Protective Role of Tacrolimus, Deleterious Role of Age and Comorbidities in Liver Transplant Recipients With Covid-19: Results From the ELITA/ELTR Multi-center European Study.

BACKGROUND AND AIMS: Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking. METHODS: Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis. RESULTS: Between March 1 and June 27, 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39 of 204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age >70 (HR, 4.16; 95% CI, 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR, 0.55; 95% CI, 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR, 1.95; 95% CI, 1.06-3.58) and chronic kidney disease (HR, 1.97; 95% CI, 1.05-3.67) emerged as associated with death CONCLUSIONS: Twenty-five percent of patients requiring hospitalization for COVID-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose.

Location and allocation: Inequity of access to liver transplantation for patients with severe acute-on-chronic liver failure in Europe.

There is growing evidence that liver transplantation (LT) is the most effective treatment for acute-on-chronic liver failure grade-3 (ACLF-3). This study examines whether and how this evidence translates into practice by analyzing the variability in intensive care unit (ICU) admissions, listing strategies, and LT activity for patients with ACLF-3 across transplantation centers in Europe. Consecutive patients who were admitted to the ICU with ACLF-3, whether or not they were listed and/or transplanted with ACLF-3, between 2018 and 2019 were included across 20 transplantation centers. A total of 351 patients with ACLF-3 were included: 33 had been listed prior to developing ACLF-3 and 318 had not been listed at the time of admission to the ICU. There was no correlation between the number of unlisted patients with ACLF-3 admitted to the ICU and the number listed or transplanted while in ACLF-3 across centers. By contrast, there was a correlation between the number of patients listed and the number transplanted while in ACLF-3. About 21% of patients who were listed while in ACLF-3 died on the waiting list or were delisted. The percentage of LT for patients with ACLF-3 varied from 0% to 29% for those transplanted with decompensated cirrhosis across centers (average = 8%), with an I2 index of 68% (95% confidence interval, 49%-80%), showing substantial heterogeneity among centers. The 1-year survival for all patients with ACLF-3 was significantly higher in centers that listed and transplanted more patients with ACLF-3 (>10 patients) than in centers that listed and transplanted fewer: 36% versus 20%, respectively (p = 0.012). Patients with ACLF-3 face inequity of access to LT across Europe. Waitlisting strategies for patients with ACLF-3 influence their access to LT and, ultimately, their survival.

Multiple Sclerosis Progressive Courses: A Clinical Cohort Long-Term Disability Progression Study.

OBJECTIVES: Improving the understanding of multiple sclerosis (MS) mechanism and disability progression over time is essential to assess the value of healthcare interventions. Poor or no data on disability progression are available for progressive courses. This study aims to fill this gap. METHODS: An observational cohort study of patients with primary MS (PPMS) and secondary progressive MS (SPMS) was conducted on 2 Italian MS centers disease registries over an observational time of 34 years. Annual transition probabilities among Expanded Disability Status Scale (EDSS) states were estimated using continuous Markov models. A sensitivity analysis was performed in relation to clinical characteristic associated to disability progression. RESULTS: The study cohort included 758 patients (274 PPMS and 434 SPMS) with a median follow-up of 8.2 years. Annual transition probability matrices of SPMS and PPMS reported different annual probabilities to move within EDSS levels. Excluding EDSS associated to relapse events or patient with relapses, the annual probability of staying stable in an EDSS level increased in both disease courses even not significantly. CONCLUSIONS: This study provides estimates of annual disability progression as EDSS changes for PPMS and SPMS. These estimates could be a useful tool for healthcare decision makers and clinicians to properly assess impact of clinical interventions.

Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS).

BACKGROUND & AIMS: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe. METHODS: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019. RESULTS: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9-15%); and the United Kingdom and Spain had low rates (3-5%) (p <0.0001). The 1-year probability of survival after LT for patients with ACLF was 81% (95% CI 74-87). Pre-LT arterial lactate levels >4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37-7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or -2 and 50% for ACLF-3. CONCLUSION: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more precise prognostic assessment of patients with ACLF. LAY SUMMARY: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes.

Health related quality of life in chronic liver diseases.

BACKGROUND & AIMS: The impact of chronic liver diseases (CLDs) on health-related quality of life (HRQoL) is relevant to understand the burden of these conditions and inform decision-making processes related to their care. Studies simultaneously comparing the HRQoL of patients affected by the major CLDs to that of the general population are still lacking and are the subject of this study. METHODS: Using the EQ-5D-3L questionnaire, we analysed and compared HRQoL data from 2962 Italian patients affected by CLDs and forming a representative sample of the general Italian population (6800 individuals). Exploratory analyses were conducted to investigate the effects of each CLD on HRQoL, using the general population as reference and adjusting for possible confounders. RESULTS: Patients with CLDs (HBV, HCV, PSC, PBC, AIH, NAFLD/NASH) in the chronic hepatitis stage and with compensated cirrhosis (CC) showed HRQoL similar to the general population. However, AIH were more likely to report problems in self-care and lower EQ-5D VAS score, while NAFLD/NASH and HCV showed an increased risk of anxiety/depression. On the other hand, with progression to more advanced stages of liver disease (DC or HCC), HRQoL decreased significantly with higher risk of reporting problems in the physical domains, and significant reductions in the VAS and utility index scores. CONCLUSIONS: Different subtypes of CLD affected different QoL domains. This study therefore provides a real estimate of the impact of CLDs on patients' HRQoL, and represents a much needed tool to inform decision-making while assessing the effectiveness and cost-effectiveness of the care of these patients.

Clinical outcome indicators in chronic hepatitis B and C: A primer for value-based medicine in hepatology.

BACKGROUND & AIMS: Chronic liver diseases (CLDs) are major health problems that require complex and costly treatments. Liver-specific clinical outcome indicators (COIs) able to assist both clinicians and administrators in improving the value of care are presently lacking. The Value-Based Medicine in Hepatology (VBMH) study aims to fill this gap, devising and testing a set of COIs for CLD, that could be easily collected during clinical practice. Here we report the COIs generated and recorded for patients with HBV or HCV infection at different stages of the disease. METHODS/RESULTS: In the first phase of VBMH study, COIs were identified, based on current international guidelines and literature, using a modified Delphi method and a RAND 9-point appropriateness scale. In the second phase, COIs were tested in an observational, longitudinal, prospective, multicentre study based in Lombardy, Italy. Eighteen COIs were identified for HBV and HCV patients. Patients with CLD secondary to HBV (547) or HCV (1391) were enrolled over an 18-month period and followed for a median of 4 years. The estimation of the proposed COIs was feasible in the real-word clinical practice and COI values compared well with literature data. Further, the COIs were able to capture the impact of new effective treatments like direct-acting antivirals (DAAs) in the clinical practice. CONCLUSIONS: The COIs efficiently measured clinical outcomes at different stages of CLDs. While specific clinical practice settings and related healthcare systems may modify their implementation, these indicators will represent an important component of the tools for a value-based approach in hepatology and will positively affect care delivery.

Impact of DAAs on liver transplantation: Major effects on the evolution of indications and results. An ELITA study based on the ELTR registry.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) have dramatically improved the outcome of patients with hepatitis C virus (HCV) infection including those with decompensated cirrhosis (DC). We analyzed the evolution of indications and results of liver transplantation (LT) in the past 10 years in Europe, focusing on the changes induced by the advent of DAAs. METHODS: This is a cohort study based on data from the European Liver Transplant Registry (ELTR). Data of adult LTs performed between January 2007 to June 2017 for HCV, hepatitis B virus (HBV), alcohol (EtOH) and non-alcoholic steatohepatitis (NASH) were analyzed. The period was divided into different eras: interferon (IFN/RBV; 2007-2010), protease inhibitor (PI; 2011-2013) and second generation DAA (DAA; 2014-June 2017). RESULTS: Out of a total number of 60,527 LTs, 36,382 were performed in patients with HCV, HBV, EtOH and NASH. The percentage of LTs due to HCV-related liver disease varied significantly over time (p <0.0001), decreasing from 22.8% in the IFN/RBV era to 17.4% in the DAA era, while those performed for NASH increased significantly (p <0.0001). In the DAA era, the percentage of LTs for HCV decreased significantly (p <0.0001) from 21.1% (first semester 2014) to 10.6% (first semester 2017). This decline was more evident in patients with DC (HCV-DC, -58.0%) than in those with hepatocellular carcinoma (HCC) associated with HCV (HCV-HCC, -41.2%). Conversely, three-year survival of LT recipients with HCV-related liver disease improved from 65.1% in the IFN/RBV era to 76.9% in the DAA era, and is now comparable to the survival of recipients with HBV infection (p = 0.3807). CONCLUSIONS: In Europe, the number of LTs due to HCV infection is rapidly declining for both HCV-DC and HCV-HCC indications and post-LT survival has dramatically improved over the last three years. This is the first comprehensive study of the overall impact of DAA treatment for HCV on liver transplantation in Europe. LAY SUMMARY: After the advent of direct-acting antivirals in 2014, a dramatic decline was observed in the number of liver transplants performed both in patients with decompensated cirrhosis due to hepatitis C virus (HCV), minus 60%, and in those with hepatocellular carcinoma associated with HCV, minus 41%. Furthermore, this is the first large-scale study demonstrating that the survival of liver transplant recipients with HCV-related liver disease has dramatically improved over the last three years and is now comparable to the survival of recipients with hepatitis B virus infection. The reduction in HCV-related indications for LT means that there is a greater availability of livers, at least 600 every year, which can be allocated to patients with indications other than HCV.

Delisting HCV-infected liver transplant candidates who improved after viral eradication: Outcome 2 years after delisting.

BACKGROUNDS & AIMS: Treating patients with decompensated cirrhosis with direct-acting antiviral (DAA) therapy while on the waiting list for liver transplantation results in substantial improvement of liver function allowing 1 in 4 patients to be removed from the waiting list or delisted, as reported in a previous study promoted by the European Liver and Intestine Transplant Association (ELITA). The aim of this study was to report on clinical outcomes of delisted patients, including mortality risk, hepatocellular carcinoma development and clinical decompensation requiring relisting. METHODS: One hundred and forty-two HCV-positive patients on the liver transplant waiting list for decompensated cirrhosis, negative for hepatocellular carcinoma, between February 2014 and June 2015 were treated with DAA therapy and were prospectively followed up. RESULTS: Forty-four patients (30.9%) were delisted following clinical improvement. This percentage was higher than in the original study because of a number of patients being delisted long after starting DAAs. The median Child-Pugh and MELD score of delisted patients was 5.5 and 9 respectively. Four patients were relisted, because of HCC diagnosis in 1 case and 3 patients developed ascites. One further patient died (2.4%) because of rapidly progressing hepatocellular carcinoma twenty-two months after delisting. Of the 70 patients who received a liver graft, 9 died (13%). CONCLUSIONS: Antiviral therapy allows for a long-term improvement of liver function and the delisting of one-third of treated patients with risk of liver-related complications after delisting being very low.

The socioeconomic burden of patients affected by hemophilia with inhibitors.

Hemophilia is associated with a high financial burden on individuals, healthcare systems, and society. The development of inhibitors significantly increases the socioeconomic burden of the diseases. This study aimed to review and describe the burden of hemophilia with inhibitors, providing a reference scenario to assess the impact of new products in the real word. Two systematic literature reviews were performed to collect data on (i) health economics and (ii) health-related quality of life evidences in hemophilic patients with inhibitors. The costs associated with patients with hemophilia and inhibitors are more than 3 times greater than the costs incurred in those without inhibitors, with an annual cost per patient that can be higher than €1 000 000. The costs of bypassing agents account for the large majority of the total healthcare direct costs for hemophilia treatment. The quality of life is more compromised in patients with hemophilia and inhibitors compared to those without inhibitors, in particular the physical domains, whereas mental domains were comparable to that of the general population. The development of an inhibitor has a high impact on costs and quality of life. New treatments have the potential to change positively the management and socioeconomic burden of hemophilia with inhibitors.

Benefits in pain perception, ability function and health-related quality of life in patients with failed back surgery syndrome undergoing spinal cord stimulation in a clinical practice setting.

BACKGROUND: Failed back surgery syndrome (FBSS) represents one main cause of chronic neuropathic or mixed pain, functional disability and reduced Health Related Quality of Life (HRQoL). Spinal Cord Stimulation (SCS) can be a value for money option to treat patients refractory to conventional medical management (CMM). We estimated from real-world data: 1) the amount of reduced levels of HRQoL of target patients compared to general population, 2) the relationship between pain intensity, functional disability, and overall HRQoL, and 3) the improvement of patients' health from SCS intervention, and 4) we give some insights and make some suggestions on the selection of a battery of patients' reported health instruments for use in routine clinical practice. METHODS: At recruitment (before SCS) and every 6 months for 2 years after SCS a battery of questionnaires/tests were completed: the generic EQ-5D and SF-36 for HRQoL, the specific Numerical Rating Scale (NRS) to measure pain intensity, and Oswestry Disability Index (ODI) to measure functional disability. We conducted multilevel regression analyses to investigate the association of HRQoL with the NRS and ODI indexes; multiple regression analyses to compare EQ-5D data with those of the general population adjusted for age, sex and education, and statistical tests to compare the changes of HRQoL, NRS and ODI estimates at baseline with those measured during the follow-up. RESULTS: Eighty patients (40% male, mean age = 58 years) participated. HRQoL was significantly worse in the patients than in the corresponding general population. Pain, functional disability and HRQoL significantly related each other during follow-up, Significant improvements (p < 0.001) in pain intensity, functional capability and HRQoL were reached after 6 months from SCS and generally remained stable during follow-up. Specific instruments provided detailed information on disability and pain, while generic instruments assessed the overall HRQoL and allowed a comparison with the general population's one. CONCLUSIONS: SCS + CMM treatment reaches a statistically significant and probably a clinically relevant improvement in pain perception, functional disability and HRQoL in patients with FBSS refractory to CMM. An appropriate selection of instruments for use in clinical practice is crucial for a routine assessment of health perception in patients, aimed to guide decisions for optimal treatment.

Direct-acting antivirals combination for elderly patients with chronic hepatitis C: A cost-effectiveness analysis.

BACKGROUND: Chronic hepatitis C (CHC) has been undertreated among elderly patients. Interferon-free treatment represents an opportunity for these patients. The aim of this study was to assess the cost-effectiveness of directly acting antivirals (DAAs) in CHC elderly patients. METHODS: A Markov model of CHC natural history was built. This study focuses on CHC patients older than 65 years, stratified according to genotype (1/4, 2 and 3), liver fibrosis (METAVIR F1 to F4), age and frailty phenotype (robust, pre-frail and frail). DAAs combination vs no treatment was simulated for each theoretical population, assessing life years, quality-adjusted life years (QALYs), costs, incremental cost-effectiveness ratios (ICERs) in a lifetime time horizon and by the Healthcare System perspective. RESULTS: Incremental cost-effectiveness ratio increased with age and frailty status in all fibrosis stages. For robust F3 and F4 patients ICERs remained below the willingness-to-pay threshold (WTP) of 40 000€/QALY up to age 75 and 86 years, respectively, depending on drug price and sustained virological response probability (sensitivity analysis). Notably, in F4 and frail subjects older than 75 years, ICER was more sensitive to non-liver-related mortality rate. In elderly F1 and F2 patients, ICERs were below WTP only up to 77 years old, with wide variability among frailty phenotypes. CONCLUSIONS: Cost-effectiveness of DAAs treatment of elderly CHC patients is solid in those with advanced fibrosis, but it depends strongly on frailty status and age, particularly in patients with milder fibrosis stages. Accurate assessment of clinical variables, including frailty, is necessary to allocate limited resources to this special population.

Long-term costs and outcomes in psoriatic arthritis patients not responding to conventional therapy treated with tumour necrosis factor inhibitors: the extension of the Psoriatic Arthritis Cost Evaluation (PACE) study.

OBJECTIVES: Poor information on long-term outcomes and costs on tumour necrosis factor (TNF) inhibitors in psoriatic arthritis (PsA) are available. Our aim was to evaluate long-term costs and benefits of TNF- inhibitors in PsA patients with inadequate response to conventional treatment with traditional disease-modifying anti-rheumatic drugs (tDMARDs). METHODS: Fifty-five out of 107 enrolled patients included in the study at one year, completed the 5-year follow-up period. These patients were enrolled in 8 of 9 centres included in the study at one year. Patients aged older than 18 years, with different forms of PsA and failure or intolerance to tDMARDs therapy were treated with anti-TNF agents. Information on resource use, health-related quality of life (HRQoL), disease activity, function and laboratory values were collected at baseline and through the 5 years of therapy. Costs (expressed in Euro 2011) and utility (measured by EQ-5D instrument) before TNF inhibitor therapy and after 1 and 5 years were compared. RESULTS: The majority of patients (46 out of 55; 83.6%) had a predominant or exclusive peripheral arthritis and 16.4% had predominant or exclusive axial involvement. There was a statistically significant improvement of the most important clinical variables after 1 year of follow-up. These improvements were maintained also after 5 years. The direct costs increased by approximately €800 per patient-month after 1 year, the indirect costs decreased by €100 and the overall costs increased by more than €700 per patient-month due to the cost of TNF inhibitor therapy. Costs at 5 year were similar to the costs at 1 year. The HRQoL parameters showed the same trends of the clinical variables. EQ-5D VAS, EQ-5D utility and SF-36 PCS score showed a significant improvement after 1 year, maintained at 5 years. SF-36 MCS showed an improvement only at 5 years. CONCLUSIONS: The results of our study suggest that TNF blockers have long-term efficacy. The higher cost of TNF inhibitor therapy was balanced by a significant improvement of HRQoL, stable at 5 years of follow-up. Our results need to be confirmed in larger samples of patients.

Health economic models in hemophilia A and utility assumptions from a clinician's perspective.

BACKGROUND: The clinical benefits of prophylaxis in patients with hemophilia are well-established and include the following: reduced bleeding episodes, prevention of joint damage, decreased inhibitor development, and improved health-related quality of life. However, the cost-effectiveness of prophylaxis is still not clear. PROCEDURES: We reviewed the published hemophilia prophylaxis economic models focusing on utility assumptions. RESULTS: We found six cost-utility studies that compared prophylaxis and on-demand regimens. These studies reported remarkably different results, using utility values based on different assumptions and data sources. CONCLUSIONS: We suggest that cooperation among key stakeholders (clinicians, patient organizations and health-care decision makers) as a means of collecting evidence-based and experiential data to represent both the utility and the quality of life changes for patients with Hemophilia A who are treated with prophylaxis or receive on-demand treatments may represent a winning strategy with which to resolve the outstanding issues related to health technology assessments in the care of patients with hemophilia.

Cost and quality of life in patients with severe chronic hand eczema refractory to standard therapy with topical potent corticosteroids.

BACKGROUND: Little is known about the socio-economic burden of severe chronic hand eczema in patients refractory to treatment with potent corticosteroids. OBJECTIVES: To estimate the socio-economic burden of severe chronic hand eczema refractory to potent topical corticosteroids, and to establish an algorithm for the estimation of the health-related quality of life EuroQol five-dimensional (EQ-5D) utility index from the Dermatology Life Quality Index (DLQI) summary score. METHODS: A multicentre cost of illness study was conducted, adopting the societal perspective. Adult patients with severe and refractory chronic hand eczema were enrolled. Direct (e.g. drug treatment and travel) and indirect (i.e. loss of productivity) mean costs/patient-month were estimated. Health-related quality of life was assessed with the EQ-5D and DLQI questionnaires. An ordinary least square regression model was used to investigate relationships between health-related quality of life scores. RESULTS: One hundred and four valid patients (mean age 44.5 years, 39.4% male) participated. Overall mean costs were €418.3/patient-month: loss of productivity contributed 43.7%, followed by hospitalization (16.1%) and travel (10.3%). Health-related quality of life scores were, on average, 0.50 (EQ-5D utility) and 11.3 (DLQI). Utility and DLQI summary were significantly related to each other. CONCLUSIONS: Wellbeing and loss of productivity are the most important consequences in these patients. Appropriate treatment is necessary to improve patient health and productivity, which will contribute to reducing societal costs.

Corrigendum: Time-Trends in Air Pollution Impact on Health in Italy, 1990-2019: An Analysis from the Global Burden of Disease Study 2019.

[This corrects the article DOI: 10.3389/ijph.2023.1605959.].

Italian population-based values of EQ-5D health states.

OBJECTIVE: To estimate a value set for the calculation of Italian-specific quality-adjusted life years (QALYs), based on preferences elicited on EuroQol five-dimensional (EQ-5D) questionnaire health states using the time trade-off technique. METHODS: The revised standard Measurement and Valuation of Health protocol was followed. Twenty-five health states, divided into three groups and given to 450 subjects, were selected to obtain 300 observations per state. Subjects aged 18 to 75 years were recruited to be representative of the Italian general adult population for age, sex, and geographical distribution. To improve efficiency, face-to-face interviews were conducted by using the Computer Assisted Personal Interviewing approach. Several random effects regression models were tested to predict the full set of EQ-5D questionnaire health states. Model selection was based on logical consistency of the estimates, sign and magnitude of the regression coefficients, goodness of fit, and parsimony. RESULTS: The model that satisfied the criteria of logical consistency and was more efficient includes 10 main effect dummy variables for the EQ-5D questionnaire domain levels and the D1 interaction term, which accounts for the number of dimensions at levels 2 or 3 beyond the first. This model has an R(2) of 0.389 and a mean absolute error of 0.03, which are comparable to or better than those of models used in other countries. The utility estimates after state 11111 range from 0.92 (21111) to -0.38 (33333). Italian utility estimates are higher than those estimated in the United Kingdom and Spain and used so far to assess QALYs and conduct cost-utility evaluations in Italy. CONCLUSIONS: A specific value set is now available to calculate QALYs for the conduction of health economic studies targeted at the Italian health care system.

Compliance, persistence, costs and quality of life in young patients treated with antipsychotic drugs: results from the COMETA study.

BACKGROUND: Little data is available on the real-world socio-economic burden and outcomes in schizophrenia. This study aimed to assess persistence, compliance, costs and Health-Related Quality-of-Life (HRQoL) in young patients undergoing antipsychotic treatment according to clinical practice. METHODS: A naturalistic, longitudinal, multicentre cohort study was conducted: we involved 637 patients aged 18-40 years, with schizophrenia or schizophreniform disorder diagnosed ≤10 years before, enrolled in 86 Italian Mental Health Centres and followed-up for 1 year. Comparisons were conducted between naïve (i.e., patients visiting the centre for the first time and starting a new treatment regimen) and non naïve patients. RESULTS: At enrolment, 84% of patients were taking atypical drugs, 3.7% typical, 10% a combination of the two classes, and 2% were untreated. During follow-up, 23% of patients switched at least once to a different class of treatment, a combination or no treatment. The mean Drug-Attitude-Inventory score was 43.4, with 94.3% of the patients considered compliant by the clinicians. On average, medical costs at baseline were 390.93€/patient-month, mostly for drug treatment (29.5%), psychotherapy (29.2%), and hospitalizations (27.1%). Patients and caregivers lost 3.5 days/patient-month of productivity. During follow-up, attitude toward treatment remained fairly similar, medical costs were generally stable, while productivity, clinical statusand HRQoL significantly improved. While no significantly different overall direct costs trends were found between naïve and non naïve patients, naïve patients showed generally a significant mean higher improvement of clinical outcomes, HRQoL and indirect costs, compared to the others. CONCLUSIONS: Our results suggest how tailoring the treatment strategy according to the complex and specific patient needs make it possible to achieve benefits and to allocate more efficiently resources. This study can also provide information on the most relevant items to be considered when conducting cost-effectiveness studies comparing specific alternatives for the treatment of target patients.

Cost-Effectiveness of the Early Arthritis Clinic Organizational Model.

OBJECTIVE: Early diagnosis and tight control improve outcomes of rheumatoid arthritis (RA). However, whether establishing an early arthritis clinic (EAC) is sustainable for national health systems is not known. This analysis aimed to compare effectiveness and costs of an EAC compared to patients followed by the current standard of care. METHODS: A retrospective study on administrative health databases of patients with a new diagnosis of RA was conducted: 430 patients followed in an EAC were enrolled, and 4 non-EAC controls were randomly matched for each. During 2 years of follow-up, the mean health care costs (outpatient, inpatient, pharmaceutical, and global) and 3 effectiveness measures (number and length of hospitalization and quality of care) of the EAC and non-EAC were estimated. The incremental cost-effectiveness ratio was calculated as well as the cost-effectiveness acceptability curve. RESULTS: The cohorts included patients with a mean age of 55.4 years, and 1,506 patients (70%) were female. The mean pharmaceutical (2,602 versus 1,945 euros) and outpatient (2,447 versus 1,778 euros) costs were higher in the EAC cohort. Conversely, a higher rate of non-EAC patients had a low adherence to quality-of-care indicators. The expected number of hospitalizations and the length of stay were statistically significantly higher in the non-EAC versus EAC. CONCLUSION: Despite an expected increase in outpatient costs (visits and diagnostic tests) and pharmaceutical costs, the reduction in terms of number and length of hospitalizations and the higher adherence to international quality-of-care guidelines support the effectiveness of the EAC model.

Time-Trends in Air Pollution Impact on Health in Italy, 1990-2019: An Analysis From the Global Burden of Disease Study 2019.

Objectives: We explored temporal variations in disease burden of ambient particulate matter 2.5 µm or less in diameter (PM2.5) and ozone in Italy using estimates from the Global Burden of Disease Study 2019. Methods: We compared temporal changes and percent variations (95% Uncertainty Intervals [95% UI]) in rates of disability adjusted life years (DALYs), years of life lost, years lived with disability and mortality from 1990 to 2019, and variations in pollutant-attributable burden with those in the overall burden of each PM2.5- and ozone-related disease. Results: In 2019, 467,000 DALYs (95% UI: 371,000, 570,000) were attributable to PM2.5 and 39,600 (95% UI: 18,300, 61,500) to ozone. The crude DALY rate attributable to PM2.5 decreased by 47.9% (95% UI: 10.3, 65.4) from 1990 to 2019. For ozone, it declined by 37.0% (95% UI: 28.9, 44.5) during 1990-2010, but it increased by 44.8% (95% UI: 35.5, 56.3) during 2010-2019. Age-standardized rates declined more than crude ones. Conclusion: In Italy, the burden of ambient PM2.5 (but not of ozone) significantly decreased, even in concurrence with population ageing. Results suggest a positive impact of air quality regulations, fostering further regulatory efforts.

A systematic literature review of the economic impact of ankylosing spondylitis.

This article reviews the last decade studies on the economic impact of ankylosing spondylitis (AS). Interestingly, a common observation is that in AS indirect costs are higher than the use of direct healthcare resources. Country, age, gender, and severity of the diseases impact on per patient annual costs AS related. Different payment and reimbursement regimes may impact on the amount and distribution of indirect costs. The differences observed among countries on absolute and relative (compared with direct costs) amounts of indirect costs can be explained with the capability of a country of actually measure productivity losses and indirect costs. Low indirect costs without other indicators should not be considered as a sign of efficiency in AS care, but may be due to an underestimation of AS-related costs; as a consequence, indirect costs may be a net loss for patients that nobody can repay. A private insurance reimbursement regime has the highest capability of inducing players to define, select and actually identify indirect costs better than in different reimbursement regimes. Therefore indirect costs may become very high in case of private insurance regimes because of their more detailed identification.