AI as a Medical Device Adverse Event Reporting in Regulatory Databases: Protocol for a Systematic Review.

BACKGROUND: The reporting of adverse events (AEs) relating to medical devices is a long-standing area of concern, with suboptimal reporting due to a range of factors including a failure to recognize the association of AEs with medical devices, lack of knowledge of how to report AEs, and a general culture of nonreporting. The introduction of artificial intelligence as a medical device (AIaMD) requires a robust safety monitoring environment that recognizes both generic risks of a medical device and some of the increasingly recognized risks of AIaMD (such as algorithmic bias). There is an urgent need to understand the limitations of current AE reporting systems and explore potential mechanisms for how AEs could be detected, attributed, and reported with a view to improving the early detection of safety signals. OBJECTIVE: The systematic review outlined in this protocol aims to yield insights into the frequency and severity of AEs while characterizing the events using existing regulatory guidance. METHODS: Publicly accessible AE databases will be searched to identify AE reports for AIaMD. Scoping searches have identified 3 regulatory territories for which public access to AE reports is provided: the United States, the United Kingdom, and Australia. AEs will be included for analysis if an artificial intelligence (AI) medical device is involved. Software as a medical device without AI is not within the scope of this review. Data extraction will be conducted using a data extraction tool designed for this review and will be done independently by AUK and a second reviewer. Descriptive analysis will be conducted to identify the types of AEs being reported, and their frequency, for different types of AIaMD. AEs will be analyzed and characterized according to existing regulatory guidance. RESULTS: Scoping searches are being conducted with screening to begin in April 2024. Data extraction and synthesis will commence in May 2024, with planned completion by August 2024. The review will highlight the types of AEs being reported for different types of AI medical devices and where the gaps are. It is anticipated that there will be particularly low rates of reporting for indirect harms associated with AIaMD. CONCLUSIONS: To our knowledge, this will be the first systematic review of 3 different regulatory sources reporting AEs associated with AIaMD. The review will focus on real-world evidence, which brings certain limitations, compounded by the opacity of regulatory databases generally. The review will outline the characteristics and frequency of AEs reported for AIaMD and help regulators and policy makers to continue developing robust safety monitoring processes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48156.

Burden of illness in patients with pulmonary hypertension due to interstitial lung disease: a real-world analysis.

BACKGROUND: Pulmonary hypertension due to interstitial lung disease (PH-ILD) is associated with high rates of respiratory failure and death. Healthcare resource utilization (HCRU) and cost data are needed to characterize PH-ILD disease burden. METHODS: A retrospective cohort analysis of the Truven Health MarketScan® Commercial Claims and Encounters Database and Medicare Supplemental Database between June 2015 to June 2019 was conducted. Patients with ILD were identified and indexed based on their first claim with a PH diagnosis. Patients were required to be 18 years of age on the index date and continuously enrolled for 12-months pre- and post-index. Patients were excluded for having a PH diagnosis prior to ILD diagnosis or the presence of other non-ILD, PH-associated conditions. Treatment patterns, HCRU, and healthcare costs were compared between the 12 months pre- versus 12 months post-index date. RESULTS: In total, 122 patients with PH-ILD were included (mean [SD] age, 63.7 [16.6] years; female, 64.8%). The same medication classes were most frequently used both pre- and post-index (corticosteroids: pre-index 43.4%, post-index 53.5%; calcium channel blockers: 25.4%, 36.9%; oxygen: 12.3%, 25.4%). All-cause hospitalizations increased 2-fold, with 29.5% of patients hospitalized pre-index vs. 59.0% post-index (P < 0.0001). Intensive care unit (ICU) utilization increased from 6.6 to 17.2% (P = 0.0433). Mean inpatient visits increased from 0.5 (SD, 0.9) to 1.1 (1.3) (P < 0.0001); length of stay (days) increased from 5.4 (5.9) to 7.5 (11.6) (P < 0.0001); bed days from 2.5 (6.6) to 8.0 (16.3) (P < 0.0001); ICU days from 3.8 (2.3) to 7.0 (13.2) (P = 0.0362); and outpatient visits from 24.5 (16.8) to 32.9 (21.8) (P < 0.0001). Mean (SD) total all-cause healthcare costs increased from $43,201 ($98,604) pre-index to $108,387 ($190,673) post-index (P < 0.0001); this was largely driven by hospitalizations (which increased from a mean [SD] of $13,133 [$28,752] to $63,218 [$75,639] [P < 0.0001]) and outpatient costs ($16,150 [$75,639] to $25,604 [$93,964] [P < 0.0001]). CONCLUSION: PH-ILD contributes to a high HCRU and cost burden. Timely identification, management, and treatment are needed to mitigate the clinical and economic consequences of PH-ILD development and progression.

PCMD: A multilevel comparison database of intra- and cross-species metabolic profiling in 530 plant species.

Comparative metabolomics plays a crucial role in investigating gene function, exploring metabolite evolution, and accelerating crop genetic improvement. However, a systematic platform for comparing intra- and cross-species metabolites is currently lacking. Here, we report the Plant Comparative Metabolome Database (PCMD; http://yanglab.hzau.edu.cn/PCMD), a multilevel comparison database based on predicted metabolic profiles in 530 plant species. PCMD serves as a platform for comparing metabolite characteristics at various levels, including species, metabolites, pathways, and biological taxonomy. The database also provides a series of user-friendly online tools, such as Species-comparison, Metabolites-enrichment, and ID conversion, enabling users to perform comparisons and enrichment analyses of metabolites across different species. In addition, PCMD establishes a unified system based on existing metabolite-related databases by standardizing metabolite numbering. PCMD is the most species-rich comparative plant metabolomics database currently available, and a case study demonstrated its capability to provide new insights into understanding plant metabolic diversity.

Association of Definitive Radiotherapy for Esophageal Cancer and the Incidence of Secondary Head and Neck Cancers: A SEER Population-Based Study.

Background: Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. Methods: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. Results: In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. Conclusion: An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.

Impact of index admission cholecystectomy vs interval cholecystectomy on readmission rate in acute cholangitis: National Readmission Database survey.

BACKGROUND: Elective cholecystectomy (CCY) is recommended for patients with gallstone-related acute cholangitis (AC) following endoscopic decompression to prevent recurrent biliary events. However, the optimal timing and implications of CCY remain unclear. AIM: To examine the impact of same-admission CCY compared to interval CCY on patients with gallstone-related AC using the National Readmission Database (NRD). METHODS: We queried the NRD to identify all gallstone-related AC hospitalizations in adult patients with and without the same admission CCY between 2016 and 2020. Our primary outcome was all-cause 30-d readmission rates, and secondary outcomes included in-hospital mortality, length of stay (LOS), and hospitalization cost. RESULTS: Among the 124964 gallstone-related AC hospitalizations, only 14.67% underwent the same admission CCY. The all-cause 30-d readmissions in the same admission CCY group were almost half that of the non-CCY group (5.56% vs 11.50%). Patients in the same admission CCY group had a longer mean LOS and higher hospitalization costs attributable to surgery. Although the most common reason for readmission was sepsis in both groups, the second most common reason was AC in the interval CCY group. CONCLUSION: Our study suggests that patients with gallstone-related AC who do not undergo the same admission CCY have twice the risk of readmission compared to those who undergo CCY during the same admission. These readmissions can potentially be prevented by performing same-admission CCY in appropriate patients, which may reduce subsequent hospitalization costs secondary to readmissions.

A bibliometric analysis of speech and language impairments in Parkinson's disease based on Web of Science.

Many individuals with Parkinson's disease suffer from speech and language impairments that significantly impact their quality of life. Despite several studies on these disorders, there is a lack of relevant bibliometric analyses. This paper conducted a bibliometric analysis of 3,610 papers on speech and language impairments in Parkinson's disease patients from January 1961 to November 2023, based on the Web of Science Core Collection database. Using Citespace software, the analysis focused on annual publication volume, cooperation among countries and institutions, author collaborations, journals, co-citation references, and keywords, aiming to explore the current research status, hotspots, and frontiers in this field. The number of annual publications related to speech and language impairment in Parkinson's disease have been increasing over the years. The USA leads in the number of publications. Research hotspots include the mechanism underlying speech and language impairments, clinical symptoms, automated diagnosis and classification of patients with PD using linguistic makers, and rehabilitation interventions.

[Status of occupational exposure limits of air toxic substances in the GESTIS Substances Database].

Objective: In order to understand the current situation of air toxic substances without occupational exposure limits (OELs) in the workplace in the Germany GESTIS Substance Database, and to provide an effective reference for formulating OELs of corresponding toxic substances and improving health standards. Methods: From March 2022 to May 2023, based on the standard of GBZ 2.1-2019 Occupational Exposure Limits for Hazardous Agents in the Workplace-Part 1: Chemical Hazardous Agents, air toxic substances without OELs in the standard of GBZ/T 300.1-2017 Determination of Toxic Substances in Workplace Air-Part 1: General Principles were screened out, then corresponding OELs in other countrie/regions were queried through the Germany GESTIS Substance Database. Results: Among the 333 kinds (classes) of air toxic substances in 160 parts of GBZ/T 300.1-2017 standard, 48 kinds (classes) of air toxic substances were screened out and had not yet been formulated OELs in GBZ 2.1-2019 standard. By querying the Germany GESTIS Substance Database, it was found that among the 48 kinds (classes) of air toxic substances, 35 kinds (classes) of air toxic substances had both 8-hour occupational exposure limit and short-term occupational exposure limit, 4 kinds (classes) of air toxic substances had 8-hour occupational exposure limit but no short-term occupational exposure limit, 9 kinds (classes) of air toxic substances hadn't been retrieved any OELs. In addition, standard test methods of 7 kinds of air toxic substances hadn't been published in the present, including trimethylchlorosilane, trimethylbenzenes, cumene, chloroethane, chloropropane, dibromoethane and acetophenone. Conclusion: In the process of formulating or revising the standards of GBZ 2.1-2019 and GBZ/T 300, the latest published OELs in the Germany GESTIS Substance Database could be used as a reference basis.

A retrospective observational study of ibrutinib in chronic lymphocytic leukaemia in a real-life setting in France using the national claims database (OSIRIS).

BACKGROUND: Ibrutinib is a Bruton's tyrosine kinase inhibitor indicated for the first-line treatment and relapse of chronic lymphocytic leukaemia (CLL), Waldenström's macroglobulinemia (WM) and mantle cell lymphoma (MCL). This study aimed to describe the characteristics of CLL patients treated with ibrutinib and its effectiveness, safety, and treatment pattern in real life. METHODS: All patients covered by the general health scheme (approximately 80% of the French population) with a first ibrutinib dispensation from August 1, 2017 (date of reimbursement in France) to December 31, 2020, were identified in the French National Health Insurance database (SNDS). An algorithm was developed to identify the disease (CLL, MCL or WM) for which ibrutinib was prescribed. This article focused on CLL patients. The time to next treatment (TTNT) was plotted using Kaplan‒Meier curves. RESULTS: During this period, 6,083 patients initiated ibrutinib, among whom 2,771 (45.6%) patients had CLL (mean age of 74 years; 61% of men). At ibrutinib initiation, 46.6% of patients had a cardiovascular comorbidity. Most patients (91.7%) were not hospitalized during the exposure period for one of the cardiovascular or bleeding events studied. Hospitalizations were more frequent in patients with a cardiovascular comorbidity (5.9% versus 11.0%, p-value < 0.0001) and aged over 70 (5.9% versus 9.4%, p-value < 0.0001). The median TTNT was not reached. CONCLUSION: This is one of the largest cohorts of ibrutinib-treated patients in the world. The profile of CLL patients treated with ibrutinib was in accordance with the marketing authorization and reimbursement. This study confirmed effectiveness and safety data.

Association between the adherence to Mediterranean diet and depression in rheumatoid arthritis patients: a cross-sectional study from the NHANES database.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease, and depression is a most frequent comorbid condition associated with RA. Studies have shown that inflammation plays a vital role in the pathophysiology of depression and RA. Mediterranean diet (MED) has been proved to be a healthy anti-inflammatory dietary pattern. This study aims to explore the association between the adherence to Mediterranean diet (aMED) and depression in RA patients. METHODS: In this study, RA patients aged ≥ 20 years old were extracted from the National Health and Nutrition Examination Survey (NAHNES) database. Dietary intake information was obtained from 24-h dietary recall interview. Covariates included sociodemographic information, lifestyles, laboratory parameters, and the history of diseases and medications were included. The weighted univariable and multivariable logistic regression models were used to assess the association between aMED and depression. Subgroup analysis was conducted to further explore the association between MED components and depression. RESULTS: Totally 1,148 patients were included, of whom 290 (25.26%) had depression. After adjusted all covariates, high aMED was associated with the lower odds of depression in RA patients (OR = 0.53, 95%CI: 0.29-0.97). Among MED components, higher consumption of vegetables (OR = 0.54, 95%CI: 0.34-0.84) and cereals (OR = 0.63, 95%CI: 0.39-0.99) contributed more to decrease the odds of depression. CONCLUSION: Greater aMED may have potential benefits for improving mental health in RA patients. Future large-scale cohort studies are needed to explore the association between aMED and depression in RA patients.

Increased Risk of Severe Cardiovascular Events Following Exacerbations of Chronic Obstructive Pulmonary Disease: Results of the EXACOS-CV Study in Japan.

INTRODUCTION: Severe exacerbations of chronic obstructive pulmonary disease (COPD) are known to increase the risk of cardiovascular events. However, this association has not been investigated specifically in patients with COPD in Japan, whose characteristics may differ from those of Western patients (i.e., western Europe, the US, and Canada). METHODS: This longitudinal retrospective cohort study analyzed secondary claims data and included patients aged ≥ 40 years with COPD (International Classification of Diseases-10 codes J41-J44). All exacerbations occurring during follow-up were measured. Time-dependent Cox models were used to estimate hazard ratios (HRs) for the association between time periods following an exacerbation of COPD (vs. time prior to a first exacerbation) and occurrence of a first hospitalization for a severe fatal or non-fatal cardiovascular event. RESULTS: The analysis included 152,712 patients with COPD with a mean age of 73.8 years and 37.6% of whom were female. During a median follow-up of 37 months, 63,182 (41.4%) patients experienced ≥ 1 exacerbation and 13,314 (8.7%) patients experienced ≥ 1 severe cardiovascular event. Following an exacerbation of COPD, the risk of a severe cardiovascular event was increased in the first 30 days [adjusted HR (aHR) 1.44, 95% confidence interval (CI) 1.33-1.55] and remained elevated for 365 days post-exacerbation (aHR 1.13, 95% CI 1.04-1.23). Specifically, the risks of acute coronary syndrome or arrhythmias remained significantly increased for up to 180 days, and the risk of decompensated heart failure for 1 year. CONCLUSION: Among Japanese patients with COPD, the risk of experiencing a severe cardiovascular event increased following a COPD exacerbation and remained elevated for 365 days, emphasizing the need to prevent exacerbations.

Perioperative complications and cost of posterior decompression with fusion in thoracic spine for ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum -a comparative study using a national inpatient database.

BACKGROUND: Although posterior decompression with fusion (PDF) are effective for treating thoracic myelopathy, surgical treatment has a high risk of various complications. There is currently no information available on the perioperative complications in thoracic ossification of the longitudinal ligament (T-OPLL) and thoracic ossification of the ligamentum flavum (T-OLF). We evaluate the perioperative complication rate and cost between T-OPLL and T-OLF for patients underwent PDF. METHODS: Patients undergoing PDF for T-OPLL and T-OLF from 2012 to 2018 were detected in Japanese nationwide inpatient database. One-to-one propensity score matching between T-OPLL and T-OLF was performed based on patient characteristics and preoperative comorbidities. We examined systemic and local complication rate, reoperation rate, length of hospital stays, costs, discharge destination, and mortality after matching. RESULTS: In a total of 2,660 patients, 828 pairs of T-OPLL and T-OLF patients were included after matching. The incidence of systemic complications did not differ significantly between the T-OPLL and OLF groups. However, local complications were more frequently occurred in T-OPLL than in T-OLF groups (11.4% vs. 7.7% P = 0.012). Transfusion rates was also significantly higher in the T-OPLL group (14.1% vs. 9.4%, P = 0.003). T-OPLL group had longer hospital stay (42.2 days vs. 36.2 days, P = 0.004) and higher medical costs (USD 32,805 vs. USD 25,134, P < 0.001). In both T-OPLL and T-OLF, the occurrence of perioperative complications led to longer hospital stay and higher medical costs. While fewer patients in T-OPLL were discharged home (51.6% vs. 65.1%, P < 0.001), patients were transferred to other hospitals more frequently (47.5% vs. 33.5%, P = 0.001). CONCLUSION: This research identified the perioperative complications of T-OPLL and T-OLF in PDF using a large national database, which revealed that the incidence of local complications was higher in the T-OPLL patients. Perioperative complications resulted in longer hospital stays and higher medical costs.

In silico analysis of the impact of toxic metals on COVID-19 complications: molecular insights.

COVID-19 can cause a range of complications, including cardiovascular, renal, and/or respiratory insufficiencies, yet little is known of its potential effects in persons exposed to toxic metals. The aim of this study was to answer this question with in silico toxicogenomic methods that can provide molecular insights into COVID-19 complications owed to exposure to arsenic, cadmium, lead, mercury, nickel, and chromium. For this purpose we relied on the Comparative Toxicogenomic Database (CTD), GeneMANIA, and ToppGene Suite portal and identified a set of five common genes (IL1B, CXCL8, IL6, IL10, TNF) for the six metals and COVID-19, all of which code for pro-inflammatory and anti-inflammatory cytokines. The list was expanded with additional 20 related genes. Physical interactions are the most common between the genes affected by the six metals (77.64 %), while the dominant interaction between the genes affected by each metal separately is co-expression (As 56.35 %, Cd 64.07 %, Pb 71.5 %, Hg 81.91 %, Ni 64.28 %, Cr 88.51 %). Biological processes, molecular functions, and pathways in which these 25 genes participate are closely related to cytokines and cytokine storm implicated in the development of COVID-19 complications. In other words, our findings confirm that exposure to toxic metals, alone or in combinations, might escalate COVID-19 severity.

Disparities in the risk of heart disease death among people with chronic lower respiratory disease.

BACKGROUND: Heart disease remains the leading cause of death in the United States, while chronic lower respiratory diseases (CLRD) are the sixth leading cause of death. Patients with CLRD have been shown to have an elevated risk of heart disease death. However, less is known regarding how this risk varies across demographic groups. METHODS: We used the Multiple Cause of Death database from the Centers for Disease Control Wide-ranging ONline Data for Epidemiologic Research to obtain 1999-2020 information on deaths with heart disease as a primary cause of death and CLRD as a contributing cause. We calculated age-adjusted mortality rates (AAMR) over time and for demographic subgroups. RESULTS: During 1999-2020, there were 1,178,048 heart disease deaths related to CLRD among people aged 45+. The AAMR for CLRD-associated heart disease deaths was 45.713 per 100,000 people. AAMR was highest among those aged 65+ (108.56 per 100,000). Elevated rates were seen among males (AAMR ratio = 1.744, 95% CI: 1.741-1.748), people living in the Midwest (AAMR ratio = 1.196, 95% CI: 1.190-1.202), and among people in rural areas (AAMR ratio = 1.309, 95% CI: 1.304-1.313) compared to their corresponding counterparts. Between 1999 and 2004 and 2016-2020 rates decreased among all demographic subgroups, except for among people aged 45-64, among whom deaths increased (AAMR ratio = 1.016, 95% CI: 1.003-1.030). CONCLUSION: Rates of CLRD-associated heart disease deaths have declined over time, but significant disparities remain. Enhanced interventions particularly among older people (65+), people living in rural areas, people living in the Midwest, and men may reduce CLRD-associated heart disease deaths in the United States.

The survival and cost-effectiveness analysis of adjunctive Chinese medicine therapy for patients with non-small cell lung cancer: a nationwide cohort study in Taiwan.

Introduction: Cancer, particularly lung cancer, is a significant global healthcare challenge. Non-Small Cell Lung Cancer (NSCLC) constitutes 85% of cases. Patients often seek alternative therapies like Chinese medicine alongside Western treatments. This study investigates the survival outcomes and cost-effectiveness of adjunctive Chinese medicine therapy for NSCLC patients in Taiwan. Methods: We utilized the National Health Insurance Research Database in a retrospective cohort study from 2000 to 2018, focusing on NSCLC patients diagnosed between 2007 and 2013. After propensity score matching 1:5 ratio, then compared patients with and without adjunctive Chinese medicine therapy. Survival outcomes, cost-effectiveness, and sensitivity analyses were conducted. Results: The study involved 43,122 NSCLC patients with 5.76% receiving adjunctive Chinese medicine. There is no significant associated between the risk of death and adjuvant Chinese medicine therapy until 181-365 days of adjuvant treatment could reduce the risk of death (HR = 0.88, 95% CI: 0.80-0.98). Cost-effectiveness analysis showed an incremental cost-effectiveness ratio of 880,908 NT$/year. Conclusion: Adjunctive Chinese medicine therapy, particularly when administered for 181-365 days, significantly reduced the mortality risk among stage IV NSCLC patients. The cost-effectiveness aligns with willingness-to-pay thresholds, indicating economic benefit.

Scabies in the Philippines: A Secondary Analysis of Local Patient Registries.

Background: Scabies is the second most common cause of disability among skin diseases in the Philippines as of 2019. There is no large nationwide study describing the epidemiologic profile of scabies in the country. Objective: This study aimed to describe the demographic, seasonal, and geographic profile of scabies in the Philippines. Methods: We compared secondary data of two local patient registries (Philippine Dermatological Society, PDS, 2010 to 2021; and Philippine Pediatric Society, PPS, 2009 to 2021) for reported cases of scabies in the Philippines. We reported the frequency and percentage distribution according to age, sex, month, year, and type of diagnosis, and region. Results: The median annual frequency of scabies cases (mostly outpatient) for PDS (from year 2010) was 4087 (range ([QR], 342-6422 [3271.5]), while it was 183 (range [IQR], 64-234 [96.5]) (all inpatient) for PPS (from year 2009). There was a reduction to one-third (PDS) and one-fourth (PPS) of pre-pandemic numbers during the pandemic years (2020-2021). The peak months for scabies cases were the cooler months: January (median, 12.1% of annual cases; range [IQR], 2.6%-31.4% [3.6%]) to February (median, 10.0% of annual cases; range [IQR], 1.5%-27.8% [2.5%]) based on PDS data, and November (median, 10.0% of annual cases; range [IQR], 0.0%-24.3% [7.0%]) to January (median, 9.0% of annual cases; range [IQR], 0.0%-24.3% [6.6%]) for PPS data. Overall, for PDS, age 1-4 years is the most affected age group (median, PDS, 17.5% of annual cases; range [IQR], 11.9%-25.4% [8.1%]), while it was the less than 1-year-olds (median annual cases, 48.9%; range [IQR], 29.1%-67.3% [13.20%]) among PPS pediatric population aged 0 to 18 years. Males (median, 53.9% of annual cases; range [IQR], 45.0%-67.2% [8.8%]) were more affected than females in PPS. While for PDS during earlier years (prior to 2015), males (median, 51.6% of annual cases from 2010 to 2014; range [IQR], 47.4%-52.9% [0.2%]) were more affected than females. However, males became less affected than females with median, 44.7% of annual cases from 2015 onwards (range [IQR], 43.4%-46.5% [1.2%]). NCR was the region with the highest frequency of cases in PPS (median, 52.6% of annual cases; range [IQR], 22.7%-75.0% [20.4%]). The 2nd most affected regions were Central/Eastern Visayas (34.2%, 2009-2013; range [IQR], 17.9%-54.1% [5.3%]), Bicol region (12%; 2014 to 2018; range [IQR], 17.9%-54.1% [7.4%]), Central Luzon (18%; 2019), Central/Eastern Visayas (29%, 2020), and Northern/Central Mindanao (17%, 2021). Conclusion: Scabies was commonly seen in the younger age group, slightly more in females in the PDS, while slightly more among males in the PPS, in the cooler months of the year, and in the urbanized NCR.

A research synthesis of humans, animals, and environmental compartments exposed to PFAS: A systematic evidence map and bibliometric analysis of secondary literature.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a class of widely used anthropogenic chemicals. Concerns regarding their persistence and potential adverse effects have led to multiple secondary research publications. Here, we aim to assess the resulting evidence base in the systematic secondary literature by examining research gaps, evaluating the quality of reviews, and exploring interdisciplinary connections. METHODS: This study employed a systematic evidence-mapping approach to assess the secondary literature on the biological, environmental, and medical aspects of exposure to 35 fluorinated compounds. The inclusion criteria encompassed systematic reviews published in peer-reviewed journals, pre-prints, and theses. Comprehensive searches across electronic databases and grey literature identified relevant reviews. Data extraction and synthesis involved mapping literature content and narrative descriptions. We employed a modified version of the AMSTAR2 checklist to evaluate the methodological rigour of the reviews. A bibliometric data analysis uncovered patterns and trends in the academic literature. A research protocol for this study was previously pre-registered (osf.io/2tpn8) and published (Vendl et al., Environment International 158 (2022) 106973). The database is freely accessible through the interactive and user-friendly web application of this systematic evidence map at https://hi-this-is-lorenzo.shinyapps.io/PFAS_SEM_Shiny_App/. RESULTS: Our map includes a total of 175 systematic reviews. Over the years, there has been a steady increase in the annual number of publications, with a notable surge in 2021. Most reviews focused on human exposure, whereas environmental and animal-related reviews were fewer and often lacked a rigorous systematic approach to literature search and screening. Review outcomes were predominantly associated with human health, particularly with reproductive and children's developmental health. Animal reviews primarily focused on studies conducted in controlled laboratory settings, and wildlife reviews were characterised by an over-representation of birds and fish species. Recent reviews increasingly incorporated quantitative synthesis methodologies. The methodological strengths of the reviews included detailed descriptions of study selection processes and disclosure of potential conflicts of interest. However, weaknesses were observed in the critical lack of detail in reporting methods. A bibliometric analysis revealed that the most productive authors collaborate within their own country, leading to limited and clustered international collaborations. CONCLUSIONS: In this overview of the available systematic secondary literature, we map literature content, assess reviews' methodological quality, highlight data gaps, and draw research network clusters. We aim to facilitate literature reviews, guide future research initiatives, and enhance opportunities for cross-country collaboration. Furthermore, we discuss how this systematic evidence map and its publicly available database benefit scientists, regulatory agencies, and other stakeholders by providing access to current systematic secondary literature on PFAS exposure.

Hepatitis-related adverse events associated with immune checkpoint inhibitors in cancer patients: an observational, retrospective, pharmacovigilance study using the FAERS database.

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However, ICIs can induce immune-related adverse events, with hepatitis-related adverse events (HRAEs) being of particular concern. Our objective is to identify and characterize HRAEs that exhibit a significant association with ICIs using real-world data. Methods: In this observational and retrospective pharmacovigilance study, we extracted real-world adverse events reports from the FDA Adverse Event Reporting System database spanning from the first quarter of 2004 to the first quarter of 2023. We conducted both Frequentist and Bayesian methodologies in the framework of disproportionality analysis, which included the reporting odds ratios (ROR) and information components (IC) to explore the intricate relationship between ICIs and HRAEs. Results: Through disproportionality analysis, we identified three categories of HRAEs as being significantly related with ICIs, including autoimmune hepatitis (634 cases, ROR 19.34 [95% CI 17.80-21.02]; IC025 2.43), immune-mediated hepatitis (546 cases, ROR 217.24 [189.95-248.45]; IC025 4.75), and hepatitis fulminant (80 cases, ROR 4.56 [3.65-5.70]; IC025 0.49). The median age of patients who report ICI-related HRAEs was 63 years (interquartile range [IQR] 53.8-72), with a fatal outcome observed in 24.9% (313/1,260) of these reports. Cases pertaining to skin cancer, lung cancer, and kidney cancer constituted the majority of these occurrences. Patients treated with anti-PD-1 or anti-PD-L1 antibodies exhibited a higher frequency of immune-mediated hepatitis in comparison to those undergoing anti-CTLA-4 monotherapy, with a ROR of 3.59 (95% CI 1.78-6.18). Moreover, the dual ICI therapy demonstrated higher reporting rates of ICI-related HRAEs compared to ICI monotherapy. Conclusion: Our findings confirm that ICI treatment carries a significant risk of severe HRAEs, in particular autoimmune hepatitis, immune-mediated hepatitis, and hepatitis fulminant. Healthcare providers should exercise heightened vigilance regarding these risks when managing patients receiving ICIs.

2024 Update of The Society of Thoracic Surgeons Short-Term Esophagectomy Risk Model: More Inclusive and Improved Calibration.

BACKGROUND: The Society of Thoracic Surgeons General Thoracic Surgery Database (STS-GTSD) previously reported short-term risk models for esophagectomy for esophageal cancer. We sought to update existing models using more inclusive contemporary cohorts, with consideration of additional risk factors based on clinical evidence. METHODS: The study population consisted of adult patients in the STS-GTSD who underwent esophagectomy for esophageal cancer between January 2015 and December 2022. Separate esophagectomy risk models were derived for three primary endpoints: operative mortality, major morbidity, and composite morbidity or mortality. Logistic regression with backward selection was used with predictors retained in models if p<0.10. All derived models were validated using 9-fold cross validation. Model discrimination and calibration were assessed for the overall cohort and specified subgroups. RESULTS: A total of 18,503 patients from 254 centers underwent esophagectomy for esophageal cancer. Operative mortality, morbidity, and composite morbidity or mortality rates were 3.4%, 30.5% and 30.9%, respectively. Novel predictors of short-term outcomes in the updated models included body surface area and insurance payor type. Overall discrimination was similar or superior to previous GTSD models for operative mortality [C-statistic = 0.72] and for composite morbidity or mortality [C-statistic = 0.62], Model discrimination was comparable across procedure- and demographic-specific sub-cohorts. Model calibration was excellent in all patient sub-groups. CONCLUSIONS: The newly derived esophagectomy risk models showed similar or superior performance compared to previous models, with broader applicability and clinical face validity. These models provide robust preoperative risk estimation and can be used for shared decision-making, assessment of provider performance, and quality improvement.

A Real-world Study of Denosumab For Reducing Refracture Risk after Percutaneous Vertebral Augmentation.

OBJECTIVE: To investigate the use of anti-osteoporotic agents and refracture incidence in patients with osteoporotic vertebral compression fracture (OVCF) following percutaneous vertebral augmentation (PVA) and to evaluate the real-world treatment of patients using denosumab following PVA. This study aims to provide spine surgeons with empirical insights derived from real-world scenarios to enhance the management of bone health in OVCF patients. METHODS: This retrospective cohort study was based on data from the MarketScan and Optum databases from the USA. Female patients aged 55-90 years who underwent PVA for OVCF between January 2013 and March 2020 were included and followed up from the day after surgery. Patients who received at least one dose of denosumab were included in the denosumab cohort and were further divided into the on-treatment and off-treatment groups according to whether they received a second dose of denosumab, with follow-up beginning on the index day (225 days after the first denosumab dose). In this study, the off-treatment group was considered as the control group. Refracture incidence after PVA, the proportion of patients using anti-osteoporotic agents in the total study population, and refracture incidence after the index day in the denosumab cohort were analyzed. RESULTS: A total of 13,451 and 21,420 patients from the MarketScan and Optum databases, respectively, were included. In the denosumab cohort, the cumulative incidence of clinical osteoporotic fractures within 3 years after the index day was significantly lower in the on-treatment group than in the off-treatment group (MarketScan database: 23.0% vs 39.0%, p = 0.002; Optum database: 28.2% vs 40.0%, p = 0.023). The cumulative incidence of clinical vertebral fractures was also lower in the on-treatment group than in the off-treatment group, with a significant difference in the MarketScan database (14.4% vs 25.5%, p = 0.002) and a numerical difference was found in the Optum database (20.2% vs 27.5%, p = 0.084).The proportion of patients using anti-osteoporotic agents was low at 6 months postoperatively, with only approximately 7% using denosumab and 13%-15% taking oral bisphosphonates. CONCLUSION: Postmenopausal women have a high refracture rate and a low proportion of anti-osteoporotic drug use after PVA. Continued denosumab treatment after PVA is associated with a lower risk of osteoporotic and clinical vertebral fractures. Therefore, denosumab may be a treatment option for patients with osteoporosis after PVA.