Cost-effectiveness of outpatient adherence to recommendations for monitoring of patients hospitalized for heart failure.

AIMS: A set of indicators to assess the quality of care for patients hospitalized for heart failure was developed by an expert working group of the Italian Health Ministry. Because a better performance profile measured using these indicators does not necessarily translate to better outcomes, a study to validate these indicators through their relationship with measurable clinical outcomes and healthcare costs supported by the Italian National Health System was carried out. METHODS AND RESULTS: Residents of four Italian regions (Lombardy, Marche, Lazio, and Sicily) who were newly hospitalized for heart failure (irrespective of stage and New York Heart Association class) during 2014-2015 entered in the cohort and followed up until 2019. Adherence to evidence-based recommendations [i.e. renin-angiotensin-aldosterone system (RAS) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and echocardiograms (ECCs)] experienced during the first year after index discharge was assessed. Composite clinical outcomes (cardiovascular hospital admissions and all-cause mortality) and healthcare costs (hospitalizations, drugs, and outpatient services) were assessed during the follow-up. The restricted mean survival time at 5 years (denoted as the number of months free from clinical outcomes), the hazard of clinical outcomes (according to the Cox model), and average annual healthcare cost (expressed in euros per person-year) were compared between adherent and non-adherent patients. A non-parametric bootstrap method based on 1000 resamples was used to account for uncertainty in cost-effectiveness estimates. A total of 41 406 patients were included in this study (46.3% males, mean age 76.9 ± 9.4 years). Adherence to RAS inhibitors, beta-blockers, MRAs, and ECCs were 64%, 57%, 62%, and 20% among the cohort members, respectively. Compared with non-adherent patients, those who adhered to ECCs, RAS inhibitors, beta-blockers, and MRAs experienced (i) a delay in the composite outcome of 1.6, 1.9, 1.6, and 0.6 months and reduced risks of 9% (95% confidence interval, 2-14%), 11% (7-14%), 8% (5-11%), and 4% (-1-8%), respectively; and (ii) lower (€262, €92, and €571 per year for RAS inhibitors, beta-blockers, and MRAs, respectively) and higher costs (€511 per year for ECC). Adherence to RAS inhibitors, beta-blockers, and MRAs showed a delay in the composite outcome and a saving of costs in 98%, 84%, and 93% of the 1000 bootstrap replications, respectively. CONCLUSIONS: Strict monitoring of patients with heart failure through regular clinical examinations and drug therapies should be considered the cornerstone of national guidelines and audits.

Comparing the effectiveness and cost-effectiveness of sulfonylureas and newer diabetes drugs as second-line therapy for patients with type 2 diabetes.

INTRODUCTION: We aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), and dipeptidyl peptidase-4 inhibitor (DPP-4i) compared with sulfonylureas and glinides (SU). RESEARCH DESIGN AND METHODS: Population-based retrospective cohort study based on linked regional healthcare utilization databases. The cohort included all residents in Lombardy aged ≥40 years, treated with metformin in 2014, who started a second-line treatment between 2015 and 2018 with SU, GLP-1-RA, SGLT2i, or DPP-4i. For each cohort member who started SU, one patient who began other second-line treatments was randomly selected and matched for sex, age, Multisource Comorbidity Score, and previous duration of metformin treatment. Cohort members were followed up until December 31, 2022. The association between second-line treatment and clinical outcomes was assessed using Cox proportional hazards models. The incremental cost-effectiveness ratios (ICERs) were calculated and compared between newer diabetes drugs and SU. RESULTS: Overall, 22 867 patients with diabetes were included in the cohort, among which 10 577, 8125, 2893 and 1272 started a second-line treatment with SU, DPP-4i, SGLT2i and GLP-1-RA, respectively. Among these, 1208 patients for each group were included in the matched cohort. As compared with SU, those treated with DPP-4i, SGLT2i and GLP-1-RA were associated to a risk reduction for hospitalization for major adverse cardiovascular events (MACE) of 22% (95% CI 3% to 37%), 29% (95% CI 12% to 44%) and 41% (95% CI 26% to 53%), respectively. The ICER values indicated an average gain of €96.2 and €75.7 each month free from MACE for patients on DPP-4i and SGLT2i, respectively. CONCLUSIONS: Newer diabetes drugs are more effective and cost-effective second-line options for the treatment of type 2 diabetes than SUs.

Adherence to GLP1-RA and SGLT2-I affects clinical outcomes and costs in patients with type 2 diabetes.

AIMS: To evaluate the impact of adherence to glucagon like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose transporter two inhibitors (SGLT2-I) on clinical outcomes and costs in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The 121,115 residents of the Lombardy Region (Italy) aged ≥40 years newly treated with metformin during 2007-2015 were followed to identify those who started therapy with GLP1-RA or SGLT2-I. Adherence to drug therapy over the first year was defined as the proportion of days covered >80%. Within each drug class, for each adherent patient, one non-adherent patient was matched for age, sex, duration, adherence to metformin treatment and propensity score. The primary clinical outcome was a composite of insulin initiation, hospitalisation for micro- and macrovascular complications and all-cause mortality after the first year of drug treatment. Costs were evaluated based on reimbursements from the national healthcare system. RESULTS: After matching, 1182 pairs of adherent and non-adherent GLP1-RA users and 1126 pairs of adherent and non-adherent SGLT2-I users were included. In both groups, adherent patients experienced a significantly lower incidence of the primary outcome (HR: 0.85, 95% CI 0.72-0.98 for GLP1-RA and HR: 0.69, 95% CI 0.55-0.87 for SGLT2-I). A significant reduction in hospitalizations was found for adherent patients in the GLP1-RA group but not for the SGLT2-I group. Results were consistent when analyses were stratified by age and sex. While higher drug-related costs in the adherent group were counterbalanced by decreased hospitalisation costs in SGLT2-I treated patients, this was not the case for GLP1-RA. CONCLUSIONS: Higher adherence to drug treatment with GLP1-RA and SGLT2-I during the first year of the drug intake is associated with a lower incidence of adverse clinical outcomes in a real-world setting.

Allocation of Users of Mental Health Services to Needs-Based Care Clusters: An Italian Pilot Study.

In Italy, despite strong community-based mental health services, needs assessment is unsatisfactory. Using the Mental Health Clustering Tool (MHCT) we adopted a multidimensional and non-diagnosis dependent approach to assign mental health services users with similar needs to groups corresponding to resources required for effective care. We tested the MHCT in nine Departments of Mental Health in four Italian regions. After a brief training, 318 professionals assessed 12,938 cases with a diagnosis of schizophrenia, depression, bipolar disorder and personality disorder through the MHCT. 53% of cases were 40-59 years, half were females, 51% had a diagnosis of schizophrenia, 48% of cases were clinically severe. Clusters included different levels of clinical severity and diagnostic groups. The largest cluster was 11 (ongoing recurrent psychosis), with 18.9% of the sample, followed by cluster 3 (non-psychotic disorders of moderate severity). The MHCT could capture a variety of problems of people with mental disorders beyond the traditional psychiatric assessment, therefore depicting service population from a different standpoint. Following a brief training, MHCT assessment proved to be feasible. The automatic allocation of cases made the attribution to clusters easy and acceptable by professionals. To what extent clustering provide a sound base for care planning will be the matter of further research.

Healthcare costs and resources utilization in children with difficult-to-control asthma treated with biologic therapies: A population-based cohort study.

INTRODUCTION: Asthma is one of the most common diseases in children, with a variable range of severity. In recent years, treatment for severe asthma has been largely improved by the availability of targeted biologic therapies. Nevertheless, studies reporting real-world data and cost-effectiveness analyses are lacking. The aim of this study was to evaluate, on a population-based cohort of children with asthma, the impact of the treatment with biologics on healthcare service utilization and associated costs. METHODS: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). A cohort of 46 asthmatic children aged 6-11 in treatment with dupilumab, mepolizumab or omalizumab was identified during 2017-2021. We compared healthcare resources use between the year before ("baseline period") and the year after the treatment initiation ("follow-up period"). Average 1-year healthcare costs were also calculated. RESULTS: Comparing the baseline with the follow-up period, the number of patients with at least one exacerbation-related hospitalization and ER access decreased by 75.0% and 85.7%, respectively. The use of biologic agents, namely omalizumab, mepolizumab and dupilumab, significantly reduced oral corticosteroids (OCS), short-acting ß2-agonists and the association inhaled corticosteroids/long-acting ß2-agonists use. ER admissions for non-respiratory causes were also significantly reduced, while discontinuation rate was low (6.5%). The overall costs increased, due to the costs of the biologic agents, but the hospital admission-related costs due to respiratory causes reduced significantly. CONCLUSIONS: Our real-world investigation suggests that biologic agents reduced hospital admissions for respiratory causes and use of anti-asthmatic drugs, including OCS. However, long-term healthcare sustainability still needs more in-depth assessments.

Assessing the quality of the care offer for people with personality disorders in Italy: the QUADIM project. A multicentre research based on the database of use of Mental Health services.

BACKGROUND: Italy can be viewed as a laboratory to assess the quality of mental healthcare delivered in a community-oriented system, especially for severe mental disorders, such as personality disorders. Although initiatives based on clinical indicators for assessing the quality of mental healthcare have been developed by transnational-organisations, there is still no widespread practice of measuring the quality of care pathways delivered to patients with severe mental disorders in a community-oriented system, especially using administrative healthcare databases. The aim of the study is to evaluate the quality of care delivered to patients with personality disorders taken-in-care by mental health services of four Italian regions (Lombardy, Emilia-Romagna, Lazio, Sicily). METHODS: A set of thirty-three clinical indicators, concerning accessibility, appropriateness, continuity, and safety of care, was implemented using regional healthcare utilization databases, containing data on mental health treatments and diagnosis, hospital admissions, outpatient interventions and exams and drug prescriptions. RESULTS: 31,688 prevalent patients with personality disorders treated in 2015 were identified, of whom 2,331 newly taken-in-care. One-in-10 patients received a standardized assessment, the treatment discontinuity affected half of the cases. 12.7% of prevalent patients received at least one hospitalization, 10.6% in the newly taken-in-care cohort. 6-out-of-10 patients had contact with community-services within 14 days from hospital discharge. Access to psychotherapy and psychoeducational treatments was low and delivered with a low intensity. The median of psychosocial interventions per person-year was 19.1 and 9.4, respectively, in prevalent and newly taken-in-care cases. Nearly 50% of patients received pharmacological treatments. CONCLUSIONS: Healthcare utilization databases were used to systematically evaluate and assess service delivery across regional mental health systems; suggesting that in Italy the public mental health services provide to individuals with personality disorders suboptimal treatment paths.

Using big data and Population Health Management to assess care and costs for patients with severe mental disorders and move toward a value-based payment system.

BACKGROUND: Mental health (MH) care often exhibits uneven quality and poor coordination of physical and MH needs, especially for patients with severe mental disorders. This study tests a Population Health Management (PHM) approach to identify patients with severe mental disorders using administrative health databases in Italy and evaluate, manage and monitor care pathways and costs. A second objective explores the feasibility of changing the payment system from fee-for-service to a value-based system (e.g., increased care integration, bundled payments) to introduce performance measures and guide improvement in outcomes. METHODS: Since diagnosis alone may poorly predict condition severity and needs, we conducted a retrospective observational study on a 9,019-patient cohort assessed in 2018 (30.5% of 29,570 patients with SMDs from three Italian regions) using the Mental Health Clustering Tool (MHCT), developed in the United Kingdom, to stratify patients according to severity and needs, providing a basis for payment for episode of care. Patients were linked (blinded) with retrospective (2014-2017) physical and MH databases to map resource use, care pathways, and assess costs globally and by cluster. Two regions (3,525 patients) provided data for generalized linear model regression to explore determinants of cost variation among clusters and regions. RESULTS: Substantial heterogeneity was observed in care organization, resource use and costs across and within 3 Italian regions and 20 clusters. Annual mean costs per patient across regions was €3,925, ranging from €3,101 to €6,501 in the three regions. Some 70% of total costs were for MH services and medications, 37% incurred in dedicated mental health facilities, 33% for MH services and medications noted in physical healthcare databases, and 30% for other conditions. Regression analysis showed comorbidities, resident psychiatric services, and consumption noted in physical health databases have considerable impact on total costs. CONCLUSIONS: The current MH care system in Italy lacks evidence of coordination of physical and mental health and matching services to patient needs, with high variation between regions. Using available assessment tools and administrative data, implementation of an episodic approach to funding MH could account for differences in disease phase and physical health for patients with SMDs and introduce performance measurement to improve outcomes and provide oversight.

Assessment and Monitoring of the Quality of Clinical Pathways in Patients with Depressive Disorders: Results from a Multiregional Italian Investigation on Mental Health Care Quality (the QUADIM Project).

Ensuring adequate quality of care to patients with severe mental disorders remains a challenge. The implementation of clinical indicators aimed at assessing the quality of health care pathways delivered is crucial for the improvement of mental health services (MHS). This study aims to evaluate the quality of care delivered to patients who are taken-into-care with depressive disorders by MHS. Thirty-four clinical indicators concerning accessibility, appropriateness, continuity, and safety were estimated using health care utilization databases from four Italian regions (Lombardy, Emilia-Romagna, Lazio, Sicily). A total of 78,924 prevalent patients treated for depressive disorders in 2015 were identified, of whom 15,234 were newly engaged by MHS. During the year of follow-up, access to psychotherapeutic interventions was low, while the intensity was adequate; 5.1% of prevalent patients received at least one hospitalization in a psychiatric ward (GHPW), and 3.3% in the cohort of newly engaged in services. Five-out-of-10 patients had contact with community services within 14 days after GHPW discharge, but less than half of patients were persistent to antidepressant drug therapy. Furthermore, prevalent patients showed an excess of mortality compared to the general population (SMR = 1.35; IC 95%: 1.26-1.44). In conclusion, the quality of health care is not delivered in accordance with evidence-based mental health standards. Evaluation of health interventions are fundamental strategies for improving the quality and equity of health care.

Effectiveness and economic impact of Dupilumab in asthma: a population-based cohort study.

RATIONALE: Severe asthma is burdened by relevant socio-economic and clinical impact. Randomized controlled trials on Dupilumab showed efficacy and a good safety profile, but post-market studies are needed. OBJECTIVES: To evaluate the impact of Dupilumab on (i) the use of anti-asthmatic drugs, including oral corticosteroids (OCS), (ii) the rates of asthma exacerbation-related hospital admissions, and (iii) the healthcare costs in patients with asthma. METHODS: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). We compared healthcare resources use between the 6 months after Dupilumab initiation ("post-intervention period") and (i) the 6 months before Dupilumab initiation ("wash-out period") and (ii) the corresponding 6 months of the prior year ("pre-intervention period"). MAIN RESULTS: In a cohort of 176 patients, Dupilumab significantly reduced anti-asthmatic drugs use (including OCS and short-acting ß2-agonists, inhaled corticosteroids (ICS)/long-acting ß2-agonists and ICS alone) when comparing the "pre-intervention" to the "post-intervention" period. When considering hospital admissions, we observed a not statistically or marginally significant reduction between both periods before Dupilumab and the post-intervention period. Six-months discontinuation rate was 8%. Overall healthcare costs had a tenfold increase between the "pre-intervention" and "post-intervention" period, which was mainly led by the biologic drug cost. Conversely, expenditures connected to hospital admissions did not change. CONCLUSIONS: Our real-world investigation suggests that Dupilumab reduced anti-asthmatic drugs use, including OCS, in comparison to a corresponding period in the prior year. However, long-term healthcare sustainability remains an open issue.

A Cohort Study on Diabetic Undocumented Migrants in Italy: Can Charitable Organizations Contribute to Higher Adherence?

The increasing presence of documented and undocumented migrants increases the commitment of the Italian National Health Service to their health needs, following its founding principle of equity. In particular, chronic diseases, such as diabetes, represent a crucial area where patients' health is affected by their adherence to care pathways, for which the recent literature has reported alarming low levels. In the case of migrants, obstacles to adherence, such as language or organizational barriers, could be overcome thanks also to charitable organizations providing healthcare services. In this study, we aimed to compare the adherence among documented and undocumented migrants who received healthcare services in Milan, Italy, either from the National Health Service (NHS) or from a charitable organization. We identified a cohort of newly taken into care diabetic patients composed of two groups: (i) documented migrants that attend the NHS; and (ii) undocumented migrants that attend a charity. Information was tracked by merging two datasets: the regional healthcare information system of Lombardy, and a unique dataset that collects data on specialistic visits and pharmaceutical prescriptions for all people visiting one of the most prominent charitable organizations in Italy. The annual diabetologist visit was used as the measure of adherence. The probability of being adherent was compared among the two groups by using a multivariate log-binomial regression model, considering a set of personal characteristics that may impact health behaviors. The cohort comprised 6429 subjects. The percentage of adherence was 52% among the documented migrants, and 74% among the undocumented. Regression results confirmed this pattern: undocumented patients have an increased probability of being adherent by 1.19 times (95% CI: 1.12 to 1.26) compared to documented ones. Our study revealed the potentiality of charitable organizations in guaranteeing continuity of care to undocumented migrants. We argue that this mechanism would benefit from central coordination by the government.

Healthcare Services for Undocumented Migrants: Organisation and Costs from the Italian NHS Perspective.

Based on the principle of health equity, the Italian National Health Service is known worldwide for being a universalistic system that guarantees healthcare services for all its population, among which there are undocumented migrants. A commitment for their health needs is further motivated by their lower utilisation rates of healthcare services, which becomes even more crucial when considering chronic conditions such as diabetes that require adherence and continuity of care. However, the need for more official data has resulted in little research documenting these healthcare usage patterns. For this reason, our objective has been to deepen, from the Italian NHS perspective, the quantity, costs, type, preventability and organisation of healthcare services directed to undocumented migrants. We used official healthcare data from the Lombardy Region, which enable the identification of people receiving the STP code (undocumented migrants) and of people with foreign citizenship (documented migrants). After quantifying the average annual amount and expenditure for healthcare services grouped by Italian citizens, documented migrants and undocumented migrants for all clinical conditions (quantity and costs), we performed three primary investigations where we enlightened differences between the three mentioned groups focusing on the diagnosis of diabetes: (i) mapping the types of healthcare services used and their characteristics (type); (ii) quantifying the impact of preventable hospital admissions (preventability); (iii) examining the healthcare patterns linking pharmaceutical prescriptions with hospital accesses (organisation). Our results reveal significant differences among the three groups, such as more urgent hospital admissions, more preventable complications, and a higher recurrence in terms of access and costs to hospital services rather than pharmaceutical prescriptions for undocumented migrants. These findings can represent the leverage to raise awareness toward the emerging challenges of the migrant health burden.

Effectiveness and Cost-Effectiveness Profile of Second-Line Treatments with Nivolumab, Pembrolizumab and Atezolizumab in Patients with Advanced Non-Small Cell Lung Cancer.

No evidence is available on the head-to-head comparison of clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) in a real-world setting. We aimed to compare the effectiveness and cost-effectiveness profile of nivolumab, pembrolizumab and atezolizumab. We used a population-based retrospective cohort study based on the healthcare utilization databases of the Lombardy Region, Italy. The study cohort included all patients with a diagnosis of lung cancer, who started a second-line treatment for advanced NSCLC with nivolumab, pembrolizumab or atezolizumab from 2015 to 30 June 2020. Overall survival and average cumulative healthcare costs were measured from the start of second-line treatment until 31 December 2020. The study cohort included 1607 patients who started a second-line treatment with ICIs, of which there were 1193 with nivolumab, 138 with pembrolizumab and 276 with atezolizumab. No differences were observed between treatment arms in terms of sex, age or comorbidities. Median OS was very similar between groups, being 8.9, 9.4 and 8.7 months, respectively, in patients treated with nivolumab, pembrolizumab and atezolizumab (p = 0.898). The adjusted hazard ratio of death of patients treated with pembrolizumab and atezolizumab, as compared to nivolumab, were 1.01 (95% CI: 0.81 to 1.25) and 1.03 (0.88 to 1.21), respectively. Healthcare cumulative costs measured in the first two years of follow-up were EUR 43,764, 46,233 and 34,116, on average, associated with nivolumab, pembrolizumab and atezolizumab, respectively. In our real-world study, atezolizumab was the ICI associated with the most favorable cost-effectiveness profile.

Research strategies in treatment of hypertension: value of retrospective real-life data.

This review will discuss the limitations of data collected by RCTs in relation to their applicability to daily life clinical management. It will then argue that these limitations are only partially overcome by modifications of RCT design and conduction (e.g. 'pragmatic trials') while being substantially attenuated by real-life-derived research, which can fill many gaps left by trial-collected evidence and have thus an important complementary value. The focus will be on the real-life research approach based on the retrospective analysis of the now widely available healthcare utilization databases (formerly known as administrative databases), which will be discussed in detail for their multiple advantages as well as challenges. Emphasis will be given to the potential of these databases to provide low-cost information over long periods on many different healthcare issues, drug therapies in particular, from the general population to clinically important subgroups, including (i) prognostic aspects of treatments implemented at the medical practice level via hospitalization and fatality data and (ii) medical practice-related phenomena such as low treatment adherence and therapeutic inertia (unsatisfactorily evaluated by RCTs). It will also be mentioned that thanks to the current availability of these data in electronic format, results can be obtained quickly, helping timely decisions under emergencies. The potential shortcomings of this approach (confounding by indication, misclassification, and selection bias) will also be discussed along with their possible minimization by suitable analytic means. Finally, examples of the contributions of studies on hypertension and other cardiovascular risk factors will be offered based on retrospective healthcare utilization databases that have provided information on real-life cardiovascular treatments unavailable via RCTs.

Cost-Effectiveness of Posthospital Management of Acute Coronary Syndrome: A Real-World Investigation From Italy.

OBJECTIVES: This study aimed to assess the cost-effectiveness profile of adherence to recommendations for the community management of patients discharged with a diagnosis of acute coronary syndrome (ACS). METHODS: The cohort of 50 282 residents in the Lombardy Region (Italy) who were discharged with a diagnosis of ACS during 2011 to 2015 was followed up until 2018. Adherence to selected recommendations including drug therapies (DTs), outpatient controls, and rehabilitation, experienced during the first year after index discharge, was considered. Adherent and nonadherent cohort members were matched on high-dimensional propensity scores. Composite clinical outcomes (cardiovascular hospital admissions and all-cause mortality) and healthcare costs were assessed for a time horizon of 5 years. Cost-effectiveness profile of adherence to recommendations was measured through the incremental cost-effectiveness ratio, that is, the incremental cost for 1 day free from the composite clinical outcome. RESULTS: Adherence to DTs, outpatient controls, and rehabilitation, respectively, regarded 39%, 81%, and 3% of cohort members. Compared with nonadherent patients, those adherent to DTs, outpatient controls, and rehabilitation had (1) a delay in the occurrence of the composite clinical outcome of 50, 43, and 73 days, respectively, and (2) lower (on average, €199 per year for DTs) and higher costs (€292 and €1024 for outpatient controls and rehabilitation). Cost-effectiveness profiles were better for patients with myocardial infarction than those with angina and for patients with more severe clinical complexity than those with milder conditions. CONCLUSIONS: Health-related and economic benefits are expected from improving adherence to international guidelines recommendations concerning outpatient treatments and monitoring of patients with ACS.

Change in healthcare during Covid-19 pandemic was assessed through observational designs.

OBJECTIVE: Methodological challenges for investigating the changes in healthcare utilization during COVID-19 pandemic must be considered for obtaining unbiased estimates. STUDY DESIGN AND SETTING: A population-based study in the Lombardy region (Italy) measured the association between the level of epidemic restrictions (increasing exposure during pre-epidemic, post-lockdown, and lockdown periods) and the recommended healthcare (outcome) for patients with schizophrenia, heart failure, chronic obstructive pulmonary disease, breast cancer, and pregnancy women. Two designs are applied: the self-controlled case series (SCCS) and the usual cohort design. Adjustments for between-patients unmeasured confounders and seasonality of medical services delivering were performed. RESULTS: Compared with pre-epidemic, reductions in delivering recommended healthcare during lockdown up to 73% (95% confidence interval: 63%-80%) for timeliness of breast cancer surgery, and up to 20% (16%-23%) for appropriated gynecologic visit during pregnancy were obtained from SCCS and cohort design, respectively. Healthcare provision came back to pre-epidemic levels during the post-lockdown, with the exception of schizophrenic patients for whom the SCCS showed a reduction in continuity of care of 11% (11%-12%). CONCLUSION: Strategies for investigating the changes in healthcare utilization during pandemic must be implemented. Recommendations for taking into account sources of systematic uncertainty are discussed and illustrated by using motivating examples.

Cost-effectiveness of the adherence with recommendations for clinical monitoring of patients with diabetes.

BACKGROUND AND AIMS: To validate a set of indicators for monitoring the quality of care of patients with diabetes in 'real-life' practice through its relationship with measurable clinical outcomes and healthcare costs. METHODS AND RESULTS: A population-based cohort study was carried out by including the 20,635 patients, residents in the Lombardy Region (Italy), who in the year 2012 were newly taken-in-care for diabetes. Adherence with clinical recommendations (i.e., controls for glycated haemoglobin, lipid profile, urine albumin excretion and serum creatinine) was recorded during the first year after the patient was taken-in-care, and categorized according whether he/she complied with none or almost none (0 or 1), just some (2) or all or almost all (3 or 4) the recommendations, respectively denoted as poor, intermediate and high adherence. Short- and long-term complications of diabetes, and healthcare cost incurred by the National Health Service, were assessed during follow-up. Compared with patients with poor adherence, those with intermediate and high adherence respectively showed (i) a delay in outcome occurrence of 13 days (95% CI, -2 to 27) and 23 days (9-38), and (ii) a lower healthcare cost of 54 € and 77 €. In average, a gain of 18 Euros and 15 Euros for each day free from diabetic complication by increasing adherence respectively from poor to intermediate and from poor to high were observed. CONCLUSION: Close control of patients with diabetes through regular clinical examinations must be considered the cornerstone of national guidance, national audits, and quality improvement incentive schemes.

Treatment Patterns, Clinical Outcomes and Healthcare Costs of Advanced Non-Small Cell Lung Cancer: A Real-World Evaluation in Italy.

We aimed at describing treatment pathways, clinical outcomes and healthcare costs of advanced non-small cell lung cancer (NSCLC) patients in Lombardy Region, Italy. Using healthcare administrative data, 37,562 patients with a new diagnosis of lung cancer between 2012 and 2019 were identified. Among these, patients who started a first-line treatment for advanced NSCLC with either pembrolizumab (n = 660) or tyrosine-kinase inhibitors (TKI) (n = 1245) before 30 June 2020 were included in the study cohort and followed-up until 31 December 2020. Among pembrolizumab users, median time-to-treatment failure (TTF) and median overall survival (OS) were 3.2 months and 13.6 months, respectively. About one third (34.1%) switched to second-line treatment (chemotherapy for all of them). Among TKI users, median TTF and median OS were 9.3 months and 18.4 months, respectively, and 37.1% of patients started second-line treatment (17.8% with TKI and 19.2% with chemotherapy). Average per-patient cumulative healthcare costs during the first year after first-line treatment start were 51,735 € and 30,708 €, respectively, in pembrolizumab and TKI first-line users. These results are coherent with those reported from other real--world studies and may help both clinicians and health decision makers.

Bortezomib-based therapy in non-transplant multiple myeloma patients: a retrospective cohort study from the FABIO project.

INTRODUCTION: Randomized clinical trials showed that bortezomib, in addition to conventional chemotherapy, improves survival and disease progression in multiple myeloma (MM) patients not eligible for stem cell transplantation. The aim of this retrospective population-based cohort study is the evaluation of both clinical and economic profile of bortezomib-based versus conventional chemotherapy in daily clinical practice. METHODS: Healthcare utilization databases of six Italian regions were used to identify adult patients with non-transplant MM, who started a first-line therapy with bortezomib-based or conventional chemotherapy. Patients were matched by propensity score and were followed from treatment start until death, lost to follow-up or study end-point. Overall survival (OS) and restricted mean survival time (RMST) were estimated using the Kaplan-Meier method. Association between first-line treatment and risk of death was estimated by a conditional Cox proportional regression model. Average mean cumulative costs were estimated and compared between groups. RESULTS: In the period 2010-2016, 3509 non-transplant MM patients met the inclusion criteria, of which 1157 treated with bortezomib-based therapy were matched to 1826 treated with conventional chemotherapy. Median OS and RMST were 33.9 and 27.9 months, and 42.9 and 38.4 months, respectively, in the two treatment arms. Overall, these values corresponded to a HR of death of 0.79 (95% CI 0.71-0.89) over a time horizon of 84 months. Average cumulative cost were 83,839 € and 54,499 €, respectively, corresponding to an incremental cost-effectiveness ratio of 54,333 € per year of life gained, a cost coherent with the willingness-to-pay thresholds frequently adopted from Western countries. CONCLUSIONS: These data suggested that, in a large cohort of non-transplant MM patients treated outside the experimental setting, first-line treatment with bortezomib-based therapy was associated with a favourable effectiveness and cost-effectiveness profile.

Sex-related differences in chronic heart failure: a community-based study.

AIMS: To evaluate sex-related differences among real-life outpatients with chronic heart failure across the ejection fraction spectrum and to evaluate whether these differences might impact therapy and outcomes. METHODS: A total of 2528 heart failure patients were examined between 2009 and 2015 [mean age 76, 42% females; 59% with heart failure with preserved ejection fraction (HFpEF), 17% with heart failure with mid-range ejection fraction (HFmrEF) and 24% with heart failure with reduced ejection fraction (HFrEF)]. Females showed a higher prevalence of HFpEF than males. RESULTS: Females were older, less obese and with less ischaemic heart disease. They have renal failure and anaemia more frequently than males. There were no differences in terms of heart failure therapy in the HFrEF group, but a lower prescription rate of angiotensin-converting enzyme-I/AT1 blockers in HFmrEF and HFpEF and a higher prescription of mineralocorticoid receptor antagonists in the female group with HFpEF were observed. Crude rate mortality and composite outcome (death/heart failure progression) run similarly across sexes regardless of the ejection fraction categories. After adjustment, risk of mortality was significantly lower in females than males in the HFmrEF and HFpEF groups, whereas similar risk was confirmed across sexes in the HFrEF group. Considering prognostic risk factors, noncardiac comorbidities emerged in the HFpEF group. CONCLUSION: In a community-based heart failure cohort, females were differently distributed within heart failure phenotypes and they presented some different characteristics across ejection fraction categories. Although in an unadjusted model there was no significant difference for adverse outcomes, in an adjusted model females showed a lower risk of mortality in HFpEF and HFmrEF. Concerning sex-related prognostic risk factors, noncardiac comorbidities significantly affected adverse prognosis in females with HFpEF.