Proportional Ratio Research Articles

Assessing the safety of bedaquiline: insight from adverse event reporting system analysis

BackgroundThe development and marketing of Bedaquiline (BDQ) represent significant advancements in treating tuberculosis, particularly multidrug-resistant forms. However, comprehensive research into BDQ’s real-world safety remains limited.PurposeWe obtained BDQ related adverse event (AE) information from the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) to assess its safety and inform drug usage.MethodsThe AE data for BDQ from 2012 Q4 to 2023 Q3 was collected and standardized. Disproportionality analysis, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN) was used to quantify signals of BDQ-related AEs. Logistic regression was used to analyze the individual data of hepatotoxicity and drug-induced liver injury, and multiple linear regression models were established. Additionally, network pharmacology was employed to identify the potential biological mechanisms of BDQ-induced liver injury.ResultsWe identified 2017 case reports directly related to BDQ. Our analysis identified 341 Preferred Terms (PTs) characterizing these AEs across 27 System Organ Classes (SOC). An important discovery was the identification of AEs associated with ear and labyrinth disorders, which had not been documented in the drug’s official leaflet before. Subgroup analysis revealed a negative correlation between BDQ-related liver injury and females (OR: 0.4, 95%CI: 0.3–0.6). In addition, via network pharmacology approach, a total of 76 potential targets for BDQ related liver injury were predicted, and 11 core target genes were selected based on the characterization of protein-protein interactions. The pathway linked to BDQ-induced liver injury was identified, and it was determined that the PI3K-Akt signaling pathway contained the highest number of associated genes.ConclusionThe analysis of the FAERS database revealed adverse events linked to BDQ, prompting the use of a network pharmacology approach to study the potential molecular mechanism of BDQ-induced liver injury. These findings emphasized the significance of drug safety and offered understanding into the mechanisms behind BDQ-induced liver injury. BDQ demonstrated distinct advantages, including reduced incidence of certain adverse events compared to traditional treatments such as injectable agents and second-line drugs. However, it is important to acknowledge the limitations of this analysis, including potential underreporting and confounding factors. This study provides valuable insights into the safety of BDQ and its role in the management of MDR-TB, emphasizing the need for continued surveillance and monitoring to ensure its safe and effective use.

Biological feasibility of discharge a local WTTP sludge to sewer network and centralized WWTP; a case study: Tehran, Iran

Over the recent years, ever-increasing population growth and higher wastewater production has been a challenge for decentralized wastewater treatment plants (WWTPs). In addition, sludge treatment due to high cost for equipment and place make authorities to find a sustainable approach in both of economical and technical perspectives. One of the proposed solutions is transferring the sludge produced from decentralized WWTP to centralized WWTP. However, the appropriate proportional ratio of raw sludge to raw sewage is a challenge, otherwise, it make anaerobic conditions and sewage rotting along the sewer network based on permissible limit of dihydrogen sulfide (H2S) gas (5 ppm). In the present study, seven reactors with different ratios of sludge to raw sewage (0, 15, 20, 25, 50, 75, 100) were used to stimulate the feasibility of transferring Shahrake Gharb WWTP sludge along the wastewater transfer pipe to the centralized sewage treatment south Tehran WWTP plant in Tehran, Iran. The septic situation and H2S emission of different reactors within 7 h (Time to reach the compound in the south treatment plant) was analyzed by gas meter. The results indicated that the optimum ratio of sludge to raw sewage was 15% without H2S production during 7 h. In addition, due to the high volume of sludge produced by the Shahrake Gharb WWTP, the optimal ratio of lime to total solids (TS) in sludge (gr/gr) (0.6) increased the sludge loading rate from 15 to 30% without any H2S emission during the stimulation study period. Therefore, the lime stabilization and transfer of sludge from a decentralized WWTP to a centralized WWTP is a feasible way to manage the sludge and enhance the treatment capacity in local WWTP.

Muscle mitochondrial bioenergetic capacities are associated with multimorbidity burden in older adults: the Study of Muscle, Mobility and Aging (SOMMA).

The geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity. The Study of Muscle, Mobility and Aging (SOMMA) assessed ex vivo muscle mitochondrial energetics in 764 older adults (mean age =76.4, 56.5% women, 85.9% non-Hispanic white) by high-resolution respirometry of permeabilized muscle fibers. We estimated the proportional odds ratio (POR [95%CI]) for the likelihood of greater multimorbidity (four levels: 0 conditions, N=332; 1 condition, N=299; 2 conditions, N=98; or 3+ conditions, N=35) from an index of 11 conditions, per SD decrement in muscle mitochondrial energetic parameters. Distribution of conditions allowed for testing the associations of maximal muscle energetics with some individual conditions. Lower oxidative phosphorylation supported by fatty acids and/or complex-I and -II linked carbohydrates (e.g., Max OXPHOSCI+CII) was associated with a greater multimorbidity index score (POR=1.32[1.13,1.54]) and separately with diabetes mellitus (OR=1.62[1.26,2.09]), depressive symptoms (OR=1.45[1.04,2.00]) and possibly chronic kidney disease (OR=1.57[0.98,2.52]) but not significantly with other conditions (e.g., cardiac arrhythmia, chronic obstructive pulmonary disease). Lower muscle mitochondrial bioenergetic capacities was associated with a worse composite multimorbidity index score. Our results suggest that decrements in muscle mitochondrial energetics may contribute to a greater global burden of disease and is more strongly related to some conditions than others.

Discovering clinical drug-drug interactions with known pharmacokinetics mechanisms using spontaneous reporting systems and electronic health records

ObjectiveAlthough the mechanisms behind pharmacokinetic (PK) drug-drug interactions (DDIs) are well-documented, bridging the gap between this knowledge and clinical evidence of DDIs, especially for serious adverse drug reactions (SADRs), remains challenging. While leveraging the FDA Adverse Event Reporting System (FAERS) database along with disproportionality analysis tends to detect a vast number of DDI signals, this abundance complicates further investigation, such as validation through clinical trials. Our study proposed a framework to efficiently prioritize these signals and assessed their reliability using multi-source Electronic Health Records (EHR) to identify top candidates for further investigation. MethodsWe analyzed FAERS data spanning from January 2004 to March 2023, employing four established disproportionality methods: Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagating Neural Network (BCPNN). Building upon these models, we developed four ranking models to prioritize DDI-SADR signals and cross-referenced signals with DrugBank. To validate the top-ranked signals, we employed longitudinal EHRs from Vanderbilt University Medical Center and the All of Us research program. The performance of each model was assessed by counting how many of the top-ranked signals were confirmed by EHRs and calculating the average ranking of these confirmed signals. ResultsOut of 189 DDI-SADR signals identified by all four disproportionality methods, only two were documented in the DrugBank database. By prioritizing the top 20 signals as determined by each of the four disproportionality methods and our four ranking models, 58 unique DDI-SADR signals were selected for EHR validations. Of these, five signals were confirmed. The ranking model, which integrated the MGPS and BCPNN, demonstrated superior performance by assigning the highest priority to those five EHR-confirmed signals. ConclusionThe fusion of disproportionality analysis with ranking models, validated through multi-source EHRs, presents a groundbreaking approach to pharmacovigilance. Our study's confirmation of five significant DDI-SADRs, previously unrecorded in the DrugBank database, highlights the essential role of advanced data analysis techniques in identifying ADRs.

Intimate Partner Violence and Human Trafficking Screening and Services in Primary Care Across Underserved Communities in the United States-Initial Examination of Trends, 2020-2021.

The Health Resources and Services Administration (HRSA) began collecting data on intimate partner violence (IPV) and human trafficking (HT) in the 2020 Uniform Data System (UDS). We examined patients affected by IPV and HT served by HRSA-funded health centers in medically underserved US communities during the COVID-19 pandemic. We established a baseline and measured trends in patient care by analyzing data from the 2020 (N = 28 590 897) and 2021 (N = 30 193 278) UDS. We conducted longitudinal ordinal logistic regression analyses to assess the association of care trends and organization-level and patient characteristics using proportional odds ratios (PORs) and 95% CIs. The number of clinical visits for patients affected by IPV and HT decreased by 29.4% and 88.3%, respectively, from 2020 to 2021. Health centers serving a higher (vs lower) percentage of pediatric patients were more likely to continuously serve patients affected by IPV (POR = 2.58; 95% CI, 1.01-6.61) and HT (POR = 6.14; 95% CI, 2.06-18.29). Health centers serving (vs not serving) patients affected by IPV were associated with a higher percentage of patients who had limited English proficiency (POR = 1.77; 95% CI, 1.02-3.05) and Medicaid beneficiaries (POR = 2.88; 95% CI, 1.48-5.62), whereas health centers serving (vs not serving) patients affected by HT were associated with a higher percentage of female patients of reproductive age (POR = 15.89; 95% CI, 1.61-157.38) and urban settings (POR = 1.74; 95% CI, 1.26-2.37). The number of clinical visits for patients affected by IPV and HT during the COVID-19 pandemic declined. Delayed care will pose challenges for future health care needs of these populations.

Safety and Effectiveness of Vedolizumab in Elderly Patients with Inflammatory Bowel Disease: A Systematic Review & Meta-Analysis.

There is limited data on Vedolizumab utilization in elderly patients. Our study aims to assess the effectiveness and safety of Vedolizumab in this subset population. Databases including Cochrane Central, Embase, Medline (via Ovid), Scopus, and Web of Science were searched in August 2022 to identify studies that assessed Vedolizumab therapy in elderly patients. Pooled proportion and risk ratios (RR) were calculated. Total 11 studies with 3546 IBD patients (1314 elderly and 2232 young) were included in the final analysis. Pooled rate of overall and serious infections in the elderly cohort was 8.45% (95% CI=6.27-11.29; I 2 23%) and 2.59% (95% CI=0.78-8.29; I 2 76%), respectively. However, there was no difference in overall infection rates between elderly and young patients. Pooled rate of endoscopic, clinical, and steroid-free remission for elderly IBD patients was 38.45% (95% CI=20.74-59.56; I 2 93%), 37.95% (95% CI=33.08-43.06; I 2 13%), and 38.8% (95% CI=31.6-46.4; I 2 77%), respectively. Elderly patients had lower steroid-free remission rates [RR 0.85, 95% CI=0.74-0.99; I 2 0%, P =0.03]; however, there was no difference in rates of clinical (RR 0.86, 95% CI=0.72-1.03; I 2 0%, P =0.10) or endoscopic remission (RR 1.06, 95% CI=0.83-1.35; I 2 0%, P =0.63) compared with younger patients. Pooled rate of IBD-related surgery and IBD-related hospitalizations was 9.76% (95% CI=5.81-15.92; I 2 78%) and 10.54% (95% CI=8.37-13.2; I 2 0%), respectively for the elderly cohort. There was no statistical difference in IBD-related surgeries between elderly and young IBD patients, RR 1.20 (95% CI=0.79-1.84; I 2 16%), P =0.4. Vedolizumab is equally safe and effective for clinical and endoscopic remission in elderly and younger populations.

Telepharmacy intervention: Can it impact medication adherence among patients with chronic disease?

Background: Medication adherence among patients with chronic diseases remains challenging for healthcare professionals. The large number and types of drugs that must be taken in the long term and the lack of knowledge related to drugs and diseases are factors that affect patient compliance. Telepharmacy is expected to improve patient medication adherence by providing easy access to consult with pharmacists. Objective: To assess the effect of telepharmacy on chronic patient medication adherence. Methods: This study had a cross-sectional study design, and the study population was Lifepack application users. The data was collected through an online questionnaire distributed through the Lifepack platform. The adherence was evaluated using the Morisky Medication Adherence Scale, and the association of telepharmacy and patient medication adherence was examined using the chi-square independence test with significance at p < 0.05. Results: In a study comprising of 94 respondents, a proportional ratio of respondents who used and did not use telepharmacy services was observed (45.75% and  54.25%, respectively). Analysis using the chi-square statistic (χ²) demonstrated a significant association between telepharmacy and patient adherence (χ² = 64.745, df = 1, p < 0.001). Furthermore, the odds ratio (OR) revealed a substantial difference in adherence, with an OR of 122.67 (95% CI [27.58, 545.66]). Conclusion: Telepharmacy has a significant impact on medication adherence in chronic patients.

Identification of asymmetries between longitudinal parameters and anthropometric proportionality ratios in children aged between 7 - 10 years

(The present study pursued the investigation of anthropometric asymmetries regarding the length of the upper and lower limbs and the indices of body proportionality and had the following ob-jectives: identifying the differences between the female and male groups, in the 4 age categories (7, 8, 9 and 10 years old), regarding anthropometric parameters and proportionality indicators; also tried to identify the differences in anthropometric parameters and proportionality indicators between the 4 age categories (7 - 10 years old) for each gender (female, respectively male). The study included 727 subjects with the age between 7-10 years, of which 383 (52.7%) female and 344 (47.3%) male, the subjects being divided into four groups according to age (7, 8, 9 and 10 years old groups). The measurements aimed at the following longitudinal anthropometric parameters and the calculation of proportionality ratios: height (cm); the length of the right upper limb (cm – LUL Right); the length of the left upper limb (cm – LUL Left); the length of the right lower limb (cm - LLL Right); the length of the left lower limb (cm - LLL Left); ratio of LUL Right X 100 / LLL Right; ratio of LUL Left x 100 / LLL Left; ratio of LUL Right x 100 / height; ratio of LUL Left x 100 / height; ratio of LLL Right x 100 / height; ratio of LLL_Left x 100/ height. Analyzing ccompara-tively the results recorded between the upper and lower right and left segments, we find asym-metry in all samples according to age and gender. The differences between the groups of girls and boys, in all age categories, were statistically significant. The ANOVA analysis reflects statis-tically significant differences between the 4 age groups (7 - 10 years) in all anthropometric evalu-ations. The largest asymmetries between the right and left upper limb were recorded in the age category of 7 years old group; respectively, the largest asymmetries between the lower limbs were recorded in the 10 year old groups depending on gender.

Signal mining and risk analysis of Alprazolam adverse events based on the FAERS database

This study aims to evaluate the safety of Alprazolam by analyzing the FAERS database, provide data analysis for monitoring adverse drug reactions. This research encompasses adverse event (AE) reports related to Alprazolam from the first quarter of 2004 to the second quarter of 2023. Four signal mining and analysis methods were utilized, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). Further exploration was conducted regarding patient characteristics and types of AEs. A total of 23,575 AE reports in which Alprazolam was the primary suspect drug were collected, identifying 347 Preferred Term (PT) signals and 27 System Organ Classes (SOCs). The number of AE reports increased annually, especially in 2015, 2018, 2019, and 2020. The main affected groups were females and the age range of 18 to 45. Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders were the most common the organ system in which the AEs occurred. There is a certain risk of drug abuse and suicide with Alprazolam. Most notably, several AEs not recorded in the Alprazolam leaflet appeared among the top 30 PTs in signal strength, including but not limited to Benzodiazepine drug level abnormal, Acquired amegakaryocytic thrombocytopenia, Cutaneous T-cell dyscrasia, and Coronary No-reflow Phenomenon. For the first time, AEs related to the cardiovascular system and platelet function were unveiled. The severe AE reports that resulted in "hospitalization" and "death" accounted for 30.96% and 21.86%. This study highlights the risks of suicide and misuse of Alprazolam. Other potential severe or fatal AEs, such as those related to the cardiovascular system, platelet function, and others, require further research to determine their precise mechanisms and risk factors.

Disaggregating Asian-American Mortality in Drug-Related Overdoses and Behavioral Disorders: A Cross-Sectional Study.

Asian Americans have been historically underrepresented in the national drug overdose discourse due to their lower substance use and overdose rates compared to other racial/ethnic groups. However, aggregated analyses fail to capture the vast diversity among Asian-American subgroups, obscuring critical disparities. We conducted a cross-sectional study between 2018 and 2021 examining Asian-American individuals within the CDC WONDER database with drug overdoses as the underlying cause of death (n = 3195; ICD-10 codes X40-X44, X60-X64, X85, and Y10-Y14) or psychoactive substance-related mental and behavioral disorders as one of multiple causes of death (n = 15,513; ICD-10 codes F10-F19). Proportional mortality ratios were calculated, comparing disaggregated Asian-American subgroups to the reference group (Asian Americans as a single aggregate group). Z-tests identified significant differences between subgroups. Compared to the reference group (0.99%), drug overdose deaths were less prevalent among Japanese (0.46%; p < 0.001), Chinese (0.47%; p < 0.001), and Filipino (0.82%; p < 0.001) subgroups, contrasting with a higher prevalence among Asian Indian (1.20%; p < 0.001), Vietnamese (1.35%; p < 0.001), Korean (1.36%; p < 0.001), and other Asian (1.79%; p < 0.001) subgroups. Similarly, compared to the reference group (4.80%), deaths from mental and behavioral disorders were less prevalent among Chinese (3.18%; p < 0.001), Filipino (4.52%; p < 0.001), and Asian Indian (4.56%; p < 0.001) subgroups, while more prevalent among Korean (5.60%; p < 0.001), Vietnamese (5.64%; p < 0.001), Japanese (5.81%; p < 0.001), and other Asian (6.14%; p < 0.001) subgroups. Disaggregated data also revealed substantial geographical variations in these deaths obscured by aggregated analyses. Our findings revealed pronounced intra-racial disparities, underscoring the importance of data disaggregation to inform targeted clinical and public health interventions.

Abstract 2134: Disaggregating breast cancer mortality trends in Asian American women from 2005-2020

Abstract Background: Breast cancer (BC) is the second leading cause of death among women and has disproportionately higher rates of mortality in certain racial groups, including Asian Americans (AA). While differences in BC mortality between AA and other racial groups have been identified, few studies have disaggregated nationwide AA mortality data. Methods: Using National Vital Statistics System mortality data, BC-related deaths were analyzed among AA groups (Asian Indian, Chinese, Filipina, Japanese, Korean, Vietnamese), Native Hawiian and Pacific Islanders (NHPIs), and non-Hispanic Whites (NHWs) from 2005-2020. We calculated cancer proportional mortality ratios (PMRs), age-adjusted mortality rates (AAMRs), standard mortality ratios, and used JoinPoint regression for average annual percentage change (AAPC). Results: Among 13677 AA, 522 NHPI, 501282 NHW descendants, 14.3% cancer deaths were due to BC. PMRs increased for all racial groups except Filipina. AAMRs significantly decreased in NHWs (AAPC -1.61; CI -1.70 to -1.48) while significantly increasing for aggregate AAs (AAPC 0.45; CI 0.08 to 0.94). Among AAs, Filipinas had the highest AAMR. AAMRs significantly increased for Asian Indians (AAPC 2.05; CI 1.20 to 3.46), Filipinas (AAPC 0.61; CI 0.15 to 1.46), Koreans (AAPC 2.72; CI 1.57 to 4.65) and Vietnamese women (AAPC 3.63; CI 2.26 to 6.20), but significantly decreased for Japanese (AAPC -1.41; CI -2.22 to -0.53). Conclusions: We observed heterogenous and converging BC mortality trends across AA groups. These trends elucidate which populations within the broader AA group have disproportionately higher death rates and therefore should be targeted for BC prevention protocols (e.g., Asian Indian and Filipina). Identifying such trends can also help elucidate disparities in cancer care and the overall social determinants that affect women with BC. Understanding disaggregated trends can inform more inclusive screening practices and culturally tailored interventions and treatments to reduce BC deaths in vulnerable populations. Citation Format: Mia Marcotte, Yashi Chauhan, Vedha Penmetcha, Caroline Thompson, Candice Thompson, Malathi Srinivasan, Gloria Kim, Xinran Qi, Robert Huang, Adrian Bacong. Disaggregating breast cancer mortality trends in Asian American women from 2005-2020 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2134.

Testing Homogeneity of Proportion Ratios for Stratified Bilateral Correlated Data

Intraclass correlation in bilateral data has been investigated in recent decades with various statistical methods. In practice, stratifying bilateral data by some control variables will provide more sophisticated statistical results to satisfy different research proposed in randomized clinical trials. In this article, we propose three test statistics (the likelihood ratio test, score test, and Wald-type test statistics) to evaluate the homogeneity of proportion ratios for stratified bilateral correlated data under an equal correlation assumption. Monte Carlo simulations of Type I error and power are performed, and the score test yields a robust outcome based on empirical Type I error and power. Lastly, two real data examples are conducted to illustrate the proposed three tests.

The Regular Polyhedra: Drawing and Computing in Euclid’s day

AbstractCan we compute what we cannot draw? How must we draw to produce measurable representations, or visual ones? This research inquires into the relationship between mathematics and figurative representation, and more precisely between drawing and computation. The scientific imagery studied here is the representation of the five platonic solids, discussing various representation techniques from classical antiquity to modern times, and their efficacy to help calculate sizes and proportional ratios. Scholars in history of architectural drawing have too often limited their observations to the very few preserved plans and front views dating back to classical antiquity, without enlarging their investigation to other scientific fields that also rely on drawing as a research tool and communication device. Among these other fields stands the mathematical research, especially solid geometry which deals with objects and entities that have shapes that needs to be somehow drawn in 3D to be studied.

Video Laryngoscopy vs Direct Laryngoscopy for Endotracheal Intubation in the Operating Room

Endotracheal tubes are typically inserted in the operating room using direct laryngoscopy. Video laryngoscopy has been reported to improve airway visualization; however, whether improved visualization reduces intubation attempts in surgical patients is unclear. To determine whether the number of intubation attempts per surgical procedure is lower when initial laryngoscopy is performed using video laryngoscopy or direct laryngoscopy. Cluster randomized multiple crossover clinical trial conducted at a single US academic hospital. Patients were adults aged 18 years or older having elective or emergent cardiac, thoracic, or vascular surgical procedures who required single-lumen endotracheal intubation for general anesthesia. Patients were enrolled from March 30, 2021, to December 31, 2022. Data analysis was based on intention to treat. Two sets of 11 operating rooms were randomized on a 1-week basis to perform hyperangulated video laryngoscopy or direct laryngoscopy for the initial intubation attempt. The primary outcome was the number of operating room intubation attempts per surgical procedure. Secondary outcomes were intubation failure, defined as the responsible clinician switching to an alternative laryngoscopy device for any reason at any time, or by more than 3 intubation attempts, and a composite of airway and dental injuries. Among 8429 surgical procedures in 7736 patients, the median patient age was 66 (IQR, 56-73) years, 35% (2950) were women, and 85% (7135) had elective surgical procedures. More than 1 intubation attempt was required in 77 of 4413 surgical procedures (1.7%) randomized to receive video laryngoscopy vs 306 of 4016 surgical procedures (7.6%) randomized to receive direct laryngoscopy, with an estimated proportional odds ratio for the number of intubation attempts of 0.20 (95% CI, 0.14-0.28; P < .001). Intubation failure occurred in 12 of 4413 surgical procedures (0.27%) using video laryngoscopy vs 161 of 4016 surgical procedures (4.0%) using direct laryngoscopy (relative risk, 0.06; 95% CI, 0.03-0.14; P < .001) with an unadjusted absolute risk difference of -3.7% (95% CI, -4.4% to -3.2%). Airway and dental injuries did not differ significantly between video laryngoscopy (41 injuries [0.93%]) vs direct laryngoscopy (42 injuries [1.1%]). In this study among adults having surgical procedures who required single-lumen endotracheal intubation for general anesthesia, hyperangulated video laryngoscopy decreased the number of attempts needed to achieve endotracheal intubation compared with direct laryngoscopy at a single academic medical center in the US. Results suggest that video laryngoscopy may be a preferable approach for intubating patients undergoing surgical procedures. ClinicalTrials.gov Identifier: NCT04701762.

Multidimensional assessment of adverse events of bupropion: A large-scale data analysis from the FAERS database

ObjectiveBupropion, a monocyclic antidepressant, aids in smoking cessation, treats major depression, and prevents severe depression in seasonal affective disorder patients. Yet, its adverse reactions remain insufficiently studied. MethodsAll data from the raw data packages for 78 quarters from the 1st quarter of 2004 to the 2nd quarter of 2023 were extracted from the FDA Adverse Event Reporting System (FAERS) database and imported into the SAS9.4 software for data cleaning and analysis. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods were used to analyze drug adverse events and assess their compliance with various screening criteria. ResultsThe results showed a total of 36,862 reports related to Bupropion use, identifying 364 positive reaction terms (PT) covering 23 System Organ Classes (SOCs). In addition to known side effects, some new potential adverse reactions were found, such as Stool analysis abnormal, Oculocephalogyric reflex absent, Suspected suicide, and so on. At the same time, reactions like Encephalopathy neonatal, Hyponatraemic coma, and Electrocardiogram QRS complex prolonged were prominently ranked. Notably, occurrences such as Urine amphetamine positive and Amphetamines positive were relatively high, suggesting extra caution for these potential adverse reactions during clinical use of Bupropion. ConclusionThese findings highlight the potential health risks of long-term Bupropion use, especially concerning efficacy, positive drug tests, and suicidal tendencies. Therefore, it is recommended to monitor and assess patients using Bupropion more stringently to use this therapeutically potential drug more safely and effectively.

Accuracy of blood-based biomarkers for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

Blood-based biomarkers have been proposed as an alternative to liver biopsy for non-invasive liver disease assessment (NILDA) in chronic liver disease (CLD). Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4) and cirrhosis (F4), as compared to biopsy in CLD. We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aminotransferase-to-platelet ratio index (APRI) and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in hepatitis B virus (HBV) and C virus (HCV), HIV-HCV/HBV co-infection, and nonalcoholic fatty liver disease (NAFLD). Positive (LR+) and negative (LR) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86 respectively; LR+ and LR for NAFLD F2-4, F3-4 and F4 were 2-65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15 respectively. Overall, proportional odds ratio indicated FIB-4 <1.45 was better than APRI <0.5 for F2-4. FIB-4 >3.25 was also better than APRI >1.5 for F3-4 and F4. There was limited data for combined tests. Blood-based biomarkers are associated with small-to-moderate change in pre-test probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV co-infection, and NAFLD, with limited comparative or combination studies for other CLD.

Electrolyte disorders induced by six multikinase inhibitors therapy for renal cell carcinoma: a large-scale pharmacovigilance analysis

To provide evidence for optimization of multi-kinase inhibitors (MKIs) use in the clinic, we use the public database to describe and evaluate electrolyte disorders (EDs) related to various MKIs treated for renal cell carcinoma. We analyzed spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System (FAERS) in an observational and retrospective manner. Selecting electrolyte disorders' adverse events to multikinase inhibitors (axitinib, cabozantinib, lenvatinib, pazopanib, sunitinib, and sorafenib). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze suspected adverse reactions of electrolyte disorders induced by MKIs (which were treated for renal cell carcinoma) between January 2004 and December 2022. As of December 2022, 2772 MKIs (which were treated for renal cell carcinoma) ICSRs were related to electrolyte disorders AEs. In general, there were more AEs cases in males, except lenvatinib and 71.8% of the cases were submitted from North America. ICSRs in this study, the age group most frequently affected by electrolyte disorders AEs was individuals aged 45–64 years for axitinib, cabozantinib, pazopanib, and sunitinib, whereas electrolyte disorders AEs were more common in older patients (65–74 years) for sorafenib and lenvatinib. For all EDs documented in ICSRs (excluding missing data), the most common adverse outcome was hospitalization(1429/2674, 53.4%), and the most serious outcome was death/life-threat(281/2674, 10.5%). The prevalence of mortality was highest for sunitinib-related EDs (145/616, 23.5%), excluding missing data (n = 68), followed by cabozantinib-related EDs (20/237, 8.4%), excluding missing data (n = 1). The distribution of time-to-onset of Each drug-related ICSRs was not all the same, and the difference was statistically significant (P = 0.001). With the criteria of ROR, the six MKIs were all significantly associated with electrolyte disorders AEs, the strongest association was the association between cabozantinib and hypermagnesaemia. MKIs have been reported to have significant electrolyte disorders AEs. Patients and physicians need to recognize and monitor these potentially fatal adverse events.

Distributed proportional likelihood ratio model with application to data integration across clinical sites

Distributed proportional likelihood ratio model with application to data integration across clinical sites

Cancer incidence among Armenians in California.

California is home to the largest population of Armenians in the United States. The historical categorization of Armenians as 'White' or 'Some Other Race' in population databases has likely masked cancer incidence patterns in this population. This is the first study considering cancer incidence among Armenians in California. We used the Armenian Surname List and birthplace information in the California Cancer Registry to identify Armenians with cancer diagnosed during 1988-2019. We calculated proportional incidence ratios (PIR) among Armenians compared with non-Hispanic Whites (NHWs). As an exploratory analysis, we calculated incidence rate ratios (IRR) during 2006-2015 using Armenian population denominators from the American Community Survey (ACS). We selected PIR as our primary method given uncertainty regarding the use of ACS population estimates for rate calculations. There were 27,212 cancer diagnoses among Armenians in California, 13,754 among males and 13,458 among females. Armenian males had notably higher proportions of stomach (PIR = 2.39), thyroid (PIR = 1.45), and tobacco-related cancers including bladder (PIR = 1.53), colorectal (PIR = 1.29), and lung (PIR = 1.16) cancers. Higher proportional incidence of cancers including stomach (PIR = 3.24), thyroid (PIR = 1.47), and colorectal (PIR = 1.29) were observed among Armenian females. Exploratory IRR analyses showed higher stomach (IRR = 1.78), bladder (IRR = 1.13), and colorectal (IRR = 1.12) cancers among Armenian males and higher stomach (IRR = 2.54) cancer among Armenian females. We observed higher stomach, colorectal and thyroid cancer incidence among males and females, and tobacco-related cancers among males. Further research is needed to refine Armenian population estimates and understand and address risk factors associated with specific cancers among Armenians in California.

Traditional Atlantic Diet and Its Effect on Health and the Environment

The universal call to action for healthier and more sustainable dietary choices is the framework of the United Nations's Sustainable Development Goals. The Atlantic diet, originating from the northwest of the Iberian Peninsula, represents an example of a traditional diet that aligns with these principles. To explore a 6-month intervention based on the Atlantic diet's effects on metabolic and environmental health, assessing metabolic syndrome (MetS) incidence and the carbon footprint. The Galician Atlantic Diet study was a 6-month randomized clinical trial designed to assess the effects of this regional traditional diet on families' eating habits. The study was conducted from March 3, 2014, to May 29, 2015, at a local primary health care center in the rural town of A Estrada in northwestern Spain and involved a multisectoral collaboration. Families were randomly selected from National Health System records and randomized 1:1 to an intervention or control group. This secondary analysis of the trial findings was performed between March 24, 2021, and November 7, 2023. Over 6 months, families in the intervention group received educational sessions, cooking classes, written supporting material, and foods characteristic of the Atlantic diet, whereas those randomized to the control group continued with their habitual lifestyle. The main outcomes were MetS incidence, defined per National Cholesterol Education Program Adult Treatment Panel III guidelines, and carbon footprint emissions as an environmental metric using life cycle assessment with daily dietary intake as the functional unit. Initially, 250 families were randomized (574 participants; mean [SD] age, 46.8 [15.7] years; 231 males [40.2%] and 343 females [59.8%]). The intervention group included 126 families (287 participants) and the control group, 124 families (287 participants). Ultimately, 231 families completed the trial. The intervention significantly reduced the risk of incident cases of MetS (rate ratio, 0.32; 95% CI, 0.13-0.79) and had fewer MetS components (proportional odds ratio, 0.58; 95% CI, 0.42-0.82) compared with the control condition. The intervention group did not have a significantly reduced environmental impact in terms of carbon footprint emissions compared with the control group (-0.17 [95% CI, -0.46 to 0.12] kg CO2 equivalents/person/d). These findings provide important evidence that a family-focused dietary intervention based on a traditional diet can reduce the risk of incident MetS. Further research is needed to understand the underlying mechanisms and determine the generalizability to other populations, taking into account regional cultural and dietary variations. ClinicalTrials.gov Identifier: NCT02391701.