Adverse Reactions Research Articles

Detection and Quantification of Drug-Protein Adducts in Human Liver.

Covalent protein adducts formed by drugs or their reactive metabolites are risk factors for adverse reactions, and inactivation of cytochrome P450 (CYP) enzymes. Characterization of drug-protein adducts is limited due to lack of methods identifying and quantifying covalent adducts in complex matrices. This study presents a workflow that combines data-dependent and data-independent acquisition (DDA and DIA) based liquid chromatography with tandem mass spectrometry (LC-MS/MS) to detect very low abundance adducts resulting from CYP mediated drug metabolism in human liver microsomes (HLMs). HLMs were incubated with raloxifene as a model compound and adducts were detected in 78 proteins, including CYP3A and CYP2C family enzymes. Experiments with recombinant CYP3A and CYP2C enzymes confirmed adduct formation in all CYPs tested, including CYPs not subject to time-dependent inhibition by raloxifene. These data suggest adducts can be benign. DIA analysis showed variable adduct abundance in many peptides between livers, but no concomitant decrease of unadducted peptides. This study sets a new standard for adduct detection in complex samples, offering insights into the human adductome resulting from reactive metabolite exposure. The methodology presented will aid mechanistic studies to identify, quantify and differentiate between adducts that result in adverse drug reactions and those that are benign.

Improvement in pain by using lidocaine combined with esketamine in elderly patients receiving local anaesthesia for percutaneous kyphoplasty: a randomized controlled study

BackgroundElderly patients often experience severe pain during percutaneous kyphoplasty under local anaesthesia. The aim of this work was to evaluate the effect of lidocaine combined with esketamine on pain improvement in elderly patients receiving local anaesthesia via percutaneous kyphoplasty.MethodsThis prospective, randomized comparative trial was conducted on 66 elderly patients, aged 60–80 years, with an American Society of Anaesthesiologists (ASA) grade of I-III, I‒III and a BMI of 18.5–25 kg/m2, who underwent single-level lumbar percutaneous kyphoplasty under local anaesthesia. Patients were divided into two equal groups (33 per group). Group LE received 200 mg of 1% lidocaine and 25 mg of esketamine (total volume of 20 ml), and Group L received 200 mg of 1% lidocaine (total volume of 20 ml). Patient characteristics, surgery, VAS scores, MAP, HR, MOAA/S scores, patient satisfaction and related adverse reactions were compared for the groups. The VAS scores during and after surgery were considered the primary outcome.ResultsThere were statistically significant differences in the VAS score between the two groups at the following time points: channel establishment by the puncture needle, balloon dilation, bone cement injection and postoperative period (P < 0.05). The VAS score decreased in the LE group, but the MAP and HR were more stable, and the difference was statistically significant (P < 0.05). The difference in the MOAA/S score between the two groups was statistically significant (P < 0.05), and the MOAA/S score in the LE group decreased. The patient satisfaction level in the LE group was 100% and 48.48% in the L group (P < 0.05). There were no related complications or adverse reactions in either group.ConclusionThe application of lidocaine combined with esketamine in local episcopal percutaneous vertebral kyphoplasty in elderly patients not only provides an effective analgesic effect but also improves surgical safety and patient comfort, which has important clinical value in promoting the optimization of surgical anaesthesia management in elderly patients.Trial registrationThe study was registered at Chictr.org.cn with the number ChiCTR2400083466 on 06/12/2023.

Construction and practice of a novel pharmaceutical health literacy intervention model in psychiatric hospital.

Pharmaceutical health literacy intervention (PHLI) plays a crucial role in influencing patients' medical decision-making, particularly concerning medication use. However, PHLI has not been widely implemented in China. This study aims to develop a novel PHLI model within a psychiatric hospital setting and evaluate its effectiveness. A PHLI model encompassing four modes-covering inpatients, outpatients, Internet+ and community-was established at The Affiliated Mental Health Center of Jiangnan University. The model's operation was detailed, and its performance data from 2022 and 2023 were evaluated. In 2022 and 2023, a total of 636 PHLI cases were reported. Of these, 386 cases (60.69%) were identified through the inpatient mode. The proportion of PHLI delivered via inpatient and Internet information subscription modes gradually increased, while interventions through other methods decreased. The age group of 18-30 accounted for 21.97% of cases, with 116 instances reported. Various types of PHLI were provided, including adverse reactions (18.87%), dosage and administration (11.64%), and therapeutic drug monitoring (9.43%). In addition, intervention strategies primarily focused on adverse reaction identification (10.22%), interpretation of pharmaceutical reports (7.23%), and routine examination reminders (6.45%). The PHLI model developed at our hospital offers an effective approach to health literacy intervention and represents an innovation advancement in pharmaceutical health literacy management. It can also serve as a reference framework for other hospitals.

The Efficacy and Safety of Liraglutide in Patients Remaining Obese 6 Months after Metabolic Surgery.

The safety and efficacy of liraglutide as a weight loss intervention in individuals who remain obese within 1year post-metabolic surgery remain unclear. This study aimed to evaluate the effects and safety of liraglutide (1.8mg) in patients with persistent obesity at 6months postoperatively. This retrospective cohort study included 61 patients who remained obese (body mass index [BMI] ≥ 28.0kg/m2) at 6months postoperatively. Among these patients, 27 were treated with 1.8mg of liraglutide for 12weeks, whereas 34 served as controls. The primary endpoint was the change in total weight loss (%TWL) after 24weeks. Changes in weight, BMI, complications, and adverse events were also assessed. The liraglutide group showed a greater reduction in %TWL than the control group (11.6% ± 1.1% vs. 4.9% ± 1.0%), with an estimated treatment difference of 6.6% (95% confidence interval [CI], 3.7-9.6%, P < 0.01). The adjusted mean differences in the reduction of weight and BMI between the liraglutide and control groups were -6.2kg (95% CI -8.9 to -3.4, P < 0.01) and -3.0kg/m2 (95% CI -4.2 to -1.7, P < 0.01), respectively. The liraglutide group exhibited increased rates of remission in non-alcoholic fatty liver disease and hypertension. No serious adverse reactions were observed. For patients who remained obese at 6months postoperatively, 12-week liraglutide treatment resulted in increased weight loss, improved metabolic control, and high rate of remission for obesity-related metabolic diseases after 24weeks. Earlier and more timely adjuvant weight loss medication intervention based on BMI within 1year postoperatively may enhance weight loss after metabolic surgery. Graphical abstract available for this article.

A comparative study of hypolipidemic effect of atorvastatin and Coriandrum sativum in triton-induced hyperlipidemic albino rat model

Background: Hyperlipidemia is the main factor responsible for coronary artery disease. Atorvastatin commonly used, as a competitive inhibitor of HMG-Co-A reductase, is known to reduce LDL and triglyceride levels and increase HDL levels. Coriandrum sativum (Coriander) belongs to the Apiaceae family and has hypolipidemic, antidiabetic, and antioxidant properties. Triton WR1339 has been used by several studies to induce hypercholesterolemia in animals which acts on both the synthesis and excretory phase. This study aimed to compare the hypolipidemic effect of Coriandrum sativum and atorvastatin in triton-induced hyperlipidemic rats. Methods: Following approval from the Institutional Animal Ethics committee, 36 Wistar albino rats were divided into 6 groups of 6 animals each. Triton 200mg IP was administered to all the groups except Group 1 (control). Groups 3 and 4 received Coriander extract 300mg/kg and Atorvastatin 80mg/kg orally with Triton. Groups 5 and 6 received Coriander extract and Atorvastatin respectively 22 hours later. Lipid profile was estimated 24 hours before, 24 and 48 hours after administering Triton. Results: In the synthesis phase, there is a statistically significant increase in the lipid levels in Groups 2, 5, and 6 compared to Groups 3 and, 4 indicating hypolipidemic effects of both Coriander extract and Atorvastatin. In the excretory phase, all groups have shown a decrease in lipid levels but a decrease in total cholesterol level in Group 5 compared to Group 3 was significant. Conclusions: Atorvastatin and Coriander extract both affect the lipid levels in the synthesis and excretory phase. Even though coriander cannot replace atorvastatin in the management of hyperlipidemia, it can be used as an adjuvant to atorvastatin to reduce the cost effects and adverse reactions caused by allopathic medicines.

Bioequivalence and Pharmacokinetic Evaluation of Regorafenib Tablets in Healthy Chinese Volunteers.

This was a single-center, randomized, open-label, 2-formulation, and 2-cycle crossover trial conducted in 48 healthy Chinese volunteers, under fasting and fed conditions. The participants received oral doses of the test formulation (regorafenib) and reference formulation (40mg) during each study period. Blood samples were collected before and up to 144hours after the formulations were administered to determine changes in the pharmacokinetic parameters and adverse reactions, which were then used to evaluate bioequivalence and safety. The geometric mean ratios of maximum blood concentration, area under the plasma concentration-time curve from time 0 to the last quantifiable concentration, and area under the plasma concentration-time curve from time 0 to infinity for regorafenib were as follows: 94.7%, 91.4%, and 91.7%, respectively, under fasting conditions; and 94.6%, 97.7%, and 98.8%, respectively, under fed conditions. The 90% confidence intervals for the geometric mean ratios were within the 80%-125% equivalence interval for both the fasting and fed tests. Ingesting high-fat and high-calorie foods increases exposure to regorafenib, leading to slower rates of absorption. The safety profiles of the 2 preparations were similar.

Subclinical hypothyroidism and plasma levels of commonly prescribed anti-seizure medications

Background: Epilepsy remains the most common neurological problem worldwide. Most commonly prescribed antiseizure medications (ASMs) like phenytoin, sodium valproate, and carbamazepine show high inter-individual variability in bioavailability due to genetic and epigenetic factors resulting in either therapeutic failure or toxicity. In our study, we aim to determine the association between subclinical hypothyroidism and the plasma levels of these commonly prescribed ASMs, leading to either therapeutic failure or adverse drug reactions. Methods: We collected demographic data, details about the antiepileptic medication, and plasma levels of ASMs (phenytoin, carbamazepine, and sodium valproate) from patients on antiseizure medications who came for routine therapeutic drug monitoring (TDM). High-performance liquid chromatography (HPLC) estimated plasma levels of the antiseizure medications as per the TDM laboratory standard operating procedure (SOP) and thyroid function test (TSH) by a standard enzyme-linked immune-sorbent assay (ELISA) kit. Results: Of the 158 patients who had TDM, 75.31% were taking sodium valproate, 15.18% were on phenytoin, and 9.49% were on carbamazepine monotherapy. In our study, we found that 12 patients (7.59%) had TSH levels between 4 to 10 mIU/l, indicating subclinical hypothyroidism (SCH). The plasma drug levels of all 12 patients who had SCH were found to be below the therapeutic range. Conclusions: This study has established a significant association between ASMs, particularly sodium valproate, and thyroid dysfunction, specifically SCH, in patients with epilepsy. Our findings suggest that prolonged ASM therapy can lead to thyroid disturbances, warranting careful monitoring of thyroid function in these patients.

Febuxostat-induced agranulocytosis in a pediatric hematopoietic stem cell transplant recipient: Case Report and literature review

This report describes a pediatric case of isolated agranulocytosis occurring months after hematopoietic stem cell transplantation (HSCT). Secondary cytopenia, or secondary transplant failure, affects 10%–25% of HSCT recipients, with potential triggers including viral infection, graft-versus-host disease (GVHD), sepsis, and certain medications. Viral reactivation was ruled out based on negative PCR results, while GVHD and sepsis were ruled out based on the patient’s clinical presentation. The patient, who received an HLA 10/10 unrelated donor T-cell transplant, underwent standard myeloablative conditioning to minimize the risk of graft rejection. However, agranulocytosis persisted even after discontinuation of myelotoxic drugs such as valganciclovir and ruxolitinib. Further investigation revealed that the patient had been taking febuxostat, which was subsequently discontinued, leading to a recovery of the neutrophil count. The European Medicines Agency lists agranulocytosis as a rare side effect of febuxostat. The effect of candidate genes and variants involved in febuxostat pharmacokinetics and pharmacodynamics was done using the Pharmacogenomics Knowledge Base (PharmGKB) to accurately evaluate an individual’s risk for neutropenia. This case suggests that genetic variants in renal transporters ABCG2 (exonic non-synonymous variant, rs2231137), SLC29A1 (rs747199 and rs628031), and ABCC4 (3′UTR SNP, rs3742106 and rs11568658) may contribute to drug-induced agranulocytosis. This finding underscores the importance of genetic profiling in the management of patients undergoing HSCT to prevent adverse drug reactions.

Assessment of knowledge, attitude, and practice of pharmacovigilance amongst undergraduate students at a tertiary care teaching hospital: a questionnaire-based study

Background: Pharmacovigilance ensures patient safety and rational medication use. Spontaneous reporting by healthcare professionals is crucial, but underreporting is a major limitation. Education and training are vital to improve Adverse Drug Reaction (ADR) reporting. Inculcating pharmacovigilance into undergraduate programs empowers medical students to report ADRs. Methods: This prospective questionnaire-based study focused on assessing knowledge, attitude, and practice (KAP) regarding pharmacovigilance. A total of 223 medical undergraduate students of which 156 were students in 2nd year and 67 in 3rd final years who gave their consent were included in this study. Participants completed a pre-questionnaire before undergoing a training session on pharmacovigilance related to KAP. Following the training session, a post-questionnaire was given. Pre- and post-test questionnaires were compared and analysed using an appropriate statistical test. Results: The study showed that knowledge and attitude scores among second and third-year medical students improved after the training program. Following training, the mean knowledge score for second-year students significantly increased from 5.56 to 8.6, while their mean attitude score increased from 5.9 to 7.24. Similarly, for third-final-year students, the mean knowledge score improved from 6.62 to 9.01, and the mean attitude score increased from 6.69 to 7.52. The results clearly showed that the training program had a positive impact on the knowledge and attitude of both student groups. The mean practice scores for second-year and third-final-year students were 0.76 and 1.34, respectively. Conclusions: The study showed significant improvement in knowledge and attitude after the educational intervention, indicating a positive impact of the training program.

A rare case report of diclofenac induced Steven Johnson syndrome

Stevens Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are acute life-threatening mucocutaneous diseases characterized by extensive necrosis involving the mucous membrane and epidermis. In this case, a 54-year-old female after intake of prescribed diclofenac tablet presented with multiple reddish maculopapular eruptions over face, abdomen, both limbs, over lips and oral cavity associated with pain and intense pruritus. This case is a rare presentation of drug induced SJS caused by commonly prescribed NSAID, diclofenac. Patient’s condition improved after withdrawal of offending drug and prompt treatment. This case suggests that emphasis on early detection, assessment and timely management of adverse drug reactions is of upmost importance. Thus, establishment of proper vigilance centre and regular monitoring is necessary and taking caution in prescribing drugs as well in elderly groups.

Inappropriate ceftriaxone utilization and predictor factors in Ethiopia: a systematic review and meta-analysis

Ceftriaxone stands as a cornerstone in global antibiotic therapy owing to its potent antibacterial activity, broad spectrum coverage, and low toxicity. Nevertheless, its efficacy is impeded by widespread inappropriate prescribing and utilization practices, significantly contributing to bacterial resistance. The aim of this study is to determine the overall national pooled prevalence of inappropriate ceftriaxone utilization and its predictor factors in Ethiopia. A systematic search was conducted across multiple databases including, PubMed, Science Direct, Hinari, Global Index Medicus, Scopus, Embase, and a search engine, Google Scholar, to identify relevant literatures that meet the research question, from March 20 to 30, 2024. This meta-analysis, which was conducted in Ethiopia by incorporating 17 full-text articles, unveiled a national pooled inappropriate ceftriaxone utilization of 55.24% (95% CI, 42.17%, 68.30%) with a substantial heterogeneity index (I2 = 99.24%, p value < 0.001). The review has also identified predictive factors for the inappropriate use of ceftriaxone: empiric therapy (AOR 21.43, 95% CI; 9.26–49.59); multiple medication co-prescription (AOR: 4.12, 95% CI; 1.62–8.05). Emergency ward (AOR: 4.22, 95% CI; 1.8-12.24), surgery ward (AOR: 2.6, 95% CI; 1.44–7.82) compared to medical ward, prophylactic use (AOR: 500, 95% CI; 41.7–1000), longer hospital stay-8-14 Days; (AOR: 0.167, 95% CI; 0.09–0.29), > 14 days; (AOR: 0.18, 95% CI; 0.1–0.32). The study reveals a high national pooled prevalence of inappropriate ceftriaxone utilization, standing at 55.24%, highlighting a significant hazard in the use of this antibiotic. This could be attributed to instances of overuse, misuse or prescription practices that deviates from established guidelines. This eminent challenge can lead to the development of antibiotic resistance, increased healthcare costs, adverse drug reactions, and treatment failures, necessitating multifaceted approach such as improved antibiotic stewardship, better adherence to guidelines, and enhanced clinician education on appropriate antibiotic use.

Is the combination of propranolol and flunarizine better than propranolol, flunarizine and amitriptyline alone in prophylaxis of migraine? An observational study at a tertiary care centre of North India

Background: Migraine is a primary headache disorder marked by recurrent attacks of pain and associated symptoms. Propranolol is traditionally considered highly effective for migraine prophylaxis, but other drugs have recently shown promise. Methods: This study was a prospective, observational, randomized, parallel-arm, unicentric trial conducted in the neurology department of a tertiary care hospital in North India. Patients with migraine without aura were randomly assigned to one of four treatment groups. After obtaining consent, patients were randomized using a random number table. Group 1 received propranolol (80 mg), group 2 received flunarizine (10 mg), group 3 received a combination of propranolol (40 mg) and flunarizine (10 mg), and group 4 received amitriptyline (10 mg) daily. The primary outcome was a change in the frequency of migraine days, while secondary outcomes included changes in moderate-to-severe headache days and disability levels. Results: The combination of propranolol (40 mg) and flunarizine (10 mg) was significantly more effective in reducing the frequency of migraine attacks at the end of 3 months compared to the group receiving amitriptyline (10 mg). However, no significant differences between the groups were observed at baseline, 1 month, and 2 months. For other outcomes, including adverse drug reactions (ADRs), there were no significant differences between the groups. Conclusions: The combination of propranolol (40 mg) and flunarizine (10 mg) demonstrated superior efficacy over amitriptyline (10 mg) after prolonged treatment, while its effectiveness was comparable to other groups at earlier time points. ADRs were similar across all groups.

Development of Minodronic Acid-Loaded Dissolving Microneedles for Enhanced Osteoporosis Therapy: Influence of Drug Loading on the Bioavailability of Minodronic Acid.

Osteoporosis is a metabolic bone disorder with impaired bone microstructure and increased bone fractures, seriously affecting the quality of life of patients. Among various bisphosphonates prescribed for managing osteoporosis, minodronic acid (MA) is the most potent inhibitor of bone context resorption. However, oral MA tablet is the only commercialized dosage form that has extremely low bioavailability, severe adverse reactions, and poor patient compliance. To tackle these issues, we developed MA-loaded dissolving microneedles (MA-MNs) with significantly improved bioavailability for osteoporosis therapy. We investigated the influence of drug loading on the physicochemical properties, transdermal permeation behavior, and pharmacokinetics of MA-MNs. The drug loading of MA-MNs exerted almost no effect on their morphology, mechanical property, and skin insertion ability, but it compromised the transdermal permeability and bioavailability of MA-MNs. Compared with oral MA, MA-MNs with the lowest drug loading (224.9μg/patch) showed a 9-fold and 25.8-fold increase in peak concentration and bioavailability, respectively. This may be ascribed to the reason that the increased drug loading can generate higher burst release, higher drug residual rate, and drug supersaturation effect in skin tissues, eventually limiting drug absorption into the systemic circulation. Moreover, MA-MNs prolonged the half-life of MA and provided more steady plasma drug concentrations than intravenously injected MA, which helps to reduce dosing frequency and side effects. Therefore, dissolving MNs with optimized drug loading provides a promising alternative for bisphosphonate drug delivery.

Chinese multidisciplinary expert consensus on the rational use of surufatinib in clinical practice（2024 edition）

Neuroendocrine neoplasms are a group of heterogeneous tumors originating from the neuroendocrine system, which can occur in any part of the body. Pulmonary and gastroenteropancreatic neuroendocrine tumors are the most common. In recent years, the global incidence of neuroendocrine tumors has increased more significantly than other types of tumors, especially in the past 40 years. The drug treatment of neuroendocrine tumors includes somatostatin analogues, anti-angiogenesis targeting drugs, nuclide therapy and chemotherapy. Surufatinib is an oral tyrosine kinase receptor inhibitors that targets for vascular endothelial growth factor receptor (VEGFR1-3), fibroblast growth factor receptor 1 (FGFR1), and colony-stimulating factor-1 receptor (CSF-1R), has received approval in 2020 and 2021 for the treatment of locally advanced or metastatic, progressive nonfunctional, well-differentiated (G1, G2) neuroendocrine tumors (NETs) of both pancreatic and extrapancreatic origin that are unresectable. Ongoing exploratory studies are investigating its potential application in other tumor types. Common adverse reactions observed during surufatinib treatment include hypertension, proteinuria, bleeding events, and hepatic lab test abnormal and diarrhea. Chinese multidisciplinary expert consensus on the rational use of surufatinib in clinical practice (2024 edition) aims to provide standardized guidance for its rational use and enhance patient compliance to maximize therapeutic benefits.

Cardiac dysfunction associated with lacosamide in a premature infant with Hypoxic Ischemic Encephalopathy: A case report.

Lacosamide [Vimpat® Harris FRC Corporation. © 2022 UCB, Inc. Smyrna, GA 30080] is an antiseizure medication which acts through blockage of voltage-gated neuronal sodium channels. Its recent implementation in the neonatal population has been extrapolated from adult and pediatric data suggesting a favorable safety profile. (1) Of note, preterm infants have unique developmental characteristics that may predispose them to increased risk of adverse reactions. We present a case of a preterm neonate who developed left ventricular (LV) dysfunction coinciding with the initiation of lacosamide.

Comparative analysis of semaglutide induced adverse reactions: Insights from FAERS database and social media reviews with a focus on oral vs subcutaneous administration

BackgroundCompared to alternative weight-loss strategies and medications, semaglutide stands out for its convenience and efficacy, resulting in a significant increase in prescriptions and raising public safety concerns. Furthermore, the safety profiles of its oral and subcutaneous formulations require further examination.ObjectiveOur goal is to investigate the potential safety risks associated with semaglutide by analyzing data from the FAERS database and social media. Additionally, we aim to compare the adverse drug reaction (ADR) signals between the oral and subcutaneous administration routes of semaglutide.MethodsWe collected semaglutide-related reports from the FAERS database spanning Q1 2018 to Q2 2023, and patient reviews on WebMD and AskaPatient up to 20 July 2023. Following data extraction and cleansing, we conducted descriptive analyses of demographic characteristics. Subsequently, we calculated adverse drug reaction (ADR) signals using the reporting odds ratio (ROR).ResultsWe identified 19,289 and 422 semaglutide-related adverse drug events (ADEs) reported in the FAERS database and online patient reviews, respectively. Gastrointestinal disorders emerged as the most commonly reported System Organ Class (SOC) in both datasets. Predominant Preferred Terms (PTs) included nausea, vomiting, and diarrhea. Serious outcomes constituted 3.07% and 2.25% of all cases for oral and subcutaneous semaglutide, respectively. At the SOC level, gastrointestinal disorders accounted for 30.19% of total ADEs in oral semaglutide, slightly surpassing the 27.76% in subcutaneous semaglutide. The median onset for gastrointestinal PTs was 4 days in both oral (Q1: 1, Q3: 32) and subcutaneous (Q1: 1, Q3: 35) formulations. Noteworthy, new serious adverse event (AE) signals were identified, including hemorrhagic diarrhea (ROR: 3.69), hepatic pain (ROR: 4.20), abnormal hormone levels (ROR: 6.51), and pancreatic failure (ROR: 36.34) in subcutaneous semaglutide, and Dupuytren’s contracture (ROR: 46.85) in oral semaglutide.ConclusionOur study delineates the safety profile of semaglutide using data from the FAERS database and social media. And identified novel ADR signals specific to oral and subcutaneous forms of semaglutide.

Adverse drug reactions following treatment of latent tuberculosis infection: a linked national tuberculosis surveillance with claims database.

Few real-world studies explored factors associated with latent tuberculosis infection (LTBI) treatment-related adverse drug reactions (ADRs). This study evaluate ADRs that lead to the discontinuation of LTBI treatment and identify the associated factors, including age groups and drug regimens. Using the Korean national tuberculosis registry and HHC investigation database linked to the National Health Insurance Service claims database, we examined treatment discontinuation due to ADRs among HHCs on LTBI treatment from January 2015 to December 2018. Multivariable logistic regression analysis was conducted to examine factors associated with ADRs, including demographics, LTBI treatment, comorbidities, and steroid use. Among 11,913 participants initiated LTBI treatment, 633 participants (5.3%) discontinued treatment due to ADRs. The primary contributors to discontinuation were adverse skin reactions (2.0%) and abnormal liver function (1.9%). Risk associated with ADRs and abnormal liver function showed age-related increase, except for the age group 66-75 (adjusted odds ratio [AOR] 3.82, 95% confidence interval [CI] 2.31-6.31) which reported lower OR to that of age group 36-65 (AOR 4.38, 95% CI 3.09-6.21). Three months isoniazid/rifampin and 4 months rifampin exhibited a lower odds of ADRs and abnormal liver function when compared to 6-9 months isoniazid. We discovered the real-world prevalence of LTBI treatment discontinuation due to ADRs among HHCs. Our findings suggest a notably increased odds of ADRs resulting in discontinuation with age of 76 years or above, emphasizing careful attention when prescribing LTBI treatment in this population. Further studies are warranted to validate these results.

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

BackgroundAmiodarone and dronedarone are both class III antiarrhythmic medications used to treat arrhythmias. The objective of this study was to enhance the current understanding of adverse drug reaction (ADR) associated with amiodarone and dronedarone by employing data mining methods on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), and providing a reference for safe and reasonable clinical use.MethodsThe ADR records were selected by searching the FAERS database from 2011 Q3 to 2023 Q3. The disproportionality analysis algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were used to detect signals of amiodarone-related and dronedarone-related ADRs. The ADR profiles of amiodarone and dronedarone categorized by organ toxicity were compared through the Z-test and the Fisher exact test.Results9,295 reports specifically mentioned the use of amiodarone and 2,485 reports mentioned the use of dronedarone among 9,972,109 reports, with the majority of ADRs occurring in males over 60 years old. The United States was responsible for the highest proportion of reported ADRs. Significant system organ classes (SOC) for both included Cardiac disorders, Respiratory, thoracic and mediastinal disorders, and Investigations, etc. At the preferred terms (PTs) level, the more frequent ADR signals for amiodarone were drug interaction (n = 856), hyperthyroidism (n = 758), and dyspnoea (n = 607), while dronedarone were atrial fibrillation (n = 371), dyspnoea (n = 204), and blood creatinine increased (n = 123). Notably, unexpected ADRs, including electrocardiogram T wave alternans (n = 16; EBGM05 = 231.27), accessory cardiac pathway (n = 11; EBGM05 = 140), thyroiditis (n = 178; EBGM05 = 125.91) for amiodarone, and cardiac ablation (n = 11; EBGM05 = 31.86), cardioversion (n = 7; EBGM05 = 22.69), and dysphagia (n = 47; EBGM05 = 3.6) for dronedarone, were uncovered in the instructions. The analysis also revealed significant differences in the ADR profiles of amiodarone and dronedarone, with dronedarone showing higher proportions of cardiac toxicity but lower thyroid toxicity compared to amiodarone.ConclusionThese findings underscore the significance of vigilantly monitoring and comprehending the potential risks linked to the use of amiodarone and dronedarone. New ADRs discovered and clear ADR profiles of amiodarone and dronedarone enhance a thorough understanding of these drugs, which is essential for clinicians to ensure safe use of amiodarone and dronedarone.

Utilizing Ziziphus spina-christi for eco-friendly synthesis of silver nanoparticles: Antimicrobial activity and promising application in wound healing

Abstract Wound healing is a critical process essential for the body’s recovery from injuries, often complicated by bacterial infections. Silver nanoparticles (AgNPs) have gained attention due to their antibacterial and tissue-regenerative properties. However, conventional chemical synthesis methods for AgNPs pose environmental risks. This study utilizes Ziziphus spina-christi (ZSC) extract for the eco-friendly synthesis of AgNPs, evaluating their antibacterial and wound-healing capabilities. The AgNPs-ZSC showed an absorption maximum at λ max of 460 nm, a particle size of 111.2 ± 1.09 nm, a polydispersity index of 0.38 ± 0.006, and a zeta potential of −27.0 ± 0.231 mV. The synthesized AgNPs-ZSC were spherical, non-aggregated, and exhibited potent antibacterial activity superior to chloramphenicol. Furthermore, the AgNPs-ZSC cream significantly promoted wound closure, epithelial tissue proliferation, and granulation tissue formation in rats, showing no signs of toxicity or adverse reactions. In conclusion, AgNPs-ZSC cream demonstrates excellent antibacterial and wound-healing properties, presenting a sustainable alternative to conventional chemical methods for AgNP synthesis.

Challenges of infectious diseases in older adults: From immunosenescence and inflammaging through antibiotic resistance to management strategies

Infectious diseases in older adults present a significant challenge to the healthcare system, marked by increased morbidity, mortality, and rising costs of care. Age-related changes (ARCs) in the immune system, including immunosenescence and inflammaging, contribute to heightened susceptibility to severe infections and reduced vaccine responsiveness. Additionally, alterations in the normal microbial flora due to aging and factors such as antibiotic therapy predispose older individuals to infections and age-related diseases. Changes in body composition also affect the pharmacokinetics and pharmacodynamics of drugs, complicating the management of antibiotics and leading to potential overdoses, adverse drug reactions, or underdoses that foster antibiotic resistance. The inappropriate use of antibiotics has exacerbated the emergence of multidrug-resistant pathogens, posing a critical global concern. This narrative review provides an overview of immunosenescence and inflammaging and focuses on three major infectious diseases affecting older adults: bacterial pneumonia, urinary tract infections, and Clostridium difficile infections. Through this exploration, we aim to highlight the need for targeted approaches in managing infectious diseases in the aging population.