[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.

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.

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.

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.

Influence of adherence with guideline-driven recommendations on survival in women operated for breast cancer: Real-life evidence from Italy.

BACKGROUND: A set of indicators to assess the quality of care for women operated for breast cancer was developed by an expert working group of the Italian Health Ministry in order to compare the Italian regions. A study to validate these indicators through their relationship with survival was carried out. METHODS: The 16,753 women who were residents in three Italian regions (Lombardy, Emilia-Romagna and Lazio) and hospitalized for breast cancer surgery during 2011 entered the cohort and were followed until 2016. Adherence to selected recommendations (i.e., surgery timeliness, medical therapy timeliness, appropriateness of complementary radiotherapy and mammographic follow-up) was assessed. Multivariable proportional hazards models were fitted to estimate hazard ratios for the association between adherence with recommendations and the risk of all-cause mortality. RESULTS: Adherence to recommendations was 53% for medical therapy timeliness, 73% for appropriateness of mammographic follow-up, 74% for surgery timeliness and 82% for appropriateness of complementary radiotherapy. Risk reductions of 26%, 62% and 56% were observed for adherence to recommendations on medical therapy timeliness, appropriateness of complementary radiotherapy and mammographic follow-up, respectively. There was no evidence that mortality was affected by surgery timeliness. CONCLUSIONS: Clinical benefits are expected from improvements in adherence to the considered recommendations. Close control of women operated for breast cancer through medical care timeliness and appropriateness of radiotherapy and mammographic monitoring must be considered the cornerstone of national guidance, national audits, and quality improvement incentive schemes.

Effectiveness and Costs Associated to Adding Cetuximab or Bevacizumab to Chemotherapy as Initial Treatment in Metastatic Colorectal Cancer: Results from the Observational FABIO Project.

Evidence available on the effectiveness and costs of biological therapies for the initial treatment of metastatic colorectal cancer (mCRC) is scarce and contrasting. We conducted a population-based cohort investigation for assessing overall survival and costs associated with their use in a real-world setting. Healthcare utilization databases were used to select patients newly diagnosed with mCRC between 2010 and 2016. Those initially treated with biological therapy (bevacizumab or cetuximab) added to chemotherapy were propensity-score-matched to those treated with standard chemotherapy alone, and were followed up to June 30th, 2018. Kaplan-Meier survival estimates, restricted mean survival time (RMST) and cumulative costs were compared between the two treatment arms. The study cohort included 1896 mCRC patients treated with biological therapy matched to 5678 patients treated with chemotherapy alone. Median overall survival was 21.8 and 20.2 months, respectively. After 84 months of follow-up, RMSTs were 30.9 and 31.9 months (p = 0.193), indicating no differences between the average survival time between treatment arms. Patients treated with biological therapy were associated with higher costs. Cumulative per capita costs were €59,663 and €44,399, respectively. In our study, first-line biological therapy did not improve long-term overall survival and was associated with higher costs as compared to standard chemotherapy.

[A&F to monitor and promote quality in healthcare during the COVID-19 emergency: the EASY-NET work]. / A&F per il monitoraggio e la promozione della qualità delle cure in emergenza COVID-19: il lavoro di EASY-NET.

We are presenting here the findings of the reaction to the COVID-19 epidemic during the period March to June 2020 of those centres participating in the research EASY-NET which is on-going in Italy, funded by the Ministry of Health and co-founded by the Regional Health Authorities. The objective of EASY-NET is to evaluate the effectiveness of the audit and feedback (A&F) strategies in different clinical and organizational settings in seven regions. As a negative consequence of the COVID-19 epidemic, the activities of the project have suddenly slowed down; nevertheless, the COVID-19 epidemic represented an opportunity to apply the A&F methodology and support the healthcare within the regional authorities in order to manage and monitor the impact of this new disease. The reaction to the crisis on behalf of EASY-NET was inconsistent across the participating regions for various reasons. Factors which influenced the reaction levels in relation to the rapidity and efficiency of the implementation of the A&F strategies were as follows: the varying epidemiological impact of the COVID-19 epidemic in the various territories, the different clinical and organizational context and availability of expert research teams together with A&F procedures which had already been tested before the start of the epidemic.

[Adherence to chronic polytherapy in secondary prevention of myocardial infarction: limits and perspectives.] / Aderenza alla politerapia cronica nella prevenzione secondaria dell'infarto: limiti e prospettive.

Patients who have had an acute myocardial infarction (MI) are at increased risk of mortality and morbidity. International guidelines agree on the use of combination of the following drugs: platelet antiplatelets, ß-blockers, ACEI/ARBs and statins. The benefits of chronic polytherapy in reducing cardiovascular disease have been clearly shown. However, observational studies reported poor adherence to chronic polytherapy. We identified about 52,000 patients discharged from hospital with a first MI diagnosis from three Italian regions: Lazio, Toscana and Sicilia. Adherence to chronic poly-therapy in the two years after hospital discharge ranged from 63% in the Lazio region to 27% in the Sicilia region. More than 75 percent of MI patients had chronic concomitant diseases. Chronic diseases played a major role among barriers to adherence. MI patients with multimorbidity have complex health needs but, due to the current traditional disease-oriented approach, they face a highly fragmented form of care that leads to incomplete, inefficient, ineffective and possibly harmful clinical interventions, and are likely to receive complex drug regimens, which increase the risk of inappropriate prescribing, drug-drug interactions, and poor adherence. In order to address patient-specific needs, a network of multidisciplinary teams should be implemented, avoiding fragmentation and ensuring continuity of care.

The effect of early surgery after hip fracture on 1-year mortality.

BACKGROUND: Hip fracture injuries are identified as one of the most serious healthcare problems affecting older people. Many studies have explored the associations among patient characteristics, treatment processes, time to surgery and various outcomes in patients hospitalized for hip fracture. The objective of the present study is to evaluate the difference in 1-year mortality after hip fracture between patients undergoing early surgery (within 2 days) and patients undergoing delayed surgery in Italy. METHODS: Observational, retrospective study based on the Hospital Information System (HIS). This cohort study included patients aged 65 years and older who were residing in Italy and were admitted to an acute care hospital for a hip fracture between 1 January 2007 and 31 December 2012. A multivariate Cox regression analysis was used to assess the effect of early surgery on the likelihood of 1-year mortality after hip fracture, adjusting for risk factors that could affect the outcome under study. The absolute number of deaths prevented by exposure to early surgery was calculated. RESULTS: We studied a total of 405,037 admissions for hip fracture. Patients who underwent surgery within 2 days had lower 1-year mortality compared to those who waited for surgery more than 2 days (Hazard Ratios -HR-: 0.83; 95 % CI: 0.82-0.85). The number of deaths prevented by the exposure to early surgery was 5691. CONCLUSIONS: This study is the first to evaluate the association between time to surgery and 1-year mortality for all Italian elderly patients hospitalized for hip fracture. The study confirmed the previous reports on the association between delayed surgery and increased mortality and complication rates in elderly patients admitted for hip fracture. Our data support the notion that deviating from surgical guidelines in hip fracture is costly, in terms of both human life and excess hospital stay.

Using clinical variables and drug prescription data to control for confounding in outcome comparisons between hospitals.

BACKGROUND: Hospital discharge records are an essential source of information when comparing health outcomes among hospitals; however, they contain limited information on acute clinical conditions. Doubts remain as to whether the addition of clinical and drug consumption information would improve the prediction of health outcomes and reduce confounding in inter-hospital comparisons. The objective of the study is to compare the performance of two multivariate risk adjustment models, with and without clinical data and drug prescription information, in terms of their capability to a) predict short-term outcome rates and b) compare hospitals' risk-adjusted outcome rates using two risk-adjustment procedures. METHODS: Observational, retrospective study based on hospital data collected at the regional level.Two cohorts of patients discharged in 2010 from hospitals located in the Lazio Region, Italy: acute myocardial infarction (AMI) and hip fracture (HF). Multivariate logistic regression models were implemented to predict 30-day mortality (AMI) or 48-hour surgery (HF), adjusting for demographic characteristics and comorbidities plus clinical data and drug prescription information. Risk-adjusted outcome rates were derived at the hospital level. RESULTS: The addition of clinical data and drug prescription information improved the capability of the models to predict the study outcomes for the two conditions investigated. The discriminatory power of the AMI model increases when the clinical data and drug prescription information are included (c-statistic increases from 0.761 to 0.797); for the HF model the increase was more slight (c-statistic increases from 0.555 to 0.574). Some differences were observed between the hospital-adjusted proportion estimated using the two different models. However, the estimated hospital outcome rates were weakly affected by the introduction of clinical data and drug prescription information. CONCLUSIONS: The results show that the available clinical variables and drug prescription information were important complements to the hospital discharge data for characterising the acute severity of the patients. However, when these variables were used for adjustment purposes their contribution was negligible. This conclusion might not apply at other locations, in other time periods and for other health conditions if there is heterogeneity in the clinical conditions between hospitals.

Facial soft tissue esthetic predictions: validation in craniomaxillofacial surgery with cone beam computed tomography data.

PURPOSE: Facial soft tissue prediction in orthognathic surgery could be a valuable aid to preview the results and determine the best surgical treatment. After many years, considerable difficulties are still present in the prediction of the clinical final aspect. The object of the present study was to validate new soft tissue simulation software (SurgiCase CMF; Materialise, Leuven, Belgium), using data acquired by cone beam computed tomography (CBCT), that makes it possible to foresee the final result. MATERIALS AND METHODS: Ten patients with craniomaxillofacial deformations underwent CBCT before surgery. Using the SurgiCase CMF software, the data were reconstructed in 3 dimensions, and various osteotomies were simulated in a 3-dimensional virtual environment by applying different surgical procedures. At 6 months after surgery, the patients underwent repeat CBCT. Thus, it was possible to superimpose the pre- and postoperative CBCT studies to evaluate the reproducibility and reliability of the software. RESULTS: CBCT simulations defined an average absolute error of 0.94 mm, a standard deviation of 0.90 mm, and a percentage of error less than 2 mm of 86.80%. CONCLUSION: The preliminary results have allowed us to conclude that simulations in orthognathic surgery for skull-maxillofacial deformities using CBCT acquisition are reliable, in addition to the low radiation exposure, and could become the reference standard to plan surgical treatment.

Underuse of lipid-lowering drugs and factors associated with poor adherence: a real practice analysis in Italy.

BACKGROUND: Many studies have indicated the adequate use of lipid-lowering drugs (LLDs) as a factor in reducing the risk of cardiovascular disease. However, in clinical practice, a very high percentage of patients are not adequately treated. OBJECTIVE: To analyze the management of hypercholesterolemia in a non-experimental setting and to estimate the factors associated with poor adherence to treatment. METHODS: A longitudinal study was performed using clinical and demographic data recorded in the General Practitioners' database. The sample included all patients, aged 30 years or over, with total blood cholesterol measured between 1 January and 31 December 2000. Utilization of LLDs was defined as the standardized daily dose of the drugs purchased during the 12 months preceding the cholesterol measurement. RESULTS: The study included 4764 patients (mean age 59.4+/-14.1 years, 40.7% males). Of the subjects with a total cholesterol higher than a 6.5 mmol/l, approximately 17% were treated with LLDs. About 39% of the patients with previous atherosclerotic diseases were taking statins. Analysis of patients taking LLDs showed that 40.6% of subjects took less than half of the defined daily dose. Factors associated with poor adherence to treatment were: absence of previous atherosclerotic diseases, absence of concomitant diseases, and smoking. A total cholesterol of less than 5 mmol/l was achieved in 19.9% of patients. CONCLUSIONS: Analyzing the data contained in the general medicine database made it possible to evaluate the use of LLDs in clinical practice and to establish the need to pay greater attention to achieving the objective set by the treatment.