Background: In patients with uncontrolled, moderate to severe asthma despite treatment with medium-dose ICS/LABA, GINA recommends to increase the dose of ICS to high-dose (HD) ICS/LABA or to add a LAMA on top of medium-dose (MD) ICS/LABA. Methods: We conducted a retrospective cohort study using healthcare data from 3 GP databases: IPCI (NL), HSD (IT) and CPRD GOLD (UK) and one prescription database: Aarhus (DK). We identified adult asthma patients from Jan 2010 to April 2020, treated with MD ICS/LABA for at least 3 months and receiving treatment step-up. We investigated determinants of choice of MD ICS/LABA+LAMA versus HD ICS/LABA. Results: 6,126 patients were stepped up to MD ICS/LABA+LAMA and 18,947 patients to HD ICS/LABA. MD ICS/LABA+LAMA was more often prescribed to older patients, concomitant COPD, gastro-esophageal reflux disease (GERD), exacerbations in previous year and current or past smoking, and less to patients with atopic disorders (table 1, meta-analysis of database results). Conclusion: In patients with uncontrolled asthma on medium dose ICS/LABA, step-up with add-on LAMA was more likely than step-up to HD ICS/LABA in case of older age, current smoking, a history of asthma exacerbations and a concomitant diagnosis of COPD.

Background: In patients with uncontrolled, moderate to severe asthma, GINA recommends to increase the dose of ICS to high-dose (HD) ICS/LABA or to add a LAMA on top of medium-dose (MD) ICS/LABA. It is yet unknown who responds best to these treatment choices. Methods: We conducted a retrospective cohort study using data from 3 GP databases: IPCI (NL), HSD (IT) and CPRD GOLD (UK) and one prescription database: Aarhus (DK). We identified adult asthma patients from Jan 2010 to April 2020, previously treated with MD ICS/LABA for ≥3 months and need of treatment step-up because of uncontrolled asthma. We investigated the proportion and predictors of treatment response defined as ≥25% reduction in severe asthma exacerbation rate and/or improvement of lung function (increase in FEV1%≥7.5%). Results: Out of 11,893 adult patients with uncontrolled asthma and requiring treatment step-up (12% in IPCI, 6% in HSD, 1% in Aarhus and 81% in CPRD) 5,490 could be used to evaluate treatment response (table 1). In both exposure groups, a history of ≥ 2 severe asthma exacerbations (ORadj 4.8 (95% CI 2.0 - 11.7)(for MD) and 3.5 (95% CI 2.5 - 5.1)(for HD)) and increasing treatment duration (ORadj per month 1.3 (95% CI 1.2 - 1.3)(MD) and 1.3 (95% CI 1.3 - 1.4)(HD)) increased the chance of treatment response. Conclusion: In real life, there was comparable treatment response between type of step-up which is important to be considered at time of treatment step-up.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent liver disease in the world. Its prevalence varies from 20 to 28% in adults. NAFLD involves a spectrum of conditions from simple steatosis to steatohepatitis (NASH) and fibrosis. Liver fibrosis is considered as an integral part in the progression of chronic liver disease ultimately leading to cirrhosis and hepatocellular carcinoma.

Introduction: Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global adult population. It is closely associated with a number of metabolic diseases. In fact, the increasing prevalence of obesity, type 2 diabetes mellitus, hypertension, and hypercholesteremia not only increases the prevalence of NAFLD but also places patients at higher risk for progressive liver disease.

Background The proper identification of chronic migraine is one of the mainstays for general practitioners. This study therefore aims to assess the epidemiology and determinants of chronic migraine in primary care in Italy by testing five operational case definition algorithms. Methods Five case definition algorithms defining chronic migraine were developed to estimate the prevalence and incidence rate of chronic migraine in the Health Search database. For each algorithm, we conducted a nested case-control analysis to quantify the level of association between certain determinants and incident cases of chronic migraine. Results Considering a cohort of 1,091,032 patients (52% were females), the prevalence rate of chronic migraine increased from the first to the fifth case definition algorithm ranging from 0.03 to 0.28%. No 95% confidence interval overlapped the others, and every confidence interval reliably maintained 2% precision. Incidence rates showed a growing trend (0.008–0.056 per 100,000 person-years) as well. All case definition algorithms were able to capture sex (i.e. female) and nonsteroidal anti-inflammatory drug (NSAID) overuse as statistically significant determinants of incident cases of chronic migraine. Depression was associated with a statistically significant increase of incidence rate of chronic migraine only for two case definition algorithms. Conclusion Our findings show that prevalence and incidence rate of chronic migraine are underestimated when compared with current literature. On the other hand, we found acceptable correctness of chronic migraine definition in the light of the association with well-known determinants.

Strontium ranelate use, compared with oral bisphosphonates, is not associated with increased risk of AMI in patients with no contraindications for SR use. However, current strontium ranelate (compared with current bisphosphonate) appears associated with 25-30% excess risk of VTE and 35% excess risk of CVDeath.INTRODUCTION:Evaluate the risk of cardiac and thromboembolic events among new users of SR and oral BPs without contraindications for SR.METHODS:We conducted three multi-national, multi-database (Aarhus-Denmark, HSD-Italy, IPCI-Netherlands, SIDIAP-Spain, THIN-UK) case-control studies nested within a cohort of new users of SR/BP. We matched cases of acute myocardial infarction (AMI), venous thromboembolism (VTE), and cardiovascular death (CVDeath), up to 10 controls on gender, year of birth, index date, and country. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) according to current SR vs current BP use and current vs past SR use, adjusting for potential confounders. Data were pooled using random effects meta-analysis.RESULTS:No excess risk of AMI (5477 cases/54,674 controls) was found with current SR vs current BP (OR 0.89 (95%CI 0.70, 1.12)) nor with current vs past SR use (0.71(0.56, 0.91)). For VTE (5614 cases/6036 controls), an excess risk was found with current SR compared with current BP use, 1.24 (0.96, 1.61), and current vs past SR use, 1.30 (1.04, 1.62). For CVDeath (3019 cases/29,871 controls), an increased risk was seen with current SR vs current BP use, 1.35 (1.02, 1.80), but not with current vs past SR use (0.68 (0.48, 0.96)).CONCLUSION:In patients without contraindications for SR, we found no evidence of an increased risk of AMI but a 25-30% excess risk of VTE and a 35% excess risk of CVDeath with current SR vs current BP users. This is despite a reduction in risk in CVDeath with current vs past SR users. The latter disparity could still be partially explained by cessation of preventative therapies in end-of-life or residual confounding by indication.

Chronic Migraine (CM) is a relevant public health concern. However, there are several clinical and sociodemographic features which make difficult the diagnosis of CM. Given the "gatekeeper" role of GPs in the public health system in Italy, the epidemiology of CM in primary care is pivotal. This study therefore aims to assess the epidemiology of CM in primary care in Italy by testing five operational algorithms defining CM. These algorithms adopted different combinations (i.e. increasing or decreasing completeness and correctness) between migraine-related contacts coded via ICD9CM and medications use with related durations among migraine sufferers. Using the Health Search Database we performed population-based cohort study. A set of algorithms defining CM were developed to estimate the prevalence and incidence rate of CM in a cohort of patients active in Health Search Database (HSD) on January 1, 2016. In addition, we conduct a nested case-control analysis in an attempt to quantify the level of association between candidate determinants of CM according to each algorithm. The prevalence rate increased from the first to the fifth algorithm ranging 0.03% - 0.28%. There was no 95% Confidence Intervals (CI) which overlapped the others, and every CI reliably maintained 2% precision. Incidence rates showed a growing trend (i.e., 0.008-0.056 per 100000 person-years) as well. Overall, all algorithms were able to capture sex (females show a greater risk than males), and NSAIDs overuse as statistically significantly determinants of incident cases of CM. The presence of depression was associated with a statistically significant increase of incidence rate of CM only for two algorithms. Our findings show that prevalence and incidence rate of CM are underestimated in HSD when compared with current literature. On the other hand, we found acceptable correctness of CM definition given the consistency across the defining algorithms in capturing significant associations with well-known determinants.

In the context of a multi-national drug safety study, we aimed to validate code list/s and/or algorithms for the identification of venous thromboembolic events (VTE), cardiovascular death (CVDeath) and gastrointestinal disease (GID) in 4 European primary care databases within the EU-ADR Alliance. A random sample of potential cases was selected within a cohort of incident users of Strontium Ranelate or oral bisphosphonate/s in the following data sources: 1.Health Search Database-HSD (Italy), 2.Integrated Primary Care Information Database-IPCI (Netherlands), 3.Sistema d’Informació pel Desenvolupament de l’Investigació en Atenció Primària-SIDIAP (Spain), and 4.The Health Improvement Network-THIN (UK). VTE and GID were identified using pre-specified code lists; CVDeath was ascertained combining death date with a code for cardiovascular event/s in primary care records in the previous 2 months. Validation methods included free text review, hospital inpatient linkage, and GP questionnaires. Positive predictive values (PPV) were calculated as proportion of true cases amongst potential cases. A total of 1,197 VTE, 921 CVDeath, and 2,887 GI diagnoses underwent validation. PPVs of VTE were 86%, 78% and 78% in HSD, THIN and SIDIAP respectively, and lower (66%) in IPCI. The proposed CVDeath algorithm showed a low PPV of 38%, 46%, 53% in IPCI, HSD, and SIDIAP, and a higher PPV of 78% in THIN. Finally, GID showed good validity in all databases, with PPV 91%, 78%, 91% and 89% in IPCI, HSD, THIN and SIDIAP, respectively. The proposed code lists provided good validity (PPV>75%) for VTE and GID in most cases, with the exception of VTE in IPCI. In contrast, the proposed algorithm for CVDeath had poor performance, with lower PPV in all except THIN-UK. Whilst VTE and GID are accurately identified using diagnostic codes, the ascertainment of CVDeath does require linkage (e.g. to mortality register/s) and/or individual free text validation of events.

The original version of this article, published on 26 November 2019 contained a mistake.

Purpose: The aim of this analysis was to identify factors associated with the choice of type 2 diabetes mellitus (T2DM) therapy at the time of intensification of antidiabetic treatment across 4 European countries. Methods: Antidiabetic drug prescription/dispensing records and patients' characteristics were obtained from the electronic health care records of patients with T2DM from the Netherlands (NL), Italy, and Spain (ES) (all, 2007-2011); and the United Kingdom (UK; 2008-2012). Oral monotherapy was defined as first-line; oral dual therapy, as second-line; >2 oral treatments or oral combined with an injectable, as third-line; and injectables only, as fourth-line treatment. Treatment intensification was defined as the start of a higher line of treatment. Comedication, comorbidities, clinical parameters, and other factors associated with treatment choice were identified using multivariate relative risk estimation by Poisson regression with robust error variance. Findings: In the 5-year study period, 485,120 patients (79% of the treated T2DM population) underwent treatment intensification. Changes in treatment choice were clearly visible over the study period, such as a decline in the use of thiazolidinediones (NL, ES, UK) and increases in the use of dipeptidyl peptidase-4 inhibitors (DPP4i) (NL, ES, UK) and glucagon-like peptide-1 receptor agonists (UK). With first-line treatment, advanced age and renal comorbidity were associated with the use of sulfonylureas (SUs; all countries), whereas high body mass index (BMI) was inversely associated with SU use in the United Kingdom and Spain. With second-line treatment, advanced age was associated with metformin + SU use (all countries); and renal comorbidity with SU + DPP4i use in the United Kingdom and the Netherlands. High BMI was associated with metformin + thiazolidinedione (TZD) use in the United Kingdom and Spain, and with metformin + DPP4i in the United Kingdom. With third-line treatment, advanced age and renal comorbidity were associated with the use of SU + insulin (NL, ES, UK). Hemoglobin Alc > 8.5% was positively associated, and high BMI was inversely associated, with the use of any third line combination containing insulin. Across treatment lines TZD and metformin were negatively associated with renal and cardiac morbidity. Second and third line treatment choices strongly depended on prior treatments. With fourth-line treatment, women were more likely to receive glucagon-like peptide-1 receptor agonists than were men in the United Kingdom and Spain. Implications: The results suggest that the main factors driving treatment choice at any stage of intensification were age, hemoglobin A(lc), BMI, renal and cardiac morbidity, and treatment history. These drivers were consistent with guidelines on, and contraindications of, specific medications. Differences between countries were generally consistent with, but not solely attributable to, differences in local guidelines and reimbursement policies. (C) 2017 Elsevier HS Journals, Inc. All rights reserved.

Three projects have been implemented to gather the Real World Data (RWD) required to answer to National and Regional decision maker’s need of estimating the impact of the introduction of PCSK9 inhibitors on the Italian National Healthcare Service at reimbursement time. RWD on PCSK9 eligible patients were collected via thee projects: IFIGENIA (observational study in 10 Italian Local Health Units [LHUs]) on heterozygous familial hypercholesterolemia [HeFH]), CORE (database analysis on secondary prevention [SP] patients), HEALTH SEARCH (database analysis on patients at high and very high risk [HR/vHR] of cardiovascular events [CV]). RWD has been then discussed by a multidisciplinary panel and organized as evidences (RWE). According to IFIGENIA interim results on 3 LHUs, 0,20% of the patients with a LDL-C determination were probable or definite HeFH . Of those, 49% were treated with statins while 16% were treated with statin plus ezetimibe. Approximately half (46%) of HeFH patients were not adherent to statin and nearly all patients(98%) had not reached their LDL-C target according to the Italian Guidelines (NOTA 13). CORE estimated that 40% of patients were not treated with statin and/or ezetimibe within the first year of follow up. One-third (37%) of these SP patients is aged above 80, 38% experienced a new CV hospitalization within 12 months from the first CV event. HEALTH SEARCH highlighted that 69% of HR and 84% of vHR treated patients were not able to reach their LDL-C target. One-half of not at target vHR patients had a LDL-C >100 mg/dL. RWD is key to decrease the uncertainties within the healthcare decisions. These projects have demonstrated that there is a specific unmet need to be covered by PCSK9 inhibitors. Epidemiological and C-LDL data were key to size the impact of their introduction within the Italian National Healthcare System.

A growing body of evidence indicates that use of low-dose aspirin (LDA) reduces the risk of certain adenocarcinomas. While there are several and consistent findings on the protective effect of LDA on colorectal and other cancers, few and conflicting evidence is available on prostate cancer (PCa). The aim of this study was to assess whether LDA reduces the incidence rate of PCa. We conducted a nationwide, population-based, retrospective cohort study by using Health Search IMS Health Longitudinal Patient Database (HSD). Patients with ischemic cardio- or cerebrovascular disease (index date) were identified. Time-dependent multivariable Cox proportional hazard models were adopted to estimate Hazard Ratios (HRs) and related 95% confidence intervals (95% CI) of PCa associated with use of LDA. The exposure was lagged by one year to consider the latency of drug effect on the outcome onset. Within a cohort 13,453 patients, the overall incidence rate of PCa was 2.5 per 1,000 person-years. Use of LDA was associated with a decreased incidence rate of PCa (HR=0.64; 95% CI: 0.48-0.86), which was primarily driven by a frequency of LDA use equal to or higher than twice per week (HR=0.60; 95% CI: 0.43-0.83). Such an association was more pronounced (HR=0.43; 95% CI: 0.21-0.91) when LDA was used for five or more years. Our findings indicate that LDA use might be associated with a reduction of risk of PCa in patients with cardio- or cerebrovascular diseases.What's new? Aspirin may reduce the risk of PCa, according to these new results. Previous work has shown that LDA, often prescribed for cardiovascular or cerebrovascular disease, reduces the incidence of colorectal cancer. To probe a possible connection with PCa, these authors undertook a large-scale, population based retrospective cohort study involving more than 13,000 participants. PCa struck less frequently among those taking LDA at least twice per week, particularly if they continued taking it for several years.

BACKGROUND:Chronic spontaneous urticaria (CSU) is a common skin disease, but there is a paucity of precise epidemiological data on this disease.OBJECTIVES:To obtain information on the epidemiology of CSU in Italy.METHODS:The data source was the Health Search IMS Health Longitudinal Patient Database. The study population was formed by patients aged ≥ 15 years, registered with a total of 700 general practitioners, homogeneously distributed across Italy. An algorithm based on the International Classification of Diseases, ninth revision, Clinical Modification was used for the identification of patients with CSU. The annual prevalence and incidence rates of CSU over a 12-year period (2002-2013) were estimated, along with demographic and clinical determinants.RESULTS:The annual prevalence of CSU ranged from 0·02% in 2002 to 0·38% in 2013. The incidence was 0·10-1·50 per 1000 person-years. For both prevalence and incidence rates, female patients outnumbered male. The risk of CSU was statistically significantly higher in the presence of the following variables: obesity; anxiety, dissociative and somatoform disorders; malignancies; use of immunosuppressive drugs; and chronic use of systemic corticosteroids. History of autoimmune thyroiditis showed a trend towards an increased risk of CSU, though it was not statistically significant. Smoking was associated with a significantly reduced risk of CSU.CONCLUSIONS:Our findings on CSU prevalence are consistent with those obtained in previous studies. Furthermore, this large population-based study provides important information regarding the association of CSU with demographic and clinical determinants, which have been examined in the primary-care setting.