Gastrointestinal adverse events associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the EudraVigilance and VigiAccess databases.

BACKGROUND: This study aimed to provide an overview of gastrointestinal (GI) adverse events associated with immune checkpoint inhibitors (ICIs) using two pharmacovigilance databases, EudraVigilance and VigiAccess. RESEARCH DESIGN AND METHODS: Data was collected from the date of ICI's marketing authorization until 30 November 2023. Reporting odds ratio (ROR) was used as a measure of ADR reporting disproportionality for signal detection. RESULTS: Overall, across both databases, EudraVigilance and VigiAccess, a total of 76,606 ADR reports were analyzed. In EudraVigilance, colitis (12,581) and diarrhea (12,108) were the most reported GI adverse events, with similar findings in VigiAccess. Furthermore, in both databases, the most ADR reports were associated with nivolumab and pembrolizumab. Durvalumab (ROR:3.96,95%CI:3.65-4.28), ipilimumab (ROR:1.95,95%CI:1.89-2.01), nivolumab (ROR:1.05,95%CI:1.02-1.07), and atezolizumab (ROR:1.04,95%CI:1.01-1.07) demonstrated higher risks of GI events compared to other ICIs. EudraVigilance analysis identified dysphagia, ascites, hematochezia, and gastroesophageal reflux disease as potential signals associated with ICI therapy. Majority of ADR reports (87.2%) comprised serious GI adverse events, a portion of which was associated with fatal outcomes (14.5%). Atezolizumab (14.9%) and pembrolizumab (11.9%) were linked to a higher incidence of fatal outcomes compared to other ICIs. CONCLUSION: The differential risk profiles of ICIs-associated-GI adverse events underscore the importance of personalized therapy in oncology.

Divine noni's protective impact on Swiss albino mice's short-term memory impairment caused by cyclophosphamide: A behavioral and biochemical approach.

Cyclophosphamide (CYL) is a first-line cancer chemotherapeutic agent widely used for the treatment of cancer that has severe toxic effects. The primary mechanism by which CYL induces toxicity through free radical generation. Morinda citrifolia (Noni) fruit juice is an herbal remedy documented to have antioxidant properties. The aim of the current study was to investigate the protective effect of noni against CYL-induced memory impairment in Swiss albino mice. Treatment schedule: Group 1: Normal: Received vehicle; Group 2: CYL treatment: Received CYL (40.0 mg/kg b.w. i.p.) on day one; Group 3: NJ treatment: Received NJ (360 mg/b.w. p.o.) once daily for 14 days. Group 4: DNG treatment: DNG (360 mg/b.w. p.o.) once daily for 14 days, Group 5: NJ + CYL treatment: Received CYL (40.0 mg/kg b.w. i.p.) on day one and after half an hour of received NJ (360 mg/b.w. p.o.) once daily for 14 days. Group 6: DNG + CYL treatment: Received CYL (40.0 mg/kg b.w. i.p.) on day one and after half an hour received DNG (360 mg/b.w. p.o.) once daily for 14 days. Mice were subjected to the Morris water maze (MWM) challenge for two weeks as part of a behavioral study. Short-term memory impairment was observed in the behavioral activity of CYL-treated mice in the MWM test in the 1st week trial, and this effect was reversed in the 2nd week trial in the combination treatment group. The behavioral analysis proved that noni supplementation reduced the risk of memory impairment caused by CYL. Biochemical analysis revealed that CYL markedly increased the levels of AChE and MDA in brain tissue. Similarly, decreases in the levels of antioxidants, i.e., GSH, CAT, SOD and GST, were detected in the brain tissue of the mice exposed to CYL. Qualitative and quantitative examinations of histopathological examination of the mouse hippocampus supported the above findings. The results demonstrated that noni supplement therapy reversed the changes in the MDA, AChE, and antioxidant enzyme levels while improving the behavioral and histological alterations caused by CYL. Long-term hippocampal growth and memory are unaffected, suggesting that CYL is less harmful. According to our research, supplementing with noni in conjunction with CYL may be a helpful treatment strategy for treating memory impairment caused by CYL.

Exploring pharmacovigilance practices and knowledge among healthcare professionals: A cross-sectional multicenter study.

Introduction: Healthcare professionals' awareness of adverse drug reaction reporting and pharmacovigilance practices differ by country. The study assesses healthcare professionals' knowledge, practice, and potential barriers to pharmacovigilance-related practices and reporting adverse drug reaction. Methods: A cross-sectional investigation was conducted in government and private healthcare settings. The study included licensed physicians, pharmacists, and nurses. To examine knowledge, practice, and potential barriers to pharmacovigilance-related practices and adverse drug reaction reporting, a 22-item validated questionnaire was used. Results: The final analysis included 311 healthcare professionals. Most healthcare professionals, 59% (N = 182), mentioned encountering patients with adverse drug reactions during the last year. On the other hand, most healthcare professionals, 54% (n = 167), mentioned that they had not reported adverse drug reactions. A good proportion of respondents mentioned that it is essential to report adverse drug reactions (N = 288, 92.6%), availability of adverse drug reactions reporting forms in practice sites (N = 216, 69.5%), had awareness regarding how to report adverse drug reactions (N = 221, 71.1%), the necessity of reporting minor/less important adverse drug reactions (N = 265, 85.2%), and were trained on how to report adverse drug reactions (N = 201, 64.6%). Adverse drug reaction reporting program in the United Arab Emirates (N = 148, 47.6) was known to many healthcare professionals. Lack of time was the major impediment to reporting adverse drug reactions at 42.7% (N = 133). The predictor variable work experience does add to the model (p < 0.05) concerning association with filling of adverse drug reaction forms (Estimate = 0.380; SE = 0.452; p = 0.400), professional role (Estimate = 0.454; SE = 0.673; p = 0.500). In addition, the predictor variable practice setting adds to the model (p < 0.05) concerning the knowledge regarding the availability of adverse drug reaction reporting forms (Estimate = -1.229; SE = 0.298; p = 0.000), training on how to report adverse drug reactions (Estimate = -0.660; SE = 0.294; p = 0.025), and awareness regarding the adverse drug reaction reporting program in the United Arab Emirates (Estimate = -1.032; SE = 0.280; p = 0.000). Conclusion: Pharmacists had the most knowledge regarding adverse drug reaction reporting and pharmacovigilance. The underreporting of adverse drug reactions was documented among physicians and nurses. Lack of time was the most significant barrier to reporting adverse drug reactions, followed by uncertainty and complicated adverse drug reaction documentation forms.

A common molecular and cellular pathway in developing Alzheimer and cancer.

Globally cancer and Alzheimer's disease (AD) are two major diseases and still, there is no clearly defined molecular mechanism. There is an opposite relation between cancer and AD which are the proportion of emerging cancer was importantly slower in AD patients, whereas slow emerging AD in patients with cancer. In cancer, regulation of cell mechanisms is interrupted by an increase in cell survival and proliferation, while on the contrary, AD is related to augmented neuronal death, that may be either produced by or associated with amyloid-ß (Aß) and tau deposition. Stated that the probability that disruption of mechanisms takes part in the regulation of cell survival/death and might be implicated in both diseases. The mechanism of actions such as DNA-methylation, genetic polymorphisms, or another mechanism of actions that induce alteration in the action of drugs with significant roles in resolving the finding to repair and live or die might take part in the pathogenesis of these two ailments. The functions of miRNA, p53, Pin1, the Wnt signaling pathway, PI3 KINASE/Akt/mTOR signaling pathway GRK2 signaling pathway, and the pathophysiological role of oxidative stress are presented in this review as potential candidates which hypothetically describe inverse relations between cancer and AD. Innovative materials almost mutual mechanisms in the aetiology of cancer and AD advocates novel treatment approaches. Among these treatment strategies, the most promising use treatment such as tyrosine kinase inhibitor, nilotinib, protein kinase C, and bexarotene.

Assessment of Prescribing Practices and Factors Related to Antibiotic Prescribing in Community Pharmacies.

Background and Objectives: Overprescribing of antibiotics is one of the important contributors of antimicrobial resistance globally. A high proportion of antibiotics prescribed in community settings are unnecessary or inappropriate. This study assesses the prescribing practices and factors related to antibiotic prescribing in community pharmacies in United Arab Emirates (UAE). Materials and Methods: A cross-sectional study utilizing a quantitative approach was carried out in the community pharmacies of Ras Al Khaimah (RAK), UAE. Six hundred and thirty prescription encounters from 21 randomly selected community pharmacies were investigated using World Health Organization (WHO) core prescribing indicators. Factors related to antibiotic prescribing were identified using logistic regression analyses. Results: In 630 prescription encounters, a total of 1814 drugs were prescribed. Out of these, the most commonly prescribed drug class was antibiotics (43.8% prescriptions) and the antibiotic was amoxicillin/clavulanic-acid (22.4%). The average number of drugs per prescription was 2.88, which was higher than the WHO recommended value of 1.6-1.8. In addition, more than half of the prescriptions (58.6%) had drugs by generic names and the majority of the drugs prescribed (83.8%) were from the essential drug list, which were lower than the optimal values of 100%. The majority of the antibiotics prescribed in the study were from the WHO's Access group antibiotics. Multivariable logistic regression analysis identified patient age (children-OR: 7.40, 95% CI: 2.32-23.62, p = 0.001 and adolescent-OR: 5.86, 95% CI: 1.57-21.86, p = 0.008), prescriber qualification as general practitioner (OR: 1.84, 95% CI:1.30-2.60, p = 0.001), and number of drugs per prescription (OR: 3.51, 95% CI: 1.98-6.21, p < 0.001) as independent factors associated with antibiotic prescribing. Conclusions: This study reveals considerable variations from the WHO recommendations for the different prescribing indicators in the community pharmacies of RAK, UAE. In addition, the study reports overprescribing of antibiotics in the community setting, indicating the need for interventions to promote rational use of antibiotics in a community setting.

Evaluation of Drug-Related Problems in Chronic Kidney Disease Patients.

Background Chronic kidney disease (CKD) is a challenging global health problem with increasing prevalence worldwide. Concurrence of CKD and comorbidities results in the use of multiple medications and exposing patients to polypharmacy. Polypharmacy in CKD is common across all the stages of the disease and leads to poor medication adherence, higher healthcare costs, and drug-related problems, such as drug-drug interactions (DDIs) and adverse drug reactions (ADRs). DDIs and ADRs in CKD patients may lower the quality of life, increase the length of hospital stay, and augment the risks of morbidity and mortality. Methodology This was a hospital-based, prospective, cross-sectional study conducted in a secondary care hospital. The study population comprised 130 adult CKD patients admitted to the nephrology department including those on maintenance hemodialysis. Study-related data were obtained from the electronic patient case records. Medications prescribed to the patients were analyzed for potential DDIs (pDDIs) using Portable Emergency and Primary Care Information Database (PEPID 12.1) drug interaction checker. All observed and reported suspected ADRs related to the prescribed drugs were evaluated for causality, severity, preventability, and predictability. Results Out of the 130 patients, majority were males (n = 71, 54.6%), in the age group of 61-70 years (n = 45, 34.6%), and belonged to CKD stage 5 (n = 105, 80.8%). The mean number of drugs prescribed was 11.1 ± 3.8 per patient. The prevalence of pDDIs was found to be 89.2%. Upon analysis by the PEPID database, 708 pDDIs with 215 different pairs of interacting drugs were identified. Polypharmacy (odds ratio (OR): 62.34, 95% confidence interval (CI): 7.97-487.64, p < 0.001) was identified as an independent predictor of the occurrence of pDDIs. Negative binomial regression analysis revealed that dyslipidemia (incidence rate ratio (IRR): 2.7, 95% CI 2.09-3.48, p < 0.001) and diabetes (IRR: 1.2, 95% CI 1.01-1.54, p = 0.040) increased the probability of occurrence of pDDI by 2.7 and 1.2 folds, respectively. Furthermore, the likelihood of pDDI increased with every one-day increase in the length of hospital stay (IRR: 1.02, 95% CI 1.00-1.03, p = 0.015) by 1.02 times and polypharmacy (IRR: 6.30, 95% CI 3.04-13.02, p < 0.001) by 6.3 times. The incidence of ADRs was found to be 10.7%. Majority of suspected ADRs were possible (n = 7, 50.0%), of mild and moderate severity (n = 7, 50.0%), and non-preventable (n = 8, 57.1%) type. Conclusions This study investigated two important drug-related problems, pDDIs, and ADRs, in the CKD population. High proportion of CKD patients in the study had pDDIs. Comorbid conditions such as dyslipidemia and diabetes mellitus, length of hospital stay, and polypharmacy were significantly associated with increased likelihood of pDDIs. Furthermore, there was a burden of ADRs in the study population, of which most ADRs were possible and of mild to moderate severity. Prevention, identification, and resolution of these problems in CKD patients is important and can be achieved through medication optimization, which requires a proactive interdisciplinary collaboration between clinicians, clinical pharmacists, and other healthcare professionals.

Effect of Polymers and Permeation Enhancers in the Release of Quetiapine Fumarate Transdermal Patch through the Dialysis Membrane.

Quetiapine Fumarate is potent, and the daily therapeutic dose can be delivered easily across the skin with the help of permeation enhancers. Quetiapine Fumarate-loaded transdermal patches were prepared by solvent evaporation technique. Various formulation parameters, excipients, and their combinations were optimized to get thin, translucent, smooth, stable, and high permeable character patches. A total number of 10 formulations were prepared. All formulations were subjected to various physicochemical evaluations. Three different formulations were prepared and F1, F2, and F3. Various physicochemical studies were carried out and found no significant difference between the three batches. The in vitro release study showed 74.29%, 82.73%, and 77.27%, respectively, up to 24 h. From the results, F2 has been selected as an optimized formulation and evaluated for skin irritation test. The results revealed that there is no irritation produced. The stability study results showed that there is no significant change from its initial nature till the period of three months in both temperatures. Quetiapine Fumarate Transdermal Patch F2 has achieved the goal of extended-release, cost-effectiveness, lowering the dose and frequency of drug administration, and thus may improve patient compliance.

The Effect of Polymers on Drug Release Kinetics in Nanoemulsion In Situ Gel Formulation.

Glaucoma is an ocular condition characterized by elevated intraocular pressure (IOP). Conventional treatments of glaucoma face poor corneal permeability and bioavailability. To address these issues, a nanoemulsion in situ gel of Timolol maleate was developed in this study by adding the polymer Carbopol 934p. Using Carbopol 934p, a novel ophthalmic pH-induced nanoemulsion in situ gel was formulated. The formulation was liquid at pH 4 and quickly gelled when the pH was raised to 7.4 (Lacrimal pH). The pH-triggered in situ gelling mechanism demonstrated continuous drug release over a 24 h cycle. A total of nine trial formulations were prepared (NEI1-NEI9) and subjected to various physicochemical and in vitro evaluations. According to the in vitro release kinetics, the drug release of Timolol maleate nanoemulsion in situ gel NEI5 followed zero-order kinetics, with a release exponent value of 0.902, indicating that the mechanism of release was non-Fickian diffusion regulated. In vivo results showed that Timolol maleate nanoemulsion in situ gel NEI5 provided a better-sustained release of the drug, compared with the Timolet OD eye drops. The formulation is stable in storage, with no distinguishable change in appearance, physical properties, quality, and percentage drug release. NEI5 also reduces drug administration frequency, which improves patient compliance. Timolol maleate nanoemulsion in situ gel NEI5 achieved the goal of controlled drug delivery with extended-release and cost-effectiveness, lowering the dosage and frequency of drug administration, and thus may improve patient compliance. In conclusion, the stable nanoemulsion in situ gel of Timolol maleate NEI5 decreases intraocular pressure (IOP) over a prolonged period.

Assessment of incidence, causality, severity, and preventability of suspected adverse drug reactions to antidepressant medications in a psychiatry outpatient setting of a secondary care hospital.

BACKGROUND: Antidepressant medications are primarily used in the management of depression and various anxiety disorders. Antidepressant medications are known to cause adverse drug reactions (ADRs). Reporting ADRs can help in the rational use of medication and better patient drug management. OBJECTIVE: The aim of this study was to monitor the incidence and nature of ADRs to antidepressant medications in a psychiatric outpatient setting of a secondary care hospital of the UAE. MATERIALS AND METHODS: It was a cross-sectional study conducted in the psychiatric outpatient setting of a secondary care hospital. Patients attending psychiatry outpatient department and prescribed with antidepressant medications were included. All clinical side effects or ADRs noted by physician and reported by patients were documented and assessed according to causality, severity, and preventability scales. RESULTS: A total of 131 patients were screened for the presence or occurrence of ADRs. During the study duration, an aggregate of 29 patients reported at least one ADR. Incidence of suspected ADR to antidepressant medications was found to be 22.1%. Most commonly documented suspected ADR was found to be weight gain in eight (18.1%) patients followed by somnolence in four (9.1%) patients. Escitalopram was the most common drug implicated with ADR in 13 (29.6%) patients followed by fluoxetine in 6 (13.6%) patients. According to World Health Organization-The Uppsala Monitoring Centre causality assessment, the predominance of the suspected ADRs was of "possible" type in 27 (61%) patients, and "mild" in severity in 40 (91%) patients, and "not preventable" in 37 (84%) patients. A statistically significant association (P = 0.019) was observed only between the presence of drug-interaction and the occurrence of ADR (relative risk: 0.429, confidence interval: 0.211-0.872). CONCLUSION: Most of the suspected ADRs related to antidepressants were "mild," "predictable," and "not preventable" in nature. Continuous monitoring may help in identifying, reducing, and preventing the risk of ADRs.

Use of Phosphate Binders in End-Stage Renal Disease: An Experience From a Secondary Care Hospital in United Arab Emirates.

OBJECTIVE: Hyperphosphatemia in end-stage renal disease (ESRD) is associated with many serious patient-level consequences including cardiovascular events and mortality. The purpose of this study was to investigate the use of phosphate binders in ESRD patients on maintenance hemodialysis. MATERIALS AND METHODS: The study was a prospective observational cohort study including adult ESRD patients undergoing hemodialysis at a secondary hospital in United Arab Emirates. Patient characteristics were compared as per type of phosphate binder used. Bivariate and multivariate multinomial logistic regression analyses were carried out to determine variables that were independently associated with use of different phosphate binders. RESULTS: Phosphate binders used at our study site were sevelamer, calcium carbonate, and a combination of sevelamer and calcium carbonate. Bivariate multinomial logistic regression analysis revealed that serum phosphorous (odds ratio [OR]: 0.14, 95% confidence interval [CI]: 0.04-1.09, P = 0.047; OR: 0.10, 95% CI: 0.03-0.89, P = 0.042), calcium (OR: 0.11, 95% CI: 0.02-0.86, P = 0.041; OR: 0.22, 95% CI: 0.01-0.96, P = 0.012), and calcium-phosphorous product (OR: 0.20, 95% CI: 0.06-0.64, P = 0.008; OR: 0.16, 95% CI: 0.05-0.54, P = 0.003) levels were significantly lower in patients on sevelamer per se as well as in patients on combination therapy, respectively when compared to calcium carbonate per se. Multivariate multinomial logistic regression analysis revealed that in sevelamer and combination groups, cardiovascular diseases (OR: 0.12, 95% CI: 0.02-0.65, P = 0.022; OR: 0.10, 95% CI: 0.01-0.88, P = 0.038) were significantly lesser compared to calcium carbonate group after being adjusted for other variables in the model. CONCLUSION: We observed that hyperphosphatemia and related events in our study population were better controlled by sevelamer per se and combination therapy than calcium carbonate per se. Further large scale, multicenter studies are required to confirm and establish these findings.

Assessment of Nature, Reasons, and Consequences of Self-medication Practice among General Population of Ras Al-Khaimah, UAE.

AIM: The aim of this study is to assess the nature, reasons, and consequences of self-medication practice among the general population of Ras Al-Khaimah, UAE. MATERIALS AND METHODS: This was a prospective, cross-sectional, survey-based study. Data with respect to knowledge, awareness, and practices regarding self-medication were collected through an interviewer-assisted questionnaire answered by the study participants. Thus, collected data from 413 survey respondents were analyzed using SPSS version 24.0. RESULTS: The prevalence of self-medication practices among our study respondents was 52.1%. A headache (155 [37.5%]) was the most common clinical condition treated through self-medication practice. Familiarity with the treatment/medication (198 [48%]) was the most common cited reasons, whereas the advertisement and friend's advice were the most (182 [44%]) cited sources of information for self-medication usage. The majority (265 [64.1%]) of the respondents were considered self-medication practice as safe. However, 19 respondents reported side-effects or complications during the due course of self-medication. It was observed that there is a statistically significant association (P < 0.05) between age and employment status of this study participants with self-medication practices. CONCLUSION: The data from this study show that the self-medication practice is very common among the study population. Variables such as younger age group and occupation status were significantly associated with self-medication practice. We emphasize the role of pharmacist in educating the community regarding safe medication practices such as harmful effects of self-medicating and inappropriate practices such as sharing the medications among family members and friends.