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Background: The present paper aims at evaluating the potential benefits of high-energy devices (HEDs) in the Italian surgical practice, defining the comparative efficacy and safety profiles, as well as the potential economic and organizational advantages for hospitals and patients, with respect to standard monopolar or bipolar devices., Methods: A Health Technology Assessment was conducted in 2021 assuming the hospital perspective, comparing HEDs and standard monopolar/bipolar devices, within eleven surgical settings: appendectomy, hepatic resections, colorectal resections, cholecystectomy, splenectomy, hemorrhoidectomy, thyroidectomy, esophago-gastrectomy, breast surgery, adrenalectomy, and pancreatectomy. The nine EUnetHTA Core Model dimensions were deployed considering a multi-methods approach. Both qualitative and quantitative methods were used: (1) a systematic literature review for the definition of the comparative efficacy and safety data; (2) administration of qualitative questionnaires, completed by 23 healthcare professionals (according to 7-item Likert scale, ranging from - 3 to + 3); and (3) health-economics tools, useful for the economic evaluation of the clinical pathway and budget impact analysis, and for the definition of the organizational and accessibility advantages, in terms of time or procedures' savings., Results: The literature declared a decrease in operating time and length of stay in using HEDs in most surgical settings. While HEDs would lead to a marginal investment for the conduction of 178,619 surgeries on annual basis, their routinely implementation would generate significant organizational savings. A decrease equal to - 5.25/-9.02% of operating room time and to - 5.03/-30.73% of length of stay emerged. An advantage in accessibility to surgery could be hypothesized in a 9% of increase, due to the gaining in operatory slots. Professionals' perceptions crystallized and confirmed literature evidence, declaring a better safety and effectiveness profile. An improvement in both patients and caregivers' quality-of-life emerged., Conclusions: The results have demonstrated the strategic relevance related to HEDs introduction, their economic sustainability, and feasibility, as well as the potentialities in process improvement., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Telerehabilitation systems represent a promising way for the management of chronic disability, delivering technology-enabled rehabilitation outside the hospital setting. However, usability and acceptability assessment with users represents a critical starting point when using digital healthcare solutions. This study aims at evaluating the user experience with a Telerehabilitation system (SIDERA ∧ B) from the end-user side., Methods: SIDERA ∧ B consists of an asynchronous delivery of rehabilitation activities through multimedia digital contents and tele-monitoring of vital parameters with technological devices for individualized, home-based management of chronic conditions. Usability (with the System Usability Scale, SUS) and acceptability (using the Technology Acceptance Model, TAM - and The Service User Technology Acceptance Questionnaire, SUTAQ) data were analyzed from the dataset of the SIDERA ∧ B project ( N = 112 patients with Chronic Heart Failure, Parkinson's Disease and Chronic Obstructive Pulmonary Disease). The possible influence of five external factors (i.e., technological expertise, education, sex, age, and level of disability) on TAM domains was tested using Spearman's Correlation analysis., Results: Results showed a satisfactory level of technological usability (SUS Median = 77.5) and good scores in usability and learnability SUS subdomains (mean scores > 2.5). Regarding technological acceptability, participants showed high scores (Median > 4) in "Behavioral Intention", "Perceived Usefulness", and "Perceived Ease of Use" TAM domains. Finally, results from the SUTAQ scale highlighted that the SIDERA ∧ B system obtained optimal scores in all domains, especially in "Increased accessibility," "Care personnel concerns," and "Satisfaction." Age (rho = -0.291, p = 0.002) and disability level (WHODAS Total score: rho = -0.218, p = 0.021) were the two external factors inversely associated with the Perceived Ease of Use., Discussion: The age of digital transformation requires everyone to understand, accept and master the changes affecting modern-day healthcare. The usability and acceptability of the SIDERA ∧ B system were high across all end-users, despite the medium-low level of the technological expertise of the sample. These findings support the efficiency and the suitability of these digital solutions in the modern digital age transition of rehabilitation from inside to outside the clinic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rossetto, Borgnis, Isernia, Foglia, Garagiola, Realdon and Baglio.)

The present study aims at defining the economic and organizational impacts of the introduction of chimeric antigen receptor T-cell therapy (CAR-T) in Italy, for the management of diffuse large B-cell lymphoma (DLBCL) patients in third-line therapy, defining the overall level of sustainability for both hospitals and the National Healthcare System (NHS). The analysis focused on CAR-T and Best Salvage Care (in the following BSC), assuming the Italian hospital and NHS perspectives, over a 36-month time horizon. Process mapping and activity-based costing methodologies were applied to collect the hospital costs related to the BSC and CAR-T pathways, including adverse event management. Anonymous administrative data on services provided (diagnostic and laboratory examinations, hospitalizations, outpatient procedures, and therapies) to 47 third-line patients with lymphoma, as well as any organizational investments required, were collected, in two different Italian Hospitals. The economic results showed that the BSC clinical pathway required less resources in comparison with CAR-T (excluding the cost related to the therapy) (BSC: 29,558.41 vs. CAR-T: EUR 71,220.84, -58.5%). The budget impact analysis depicts that the introduction of CAR-T would generate an increase in costs ranging from 15% to 23%, without considering treatment costs. The assessment of the organizational impact reveals that the introduction of CAR-T therapy would require additional investments equal to a minimum of EUR 15,500 to a maximum of EUR 100,897.49, from the hospital perspective. Results show new economic evidence for healthcare decision makers, to optimize the appropriateness of resource allocation. The present analysis suggests the need to introduce a specific reimbursement tariff, both at the hospital and at NHS levels, since no consensus exists, at least in the Italian setting, concerning the proper remuneration for the hospitals who guarantee this innovative pathway, assuming high risks related to timely management of adverse events.

Objectives: The study aims to define the economic resources needed to manage chronic rhinosinusitis with nasal polyposis (CRSwNP), assuming the hospital perspective, based on different patient characteristics, within a 24-month time horizon., Methods: Real-world data were collected in 3 Italian hospitals. A time-driven activity-based costing approach was implemented to map and assess the pathways for CRSwNP. The following drivers were considered: diagnostic services, drugs, consumables, human resources, equipment and overhead costs based on the length of stay. Costs related to management of comorbidities and adverse events were evaluated. Three main groups of patients were identified: ineligible for surgery; having 1 intervention; having more than 1 intervention. The economic absorption of patients who continued corticosteroid treatment was analysed., Results: Patients experiencing 1 intervention had a cost of 3,453.31 € that increased to 4,705.03 € for those who required additional surgery. The cost of intranasal corticosteroids was 649.20 €, whereas the cost of oral corticosteroids was 37.60 € per patient., Conclusions: The results demonstrate the strategic relevance of analytical cost definitions of the clinical pathway for CRSwNP, which can help to support decision makers in the review of internal procedures and in the definition of proper reimbursement tariffs., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: This article investigates the hospital costs related to the management of COVID-19 positive patients, requiring a hospitalization (from the positivity confirmation to discharge, including rehabilitation activities)., Methods: A time-driven activity-based costing analysis, grounding on administrative and accounting flows provided by the management control, was implemented to define costs related to the hospital management of COVID-19 positive patients, according to real-word data, derived from six public Italian Hospitals, in 2020., Results: Results reported that the higher the complexity of care, the higher the hospitalization cost per day (low-complexity = €475.86; medium-complexity = €700.20; high-complexity = €1,401.65). Focusing on the entire clinical pathway, the overall resources absorption, with the inclusion of rehabilitation costs, ranged from 6,198.02€ to 32,141.20€, dependent from the patient's clinical condition., Conclusions: Data could represent the baseline cost for COVID-19 hospital management, thus being useful for the further development of proper reimbursement tariffs devoted to hospitalized infected patients., (© 2022. The Author(s).)

(1) Background: Patent foramen ovale (PFO) is a congenital abnormality present in up to 25% of the general population, and it is a relevant cause of cryptogenic stroke. We applied the hospital-based HTA model (AdHopHTA) to conduct a multidimensional assessment of NobleStitch EL, an innovative suture-mediated PFO closure device. We compared it to Amplatzer PFO Occluder (APO) to provide evidence to inform technologies' governance in hospital settings. (2) Methods: For each AdHopHTA dimension we: systematically retrieved available evidence from the literature applying the PRISMA guidelines and then analyzed original clinical and cost data of a NobleStitch EL device at San Raffaele research hospital in Milan (Italy). The economic dimension was analyzed through activity-based costing and a cost analysis. We conducted semi-structured interviews with selected healthcare professionals to explore the organizational, legal, social, and ethical impact. (3) Results: A single study was included for the NobleStitch EL, with 10 for APO. Both literature data and original data showed comparable safety. Efficacy data analysis found that the PFO closure was at 89% for NobleStitch EL vs. 89-97% for APO. APO has a better impact on the budget and minor process costs. Consulted experts reported that the organizational impact of NobleStitch EL in the short and the long run as null, albeit a better impact under the social and the ethical aspects. (4) Conclusion: We suggest that there is inadequate evidence to conclude the relative efficacy of NobleStitch EL as compared to APO. Nevertheless, this report shows a good safety profile and higher costs for NobleStitch EL, with no organizational or legal impact. Further studies in selected population are recommended.

Background and Aims: INTERCheckWEB is one of the most outstanding digital technologies, that could be implemented at the hospital level, supporting the clinicians in the evaluation of the therapy appropriateness, reducing the potentially inappropriate prescriptions, for the improvement of the clinical decision-making process. The paper aims at investigating the relationship between clinicians' behaviors towards digital decision support system in therapy appropriateness for elderly patients in polytherapy in medical departments, defining the factors that could influence clinicians to use INTERCheckWEB, for supporting drugs' prescription., Methods: A questionnaire was administered to 70 clinicians referring to Internal Medicine wards, of four Italian hospitals. The authors assessed how perceived usefulness, perceived ease of use, image, and output quality, would affect INTERCheckWeb intention to use. Inferential statistics, by means of a regression analysis, were conducted to define the main aspects useful to understand the factors impacting on such digital technology adoption in clinical practice., Results: The regression analysis reported that image, perceived ease of use and perceived usefulness, as well as the moderator effect of the voluntary use between the perceived usefulness and the intention to use, are the factors that most influence the use of INTERCheckWEB (adjusted R 2  = 0.870)., Conclusions: Results demonstrated that clinicians would use INTERCheckWEB, when available, to identify all the information on situations that could be dangerous for the patients, thus limiting the drug-drug interactions, optimizing the overall patient's clinical pathway. Furthermore, the implementation of INTERCheckWEB could also contribute to the proper management of COVID-19 patients, since both hospitalized and symptomatic COVID-19 patients are frequently older, with comorbidities., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Introduction: The study aims to assess the implications of using a specific checklist in the production and review of care pathways. Care pathways have been developed to plan and standardize clinical practice, although the way they are designed remains unclear., Methods: This study was implemented through a Health Technology Assessment model, assuming the hospital perspective. The checklist consists of 7 different domains, subdivided into 14 subdomains and 77 items., Results: After a prioritization phase, our analysis reported a better performance of the checklist in terms of safety [2.00 vs -0.04; p<0.001], effectiveness [1.33 vs 0.00; p<0.001], social and ethical impact [1.15 vs 0.33; p<0.001], and legal perception from healthcare professionals [1.23 vs 0.25; p<0.001]. The Cost-Effectiveness Analysis and Budget Impact Analysis showed an advantage of the checklist (5.75% annual economic saving)., Conclusions: A dedicated checklist may lead to potential benefits in terms of quality of care pathway processes.

Peripheral Venous Catheter (PVC) is a widely used device in the hospital setting and is often associated with significant adverse events that may impair treatment administration and patient health. The aim of the present study is to define the incremental benefits related to the implementation and the standardized and simultaneous use of three disposable devices for skin antisepsis, infusion, and cleaning, assuming the hospital's point of view, from an effectiveness, efficiency, and organizational perspective. For the achievement of the above objective, real-life data were collected by means of an observational prospective study, involving two hospitals in the Liguria Region (Northern Italy). Consecutive cases were enrolled and placed into two different scenarios: 1) use of all the three disposable devices, thus representing the scenario related to the implementation of a standardized optimal procedure (Scenario 1); 2) use of only one or two disposable devices, representing the scenario related to not being in a standardized optimal procedure (Scenario 2). For the definition of effectiveness indicators, the reason for PVC removal and the PVC-related adverse events occurrence were collected for each patient enrolled. In addition, an activity-based costing analysis grounded on a process-mapping technique was conducted to define the overall economic absorption sustained by hospitals when taking in charge patients requiring a PVC. Among the 380 patients enrolled in the study, 18% were treated with the standardized optimal procedure (Scenario 1). The two Scenarios differed in terms of number of patients for whom the PCV was removed due to the end of therapy (86.8% versus 39.40%, p-value = 0.000), with a consequent decrease in the adverse events occurrence rate. The economic evaluation demonstrated the sustainability and feasibility of implementing the standardized optimal procedure specifically related to the need for lower economic resources for the hospital management of adverse events occurred (€19.60 versus €21.71, p-value = 0.0019). An organizational advantage also emerged concerning an overall lower time to execute all the PVC-related activities (4.39 versus 5.72 minutes, p-value = 0.00). Results demonstrate the feasibility in the adoption of the standardized optimal procedure for PVC management, with significant advantages not only from a clinical point of view, but also from an organizational and economic perspective, thus being able to increase the overall operational efficiency of the hospitals., Competing Interests: The authors have declared that no competing interests exist.

Objective: To systematically examine the effect of dehydration on health outcomes, identify associated financial costs and consider impacts on cognitive performance in older adults., Design: A systematic review of English-language articles via OVID using MEDLINE, PsychINFO, EMBASE, and others, to March 2018. Included studies examined the relationship between hydration status and health, care costs or cognitive outcome., Setting: Cross sectional and cohort data from studies reporting on dehydration in older adults., Participants: Adults aged 60 years and older., Measurements: Independent quality ratings were assessed for all extracted articles., Results: Of 1684 articles screened, 18 papers (N = 33,707) met inclusion criteria. Participants were recruited from hospital settings, medical long-term care centres and the community dwelling population. Data were synthesised using a narrative summary. Mortality rates were higher in dehydrated patients. Furthermore, health outcomes, including frailty, bradyarrhythmia, transient ischemic attacks, oral health and surgery recovery are linked to and worsened by dehydration. Length of hospital stay, either as a principal or secondary diagnosis, is greater in those with dehydration, compared to those who are euhydrated. Finally, neurocognitive functioning may be impacted by dehydration. There are issues with study design, inconsistency in hydration status measurement and different measures used for outcome assessment., Conclusion: Dehydration in older people is associated with increased mortality, poorer course of illness and increased costs for health services. In addition, there is some, but sparse evidence that dehydration in older people is linked to poorer cognitive performance. Intervention studies should test strategies for reducing dehydration in older adults., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Context: Parent/family presence at pediatric resuscitations has been slow to become consistent practice in hospital settings and has not been universally implemented. A systematic review of the literature on family presence during pediatric and neonatal resuscitation has not been previously conducted., Objective: To conduct a systematic review of the published evidence related to family presence during pediatric and neonatal resuscitation., Data Sources: Six major bibliographic databases was undertaken with defined search terms and including literature up to June 14, 2020., Study Selection: 3200 titles were retrieved in the initial search; 36 ultimately included for review., Data Extraction: Data was double extracted independently by two reviewers and confirmed with the review team. All eligible studies were either survey or interview-based and as such we turned to narrative systematic review methodology., Results: The authors identified two key sets of findings: first, parents/family members want to be offered the option to be present for their child's resuscitation. Secondly, health care provider attitudes varied widely (ranging from 15% to >85%), however, support for family presence increased with previous experience and level of seniority., Limitations: English language only; lack of randomized control trials; quality of the publications., Conclusions: Parents wish to be offered the opportunity to be present but opinions and perspectives on the family presence vary greatly among health care providers. This topic urgently needs high quality, comparative research to measure the actual impact of family presence on patient, family and staff outcomes., Prospero Registration Number: CRD42020140363., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Intubations are frequently performed procedures in neonatal intensive care units (NICU) and delivery rooms (DR). Unsuccessful first attempts are common as are tracheal intubation-associated events (TIAEs) and severe desaturations. Stylets are often used during intubation, but their association with intubation outcomes is unclear., Objective: To compare intubation success, rate of relevant TIAEs, and severe desaturations in neonates intubated with and without stylets., Methods: Tracheal intubations of neonates in the NICU or DR from 16 centers between October 2014 and December 2018, performed by neonatology or pediatric providers, were collected from the NEAR4NEOs international registry. Primary oral intubations with a laryngoscope were included in the analysis. First-attempt success, the occurrence of relevant TIAEs, and severe oxygen desaturation (≥20% saturation drop from baseline) were compared between intubations performed with versus without a stylet. Logistic regression with generalized estimate equations was used to control for covariates and clustering by sites., Results: Out of 5,292 primary oral intubations, 3,877 (73%) utilized stylets. Stylet use varied considerably across the centers with a range between 0.5 and 100%. Stylet use was not associated with first-attempt intubation success, esophageal intubation, mainstem intubation, or severe desaturations after controlling for confounders. Patient size was associated with these outcomes and much more predictive of success., Conclusions: Stylet use during neonatal intubation was not associated with higher first-attempt intubation success, fewer relevant TIAEs, or less severe desaturations. These data suggest that stylets can be used based on individual preference, but stylet use may not be associated with better intubation outcomes., (© 2021 S. Karger AG, Basel.)

Introduction: Neonatal tracheal intubation (TI) outcomes have been assessed by role, but training level may impact TI success and safety. Effect of physician training level (PTL) on the first-attempt success, adverse TI-associated events (TIAEs), and oxygen desaturation was assessed., Methods: Prospective cohort study in 11 international NEAR4NEOS sites between October 2014 and December 2017. Primary TIs performed by pediatric/neonatal physicians were included. Univariable analysis evaluated association between PTL, patient/practice characteristics, and outcomes. Multivariable analysis with generalized estimating equation assessed for independent association between PTL and outcomes (first-attempt success, TIAEs, and oxygen desaturation ≥20%; attending as reference)., Results: Of 2,608 primary TIs, 1,298 were first attempted by pediatric/neonatal physicians. PTL was associated with patient age, weight, comorbidities, TI indication, difficult airway history, premedication, and device. First-attempt success rate differed across PTL (resident 23%, fellow 53%, and attending 60%; p < 0.001). There was no statistically significant difference in TIAEs (resident 22%, fellow 20%, and attending 25%; p = 0.34). Desaturation occurred more frequently with residents (60%), compared to fellows and attendings (46 and 53%; p < 0.001). In multivariable analysis, adjusted odds ratio of the first-attempt success was 0.18 (95% CI: 0.11-0.30) for residents and 0.80 (95% CI: 0.51-1.24) for fellows. PTL was not independently associated with adjusted odds of TIAEs or severe oxygen desaturation., Conclusion: Higher PTL was associated with increased first-attempt success but not TIAE/oxygen desaturation. Identifying strategies to decrease adverse events during neonatal TI remains critical., (© 2021 S. Karger AG, Basel.)

The aim of this study is to analyze the potential advantages of emtricitabine/tenofovir alafenamide (FTC/TAF) introduction, creating evidence-based information to orient strategies to reduce costs, thus preserving effectiveness and appropriateness. An Health Technology Assessment (HTA) was implemented in the years 2017-2018 comparing the dual backbones available in the Italian market: FTC/TAF, FTC/TDF (tenofovir disoproxil fumarate/emtricitabine) and ABC/3TC (abacavir/lamivudine). From an efficacy point of view, FTC/TAF ensured a higher percentage of virologic control and a better safety impact than FTC/TDF (improving the renal and bone safety profile, as well as the lipid picture). From an economic point of view, the results revealed a 4% cost saving for the Italian National Healthcare Service NHS with FTC/TAF introduction compared with the baseline scenario. Qualitative perceptions' results showed that FTC/TAF would decrease the burden of adverse events management, increasing the accessibility of patients to healthcare providers (FTC/TAF: 0.95, FTC/TDF: 0.10, ABC/3TC: 0.28; p -value: 0.016) and social costs (FTC/TDF: -0.23, FTC/TAF: 1.04, ABC/3TC: 0.23; p -value < 0.001), improving patient quality of life (FTC/TDF: 0.31, FTC/TAF: 1.85, ABC/3TC: 0.38; p -value < 0.001). Healthcare services may consider the evidence provided by the present study as an opportunity to include HIV patients in a more adequate antiretroviral treatment arm, guaranteeing a personalized clinical pathway, thus becoming more efficient and effective over time., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Introduction: The use of oral tenofovir/emtricitabine (FTC/TDF) for pre-exposure prophylaxis (PrEP) among high-risk people without Human Immunodeficiency Virus (HIV), is emerging as an innovative strategy to decrease HIV epidemic. The study aims at evaluating the implications related to PrEP introduction, from a multidimensional point of view, as required by Health Technology Assessment (HTA) approach, with a particular attention on sustainability and social factors, influencing PrEP implementation., Methods: An analysis was conducted involving 35 Italian Infectious Disease Departments. The introduction of PrEP (applied both as "add-on" and "substitute" prevention strategy) into the clinical practice was compared with a baseline scenario, consisting of condoms among men who have sex with men, and serodiscordant couples, and the use of Needle Syringe Programme among injection drugs users The above scenarios were analysed by means of a Health Technology Assessment (HTA) approach. The 9 EUnetHTA Core Model domains were assessed through comparative information, retrieved from literature evidence, and collection of qualitative and quantitative information, derived from real-world evidence, in particular from 35 Infectious Disease Departments and potential PrEP' users involved. A final multi-criteria decision analysis approach (MCDA) was implemented to simulate the appraisal phase and providing evidence-based information with regard to the preferable technology., Results: Despite the improvement in patients' quality of life, PrEP would generate the development of other sexually transmitted and blood-borne diseases, with a consequent decrease of patients' safety in case of PrEP applied as a "substitute" prevention strategy. In addition, PrEP would generate an increase in staff workflow, with investment in medical supplies and training courses. PrEP would lead to significant economic investments both for the NHS (+40%), and for citizens (+2,377%) if used as an add-on strategy, assuming FTC/TDF patent cost. With the off-patent drug, the NHS would benefit from an advantage (37%), and a shrink of the patients' expenditure emerged (+682%). More economic resources are required if PrEP is applied as a substitute strategy, considering both the patent (NHS: 212%; citizens: 3,423%) and the off-patent drug (NHS: 73%; citizens: 1,077%). Conclusions. The most cost-containing strategy would be the use of PrEP, as an add-on strategy, with a consequent improvement in patients' safety, even if drug-related adverse events would be considered. The implementation of the off-patent drug would decrease the economic burden of the innovative prevention strategy. Hence, the organizational aspects related to its adoption would be deeply investigated, with the potential opportunity to create specific ambulatories devoted to PrEP users' especially for medium and big size hospitals., (©2020 Pacini Editore SRL, Pisa, Italy.)

Background: Since HIV+ treatment has become more effective, the average age of people living with HIV (PLWHIV) has increased, and consequently the incidence of developing comorbidities, making the clinical and economic management of HIV+ patients more complex. Limited literature exists regarding the management of comorbidities costs. This study is aimed at defining and comparing the total annual costs of comorbidities, in an Italian cohort of HIV and HIV/HCV patients, from the National Healthcare Service perspective. The authors hypothesised that there are higher costs, for patients with multiple comorbidities, and a greater consumption of resources for HIV/HCV co-infected patients versus HIV mono-infected patients., Methods: An observational retrospective multi-centre health-economics study, enrolling HIV+ and HIV/HCV consecutive patients with at least one comorbidity, was conducted. The consecutive cases, provided by three Italian infectious diseases centres, were related to the year 2016. The enrolled patients were on a stable antiviral therapy for at least six months. Demographic and clinical information was recorded. Costs related to HIV and HCV therapies, other treatments, medical examinations, hospitalizations and outpatient visits were evaluated. Data from mono-infected and co-infected groups of patients were compared, and the statistical analysis was performed by t-tests, chi-square and ANOVA. A sub-analysis excluding HCV therapy costs, was also conducted. The hierarchical sequential linear regression model was used to explore the determinants of costs, considering the investigated comorbidities. All analyses were conducted with a significant level of 0.05., Results: A total of 676 patients, 82% male, mean age 52, were identified and divided into groups (338 mono-infected HIV+ and 338 co-infected HIV/HCV patients), comparable in terms of age, gender, and demographic characteristics. A trend towards higher annual costs, for patients with multiple comorbidities was observed in HIV mono-infected patients (respectively € 8272.18 for patients without comorbidities and € 12,532.49 for patients with three or more comorbidities, p-value: 0.001). Excluding anti-HCV therapies costs, HIV/HCV co-infected patients generally required more resources, with statistically significant differences related to cardiovascular events (€10,116.58 vs €11,004.28, p-value: 0.001), and neurocognitive impairments events (€7706.43 vs €11,641.29 p- value: < 0.001)., Conclusions: This study provides a differentiated and comprehensive analysis of the healthcare resources needed by HIV and HIV/HCV patients with comorbidities and may contribute to the decision process of resources allocation, in the clinical management of different HIV+ patient populations.

Background: The number of patients undergoing joint arthroplasty is increasing worldwide. An Enhanced Recovery After Surgery (ERAS) pathway for hip and knee arthroplasty was introduced in an Italian high-volume research hospital in March 2018., Methods: The aim of this mixed methods observational study is to perform a health technology assessment (HTA) of the ERAS pathway, considering 938 procedures performed after its implementation, by means of a hospital-based approach derived from the EUnetHTA (European Network for Health Technology Assessment) Core Model. The assessment process is based on dimensions of general relevance, safety, efficacy, effectiveness, economic and financial impact, equity, legal aspects, social and ethical impact, and organizational impact. A narrative review of the literature helped to identify general relevance, safety and efficacy factors, and a set of relevant sub-dimensions submitted to the evaluation of the professionals who use the technology through a 7-item Likert Scale. The economic and financial impact of the ERAS pathway on the hospital budget was supported by quantitative data collected from internal or national registries, employing economic modelling strategies to identify the amount of resources required to implement it., Results: The relevance of technology under assessment is recognized worldwide. A number of studies show accelerated pathways to dominate conventional approaches on pain reduction, functional recovery, prevention of complications, improvements in tolerability and quality of life, including fragile or vulnerable patients. Qualitative surveys on clinical and functional outcomes confirm most of these benefits. The ERAS pathway is associated with a reduced length of stay in comparison with the Italian hospitalization average for the same procedures, despite the poor spread of the pathway within the country may generate postcode inequalities. The economic analyses show how the resources invested in training activities are largely depreciated by benefits once the technology is permanently introduced, which may generate hospital cost savings of up to 2054,123.44 € per year., Conclusions: Galeazzi Hospital's ERAS pathway for hip and knee arthroplasty results preferable to traditional approaches following most of the HTA dimensions, and offers room for further improvement. The more comparable practices are shared, the before this potential improvement can be identified and addressed.

A cross-sectional study was carried out to determine foot-and-mouth disease (FMD) seroprevalence and identify risk factors of exposure among cattle herds raised in three zones with different types of land use and progressively distant from the Maasai Mara National Reserve (MMNR) boundary. We selected five villages purposively; two in zone 1 (area < 20 km from the MMNR), another two in zone 2 (area between 20-40 km away from the MMNR) and one in zone 3 (area >40 km away from the MMNR). A total of 1170 cattle sera were collected from 390 herds in all the zones and tested for antibodies against the non-structural proteins (NSPs) of FMD virus (FMDV) using two 3ABC-based Enzyme-Linked Immunosorbent Assay ELISA kits. All sera samples were also screened for serotype-specific antibodies using Solid Phase Competitive ELISA (SPCE) kits (IZSLER, Italy). We targeted FMDV serotypes A, O, South African Territory [SAT] 1 and SAT 2, known to be endemic in East Africa including Kenya. Data on putative risk factors for FMD seropositivity in cattle were collected using a questionnaire. The overall apparent animal-level FMD seroprevalence based on the parallel comparison of the two anti-NSPs ELISA kits was 83.8 % (95 % CI; 81.8-85.9), and differed significantly across zones. Zone 1 had a higher seroprevalence than zones 2 and 3 (χ 2  = 116.1, df = 2, p < 0.001). In decreasing order, the overall seroprevalences of FMDV serotypes A, SAT 2, O and SAT 1 were 26.3 % (95 % CI; 23.5-29.2), 21.4 % (95 % CI; 18.8-24.0), 21.2 % (95 % CI; 18.7-23.9) and 13.1 % (95 % CI; 11.1-15.3), respectively. The distribution of these serotypes differed significantly between zones (p < 0.05) except for SAT 2 serotype (χ 2  = 0.90, df = 2, p = 0.639). Both serotypes A and O were more prevalent in zones 1 and 2 than zone 3 while serotype SAT 1, was higher in zone 3 compared to other zones. The results of multivariable analyses identified animal sex (i.e., female), raising of cattle in zones 1 and 2 (areas < 40 km away from the MMNR); mixing of cattle from multiple herds at watering points, and pastoral husbandry practices, as significant predictors of animal-level FMD seropositivity. This study established that FMD seroprevalence declined with distance from the MMNR., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Hospital wards are required to exploit current knowledge and explore for new knowledge. Ambidexterity (i.e., the capability to combine both exploitation and exploration) is a major issue in healthcare as result of the growing expectations that hospitals wards have the capability to manage the trade-off between high-quality delivery of care and cost-containment. This study sheds novel light on the determinants of ambidextrous behaviours in hospital wards., Methods: A theoretical framework has been built on the extant literature. The main determinants of ambidexterity are opening/closing leadership, organisational support, organisational creativity and environmental dynamism. The model has been tested empirically through data collected via survey administered to head physicians in charge of hospital wards. After the quality check, 80 questionnaires were available for the statistical analysis based on a hierarchical sequential linear regression model (with enter methodology)., Results: Results showed that opening (β = 0.389;p < 0.001) and closing (β = 0.288;p < 0.01) leadership, as well as organisational creativity (β = 0.499 p < 0.001) are necessary to materialize ambidextrous behaviours (Adj.R² = 0.529). Environmental dynamism does not moderate these relationships. While opening leadership (β = 0.375;p < 0.01), organisational creativity (β = 0.270;p < 0.05) and environmental dynamism (β = 0.224;p < 0.1) are determinants of exploration, closing leadership (β = 0.506;p < 0.001) and organisational creativity (β = 0.529;p < 0.001) are determinants of exploitation., Conclusions: Head physicians' leadership style as well as organizational creativity play a pivotal role in materializing ambidextrous behaviours in wards., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Hospitalized children with underlying heart disease are at high risk for cardiac arrest, particularly when they undergo invasive catheterization procedures for diagnostic and therapeutic interventions. Outcomes for children experiencing cardiac arrest in the cardiac catheterization laboratory remain under-reported with few studies reporting survival beyond the catheterization laboratory. We aim to describe survival outcomes after cardiac arrest in the cardiac catheterization laboratory while identifying risk factors associated with hospital mortality after these events., Design: Retrospective observational study of data from a multicenter cardiac arrest registry from November 2005 to November 2016. Cardiac arrest in the cardiac catheterization laboratory was defined as the need for chest compressions greater than or equal to 1 minute in the cardiac catheterization laboratory. Primary outcome was survival to discharge. Variables analyzed using generalized estimating equations for association with survival included age, illness category (surgical cardiac, medical cardiac), preexisting conditions, pharmacologic interventions, and event duration., Setting: American Heart Association's Get With the Guidelines-Resuscitation registry of in-hospital cardiac arrest., Patients: Consecutive patients less than 18 years old experiencing an index (i.e., first) cardiac arrest event reported to the Get With the Guidelines-Resuscitation., Interventions: None., Measurements and Main Results: A total of 203 patients met definition of index cardiac arrest in the cardiac catheterization laboratory composed primarily of surgical and medical cardiac patients (54% and 41%, respectively). Children less than 1 year old comprised the majority of patients, 58% (117/203). Overall survival to hospital discharge was 69% (141/203). No differences in survival were observed between surgical and medical cardiac patients (p = 0.15). The majority of deaths (69%, 43/62) occurred in patients less than 1 year old. Bradycardia (with pulse) followed by pulseless electrical activity/asystole were the most common first documented rhythms observed (50% and 27%, respectively). Preexisting metabolic/electrolyte abnormalities (p = 0.02), need for vasoactive infusions (p = 0.03) prior to arrest, and use of calcium products (p = 0.005) were found to be significantly associated with lower rates of survival to discharge on multivariable regression., Conclusions: The majority of children experiencing cardiac arrest in the cardiac catheterization laboratory in this large multicenter registry analysis survived to hospital discharge, with no observable difference in outcomes between surgical and medical cardiac patients. Future investigations that focus on stratifying medical complexity in addition to procedural characteristics at the time of catheterization are needed to better identify risks for mortality after cardiac arrest in the cardiac catheterization laboratory.

Purpose: To investigate the implications of the introduction of two hormonal therapies, abiraterone acetate + prednisone (AA+P) and enzalutamide (ENZA), for the treatment of naïve patients with metastatic castration-resistant prostate cancer (mCRPC) in the Italian setting. Methods: In 2017-2018, a Health Technology Assessment was conducted in Italy, considering the National Healthcare Service (NHS) perspective. Data were retrieved from literature evidence, economic evaluations, and qualitative questionnaires, considering the 9 EUnetHTA dimensions, and a final multi-criteria approach. Results: On the basis of mCRPC prevalence and incidence rates in Italy, the analysis considered 11,212 males eligible to either AA+P or ENZA treatments. Both drugs led to an improvement of the patients' overall survival, with respect to the standard of care, composed of docetaxel chemotherapy. However, AA+P showed a higher rate of drug-related moderate adverse events and a monitoring activities incidence superior to ENZA (+70%, p -value=0.00), which led to a major resources absorption (€ 1,056.02 vs € 316.25, p -value=0.00), whereas ENZA showed a better cost-effectiveness average value (CEV: 54,586.12 vs 57,624.15). Economic savings ranging from 1.46% to 1.61% emerged for the NHS, as well as organizational advantages, with fewer minutes required for the mCRPC management (AA+P: 815 mins vs ENZA: 500 mins). According to experts' perceptions, based on a 7-item Likert scale (ranging from -3 to +3), similar results emerged on ethical and social impact (ENZA: 1.35 vs AA+P: 1.48, p -value>0.05), and on legal dimension (ENZA: 0.67 vs AA+P: 0.67, p -value>0.05), since both drugs improved the patients' quality of life and received approval for use. High-level perceptions related to ENZA adoption emerged with regard to equity (ENZA: 0.69 vs AA+P: 0.25, p -value<0.05), since it is cortisone-free. Multi-criteria approach analysis highlighted a higher score of ENZA than comparator (0.79 vs 0.60, p -value=0.00). Conclusion: The evidence-based information underlined the advantages of ENZA and AA+P treatments as therapeutic options for mCRPC patients. In the appraisal phase, the higher score than the comparator suggested ENZA as the preferred treatment for mCRPC., Competing Interests: The authors report no conflicts of interest in this work.

Objective: To develop a risk-scoring tool to predict multidrug-resistant (MDR) etiology in patients with bloodstream infections (BSI) caused by Gram-negative bacilli (GNB)., Methods: A prospective multicenter study analyzed patients with BSI hospitalized in 31 Internal Medicine wards in Italy from March 2012 to December 2012. Patients with BSI caused by MDR-GNB (non-susceptible to at least one agent in three antimicrobial categories) were compared to those with BSI due to susceptible GNB. A logistic regression to identify predictive factors of MDR-GNB was performed and the odds ratio (OR) were calculated. A score to predict the risk of MDR was developed., Results: Of 533 BSI episodes, 253 (47.5%) were caused by GNB. Among GNB-BSI, 122 (48.2%) were caused by MDR-GNB while 131 (51.8%) by non-MDR GNB. At multivariate analysis transfer from long-term care facility (OR 9.013, 95% CI 1.089-74.579, p = 0.041), hospitalization in the last 3 months (OR 2.882, 95% CI 1.580-5.259, p = 0.001), urinary catheter (OR 2.315, 95% CI 1.202-4.459, p = 0.012), antibiotic therapy in the last 3 months (OR 1.882, 95% CI 1.041-3.405, p = 0.036), age ≥ 75 years (OR 1.866, 95% CI 1.076-3.237, p = 0.026) were factors independently associated with MDR etiology. A score ranging from 0 to 10 was useful to recognize patients at lowest risk (0 points: Negative Likelihood Ratio 0.10) and those at highest risk (>6 points, Positive Likelihood Ratio 11.8) of GNB bacteremia due to a MDR strain., Conclusions: Specific predictors of MDR etiology are useful to calculate probabilities of MDR etiology among hospitalized patients with blood cultures positive for GNB., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of the present study was to compare 2 clinical assessment tools, the Modified Barthel Index (currently administered to patients admitted into inpatient rehabilitation units after elective hip or knee arthroplasty) with the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 scale, in order to identify which tool is more suitable for assessing the disability and the "recovery rate"., Patients and Methods: A perspective multicenter observational study was developed, involving 2 hospital authorities in Italy. Eighty consecutive cases of inpatients were enrolled. Patient's disability was evaluated using both of the aforementioned tools, before and after the rehabilitation program., Results: The WHODAS 2.0 score was, on average, 12.21% higher than the Modified Barthel Index, before the surgical intervention. Modified Barthel Index measures could be considered as a determinant and a predictor of length of stay., Conclusion: The Modified Barthel Index is limited, since it does not consider a patient's perspective. The WHODAS 2.0 scale fully considers a patient's perception of disability. Therefore, both assessment scales should be administered in clinical practice, in order to provide integration of clinical information with a patient's reported outcome measures., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Three-dimensional view in laparoscopic general, gynaecologic and urologic surgery is an efficient, safe and sustainable innovation. The present paper is an extract taken from a full health technology assessment report on three-dimensional vision technology compared with standard two-dimensional laparoscopic systems., Methods: A health technology assessment approach was implemented in order to investigate all the economic, social, ethical and organisational implications related to the adoption of the innovative three-dimensional view. With the support of a multi-disciplinary team, composed of eight experts working in Italian hospitals and Universities, qualitative and quantitative data were collected, by means of literature evidence, validated questionnaire and self-reported interviews, applying a final MCDA quantitative approach, and considering the dimensions resulting from the EUnetHTA Core Model., Results: From systematic search of literature, we retrieved the following studies: 9 on general surgery, 35 on gynaecology and urology, both concerning clinical setting. Considering simulated setting we included: 8 studies regarding pitfalls and drawbacks, 44 on teaching, 12 on surgeons' confidence and comfort and 34 on surgeons' performances. Three-dimensional laparoscopy was shown to have advantages for both the patients and the surgeons, and is confirmed to be a safe, efficacious and sustainable vision technology., Conclusions: The objective of the present paper, under the patronage of Italian Society of Endoscopic Surgery, was achieved in that there has now been produced a scientific report, based on a HTA approach, that may be placed in the hands of surgeons and used to support the decision-making process of the health providers.

Purpose: Diabetic macular edema (DME) is a leading cause of vision loss and blindness. The aim of this study was to evaluate the economic benefits of introducing additional alternative technologies (Dexamethasone intravitreal implant - DEX - and Aflibercept injections), compared with the historical scenario of Ranibizumab intravitreal injections., Methods: A 3-year budget impact model was developed, taking into consideration the perspective of the Lombardy Region Healthcare Service (LRHS). Total administration costs (real-life data retrieved from clinical practice at three Departments of Ophthalmology) as well as costs related to the management of potential adverse events (information collected from the literature) were analysed., Results: Over a 36-month horizon, the results showed that a higher consumption of DEX could lead to significant economic savings for the Regional Healthcare Service, ranging from a minimum of -4.35% (if DEX were used only in the second-line of treatment) to a maximum of -12.97% (if DEX were used in both the first-line and second-line), including the potential impact of adverse events. Therapy costs with Aflibercept and Ranibizumab were similar., Conclusions: This study demonstrates that concentrating all eligible patients within the Ranibizumab regimen is unlikely to represent a cost-effective strategy. Indeed, significant economic advantages would be achieved by introducing the other licensed alternatives, Dexamethasone implant and Aflibercept, thus optimising DME Italian healthcare expenditure. The results demonstrate DEX as an advantageous technological alternative for the target population affected by DME, both as a first- and second-line treatment option, reducing the economic burden of the pathology for the Regional/National Health Service., (© 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

A study is presented based on the use of entirely non-destructive spectroscopic techniques to analyze the chemical composition of the painted surface layer of archaeological pottery. This study aims to define both the raw materials and the working technology of ancient potters. Energy-dispersive X-ray analysis, micro-Raman spectroscopy, visible and near infrared (NIR) diffuse reflection spectroscopy and external reflection Fourier-transform infrared (FTIR) spectroscopy were applied to matt-painted bichrome pottery sherds (VIII-VII century B.C.) from the site of Incoronata near Metaponto in southern Italy. Two different raw materials, ochre and iron-rich clay, were recognized for the red decoration, while the dark areas resulted to have been obtained by the so-called manganese black technique. In any case, it was demonstrated that the decoration was applied before firing, in spite of its sometimes grainy aspect that could suggest a post-firing application. For the samples with a more sophisticated decorative pattern a red/black/white polychromy was recognized, as the lighter areas correspond to an "intentional white" obtained by the firing of a calcium-rich clay. Reflection spectroscopy in the visible-NIR and mid-IR as well as micro-Raman spectroscopy were then employed to characterize the decoration of an intact ceramic urn from the Etruscan town of Chiusi, evidencing a post-firing painting based on the use of red ochre, carbon black and lime, possibly imitating the "fresco" technique used in wall paintings., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Lumbar arthrodesis is a common surgical technique that consists of the fixation of one or more motion segments with pedicle screws and rods. However, spinal surgery using these techniques is expensive and has a significant impact on the budgets of hospitals and Healthcare Systems. While reusable and disposable instruments for laparoscopic interventions have been studied in literature, no specific information exists regarding instrument kits for lumbar arthrodesis. The aim of the present study was to perform a complete health technology assessment comparing a disposable instrument kit for lumbar arthrodesis (innovative device) with the standard reusable instrument., Methods: A prospective and observational study was implemented, by means of investigation of administrative records of patients undergoing a lumbar arthrodesis surgical procedure. The evaluation was conducted in 2013, over a 12- month time horizon, considering all the procedures carried out using the two technologies. A complete health technology assessment and a multi-criteria decision analysis approach were implemented in order to compare the two alternative technologies. Economic impact (with the implementation of an activity based costing approach), social, ethical, organisational, and technology-related aspects were taken into account., Results: Although the cost analysis produced similar results in the comparison of the two technologies (total cost equal to € 4,279.1 and € 4,242.6 for reusable instrument kit and the disposable one respectively), a significant difference between the two instrument kits was noted, in particular concerning the organisational impact and the patient safety., Conclusions: The replacement of a reusable instrument kit for lumbar arthrodesis, with a disposable one, could improve the management of this kind of devices in hospital settings.

Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory complication of preterm birth. Preterm infants are at risk for acute lung injury immediately after birth, which predisposes to BPD. In this article, we review the current evidence for interventions applied during neonatal transition (delivery room and first postnatal hours of life) to prevent BPD in extremely preterm infants: continuous positive airway pressure (CPAP), sustained lung inflation, supplemental oxygen use during neonatal resuscitation, and surfactant therapy including less-invasive surfactant administration. Preterm infants should be stabilized with CPAP in the delivery room, reserving invasive mechanical ventilation for infants who fail non-invasive respiratory support. For infants who require endotracheal intubation and mechanical ventilation soon after birth, surfactant should be given early (<2 h of life). We recommend prudent titration of supplemental oxygen in the delivery room to achieve targeted oxygen saturations. Promising interventions that may further reduce BPD, such as sustained inflation and non-invasive surfactant administration, are currently under investigation.

Uncertainty exists whether the use of non-prescription psychoactive substances following onset of a first episode of psychosis (FEP), in particular cannabis use, affects medication adherence. Data from FEP patients (N=233) obtained through prospective assessments measured medication adherence and pattern of cannabis and other substance use in the first two years following onset of psychosis. Multiple logistic regression analyses were employed to compare the different substance use groups with regard to risk of medication non-adherence, while controlling for confounders. The proportion of non-adherent patients was higher in those who continued using high-potency forms of cannabis (skunk-like) following the onset (83%) when compared to never regular users (51%), corresponding to an Odds Ratio (OR) of 5.26[95% Confidence Interval (CI) 1.91-15.68]. No significant increases in risk were present in those who used cannabis more sporadically or used milder forms of cannabis (hash-like). Other substances did not make an independent contribution in this model, including cigarette use ([OR 0.88, 95% CI 0.41-1.89]), alcohol use ([OR 0.66, 95% CI 0.27-1.64]) or regular use of other illicit drugs ([OR 1.03, 95% CI 0.34-3.15]) following the onset. These results suggest that continued use of high-potency cannabis following the onset of psychosis may adversely affect medication adherence., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Cannabis use following the onset of first-episode psychosis has been linked to both increased risk of relapse and non-adherence with antipsychotic medication. Whether poor outcome associated with cannabis use is mediated through an adverse effect of cannabis on medication adherence is unclear., Methods: In a prospective analysis of data acquired from four different adult inpatient and outpatient units of the South London and Maudsley Mental Health National Health Service Foundation Trust in London, UK, 245 patients were followed up for 2 years from the onset of first-episode psychosis. Cannabis use after onset of psychosis was assessed by self-reports in face-to-face follow-up interviews. Relapse data were collected from clinical notes using the WHO Life Chart Schedule. This measure was also used to assess medication adherence on the basis of both face-to-face interviews and clinical notes. Patients were included if they had a diagnosis of first-episode non-organic or affective psychosis according to ICD-10 criteria, and were aged between 18 and 65 years when referred to local psychiatric services. We used structural equation modelling analysis to estimate whether medication adherence partly mediated the effects of continued cannabis use on risk of relapse. The primary outcome variable was relapse, defined as admission to a psychiatric inpatient unit after exacerbation of symptoms within 2 years of first presentation to psychiatric services. Information on cannabis use over the first 2 years after onset of psychosis was investigated as a predictor variable for relapse. Medication adherence was assessed as a mediator variable on the basis of clinical records and self-report data. Study researchers (TS, NP, EK, and EF) rated the adherence., Findings: 397 patients who presented with their first episode of psychosis between April 12, 2002, and July 26, 2013 had a follow-up assessment until September, 2015. Of the 397 patients approached for followed up, 133 refused to take part in this study and 19 could not be included because of missing data. 91 (37%) of 245 patients with first-episode psychosis had a relapse over the 2 years of follow-up. Continued cannabis use predicted poor outcome, including risk of relapse, number of relapses, length of relapse, and care intensity at follow-up. In controlled structural equation modelling analyses, medication adherence partly mediated the effect of continued cannabis use on outcome, including risk of relapse (proportion mediated=26%, β indirect effects =0·08, 95% CI 0·004 to 0·16), number of relapses (36%, β indirect effects =0·07, 0·003 to 0·14), time until relapse (28%, β indirect effects =-0·26, -0·53 to 0·001) and care intensity (20%, β indirect effects =0·06, 0·004 to 0·11) but not length of relapse (6%, β indirect effects =0·03, -0·03 to 0·09). The adjusted models explained moderate amounts of variance for outcomes defined as risk of relapse (R 2 =0·25), number of relapses (R 2 =0·21), length of relapse (R 2 =0·07), time until relapse (R 2 =0·08), and care intensity index (R 2 =0·15)., Interpretation: Between 20% and 36% of the adverse effects of continued cannabis use on outcome in psychosis might be mediated through the effects of cannabis use on medication adherence. Interventions directed at medication adherence could partly help mitigate the harm from cannabis use in psychosis., Funding: This study is funded by the National Institute of Health Research (NIHR) Clinician Scientist award., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Substance use may increase the risk of non-adherence to antipsychotics, resulting in negative outcomes in patients with psychosis., Method: We aimed to quantitatively summarize evidence regarding the effect of cannabis use, the most commonly used illicit drug amongst those with psychosis, on adherence to antipsychotic medication. Studies were identified through a systematic database search. Adopting random-effects models, pooled odds ratios (OR) for risk of non-adherence to antipsychotic medications were calculated comparing: cannabis-users at baseline v. non-users at baseline; non users v. continued cannabis users at follow-up; non-users v. former users at follow-up; former users v. current users., Results: Fifteen observational studies (n = 3678) were included. Increased risk of non-adherence was observed for cannabis users compared to non-users (OR 2.46, n = 3055). At follow-up, increased risk of non-adherence was observed for current users compared to non-users (OR 5.79, n = 175) and former users (OR 5.5, n = 192), while there was no difference between former users and non-users (OR 1.12, n = 187)., Conclusions: Cannabis use increases the risk of non-adherence and quitting cannabis use may help adherence to antipsychotics. Thus, cannabis use may represent a potential target for intervention to improve medication adherence in those with psychosis.

Purpose: Surgical-site complications (SSCs) affect patients' clinical pathway, prolonging their hospitalization and incrementing their management costs. The present study aimed to assess the economic and organizational implications of a portable device for negative-pressure wound therapy (NPWT) implementation, compared with the administration of pharmacological therapies alone for preventing surgical complications in patients undergoing general, cardiac, obstetrical-gynecological, or orthopedic surgical procedures., Patients and Methods: A total of 8,566 hospital procedures, related to the year 2015 from one hospital, were evaluated considering infection risk index, occurrence rates of SSCs, drug therapies, and surgical, diagnostic, and specialist procedures and hematological exams. Activity-based costing and budget impact analyses were implemented for the economic assessment., Results: Patients developing an SSC absorbed i) 64.27% more economic resources considering the length of stay (€ 8,269±2,096 versus € 5,034±2,901, p <0.05) and ii) 42.43% more economic resources related to hematological and diagnostic procedures (€ 639±117 versus € 449±72, p <0.05). If the innovative device had been used over the 12-month time period, it would have decreased the risk of developing SSCs; the hospital would have realized an average reduction in health care expenditure equal to -0.69% (-€ 483,787.92) and an organizational saving in terms of length of stay equal to -1.10% (-898 days), thus allowing 95 additional procedures., Conclusion: The implementation of a portable device for NPWT would represent an effective and sustainable strategy for reducing the management costs of patients. Economic and organizational savings could be reinvested, thus i) treating a wider population and ii) reducing waiting lists, with a higher effectiveness in terms of a decrease in complications., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objectives: Hospital Based Health Technology Assessment (HBHTA) practices, to inform decision making at the hospital level, emerged as urgent priority for policy makers, hospital managers, and professionals. The present study crystallized the results achieved by the testing of an original framework for HBHTA, developed within Lombardy Region: the IMPlementation of A Quick hospital-based HTA (IMPAQHTA). The study tested: (i) the HBHTA framework efficiency, (ii) feasibility, (iii) the tool utility and completeness, considering dimensions and sub-dimensions., Methods: The IMPAQHTA framework deployed the Regional HTA program, activated in 2008 in Lombardy, at the hospital level. The relevance and feasibility of the framework were tested over a 3-year period through a large-scale empirical experiment, involving seventy-four healthcare professionals organized in different HBHTA teams for assessing thirty-two different technologies within twenty-two different hospitals. Semi-structured interviews and self-reported questionnaires were used to collect data regarding the relevance and feasibility of the IMPAQHTA framework., Results: The proposed HBHTA framework proved to be suitable for application at the hospital level, in the Italian context, permitting a quick assessment (11 working days) and providing hospital decision makers with relevant and quantitative information. Performances in terms of feasibility, utility, completeness, and easiness proved to be satisfactory., Conclusions: The IMPAQHTA was considered to be a complete and feasible HBHTA framework, as well as being replicable to different technologies within any hospital settings, thus demonstrating the capability of a hospital to develop a complete HTA, if supported by adequate and well defined tools and quantitative metrics.

The present article describes the case study of a "real world" HIV practice within the debate concerning the strategic role of Clinical Governance (CG) tools in the management of a National Healthcare System's sustainability. The study aimed at assessing the impact of a Clinical Pathway (CP) implementation, required by the Regional Healthcare Service, in terms of effectiveness (virological and immunological conditions) and efficiency (economic resources absorption), from the budget holder perspective. Data derived from a multi-centre cohort of patients treated in 6 Hospitals that provided care to approximately 42% of the total HIV+ patients, in Lombardy Region, Italy. Two phases were compared: Pre-CP (2009-2010) vs. Post-CP implementation (2011-2012). All HIV infected adults, observed in the participating hospitals during the study periods, were enrolled and stratified into the 3 categories defined by the Regional CP: first-line, switch for toxicity/other, and switch for failure. The study population was composed of 1,284 patients (Pre-CP phase) and 1,135 patients (Post-CP phase). The results showed that the same level of virological and immunological effectiveness was guaranteed to HIV+ patients: 81.2% of Pre-CP phase population and 83.2% of Post-CP phase population had undetectable HIV-RNA (defined as <50 copies/mL) at 12-month follow up. CD4+ cell counts increased by 28 ± 4 cells/mm3 in Pre-CP Phase and 39 ± 5 cells/mm3 in Post-CP Phase. From an economic point of view, the CP implementation led to a substantial advantage: the mean total costs related to the management of the HIV disease (ART, hospital admission and laboratory tests) decreased (-8.60%) in the Post-CP phase (p-value < 0.0001). Results confirmed that the CP provided appropriateness and quality of care, with a cost reduction for the budget holder., Competing Interests: We confirm that we have read the journal’s policy and the authors of this manuscript had the following competing interests: consulting fees, support for travel to conferences, participation in scientific board for MSD, BMS, Gilead, Abbott, Janssen Cilag, GlaxoSmithline, Pfizer, ViiV Healthcare and AbbVie. Francesca Scolari, Elisabetta Garagiola and Elena Ricci have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Importance: Cannabis use after first-episode psychosis is associated with poor outcomes, but the causal nature of this association is unclear., Objective: To examine the precise nature of the association between continued cannabis use after the onset of psychosis and risk of relapse of psychosis., Design, Setting, and Participants: This prospective cohort study followed up for at least 2 years after the onset of psychosis 220 patients who presented to psychiatric services in South London, England, from April 12, 2002, to July 26, 2013, with first-episode psychosis. Longitudinal modeling (fixed-effects analysis, cross-lagged path analysis) was used to examine whether the association between changes in cannabis use and risk of relapse over time is the result of shared vulnerability between psychosis and cannabis use, psychosis increasing the risk of cannabis use (reverse causation), or a causal effect of cannabis use on psychosis relapse., Interventions: Exposure to cannabis within the first and second years after onset of psychosis., Main Outcomes and Measures: The main outcome measure was relapse of psychosis, defined as subsequent hospitalization for psychosis. Effect of cannabis use status in the first year (Ct1) and second year (Ct2) and pattern of cannabis use continuation in the first year and second year were modeled for risk of relapse in the first year (Rt1) and risk of relapse in the second year (Rt2) after psychosis onset., Results: A total of 220 patients with first-episode psychosis were included in the analysis (mean [SD] age, 28.62 [8.58] years; age range, 18-65 years; 90 women [40.9%] and 130 men [59.1%]). Fixed-effects models that adjusted for time-variant (other illicit drug use, antipsychotic medication adherence) and time-invariant (eg, genetic or premorbid environment) unobserved confounders revealed that there was an increase in the odds of experiencing a relapse of psychosis during periods of cannabis use relative to periods of no use (odds ratio, 1.13; 95% CI, 1.03-1.24). Change in the pattern of continuation significantly increased the risk (odds ratio, 1.07; 95% CI, 1.02-1.13), suggesting a dose-dependent association. Cross-lagged analysis confirmed that this association reflected an effect of cannabis use on subsequent risk of relapse (Ct1→Rt2: β = 0.44, P = .04) rather than an effect of relapse on subsequent cannabis use (Rt1→Ct2: β = -0.29, P = .59)., Conclusions and Relevance: These results reveal a dose-dependent association between change in cannabis use and relapse of psychosis that is unlikely to be a result of self-medication or genetic and environmental confounding.

Background: The advent of new HCV drugs has generated widespread economic concerns, particularly within the Italian setting, characterized by continuous linear cuts and spending review actions. The overall trade-off between investments and savings needs an in depth analysis., Aims: The study aimed to estimate the budget impact of the introduction of the novel drugs approved during the year 2015, compared with the historical situation based on the different treatment options available prior to 2015., Methods: A three-year budget impact model was developed, taking into consideration the Lombardy Region (Northern Italy) Health Service perspective. The degree of liver fibrosis, genotypes, presence of only HCV or HIV/HCV co-infections, presence or absence of sustained virological response, and direct healthcare total costs were the variables of the model., Results: With the introduction of the novel regimens, a higher number of HCV patients achieved a sustained virological response (+20%). Further analysis showed that an investment in innovative technologies would have given the Regional System significant economic savings within the 36-month period (-6.64%/-7.15%)., Conclusions: Treating HCV-infected persons in the Lombardy Region with the new drugs would reduce healthcare expenditure on this specific disease, in each forecast implemented, thus reducing the economic burden of the pathology., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Although cannabis use after a first episode of psychosis has been associated with relapse, little is known about the determinants of this most preventable risk factor for relapse of psychosis. Here we aimed to study whether the effects on outcome vary depending on the type of cannabis consumed and usage pattern., Methods: In this observational study, we prospectively recruited and followed up patients aged 18-65 years who presented with their first episode of psychosis to psychiatric services in south London, London, UK. Relapse of psychosis within 2 years after onset of psychosis was defined as risk of subsequent admission to hospital. We classified patients into different patterns of cannabis use based on continuity of use after onset of psychosis, potency of cannabis consumed, and frequency of use after the onset of their illness. We used multiple regression analyses (logistic or binominal) to compare the different cannabis use groups and propensity score analysis to validate the results., Findings: Between April 12, 2002, and July 26, 2013, 256 patients presented with a first episode of psychosis. We did follow-up assessments for these patients until September, 2015. Simple analyses showed that former regular users of cannabis who stopped after the onset of psychosis had the most favourable illness course with regards to relapse. In multiple analysis, continued high-frequency users (ie, daily use in all 24 months) of high-potency (skunk-like) cannabis had the worst outcome, indexed as an increased risk for a subsequent relapse (odds ratio [OR] 3·28; 95% CI 1·22-9·18), more relapses (incidence rate ratio 1·77; 95% CI 0·96-3·25), fewer months until a relapse occurred (b -0·22; 95% CI -0·40 to -0·04), and more intense psychiatric care (OR 3·16; 95% CI 1·26-8·09) after the onset of psychosis., Interpretation: Adverse effects associated with continued use of cannabis after the onset of a first episode of psychosis depend on the specific patterns of use. Possible interventions could focus on persuading cannabis-using patients with psychosis to reduce use or shift to less potent forms of cannabis., Funding: National Institute for Health Research (NIHR)., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Relapse in psychosis typically necessitates admission to hospital placing a significant financial burden on the health service. Exposure to childhood trauma is associated with an increased risk of psychosis, however, the extent to which this influences relapse is unclear. This report summarises current research investigating the influence of childhood trauma on relapse requiring psychiatric hospital admission for psychosis. Seven studies were included; two revealed a positive association between childhood trauma and relapse admission, two studies found a negative relationship and three found no significant difference. Inconsistent current evidence suggests a need for further research in this area., (© The Royal College of Psychiatrists 2016.)

Background: Although the link between cannabis use and development of psychosis is well established, less is known about the effect of continued versus discontinued cannabis use after the onset of psychosis. We aimed to summarise available evidence focusing on the relationship between continued and discontinued cannabis use after onset of psychosis and its relapse., Methods: In this systematic review and meta-analysis, we searched MEDLINE for articles published in any language from the database inception date up until April 21, 2015 that included a sample of patients with a pre-existing psychotic disorder with a follow-up duration of at least 6 months. We used a combination of search terms for describing cannabis, the outcome of interest (relapse of psychosis), and the study population. We excluded studies if continued cannabis use or discontinued cannabis use could not be established. We compared relapse outcomes between those who continued (CC) or discontinued (DC) cannabis use or were non-users (NC). We used summary data (individual patient data were not sought out) to estimate Cohen's d, which was entered into random effects models (REM) to compare CC with NC, CC with DC, and DC with NC. Meta-regression and sensitivity analyses were used to address the issue of heterogeneity., Findings: Of 1903 citations identified, 24 studies (16 565 participants) met the inclusion criteria. Independent of the stage of illness, continued cannabis users had a greater increase in relapse of psychosis than did both non-users (dCC-NC=0·36, 95% CI 0·22-0·50, p<0·0001) and discontinued users (dCC-DC=0·28, 0·12-0·44, p=0·0005), as well as longer hospital admissions than non-users (dCC-NC=0·36, 0·13 to 0·58, p=0·02). By contrast, cannabis discontinuation was not associated with relapse (dDC-NC=0·02, -0·12 to 0·15; p=0·82). Meta-regression suggested greater effects of continued cannabis use than discontinued use on relapse (dCC-NC=0·36 vs dDC-NC=0·02, p=0·04), positive symptoms (dCC-NC=0·15 vs dDC-NC=-0·30, p=0·05) and level of functioning (dCC-NC=0·04 vs dDC-NC=-0·49, p=0·008) but not on negative symptoms (dCC-NC=-0·09 vs dDC-NC=-0·31, p=0·41)., Interpretation: Continued cannabis use after onset of psychosis predicts adverse outcome, including higher relapse rates, longer hospital admissions, and more severe positive symptoms than for individuals who discontinue cannabis use and those who are non-users. These findings point to reductions in cannabis use as a crucial interventional target to improve outcome in patients with psychosis., Funding: UK National Institute of Health Research., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Only a few studies provided data on the clinical history of sepsis within internal Medicine units. The aim of the study was to assess the short-term mortality and to evaluate the prognostic risk factors in a large cohort of septic patients treated in internal medicine units. Thirty-one internal medicine units participated to the study. Within each participating unit, all admitted patients were screened for the presence of sepsis. A total of 533 patients were included; 78 patients (14.6%, 95%CI 11.9, 18.0%) died during hospitalization; mortality rate was 5.5% (95% CI 3.1, 9.6%) in patients with nonsevere sepsis and 20.1% (95%CI 16.2, 28.8%) in patients with severe sepsis or septic shock. Severe sepsis or septic shock (OR 4.41, 95%CI 1.93, 10.05), immune system weakening (OR 2.10, 95%CI 1.12, 3.94), active solid cancer (OR 2.14, 95% CI 1.16, 3.94), and age (OR 1.03 per year, 95% CI 1.01, 1.06) were significantly associated with an increased mortality risk, whereas blood culture positive for Escherichia coli was significantly associated with a reduced mortality risk (OR 0.46, 95%CI 0.24, 0.88). In-hospital mortality of septic patients treated in internal medicine units appeared similar to the mortality rate obtained in recent studies conducted in the ICU setting., Competing Interests: The authors have no conflicts of interest to disclose.

Aims . The study aimed to present the experience of a screening programme for early detection of diabetic retinopathy (DR) using a nonmydriatic fundus camera, evaluating the feasibility in terms of validity, resources absorption, and future advantages of a potential application, in an Italian local health authority. Methods . Diabetic patients living in the town of Ponzano, Veneto Region (Northern Italy), were invited to be enrolled in the screening programme. The "no prevention strategy" with the inclusion of the estimation of blindness related costs was compared with screening costs in order to evaluate a future extensive and feasible implementation of the procedure, through a budget impact approach. Results . Out of 498 diabetic patients eligible, 80% was enrolled in the screening programme. 115 patients (34%) were referred to an ophthalmologist and 9 cases required prompt treatment for either proliferative DR or macular edema. Based on the pilot data, it emerged that an extensive use of the investigated screening programme, within the Greater Treviso area, could prevent 6 cases of blindness every year, resulting in a saving of €271,543.32 (-13.71%). Conclusions . Fundus images obtained with a nonmydriatic fundus camera could be considered an effective, cost-sparing, and feasible screening tool for the early detection of DR, preventing blindness as a result of diabetes., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Cardiomyopathy is a frequent complication in propionic acidemia. It is mostly rapidly fatal and independent of the metabolic control or medical intervention. Here, we present the reversal of a severe cardiomyopathy after liver transplantation in a patient with propionic acidemia and the long-term stability after ten years. Liver transplantation in patients with propionic acidemia may be considered a valid and long-lasting treatment when cardiomyopathy is progressive and unresponsive to medical therapy., (© 2015 Steunstichting ESOT.)

Introduction: The objective of this paper is the comparison between two different technologies used for the removal of a uterine myoma, a frequent benign tumor: the standard technology currently used, laparoscopy, and an innovative one, colpoceliotomy. It was considered relevant to evaluate the real and the potential effects of the two technologies implementation and, in addition, the consequences that the introduction or exclusion of the innovative technology would have for both the National Health System (NHS) and the entire community., Methods: The comparison between these two different technologies, the standard and the innovative one, was conducted using a Health Technology Assessment (HTA). In particular, in order to analyse their differences, a multi-dimensional approach was considered: effectiveness, costs and budget impact analysis data were collected, applying different instruments, such as the Activity Based Costing methodology (ABC), the Cost-Effectiveness Analysis (CEA) and the Budget Impact Analysis (BIA). Organisational, equity and social impact were also evaluated., Results: The results showed that the introduction of colpoceliotomy would provide significant economic savings to the Regional and National Health Service; in particular, a saving of € 453.27 for each surgical procedure., Discussion: The introduction of the innovative technology, colpoceliotomy, could be considered a valuable tool; one offering many advantages related to less invasiveness and a shorter surgical procedure than the standard technology currently used (laparoscopy).

Background Context: In spinal surgery, newly developed technology seems to play a key role, especially with the use of computer-assisted image-guided navigation, giving excellent results. However, these tools are expensive and may not be affordable for many facilities., Purpose: To compare the cost-effectiveness of preoperative versus intraoperative CT (computed tomography) guidance in spinal surgery., Study Design: A retrospective economic study., Methods: A cost-effectiveness study was performed analyzing the overall costs of a population of patients operated on for lumbar degenerative spondylolisthesis using an image-guided system (IGS) based on a CT scan. The population was divided into two groups according to the type of CT data set acquisition adopted: Group I (IGS based on a preoperative spiral CT scan), Group II (IGS based on an intraoperative CT scan-O-Arm system). The costs associated with each procedure were assessed through a process analysis, where clinical procedures were broken down into single phases and the related costs from each phase were evaluated. No benefits in any form have been or will be received from commercial parties directly or indirectly related to the subject of this article., Results: Four hundred ninety-nine patients met the criteria for this study. In total, 2,542 screws were inserted with IGS. Baseline data were similar for the two groups, as were hospitalization and complications. The surgical time was 119±43 minutes in Group I and 92±31 minutes in Group II. The full cost of the two procedures was analyzed: the mean cost, using the O-Arm system (Group II), was found to be €255.83 (3.80%) less than the cost of Group I. Moreover, the O-Arm system was also used in other surgical procedures as an intraoperative control, thus reducing the final costs of radiologic examinations (a reduction of around 550 CT scans/year)., Conclusions: In conclusion, the authors of the study are of the opinion that the surgical procedure of pedicle screw fixation, using a CT-based computer-guidance system with support of the O-Arm system, allows a shortening of procedure time that might improve the clinical result. However, the present study failed to determine a clear cost-effectiveness with respect to other CT-based IGS., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Despite the success of multiple-drug therapy regimens, the idea of treating human immunodeficiency virus (HIV) infection with fewer drugs is captivating due to issues of convenience, long-term toxicities and costs. This study investigated the impact on a local health budget of the introduction of a protease inhibitor (PI)-based antiretroviral monotherapy. An analysis of 23,721 administrative records of HIV-infected patients and a health technology assessment (HTA) were performed to assess cost-effectiveness, budget, organizational, ethics, and equity impact. Data showed that monotherapy had a annual cost of € 7,076 (patient with undetectable viral load) and € 7,860 (patient with detectable viral load), and that its implementation would realise economic savings of between 12 and 24 million euro (between 4.80% and 9.72% of the 2010 total regional budget expenditure for HIV management) in the first year, with cumulated savings of between 48 and 145 million euro over the following five years. Organizational, ethical and equity impact did not indicate any significant differences. The study suggests that for specific categories of patients monotherapy may be an alternative to existing therapies. Its implementation would not result in higher operating costs, and would lead to a reduction in total expenditure.

Aim: Medical providers often do not perform chest compressions in accordance with recommended resuscitation guidelines for adults and children. Little is known regarding how well neonatal providers perform coordinated chest compressions and ventilations. The objective of this study was to characterize Neonatal Resuscitation Program (NRP) trained providers' adherence to NRP recommendations for coordinated chest compressions and ventilations in a simulated setting., Methods: Fifty NRP providers performed coordinated chest compressions for three minutes on a neonatal manikin. A compression sensor (accelerometer) was used to monitor and record compression data. Data analyzed included ratio of compressions to ventilation pauses, delivered chest compressions per minute (CC/min), and duration of ventilation pauses., Results: Delivered CC/min ranged from 61 to 136. The mean CC/min (99, SD 16) was significantly higher than the NRP-recommended value of 90 (p=0.002). Delivered CC/min did not differ from the first 30 seconds to the last 30 seconds of compressions (p=0.91). Duration of ventilation pauses was highly correlated with CC/min (Spearman's rho= -0.98, p<0.001), with a median duration of 0.92 seconds (IQ range (0.84, 1.02)., Conclusions: NRP trained providers often do not adhere to NRP recommendations for delivery of coordinated chest compressions during simulated cardiac depression. The mean CC/min performed is higher than recommended. Duration of ventilation pauses is highly correlated with delivered CC/min. Future studies should focus on methods to improve the timing of delivered chest compressions by NRP providers to conform to NRP recommendations.

During mouse skeletal muscle development, the Nfix gene has a pivotal role in regulating fetal-specific transcription. Zebrafish and mice share related programs for muscle development, although zebrafish develops at a much faster rate. In fact, although mouse fetal muscle fibers form after 15 days of development, in fish secondary muscle fibers form by 48 hours post-fertilization in a process that until now has been poorly characterized mechanically. In this work, we studied the zebrafish ortholog Nfix (nfixa) and its role in the proper switch to the secondary myogenic wave. This allowed us to highlight evolutionarily conserved and divergent functions of Nfix. In fact, the knock down of nfixa in zebrafish blocks secondary myogenesis, as in mouse, but also alters primary slow muscle fiber formation. Moreover, whereas Nfix mutant mice are motile, nfixa knockdown zebrafish display impaired motility that probably depends upon disruption of the sarcoplasmic reticulum. We conclude that, during vertebrate evolution, the transcription factor Nfix lost some specific functions, probably as a consequence of the different environment in which teleosts and mammals develop.