Probable Relationship Research Articles

Predictors on outcomes of cardiovascular disease of male patients in Malaysia using Bayesian network analysis

ObjectivesDespite extensive advances in medical and surgical treatment, cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Identifying the significant predictors will help clinicians with the prognosis of the...

Assessment of the relationship between self-efficacy criteria and rate of lower limb amputation in diabetic patients; a cross-sectional study.

According to the high prevalence of diabetes Mellitus (DM), as a harmful metabolic disease, the adoption of self-care (SC) behaviors along with modern medications seems necessary for diabetes Mellitus patients (DMPs). Since self-efficacy (SE) affects the quality of SC behaviors in DMPs to prevent limb amputation as one of the most common DM-related complications, the present study aimed to investigate the probable relationship between the effect of the Diabetes Management Self-Efficacy (DMSE) with limb amputation rate in DMPs. DMPs with ages of 18-65 years were selected and divided into two groups of the case (DMPs with experiences of DM ≥ 4 years and limb amputation, n = 300), and control (DMPs with no experience of limb amputation, n = 600). Data were collected through demographics, clinical checklists, and the DMSES tool, and were analyzed using SPSS (v.25). The mean age of DMPs was 55.2 ± 8.2 years, and 59.3% and 40.7% of patients had type I and type II DM, respectively. A significant relationship was found between the mean of DMSES in terms of groups of the case (Mean: 60.6) and control (mean 67.7) (P = 0.001), living place, education, family background in non-close relatives, underlying disease, high blood pressure, hyperlipidemia, and the type of DM. The odds ratio (OR) of amputation was also found higher in DMPs with a lower mean of DMSES OR = 1.03, CI 95%=1.01-1.04, P = 0.001). In this study, DMSE had a significant relationship with reducing limb amputation rate in DMPs. Furthermore, The average self-efficacy score according to gender, place of residence, education, family history in non-close relatives, underlying disease, and type of diabetes was significantly difference. It is suggested, that self-efficacy would be enhanced through systematic education in diabetes clinics. The online version contains supplementary material available at 10.1007/s40200-023-01331-0.

Assessment of the relationship between miR-499C/T (rs3746444) polymorphism and lung carcinoma in Iranian population; a case-control study.

Lung carcinoma is characterized by uncontrollable division of respiratory system cells with detrimental and lethal consequences on human health. Critical roles of microRNAs (miR) are scientifically approved in biological and pathological pathways, such as the role of miR-499 (rs3746444) in lung carcinomas. Thus, in this case-control investigation, we aimed to assess the probable relationship between miR-499C/T variant and the occurrence of lung carcinoma in Iranian population for the first time. Genotype of miR-499 polymorphism was described by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay in patients and healthy individuals. Following definite diagnosis of lung carcinoma, the blood samples were collected, and the DNA extraction was performed by Salting-Out method. Finally, data were analysed by SPSS (v. 20) and the significant level was considered p-value<0.05. Statistically, the frequency of combined genotypes of CC+CT were 83.33% and 35% and TT+CT were 100% and 92% in case and control individuals, respectively. Also, individuals with genotypes of TC (OR: 3.08, CI95%: 3.03-3.17, p<0.0001), TC+CC (OR: 0.10, CI95%: 0.05-0.23, p<0.0001), CC (OR: 0, CI95%: 0.00-0.60, p=0.0214), and TC (OR: 0.07, CI95%: 0.030.15, p<0.0001) represented statistically significant (p<0.05) differences lung carcinoma than those with TT, TT, TT+TC, and TT+CC genotypes, respectively. The frequency of miR-499C (78.5%) and miR-499T (21.5%) alleles were also statistically significantly (p<0.05) difference associated with lung carcinoma in patients than controls. In this study, a possible relationship among miR-499C/T polymorphism and lung carcinoma was detected in Iranian population. Since this study was conducted for the first time, thus other supplementary assessments are needed for definite conclusion.

Impact of wartime stress factors on the metabolic status of the civilian population

Materials and methods. As part of the longitudinal study, 29 civilians were examined; all of them remained in their place of residence during the war, were not directly in the combat areas and did not receive physical damage. Body composition was determined by the method of bioelectrical impedance using Composition Monitor BF511, Omron, including body fat percentage (FAT, %), skeletal muscle percentage (MUS, %), visceral fat level (VIS, %). Hematological and biochemical investigations were conducted according to the standard methods. The enzyme immunoassay with appropriate sets of reagents was used to determine serum levels of insulin, C­reactive protein, sirtuin­1 (SIRT1), tumor necrosis factor α (TNF­α), and dehydroepiandrosterone (DHEA). The saliva cortisol levels were measured by enzyme immunoassay as well. Molecular genetic studies included determination of the relative length of telomeres of blood leukocytes. Results. The mean age of the examined subjects was 53.05 ± 12.06 years, women made up 55.2 % (n = 16). The average time between the prewar visit and the wartime visit was 12.1 ± 2.4 months. When assessing the anthropometric status of the increase in the body mass index, waist circumference and hips: (26.82 ± 3.58 vs 29.67 ± 3.92 kg/m2, p = 0.0184; 84.93 ± 15.58 vs 100.03 ± 12.57 cm, p = 0.0021; 98.57 ± 6.69 vs 106.75 ± 6.73 cm, p = 0.0004), respectively. The most significant changes occurred in the VIS indicator (8.77 ± 3.44 vs 12.88 ± 4.57, p = 0.0003). The significant changes of other parameters were not observed during the study. Correlation analysis of stress indicators (cortisol, DHEA and their ratio) with clinical anthropometric and metabolic indicators, demonstrated their probable association with body composition (cortisol/DHEA &amp; MUS, cortisol/DHEA &amp; FAT), lipid metabolism disorder (cortisol/DHEA &amp; total cholesterol, cortisol/DHEA &amp; low­density lipoprotein cholesterol) and the number of leukocytes (p &lt; 0.05). Conclusions. Among the civilian population, persons who remained in their place of residence during the war showed negative changes in anthropometric status compared to the pre­war period. The impact of a psychotraumatic factor on the anthropometric status, body composition and lipid metabolism in persons who did not change their place of residence during the war is confirmed by the highly probable relationship of the stress indicator (cortisol/DHEA ratio) with the corresponding indicators. Among the civilian population, in persons who did not change their place of residence during the war, no reliable changes in the parameters related to aging (telomeres, SIRT1) compared to the pre­war period were demonstrated.

A probabilistic reasoning approach to analyze the severity of single-vehicle crashes at mid-ramp locations

Freeway ramps are one of the roadway elements that are considered as crash-prone sites with relatively more crashes per mile than other freeway segments. Among other crash types that occurred on freeway ramps, single-vehicle crashes have been found to be more severe. Thus, understanding the factors influencing the severity of single-vehicle crashes on freeway ramps is essential in improving the safety of our limited-access facilities. This study adopted a discrete Bayesian network (BN) approach to explore the probabilistic relationship among the potential factors associated with the severity of single-vehicle crashes at mid-ramp locations. The analysis was based on 6 041 single-vehicle crashes that occurred at the mid-ramp locations in California from 2009 to 2017. The findings indicated that ramp type, ramp traffic volume, road surface condition, and time of day were directly associated with the severity of single-vehicle crashes at the mid-ramp locations. The interdependency of off-ramps, ramp AADT of less than 13 000 vehicles per day, dry road surface condition, and off-peak hours were associated with the highest risk of fatal/severe injury crashes involving a single-vehicle. The study findings could potentially be used by transportation agencies in planning and implementing several strategies to improve the safety of freeway ramps.

Exploring the Influence of Sociodemographic Backgrounds on Money Mule Recruitment Types in South Korea: An Analysis of Probabilities from Machine Learning Classifiers

ABSTRACT This study explores the influence of socio-demographic characteristics on money mule recruitment types in South Korea. Analyzing data from 543 apprehended money mules, probabilities were calculated for each group’s involvement in recruitment types. Using class membership probability estimates from six machine learning methods, the research investigates the probability relationship between socio-demographic characteristics and recruitment types. Findings indicate that unemployed individuals in their 20s with intermediate education levels are more likely to be recruited through social media, while offline recruitment is prevalent among unemployed teenagers with low education levels and men over 50s with criminal records. Highly educated unemployed individuals in their 20s and 30s show a higher probability of using online job search channels. The study provides valuable insights into the complex interplay between sociodemographic factors and money mule recruitment, offering potential implications for law enforcement agencies in developing effective crime prevention strategies. Further analysis will shed light on the underlying reasons behind these results.

An examiner of China commercial banks loans through credit channel prior COVID-19

Purpose- China's economy has greatly developed in the last few decades, catapulting the nation to the second-biggest economy in the world. Financial growth took off over the last couple of decades because of the nation's expansion into the world economy and support for monetary policy. The purpose of this study is to analyse commercial bank-level data to examine a credit channel of the monetary policy transmission mechanism in emerging economies, such as China, from BRICS countries. Among the important questions that central banks, economists, and policymakers have raised in this area are: Does the impact of bank characteristics and macroeconomic variables affect the amount of loans in China? Do interacting bank characteristics and macroeconomic elements affect the amount of a loan in China? Methodology- Data analysis is achieved using static panel data with a random-effect model. 216 commercial banks in China were used as a sample, and the study was conducted from 2009 to 2018. The statistical software Stata is utilised for data analysis. Findings- According to findings from China's statistics, the capital ratio, GDP, inflation, and ROA interactions have a statistically significant but negative impact on the loan amount. The hypothesis is that capital ratio, total assets, and return on assets have a statistically significant and positive effect on the amount of the loan. The robust standard error coefficient showing a probable causal relationship between the variables was positive. Also,the results demonstrate that macroeconomic factors like interest rates, GDP, and inflation have a statistically insignificant positive impact on loan amounts. Hence, this study found enough evidence to accept the hypothesis that the loan amount had an insignificant effect. Conclusion- The authors contribute to the existing literature by identifying the key determinants of monetary policy transmission channels through credit in China and, furthermore, through a country-level data analysis and disaggregation at the commercial bank level, as well as economic conditions. Keywords: Panel Data, Banks, Monetary Policy Transmission Mechanism, Credit Channel, China economy. JEL Codes: C23; E51; E52

Development of seismic fragilities for a base station steel lattice cellular tower

A large portion of the country of Turkey is located in a very high seismic region known as a first-degree earthquake zone where earthquakes occur frequently. Earthquakes result in damage to infrastructure including base station towers and subsequently failure of mobile communication networks. The loss of functionality of mobile communication networks following an earthquake has a direct impact on emergency response and both short and long-term recovery phases. Understanding both these phases requires systematic modeling of infrastructure components, which rely on fragility curves representing the probabilistic relationship between seismic intensity and damage. This study focuses on the development of damage fragility curves (fragilities) for an archetypical mobile cellular tower, namely a 55 m tall steel lattice tower (SLT) used in base station towers in Turkey. Nonlinear time history analysis was performed using a robust suite of far field ground motion records to model the performance of the archetype tower and develop damage fragilities for five specific damage states which were defined in terms of likely performance: damage state 0 (no damage), damage state 1 (uninterrupted communication), damage state 2 (communication interruption), damage state 3 (communication failure), damage state 4 (structural failure). While fragility curve has been developed for lattice towers of different types and sizes in the literature, there is no specific study for 55 m SLT and the novelty of this study is that the resulting SLT archetype fragilities can serve as a benchmark dataset for use in community-level risk and resilience analyses to improve response and recovery planning following earthquakes.

Data-driven Bayesian network approach to maritime accidents involved by dry bulk carriers in Turkish search and rescue areas

In the case of maritime accidents, they cause very serious vital, economic, and environmental problems. As a matter of fact, maritime accidents emerge as an important issue due to the risks brought by the increasing ship tonnage and ship traffic. In this sense, the Turkish Search and Rescue Areas, which include the Aegean Sea islands, the Turkish coasts, and the Turkish Straits, are among the regions with risks in maritime accidents. In this study, the accidents that took place between the years 2001–2019 in the Turkish Search and Rescue Areas were examined, and maritime accident analysis was carried out using Bayesian networks on the accidents involving dry-bulk carriers. Considering accident type as a target variable, this study concentrates on the probabilistic relationships among the factors (i.e., ship type, grt, flag, survival status, navigation region, accident month, accident time, and accident causes) which are thought to influence the occurrence of accidents. According to the research outcomes, it has been determined as probabilistic that there are seasonal and regional differences in the occurrence of accident causes and the occurrence of accidents. In dry bulk carriers, it has been determined that the white flag ships in the Paris Mou ranking are much less likely to be involved in a fatal accident at night. In addition, while the probability of fatal maritime accidents occurring during the daylight hours (06:00–17:59) in accidents in the Çanakkale navigational area is 28%; at night (18:00–05:59), this rate is 41%. Another important matter is that some ships have been found to be involved in accidents repeatedly. In this sense, suggestions have been made for the stakeholders.

Survival analysis over a 20-year period of a Brazilian cohort of blood donors coinfected HIV-HCV.

Among individuals coinfected with HCV and HIV, studies of mortality from non-hepatic causes have shown inconsistent results. The aim of this study was to investigate the contribution of HCV and HIV co-infection to mortality from hepatic and non-hepatic causes in Brazil. This retrospective cohort study included blood donors from Fundação Pró-Sangue de São Paulo (FPS) who were followed from 1994 to 2016 to compare mortality and its causes between HIV-HCV coinfected individuals versus those seronegative for all tested infections. Records from the FPS database and the Mortality Information System were linked through a probabilistic record Relationship (RL). The Hazard Ratio (HR) was estimated using Cox multiple regression models. HCV-HIV coinfected individuals compared to seronegative individuals had a higher risk of death from all causes (HR=14.54), non-liver neoplasms (HR=2.55), infections (HR=10.37) and liver disease (HR=7.0). In addition, HCV mono-infected individuals compared to seronegative individuals had a higher risk of death from all causes (HR=2.23), liver cancer (HR=32.21), liver disease (HR=14.92), infection (HR=3.22), and trauma (HR=1.68). Individuals coinfected with HCV and HIV have increased overall mortality and death due to infections, liver diseases and non-liver neoplasms as compared to those uninfected with HCV and HIV.

CA-CD: context-aware clickbait detection using new Chinese clickbait dataset with transfer learning method

PurposeA clickbait is a deceptive headline designed to boost ad revenue without presenting closely relevant content. There are numerous negative repercussions of clickbait, such as causing viewers to feel tricked and unhappy, causing long-term confusion, and even attracting cyber criminals. Automatic detection algorithms for clickbait have been developed to address this issue. The fact that there is only one semantic representation for the same term and a limited dataset in Chinese is a need for the existing technologies for detecting clickbait. This study aims to solve the limitations of automated clickbait detection in the Chinese dataset.Design/methodology/approachThis study combines both to train the model to capture the probable relationship between clickbait news headlines and news content. In addition, part-of-speech elements are used to generate the most appropriate semantic representation for clickbait detection, improving clickbait detection performance.FindingsThis research successfully compiled a dataset containing up to 20,896 Chinese clickbait news articles. This collection contains news headlines, articles, categories and supplementary metadata. The suggested context-aware clickbait detection (CA-CD) model outperforms existing clickbait detection approaches on many criteria, demonstrating the proposed strategy's efficacy.Originality/valueThe originality of this study resides in the newly compiled Chinese clickbait dataset and contextual semantic representation-based clickbait detection approach employing transfer learning. This method can modify the semantic representation of each word based on context and assist the model in more precisely interpreting the original meaning of news articles.

Bayesian inference of pit corrosion in prestressing strands using Markov Chain Monte Carlo method

Corrosion monitoring has been widely studied to maintain the structural capacity of bridges through direct visual and nondestructive inspections or indirect inverse analysis-based methods. This study proposes a Bayesian inference method for inferring pit corrosion in the prestressing strands of prestressed concrete (PSC) bridges, which is an indirect method for corrosion monitoring. First, the probabilistic relationship between the mechanical properties of the strands and the amount of pit corrosion was defined using Bayes’ rule. Subsequently, a Markov chain Monte Carlo method was introduced to infer the posterior probability, which is a conditional probability distribution of the amount of corrosion given a certain mechanical property. Based on the inference results, probabilistic bounds for the amount of corrosion were derived. The proposed method was applied to two examples: (a) probabilistic corrosion inference of strands based on the tensile test results, and (b) probabilistic corrosion inference of embedded strands in PSC girders based on the bending test results. The inference results demonstrated the applicability of the proposed method.

Causal learning with delays up to 21hours.

Considerable delays between causes and effects are commonly found in real life. However, previous studies have only investigated how well people can learn probabilistic relations with delays on the order of seconds. In the current study we tested whether people can learn a cause-effect relation with delays of 0, 3, 9, or 21hours, and the study lasted 16 days. We found that learning was slowed with longer delays, but by the end of 16 days participants had learned the cause-effect relation in all four conditions, and they had learned the relation about equally well in all four conditions. This suggests that in real-world situations people may still be fairly accurate at inferring cause-effect relations with delays if they have enough experience. We also discuss ways that delays may interact with other real-world factors that could complicate learning.

The Association between Serum Vitamin D Levels and Male Fertility: A Systematic Review and Meta-Analysis

Objective. The probable relationship between serum vitamin D levels and male fertility is being increasingly investigated; however, the findings have been controversial. This review dealt with assessing the relationship between serum vitamin D levels and male fertility and sperm quality by executing systematic review and meta-analysis of the published data. Methods. The meta-analysis was executed as per the PRISMA 2020 statement. The protocol was registered with PROSPERO (CRD42022327583). Relevant literature was retrieved by searching online databases, including Embase, Scopus, PubMed, Web of Science, and the Cochrane Library, up to December 1st, 2022. Additionally, Google Scholar was searched to assess relevant articles. To ensure a more comprehensive review, unpublished articles, gray literature, and references of suitable articles were also assessed to find additional eligible publications. The articles that satisfied the inclusion criteria were evaluated for their quality using the Joanna Briggs Institute Critical Appraisal Tool. Meta-analysis was conducted through STATA 12. Results. Twenty-four articles, comprising 7,345 participants in total, were chosen for the systematic review and meta-analysis. The resulting data indicated that serum vitamin D levels infertile males were remarkably elevated compared with that in infertile males (weighted mean difference (WMD) = 7.06, 95% confidence interval (95% CI) = 2.51–11.62, P = 0.002 ), and its deficiency (&lt;20 ng/mL or 50 nmol/L) significantly reduced sperm concentration (WMD = 8.54, 95% CI = 4.01–13.06, P &lt; 0.001 ), total sperm count (WMD = 14.43, 95% CI = 1.30–27.55, P = 0.031 ), sperm motility (WMD = 6.40, 95% CI = 3.15–9.64, P &lt; 0.001 ), sperm progressive motility (WMD = 5.00, 95% CI 1.09–8.92, P = 0.012 ), and altered sperm morphology (WMD = 0.74, 95% CI = 0.20–1.27, P = 0.007 ). The data analysis determined that vitamin D did not remarkably influence sperm volume (WMD = 0.17; 95% CI = −0.00–0.34; P = 0.050 ). Conclusion. The acquired data implied that serum vitamin D is significantly associated with male fertility and sperm quality. This finding holds crucial implications for patients suffering from male infertility.

A Rare Case Series on Cefoperazone Sulbactam Induced Uremia: A Matter of Concern and Awareness

Uraemia is a clinical syndrome marked by elevated concentrations of urea in the blood and is associated with fluid, electrolyte, hormone imbalances and metabolic abnormalities. Cefoperazone + sulbactam is a combination of two medicines: cefoperazone and sulbactam. Cefoperazone is an antibiotic that works by preventing the formation of the bacterial protective covering, which is essential for the survival of bacteria [1]. Sulbactam is a beta-lactamase inhibitor that reduces resistance and enhances the activity of cefoperazone against bacteria [2].&#x0D; Pharmaceutical agents play a central role in diagnostic and therapeutic activities for patient care. However, all agents carry the risk of adverse drug effects. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that negatively impacts patient morbidity and mortality [3]. Recognizing adverse effects is important for administering appropriate drug doses, implementing preventive strategies, and discontinuing the offending agent when toxicity occurs [2]. In most cases, nephrotoxicity leads to discontinuation of the causative drug, thereby limiting treatment options.&#x0D; One of the biggest challenges lies in our ability to identify nephrotoxicity in its early stages. Monitoring serum creatinine and blood urea nitrogen (BUN) levels is an effective method for identifying renal diseases [4]. In this study, the authors report three cases of isolated cefoperazone-sulbactam-induced uraemia in patients without chronic kidney disease (CKD). A Naranjo assessment score of 5 was obtained for the three case scenarios, indicating a probable relationship between the patient’s uraemia and use of the suspected drug.

Ribociclib-induced pulmonary infiltrates in a patient with breast cancer.

Breast cancer is the most common cancer in women worldwide. One of the treatment choices used in hormone receptor positive and HER2 expression negative metastatic breast cancer is cyclin dependent kinase 4/6 (CDK) inhibitors. There are differences between the effects and adverse events of all CDK4/6 inhibitors. In this report, we describe a 48-year-old female patient with breast cancer who developed pulmonary infiltrates secondary to drug in the second year of follow-up with Ribociclib therapy. The patient who used ribociclib for metastatic breast cancer was admitted to hospital for routine controls. The patient, in the eighth month of ribociclib treatment, had no active complaints. In the patient's imaging, pulmonary infiltrates were detected in the lower lobe of the right lung. The drug was continued in the patient who was asymptomatic and had no infectious signs. Pneumonitis, interstitial lung disease, tuberculosis, COVID-19 and other viral agents were excluded in the patient. A minimal increase in pulmonary infiltrates was observed in the follow-up. However, the patient who does not have any complaints is currently continuing ribociclib at 600 mg/day. The pulmonary infiltrates that developed in the patient increased with continued use of ribociclib, suggesting that this was due to ribociclib. The Naranjo Adverse Drug Reaction Probability Scale also indicates probable relationship.

Screening of the shared pathogenic genes of ulcerative colitis and colorectal cancer by integrated bioinformatics analysis.

Ulcerative colitis (UC) is one of the high-risk pathogenic factors for colorectal cancer (CRC). However, the shared gene and signalling mechanisms between UC and CRC remain unclear. The goal of this study was to delve more into the probable causal relationship between UC and CRC. CRC and UC datasets were downloaded from the Gene Expression Omnibus database. Using R software and Perl, differentially expressed genes (DEGs) in both UC and CRC tissues were re-annotated and screened. The biological activities and signalling pathways involved in DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The STRING database and Cytoscape software were used to construct the gene interaction network. A total of 384 DEGs were selected for further investigation, and functional analysis revealed that inflammatory and immunological responses were crucial in the development of the two diseases. Moreover, the top 15 key genes involved in the UC and CRC were screened using cytoHubba, including IL1B, CXCL10, CCL20, MMP9, ICAM1, CCL4, CXCR1, MMP3, TLR2, PTGS2, IL1RN, IL6, COL1A2, TIMP1 and CXCL1. The identification of these genes in the present study may provide a novel perspective for the prediction, prevention and personalized medicine of UC and CRC patients.

Exploiting the implicit independence assumption for learning directed graphical models

Bayesian network classifiers (BNCs) provide a sound formalism for representing probabilistic knowledge and reasoning with uncertainty. Explicit independence assumptions can effectively and efficiently reduce the size of the search space for solving the NP-complete problem of structure learning. Strong conditional dependencies, when added to the network topology of BNC, can relax the independence assumptions, whereas the weak ones may result in biased estimates of conditional probability and degradation in generalization performance. In this paper, we propose an extension to the k-dependence Bayesian classifier (KDB) that achieves the bias/variance trade-off by verifying the rationality of implicit independence assumptions implicated. The informational and probabilistic dependency relationships represented in the learned robust topologies will be more appropriate for fitting labeled and unlabeled data, respectively. The comprehensive experimental results on 40 UCI datasets show that our proposed algorithm achieves competitive classification performance when compared to state-of-the-art BNC learners and their efficient variants in terms of zero-one loss, root mean square error (RMSE), bias and variance.

Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Associated With Antibiotic Use: A Case-Crossover Study

Evidence is lacking on the association between antibiotic use and risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Asians. We assessed the risk of SJS/TEN associated with different antibiotic classes in Japanese. We conducted a case-crossover study using a claims database. Firth conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of SJS/TEN associated with antibiotic use in a 56-day hazard period versus three control periods. We created 18 cohorts for each antibiotic class and calculated 56-day cumulative incidence per 100,000 new users. The association between antibiotic class and SJS/TEN was also evaluated in each case using the ALgorithm of Drug causality for Epidermal Necrolysis (ALDEN). Our case-crossover study included 170 SJS/TEN cases. Increased ORs were observed for lincomycins (33.00 [3.74-4332.05]), trimethoprim-sulfamethoxazole (21.20 [6.73-105.98]), penicillins (14.39 [6.95-34.21]), glycopeptides (14.37 [3.17-136.10]), cephalosporins (OR, 7.06 [95% CI, 4.25-12.21]), aminoglycosides (6.55 [1.97-26.84]), quinolones (5.98 [3.34-11.20]), fosfomycin (5.40 [1.20-30.97]), carbapenems (5.09 [1.85-15.64]), tetracyclines (4.95 [1.78-15.27]), and macrolides (3.78 [2.13-6.83]). Cumulative incidence of SJS/TEN was 67.4 for trimethoprim-sulfamethoxazole, 86.2 for glycopeptides, and below 10.0 for the others. Despite the high incidence, only two cases had a probable causal relationship with glycopeptides. Some antibiotic classes, including lincomycins, glycopeptides, aminoglycosides, fosfomycin, and carbapenems, were newly suggested to be associated with risk of SJS/TEN; considered together with the high incidence for trimethoprim-sulfamethoxazole and glycopeptides, these findings warrant caution in clinical practice.

Neuropsychiatric adverse reactions in patients treated with denosumab: two case reports and a review of data from the FDA Adverse Event Reporting System (FAERS).

Denosumab is a human monoclonal antibody indicated for patients with osteoporosis and a high risk of fractures. It targets RANKL, the receptor activator of NF-κB (RANK) ligand, blocking RANKL-RANK interaction and leading to rapid osteoclast-mediated bone resorption inhibition. But RANK is widely expressed in neurons, microglia, and astrocytes. RANKL/RANK/NF-κB system can play an important role in the neuroinflammatory response, depressive behavior, memory impairments, and neurotrophism. We present two well-documented case reports of recurrent neuropsychiatric manifestations in patients treated with denosumab and a descriptive review of similar cases reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database between 2012 and 2022. Only those reported by healthcare professionals, coding denosumab as the only suspected drug, were retained. An 81-year-old woman with pre-existing mild cognitive impairment suffered two acute confusional episodes and another 81-year-old woman with depression in remission suffered two depressive recurrences with anxiety and psychomotor inhibition, in both cases following sequential administrations of denosumab without underlying calcium/phosphate imbalance. Scores on Naranjo Adverse Drug Reaction Probability Scale were 6 and 7, respectively, suggesting a probable causal relationship. Of the 91,151 cases with denosumab exposure reported to FAERS, 5.7% were related to psychiatric/neurological disorders and 23.8% of these corresponded to cognitive impairment, depressive/mood disturbances, or psychomotor retardation. Denosumab may cause transient but severe neuropsychiatric symptoms by several mechanisms involving RANKL blockade and subsequent immuno-inflammatory changes, at least in subjects with pre-existing neurobiological vulnerability. We recommend caution and careful monitoring of these patients following denosumab administrations.