Andrea Marcellusi

Quality of life and emotional distress in early stage and locally advanced cervical cancer patients: a prospective, longitudinal study

OBJECTIVES This prospective, longitudinal study investigates QoL issues and emotional distress in early stage cervical cancer (ECC) patients undergoing radical surgery (RS) and in locally advanced cervical cancer (LACC) patients triaged to chemoradiation (CT/RT) followed by RS. METHODS The Global Health Status scale of EORTC QLQ-C30 (GHS), the EORTC QLQ-CX24 (CX24) and the Hospital Anxiety and Depression Scale (HADS) questionnaire were administered at baseline, and after 3, 6, and 12 months from surgery. For LACC patients QoL assessment was also performed after CT/RT. Statistical analysis was performed by the ANOVA for repeated measures and the Between Subject test. RESULTS In ECC and LACC patients, the GHS scores improved over time (5.5% difference in mean scores compared to baseline in ECC, and 7.0% difference in mean score compared to baseline in LACC patients). An early worsening of lymphedema scores was documented in ECC cases (14.6% difference in mean values compared to baseline, p value=0.001), and in LACC patients (difference up to 28.3% of mean values, value=0.0001). Menopausal symptoms persistently worsened over time reaching >15% difference of mean values compared to baseline in both groups. Sexual activity scores markedly improved both in ECC and LACC patients (difference of mean score values compared to baseline was 16.5% in ECC, and 6.7% in LACC patients). Both ECC and LACC patients experienced an improvement of anxiety scores. CONCLUSIONS Lymphedema and menopausal symptoms were the most disabling treatment-related sequelae; the amount of QoL issues and their multifaceted aspects require the cooperation of multidisciplinary teams.

Economic burden of human papillomavirus-related diseases in Italy

Introduction Human papilloma virus (HPV) genotypes 6, 11, 16, and 18 impose a substantial burden of direct costs on the Italian National Health Service that has never been quantified fully. The main objective of the present study was to address this gap: (1) by estimating the total direct medical costs associated with nine major HPV-related diseases, namely invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, and head and neck, anogenital warts, and recurrent respiratory papillomatosis, and (2) by providing an aggregate measure of the total economic burden attributable to HPV 6, 11, 16, and 18 infection. Methods For each of the nine conditions, we used available Italian secondary data to estimate the lifetime cost per case, the number of incident cases of each disease, the total economic burden, and the relative prevalence of HPV types 6, 11, 16, and 18, in order to estimate the aggregate fraction of the total economic burden attributable to HPV infection. Results The total direct costs (expressed in 2011 Euro) associated with the annual incident cases of the nine HPV-related conditions included in the analysis were estimated to be €528.6 million, with a plausible range of €480.1–686.2 million. The fraction attributable to HPV 6, 11, 16, and 18 was €291.0 (range €274.5–315.7 million), accounting for approximately 55% of the total annual burden of HPV-related disease in Italy. Conclusions The results provided a plausible estimate of the significant economic burden imposed by the most prevalent HPV-related diseases on the Italian welfare system. The fraction of the total direct lifetime costs attributable to HPV 6, 11, 16, and 18 infections, and the economic burden of noncervical HPV-related diseases carried by men, were found to be cost drivers relevant to the making of informed decisions about future investments in programmes of HPV prevention.

Evaluation of quality of life and emotional distress in endometrial cancer patients: A 2-year prospective, longitudinal study

OBJECTIVES The aim of the study was to prospectively, and longitudinally assess Quality of Life (QoL) and emotional distress in a large series of endometrial cancer (EC) patients. METHODS Global Health Status of the EORTC QLQ-C30 (GHS), the EORTC QLQ-CX24 (CX24), and the Hospital Anxiety and Depression Scale (HADS) questionnaires were administered at diagnosis, and after 3, 6, 12, and 24months since surgery. The Generalized Linear Model and the Between Subject test were used to analyze QoL changes over time, and the association between factors and patient QoL. RESULTS GHS scores improved over time, although the statistical significance was not reached. Worse lymphedema scores were documented worsened over time with a trend to recover at the 12- and 24month evaluation (p-value=0.028). Scores for Menopausal Symptoms (MS) dramatically worsened over time reaching a 38.5 difference of mean±SE compared to baseline (p-value=0.011). Sexual Activity (SxA) scores improved until the 12-month evaluation (p-value=0.048), and showed a return to baseline levels at the last assessment (p-value=0.025). A significant improvement of anxiety scores was documented at the 3-month evaluation, and persisted over time. In multivariate analysis, unmarried status was associated with poor scores for sexual activity, while living with someone was associated with worse MS scores. CONCLUSIONS Menopausal and lymphedema symptoms heavily affect QoL in EC patients. Since socio-demographic features play a major role in deteriorating SxA and MS, psycho-social intervention and patient education should be considered as an integral part of EC patient treatment.

Hospital costs incurred by the Italian National Health Service for invasive cervical cancer

METHODS A longitudinal, retrospective, cohort study was designed to assess the mean treatment cost of invasive cervical cancer, cross-linking clinical and administrative databases. The study was performed from the Italian NHS perspective. Costs were estimated using DRG charges. All patients with histological diagnosis of invasive cervical cancer admitted to Gynecologic Oncology centres of the Catholic University of the Sacred Heart between 2000 and 2007 were enrolled. RESULTS Overall, 351 patients (212 with LACC and 139 with ECC) were eligible for analysis. The mean direct medical cost by patient was € 22,200 ± 21,600 with a significantly higher burden for LACC compared with ECC patients (€ 28,696 ± 24,874 versus € 12,329 ± 8,726). Radical surgery accounted for € 6,851 ± 1,406, and € 7,709 ± 3,710 in ECC and LACC group, respectively; the resulting difference achieved a statistical significance. The extent of disease, disease progression/recurrence, and length of hospitalization confirmed their independent role as cost predictive factors. CONCLUSIONS The combined use of administrative and clinical databases allowed a feasible assessment of the mean cost induced by the invasive cervical cancer. Management of LACC patients was associated with higher costs due to the utilization of several therapeutic strategies and more frequent appearance of disease progression/recurrence.

Novel Health Economic Evaluation of a Vaccination Strategy to Prevent HPV-related Diseases The BEST Study

Background:The development of human papillomavirus (HPV)-related diseases is not understood perfectly and uncertainties associated with commonly utilized probabilistic models must be considered. The study assessed the cost-effectiveness of a quadrivalent-based multicohort HPV vaccination strategy within a Bayesian framework. Methods:A full Bayesian multicohort Markov model was used, in which all unknown quantities were associated with suitable probability distributions reflecting the state of currently available knowledge. These distributions were informed by observed data or expert opinion. The model cycle lasted 1 year, whereas the follow-up time horizon was 90 years. Precancerous cervical lesions, cervical cancers, and anogenital warts were considered as outcomes. Results:The base case scenario (2 cohorts of girls aged 12 and 15 y) and other multicohort vaccination strategies (additional cohorts aged 18 and 25 y) were cost-effective, with a discounted cost per quality-adjusted life-year gained that corresponded to &OV0556;12,013, &OV0556;13,232, and &OV0556;15,890 for vaccination programs based on 2, 3, and 4 cohorts, respectively. With multicohort vaccination strategies, the reduction in the number of HPV-related events occurred earlier (range, 3.8–6.4 y) when compared with a single cohort. The analysis of the expected value of information showed that the results of the model were subject to limited uncertainty (cost per patient=&OV0556;12.6). Conclusions:This methodological approach is designed to incorporate the uncertainty associated with HPV vaccination. Modeling the cost-effectiveness of a multicohort vaccination program with Bayesian statistics confirmed the value for money of quadrivalent-based HPV vaccination. The expected value of information gave the most appropriate and feasible representation of the true value of this program.

Cost-Effectiveness Analysis of Universal Human Papillomavirus Vaccination Using a Dynamic Bayesian Methodology: The BEST II Study

BACKGROUND Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. OBJECTIVE The objective of this study was to evaluate whether female-only vaccination or universal vaccination is the most cost-effective intervention against HPV. METHODS We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. RESULTS In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of €1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of €11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. CONCLUSIONS Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context.

Health policy model: long-term predictive results associated with the management of hepatitis C virus-induced diseases in Italy.

Background At present, there are no specific nationwide epidemiological studies representing the whole Italian population. This study is aimed at describing the epidemiological and economic burden that HCV will generate in the next few years in Italy. Furthermore, the impact that future anti-HCV treatments may have on the burden of disease was considered. This analysis was developed for the period 2012–2030 from the perspective of the Italian National Health Service (NHS). Methods A published system dynamic model was adapted for Italy in order to quantify the HCV-infected population in terms of disease progression and the associated costs from 1950 to 2030. The model structure was based on transition probabilities reflecting the natural history of the disease. In order to estimate the efficacy of current anti-HCV treatment strategies for genotypes 1 and 4, the sustained virological response (SVR) rate in registration clinical trials for both boceprevir and telaprevir was estimated. It was assumed that the efficacy for patients treated with peginterferon + ribavirin was equal to the placebo arm of a randomized clinical trial (RCT) relating to boceprevir and telaprevir. For genotypes 2/3 patients it was assumed that treatment efficacy with dual therapy was equal to a SVR rate from the literature. According to the aim of this study, only direct health care costs (hospital admissions, drugs, treatment, and care of patients) incurred by the Italian NHS have been included in the model. Costs have been extrapolated using the published scientific literature available in Italy and actualized with the 2012 ISTAT (Istituto Nazionale di Statistica) Price Index system for monetary revaluation. Three different scenarios were assumed in order to evaluate the impact of future anti-HCV treatments on the burden of disease. Results Overall, in Italy, 1.2 million infected subjects were estimated in 2012. Of these, about 211,000 patients were diagnosed, while only about 11,800 subjects were actually being treated with anti-HCV drugs. A reduction of health care costs is associated with a prevalence decrease. Indeed, once the spending peak is reached during this decade (about €527 million), the model predicts a cost reduction in the following 18 years. In 2030, based on the more effective treatments currently available, the direct health care cost associated with the management of HCV patients may reach €346 million (−34.3% compared to 2012). The first scenario (new treatment in 2015 with SVR =90% and same number of treated patients) was associated with a significant reduction in HCV-induced clinical consequences (prevalence =−3%) and a decrease in direct health care expenses, corresponding to €11.1 million. The second scenario (increase in treated patients to 12,790) produced an incremental cost reduction of €7.3 million, reaching a net decrease equal to €18.4 million. In the third scenario (treated patients =16,770), a higher net direct health care cost decrease versus the base-case (€44.0 million) was estimated. Conclusion Our model showed that the introduction of new treatments that are more effective could result in a quasi-eradication of HCV, with a very strong reduction in prevalence.

Costi diretti e indiretti associati a malattie allergiche respiratorie in Italia. Uno studio probabilistico di cost of illness

BACKGROUND The respiratory allergies, including allergic rhinitis and allergic asthma, represent a substantial medical and economic burden worldwide. Despite their dimension and huge economic-social burden, no data are available on the costs associated with the management of respiratory allergic diseases in Italy. The objective of this study was to estimate the average annual cost incurred by the National Health Service (NHS), as well as society, due to respiratory allergies and their main co-morbidities in Italy. METHODS A probabilistic prevalence-based cost of illness model was developed to estimate an aggregate measure of the economic burden associated with respiratory allergies and their main co-morbidities in terms of direct and indirect costs. A systematic literature review was performed in order to identify both the cost per case (expressed in present value) and the number of affected patients, by applying an incidence-based estimation method. Direct costs were estimated multiplying the hospitalization, drugs and management costs derived by the literature with the Italian epidemiological data. Indirect costs were calculated based on lost productivity according to the human capital approach. Furthermore, a one-way and probabilistic sensitivity analysis with 5,000 Monte Carlo simulations were performed, in order to test the robustness of the results and define the proper 95% Confidence Interval (CI). RESULTS Overall, the total economic burden associated with respiratory allergies and their main co-morbidities was € 7.33 billion (95% CI: € 5.99-€ 8.82). A percentage of 27.5% was associated with indirect costs (€ 2.02; 95% CI: € 1.72-€ 2.34 billion) and 72.5% with direct costs (€ 5.32; 95% CI: € 4.04-€ 6.77 billion). In allergic asthma, allergic rhinitis, combined allergic rhinitis and asthma, turbinate hypertrophy and allergic conjunctivitis, the model estimate an average annual economic burden of € 1,35 (95% CI: € 1,14-€ 1,58) billion, € 1,72 (95% CI: € 1,14-€ 2,43) billion, € 1,62 billion (€ 0,91-€ 2,53) billion, € 0,12 (€ 0,07-€ 0,17) billion, € 0,46 (€ 0,16-€ 0,92) billion respectively. CONCLUSIONS To our knowledge, this is the first study in which direct costs (incurred by NHS) and indirect ones (incurred by the society) were taken into account to estimate the overall burden associated with respiratory allergies and their main co-morbidities in our Country. In conclusion, this work may be considered an efficient tool for public decision-makers to correctly understand the economic aspects involved by the management and treatment of respiratory allergies-induced diseases in Italy.Background The respiratory allergies, including allergic rhinitis and allergic asthma, represent a substantial medical and economic burden worldwide. Despite their dimension and huge economic-social burden, no data are available on the costs associated with the management of respiratory allergic diseases in Italy. The objective of this study was to estimate the average annual cost incurred by the National Health Service (NHS), as well as society, due to respiratory allergies and their main co-morbidities in Italy. Methods A probabilistic prevalence-based cost of illness model was developed to estimate an aggregate measure of the economic burden associated with respiratory allergies and their main co-morbidities in terms of direct and indirect costs. A systematic literature review was performed in order to identify both the cost per case (expressed in present value) and the number of affected patients, by applying an incidence-based estimation method. Direct costs were estimated multiplying the hospitalization, drugs and management costs derived by the literature with the Italian epidemiological data. Indirect costs were calculated based on lost productivity according to the human capital approach. Furthermore, a one-way and probabilistic sensitivity analysis with 5,000 Monte Carlo simulations were performed, in order to test the robustness of the results and define the proper 95% Confidence Interval (CI). Results Overall, the total economic burden associated with respiratory allergies and their main co-morbidities was € 7.33 billion (95% CI: € 5.99-€ 8.82). A percentage of 27.5% was associated with indirect costs (€ 2.02; 95% CI: € 1.72-€ 2.34 billion) and 72.5% with direct costs (€ 5.32; 95% CI: € 4.04-€ 6.77 billion). In allergic asthma, allergic rhinitis, combined allergic rhinitis and asthma, turbinate hypertrophy and allergic conjunctivitis, the model estimate an average annual economic burden of € 1,35 (95% CI: € 1,14-€ 1,58) billion, € 1,72 (95% CI: € 1,14-€ 2,43) billion, € 1,62 billion (€ 0,91-€ 2,53) billion, € 0,12 (€ 0,07-€ 0,17) billion, € 0,46 (€ 0,16-€ 0,92) billion respectively. Conclusions To our knowledge, this is the first study in which direct costs (incurred by NHS) and indirect ones (incurred by the society) were taken into account to estimate the overall burden associated with respiratory allergies and their main co-morbidities in our Country. In conclusion, this work may be considered an efficient tool for public decision-makers to correctly understand the economic aspects involved by the management and treatment of respiratory allergies-induced diseases in Italy.

Governance of preventive Health Intervention and On time Verification of its Efficiency: the GIOVE Study

Objectives The GIOVE Study was aimed to the achievement of allocative efficiency of the budget allocated to the prevention of human papillomavirus (HPV)-induced diseases. An ex-ante determination of the most efficient allocation of resources between screening and multicohort quadrivalent immunisation programmes was followed by the ex-post assessment of the allocative efficiency actually achieved after a 12-month period. Design A bound optimisation model was developed to determine the ex-ante allocative efficiency of resources. The alternatives compared were the screening programme alone and the quadrivalent immunisation with access to screening. A sensitivity analysis was carried out to assess the uncertainty associated with the main inputs of the model. Subsequently, a cohort of girls with a complete recorded vaccination history were enrolled in an observational retrospective study for 18 months to ensure full compliance with the recommended schedule of vaccination (0, 2, 6 months) within a 12-month time horizon. Setting Basilicata region, in the south of Italy. Participants 12 848 girls aged 12, 15, 18 or 25 years. Intervention Immunisation with quadrivalent anti-HPV vaccine. Outcome measures The vaccination coverage rate was considered to be the indicator of the best achievable benefit, given the budgetary constraints. Results Assuming a vaccine price of €100 per dose, a vaccination coverage rate of 59.6% was required for the most effective allocation of resources. The optimal rate of coverage was initially in favour of the multicohort strategy of vaccination against HPV (72.8%±2%). When the price paid for the quadrivalent vaccine dropped to €85 per dose, the most efficient coverage rate (69.5%) shifted closer to the immunisation rate actually achieved during the 12-month observation period. Conclusions The bound optimisation model demonstrated to be a useful approach to the ex-ante allocation and the ex-post assessment of the resources allocated to the implementation of a multicohort quadrivalent anti-HPV vaccination programme.

The economic burden of musculoskeletal disorders on the Italian social security pension system estimated by a Monte Carlo simulation

The aim of the study is to estimate the pension costs incurred for patients with musculoskeletal disorders (MDs) and specifically with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in Italy between 2009 and 2012. We analyzed the database of the Italian National Social Security Institute (Istituto Nazionale Previdenza Sociale i.e. INPS) to estimate the total costs of three types of social security benefits granted to patients with MDs, RA and AS: disability benefits (for people with reduced working ability), disability pensions (for people who cannot qualify as workers) and incapacity pensions (for people without working ability). We developed a probabilistic model with a Monte Carlo simulation to estimate the total costs for each type of benefit associated with MDs, RA and AS. We also estimated the productivity loss resulting from RA in 2013. From 2009 to 2012 about 393 thousand treatments were paid for a total of approximately €2.7 billion. The annual number of treatments was on average 98 thousand and cost in total €674 million per year. In particular, the total pension burden was about €99 million for RA and €26 million for AS. The productivity loss for AR in 2013 was equal to €707,425,191 due to 9,174,221 working days lost. Our study is the fi rst to estimate the burden of social security pensions for MDs based on data of both approved claims and benefits paid by the national security system. From 2009 to 2012, in Italy, the highest indirect costs were associated with disability pensions (54% of the total indirect cost), followed by disability benefits (44.1% of cost) and incapacity pensions (1.8% of cost). In conclusion, MDs are chronic and highly debilitating diseases with a strong female predominance and very significant economic and social costs that are set to increase due to the aging of the population.