The Value of Tucatinib in Metastatic HER2-Positive Breast Cancer Patients: An Italian Cost-Effectiveness Analysis.

BACKGROUND: This study was aimed at estimating the appropriate price of tucatinib plus trastuzumab and capecitabine (TXC), as third-line treatment, in HER2+ breast cancer (BC) patients from the Italian National Health System (NHS) perspective. METHODS: A partitioned survival model with three mutually exclusive health states (i.e., progression-free survival (PFS), progressive disease (PD), and death) was used to estimate the price of tucatinib vs trastuzumab emtansine (TDM-1), considering a willingness to pay (WTP) of 60,000 EUR. Data from the HER2CLIMB trial, the Italian population, and the literature were used as input. The model also estimated the total costs and the life-years (LY) of TXC and TDM1. Deterministic and probabilistic (PSA) sensitivity analyses were conducted to evaluate the robustness of the model. RESULTS: In the base case scenario, the appropriate price of tucatinib was 4828.44 EUR per cycle. The TXC resulted in +0.28 LYs and +16,628 EUR compared with TDM-1. Results were mainly sensitive to therapy intensity variation. In PSA analysis, TXC resulted cost-effective in 53% of the simulations. Assuming a WTP ranging 20,000-80,000 EUR, the tucatinib price ranged from 4090.60 to 5197.41 EUR. CONCLUSIONS: This study estimated the appropriate price for tucatinib according to different WTP in order to help healthcare decision makers to better understand the treatment value.

Occupational Exposure in the Lombardy Region (Italy) to SARS-CoV-2 Infection: Results from the MUSTANG-OCCUPATION-COVID-19 Study.

Sero-epidemiological surveys are valuable attempts to estimate the circulation of SARS-CoV-2 in general or selected populations. Within this context, a prospective observational study was conducted to estimate the prevalence and persistence of SARS-CoV-2 antibodies in different categories of workers and factors associated with positivity, through the detection of virus-specific immunoglobulin G and M (IgG/IgM) in serum samples. Enrollees were divided in low exposure and medium-high groups on the basis of their work activity. Antibody responders were re-contacted after 3 months for the follow-up. Of 2255 sampled workers, 4.8% tested positive for SARS-CoV-2 IgG/IgM antibodies, with 81.7% to IgG only. Workers who continued to go to their place of work, were healthcare workers, or experienced at least one COVID-19-related symptom were more likely to test positive for SARS-CoV-2 antibodies. SARS-CoV-2 antibodies prevalence was significantly higher in the medium-high risk vs. low-risk group (7.2% vs. 3.0%, p < 0.0001). At 3-month follow-up, 81.3% of subjects still had antibody response. This study provided important information of SARS-CoV-2 infection prevalence among workers in northern Italy, where the impact of COVID-19 was particularly intense. The presented surveillance data give a contribution to refine current estimates of the disease burden expected from the SARS-CoV-2.

Global cardiovascular risk evaluation: pattern of algorithm use and risk modification in 'real life'.

AIMS: Although calculation of the global cardiovascular risk is strongly recommended, limited data are available regarding the use and the utility of this tool in clinical practice. We aimed at answering the following questions in the setting of Italian general practice: how many patients are evaluated via the cardiovascular risk algorithm; what are their characteristics; and what happens after their evaluation. METHODS: We used the Health Search/CSD Longitudinal Patient Database. The software used by about 800 participating GPs allows the calculation of the global cardiovascular risk in automatic. The following data were yearly extracted from the database within 2004-2008: age, sex, and recorded diagnosis of the main cardiovascular and other information encompassing smoking habits, blood pressure, total cholesterol, high density lipoprotein cholesterol (i.e., variables used to calculate cardiovascular risk), BMI, physical activity, triglycerides, glucose and creatinine; wherever available, current cardiovascular therapy and the automatically computed global cardiovascular risk were also extracted. RESULTS: In 2008, the observed population, aged 35-69 years, numbered 438 922 individuals; 78 617 (17.9%) had at least one calculation of cardiovascular risk; 20 181 patients were re-evaluated at least once: 61.1% among high-risk patients, 43.8% among moderate-risk patients, and 27.2% among low-risk patients. The level of cardiovascular risk measured at baseline increased in 6863 (34%), decreased in 11 791 (58.4%), and did not change in 1527 (7.6%) individuals. Overall, mean cardiovascular risk decreased over 4 years in 2.25% (SD 6.41%; P < 0.01) of patients. CONCLUSION: The calculation of global cardiovascular risk is underused by GPs, who generally assign a higher priority to high-risk individuals. In addition, the use of this algorithm seems to favor a reduction of risk in moderate-risk and high-risk patients.

Development and Validation of a Score for Adjusting Health Care Costs in General Practice.

OBJECTIVE: To develop and validate the Italian Health Search Morbidity (HSM) Index to adjust health care costs in general practice. METHODS: The study population comprised 1,076,311 patients registered in the Health Search CSD Longitudinal Patient Database between January 1, 2008, and December 31, 2010. We randomly selected 538,254 and 538,057 patients to form the development and validation cohorts, respectively. To ensure model convergence, 5% of the aforementioned cohorts were selected randomly to create development and validation samples. The outcome was the total direct health care costs covered by the national health system. Interaction between age and sex, chronic diseases, and acute diseases were entered in a multilevel generalized linear latent mixed model with random intercepts (province of residence and general practitioner) to identify determinants associated with increased or decreased costs. The estimated coefficients were linearly combined to create the HSM Index for individual patients. The score was applied to the validation sample, and measures of predictive accuracy, explained variance, and the observed/predicted ratio were computed to evaluate the model's accuracy. RESULTS: The mean yearly cost was €414.57 per patient, and the HSM Index had a median value of 5.08 (25th-75th range 4.44-5.98). The HSM Index explained 50.17% of the variation in costs. Concerning calibration, in 80% of the population, the margin of error in the estimation of costs was around 10%. CONCLUSIONS: The HSM Index is a reliable case-mix system that could be implemented in general practice for costs adjustment. This tool should ensure fairer scrutiny of resource use and allocation of budgets among general practitioners.

Venous thromboembolism in medical patients treated in the setting of primary care: a nationwide case-control study in Italy.

OBJECTIVES: The risk of venous thrombotic events (VTE) among medical outpatients is still not clear and it remains to be clarified whether medical diseases involve the same risk if managed at home or in hospital. The aim of this study was to evaluate in the setting of outpatient family medicine the relationship between VTE and medical conditions known to be at risk during a hospital stay. DESIGN AND SETTING: The study involved a nationwide retrospective observation according to a nested case-control method; 400 general practitioners throughout Italy constituted the network for data collection. Between 2001 and 2004, all cases recorded as having VTE were entered; ten control patients without VTE, matched by sex, physician, and age, were selected from the database for each case. RESULTS: The eligible population comprised 372,000 patients and 1,624 incident VTE were recorded. Univariate analysis indicated hospitalization (OR 5.02; 95% CI 4.01-6.29), cancer (OR 3.06; 95% CI 2.47-3.79), acute infectious disease (OR 2.93; 95% CI 1.94-4.43), neurological disease (OR 2.60; 95% CI 1.56-4.33), congestive heart failure (CHF) (OR 2.48; 95% CI 1.68-3.69), paralysis (OR 1.87; 95% CI 1.51-2.32), COPD (OR 1.58; 95% CI 1.29-1.95), stroke (OR 1.62; 95% CI 1.24-2.12), superficial venous thrombosis (OR 1.51; 95% CI 1.11-2.04, and rheumatic diseases (OR 1.49; 95% CI 1.28-1.74) as significantly associated with an increased risk for VTE. After adjustment, only transient or definitive paralysis, cancer, acute infectious disease, congestive heart failure, neurological diseases, and previous hospitalization remained associated. CONCLUSIONS: This large study indicates that VTE outpatients seen by general practitioners in Italy have a high prevalence of the same medical diseases associated with VTE among patients treated in hospital.

Opportunistic prostate-specific antigen screening in Italy: 6 years of monitoring from the Italian general practice database.

The practice of prostate-specific antigen (PSA) screening has been increasing in Italy despite uncertain scientific evidence and contrary recommendations from most scientific societies. In 2002, a survey of PSA screening diffusion among general practices was performed, looking for screening frequency and age pattern of screened individuals. The objective of this study was to assess whether the features of PSA screening did change after 6 years in the same considered setting. Using the data obtained from 500 Italian general practitioners providing information to the Health Search/CSD Patient database, we selected, for the study purpose 351,091 male individuals. We assumed PSA prescriptions performed during 2005-2008 in individuals without prostate cancer, or benign prostate disease, or urological symptoms history to have a screening purpose. Screening frequency was analyzed in the overall series, by year and by patient's age. Exposure to PSA screening (at least on PSA test in the considered period) of males aged over 50 years raised from 31.4% (confidence interval 95% 31.08-31.70%) during 2002 to 46.4% (confidence interval 95% 46.19-46.68%) during 2008. The highest yearly exposure to PSA screening (55%) and the highest frequency of repeat testing was observed in the 70-79 age range. PSA screening practice has continued to increase in Italy and is often performed in elderly people without any scientific rationale.

Epidemiology of suboptimal prescribing in older, community dwellers: a two-wave, population-based survey in Dicomano, Italy.

BACKGROUND: Because of co-morbidity, older persons are often exposed to use of an excessive number of drugs, which per se implies also use of inappropriate drugs or of potentially interacting drugs ('suboptimal prescribing'). Time trends of suboptimal prescribing in older, community dwellers have been poorly investigated, particularly in Italy. OBJECTIVE: To evaluate the time-course modification of suboptimal prescribing in older, community dwellers. METHODS: We conducted a study on an Italian cohort of older (aged>or=65 years), community dwellers for whom data were collected in a two-wave (1995 and 1999), population-based survey. Suboptimal prescribing was defined as occurrence of polypharmacy (>or=5 medications), prescription of inappropriate medications (according to 1991 Beers' criteria) and prescription of potentially interacting drugs (as identified by the Micromedex Drug-Reax system). All outcome variables were modelled as continuous and dichotomous. RESULTS: In 568 participants (59.9% women, mean+/-standard error age 72.7+/-0.2 years), polypharmacy and potentially interacting drugs were more prevalent in 1999 than in 1995, while prevalence of inappropriate drugs was lower in 1999. The proportion of participants receiving polypharmacy was nearly 3-fold greater in 1999 than in 1995 (21.6% vs 8.8%; p<0.001). After adjustment for disability, coronary artery disease/stroke, heart failure and other co-morbidities, polypharmacy was twice as prevalent in 1999 as in 1995, with a mean increase of 0.5 drugs per participant. In contrast, in models adjusted for the same variables and also for polypharmacy, inappropriate prescribing was reduced (60% lower prevalence, 0.06 mean reduction in prescriptions per participant) in 1999 compared with 1995. In multivariable models, no change was observed in the number of potentially interacting prescriptions. CONCLUSIONS: Between 1995 and 1999, the number of prescriptions received by a cohort of older, community dwellers increased substantially, even after controlling for co-morbidity. On the other hand, when controlling for polypharmacy, other indicators of suboptimal prescribing remained unaffected or even decreased, suggesting that even increasing levels of polypharmacy do not necessarily imply other forms of suboptimal prescribing among older persons.

Screening of older community-dwelling people at risk for death and hospitalization: the Assistenza Socio-Sanitaria in Italia project.

OBJECTIVES: To develop and validate mortality and hospitalization prognostic tools based upon information readily available to primary care physicians (PCPs). DESIGN: Population-based cohort study. Baseline predictors were patient demographics, a seven-item questionnaire on functional status and general health, use of five or more drugs, and previous hospitalization. SETTING: Community-based study. PARTICIPANTS: Prognostic indexes were developed in 2,470 subjects and validated in 2,926 subjects, all community-dwelling, aged 65 and older, and randomly sampled from the rosters of 98 PCPs in Florence, Italy. MEASUREMENTS: Fifteen-month mortality and hospitalization. RESULTS: Two scores were derived from logistic regression models and used to stratify participants into four groups. With Model 1, based upon the seven-item questionnaire, mortality rate ranged from 0.8% in the lowest-risk group (0-1 point) to 9.4% in the highest risk group (> or = 3 points), and hospitalization rate ranged from 12.4% to 29.3%; area under the receiver operating characteristic curves (AUC) was 0.75 and 0.60, respectively. With Model 2, considering also drug use and previous hospitalization, mortality and hospitalization rates ranged from 0.3% to 8.2% and from 8.1% to 29.7%, for the lowest-risk to the highest-risk group; the AUC increased significantly only for hospitalization (0.67). CONCLUSION: Prediction of death and hospitalization in older community-dwelling people can be easily obtained with two indexes using information promptly available to PCPs. These tools might be useful for guiding clinical care and targeting interventions to reduce the need for hospital care in older persons.

Co-prescriptions with itraconazole and fluconazole as a signal for possible risk of drug-drug interactions: a four-year analysis from Italian general practice.

PURPOSE: To determine the prevalence of concomitant use of drugs potentially responsible for interactions among itraconazole and fluconazole users in general practice. METHODS: During the years 1999-2002, we obtained information from the 'Health Search Database', (HSD) an Italian general practice research database. Among a total sample of 457 672 eligible patients, we included those aged >16 years, and whose diagnoses could be classified as mycosis. Itraconazole and fluconazole users were then selected. A potentially drug-drug interaction (DDI) occurred when the use of concomitant drugs were recorded within +/-30 days from the date of the first azoles prescription. Interacting drugs were classified according to the summary of product characteristics (SPC) as provided by the Italian Pharmaceutical Repertory (REFI). RESULTS: From 18 323 cases of mycosis, we selected 4843 itraconazole and 1446 fluconazole users. Potentially interacting drugs were prescribed in 8.7% of itraconazole and 6.1% of fluconazole users. For itraconazole, calcium channel blockers were the most common interacting drugs (3.3%), followed by statins (1.7%) and clarithromycin (1.3%), whereas gestoden + ethynylestradiol (2.5%) and benzodiazepines (1.8%) resulted as the most common interacting drugs among fluconazole users. CONCLUSION: Data indicate a relevant prevalence of concomitant use of medications potentially leading to drug interactions among azoles users. Because of the wide use of these medications in general practice, they should be used with clinical monitoring in view of their known side effects as well as their potential risk for drug interaction.

Antibiotic prescribing for acute and recurrent cystitis in primary care: a 4 year descriptive study.

OBJECTIVES: To explore the antibiotic prescribing pattern for cystitis and the patient-related variables associated with prescription during a 4 year period among Italian general practitioners (GPs). METHODS: We obtained information from the 'Health Search Database' (HSD), an Italian general practice research database. From a total sample of 457 672 eligible patients aged >16 years registered up to December 2002, we included those whose diagnoses could be classified as acute (uncomplicated and complicated) and recurrent cystitis. Patients' features and prevalence of antibiotic users were assessed. RESULTS: Of 35 129 cases diagnosed during the period 1999-2002, 96.0% of them were acute cystitis (39.2% recorded as uncomplicated). The prevalence of cases with acute complicated and uncomplicated cystitis slightly increased during the 4 year period, whereas it remained stable for recurrent cystitis. Most of the cystitis cases reported no diagnostic tests. More than 70% of patients were prescribed with at least one antibiotic, with a 4-fold increased risk of antibiotic use for acute cystitis throughout the study period. The prevalence of antibiotic users reached 86.2% for both acute uncomplicated and complicated cystitis in 2002, and 81.5% for recurrent cystitis. Fluoroquinolones represented the most common antibiotics being prescribed although they markedly decreased during these years. Fosfomycin trometamol use increased dramatically, becoming the first choice for any type of cystitis. CONCLUSIONS: Data indicate an evident rise in antibiotic use mostly related to fosfomycin trometamol. They also indicate that such a prescriptive trend finds confirmation from the available evidence for acute uncomplicated cystitis, although the management of recurrent cystitis could be further improved.