Search

Lombardy was affected in the early months of 2020 by the SARS-CoV-2 pandemic with very high morbidity and mortality. The post-COVID-19 condition and related public health burden are scarcely known.Using the regional population administrative database including all the 48,932 individuals who survived COVID-19 and became polymerase-chain-reaction negative for SARS-CoV-2 by 31 May 2020, incident mortality, rehospitalizations, attendances to hospital emergency room, and outpatient medical visits were evaluated over a mid-term period of 6 months in 20,521 individuals managed at home, 26,016 hospitalized in medical wards, and 1611 in intensive care units (ICUs). These data were also evaluated in the corresponding period of 2019, when the region was not yet affected by the pandemic. Other indicators and proxies of the health-care burden related to the post-COVID condition were also evaluated.In individuals previously admitted to the ICU and medical wards, rehospitalizations, attendances to hospital emergency rooms, and out-patient medical visits were much more frequent in the 6-month period after SARS-CoV-2 negativization than in the same prepandemic period. Performances of spirometry increased more than 50-fold, chest CT scans 32-fold in ICU-admitted cases and 5.5-fold in non-ICU cases, and electrocardiography 5.6-fold in ICU cases and twofold in non-ICU cases. Use of drugs and biochemical tests increased in all cases.These results provide a real-life picture of the post-COVID condition and of its effects on the increased consumption of health-care resources, considered proxies of comorbidities.

The Lombardy Region has one of the most widespread and advanced models of Palliative Care (PC) in the country. However, there is a relative lack of updated data referring to the activity of the Lombardy PC network.This work aims to describe the activity carried out in the two main PC care settings (home care and hospice) in 2019 through the analysis of the data sent by each Unit to the Lombardy Region. Data were analysed on a regional basis and considering the 8 Health Protection Agencies (ATS) separately.In 2019, PC activity was provided by 114 home care units (1.14/100,000 inhabitants) and 70 hospice for a total of 812 beds (8.1 beds/100,000 inhabitants). Overall, 25,514 patients were assisted for a total of 29,892 care pathway. 77.6% of the patients assisted were oncologic and about 67% of the patients who died of cancer in Lombardy were intercepted by CP. 54.4% of patients were taken care of in home care, although with a significant difference between cancer patients (58%) and non-cancer patients (42%). In home care, average activation time was 2.8 days and in 81% of cases the assistance was activated within 24-48 hours; in hospice, average activation time was 3.5 days, with 60% of admissions within 24 hours and over 30% with waiting time ≥3 days. The median duration of home palliative care was approximately 21 days (average 40.5), that in hospice was 9 days (average 17.2). In the home care pathways, the prevalent outcome was the death of the patient at home (64%) and hospitalization in hospice (17.2%), while 86% of hospitalizations in hospice ended with death.This accurate report of the Lombardy PC activity indicates that PC satisfy various qualitative indicators of structural and care process identified by national regulations. However, PC still remain predominantly intended for cancer patients, with relatively short duration of care, particularly in the hospice setting.

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.

Aim To examine the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with other antihyperglycaemic agents (AHAs) in large and unselected populations of the Lombardy and Apulia regions in Italy. Materials and methods An observational cohort study of first-time users of GLP-1RAs, SGLT2 inhibitors or other AHAs was conducted from 2010 to 2018. Death and cardiovascular (CV) events were evaluated using conditional Cox models in propensity-score-matched populations. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for each region and in a meta-analysis for pooled risks. Results After propensity-score matching, the Lombardy cohort included 18 716 and 11 683 patients and the Apulia cohort 9772 and 6046 patients for the GLP-1RA and SGLT2 inhibitor groups, respectively. Use of GLP-1RAs was associated with lower rates of death (HR 0.61, CI 0.56-0.65, Lombardy; HR 0.63, CI 0.55-0.71, Apulia), cerebrovascular disease and ischaemic stroke (HR 0.70, CI 0.63-0.79; HR 0.72, CI 0.60-0.87, Lombardy), peripheral vascular disease (HR 0.72, CI 0.64-0.82, Lombardy; HR 0.80, CI 0.67-0.98, Apulia), and lower limb complications (HR 0.67, CI 0.56-0.81, Lombardy; HR 0.69, CI 0.51-0.93, Apulia). Compared with other AHAs, SGLT2 inhibitor use decreased the risk of death (HR 0.47, CI 0.40-0.54, Lombardy; HR 0.43, CI 0.32-0.57, Apulia), cerebrovascular disease (HR 0.75, CI 0.61-0.91, Lombardy; HR 0.72, CI 0.54-0.96, Apulia), and heart failure (HR 0.56, CI 0.46-0.70, Lombardy; HR 0.57, CI 0.42-0.77, Apulia). In the pooled cohorts, a reduction in heart failure was also observed with GLP-1RAs (HR 0.89, 95% CI 0.82-0.97). Serious adverse events were quite low in frequency. Conclusion Our findings from real-world practice confirm the favourable effect of GLP-1RAs and SGLT2 inhibitors on death and CV outcomes across both regions consistently. Thus, these drug classes should be preferentially considered in a broad type 2 diabetes population beyond those with CV disease.

Although rheumatoid arthritis (RA) is associated with an increased risk of death and cardiovascular (CV) disease, the excess of these risks is expected to have diminished over time, in more recent incident cohorts with RA. We analysed the risk of all-cause death, stroke, and myocardial infarction as primary outcomes and all CV events as secondary outcomes in RA subjects compared to the general population, from 2005 to 2018. The risk outcomes were also evaluated in relation to the time since RA diagnosis. We conducted a cohort study using linkable administrative healthcare databases of the Lombardy Region, Northern Italy. Analyses included subjects newly diagnosed RA subjects and a random sample of No-RA subjects. An adjusted Cox proportional hazard regression model was used to calculate hazard ratios and 95% CIs for all outcomes. The study population comprised 16,047 RA subjects and 500,000 without RA. The risks of dying (HR 1.22, 95% CI 1.15–1.30), stroke (HR 1.39, 95% CI 1.22–1.58), myocardial infarction (HR 2.00, 95% CI 1.78–2.26) were significantly higher in the RA cohort, as were those that for secondary outcomes. Differences between RA and No-RA already emerged during the first five years after diagnosis. Risk patterns remained statistically significant during the next 5 years or more. Subjects with RA still have a higher risk of death and worse CV outcomes than the general population, appearing early and not decreasing with time. Preventive interventions are urgently needed.

Poor medication adherence compromises treatment efficacy and adversely affects patients’ clinical outcomes. This study aims to assess (1) multiple medication adherence to the most common drug classes chronically prescribed to older people, (2) the factors associated, and (3) the clinical outcomes. This retrospective cohort study included 122,655 community-dwelling patients aged 65–94 years old, newly exposed to chronic polypharmacy, and recorded in the Lombardy Region (northern Italy) administrative database from 2016 to 2018. Multiple medication adherence was assessed for drugs for diabetes, antithrombotics, antihypertensives, statins, and bisphosphonates, by calculating the daily polypharmacy possession ratio (DPPR). One-year mortality, nursing home, emergency department (ED), and hospital admission rates were calculated for 2019. The most prescribed drugs were antihypertensives (89.0%). The mean (std.dev) DPPR was 82.9% (15.6). Being female (OR = 0.85, 95%CI: 0.84–0.86), age ≥85 years (OR = 0.77, 95%CI: 0.76–0.79), and multimorbidity (≥4 diseases, OR = 0.88, 95%CI: 0.86–0.90) were associated with lower medication adherence. A higher DPPR was associated with clinical outcomes—in particular, improved survival (HR = 0.93 for 10/100-point increase, 95%CI: 0.92–0.94) and lower incidence in nursing home admissions (SDHR = 0.95, 95%CI: 0.93–0.97). Adherence to the most common chronic drugs co-prescribed to the older population was high. Better multiple medication adherence was associated with better clinical outcomes.

Aim: To compare the association of metformin use and coronavirus disease 2019 (COVID-19) outcomes in a cohort of 31 966 patients with diabetes in Lombardy. Methods: We used a COVID-19 linkable administrative regional database to select patients with diabetes who were aged 40 years or older. They had at least two prescriptions of antidiabetic drugs in 2019 and a positive test for severe acute respiratory syndrome coronavirus-2 from 15 February 2020 to 15 March 2021. The association of metformin use and clinical outcomes was assessed by multivariable logistic regression analyses and after propensity score matching (PSM). Clinical outcomes were all-cause mortality, in-hospital mortality, hospitalization for COVID-19, and admission to an intensive care unit (ICU). Results: In multivariable models, metformin use was associated with a significantly lower risk of total mortality (OR 0.70; 95% CI 0.66-0.75), in-hospital mortality (OR 0.68; 95% CI 0.63-0.73), hospitalization for COVID-19 (OR 0.86; 95% CI 0.81-0.91), and ICU admission (OR 0.81; 95% CI 0.69-0.94) compared with metformin non-users. Results were similar after PSM; metformin was associated with a significantly lower risk of total mortality (OR 0.79; 95% CI 0.73-0.86), in-hospital mortality (OR 0.74; 95% CI 0.67-0.81), and ICU admission (OR 0.77; 95% CI 0.63-0.95). Conclusions: In this large cohort, metformin use was associated with a protective effect in COVID-19 clinical outcomes, suggesting that it might be a potentially useful drug to prevent severe COVID-19 disease, although randomized controlled trials (RCTs) are needed to confirm this. While awaiting the results of RCTs, we suggest continuing prescribing metformin to COVID-19 patients with diabetes.

ObjectivesHospice and home palliative care have been associated to a reduction of aggressive treatments in the end-of-life, but data in the Italian context are scanty. Therefore, we aim to investigate the role of palliative care on indicators of end-of-life intensity of care among patients with cancer in Lombardy, the largest Italian region.MethodsWithin a retrospective study using the healthcare utilisation databases of Lombardy, Italy, we selected all residents who died in 2019 with a diagnosis of cancer. We considered as exposure variables admission to palliative care and time at palliative care admission, and as indicators of aggressive care hospitalisations, diagnostic/therapeutic procedures, in-hospital death, emergency department visits and chemotherapy over a time window of 30 days before death; chemotherapy in the last 14 days was also considered.ResultsOur cohort included 26 539 individuals; of these, 14 320 (54%) were admitted to palliative care before death. Individuals who were admitted to palliative care had an odds ratio (OR) of 0.27 for one hospitalisation, 0.14 for ≥2 hospitalisations, 0.25 for hospital stay ≥12 days, 0.38 for minor diagnostic/therapeutic procedures, 0.18 for major diagnostic/therapeutic procedures, 0.02 for in-hospital death, 0.35 for one emergency department visit, 0.29 for ≥2 emergency department visits and 0.66 for chemotherapy use in the last 30 days; the OR was 0.56 for chemotherapy use in the last 14 days.ConclusionsThis large real-world analysis confirms and further support the importance of palliative care assistance for patients with cancer in the end- of- life; this is associated to a significant reduction in unnecessary treatments.

The aims of the study were to assess the changes in 19‐years use of antibiotics (overall, by age, sex and geographical area) and of those classes deemed to be quality indicators for their consumption and to evaluate factors associated to antibiotic use. We analyzed drug prescription data collected in the administrative database of the Lombardy Region (Northern Italy) for outpatients aged 40+ years from 2000 to 2019. Logistic regression analyses were performed to evaluate the association between receiving at least one antibiotic prescription and year of observation, gender, age groups, area of residence, polypharmacy and hospitalizations in the index year. The prevalence of patients prescribed with antibiotics remained high from 2000 (33.8%) to 2019 (32.6%). Prevalence of use of second‐line choice antibiotics (penicillin combinations with beta‐lactamase inhibitors, third and fourth generation cephalosporins, macrolides) continued to increase, only fluoroquinolones decreased in 2019 (19%) comparing to 2018 (26%), at the time when the Italian Medicines Agency promulgated safety warnings. Females (OR 1.28, 95%CI 1.27–1.28), people living in Brescia (OR 1.24, 95%CI 1.24–1.25), those exposed to polypharmacy (OR 2.57, 95%CI 2.56–2.57) and those hospitalized 1 to 3 (OR 1.86, 95%CI 1.85–1.86) or more than 3 (OR 2.02, 95%CI 2.01–2.03) times a year had a statistically significant higher risk of receiving antibiotics. The high use of antibiotics over the study period further reinforces the need of impactful interventions, in order to improve the rational use of antibiotics and to reduce the risks of antimicrobial resistance. The differences outlined should be considered when monitoring and planning these interventions., We analyzed drug prescription data collected in the administrative database of the Lombardy Region (Northern Italy) for outpatients aged 40+ years from 2000 to 2019, in order to assess the changes in the use of antibiotics and of those classes deemed to be quality indicators for their consumption and to evaluate factors associated to antibiotic use. The prevalence of patients prescribed with antibiotics remained high from 2000 (33.8%) to 2019 (32.6%). Prevalence of use of second‐line choice antibiotics (penicillin combinations with beta‐lactamase inhibitors, third and fourth generation cephalosporins, macrolides) continued to increase, only fluoroquinolones decreased in 2019 (19%) comparing to 2018 (26%), at the time when the Italian Medicines Agency promulgated safety warnings.

Aim To describe the antiepileptic drug (AED) prescription pattern in pregnant women and women of childbearing age in the 2010-2019 period in the Lombardy region, Italy. Methods The Lombardy region administrative healthcare databases (2010-2019) were analysed. AEDs were classified as drugs belonging to the N03A subgroup of the Anatomical Therapeutic Chemical Classification System. Women 15-49 years old were considered as women of childbearing age, while exposure during pregnancy was estimated taking into account the 12 months before delivery (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes in the diagnosis record from 650 to 659). Results During 2019, 16,605 women of childbearing age (prevalence: 14.8‰) received at least one AED prescription. Pregabalin was the most widely used antiepileptic in women of childbearing age (22.3%), followed by valproic acid (20.0%). The prevalence of AED prescription in pregnant women was 3.8‰, and levetiracetam and lamotrigine (16.6%) were the most commonly prescribed drugs. The prevalence of AED prescription did not change from 2010 to 2019 in women of childbearing age or in pregnant women. Valproic acid was one of the most used AEDs in pregnancy until 2016, after which its prescription declined from 19% to 14% of AED users. Conclusions Despite the decrease in valproic acid prescription over time, this drug is still among the most used AEDs, in particular in women of childbearing age. Educational interventions for healthcare professionals and women are needed in order to reduce the risk of unplanned pregnancy.

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

Background:GLP-1 receptor agonists (G LP-1 RA) and SGLT-2 inhibitors (SGLT-2i) are recommended in type 2 diabetes subjects with established cardiovascular (CV) disease or at high CV risk. The efficacy and safety of GLP-1 RA and SGLT-2i compared with other anti-hyperglycemic agents (AHAs) was examined in large unselected populations of Lombardy and Apulia regions in Italy.Methods:An observational cohort study of new users of GLP-1 RA, SGLT-2i and other AHAs was conducted from 2010 to 2018. Death and cardiovascular events were evaluated using conditional Cox models in propensity-score matched populations. Adjusted hazard ratios (95%, CI) were calculated for each region and as meta-analysis for pooled risks.Results:After propensity-matching, the Lombardy cohort included 18,716 and 11,683 pairs and the Apulia cohort 9,772 and 6,046 pairs for the GLP-1 RA and SGLT-2i groups, respectively. Use of GLP-1 RA was associated with lower rates of death (HR 0.61, CI 0.56-0.65, Lombardy; HR 0.63, CI 0.55-0.71, Apulia), cerebrovascular disease and ischemic stroke (HR 0.70, CI 0.63-0.79; HR 0.72, CI 0.60-0.87, Lombardy) peripheral vascular disease (HR 0.72, CI 0.64-0.82, Lombardy; HR 0.80, CI 0.67-0.98, Apulia) and, lower limb complications (HR 0.67, CI 0.56-0.81, Lombardy; HR 0.69, CI 0.51-0.93, Apulia). Compared to other AHAs, SGLT-2i use decreased the risk of death (HR 0.47, CI 0.40-0.54, Lombardy; HR 0.43, CI 0.32-0.57, Apulia), cerebrovascular disease (HR 0.75, CI 0.61-0.91, Lombardy, HR 0.72, CI 0.54-0.96, Apulia), and heart failure (HR 0.56, CI 0.46-0.70, Lombardy, HR 0.57, CI 0.42-0.77, Apulia). In the pooled cohorts, a reduction in heart failure was also observed with GLP-1 RA (HR 0.89, 95% CI 0.82-0.97). Serious adverse events were quite low in frequency. Conclusions: Our findings from real world practice confirm the favorable effect of GLP-1 RA and SGLT-2i on death and CV outcomes consistent across both regions. Thus, these drug classes should be preferentially considered in a broad type 2 diabetes population beyond subjects with CV disease.

Although rheumatoid arthritis (RA) is associated with an increased risk of death and cardiovascular (CV) disease, the excess of these risks is expected to have diminished over time, in more recent incident cohorts with RA. We analysed the risk of all-cause death, stroke, and myocardial infarction as primary outcomes and all CV events as secondary outcomes in RA subjects compared to the general population, from 2005 to 2018. The risk outcomes were also evaluated in relation to the time since RA diagnosis. We conducted a cohort study using linkable administrative healthcare databases of the Lombardy Region, Northern Italy. Analyses included subjects newly diagnosed RA subjects and a random sample of No-RA subjects. An adjusted Cox proportional hazard regression model was used to calculate hazard ratios and 95% CIs for all outcomes. The study population comprised 16,047 RA subjects and 500,000 without RA. The risks of dying (HR 1.22, 95% CI 1.15-1.30), stroke (HR 1.39, 95% CI 1.22-1.58), myocardial infarction (HR 2.00, 95% CI 1.78-2.26) were significantly higher in the RA cohort, as were those that for secondary outcomes. Differences between RA and No-RA already emerged during the first five years after diagnosis. Risk patterns remained statistically significant during the next 5 years or more. Subjects with RA still have a higher risk of death and worse CV outcomes than the general population, appearing early and not decreasing with time. Preventive interventions are urgently needed.

Italy was used as a case study to investigate the determinants of the difference between the price proposal for medicines submitted by the industry and the final negotiated price (∆P). Data was gathered through the information system used by Italian Medicines Agency (AIFA) and the time-frame for this analysis is 2013-2017. Factors influencing the delta price were analyzed through a regression analysis. Forty four orphan drugs and 89 new other molecular entities obtained reimbursement in the period considered. Following the negotiation process, prices proposed by Marketing Authorization Holders (MAH) were lowered during the negotiation process by 25.1% and 28.6% on average for orphan drugs and other molecules respectively. The price reduction was higher for innovative drugs (-32.2%). Statistically significant determinants associated to higher price reduction were: i) the implementation of a product specific monitoring registry, ii) the negotiation of a financial-based (FB) Managed Entry Agreement, iii) a target population larger than 20,000 patients, iv) an expected National Health Service expenditure larger than € 200 million. The impact of some variables on the delta price was predictable (e.g. for drugs with an expected higher budget impact and a larger target population), others were more surprising (e.g. a significant price reduction for "innovative" drugs). The implementation of FB agreements, which often rely on confidential arrangements, was one of the determinants with higher impact on price reduction.

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.

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.

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.

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.

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

Objectives The aim of this paper is to investigate the determinants of the difference between the price proposal submitted by the industry and the final negotiated price. We used Italy as a case-study. Methods Data were gathered through the information system used by Italian Medicines Agency. The time-frame for this analysis is 2013–2017. Factors influencing the delta price were analyzed through a regression analysis. Results 44 orphan drugs and 89 new other molecular entities obtained reimbursement in the last five years. Following the negotiation process, prices were lowered by 25.1% and 28.6% on average for orphan drugs and other molecules respectively. The price reduction was higher for innovative drugs (-32.2%). Statistically significant determinants associated to higher price reduction were: i) the implementation of a product specific monitoring registry, ii) the negotiation of a financial-based Managed Entry Agreement, iii) a target population larger than 20,000 patients, iv) an expected National Health Service expenditure larger than €200 million. Discussion The impact of some variables on the delta price was predictable (e.g. for drugs with an expected higher budget impact and a larger population target), others were more surprising (e.g. a significant price reduction for “innovative” drugs). The implementation of financial-based agreements, which often rely on confidential arrangements, was one of the determinants with higher impact on price reduction.

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).

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

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.

To describe the incidence of ischemic stroke, short-term mortality, recurrences, and prescription patterns.Data from administrative health databases of the Lombardy Region from 2002 to 2010 (about 4 million people) were analyzed for stroke incidence and recurrence, mortality, and drug prescriptions after an ischemic stroke.A total of 43,352 patients with a first hospital admission for ischemic stroke were identified. During 8 years, stroke incidence decreased from 3.2 of 1000 to 2.4 of 1000 (P.001) in people aged 65-74 years, from 7.1 of 1000 to 5.3 of 1000 (P.001) at ages 75-84 years and from 11.9 of 1000 to 9.4 of 1000 (P.001) at age 85 years or older. Stroke recurrences dropped by 30% (from 10.0% to 7.0%, P.001) and 30-day mortality rate also decreased. Prescription trends showed linear increase in antiplatelets and lipid-lowering drugs, respectively, from 60.2% to 65.0% (P.001) and from 19.1% to 34.6% (P.001), whereas antihypertensive prescriptions did not change appreciably. Anticoagulant prescription increased in patients with atrial fibrillation, from 64.8% to 72.1% in the 65-74 years age group, (P = .004) and from 40.2% to 53.7% in the 75-84 years age group (P.001); less than 20% of the 85 years or older age group were treated with anticoagulants (P.0001).Stroke incidence, recurrence, and 30-day mortality decreased from 2002 to 2010 concomitant with an increase in prescriptions of secondary stroke prevention drugs.