Risk Of Toxicity Research Articles

Predictors Of Marketing Authorization Status Of Dipyrone Within A Country

Introduction. Although there are numerous data about increased risk of bone marrow toxicity with dipyrone when compared to other nonsteroid anti-infl ammatory drugs, it continues to be marketed in many countries. The aim of this study was to identify currently unknown putative predictors of dipyrone having marketing authorization in a country. Methods. The study was designed as secondary research of a cross-sectional type. The data were collected from web pages of relevant international and national entities. The main outcome variable of the study was dipyrone marketing authorization status within a country. The data were analyzed by both uni- and multi-variate statistics, including logistic regression. Results. The following factors showed signifi cant infl uence on marketing authorization status of dipyrone: Current Health Expenditure per capita (p = 0.02), Gross Domestic Product per capita (p = 0.02), Incarceration Rate (per 100.000 population) (p = 0.04), and overall Global Innovati-on Index (p = 0.04). However, after adjustment, the multivariate analysis showed that the most important predictor was Current Health Expenditure per capita (p = 0.01). Conclusion. The use of medications already considered by many to be obsolete and even dan-gerous due to their low benefi ts/harm ratio seems related to the underdevelopment of a country. There is a need for further research into ways to help these countries make better choices about the use of potentially harmful drugs and other health technologies.

Disseminated Histoplasmosis with Secondary Hemophagocytic Lymphohistiocytosis in a Renal Transplant Recipient on Belatacept-based Immunosuppression

Effective post-transplant immunosuppression is essential to induce tolerance to allogeneic tissues and promote long-term graft survival. However, suppression of the immune system significantly increases the risk of opportunistic infections. In addition to the ongoing challenge of balancing graft survival and preventing infections, previous gold-standard calcineurin inhibitor-based immunosuppression also posed an increased risk of nephrotoxicity, cardiac disease, and diabetes. Belatacept is approved as an alternative to calcineurin inhibitor-based regimens. Although belatacept has improved cardiovascular and metabolic adverse events in renal transplant patients’ but it carries a notably higher risk of long-term graft survival and renal toxicity, similar to calcineurin inhibitor-based regimens. However, there may be an increased risk of infections with its mechanism of action. We present a case of a 62-year-old female who developed disseminated histoplasmosis 18 months after being on belatacept-based immunosuppression after a deceased donor renal transplant for end-stage renal disease secondary to focal segmental glomerulosclerosis. Grocott Methenamine Stain (GMS) of peripheral blood smear showed intracellular yeast in neutrophils, consistent with histoplasmosis. Disseminated histoplasmosis was confirmed with positive bronchoalveolar lavage (BAL) and urine culture. The patient later developed hemophagocytic lymphohistiocytosis (HLH) secondary to immunosuppression and disseminated histoplasmosis. The patient succumbed to the disease despite maximal medical therapy. To our knowledge, there is one other published report of disseminated histoplasmosis in a patient with belatacept-based immunosuppression. The unique feature of this case is the development of HLH secondary to disseminated histoplasmosis while on belatacept. Further research is needed to evaluate the need for antifungal prophylaxis in patients on belatacept therapy.

Study on the adsorption performance of fly ash loaded on nano-FeS for chromium-containing wastewater treatment

In view of the problems caused by chromium-containing wastewater, such as environmental pollution, biological toxicity, and human health risks. Based on fly ash adsorption and nano-FeS reduction characteristics, fly ash loaded nano-FeS composite (nFeS-FA) was synthesized using mineral supported modification technology and ultrasonic precipitation method. The effect of adsorbent dosage, initial pH, contact time, and initial concentration of the solution on the adsorption of Cr(VI) and total Cr by nFeS-FA was investigated. The characteristics of Cr(VI) and total Cr adsorption by nFeS-FA were studied using adsorption isotherms, adsorption kinetics principles, as well as XRD, TEM, SEM-EDS, and BET analysis. The results demonstrated that under the conditions of nFeS-FA of 8 g/L, initial pH of 4, contact time of 150 min, and initial concentration of the solution at 100 mg/L, nFeS-FA achieved removal efficiency of 87.85 % for Cr(VI) and 71.77 % for total Cr. The adsorption of Cr(VI) and total Cr by nFeS-FA followed the Langmuir model and pseudo-second-order kinetic model, indicating monolayer adsorption with chemical adsorption as the dominant mechanism. XRD, TEM, SEM-EDS, and BET revealed that the flaky nano-FeS was uniformly distributed on the surface of fly ash, exhibiting good dispersion and thereby increasing the specific surface area. During the adsorption experiments, nFeS-FA reacted with Cr(VI), and the generated Fe3+ mainly existed as FeOOH precipitation, while S2− reacted with Cr(III) to produce Cr2S3 precipitation. Therefore, nFeS-FA exhibited excellent adsorption performance towards Cr(VI) and total Cr. It can serve as a technological reference for the remediation of heavy metal chromium pollution in the field of water treatment.

Real-World Acute Toxicity and 90-Day Mortality in Patients With Stage I NSCLC Treated With Stereotactic Body Radiotherapy

IntroductionStereotactic body radiotherapy (SBRT) has firmly established its role in stage I NSCLC. Clinical trial results may not fully apply to real-world scenarios. This study aimed to uncover the real-world incidence of acute toxicity and 90-day mortality in patients with SBRT-treated stage I NSCLC and develop prediction models for these outcomes. MethodsProspective data from the Dutch Lung Cancer Audit for Radiotherapy (DLCA-R) were collected nationally. Patients with stage I NSCLC (cT1-2aN0M0) treated with SBRT in 2017 to 2021 were included. Acute toxicity was assessed, defined as grade greater than or equal to 2 radiation pneumonitis or grade greater than or equal to 3 non-hematologic toxicity less than or equal to 90 days after SBRT. Prediction models for acute toxicity and 90-day mortality were developed and internally validated. ResultsAmong 7279 patients, the mean age was 72.5 years, with 21.6% being above 80 years. Most were male (50.7%), had WHO scores 0 to 1 (73.3%), and had cT1a-b tumors (64.6%), predominantly in the upper lobes (65.2%). Acute toxicity was observed in 280 (3.8%) of patients and 90-day mortality in 122 (1.7%). Predictors for acute toxicity included WHO greater than or equal to 2, lower forced expiratory volume in 1 second and diffusion capacity for carbon monoxide, no pathology confirmation, middle or lower lobe tumor location, cT1c-cT2a stage, and higher mean lung dose (c-statistic 0.68). Male sex, WHO greater than or equal to 2, and acute toxicity predicted higher 90-day mortality (c-statistic 0.73). ConclusionsThis nationwide study revealed a low rate of acute toxicity and an acceptable 90-day mortality rate in patients with SBRT-treated stage I NSCLC. Notably, advanced age did not increase acute toxicity or mortality risk. Our predictive models, with satisfactory performance, offer valuable tools for identifying high-risk patients.

Re-irradiation practice and ESTRO/EORTC consensus recommendations: 2023 ASTRO education panel.

Indications for re-irradiation are increasing both for palliation and potentially curative attempts to achieve durable local control. This has been in part driven by the technological advances in the last decade including image-guided brachytherapy, volumetric-modulated arc therapy and stereotactic body radiotherapy. These enable high dose focal irradiation to be delivered to a limited target volume with minimal normal tissue re-irradiation. The European Society for Radiotherapy and Oncology (ESTRO) and the European Organisation for Research and Treatment of Cancer (EORTC) have collaboratively developed a comprehensive consensus on re-irradiation practices, aiming to standardise definitions, reporting, and clinical decision-making processes. The document introduces a universally applicable definition for re-irradiation, categorised into two primary types based on the presence of geometric overlap of irradiated volumes and concerns for cumulative dose toxicity. It also identifies "repeat organ irradiation" and "repeat irradiation" for cases without such overlap, emphasising the need to consider toxicity risks associated with cumulative doses. Additionally, the document presents detailed reporting guidelines for re-irradiation studies, specifying essential patient and tumour characteristics, treatment planning and delivery details, and follow-up protocols. These guidelines are designed to improve the quality and reproducibility of clinical research, thus fostering a more robust evidence base for future re-irradiation practices. The consensus underscores the necessity of interdisciplinary collaboration and shared decision-making, highlighting performance status, patient survival estimates, and response to initial radiotherapy as critical factors in determining eligibility for re-irradiation. It advocates for a patient-centric approach, with transparent communication about treatment intent and potential risks. Radiobiological considerations, including the application of the linear-quadratic model, are recommended for assessing cumulative doses and guiding re-irradiation strategies. By providing these comprehensive recommendations, the ESTRO-EORTC consensus aims to enhance the safety, efficacy, and quality of life for patients undergoing re-irradiation, while paving the way for future research and refinement of treatment protocols in the field of oncology.

Rheumatic diseases in the elderly: Challenges and management

Abstract The elderly demographic is seeing a gradual rise as a proportion of the overall global population, whilst also experiencing high rates of musculoskeletal issues, requiring specialized care. The management of rheumatic diseases in the elderly presents unique challenges due to the complex interplay among physiological changes, cognitive decline, and altered immune responses. Such conditions can be categorized into those progressing from earlier life stages (such as rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis, and gout) and those predominantly emerging in old age (such as polymyalgia rheumatica, giant cell arteritis, osteoarthritis, crystal arthropathies, and osteoporosis), each with distinct characteristics and management needs. These diseases often present atypically with nonspecific symptoms and altered serological markers, complicating diagnosis and management due to increased toxicity risks and comorbidities. Comprehensive, multidisciplinary care that includes cardiovascular health monitoring, bone density maintenance, gastrointestinal tolerance management, infection prevention, and mental health support are essential to improve outcomes and quality of life for elderly patients with rheumatic diseases.

A review of food contamination with nitrated and oxygenated polycyclic aromatic hydrocarbons: toxicity, analysis, occurrence, and risk assessment.

Prolonged exposure to polycyclic aromatic hydrocarbons (PAHs) and their derivatives, particularly nitrated polycyclic aromatic hydrocarbons (NPAHs) and oxygenated polycyclic aromatic hydrocarbons (OPAHs), can result in adverse health effects and may carry higher toxicity risks compared to PAHs alone. Various extraction methods have been utilized for PAHs derivatives from food samples. The analytes are then analyzed using gas chromatography/mass spectrometry and high-performance liquid chromatography techniques. PAHs derivatives are increasingly being detected in the environment, prompting scrutiny from numerous researchers. Similarly, their presence in food is becoming a significant concern. The elevated levels of PAH derivatives found in smoked food may result in detrimental dietary exposure and pose potential health hazards. Furthermore, investigating the level of exposure to these contaminants in food is imperative, as their consumption by humans carries inherent risks. Consequently, this review concentrates on the toxicity, analysis, occurrence, and risk evaluation of NPAHs and OPAHs present in food sources.

Evaluating the cancer aging and research group model in predicting immunochemotherapy toxicity among elderly patients with diffuse large B-cell lymphoma

BackgroundThe management of diffuse large B-cell lymphoma (DLBCL) in elderly patients is complicated by an increased risk of treatment-related toxicity associated with aging. This study aimed to validate the effectiveness of the Cancer Aging and Research Group (CARG) model in elderly patients with DLBCL receiving rituximab-based chemotherapy. MethodsIn this prospective study, elderly DLBCL patients (aged 65 years or older) receiving rituximab-based chemotherapy were consecutively assessed between August 2016 and December 2021 at one medical center in Taiwan using the CARG model to predict treatment-related toxicity. Patients were categorized into low-, medium-, and high-risk groups based on their CARG scores. Comparisons were made regarding toxicities and survival rates among these groups. ResultsNinety-one patients, with a median age of 70 years (range 65–96), were included. A substantial 81 % (74 patients) experienced grade 3–5 toxicity. The overall 2-year survival rate was 63.8 % after a median follow-up of 28 months (range, 2–46). The risk of grade 3–5 toxicity was 83 %, 78 %, and 87 %, respectively, among the low-, medium-, and high-risk groups (p = 0.60). The receiver operating characteristic (ROC) curve for CARG was 0.521 (95 % CI, 0.376–0.666), which was significantly lower than that for the Eastern Cancer Oncology Group score (ROC = 0.701, 95 % CI, 0.571–0.831). Similarly, compared with those of low-risk patients, hazard ratios for overall survival were 9.22 (95 % CI, 1.23–69.1; p = 0.031) and 14.6 (95 % CI, 1.90–112; p = 0.010) for medium- and high-risk patients, respectively. ConclusionWhile CARG exhibited limitations in predicting treatment-related toxicity in elderly DLBCL patients, it demonstrated potential efficacy in predicting survival outcomes.

Nomograph derivation for underwater sour gas releases in shallow waters based on computational fluid dynamics simulations

Ruptured underwater pipelines releasing sour gas (i.e., natural gas with high concentrations of H2S) pose significant threats to environmental safety due to their toxic and contaminative properties. This study suggests a transient Eulerian-Eulerian multiphase computational fluid dynamics (CFD) model for assessing the environmental impact of sour gas releases in shallow, ecologically sensitive waters. Employing the Realizable k-ε turbulence model and additional bubble plume mechanisms, the model was rigorously validated against well-documented experimental data, showing high levels of agreement across multiple metrics. Key environmental safety parameters—such as rise time and H2S surface gas concentration, indicative of toxic exposure risk to aquatic life and human health—were extracted for multiple release scenarios. To present generalized and easily accessible data, these parameters were nondimensionalized and incorporated into a nomograph, enabling environmental risk assessments to be conducted four orders of magnitude faster than with high-fidelity simulations. The study emphasizes the nomograph's utility in rapid, environmentally relevant risk assessment and emergency planning for mitigating the impact of sour gas spills. An error and sensitivity analysis revealed uncertainties of ±7 % for rise time and ±58 % for surface gas concentration, pinpointing avenues for future research.

The Risk of Financial Toxicity in Patients With Head & Neck Cancer

The Risk of Financial Toxicity in Patients With Head & Neck Cancer

Prediction of Potential Risk for Flupyradifurone and Its Transformation Products to Hydrobionts.

Flupyradifurone (FPF) is considered the latest generation of neonicotinoid insecticides. Here, we investigated the toxicity and ecological risk of FPF and its aerobic transformation products (TPs) to aquatic species using the method of prediction. We found that FPF exhibited moderate or high toxicity to some aquatic species. The 5% hazardous concentration of FPF was 3.84 μg/L for aquatic organisms. We obtained 91 aerobic TPs for FPF, and almost half of FPF TPs exhibited toxicity to fish or Daphnia. Eleven of the TPs of FPF exhibited a high or moderate risk to aquatic ecosystems. All FPF TPs with high and moderate risks contained a 6-chloropyridine ring structure, indicating that the derivant of a pyridine ring exhibits potential risks to aquatic ecosystems. Our results provide insight into the potential risk of FPF to aquatic ecosystems and could be used to help set criteria to control pollution caused by FPF.

Association of Lamotrigine Plasma Concentrations With Efficacy and Toxicity in Patients With Epilepsy: A Retrospective Study.

There is limited evidence to support the currently suggested lamotrigine (LTG) therapeutic reference range of 2.5-15 mg/L for the treatment of seizures. The objective of this study was to evaluate the association of LTG plasma concentrations with the efficacy and toxicity of the treatment in patients with epilepsy. Patients whose LTG plasma concentration was measured between January 2013 and February 2022 were included. Efficacy was defined as seizure freedom for at least 6 months around the time of measured LTG concentration. Toxicity was defined as any LTG-related adverse drug effect documented in each patient's health record or when the reason for measuring the LTG concentration was toxicity. In addition, the dose-concentration relationship of LTG was assessed. In total, 549 concentrations from 259 patients with epilepsy were included. The most common reasons for therapeutic drug monitoring were suspected inefficacy (39%) and pregnancy (21%). The LTG plasma concentration was not associated with efficacy (adjusted odds ratio = 0.94; 95% confidence interval, 0.85-1.04). The LTG plasma concentration was positively associated with the incidence of toxicity after adjusting for age, sex, and number of antiepileptic drugs (odds ratio = 1.11; 95% confidence interval, 1.04-1.19). The daily dose had a significant linear correlation with the LTG plasma concentration ( P < 0.001). The LTG plasma concentration was associated with toxicity, whereas no association with efficacy was found. A reference range of 2.5-10 mg/L may be considered to decrease the risk of toxicity while maintaining similar efficacy. Therapeutic drug monitoring may be useful when LTG-related toxicity is suspected and in cases of pharmacokinetic changes (eg, pregnancy and concomitant use of interacting drugs) that can influence the LTG plasma concentration.

Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for locally advanced head and neck squamous cell carcinoma

PurposeAnatomical structures and organ preservation concepts of the head and neck are important for patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC). Neoadjuvant chemotherapy has been applied to improve organ preservation; however, pathological complete remission is still unsatisfactory. The purpose of this study was to explore the pathological complete response (pCR) rate and safety of immune checkpoint blockade combined with neoadjuvant chemotherapy (NAC) in patients with LA HNSCC.MethodsFifty-one patients participated in this retrospective study, and of these, 25 received NAC only (cisplatin+5-fluorouracil+nab-paclitaxel), and 26 received NAC (cisplatin+5-fluorouracil) plus pembrolizumab. Pathological complete remission, the objective response rate (ORR), delayed surgery and toxicity were compared between the two groups.ResultsA significant difference was observed in the pCR rate and ORR between the NAC+ICB group and the NAC group. Delaying surgery and Grade 3 or 4 AEs occurred more frequently in the NAC group. In the NAC-only group, during a median follow-up period of 31.80 months, the recurrence-free survival (RFS) rate was 80.0%, the disease-free survival (DFS) rate was 80.0% and the overall survival (OS) rate was 88.0%. In the NAC+ICB group, during the median follow-up period of 22.99 months, the RFS rate was 96.2%, the DFS rate was 96.2% and the OS rate was 100%.ConclusionThe combination of pembrolizumab with NAC could improve the pathological response without increasing the risk of toxicity, which provides pathological evidence for the treatment of LA HNSCC patients with NAC+ICB.

Anti-cancer Therapies in Adults and Their Effects on Cardiovascular System: A Review

The cardio-oncology as a field has been expanded by the rapid development of innovative cancer therapies. While these treatments had significantly improved the overall survival rates for cancer patients, they also carried the risk of cardiovascular and metabolic toxicities. A comprehensive and accurate diagnosis of cancer was paramount to initiate appropriate and effective treatment strategies. It was essential to recognize that each type of cancer presents unique characteristics and complexities, necessitating personalized treatment approaches tailored to individual patients. These treatment regimens often encompassed a combination of modalities such as surgery, radiotherapy, systemic therapy, including chemotherapy, antineoplastic hormonal agents, targeted therapies, and supportive care interventions. By implementing a tailored treatment plan based on the specific nature of the cancer, healthcare professionals might optimize therapeutic outcomes while minimizing adverse effects, ultimately improving the overall prognosis and quality of life for cancer patients. The concise review aims to underscore the effects of cancer and its treatments on cardiovascular health, drawing insights from prior research. By synthesizing findings from existing studies, we aim to elucidate the intricate relationship between cancer therapies and cardiovascular outcomes. Consequently, there is a pressing need for an updated summary to inform contemporary clinical practice, ensuring that healthcare professionals are equipped with the latest knowledge to provide optimal care for cancer patients while safeguarding their cardiovascular well-being.

Acyclovir Dosing Practices Across a Multicenter Cohort of Neonatal Intensive Care Units.

Acyclovir is the first-line therapy for neonatal herpes simplex virus infections. Therapy can mitigate morbidity and mortality but carries a risk for toxicity. We aimed to compare acyclovir dosing in neonatal intensive care units to published recommendations based on population pharmacokinetic (PopPK) analysis. We performed a multicenter cohort study of infants in neonatal intensive care units managed by the Pediatrix Medical Group from 1997 to 2020. We included all infants who received acyclovir with complete dosing information. Our primary outcome was the proportion of courses with dosing within 80%-120% of the PopPK recommended daily dose and at the recommended dosing frequency. We compared dosing before and after the publication of the 2014 PopPK recommendations using linear probability modeling. We identified 6862 infants with complete dosing information across 308 centers. Dosing met PopPK recommendations for 41% of treatment courses for infants <30 weeks postmenstrual age (PMA), 71% for infants 30 to <36 weeks PMA and <1% for infants ≥ 36 weeks PMA. Comparison of dosing from 1997 to 2013 with that from 2015 to 2020 showed a significant increase in dosing meeting PopPK recommendations for infants <30 weeks PMA (P = 0.008) and infants 30 to <36 weeks PMA (P = 0.02) but not infants ≥ 36 weeks PMA (P = 0.29). No significant increase in dosing meeting PopPK recommendations was seen for any PMA group when comparison was limited to more recent years (2008-2013 vs. 2015-2020). Dosing meeting PopPK recommendations increased over time for some PMA groups, but dosing different than PopPK recommendations remains common. More research is needed to clarify optimal dosing strategies in these infants.

How to treat advanced Hodgkin lymphoma?

In this review, we analyzed the different therapy options in patients with advanced Hodgkin lymphoma (HL). The treatment of advanced HL has greatly evolved during the last decade even still based on polychemotherapy. Mature data established that the better strategies require Positron emission tomography (PET)-driven treatments which allow to optimize the balance between disease control and both immediate and late treatment adverse effects, leading to cure most patients while minimizing the risk of toxicity. Indeed, PET-driven deescalated strategies offer the better treatment option. The recent incorporation of targeted therapies, anti-CD30 or anti-programmed cell death protein 1 (PD1) in combination with chemotherapy should quickly change the game and be a step forward to still decrease the risk of treatment toxicity and improve the cure rate. The standard of care for advanced HL remains currently PET-driven chemotherapy and should rapidly evolve with the addition of targeted therapy combined with chemotherapy.

Impact of Vancomycin trough levels monitoring on uncomplicated methilcillin-resistant Staphylococcus aureus bacteremia in chronic kidney disease on hemodialysis, retrospective cohort

BackgroundCKD patients on hemodialysis (HD) with Staphylococcus aureus (SA) bacteremia present high morbidity, mortality and increased risk of MRSA. Vancomycin is the antibiotic of choice in these cases, it has a narrow therapeutic margin and inadequate dosage generates a risk of toxicity, therefore, the recommendation is to dosage it through serum levels.MethodsThis is a retrospective cohort study in 3 hospitals of third level of complexity in the city of Medellin in which there were differences in the measurement and implementation of vancomycin25 dosage based on trough levels (VL) in patients with chronic kidney disease on hemodialysis (CKD- HD) with uncomplicated bacteremia based infection by methilcillin-resistant Staphyloccocus aureus (MRSA). The primary outcome was the composite of hospital mortality, clinical response (fever, hemodynamic instability and altered consciousness), complications associated with bacteremia, or bacteriological response failure (positive cultures at first week follow-up) at 7 days. The composite variables were analyzed individually as secondary outcomes.ResultsThe main unadjusted outcome (OR 1.3, CI 0.6 - 2.7) and adjusted for age, Charlson index, loading dose, initial dose, dosing frequency and MIC to vancomycin (OR 1.2, CI 0.5 - 2.7). Regarding adjusted secondary outcomes: clinical response (OR 1.4 CI 0.3 - 5.8), death (OR 1.3 CI 0.3 - 4.6) and complications (OR 0.9, CI 0.37 - 2.2).ConclusionsWe conclude that the measurement of trough levels in patients with HD-CKD does not modify the composite outcome. The main limitation is the sample size and type of study, randomized control trials may be required to confirm the results presented.

Chlorinated Anthracenes Induced Pulmonary Immunotoxicity in 3D Coculture Spheroids Simulating the Lung Microenvironment.

Chlorinated anthracenes (Cl-Ants), persistent organic pollutants, are widely detected in the environment, posing potential lung toxicity risks due to frequent respiratory exposure. However, direct evidence and a comprehensive understanding of their toxicity mechanisms are lacking. Building on our prior findings of Cl-Ants' immunotoxic risks, this study developed a three-dimensional coculture spheroid model mimicking the lung's immune microenvironment. The objective is to explore the pulmonary immunotoxicity and comprehend its mechanisms, taking into account the heightened immune reactivity and frequent lung exposure of Cl-Ants. The results demonstrated that Cl-Ants exposure led to reduced spheroid size, increased macrophage migration outward, lowered cell viability, elevated 8-OHdG levels, disturbed anti-infection balance, and altered cytokine production. Specifically, the chlorine substituent number correlates with the extent of disruption of spheroid indicators caused by Cl-Ants, with stronger immunotoxic effects observed in dichlorinated Ant compared to those in monochlorinated Ant. Furthermore, we identified critical regulatory genes associated with cell viability (ALDOC and ALDOA), bacterial response (TLR5 and MAP2K6), and GM-CSF production (CEBPB). Overall, this study offers initial in vitro evidence of low-dose Cl-PAHs' pulmonary immunotoxicity, advancing the understanding of Cl-Ants' structure-related toxicity and improving external toxicity assessment methods for environmental pollutants, which holds significance for future monitoring and evaluation.

Thirty-day risk of digoxin toxicity among older adults co-prescribed trimethoprim-sulfamethoxazole versus amoxicillin: A population-based cohort study.

Trimethoprim-sulfamethoxazole (TMP-SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity. To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin. Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688). Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin. The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD. A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]). In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.

Enhancing aquaculture using nanotechnology: a review

The advent of nanotechnology is a laudable discovery, and to a large extent, it has potentials to solve many nagging problems in aquaculture industry. For instance, the challenge of recurring resistance of bacteria to antibiotics, and the myriad of different antibiotics in the market coupled with their toxic effect on fish and water is a serious concern. Nanotechnology provides new tools (Nanomaterials) which can find applications in various aspect of aquaculture with little or no risk of toxicity. These include: Nanosensors, DNA nanovaccines, nanogene delivery, smart drug delivery, nanobarcoding, fish growth enhancement using nanoselenite, nanodelivery of nutraceuticals, nanofilteration, nanopolymers, nanocoating, nanofeed to improve buoyancy and availability of feed during feeding, and nanonet treatment and so on. These products are readily available in the market. They can also be synthesized for application in the areas highlighted above. This paper presents a review on nanotechnology and its application to enhance various aspects of aquaculture with a view to finding effective management strategy to solve hydra-headed challenges bedevilling aquaculture industry by maximizing the full potential of nanomaterials