Use Of Databases Research Articles

Abstract TMP80: Outcomes in a national cohort of patients with ischemic stroke who underwent mechanical thrombectomy and decompressive craniectomy were unchanged following extension of the thrombectomy window

Introduction: In 2015, mechanical thrombectomy (MT) was established as an essential treatment for large-vessel occlusion ischemic stroke (LVO). Since then, trials have expanded the population eligible for MT by demonstrating its benefit in patients with LVO who present later to care and with more extensive infarct. As the eligibility criteria for MT ease, more patients will undergo the procedure who have risk factors for complications – such as malignant edema or hemorrhagic conversion – that require decompressive craniectomy (DC). Though MT and DC in ischemic stroke have been studied independently, the outcomes of patients who undergo both procedures is unknown. We present a case series using a national database of patients who underwent MT and required DC to understand their profile and health outcomes. Methods: Using the National Inpatient Sample (NIS), an all-payer national healthcare utilization database, patients admitted between the years 2016 and 2021 for ischemic stroke who underwent MT and required DC were identified via ICD-10 codes. Logistic regression was performed to identify patient factors independently associated with DC after MT. Results: Of the 31,234 patients admitted for LVO who received MT between 2016-2021, 764 (2%) underwent DC (Table 1). Younger age (p < 0.001), non-white race (p < 0.001), a higher NIHSS (p < 0.001), and lower rates of atrial fibrillation were independently associated with DC after MT. Although the number of patients undergoing MT plus DC increased annually, this rise was proportional to the overall number of MT patients. Admissions with MT and DC were nearly 2.5 times longer than those with MT alone (20 days versus 8.4 days, p < .001, Table 2) and associated with increased rates of mortality (25% versus 12%, p < 0.001) and a higher level of care after discharge (p < 0.001). Conclusion: Rates of DC after MT did not change following extension of the thrombectomy window to 24 hours. DC after MT resulted in a heavy burden of morbidity and mortality, similar to levels previously published for DC after ischemic stroke without MT. In conclusion, our findings suggest that expansion of MT eligibility criteria has not increased the risk for DC and that practice guidelines developed from trials in stroke patients who underwent DC but not MT may also be applicable to patients with DC after MT. Recent large core trials have further expanded the MT population, necessitating continued examination of the relationship between MT and DC.

Clinical outcomes after transcatheter aortic valve implantation in nonagenarian patients: A retrospective population-based cohort study.

To compare the overall survival and the risk of all-cause and heart failure-specific hospitalization in nonagenarian patients hospitalized for symptomatic severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI) or conservative treatment. Population-based retrospective cohort study based on healthcare utilization databases of the Italian region of Lombardy. The cohort included all nonagenarians hospitalized for AS between 2017 and 2021, who underwent TAVI within 90 days from first diagnosis or conservative treatment. The association between TAVI and clinical outcomes was assessed through Cox or Fine&Grey regression models. High-dimensional propensity score matching was used to reduce the heterogeneity between groups. Overall, 16,848 nonagenarians hospitalized for AS were identified. Among these, 320 patients underwent TAVI, of which 193 were matched to as many control patients. The 2-year survival rates were 76.0 % and 37.7 %, respectively, in TAVI and control patients, corresponding to an HR of 0.24 (95 % CI 0.15-0.37). The 2-year cumulative incidence of rehospitalization for heart failure was 11.1 % and 26.5 %, respectively, corresponding to an HR of 0.64 (95 % CI 0.40-0.99). This study further supports the usefulness of TAVI in nonagenarians, as it showed to improve their survival rate, reduce their risk of rehospitalization, and likely increase their quality of life.

Does syndromic surveillance assist public health practice in early detecting respiratory epidemics? Evidence from a wide Italian retrospective experience.

Large-scale diagnostic testing has been proven ineffective for prompt monitoring of the spread of COVID-19. Electronic resources may facilitate enhanced early detection of epidemics. Here, we aimed to retrospectively explore whether examining trends in the use of emergency and healthcare services and the Google search engine is useful in detecting Severe Acute Respiratory Syndrome Coronavirus outbreaks early compared with the currently used swab-based surveillance system. Healthcare Utilization databases of the Italian region of Lombardy and the Google Trends website were used to measure the weekly utilization of emergency and healthcare services and determining the volume of Google searches from 2020 to 2022. Improved Farrington algorithm (IMPF) and Exponentially Weighted Moving Average (EWMA) control chart were both fitted to detect outliers in weekly searches of nine syndromic tracers. AND/OR Boolean operators were tested aimed for joint using tracers and models. Signals that occurred during periods labelled as free from epidemics were used to measure positive predictive values (PPV) and false negative values (FNV) in anticipating the epidemic wave. Out of the 156 weeks of interest, 70 (45 %) were affected by epidemic waves. Overall, 54 syndromic signals were obtained from any one of the 7 healthcare or Google tracers, generating an outlier from both the EWMA and IMPF models. PPV values of 0.95, 1.00, 0.96 admitting a delay of 0, 1, and 2 weeks, respectively, between signal and epidemic wave. The values of FNP ranged from 0.19 to 0.21. High predictive power for anticipating COVID-19 epidemic waves, even two weeks ahead of the official reports, was obtained from electronic syndromic tracers of healthcare-seeking trends and Google search engine use. Following verification via a prospective approach, public health organizations are encouraged to take advantage of this free forecasting system to anticipate and effectively manage respiratory outbreaks.

P-210. Real-World Utilization and Cost of Fidaxomicin versus Oral Vancomycin: A Comparative Analysis of Outpatient Medicaid Prescription Reimbursements

Abstract Background Clostridioides Difficile Infection (CDI) is a leading cause of infectious diarrhea in the United States. In 2017, the Infectious Diseases Society of America (IDSA) and Society of Healthcare Epidemiology of America (SHEA) joint guidelines added fidaxomicin (FX) as a first line therapy for initial and first recurrence of non-fulminant CDI alongside oral vancomycin (OV). Under a 2021 guideline revision FX became the preferred therapy based on lower CDI recurrence among those treated with FX. Multiple analyses have attempted to predict the economic impact of increased FX use but have yielded conflicting results. The use of real-world data on actual cost and utilization has been limited.Figure 1:Total Annual Outpatient Medicaid CDI Therapy Prescription CountCDI: Clostridioides Difficile Infection Methods We conducted a retrospective analysis of utilization and cost of FX and OV between January 1st, 2013 and December 31st, 2022 in the Medicaid State Drug Utilization Database (SDUD). The SDUD contains covered outpatient medications excluding those reimbursed under bundled services. Prescriptions for OV were distinguished from other vancomycin formulations using national drug codes. Utilization was estimated by the number of prescriptions reimbursed. Total cost was calculated as the sum of Medicaid and non-Medicaid reimbursement. We approximated the annual per prescription cost (APPC) as the quotient of total cost and prescription count.Figure 2:Total Annual Outpatient Medicaid CDI Therapy Prescription CostCDI: Clostridioides Difficile Infection Results Following the 2017 guidelines the average annual FX prescription count (Figure 1) increased by 32% compared to a 2013-2016 baseline. After the 2021 guideline revision, average annual FX prescription count grew by 113% as compared to a 2017-2020 baseline. The total annual cost of FX (Figure 2) surpassed the total annual cost of OV in 2019 with FX reaching $17,984,998 in 2022 as compared to $3,135,523 for OV. Throughout the study period the FX APPC (Figure 3) was substantially greater ($2,614-$3,956) than the OV APPC ($134-$1,579).Figure 3:Annual Per Prescription Cost of Outpatient Medicaid CDI TherapyCDI: Clostridioides Difficile Infection Conclusion Among Medicaid beneficiaries, outpatient FX use increased in time periods following the 2017 and 2021 guideline changes. While FX use was significantly lower than OV from 2013-2022, FX total cost and APPC far outweighed that of OV. Further analysis is necessary to determine the real-world cost effectiveness of FX, but our results highlight the budgetary impact associated with these IDSA/SHEA guideline changes. Disclosures All Authors: No reported disclosures

P-1636. Real World Outpatient Utilization of Novel Anti-MRSA Antimicrobials: Patterns in Prescribing and Cost of Oral and Long-Acting Injectable Anti-MRSA Therapies in United States Medicaid Beneficiaries

Abstract Background Methicillin Resistant Staph Aureus (MRSA) isolates with resistance to traditional oral anti-MRSA antimicrobials represent a major public health concern. Since 2014, the United States (US) Food and Drug Administration (FDA) approved three oral (tedizolid [2014], delafloxacin [2017], omadacycline [2018]) and two long-acting injectable (LAI) antimicrobials (dalbavancin [2014], oritavancin [2014]) with potent activity against MRSA. Little has been reported about the real-world outpatient utilization and cost of these important therapies. Methods We conducted a retrospective analysis of utilization and cost of these 5 antimicrobials between January 1st, 2014 and December 31st, 2022 in the Medicaid State Drug Utilization Database (SDUD). The SDUD contains all covered outpatient medications excluding those reimbursed under bundled services and suppresses medication data for years with fewer than 11 prescriptions. Annual cost was calculated as the sum of Medicaid and non-Medicaid reimbursement. We approximated the annual per prescription cost (APPC) as the quotient of total cost and prescription count. Results Trends in utilization, total cost and APPC are depicted in Figures 1, 2 and 3 respectively. There was a 1–2-year lag between FDA approval and utilization. Dalbavancin utilization and cost rose from 13 prescriptions and $26,224 in 2014 to 4970 prescriptions and $16,403,304 in 2022, while oritavancin increased from 27 to 566 prescriptions and from $62,309 in $944,657costs. The dalbavancin APPC increased over the study period ending in 2022 at $3,300 while the oritavancin APPC declined to $1669 in 2022. Of the oral antimicrobials, tedizolid utilization and total cost peaked in 2019 at 755 prescriptions and $3,193,571, after which total cost and utilization fell to 283 prescriptions and $1,773,238 by 2022. Delafloxacin utilization and total cost remained low while omadacycline had an increasing trend in utilization, total cost and APPC in the three years it was included. Conclusion Utilization and total cost of dalbavancin rose substantially over the study dwarfing that of oritavancin and the novel oral antimicrobials by the latter half of the study period. Omadacycline, the newest approved antimicrobial included, demonstrated a prompt rise in utilization and total cost. Disclosures All Authors: No reported disclosures

Therapeutic Advantages of Nanoparticle-Impregnated Lysozyme Conjugates toward Amyloid-β Fibrillation and Antimicrobial Activity.

The interaction of protein with nanoparticles (NPs) of varying shape and/or size boosts our understanding on their bioreactivity and establishes a comprehensive database for use in medicine, diagnosis, and therapeutic applications. The present study explores the interaction between lysozyme (LYZ) and different NPs like graphene oxide (GO) and zinc oxide (ZnO) having various shapes (spherical, 's', and rod-shaped, 'r') and sizes, focusing on their binding dynamics and subsequent effects on both the protein fibrillation and antimicrobial properties. Typically, GO is considered a promising medium due to its apparent inhibition and prolonged lag phase for LYZ fibrillation. However, the present results showed that spherical ZnO NPs (sZnO) offer superior efficacy in modulating fibrillation with an extended lag time of about 158.70 h, further emphasizing the importance of detailed investigation on the nanomaterial characteristics and fibril formation kinetics beyond initial observations. The experimental findings further confirmed a strong correlation between the binding affinity of NPs to the native protein and their effective inhibition of protein denaturation, ultimately preventing fibril formation. Interestingly, the lysozyme nanoconjugates showed intriguing bactericidal effects, as confirmed through the agar plate assay and SEM imaging, over the native protein. Overall, this study shows that appropriate bionanomaterials can exhibit multifunctional properties, which paves the way for a deeper investigation of NP characteristics, ultimately benefiting a wide array of intriguing research.

Genetic characterization of paternal lineages by Y-STR in three sample populations in Northeastern Brazil.

Genetic markers of the Y chromosome are powerful tools for investigating paternal ancestry and are widely used in population and forensic genetics. However, in order to obtain statistics with a higher degree of certainty using these markers, it is necessary to obtain haplotypic frequencies from a representative database, as well as knowing the diversity and structure of the population. The aim of this study was to investigate the genetic diversity of a sample of 1114 unrelated men from three states in the Northeast of Brazil: Paraíba, Pernambuco and Ceará, through the analysis of 23 Y-STRs and to contribute to the expansion of the Brazilian database on these markers. The PPY23 panel had a high discriminatory power, and the population structure was consistent with the historical aspects of the colonization of the Northeast of Brazil. Population comparisons based on paired genetic differentiation values (Fst) revealed no statistically significant differences between the three populations in this study. However, it was observed that Pernambuco and Paraíba were genetically closer to states outside the Northeast region. Y-STR-based haplogroup prediction, carried out using the NevGen software, revealed that the paternal lineage of the populations in this study is essentially European, with little African or Native American influence, just like the rest of the Brazilian population. Additionally, this work contributes to a more representative database for use in forensic and population genetics.

Adherence to perindopril/amlodipine/atorvastatin combination according to the administration strategy

Abstract Aims To compare adherence to perindopril/amlodipine/atorvastatin combination administrated as a polypill (one pill) vs. separate tablets. Methods and results Using the healthcare utilization database of Lombardy (Italy), 1110 patients who received the perindopril/amlodipine/atorvastatin polypill during 2019–2021 were matched with 1110 patients prescribed the same combination in separate tablets or as two antihypertensive drugs in a single tablet and the lipid-lowering drug tablet separately. Adherence to treatment was assessed over the year after the first perindopril/amlodipine/atorvastatin dispensation as the proportion of the follow-up days covered by prescription (PDC). Patients with a PDC >75% and <25% were defined as highly and poorly adherent, respectively. Adherence dynamics over time were evaluated through group-based trajectory modelling. Cardiovascular-related healthcare costs were also assessed. Log-binomial regression models were fitted to estimate the risk ratio (RR) of treatment adherence associated with the administration strategy. Among the polypill and the separate-pill combination users, 60% and 18% of patients showed high adherence, respectively; the corresponding figures for the low adherence were 5% and 37%. Compared with the separate-pill combination, the polypill increased the propensity to be highly adherent to treatment by 3.29 times (95% confidence interval: 2.88–3.75) and reduced the low adherence risk (RR = 0.13, 0.10–0.18), irrespective of sex, age, comorbidities, and co-treatment burden also throughout the entire follow-up. The polypill was also associated with lower costs (€676 vs. €1068, P = 0.003). Conclusion In a real-life setting, the polypill improved treatment adherence and reduced healthcare costs compared to the corresponding separate-pill combination. These findings support current guidelines in favour of the polypill.

Healthcare workers safety: a cohort study using healthcare utilisation databases on vaccination and vaccine timeliness impact against SARS-CoV-2 infection

Healthcare Workers (HCWs) are at ongoing risk of SARS-CoV-2 infection, potentially contributing to its transmission. This study assessed full vaccination and vaccination timeliness impact on SARS-CoV-2 infections among HCWs in Italy’s Marche Region, using Healthcare Utilization Databases. We evaluated vaccination coverage and its associated factors. The cohort comprised 21,118 HCWs aged 18–70 from the region’s five Local Health Authorities (LHA), enrolled between February 2020 - May 2021. Factors associated with full vaccination were assessed using multiple logistic regression. The impact of vaccination status, time to vaccination, occupational role, age, gender, and health status on infection risk was analysed with a multiple Cox regression model, adjusting for vaccination coverage velocity, swabbing probability, and monthly intensive care unit admissions rate in each LHA. Of the cohort, 81.2% were fully vaccinated. Factors associated with full vaccination included age, role, LHA, prior infection, and health status. Vaccination reduced infection risk by 77% (95% CI: 70–82). Infection risk was higher among healthcare assistants, nurses/physiotherapists/technicians compared to physicians, among male HCWs, and it decreased as vaccination timeliness increased. Vaccination timeliness is crucial for reducing SARS-CoV-2 infection risk among HCWs, regardless of their characteristics. This underscores the importance of efficiently organizing vaccination administration across different territories and for all HCW categories.

Operative and non-operative management of acute appendicitis during pregnancy: a population-based study.

Acute appendicitis during pregnancy poses unique challenges due to altered anatomical and physiological dynamics and concern about foetal well-being. This study aimed to assess management strategies and outcomes of acute appendicitis during pregnancy, focusing on non-operative management versus surgical intervention. The study is based on the computerized healthcare utilization database of Lombardy. In Lombardy, a total of 1,231,040 deliveries were identified. Acute appendicitis during pregnancy occurred in 0.03% of cases, with 74.49% of these cases classified as uncomplicated. Appendicitis during pregnancy was associated with worse maternal and perinatal outcomes. Among uncomplicated cases, 38.46% were treated with non-operative management. Perinatal outcomes did not significantly differ between non-operative management and surgery groups. Additionally, a declining trend in surgical treatment over the study period was observed (P = 0.0477), possibly indicating a shift towards conservative management. The findings suggest that non-operative management may be a viable option for selected pregnant patients with uncomplicated appendicitis, potentially avoiding surgical complications and allowing for faster recovery. Further research is warranted to validate these findings, explore evolving trends, and refine clinical guidelines for managing acute appendicitis during pregnancy.

Machine Condition Monitoring System Based on Edge Computing Technology.

The core of this publication is the design of a system for evaluating the condition of production equipment and machines by monitoring selected parameters of the production process with an additional sensor subsystem. The main positive of the design is the processing of data from the sensor layer using artificial intelligence (AI) and expert systems (ESs) with the use of edge computing (EC). Sensor information is processed directly at the sensor level on the monitored equipment, and the results of the individual subsystems are stored in the form of triggers in a database for use in the predictive maintenance process. The whole solution includes the design of suitable sensors and of the implementation of the sensor layer, the description of data processing algorithms, the design on the communication infrastructure for the whole system, and tests in the form of experimental operation of the device in laboratory conditions. The solution includes the visualisation of the production system status for the operator using an interactive online map.

The clinical significance and burden of thyroid nodules discovered incidentally.

The majority of thyroid nodules are benign; however current guidelines suggest that thyroid incidentalomas should be appropriately evaluated to rule out malignancy. This study aims to determine the incidence of thyroid incidentalomas and the likelihood that they harbour sinister pathology in the largest Irish cohort studied to-date. A retrospective observational chart review was conducted using data from July 2018 to December 2018 using the Radiology Database in use at Cork University Hospital. The text of 1000 imaging reports (500 carotid Doppler and 500 computed tomography thorax) was manually screened for phrases such as "thyroid mass" or "thyroid nodule". On 1000 scans, 14 (1.4%) thyroid incidentalomas were discovered. The occurrence of incidentalomas by imaging was 2/500 (0.4%) for ultrasound and 12/500 (2.4%) for computed tomography. Three of these nodules (21.4%) were further evaluated with a subsequent ultrasound and due to a size of more than 1cm underwent fine needle aspiration. Using the Thy classification, all three were given a Thy 2 (non-neoplastic) grading. This study found that there was no clinical benefit to reporting the presence of thyroid incidentalomas incidentally noted on radiology investigations. Although the overall percentage of thyroid incidentalomas is low, this number may be enough to cause unnecessary strain on the healthcare system and burden patients with invasive investigations in addition to causing unnecessary anxiety.

Multi-Platform Collaboration in Integrated Surveying: Ensuring Completeness and Reliability of Geospatial Data—A Case Study

Multi-platform geospatial data synergy is critical for complete and reliable surveys. This study investigates various methods for combining data from terrestrial laser scanning (TLS), orthophotos, databases of topographic objects, utility databases, tacheometry, and GNSS to assess and improve positioning accuracy and consistency of data in spatial databases. The study highlights the challenges and solutions regarding integrating various datasets to yield a complete and reliable geospatial database for building surveys and the construction and keeping of spatial databases. Input from diversified surveying technologies, such as TLS, GNSS, and orthophotos, offers detailed and precise data necessary to create and update accurate base maps and databases of topographic objects. A complete survey of a structure and its surroundings demonstrates how the synergistic application of diverse data sources helps improve the positioning accuracy and consistency of spatial databases. The results indicate the importance of multi-platform collaboration for high data quality standards in surveying, which is critical for effective planning and implementation of surveying projects.

Survival, treatment duration and costs of patients with prostate cancer treated with triptorelin in Italy: a study of administrative databases.

Several data support the efficacy/effectiveness, safety and favorable impact on quality of life of triptorelin treatment in patients with prostate cancer. However, little evidence is available concerning triptorelin use in the long term. We analyzed data on triptorelin treatment in patients with prostate cancer in an integrated Italian administrative database, covering around 6 million health-assisted subjects throughout the country. Patients with at least one prescription for triptorelin in the period 2010-2020 and with no evidence of metastasis were included and followed up until 2021. Overall survival (OS) and duration of treatment were analyzed using Kaplan-Meier curves, starting from the date of first prescription. The cohort included a total of 3,411 patients (mean age: 76.8 ± 8.7 years), of whom 1,326 (38.9%) were treated with triptorelin only and 2,085 (61.1%) with triptorelin combined with an anti-androgen. Overall, 847 (24.8%) patients with prostate cancer died and 1,037 (30.4%) had a treatment switch during the follow-up period, and both the median OS and median duration of treatment were not reached in both groups. The mean annual total cost per patient was estimated as 5,574 €, with almost half of the costs related to medication expenses (2,737 €). We found a long survival and duration of triptorelin treatment in this population of Italian patients with prostate cancer. This study with a long follow-up period further highlights the usefulness of healthcare utilization databases to integrate results obtained from clinical studies with those from everyday clinical practice.

2001-2021 Comparative Persistence of Oral Antipsychotics in Patients Initiating Treatment: Superiority of Clozapine in Time-to-Treatment Discontinuation.

Continuous antipsychotic (AP) therapy is crucial for managing psychotic disorders, and its early interruption reflects the drug's failure. Real-world epidemiological research is essential for confirming experimental data and generating new research hypotheses. The persistence of oral APs in a large population sample from 2000 to 2021 was analyzed by comparing AP prescriptions over this period across four Italian provinces, using dispensing data linked via a record-linkage procedure among regional healthcare utilization databases. We calculated personalized daily dosages and assessed time-to-treatment discontinuation over a 3-month period for patients initiating AP treatment. Treatment persistence was evaluated using Kaplan-Meier curves and Cox regression, with adjustments for age and sex. Second-generation antipsychotics (SGAs) were favored over first-generation antipsychotics (FGAs), with olanzapine as the most prescribed. Within the study time frame, 42,434 individuals were prescribed a new continuous AP regimen. The analysis revealed 24 significant differences within 28 comparisons. As a class, SGAs demonstrated better treatment persistence than FGAs (HR: 0.76; 95%CI: 0.73, 0.79). Clozapine stood out for its superior persistence, surpassing all other SGAs, notably olanzapine (HR: 0.85; 95%CI: 0.79-0.91) and risperidone (HR: 0.80; 95%CI: 0.74-0.87). Olanzapine and aripiprazole showed better results than both risperidone and quetiapine. Quetiapine showed inferior 3-month persistence in all pairwise comparisons. The study results provide insight into the performance dynamics among SGAs: clozapine, despite being one of the less frequently dispensed APs in our sample, emerged as a significant prescription choice. The significance of pharmacoepidemiological studies in complementing experimental findings is also underscored.

Respiratory phenotype and health care utilization patterns by adults with sickle cell disease

Adults with sickle cell disease (SCD) and asthma have increased mortality and health care utilization; however, there are individuals with respiratory symptoms (including cough and wheeze) without asthma. These individuals may have similar patterns of increased mortality and health care utilization. To characterize the association between respiratory phenotype and health care utilization by adults with SCD. Cross-sectional study of adults with SCD presenting for emergency and inpatient hospital care from 2012 to 2014 in Florida, Iowa, and New York using state-level health care utilization databases. Outcomes of interest included all-cause, SCD-related acute, painful episode, and acute chest syndrome-related care. Respiratory phenotype was defined as SCD+ asthma, SCD+ respiratory symptoms, and SCD+ none. We built multivariable logistic regression and negative binomial regression models to evaluate the association adjusting for demographics, social determinant of health proxies, year of care, and state. Of 29 952 identified individuals, 3.4% had intermittent respiratory symptoms, and a larger proportion (15.6%) had asthma. There was a high rate of inpatient hospitalizations (43%) and emergency department visits (60%). Individuals with asthma had a higher annual risk of inpatient hospitalizations (48% vs 37%) but lower annual risk of an emergency department visit (62% vs 86%) than individuals with intermittent respiratory symptoms. The pattern of increased health care utilization among individuals with intermittent respiratory symptoms was consistent across each utilization type. In this large cohort of adults with SCD, we identified some with intermittent respiratory symptoms who had significantly increased health care utilization. This warrants further evaluation to understand potential etiologies and interventions.

P53motifDB: integration of genomic information and tumor suppressor p53 binding motifs.

The tumor suppressor gene TP53 encodes the DNA binding transcription factor p53 and is one of the most commonly mutated genes in human cancer. Tumor suppressor activity requires binding of p53 to its DNA response elements and subsequent transcriptional activation of a diverse set of target genes. Despite decades of close study, the logic underlying p53 interactions with its numerous potential genomic binding sites and target genes is not yet fully understood. Here, we present a database of DNA and chromatin-based information focused on putative p53 binding sites in the human genome to allow users to generate and test new hypotheses related to p53 activity in the genome. Users can query genomic locations based on experimentally observed p53 binding, regulatory element activity, genetic variation, evolutionary conservation, chromatin modification state, and chromatin structure. We present multiple use cases demonstrating the utility of this database for generating novel biological hypotheses, such as chromatin-based determinants of p53 binding and potential cell type-specific p53 activity. All database information is also available as a precompiled sqlite database for use in local analysis or as a Shiny web application.

Development and validation of claims-based algorithms for estimating gestational age of spontaneous abortion and termination.

To study the risk of spontaneous abortion (SAB) or termination using healthcare utilization databases, algorithms to estimate the gestational age (GA) are needed. Using Medicaid data, we developed a hierarchical algorithm to classify pregnancy outcomes. We identified the subset of potential SAB and termination cases, and abstracted the GA from linked electronic medical records (gold standard). We developed three approaches: (1) assign median GA for SAB and termination cases in the US; (2) draw a random GA from the population distributions; (3) estimate GA based on regression models. Algorithm performance was assessed based on the proportion of pregnancies with estimated GA within 1-4 weeks of the gold standard, the mean squared error (MSE) and the R-squared. Approach 1 and Approach 3 had similar performance, though approach 3 using random forest models with variables selected via the Boruta algorithm had better MSE and R-squared. For SAB, 58.0% of pregnancies were correctly classified within 2 weeks of the gold standard (MSE: 8.7, R-squared: 0.09). For termination, the proportions were 66.3% (MSE: 11.7; R-squared: 0.35). SABs and terminations can be studied in healthcare utilization data with careful implementation of validated algorithms though higher level of GA misclassification is expected compared to live births.

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

To develop and validate a novel score predictive of nursing home placement in elderly. Population-based case-control study based on healthcare utilization databases of Lombardy, a region of Northern Italy. The 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. Twenty-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. A 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.