Sex differences in factors associated with heart failure and diastolic left ventricular dysfunction: a cross-sectional population-based study.

BACKGROUND: Although sex differences in cardiovascular diseases are recognised, including differences in incidence, clinical presentation, response to treatments, and outcomes, most of the practice guidelines are not sex-specific. Heart failure (HF) is a major public health challenge, with high health care expenditures, high prevalence, and poor clinical outcomes. The objective was to analyse the sex-specific association of socio-demographics, life-style factors and health characteristics with the prevalence of HF and diastolic left ventricular dysfunction (DLVD) in a cross-sectional population-based study. METHODS: A random sample of 2001 65-84 year-olds underwent physical examination, laboratory measurements, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiography, and echocardiography. We selected the subjects with no missing values in covariates and echocardiographic parameters and performed a complete case analysis. Sex-specific multivariable logistic regression models were used to identify the factors associated with the prevalence of the diseases, multinomial logistic regression was used to investigate the factors associated to asymptomatic and symptomatic LVD, and spline curves to display the relationship between the conditions and both age and NT-proBNP. RESULTS: In 857 men included, there were 66 cases of HF and 408 cases of DLVD (77% not reporting symptoms). In 819 women, there were 51 cases of HF and 382 of DLVD (79% not reporting symptoms). In men, the factors associated with prevalence of HF were age, ischemic heart disease (IHD), and suffering from three or more comorbid conditions. In women, the factors associated with HF were age, lifestyles (smoking and alcohol), BMI, hypertension, and atrial fibrillation. Age and diabetes were associated to asymptomatic DLVD in both genders. NT-proBNP levels were more strongly associated with HF in men than in women. CONCLUSIONS: There were sex differences in the factors associated with HF. The results suggest that prevention policies should consider the sex-specific impact on cardiac function of modifiable cardiovascular risk factors.

Anticancer drug prices and clinical outcomes: a cross-sectional study in Italy.

OBJECTIVE: To investigate whether the prices of new anticancer drugs correlated with their relative benefit despite negotiation. DESIGN: Retrospective cross-sectional study correlating new anticancer drugs prices with clinical outcomes. SETTING: We did a retrospective cross-sectional study including all new anticancer drugs approved by the European Medicines Agency (EMA) (2010-2016) and reimbursed in Italy. MAIN OUTCOMES AND MEASURES: Information on clinical outcomes-in terms of median overall survival (OS), median progression-free survival (PFS) and objective response rate (ORR)-was extracted from pivotal trials as reported in the European Public Assessment Reports available on the EMA website. Cost of a full course treatment was estimated on negotiated official and discounted prices. Regression coefficients ß, their levels of significance p and the coefficients of determination R2 were estimated adjusting by tumour type. RESULTS: Overall, 30 new anticancer drugs (with 35 indications) were available for analysis. Where data on OS were available, we observed no correlation between the improvement in median OS (in weeks) and negotiated price (R2=0.067, n=16 drugs for 17 indications). When the clinical outcomes were expressed as improvements in the median PFS or ORR, 25 drugs (29 indications) were available for the analysis, and again, there was no correlation with prices (R2=0.004 and 0.006, respectively). CONCLUSIONS AND RELEVANCE: Our results suggest that the prices of anticancer drugs in Italy do not reflect their therapeutic benefit. Drug price negotiations, which is mandatory by law in Italy, do not seem to ensure that prices correlate with clinical benefits provided by the cancer drugs. These results call for further efforts to establish the standard determinants of drug prices available at the time of negotiation. These findings need to be confirmed in other countries where price negotiations are in place. Moreover, further investigations may verify whether outcome data obtained after drug marketing would improve the correlation between prices and therapeutic benefit.

Prevalence and Incidence of Multiple Sclerosis in the City of Biancavilla.

BACKGROUND: It is common that the epidemiology of multiple sclerosis (MS) varies with geography and ethnicity. Recent studies show a continuous growth of incidence and prevalence in Sicily, despite the controversial "latitude gradient theory." OBJECTIVES: The aim of our study is to ascertain incidence and prevalence rates of MS in the city of Biancavilla, Sicily, Southern Italy. METHOD: Case ascertainment approach and a clinical database collecting data of MS cases to Biancavilla, according to McDonald 2011 and Thompson 2018 criteria, from 1992 to 2018, have been used to the study. We further collected information regarding the familiarity of patients with Mesothelioma, highly incident in this geographic area. RESULTS: The results showed an increase of the mean annual incidence for the period 2012-2018 (16.8/100,000) compared to 1992-1996 (4.5/100,000), and a standardized incidence ratio of 1.41 (95% CI 0.74-2.45). On December 31, 2018, 70 patients suffering from definite MS and living in Biancavilla yielded a crude prevalence of 292.3 per 100,000 (198.2/100,000 for men; 380.7/100,000 for women) with a standardized morbidity ratio of 2.3 (95% CI 1.8-2.9). CONCLUSIONS: Our data confirmed Biancavilla is an area at high risk for MS, ascribable to increased survival, improved ascertainment, or maybe related to a genetic or environmental risk. At the time, any relation with mesothelioma was excluded.

Predictors of Oral Feeding Resumption after Stroke in a Rehabilitation Hospital: A Retrospective Study.

BACKGROUND: Dysphagia is common after stroke, requiring exclusive enteral feeding in 20% of patients. Recovery of oral feeding is associated with increased quality of life, better functional outcomes, and decreased mortality rates. However, evidence is heterogeneous and not conclusive on which factors are predictive of oral feeding recovery for stroke patients in rehabilitation units. AIM: To investigate predictors of complete oral feeding recovery. DESIGN: Retrospective study. SETTING: Intensive inpatient rehabilitation hospital. POPULATION: Poststroke dysphagic individuals with enteral feeding. METHODS: Retrospective chart review of demographic, clinical, rehabilitation, and swallowing factors. Univariate analysis and multivariate regression analysis were used to compare variables between the oral feeding recovery group and the enteral feeding group at discharge. RESULTS: One hundred thirty-nine patients were included in the analysis. A total of 61.9% of the sample population resumed complete oral intake at discharge. There were statistically significant differences between the 2 groups in Functional Independence Measure cognitive score, clinical swallow evaluation, and instrumental swallow evaluation at admittance, and dysphagia rehabilitation. Multiple logistic regression analysis identified the absence of aspiration signs with liquids associated with a higher probability of the resumption of complete oral feeding (odds ratio [OR] 3.57; 95% confidence interval [CI] 1.07-11.89). Age between 73 and 79 years (OR .96; 95% CI .01-.58), the presence of aspiration and/or penetration (OR .22; 95% CI .07-.72), and the presence of residue (OR .14; 95%CI .04-.43) during fiberoptic endoscopic evaluation of swallowing presented lower probability of returning to complete oral feeding. CONCLUSION: Several demographic and swallowing characteristics predicted oral feeding recovery. Absence of dysphagia signs documented on fiberoptic endoscopic evaluation of swallowing was the strongest predictor of complete oral feeding resumption.

An Estimate of Attributable Cases of Alzheimer Disease and Vascular Dementia due to Modifiable Risk Factors: The Impact of Primary Prevention in Europe and in Italy.

BACKGROUND: Up to 53.7% of all cases of dementia are assumed to be due to Alzheimer disease (AD), while 15.8% are considered to be due to vascular dementia (VaD). In Europe, about 3 million cases of AD could be due to 7 potentially modifiable risk factors: diabetes, midlife hypertension and/or obesity, physical inactivity, depression, smoking, and low educational level. AIMS: To estimate the number of VaD cases in Europe and the number of AD and VaD cases in Italy attributable to these 7 potentially modifiable risk factors. METHODS: Assuming the nonindependence of the 7 risk factors, the adjusted combined population attributable risk (PAR) was estimated for AD and VaD. RESULTS: In Europe, adjusted combined PAR was 31.4% for AD and 37.8% for VaD. The total number of attributable cases was 3,033,000 for AD and 873,000 for VaD. In Italy, assuming a 20% reduction of the prevalence of each risk factor, adjusted combined PAR decreased from 45.2 to 38.9% for AD and from 53.1 to 46.6% for VaD, implying a 6.4 and 6.5% reduction in the prevalence of AD and VaD, respectively. CONCLUSION: A relevant reduction of AD and VaD cases in Europe and Italy could be obtained through primary prevention.

A Population-Based Study on Myelodysplastic Syndromes in the Lazio Region (Italy), Medical Miscoding and 11-Year Mortality Follow-Up: the Gruppo Romano-Laziale Mielodisplasie Experience of Retrospective Multicentric Registry.

Data on Myelodysplastic Syndromes (MDS) are difficult to collect by cancer registries because of the lack of reporting and the use of different classifications of the disease. In the Lazio Region, data from patients with a confirmed diagnosis of MDS, treated by a hematology center, have been collected since 2002 by the Gruppo Romano-Laziale Mielodisplasie (GROM-L) registry, the second MDS registry existing in Italy. This study aimed at evaluating MDS medical miscoding during hospitalizations, and patients' survival. For these purposes, we selected 644 MDS patients enrolled in the GROM-L registry. This cohort was linked with two regional health information systems: the Hospital Information System (HIS) and the Mortality Information System (MIS) in the 2002-2012 period. Of the 442 patients who were hospitalized at least once during the study period, 92% had up to 12 hospitalizations. 28.5% of patients had no hospitalization episodes scored like MDS, code 238.7 of the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM). The rate of death during a median follow-up of 46 months (range 0.9-130) was 45.5%. Acute myeloid leukemia (AML) was the first cause of mortality, interestingly a relevant portion of deaths is due to cerebro-cardiovascular events and second tumors. This study highlights that MDS diagnosis and treatment, which require considerable healthcare resources, tend to be under-documented in the HIS archive. Thus we need to improve the HIS to better identify information on MDS hospitalizations and outcome. Moreover, we underline the importance of comorbidity in MDS patients' survival.

Impact of Guidance on the Prescription Patterns of G-CSFs for the Prevention of Febrile Neutropenia Following Anticancer Chemotherapy: A Population-Based Utilization Study in the Lazio Region.

BACKGROUND: Current guidelines recommend prophylaxis with granulocyte colony-stimulating factors (G-CSFs) for patients with cancer who are at greater risk of febrile neutropenia (FN) while receiving chemotherapy. G-CSF biosimilars are available and represent a savings opportunity; however, their uptake has thus far been low. OBJECTIVE: Our objective was to evaluate prescribing patterns for G-CSFs in the prevention of chemotherapy-related FN and to evaluate the impact of regional guidance on G-CSF prescription. METHODS: We conducted an observational drug-utilization study in the Lazio region of Italy using the Electronic Therapeutic Plan Registry, which collects information on G-CSF prescriptions reimbursed by the regional health service. This registry includes information on demographics, tumour, indication for G-CSF use and previous G-CSF exposure. All therapeutic plans (TPs) registered from 1 July 2015 to 30 June 2016 were selected. A pharmaceutical policy intervention was implemented in November 2015. We evaluated temporal trends regarding G-CSF substances and compared the frequency of TPs for each G-CSF substance during the pre- and post-intervention periods. RESULTS: A total of 7082 TPs were eligible for the analysis, corresponding to 6592 patients. The frequency of TPs prescribed after the intervention indicated a significant increase in the use of a filgrastim biosimilar (% difference: 14.4; p < 0.001) and significant decreases in the use of lenograstim (% difference: -6.0; p < 0.001) and pegfilgrastim (% difference: -7.8; p < 0.001). The temporal trends analysis showed an increase in TPs using a filgrastim biosimilar (from 34.4% in July 2015 to 49.8% in June 2016; p < 0.0001) and a decrease in TPs using lenograstim and pegfilgrastim. CONCLUSIONS: This study shows it is possible to change attitudes towards the prescription of less expensive G-CSFs in the FN setting when the prescriber's decision-making processes are supported by evidence that includes both regulatory and clinical information and the analysis of clinical practice data.

Comparative effectiveness and safety of erythropoiesis-stimulating agents (biosimilars vs originators) in clinical practice: a population-based cohort study in Italy.

OBJECTIVES: To evaluate the benefit/risk profile of epoetin α biosimilar with the erythropoiesis-stimulating agents (ESAs) originators when administered to naïve patients from clinical practice. DESIGN: Population-based observational cohort study. SETTING: All residents in the Lazio Region, Italy, with chronic kidney disease (CKD) or cancer retrieved from the Electronic Therapeutic Plan (ETP) Register for ESA between 2012 and 2014. PARTICIPANTS: Overall, 13 470 incident ESA users were available for the analysis, 8161 in the CKD and 5309 in the oncology setting, respectively. INTERVENTIONS: ESAs identified through the ATC B03XA were divided into 3 groups: (1) biosimilars; (2) epoetin α originator and (3) other originators. Patients were exposed to ESAs from the date of activation of the ETP, until the end of a 6-month follow-up period. OUTCOME MEASURES: Effectiveness (all-cause mortality and blood transfusion) and safety (major cardiovascular events, blood dyscrasia). A composite outcome including all-cause mortality, blood transfusion and major cardiovascular events was predefined. HRs of any outcome were estimated through Cox regression. RESULTS: We found no differences between patients on biosimilars or all originators with regard to the risk estimates of all-cause mortality, blood transfusion, major cardiovascular events and blood dyscrasia in the CKD setting. The composite outcome confirmed these results (biosimilars vs epoetin α originators: adjusted HR=1.02, 95% CI 0.78 to 1.33; biosimilars vs other originators: adjusted HR=1.09, 95% CI 0.85 to 1.41). Comparable risk estimates were observed between biosimilars and all originators in the oncology setting. CONCLUSIONS: In both settings, our findings are suggestive of no difference between biosimilars and originators on relevant effectiveness and safety outcomes. This study may contribute to settling future drug policy for the health services and provides reassurance on the approval pathway for biosimilars. The oncology setting merits further research, taking into account tumour types, tumour stage and anticancer chemotherapy administered.