Validity of Italian administrative healthcare data in describing the real-world utilization of infusive antineoplastic drugs: the study case of rituximab use in patients treated at the University Hospital of Siena for onco-haematological indications.

Introduction: Italian administrative healthcare databases are frequently used for studies on real-world drug utilization. However, there is currently a lack of evidence on the accuracy of administrative data in describing the use of infusive antineoplastics. In this study, we used rituximab as a case study to investigate the validity of the regional administrative healthcare database of Tuscany (RAD) in describing the utilization of infusive antineoplastics. Methods: We identified patients aged 18 years or older who had received ≥1 rituximab administration between 2011 and 2014 in the onco-haematology ward of the University Hospital of Siena. We retrieved this information from the Hospital Pharmacy Database (HPD-UHS) and linked the person-level information to RAD. Patients who had received ≥1dispensing of rituximab, single administration episodes, and patients treated for non-Hodgkin Lymphoma (nHL) or Chronic Lymphocytic Leukemia (CLL) were identified in RAD and validated using HPD-UHS as the reference standard. We identified the indications of use using algorithms based on diagnostic codes (ICD9CM codes, nHL=200*, 202*; CLL=204.1). We tested 22 algorithms of different complexity for each indication of use and calculated sensitivity and positive predictive value (PPV), with 95% confidence intervals (95%CI), as measures of validity. Results: According to HPD-UHS, 307 patients received rituximab for nHL (N=174), CLL (N=21), or other unspecified indications (N=112) in the onco-haematology ward of the University Hospital of Siena. We identified 295 rituximab users in RAD (sensitivity=96.1%), but PPV could not be assessed due to missing information in RAD on dispensing hospital wards. We identified individual rituximab administration episodes with sensitivity=78.6% [95%CI: 76.4-80.6] and PPV=87.6% [95%CI: 86.1-89.2]. Sensitivity of algorithms tested for identifying nHL and CLL ranged from 87.7% to 91.9% for nHL and from 52.4% to 82.7% for CLL. PPV ranged from 64.7% to 66.1% for nHL and from 32.4% to 37.5% for CLL. Discussion: Our findings suggest that RAD is a very sensitive source of information for identifying patients who received rituximab for onco-haematological indications. Single administration episodes were identified with good-to-high accuracy. Patients receiving rituximab for nHL were identified with high sensitivity and acceptable PPV, while the validity for CLL was suboptimal.

Impact of Rhabdomyosarcoma Treatment Modalities by Age in a Population-Based Setting.

Purpose: Rhabdomyosarcoma (RMS) has a worse prognosis in adults than in children, but there is evidence of a better outcome in the former if treated using a pediatric-like approach. This study describes treatment for RMS in patients more than 10 years old and examines to what extent treatment contributes to explain the different age-related survival observed and to what extent treatment centers impact treatment appropriateness. Methods: A retrospective population-based study was developed considering 104 RMS cases (excluding the pleomorphic subtype) diagnosed in Italy between 2000 and 2015. Patients were grouped by age (10-19 vs. 20-60 years old) and scored according to whether or not their chemotherapy was consistent with the schemes used in pediatric protocols (score 1 = chemotherapy in line with pediatric protocols). Treatment centers were grouped according to whether or not they have a pediatric-dedicated unit affiliated to the national pediatric oncology network (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]). Results: Older patients were more likely to have tumors at unfavorable sites (p = 0.045). A treatment score of 1 was assigned to 85% of younger patients, but only to 32% of older patients (p < 0.001). Furthermore, the proportion of score 1 was higher in younger patients treated in centers with an AIEOP Unit. A multivariate model confirmed age as a significant prognostic factor (Hazard rate ratio [HR] = 2.06; p = 0.04) and showed a significant impact of treatment on survival (HR = 2.13; p = 0.03). Conclusions: Adult RMS patients are still relatively unlikely to be treated with pediatric protocols and in centers with a pediatric oncology expertise. This may explain the survival gap between older and younger patients.

Patterns of care and cost profiles of women with breast cancer in Italy: EPICOST study based on real world data.

OBJECTIVES: To estimate total direct health care costs associated to diagnosis and treatment of women with breast cancer in Italy, and to investigate their distribution by service type according to the disease pathway and patient characteristics. METHODS: Data on patients provided by population-based Cancer Registries are linked at individual level with data on health-care services and corresponding claims from administrative databases. A combination of cross-sectional approach and a threephase of care decomposition model with initial, continuing and final phases-of-care defined according to time occurred since diagnosis and disease outcome is adopted. Direct estimation of cancer-related costs is obtained. RESULTS: Study cohort included 49,272 patients, 15.2% were in the initial phase absorbing 42% of resources, 79.7% in the continuing phase absorbing 44% of resources and 5.1% in the final phase absorbing 14% of resources. Hospitalization was the most important cost driver, accounting for over 55% of the total costs. CONCLUSIONS: This paper represents the first attempt in Italy to estimate the economic burden of cancer at population level taking into account the entire disease pathway and using multiple current health care databases. The evidence produced by the study can be used to better plan resources allocation. The model proposed is replicable to countries with individual health care information on services and claims.

Real word evidence on rituximab utilization: Combining administrative and hospital-pharmacy data.

PURPOSE: To describe patterns of utilization, survival and infectious events in patients treated with rituximab at the University Hospital of Siena (UHS) to explore the feasibility of combining routinely collected administrative and hospital-pharmacy data for examining the real-world use of intravenous antineoplastic drugs. METHODS: A retrospective, longitudinal cohort study was conducted using data from the Hospital Pharmacy of Siena (HPS) and the Regional Administrative Database of Tuscany (RAD). Patients aged ≥18 years with ≥1 rituximab administration recorded between January 2012 and June 2016 were identified in the HPS database. Anonymized patient-level data were linked to RAD. Rituximab utilization during the first year of treatment was described using HPS. Hospital diagnoses of adverse infectious events that occurred during the first year of follow-up and four-year survival were observed using RAD. RESULTS: A total of 311 new users of rituximab were identified: 264 patients received rituximab for non-Hodgkin's lymphoma (NHL) and 47 were treated for chronic lymphocytic leukemia (CLL). Among new users with one complete year of follow-up (n = 203) over 95% received rituximab as the first-line treatment, and approximately 70% of them received 5-8 doses. No patient in the CLL group received >8 administrations. Four-year survival was approximately 70% in both CLL and NHL patients. Sepsis was the most frequent infectious event observed (5.1%). CONCLUSION: HPS and RAD provided complementary information on rituximab utilization, demonstrating their potential for future pharmacoepidemiological studies on antineoplastic medications administered in the Italian hospital setting. Overall, this general description of the real-world utilization of rituximab in patients treated for NHL and CLL at UHS was in line with treatment guidelines and current knowledge on the rituximab safety profile.

Differential Network Analysis Reveals Metabolic Determinants Associated with Mortality in Acute Myocardial Infarction Patients and Suggests Potential Mechanisms Underlying Different Clinical Scores Used To Predict Death.

We present here the differential analysis of metabolite-metabolite association networks constructed from an array of 24 serum metabolites identified and quantified via nuclear magnetic resonance spectroscopy in a cohort of 825 patients of which 123 died within 2 years from acute myocardial infarction (AMI). We investigated differences in metabolite connectivity of patients who survived, at 2 years, the AMI event, and we characterized metabolite-metabolite association networks specific to high and low risks of death according to four different risk parameters, namely, acute coronary syndrome classification, Killip, Global Registry of Acute Coronary Events risk score, and metabolomics NOESY RF risk score. We show significant differences in the connectivity patterns of several low-molecular-weight molecules, implying variations in the regulation of several metabolic pathways regarding branched-chain amino acids, alanine, creatinine, mannose, ketone bodies, and energetic metabolism. Our results demonstrate that the characterization of metabolite-metabolite association networks is a promising and powerful tool to investigate AMI patients according to their outcomes at a molecular level.

Decreased cardiovascular mortality in the ITALUNG lung cancer screening trial: Analysis of underlying factors.

OBJECTIVES: In the ITALUNG lung cancer screening trial after 9.3 years of follow-up we observed an unexpected significant decrease of cardiovascular (CV) mortality in subjects invited for low-dose CT (LDCT) screening as compared to controls undergoing usual care. Herein we extended the mortality follow-up and analyzed the potential factors underlying such a decrease. MATERIALS AND METHODS: The following factors were assessed in screenes and controls: burden of CV disease at baseline, changes in smoking habits, use of CV drugs and frequency of planned vascular procedures after randomisation. Moreover, in the screenes we evaluated inclusion of presence of coronary artery calcification (CAC) in the LDCT report form that was transmitted to the participant and his/her General Practitioner. RESULTS: The 2-years extension of follow-up confirmed a significant decrease of CV mortality in the subjects of the active group compared to control subjects (15.6 vs 34.0 per 10,000; p = 0.001) that was not observed in the drops-out of the active group. None of the explaining factors we considered significantly differed between active and control group. However, the subjects of the active group with reported CAC experienced a not significantly lower CV mortality and showed a significantly higher use of CV drugs and frequency of planned vascular procedures than the control group. CONCLUSIONS: LDCT screening for lung cancer offers the opportunity for detection of CAC that is an important CV risk factor. Although the underlying mechanisms are not clear, our results suggest that the inclusion of information about CAC presence in the LDCT report may represent a candidate factor to explain the decreased CV mortality observed in screened subjects of the ITALUNG trial, possibly resulting in intervention for patient care to prevent CV deaths. Further studies investigating whether prospective reporting and rating of CAC have independent impact on such interventions and CV mortality are worthy.

NMR-based metabolomics identifies patients at high risk of death within two years after acute myocardial infarction in the AMI-Florence II cohort.

BACKGROUND: Risk stratification and management of acute myocardial infarction patients continue to be challenging despite considerable efforts made in the last decades by many clinicians and researchers. The aim of this study was to investigate the metabolomic fingerprint of acute myocardial infarction using nuclear magnetic resonance spectroscopy on patient serum samples and to evaluate the possible role of metabolomics in the prognostic stratification of acute myocardial infarction patients. METHODS: In total, 978 acute myocardial infarction patients were enrolled in this study; of these, 146 died and 832 survived during 2 years of follow-up after the acute myocardial infarction. Serum samples were analyzed via high-resolution 1H-nuclear magnetic resonance spectroscopy and the spectra were used to characterize the metabolic fingerprint of patients. Multivariate statistics were used to create a prognostic model for the prediction of death within 2 years after the cardiovascular event. RESULTS: In the training set, metabolomics showed significant differential clustering of the two outcomes cohorts. A prognostic risk model predicted death with 76.9% sensitivity, 79.5% specificity, and 78.2% accuracy, and an area under the receiver operating characteristics curve of 0.859. These results were reproduced in the validation set, obtaining 72.6% sensitivity, 72.6% specificity, and 72.6% accuracy. Cox models were used to compare the known prognostic factors (for example, Global Registry of Acute Coronary Events score, age, sex, Killip class) with the metabolomic random forest risk score. In the univariate analysis, many prognostic factors were statistically associated with the outcomes; among them, the random forest score calculated from the nuclear magnetic resonance data showed a statistically relevant hazard ratio of 6.45 (p = 2.16×10-16). Moreover, in the multivariate regression only age, dyslipidemia, previous cerebrovascular disease, Killip class, and random forest score remained statistically significant, demonstrating their independence from the other variables. CONCLUSIONS: For the first time, metabolomic profiling technologies were used to discriminate between patients with different outcomes after an acute myocardial infarction. These technologies seem to be a valid and accurate addition to standard stratification based on clinical and biohumoral parameters.

Ticagrelor-related late-onset dyspnea as cause of emergency department visit: a 3-year outpatient study.

INTRODUCTION: The aim of the current study was to define the rate of emergency department visits for late-onset dyspnea in acute coronary syndrome patients treated with ticagrelor. METHODS: We conducted a population-based study on about 850 000 residents of Florence metropolitan area, by using data from healthcare records. RESULTS: Between 2012 and 2014, 1073 subjects in Florence metropolitan area had at least one prescription of ticagrelor. Two-hundred and thirty-four patients were diagnosed with 'respiratory system or other chest symptoms' or 'other diseases of lung', and among them we identified 20 subjects with ticagrelor-related late-onset dyspnea. These, and the 979 nonevent subjects (receiving ticagrelor but not developing dyspnea), contributed to 413 person-years overall. The dyspnea rate was 4.84 per 100 person-years (95% confidence interval: 3.12-7.51). CONCLUSION: Late-onset dyspnea rate is notably lower than early-onset one; nevertheless prescribing clinicians should be aware that about one in 20 outpatients with a stabilized ticagrelor treatment might develop a dyspnea leading to an emergency department visit, and they should consider ticagrelor replacement only in patients who cannot tolerate dyspnea.

Does low-dose aspirin use for cardiovascular disease prevention reduce colorectal cancer deaths? A comparison of two cohorts in the Florence district, Italy.

Aspirin has been associated with reduced incidence and mortality of colorectal and a few other cancers. The aim of our paper was to study the effect of low-dose aspirin intake on cancer mortality in a population-based cohort study. The study included inhabitants of the Florence district (Italy) at the beginning of 2007. We considered two cohorts: patients who received prescriptions of low-dose aspirin for the whole year and patients who did not have any prescriptions over the same period. We followed the two cohorts until 31 December 2013. By linking with the Tuscany Mortality Registry, we analysed cause-specific mortality. We used a Cox semiparametric model to compare the mortality of the two cohorts. There was an 18% higher probability [hazard ratio (HR)=1.18, 95% confidence interval (CI): 1.12-1.23] for all causes of death among the cohort of aspirin users, almost completely caused by cardiovascular diseases (CVDs) (HR=1.39, 95% CI: 1.29-1.49). Colorectal cancer mortality was reduced by almost 30% (HR=0.71, 95% CI: 0.52-0.97). Death caused by major bleeding was 11% higher (HR=1.11, 95% CI: 0.86-1.44), but not statistically significant. Our results support the hypothesis that the use of low-dose aspirin for CVD prevention reduces colorectal cancer mortality. Given the growing ability to identify subgroups of individuals with an increased risk of developing cancer, further studies are needed to study the effectiveness of different cancer screening strategies tailored to these specific subgroups. Our study suggests the importance of focusing on this issue from the opposite perspective, that is, considering subgroups of individuals at decreased risk, such as the subgroup of individuals who take low-dose aspirin for CVD prevention. Thus, further assessments are needed to possibly identify subgroup-specific screening strategies that would be more effective than those developed for average-risk individuals.

Prognostic role of progesterone receptor expression in a population-based analysis.

PURPOSE: The role of progesterone (PR) expression in the management of breast cancer is controversial. The aim of this study is to evaluate the characteristics and prognosis of progesterone status among breast cancers patients in a population-based analysis. MATERIALS AND METHODS: Through the Tuscan Cancer Registry data on all the invasive breast cancer cases diagnosed during the period 2004-2005 in the provinces of Florence and Prato, central Italy, were retrieved. Histological reports were re-examined to obtain information on the percentage of positive tumor cells for estrogen (ER), progesterone (PR) receptors, Ki67 marker and human epidermal growth factor 2 (HER2). Information on age, stage, differentiation grade were also obtained. RESULTS: Out of 1487 patients, 28% had PR- breast cancer. These patients were older (p 0.006) than PR+ cancer patients, with more frequently high Ki67 (p < 0.0001), HER2 + (p < 0.0001), ER- (p < 0.0001) tumoral expression. The ER+/PR+ subtype was the most represented (n.1053), while ER-/PR+ was the most rare (n.23); 210 cases (14.1%) ER+ PR- and 201 (13.5%) ER-/PR- cases were found. Analysis of survival by the Cox proportional hazards model showed an independent prognostic value of PR expression (p < 0.0001), also when estrogen, Ki67, HER2 status and age were included. The 5-year cancer-specific survival was 82.1, 86.5, 100, 92% for ER-/PR-, ER+/PR-, ER-/PR+, ER+/PR+ subtype, respectively. CONCLUSIONS: Our study revealed significant differences in clinicopathological characteristics among breast cancer according to PR expression and confirmed its prognostic independent role, suggesting a role of PR in the improvement of breast cancer prognostic characterization.

Survival of cancer patients in Italy. / La sopravvivenza dei pazienti oncologici in Italia.

OBJECTIVES: Population-based survival statistics are fundamental to assess the efficacy of services offered to improve cancer patients' prognosis. This study aims to update cancer survival estimates for the Italian population, as well as provide new measures, such as the crude probability of death, which takes into account the possibility of dying from causes other than cancer, and the change in life expectancy after a cancer diagnosis, to properly address various questions. RESULTS: The study includes 1,932,450 cancer cases detected by the Network of Italian Cancer Registries (AIRTUM) from 1994 to 2011 and provides estimates for 38 cancer sites and for allsites cancer. For most common cancers diagnosed from 2005 to 2009, age-standardized 5-year net survival was: colon-rectum - males 65%, females 65%; lung - males 15%, females 19%; breast 87%; prostate 91%. For cancer sites such as stomach, colon, rectum, lung, skin melanoma, breast, cervix, prostate, and kidney, 5-year net survival is consistent between Central and Northern Italy, while it is a few percentage points lower in Southern Italy. Funnel plots expose these differences more in detail by showing the survival estimates in 13 Italian regions. For all sites but skin, 5- and 10-year net survival increased by about 10 percentage points in men and 7 points in women from 1994 to 2011. DISCUSSION: Specific articles deal with results on solid and haematological malignancies, international comparisons and analysis of time trends of incidence, mortality, and survival in combination for key cancer sites, aiming to interpret overall progress in the control of cancer in Italy.

Residual thrombin potential predicts cardiovascular death in acute coronary syndrome patients undergoing percutaneous coronary intervention.

INTRODUCTION: Thrombin generation (TG) is a central step of the coagulation system involved in hemostatic and thrombotic roles. Scarce data evaluating in the acute phase the association between TG and the risk of cardiovascular death of acute coronary syndrome (ACS) patients are available, in the era of percutaneous coronary intervention (PCI) and stenting with the use of dual antiplatelet treatment. MATERIALS AND METHODS: We investigated TG in 292 ACS patients undergoing PCI with stent implantation on dual antiplatelet treatment. Venous samples were obtained 12-24h after PCI. TG was assessed using the Calibrated Automated Thrombogram (CAT). RESULTS: At two years of follow-up, 57 out of 292 patients (19.5%) died from cardiovascular causes. Higher values of endogenous thrombin potential (ETP) [1115.9 (705-1441.3) vs 940.2 (666.0-1253.1), p=0.049], peak [176.1 (80.5-259.4) vs 107.3 (59.9-181.1), p=0.002] and velocity index [61.75 (21.03-97.88) vs 25.64 (11.95-50.90), p<0.001] were observed in relation to survival patients. At the multivariate model adjusted for the Global Registry of Acute Coronary Events risk score, the association between TG and cardiovascular death remained significant for ETP [OR (95% CI): 2.58 (1.10-6.03), p=0.029], peak [OR (95%CI): 3.27 (1.35-7.92), p=0.009] and velocity index [OR (95% CI): 3.06 (1.27-7.39), p=0.013]. This result was confirmed after adjustment for high on-treatment platelet reactivity [ETP: OR (95% CI) 2.35 (1.11-5.00), p=0.027; peak: OR (95% CI) 2.42 (1.13-5.15), p=0.022; velocity index: OR (95% CI) 2.43 (1.14-5.20), p=0.022]. CONCLUSIONS: ACS patients with a residual TG after PCI and stent implantation have a significantly higher risk of long-term cardiovascular death. These results might be useful in improving risk stratification for ACS patients and support the need of a tailored antithrombotic therapy.

Does the hospitalization after a cancer diagnosis modify adherence to process indicators of diabetes care quality?

AIMS: This study was designed to answer the question whether surgery due to newly diagnosed cancer may modify quality of diabetes' management, as suggested by current guidelines. METHODS: Adherence to guideline composite indicator (GCI), a process indicator including one annual assessment of HbA1c and at least two among eye examination, serum lipids measurement and microalbuminuria, was evaluated between years 2011-2012 and 2014-2015 in 158,069 diabetic patients living in Tuscany, Italy, on 1 January 2011 and surviving on 31 December 2015, of whom 661 were hospitalized in index year 2013 for a surgery procedure due to a newly incident cancer. Difference in GCI modification (DELTA_GCI) of these patients was compared with that of diabetic people without cancer, strictly matched for main confounders by means of a propensity score. RESULTS: In diabetic patients with cancer, GCI adherence increased by about 8 % between years 2011-2012 and 2014-2015. When compared with controls, DELTA_GCI increased by 6 % in cancer group compared with controls (p < 0.05), but any significance was lost after matching the groups by propensity score (3 %; p = NS). CONCLUSIONS: Our study suggests that a hospitalization for a surgical procedure due to a newly diagnosed cancer does not influence the compliance to a quality process indicator of diabetes care such as GCI.

[Use of regional health administrative databases to estimate the prevalence of mental disorders and health service utilization in a Local Health Unit of Tuscany Region (Central Italy)]. / Uso dei flussi informativi sanitari regionali per stimare la prevalenza dei disturbi mentali e il ricorso ai servizi sanitari nella popolazione di una Asl della Toscana.

OBJECTIVES: prevalence estimation of mental disorders and mental health services (SSM) utilization in 2011, using the administrative regional health databases (hospital discharge records, pharmaceutical prescriptions) and the Regional Database on Mental Health (SIRSM). STUDY DESIGN: descriptive population-based study. SETTING AND PARTICIPANTS: residents in a Local Health Unit (Florence) of Tuscany Region (Central Italy) who have access to SSM and/or to hospital departments of psychiatry/neuropsychiatry and/ or have psycholeptic/psychoanalectic prescriptions. MAIN OUTCOME MEASURES: frequencies; crude and age-standardized prevalence of patients who have access to the SSM or have admission to a hospital psychiatric ward or have psycholeptic/psychoanalectic prescriptions. RESULTS: a high prevalence (11.2%) of residents had at least one contact with health services for mental health problems, mostly (84%) for drug prescriptions only (20% of patients had a unique prescription during 2011). Depression is the most important disease (9.8% of residents had at least one prescription of antidepressants); mood disorders are the most common cause of adult access to SSM (35%-36%) and hospitalization in psychiatric ward (about 36% of admissions). Only a small proportion (about 15%) of patients with mental health problems have access to the SSM, presumably those with more severe diseases. CONCLUSIONS: results show that the information of the SIRSM database, together with pharmaceutical prescriptions (psycholeptic/ psychoanalectic) and hospitalisation in psychiatric ward, is a useful tool for assessing the prevalence of mental health problems in a population.

Gender differences in statin prescription rates, adequacy of dosing, and association of statin therapy with outcome after heart failure hospitalization: a retrospective analysis in a community setting.

PURPOSE: The existence of gender differences in the management of statin therapy among patients with chronic heart failure (HF) is still poorly investigated. We aimed at exploring the effect of gender on statin prescription rates and adequacy of dosing and on the association between statin therapy and all-cause 1-year mortality, after HF hospitalization in a community setting. METHODS: Statin prescription rates, adequacy of dosing (estimated as a PDD/DDD ratio >0.80), and 1-year mortality were retrospectively assessed in 2088 consecutive patients discharged from 5 local community hospitals with a definite diagnosis of HF after a mean length of stay of 7.6 days. The effect of gender was explored using multivariable logistic and Cox analyses adjusting to confounders. RESULTS: Women showed a lower statin prescription rate (25.7 vs 35.3%, P < 0.0001) and a lower prevalence of adequate statin dose (32.6 vs 42.3%, P < 0.0001) than men. Female gender was independently associated with a 24% lower probability of statin prescription and a 48% higher probability of inadequate statin dose. Statin prescription and adequacy of dosing were associated with 35 and 44% decreases in the risk of 1-year mortality, respectively, irrespective of gender. A nested case/control analysis confirmed that adequate statin dose was associated with 48% lower 1-year mortality, again without interaction with gender. CONCLUSIONS: In patients with chronic HF, female gender is independently associated with lower statin prescription rates and higher probability of inadequate dose. Statin therapy in these subjects is associated with improved 1-year survival in both men and women. This prognostic benefit is not affected by gender.

Prognostic role of N-terminal pro-brain natriuretic peptide in asymptomatic hypertensive and diabetic patients in primary care: impact of age and gender : Results from the PROBE-HF study.

BACKGROUND: The association between natriuretic peptides and clinical outcome in asymptomatic hypertensive and diabetic patients with no clinical evidence of heart failure (HF) is still unclear. We assessed the prognostic value of NT-pro BNP, and its interactions with age and gender, in a cohort of asymptomatic, stage A/B HF hypertensive and diabetic patients enrolled in primary care. METHODS: NT-proBNP was measured in 1012 asymptomatic subjects with systemic hypertension and/or type-2 diabetes (age 66.6 ± 7.8 years, 48 % males) with no clinical evidence of HF. Patients were prospectively followed over 49.8 ± 6.7 months for the development of cardiac death, HF hospitalization, and nonfatal myocardial infarction. RESULTS: Patients with NT-proBNP above the 80th age- and gender-specific percentile showed a threefold risk of events as compared to those with NT-proBNP under this cut-off [hazard ratio 3.2 (2.6-8.3), p < 0.0001]. In multivariable analysis, NT-proBNP added independent and incremental prognostic information to a predictive model including established risk factors (p < 0.0001). After stratification by age, increased NT-proBNP predicted outcome among patients in the second and third age tertiles, but not among those in the first tertile. Increased NT-proBNP was associated with a 3.6-fold risk in women and a 2.9-fold risk in men. Addition of the gender-NT-proBNP interaction to prognostic models further improved prediction of events (p = 0.014). CONCLUSIONS: NT-proBNP measurement adds independent and incremental information for the prediction of clinical outcome in asymptomatic, stage A-B HF hypertensive and diabetic patients taken from primary care. This prognostic value might be further evident in the elderly and among women.

[Trends in occurrence, treatment, and outcomes of acute myocardial infarction in Tuscany Region (Central Italy), 1997-2010]. / Trend temporali di occorrenza, trattamento ed esiti dell'infarto miocardico acuto in Toscana, 1997-2010.

OBJECTIVES: to describe trends in attack rate, treatment, and outcomes of acute myocardial infarction (AMI) in Tuscany Region (Central Italy). DESIGN: population-based epidemiological study using the Tuscany Acute Myocardial Infarction Registry. SETTING AND PARTICIPANTS: cases have been identified by record linkage between the hospital discharge database and the mortality registry, and divided into hospitalised AMI (1997-2012) and out-of-hospital coronary deaths (1997-2010). Details on hospitalised cases based on the presence/absence of ST-segment elevation (STEMI / NSTEMI) can be detected for the period 2001-2012. MAIN OUTCOMEMEASURES: distribution by calendar time, gender, and type of event of absolute frequencies, age-standardised attack rates (per 100,000; standard Tuscany population, 2001) and percentages (standard: total hospitalised cases in 2011) of invasive cardiac procedures and 28-day case fatality in hospitalised cases. RESULTS: a reduction in both out-of-hospital coronary deaths and STEMI hospitalisations (attack rates, respectively, - 2.3% and -3.9% in males, -3.3% and -4.1% in females) and an increase in NSTEMI hospitalisations (+13.1% in males and +13.3% in females) were shown. The use of invasive cardiac procedures (PCI, coronary angiography) in hospitalised cases shows a considerable increase over time both in STEMI and in NSTEMI. The proportion, however, always remains lower in the whole period after the age of 70 and in women. The short term prognosis in hospitalised AMI cases shows an improvement over time, which, however, disappears when stratified by type of AMI. This trend is mainly related to the different weight that STEMI and NSTEMI have on incidence over time (increase in attack rates for NSTEMI and reduction for STEMI, with worst prognosis). CONCLUSIONS: results confirm the important changes in epidemiology, clinical presentation, and treatment of acute coronary disease in Tuscany, previously identified in the international literature. Differences in coronary reperfusion treatment of hospitalised cases still persist by age and gender. Additional efforts are needed to ensure equity in access to the best treatment for AMI.

A time course study of high on treatment platelet reactivity in acute coronary syndrome male patients on dual antiplatelet therapy.

INTRODUCTION: Limited data are available on the natural history of high on treatment platelet reactivity (HPR) by arachidonic acid and ADP - markers of unfavorable prognosis in acute coronary syndrome patients -. MATERIAL AND METHODS: In a cohort of acute coronary syndrome male patients (n=101), we evaluated the time-course of HPR by ADP (platelet aggregation by 10µM ADP≥70%) and arachidonic acid (platelet aggregation by 1mmol arachidonic acid≥20%) measuring platelet function in the acute phase (T0), at 6months (T1) and 1year (T2). RESULTS: We identified persistent (HPR at T0,T1 and T2), acute non persistent (HPR only at T0), and late (HPR only at T1 or T2). Patients with persistent HPR by ADP were more frequently with higher values of BMI. Patients carrying CYP2C19*2 variant were more prevalent in the group of persistent HPR (33%). Significant higher values of immature platelet fraction and high immature platelet fraction at 6 and 12months and mean platelet volume were present in patients with late HPR. Immature platelet fraction was the only variable significantly associated with late HPR by ADP at multivariate analysis (OR=1.6 (1.08-2.3), p=0.016). Patients with persistent HPR by arachidonic acid were more frequently diabetics. Immature platelet fraction at 6months and high immature platelet fraction at 6 and 12months were the parameters associated with late HPR by AA (OR=1.4 (1.0-1.9), p=0.036; OR=1.5 (1.08-2.4), p=0.05; OR=4.9 (1.3-18.8), p=0.018, respectively). CONCLUSIONS: About 25% of 101 patients has persistent HPR; they are more frequently diabetics, overweight or carriers of CYP2C19*2. The occurrence of an inflammatory state, indicated by the increase of immature platelet fraction, is associated with the occurrence of late HPR.