Incidence and Risk Factors Epilepsy in Patients with Dementia: A Population-Based Study Using Regional Healthcare Databases in Umbria.

Background: Dementia is prevalent among the elderly, also representing a risk for seizures/epilepsy. Estimations of epilepsy risk in dementia patients are not widely available. Objective: Our research aims to ascertain the incidence of epilepsy and its associated risk factors in subjects with dementia in the Umbria region, based on data from healthcare databases. Methods: In this retrospective study based on the healthcare administrative database of Umbria, we identified all patients diagnosed with dementia from 2013 to 2017, based on ICD-9-CM codes. For epilepsy ascertainment, we used a validated algorithm that required an EEG and the prescription of one or more anti-seizure medications post-dementia diagnosis. A case-control analysis was conducted, matching five non-dementia subjects by gender and age to each dementia patient. Cox proportional hazards models were then utilized in the analysis. Results: We identified 7,314 dementia cases, also including 35,280 age- and sex-matched control subjects. Out of patients with dementia, 148 individuals (2.02%) were diagnosed with epilepsy. We observed a progressive increase in the cumulative incidence of seizures over time, registering 1.45% in the first year following the diagnosis, and rising to 1.96% after three years. Analysis using Cox regression revealed a significant association between the development of epilepsy and dementia (HR = 4.58, 95% CI = 3.67-5.72). Additional risk factors were male gender (HR = 1.35, 95% CI = 1.07-1.69) and a younger age at dementia onset (HR = 1.03, 95% CI=1.02-1.04). Conclusions: Dementia increases epilepsy risk, especially with early onset and male gender. Clinicians should have a low threshold to suspect seizures in dementia cases.

Large-Scale Postmarketing Surveillance of Biological Drugs for Immune-Mediated Inflammatory Diseases Through an Italian Distributed Multi-Database Healthcare Network: The VALORE Project.

BACKGROUND: Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings. OBJECTIVE: The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID. METHODS: A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010-2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association. RESULTS: From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015-2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively. CONCLUSION: The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010-2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings.

Incidence and Antiseizure Medications of Post-stroke Epilepsy in Umbria: A Population-Based Study Using Healthcare Administrative Databases.

Introduction: Post-stroke epilepsy (PSE) requires long-term treatment with antiseizure medications (ASMs). However, epidemiology of PSE and long-term compliance with ASM in this population are still unclear. Here we report, through population-level healthcare administrative data, incidence, risk factors, ASM choice, and ASM switch over long-term follow-up. Materials and Methods: This is a population-based retrospective study using Umbria healthcare administrative database. Population consisted of all patients with acute stroke, either ischaemic or hemorrhagic, between 2013 and 2018. ICD-9-CM codes were implemented to identify people with stroke, while PSE was adjudicated according to previously validated algorithm, such as EEG and ≥1 ASM 7 days after stroke. Results: Overall, among 11,093 incident cases of acute stroke (75.9% ischemic), 275 subjects presented PSE, for a cumulative incidence of 2.5%. Patients with PSE were younger (64 vs. 76 years), more frequently presented with hemorrhagic stroke, and had longer hospital stay (15.5 vs. 11.2 days) compared with patients without PSE. Multivariable Cox proportional hazards models confirmed that PSE associated with hemorrhagic stroke, younger age, and longer duration of hospital stay. Levetiracetam was the most prescribed ASM (55.3%), followed by valproate and oxcarbazepine. Almost 30% of patients prescribed with these ASMs switched treatment during follow-up, mostly toward non-enzyme-inducing ASMs. About 12% of patients was prescribed ASM polytherapy over follow-up. Conclusions: Post-stroke epilepsy is associated with hemorrhagic stroke, younger age, and longer hospital stay. First ASM is switched every one in three patients, suggesting the need for treatment tailoring in line with secondary prevention.

Accuracy of ICD-9 codes in identifying patients with peptic ulcer and gastrointestinal hemorrhage in the regional healthcare administrative database of Umbria.

BACKGROUND: Peptic ulcer is a widespread disease, frequently complicated by perforation and bleeding. Administrative databases are useful tool to perform epidemiological and drug utilization studies, but they need a validation process based on a comparison with the original data contained in the medical charts. Our aim was to evaluate the accuracy of the ICD-9 codes in identifying patients with peptic ulcer and gastrointestinal hemorrhage in the regional administrative database of Umbria. METHODS: The index test of our study was the hospital discharge abstract database of the Umbria region (Italy), while the reference standard was the clinical information collected in the medical charts. The study population were adult patients with a hospital discharge for peptic ulcer or gastrointestinal hemorrhage in the period 2012-2014. A random sample of cases and non-cases was selected and the corresponding medical charts were reviewed. Cases of peptic ulcer were confirmed based on endoscopy, radiology, and surgery, while adjudication of gastrointestinal hemorrhage was based on presence of hematemesis, melena, and rectal bleeding. RESULTS: Overall, we reviewed 445 clinical charts of cases and 80 clinical charts of non-cases. The diagnostic accuracy results were: code 531 (gastric ulcer), sensitivity and NPV 98%, specificity 88%, and PPV 91%; code 532 (duodenal ulcer), sensitivity and NPV 100%, specificity and PPV 98%; code 534 (gastrojejunal ulcer), sensitivity and NPV 100%, specificity 70%, and PPV 45%; code 578 (gastrointestinal hemorrhage), sensitivity 96%, specificity 90%, PPV and NPV 94%. CONCLUSIONS: Our results showed a high level of diagnostic accuracy for most of the codes considered. The ICD-9 code 534 of gastrojejunal ulcer had a lower level of specificity and PPV due to false positives, being mainly misclassifications for coding errors. These validated codes can be used for future epidemiological studies and for health services research.

Validity of cerebrovascular ICD-9-CM codes in healthcare administrative databases. The Umbria Data-Value Project.

BACKGROUND: Validation of administrative databases for cerebrovascular diseases is crucial for epidemiological, outcome, and health services research. The aim of this study was to validate ICD-9 codes for hemorrhagic or ischemic stroke in administrative databases, to use them for a comprehensive assessment of the burden of disease in terms of major outcomes, such as mortality, hospital readmissions, and use of healthcare resources. METHODS: We considered the hospital discharge abstract database of the Umbria Region (890,000 residents). Source population was represented by patients aged >18 discharged from hospital with a diagnosis of hemorrhagic or ischemic stroke between 2012 and 2014 using ICD-9-CM codes in primary position. We randomly selected and reviewed medical charts of cases and non-cases from hospitals. For case ascertainment we considered symptoms and instrumental tests reported in the medical charts. Diagnostic accuracy measures were computed using 2x2 tables. RESULTS: We reviewed 767 medical charts for cases and 78 charts for non-cases. Diagnostic accuracy measures were: subarachnoid hemorrhage: sensitivity (SE) 100% (95% CI: 97%-100%), specificity (SP) 96% (90-99), positive predictive value (PPV) 98% (93-100), negative predictive value (NPV) 100% (95-100); intracerebral hemorrhage: SE 100% (97-100), SP 98% (91-100), PPV 98% (94-100), NPV 100% (95-100); other and unspecified intracranial hemorrhage: SE 100% (97-100), SP 96% (90-99), PPV 98% (93-100), NPV 100% (95-100); ischemic stroke due to occlusion and stenosis of precerebral arteries: SE 99% (94-100), SP 66 (57-75), PPV 70% (61-77), NPV 99% (93-100); occlusion of cerebral arteries: SE 100% (97-100), SP 87% (78-93), PPV 91% (84-95), NPV 100% (95-100); acute, but ill-defined, cerebrovascular disease: SE 100% (97-100), SP 78% (69-86), PPV % 83 (75-89), NPV 100% (95-100). CONCLUSIONS: Case ascertainment for both ischemic and hemorrhagic stroke showed good or high levels of accuracy within the regional healthcare databases in Umbria. This database can confidently be employed for epidemiological, outcome, and health services research related to any type of stroke.

[Evaluating health care of the immigrant population in Italy through indicators of a national monitoring system]. / Valutazione dell'assistenza sanitaria della popolazione immigrata in Italia attraverso alcuni indicatori di un sistema nazionale di monitoraggio.

OBJECTIVES: to evaluate maternal and child healthcare, avoidable hospitalisation, access to emergency services among immigrants in Italy. DESIGN: cross sectional study of some health and health care indicators among Italian and foreign population residing in Italy in 2016-2017. SETTING AND PARTICIPANTS: indicators based on the national monitoring system coordinated by the Italian National Institute for Health, Migration and Poverty (INMP) of Rome, calculated on perinatal care (CedAP), hospital discharge (SDO), emergency services (EMUR) archives for the years 2016-2017, by of the following regions: Piedmont, Trento, Bolzano, Emilia-Romagna, Tuscany, Umbria, Lazio, Basilicata, Sicily. MAIN OUTCOME MEASURES: number and timeliness of pregnancy visits, number of ultrasounds, invasive prenatal investigations; perinatal mortality rates, birth weight, Apgar score at 5 minutes, need for neonatal resuscitation; standardized rates of avoidable hospitalisation and access to emergency services by triage code. RESULTS: more often than Italians, immigrant women have during pregnancy: less than 5 gynaecological examination (16.3% vs 8.5%), first examination after the 12th week of gestational age (12.5% vs 3.8%), less than 2 ultrasounds (3.8% vs 1.0%). Higher perinatal mortality rates among immigrants compared to Italians (3.6 vs 2.3 x1,000). Higher standardized rates (x1,000) among immigrants compared to Italians of avoidable hospitalisation (men: 2.1 vs 1.4; women: 0.9 vs 0.7) and of white triage codes in emergency (men: 62.0 vs 32.7; women: 52.9 vs 31.4). CONCLUSIONS: study findings show differences in access and outcomes of healthcare between Italians and immigrants. National monitoring system of indicators, coordinated by INMP, represents a useful tool for healthcare intervention policies aimed to health equity.

[Epidemiology of postpartum hemorrhages in the Umbrian population in the years 2006-2017.] / Epidemiologia delle emorragie post partum nella popolazione umbra nel periodo 2006-2017.

INTRODUCTION: Postpartum haemorrhage (PPH) is one of the main causes of mortality and severe maternal morbidity and its incidence is increasing also in Western countries. Aim of this study is to estimate the incidence and the trend of PPH in the Umbrian population using the validated Umbrian health database and to identify possible determinants for the development of PPH. METHODS: The source of the data was the regional Healthcare Database of the Umbria Region. The population of interest was represented by women who gave birth in Umbria between 2006 and 2017. The PPH was identified from the hospital data using the ICD-9-CM 666.x codes. Demographic data, principal and secondary diagnoses and data on maternal morbidity and blood component transfusion were collected. The incidence of PPH was calculated taking into account cases of PPH over the total number of births. The determinants of PPH, the associated morbidity and the variation in the severity of the PPH over time have been identified by logistic regression models. RESULTS: In Umbria, between 2006 and 2017, 93,403 births were registered (69% by vaginal delivery and 31% by caesarean section) and the rate of caesarean sections decreased by about 4%. The incidence of PPH increased three-fold during this period with an increase (p<0.001) of women with PPH who received transfusions. Regarding the caesarean sections, the PPH trend increased by 53% (p=0.3), while in the vaginal deliveries the PPHs increased by 233% (p<0.001). Logistic regression analysis showed that possible risk factors for the occurrence of PPH are maternal morbidity (OR 22.8, 95% CI 18.5-30.0), twin birth (OR 2.0, 95% CI 1.3-3.2) and antepartum haemorrhage (OR 5.7, 95% CI 3.1-10.4). CONCLUSIONS: The incidence of PPH has increased in recent years, while the morbidity associated with PPH has remained substantially unchanged. The study identified several risk factors responsible for PPH that can be used in the monitoring of pregnant women and for planning prevention strategies such as Patient Blood Management.

[Postpartum haemorrhage in Umbria: accuracy of the regional health information system for the code ICD-9-CM 666.x.] / Emorragia post partum in Umbria: accuratezza del sistema informativo sanitario regionale per il codice ICD-9-CM 666.x.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of morbidity and mortality for pregnant women. Administrative databases are useful sources of information for the assessment of PPH and related outcomes, once the corresponding ICD-9-CM code is validated. The objective of the present study is to evaluate the accuracy of the ICD-9-CM code related to PPH. MATERIAL AND METHODS: Source of the data was the Regional Healthcare Database of the Umbria Region. The population of interest were women with at least 20 weeks of gestation that delivered in any hospital in the Umbria Region during 2012-2016. Cases of interest were identified using the ICD-9-CM 666.x code. For validation purposes, both cases (women who delivered and developed PPH) and non-cases (women who delivered without occurrence of PPH) were considered and algorithms proposed. The basic criterion used for the validity of ICD-9-CM codes was the presence of bleeding ≥500 ml. Additional criteria based on values of haemoglobin or transfusion of red blood cells were considered. Sensitivity, specificity and predictive values were calculated. RESULTS: Medical charts of 422 cases and 200 non-cases were examined. Accuracy results for code 666.x related to the presence of bleeding ≥500 ml were: sensitivity 97% (95% CI, 96-99%), specificity 70% (65-76%), positive predictive value (PPV) 79% (76-82%) and negative predictive value (NPV) 95% (91-97%). The best algorithm was the one that, in addition to the basic criterion, considered both the haemoglobin values and red blood cell transfusion: sensitivity 93% (90-95%), specificity 85% (80-90%), PPV 92% (89-94%) and NPV 86% (81-90%). ICD-9 subcodes showed a higher specificity and PPV for immediate bleeding (666.0, 666.1) than delayed or secondary haemorrhage (666.2). CONCLUSIONS: The accuracy data from the present study confirm that the Regional Healthcare Database of the Umbria Region can be used as a reliable source for the evaluation of epidemiological studies relating to PPHs, in order to improve the quality of maternity care.

Incidence and prevalence of Parkinson's disease in the Italian region of Umbria: a population-based study using healthcare administrative databases.

Parkinson's disease is known to pose a significant burden on society in industrialized countries. However, few studies have been conducted in Italy using administrative healthcare databases for epidemiological purposes. We wanted to estimate the incidence and prevalence rates of Parkinson's disease in the Italian region of Umbria by means of linkage between several sources of administrative healthcare data: hospitalization episodes, exemptions from medical charges, drug prescriptions from general practitioners and physicians working in the public sector. Using a pre-defined algorithm, we estimated incident and prevalent cases of Parkinson's disease for the year 2016. The regional incidence rate, adjusted with Italian standard population data, was 0.40 new cases/1000 person-years (0.41 in females, 0.39 in males). We estimated that 5550 subjects were affected by Parkinson's disease, leading to an age-adjusted prevalence rate of 5.42/1000 inhabitants. Prevalence and incidence increased with age and male gender. However, due to the longer life expectancy of females, the absolute number of prevalent cases was greater among females. The heterogeneity of spatial distribution of disease was high. A considerable proportion of prevalent cases was hospitalized in 2016. The most recurrent reasons for hospitalization episodes were disorders related to the nervous system, respiratory system, cardiovascular system, and musculoskeletal and connective tissue apparatus. The study findings support the feasibility of future epidemiological studies of Parkinson's disease with administrative data as well as the need for an integrative care pathway for the patients with Parkinson's disease.

Accuracy of lung cancer ICD-9-CM codes in Umbria, Napoli 3 Sud and Friuli Venezia Giulia administrative healthcare databases: a diagnostic accuracy study.

OBJECTIVES: To assess the accuracy of International Classification of Diseases 9th Revision-Clinical Modification (ICD-9-CM) codes in identifying subjects with lung cancer. DESIGN: A cross-sectional diagnostic accuracy study comparing ICD-9-CM 162.x code (index test) in primary position with medical chart (reference standard). Case ascertainment was based on the presence of a primary nodular lesion in the lung and cytological or histological documentation of cancer from a primary or metastatic site. SETTING: Three operative units: administrative databases from Umbria Region (890 000 residents), ASL Napoli 3 Sud (NA) (1 170 000 residents) and Friuli Venezia Giulia (FVG) Region (1 227 000 residents). PARTICIPANTS: Incident subjects with lung cancer (n=386) diagnosed in primary position between 2012 and 2014 and a population of non-cases (n=280). OUTCOME MEASURES: Sensitivity, specificity and positive predictive value (PPV) for 162.x code. RESULTS: 130 cases and 94 non-cases were randomly selected from each database and the corresponding medical charts were reviewed. Most of the diagnoses for lung cancer were performed in medical departments.True positive rates were high for all the three units. Sensitivity was 99% (95% CI 95% to 100%) for Umbria, 97% (95% CI 91% to 100%) for NA, and 99% (95% CI 95% to 100%) for FVG. The false positive rates were 24%, 37% and 23% for Umbria, NA and FVG, respectively. PPVs were 79% (73% to 83%)%) for Umbria, 58% (53% to 63%)%) for NA and 79% (73% to 84%)%) for FVG. CONCLUSIONS: Case ascertainment for lung cancer based on imaging or endoscopy associated with histological examination yielded an excellent sensitivity in all the three administrative databases. PPV was moderate for Umbria and FVG but lower for NA.

Is the Robson's classification system burdened by obstetric pathologies, maternal characteristics and assistential levels in comparing hospitals cesarean rates? A regional analysis of class 1 and 3.

OBJECTIVE: To assess if maternal risk profile and Hospital assistential levels were able to influence the inter-Hospitals comparison in the class 1 and 3 of the "The Ten Group Classification System" (TGCS). METHODS: A population-based analysis using data from Institutional data-base of an Italian Region was carried out. The 11 maternity wards were divided into two categories: second-level hospitals (SLH), and first-level hospitals (FLH). The recorded deliveries were classified according to the TGCS. To analyze if different maternal characteristics and the hospitals assistential level could influence the cesarean section (CS) risk, a multivariate analysis was done considering separately women in the TGCS class 1 and 3. RESULTS: From January 2011 to December 2013 were recorded 19,987 deliveries. Of those 7,693 were in the TGCS class 1 and 4,919 in the class 3. The CS rates were 20.8% and 14.7% in class 1 (p < 0.0001) and 6.9% and 5.3% (p < 0.0230) in class 3, respectively in the FLH and SLH. The multivariate logistic regression showed that the FLH, older maternal age and gestational diabetes were independent risk factors for CS in groups 1 and 3. Obesity and gestational hypertension were also independent risk factors for group 1. CONCLUSIONS: TGCS is a useful tool to analyze the incidence of CS in a single center but in comparing different Hospitals, maternal characteristics and different assistential levels should be considered as potential bias.

Validity of ICD-9-CM codes for breast, lung and colorectal cancers in three Italian administrative healthcare databases: a diagnostic accuracy study protocol.

INTRODUCTION: Administrative healthcare databases are useful tools to study healthcare outcomes and to monitor the health status of a population. Patients with cancer can be identified through disease-specific codes, prescriptions and physician claims, but prior validation is required to achieve an accurate case definition. The objective of this protocol is to assess the accuracy of International Classification of Diseases Ninth Revision-Clinical Modification (ICD-9-CM) codes for breast, lung and colorectal cancers in identifying patients diagnosed with the relative disease in three Italian administrative databases. METHODS AND ANALYSIS: Data from the administrative databases of Umbria Region (910,000 residents), Local Health Unit 3 of Napoli (1,170,000 residents) and Friuli--Venezia Giulia Region (1,227,000 residents) will be considered. In each administrative database, patients with the first occurrence of diagnosis of breast, lung or colorectal cancer between 2012 and 2014 will be identified using the following groups of ICD-9-CM codes in primary position: (1) 233.0 and (2) 174.x for breast cancer; (3) 162.x for lung cancer; (4) 153.x for colon cancer and (5) 154.0-154.1 and 154.8 for rectal cancer. Only incident cases will be considered, that is, excluding cases that have the same diagnosis in the 5 years (2007-2011) before the period of interest. A random sample of cases and non-cases will be selected from each administrative database and the corresponding medical charts will be assessed for validation by pairs of trained, independent reviewers. Case ascertainment within the medical charts will be based on (1) the presence of a primary nodular lesion in the breast, lung or colon-rectum, documented with imaging or endoscopy and (2) a cytological or histological documentation of cancer from a primary or metastatic site. Sensitivity and specificity with 95% CIs will be calculated. DISSEMINATION: Study results will be disseminated widely through peer-reviewed publications and presentations at national and international conferences.