Anna Citarella

Hormone therapy and risk of cardiovascular outcomes and mortality in women treated with statins.

ObjectiveThis work aims to study the effects of hormone therapy (HT) on the risk of cardiovascular outcomes and all-cause mortality in women treated with statins. MethodsWe included women aged 40 to 74 years and living in Sweden who filled a first statin prescription between 2006 and 2007. Women were categorized as HT users or as nonusers. Information on dispensed drugs, comorbidity, cardiovascular outcomes, and all-cause mortality was obtained from national health registers. ResultsA total of 40,958 statin users—2,862 (7%) HT users and 38,096 nonusers—were followed for a mean of 4.0 years. In total, 70% of the women used statins as primary prevention. Among HT users, there were five cardiovascular deaths per 10,000 person-years. The corresponding rate among nonusers was 18, which yielded a hazard ratio of 0.38 (95% CI, 0.12-1.19). The all-cause mortality rates were 33 and 87, respectively, and the hazard ratio was 0.53 (95% CI, 0.34-0.81). There were no associations with cardiovascular events. A similar pattern was found for both primary and secondary prevention. ConclusionsHT is associated with a reduced risk of all-cause mortality in women treated with statins. Although confounding factors, such as lifestyle and disease severity, might have influenced the results, HT does not seem to be detrimental to statin-treated women.

Hormone therapy after uterine cervical cancer treatment: a Swedish population-based study.

ObjectiveThis study aims to assess use of hormone therapy (HT) after cervical cancer treatment in women of premenopause age. MethodsWe identified 837 women aged 45 years or younger at diagnosis of cervical cancer in the Swedish Cancer Register from January 1, 2005 to September 30, 2009 with a minimal follow-up of 1.5 years. Information on cancer treatment (surgical operation, radiotherapy, and/or chemotherapy) was obtained through the National Patient Register. Use of HT was estimated through HT dispensing during follow-up as recorded in the Prescribed Drug Register. Percentage of recommended dose was assessed by frequency of HT dispensing at half-year intervals up to April 1, 2011 or a maximal age of 50 years. ResultsA total of 257 women (31%) received acute estrogen deprivation due to bilateral salpingo-oophorectomy and/or radiotherapy. Among these women, 171 (67%) of 257 had at least one dispensing of HT during the period 0.5 to 1 year after diagnosis, and 118 (46%) of 257 were dispensed 75% or more of the recommended dose. Proportion users decreased to 39% at 4.5 to 5 years after diagnosis (21% with ≥75% of the recommended dose). Women younger than 40 years had a higher prevalence of HT use at 0.5 to 1 year (79%), decreasing to 45% after 4.5 to 5 years. The results did not vary by cancer histology. ConclusionsFewer than half of cervical cancer survivors with therapy-induced early menopause used HT at or close to the recommended dose, and the use decreased during follow-up. Increased awareness of the health benefits of HT for this patient group is needed among professionals and women.

Lower Rate of Cardiovascular Complications in Patients on Bolus Insulin Analogues: A Retrospective Population-Based Cohort Study

Background Few studies are available evaluating the impact of rapid-acting insulin analogues on long-term diabetes outcomes. Our aim was to compare the use of rapid-acting insulin analogues versus human regular insulin in relation to the occurrence of diabetic complications in a cohort of diabetic patients through the analysis of administrative databases. Methods A population-based cohort study was conducted using administrative data from four local health authorities in the Abruzzo Region (900,000 inhabitants). Diabetic patients free of macrovascular disease at baseline and treated either with human regular insulin or rapid-acting insulin analogues were followed for a maximum of 3 years. The incidence of diabetic complications was ascertained by hospital discharge claims. Hazard ratios (HRs) and 95% CIs of any diabetic complication and macrovascular, microvascular and metabolic complications were estimated separately using Cox proportional hazard models adjusted for patients’ characteristics and anti-diabetic drug use. Propensity score matching was also used to adjust for significant difference in the baseline characteristics between the two treatment groups. Results A total of 2,286 patients were included: 914 receiving human regular insulin and 1,372 rapid-acting insulin analogues. During the follow-up, 286 (31.3%) incident events occurred in the human regular insulin group and 235 (17.1%) in the rapid-acting insulin analogue group. After propensity score-based matched-pair analyses, rapid-acting insulin analogues users had a HR of 0.73 (0.58–0.92) for any diabetes-related complication and HRs of 0.73 (0.55–0.93) and 0.55 (0.32–0.96) for macrovascular and metabolic complications respectively, as compared with human regular insulin users. No difference between the two groups was found for microvascular complications. Conclusions Our findings suggest that the use of rapid-acting insulin analogues is associated with a lower risk of cardiovascular and metabolic complications compared with human regular insulin use.

Characterization of new users of cilostazol in the UK, Spain, Sweden, and Germany

To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency.

Increasing trend in admission rates and costs for acute diverticulitis during 2005–2015: real-life data from the Abruzzo Region:

Background: Scarce data are available on the epidemiological trend of diverticulitis and its financial burden in Italy. The aim of this work was to explore a potential variation in the rate and costs of hospital admissions for uncomplicated and complicated diverticulitis over the last decade. Methods: We selected all hospitalizations for diverticulitis of residents in the Abruzzo Region, Italy between 2005 and 2015. Age-standardized hospitalization rates (HRs) per 100,000 inhabitants for overall, uncomplicated and complicated diverticulitis were calculated. A linear model on the log of the age-standardized rates was used to calculate annual percentage changes (APC). Costs were derived from the official DRG tariff. Results: From 2005 to 2015, the HR for acute diverticulitis increased from 38.9 to 45.2 per 100,000 inhabitants (APC + 1.9%). The HR for complicated diverticulitis increased from 5.9 to 13.3 (APC + 7.6%), whereas it remained stable for uncomplicated diverticulitis. The mean hospital cost was 1.8-times higher for complicated diverticulitis compared with that for uncomplicated disease and 3.5-times higher for patients with a surgery stay compared with that for patients with a medical stay. Conclusion: During the last decade, in the Abruzzo Region, the HRs for diverticulitis and their costs increased significantly, mainly due to disease complications. Further studies are needed to explore strategies to prevent complications and to realise cost-saving policies.

Impact of comorbidity on the risk and cost of hospitalization in HIV-infected patients: real-world data from Abruzzo Region

Background Due to the success of antiretroviral therapy, human immunodeficiency virus (HIV) infection has been transformed into a lifelong condition. In Italy, little is known about the impact of comorbidities (CMs) on the risk of hospitalization and related costs for people who live with HIV (PWLHIV). The objective of the study was to quantify the risk of hospitalization and costs associated with CMs in an Italian cohort of PWLHIV. Methods The study population included subjects aged ≥18 years with HIV infection, identified in the Abruzzo’s hospital discharge database among files stored from 2004 until 2013 and then followed up until December 2015. Patients’ CMs (Charlson Comorbidity Index [CCI)] were extracted from International Classification of Diseases, Ninth Revision, Clinical Modification codes in the hospital discharge abstracts. Poisson regression was used to compare the incidence rate of hospital admissions in patients with and without each CM class. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were adjusted for age, sex and the other CMs. A generalized linear model under gamma distribution was used to estimate adjusted mean hospital costs. Costs were derived from official Italian Diagnosis-related group (DRG) based reimbursements. Results Among 1,026 HIV patients identified (mean age 47 years), 30% had at least one CM and 14.5% underwent hospital admission during the follow-up period. The risk of acute hospitalization significantly increased among patients with hepatitis C virus (HCV) coinfection (adjusted IRR 1.98; 95% CI: 1.59–2.47), renal (adjusted IRR 2.27; 95% CI: 1.45–3.56), liver (adjusted IRR 2.21; 1.57–3.13) and chronic pulmonary CMs (adjusted IRR 2.31; 1.63–3.32). Adjusted mean hospital costs were €2,494 in patients without CMs and €4,422 and €9,734 in those with CCI=1 or CCI ≥2, respectively. Conclusion The presence of renal, liver and chronic pulmonary CMs, as well as HCV coinfection doubled the risk of hospitalization in the PWLHIV cohort. A CCI ≥2 is associated with a fourfold increase in hospitalization costs. Our study provides new evidence that CMs in PWLHIV increase the risk of hospitalization and local health service facilities.

Evaluation of antimicrobial consumption in Campania Region, Italy

Introduction: the antibiotic usage in Italy is above the European average. From several years the Campania was the first Italian region in terms of antimicrobial consumption. Aim: to evaluate antibiotic utilisation in primary health care in Campania, a region of approximately 5.7 million inhabitants in the south of Italy. Method: we collected, from an electronic database, all prescription drugs reimbursed in 2005. The cohort was defined as the population of subjects receiving at least one prescription of any antimicrobial agent for systemic use, classified according to their therapeutic role using Anatomic Therapeutic Chemical (ATC) classification. Drugs cost and consumption were quantified using National Health Service (NHS) prospective and Defined Daily Dose system (DDD) respectively. All costs were expressed in Euro 2005. Results: antiinfectives agents (ATC J) was the second class of drugs in terms of cost, representing 16.1% of the regional drug expenditure. Their consumption were 33 DDD/1000 inhabitants/day. Stratifying by age antibiotic use was highest in children and elderly subjects. Penicillins, macrolides and cephalosporins were the most prescribed antibiotic classes in all age groups. Discussion: despite guidelines introduced to limit the prescription of parenteral antibiotics to the patients who are most likely to benefit from it, they were mostly prescribed. This represented a serious problem for the development of drug-resistant bacteria.

IDEAL trial: economic analysis

Introduction: the IDEAL (“High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction”) study was carried out to compare intensive lowering of low-density lipoprotein (LDL)-cholesterol using the highest recommended dose of atorvastatin 80 mg with simvastatin 20 mg. Aim: our aim was to investigate the economic consequence of high dose of atorvastatin vs usual-dose of simvastatin in reducing major coronary events in patients with a history of acute myocardial infarction (AMI). Methods: the analysis is based on clinical outcome data from the IDEAL study. We conducted a cost-effectiveness analysis, comparing high dose of atorvastatin (80 mg/die) versus usual-dose of simvastatin (20 mg/die) in the perspective of the Italian National Health Service. We identified and quantified medical costs: drug costs according to the Italian National Therapeutic Formulary and hospitalizations were quantified based on the Italian National Health Service tariffs (2008). Effects were measured in terms of morbidity reduction (frequency of hospitalizations). We considered an observation period of 4.8 years. The costs borne after the first 12 months were discounted using an annual rate of 3%. We conducted one and multi-way sensitivity analyses on unit cost and effectiveness. Results: the cost of atorvastatin therapy over the 4.8 years period amounted to approximately 2.4 millions euro per 1,000 patients. The total cost of atorvastatin high dose was about 3.9 millions euro, the incremental cost per patient free from event is 31.176,03 euro. Discussion: this evaluation found that atorvastatin therapy is cost-effective. Results were sensitive to either clinical or economic variables.

Epidemiological and economic aspects of diabetes in the Campania Region, Italy

Aim: to assess the economic and epidemiologic impact of diabetes in Campania, a region of approximately 5.7 million inhabitants in the south of Italy. Method: we collected, from an electronic database, all prescriptions for antidiabetic drugs reimbursed in the first half year of 2005 in 8 local health authorities (60% of the overall population) of Campania. The diabetic cohort was defined as the population of subjects receiving at least 2 prescriptions of an antidiabetic agent in 6-month, classified according to their therapeutic role using Anatomic Therapeutic Chemical (ATC) classification. Characterization is given of the patients and their antidiabetic medication. Subsequently, the prescription of concomitant treatment, in comparison with a control group, is presented. Drugs cost and drugs consumption were quantified using NHS prospective (expressed in Euro 2005) and Defined Daily Dose system (DDD) respectively. Results: the diabetic cohort included 183,614 subjects (5.3% of the observed population), mean age was 65.0 years and female represented 54.8% of the sample. Total cost for diabetic patients represents 16.8% of the total drug expenditure. The average drug/cost/patient was € 355.7; only 19.0% was spent for antidiabetic drugs. The reported use of medication was higher for subjects with diabetes compared with the control population regarding overall use (2,363.5 versus 1259.8 DDD/1,000 inhabitants/die), the use of cardiovascular drugs (1,499.3 versus 663.5 DDD/1,000 inhabitants/day), use of haematologic drugs (277.1 versus 120.3 DDD/1,000 inhabitants/day), and use of ophthalmological drugs (48.3 versus 21.0 DDD/1,000 inhabitants/day). Discussion: chronic-degenerative pathologies, such as diabetes, implies a relevant social and economic impact. Expenses that are associated to the treatment and the prevention of complications, in particular cardiovascular problems, are registered among the main items listed in the healthcare budget.

Valutazione economica dello studio PROVE-IT

Introduction: the PROVE-IT (“Intensive versus moderate lipid lowering with statins after acute coronary syndromes”) was a comparison of pravastatin 40 mg/die versus atorvastatin 80 mg/die in patients with an acute coronary syndrome (ACS). Aim: our aim was to investigate the economic consequence of high dose of atorvastatin vs usual-dose of pravastatin in Italian patients with a history of acute coronary syndrome. Methods: the analysis is conducted on the basis of clinical outcomes of the PROVE-IT study. We conducted a cost-effectiveness analysis, comparing high dose of atorvastatin (80 mg/die) versus usual-dose of pravastatin (40 mg/die) in the perspective of the Italian National Health Service. We identified and quantified medical costs: drug costs according to the Italian National Therapeutic Formulary and hospitalizations were quantified based on the Italian National Health Service tariffs (2006). Effects were measured in terms of mortality and morbidity reduction (number of deaths, life years gained and frequency of hospitalizations). We considered an observation period of 24 months. The costs borne after the first 12 months were discounted using an annual rate of 3%. We conducted one and multi-way sensitivity analyses on unit cost and effectiveness. We also conducted a threshold analysis. Results: the cost of pravastatin or atorvastatin therapy over the 2 years period amounted to approximately 1.3 millions euro and 870,000 euro per 1,000 patients respectively. Atorvastatin was more efficacious compared to pravastatin and the overall cost of care per 1,000 patients over 24 months of follow-up was estimated at 3.2 millions euro in the pravastatin and 2.5 millions euro in the atorvastatin group, resulting into a cost saving of about 700,000 euro that is 27% of total costs occurred in the pravastatin group. Discussion: this study demonstrates that high does atorvastatin treatment leads to a reduction of direct costs for the National Health System. Atorvastatin therapy is dominant since it is both less costly and more effective than pravastatin. Results of sensitivity analysis showed that atorvastatin therapy remains dominant even in the most unfavourable hypotheses.