group (298 versus 328 per 1000 patients in the sample), while the average number of specialist examinations was lower in the fixed-combination group (30.1 versus 35.1). Patients on monotherapy showed a better percentage of adherence for glimepiride (70.5%) and pioglitazone (70.4%), whereas the best adherence in the fixed-combination therapy group was recorded for metformin + pioglitazone (75.5%). The average annual cost per diabetic patient was €2388, with differences between the monotherapy (€2321), fixed-combination (€2270), and dual therapy (€2465) groups. Fixed combination therapy involved a lower mean expenditure for insulin, other drugs, and specialist and diagnostic care. Thiazolidinediones (such as pioglitazone) showed the lowest average annual cost per patient among the monotherapies, with a marked decrease in costs for hospitalization, specialist care, and diagnostics. CONCLUSION: The results of our study should be extended to other regional/national reference local health care units in order to define and compare average standard costs per pathology throughout the wide sample considered in this research work. Appropriate drug prescribing is of critical importance in order to achieve therapeutic objectives and to optimize the use of resources in modern health care systems.

Use of aliskiren in a 'real-life' model of hypertension management: analysis of national Web-based drug-monitoring system in Italy.

INTRODUCTION: In Italy, prescriptions of the direct renin inhibitor aliskiren (aliskiren) to high-risk hypertensive patients must be electronically filled by specialized physicians only when at least two antihypertensive drug classes (independently of the dosages), fails to normalize blood pressure (BP) levels. AIM: To analyze the effects of the addition of aliskiren 150-300 mg daily to antihypertensive therapy in a population of high cardiovascular risk hypertensive patients with uncontrolled BP levels. METHODS: Clinical data were derived from patients included in the national Web-based drug-monitoring system. Follow-up visits were required for measuring BP levels, and collecting data on drug safety and tolerability. RESULTS: Between March 2009 and February 2010, aliskiren was prescribed by 6464 specialized physicians to 11 511 treated, uncontrolled hypertensive patients (47.6% women, aged 68.0 ±â€Š11.1 years, BMI 28.4 ±â€Š4.9 kg/m) with organ damage or comorbidities. During 6-month observation, only a few drug-related side-effects were reported (n = 33). At the entry and 1-month follow-up visits (n = 8197; 70.6%), BP levels were 158.9 ±â€Š16.8 and 142.1 ±â€Š15.2 mmHg for SBP and 90.8 ±â€Š9.6 and 83.1 ±â€Š8.5 mmHg for DBP, respectively. At 6-month (n = 4907; 42.3%), SBP and DBP levels were 137.9 ±â€Š13.9 and 81.3 ±â€Š8.0 mmHg, respectively. A consistent reduction in the use of all classes of concomitant antihypertensive drugs was recorded. CONCLUSION: Although data derived from national registries need to be interpreted with caution, the Italian Web-based drug-monitoring system provided information on 'real-life' use of aliskiren in hypertension. In this uncontrolled, high-risk treated hypertensive population, SBP and DBP levels recorded during treatment with aliskiren were consistently lower than those recorded at entry visits in a context of a very low rate of reported side-effects.

Foreign children with cancer in Italy.

BACKGROUND: There has been a noticeable annual increase in the number of children coming to Italy for medical treatment, just like it has happened in the rest of the European Union. In Italy, the assistance to children suffering from cancer is assured by the current network of 54 centres members of the Italian Association of Paediatric Haematology and Oncology (AIEOP), which has kept records of all demographic and clinical data in the database of Mod.1.01 Registry since 1989. METHODS: We used the information stored in the already mentioned database to assess the impact of immigration of foreign children with cancer on centres' activity, with the scope of drawing a map of the assistance to these cases. RESULTS: Out of 14,738 cases recorded by all centres in the period from 1999 to 2008, 92.2% were born and resident in Italy, 4.1% (608) were born abroad and living abroad and 3.7% (538) were born abroad and living in Italy. Foreign children cases have increased over the years from 2.5% in 1999 to. 8.1% in 2008.Most immigrant children came from Europe (65.7%), whereas patients who came from America, Asia and Oceania amounted to 13.2%, 10.1%, 0.2%, respectively. The immigrant survival rate was lower compared to that of children who were born in Italy. This is especially true for acute lymphoblastic leukaemia patients entered an AIEOP protocol, who showed a 10-years survival rate of 71.0% vs. 80.7% (p < 0.001) for immigrants and patients born in Italy, respectively. CONCLUSIONS: Children and adolescents are an increasingly important part of the immigration phenomenon, which occurs in many parts of the world. In Italy the vast majority of children affected by malignancies are treated in AIEOP centres. Since immigrant children are predominantly treated in northern Italy, these centres have developed a special expertise in treating immigrant patients, which is certainly very useful for the entire AIEOP network.

[Cardiovascular Risk Assessment: preliminary results]. / Osservatorio del Rischio Cardiovascolare: primi risultati.

BACKGROUND: The Italian National Prevention plan includes 10-year cardiovascular risk (CR) assessment of the Italian general population aged 35-69 years using the CUORE Project risk score. A national training program for general practitioners (GPs) was launched by the Ministry of Health in 2003. GPs were encouraged to collect data on risk factors and risk assessment and to contribute to the CUORE Project Cardiovascular Risk Observatory (CRO). The aim of this analysis is to demonstrate the feasibility and effectiveness of risk assessment in primary care. METHODS: The cuore.exe software, free of charge for GPs and easily downloadable from the CUORE Project web site (www.cuore.iss.it), is the frame for the GP data collection. The CRO provides a platform to analyze data collected on risk assessment and risk factors, and compare results at regional and national level in order to support health policy makers in their decision process. RESULTS: From January 2007 to April 2009, 2858 GPs have downloaded the cuore.exe software; 102,113 risk assessments were sent to the CRO based on risk factors profile of 87,556 persons (3617 persons had more than 1 risk assessment). Mean level of CR was 3.1% in women and 8.4% in men; 30% of men and 65% of women were at low risk (CR < 3%), 9% of men and 0.4% of women were found at high risk (CR > or = 20%). Among those with at least 2 risk assessments, 8% shifted to a lower class of risk after 1 year. Mean level of systolic and diastolic blood pressure decreased by about 1% in 1 year; total cholesterol more than 2%, and prevalence of smokers decreased by about 3% in the second risk assessment. CONCLUSIONS: These data demonstrate that risk assessment can be included as a first step of prevention in primary care. The CUORE Project individual score is expected to become an important tool for GPs to assess their patients' CR, to promote primary prevention, and to focus attention to healthy lifestyle adoption.

Approaches to interim analysis of cancer randomised clinical trials with time to event endpoints: a survey from the Italian National Monitoring Centre for Clinical Trials.

BACKGROUND: Although interim analysis approaches in clinical trials are widely known, information on current practice of planned monitoring is still scarce. Reports of studies rarely include details on the strategies for both data monitoring and interim analysis. The aim of this project is to investigate the forms of monitoring used in cancer clinical trials and in particular to gather information on the role of interim analyses in the data monitoring process of a clinical trial. This study focused on the prevalence of different types of interim analyses and data monitoring in cancer clinical trials. METHODS: Source of investigation were the protocols of cancer clinical trials included in the Italian registry of clinical trials from 2000 to 2005. Evaluation was restricted to protocols of randomised studies with a time to event endpoint, such as overall survival (OS) or progression free survival (PFS). A template data extraction form was developed and tested in a pilot phase. Selection of relevant protocols and data extraction were performed independently by two evaluators, with differences in the data assessment resolved by consensus with a third reviewer, referring back to the original protocol. Information was obtained on a) general characteristics of the protocol b) disease localization and patient setting; c) study design d) interim analyses; e) DSMC. RESULTS: The analysis of the collected protocols reveals that 70.7% of the protocols incorporate statistical interim analysis plans, but only 56% have also a DSMC and be considered adequately planned. The most concerning cases are related to lack of any form of monitoring (20.0% of the protocols), and the planning of interim analysis, without DSMC (14.7%). CONCLUSION: The results indicate that there is still insufficient attention paid to the implementation of interim analysis.

Patterns of domestic migrations and access to childhood cancer care centres in Italy: a report from the hospital based registry of the Italian Association of Pediatric Hematology and Oncology (AIEOP).

Tertiary care centres, grouped in the Italian Association of Paediatric Haematology and Oncology (AIEOP) are unevenly distributed across the country. In an attempt to describe their perceived efficacy, we matched the residence and the location of the treatment centre in 18,441 patients aged