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.

[Multidistrict atherosclerotic disease: epidemiological and clinical framework]. / Malattia aterosclerotica polidistrettuale: inquadramento epidemiologico e clinico.

Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.

Impact of adherence to disease-modifying drugs in multiple sclerosis: A study on Italian real-world data.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system requiring complex diagnostic and therapeutic management. Treatment with Disease Modifying Drugs (DMDs) is aimed at reducing relapse rate and disease disability. Few real-world, population-based data are available on the impact of adherence on relapse rate. The objective of this study was to assess the impact of adherence to DMDs on relapses in a real-world Italian setting. METHODS: Population-based cohort study. People with MS (PwMS) older than 18 years and residing in the Emilia-Romagna region, Northern Italy, were identified through administrative databases using a validated algorithm. A Cox regression model with a time-varying exposure was performed to assess the association between level of adherence to DMDs and relapses over a 5-year period. RESULTS: A total of 2,528 PwMS receiving a first prescription of DMDs between 2015 and 2019 were included (average age of 42, two-thirds female). Highly adherent PwMS had a 25 % lower hazard of experiencing moderate or severe relapses than non-adherent PwMS (Hazard Ratio 0.75, 95 % CI 0.58 to 0.98), after adjusting for age and sex. Several sensitivity analyses supported the main result. CONCLUSION: The results of our study support the hypothesis that a high level of DMD adherence in MS is associated with a lower risk of moderate or severe relapse. Therefore, choosing the DMD with which to start drug treatment and recommending adherence to treatment appear to be crucial aspects involving both physicians and patients.

Use of inhaled corticosteroids in preschool children and variability among pediatricians: a real-world analysis before and during the SARS-CoV-2 pandemic.

BACKGROUND: In Italy, inhaled corticosteroids (ICSs) are inappropriately prescribed to provide relief in URTI symptoms. Extreme variation in ICS prescribing has been described at regional and sub-regional level. During 2020, extraordinary containment measures were implemented in attempt to halt Coronavirus, such as social distancing, lockdown, and the use of mask. Our objectives were to evaluate the indirect impact of the SARS-CoV-2 pandemic on prescribing patterns of ICSs in preschool children and to estimate the prescribing variability among pediatricians before and during the pandemic. METHODS: In this real-world study, we enrolled all children residing in the Lazio region (Italy), aged 5 years or less during the period 2017-2020. The main outcome measures were the annual ICS prescription prevalence, and the variability in ICS prescribing, for each study year. Variability was expressed as Median Odds Ratios (MORs). If the MOR is 1.00, there is no variation between clusters (e.g., pediatricians). If there is considerable between-cluster variation, the MOR will be large. RESULTS: The study population consisted of 210,996 children, cared by 738 pediatricians located in the 46 local health districts (LHDs). Before the pandemic, the percentage of children exposed to ICS was almost stable, ranging from 27.3 to 29.1%. During the SARS-CoV-2 pandemic, the ICS prescription prevalence dropped to 17.0% (p < 0.001). In each study year, a relevant (p < 0.001) variability was detected among both LHDs and pediatricians working in the same LHD. However, the variability among individual pediatricians was always higher. In 2020, the MOR among pediatricians was 1.77 (95% CI: 1.71-1.83) whereas the MOR among LHDs was 1.29 (1.21-1.40). Furthermore, MORs remained stable over time, and no differences were detected in ICS prescription variability before and after pandemic outbreak. CONCLUSIONS: If on one hand the SARS-CoV-2 pandemic indirectly caused the reduction in ICS prescriptions, on the other the variability in ICS prescribing habits among both LHDs and pediatricians remained stable over the whole study time span (2017-2020), showing no differences between pre- pandemic and pandemic periods. The intra-regional drug prescribing variability underlines the lack of shared guidelines for appropriate ICS therapy in preschool children, and raises equity issues in access to optimal care.

[Twenty years of epidemiology of acute coronary syndromes in Italy: how cardiovascular epidemiology can guide secondary prevention strategies]. / Vent'anni di epidemiologia delle sindromi coronariche acute in Italia: come l'epidemiologia cardiovascolare può orientare la clinica e le strategie di prevenzione secondaria.

Over the last 20 years the epidemiology of acute coronary syndromes (ACS) has significantly changed, affecting both the acute and post-acute phases. In particular, although the progressive reduction in in-hospital mortality, the trend in post-hospital mortality was found to be stable or increasing. This trend was at least in part attributed to the improved short-term prognosis due to coronary interventions in the acute phase, which ultimately have increased the population of survivors at high risk of relapse. Thus, while hospital management of ACS has shown great progress in terms of diagnostic and therapeutic efficacy, post-hospital care has not had a parallel development. This is certainly partly attributable to the inadequacy of post-discharge cardiologic facilities, so far not planned according to the level of risk of individual patients. Hence, it is crucial that patients at high risk of relapse are identified and initiated into more intensive secondary prevention strategies. On the basis of epidemiological data, the cornerstones of post-ACS prognostic stratification are represented on the one hand by the identification of heart failure (HF) at index hospitalization, on the other hand by the assessment of residual ischemic risk. In patients presenting with HF at index hospitalization, the fatal rehospitalization rate increases by 0.90% per year from 2001 to 2011, with a mortality between discharge and the first year which in 2011 was equal to 10%. The risk of fatal readmission at 1 year is therefore strongly conditioned by the presence of HF which, together with age, is the major predictor of new events. The effect of high residual ischemic risk on subsequent mortality shows increasing trend up to the second year of follow-up, moderately increasing over the years until reaching a plateau around the fifth year. These observations confirm the need for long-term secondary prevention programs and implementation of a continuous surveillance in selected patients.

[Evaluation of the indirect impact of the Sars-CoV-2 epidemic on primary and ambulatory care processes using synthetic quality measures and graphic representations.] / Valutazione dell'impatto indiretto dell'epidemia da Sars-CoV-2 sui processi assistenziali del territorio attraverso rappresentazioni sintetiche della qualità delle cure.

INTRODUCTION: A concise representation of different primary and ambulatory care quality indicators can be very useful for quickly understanding the data and defining appropriate intervention strategies. The objectives of this study are to implement a graphical representation based on the TreeMap, a tool capable of summarizing results from heterogeneous indicators, with different measurement scales and thresholds, and take advantage of TreeMap's potential to measure the indirect impact of the Sars-CoV-2 epidemic on primary and ambulatory care processes. METHODS: Seven healthcare areas were considered each defined by a set of different indicators representative of the area. A discrete score ranging from 1 (very high quality) to 5 (very low quality) was assigned to the value of each indicator, based on the level of adherence to evidence-based recommendations. Finally, the score of each healthcare area is obtained as the weighted average of the scores of the representative indicators. The TreeMap is calculated for each Local health authority (Lha) of the Lazio Region. In order to assess the impact of the epidemic, a comparison was made between the results observed in 2019 and those observed in 2020. RESULTS: As an example, the results of one of the 10 Lhas of the Lazio Region have been reported. Compared to 2019, in 2020 there was an improvement in primary and ambulatory healthcare regarding all of the evaluated areas, with the exception of the metabolic area which remained stable. "Avoidable" hospitalizations have decreased, such as those for heart failure, Copd and diabetes. The incidence of cardio-cerebrovascular events following myocardial infarction or ischemic stroke has decreased, and inappropriate visits to emergency room have reduced. Furthermore, after decades of overprescribing, the use of drugs with a high risk of inappropriateness, such as antibiotics and aerosolized corticosteroids, has significantly decreased. DISCUSSION: The TreeMap has proven to be a valid tool for evaluating the quality of primary care, summarizing evidence from different and heterogeneous indicators. The improvements in quality levels observed in 2020, compared to 2019, should be interpreted with extreme caution because they could represent a paradox generated by the indirect effects of the Sars-CoV-2 epidemic. If, in the case of the epidemic, the distorting factors can be easily identified, in different and more ordinary evaluative analyses the "research for the causes" could be much more complex.

[The EASY-NET research programme: background, structure, and methodology]. / Il programma di rete EASY-NET: razionale, struttura e metodologie.

This is the first contribution of a series of interventions describing the EASY-NET research program (Bando Ricerca Finalizzata 2016, funds 2014-2015; NET-2016-02364191). Here, the objective is to illustrate the background and the research question, the structure and organization, the methodologies and the expected results of the programme. The main theme is audit&feedback (A&F), a proven and widespread technique for improving the quality of health care. EASY-NET, funded by the Italian Ministry of Health and by the governments of the participating Italian Regions, starts its research activities in 2019 with the aim of evaluating the effectiveness of A&F in improving care for different clinical conditions in various organizational and legislative contexts. The research network involves seven Italian Regions, each conducting specific research activities described by as many work packages (WP): Lazio (the leading Region, coordinator of the research activities), Friuli Venezia Giulia, Piedmont, Lombardy, Emilia-Romagna, Calabria, and Sicily. The involved clinical areas include the management of chronic diseases, emergency care for acute conditions, surgery in the oncological area, the treatment of heart disease, obstetrics, and the use of caesarean section and post-acute rehabilitation. The involved settings concern the community, the hospital, the emergency room, and the rehabilitation facilities. Different experimental or quasi-experimental study designs are applied in each WP to achieve specific objectives of the specific clinical and organizational context. In all WPs, the process and outcome indicators are calculated on the basis of the Health Information Systems (HIS) and, in some cases, they are integrated with measures obtained from ad hoc data collections. The programme aims to contribute to the scientific evidence on A&F also exploring the obstacles and favourable factors for its effectiveness and to promote its implementation in the health service, with the ultimate aim of improving the access to healthcare and the health outcomes for citizens.

SARS-CoV-2 spread and area economic disadvantage in the italian three-tier restrictions: a multilevel approach.

BACKGROUND: To face the second wave of COVID-19, Italy implemented a tiered restriction system with different limitation levels (yellow = medium; orange = medium-high, red = high) at the beginning of November 2020. The restrictions systematically reduced the transmission of SARS-CoV-2 with increasing strength for increasing tier. However, it is unknown whether the effect of limitations was equal between provinces with different socioeconomic levels. Therefore, we investigated the association between the province's socioeconomic level and SARS-CoV-2 infection daily reproduction number in each restriction level. METHODS: We measured the province's socioeconomic level as the percentage of individuals whose 2019 total yearly income was lower than 10,000€, using the measure as a proxy of economic disadvantage. We estimated the daily reproduction number (Rt) at the province level using the SARS-CoV-2 daily incidence data from November 2020 to May 2021. We then used multilevel linear regression models with random intercepts stratified by restriction level to estimate the association between economic disadvantage and Rt. We also adjusted the analyses for potential confounders of the association between the province's economic disadvantage and the Rt: the percentage of people with 0-5 years, the quartiles of population density, and the geographical repartition. RESULTS: Overall, we found increasing Rt in yellow (+ 0.004 p < 0.01, from Rt = 0.99 to 1.08 in three weeks) and containing effects for the orange (-0.005 p < 0.01, from Rt = 1.03 to 0.93) and the red tier (-0.014 p < 0.01, from Rt = 1.05 to 0.76). More economically disadvantaged provinces had higher Rt levels in every tier, although non-significantly in the yellow level (yellow = 0.001 p = 0.19; orange = 0.002 p = 0.02; red = 0.004 p < 0.01). The results showed that the association between economic disadvantage and Rt differed by level of restriction. The number of days into the restriction and the economic disadvantage had statistically significant interactions in every adjusted model. Compared to better off, more economically disadvantaged provinces had slower increasing trends in yellow and steeper Rt reductions in orange, but they showed slower Rt reductions in the highest tier. CONCLUSION: Lower tiers were more effective in more economically disadvantaged provinces, while the highest restriction level had milder effects. These results underline the importance of accounting for socioeconomic level when implementing public health measures.

Audit and feedback in cardio- and cerebrovascular setting: Toward a path of high reliability in Italian healthcare.

Adopting audit and feedback (A&F) strategies could be a suitable healthcare intervention to fulfill the challenge of monitoring and improving clinical guidelines in evidence-based medicine. Indeed, A&F is used to encourage professionals to better adhere to standard guidelines to improve healthcare performance. Briefly, an audit is an inspection of professional practice in comparison to professional standards or targets whose results are subsequently communicated to professionals in a structured manner. Although A&F strategies have been adopted in several time-dependent settings, such as for acute myocardial infarction (AMI) and stroke, interest of audits in rehabilitation care is also emerging. Recently, the Italian Ministry of Health has funded a national network project called EASY-NET, whose main objective is to evaluate the effectiveness of A&F strategies to improve healthcare practice and equity in various clinical and organizational settings in seven Italian regions. Last but not the least of these regions is the Sicily, represented within the project by the IRCCS Centro Neurolesi Bonino-Pulejo of Messina as the work package 7 (WP7). The EASY-NET WP7 is focused on the effectiveness of A&F strategies in both AMI and ischemic stroke setting, from acute to rehabilitation process of care. In this study, we described the study protocol, including the study design and methodology, providing a detailed description of the new model of A&F based on telemedicine, and discussing the possible challenges of this project.

Educational Inequalities in COVID-19 Vaccination: A Cross-Sectional Study of the Adult Population in the Lazio Region, Italy.

Several studies reported socioeconomic inequalities during the COVID-19 pandemic. We aimed at investigating educational inequalities in COVID-19 vaccination on 22 December 2021. We used the cohort of all residents in the Lazio Region, Central Italy, established at the beginning of the pandemic to investigate the effects of COVID-19. The Lazio Region has 5.5 million residents, mostly distributed in the Metropolitan Area of Rome (4.3 million inhabitants). We selected those aged 35 years or more who were alive and still residents on 22 December 2021. The cohort included data on sociodemographic, health characteristics, COVID-19 vaccination (none, partial, or complete), and SARS-CoV-2 infection. We used adjusted logistic regression models to analyze the association between level of education and no vaccination. We investigated 3,186,728 subjects (54% women). By the end of 2021, 88.1% of the population was fully vaccinated, and 10.3% were not vaccinated. There were strong socioeconomic inequalities in not getting vaccinated: compared with those with a university degree, residents with a high school degree had an odds ratio (OR) of 1.29 (95% confidence interval, CI, 1.27-1.30), and subjects with a junior high or primary school attainment had an OR = 1.41 (95% CI: 1.40-1.43). Since a comprehensive vaccination against COVID-19 could help reduce socioeconomic inequalities raised with the pandemic, further efforts in reaching the low socioeconomic strata of the population are crucial.

[Population segmentation as a tool for planning community healthcare networks: the key role of social and health information systems.] / La stratificazione della popolazione come strumento per rimodulare la rete assistenziale sul territorio: il ruolo determinante dei sistemi informativi socio-sanitari.

INTRODUCTION: Due to the ongoing demographic and epidemiological changes, today stakeholders need to have available information, based on population stratification, in order to plan the most suitable organizational model to meet the population health needs. METHODS: The legally adult population assisted and resident in Lazio Region on 31/12/2019 was equally and casually divided in two samples: the training sample (to define the model) and the validation sample (to measure model performances). On the base of the more complex model of Lazio Region, three population strata were defined: multi-chronic population, multi-chronic population with a high clinical complexity, multi-chronic population with socioeconomic vulnerability. Hospital discharge records were identified in the previous five years prior to 31/12/2019. Through appropriate classification models, it was evaluated the level with which the simplified system "from SDO" is able to approximate the more complex algorithm developed by the Lazio Region. RESULTS: Model performances, which has examined only information "from SDO", results inadequate. In fact, the Positive Predictive Value (PVV) results equal to 46.3%, 16.3% and 30.3%, respectively for the three analyzed strata. DISCUSSION: This study demonstrated that using the hospital system as the only Health Information System reduces the possibility to stratify and predict population health needs. For this reason, the improvement of the completeness and of the quality of data from different social and health information systems and their interconnection, represent the essential starting point. In addition, updating record track is needed to simplify the workload of compilers and improve data availability. These actions must also be accompanied by supportive interventions by central bodies for the regions that show the greatest weaknesses, as well as training actions that improve the level of knowledge of compilers.

Incidence of SARS-CoV-2 Infection and Related Mortality by Education Level during Three Phases of the 2020 Pandemic: A Population-Based Cohort Study in Rome.

Evidence on social determinants of health on the risk of SARS-CoV-2 infection and adverse outcomes is still limited. Therefore, this work investigates educational disparities in the incidence of infection and mortality within 30 days of the onset of infection during 2020 in Rome, with particular attention to changes in socioeconomic inequalities over time. A cohort of 1,538,231 residents in Rome on 1 January 2020, aged 35+, followed from 1 March to 31 December 2020, were considered. Cumulative incidence and mortality rates by education were estimated. Multivariable log-binomial and Cox regression models were used to investigate educational disparities in the incidence of SARS-CoV-2 infection and mortality during the entire study period and in three phases of the pandemic. During 2020, there were 47,736 incident cases and 2281 deaths. The association between education and the incidence of infection changed over time. Till May 2020, low- and medium-educated individuals had a lower risk of infection than that of the highly educated. However, there was no evidence of an association between education and the incidence of SARS-CoV-2 infection during the summer. Lastly, low-educated adults had a 25% higher risk of infection from September to December than that of the highly educated. Similarly, there was substantial evidence of educational inequalities in mortality within 30 days of the onset of infection in the last term of 2020. In Rome, social inequalities in COVID-19 appeared in the last term of 2020, and they strengthen the need for monitoring inequalities emerging from this pandemic.

The impact of in-hospital cardiac rehabilitation program on medication adherence and clinical outcomes in patients with acute myocardial infarction in the Lazio region of Italy.

BACKGROUND: Medication adherence is a recognized key factor of secondary cardiovascular disease prevention. Cardiac rehabilitation increases medication adherence and adherence to lifestyle changes. This study aimed to evaluate the impact of in-hospital cardiac rehabilitation (IH-CR) on medication adherence as well as other cardiovascular outcomes, following an acute myocardial infarction (AMI). METHODS: This is a population-based study. Data were obtained from the Health Information Systems of the Lazio Region, Italy (5 million inhabitants). Hospitalized patients aged ≥ 18 years with an incident AMI in 2013-2015 were investigated. We divided the whole cohort into 4 groups of patients: ST-elevation AMI (STEMI) and non-ST-elevation AMI (NSTEMI) who underwent or not percutaneous coronary intervention (PCI) during the hospitalization. Primary outcome was medication adherence. Adherence to chronic poly-therapy, based on prescription claims for both 6- and 12-month follow-up, was defined as Medication Possession Ratio (MPR) ≥ 75% to at least 3 of the following medications: antiplatelets, ß-blockers, ACEI/ARBs, statins. Secondary outcomes were all-cause mortality, hospital readmission for cardiovascular and cerebrovascular event (MACCE), and admission to the emergency department (ED) occurring within a 3-year follow-up period. RESULTS: A total of 13.540 patients were enrolled. The median age was 67 years, 4.552 (34%) patients were female. Among the entire cohort, 1.101 (8%) patients attended IH-CR at 33 regional sites. Relevant differences were observed among the 4 groups previously identified (from 3 to 17%). A strong association between the IH-CR participation and medication adherence was observed among AMI patients who did not undergo PCI, for both 6- and 12-month follow-up. Moreover, NSTEMI-NO-PCI participants had lower risk of all-cause mortality (adjusted IRR 0.76; 95% CI 0.60-0.95), hospital readmission due to MACCE (IRR 0.78; 95% CI 0.65-0.94) and admission to the ED (IRR 0.80; 95% CI 0.70-0.91). CONCLUSIONS: Our findings highlight the benefits of IH-CR and support clinical guidelines that consider CR an integral part in the treatment of coronary artery disease. However, IH-CR participation was extremely low, suggesting the need to identify and correct the barriers to CR participation for this higher-risk group of patients.

[Methodology and rules for measuring adherence: beyond the doctor-patient combination.] / Metodologia e regole per misurare l'aderenza: oltre il binomio medico-paziente.

Observational studies report low adherence to chronic polytherapy indicated by the international guidelines for the secondary prevention of acute myocardial infarction. However, current scientific evidence does not allow to quantify how much of the distance from the guidelines is attributable to the patient's behavior, to the providers of local care (general practitioners, district, Local Health Authority) or to the hospital of discharge. A cohort of about 17,600 patients with incident myocardial infarction, discharged from hospitals of Lazio region was selected, with the aim to measure the adherence in real clinical practice. Pharmaceutical prescriptions recorded in the two years following discharge were collected and analyzed. Results show low adherence to polytherapy and substantial intra-regional variability and identify in the hospital of discharge the care setting most responsible for the variability found in adherence levels, even after two years from acute episode.

Chronic polytherapy after myocardial infarction: the trade-off between hospital and community-based providers in determining adherence to medication.

BACKGROUND: The benefits of chronic polytherapy in reducing readmissions and death after myocardial infarction (MI) have been clearly shown. However, real-world evidence shows poor medication adherence and large geographic variation, suggesting critical issues in access to optimal care. Our objectives were to measure adherence to polytherapy, to compare the amount of variation attributable to hospitals of discharge and to community-based providers, and to identify determinants of adherence to medications. METHODS: This is a population-based study. Data were obtained from the information systems of the Lazio and Tuscany Regions, Italy (9.5 million inhabitants). Patients hospitalized with incident MI in 2010-2014 were analyzed. The outcome measure was medication adherence, defined as a Medication Possession Ratio (MPR) ≥ 0.75 for at least 3 of the following drugs: antiplatelets, ß-blockers, ACEI/ARBs, statins. A 2-year cohort-study was performed. Cross-classified multilevel models were applied to analyze geographic variation. The variance components attributable to hospitals of discharge and community-based providers were expressed as Median Odds Ratio (MOR). RESULTS: A total of 32,962 patients were enrolled. About 63% of patients in the Lazio cohort and 59% of the Tuscan cohort were adherent to chronic polytherapy. Women and patients aged 85 years and over were most at risk of non-adherence. In both regions, adherence was higher for patients discharged from cardiology wards (Lazio: OR = 1.58, p < 0.001, Tuscany: OR = 1.59, p < 0.001) and for patients with a percutaneous coronary intervention during the index admission. Relevant variation between community-based providers was observed, though when the hospital of discharge was included as a cross-classified level, in both Lazio and Tuscany regions the variation attributable to hospitals of discharge was the only significant component (Lazio: MOR = 1.30, p = 0.001; Tuscany: MOR = 1.31, p = 0.001). CONCLUSION: Adherence to best practice treatments after MI is not consistent with clinical guidelines, and varies between patient groups as well as within and between regions. The variation attributable to providers is affected by the hospital of discharge, up to two years from the acute episode. This variation is likely to be attributable to hospital discharge processes, and could be reduced through appropriate policy levers.

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.

In-hospital myocardial infarction and adherence to evidence-based drug therapies: a real-world evaluation.

OBJECTIVES: This study aimed to measure adherence to chronic polytherapy following an acute myocardial infarction (AMI) and to find out associations between adherence and the setting of AMI onset (in vs out of hospital) as well as other determinants. DESIGN: Retrospective follow-up study. SETTING: Population living in the Lazio Region, Italy. PARTICIPANTS: This study included 25 779 hospitalised patients with a first diagnosis of AMI in 2012-2016, after the exclusion of those with hospital admission for AMI or related causes in the previous 5 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients were classified as in-hospital AMI (IH-AMI) or out of hospital AMI (OH-AMI) according to present-on-admission codes. Adherence was measured based on prescription claims during a 6-month follow-up after hospital discharge, using medication possession ratio (MPR). Adherence to chronic polytherapy was defined as MPR ≥75% to at least 3 of the following medications: antithrombotics, betablockers, ACE inhibitors/angiotensin receptor blockers and statins. RESULTS: Among the entire cohort, 1 044 (4%) patients suffered IH-AMI. Overall, 15 440 (60%) patients were deemed adherent to chronic polytherapy. Female gender, older age, mental disorders, renal disease, asthma and ongoing concomitant treatments were factors associated with poor adherence. By contrast, patients with more severe AMI and those already taking evidence-based (E-B) drugs were more likely to be adherent. A strong association between the setting of AMI onset and adherence was observed: IH-AMI patients were 46% less likely to be adherent to E-B medications during their 6-month follow-up as compared with OH-AMI patients (OR 0.54; 95% CI 0.47 to 0.62; p<0.001). CONCLUSION: Pharmacotherapy is not consistent with clinical guidelines, especially for IH-AMI patients. Our findings provide evidence on a previously unidentified groups of patients at risk for poor adherence, who might benefit from greater medical attention and dedicated healthcare interventions.

Cardiovascular Risk After Adjuvant Trastuzumab in Early Breast Cancer: An Italian Population-Based Cohort Study.

BACKGROUND: Although trastuzumab (T) represents the standard of care for the adjuvant treatment of HER2-positive early-stage breast cancer, contrasting results are available about the cardiac toxicity associated to its use. We conducted a multiregional population-based cohort investigation aimed to assess both the short- and long-term cardiovascular (CV) outcomes in women with early breast cancer treated with T-based or standard adjuvant chemotherapy (CT). MATERIALS AND METHODS: We used health care use databases of six Italian regions, overall accounting for 42% of the Italian population. The study cohort was made by all women surgically treated for breast cancer who started a first-line adjuvant T-based or CT treatment. Patients treated with T were 1:2 matched to those treated with CT based on date of treatment start, age, and presence of CV risk factors. Short- and long-term CV outcomes (heart failure and cardiomyopathy) were measured, respectively, after 1 year and at the end of follow-up. RESULTS: Among 28,599 women who met the inclusion criteria, 6,208 T users were matched to 12,416 CT users. After a mean follow-up of 5.88 years, short- and long-term cumulative CV risk were 0.8% and 2.6% in patients treated with T and 0.2% and 2.8% in those treated with CT, respectively. Adjusted hazard ratios were 4.6 (95% confidence interval [CI], 2.6-8.0) for short-term and 1.2 (95% CI, 0.9-1.6) for long-term CV risk. DISCUSSION: In our large real-world investigation, T-associated cardiotoxicity was limited to the treatment period. The addition of T to adjuvant CT did not result in long-term worsening of CV events. IMPLICATIONS FOR PRACTICE: Adjuvant trastuzumab-based chemotherapy represents the backbone therapy in patients with HER2-positive early breast cancer. Although well tolerated, cardiovascular events can manifest during or after therapy because of treatment-related toxicities. In this wide multicenter and unselected cohort, long-term symptomatic cardiotoxicity was low and limited to the treatment period. The findings suggest that developing tools that would be adequately able to predict cardiac toxicity at an early stage remains an important area in which additional research efforts are needed.