Intentional rounding: a realist evaluation using case studies in acute and care of older people hospital wards.

BACKGROUND: In response to concerns about high hospital mortality rates, patient and carer complaints, a Mid Staffordshire NHS Foundation Trust public inquiry was conducted at the request of the UK government. This inquiry found serious failures in the quality of basic care provided and as a consequence, recommended that patients should have more regular visits, organised at predictable times from nursing staff. Intentional rounding, also known as nursing ward rounds, was widely adopted to meet this need. OBJECTIVE: To test, refine or refute eight programme theories to understand what works, for whom, and in what circumstances. SETTING: Six wards (older people and acute wards) in three NHS trusts in England. PARTICIPANTS: Board level and senior nursing managers (N = 17), nursing ward staff (N = 33), allied health and medical professionals (N = 26), patients (N = 34) and relatives (N = 28) participated in an individual, in-depth interview using the realist method. In addition, ward-based nurses (N = 39) were shadowed whilst they conduced intentional rounds (240 rounds in total) and the direct care of patients (188 h of patient care in total) was observed. METHODS: The mixed methods design included: Phase (1) Theory development - A realist synthesis was undertaken to identify any programme theories which were tested, refined and/or refuted, using data from phases 2 and 3; Phase (2) A survey of all English NHS acute Trusts; Phase (3) Six case studies of wards involving realist interviews, shadowing and non-participant observations, analysis of ward outcome and cost data; and Phase (4) Synthesis of findings from phases 1, 2 and 3. RESULTS: The realist synthesis identified eight programme theories of intentional rounding: 'Consistency and comprehensiveness', 'Accountability', 'Visibility of nurses', 'Anticipation', 'Allocated time to care', 'Nurse-patient relationships', 'Multi-disciplinary teamwork and communication' and 'Patient empowerment'. Key findings showed that of the original eight programme theories of intentional rounding, only two partially explained how the intervention worked ('Consistency and comprehensiveness' and 'Accountability'). Of the remaining six programme theories, the evidence for two was inconclusive ('Visibility of nurses' and 'Anticipation') and there was no evidence for four ('Allocated time to care'; 'Nurse-patient relationships'; 'Multi-disciplinary teamwork and communication'; and 'Patient empowerment'). CONCLUSIONS: This first theory-informed evaluation of intentional rounding, demonstrates that the effectiveness of intentional rounding in the English healthcare context is very weak. Furthermore, the evidence collected in this study has challenged and refuted some of the underlying assumptions about how intentional rounding works. This study has demonstrated the crucial role context plays in determining the effectiveness of an intervention and how caution is needed when implementing interventions developed for the health system of one country into another.

Drug Prices and Value of Oncology Drugs in Italy.

OBJECTIVE: The main objective of this study was to evaluate the potential role of efficacy data and other information available at the time of price and reimbursement (P&R) decision-making process within the definition of oncology treatment costs in Italy. METHODS: The study included all P&R dossiers submitted to the Italian Medicines Agency between July 2015 and December 2017. It prospectively collected the data of the P&R process starting from dossier submission up to the Italian Health Service reimbursement decision. The cost of treatment per patient was estimated using both the list price ("gross cost") and the confidential net price ("net cost") of drug packages and applied to the median duration of treatment. A 2-sample stage Heckman decomposition model was used to evaluate the potential role of efficacy data and other information available at the time of P&R decision making on the gross and net cost. RESULTS: A total of 37 oncology drugs related to 58 therapeutic indications were analyzed. The multivariate model showed that the variation of progression-free survival is the only variable predictor statistically associated with treatment cost, but this effect was observed only when confidential net prices were used (P=.026). CONCLUSIONS: Considering the perspective of a developed country having a public healthcare service with a central reimbursement negotiation is determined a relevant reduction in the treatment cost purchased by public payers. This is a useful approach to guarantee the affordability of innovative oncology drugs and to contain public expenditures on healthcare. Furthermore, the negotiation of confidential discounts and agreement clauses in managed entry agreements seemed to reward oncology drugs displaying an added therapeutic benefit.

Cross-regional variations of Covid-19 mortality in Italy: an ecological study.

BACKGROUND: Disparities in cross-regional coronavirus disease 2019 (Covid-19) mortality remain poorly understood. The association between pre-epidemic health and epidemic mortality can inform a policy response to future outbreaks. METHOD: We conducted an ecological study of the association between the cumulative deaths attributed to Covid-19 epidemic in the 20 Italian regions and nine determinants of population health derived from a systematic review of the literature. We used a multiple least square regression to predict the cross-regional variation in mortality observed from the onset of the epidemic to 23 September 2020. RESULTS: Four independent variables best explained the cross-regional differences in the number of deaths attributed to Covid-19: the force of infection, population density, number of elderly living in assisted facilities and the standard rate of diabetes. The semi-partial correlation coefficients suggest that the force of infection and the number of elderly residents in nursing homes were the dominant predictors of the number of deaths attributed to Covid-19. Statistical controls and validation confirmed the generalizability of the predictive model. CONCLUSIONS: Our findings indicate that a significant reduction of social contacts in main metropolitan areas and the timely isolation of elderly and diabetic residents could significantly reduce the death toll of the next wave of Covid-19 infection in Italy.

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.

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 €12,013, €13,232, and €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 = €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.

From 15 Minutes to 15 Seconds: How the Delta Variant Changed the Risk of Exposure to COVID-19. A Comparative Epidemiological Investigation Using Community Mobility Data From the Metropolitan Area of Genoa, Italy.

The Delta variant became dominant during the second wave of the Covid-19 pandemic due to its competitive advantage, the ability to reduce close contact duration from minutes to seconds, and, consequently, increase the risk of exposure to COVID-19. We used game theory to model the most effective public health response to this new threat. We compared the absolute and relative risk of exposure to COVID-19 before and after the emergence of the Delta variant. The absolute risk of exposure was defined as the product of crowding (people within a six feet distance) and visit duration. Our epidemiological investigation used aggregated and anonymized mobility data from Google Maps to estimate the visit duration for 808 premises in the metropolitan area of Genoa, Italy, in June 2021. The relative risk of exposure was obtained by dividing the risk of exposure of each activity by the lowest value (gas stations = 1). The median absolute risk of exposure to COVID-19 increased by sixty-fold in the first semester of 2021, while the relative risk did not significantly differ from the risk of exposure to the ancestral form of Covid-19 (5.9 in 2021 vs. 2.5 in 2021). The Delta variant represents an evolution of the game against COVID-19, but it is not a game-changer. The best response is to commit to our original strategy based on population-wide vaccination and social distancing. Unilateral deviations from the dominant strategy could offer COVID-19 a fighting chance against humanity.

Assessing the Health and Economic Outcomes of a 9-Valent HPV Vaccination Program in the United Kingdom.

Background: The United Kingdom (UK) switched from using the 4-valent human papillomavirus (HPV) vaccine (Gardasil®) to the 9-valent vaccine (Gardasil 9®) in 2021. Objective: To estimate and compare the health and economic outcomes of 2 HPV vaccination programs in the UK targeting girls and boys aged 12-13 years from the perspective of the UK National Health Service. The 2 vaccination strategies were (1) universal vaccination 4-valent (UV4V), using the 4-valent HPV vaccine (4vHPV), and (2) universal vaccination 9-valent (UV9V), using the 9-valent HPV vaccine (9vHPV). Methods: A deterministic heterosexual compartmental disease transmission model was used to track health and economic outcomes over a 100-year time horizon. Outcomes were discounted at an annual rate of 3.5% and 1.5%. All costs were adjusted to 2020 British pounds (£). Health outcomes were measured in quality-adjusted life-years (QALYs), and the summary results were presented as incremental cost-effectiveness ratios (£/QALY gained) when comparing UV4V with UV9V. Results: Using the same vaccine coverage for both programs, the total cumulative cases of HPV-related health outcomes tracked over the 100-year horizon indicated that the relative number of cases averted (UV9V vs UV4V) ranged from 4% (anal male cancers and deaths) to 56% (cervical intraepithelial neoplasia [CIN1]). Assuming that 9vHPV cost £15.18 more than 4vHPV (a cost differential based on discounted list prices), the estimated incremental cost-effectiveness ratio was £8600/QALY gained when discounted at 3.5%, and £3300/QALY gained when discounted at 1.5%. The estimated incremental cost-effectiveness ratios from the sensitivity analyses remained <£28000/QALY over a wide range of parameter inputs and demonstrated that disease utilities, discount rate, and vaccine efficacy were the 3 most influential parameters. Discussion: Consistent with other published studies, the results from this study found that the 9vHPV vaccine prevented a substantial number of cases when compared with the 4vHPV vaccine and was highly cost-effective. Conclusions: These results demonstrate that replacing universal 4vHPV with 9vHPV can prevent a substantial additional number of HPV-related cases/deaths (in both women and men) and remain cost-effective over a range of 9vHPV price premiums.

Risk of Exposure to COVID-19: Visit Duration Data Can Inform Our Daily Activities Choices: An Epidemiological Investigation Using Community Mobility Data from the Metropolitan Area of Genoa, Italy.

COVID-19 spreads mainly among people who are in close contact. Policymakers mostly resorted to normative measures to limit close contacts and impose social distancing. Our study aimed to estimate the risk of exposure to COVID-19 by location and activity in crowded metropolitan areas. The risk of exposure to COVID-19 was defined as the product of crowding (people within a six feet distance) and exposure duration (fraction of 15 min). Our epidemiological investigation used aggregated and anonymized mobility data from Google Maps to estimate the visit duration. We collected visit duration data for 561 premises in the metropolitan area of Genoa, Italy from October 2020 to January 2021. The sample was then clustered into 14 everyday activities, from grocery shopping to the post office. Crowding data by activity were obtained from pre-existing building norms and new government measures to contain the pandemic. The study found significant variance in the risk of exposure to COVID-19 among activities and, for the same activity, among locations. The empirical determination of the risk of exposure to COVID-19 can inform national and local public health policies to contain the pandemic's diffusion. Its simple numerical form can help policymakers effectively communicate difficult decisions affecting our daily lives. Most importantly, risk data by location can help us rethink our daily routine and make informed, responsible choices when we decide to go out.

Budget Impact Analysis of Dalbavancin in the Treatment of Acute Bacterial Skin and Skin Structure Infections in Three European Countries.

BACKGROUND AND OBJECTIVE: Acute bacterial skin and skin structure infections (ABSSSIs) have been defined by the US Food and Drug Administration (FDA) in 2013 to include a subset of complicated skin and skin structure infections commonly treated with parenteral antibiotic therapy. Inpatient treatment of ABSSSIs involves a significant economic burden on the healthcare system. This study aimed to evaluate the economic impact on the National Health System associated with the management of non-severe ABSSSIs treated in hospitals with innovative long-acting dalbavancin compared to standard antibiotic therapy in Italy, Spain, and Austria. METHODS: A budget impact analysis was developed to evaluate the direct costs associated with the management of ABSSSI from the national public health system perspective. The model considered the possibility of early discharge of patients directly from the Emergency Department (ED), after 1 night in the hospital, or after two or three nights in the hospital. A scenario with Standard of Care was compared with a dalbavancin scenario, where patients had the possibility of being discharged early. The epidemiological and cost parameters were extrapolated from national administrative databases and from a systematic literature review for each country. The analysis was conducted in a 3-year time horizon. A one-way deterministic sensitivity analysis was conducted to examine the robustness of the results. RESULTS: The model estimated an average annual number of patients with non-severe ABSSSI in Italy, Spain, and Austria equal to 5396, 7884, and 1788, respectively. A total annual expenditure of about €9.9 million, €13.5 million, and €3.4 million was estimated for treating the full set of ABSSSI patients in Italy, Spain, and Austria, respectively. Dalbavancin reduced the in-hospital length of stay in each country. In the first year of its introduction, dalbavancin significantly reduced the total economic burden in Italy and Spain (- €352,252 and - €233,991, respectively), while it increased the total economic burden in Austria (€80,769, 0.7% of the total expenditure for these patients); in the third year of its introduction, dalbavancin reduced the total economic burden in each Country (- €1.1 million, - €810,650, and - €70,269, respectively). CONCLUSIONS: The introduction of dalbavancin in a new patient pathway to treat non-severe ABSSSI could generate a significant reduction in hospitalized patients and the overall patient length of stay in hospital.

Cost-effectiveness of direct acting oral anticoagulants in the prevention of thromboembolic complications: limits and concerns of economic evaluations.

: Economic evaluations have a widespread application in many areas of clinical research and play a key role in the clinical decision-making process. However, economic analyses have been sometimes used to produce new 'evidence' that is not adequately tested in the target population. This is the case of data arising from a systematic review of clinical trials evaluating the use of direct acting oral anticoagulants for the prevention of stroke in patients with atrial fibrillation. Taking into account this example, here we discuss the concerns raised by the improper interpretation of the results. Our conclusions are three-fold. Data from economic analyses should not be shifted to a clinical recommendation. Simulation models should not be used to generate new 'evidence' that is not supported by experimental data and is misleading. Clinical judgment is therefore pivotal to interpret results emerging from economic analyses.

Ecological validity of cost-effectiveness models of universal HPV vaccination: a protocol for a systematic review.

BACKGROUND: Sexually transmitted infection with high-risk, oncogenic strains of human papillomavirus (HPV) still induces a relevant burden of diseases on both men and women. Although vaccines appear to be highly efficacious in preventing the infection of the most common high-risk strains (HPV 6, 11, 16, 18), important questions regarding the appropriate target population for prophylactic vaccination are still debated. Models in the extant literature seem to converge on the cost-effectiveness of high coverage (>80%) of a single cohort of 12-year-old girls. This vaccination strategy should provide an adequate level of indirect protection (herd immunity) to the unvaccinated boys. This argument presupposes the ecological validity of the cost-effectiveness models; the implicit condition that the characteristics of the individuals and the sexual behaviours observed in the models is generalisable to the natural behaviours of the population. The primary aim of this review is to test the ecological validity of the cost-effectiveness models of universal HPV vaccination available in the literature. The ecological validity of each model will be defined by the number of representative characteristics and behaviours taken into consideration. METHODS: Nine bibliographic databases will be searched: MEDLINE (via PubMed); Scopus; Science Direct; EMBASE via OVID SP, Web of Science, DARE, NHIR EED and HTA (via NHIR CRD); and CINHAL Plus. An additional search for grey literature will be conducted on Google Scholar and Open Grey. A search strategy will be developed for each of the databases. Data will be extracted following a pre-determined spreadsheet and then clustered and prioritised: the main outcomes will report the inputs to the demographic and epidemiological model, while additional outcomes will refer to basic inputs to the cost-effectiveness valuation. Each study included in the review will be scored by the number of representative characteristics and behaviours taken into consideration (yes or no) on both dimensions. Individual study's scores will be plotted in a 2 by 2 matrix: studies included in the upper right quadrant will be defined as ecologically valid, since which both individuals' characteristics and their sexual behaviours are representative. DISCUSSION: The proposed systematic review will be the first to assess the ecological validity of cost-effectiveness studies. In the context of sexually transmitted diseases, when this condition is violated, an error in predicting the protective impact of herd immunity would occur. Hence, a vaccination policy informed on ecologically invalid models would potentially expose boys to a residual risk of contracting HPV-induced malignancies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016034145.

Ecological validity of cost-effectiveness models of universal HPV vaccination: A systematic literature review.

BACKGROUND: The protective (herd) effect of the selective vaccination of pubertal girls against human papillomavirus (HPV) implies a high probability that one of the two partners involved in intercourse is immunised, hence preventing the other from this sexually transmitted infection. The dynamic transmission models used to inform immunisation policy should include consideration of sexual behaviours and population mixing in order to demonstrate an ecological validity, whereby the scenarios modelled remain faithful to the real-life social and cultural context. The primary aim of this review is to test the ecological validity of the universal HPV vaccination cost-effectiveness modelling available in the published literature. METHODS: The research protocol related to this systematic review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42016034145). Eight published economic evaluations were reviewed. RESULTS: None of the studies showed due consideration of the complexities of human sexual behaviour and the impact this may have on the transmission of HPV. DISCUSSION: Our findings indicate that all the included models might be affected by a different degree of ecological bias, which implies an inability to reflect the natural demographic and behavioural trends in their outcomes and, consequently, to accurately inform public healthcare policy. In particular, ecological bias have the effect to over-estimate the preference-based outcomes of selective immunisation. A relatively small (15-20%) over-estimation of quality-adjusted life years (QALYs) gained with selective immunisation programmes could induce a significant error in the estimate of cost-effectiveness of universal immunisation, by inflating its incremental cost effectiveness ratio (ICER) beyond the acceptability threshold. The results modelled here demonstrate the limitations of the cost-effectiveness studies for HPV vaccination, and highlight the concern that public healthcare policy might have been built upon incomplete studies.

What aspects of intentional rounding work in hospital wards, for whom and in what circumstances? A realist evaluation protocol.

INTRODUCTION: Intentional rounding (IR) is a structured process whereby nurses in hospitals carry out regular checks, usually hourly, with individual patients using a standardised protocol to address issues of positioning, pain, personal needs and placement of items. The widespread implementation of IR across the UK has been driven by the recommendations of the Francis Inquiry although empirical evidence of its effectiveness is poor. This paper presents a protocol of a multimethod study using a realist evaluation approach to investigate the impact and effectiveness of IR in hospital wards on the organisation, delivery and experience of care from the perspective of patients, their family members and staff. METHODS AND ANALYSIS: The study will be conducted in four phases. Phase 1: theory development using realist synthesis to generate hypotheses about what the mechanisms of IR may be, what particular groups may benefit most or least and what contextual factors might be important to its success or failure which will be tested in subsequent phases of the study. Phase 2: a national survey of all NHS acute trusts to explore how IR is implemented and supported across England. Phase 3: case studies to explore how IR is implemented 'on the ground', including individual interviews with patients, family members and staff, non-participant observation, retrieval of routinely collected patient outcomes and cost analysis. Phase 4: accumulative data analysis across the phases to scrutinise data for patterns of congruence and discordance and develop an overall evaluation of what aspects of IR work, for whom and in what circumstances. ETHICS AND DISSEMINATION: The study has been approved by NHS South East Coast-Surrey Research Ethics Committee. Findings will be published in a wide range of outputs targeted at key audiences, including patient and carer organisations, nursing staff and healthcare managers.

Health utilities lost and risk factors associated with HPV-induced diseases in men and women: the HPV Italian collaborative study group.

PURPOSE: A complete economic evaluation requires accurate data concerning the resources used, outcomes, and utilities (patient's preferences) to properly value the cost utility of human papillomavirus (HPV) vaccination strategies. This study was designed to measure the utility loss in health states affected by a broad range of HPV-induced pathologies in both sexes in Italy. As a secondary objective, risk factors influencing the viral transmission and development of HPV infections were also investigated. METHODS: Patients with a diagnosis of several HPV-induced pathologies including atypical squamous cells of undetermined significance (ASC-US), cervical intraepithelial neoplasia (CIN), cervical and anal-colorectal cancer, head and neck squamous cell carcinoma (HNSCC) and anogenital warts (AWs) were evaluated. Utilities, quality of life, and risk factors were elicited using a standardized and computer-guided administration of time trade-off, European Quality of Life 5 Dimensions (EQ-5D), 3 levels, and risk factor questionnaires. Utilities were measured at 6 clinical research centers across Italy. A group of healthy subjects was used as a control. A mean number of 20 healthy subjects was used as a control for each pathology group. FINDINGS: Overall, 600 respondents were eligible for analysis: 465 patients (mean [SD] age, 44.0 [16.3] years) and 135 controls (mean [SD] age, 44.0 [13.2] years). With the exception of anal and HNSCC cancer, no statistically significant differences were observed between case and control groups, in terms of either age or quality of life at the time of interview. The patients' perception of their health condition at baseline was equal to an EQ-5D score of 0.87 (0.22). The mean (SD) value of utilities associated with the HPV-induced pathologies corresponded to 0.83 (0.24), 0.78 (0.27), 0.83 (0.22), 0.81 (0.27), 0.58 (0.31), 0.51 (0.26), and 0.69 (0.30) for ASC-US, AWs, CIN 1 (mild), CIN 2-3 (moderate to severe), cervical cancer, anal cancer and HNSCC, respectively. Utility lost due to AWs was significantly higher in females compared with males (0.71 [0.29] vs 0.83 [0.25]; P = 0.018). Having >5 sexual partners increased the risk of acquiring HPV-induced infections as much as 2.52-fold (P = 0.004), whereas for smoking or the age at start of sexual activity younger than 18 years, the risk increased by ~1.62-fold (P = 0.034). High levels of education were associated with a statistically significant protective effect (P < 0.001). IMPLICATIONS: Risk factors and utilities elicited in this study can be used as part of future economic assessments of other HPV vaccination strategies, including an immunization program for preadolescents of both sexes in Italy.

A novel method to value real options in health care: the case of a multicohort human papillomavirus vaccination strategy.

BACKGROUND: A large number of economic evaluations have already confirmed the cost-effectiveness of different human papillomavirus (HPV) vaccination strategies. Standard analyses might not capture the full economic value of novel vaccination programs because the cost-effectiveness paradigm fails to take into account the value of active management. Management decisions can be seen as real options, a term used to refer to the application of option pricing theory to the valuation of investments in nonfinancial assets in which much of the value is attributable to flexibility and learning over time. OBJECTIVE: The aim of this article was to discuss the potential advantages shown by using the payoff method in the valuation of the cost-effectiveness of competing HPV immunization programs. METHODS: This was the first study, to the best of our knowledge, to use the payoff method to determine the real option values of 4 different HPV vaccination strategies targeting female subjects aged 12, 15, 18, and 25 years. The payoff method derives the real option value from the triangular payoff distribution of the project's net present value, which is treated as a triangular fuzzy number. To inform the real option model, cost-effectiveness data were derived from an empirically calibrated Bayesian model designed to assess the cost-effectiveness of a multicohort HPV vaccination strategy in the context of the current cervical cancer screening program in Italy. A net health benefit approach was used to calculate the expected fuzzy net present value for each of the 4 vaccination strategies evaluated. RESULTS: Costs per quality-adjusted life-year gained seemed to be related to the number of cohorts targeted: a single cohort of girls aged 12 years (€10,955 [95% CI, -1,021 to 28,212]) revealed the lowest cost among the 4 alternative strategies evaluated. The real option valuation challenged the cost-effectiveness dominance of a single cohort of 12-year-old girls. The simultaneous vaccination of 2 cohorts of girls aged 12 and 15 years yielded a real option value (€17,723) equivalent to that attributed to a single cohort of 12-year-old girls (€17,460). CONCLUSIONS: The payoff method showed distinctive advantages in the valuation of the cost-effectiveness of competing health care interventions, essentially determined by the replacement of the nonfuzzy numbers that are commonly used in cost-effectiveness analysis models, with fuzzy numbers as an input to inform the real option pricing method. The real option approach to value uncertainty makes policy making in health care an evolutionary process and creates a new "space" for decision-making choices.

Correction: Economic Burden of Human Papillomavirus-Related Diseases in Italy.

[This corrects the article on p. e49699 in vol. 7.].

Prevalence of the prescription of potentially interacting drugs.

The use of multiple medications is becoming more common, with a correspondingly increased risk of untoward effects and drug-related morbidity and mortality. We aimed at estimating the prevalence of prescription of relevant potentially interacting drugs and at evaluating possible predictors of potentially interacting drug exposure. We retrospectively analyzed data on prescriptions dispensed from January 2004 to August 2005 to individuals of two Italian regions with a population of almost 2.1 million individuals. We identified 27 pairs of potentially interacting drugs by examining clinical relevance, documentation, and volume of use in Italy. Subjects who received at least one prescription of both drugs were selected. Co-prescribing denotes "two prescriptions in the same day", and concomitant medication "the prescription of two drugs with overlapping coverage". A logistic regression analysis was conducted to examine the predictors of potential Drug-Drug Interaction (pDDIs). 957,553 subjects (45.3% of study population) were exposed to at least one of the drugs/classes of the 27 pairs. Overall, pDDIs occurred 2,465,819 times. The highest rates of concomitant prescription and of co-prescription were for ACE inhibitors+NSAIDs (6,253 and 4,621/100,000 plan participants). Considering concomitance, the male/female ratio was <1 in 17/27 pairs (from 0.31 for NSAIDs-ASA+SSRI to 0.74 for omeprazole+clopidogrel). The mean age was lowest for methotrexate pairs (+omeprazole, 59.9 years; +NSAIDs-ASA, 59.1 years) and highest for digoxin+verapamil (75.4 years). In 13/27 pairs, the mean ages were ≥70 years. On average, subjects involved in pDDIs received ≥10 drugs. The odds of exposure were more frequently higher for age ≥65 years, males, and those taking a large number of drugs. A substantial number of clinically important pDDIs were observed, particularly among warfarin users. Awareness of the most prevalent pDDIs could help practitioners in preventing concomitant use, resulting in a better quality of drug prescription and potentially avoiding unwanted side effects.

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.