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Healthcare utilisation databases, and other secondary data sources, have been used with growing frequency to assess health outcomes and healthcare interventions worldwide. Their increased popularity as a research tool is due to their timely availability, the large patient populations covered, low cost, and applicability for studying real-world clinical practice. Despite the need to measure Italian National Health Service performance both at regional and national levels, the wealth of good quality electronic data and the high standards of scientific research in this field, healthcare research and public health policies seem to progress along orthogonal dimensions in Italy. The main barriers to the development of evidence-based public health include the lack of understanding of evidence-based methodologies by policy makers, and of involvement of researchers in the policy process. The CRACK programme was launched by some academics from the Lombardy Region. By extensively using electronically stored data, epidemiologists, biostatisticians, pharmacologists and clinicians applied methods and evidence to several issues of healthcare research. The CRACK programme was based on their intention to remove barriers that thwart the process of bridging methods and findings from scientific journals to public health practice. This paper briefly describes aim, articulation and management of the CRACK programme, and discusses why it might find articulated application in Italy.

PURPOSE To evaluate the prescription of preventive medications with questionable usefulness in community dwelling elderly adults with cancer or chronic progressive diseases during the last year of life. METHODS Through the utilization of the healthcare databases of the Lombardy region, Italy, we identified two retrospective cohorts of patients aged 65 years or more, who died in 2018 and had a diagnosis of either a solid cancer (N = 19 367) or a chronic progressive disease (N = 27 819). We estimated prescription of eight major classes of preventive drugs 1 year and 1 month before death; continuation or initiation of preventive drug use during the last month of life was also investigated. RESULTS Over the last year of life, in both oncologic and non-oncologic patients, we observed a modest decrease in the prescription of blood glucose-lowering drugs, anti-hypertensives, lipid-modifying agents, and bisphosphonates, and a slight increase in the prescription of vitamins, minerals, antianemic drugs, and antithrombotic agents (among oncologic patients only). One month before death, the prescription of preventive drugs was still common, particularly for anti-hypertensives, antithrombotics, and antianemics, with more than 60% of patients continuing to be prescribed most preventive drugs and an over 10% starting a therapy with an antithrombotic, an antianemic, or a vitamin or mineral supplement. CONCLUSION These findings support the need for an appropriate drug review and improvement in the quality of drug prescription for vulnerable populations at the end-of-life.

To date, the pandemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has involved over 100 countries in a matter of weeks, and Italy suffers from almost 1/3 of the dead cases worldwide. In this report, we show the strategies adopted to face the emergency at Centro Cardiologico Monzino, a mono-specialist cardiology hospital sited in the region of Italy most affected by the pandemic, and specifically we describe how we have progressively modified in a few weeks the organization of our Heart Failure Unit in order to cope with the new COVID-19 outbreak. In fact, on the background of the pandemic, cardiovascular diseases still occur frequently in the general population, but we observed consistent reduction in hospital admissions for acute cardiovascular events and a dramatic increase of late presentation acute myocardial infarction. Despite a reduction of healthcare workers number, our ward has been rearranged in order to take care of both COVID-19 and cardiovascular patients. In particular according to a triple step procedure we divided admitted patients in confirmed, suspected and excluded cases (respectively allocated in “red”, “pink” and “green” separated areas). Due to the absence of definite guidelines, our aim was to describe our strategy in facing the current emergency, in order to reorganize our hospital in a dynamic and proactive manner. To quote the famous Italian writer Alessandro Manzoni ‘It is less bad to be agitated in doubt than to rest in error.’

OBJECTIVES Although it has been postulated that patients might benefit from the centralization of high-volume specialized centres, conflicting results have been reported on the relationship between the number of lung resections performed and the long-term, all-cause mortality rates among patients who underwent surgery for lung cancer. A population-based observational study was performed to contribute to the ongoing debate. METHODS The 2613 patients, all residents of the Lombardy region (Italy), who underwent lung resection for lung cancer from 2012 to 2014 were entered into the cohort and were followed until 2018. The hospitals were classified according to the annual number of pulmonary resections performed. Three categories of lung resection cases were identified: low (≤30), intermediate (31–95) and high (>95). The outcome of interest was all-cause death. A frailty model was used to estimate the death risk associated with the categories of numbers of lung resections performed, taking into account the multilevel structure of the data. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. RESULTS The 1-year and 5-year survival rates of cohort members were 90% and 63%. Patients operated on in high-volume centres were on average younger and more often women. Compared to patients operated on in a low-volume centre, the mortality risk exhibited a significant, progressive reduction as the numbers of lung resections performed increased to intermediate (−13%; 95% confidence interval +10% to −31%) and high (−26%; 0% to −45%). Sensitivity analyses revealed that the association was consistent. CONCLUSIONS Further evidence that the volume of lung resection cases performed strongly affects the long-term survival of lung cancer patients has been supplied.

Objective Several factors affect adherence to antihypertensive drug treatment, but whether these factors include a sex difference is unclear. Aim of the study was to compare persistence with antihypertensive drug therapy between men and women in a large cohort of patients. Methods The 60 526 residents of the Italian Lombardy Region aged 40-80 years newly treated with antihypertensive drugs during 2010 were identified and followed for 1 year after the first prescription. Discontinuation of treatment was defined as lack of prescription renewal for at least 90 days. Log-binomial regression models were fitted to estimate the risk ratio of treatment discontinuation in relation to sex. Other than for the whole population, analyses were stratified according to age, comorbidity status and the initial antihypertensive treatment strategy. Results Thirty-seven percent of the patients discontinued the drug treatment during follow-up. Compared with women, men had a 10% lower risk of discontinuation of drug treatment (95% confidence interval: 8-12). Persistence on antihypertensive treatment was better in men than in women, this being the case in both younger (40-64 years) and older patients (65-80 years), in patients starting treatment with any major antihypertensive drug and in patients who had a low comorbidity status. There was no evidence that men and women had a different risk of treatment discontinuation when their comorbidity status was worse, or initial antihypertensive treatment was based on drug combinations. Conclusion Our data show that in a real-life setting, men are more persistent to antihypertensive drug therapy than women.

Antenatal care (ANC) aims of monitoring wellbeing of mother and foetus during pregnancy. We validate a set of indicators aimed of measuring the quality of ANC of women on low-risk, uncomplicated pregnancy through their relationship with maternal and neonatal outcomes. We conducted a population-based cohort study including 122,563 deliveries that occurred between 2015 and 2017 in the Lombardy Region, Italy. Promptness and appropriateness of number and timing of gynaecological visits, ultrasounds and laboratory tests were evaluated. We assessed several maternal and neonatal outcomes. Log-binomial regression models were used to estimate prevalence ratio (PR), and corresponding 95% confidence interval (95% CI), for the exposure&rarr, outcome association. Compared with women who adhered with recommendations, those who were no adherent had a significant higher prevalence of maternal intensive care units admission (PR: 3.1, 95%CI: 1.2&ndash, 7.9, and 2.7, 1.1&ndash, 7.0 respectively for promptness of gynaecological visits, and appropriateness of ultrasound examinations), low Apgar score (1.6, 1.1&ndash, 1.2, 1.9, 1.3&ndash, 2.7, and 2.1, 1.5&ndash, 2.8 respectively for appropriateness and promptness of gynaecological visits, and appropriateness of ultrasound examinations), and low birth weight (1.8, 1.5&ndash, 2.3 for appropriateness of laboratory test examinations). Benefits for mothers and newborn are expected from improving adherence to guidelines-driven recommendations regarding antenatal care even for low-risk, uncomplicated pregnancies.

BACKGROUND Observational studies showed that exposure to exogenous insulin increases fracture risk. However, it remains unclear whether the observed association is a function of the severity of underlying type 2 diabetes mellitus, complications, therapies, comorbidities, or all these factors combined. That being so, and because of the relative infrequency of these events, it is important to study this further in a large-database setting. QUESTION/PURPOSES: (1) Is switching from oral antidiabetic agents to insulin associated with an increased fracture risk? (2) How soon after switching does the increased risk appear, and for how long does this increased risk persist? METHODS Data from healthcare utilization databases of the Italian region of Lombardy were used. These healthcare utilization databases report accurate, complete, and interconnectable information of inpatient and outpatient diagnoses, therapies, and services provided to the almost 10 million residents in the region. The 216,624 patients on treatment with oral antidiabetic therapy from 2005 to 2009 were followed until 2010 to identify those who modified their antidiabetic therapy (step 1 cohort). Among the 63% (136,307 patients) who experienced a therapy modification, 21% (28,420 patients) switched to insulin (active exposure), and the remaining 79% (107,887 patients) changed to another oral medication (referent exposure). A 1:1 high-dimension propensity score matching design was adopted for balancing patients on active and referent exposure. Matching failed for 3% of patients (926 patients), so the cohort of interest was formed by 27,494 insulin-referent couples. The latter were followed until 2012 to identify those who experienced hospital admission for fracture (outcome). A Cox proportional hazard model was fitted to estimate the hazard ratio (HR) for the outcome risk associated with active-exposure (first research question). Between-exposure comparison of daily fracture hazard rates from switching until the 24 successive months was explored through the Kernel-smoothed estimator (second research question). RESULTS Compared with patients on referent exposure, those who switched to insulin had an increased risk of experiencing any fracture (HR = 1.5 [95% CI 1.3 to 1.6]; p < 0.001). The same risk was observed for hip and vertebral fractures, with HRs of 1.6 (95% CI 1.4 to 1.8; p < 0.001) and 1.8 (95% 1.5 to 2.3; p < 0.001), respectively. Differences in the daily pattern of outcome rates mainly appeared the first 2 months after switching, when the hazard rate of patients on active exposure (9 cases for every 100,000 person-days) was higher than that of patients on referent exposure (4 cases for every 100,000 person-days). These differences persisted during the remaining follow-up, though with reduced intensity. CONCLUSIONS We found quantitative evidence that switching from oral antidiabetic therapy to insulin is associated with an increased fracture risk, mainly in the period immediately after the start of insulin therapy. The observed association may result from higher hypoglycemia risk among patients on insulin, which leads to a greater number of falls and resulting fractures. However, although our study was based on a large sample size and highly accurate data, its observational design and the lack of clinical data suggest that future research will need to replicate or refute our findings and address the issue of causality, if any. Until then, though, prescribers and patients should be aware of this risk. Careful control of insulin dosage should be maintained and measures taken to reduce fall risk in these patients. LEVEL OF EVIDENCE Level III, therapeutic study.

Objectives The aim of this study was to develop a new population-based risk stratification tool (Chronic Related Score [CReSc]) for predicting 5-year mortality and other outcomes. Study Design and Setting The score included 31 conditions selected from a list of 65 candidates whose weights were assigned according to the Cox model coefficients. The model was built from a sample of 5.4 million National Health Service (NHS) beneficiaries from the Italian Lombardy Region and applied to the remaining 2.7 million NHS beneficiaries. Predictive performance was assessed by discrimination and calibration. CReSc ability in predicting secondary endpoints (i.e., hospital admissions and health care costs) was investigated. Finally, the relationship between CReSc and income was considered. Results Among individuals aged 50–85 years, CReSc performance showed (1) an area under the receiver operating characteristic curve of 0.730, (2) an improved reclassification from 44% to 52% with respect to other scores, and (3) a remarkable calibration. A trend toward increasing rates of all the considered endpoints as CReSc increases was observed. Compared with individuals on low–intermediate income, NHS beneficiaries on high income showed better CReSc profile. Conclusion We developed a risk stratification tool able to predict mortality, costs, and hospital admissions. The application of CReSc may generate clinically and operationally important effects.

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

Aims Data on the impact of liver disease (LD) in patients with atrial fibrillation (AF) and the role of oral anticoagulant (OAC) drugs for stroke prevention, are limited. We analysed the impact of LD and OAC treatment in determining stroke, major bleeding, all-cause death and secondary bleeding outcomes. Methods A retrospective observational population-based cohort study. The study cohort is derived from the administrative health databases of Lombardy region (>10 million inhabitants), Italy. All AF patients ≥40 years admitted to hospital from 2000 to 2018 were considered. AF and LD diagnosis were established using ICD9-CM codes. Use of OAC was determined with Anatomical Therapeutic Chemical (ATC) codes. Primary study outcomes were stroke, major bleeding and all-cause death. Results Among 393,507 AF patients, 16,168 (4.1%) had concomitant LD. LD AF patients were significantly less treated with OAC independent of associated clinical characteristics (OR: 0.96, 95% CI: 0.92–0.98). Concomitant LD was found associated with an increased risk in all the study outcomes (HR: 1.18, 95% CI: 1.11–1.25 for stroke; HR: 1.57, 95% CI: 1.47–1.66 for major bleeding; HR: 1.41, 95% CI: 1.39–1.44 for all-cause death. Use of OAC in patients with AF and LD resulted in a reduction in stroke (HR: 0.80, 95% CI: 0.70–0.92), major bleeding (HR: 0.86, 95% CI: 0.74–0.99) and all-cause death (HR: 0.85, 95% CI: 0.80–0.90), with similar results according to several clinically relevant subgroups. A net clinical benefit (NCB) analysis suggested a positive benefit/risk ratio in using OAC in AF patients with LD (NCB: 0.408, 95% CI: 0.375–0.472). Conclusions In AF patients, concomitant LD carries a significantly higher risk for all clinical outcomes. Use of OAC in AF patients with LD was associated with a significant benefit/risk ratio, even in high-risk patient subgroups. Funding Acknowledgement Type of funding source: None

The highly contagious coronavirus that causes COVID-19 disease is affecting daily clinical practice. The anticipated fast growth in cases has led to development of a regional restructuring model to preserve time-sensitive pathologies in northern Italy. On this way, the Lombardy Region Government built up a big hub-and-spoke model to converge treatment of acute coronary syndrome (ACS) in 13 dedicated centres active 24/7 in the region, implementing availability of intensive care unit beds in general hospitals converted to COVID-19 treatment.1Our institute is one of the 4 selected hubs in Milan for cardiovascular emergences, therefore, to prevent in-hospital infection spread and to proactively minimize in-hospital patients to exposure risk, we set an internal pathway for ACS, allowing all patients to be timely treated and admitted to isolated intensive care unit or ordinary ward beds, according to nasopharyngeal swab result. Hospital admissions due to ACS of patients living in the hospital area only, were screened between March 8 and April 10, a period of national lockdown, and compared with the same timeframe in2019.

Aim of our study was to assess the relationship between adherence with antihypertensive drugs and the risk of death in frail versus nonfrail old individuals. Using the database of the Lombardy Region (Italy), we identified 1 283 602 residents aged ≥65 years (mean age 76) who had ≥3 prescriptions of antihypertensive drugs between 2011 and 2012. A nested case-control design was applied, with cases being the cohort members who died during the observation period (7 years). Logistic regression was used to model the association of interest, with adjustment for potential confounders. Adherence was measured by the proportion of the follow-up covered by prescriptions, and the analysis was separately performed in patients with a good, medium, poor, and very poor clinical status, as assessed by a score that has been shown to be a sensitive predictor of death in the Italian population. The 7-year death probability increased from 16% (good) to 64% (very poor) clinical status. Compared with patients with very low adherence with antihypertensive treatment (75% of time covered by prescriptions) exhibited a lower risk of all-cause mortality in each group, the difference decreasing progressively (−44%, −43%, −40%, and −33%) from the good to the very poor clinical status. Adherence with antihypertensive drug treatment was also associated with a lower risk of cardiovascular mortality. Adherence with antihypertensive appears to be protective in frail old patients, but the benefit is less marked than in patients with a good clinical status.

Background and objectivesHospital readmissions are a frequent complication of pneumonia. Most data regarding readmissions are obtained from the United States, whereas few data are available from the European healthcare utilization (HCU) systems. In a large cohort of Italian patients with a previous hospitalization for pneumonia, our aim was to evaluate the incidence and predictors of early readmissions due to pneumonia.MethodsThis is a observational retrospective, population based, cohort study. Data were retrieved from the HCU databases of the Italian Lombardy region. 203,768 patients were hospitalized for pneumonia between 2003 and 2012. The outcome was the first rehospitalization for pneumonia. The patients were followed up after the index hospital admission to estimate the hazard ratio, and relative 95% confidence interval, of the outcome associated with the risk factors that we had identified.Results7,275 patients (3.6%) had an early pneumonia readmission. Male gender, age ≥70 years, length of stay of the first admission and a higher burden of comorbidities were significantly associated with the outcome. Chronic use of antidepressants, antiarrhythmics, glucocorticoids and drugs for obstructive airway diseases were also more frequently prescribed in patients requiring rehospitalization. Previous use of inhaled broncodilators, including both beta2-agonists and anticholinergics, but not inhaled steroids, were associated with an increased risk of hospital readmission.ConclusionsFrail elderly patients with multiple comorbidities and complex drug regimens were at higher risk of early rehospitalization and, thus, may require closer follow-up and prevention strategies.

Owing to the COVID-19 outbreak in Lombardy, Italy) there is an urgent need to manage cardiovascular emergencies, including acute coronary syndrome (ACS), with appropriate standards of care and dedicated preventive measures and pathways against the risk of SARS-CoV-2 infection. For this reason, the Government of Lombardy decided to centralize the treatment of ACS patients in a limited number of centers, including our university cardiology institute, which in the past 4 weeks became a cardiovascular emergency referral center in a regional hub-and-spoke system. Therefore, we rapidly developed a customized pathway to allocate patients to the appropriate hospital ward, and treat them according to ACS severity and risk of suspected SARS-CoV-2 infection. We present here the protocol dedicated to ACS patients adopted in our center since March 13, 2020, and our initial experience in the management of ACS patients during the first 4 weeks of its use. Certainly, the protocol has room for further improvement as everyone's experience grows, but we hope that it could be a starting point, adaptable to different realities and local resources.

BackgroundTo evaluate medication adherence and associated factors of seven of the most common drug classes prescribed to community-dwelling older people.MethodsThis is a retrospective cohort study on medication adherence in community-dwelling older people (65–94 years old) on chronic polypharmacy and recorded from 2013 to 2015 in the administrative database of the Lombardy region (Northern Italy). Adherence was assessed for diabetic drugs, antithrombotic agents, drugs acting on the renin–angiotensin system, statins, bisphosphonates, antidepressants and drugs for obstructive airway diseases by calculating the medication possession ratio (MPR). Patients were then divided in fully (MPR ≥80%), partially (40%≤MPRResultsAmong 140 537 patients included in the study, only 19.3% was fully adherent to all the therapies considered. Almost 40% of them were poorly adherent to at least one drug class, becoming 50% when patients exposed to four or more drug classes were considered. In adjusted regression model, being women (OR=1.14, 95% CI 1.13 to 1.16) and aged ≥80 years old (OR=1.22, 95% CI 1.20 to 1.24) were associated with an overall lower adherence. Instead, the participation to an experimental healthcare programme was associated with higher adherence (OR=0.92, 95% CI 0.87 to 0.96). Furthermore, being coprescribed with ≥10 drugs was associated with lower adherence to all the drug classes, with different effects (ORs from 0.42 to 0.73).ConclusionThis study overall shows a low medication adherence in community-dwelling older people on chronic polypharmacy, especially in women and oldest old. The implementation and promotion of healthcare programmes for these patients could help improve overall adherence to chronic drug therapies.

Aim To provide information on the balance between the cardiovascular (CV) benefit and the diabetogenic harm of statin therapy in the current clinical practice. Methods All the 115,939 residents (older than 50 years) in the Italian Lombardy Region newly treated with statins between 2003 and 2005, were followed from the first statin prescription until 2012 to identify those experiencing a macrovascular complication and those with at least one sign suggestive of new onset diabetes. The proportion of days of follow-up covered by statin prescriptions measured adherence with statins. Hazard ratio, and relative 95% confidence interval (CI), for the two considered outcomes associated with statin adherence, were separately estimated (proportional hazard models). Number needed to treat (NNT) and number needed to harm (NNH), i.e., number of individuals who must be treated with statins in order to prevent a macrovascular complication, or to generate a new onset diabetes, respectively, were calculated to evaluate the balance between CV benefit and diabetogenic harm of statin therapy. Results Compared to those at very low adherence with statins, patients at high adherence showed a significant reduction of macrovascular risk (28%, 95% CI: 23%–33%) and a greater risk of developing diabetic condition (67%, 50%-86%). In the whole cohort, the NNT was 26, whereas the NNH 65. NNT was lower than NNH also in all considered strata of age, gender, clinical profile. Conclusions This large cohort investigation provides real-world evidence that the balance between CV benefit and diabetogenic harm of statin therapy is largely favourable to treatment benefits.

Background Multimorbidity is a growing concern for healthcare systems, with many countries experiencing demographic transition to older population profiles. A simple multisource comorbidity score (MCS) has been recently developed and validated. A very large real-world investigation was conducted with the aim of measuring inequalities in the MCS distribution across Italy. Methods Beneficiaries of the Italian National Health Service aged 50–85 years who in 2018 were resident in one of the 10 participant regions formed the study population (15.7 million of the 24.9 million overall resident in Italy). MCS was assigned to each beneficiary by categorizing the individual sum of the comorbid values (i.e. the weights corresponding to the comorbid conditions of which the individual suffered) into one of the six categories denoting a progressive worsening comorbidity status. MCS distributions in women and men across geographic partitions were compared. Results Compared with beneficiaries from northern Italy, those from centre and south showed worse comorbidity profile for both women and men. MCS median age (i.e. the age above which half of the beneficiaries suffered at least one comorbidity) ranged from 60 (centre and south) to 68 years (north) in women and from 63 (centre and south) to 68 years (north) in men. The percentage of comorbid population was lower than 50% for northern population, whereas it was around 60% for central and southern ones. Conclusion MCS allowed of capturing geographic variability of multimorbidity prevalence, thus showing up its value for addressing health policy in order to guide national health planning.

Background Patients who experience a hospital admission for acute coronary syndromes (ACS) exhibit poor prognosis over the years. The purposes of this study were to evaluate the real-world patterns of out-of-hospital practice in the management of ACS patients and to assess their impact on the risk of selected outcomes. Methods The cohort of 87,530 residents in the Lombardy Region (Italy) who were newly hospitalised for ACS during 2011–2015 was followed until 2018. Exposure to medical treatment including use of selected drugs, diagnostic procedures and laboratory tests was recorded. The main outcome of interest was re-hospitalisation for cardiovascular (CV) outcomes. Proportional hazards models were fitted to estimate hazard ratio, and 95% confidence intervals (CI), for the exposure-outcome association. Analyses were stratified according to the ACS type. Results The cumulative incidence of re-hospitalisation for CV disease was 33%, 42% and 38% at 5 years after index discharge among STEMI, NSTEMI and unstable angina patients. Within one year from index discharge, between 70% and 80% of patients had at least a prescription of statins, beta-blockers and renin–angiotensin-system blocking agents, underwent ECG and lipid profile examination, and had a cardiologic examination. One patient in five underwent cardiac rehabilitation. Compared with patients who did not adhere to healthcare recommendations, the risk of CV hospital readmission was reduced from 10% (95% CI: 4%–10%) to 23% (12%–32%) among patients who underwent lipid profile examinations and who experienced cardiac rehabilitation. Conclusion Close out-of-hospital healthcare must be considered the cornerstone for improving the long-term prognosis of ACS patients.

In many hypertensive patients, treatment is not upgraded despite lack of blood pressure control because of therapeutic inertia. Information is limited, however, on the extent of this phenomenon in real-life medicine. We studied 125 635 patients (age 40–85 years) from the Lombardy region (Italy) who started antihypertensive treatment with 1 drug (n=100 982) or a 2-drug fixed-dose or free combination (n=24 653). A log-binomial regression model was used to estimate the prevalence ratio of combination therapy in relation to the initial treatment strategy. In the initial monotherapy group, patients under drug combinations were 22%, 27%, 32%, and 36% at 6 months, 1, 2, and 3 years later. In the initial combination treatment group, the corresponding percentages were 85%, 82%, 79%, and 78%. This translated into a markedly greater covariate-adjusted propensity of being under a multidrug prescription throughout the follow-up: 3.92 (95% CI, 3.84–4.00) after 6 months and 3.18 (3.12–3.25), 2.56 (2.51–2.60), and 2.23 (2.19–2.27) after 1, 2 and 3 years of treatment. In a propensity score analysis, initial 2-drug combination treatment was also associated with significant reductions in the risk of death (−20%, 11% to 28%) and hospitalization for cardiovascular events (−16%, 10% to 21%) compared with initial monotherapy. Thus, in real life, a large number of patients prescribed initial monotherapy fails to move to combination treatment, as recommended by guidelines. This implies that therapeutic inertia frequently prevents proper treatment uptitration, thereby playing a major role in the low rate of hypertension control that exists worldwide.

Aims: Guidelines support use of drug combinations in most hypertensive patients, and recently treatment initiation with two drugs has been also recommended. However, limited evidence is available on whether this leads to greater cardiovascular (CV) protection compared to initial monotherapy. Methods and results: Using the healthcare utilization database of the Lombardy Region (Italy), the 44 534 residents of the region (age 40-80 years) who in 2010 started treatment with one antihypertensive drug (n = 37 078) or a two-drug fixed-dose combination (FDC, n = 7456) were followed for 1 year after treatment initiation to compare the risk of hospitalization for CV disease associated with the two treatment strategies. To limit the confounding associated with non-randomized between-group comparisons, data were also analysed by: (i) matching the two groups by the high-dimensional propensity score (HDPS) and (ii) comparing, in patients experiencing one or more CV events (n = 2212), the CV event incidence during subperiods in which patients were prescribed mono- or FDC therapy (self-controlled case series design). Compared to initial monotherapy, patients on initial FDC therapy showed a reduced 1 year risk of hospitalization for any CV event (-21%, P

Introduction: Nimesulide is the most prescribed non-steroidal anti-inflammatory drug in Italy, and it is currently marketed in about 50 countries worldwide. The association between the use of nimesulide in early pregnancy and the risk of birth defects was investigated in a large cohort of pregnant women from Italy. Methods: Data were from the healthcare utilization databases of the Italian region of Lombardy. The cohort of 353,081 newborns occurring in Lombardy during the period 2005–2010 was investigated. Exposure to nimesulide during the first trimester of pregnancy, and congenital malformations detected at presentation and within 90 days after birth (outcome), were investigated. Exposure–outcome association was measured by the ratio between the prevalence of congenital malformations among users and non-users of nimesulide. Propensity score stratification was used to control for potential confounders, including maternal medical comorbidities, concomitant medications and sociodemographic characteristics. Results: The 627 (0.18%) women who filled prescriptions for nimesulide in the first trimester of pregnancy had a 2.6-fold risk of having children with congenital urinary tract anomalies compared to those who did not (adjusted prevalence ratio 2.6; 95% CI 1.2–5.7). Weaker and non-significant evidence for congenital malformations as a whole was found (adjusted prevalence ratio 1.2, 95% CI 0.9–1.6). Conclusion: Our study suggests that the use of nimesulide in early pregnancy may result in a greater risk of having births with congenital urinary tract anomalies. Funding: This study was funded by grants from the Italian Ministry of the Education, University and Research (’Fondo d’Ateneo per la Ricerca’ portion, year 2015)

Background The aim of our study was to evaluate whether treatments for peripheral artery disease changed in two different cohorts identified in 2002 and 2008, and whether this had an impact on mortality and major clinical outcomes after six years of follow-up. Methods Using administrative health databases of the largest region in Northern Italy, we identified patients admitted to hospital for peripheral artery disease in 2002 and 2008. Both cohorts were followed for six years. All cause death, acute coronary syndrome, stroke and major amputations, cardiovascular prevention drugs and revascularization procedures were collected. Incidence of events was plotted using adjusted cumulative incidence function estimates. The risk, for each outcome, was compared between 2002–2008 and 2008–2014 using a multivariable Fine and Gray’s semiparametric proportional subdistribution hazards model. Results In 2002 and 2008, 2885 and 2848 patients were identified. Adjusting for age, sex, Charlson comorbidity index and severity of peripheral artery disease we observed a significant reduction (in 2008 vs. 2002) in the risk of acute coronary syndrome (28%), stroke (27%) and major amputation (17%). No change was observed in the risk of death. The percentages of patients with peripheral artery revascularizations, during the hospital stay, increased: 43.8% in 2002 vs. 49.0% in 2008, p Conclusions In six years of follow-up we observed a reduction in risk of major cardiovascular events in 2008–2014 in comparison with the 2002–2008 cohort. Increasing use of revascularization interventions and cardiovascular prevention drugs could have contributed to the better prognosis.

Background Untreated depression and antidepressant use during pregnancy may have negative consequences for births. There are still conflicting data on the potential harmful effects of prenatal antidepressant treatment on child health. Objective To investigate the relationship between the use of antidepressant medication during pregnancy and selected neonatal outcomes. Methods A population-based cohort study including 9825 deliveries exposed to an antidepressant between 9 months before last menstrual date through to delivery, from January 2005 to December 2010 in the Lombardy region of Italy, was conducted. We evaluated the prevalence ratio (PR) of low Apgar score, small for gestational age, intrauterine hypoxia and birth asphyxia, neonatal convulsion, and other respiratory conditions, among infants born to mothers exposed to an antidepressant during pregnancy using log-binomial regression analysis. Fine stratification was applied to the propensity score to account for all potential confounders. Sensitivity and subgroup analyses restricted to specific types of antidepressant, time of exposure, and women with vaginal deliveries and full-term births were also performed. Results A total of 33.4% of women filled at least one prescription during pregnancy. Compared to infants born to mothers with exposure to antidepressants only before pregnancy, those with exposure to antidepressants during pregnancy had an increased prevalence ratio of a low Apgar score (PR, 1.63, 95% CI, 1.01-2.61), intrauterine hypoxia and birth asphyxia (aPR, 1.37, 1.08-1.73), neonatal convulsion (aPR, 2.81, 1.07-7.36), and other respiratory condition (aPR, 1.24, 1.00-1.52). Results were similar in the sensitivity and subgroup analyses. Conclusions Use of antidepressants during pregnancy may have an increased risk for several neonatal outcomes. KEY POINTS In this population-based cohort study, we found a significant increase in the prevalence ratio of low Apgar score, intrauterine hypoxia and birth asphyxia, neonatal convulsion, and other respiratory conditions among who were exposed in utero to antidepressant drugs. These effects seem to be attributable to the treatment rather than to the disease itself. Further researches are needed to evaluate the longer-term developmental outcomes.

Introduction Cesarean delivery rates are rising due to multiple factors, including less use of operative vaginal delivery and vaginal birth after cesarean delivery, which often reflect local obstetric practices. Objectives of the study were to analyze the relations between cesarean delivery, these practices, and perinatal outcomes. Material and methods We included all deliveries in the 72 hospitals of Lombardia, a region in northern Italy, during the year 2013. The delivery certificate was used as data source. Pearson's correlation coefficient and logistic regression were used for statistical analysis. Results We included 87 896 deliveries. The number of deliveries per hospital ranged from 140 to 6123. The rate of cesarean delivery was 28.3% (range 9.9–86.4%), operative vaginal delivery 4.7% (range 0.2–10.0%), and vaginal birth after cesarean 17.3% (range 0–79.2%). We found a significant inverse correlation between rates of overall cesarean delivery and operative vaginal delivery (r = −0.25, p = 0.04). The correlation between rate of overall cesarean delivery and vaginal birth after cesarean was also inverse and significant (r = −0.57, p < 0.001). There was no association between overall cesarean delivery rate and the rates of Apgar score at 5 min

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., Highlights • 4 indicators to assess the quality of care in operated breast cancer were developed. • High heterogeneity across regions in breast cancer-related care was observed. • Almost all the indicators are associated with improved overall survival. • Benefits are expected from improving adherence with the considered recommendations.

ObjectivesThis study aimed to assess the appropriateness of antibiotic prescription in children seen in emergency departments (EDs) and to compare prescription profiles in ED and primary care.DesignThis is a retrospective analysis of healthcare administrative databases.SettingThe study analysed data collected in emergency departments (EDs) and primary care practices (PCPs) in Lombardy, Italy.ParticipantsChildren and adolescents between 1 and 13 years old with an ED access and/or an antibiotic prescription in the first semester of 2012 participated in the study. Only those with an index event (ie, without ED access, hospital admissions or antibiotic prescriptions in the previous 60 days) were included.Main outcome measuresThe main outcomes are percentage of subjects receiving amoxicillin (first-choice antibiotic) and percentages receiving macrolides/cephalosporins (second-choice therapies).ResultsDuring the observation period, 133 275 children had one ED access, and 26 087 (19.6%) received an antibiotic prescription. In all, 56.1% of children seen for upper respiratory tract infections (URTIs) received an antibiotic, with a prevalence of 67.8% for otitis media and 56.4% for pharyngotonsillitis; 22.3% of children were given amoxicillin after a visit for URTIs, with no differences among infections, and 19.6% received macrolides and cephalosporins. Few differences were found when comparing the index antibiotic prescriptions in ED and PCP settings. A higher prescription of second-choice antibiotics was observed among children cared for by PCPs compared with children attending EDs (31.3% vs 23.4%, χ2M-H=720, pConclusionsMore must be done to improve rational use of antibiotics in the ED and PCP setting, and educational interventions including physicians in both setting are strongly needed.

To analyze sex-related differences about AF prevalence, use of OAC and outcomes focusing on the older age classes. We used administrative data of the Lombardy Region, describing period prevalence, use of OAC and outcomes from 2002 to 2014 for all patients diagnosed with AF. AF prevalence over the 2002–2014 period was higher in males than in females (2.7% vs. 2.1%, p

Objectives: To analyze the relationship between atrial fibrillation (AF) and Charlson comorbidity index (CCI) in a population-based cohort study over a long-term follow-up period, in relation to oral anticoagulant (OAC) prescriptions and outcomes. Patients and Methods: We used data from the administrative health databases of Lombardy. All patients with AF and age 40 years and older and who were admitted to the hospital in 2002 were considered for analysis and followed up to 2014. AF diagnosis and CCI were established according to codes from the International Classification of Diseases, Ninth Revision. Results: In 2002, 24,040 patients were admitted with a diagnosis of AF. CCI was higher in patients with AF than in those without AF (1.8±2.1 vs 0.2±0.9; P

Aims: Women with pre-existing diabetes should plan for optimal care of the disease before, during and after pregnancy. The aim of this study was to assess the quality of diabetes mellitus monitoring and care before, during and after pregnancy in a large cohort of women. Methods: 1913 diabetic women resident in the Lombardy Region (Italy) who experienced at least a birth between 2011 and 2015 and exhibited signs of diabetes ≥2 years before delivery were identified using the healthcare utilization database. Antidiabetic care was defined via outpatient examinations (i.e., assessments of glycated haemoglobin, lipid profile, urine albumin excretion and serum creatinine, and dilated eye exams) and use of antidiabetic drugs. Differences in adherence to recommendations before, during and after pregnancy were assessed by the non-parametric McNemar's test among the whole cohort and among the subgroup with type 1 diabetes. Results: Adherence to recommendations was very poor before pregnancy, ranging from 13% to 42% for dilated eye and serum creatinine exam, respectively. During pregnancy, a significant portion of women increased adherence to all recommendations (e.g., glycated haemoglobin from 20% to 47%, p-value < 0.001), with the exception of lipid profile control. After pregnancy, adherence dropped to pre-pregnancy levels. A similar trend was observed in the use of antidiabetic drugs. Although women with type 1 diabetes showed better adherence across all periods, the same patterns emerged. Conclusions: Besides an improvement in the indicators of clinical adherence during pregnancy, the management of diabetes among pregnant women remains sub-optimal both before and after the birth.

Objective: To determine whether out-of-hospital healthcare and adverse outcomes are better in stroke patients admitted to a neurology ward compared with those admitted to general wards. Methods: Beneficiaries of the National Health Service from the Italian Lombardy Region who were discharged alive after hospital admission during the year 2009 for ischemic stroke (9776 patients) or intracerebral or subarachnoid hemorrhage (1102 patients) entered into the cohort and were followed until 2012. Exposure of interest was the ward type where inpatients were admitted (neuro vs. general wards). Outcomes were out-of-hospital healthcare (i.e., drug prescriptions, diagnostic procedures, and laboratory clinical evaluations) and adverse clinical outcomes (i.e., all-cause death and hospital readmission). Exposure-outcome associations were investigated. High-dimensional propensity score methodology was used for taking into account confounders. Mediation analysis was used to verify whether the association between ward type and clinical outcomes is mediated by out-of-hospital adherence to healthcare. Results: Better adherence to out-of-hospital healthcare received from patients discharged from neuro, rather than general, wards was observed being the proportions of adherent patients 42.4% and 39.5%, respectively. Compared with general wards, discharge from neuro was associated with reduced 3-year emergency admissions (from 50.1 to 47.5% among ischemic stroke patients) and reduced 3-year mortality (from 37.5 to 27.0% among hemorrhagic stroke patients). From 10 to 15% of outcome risk, reductions were mediated by better adherence to out-of-hospital healthcare. Conclusions: For patients with acute ischemic and hemorrhagic stroke, admission to neuro vs. general wards is associated with better out-of-hospital healthcare and long-term adverse outcomes.

The aim of the study was to evaluate prescription profiles of antiepileptic drugs (AEDs) and to assess hospitalizations and specialist visits in pediatric patients with epilepsy. The data sources were administrative health databases of Italy’s Lombardy Region, which collect prescriptions for drugs, diagnostic tests, specialist visits, and hospital discharge forms. All patients aged 0–16 years with at least seven AED (group N03A of the International Anatomical Therapeutic Chemical Classification) prescriptions over two consecutive years between 2003 and 2010 were identified and classified as prevalent or incident cases (no prescriptions in two previous years). The first prescription to incident cases was analyzed. For each incident case, drug prescriptions, specialist visits, diagnostic tests, and hospitalizations in the 24 months following the first (index) prescription were monitored. A total of 6527 incident cases (5.4/10,000 person-years, 95% CI 5.4–5.5) were identified. Valproic acid and carbamazepine were the most prescribed drugs (65.9 and 15.0%, respectively). The use of newer AEDs increased over time. In the 24-month observation period, 74% of incident cases continued the treatment with the index AED. The percentage of cases who changed therapy was higher in preschoolers (34%) and decreased with age. In all, 21% of incident cases were hospitalized for epilepsy and 86% had a specialist visit in the 24 months after the first AED prescription. In conclusion, older AEDs, particularly valproic acid, remained the first therapeutic approach to pediatric epilepsy in Italy. For three quarters of cases, the initial AED treatment was likely effective and well tolerated.

to characterise the adverse drugs reactions (ADRs) reported in the Lombard and Croatian paediatric population and to compare data to specific paediatric age groups, in terms of trend, pattern and severity of ADRs, increasing understanding of paediatric ADRs.We selected and analysed all the spontaneous reports in which children were involved (0 18 years old) reported in the Lombardy and in Croatian pharmacovigilance databases from 19175 ADR reports were reported in the Lombardy, 2457 were included in the Croatian database. The age groups most involved were 2-11 for both countries. The 13.2% and 40.3% of reports retrieved in Lombardy and Croatia were classified as serious, respectively. Fatalities account for 0.09% and 0.12% in Lombardy and Croatia, respectively.Data on serious reports reflect a similar scenario in terms of age range; strikingly different therapeutic subgroups were involved in reporting activity likely due to greater self-medication practices with penicillins and anti-inflammatory, analgesic and antipyretics drugs in Lombardy than in Croatia, highlighting the need to closely monitor this paediatric therapeutic area to ensure a safe use of these drugs.

AIM To evaluate the temporal trend and extent of screening for celiac disease in an Italian pediatric population of incident type 1 diabetes in the period 2006-2011, providing information on adherence to guidelines in primary care. METHODS Using the Lombardy region's administrative database, 1-17-year-old children and adolescents diagnosed with type 1 diabetes during the 2006-2011 period were identified. Among these patients, the number screened for celiac disease was calculated on the basis of specific antibodies. RESULTS Of the 1563 children and adolescents receiving a diagnosis of type 1 diabetes during the observational period, 53% were tested for celiac disease compared with 12% of individuals without diabetes. The extent to which screening was performed increased two-fold from the 2006-2008 to the 2009-2011 period (P

Aims Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently co-exist, and each is a major public health issue. In a large cohort of hospitalized HF patients, we evaluated: (i) the impact of COPD on clinical outcomes; (ii) whether outcomes and treatments changed from 2002 to 2009; and (iii) the relationship between outcomes and treatments focusing on beta-blockers (BBs) and bronchodilators (BDs). Methods and results From linkable Lombardy administrative health databases, we selected individuals with a discharge diagnosis of HF with or without concomitant COPD (HF yesCOPD and HF noCOPD) in 2002 and 2009. Patients were followed up for 4 years. Outcomes were total mortality, first readmission for HF, and their combination. Unadjusted and adjusted Cox proportional models and competing risk analyses were used. We identified 11 274 patients with HF noCOPD and 2837 with HF yesCOPD. HF yesCOPD patients in 2002 and 2009 had a 20% higher risk of the outcomes. From 2002 to 2009, BB and BD prescriptions increased significantly. In HF noCOPD patients, risks for mortality [adjusted hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.86–0.97], first HF readmission (HR 0.79, 95% CI 0.74–0.85), and the combined endpoint (HR 0.88, 95% CI 0.84–0.92) declined (all P < 0.003) while in HF yesCOPD only the risk for first HF readmission dropped (HR 0.86, 95% CI 0.76–0.97; P = 0.018). BBs were associated with significantly lower mortality in both groups, but with a higher risk for first HF readmission in HF noCOPD. Outcomes did not significantly differ in HF yesCOPD treated or not with BDs. Conclusions The prognosis of patients hospitalized for HF, either with or without COPD, seemed to improve between 2002 and 2009, with possibly better survival of those on BBs. Because of residual confounding in observational studies, a randomized controlled trial should be considered to confirm these results.

Background and objective Real-world evidence suggests that persistence with inhaled corticosteroids (ICS), the mainstay of asthma drug therapy, is generally poor. The effect of persistence with ICS on the risk of asthma exacerbation was addressed in a population-based study. Methods The cohort of 2335 beneficiaries of the National Health Service provided by the Italian Region of Lombardy, aged 18–40 years and newly treated with ICS during 2005–2008, was followed from their first ICS dispensation until 2010. Discontinuation of treatment with ICS and starting oral corticosteroid therapy during follow-up were respectively regarded as proxies of poor persistence with asthma medication and asthma exacerbation (outcomes). A proportional hazards model was fitted to identify predictors of ICS discontinuation. Case-crossover and case-case-time-control designs and conditional logistic regressions were used to estimate the association between persistence with ICS and asthma exacerbation. Results Cumulative incidences of discontinuation were 36%, 57% and 78% at 6 months, 1 year and 5 years, respectively. Predictors of poor persistence were female gender, use of antibiotics during follow-up, absence of use of short-acting beta-agonists prior to and after starting treatment with ICS and starting and maintaining ICS monotherapy during follow-up. The odds ratios of asthma exacerbation (and 95% confidence intervals) associated with ICS exposure during the current period, contrasted with exposure during the reference period, were 0.4 (0.2, 0.9) and 0.3 (0.1, 1.0) from case-crossover and case-case-time-control estimates, respectively. Conclusion Persistence with ICS treatment in adults with asthma reduces the risk of exacerbation in the real-life setting.

To assess the pattern of use of Emergency Departments (EDs), factors contributing to the visits, geographical distribution and outcomes in people aged 65 years or more living in the Italian Lombardy Region in 2012. Based on an administrative database the study population was divided into groups according to the number of ED visits. A multinomial logistic regression model was performed to compare the characteristics of each group. The Getis–Ord’s G statistic was used to evaluate the clusters of high and low visit prevalence odd ratios (OR) at district level. To estimate the severity of the disease leading to ED attendance, visits were stratified based on the level of emergency and outcome. About 2 million older people were included in the analyses: 78 % had no ED visit, 15 % only 1, 7 % 2 or more. Male sex, age 85 years or more, high number of drugs, ED visits and hospital admissions in the previous year and the location of an ED within 10 km from the patient’s place were all factors associated with a higher risk to have more ED visits. Clusters of high and low prevalence of visits were found for occasional users. Overall, 83 % of ED visit with a low emergency triage code at admission had as visit outcome discharge at home. In older people several variables were associated with an increased risk to have a high number of ED visits. Most of the visits were done for non-urgent problems and significant geographic differences were observed for occasional users.

ObjectivesTo evaluate the diagnostic and therapeutic approaches in a cohort of asthmatic children before and after starting drug therapy.MethodsData were retrieved from administrative databases of the Lombardy Region. The study population was composed of 78 184 children born in the Lombardy Region in 2002 and followed until their 10th birthday.Children with at least one antiasthmatic drug prescription per year (with the exclusion of nebulised suspension/solution formulations) in 2 consecutive years and at least one antiasthmatic drug prescription after the fifth birthday were identified as potential asthmatics (PA).Each PA was monitored for a period starting from 12 months before and ending 24 months after the first prescription (index prescription, IP). During the monitoring period antiasthmatic drug prescriptions were analysed, as well as spirometry and/or specialist visits.ResultsA total of 59 975 children (76.7%) received ≥1 prescription of antiasthmatic drugs in their first 10 years of life, and 4475 (5.7%) were identified as PAs. In all, 24% of PAs started with short-acting β2-agonists (SABA), 23% with inhaled corticosteroids (ICS) and 20% with SABA+ICS.A total of 33% of PAs had at least one prescription for specialist visit/spirometry: 11% before and 28% after the IP. The factors associated with a greater likelihood of receiving visit/spirometry prescriptions were local health unit of residence, age and high use of asthma drugs.ConclusionsDespite international guideline recommendations, spirometry monitoring is still underused in asthmatic children, even in subjects who initiated pharmacological treatment and therefore need an airway function evaluation. Moreover, the choice of drug therapy appears not always rational, since one out of four children were commenced on ICS as monotherapy.

Healthcare administrative databases of Italy's Lombardy Region were analyzed with the aim to assess perinatal outcomes and healthcare resource utilization during the first year of life in infants exposed to antiepileptic drugs (AEDs) during pregnancy. Drug prescriptions dispensed in the 12 months before delivery to women, who delivered between 2005 and 2011, were analyzed. Neonates were classified as cases if exposed to AEDs, and each case was randomly matched to seven controls. No significant differences were observed in the risk of congenital malformations between 526 cases and 3682 controls except for valproic acid (odds ratio (OR): 2.29; 95% confidence interval (CI): 1.24–4.22) where cases were more likely to be small for gestational age (χ2 = 7.66; p = 0.006). Cases also had a higher probability than controls of needing at least one specialist visit in a child neuropsychiatry outpatient service (OR: 1.74; 95% CI: 1.22–2.49).

Background and aims There are concerns that incretin-based antidiabetic drugs – including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists – increase the risk of hospitalization for heart failure (HF). To further analyse this issue, we conducted a nested case-control study within a cohort of antidiabetic users in a real world setting. Methods and results Within a cohort of 133,639 subjects with a first prescription of an antidiabetic drug (new-users) between 2010 and 2016 in Lombardy, Italy, and were followed-up to 2016, we identified 4057 subjects with a first hospitalization for HF and 80,450 controls matched on sex, age, and date of cohort-entry. The multivariate odds ratios (ORs) of HF in relation to current use of incretin-based drugs as compared to current use of two or more oral antidiabetics was 1.06 (95% confidence interval, CI, 0.83–1.35), with no evidence of a trend in risk with increasing duration of use. The corresponding ORs were 1.10 (95% CI 0.85–1.41) for DPP-4 inhibitors and 0.84 (95% CI 0.48–1.47) for GLP-1 receptor agonists. Estimates were consistent in various sensitivity analyses. Conclusions This study indicates that incretin-based drugs are not associated with an increased risk of hospitalization for HF, thus providing further reassurance on the cardiovascular safety of these antidiabetic drugs in the clinical practice.

Objectives To estimate the rate of paediatric attendance at emergency departments (EDs) in the Lombardy Region, Italy, and to determine the factors contributing to different patterns of use. Methods: By analysing healthcare administrative databases, ED attendance by 1.6 million youths

Objective To validate a set of indicators for quality of diabetes care through their relationship with measurable clinical outcomes. Design A retrospective cohort study was carried out from 2010 to 2015. Setting Population-based study. Data were retrieved from healthcare utilization databases of three Italian regions (Lombardy, Emilia Romagna and Lazio) on the whole covering 20 million citizens. Participants The 77 285 individuals who were newly taken in care for diabetes during 2010 entered into the cohort. Interventions Exposure to selected clinical recommendations (i.e. periodic controls for glycated hemoglobin, lipid profile, urine albumin excretion, serum creatinine and dilated eye exams) was recorded. Main outcomes measures A composite outcome was employed taking into account hospitalizations for brief-term diabetes complications, uncontrolled diabetes, long-term vascular outcomes and no traumatic lower limb amputation. A multivariable proportional hazards model was fitted to estimate hazard ratio, and 95% confidence intervals (CI), for the exposure-outcome association. Results Among the newly taken in care patients with diabetes, those who adhered to almost none (0 or 1), just some (2 or 3) or almost all (4 or 5) recommendations during the first year after diagnosis were 44%, 36% and 20%, respectively. Compared patients who adhered to almost none recommendation, significant risk reductions of 16% (95% CI, 6–24%) and 20% (7–28%) were observed for those who adhered to just some and almost all recommendations, respectively. Conclusions Tight control of patients with diabetes through regular clinical examinations must to be considered the cornerstone of national guidance, national audits and quality improvement incentives schemes.

BACKGROUND. Statins, are to date the most effective drugs for the treatment of hypercholesterolemia, and their important protective role in the prevention of cardiovascular (CV) morbidity and mortality is well-established [1]. Since people aged between 60 and 79 years were well represented in many trials, this applies also to elderly patients [2]. However, it does not apply to patients aged 80 years or older, because (i) none or few octogenarians have been included in outcome-based trials and (ii) evidence on the protective effects of statins among them is limited to only few observational studies with inconsistent results [3,4]. This represents an important limitation because the increasing life expectancy makes octogenarians the fastest growing subgroup of the population and, furthermore, this highly advanced aged subgroup accounts for a considerable portion of the overall CV events, hospitalizations and deaths [5]. AIM. To assess whether in individuals aged 80 years or older adherence to statins is accompanied by a reduced risk of all-cause mortality and major cardiovascular events. METHODS. A nested case–control study was carried out including a cohort of patients aged 80 years or older, who were under treatment with statins between 2008 and 2009, using the administrative databases of Lombardy region (Italy). Cases were the cohort members who experienced death or hospitalization for stroke, myocardial infarction or heart failure from the initial prescription until 2012. Up to five controls were randomly selected for each case. Logistic regression was fitted to estimate the odds ratio (OR), and its 95% confidence interval (CI), for the considered outcomes in relation to the adherence to therapy with statins, measured by the proportion of days covered (PDC). Four categories of adherence were employed (i.e., =75%), using the lowest one (

Objective: Our objective was to assess the relationship between antihypertensive drugs, loop diuretics, and the risk of hospitalization for hip fracture (HF). Design: We conducted a population-based study in a cohort of 81,617 patients from Lombardy (Italy) aged 70–90years who were newly treated with antihypertensive agents or loop diuretics between 2005 and 2009. Cases were the 2153 patients who experienced the outcome (hospitalization for HF before 31 December 2012). For each case, up to three controls were randomly selected from the cohort to be matched for sex, age at cohort entry, and date of initial prescription. The case–control and case-crossover designs and the logistic regression for matched sets were used to measure the strength of the association between current use of an antihypertensive drug (within 30days before the HF hospitalization) and the risk of outcome. Results: Case–control and case-crossover odds ratios (ORs) for current use of loop diuretics were 1.67 (95% confidence interval [CI] 1.28–2.18) and 1.49 (95% CI 1.05–2.10), respectively. Among patients aged 81–90years, case–control and case-crossover ORs were 1.52 (95% CI 1.04–2.21) and 1.82 (95% CI 1.10–3.00) for current use of loop diuretics and 1.86 (95% CI 1.03–3.35) and 1.88 (95% CI 1.01–3.48) for α-blockers. No other agent was associated with the outcome. Conclusions: Evidence that loop diuretics and α-blockers are associated with a higher risk of HF was consistent in the two observational approaches. Clinicians should carefully consider the risk of falls in their selection of drugs for hypertension and in the clinical use of loop diuretics.

Diabetes mellitus (DM) and atrial fibrillation (AF) are worldwide public health challenges and major causes of death and cardiovascular events. The association between DM and AF is controversial in literature and data on outcomes of individuals with both diseases have not been evaluated in population studies. We tested the hypothesis that DM is independently associated to AF hospitalization and assessed the risk of stroke and mortality in people with both conditions.We conducted a population-based cohort-study of DM patients and their corresponding controls identified in a administrative health database of the Lombardy Region. Both cohorts were followed for nine years. A multivariable Cox proportional-hazards-regression model was used to estimate the hazard ratio (HR) for first hospitalization for AF and for clinical outcomes.Out of 9,061,258 residents, 285,428 (3.14%) DM subjects were identified, mean age 65.8±15 years, 49% were women. The cumulative incidence of AF in DM was 10.4% vs. 7.4% in non-DM. DM was a risk factor for AF (HR 1.32, 95% CI 1.30-1.34; p0.0001). Oral anticoagulants were prescribed in 34.8% of DM patients with AF. DM associated with AF, presented the highest HR for stroke: 2.63; 95% CI 2.47-2.80 and for total death, HR 2.41; 95% CI 2.36-2.47.In this population study, DM was an independent risk factor for AF hospitalization. DM patients with AF had the highest risk of stroke and total mortality. Early identification of AF and a structured plan to optimize the comprehensive management of DM and AF patients is mandatory.