Proportional Ratio Research Articles

Mining and analysis of adverse event signals of trastuzumab deruxtecan via real-world data of FDA adverse event reporting system database from 2019 to 2023

ABSTRACT Background Trastuzumab deruxtecan (T-DXd) is a novel generation antibody-drug conjugate. However, current evidence for the safety of T-DXd is mostly limited to clinical trials. It resulted in inability to timely update the adverse event (AE) for drug. Therefore, we mine and analyze AE signals caused by T-DXd based on the FAERS database, and to provide reference for the safe use of drug in clinical practice and reduce the occurrence of AE. Research design and methods This study analyzed real-world data on AEs associated with T-DXd reported in the FAERS database from December 2019 to December 2023, and the reporting odds ratio, proportional report ratio, bayesian confidence propagation neural network and multi-item gamma Poisson shrinker methods were combined to identify and evaluate reports, which can reduce the number of false positive and false negative signals with good sensitivity. Results A total of 4651 AE reports of T-DXd as the ‘primary suspect’ were collected. The median time to onset of T-DXd -related AEs was 25 days. The proportion of serious AEs was 69.40%. Hospitalization (25.67%) and death (24.19%) accounted for the highest occurrence frequency of clinical serious outcomes. The top three AE in both occurrence frequency and signal intensity were interstitial lung disease. We also found twelve kinds of potential novel danger signals not recorded in the drug lable, such as ascites, sepsis, pneumocystis jirovecii pneumonia, and gastroenteritis listeria, which need further attention and verification in clinical practice. Conclusion The results of this study indicate the importance of timely mining and updating information of adverse drug reactions. Drug evaluation should be performed well before using T-DXd, and during treatment, the indexes of pulmonary, bone marrow hematopoietic and cardiac function should be closely monitored, timely intervention measures should be taken to avoid related injury caused by AEs.

Pharmacovigilance insights into drug-induced cystitis: analysis of FDA data from 2004 to 2024

ABSTRACT Background Drug-induced cystitis (DIC) significantly impacts patient quality of life and treatment outcomes. This study investigates the incidence and characteristics of DIC using data from the FDA Adverse Event Reporting System (FAERS). Methods We reviewed FAERS reports related to cystitis from Q1 2004 to Q1 2024, compiling a list of potential causative drugs. The top 50 drugs with the highest number of cystitis reports were ranked. Statistical disproportionality analyses, including Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), were used to detect unusually high reporting frequencies of cystitis associated with specific drugs. Results From 17,703,515 FAERS reports spanning 2004–2024, 36399 involved cystitis. The majority of implicated drugs were antineoplastics. Busulfan, BCG, and mitomycin had the highest ROR and PRR values. Additionally, drugs such as defibrotide sodium, milrinone, and dyazide, which do not have cystitis listed on their labels, were identified, highlighting the need for increased clinical vigilance and awareness. Conclusion The findings underscore the importance of ongoing pharmacovigilance in identifying and characterizing DIC. Further clinical studies are warranted to validate these associations and to develop strategies for mitigating the risk of DIC, thereby improving patient safety and treatment outcomes.

A real-world pharmacovigilance analysis of adverse events associated with irbesartan using the FAERS and JADER databases.

Hypertension is a leading global risk factor for disability and death. Irbesartan, a potent angiotensin II receptor blocker, requires continuous safety monitoring. We conducted a disproportionality analysis of irbesartan-related adverse drug events (ADEs) using the FDA's FAERS and Japan's JADER databases. We extracted irbesartan-related ADE reports from FAERS (Q1 2004 to Q1 2024) and JADER (Q2 2008 to Q4 2023). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) for signal detection. Sensitivity analyses were conducted to exclude comorbid medications, and subgroup analyses by age and gender were performed to explore ADE occurrence in specific populations. Th time to onset (TTO) of ADEs was assessed using Weibull distribution test and Kaplan-Meier curves. A total of 5,816 (FAERS) and 366 (JADER) reports were analyzed, with irbesartan-related preferred terms (PTs) involving 27 System Organ Classes (SOCs) in FAERS and 22 in JADER. Three SOCs met detection thresholds in both databases: "metabolism and nutrition disorders," "cardiac disorders," and "renal and urinary disorders." We identified 219 positive signals in FAERS and 20 in JADER, including known signals like hyperkalemia, hypotension, and acute kidney injury. Notably, newly identified signals such as acute pancreatitis (n = 50, ROR: 7.76 [5.88-10.25]) and rhabdomyolysis (n = 50, ROR: 7.76 [5.88-10.25]) in FAERS and respiratory failure (n = 7, ROR: 6.76 [3.20-14.26]) in JADER could have significant clinical implications, as they may lead to severe outcomes if not recognized and managed promptly. Subgroup analyses revealed both similarities and differences in signal detection across gender and age groups. Sensitivity analyses, excluding concomitant medications, confirmed the persistence of key positive signals, including hyperkalemia, angioedema, acute pancreatitis, and agranulocytosis. ADEs mainly occurred within 1month (34.14%) and after 1year (32.32%) after dosing, with a median onset of 107days. This study provides valuable real-world evidence on the safety profile of irbesartan. The identification of new safety signals underscores the necessity of updating drug labels, particularly for assessing and managing high-risk patients. Additionally, the TTO analysis emphasizes the importance of sustained vigilance for adverse events over time. In conclusion, our findings contribute to a more comprehensive understanding of irbesartan's safety, aiding healthcare professionals in optimizing its use in clinical practice.

Effects of Tirzepatide on the Clinical Trajectory of Patients with Heart Failure, a Preserved Ejection Fraction, and Obesity.

Patients with heart failure, a preserved ejection fraction (HFpEF), and obesity have significant disability and suffer frequent exacerbations of heart failure. We hypothesized that tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, would improve a comprehensive suite of clinical endpoints, including measures of health status, functional capacity, quality of life, exercise tolerance, patient well-being, and medication burden in these patients. 731 patients in class II-IV heart failure, ejection fraction ≥50%, and body mass index ≥30 kg/m2 were randomized(double-blind) to tirzepatide(titrated up to 15mg subcutaneously weekly)(n=364) or placebo(n=367), added to background therapy for a median of 104 weeks (Q1=66, Q3=126 weeks). tirzepatide reduced the combined risk of cardiovascular death or worsening heart failure and improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score(KCCQ-CSS). The current expanded analysis included sensitivity analyses of the primary endpoints, 6-minute walk distance(6MWD), EQ-5D-5L health state index, Patient Global Impression of Severity Overall Health(PGIS), NYHA class, use of heart failure medications, and a hierarchical composite based on all-cause death, worsening heart failure, and 52-week changes in KCCQ-CSS and 6MWD. Patients were aged 65.2±10.7, 53.8%(n=393) were female; BMI 38.2±6.7kg/m2, KCCQ-CSS 53.5±18.5, 6MWD 302.8±81.7meters, and 53%(n=388) had a worsening heart failure event in the prior 12 months. Compared with placebo, tirzepatide produced a consistent beneficial effect across all composites of death and worsening heart failure events, analyzed as time-to-first-event (hazard ratios 0.41-0.67). At 52 weeks, tirzepatide increased KCCQ-CSS 6.9 points (95%CI, 3.3, 10.6, P<0.001), 6MWD 18.3 meters (95%CI, 9.9, 26.7, P<0.001) and EQ-5D-5L 0.06 (95%CI, 0.03, 0.09, P<0.001). The tirzepatide group shifted to a more favorable PGIS (proportional odds ratio 1.99 (95%CI, 1.44, 2.76) and NYHA class (proportional odds ratio 2.26 (95%CI, 1.54, 3.31), both P<0.001 and required less heart failure medications (P=0.015). The broad spectrum of effects was reflected in benefits on the hierarchical composite (win ratio 1.63, 95%CI, 1.17, 2.28;P=0.004). Tirzepatide produced a comprehensive, meaningful improvement in heart failure across multiple complementary domains; enhanced health status, quality of life, functional capacity, exercise tolerance and well-being; and reduced symptoms and medication burden in patients with HFpEF and obesity.

Mining and influencing factors analysis of sacituzumab govitecan adverse drug event based on FAERS database

ABSTRACT Objective Utilizing the FAERS database, this study aims to analyze the ADE signals of sacituzumab govitecan to provide references for clinical safety. Methods By searching the US FAERS database, we applied Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods to analyze ADE reports for sacituzumab govitecan from Q2 2020 to Q4 2023, covering 15 quarters, and the priority System Organ Classes (SOCs) are also analyzed at the level of the influencing factors. Results The total number of reports with sacituzumab govitecan as the first suspicion was 2854. A total of 139 signals involving 26 SOCs were obtained. The most reported were general disorders and administration site conditions (2,307 cases, 25.66%), followed by gastrointestinal disorders (1,125 cases, 12.52%), and investigations (810 cases, 9.01%). Frequent ADEs included disease progression and neutropenia, while conditions like sepsis and COVID-19 were not listed in the prescribing information. The signal strength analysis highlighted conditions such as cholinergic syndrome and triple-negative breast cancer, with conditions like cholestasis and epilepsy not mentioned in the prescribing information. Furthermore, an analysis of influencing factors revealed differences in infections and infestations by gender and nationality (p < 0.05), and in gastrointestinal disorders and blood and lymphatic system disorders by gender, treatment duration, and nationality (p < 0.05). Conclusions Common ADEs and the involved organ systems generally correspond with the prescribing information. Clinicians should be vigilant regarding unlisted ADEs when using sacituzumab govitecan, and close monitoring of laboratory indicators ensure patient medication safety.

Identification of Mycoplasma Species in Cattle Associated with Bovine Respiratory Disease Mortality.

Approximately 30 distinct Mycoplasma species have been isolated from cattle, but only a few are pathogenic and can cause serious respiratory diseases. Consequently, this study aimed to identify Mycoplasma spp. infections in cattle with bovine respiratory disease (BRD), considering factors such as animal demographics, concurrent infections with other pathogens, post-mortem clinical findings and histological examinations, and seasonality. A total of 326 samples were collected from 322 cattle that had died from BRD in Northwestern Italy. A total of 54 animals (16.8%) tested positive for Mycoplasma spp., and Mycoplasma bovis (n = 22, 40.7%) and Mycoplasma dispar (n = 13, 24.1%) were the most frequently detected species among the examined cattle. Among positive cattle, those aged five months or younger were approximately five times more likely to be infected by Mycoplasma dispar than by Mycoplasma bovis compared to those older than five months (proportional incidence ratio: 5.1, 95% CI 1.2-21.2). The main bacterial pathogens identified in cattle exhibiting co-infection was Pasteurella multocida, whereas the main viral pathogens were BRSV and BoHV-1. Histopathological investigations predominantly revealed catarrhal bronchopneumonia or purulent catarrhal bronchopneumonia among the examined cattle. Finally, Mycoplasma hyopharyngis, a species isolated from the pharyngeal and nasal cavities of pigs so far, was detected for the first time in the pneumonic lung of a bovine infected with BRD. Further investigations are necessary to thoroughly characterize its host range and pathogenic potential.

Analysis of tirzepatide in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and sex-specific subgroups.

Tirzepatide, a novel GIP and GLP1 agonist, has been extensively examined in clinical trials. However, specific data on its adverse drug events (ADEs) remain limited. This study aims to comprehensively assess real-world ADEs associated with tirzepatide by mining data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. ADE reports from the FAERS database were retrieved for the second quarter of 2022 through the first quarter of 2024. Significant associations between ADEs and tirzepatide were evaluated using proportional disproportionality analyses, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinkage (MGPS). A total of 37,827 ADE reports associated with tirzepatide were identified, with 100 significantly disproportionate preferred terms (PTs) recognized by all four algorithms. The top five PTs with the highest reporting rates were incorrect dose administered, injection site pain, off-label use, nausea, and injection site hemorrhage. Additionally, unexpected signals such as starvation ketoacidosis were identified. The median time to onset for all ADEs was 23 days. Furthermore, sex-specific high-intensity signals were found, with males primarily experiencing gastrointestinal disorders and females experiencing general disorders and administration site conditions. This study provides valuable insights into the occurrence of ADEs following tirzepatide administration, potentially supporting clinical monitoring and risk identification efforts.

Cardiac adverse events associated with statins in myocardial infarction patients: a pharmacovigilance analysis of the FDA Adverse Event Reporting System.

Despite the advent of new pharmacotherapies, statins remain a cornerstone in the secondary prevention of myocardial infarction (MI). However, the cardiac adverse events (AEs) linked to statins are not well-documented. This pharmacovigilance study used data from the FDA Adverse Event Reporting System (FAERS) to investigate the association between statin use and cardiac AEs in MI patients. Reports from the FAERS database (2004-2023) identifying statins as the primary suspect in MI patients were analyzed. The study evaluated seven types of statins: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. Disproportionality analysis using four major indices, Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma-Poisson Shrinker (MGPS), was conducted to detect signals of statin-related cardiac AEs. Of the 20,346,289 reports reviewed, 150 identified statins as the primary suspect drug in MI patients. The most common cardiac AEs were recurrent MI (50 reports), acute MI (14 reports), followed by tachycardia (10), angina pectoris (8), coronary artery occlusion (6), cardiac failure (6), and arrhythmia (6). The analysis revealed no significant signals of statin-induced cardiac AEs. The findings confirm that statin use in MI patients does not significantly increase the risk of cardiac adverse effects, supporting their safety profile in this context.

Drug-induced noninfectious myocarditis: a disproportionality analysis of the FAERS database

ABSTRACT Background This investigation aims to identify and evaluate the most common and critical drugs associated with the risk of noninfectious myocarditis utilizing the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods Data pertaining to noninfectious myocarditis from 2004 Q1 to 2024 Q2 were extracted. Following data standardization, multiple signal quantification techniques, including Reporting Odds Ratio (ROR) and Proportional Reporting Ratio, were employed for analysis. Results The study identified a total of 10,763 adverse event reports associated with noninfectious myocarditis. Disproportionality analysis revealed that the top 5 drugs by ROR were phendimetrazine tartrate (ROR 104.64), trimethoprim + sulfamethoxazole (ROR 67.65), aldesleukin (ROR 52.67), mesalazine (ROR 49.73), and balsalazide disodium (ROR 45.26). Notably, among the 30 drugs with the strongest ROR signals, 8 drugs lacked myocarditis risk information in their package inserts. Conclusion Through comprehensive analysis of the FAERS database, our study identified drugs with a strong signal for myocarditis that are not currently indicated on their labels. The findings suggest that the potential risk of myocarditis associated with these medications is significant and warrants close monitoring in clinical practice.

Injury Characteristics Among Japanese International Athletes: Report on the Pre-competition Medical Check-Up Data of the Japanese Olympic Committee.

Introduction Injury trends among international athletes across sports remain underexplored in out-of-competition settings, particularly among Asians. The aim of this descriptive epidemiological study is to investigate the characteristics of injuries among Japanese international athletes during pre-competition medical check-ups from 2008 to 2019. Methods We analyzed the medical check-up data of candidates for international multi-sport events according to the International Olympic Committee consensus statement. At the medical check-up, athletes' injuries were categorized into two groups based on clinical assessment. "Injuries" refer to conditions that necessitate immediate treatment or further detailed examination. On the other hand, "complaints" encompass both such "injuries" and conditions for which treatment has already commenced, allowing athletes to continue participating in competitions or training while still requiring ongoing medical monitoring. The cohort was categorized into youth and adult groups, with adults defined as those aged ≥18 years. Results Overall, 10,854 athletes (4,966 females, 45.8%; 5,888 males, 54.2%; median age 22.0 {20.0-25.0} years, 56 sports) were enrolled; 2,333 "injuries" were registered (21.5 "injuries" per 100 athletes). The "injury" prevalence was 16.2% (95% CI, 0.16-0.17) and significantly associated with females (odds ratio {OR} 1.21; 95% CI, 1.09-1.34) and adult group (OR, 1.35; 95% CI, 1.08-1.69) based on binomial logistic regression analysis. Of a total of 10,027 "complaints" (92.4 "complaints" per 100 athletes), the "complaint" prevalence was 55.3% (95% CI, 0.54-0.56) and higher in females (OR, 1.44; 95% CI, 1.33-1.55) and adult group (OR, 1.50; 95% CI, 1.29-1.75). Stratified by sport, male soccer players had a higher "injury" prevalence than females (95% CI, 0.45-0.98), whereas females had a higher "injury" prevalence in hockey (1.70-7.29) and fencing (1.12-5.44). The "complaint" prevalence was higher in females for athletics, skiing, swimming, hockey, judo, badminton, fencing, water polo, weightlifting, and golf. There was no significant difference between the sexes in other sports. The knee ("injury," 20.1%; "complaint," 20.2%), lumbosacral (15.5%; 17.0%), ankle (13.0%; 15.4%), and shoulder (13.0%; 12.1%) were most commonly affected. The injury proportion ratio for the ankle was "injury"/"complaint" 0.82 (95% CI, 0.72-0.94), with the ankle "complaint" proportion being higher than "injury." When stratified by injury location and sex, knee "injury" was more common in males (206 in females vs. 262 in males; 95% CI, 0.59-0.88), whereas ankle "complaint" was more common in females (842 in females vs. 700 in males; 95% CI, 1.04-1.29). Conclusion This is the first cross-sectional report of injuries in Asian international athletes outside of competition periods. Injury prevalence was higher in females than in males and in adults than in youths. Sex differences in injury varied by site and severity. These findings may suggest the need for more tailored injury prevention and performance support strategies for international competitions.

Adverse events associated with azithromycin and clarithromycin in adults aged ≥65: a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database

ABSTRACT Background Azithromycin and clarithromycin are commonly used to treat community-acquired pneumonia in adults aged ≥ 65, such as mycoplasma pneumonia. This study aims to evaluate adverse events (AEs) associated with azithromycin and clarithromycin in this age group by analyzing the FDA Adverse Event Reporting System (FAERS), providing insights for clinical use and management of AEs in this population. Research design and methods We retrieved reports of AEs related to azithromycin and clarithromycin from the FAERS database. Disproportionality analysis was conducted using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Gamma Poisson Shrinkage (MGPS) to identify AEs associated with azithromycin and clarithromycin in adults aged ≥ 65. Results A total of 2,019 adverse event reports were retrieved for azithromycin, and 2,392 for clarithromycin. Off-label use (n = 349) and drug interactions (n = 487) were the most reported AEs in adults aged ≥ 65 for azithromycin and clarithromycin, respectively. Prolonged QT interval showed the strongest signal among AEs for azithromycin in this age group. Drug interaction-related medication errors had the strongest signal for clarithromycin. Seven signals not explicitly included in the azithromycin package insert were identified in adults aged ≥ 65. Fourteen signals not explicitly included in the clarithromycin package insert were identified. Conclusions Among adults aged ≥ 65, cardiac-related adverse events are more closely associated with azithromycin than with clarithromycin. Conversely, AEs related to drug interactions and psychiatric symptoms are more associated with clarithromycin. Additionally, clinicians should be vigilant regarding AEs not specified in the package inserts. The findings of this study may help optimize the selection of azithromycin and clarithromycin based on patient circumstances and assist clinicians in focusing on relevant AEs for early intervention.

A prospective cohort study comparing efficacy of 1 dose of quadrivalent human papillomavirus vaccine to 2 and 3 doses at an average follow up of 12 years postvaccination.

While recommending a human papillomavirus (HPV) single-dose vaccination schedule in 2022, the World Health Organization highlighted the need for long-term follow-up studies to monitor waning of protection. We report on vaccine efficacy against HPV infections in 1-, 2-, and 3-dose schedules and protection against cervical precancers at a median follow-up of 12 years postvaccination. This randomized multicenter study in India was originally designed to vaccinate unmarried girls aged 10-18 years with either 2 or 3 doses of quadrivalent HPV vaccine. A ministerial decree to halt vaccination in trials resulted in the creation of cohorts receiving different doses, including just a single dose. Cohorts were assessed for incident and persistent infections by genotyping cervical samples collected yearly for 4 consecutive years after participants were married. Cervical screening with an HPV test was initiated at age 25 years for married participants. Age- and site-matched unvaccinated married women were recruited to be compared with vaccinated cohorts. Vaccine efficacy was assessed using proportional incidence ratios. The number of participants in the 1-, 2- (at 0 and 6 months), and 3-dose cohorts was 4949, 4980, and 4348, respectively. Of the recipients, 71%-82% in the different cohorts were eligible to provide samples for genotyping. Vaccine efficacy against persistent HPV 16 and 18 infection was 92.0% (95% confidence interval [CI] = 87.0% to 95.0%) in 3022 recipients of the single dose; and comparable with that observed in the 2-dose arm (94.8%, 95% CI = 90.0% to 97.3%) and the 3-dose arm (95.3%, 95% CI = 90.9% to 97.5%). No high-grade precancer associated with HPV 16 and 18 was detected among vaccinated participants compared with 8 precancers detected among the unvaccinated women. This observational cohort study has established that a single dose of HPV vaccine provides high protective efficacy against persistent HPV 16 and 18 infections and associated neoplasia 15 years postvaccination.

Comprehensive evaluation of leuprorelin-associated adverse events: insights from FDA adverse event reporting system

ABSTRACT Background Leuprorelin, a gonadotropin-releasing hormone agonist, is widely used to treat hormone-related disorders. This study aims to explore and analyze the safety profile of leuprorelin by examining adverse event reports from the FDA Adverse Event Reporting System (FAERS) database. Methods This study conducted a retrospective pharmacovigilance analysis using FAERS data from Q1 2004 to Q1 2024. Adverse drug events (ADEs) related to leuprorelin were identified and categorized by system organ class and specific adverse events. Statistical methods such as Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) were used to detect safety signals. Results A total of 63,928 ADE reports implicated leuprorelin, with 500 preferred terms and 25 system organ classes showing significant disproportionality. Notable rare ADEs identified were bulbospinal muscular atrophy congenital (n = 26; ROR 1282.72, PRR 1282.52, IC 7.91, EBGM 241.28), follicular cystitis (n = 3; ROR 126.84, PRR 126.84, IC 6.48, EBGM 89.09), and anaplastic meningioma (n = 3; ROR 46.73, PRR 46.73, IC 5.34, EBGM 40.5). Conclusion Most findings were expected, but new signals like follicular cystitis, previously unreported, emerged. Further studies are essential to validate these findings, crucial for clinical monitoring and risk identification of leuprorelin.

Analysis of thermoacoustic instability and emission behaviors of lean premixed biogas/ammonia flame

Ammonia and biogas are promising renewable fuels that can reduce carbon emissions. This paper studies thermoacoustic instability and emission behaviors of biogas/ammonia co-firing swirl flame. The effects of CO2 proportion in biogas (), ammonia proportion () and equivalence ratio (Φ) on combustion characteristics were considered. A chemical reactor network (CRN) was established to advance comprehension regarding NO emission. The results show that high Φ and are more conducive to simultaneously suppressing thermoacoustic instability and NO emissions. Lower flame appears to have intense thermoacoustic instability when Φ near 0.90, and the instability intensity is significantly weakened when exceeds 20%. The CO2 in the mixture inhibits NO formation but promotes CO formation. The CRN results show that CO2 in biogas reduces NO emissions by inhibiting the HNO pathway and promoting the NHi pathway. This study furnishes a foundation for advancing clean and efficient low-carbon combustion systems.

Population trends and demographic disparities in sexual identity in Stockholm County, 2010 to 2021

Abstract Background Sexual identity, linked to experiences of disadvantage and discrimination, is crucial in equality monitoring. Sweden’s gender-neutral marriage laws, introduced in 2009, provide a unique context. This study examines the population trends and demographic disparities in sexual identity over time. Methods We analyzed three population surveys (2010, 2014, 2021) from the Stockholm Public Health Cohort, including around 50,000 individuals per survey. Sexual identity was assessed via self-administered questionnaires. Demographic data were sourced from Swedish national registers. Weighted multivariate Poisson regression with robust variance estimators was used to identify demographic disparities in sexual identity. Results were presented as proportion ratio (PR) with 95% confidence interval (CI). Results Overall, 29,607 (2010), 20,249 (2014), and 22,558 (2021) individuals reported sexual identity. Heterosexual identity decreased from 95.7% (95% CI 95.4-96.0%) in 2010 to 89.0% (88.5-89.4%) in 2021, while bisexual identity increased from 1.4% (1.2-1.6%) in 2010 to 2.0% (1.8-2.3%) in 2014, and further up to 2.7% (2.4-2.9%) in 2021. Homosexual identity increased slightly from 1.5% (1.4-1.7%) in 2010 to 1.8% (1.6-2.0%) in 2021. Multivariate analyses showed that female, older age, and lower education were inversely associated, while never-married status and living alone were positively associated, with homosexual identity. In contrast, female, younger age, lower income (100 SEK/year) ( &amp;lt; =2,500 vs &amp;gt; 4,500: 2010: PR 3.32 [95% CI 1.92-5.75]; 2014: 1.83 [1.28-2.60]; 2021: 1.51 [1.14-2.01]), and never-married status (never vs currently married: 2010: 2.03 [1.47-2.80]; 2014: 1.92 [1.39-2.65]; 2021: 1.50 [1.15-1.95]) were positively associated with bisexual identity. Conclusions Heterosexual identity decreased while homosexual/bisexual identities increased in Stockholm County during 2010-2021. Socioeconomic disparities persist in sexual minorities and vary by sexual identity. Key messages • Marked socioeconomic disparities persist in sexual minorities and vary by sexual identity in Stockholm County, although income and marital status disparities in bisexual group seem narrowing. • Future studies are warranted to investigate the social dynamics that continue to produce sexual minority disadvantages.

Individual fluidity of sexual identity in Stockholm County, 2010 to 2021

Abstract Background Sexual fluidity is key to understanding the size of sexual minority populations and analyzing the socioeconomic disparities these populations face. This study explores the stability and changes in sexual identity over time, and identifies key demographic factors that predict shifts in sexual identity. Methods We analyzed longitudinal data from the Stockholm Public Health Cohort, following 36,398 participants from 2010 to 2021. Sexual identity was measured using a self-administered questionnaire in 2010, 2014, and 2021. Demographic data from 2010 were collected from the Swedish national registers. Multivariate Poisson regression with robust variance estimators was used to identify demographic factors that predicted identity changes. Results were presented as proportion or risk ratio (RR) with 95% confidence interval (CI). Results Overall, 12.1% (95% CI 11.8%-12.5%) changed sexual identity at least once in 2010-2021, including 10.4% (10.0%-10.7%) among those initially identifying as heterosexual in 2010, 41.3% (37.1%-45.6%) as homosexual, 59.6% (55.0%-64.0%) as bisexual, and 65.0% (59.4%-70.3%) as uncertain. Multivariate analyses showed that sexual minorities (homosexual: RR 5.00, 95% CI 4.45-5.61; bisexual: 6.68, 6.04-7.38; uncertain: 3.88, 3.30-4.55), females (1.28, 1.21-1.35), younger (18-29 years: 1.49, 1.30-1.70) and older ( &amp;gt; =60 years: 2.07, 1.92-2.22) ages, born outside Sweden (Europe: 1.21, 1.11-1.32; Outside Europe: 2.90, 2.62-3.21), and lower education ( &amp;lt; =9 years: 2.14, 1.98-2.31; 10-12 years: 1.43, 1.34-1.53) and income (100 SEK/year) ( &amp;lt; =2,500: 1.83, 1.66-2.02; (2,500, 3,500]: 1.32, 1.19-1.46) independently predicted a higher probability of identity changes. Conclusions This study provides the first insights into sexual identity fluidity in a large general population sample in Sweden, highlighting its fluid nature. Future research is needed to unravel the intricate mechanisms underlying the demographic disparities in sexual identity fluidity. Key messages • This study provides the first insights into sexual identity fluidity in Sweden, highlighting its fluid nature. • Future research is needed to unravel the intricate mechanisms underlying the demographic disparities in sexual identity fluidity.

Pathology-Based Animal Cancer Registry of Abruzzo and Molise Regions (Central Italy): A Ten-Year Retrospective Study (2014-2023).

Pets have a crucial role in cancer research. Specifically, dogs and cats share the same environment as their owners and thus may serve as sentinels of naturally occurring tumors that are linked to the exposure to environmental hazards. Quantitative comparison of tumor types may reveal unusual cancer frequencies, providing directions for research and generation of hypotheses of cancer causation in a specific area and identification of risk factors. The aim of this study was to describe the data collected by the pathology-based animal cancer registry, managed by Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise (IZSAM), during 10 years of activity (2014-2023) and to assess its potential epidemiological relevance. Frequencies of tumor topography and morphology in dogs and cats were described, analyzed and compared. Proportional morbidity ratios (PMRs) were calculated, taking into consideration some potential risk factors such as species, breed, sex, diet and living environment. The database comprises 5311 tumors (n = 4719 in dogs and n = 592 in cats), with a higher prevalence in females (67.3% in dogs and 61.2% in cats). The mean age at the first diagnosis of tumors was similar between sexes and slightly lower in dogs compared to cats. PMRs highlighted certain risk and "protective" factors for the development of tumors in specific topography. The risk of developing tumors of the blood and hematopoietic system (PMR = 0.44; 95% CI: 0.21-0.94), skin and subcutaneous tissues (PMR = 0.70; 95% CI: 0.61-0.80), oral cavity and pharynx (PMR = 0.60; 95% CI: 0.24-0.89), urinary organs (PMR = 0.33; 95% CI: 0.11-0.99) and bones, joints and cartilage (PMR = 0.72; 95% CI: 0.22-0.98) was lower in non-neutered male dogs than in neutered male dogs. Non-spayed female dogs had a greater risk of developing tumors of the mammary gland (PMR = 1.75; 95% CI: 1.57-1.96), female sexual organs (PMR = 2.12; 95% CI: 1.01-4.36) and respiratory system (PMR = 2.25; 95% CI: 1.55-6.74) but less risk for cutaneous and subcutaneous tissue tumors (PMR = 0.44; 95% CI: 0.38-0.51) and blood/hematopoietic system tumors (PMR = 0.47; 95% CI: 0.26-0.85) compared to spayed female dogs. Compared with mixed breed, purebred dogs had a significantly greater risk of developing mammary gland tumors (PMR = 1.36; 95% CI: 1.20-1.54) and lower risk for respiratory (PMR = 0.15; 95% CI: 0.07-0.32), gastrointestinal (PMR = 0.63; 95% CI: 0.34-0.94) and oral (PMR = 0.59; 95% CI: 0.36-0.96) neoplasia. Non-neutered male cats had a lower risk of developing skin and subcutaneous tumors (PMR = 0.68; 95% CI: 0.50-0.92) compared with neutered cats. The risk of developing skin and subcutaneous tissues tumors was higher for dogs and cats that lived mostly outdoor (PMR dogs = 1.21; 95% CI: 1.10-1.33; PMR cats = 1.18; 95% CI: 1.08-1.47), while dogs that live mainly indoor had a greater risk to develop mammary gland tumors (PMR = 0.78; 95% CI: 0.68-0.89). Results described herein highlight the fundamental role of animal cancer registration initiatives. These efforts would contribute to the possibility of conducting multicentric collaborative studies to deepen the knowledge of the epidemiology of tumors in dogs and cats from a comparative perspective, thus fulfilling the One Health approach.

Safety assessment of sapropterin dihydrochloride: real-world adverse event analysis based on the FDA adverse event reporting system (FAERS).

Sapropterin dihydrochloride is the first drug for the therapy of phenylketonuria, which is a rare disease that occurs one of 10,000-15,000 newborns. As a result, detailed and comprehensive reports on the safety of sapropterin in large, real-world populations are required. The purpose of this study is to undertake a complete analysis of sapropterin's adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS) database. We retrieved reports of adverse events with sapropterin as the principal suspect from FAERS between the first quarter of 2008 and the first quarter of 2024. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) were utilized to detect AE signals. The study collected 4,953 suspected AE cases from the FAERS database, with sapropterin as the major suspect. A total of 130 positive signals were obtained utilizing the ROR, PRP, and BCPNN. The FAERS database revealed that common clinical AEs of sapropterin included vomiting, upper respiratory infection, rhinorrhea, and a reduction in amino acid concentrations. Furthermore, we detected probable unexpected adverse events (AEs) using disproportionality analysis, including gastroesophageal reflux disease, flatulence, influenza, ear infection, viral infection, pharyngitis streptococcal, spontaneous abortion, and nephrolithiasis. By analyzing huge amounts of real-world data from the FAERS database, we found potential novel AEs of sapropterin using disproportionate analysis. It is advantageous for healthcare professionals and pharmacists to focus on efficiently managing sapropterin's high-risk adverse events, improving drug levels in clinical settings, and ensuring patient medication safety.

Adverse drug reaction signals mining comparison of amiodarone and dronedarone: a pharmacovigilance study based on FAERS.

Amiodarone and dronedarone are both class III antiarrhythmic medications used to treat arrhythmias. The objective of this study was to enhance the current understanding of adverse drug reaction (ADR) associated with amiodarone and dronedarone by employing data mining methods on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), and providing a reference for safe and reasonable clinical use. The ADR records were selected by searching the FAERS database from 2011 Q3 to 2023 Q3. The disproportionality analysis algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were used to detect signals of amiodarone-related and dronedarone-related ADRs. The ADR profiles of amiodarone and dronedarone categorized by organ toxicity were compared through the Z-test and the Fisher exact test. 9,295 reports specifically mentioned the use of amiodarone and 2,485 reports mentioned the use of dronedarone among 9,972,109 reports, with the majority of ADRs occurring in males over 60years old. The United States was responsible for the highest proportion of reported ADRs. Significant system organ classes (SOC) for both included Cardiac disorders, Respiratory, thoracic and mediastinal disorders, and Investigations, etc. At the preferred terms (PTs) level, the more frequent ADR signals for amiodarone were drug interaction (n = 856), hyperthyroidism (n = 758), and dyspnoea (n = 607), while dronedarone were atrial fibrillation (n = 371), dyspnoea (n = 204), and blood creatinine increased (n = 123). Notably, unexpected ADRs, including electrocardiogram T wave alternans (n = 16; EBGM05 = 231.27), accessory cardiac pathway (n = 11; EBGM05 = 140), thyroiditis (n = 178; EBGM05 = 125.91) for amiodarone, and cardiac ablation (n = 11; EBGM05 = 31.86), cardioversion (n = 7; EBGM05 = 22.69), and dysphagia (n = 47; EBGM05 = 3.6) for dronedarone, were uncovered in the instructions. The analysis also revealed significant differences in the ADR profiles of amiodarone and dronedarone, with dronedarone showing higher proportions of cardiac toxicity but lower thyroid toxicity compared to amiodarone. These findings underscore the significance of vigilantly monitoring and comprehending the potential risks linked to the use of amiodarone and dronedarone. New ADRs discovered and clear ADR profiles of amiodarone and dronedarone enhance a thorough understanding of these drugs, which is essential for clinicians to ensure safe use of amiodarone and dronedarone.

A Retrospective Observational Study of Adverse Drug Reactions (ADR) Reported to ADR Monitoring Centre from 2010 to 2020.

Adverse Drug Reactions (ADR) are one of the essential causes of hospital admissions and pose a significant clinical and economic burden on the healthcare system. The Adverse Drug Reaction Monitoring Centre (AMC) in JIPMER functioning under the Pharmacovigilance Programme of India (PvPI) plays a vital role in ensuring medication safety by routinely detecting and monitoring ADRs. Hence, this study aimed to assess the characteristics of ADR reported from 2010 to 2020 in AMC JIPMER and to detect signals, if any. To study the characteristics of Adverse Drug Reactions (ADR) reported to a regional ADR monitoring center from 2010 to 2020 and to detect signals of disproportionate reporting (SDRs) if any from the reported ADRs. A total of 6007 ADR reports with a single suspect drug were included for analysis from 2010 to 2020. The characteristics of these reports, including patient's age and gender, Number and percentage of ADRs, the causality of ADR using WHO UMC (World Health Organization-Uppsala Monitoring Scale), the seriousness of the ADR, and outcome were collected from the ADR reports. MedDRA (Medical Dictionary for Regulatory Activities) Preferred Terms (PT) were used to classify adverse drug reactions. Causality analysis using the Naranjo Algorithm and Preventability using Modified Schumock and Thornton criteria were performed for the ADRs. The number and percentage of severe ADRs were analyzed. The System Organ class of all the ADRs was enumerated. ADRs not mentioned in the US FDA (United States Food and Drug Administration) product label (unlabelled reactions) were documented. Unlabeled reactions with ≥3 ADR reports were included for signal detection by disproportionality analysis. Antineoplastic drugs, followed by antimicrobials, anticonvulsants, Anti snake venom, and NSAID were the most common drugs implicated in ADRs. Skin and subcutaneous tissue disorders were the most common System Organ Class (SOC) involved in the ADRs. Among the 6007 reports, 19.2% were serious ADRs. Most of the ADR reports were of possible causality followed by probable and certain as per WHO UMC and Naranjo causality scales. Only ten ADRs were preventable and one reaction (Tamoxifen-induced neuropathy) was eligible for signal detection. Disproportionality analysis using a 2x2 contingency table showed insignificant signal detection using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). Analysis of ADRs from an ADR Monitoring center functioning in a tertiary care hospital shows antineoplastic drugs to be the most common drugs associated with adverse drug reactions, with rash being the most common adverse effect. The majority of the ADRs were not preventable. No Signals of Disproportionate Reporting (SDR) were detected in our study.