Treatment pathway analysis of newly diagnosed dementia patients in four electronic health record databases in Europe.

PURPOSE: Real-world studies to describe the use of first, second and third line therapies for the management and symptomatic treatment of dementia are lacking. This retrospective cohort study describes the first-, second- and third-line therapies used for the management and symptomatic treatment of dementia, and in particular Alzheimer's Disease. METHODS: Medical records of patients with newly diagnosed dementia between 1997 and 2017 were collected using four databases from the UK, Denmark, Italy and the Netherlands. RESULTS: We identified 191,933 newly diagnosed dementia patients in the four databases between 1997 and 2017 with 39,836 (IPCI (NL): 3281, HSD (IT): 1601, AUH (DK): 4474, THIN (UK): 30,480) fulfilling the inclusion criteria, and of these, 21,131 had received a specific diagnosis of Alzheimer's disease. The most common first line therapy initiated within a year (± 365 days) of diagnosis were Acetylcholinesterase inhibitors, namely rivastigmine in IPCI, donepezil in HSD and the THIN and the N-methyl-D-aspartate blocker memantine in AUH. CONCLUSION: We provide a real-world insight into the heterogeneous management and treatment pathways of newly diagnosed dementia patients and a subset of Alzheimer's Disease patients from across Europe.

Vascular and metabolic risk factor differences prior to dementia diagnosis: a multidatabase case-control study using European electronic health records.

OBJECTIVE: The objective of the study is to compare body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP) and serum total cholesterol levels between dementia cases and controls at multiple time intervals prior to dementia onset, and to test time interval as a modifying factor for these associations. DESIGN: Case-control study. SETTING: Six European electronic health records databases. PARTICIPANTS: 291 780 cases at the date of first-recorded dementia diagnosis, compared with 29 170 549 controls randomly selected from the same databases, age matched and sex matched at this index date. EXPOSURE: The following measures were extracted whenever recorded within each dataset: BMI (kg/m2), SBP and DBP (mm Hg) and serum total cholesterol (mmol/L). Levels for each of these variables were defined within six 2-year time intervals over the 12 years prior to the index date. MAIN OUTCOMES: Case-control differences in exposures of interest were modelled for each time period and adjusted for demographic and clinical factors (ischaemic/unspecified stroke, type 2 diabetes mellitus, acute myocardial infarction, hypertension diagnosis, antihypertensive medication, cholesterol-lowering medication). Coefficients and interactions with time period were meta-analysed across the six databases. RESULTS: Mean BMI (coefficient -1.16 kg/m2; 95% CI -1.38 to 0.93) and SBP (-2.83 mm Hg; 95% CI -4.49 to -1.16) were lower in cases at diagnosis, and case-control differences were greater in more recent time periods, as indicated by significant case-x-time interaction and case-x-time-squared interaction terms. Time variations in coefficients for cholesterol levels were less consistent between databases and those for DBP were largely not significant. CONCLUSION: Routine clinical data show emerging divergence in levels of BMI and SBP prior to the diagnosis of dementia but less evidence for DBP or total cholesterol levels. These divergences should receive at least some consideration in routine dementia risk screening, although underlying mechanisms still require further investigation.

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.

Measuring the Effectiveness of Safety Warnings on the Risk of Stroke in Older Antipsychotic Users: A Nationwide Cohort Study in Two Large Electronic Medical Records Databases in the United Kingdom and Italy.

INTRODUCTION: Safety warnings relating to antipsychotic-associated stroke among older persons in the UK and Italy were issued. However, the impact of these safety warnings on stroke risk has not been measured to date. OBJECTIVE: The aim of this study was to measure the change in stroke incidence after two safety warnings in both the UK and Italy. METHOD: A cohort study was conducted using electronic medical records representative of the UK (The Health Improvement Network) and Italy (Health Search-IQVIA Health LPD), containing data on 11 million and 1 million patients, respectively. After each drug safety warning, elderly antipsychotic new initiators were propensity-score matched 1:1:1 on antipsychotic initiators before any safety warning. Stroke incidence within 6 months of antipsychotic initiation, using an intention-to-treat approach, was the main outcome. RESULTS: In the UK and Italy, 6342 and 7587 elderly antipsychotic initiators were identified, respectively. A 42% stroke incidence reduction was seen in the UK after the first safety warning [42.3 (95% confidence interval (CI) 35.2-50.8) vs. 24.4 [95% CI 19.0-31.2] events per 1000 person-years (PYs)], while there was a 60% stroke incidence reduction after the second warning (16.9 [95% CI 12.2-23.4] events per 1000 PYs) compared to before the first warning. There was no significant reduction in stroke incidence in Italy. CONCLUSION: Antipsychotic safety warnings were followed by a reduction in stroke incidence among older antipsychotic users in the UK, but not Italy.

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.

Real-world data reveal a diagnostic gap in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. It affects an estimated 20% of the general population, based on cohort studies of varying size and heterogeneous selection. However, the prevalence and incidence of recorded NAFLD diagnoses in unselected real-world health-care records is unknown. We harmonised health records from four major European territories and assessed age- and sex-specific point prevalence and incidence of NAFLD over the past decade. METHODS: Data were extracted from The Health Improvement Network (UK), Health Search Database (Italy), Information System for Research in Primary Care (Spain) and Integrated Primary Care Information (Netherlands). Each database uses a different coding system. Prevalence and incidence estimates were pooled across databases by random-effects meta-analysis after a log-transformation. RESULTS: Data were available for 17,669,973 adults, of which 176,114 had a recorded diagnosis of NAFLD. Pooled prevalence trebled from 0.60% in 2007 (95% confidence interval: 0.41-0.79) to 1.85% (0.91-2.79) in 2014. Incidence doubled from 1.32 (0.83-1.82) to 2.35 (1.29-3.40) per 1000 person-years. The FIB-4 non-invasive estimate of liver fibrosis could be calculated in 40.6% of patients, of whom 29.6-35.7% had indeterminate or high-risk scores. CONCLUSIONS: In the largest primary-care record study of its kind to date, rates of recorded NAFLD are much lower than expected suggesting under-diagnosis and under-recording. Despite this, we have identified rising incidence and prevalence of the diagnosis. Improved recognition of NAFLD may identify people who will benefit from risk factor modification or emerging therapies to prevent progression to cardiometabolic and hepatic complications.

Improvement in the management of chronic obstructive pulmonary disease following a clinical educational program: results from a prospective cohort study in the Sicilian general practice setting.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lungs associated with progressive disability. Although general practitioners (GPs) should play an important role in the COPD management, critical issues have been documented in the primary care setting. The aim of this study was to evaluate the effectiveness of an educational program for the improvement of the COPD management in a Sicilian general practice setting. The effectiveness of the program, was evaluated by comparing 15 quality-of-care indicators developed from data extracted by 33 GPs, at baseline vs. 12 and 24 months, and compared with data from a national primary care database (HSD). Moreover, data on COPD-related and all-cause hospitalizations over time of COPD patients, was measured. Overall, 1,465 patients (3.2%) had a registered diagnosis of COPD at baseline vs. 1,395 (3.0%) and 1,388 (3.0%) over time (vs. 3.0% in HSD). COPD patients with one spirometry registered increased from 59.7% at baseline to 73.0% after 2 years (vs. 64.8% in HSD). Instead, some quality of care indicators where not modified such as proportion of COPD patients treated with ICS in monotherapy that was almost stable during the study period: 9.6% (baseline) vs. 9.9% (after 2 years), vs. 7.7% in HSD. COPD-related and all-cause hospitalizations of patients affected by COPD decreased during the two observation years (from 6.9% vs. 4.0%; from 23.0% vs. 18.9%, respectively). Our study showed that educational program involving specialists, clinical pharmacologists and GPs based on training events and clinical audit may contribute to partly improve both diagnostic and therapeutic management of COPD in primary care setting, despite this effect may vary across GPs and indicators of COPD quality of care.

Monitoring compliance with standards of care for chronic diseases using healthcare administrative databases in Italy: Strengths and limitations.

BACKGROUND: A recent comprehensive report on healthcare quality in Italy published by the Organization of Economic Co-operation and Development (OECD) recommended that regular monitoring of quality of primary care by means of compliance with standards of care for chronic diseases is performed. A previous ecological study demonstrated that compliance with standards of care could be reliably estimated on regional level using administrative databases. This study compares estimates based on administrative data with estimates based on GP records for the same persons, to understand whether ecological fallacy played a role in the results of the previous study. METHODS: We compared estimates of compliance with diagnostic and therapeutic standards of care for type 2 diabetes (T2DM), hypertension and ischaemic heart disease (IHD) from administrative data (IAD) with estimates from medical records (MR) for the same persons registered with 24 GP's in 2012. Data were linked at an individual level. RESULTS: 32,688 persons entered the study, 12,673 having at least one of the three diseases according to at least one data source. Patients not detected by IAD were many, for all three conditions: adding MR increased the number of cases of T2DM, hypertension, and IHD by +40%, +42%, and +104%, respectively. IAD had imperfect sensitivity in detecting population compliance with therapies (adding MR increased the estimate, from +11.5% for statins to +14.7% for antithrombotics), and, more substantially, with diagnostic recommendations (adding MR increased the estimate, from +23.7% in glycated hemoglobin tests, to +50.5% in electrocardiogram). Patients not detected by IAD were less compliant with respect to those that IAD correctly identified (from -4.8 percentage points in proportion of IHD patients compliant with a yearly glycated hemoglobin test, to -40.1 points in the proportion of T2DM patients compliant with the same recommendation). IAD overestimated indicators of compliance with therapeutic standards (significant differences ranged from 3.3. to 3.6 percentage points) and underestimated indicators of compliance with diagnostic standards (significant differences ranged from -2.3 to -14.1 percentage points). CONCLUSION: IAD overestimated the percentage of patients compliant with therapeutic standards by less than 6 percentage points, and underestimated the percentage of patients compliant with diagnostic standards by a maximum of 14 percentage points. Therefore, both discussions at local level between GP's and local health unit managers and discussions at central level between national and regional policy makers can be informed by indicators of compliance estimated by IAD, which, based on those results, have the ability of signalling critical or excellent clusters. However, this study found that estimates are partly flawed, because a high number of patients with chronic diseases are not detected by IAD, patients detected are not representative of the whole population of patients, and some categories of diagnostic tests are markedly underrecorded in IAD (up to 50% in the case of electrocardiograms). Those results call to caution when interpreting IAD estimates. Audits based on medical records, on the local level, and an interpretation taking into account information external to IAD, on the central level, are needed to assess a more comprehensive compliance with standards.

Automatic identification of type 2 diabetes, hypertension, ischaemic heart disease, heart failure and their levels of severity from Italian General Practitioners' electronic medical records: a validation study.

OBJECTIVES: The Italian project MATRICE aimed to assess how well cases of type 2 diabetes (T2DM), hypertension, ischaemic heart disease (IHD) and heart failure (HF) and their levels of severity can be automatically extracted from the Health Search/CSD Longitudinal Patient Database (HSD). From the medical records of the general practitioners (GP) who volunteered to participate, cases were extracted by algorithms based on diagnosis codes, keywords, drug prescriptions and results of diagnostic tests. A random sample of identified cases was validated by interviewing their GPs. SETTING: HSD is a database of primary care medical records. A panel of 12 GPs participated in this validation study. PARTICIPANTS: 300 patients were sampled for each disease, except for HF, where 243 patients were assessed. OUTCOME MEASURES: The positive predictive value (PPV) was assessed for the presence/absence of each condition against the GP's response to the questionnaire, and Cohen's κ was calculated for agreement on the severity level. RESULTS: The PPV was 100% (99% to 100%) for T2DM and hypertension, 98% (96% to 100%) for IHD and 55% (49% to 61%) for HF. Cohen's kappa for agreement on the severity level was 0.70 for T2DM and 0.69 for hypertension and IHD. CONCLUSIONS: This study shows that individuals with T2DM, hypertension or IHD can be validly identified in HSD by automated identification algorithms. Automatic queries for levels of severity of the same diseases compare well with the corresponding clinical definitions, but some misclassification occurs. For HF, further research is needed to refine the current algorithm.

Identifying Cases of Type 2 Diabetes in Heterogeneous Data Sources: Strategy from the EMIF Project.

Due to the heterogeneity of existing European sources of observational healthcare data, data source-tailored choices are needed to execute multi-data source, multi-national epidemiological studies. This makes transparent documentation paramount. In this proof-of-concept study, a novel standard data derivation procedure was tested in a set of heterogeneous data sources. Identification of subjects with type 2 diabetes (T2DM) was the test case. We included three primary care data sources (PCDs), three record linkage of administrative and/or registry data sources (RLDs), one hospital and one biobank. Overall, data from 12 million subjects from six European countries were extracted. Based on a shared event definition, sixteeen standard algorithms (components) useful to identify T2DM cases were generated through a top-down/bottom-up iterative approach. Each component was based on one single data domain among diagnoses, drugs, diagnostic test utilization and laboratory results. Diagnoses-based components were subclassified considering the healthcare setting (primary, secondary, inpatient care). The Unified Medical Language System was used for semantic harmonization within data domains. Individual components were extracted and proportion of population identified was compared across data sources. Drug-based components performed similarly in RLDs and PCDs, unlike diagnoses-based components. Using components as building blocks, logical combinations with AND, OR, AND NOT were tested and local experts recommended their preferred data source-tailored combination. The population identified per data sources by resulting algorithms varied from 3.5% to 15.7%, however, age-specific results were fairly comparable. The impact of individual components was assessed: diagnoses-based components identified the majority of cases in PCDs (93-100%), while drug-based components were the main contributors in RLDs (81-100%). The proposed data derivation procedure allowed the generation of data source-tailored case-finding algorithms in a standardized fashion, facilitated transparent documentation of the process and benchmarking of data sources, and provided bases for interpretation of possible inter-data source inconsistency of findings in future studies.

Epidemiology of Parkinson's Disease: A Population-Based Study in Primary Care in Italy.

BACKGROUND: There are no studies on prevalence, incidence and comorbidities of Parkinson's disease (PD) in the Italian population. METHODS: The database of 700 Italian general practitioners (population, 923,356) was investigated. All patients with International Classification of Diseases Ninth Revision - Clinical Modification (ICD-9-CM) diagnosis of PD during the period 2002-2012 were included. Parkinsonisms were excluded. Clinical conditions preceding PD were identified through ICD-9-CM codes. The Charlson Comorbidity Index was used. PD crude and standardized prevalence and annual incidence were calculated. Crude and adjusted hazard ratios were calculated for comorbidities. RESULTS: A total of 2,204 patients (1,140 men, 1,064 women, age 22-95 years) were included. The crude prevalence of PD was 239/100,000. Prevalence increased exponentially with age. Standardized prevalence was 233 (95% CI 232-235). One hundred ninety-four patients were newly diagnosed, giving a crude incidence of 22/100,000 and a standardized incidence of 23.1/100,000 (95% CI 22.9-23.2). Incidence increased steadily until age 75-84 years and then decreased. Older age, cardiovascular and gastrointestinal disorders, diabetes, and restless-legs syndrome were associated with increased PD risk and smoking and hypersomnia with decreased PD risk. The Charlson Comorbidity Index was associated with PD risk with a documented gradient. CONCLUSIONS: Prevalence and incidence of PD in Italy are in line with studies with the highest case ascertainment. PD risk varies with the number and type of comorbidities.

The Effect of Safety Warnings on Antipsychotic Drug Prescribing in Elderly Persons with Dementia in the United Kingdom and Italy: A Population-Based Study.

BACKGROUND: Antipsychotic (AP) drugs are commonly used to manage the behavioural symptoms of dementia. Nevertheless, international (i.e. the European Medicines Agency in Europe) and national (i.e. the Medicines and Healthcare products Regulatory Agency in the UK and the Italian Drug Agency) regulatory agencies issued safety warnings against AP use in dementia in 2004 and 2009. OBJECTIVE: The aim of this study is to investigate the short- and long-term impact of safety warnings on the use of APs in UK and Italian persons with dementia using two nationwide databases: The Health Improvement Network (THIN) from the UK and the Health Search Database-Cegedim-Strategic Data-Longitudinal Patient Database (HSD-CSD-LPD) from Italy. METHODS: We calculated the overall quarterly prevalence of AP use by class and by individual drug in persons with dementia aged ≥65 years and used generalized linear models to explore the effect of the safety warnings. RESULTS: We identified 58,497 and 10,857 individuals aged ≥65 years with dementia from the THIN and HSD-CSD-LPD databases, respectively, over the period 2000-2012. After the 2004 warnings, the use of atypical APs decreased, whereas the use of conventional APs increased, in Italy and the UK until 2009. However, the trend for APs individually showed that the use of risperidone/olanzapine decreased, whereas the use of quetiapine increased in both countries. After the 2009 warnings (until 2012), the use of atypical and conventional APs decreased in the UK (from 11 to 9 and 5 to 3 %, respectively), but such use increased in Italy (from 11 to 18 and 9 to 14 %, respectively). CONCLUSION: The 2004 warnings led to a reduction in the use of olanzapine and risperidone and increased the use of quetiapine/conventional APs in both countries. From 2009, the use of APs decreased in persons with dementia in the UK but not in Italy. Possible reasons for the difference in AP use between the two countries include a more proactive approach towards reducing the use of APs in the UK than in Italy.

Patient Adherence to Olmesartan/Amlodipine Combinations: Fixed Versus Extemporaneous Combinations.

BACKGROUND: Lack of adherence to prescribed therapies is often a cause of suboptimal blood pressure control in patients with hypertension. To enhance patients' adherence to treatment, fixed-dose combinations of active substances with complementary mechanisms of action have been developed. An angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker (ARB) is often combined with a calcium channel blocker. Olmesartan is the most used ARB in combination therapy. In Italy, in September 2011, a fixed-dose combination of olmesartan/amlodipine (olmesartan/amlodipine 20/5 mg, 40/5 mg, or 40/10 mg) was introduced to treat patients with hypertension for whom control of blood pressure is not reached with either olmesartan or amlodipine alone. Prior research on adherence to olmesartan/amlodipine combinations was carried out in local contexts (e.g., claims databases of Italian regions or local health authorities), and/or it was limited by the fact that adherence was assessed against monotherapies already known for their low compliance profile, such as diuretics. OBJECTIVE: To compare adherence with olmesartan/amlodipine fixed-dose combination (FDC) and extemporaneous combination in primary care in Italy. METHODS: A nationwide, population-based study was conducted by using the Health Search IMS Health Longitudinal Patient Database. Patients aged > 17 years, affected by hypertension and treated with the FDC or extemporaneous combination of olmesartan/amlodipine, were identified. Adherence to these 2 therapeutic regimens was estimated by calculating the proportion of days covered (PDC). Patients were classified into 3 levels of adherence: high (PDC ≥ 80%), intermediate (PDC = 40%-79%), or low (PDC < 40%). RESULTS: In the 6-month follow-up, FDC showed higher adherence compared with an extemporaneous combination (55.1% vs. 15.9%, P < 0.001). This difference was confirmed in a multivariable logistic regression model clustered on patient identifier (odds ratio = 6.65; 95% CI = 3.10-14.26; P < 0.001). The proportion of patients adherent to FDC varied from 60.4% for the 40/5 mg formulation to 47.5% for the 40/10 mg formulation. CONCLUSIONS: These findings suggest that higher adherence may be achieved with FDCs than with extemporaneous combinations. To improve the degree of adherence, general practitioners may consider prescribing fixed combinations of antihypertensive agents as soon as monotherapies fail to achieve the expected therapeutic objective.

Prevalence and incidence of epilepsy in Italy based on a nationwide database.

OBJECTIVES: To estimate the prevalence and incidence of epilepsy in Italy using a national database of general practitioners (GPs). METHODS: The Health Search CSD Longitudinal Patient Database (HSD) has been established in 1998 by the Italian College of GPs. Participants were 700 GPs, representing a population of 912,458. For each patient, information on age and sex, EEG, CT scan, and MRI was included. Prevalent cases with a diagnosis of 'epilepsy' (ICD9CM: 345*) were selected in the 2011 population. Incident cases of epilepsy were identified in 2011 by excluding patients diagnosed for epilepsy and convulsions and those with EEG, CT scan, MRI prescribed for epilepsy and/or convulsions in the previous years. Crude and standardized (Italian population) prevalence and incidence were calculated. RESULTS: Crude prevalence of epilepsy was 7.9 per 1,000 (men 8.1; women 7.7). The highest prevalence was in patients <25 years and ≥75 years. The incidence of epilepsy was 33.5 per 100,000 (women 35.3; men 31.5). The highest incidence was in women <25 years and in men 75 years or older. CONCLUSIONS: Prevalence and incidence of epilepsy in this study were similar to those of other industrialized countries. HSD appears as a reliable data source for the surveillance of epilepsy in Italy.

Can Italian healthcare administrative databases be used to compare regions with respect to compliance with standards of care for chronic diseases?

BACKGROUND: Italy has a population of 60 million and a universal coverage single-payer healthcare system, which mandates collection of healthcare administrative data in a uniform fashion throughout the country. On the other hand, organization of the health system takes place at the regional level, and local initiatives generate natural experiments. This is happening in particular in primary care, due to the need to face the growing burden of chronic diseases. Health services research can compare and evaluate local initiatives on the basis of the common healthcare administrative data.However reliability of such data in this context needs to be assessed, especially when comparing different regions of the country. In this paper we investigated the validity of healthcare administrative databases to compute indicators of compliance with standards of care for diabetes, ischaemic heart disease (IHD) and heart failure (HF). METHODS: We compared indicators estimated from healthcare administrative data collected by Local Health Authorities in five Italian regions with corresponding estimates from clinical data collected by General Practitioners (GPs). Four indicators of diagnostic follow-up (two for diabetes, one for IHD and one for HF) and four indicators of appropriate therapy (two each for IHD and HF) were considered. RESULTS: Agreement between the two data sources was very good, except for indicators of laboratory diagnostic follow-up in one region and for the indicator of bioimaging diagnostic follow-up in all regions, where measurement with administrative data underestimated quality. CONCLUSION: According to evidence presented in this study, estimating compliance with standards of care for diabetes, ischaemic heart disease and heart failure from healthcare databases is likely to produce reliable results, even though completeness of data on diagnostic procedures should be assessed first. Performing studies comparing regions using such indicators as outcomes is a promising development with potential to improve quality governance in the Italian healthcare system.

Chronic disease prevalence from Italian administrative databases in the VALORE project: a validation through comparison of population estimates with general practice databases and national survey.

BACKGROUND: Administrative databases are widely available and have been extensively used to provide estimates of chronic disease prevalence for the purpose of surveillance of both geographical and temporal trends. There are, however, other sources of data available, such as medical records from primary care and national surveys. In this paper we compare disease prevalence estimates obtained from these three different data sources. METHODS: Data from general practitioners (GP) and administrative transactions for health services were collected from five Italian regions (Veneto, Emilia Romagna, Tuscany, Marche and Sicily) belonging to all the three macroareas of the country (North, Center, South). Crude prevalence estimates were calculated by data source and region for diabetes, ischaemic heart disease, heart failure and chronic obstructive pulmonary disease (COPD). For diabetes and COPD, prevalence estimates were also obtained from a national health survey. When necessary, estimates were adjusted for completeness of data ascertainment. RESULTS: Crude prevalence estimates of diabetes in administrative databases (range: from 4.8% to 7.1%) were lower than corresponding GP (6.2%-8.5%) and survey-based estimates (5.1%-7.5%). Geographical trends were similar in the three sources and estimates based on treatment were the same, while estimates adjusted for completeness of ascertainment (6.1%-8.8%) were slightly higher. For ischaemic heart disease administrative and GP data sources were fairly consistent, with prevalence ranging from 3.7% to 4.7% and from 3.3% to 4.9%, respectively. In the case of heart failure administrative estimates were consistently higher than GPs' estimates in all five regions, the highest difference being 1.4% vs 1.1%. For COPD the estimates from administrative data, ranging from 3.1% to 5.2%, fell into the confidence interval of the Survey estimates in four regions, but failed to detect the higher prevalence in the most Southern region (4.0% in administrative data vs 6.8% in survey data). The prevalence estimates for COPD from GP data were consistently higher than the corresponding estimates from the other two sources. CONCLUSION: This study supports the use of data from Italian administrative databases to estimate geographic differences in population prevalence of ischaemic heart disease, treated diabetes, diabetes mellitus and heart failure. The algorithm for COPD used in this study requires further refinement.

Adipokines as possible new predictors of cardiovascular diseases: a case control study.

Background and Aims. The secretion of several adipocytokines, such as adiponectin, retinol-binding protein 4 (RBP4), adipocyte fatty acid binding protein (aFABP), and visfatin, is altered in subjects with abdominal adiposity; these endocrine alterations could contribute to increased cardiovascular risk. The aim of the study was to assess the relationship among adiponectin, RBP4, aFABP, and visfatin, and incident cardiovascular disease. Methods and Results. A case-control study, nested within a prospective cohort, on 2945 subjects enrolled for a diabetes screening program was performed. We studied 18 patients with incident fatal or nonfatal IHD (Ischemic Heart Disease) or CVD (Cerebrovascular Disease), compared with 18 matched control subjects. Circulating adiponectin levels were significantly lower in cases of IHD with respect to controls. Circulating RBP4 levels were significantly increased in CVD and decreased in IHD with respect to controls. Circulating aFABP4 levels were significantly increased in CVD, while no difference was associated with IHD. Circulating visfatin levels were significantly lower in cases of both CVD and IHD with respect to controls, while no difference was associated with CVD. Conclusions. The present study confirms that low adiponectin is associated with increased incidents of IHD, but not CVD, and suggests, for the first time, a major effect of visfatin, aFABP, and RBP4 in the development of cardiovascular disease.

Predictors of recovery of ovarian function after weight gain in subjects with amenorrhea related to restrictive eating disorders.

OBJECTIVE: The aim of the present study was to investigate the anthropometric and endocrine characteristics of subjects with amenorrhea related to eating disorders after weight recovery, in order to identify factors connected with the resumption of menses. METHODS: Clinical data, body composition parameters and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, cortisol, leptin and insulin were assessed in two groups of young women classified according to menstrual status after weight rehabilitation: 43 subjects who displayed persistent amenorrhea and 34 who resumed menses. Univariate and multivariate logistic regression analyses were used to examine the relationships between the different parameters and menstrual recovery. RESULTS: The patients who resumed menses had low initial weight and BMI, and a greater difference between current and initial BMI (DeltaBMI), than those with amenorrhea. No differences were observed in lean mass, body fat or bone density between the two groups. Moreover, the reduction in FSH and the increase in LH, insulin and leptin emerged as significant predictors of menstrual recovery. Increased DeltaBMI and insulin continued to be positive predictors in the multivariate analysis. CONCLUSION: Following weight rehabilitation, the individual's metabolic set point before weight loss and the current insulin levels appear significant in predicting the reactivation of reproductive function.