Drug utilization analysis of osteoporosis medications in seven European electronic health databases.

We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments. PURPOSE: To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns. METHODS: We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022. RESULTS: Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52-73% at 6 months to 29-53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50-66% at 6 months and decreased to 30-44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40-73% and decreased to 25-59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50-85% (6 month), 30-63% (12 month) and with teriparatide 40-75% (6 month) decreasing to 21-54% (12 month). Switching occurred most frequently in the alendronate group (2.8-5.8%) and in the teriparatide group (7.1-14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab. CONCLUSION: Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare.

How many and who are patients with heart failure eligible to SGLT2 inhibitors? Responses from the combination of administrative healthcare and primary care databases.

BACKGROUND: Recent successful findings (i.e. DAPA-HF trial) in patients with heart failure (HF) with/without diabetes treated with sodium-glucose co-transporter inhibitors (SGLT2-I) have fostered real-world data analyses. Fondazione Ricerca e Salute's (ReSD) administrative and Health Search's (HSD) primary healthcare databases were combined in the ReS-HS DB Consortium, to identify and characterize HF-patients eligible to SGLT2-I, and assess their costs charged to the Italian National Health Service (INHS). METHODS AND RESULTS: Eligibility to SGLT2-I was HF diagnosis, age ≥ 18 years, reduced (≤40%) ejection fraction (HFrEF) and glomerular filtration rate (GFR) ≥30 ml/min. The HSD, including 13,313 HF-patients (1.5% of the total HSD population) was used to develop and test the algorithms for imputing HFrEF and GFR ≥ 30 ml/min, based on a set of covariates, to the ReSD, including 67,369 (1.5% of the total ReSD population). Subjects eligible to SGLT2-I were 2187 in HSD (61.1% of HFrEF); after the imputation, 15,145 in ReSD (58.8% of HFrEF). Prevalence of eligibility to SGLT2-I was higher in males then in females and increased with age; diabetic patients were 44.3% and 33.4% of HSD and ReSD populations eligible to SGLT2-I, respectively. Estimated from ReSD, the mean annual cost charged to the INHS per patient with HF eligible to SGLT2-I was €7122 (68% due to hospitalizations). CONCLUSIONS: Approximately 20% of patients with HF was eligible to SGLT2-I. Real-world data can identify, quantify and characterize patients eligible to SGLT2-Is and assess related costs for the health care system, thus providing useful information to Regulatory Decision makers.

Characterization of Asthma by Age of Onset: A Multi-Database Cohort Study.

BACKGROUND: Asthma can occur at any age but the differences in patient characteristics between childhood-, adult-, and late-onset asthma are not well understood. OBJECTIVE: To investigate differences in patients' characteristics by age at asthma onset. METHODS: From 5 European electronic databases, we created a cohort encompassing adult patients with doctor-diagnosed asthma in 2008 to 2013. Patients were categorized based on their age at asthma onset: childhood-onset (age at onset < 18 y), adult-onset (age at onset 18-40 y), and late-onset asthma (age at onset ≥ 40 y). Comorbidities were assessed at study entry. For each characteristic and comorbidity, odds ratios and age- and sex-adjusted odds ratios (ORadj) comparing asthma-onset categories were estimated per database and combined in a meta-analysis using a random effect model. RESULTS: In total, 586,436 adult asthma patients were included, 81,691 had childhood-onset, 218,184 adult-onset, and 286,561 late-onset asthma. Overall, 7.3% had severe asthma. Subjects with adult-onset compared with childhood-asthma had higher risks for overweight/obesity (ORadj 1.4; 95% CI 1.1-1.8) and lower risks for atopic disorders (ORadj 0.8; 95% CI 0.7-0.95). Patients with late-onset compared with adult-onset asthma had higher risks for nasal polyposis (ORadj 1.8; 95% CI 1.2-2.6), overweight/obesity (ORadj 1.3; 95% CI 1.2-1.4), gastroesophageal reflux disease (ORadj 1.4; 95% CI 1.2-1.7), and diabetes (ORadj 2.3; 95% CI 1.8-2.9). A significant association between late-onset asthma and uncontrolled asthma was observed (ORadj 2.8; 95% CI 1.7-4.5). CONCLUSIONS: This international study demonstrates clear differences in comorbidities between childhood-, adult-, and late-onset asthma phenotypes in adults. Furthermore, patients with late-onset asthma had more frequent uncontrolled asthma.

Determinants of HCV-related complications in Italian primary care patients.

BACKGROUND AND AIMS: This study aimed to assess the demographic and clinical determinants of liver complications in Hepatitis C virus (HCV)-positive patients in primary care setting. METHODS: Using the Health Search database, we selected a cohort of patients aged ≥14 diagnosed with HCV between 2002 and 2017. Patients were followed up until the occurrence of cirrhosis and other disease progressions such as oesophageal varices, hepatocellular carcinoma and/or liver transplantation. The candidate determinants for the risk of HCV-related complications included sex, age, smoking status, liver fibrosis (measured by fibrosis 4 index [FIB-4]), infections by the human immunodeficiency virus (HIV), hepatitis B virus (HBV), other forms of hepatitis, abuse of alcohol or illicit substances or drugs, obesity, metabolic syndrome, diabetes mellitus and renal disease. Cox regression was used to test the association between candidate determinants and the outcome. RESULTS: The cohort included 8299 HCV-positive patients (50.93% men) with an overall prevalence rate equal to 0.61%. At least one HCV-related complication was found in 12.2% of patients, with a mean time-to-event equal to 8.1 year. Along with male sex and advanced age, a FIB-4 greater than 3.25 and the presence of diabetes were associated with a greater risk of HCV-related complications. CONCLUSION: Our study shows that patients with certain demographics and clinical characteristics are more prone to incur in HCV-related complications. The knowledge and early identification of these determinants by GPs may result in reducing disease progression and related healthcare costs through a closer monitoring.

Prediagnostic use of low-dose aspirin and risk of incident metastasis and all-cause mortality among patients with colorectal cancer.

AIMS: Previous studies suggest that the use of low-dose aspirin before a colorectal cancer (CRC) diagnosis may be associated with a decreased risk of CRC progression. Data supporting this association, however, have been inconsistent. We evaluate whether the use of prediagnostic low-dose aspirin is associated with a lower risk of metastases and all-cause mortality in CRC patients. METHODS: Using a large Italian population-based primary care database, we identified a cohort of 7478 patients newly diagnosed with nonmetastatic CRC between 2000 and 2013. Use of prediagnostic low-dose aspirin was compared with no use of low-dose aspirin. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of incident metastasis and of all-cause mortality associated with prediagnostic low-dose aspirin use, both overall and by duration of use. RESULTS: There were 314 incident metastatic events and 2189 deaths during a mean follow-up time of 4.4 and 4.7 years, respectively. Overall prediagnostic use of low-dose aspirin was not associated with a decreased risk of incident metastasis (HR 0.88; 95% CI 0.63-1.22) or all-cause mortality (HR 1.09; 95% CI 0.96-1.22) in CRC patients. Cumulative duration of aspirin use was not associated with a decreased risk of incident metastasis (P-trend = .22) or all-cause mortality (P-trend = .38). These findings remained consistent in sensitivity analyses. CONCLUSION: In this real-world, population-based study, the prediagnostic use of low-dose aspirin was not associated with a decreased risk of incident metastasis or all-cause mortality in CRC patients.

Adherence to COPD free triple inhaled therapy in the real world: a primary care based study.

INTRODUCTION: The development of new pharmacological treatments for chronic obstructive pulmonary disease (COPD) has improved health-related quality of life of patients. However, suboptimal adherence may limit its potential. OBJECTIVE: The aim of the present study was to assess the adherence to free triple inhaled therapy and to investigate poor adherence determinants among primary care patients. METHODS: Data were derived from a primary care database in Italy. Patients aged 40+ affected by COPD and prescribed with inhaled corticosteroids, long-acting beta agonists and long-acting muscarinic antagonists (N = 3177) were enrolled. Low adherence was defined as a proportion of days covered (PDC) by medications prescription lower than 80%. Predictors of low adherence were tested using logistic regression models. RESULTS AND CONCLUSIONS: The 85% of enrolled patients showed poor adherence to free triple inhaled therapy. Comorbidities, such as heart failure (OR 1.78, 95%CI 1.19-2.75), depression (OR 1.41, 95%CI 1.06-1.88) and peripheral vascular disease (OR 1.32, 95%CI 1.01-1.74) were associated with poor adherence. Former (OR 0.52, 95%CI 0.34-0.78) or current smokers (OR 0.61, 95%CI 0.41-0.93) and patients with more severe airways obstruction or history of severe exacerbations (OR 0.64, 95%CI 0.52-0.79) were less likely to exhibit poor adherence. Real-world adherence to triple inhaled therapy with different inhalers is generally low. Higher GOLD airways obstruction stage and current or former smoking status are associated with increased adherence to treatment. Reduced perceived benefit on symptoms control is probably linked to poorer adherence to free triple therapy.

Multinational cohort study of mortality in patients with asthma and severe asthma.

BACKGROUND: Data on the risk of death following an asthma exacerbation are scarce. With this multinational cohort study, we assessed all-cause mortality rates, mortality rates following an exacerbation, and patient characteristics associated with all-cause mortality in asthma. METHODS: Asthma patients aged ≥18 years and with ≥1 year of follow-up were identified in 5 European electronic databases from the Netherlands, Italy, UK, Denmark and Spain during the study period January 1, 2008-December 31, 2013. Patients with asthma-COPD overlap were excluded. Severe asthma was defined as use of high dose ICS + use of a second controller. Severe asthma exacerbations were defined as emergency department visits, hospitalizations or systemic corticosteroid use, all for reason of asthma. RESULTS: The cohort consisted of 586,436 asthma patients of which 42,611 patients (7.3%) had severe asthma. The age and sex standardized all-cause mortality rates ranged between databases from 5.2 to 9.5/1000 person-years (PY) in asthma, and between 11.3 and 14.8/1000 PY in severe asthma. The all-cause mortality rate in the first week following a severe asthma exacerbation ranged between 14.1 and 59.9/1000 PY. Mortality rates remained high in the first month following a severe asthma exacerbation and decreased thereafter. Higher age, male gender, comorbidity, smoking, and previous severe asthma exacerbations were associated with mortality. CONCLUSION: All-cause mortality following a severe exacerbation is high, especially in the first month following the event. Smoking cessation, comorbidity-management and asthma-treatment focusing on the prevention of exacerbations might reduce associated mortality.

Prevalence and incidence of bronchiectasis in Italy.

BACKGROUND: The understanding of the epidemiology of bronchiectasis is still affected by major limitations with very few data published worldwide. The aim of this study was to estimate the epidemiological burden of bronchiectasis in Italy in the adult population followed-up by primary care physicians. METHODS: This study analyzed data coming from a large primary care database with 1,054,376 subjects in the period of time 2002-2015. Patients with bronchiectasis were selected by the use of International Statistical Classification of Diseases, 9th revision, Clinical Modification codes (ICD-9-CM). RESULTS: Patients with bronchiectasis were more likely to have a history of tuberculosis (0.47% vs. 0.06%, p < 0.0001), had higher rates of asthma (16.6% vs. 6.2%, p < 0.0001), COPD (23.3% vs. 6.4%, p < 0.0001) and rheumatoid arthritis (1.9% vs. 0.8%, p < 0.0001). The prevalence and incidence of bronchiectasis in primary care in Italy in 2015 were 163 per 100,000 population and 16.3 per 100,000 person-years, respectively. Prevalence and incidence increased with age and overall rates were highest in men over 75 years old. Prevalence and incidence computed after the exclusion of patients with a diagnosis of either asthma or COPD is 130 per 100,000 and 11.1 cases per 100,000 person-years, respectively. CONCLUSIONS: Bronchiectasis is not a rare condition in Italian adult population. Further studies are needed to confirm our results and provide a better insight on etiology of bronchiectasis in Italy. TRIAL REGISTRATION: not applicable.

Predictors of iron-deficiency anemia in primary care older adults: a real-world European multi-country longitudinal study.

BACKGROUND: Iron deficiency is a major cause of anemia in older people. Increasing the knowledge on the predictors of iron-deficiency anemia (IDA) may facilitate its timely diagnosis. AIM: To investigate the predictors of IDA in older people in four European countries. DESIGN AND SETTING: Retrospective longitudinal study. Primary care patients aged 65 or older (N = 24,051) in four European countries. METHODS: IDA predictors were estimated using multivariate Cox regression based on information gathered from national primary care databases: Italy (years 2002-2013), Belgium, Germany and Spain (years 2007-2012). Adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) were estimated. RESULTS: In Spain and Belgium, men were at greater risk of IDA than women, while they had a lower risk in Italy. Weakness, irritability, alopecia and xerostomia were signs and symptoms significantly associated with IDA. Concurrent diseases, potential causes of anemia, positively associated with IDA were small bowel polyposis, stomach cancer, obesity, gastritis and peptic ulcer, esophagitis, Crohn's disease, celiac disease, lymphangiectasis, gastrectomy or gastric atrophy, gut resection or bypass, and cardiac prosthetic valve. Aspirin users had a 12-35% higher hazard of IDA than non-users. Similarly, corticosteroids and anti-acids were positively associated with IDA. A higher level of comorbidity was associated with an increased hazard of IDA in all countries. CONCLUSIONS: Specific signs and symptoms, chronic conditions, a greater comorbidity burden, and specific pharmacological treatments registered in primary care databases represent relevant predictors and correlates of incident IDA in older people in Europe. General practitioners might employ this information to obtain early diagnosis of IDA in community-dwelling older adults.

Epidemiology of idiopathic pulmonary fibrosis: a population-based study in primary care.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease with unknown etiology and poor prognosis. Little is known about the epidemiology of this disease; most of the studies are limited by small and restricted cohort studies. We aim to investigate the epidemiology of IPF in the Italian primary care setting using the Health Search Database (HSD) between January 2002 and June 2017. In an attempt to define cases of IPF we adopted iterative combinations of International Classification of Diseases Ninth Revision (ICD-9-CM) and other clinical investigations according to three different operational Algorithms. Incidence and prevalence rate, according to the three Algorithms defining IPF, were calculated and the association with candidate determinants [sex, age, gastro-esophageal reflux (GERD) and smoking status] was evaluated. We identified 1,104,307 eligible patients. The prevalence rate of IPF varies between 2.6 to 24.3 per 100.000 person-year, using algorithm 1 and from 0.8 to 7 using algorithm 3. The incidence rate of IPF varies between 1.25 and 3.77 per 100.000 person-years, using algorithm 1 and from 0.10 to 1.61 using algorithm 3. The mean adjusted incidence rate ratio of IPF, using algorithm 1, is 2.33 (95% CI 2.11-2.57) per 100.000 person-years. Over the study years, the trend of prevalence was statistically significantly increasing while the incidence rate started to increase in the last 3 years. The analyses on candidate determinants showed that patients aged 61 years or older, those suffering from GERD, and former smokers were statistically significantly at greater risk of incurring IPF. To our knowledge, this is one of the first European IPF epidemiological studies conducted in primary care. The increase of the incidence rates is likely due to a growing awareness for IPF among General Practitioners, while the increase of prevalence rates may be due to an increase of survival, a result of recent advances in the diagnosis, management and therapies for the disease.

STELO: a new tool for family physicians for the correct identification of inherited cancer syndromes.

BACKGROUND: The hereditary cancer syndromes represent overall <10% of all cancers. These syndromes are not irrelevant for public health because all the cancers typical of these syndromes affected young people and many members of the same family and the cancers are more aggressive than the sporadic ones and need specific surgery and medical therapy. We developed a new family assessment tool: STELO designed for family physicians to identify patients could benefit from Cancer Genetic Counselling. OBJECTIVE: Test the sensitivity and specificity of a new assessment tool for the correct identification of inherited cancer syndromes. METHODS: Retrospectively we tested the new tool on a subset of patients who had already undergone genetic counselling at the Cancer Genetic Counselling Service of ASST (Azienda Socio Sanitaria Territoriale) Settelaghi Varese, to investigate sensitivity, specificity and applicability of this new tool in routine genetic screening. STELO responses were matched against the opinion of two cancer geneticists (i.e. gold standard) who blinded each other decided if the history of these patients was properly suspected as a hereditary cancer syndrome. RESULTS: The Genetic Counselling Service followed 546 subjects from 2014 to 2015. STELO tool was tested retrospectively on these clinical records and resulted positive in 418 cases, out of 546 (76.5%). STELO reported, towards the gold standard, 88.5% and 52.3% of sensitivity and specificity, respectively. CONCLUSIONS: STELO has demonstrated to have a good sensitivity. The specificity was expectedly low given that STELO has been developed for general medicine, so it needs to be simple, practical, of rapid consultation and effectively used in clinical practice.

Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults.

OBJECTIVE: To estimate the risk of acute myocardial infarction (AMI) or stroke in adults with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). DESIGN: Matched cohort study. SETTING: Population based, electronic primary healthcare databases before 31 December 2015 from four European countries: Italy (n=1 542 672), Netherlands (n=2 225 925), Spain (n=5 488 397), and UK (n=12 695 046). PARTICIPANTS: 120 795 adults with a recorded diagnosis of NAFLD or NASH and no other liver diseases, matched at time of NAFLD diagnosis (index date) by age, sex, practice site, and visit, recorded at six months before or after the date of diagnosis, with up to 100 patients without NAFLD or NASH in the same database. MAIN OUTCOME MEASURES: Primary outcome was incident fatal or non-fatal AMI and ischaemic or unspecified stroke. Hazard ratios were estimated using Cox models and pooled across databases by random effect meta-analyses. RESULTS: 120 795 patients with recorded NAFLD or NASH diagnoses were identified with mean follow-up 2.1-5.5 years. After adjustment for age and smoking the pooled hazard ratio for AMI was 1.17 (95% confidence interval 1.05 to 1.30; 1035 events in participants with NAFLD or NASH, 67 823 in matched controls). In a group with more complete data on risk factors (86 098 NAFLD and 4 664 988 matched controls), the hazard ratio for AMI after adjustment for systolic blood pressure, type 2 diabetes, total cholesterol level, statin use, and hypertension was 1.01 (0.91 to 1.12; 747 events in participants with NAFLD or NASH, 37 462 in matched controls). After adjustment for age and smoking status the pooled hazard ratio for stroke was 1.18 (1.11 to 1.24; 2187 events in participants with NAFLD or NASH, 134 001 in matched controls). In the group with more complete data on risk factors, the hazard ratio for stroke was 1.04 (0.99 to 1.09; 1666 events in participants with NAFLD, 83 882 in matched controls) after further adjustment for type 2 diabetes, systolic blood pressure, total cholesterol level, statin use, and hypertension. CONCLUSIONS: The diagnosis of NAFLD in current routine care of 17.7 million patient appears not to be associated with AMI or stroke risk after adjustment for established cardiovascular risk factors. Cardiovascular risk assessment in adults with a diagnosis of NAFLD is important but should be done in the same way as for the general population.

Triple inhaled therapy in COPD patients: determinants of prescription in primary care.

OBJECTIVE: To assess the incidence and determinants of the triple inhaled therapy in chronic obstructive pulmonary disease (COPD) primary care patients. METHODS: Data derived from the Health Search Database (HSD) gathering information on 700 Italian general practitioners. A cohort of COPD patients, prescribed for the first time with inhaled treatments, was followed-up between January 2002 and December 2014. The outcome was the first incident prescription of a triple inhaled therapy, namely the combination of inhaled corticosteroids (ICS), long-acting beta agonists (LABA), and long-acting muscarinic antagonists (LAMA). Cox regressions were used to test the association (hazard ratios, HR) between candidate determinants and the outcome. RESULTS: Out of 17589 patients (mean age 71.1 ±â€¯11.3 years; 37.4% females), 3693 (21%) were prescribed with a triple inhaled therapy during follow-up. Older age (HR = 1.79 to 2.61), current and former smoking habit (HR = 1.72 and 1.66), higher GOLD stage (HR = 1.45 to 2.79), the number of moderate and severe COPD exacerbations (HR = 1.10 to 2.63), and heart failure (HR = 1.17) resulted statistically significantly associated with an increased incident prescription of the triple inhaled therapy. Female sex (HR = 0.80) and some comorbidities (HR = 0.21 to 0.87) resulted negatively associated with the outcome. Furthermore, patients initially treated with LAMA (HR = 1.5) and LABA/ICS (HR = 1.23) were more likely to escalate to the triple therapy, than those on LABA. Conversely, patients initially treated with ICS presented a negative hazard (HR = 0.72). CONCLUSIONS: The knowledge of demographic and clinical determinants of the escalation to the triple inhaled therapy in real-world COPD patients may help clinicians to better personalize respiratory pharmacological treatments of their patients, and inform international societies that issue clinical guidelines.

Gender differences in determinants of iron-deficiency anemia: a population-based study conducted in four European countries.

Iron-deficiency anemia (IDA) was the main condition contributing to higher rates of years lived with disabilities in women in 2016. To date, few studies have investigated gender differences in determinants of IDA in Europe. The aim of the present study was to evaluate the determinants of IDA among females and males in four European countries. IDA determinants were estimated using multivariable Cox regression based on information gathered from national primary care databases, namely Italy (for years 2002-2013), Belgium, Germany, and Spain (for years 2007-2012). Adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) were estimated. Age was significantly associated with IDA in females of childbearing age in all four countries, as well as pregnancy, for which the aHR ranged from 1.20 (95% CI 1.15-1.25) in Italy to 1.88 (95% CI 1.53-2.31) in Germany. In males, the aHR increased with age starting from the 65-69 age group. Menometrorrhagia was associated with IDA in Germany (aHR 2.71, 95% CI 1.96-3.73), Italy (aHR 1.80, 95% CI 1.60-2.03), and Spain (aHR 1.52, 95% CI 1.31-1.76). A greater risk for women with alopecia was also observed. Weakness and headache indicated a higher risk in both men and women. Patients with diseases characterized by blood loss or gastrointestinal malabsorption were also at significantly increased risk. Physicians should encourage women of childbearing age to adhere to dietary recommendations regarding iron intake and regularly prescribe screening of iron status. Upper and lower gastrointestinal investigations should be recommended for patients with a confirmed diagnosis of IDA.

Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common condition that progresses in some patients to steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Here we used healthcare records of 18 million adults to estimate risk of acquiring advanced liver disease diagnoses in patients with NAFLD or NASH compared to individually matched controls. METHODS: Data were extracted from four European primary care databases representing the UK, Netherlands, Italy and Spain. Patients with a recorded diagnosis of NAFLD or NASH (NAFLD/NASH) were followed up for incident cirrhosis and HCC diagnoses. Each coded NAFLD/NASH patient was matched to up to 100 "non-NAFLD" patients by practice site, gender, age ± 5 years and visit recorded within ± 6 months. Hazard ratios (HR) were estimated using Cox models adjusted for age and smoking status and pooled across databases by random effects meta-analyses. RESULTS: Out of 18,782,281 adults, we identified 136,703 patients with coded NAFLD/NASH. Coded NAFLD/NASH patients were more likely to have diabetes, hypertension and obesity than matched controls. HR for cirrhosis in patients compared to controls was 4.73 (95% CI 2.43-9.19) and for HCC, 3.51 (95% CI 1.72-7.16). HR for either outcome was higher in patients with NASH and those with high-risk Fib-4 scores. The strongest independent predictor of a diagnosis of HCC or cirrhosis was baseline diagnosis of diabetes. CONCLUSIONS: Real-world population data show that recorded diagnosis of NAFLD/NASH increases risk of life-threatening liver outcomes. Diabetes is an independent predictor of advanced liver disease diagnosis, emphasising the need to identify specific groups of patients at highest risk.

Overview on the management of diverticular disease by Italian General Practitioners.

BACKGROUND: Although very common in Western countries, poor epidemiological data on diverticular disease (DD) is available from the family practice. AIMS: To evaluate the behavior of Italian General Practitioners (GPs) on approaching DD. METHODS: Health Search Database was analyzed retrospectively. RESULTS: On a population of 975,523 individuals, 33,597 patients had a registered diagnosis of DD ("lifetime" prevalence = 3.4%, M = 3.2%, F = 3.7%; higher values are found in females over-65 years old; low rates of complications: diverticulitis = 0.3%, bleeding = 0.002%). As risk factors, NSAIDs and ASA were taken by 14.8% and 26.5% respectively, opioids by 7.5%, corticosteroids by 5.2%; as protective factors, 30.4% were under statins and 17.7% under calcium-antagonists. Approximately 13% of patients were referred to specialists. Colonoscopy and abdominal CT were prescribed to 48.5% and to 13% of already diagnosed patients. Among DD sufferers, 27% experienced hospitalization, but only 3.4% of cases were for a DD-linked problem. Treatment included rifaximin (61%), mesalazine (14.7%), probiotics (12.4%), ciprofloxacin (7.6%). CONCLUSION: DD has a large impact in general practice with a higher prevalence in the elderly. GPs are required to pay particular attention to risk factors both for disease development and for its complications in order to reduce the costs deriving from diagnostic procedures, referral and hospitalization.

The Role of European Healthcare Databases for Post-Marketing Drug Effectiveness, Safety and Value Evaluation: Where Does Italy Stand?

Enormous progress has been made globally in the use of evidence derived from patients' clinical information as they access their routine medical care. The value of real-world data lies in their complementary nature compared with data from randomised controlled trials: less detailed information on drug efficacy but longer observational periods and larger, more heterogeneous study populations reflecting clinical practice because individuals are included who would not usually be recruited in trials. Real-world data can be collected in various types of electronic sources, such as electronic health records, claims databases and drug or disease registries. These data sources vary in nature from country to country, according to national healthcare system structures and national policies. In Italy, a growing number of healthcare databases have been used to evaluate post-marketing drug utilisation and safety in the last two decades. The aim of this narrative review is to describe the available Italian sources of real-world data and their contribution to generating post-marketing evidence on drug use and safety. We also discuss the strengths and limitations of the most commonly used Italian healthcare databases in addressing various research questions concerning drug utilisation, comparative effectiveness and safety studies, as well as health technology assessment and other areas.

Trends in age-related disease burden and healthcare utilization.

Aging is a strong risk factor for many chronic diseases. However, the impact of an aging population on the prevalence of chronic diseases and related healthcare costs are not known. We used a prevalence-based approach that combines accurate clinical and drug prescription data from Health Search CSD-LPD. This is a longitudinal observational data set containing computer-based patient records collected by Italian general practitioners (GP) and up-to-date healthcare expenditures data from the SiSSI Project. The analysis is based on data collected by 900 GP on an unbalanced sample of more than 1 million patients aged 35+, observed in different time periods between 2005 and 2014. In 2014, 86% of the Italian adults older than 65 had at least one chronic condition, and 56.7% had two or more. Prevalence of multiple chronic diseases and healthcare utilization increased among older and younger adults between 2004 and 2014. Indeed, in the last 10 years, average number of prescriptions increased by approximately 26%, while laboratory and diagnostic tests by 27%. The average number of DDD prescribed increased with age in all the observed years (from 114 in 2005 to 119.9 in 2014 for the 35-50 age group and from 774.9 to 1,178.1 for the 81+ patients). The alarming rising trends in the prevalence of chronic disease and associated healthcare costs in Italy, as well as in many other developed countries, call for an urgent implementation of interventions that prevent or slow the accumulation of metabolic and molecular damage associated with multiple chronic disease.

Prescribing patterns of allopurinol and febuxostat according to directives on the reimbursement criteria and clinical guidelines: analysis of a primary care database.

OBJECTIVE: According to American clinical guidelines, allopurinol and febuxostat may be prescribed as first-line therapy to treat hyperuricemia. However, the Italian Medicines Agency directive, called Nota 91, allows the reimbursement of second-line febuxostat in the case of failure and/or intolerance of a previous allopurinol therapy, so partially embracing European League Against Rheumatism recommendations and the British Society for Rheumatology Guideline. Such inconsistency might lead to heterogeneity among General Practitioners (GPs) in treatment of hyperuricemia. This study, therefore, aimed to evaluate the prescribing behavior of GPs in terms of compliance with Nota 91 and/or official guidelines. METHODS: Using the Health Search Database, a retrospective cohort study was conducted to evaluate the patterns of use of allopurinol and febuxostat between 2011 and 2016. RESULTS: In total, 44,257 and 5837 patients were prescribed with allopurinol and febuxostat, respectively. Among febuxostat users, 4321 (74%) had a previous allopurinol treatment; 92% of switches to febuxostat were related to hyperuricemia, whereas 9% of switchers presented intolerance to allopurinol; 26% of patients were prescribed with febuxostat as first-line therapy. The presence of diabetes and/or moderate/severe renal disease were statistically significant determinants of febuxostat use as first-line therapy. CONCLUSION: Prescriptions of febuxostat were highly compliant to Nota 91. Only a sub-group of frontline prescriptions of febuxostat were mainly driven by the presence of renal dysfunction, which is able to increase the risk of allopurinol intolerance and/or inefficacy. These findings indicate that GPs' prescribing behavior for hyperuricemia is highly compliant with both regulatory directives and clinical guidelines.

Poor adherence to chronic obstructive pulmonary disease medications in primary care: Role of age, disease burden and polypharmacy.

AIM: The aim of the present study was to assess the occurrence and determinants of poor adherence to pharmacological treatment in a cohort of primary care patients with chronic obstructive pulmonary disease (COPD), paying special attention to the role of age, comorbidity and polypharmacy. METHODS: We identified a cohort of COPD patients using the primary care Italian Health Search - IMS Longitudinal Patient Database. We assessed 1-year adherence to COPD maintenance pharmacotherapy (encompassing inhaled corticosteroids, long-acting beta agonists and long-acting anticholinergics). Poor adherence was defined as <80% of proportion of days covered by pharmacological treatment over a 1-year period. RESULTS: Of 22 505 patients (mean age 67.3 ± 13.2; 41.3% women) entering the study, 17 486 (77.7%) were poorly adherent. According to multivariate analysis, poor adherence is less likely in older adults (OR 0.51, 95% CI 0.40-0.66), in non-smokers (OR 0.77, 95% CI 0.69-0.86) and in those with a history of alcohol abuse (OR 0.74, 95% CI 0.58-0.94). Higher comorbidity (OR 1.43, 95% CI 1.13-1.80) was positively associated with poor adherence. Polypharmacy was associated with poor adherence only in patients aged ≥65 years (OR 1.34, 95% CI 1.13-1.59). Finally, COPD severity was associated with a reduced likelihood of poor adherence (OR 0.20, 95% CI 0.07-0.61 for stage IV). CONCLUSIONS: The present findings show that poor medication adherence is common in patients with COPD receiving long-term treatment. The interaction between age and polypharmacy, and the role of comorbidity suggest a pivotal role of biological age as a steering determinant of poor adherence. Geriatr Gerontol Int 2017; 17: 2500-2506.