Drug-related Adverse Reactions Research Articles

A Rare Case of Tremor Induces by Cycloserine in Drug-Resistant Tuberculosis Patient

Background: Tuberculosis is a contagious disease that generated by Mycobacterium tuberculosis. Drug-Resistant tuberculosis (DR-TB) is inculpated the use of the second-line anti-tubercular treatment which is associated with many drug side effects or so called, Adverse Drug Reactions (ADR). Cycloserine (Cs) is an important drug against drug resistant tuberculosis (DR-TB). Cycloserine has been used in tuberculosis therapy since the late 1950s. Identical with most drug, Cycloserine can cause many Adverse Drug Reactions (ADR). Case Illustration: A 23-year-old woman diagnosed with drug-resistant tuberculosis is undergoing long-term treatment. The patient received treatment for DR-TB with the Bdq-Lfx-Cfz-Cs-E regimen. After the patient underwent the 10th month of advanced phase treatment, the patient complained of shaking in both hands (tremors). The tremor is felt to be more severe in the right hand and the patient cannot grip objects tightly. Discussion: Cycloserine (Cs) play an important role in second-line drug management of DR-TB. Cs-Induced psychosis and other neurological side-effects can be detrimental towards patients yet they are rarely reports in DR-TB cases. Cs is correlated with severe psychiatric cases and Central Nervous System related ADRs. Cs-associated ADR is most likely because of production of gamma-aminobutyric acid as a result of inhibition of glutamic decarboxylase. Study Shown that among 132 patients who reported side effects in the cycloserine group, 2 (1.4%) experienced major side effects, namely tremors. Side effects possibly or probably related to Cs appeared after a median of 71 days (range 10–331 days) of Cs treatment. Conclusion: the drug side effects such as tremors are very rare in drug-resistant tuberculosis patients. In this case, the patient's complaint of tremors could be caused by cycloserine as an anti-tuberculosis drug.

Efficacy and Safety of Ciprofol Versus Propofol as Anesthetic for Patients Undergoing Painless Colonoscopy.

Ciprofol is a novel propofol analogue with a characteristic of hemodynamic stability. At present, there is a lack of research comparing the hemodynamic stability of ciprofol and propofol during painless colonoscopy. In this study, we aim to test the hypothesis that ciprofol is superior to propofol in terms of hemodynamic stability for sedation anesthesia in patients undergoing colonoscopy. A total of 222 patients were randomized into two groups. Patients in group P (n=112) and group C (n=110) received propofol and ciprofol sedation, respectively. Noninvasive blood pressure were monitored starting from induction (T0) to the end of the procedure, at 2-min intervals (T1 to T10). Heart rate variability (HRV), pain injection, Modified Observer's Assessment of Alertness and Sedation(MOAA/S) score, body movement, doses of norepinephrine, modified Aldrete score, drug-related adverse reactions, and patient satisfaction and endoscopist satisfaction were recorded. In group C, fewer patients experienced a decrease in blood pressure with a higher HRV after induction sedation, the incidence of pain injection was reduced, the amount of norepinephrine dose was decreased, patient satisfaction was increased compared with group P (all P<0.05). There were no significant differences in induction time, modified Aldrete score, alertness time, drug-related adverse reactions, and endoscopist satisfaction. Our study indicated intravenous induction with ciprofol was superior, with regard to hemodynamic stability and reduced injection pain, than induction with propofol for anesthesia in patients undergoing painless colonoscopy. Chinese Clinical Trial Registry (ChiCTR2200061814).

Real-World Large Sample Assessment of Drug-related Dry Eye Risk: Based on the FDA Adverse Event Reporting System Database

Purpose and designThis study aimed to evaluate the risk of drug-related dry eye using real-world data, underscoring the significance of tracing pharmacological etiology for distinct clinical types of dry eye. MethodsAnalyzing adverse event reports in the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to September 2023, we employed disproportionality analysis and the Bayesian confidence propagation neural network algorithm. The analysis involved categorizing drugs causing dry eye, assessing risk levels, and conducting segmental assessments based on the time of onset of drug-related dry eye adverse reactions. ResultsIn the FAERS database, adverse reactions related to dry eye were linked to 1160 drugs. Disproportionality analysis identified 33 drugs with significant risk, notably in ophthalmic (brimonidine, bimatoprost), oncology (tisotumab vedotin, erdafitinib), and other medications (isotretinoin, oxymetazoline). The top three drugs with the highest risk of drug-related dry eye are isotretinoin (Bayesian confidence propagation neural network (BCPNN) = 6.88), tisotumab vedotin (BCPNN = 6.88), and brimonidine (BCPNN = 6.77). Among different categories of drugs, respiratory medications have the shortest mean onset time for drug-related dry eye, averaging 50.99 days. The prevalence skewed towards females (69.9 %), particularly in menopausal and elderly individuals (45–70 years old, mean age 54.7 ± 18.2). Reports of drug-related dry eye adverse reactions showed an annual increase. ConclusionInformed clinical decision-making is crucial for preventing drug-related dry eye. Assessing the risk of dry eyes associated with both local and systemic medications helps optimize treatment and provide necessary cautionary information.

Efficacy of immune checkpoint inhibitors combined with bevacizumab in MSS/pMMR advanced colorectal cancer after first-line treatment failure.

To investigate the effects of a PD-1 inhibitor combined with a bevacizumab monoclonal antibody on tumor immune cells in patients with first-line treatment failure in MSS/pMMR advanced colorectal cancer. Control group consisted of 50 patients treated with the FOLFIRI combined with Bevacizumab regimen. The experimental group consisted of 60 patients treated with the Sintilimab combined with Bevacizumab regimen. By comparing the expression levels of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment, short-term efficacy after treatment, and adverse drug reactions between the two groups, we comprehensively evaluated the impact of Sintilimab combined with Bevacizumab on patients with MSS/pMMR advanced colorectal cancer who failed first-line treatment. There was a statistically significant difference in the percentage of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment between the two groups (P<0.05);Immunohistochemical scoring of CD8+ T lymphocytes, TAMs, and CAFs showed significant differences between the groups post-treatment (P<0.05). The experimental group demonstrated statistically significant differences in immunohistochemical scoring of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment (P<0.05). There was a statistically significant difference in the therapeutic effect between the two groups of tumors (P<0.05). The experimental group had greater PFS, mPFS, ORR, and DCR than did the control group. There was no statistically significant difference in the occurrence rate of drug-related adverse reactions after treatment between the two groups (P>0.05). The results of the Cox proportional hazards model analysis indicate that age, gender, and group are independent risk factors affecting MSS/pMMR advanced colorectal cancer patients treated with second-line therapy in this study. Patients aged ≤60 years, male patients, and those in the experimental group showed better treatment responses in this study. By administering immune checkpoint inhibitors in combination with bevacizumab to patients with advanced colorectal cancer with MSS/pMMR disease for whom first-line treatment failed, not only did the patients' prognosis improve, but the adverse drug reactions were also safe and controllable.

Prevalence of cardiovascular drug-related adverse drug reactions consultations in UK primary care: A cross-sectional study.

Adverse drug reactions (ADRs) represent a significant barrier to achieve optimal treatment outcomes. Cardiovascular drugs, including antihypertensive drugs, lipid-lowering drugs, and antithrombotic drugs, are among the most prescribed medications in the primary care setting. To estimate the prevalence of cardiovascular drug-related ADRs consultations in United Kingdom (UK) primary care and identify risk factors of these ADRs. This was a cross-sectional study of cardiovascular drug users between 2000-2019 using UK IQVIA Medical Research Data. ADRs consultations were identified using database screening method employing standardised designated codes. The overall and annual age-standardised prevalence was estimated using direct standardisation method using 2019 mid-year UK population. Risk factors of ADRs consultations were estimated using logistic regression model stratified by therapeutic areas. The standardised prevalence of consultations related to cardiovascular drugs ADRs was 10.60 (95% CI. 10.46, 10.75) per 1000 patients. Patients aged 70-79 years had the highest occurrence of ADRs consultations. The most frequently drug classes implicated in the ADRs consultations were statins (n = 9,993 events, 27.09%), beta-blockers (n = 8,538 events, 23.15%), ACEIs/ARBs (n = 8,345 events, 22.62%), and aspirin (n = 6,482 events, 17.57%). Risk factors of ADRs consultations were previous history of cardiovascular diseases, e.g., myocardial infarction and stroke; advanced age, comorbidities; diabetes and dyslipidaemia; and polypharmacy. The burden of cardiovascular drug-related ADRs consultations in primary care was considerable. Statins, beta-blockers, ACEIs/ARBs, and aspirin were the most frequently implicated drug classes. Closer clinical monitoring should be performed for patients affected by the ADRs to mitigate the risk of suboptimal treatment outcomes.

Integrated management of multiple drugs for cardiovascular disease in older adults

Background: Older people have a high frequency of use of medical institutions due to their multiple comorbidities, which increases the frequency of drug-related problems or adverse drug reactions, such as duplicate prescriptions and inappropriate drug use. Polypharmacy in older people increases the risk of side effects and drug-drug interactions, thereby affecting health outcomes and quality of life. Because most elderly person with cardiovascular disease are already taking multiple drugs, the risk is inevitably high. Therefore, there is a need to develop strategies to mitigate the adverse effects of multidrug therapy in older adults with cardiovascular diseases.Current Concepts: We reviewed the latest relevant guidelines and literature in order to provide practical considerations for appropriate prescriptions for older people with cardiovascular disease, balancing unnecessary or harmful drugs with proven long-term benefits.Discussion and Conclusion: Continuous dialogue between healthcare providers and patients allows the close monitoring of drug efficacy and the prevention of adverse events. Drug therapy requires individualization as treatment goals vary with advancing age.

Construction of a microfluidic electrochemical sensor based on screen printing electrode for the detection of fluoxetine

Fluoxetine (FLX) is a widely-used antidepressant, and monitoring its blood drug concentration is crucial to ensure treatment effectiveness and prevent drug-related adverse reactions. This study constructed a microfluidic electrochemical sensor (COFTpTt@c-MWCNTs/SPCE) for the detection FLX in microliter-scale samples. Firstly, polydimethylsiloxane (PDMS) to construct microfluidic chip, the internal microchannels and structures significantly reduced the necessary sample volume for detection. Subsequently, the covalent organic framework material (COFTpTt) was synthesized by the solvothermal reaction of 1,3,5-triformylphloroglucinol (Tp) and melamine (Tt). This material was then combined with carboxylated multi-walled carbon nanotubes (c-MWCNTs) to form COFTpTt@c-MWCNTs, serving as the electrode modification material. COFTpTt with strong loading capacity and a large specific surface area, forming hydrogen bonds with FLX molecules and enhanced sensor selectivity. c-MWCNTs have excellent electron transfer capability. COFTpTt@c-MWCNTs were drop-coated onto the screen-printed carbon electrode (SPCE), integrated with the chip, forming the sensor. The inherent electrochemical activity of FLX enabled label-free detection. After optimizing the COFTpTt and c-MWCNTs ratio, the amount of COFTpTt@c-MWCNTs modification, and FLX solution pH, differential pulse voltammetry (DPV) was used to detect FLX solutions. The sensor showed a good linear relationship of FLX in the range 62.5–2000 ng mL−1 with a low limit of detection (LOD) of 24.3 ng mL−1 (S/N = 3) and good reproducibility and selectivity. This sensor had been successfully used for FLX detection in spiked rat serum samples, offering the potential for point-of-care testing of FLX.

Promoting dental patient safety toward judicious medication usage: a review

Objective: This critical review aimed to review strategies for health promotion and patient safety regarding the usage of drugs prescribed by dental practitioners. Methods: Manual searches were conducted on PubMed, Embase, and in the Cochrane database of systematic reviews using the keywords “dentistry”, “medication error”, “drug-related side effects and adverse reactions”, and “patient safety”. Publications by the World Health Organization, and the World Dental Federation were also searched to organize this review. Results: Several approaches have been identified to promote patient safety, including continuum education and training of practitioners, interdisciplinary work with clinical pharmacists, and electronic tools to aid practitioners in prescribing the adequate therapeutic regimen avoiding dosage errors and checking for potential drug interactions. Conclusion: Medication errors are common in dentistry, as such, it is fundamental that health professionals, patients, governments, and communities commit to advancing improvements and medication safety.

Antiviral Use in Mild-to-Moderate SARS-CoV-2 Infections during the Omicron Wave in Geriatric Patients.

(1) Background: Geriatric patients are at high risk of complications of Coronavirus disease-2019 (COVID-19) and are good candidates for antiviral drugs. (2) Methods: A retrospective study of electronic health records (EHRs) aiming to describe antiviral (nirmatrelvir and ritonavir (nirmatrelvir/r) or remdesivir) use, drug-drug interactions (DDIs) and adverse drug reactions (ADRs) in elderly patients (75 and over), hospitalized with mild-to-moderate COVID-19 between July 2022 and June 2023. (3) Results: Out of 491 patients (mean age: 86.9 years), 180 (36.7%) received nirmatrelvir/r, 78 (15.9%) received remdesivir, and 233 (47.4%) received no antiviral therapy. No association was found between the choice of antiviral and the demographic or medical data. No serious ADR was observed. Nirmatrelvir/r dosage adjustment was inadequate in 65% of patients with renal impairment. In total, 128 patients (71%) on nirmatrelvir/r had potential pharmacokinetic DDIs, with 43 resulting in a possibly related ADR. In the remdesivir group, pharmacodynamic DDIs were more frequent, with QTc prolongation risk in 56 patients (72%). Only 20 patients underwent follow-up ECG, revealing QTc prolongation in 4. (4) Conclusions: There is an underutilization of antivirals despite their justified indications. Nirmatrelvir/r dosage was rarely adjusted to renal function. Dose adjustments and closer monitoring are needed due to the high risk of drug interactions.

#1187 Acute kidney injury and tubulointerstitial nephritis following prescription of anticancer drugs: VigiBase analysis

Abstract Background and Aims Anticancer drugs can have varying effects on the kidneys, depending on their characteristics. Various anticancer drugs may be nephrotoxic and can potentially cause renal impairment. We aimed to analyze the risk of renal adverse reactions according to different types of anticancer drugs using a global reporting system. Method We conducted an analysis on VigiBase, the World Health Organization pharmacovigilance database from Dec 1967 to Jul 2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) compares observed and expected values to find the associations of each category of anticancer drugs with acute kidney injury (AKI) and tubulointerstitial nephritis (TIN). Results We observed 32,722 AKI and 2,056 TIN reports which were reported as anticancer drug-related renal adverse reactions. Noteworthy trends emerged in AKI reports following anticancer drugs: cytotoxic therapies consistently dominated with 13,925 cases, while AKI cases related to targeted therapies and immunotherapies surged to 14,236 and 3,816 cases over three decades, respectively. Notably, TIN exhibited a significant increase, particularly after the popular usage of immunotherapy between 2015 and 2020, surpassing other categories of anticancer drugs. The highest disproportionality signal for AKI was associated with immunotherapies (ROR, 8.92; confidence interval [CI], 8.63–9.21, followed by cytotoxic therapies (ROR, 7.14; 95% CI, 7.01–7.26), targeted therapies (ROR, 5.83; 95% CI, 5.73–5.93), and hormone therapies (ROR, 2.59; 95% CI, 2.41–2.79). In the case of TIN, a significantly higher disproportionality signal was found for immunotherapies (ROR, 21.74; 95% CI, 20.39–23.18), followed by cytotoxic therapies (ROR, 2.60; 95% CI, 2.40–2.82), and targeted therapies (ROR, 1.54; 95% CI, 1.40–1.69). Hormone therapies did not exhibit a significant disproportionality signal. Separate analyses were also conducted for the ROR of AKI and TIN for each individual anticancer drug. Conclusion AKI and TIN were substantially observed following the administration of anticancer drugs. Noticeably, renal adverse reactions following immunotherapy, which have been experiencing an increase in utilization, were more prominent than other types of anticancer drugs. Clinicians should consider the increased risk of renal adverse reactions after specific anticancer drugs.

Polypharmacy, drug-drug interactions, and adverse drug reactions among systemic sclerosis patients: A cross-sectional risk factor study.

ObjectivesPolypharmacy, drug-drug interactions (DDI) and related adverse drug reaction (ADR) are understudied in SSc. The aim of this work was to determine the prevalence and determinants of DDI and ADR in a real-life prospective cohort of SSc patients. MethodsWe performed a retrospective analysis of the drug prescriptions of SSc patients admitted to the daily scleroderma clinic between January 2020 and April 2022. DDI were identified using 2 prescription analysis applications, and adjudicated related ADRs occurring during a one-year follow-up were reported. Risk factors for DDI and ADR were identified using multivariate analysis. ResultsOne hundred and eight SSc patients were included. The median number of medications per patient was 6 [4–9]. Seventy-one (65.7 %) patients had 5 or more medications, and 23 (21.3 %) had 10 or more. Seventy-two (66.7 %) patients had DDIs on their prescriptions at inclusion. Patients with DDIs had more medications than patients without DDIs (7 [5–10] versus 3 [2–5], p < 0.0001). Six (8.3) patients experienced ADRs during the one-year follow-up. Patients with ADRs had more medications (14 [10–18] versus 7 [5–10] p < 0.001) and more DDIs (12 [7–32] versus 3 [1–6]; p < 0.001) than patients without ADRs. Multivariate analysis confirmed that the number of prescribed medications was independently positively associated with DDIs (OR: 2.25 [1.52–3.32], p < 0.0001) as well as with ADRs (OR: 1.68 [1.17–2.40], p < 0.01). ConclusionsSSc patients are significantly exposed to polypharmacy, DDIs and related ADRs, particularly in cases of severe illness, and especially if 5 or more medications are prescribed.

Pharmacovigilance of carbamazepine in the treatment of Central Nervous System conditions

Anticonvulsants are crucial for treating neurological diseases, necessitating close pharmacovigilance due to their potential risks. For this reason, a prospective descriptive study was conducted to characterize drug-related adverse reactions associated with the use of carbamazepine in the health area of the "Ramon Lopez Peña" Polyclinic, covering the period from July to December 2022. The sample consisted of 35 patients, characterized based on demographic, clinical, and pharmacotherapeutic variables. The detected drug-related adverse events were classified according to causality, severity, and frequency of occurrence. The results showed that the age group of 40-75 years (45.7%) predominated, along with female gender, mixed ethnicity, pre-university education level, and 54.2% did not have any unhealthy habits. The most common diagnosis was epilepsy (68.4%) and among the associated diseases, hypertension was prevalent. The most consumed medications were captopril, hydrochlorothiazide, paracetamol, and metamizole (dipirona). Drug interactions were detected, and 73 adverse reactions occurred, with the nervous system being the most affected at 56.0%. Possible adverse reactions (42.5%), frequent (49.4%), and mild (58.9%) predominated. This study underscores the importance of continuous and effective monitoring in pharmacovigilance to enhance patient safety under carbamazepine treatment, thereby promoting a more rational use of this medication.

Triptolide, a Cancer Cell Proliferation Inhibitor, Causes Zebrafish Muscle Defects by Regulating Notch and STAT3 Signaling Pathways.

Triptolide is a natural compound in herbal remedies with anti-inflammatory and anti-proliferative properties. We studied its effects on critical signaling processes within the cell, including Notch1 and STAT3 signaling. Our research showed that triptolide reduces cancer cell proliferation by decreasing the expression of downstream targets of these signals. The levels of each signal-related protein and mRNA were analyzed using Western blot and qPCR methods. Interestingly, inhibiting one signal with a single inhibitor alone did not significantly reduce cancer cell proliferation. Instead, MTT assays showed that the simultaneous inhibition of Notch1 and STAT3 signaling reduced cell proliferation. The effect of triptolide was similar to a combination treatment with inhibitors for both signals. When we conducted a study on the impact of triptolide on zebrafish larvae, we found that it inhibited muscle development and interfered with muscle cell proliferation, as evidenced by differences in the staining of myosin heavy chain and F-actin proteins in confocal fluorescence microscopy. Additionally, we noticed that inhibiting a single type of signaling did not lead to any significant muscle defects. This implies that triptolide obstructs multiple signals simultaneously, including Notch1 and STAT3, during muscle development. Chemotherapy is commonly used to treat cancer, but it may cause muscle loss due to drug-related adverse reactions or other complex mechanisms. Our study suggests that anticancer agents like triptolide, inhibiting essential signaling pathways including Notch1 and STAT3 signaling, may cause muscle atrophy through anti-proliferative activity.

Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations.

Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations. From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable. A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events. NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.

Breastfeeding-Related Adverse Drug Reactions of Triptans: A Descriptive Analysis Using Four Pharmacovigilance Databases.

Objective: Migraine attacks are common in women of reproductive age. Although attacks are often less severe and less frequent during pregnancy, they regularly reoccur shortly after delivery. When first-line analgesic treatment is insufficient, triptans may be used for acute treatment of migraine attacks. Milk levels of occasional triptan use have shown to be low, and no adverse effects in breastfed infants have been reported. However, the available knowledge on the safety of triptans during breastfeeding is still limited. Methods: Four (inter)national pharmacovigilance databases were searched for breastfeeding related adverse drug reactions of triptans. These included the Dutch Pregnancy Drug Register and three databases of spontaneous reports (Netherlands Pharmacovigilance Centre Lareb, the European Medicines Agency [EudraVigilance], and the World Health Organization [VigiBase]). Results: A total of 26 reports on 27 breastfeeding related adverse drug reactions were identified (one report involved two separate adverse drug reactions). These involve three main complaints: painful breasts and/or nipples, painful milk ejection reflex, and a decrease in milk production. Discussion and Conclusion: The hypothesized pharmacological mechanism relates to the serotonin-receptor agonistic properties of triptans. These may lead to vasoconstriction in the breasts and nipples, including the vasculature surrounding the milk ducts and alveoli, and may also influence the hormonal function and levels of prolactin. The reported adverse drug reactions do not negatively impact the overall compatibility of triptans with breastfeeding. However, breastfeeding women may experience them as unsettling. Awareness of these potential adverse drug reactions is essential and should be weighed against the potential adverse effects of (untreated) symptoms of migraine attacks.

Abstract 477: Tumor treating fields (TTFields) targeted self assembling nanoparticles for pancreatic cancer treatment: In vitro and in vivo assessment

Abstract Tumor Treating Fields (TTFields) is a novel, non-invasive and safe treatment modality, which is prescribed to be used in conjunction with classical anticancer chemotherapeutic drugs. TTFields when used alone are safe, but their use in combination with classical chemotherapy continues to offer drug related adverse reactions which ultimately impacts the patient compliance. To address this challenge, we earlier reported meticulously optimized self-assembling cationic-anionic polymer nanoparticles (S-CAP NPs) with average particle size of about 200 nM, encapsulation efficiency of 55-65 % and sustained drug release over 60 h. We also reported that, TTFields were capable of destabilizing the S-CAP NPs leading to targeted drug release. The results were also corroborated with in vitro cytotoxicity and colony formation studies in presence of TTFields using multiple pancreatic cancer cell lines. After establishing the proof-of-concept, the objective was to assess the in vitro cellular uptake of S-CAP NPs. For this, fluorescent dye loaded S-CAP NPs were developed and subjected to cellular uptake analysis. The in vitro cellular uptake studies confirmed the enhanced uptake of S-Cap NPs by passive diffusion in the pancreatic cancer cell lines compared to normal pancreatic epithelial cell line. The studies corroborated preferential cellular uptake of S-Cap NPs by the pancreatic tumor. Among all the formulations, the chitosan- bovine serum albumin S-CAP NPs was most optimum and was used for in vivo safety studies. For this, in vivo acute and repeated dose 28-day toxicity of the optimum placebo S-CAP NPs was conducted in Sprague Dawley rats (Western University of Health Sciences Protocol #R20IACUC031) and OECD guidelines. The in vivo studies showed a LD50 value above 2000 mg/kg and NOAEL value of 1000 mg/kg. These high doses safety of S-CAP NPs confirmed the potential of this approach for future preclinical efficacy studies followed by clinical translation. Lastly, the in vitro stability studies were conducted as per the ICH guidelines for a period of 36 months and the formulations were concluded to be stable. The tumor targeting potential, in vivo safety and stability of S-CAP NPs, establish their translational potential for TTFields triggered targeted drug release in cancer treatment. This approach will not only reduce the adverse effect associated with combination of TTFields and chemotherapy but can also be explored as a platform technology for management of other cancers. This study is supported by AACR-Novocure tumor treating fields research fellowship. Citation Format: Preshita Prafulla Desai, Sunil Prabhu. Tumor treating fields (TTFields) targeted self assembling nanoparticles for pancreatic cancer treatment: In vitro and in vivo assessment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 477.

Comparison of the efficacy and safety of sodium valproate versus levetiracetam in the treatment of severe traumatic brain injury

Objective To observe the efficacy and safety of sodium valproate (VPA) compared to levetiracetam (LEV) in the treatment of severe traumatic brain injury (sTBI). Methods In this blind, prospective study, eighty-four sTBI patients who had craniotomy from August 2021 to August 2023 were randomly split into two groups through random number table method: LEV and VPA, each with 42 patients. Both received comprehensive treatment post-craniotomy. LEV group: LEV injection on surgery day, transitioning to LEV tablets from day two. VPA group: VPA injection on surgery day, switching to VPA extended-release tablets from day two. The study compared hospital stay, neurological function, clinical outcomes, seizures, and drug reactions between groups. Results The length of hospital stay showed no significant difference between the LEV and VPA groups. Both groups demonstrated improved neurological function post-treatment (NIHSS and BI scores), with no significant between-group differences. Clinical outcomes at 3 months post-treatment were similar in both groups. Seizure occurrence within 3 months after treatment showed no significant difference between the LEV (19.05%) and VPA (23.81%) groups. However, the VPA group experienced a significantly higher rate of drug-related adverse reactions (40.48%) compared to the LEV group (21.43%). Conclusion Both VPA and LEV are effective in treating sTBI, showing no significant difference in improving neurological function, daily life abilities, treatment outcomes, and seizure occurrence. However, VPA treatment exhibited a significantly higher incidence of drug-related adverse reactions compared to LEV, indicating that LEV might be a safer option for sTBI treatment.

Drug-related side effects and adverse reactions in the treatment of migraine: a bibliometric and visual analysis.

Migraine imposes a substantial global burden, impacting patients and society. Pharmacotherapy, as a primary treatment, entails specific adverse reactions. Emphasizing these reactions is pivotal for improving treatment strategies and enhancing patients' well-being. Thus, we conducted a comprehensive bibliometric and visual analysis of relevant literature. We conducted a comprehensive search on the Science Citation Index Expanded within the Web of Science, restricting the literature for analysis based on criteria such as document type, publication date, and language. Subsequently, we utilized various analytical tools, including VOSviewer, Scimago Graphica, the R package 'bibliometrix', CiteSpace, and Excel programs, for a meticulous examination and systematic organization of data concerning journals, authors, countries/regions, institutions, keywords, and references. By August 31, 2023, the literature was distributed across 379 journals worldwide, authored by 4,235 individuals from 1726 institutions. It featured 2,363 keywords and 38,412 references. 'HEADACHE' led in publication count, with 'SILBERSTEIN S' as the most prolific author. The United States ranked highest in publication volume, with 'UNIV COPENHAGEN' leading among institutions. Our research findings indicate that researchers in the field continue to maintain a focus on the calcitonin gene-related peptide (CGRP) system and explore diverse mechanisms for drug development through the application of novel biotechnological approaches. Furthermore, it is imperative to enhance the assessment of clinical trial outcomes, consistently monitor the efficacy and safety of prominent drugs such as Erenumab and Fremanezumab. There is a need for further evaluation of acute and preventive treatments tailored to different populations and varying types of migraine.

Pattern of central nervous system related adverse drug reactions (ADRs) due to anti-retroviral therapy in HIV infected patients in tertiary care hospitals in North India

Background: Anti-retroviral therapy is associated with myriads of side-effects. Central nervous system related side effects are troublesome and mostly self limiting. Working knowledge of these side effects can improve the prescription habits of physicians. The study aimed pattern of central system related adverse drug reactions (ADRs) due to anti-retroviral therapy in HIV infected patients in tertiary care hospitals in North India. Materials and methods: A prospective observational study was conducted and all HIV positive patients, previously registered and new; attending OPD who encountered ADRs were enrolled in our study irrespective of their age and sex. Data was collected using ADR reporting form issued by Indian Pharmacopoeia Commission. Causality assessment was done by using Naranjo’s Probability Scale. Modified Hartwig severity scale was used to evaluate severity, WHO criteria for seriousness and guidelines of council for international organizations of medical sciences to decide the predictability of ADRs. Results: A total of 250 patients encountered various types of ADRs during the study period. Total number of ADRs recorded was 452. Out of total ADRs (n=452) recorded, 20.35% (n=92) were central system related ADRs. Most common central nervous system related ADR was dizziness. Most central nervous system related ADRs were of moderate type and possible in nature on causality assessment. Conclusion: Relatively overweight, older age and baseline CD4 absolute count below 250 cells/mm3, were predictors for central nervous system related side effects due to anti-retroviral therapy in HIV patients. We suggest that more stringent evaluation and monitoring should be carefully done in all HIV/AIDS patients who will receive and on efavirenz based anti-retroviral therapy, especially if they have the above predictors.

Prognosis and Factors 4 to 10 Years After Deep Vein Thrombosis: A Long-Term Follow-up Cohort Study.

Post-thrombotic syndrome (PTS) is one of the most common long-term complications of lower extremity deep vein thrombosis (DVT). In order to study the long-term adverse prognosis of patients with DVT, explore the influencing factors for the prognosis of DVT, and provide a reliable reference for future research in the field of venous thrombosis, we collected and summarized information about the incidence of PTS, the PTS score and grading, the associated symptoms and drug-related adverse reactions in 501 patients with DVT. In our study, 54.1% of patients with DVT (271 of 501) experienced indications and manifestations of PTS, the male to female ratio was approximately 1:1. During the long-term follow up, the most common symptoms of PTS were anterior tibial edema and pain. By statistical analysis, we found that the outcome of thrombosis was the influencing factor of PTS score (1-4 points, P<.05). The grading of PTS was primarily influenced by the history of varicose veins and DVT in the lower extremities. The duration of taking antithrombotic drugs affected the outcome of thrombosis (P<.05), especially among the female patients. In addition, varied factors, such as lower extremity DVT complicated with pulmonary embolism and the duration of antithrombotic drug use were found to increase the chances of experiencing drug-related adverse reactions (odds ratio [OR]=2.798, 95% confidence interval [CI]: 1.413-5.541 / OR=2.778, 95% CI: 1.231-6.269). The above 2 factors were significant only among female patients with DVT (OR=4.03, 95% CI: 1.608-10.103 / OR=3.918, 95% CI: 1.123-13.669).