Healthcare Utilization Databases Research Articles

Predicting the risk of nursing home placement of elderly persons using a population-based stratification score

ObjectiveTo develop and validate a novel score predictive of nursing home placement in elderly. Study designPopulation-based case-control study based on healthcare utilization databases of Lombardy, a region of Northern Italy. MethodsThe 2.4 million citizens aged ≥65 years who on January 1, 2018 lived outside nursing home formed the target population. Cases were citizens who experienced nursing home admission (the outcome of interest) until December 31, 2019. Cases were matched 1:1 by gender, age, and municipality of residence to one control. Conditional logistic regression was fitted to select candidate predictors (the exposure to 69 clinical conditions and 11 social and healthcare services) independently associated with the outcome. The model was built from the 26,156 cases, and as many controls (training set), and applied to a validation set (15,807 case-control couples). Predictive performance was assessed by discrimination and calibration. ResultsTwenty-one factors were identified as predictive of nursing home admission and were included in the “Elderly Nursing Home Placement” (ENHP) score. Mental health disorders and chronic neurological illnesses contributed most to prediction of nursing home admission. ENHP performance showed an area under the receiver operating characteristic curve of 0.77 and a remarkable calibration of observed and predicted outcome risk. ConclusionsA simple score derived from data used for public health management may reliably predict the risk of nursing home placement in elderly. Its use by healthcare decision makers allows to accurately identify high-risk individuals who need home services, thereby avoiding admission to nursing homes.

Long-term exposure to antihypertensive drugs and the risk of cancer occurrence: evidence from a large population-based study.

Available data on the association between antihypertensive drugs and cancer are characterized by a few years follow-up. Our aim has been to evaluate the association between long-term exposure to antihypertensive drugs and the risk of cancer occurrence. Using the healthcare utilization databases of the Lombardy region (Italy), individuals aged 40-85 years who had no previous history of cancer and were newly dispensed with at least one antihypertensive drug from the major drug classes between 2009 and 2011 were followed from the first drug dispensation to December 31, 2020. Data were analyzed according to the first drug used and the intention to treat principle, but also via an "as treated" approach, that is, by considering changes of and exposure to drugs during follow-up. The association between the duration of exposure to each drug class and the risk of cancer occurrence was evaluated using the adjusted Cox regression models. The study cohort included 338 910 new drug users (median age, 59 years; 49.5% males). During a median follow-up of 10.2 years, 36 556 cancers occurred. There was no consistent significant association between the risk of cancer occurrence and angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, or thiazides. A progressive, weak increase in cancer occurrence was associated with progressive exposure to calcium channel blockers and, limited to long-term exposure, to beta-blockers. A modest progressive increase in risk was observed also for thiazide-like and loop diuretics in the as treated, although not in the intention to treat approach. Long-term evaluation of exposure to antihypertensive drugs did not show consistent associations between thiazides, angiotensin-receptor blockers, or angiotensin-converting-enzyme inhibitors and the risk of cancer occurrence. A weak association was observed between cancer and the duration of exposure to calcium channel blockers and beta-blockers.

Cost-effectiveness of single-pill and separate-pill administration of antihypertensive triple combination therapy: a population-based microsimulation study

BackgroundSingle-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective.MethodsA cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty.ResultsCompared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61–1.14), with a mean cost differential of -€12 (95% CI -9,719–8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871–€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17–7,813) and €2,027 (95% CI 19–8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574–10,640 vs. €3,710, 95% CI 263–11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status.ConclusionsThe SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.

Multiple births from medically assisted reproduction: contribution of different types of procedures and trends over time

ObjectiveTo evaluate the relative impact of different strategies of medically assisted reproduction (MAR), i.e. first line treatment (ovarian stimulation with or without intrauterine insemination) and in vitro fertilization (IVF) procedures (conventional IVF or intracytoplasmic sperm injection), on the risk of multiple births. Study designWe utilized the health care utilization databases of the Lombardy region to identify births resulting from MAR between 2007 and 2022. We gathered data on the total number of multiple births and calculated the prevalence rate by dividing the number of multiples by the total number of births. To examine the temporal trend in the proportion of multiple births after MAR over time, a linear regression model was employed separately for different types of techniques and in strata of maternal age. ResultsA total of 30,900 births after MAR were included; 4485 (14.5 %) first line treatments and 26,415 (85.5 %) IVF techniques. Overall, 4823 (15.6 %) multiple births were identified. The frequency of multiple births over the study period decreased from 22.0 % in 2007 to 8.7 % in 2022 (p < 0.01). Multiple births from first line treatments were stable ranging from 13.5 % in 2007–2008 to 12.0 % in 2021–2022 (p = 0.29). Multiple births from IVF procedures decreased from 23.8 % in 2007–2008 to 8.4 % in 2021–2022 (p < 0.01). Stratifying for maternal age (i.e. < 35 and ≥ 35 years), the trends remained consistent. ConclusionsThe reduction in multiple births has been influenced by changes in IVF strategy and procedures. The decline has been gradual but steady since 2009, when a law restricting embryo freezing was repealed in Italy. In contrast, the proportion of multiple births resulting from first line treatments has remained constant over time. Despite declining, multiple births from MAR remained about one order of magnitude higher than those from spontaneous pregnancies.

Sirt1 in focus: unveiling molecular insights and therapeutic prospects in calcific aortic stenosis with sglt2i inhibitors

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Fondazione Gigi &amp; Pupa Ferrari ONLUS Background Calcific aortic stenosis (AS) affects 3% of older adults and lacks medical treatment. The well-known deacetylase Sirtuin1 (SIRT1) could be involved in many pathways linked to AS progression. Sodium-glucose co-transporter 2 inhibitors (SGLT2i), a class of antihyperglycemic agents, have been shown to reduce cardiovascular events and hospitalization for heart failure (possibly via SIRT1), but their possible benefits in AS are not yet known. Purpose Our study aims to uncover if SIRT1 plays a key role in AS progression and if SGLT2i can potentially slow the valve fibro-calcification processes, potentially via SIRT1 modulation. Methods RNA sequencing of control (n=27) and AS (n=39) aortic valves was performed. SIRT1 knockdown (SIRT1-) and overexpressing (SIRT1+) valve interstitial cells (VIC) were generated by CRISPR/Cas9. A calcification assay with or without dapagliflozin (dapa 1uM as SGLT2i) was employed to evaluate valve endothelial cells (VEC) and VIC crass-talk on calcification potential. Patient data were collected from the Lombardy regional healthcare utilization database and diabetic patients who were taking sulphonylureas (sul; not affecting SIRT1) and SGLT2i (acting on SIRT1) were selected. Patients were matched 1:1 by age, sex, and multisource comorbidity score. Kaplan-Maier analysis was used to generate time-to-event curves for aortic valve replacement (AVR) cumulative incidence at 2 years and Cox regression analysis was used to account for confounding effects. Results Whole tissue RNA-seq showed that SIRT1 could be a master regulator of multiple pathways linked to AS. Functional analysis and validations on mutant VIC revealed that inflammation, extracellular-matrix remodeling, and calcification mechanisms are directly regulated by SIRT1. Calcium assays unveiled an increment of calcification in SIRT1- VICs (+50.8%, p&amp;lt;0.01), while SIRT1+ VICs deposited less calcium (-23.6%; p&amp;lt;0.01) compared to wild-type ones. VIC exposed to dapa-treated VEC medium showed reduced calcification (-35.2%, p&amp;lt;0.01). In the dapa-treated VEC medium, we found an increase in NO levels (+19.9%, p&amp;lt;0.01) and VIC treated with an NO donor (detanonate 50uM) showed reduced calcification (-23.2%, p&amp;lt;0.05), while VIC treated with a SIRT1 inhibitor (EX527 25uM) showed an increased calcification (+68.1%, p&amp;lt;0.01). To corroborate these findings, we retrospectively enrolled 233,546 diabetic patients, and after matching, we obtained two groups (sul and SGLT2i) with 37,081 patients each. Adjusted Cox regression analysis revealed that patients taking SGLT2i had a lower AVR incidence than patients taking sulp with a hazard ratio of 0.65 (95%CI 0.47-0.89) resulting in a 35% risk reduction. Conclusion Our data highlights SIRT1 as a key regulator of fibro-calcific processes involved in AS and SGLT2i exhibit potential in slowing AS progression, via SIRT1 modulation. This study unveils promising molecular insights and suggests SGLT2i as a potential therapeutic avenue for AS.

Comparing the effectiveness and cost-effectiveness of sulfonylureas and newer diabetes drugs as second-line therapy for patients with type 2 diabetes

IntroductionWe aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), and dipeptidyl peptidase-4 inhibitor (DPP-4i) compared with sulfonylureas and glinides...

Understanding Patterns of Adherence to Antifibrotic Treatment in Idiopathic Pulmonary Fibrosis: Insights from an Italian Prospective Cohort Study.

Background: Pirfenidone and Nintedanib have significantly improved the prognosis of patients with idiopathic pulmonary fibrosis (IPF), reducing mortality risk and exacerbations. This study aimed to analyze antifibrotic treatment utilization and its association with clinical outcomes (i.e., acute exacerbation or death) during 2014-2021 in newly diagnosed IPF patients, using Healthcare Utilization Databases of the Marche Region, Italy. Methods: The first 12-month adherence to antifibrotic was estimated using the Proportion of Days Covered (PDC), defining adherence as PDC ≥ 75%. State Sequence Analysis over the initial 52 weeks of treatment was used to identify adherence patterns. The role of adherence patterns on acute exacerbations/death, adjusted by demographic, clinical features, and monthly adherence after the 52-week period (time-dependent variable), was assessed with Cox regression. Results: Among 667 new IPF cases, 296 received antifibrotic prescriptions, with 62.8% being adherent in the first year. Three antifibrotic utilization patterns emerged-high adherence (37.2%), medium adherence (42.5%), and low adherence (20.3%)-with median PDCs of 95.3%, 79.5%, and 18.6%, respectively. These patterns did not directly influence three-year mortality/exacerbation probability, but sustained adherence reduced risk over time. Conclusions: Good adherence was observed in in this population-based study, emphasizing the importance of continuous antifibrotics therapy over time to mitigate adverse outcomes.

COST-EFFECTIVENESS OF SINGLE-PILL AND SEPARATE-PILL ADMINISTRATION OF ANTIHYPERTENSIVE TRIPLE-COMBINATION THERAPY: A POPULATION-BASED MICROSIMULATION STUDY

Objective: To evaluate the lifetime cost-effectiveness profile of the perindopril/amlodipine/indapamide single-pill combination (SPC) compared with the combination of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic as a SPC of two drugs plus the third drug separately from the Italian payer perspective. Design and method: A cost-effectiveness analysis was conducted employing multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged &gt;=40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug prescription until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty. Results: Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61–1.14), with a reduction in total cost of –€12 (95% CI –9,719 to 8,131), making it the dominant strategy (ICER of –14, 95% CI –€15,871 to €7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17 to 7,813) and €2,027 (95% CI 19 to 8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574 to 10,640 vs. €3,710, 95% CI 263 to 11,955). This was the case for all strata of age, sex, and clinical status. Conclusions: The SPC was projected to increase survival and reduce costs compared with the two-pill combination. This is likely explained by an improvement in drug compliance. As three-drug SPC is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.

The COVID-19 Pandemic Was Associated with a Change in Therapeutic Management and Mortality in Heart Failure Patients.

Background: Heart failure (HF)-related mortality has been exacerbated by the COVID-19 pandemic; however, it is unclear how healthcare reassessment has contributed to the excess mortality versus SARS-CoV-2 infection itself. We aimed to assess how the pandemic affected the therapeutic management and prognosis of HF patients. Methods: We retrospectively reviewed the healthcare utilization databases of the Lombardy region (Italy) to identify all newly-diagnosed HF patients from January 2018 to December 2021. Outcomes were the utilization of HF therapies (Sacubitril/Valsartan; cardiac resynchronization therapy [CRT] and/or implantable cardioverter-defibrillator [ICD]; mechanical circulatory support [MCS]; heart transplantation [HTX]) and mortality. Cox regression models were fitted to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with the pandemic. Results: 36,130 and 17,263 patients were identified in the pre-pandemic and pandemic eras, respectively. The pandemic reduced Sacubitril/Valsartan utilization (HR = 0.77, 95% CI: 0.65-0.91) and CRT/ICD implantation (HR = 0.85, 95% CI: 0.78-0.92), but not MCS (HR = 1.11, 95% CI: 0.86-1.43) and HTX (HR = 0.88, 95% CI: 0.70-1.09). An increased mortality risk was observed during the pandemic (HR = 1.19, 95% CI: 1.15-1.23), which was attributable to SARS-CoV-2 infection (HR for non-COVID-19-related mortality = 1.01, 95% CI: 0.97-1.04). Conclusions: The COVID-19 pandemic was associated with a reduction in medical and interventional therapies for HF and an increase in mortality for HF patients.

Incidence of amyotrophic lateral sclerosis before and during the COVID-19 pandemic: evidence from an 8-year population-based study in Central Italy based on healthcare utilization databases

Background Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder with a high multidimensional burden, with an obscure etiopathogenesis. Methods We designed a longitudinal, population-based study of people residing in Central Italy (Marche Region) who were beneficiaries of the National Health System. People with an unprecedented ALS hospitalization (335.20 ICD-9 CM) or tagged with an ALS exemption between 2014 and 2021 were considered incident cases. ALS cases residing in the region for <3 years or with an active ALS exemption or hospitalized for ALS before 2014 were excluded. We used secondary sources to identify new ALS diagnoses. The regional referral center for ALS’s database was used to test the accuracy of secondary sources in detecting cases. ALS mean incidence was compared to that reported in similar studies conducted in Italy. The incidence rate trend adjusted by sex and age was evaluated using the Poisson regression model. Results We detected 425 new ALS cases (median age: 70y) in the 2014–2021 period, with a mean incidence of 3.5:100,000 py (95%CI: 3.2–3.8; M:F = 1.2), similar to that reported in similar studies conducted in Italy. No trend was observed during 2014–2019. After including 2020–2021 in the model, we observed a mean decrease in incidence of 5.8% (95% CI 2.0%; 9.5%, p = 0.003). Conclusion We show a decrease in the incidence rate of ALS in Marche, during the 2014–2021 period, as a possible outcome of a delayed neurological assessment and diagnosis during the pandemic. An ad hoc developed identification algorithm, based on healthcare utilization databases, is a valuable tool to assess the health impact of global contingencies.

Physical healthcare gap among patients with severe mental illness through the COVID-19 pandemic. Preliminary results from a real-world investigation in Lombardy, Italy

IntroductionPatients suffering from mental disorders tend to be less adherent to the recommended therapies. Moreover, the COVID-19 pandemic had a global impact on physical and social well-being, which turned out stronger in the most fragile patients, like those with a mental condition.ObjectivesTo assess whether the COVID-19 pandemic influenced the physical healthcare gap between patients with and without severe mental illness (SMI) treated for chronic conditions.MethodsData were retrieved from Healthcare Utilization Databases of Lombardy region (Italy). Prevalent users of antihypertensive drugs, statins or antidiabetic drugs, receiving healthcare in Lombardy during 2020, were identified. Among them, those with a previous diagnosis of schizophrenic or bipolar disorder were selected and matched with up to 3 patients without any sign of mental disorder by sex, age and number of contacts with the NHS during the previous year. 3 cohorts (not necessarily independent) were formed.High adherence to specific recommended drug therapies and discontinuation during 2020 were evaluated.Association between presence of SMI and high adherence was evaluated by using a log-binomial model (risk ratios, RR with 95% CI); a Cox model (hazard ratios, HR) was used for discontinuation.As comparison, same analyses were performed to the cohorts of prevalent users in 2019, to evaluate the impact of the COVID-19 pandemic. Results were stratified according to the type of mental disorder.Results36'436, 14'136 and 12'597 prevalent users of antihypertensives, statins or antidiabetics respectively were identified, of which 25% with SMI (9'109, 3'536 and 3'152 respectively).During the pandemic period, for all the three cohorts, patients with mental illness had 10% lower probability of being adherent to the recommended drug therapies.The association between SMI and discontinuation was significant and varied among the three cohorts, with HR (95% CI): 1.27 (1.21; 1.33) for antihypertensives users, 1.16 (1.07; 1.26) for antidiabetics users and 1.08 (1.01; 1.16) for statins users.Compared with 2019 the gap remained similar, except for discontinuation of antidiabetics, where the gap diminished from 34% in 2019 to 16% in 2020.No differences between the two mental disorders were found.ConclusionsResults show that suffering from a mental disorder in people with chronic physical conditions affects their adherence to recommended drug therapies. During the pandemic period, the restrictive measures adopted may have led to a better care by family members, counteracting any increase in the gap.The healthcare gap in patients suffering from mental illness remains an unsolved problem of primary importance for public health.Disclosure of InterestNone Declared

Does preterm birth increase the initiation of antidepressant use during the postpartum? A population-based investigation.

Preterm birth may affect maternal mental health. We explored the relationship between preterm birth and the risk of initiating antidepressant use during the year after birth. We conducted a population-based investigation using regional healthcare utilization databases. The exposure considered was preterm birth. The outcome was having at least one prescription for antidepressant medications during the year after birth. We used a log-binomial regression model including terms for maternal age at birth, nationality, educational level, parity, modality of conception, modality of delivery, use of other psychotropic drugs, and diabetes to estimate relative risk (RR) and 95% confidence intervals (CI) for the association between preterm birth and the initiation of antidepressant use. In addition, the absolute risk differences (ARD) were also computed according to the timing of birth. The cohort included 727,701 deliveries between 2010 and 2020 in Lombardy, Northern Italy. Out of these, 6,522 (0.9%) women had at least one prescription for antidepressant drugs during the year after birth. Preterm births were related to a 38% increased risk of initiation of antidepressant use during the year after birth (adjusted RR = 1.38; 95% CI: 1.25-1.52) for moderate to late preterm and to 83% (adjusted RR = 1.83; 95% CI: 1.46-2.28) for extremely and very preterm. Excluding women with only one antidepressant prescription, the association was consistent (adjusted RR = 1.41, 95%CI: 1.23-1.61 for moderate to late preterm and adjusted RR = 1.81, 95% CI: 1.31-2.49 for extremely and very preterm). Also, excluding women who used other psychotropics, the association remained consistent (adjusted RR = 1.39, 95%CI: 1.26-1.54 and adjusted RR = 1.91, 95% CI: 1.53-2.38, respectively for moderate to late and extremely and very preterm). Women who delivered preterm may have an excess risk of initiation of antidepressant consumption during the first year after birth.

Risk of Autism after Prenatal Topiramate, Valproate, or Lamotrigine Exposure

BackgroundMaternal use of valproate during pregnancy has been associated with an increased risk of neurodevelopmental disorders in children. Although most studies of other antiseizure medications have not shown increased risks of these disorders, there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use.MethodsWe identified a population-based cohort of pregnant women and their children within two health care utilization databases in the United States, with data from 2000 through 2020. Exposure to specific antiseizure medications was defined on the basis of prescription fills from gestational week 19 until delivery. Children who had been exposed to topiramate during the second half of pregnancy were compared with those unexposed to any antiseizure medication during pregnancy with respect to the risk of autism spectrum disorder. Valproate was used as a positive control, and lamotrigine was used as a negative control.ResultsThe estimated cumulative incidence of autism spectrum disorder at 8 years of age was 1.9% for the full population of children who had not been exposed to antiseizure medication (4,199,796 children). With restriction to children born to mothers with epilepsy, the incidence was 4.2% with no exposure to antiseizure medication (8815 children), 6.2% with exposure to topiramate (1030 children), 10.5% with exposure to valproate (800 children), and 4.1% with exposure to lamotrigine (4205 children). Propensity score–adjusted hazard ratios in a comparison with no exposure to antiseizure medication were 0.96 (95% confidence interval [CI], 0.56 to 1.65) for exposure to topiramate, 2.67 (95% CI, 1.69 to 4.20) for exposure to valproate, and 1.00 (95% CI, 0.69 to 1.46) for exposure to lamotrigine.ConclusionsThe incidence of autism spectrum disorder was higher among children prenatally exposed to the studied antiseizure medications than in the general population. However, after adjustment for indication and other confounders, the association was substantially attenuated for topiramate and lamotrigine, whereas an increased risk remained for valproate. (Funded by the National Institute of Mental Health.)

Time Trends in Liver-Related Mortality in People With and Without Diabetes: Results From a Population-Based Study.

Patients with diabetes are at increased risk of dying from liver-related events, but little is known on whether this increased risk has changed in recent years. The aim of the present study is to describe time trends in cause-specific liver-related mortality in people with and without diabetes from the general Italian population. Data were retrieved from the health care utilization databases of Lombardy, a region of Italy that accounts for about 16% (almost 10 million) of its population. Annual cause-specific mortality rates and proportionate mortality were computed among individuals with and without diabetes from 2010 to 2019. Liver-related deaths were categorized as viral, alcohol related, and nonviral nonalcohol related (NVNA). Liver diseases were responsible for 2% and 1% of deaths in people with and without diabetes (2019). Among patients with diabetes, the crude mortality rate for liver diseases decreased from 1.13 to 0.64 deaths per 1000 person-years from 2010 to 2019. The largest proportion of liver-related deaths was attributable to NVNA diseases and it increased from 63% in 2010 to 68% in 2019, with a corresponding relative reduction of viral causes (from 27% to 23%). The standardized mortality ratio for patients with diabetes was 3.35 (95% CI 2.96-3.76) for NVNA, 1.66 (95% CI 1.33-2.01) for viral hepatitis, and 1.61 (95% CI 1.13-2.17) for alcoholic liver disease and it remained relatively stable over time. Excess mortality risk in patients with diabetes for liver-related mortality was higher than for cardiovascular mortality and cancer. While liver-related mortality rates decreased significantly among patients with diabetes, NVNA causes made up the majority of cases. Excess mortality for liver-related causes in patients with diabetes compared with controls remained constant in the studied period.

Prescription medication use during pregnancy in the United States from 2011 to 2020: trends and safety evidence

Medication use during pregnancy has increased in the United States despite the lack of safety data for many medications. This study aimed to inform research priorities by examining trends in medication use during pregnancy and identifying gaps in safety information on the most commonly prescribed medications. We identified population-based cohorts of commercially (MarketScan 2011-2020) and publicly (Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files 2011-2018) insured pregnancies ending in live birth from 2 health care utilization databases. Medication use was based on filled prescriptions between the date of last menstrual period through delivery, as well as the period before the last menstrual period and during specific trimesters. We also included a cross-sectional representative sample of pregnancies ascertained by the National Health and Nutrition Examination Survey (2011-2020), with information on prescription medication use during the preceding month obtained through maternal interviews. Teratogen Information System was used to classify the available evidence on teratogenic risk. Among over 3 million pregnancies, the medications most commonly dispensed at any time during pregnancy were analgesics, antibiotics, and antiemetics. The top medications were ondansetron (16.8%), amoxicillin (13.5%), and azithromycin (12.4%) in MarketScan, nitrofurantoin (22.2%), acetaminophen (21.3%; mostly as part of acetaminophen-hydrocodone products), and ondansetron (19.5%) in Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files, and levothyroxine (5.0%), sertraline (2.9%), and insulin (2.9%) in the National Health and Nutrition Examination Survey group. The most commonly dispensed suspected teratogens during the first trimester were antithyroid medications. The use of antidiabetic and psychotropic medications has continued to increase in the United States during the last decade, opioid dispensation has decreased by half, and antibiotics and antiemetics continue to be common. For one-quarter of medications, there is insufficient evidence available to characterize their safety profile in pregnancy. There is a need for more drug research in pregnant patients. Future research should focus on anti-infectives with high utilization and limited level of evidence on safety for use during pregnancy. Although lack of evidence is not evidence of safety concerns, it does not indicate risk either. In many instances, the benefits outweigh the risks when these medications are used clinically, and some of the medications with no proven safety may be necessary to treat patients.

A Population-Based Study on Survival of 652 Higher Risks Myelofibrosis Patients Treated with Ruxolitinib in Italy

Introduction Myelofibrosis (MF) is a severe disease, and patients in the higher prognostic risk categories have a median overall survival (OS) ranging between 2 and 4 years after diagnosis. Ruxolitinib (RUX) is the first approved drug for MF, with an impact on OS reported in different studies, such as a post-hoc analysis of the registration trials ( Verstovsek et al, 2017) and in the real-world setting ( Guglielmelli et al, 2022). In Italy, RUX is available since October 2014 for intermediate-2 (INT-2) and high risk (HR) patients and since January 2018 also for intermediate-1 MF cases. High-cost drugs are delivered and monitored by each regional health authority. In this study, we analyzed the outcome of INT-2 and HR MF patients treated with RUX in three Italian regions, accounting for a population of almost 20 million people. Methods This is a population-based retrospective cohort study based on healthcare utilization databases of Lombardy, Tuscany, and Lazio regions, including data on hospital admissions, drug prescriptions, outpatient's health services and demographics. The study cohort included all beneficiaries of the Regional Health Service who started RUX between October 2014 and December 2017 (to include only INT-2 and HR MF patients) and followed up until 31st July 2021 (minimum observation period of the study: 3.5 years). The Multisource Comorbidity Score (MCS) was calculated to assess concurrent medical conditions ( Corrao et al, 2017). The primary outcome of the study was OS, defined as the time between RUX start and death for any cause or censoring due to migration, end of data availability or stem cell transplant (SCT). OS was estimated by the Kaplan-Meier method and 95% confidence interval (95%CI) was calculated. The secondary outcome was identification of risk factors associated with mortality via a multivariable Cox regression model evaluating the following variables: gender, age, year of RUX start and initial dose, SCT (included as time-dependent variable) and MCS score (low, intermediate, high). Data were analyzed separately for each region and subsequently pooled together by using fixed-effects meta-analyses. The incidence of adverse events (AEs) and secondary malignancies (included blast phase, BP, or post MF-myelodysplastic syndromes, MDS) that required hospital admission and occurring during follow-up was assessed and expressed as incidence rate (IR) x100 person-years (p-y). Infections, bleedings, and major thrombotic events were considered if they occurred within 90 days from the last RUX prescription and before evolution into BP/MDS. Results During the study period, 652 MF patients were started on RUX. Mean age at first administration was 68.7 years. In details, 317 (48.6%) subjects were younger than 70 years and 69 (10.6%) 80 years or older. Males represented 56% of the total cohort. Region of residence was Lombardy in 290 (44.5%), Lazio in 215 (33%) and Tuscany in 147 (22.5%) of the cases. The MCS was intermediate in 58.3% of the subjects. SCT was performed in 71 (10.9%) patients. RUX initial dose was 5 mg BID in 32% of cases and at least 20 mg BID in 25.6% of the whole cohort. At a median study follow-up of 39.8 months, overall, 364 (55.8%) deaths occurred. Median OS was 47.7 months (95%CI: 38.7-52.2), as reported in Figure 1. The 1-, 3- and 6-years OS rates were 85%, 63% and 34%, respectively. Factors independently associated with mortality were male gender, older age classes, high MCS score and less than 20 mg BID as RUX initial dose (Table 1). The most frequent AEs were infections (IR: 11 x100 p-y), bleeding events (3.9 x100 p-y) and thrombosis (1.5 x100 p-y). Secondary solid tumors had an IR of 5.6 x100 p-y, while the latter was 1.1 x100 p-y for lymphoproliferative disorders. Evolution into BP/MDS was reported in 103 (15.8%) patients of the cohort, with an IR of 5.5 x100 p-y. Conclusions Our study provides RUX treatment outcomes in an unselected real-world population-based cohort of 652 patients with higher risks MF, in residents of three Italian regions accounting for 20 million inhabitants. In this study on 652 INT-2 and HR MF patients observed for a minimum follow-up period of 3.5 years, RUX demonstrates to have a robust effect on survival, underpinning its use at appropriate doses in the management of these patients. MF progression rate into BP/MDS after RUX start seems not to be modified with respect to pre-RUX historical data ( Mora et al, 2023).

Healthcare costs and resources utilization in children with difficult-to-control asthma treated with biologic therapies: A population-based cohort study.

Asthma is one of the most common diseases in children, with a variable range of severity. In recent years, treatment for severe asthma has been largely improved by the availability of targeted biologic therapies. Nevertheless, studies reporting real-world data and cost-effectiveness analyses are lacking. The aim of this study was to evaluate, on a population-based cohort of children with asthma, the impact of the treatment with biologics on healthcare service utilization and associated costs. Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). A cohort of 46 asthmatic children aged 6-11 in treatment with dupilumab, mepolizumab or omalizumab was identified during 2017-2021. We compared healthcare resources use between the year before ("baseline period") and the year after the treatment initiation ("follow-up period"). Average 1-year healthcare costs were also calculated. Comparing the baseline with the follow-up period, the number of patients with at least one exacerbation-related hospitalization and ER access decreased by 75.0% and 85.7%, respectively. The use of biologic agents, namely omalizumab, mepolizumab and dupilumab, significantly reduced oral corticosteroids (OCS), short-acting β2-agonists and the association inhaled corticosteroids/long-acting β2-agonists use. ER admissions for non-respiratory causes were also significantly reduced, while discontinuation rate was low (6.5%). The overall costs increased, due to the costs of the biologic agents, but the hospital admission-related costs due to respiratory causes reduced significantly. Our real-world investigation suggests that biologic agents reduced hospital admissions for respiratory causes and use of anti-asthmatic drugs, including OCS. However, long-term healthcare sustainability still needs more in-depth assessments.

Spontaneous and induced abortions in women with a diagnosis of gestational related neoplasm: a population-based linkage study in Lombardy, 2010–2020

BackgroundA diagnosis of cancer during pregnancy or within one year after the end of pregnancy is a major clinical and public health issue. The current study aimed at estimating the incidence of pregnancy-associated cancer (PAC) and assessing whether the risk of abortion is increased in women diagnosed with cancer.MethodsThis population-based cohort study used the regional healthcare utilization (HCU) databases of Lombardy, the largest region in Italy, to identify the women who delivered between 2010 and 2020. PAC were identified by oncological ICD-9-CM codes reported in the hospital discharge forms. We computed the ratio of PAC cases to the total number of pregnancies. Following a diagnosis of PAC, the prevalence ratio (PR) of abortion and the corresponding 95% confidence interval (CI), was estimated using a log-binomial model adjusted for maternal age.ResultsDuring the study period, 926 women who gave birth (1.29 cases per 1000 births) and 341 women who had an abortion (1.52 cases per 1000 abortions) were diagnosed with PAC. Regardless of the outcome of pregnancy, the risk of PAC increased with increasing age. The rate of PAC was initially lower among births, but it came very close to the rate of PAC among abortions in the last two calendar years. The proportion of abortions among women with PAC gradually decreased from 27.7% in 2010–2012 to 18.5% in 2019–2020 (p-value < 0.001). Overall, a diagnosis of PAC was related to an approximately 10% increased risk of abortion (PR = 1.11, 95%CI:1.01–1.22). However, no association was observed in 2019–2020 (PR = 0.87, 95%CI:0.65–1.17). Considering only diagnoses made during the first trimester of pregnancy, the risk of abortion was about 2.5 times higher (PR = 2.53, 95%CI:2.05–3.11) and the risk of induced abortion was almost 4 times higher (PR = 3.71, 95%CI:2.82–4.90).ConclusionIn this population the risk of abortion was about 10% higher in women with PAC than in women without PAC. However, this association tended to decrease in more recent calendar periods. This trend seemed to be influenced more by spontaneous than by induced abortions.

Care trajectory differences in women and men with end-stage renal disease after dialysis initiation

Abstract Introduction End-Stage Kidney Disease (ESKD) is a major public health issue with an important burden for patients. Some sex and gender differences related to ESKD are well documented. For example, more men initiate dialysis. However, less is known about the differences in the care that follows dialysis start. The objective of this study was to describe the differences in healthcare utilization in the year following dialysis initiation between men and women. Methods Data from the French National Renal Epidemiology and Information Network (REIN) registry linked with the French National Health Data System (SNDS) were used. All adults patients with ESKD who initiated dialysis in France in 2015 were included. Characteristics at dialysis start, including co-morbidities, were compared between men and women. The healthcare utilization, outpatient and inpatient, in the year following dialysis start was examined as frequencies and compared by sex using Chi-2 and Student or Welch test. Results We included 8856 patients (36% of women). Women had fewer hospital stays &amp;lt;24 hours than men (53% with &amp;gt; =1 hospitalization &amp;lt;24 hours vs 57% among men, p-value=0.02) and fewer hospital stays for other problems than renal (44% had &amp;gt;2 hospital stays vs 46% in men, p-value=0.04). Hospital stays for vascular access preparation or maintenance were longer in women than men (median duration: 2 days vs 1 day, p-value&amp;lt;0.001). No significant difference was observed between women and men about hospital stays for kidney problems and consultations with a general practitioner. Conclusions Taking advantage of the linkage of national clinical and healthcare utilization databases, this study shed light on the care trajectory that follows dialysis initiation between men and women. Similarities were observed, including outpatient follow-up with a GP. Some specific differences, such as longer hospital stays for vascular access preparation or maintenance, calls for further studies to improve the care of women with ESKD. Key messages • Few differences exist between men and women in their care trajectory notably an outpatient follow-up with a GP. • Some differences have been highlighted, especially in some hospital stay duration that could be a subject of futures studies.

Effectiveness of community care for patients with severe mental disorders in Italy

Abstract Background The quality of care provided to patients with severe mental disorders (SMD) often does not correspond to the standards set by the recommendations. In addition to monitoring the coverage rate achieved by services, the evaluation of the effectiveness of interventions provided by mental health services for the treatment of SMD, in preventing an exacerbation of psychiatric symptoms, becomes of relevant importance. Methods Data were retrieved from Healthcare Utilization databases of four Italian Regions (Lombardy, Emilia-Romagna, Lazio, Sicily). 45,761 newly referred cases of depression, schizophrenia, bipolar and personality disorder were included. A variant of the self-controlled case series method was adopted to estimate the incidence rate ratio (IRR) for the relationship between exposure (use of different types of mental healthcare such as pharmacotherapy, generic contact with outpatient services, psychosocial intervention, psychotherapy) and relapse (emergency hospital admissions for mental illness). Results 11,500 relapses occurred. Relapse risk was reduced during periods covered by (i) psychotherapy for patients with depression (IRR 0.67; 95% CI: 0.49-0.91) and bipolar disorder (0.64; 0.29-0.99); (ii) psychosocial interventions for those with depression (0.74; 0.56 to 0.98), schizophrenia (0.83; 0.68-0.99) and bipolar disorder (0.55; 0.36-0.84), (iii) pharmacotherapy for patients with schizophrenia (0.58; 0.49-0.69) and bipolar disorder (0.59; 0.44-0.78). Coverage with generic care, in absence of psychosocial/psychotherapeutic interventions, did not affect relapse risk. Conclusions Psychosocial interventions, psychotherapies and specific pharmacotherapies can be considered particularly effective in treating patients with bipolar, depressive, and schizophrenic disorders. This study showed that real-world data can represent a useful resource to monitor mental healthcare paths and to assess the effectiveness of a mental health system. Key messages • Real-world data can represent a useful resource to monitor mental healthcare paths and to assess the effectiveness of a mental health system. • To evaluate the effectiveness of interventions provided by mental health services in preventing an exacerbation of psychiatric symptoms becomes important in the transition to community mental health.