Incidence and Prevalence of Dementia: A 2015-2020 Population-Based Study in the Campania Region of Italy.

OBJECTIVE: The aims of this study were to provide population-based estimates of prevalence and incidence of any dementia and Alzheimer's dementia (AD) in the Campania region (South Italy) and to validate towards a clinical registry. METHODS: This was a population-based study, using routinely collected healthcare data of individuals living in the Campania region (South Italy) from 2015 to 2020. We included individuals aged ≥65 years alive at the prevalence day (January 1, 2021) who had at least one administrative record for dementia and/or AD from 2015 to 2020. Age-and sex-standardised prevalence rates were calculated using direct standardisation method (European population in 2020 as the reference population). To estimate the incidence, we tested three possible algorithms, which differed for the duration of the time interval between study baseline (January 1, 2015) and index date (first record for dementia and/or AD in administrative databases). We employed a clinical database for the validation of our algorithms towards neuropsychological test results. RESULTS: Among individuals aged over 65 years, 80,392 had dementia, of which 35,748 had AD. The age- and sex-standardised prevalence rates per 1,000 individuals for any dementia and AD were 77.64 (95% confidence interval [CI] = 77.57; 77.68) and 34.05 (95% CI = 34.01; 34.09), respectively. There were 82.10 incident cases of any dementia per 100,000 per year (0.79 sensitivity and 0.62 specificity) and 59.89 incident cases of AD per 100,000 per year (0.80 sensitivity and 0.59 specificity). The capture-recapture method showed a very low number of undetected cases (1.7% for any dementia and 3.0% for AD). Our algorithms showed acceptable performance with the area under the curve ranging from 0.59 to 0.72 and a double likelihood ratio of correctly identifying individuals above and below mini-mental status examination (MMSE) standard cut-offs (24 and 26). CONCLUSIONS: Prevalence and incidence of any dementia and AD in the Campania region (South Italy) from 2015 to 2020 are in line with previous estimates from other countries. Our algorithm, integrating administrative and clinical data, holds potential for assessing dementia's epidemiological burden, identifying risk factors, planning healthcare access, and developing prevention strategies.

Fertility, pregnancy and childbirth in women with multiple sclerosis: a population-based study from 2018 to 2020.

BACKGROUND: We aim to evaluate whether fertility, pregnancy, delivery and breastfeeding have been actually improving in women with multiple sclerosis (MS), compared with general population, and in relation to treatment features. METHODS: We included 2018-2020 population-level healthcare data on women with MS living in the Campania region (Italy). Fertility, pregnancy and delivery outcomes were obtained from Certificate of Delivery Assistance; breastfeeding was collected up to 6 months after delivery by trained personnel. RESULTS: Out of 2748 women with MS in childbearing age, 151 women delivered 156 babies. Fertility rate was 0.58 live births per woman with MS, compared with 1.29 in Campania region and 1.25 in Italy. Disease-modifying treatment (DMT) continuation during pregnancy was associated with lower birth weight (coeff -107.09; 95% CI -207.91 to -6.26; p=0.03). Exposure to DMTs with unknown/negative effects on pregnancy was associated with birth defects (OR 8.88; 95% CI 1.35 to 58.41; p=0.02). Birth defects occurred in pregnancies exposed to dimethyl fumarate (2/21 exposed pregnancies), fingolimod (1/11 exposed pregnancies) and natalizumab (2/30 exposed pregnancies). After delivery, 18.8% of women with MS were escalated of DMT efficacy, while 50.7% started on same/similar-efficacy DMTs, and 30.5% did not receive DMT. The probability of breastfeeding was higher in women who were treated with breastfeeding-safe DMTs (OR 5.57; 95% CI 1.09 to 28.55; p=0.03). CONCLUSIONS: Fertility rate in women with MS remains below the general population. Family planning and subsequent DMT decisions should aim to achieve successful pregnancy, delivery and breastfeeding outcomes, while controlling disease activity.

Impact of COVID-19 and system recovery in delivering healthcare to people with multiple sclerosis: a population-based Study.

BACKGROUND: COVID-19 pandemic has affected the management of multiple sclerosis (MS). OBJECTIVE: To explore the impact of COVID-19 on healthcare delivery to people with MS and the subsequent recovery of the system. METHODS: In this population-based study in the Campania Region (Italy), we included people with MS across pre-COVID-19, lockdown, pre-vaccination, and vaccination periods. Differences in continuous outcomes between periods were explored using linear mixed models (annualized hospitalization rate (AHR) and adherence measured as medication possession ratio (MPR)). Differences in disease-modifying treatment (DMT) prescription rates (first DMT prescription, any DMT switch, switch from platform to highly effective DMT, and combination of first DMT prescription and any DMT switch) were assessed using an interrupted time series design. RESULTS: Compared with pre-COVID-19, AHR decreased during the lockdown (Coeff = 0.64;95%CI = -0.69, -0.59; p < 0.01), and remained lower during pre-vaccination and vaccination periods. Adherence decreased during pre-vaccination (Coeff = -0.04;95%CI = -0.05, -0.03; p < 0.01) and vaccination periods (Coeff = -0.07;95%CI = -0.08, -0.07; p < 0.01). After the lockdown, there was an increase in any DMT switch (IRR 2.05 95%CI 1.38,3.05; p < 0.01), in switch from platform to highly effective DMTs (IRR 4.45;95%CI 2.48,8.26; p < 0.01) and in first DMT prescriptions (IRR 2.48;95%CI 1.64,3.74; p < 0.01). CONCLUSIONS: DMT prescriptions quickly returned to pre-pandemic levels, reflecting good health system recovery. However, adherence has remained lower than the past, as from suboptimal care. Assessing long-term COVID-19 impact on MS healthcare is warranted.

Emergency medical care for multiple sclerosis: A five-year population study in the Campania Region (South Italy).

BACKGROUND: Emergency hospital admissions are common in multiple sclerosis (MS), and can highlight unmet medical needs. OBJECTIVES: To evaluate burden, predictors and outcomes of MS emergency admissions. METHODS: This is a population-based study, conducted in the Campania Region (South Italy) from 2015 to 2019, using hospital discharge records, drug prescriptions and outpatients. The risk of emergency hospital admissions and the likelihood of worse outcomes were evaluated using the Cox regression and multinomial logistic regression models, respectively, in relation to age, sex, disease-modifying treatments (DMTs), comorbidities and adherence. RESULTS: We recorded 1225 emergency admissions for 1001 patients (out of 5765 prevalent MS patients), overall costing 4,143,764.67 EUR. The risk of emergency admissions increased with age (hazard ratio (HR) = 1.02; 95% confidence interval (CI) = 1.01, 1.03; p < 0.01) and comorbidities (HR = 1.62; p < 0.01), and decreased in patients using DMTs (interferon beta/peg-interferon beta/glatiramer acetate HR = 0.19; p < 0.01; teriflunomide/dimethyl-fumarate/fingolimod HR = 0.18; p < 0.01, and alemtuzumab/cladribine/natalizumab/ocrelizumab HR = 0.21; p < 0.01), and with higher adherence (HR = 0.18; 95% CI = 0.13, 0.26; p < 0.01). Following emergency admission, older age was associated with probability of death (n = 63) (odds ratio (OR) = 1.06; p < 0.01) and discharge to long-term facility (n = 65) (OR = 1.03; p = 0.01). CONCLUSION: With 17% people with MS requiring emergency medical care over 5 years, improved management of DMTs and comorbidities could potentially reduce their medical, social and financial burden.

An Analysis of the Distribution of Direct Cost of Diabetes Care in Selected Districts in Italy.

INTRODUCTION: This study aims to define the distribution of direct healthcare costs for people with diabetes treated in two healthcare regions in Italy, based on number of comorbidities and treatment regimen. METHODS: This was a retrospective analysis using data from two local health authority administrative databases (Campania and Umbria) in Italy for the years 2014-2018. Data on hospital care, pharmaceutical and specialist outpatient and laboratory assistance were collected. All people with diabetes in 2014-2018 were identified on the basis of at least one prescription of hypoglycemic drugs (ATC A10), hospitalization with primary or secondary diagnosis of diabetes mellitus (ICD9CM 250.xx) or diabetes exemption code (code 013). Subjects were stratified into three groups according to their pharmaceutical prescriptions during the year: Type 1/type 2 diabetes (T1D/T2D) treated with multiple daily injections with insulin (MDI), type 2 diabetes on basal insulin only (T2D-Basal) and type 2 diabetes not on insulin therapy (T2D-Oral). RESULTS: We identified 304,779 people with diabetes during the period for which data was obtained. Analysis was undertaken on 288,097 subjects treated with glucose-lowering drugs (13% T1D/T2D-MDI, 13% T2D-Basal, 74% T2D-Oral). Average annual cost per patient for the year 2018 across the total cohort was similar for people with T1D/T2D-MDI and people with T2D-Basal (respectively €2580 and €2254) and significantly lower for T2D-Oral (€1145). Cost of hospitalization was the main driver (47% for T1D/T2D-MDI, 45% for T2D-Basal, 45% for T2D-Oral) followed by drugs/devices (35%, 39%, 43%) and outpatient services (18%, 16%, 12%). Average costs increased considerably with increasing comorbidities: from €459 with diabetes only to €7464 for a patient with four comorbidities. Similar trends were found across all subgroups analysis. CONCLUSION: Annual cost of treatment for people with diabetes is similar for those treated with MDI or with basal insulin only, with hospitalization being the main cost driver. This indicates that both patient groups should benefit from having access to scanning continuous glucose monitoring (CGM) technology which is known to be associated with significantly reduced hospitalization for acute diabetes events, compared to self-monitored blood glucose (SMBG) testing.

Epidemiology of multiple sclerosis in the Campania Region (Italy): Derivation and validation of an algorithm to calculate the 2015-2020 incidence.

OBJECTIVE: We aim to validate an algorithm based on routinely-collected healthcare data to detect incidence of multiple sclerosis (MS) in the Campania Region (South Italy) and to explore its spatial and temporal variations. METHODS: We included individuals resident in the Campania Region who had at least one MS record in administrative datasets (drug prescriptions, hospital discharge, outpatients), from 2015 to 2020. We merged administrative to the clinical datasets to ascertain the actual date of diagnosis, and validated the minimum interval from our study baseline (Jan 1, 2015) to first MS records in administrative datasets to detect incident cases. We used Bayesian approach to explore geographical distribution, also including deprivation index as a covariate in the estimation model. We used the capture-recapture method to estimate the proportion of undetected cases. RESULTS: The best performance was achieved by the 12-month interval algorithm, detecting 2,150 incident MS cases, with 74.4% sensitivity (95%CI = 64.1%, 85.9%) and 95.3% specificity (95%CI = 90.7%, 99.8%). The cumulative incidence was 36.68 (95%CI = 35.15, 38.26) per 100,000 from 2016 to 2020. The mean annual incidence was 7.34 (95%CI = 7.03, 7.65) per 100,000 people-year. The geographical distribution of MS relative risk shows a decreasing east-west incidence gradient. The number of expected MS cases was 11% higher than the detected cases. CONCLUSIONS: We validated a case-finding algorithm based on administrative data to estimate MS incidence, and its spatial/temporal variations. This algorithm provides up-to-date estimates of MS incidence, and will be used in future studies to evaluate changes in MS incidence in relation to different risk factors.

Rifaximin Use, Adherence and Persistence in Patients with Hepatic Encephalopathy: A Real-World Study in the South of Italy.

Real-world data on the therapeutic management of hepatic encephalopathy (HE) patients are limited. The aim of this study was to evaluate the HE medications prescribed in an Italian cohort of HE patients post-discharge and to assess the real-world rifaximin adherence and persistence over 1 year. An observation retrospective study was conducted using data retrieved from outpatient pharmaceutical databases and hospital discharge records of the Campania region. For all subjects hospitalized for HE during 2019 (cohort 1), the HE medications prescribed within 60 days after discharge were evaluated. Adherence (proportion of days covered, PDC) and persistence were estimated for rifaximin 550 mg incident users over 1 year (cohort 2). Patients with PDC ≥80% were considered adherents. Persistence was defined as the period of time from the first rifaximin prescription to the date of discontinuation. Discontinuation was assessed using the permissible gap method. In cohort 1, 544 patients were identified; 58.5% received rifaximin while 15.6% only received non-absorbable disaccharides and 25.9% did not receive any HE medications. In cohort 2, 650 users were selected; only 54.5% were adherents and 35% were persistent users at 1 year. This real-world study highlights that quality improvement in therapeutic management is needed to potentially improve the outcomes of HE patients.

[Real-world analysis of the use of rifaximin 200 mg in the Campania Region.] / Analisi real world sull'utilizzo di rifaximina 200 mg nella Regione Campania.

INTRODUCTION: Since its approval in Italy in 1987, rifaximin has been licensed in over 30 countries for the treatment of a wide range gastrointestinal diseases. The aim of the study was to analyze the real world use of rifaximin 200 mg in the Campania region. METHODS: An observation retrospective study was conducted analysing the prescriptions of rifaximin received by the subjects ≥18 years old resident in the Campania Region. For each user the first rifaximin prescription in 2019 was defined as index date. All the prescriptions during the 12 months following the index date were analyzed. The subjects were categorized according to the number of packages/year received (1-4, 5-12, 13-24, >24). RESULTS: 231,207 subjects received at least one package/year of rifaximin 200 mg with a prevalence of use of 4.9% and a total annual expenditure of 9.2 million euros. The 73.9% of users received 1-4 packages/year, 16.4% between 5-12 packages/year and 7.7% between 13-24 packages/year. The 2.0% of the users received more than 24 packages/year with an incidence on total expenditure equal to 14.8% (5% is due to those who received more than 40 packages/year). DISCUSSION: About two thirds of rifaximin users received no more than three packages, presumably for the treatment of the infectious gastroenteritis or diarrheal syndromes, while 24% received 5-24 packages/year probably for the relapsing chronic intestinal pathologies. The 15% of the expenditure and consumption is related to subjects receiving more than 24 packages/year, probably due to the treatment of chronic liver diseases. CONCLUSIONS: The use of rifaximin 200 mg should be further investigated in different recurrent chronic diseases, especially to verify which schemes and dosages are used in real life compared to those tested in clinical trials.

Identification of dementia and MCI cases in health information systems: An Italian validation study.

Introduction: The identification of dementia cases through routinely collected health data represents an easily accessible and inexpensive method to estimate the prevalence of dementia. In Italy, a project aimed at the validation of an algorithm was conducted. Methods: The project included cases (patients with dementia or mild cognitive impairment [MCI]) recruited in centers for cognitive disorders and dementias and controls recruited in outpatient units of geriatrics and neurology. The algorithm based on pharmaceutical prescriptions, hospital discharge records, residential long-term care records, and information on exemption from health-care co-payment, was applied to the validation population. Results: The main analysis was conducted on 1110 cases and 1114 controls. The sensitivity, specificity, and positive and negative predictive values in discerning cases of dementia were 74.5%, 96.0%, 94.9%, and 79.1%, respectively, whereas in detecting cases of MCI these values were 29.7%, 97.5%, 92.2%, and 58.1%, respectively. The variables associated with misclassification of cases were also identified. Discussion: This study provided a validated algorithm, based on administrative data, which can be used to identify cases with dementia and, with lower sensitivity, also early onset dementia but not cases with MCI.

Kidney Replacement Treatment in South-Western Italy (Campania): Population-Based Study on Gender and Residence Inequalities in Health Care Access.

The aim of this study was to investigate the epidemiology of kidney replacement treatment (KRT) in Italy with a focus on gender and residence. As a population-based study using administrative databases from the Campania region of Italy between 2015 and 2018, the study outcomes included diagnoses of haemodialysis, peritoneal dialysis, kidney transplant, and mortality. A total of 11,713 residents in Campania were on KRT from 2015 to 2018. The annual prevalence ranged between 1000 and 1015 patients per million population (pmp) for haemodialysis, between 115 and 133 pmp for peritoneal dialysis, and between 2081 and 2245 pmp for kidney transplant. The annual incidence ranged between 160 and 185 pmp for de novo haemodialysis and between 59 and 191 pmp for kidney transplant. Annual mortality ranged between 12.8% and 14.2% in haemodialysis, between 5.2% and 13.8% in peritoneal dialysis, and between 2.4% and 3.3% in kidney transplant. In Cox regression targeting mortality, significant HRs were found for age (95%CI = 1.05/1.05), kidney transplant (compared to haemodialysis: 0.37/0.47), residence in suburban areas (1.03/1.24), and de novo dialysis incidence in years 2015-2018 (1.01/1.17). The annual rate of kidney transplant was 2.6%. In regression targeting kidney transplant rate, significant HRs were found for female gender (0.67/0.92), age (0.93/0.94), residence in suburban areas (0.65/0.98), and de novo incidence of dialysis in 2015-2018 (0.49/0.71). The existence of socioeconomic inequities in KRT is suggested by the evidence that gender and suburban residence predicted mortality and/or access to kidney transplant.

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.

Multiple Sclerosis in the Campania Region (South Italy): Algorithm Validation and 2015-2017 Prevalence.

We aim to validate a case-finding algorithm to detect individuals with multiple sclerosis (MS) using routinely collected healthcare data, and to assess the prevalence of MS in the Campania Region (South Italy). To identify individuals with MS living in the Campania Region, we employed an algorithm using different routinely collected healthcare administrative databases (hospital discharges, drug prescriptions, outpatient consultations with payment exemptions), from 1 January 2015 to 31 December 2017. The algorithm was validated towards the clinical registry from the largest regional MS centre (n = 1460). We used the direct method to standardise the prevalence rate and the capture-recapture method to estimate the proportion of undetected cases. The case-finding algorithm including individuals with at least one MS record during the study period captured 5362 MS patients (females = 64.4%; age = 44.6 ± 12.9 years), with 99.0% sensitivity (95% CI = 98.3%, 99.4%). Standardised prevalence rate per 100,000 people was 89.8 (95% CI = 87.4, 92.2) (111.8 for females [95% CI = 108.1, 115.6] and 66.2 for males [95% CI = 63.2, 69.2]). The number of expected MS cases was 2.7% higher than cases we detected. We developed a case-finding algorithm for MS using routinely collected healthcare data from the Campania Region, which was validated towards a clinical dataset, with high sensitivity and low proportion of undetected cases. Our prevalence estimates are in line with those reported by international studies conducted using similar methods. In the future, this cohort could be used for studies with high granularity of clinical, environmental, healthcare resource utilisation, and pharmacoeconomic variables.