The Impact of the COVID-19 Pandemic on the Neck of the Femur and Hip Fracture Surgery Volumes in the Lazio Region.

This study compares surgery volumes for fractures of the neck of the femur (FNF) and hip replacements during the COVID-19 pandemic compared with previous years. Historical (2018-2019) and pandemic (2020-2021) surgery rates for FNF and hip replacement in Lazio, adjusted for age and gender, were calculated per period and compared with a Poisson regression model. For hip replacement surgery, a comparison of different types of hospitals was also made. Before COVID-19's spread, no difference was found in the volume of surgery of both interventions. From the lockdown to the end of 2021, a decrease in surgery volumes for FNF with stabilization between summer 2020 and summer 2021, as well as an additional decline beginning at the start of Omicron's spread, were found. Hip replacement surgeries showed a greater decline during the lockdown period and increased during summer 2020 and during the Delta wave period. The increment in hip replacements, mainly observed in 2021, is due to private and religious hospitals. These results highlight that the pandemic emergency, caused by SARS-CoV-2, has had an important indirect effect on the population's health assistance in the field of orthopedics.

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.

COVID-19 Rapid Antigen Test as Screening Strategy at Points of Entry: Experience in Lazio Region, Central Italy, August-October 2020.

COVID-19 pandemic is a dramatic health, social and economic global challenge. There is urgent need to maximize testing capacity. Rapid Antigen Tests (RAT) represent good candidates for point-of-care and mass surveillance testing to rapidly identify SARS-CoV-2-infected people, counterbalancing lower sensitivity vs. gold standard molecular tests with fast results and possible recurrent testing. We describe the results obtained with the testing algorithm implemented at points of entry (airports and ports) in the Lazio Region (Italy), using the STANDARD F COVID-19 Antigen Fluorescence ImmunoAssay (FIA), followed by molecular confirmation of FIA-positive samples. From mid-August to mid-October 2020, 73,643 RAT were reported to the Regional Surveillance Information System for travelers at points of entry in Lazio Region. Of these, 1176 (1.6%) were FIA-positive, and the proportion of RT-PCR-confirmed samples was 40.5%. Our data show that the probability of confirmation was directly dependent from the semi-quantitative FIA results. In addition, the molecularly confirmed samples were those with high levels of virus and that were actually harboring infectious virus. These results support public health strategies based on early mass screening campaigns by RAT in settings where molecular testing is not feasible or easily accessible, such as points of entry. This approach would contribute to promptly controlling viral spread through travel, which is now of particular concern due to the spread of SARS-CoV-2 variants.

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.

Evaluation of the breast cancer care network within the Lazio Region (Central Italy).

BACKGROUND AND OBJECTIVES: A summary indicator for evaluating the breast cancer network has never been measured at the regional level. The aim is to design treemaps providing a summary description of hospitals (including breast units) and Local Health Units (LHUs) in terms of their levels of performance within the breast cancer network of the Lazio region (central Italy). The treemap structure has an intuitive design and displays information from both general and specific analyses. METHODS: Patients admitted to the regional hospitals for malignant breast cancer (MBC) surgery in 2010-2017 were selected in a population-based cohort study. These quality indicators were calculated based on the international guidelines (EUSOMA, ESMO) to assess the performance in terms of volume of activity, surgery procedure, post-surgery assistance and timeliness of medical therapy or radiotherapy beginning. The quality indicators were calculated using administrative health data systematically collected at the regional level and were included in the treemap to represent the surgery or the post-surgery areas of the breast cancer clinical pathway. In order to allow aggregation of scores for different indicators belonging to the same clinical area, up to five evaluation classes were defined using the "Jenks Natural Breaks" algorithm. A score and a colour were assigned to each clinical area based on the ranking of the indicators involved. The analyses were performed on an annual basis, by the LHU of residence and by the hospital which performed the surgical intervention. RESULTS: In 2017, 6218 surgical interventions for MBC were performed in the hospitals of Lazio. The results showed a continuous increase of the level of performance over the years. Hospitals showed higher variability in the levels of performance than the LHUs. 36% of the evaluated hospitals reached a high level of performance. An audit of the S. Filippo Neri breast unit revealed incorrect coding of the input data. For this reason, the score for the indicator for the volume of wards was re-calculated and re-evaluated, with a subsequent improvement of the level of performance. Most LHUs achieved at least an average overall level of performance, with 20% of the LHUs reaching a high level of performance. CONCLUSIONS: This is the first attempt to apply the treemap logic to a single clinical network, in order to obtain a summary indicator for the evaluation of the breast cancer care network. Our results supply decision makers with a transparent instrument of governance for heterogeneous users, directing efforts improving and promoting equity of care. The treemaps could be reproduced and adapted for other local contexts, in order to limit inappropriateness and ensure uniform levels of breast cancer care within local areas. The next step is the evaluation of audit and feedback interventions to improve the quality of care and to guarantee homogeneous levels of care throughout the region.

[More equity in Lazio region health care: results from the Regional Outcome Evaluation Program (PReValE), 2012-2017]. / Accesso alle cure più equo nella regione Lazio: risultati del Programma regionale di valutazione degli esiti (PReValE) 2012-2017.

OBJECTIVES: to evaluate equity in the Lazio regional Health System, both in terms of unequal access to health care among individuals with different educational levels and of heterogeneity in hospital performance, between 2012 and 2017. DESIGN: retrospective cohort study. SETTING AND PARTICIPANTS: all patients living in Lazio region and discharged from a regional facility between 2012 and 2017 were enrolled. Three cohorts of hospitalizations were selected: acute myocardial infarctions with ST segment elevation (STEMI), hip fractures, and deliveries. MAIN OUTCOME MEASURES: the proportions of STEMIs with PCI within 90 minutes, of patients with a hip fracture who underwent surgery within 2 days, and of deliveries with primary caesarean section were evaluated, accounting for patient demographic characteristics and comorbidities that could affect the outcome under study. These proportions were calculated by education and by hospital of admission. The heterogeneity among facilities was assessed through the median odds ratio (MOR). RESULTS: in Lazio region, between 2012 and 2017, an improvement of the quality of care was observed: in 2017, 50.4% of STEMI patients underwent to a PCI within 90 minutes, 54.4% of patients with a hip fracture underwent surgery within 2 days, and 26.2% of women had a C-section. In 2012, when comparing the adjusted proportions of outcomes by educational level, the probability of being treated with a PCI within 90 minutes for STEMIs and with surgery within 2 days for hip fractures was higher for graduated patients than for those with the lowest education. In contrast, graduated women had the highest risk of having a C-section. In 2017, there was no difference anymore between classes of education in STEMIs and C-sections, while in patients with hip fracture the difference was decreased, but still present. For hip fractures, a reduction of heterogeneity of hospital performances was also detected. CONCLUSION: in Lazio region, a reduction in inequalities in access to health care was observed for different clinical areas. The "public disclosure" of the PReValE results and the management strategy applied in mid-2013 could have driven the overall improvement of the health system for the conditions under study, helping to achieve a fairer access to health.

[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.

Transcatheter or surgical treatment of severe aortic stenosis and coronary artery disease: A comparative analysis from the Italian OBSERVANT study.

BACKGROUND: To assess clinical outcomes of patients with concomitant severe aortic stenosis (AS) and coronary artery disease (CAD) who underwent transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) or surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG). METHODS: Data were extracted from the multicenter OBSERVANT study. For the purposes of the present analysis, we included only patients with established stable CAD meeting any of the following inclusion criteria: 1) TAVI patients with CAD undergoing staged PCI or TAVI and PCI in the same session; 2) SAVR patients undergoing combined SAVR and CABG in the same session. RESULTS: After propensity-score matching, a total of 472 patients (236 per group) were identified. Among TAVI patients, PCI was performed prior to the procedure in 217 patients (92.0%), whereas concomitant TAVI and PCI were performed in 19 patients (8.0%). At 3-year, there was no difference in survival between the two groups (KM estimate of freedom from death for SAVR and TAVI patients of 0.742 and 0.650, respectively; log-rank p-value of 0.105). The rate of MACCE was comparable between the two groups (KM estimate of freedom from MACCE for SAVR and TAVI patients of 0.683 and 0.582, respectively; log-rank p-value of 0.115). CONCLUSIONS: In patients with associated severe AS and CAD, percutaneous treatment (TAVR and staged or concomitant PCI) was comparable to surgical treatment (SAVR and concomitant CABG) with respect to the early and mid-term risk of death from any cause, myocardial infarction, stroke and unplanned revascularization.

Regional Outcome Evaluation Program (P.Re.Val.E.): Reduction of inequality in access to effective health care in the Lazio region of Italy (2012-2015).

BACKGROUND: Inequalities in health among groups of various socio-economic status (as measured by education, occupation, and income) constitute one of the main challenges for public health. Since 2006, the Lazio Regional Outcome Evaluation Program (P.Re.Val.E.), presents a set of indicators of hospital performance based on quality standards driven by strong clinical recommendations, and measures the variation in the access to effective health care for different population groups and providers in the Lazio Region. One of the aims of the program was to compare population subgroups in order to promote equity in service provision. Since June 2013, a new management strategy has been put in place that assigned specific goals based on performance assessment to the chief executive officers of the hospitals. AIM: To evaluate whether, in recent years, there has been a reduction in the differential access to effective health care, among individuals with different educational levels. METHODS: We enrolled all patients discharged from both public and private hospitals of the Lazio region between 2012 and 2015, living in Lazio region. We analysed the proportion of patients with ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention within 90 minutes (primary PCI), the proportion of patients with hip fracture (HF) who underwent surgery within 2 days, and the proportion of women with primary C-section. We applied multivariate logistic regression models to assess the effect of educational level on health outcomes, adjusting for demographic characteristics and comorbidities that could affect the outcomes. For each year of the study period, we compared adjusted proportions of outcomes for the highest and the lowest level of education by using percentage differences. RESULTS: In the Lazio region, 44.6% of STEMI patients (N = 3,299) were treated with primary PCI, 54.4% of patients with hip fractures (N = 6,602) underwent surgery within 2 days, and 27.7% of women without a previous C-section (N = 34,718) delivered via C-section, in 2015. The corresponding proportions in 2012 were 27.8%, 31.3% and 31.5%, respectively. By comparing the adjusted proportions in patients with the highest education level (a university degree or higher) to those with the lowest level education level (None/Primary school), a decrease in the percentage difference was observed during the study period. In STEMI and delivery cohorts, the improvement of outcomes involved the least and the most educated patients, respectively, and the difference between the two educational levels was close to zero in 2015, whereas for hip patients, the improvement was more evident among the less educated patients. CONCLUSIONS: In the Lazio region, we observed a reduction in the differential access to effective heath care by educational level, in different clinical areas. Different factors might explain these results. On top of the public disclosure of outcome data, the management strategy applied in mid-2013 might have driven the overall improvement of the health system for the considered conditions, helping to achieve a fairer access to health.

Volume and health outcomes: evidence from systematic reviews and from evaluation of Italian hospital data. / Volumi di attività ed esiti delle cure: prove scientifiche in letteratura ed evidenze empiriche in Italia.

BACKGROUND Improving quality and effectiveness of healthcare is one of the priorities of health policies. Hospital or physician volume represents a measurable variable with an impact on effectiveness of healthcare. An Italian law calls for the definition of «qualitative, structural, technological, and quantitative standards of hospital care¼. There is a need for an evaluation of the available scientific evidence in order to identify qualitative, structural, technological, and quantitative standards of hospital care, including the volume of care above or below which the public and private hospitals may be accredited (or not) to provide specific healthcare interventions. OBJECTIVES To identify conditions/interventions for which an association between volume and outcome has been investigated. To identify conditions/interventions for which an association between volume and outcome has been proved. To analyze the distribution of Italian health providers by volume of activity. To measure the association between volume of care and outcomes of the health providers of the Italian National Health Service (NHS). METHODS Systematic review An overview of systematic reviews was performed searching PubMed, EMBASE, and The Cochrane Library up to November 2016. Studies were evaluated by 2 researchers independently; quality assessment was performed using the AMSTAR checklist. For each health condition and outcome, if available, total number of studies, participants, high volume cut-off values, and metanalysis have been reported. According to the considered outcomes, health topics were classified into 3 groups: positive association: a positive association was demonstrated in the majority of studies/participants and/or a pooled measure (metanalysis) with positive results was reported; lack of association: both studies and/or metanalysis showed no association; no sufficient evidence of association: both results of single studies and metanalysis do not allow to draw firm conclusions on the association between volume and outcome. Analysis of the distribution of Italian hospitals by volume of activity and the association between volume of activity and outcomes: the Italian National Outcome evaluation Programme 2016 The analyses were performed using the Hospital Information System and the National Tax Register (year 2015). For each condition, the number of hospitals by volume of activity was calculated. Hospitals with a volume lower than 3-5 cases/year were excluded. For conditions with more than 1,500 cases/year and frequency of outcome ≥1%, the association between volume of care and outcome was analyzed estimating risk-adjusted outcomes. RESULTS Bibliographic searches identified 80 reviews, evaluating 48 different clinical areas. The main outcome considered was intrahospital/30-day mortality. The other outcomes vary depending on the type of condition or intervention in study. The relationship between hospital volume and outcomes was considered in 47 out of 48 conditions: 34 conditions showed evidence of a positive association; • 14 conditions consider cancer surgery for bladder, breast, colon, rectum, colon rectum, oesophagus, kidney, liver, lung, ovaries, pancreas, prostate, stomach, head and neck; • 11 conditions consider cardiocerebrovascular area: nonruptured and ruptured abdominal aortic aneurysm, acute myocardial infarction, brain aneurysm, carotid endarterectomy, coronary angioplasty, coronary artery bypass, paediatric heart surgery, revascularization of lower limbs, stroke, subarachnoid haemorrhage; • 2 conditions consider orthopaedic area: knee arthroplasty, hip fracture; • 7 conditions consider other areas: AIDS, bariatric surgery, cholecystectomy, intensive care unit, neonatal intensive care unit, sepsis, and traumas; for 3 conditions, no association was demonstrated: hip arthroplasty, dialysis, and thyroidectomy. for the remaining 10 conditions, the available evidence does not allow to draw firm conclusions about the association between hospital volume and considered outcomes: surgery for testicular cancer and intracranial tumours, paediatric oncology, aortofemoral bypass, cardiac catheterization, appendectomy, colectomy, inguinal hernia, respiratory failure, and hysterectomy. The relationship between volume of clinician/surgeon and outcomes was assessed only through the literature re view; to date, it is not possible to analyze this association for Italian health provider hospitals, since information on the clinician/surgeon on the hospital discharge chart is missing. The literature found a positive association for 21 conditions: 9 consider surgery for cancer: bladder, breast, colon, colon rectum, pancreas, prostate, rectum, stomach, and head and neck; 5 consider the cardiocerebrovascular area: ruptured and nonruptured abdominal aortic aneurysm, carotid endarterectomy, paediatric heart surgery, and revascularization of the lower limbs; 2 consider the orthopaedic area: knee and hip arthroplasty; 5 consider other areas: AIDS, bariatric surgery, hysterectomy, intensive care unit, and thyroidectomy. The analysis of the distribution of Italian hospitals concerned the 34 conditions for which the systematic review has shown a positive volume-outcome association. For the following, it was possible to conduct the analysis of the association using national data: unruptured abdominal aortic aneurysm, coronary angioplasty, hip arthroplasty, knee arthroplasty, coronary artery bypass, cancer surgery (colon, liver, breast, pancreas, lung, prostate, kidney, and stomach), laparoscopic cholecystectomy, hip fracture, stroke, acute myocardial infarction. For these conditions, the association between volume and outcome of care was observed. For laparoscopic cholecystectomy and surgery of the breast and stomach cancer, the association between the volume of the discharge (o dismissal) operating unit and the outcome was analyzed. The outcomes differ depending on the condition studied. The shape of the relationship is variable among different conditions, with heterogeneous slope of the curves. DISCUSSION For many conditions, the overview of systematic reviews has shown a strong evidence of association between higher volumes and better outcomes. The quality of the available reviews can be considered good for the consistency of the results between the studies and for the strength of the association; however, this does not mean that the included studies are of good quality. Analyzing national data, potential confounders, including age and comorbidities, have been considered. The systematic review of the literature does not permit to identify predefined volume thresholds. The analysis of national data shows a strong improvement in outcomes in the first part of the curve (from very low to higher volumes) for most conditions. In some cases, the improvement in outcomes remains gradual or constant with the increasing volume of care; in other, the analysis could allow the identification of threshold values beyond which the outcome does not further improve. However, a good knowledge of the relationship between effectiveness of treatments and costs, the geographical distribution and the accessibility to healthcare services are necessary to choose the minimum volumes of care, under which specific health procedures could not been provided in the NHS. Some potential biases due to the use of information systems data should also be considered. The different way of coding among hospitals could lead to a different selection of cases for some conditions. Regarding the definition of the exposure (volume of care), a possible bias could result from misclassification of health providers with high volume of activity. Performing the intervention in different departments/ units of the same hospital would result in an overestimation of the volume of care measured for hospital rather than for department/unit. For the conditions with a further fragmentation within the same structure, the association between volumes of discharge department and outcomes has also been evaluated. In this case, the two curves were different. The limit is to attribute the outcome to the discharge unit, which in case of surgery may not be the intervention unit. A similar bias could occur if the main determinant of the outcome of treatment was the caseload of each surgeon. The results of the analysis may be biased when different operators in the same hospital/unit carried out the same procedure. In any case, the observed association between volumes and outcome is very strong, and it is unlikely to be attributable to biases of the study design. Another aspect on which there is still little evidence is the interaction between volume of the hospital and of the surgeon. A MEDICARE study suggests that in some conditions, especially for specialized surgery, the effect of the surgeon's volume of activity is different depending on the structure volume, whereas it would not differ for some less specialized surgery conditions. The data here presented still show extremely fragmented volumes of both clinical and surgical areas, with a predominance of very low volume structures. Health systems operate, by definition, in a context of limited resources, especially when the amount of resources to allocate to the health system is reduced. In such conditions, the rationalization of the organization of health services based on the volume of care may make resources available to improve the effectiveness of interventions. The identification and certification of services and providers with high volume of activity can help to reduce differences in the access to non-effective procedures. To produce additional evidence to guide the reorganization of the national healthcare system, it will be necessary to design further primary studies to evaluate the effectiveness and safety of policies aimed at concentrating interventions in structures with high volumes of activity.

Comparative effectiveness and safety of erythropoiesis-stimulating agents (biosimilars vs originators) in clinical practice: a population-based cohort study in Italy.

OBJECTIVES: To evaluate the benefit/risk profile of epoetin α biosimilar with the erythropoiesis-stimulating agents (ESAs) originators when administered to naïve patients from clinical practice. DESIGN: Population-based observational cohort study. SETTING: All residents in the Lazio Region, Italy, with chronic kidney disease (CKD) or cancer retrieved from the Electronic Therapeutic Plan (ETP) Register for ESA between 2012 and 2014. PARTICIPANTS: Overall, 13 470 incident ESA users were available for the analysis, 8161 in the CKD and 5309 in the oncology setting, respectively. INTERVENTIONS: ESAs identified through the ATC B03XA were divided into 3 groups: (1) biosimilars; (2) epoetin α originator and (3) other originators. Patients were exposed to ESAs from the date of activation of the ETP, until the end of a 6-month follow-up period. OUTCOME MEASURES: Effectiveness (all-cause mortality and blood transfusion) and safety (major cardiovascular events, blood dyscrasia). A composite outcome including all-cause mortality, blood transfusion and major cardiovascular events was predefined. HRs of any outcome were estimated through Cox regression. RESULTS: We found no differences between patients on biosimilars or all originators with regard to the risk estimates of all-cause mortality, blood transfusion, major cardiovascular events and blood dyscrasia in the CKD setting. The composite outcome confirmed these results (biosimilars vs epoetin α originators: adjusted HR=1.02, 95% CI 0.78 to 1.33; biosimilars vs other originators: adjusted HR=1.09, 95% CI 0.85 to 1.41). Comparable risk estimates were observed between biosimilars and all originators in the oncology setting. CONCLUSIONS: In both settings, our findings are suggestive of no difference between biosimilars and originators on relevant effectiveness and safety outcomes. This study may contribute to settling future drug policy for the health services and provides reassurance on the approval pathway for biosimilars. The oncology setting merits further research, taking into account tumour types, tumour stage and anticancer chemotherapy administered.

Outcomes of early invasive treatment strategy in elderly patients with non-ST elevation acute coronary syndromes.

BACKGROUND: As benefits of revascularization in non-ST elevation acute coronary syndromes (NSTEACSs) in the elderly are still unproven, we sought to assess the association between invasive or conservative management of NSTEACS and short-, mid- and long-term mortality or composite outcome of all-cause mortality and myocardial infarction in a cohort of consecutive elderly patients. METHODS AND RESULTS: Consecutive NSTEACS patients older than 75 years discharged between 2006 and 2010 from a single intensive cardiac care unit, and managed with invasive or conservative strategy according to available guidelines were retrospectively surveyed. By multivariate regression and sensitivity analysis, crude and adjusted mortality and composite outcome were estimated at prespecified time points of short-term (in-hospital or 30 days mortality), mid-term (T1: 31 days to 6 months), and long-term (T2: 31 days to 12 months). A total of 453 patients (median age 80 years, 47% men) were evaluated; 301 (66.5%) underwent invasive treatment. Invasive was associated with significantly lower risk of short- [odds ratio (OR) 0.28, 95% confidence interval (CI) 0.12-0.67, P = 0.004], mid- (OR 0.33, 95% CI 0.16-0.67, P = 0.003) and long-term mortality (OR 0.34, 95% CI 0.20-0.58, P < .0001). Invasive strategy was also associated with nonsignificant lower short- (OR 0.55, 95% CI 0.28-1.07, P = 0.077), and highly significant lower mid- (OR 0.52, 95% CI 0.34-0.81, P = 0.003) and long-term adjusted cumulative composite outcome rate (OR 0.68, 95% CI 0.46-0.98, P = 0.004). CONCLUSION: In NSTEACS elderly patients, invasive strategy is independently associated with lower short-, mid- and long-term mortality and composite outcome.

The Impact of EuroSCORE II Risk Factors on Prediction of Long-Term Mortality.

BACKGROUND: The European System for Cardiac Operation Risk Evaluation (EuroSCORE) II has not been tested yet for predicting long-term mortality. This study was undertaken to evaluate the relationship between EuroSCORE II and long-term mortality and to develop a new algorithm based on EuroSCORE II factors to predict long-term survival after cardiac surgery. METHODS: Complete data on 10,033 patients who underwent major cardiac surgery during a 7-year period were retrieved from three prospective institutional databases and linked with the Italian Tax Register Information System. Mortality at follow-up was analyzed with time-to-event analysis. RESULTS: The Kaplan-Meier estimates of survival at 1 and 5 were, respectively, 95.0% ± 0.2% and 84.7% ± 0.4%. Both discrimination and calibration of EuroSCORE II decreased in the prediction of 1-year and 5-year mortality. Nonetheless, EuroSCORE II was confirmed to be an independent predictor of long-term mortality with a nonlinear trend. Several EuroSCORE II variables were independent risk factors for long-term mortality in a regression model, most of all very low ejection fraction (less than 20%), salvage operation, and dialysis. In the final model, isolated mitral valve surgery and isolated coronary artery bypass graft surgery were associated with improved long-term survival. CONCLUSIONS: The EuroSCORE II cannot be considered a direct estimator of long-term risk of death, as its performance fades for mortality at follow-up longer than 30 days. Nonetheless, it is nonlinearly associated with long-term mortality, and most of its variables are risk factors for long-term mortality. Hence, they can be used in a different algorithm to stratify the risk of long-term mortality after surgery.

Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement for Severe Aortic Stenosis in Patients With Chronic Kidney Disease Stages 3b to 5.

BACKGROUND: There are scarce data on outcomes after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in patients with renal failure. METHODS: We evaluated the impact of renal failure on outcomes after TAVI and SAVR and compared the results of these procedures in patients with chronic kidney disease stages 3b to 5 from the Observational Study of Effectiveness of AVR-TAVI Procedures for Severe Aortic Stenosis Treatment (OBSERVANT) study. RESULTS: Chronic kidney disease (CKD) stages 3b to 5 was associated with an increased risk of mortality after either TAVI or SAVR compared with CKD stages 1 to 3a. Among 170 propensity score-matched pairs with CKD stages 3b to 5, patients who underwent TAVI had a significantly higher rate of permanent pacemaker implantation, vascular damage, and mild to moderate paravalvular regurgitation, and tended to have a higher 30-day mortality (7.1% versus 2.9%; p = 0.09). Thirty-day mortality after transapical TAVI was 7.1%. SAVR had a significantly higher rate of blood transfusions, stroke, and acute kidney injury. At 2 years, patients undergoing TAVI had somewhat higher all-cause mortality (31.2% versus 23.4%; p = 0.118), major cardiac and cerebrovascular events (37.2% versus 31.0%; p = 0.270), and a lower risk of dialysis (12.4% versus 21.2%; p = 0.052) compared with SAVR. CONCLUSIONS: CKD stages 3b to 5 increases the risk of mortality after TAVI and SAVR. In this subset of patients, SAVR was associated with somewhat better early and late survival. The risk of acute kidney injury was higher after SAVR. These findings suggest that CKD stages 3b to 5 does not contraindicate SAVR. Strategies to prevent severe acute kidney injury should be implemented with either SAVR or TAVI.

Reliability of Modern Scores to Predict Long-Term Mortality After Isolated Aortic Valve Operations.

BACKGROUND: Contemporary scores for estimating perioperative death have been proposed to also predict also long-term death. The aim of the study was to evaluate the performance of the updated European System for Cardiac Operative Risk Evaluation II, The Society of Thoracic Surgeons Predicted Risk of Mortality score, and the Age, Creatinine, Left Ventricular Ejection Fraction score for predicting long-term mortality in a contemporary cohort of isolated aortic valve replacement (AVR). We also sought to develop for each score a simple algorithm based on predicted perioperative risk to predict long-term survival. METHODS: Complete data on 1,444 patients who underwent isolated AVR in a 7-year period were retrieved from three prospective institutional databases and linked with the Italian Tax Register Information System. Data were evaluated with performance analyses and time-to-event semiparametric regression. RESULTS: Survival was 83.0% ± 1.1% at 5 years and 67.8 ± 1.9% at 8 years. Discrimination and calibration of all three scores both worsened for prediction of death at 1 year and 5 years. Nonetheless, a significant relationship was found between long-term survival and quartiles of scores (p < 0.0001). The estimated perioperative risk by each model was used to develop an algorithm to predict long-term death. The hazard ratios for death were 1.1 (95% confidence interval, 1.07 to 1.12) for European System for Cardiac Operative Risk Evaluation II, 1.34 (95% CI, 1.28 to 1.40) for the Society of Thoracic Surgeons score, and 1.08 (95% CI, 1.06 to 1.10) for the Age, Creatinine, Left Ventricular Ejection Fraction score. CONCLUSIONS: The predicted risk generated by European System for Cardiac Operative Risk Evaluation II, The Society of Thoracic Surgeons score, and Age, Creatinine, Left Ventricular Ejection Fraction scores cannot also be considered a direct estimate of the long-term risk for death. Nonetheless, the three scores can be used to derive an estimate of long-term risk of death in patients who undergo isolated AVR with the use of a simple algorithm.

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.

Impact of off-pump coronary artery bypass grafting on long-term percutaneous coronary interventions.

OBJECTIVES: The debate regarding the advantages and limitations of off-pump versus on-pump coronary artery bypass grafting (CABG) has yet to be resolved. This study was designed to compare the impact of surgical technique on long-term mortality and subsequent revascularization. METHODS: The Predicting Long-Term Outcomes After Isolated Coronary Artery Bypass Surgery (PRIORITY) project was designed to evaluate the long-term outcomes of 2 large, prospective multicenter cohort studies on CABG conducted in Italy between 2002 and 2004 and in 2007 and 2008. Clinical data on isolated CABG were compiled from 2 administrative databases. RESULTS: The study population consisted of 11,021 patients who underwent isolated CABG (27.2% off-pump CABG). Surgical strategy did not affect in-hospital mortality. Multivariate logistic regression demonstrated that on-pump CABG was the only factor that protected from in-hospital percutaneous coronary intervention after surgery (odds ratio, 0.61). Although unadjusted long-term survival was significantly worse for off-pump CABG, adjustment did not confirm off-pump CABG as a risk factor for mortality (hazard ratio, 0.96; 95% confidence interval, 0.87-1.06). The on-pump CABG group had a significantly lower hospitalization for subsequent percutaneous coronary intervention, a finding confirmed even with adjustment for confounding factors (hazard ratio, 0.70; 95% confidence interval, 0.62-0.80; P < .001). Off-pump CABG thus carried a 42% higher risk for subsequent percutaneous coronary intervention than on-pump CABG. The incidence of repeat CABG was similar between groups. CONCLUSIONS: This study demonstrated that off-pump OPCAB did not affect short- and long-term mortality, but it was a significant risk factor for rehospitalization for percutaneous coronary intervention.

Midterm Outcome of Coronary Artery Bypass Grafting in Young Patients: A Multicenter Italian Study.

BACKGROUND: Myocardial revascularization in young patients should be durable enough to avoid new cardiovascular events or repeated revascularization procedures. The aim of this study was to evaluate the late outcomes of patients less than 50 years of age undergoing coronary artery bypass grafting (CABG) in comparison with older patients. METHODS: This study was a survival analysis of a pooled multicenter prospective cohort of patients who underwent CABG. RESULTS: Five percent of patients (572 of 11,087) were less than 50 years of age. The prevalence of female sex, pulmonary disease, diabetes, stroke, and extracardiac arteriopathy was lower compared with that in older patients. Left ventricular function was more well preserved in patients less than 50 years of age, but the prevalence of recent myocardial infarction and the need for emergency surgical intervention was significantly higher in young patients. Multiple propensity score-adjusted analysis showed that patients aged less than 50 years had a significantly lower risk of mortality, even when compared with the 50- to 59-year stratum. In the propensity score-matched population (544 pairs), patients less than 50 years of age had significantly better 7-year outcomes compared with patients aged 50 years or more: survival (95.6% versus 81.1%; p < 0.0001), freedom from stroke (97.4% versus 95.3%; p = 0.009), freedom from major adverse cardiac and cerebrovascular events (MACCE) (76.6% versus 63.9%; p = 0.002). Similar freedom from myocardial infarction (90.1% versus 90.1%; p = 0.68) and repeated revascularization (87.1% versus 87.2%; p = 0.65) was observed in patients less than 50 years of age and those older than 50 years. CONCLUSIONS: Patients less than 50 years of age undergoing CABG have an excellent outcome compared with elderly patients. These data indicate that despite its premature onset, coronary artery disease in young patients does not have a more aggressive course than that in older patients.

Idiopathic Pulmonary Fibrosis (IPF) incidence and prevalence in Italy.

BACKGROUND: Studies of Idiopathic Pulmonary Fibrosis (IPF) epidemiology show regional variations of incidence and prevalence; no epidemiological studies have been carried out in Italy. OBJECTIVE: To determine incidence and prevalence rates of IPF in the population of a large Italian region. METHODS: in this cross-sectional study study data were collected on all patients of 18 years of age and older admitted as primary or secondary idiopathic fibrosing alveolitis (ICD9-CM 516.3) to Lazio hospitals, from 1/1/2005 to 31/12/2009, using regional hospital discharge, population and cause of death databases. Reporting accuracy was assessed on a random sample of hospital charts carrying the ICD9-CM 516.3, 516.8, 516.9 and 515 codes, by reviewing radiology and pathology findings to define cases as IPF "confident", "possible" or "inconsistent". RESULTS: Annual prevalence and incidence of IPF were estimated at 25.6 per 100,000 and 7.5 per 100,000 using the ICD9-CM code 516.3 without chart audit while they were estimated at 31.6 per 100,000 and at 9,3 per 100,000 for the IPF "confident" definition after hospital chart audit. CONCLUSION: The data provide a first estimate of IPF incidence in Italy and indicate that incidence and prevalence in southern European regions may be similar to those observed in northern Europe and North America.

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.