Pharmazie. 2024 Oct 1;79(9):209-214. doi: 10.1691/ph.2024.4540.

ABSTRACT

Background: Of all adverse drug reactions, 35-45% are due to medication errors and would therefore be preventable. Thus, it is essential to implement effective strategies to prevent medication errors. However, it remains unclear whether medication reviews provide an additional benefit compared to medication reconciliation regarding medication safety. Aim: The present study aimed to evaluate whether medication reconciliation and medication reviews affect the incidence of preventable adverse drug reactions in elderly patients. Method: Non-elective patients 65 years and above admitted to the hospital, taking at least one high-risk drug, were eligible for participation in a three-armed randomized controlled trial. One group went through the medication reconciliation process, a second group received a comprehensive medication review, including medication reconciliation, and the third group did not receive any pharmaceutical intervention (control group). The incidence of preventable adverse drug reactions during hospitalization was set as the primary endpoint. The severity of the preventable adverse drug reactions and the number and clinical relevance of drug-related problems and discrepancies were defined as secondary endpoints. Results: In 207 patients, 74 preventable adverse drug reactions were detected. Neither medication reconciliation nor medication reviews showed a significant impact on the incidence of preventable adverse drug reactions compared to the control group. However, medication reviews significantly reduced the severity of preventable adverse drug reactions (p=0.017). Conclusion: The current study results suggest that medication reviews may have an impact on a clinically relevant outcome by reducing the severity of preventable adverse drug reactions. A significant impact of medication reconciliation on clinically relevant outcomes could not be demonstrated. Based on the results of this study, when deciding on a pharmaceutical intervention comprehensive medication reviews should be preferred over sole medication reconciliation whenever possible.

PMID:39407421 | DOI:10.1691/ph.2024.4540

BMC Public Health. 2024 Oct 15;24(1):2837. doi: 10.1186/s12889-024-20353-8.

ABSTRACT

BACKGROUND: To prevent the recurrence of Adverse Drug Events (ADEs), particularly drug allergies, it is essential to avoid re-exposure to causative drugs. Awareness of previous ADEs is crucial for patients because they can share accurate information with healthcare providers (HCPs). This study aims to assess users' willingness to share ADE information and evaluate the factors related to this willingness by utilizing a prospective ADE information-sharing system currently under consideration in South Korea.

METHODS: In September 2023, a self-administered questionnaire was collected from a sex-, age-, and regionally stratified nationwide convenience sample of adults recruited through a commercial panel in South Korea. Factors contributing to the willingness to share ADE information and create electronic ADE cards (e-ADE cards) were investigated using multivariate logistic regression analysis.

RESULTS: Among the 1,000 respondents, 458 (45.8%) were willing to share ADE information, and 521 (52.1%) were willing to create e-ADE cards. The willingness to share personal ADE information and create e-ADE cards was positively associated with the perceived benefits of sharing ADE, trust in HCPs and positive experiences. Notably, older adult patients demonstrated a higher willingness to share information and use e-ADE cards, with rates of 56% and 62%, respectively.

CONCLUSIONS: Our findings indicate that the approach to sharing personal ADE information should be distinct from that of sharing comprehensive health information. Notably, users are likely to willingly disclose their personal information even if they are not anonymized, owing to the significant perceived benefits of sharing. The findings of this study can enhance awareness about sharing personal ADE information and contribute to the successful establishment of an ADE information-sharing system, thereby improving the patient safety environment.

PMID:39407197 | DOI:10.1186/s12889-024-20353-8

BMC Geriatr. 2024 Oct 15;24(1):841. doi: 10.1186/s12877-024-05449-5.

ABSTRACT

BACKGROUND: This study aimed to systematically evaluate interventions and effects that promote involvement in medication safety among older people with chronic diseases and to provide new ideas and references for developing standardized and effective intervention strategies to improve patient involvement in medication safety.

METHODS: A comprehensive literature search across twelve databases was conducted using both computerized and manual methods. The search was limited to studies designated as randomized controlled trials or quasi-experimental studies and was conducted from the time of each database's inception until September 2023. Two researchers independently carried out qualitative analyses, which included screening the literature, extracting the data, and assessing the quality of the selected studies.

RESULTS: This study included five studies involving a total of 388 participants, with interventions aimed at enhancing patient involvement in medication safety, including interactive health education, motivational interviewing, and medication reconciliation. However, direct evidence confirming the positive impact of these interventions in promoting medication safety behaviors among older people with chronic diseases is still lacking.

CONCLUSIONS: Patient involvement in medication safety behaviors is essential for promoting healthy aging. Medication education, motivational interviewing, and medication reconciliation may improve the willingness and ability of older people to participate. However, limitations in the methodological quality of current studies prevent drawing definitive conclusions, highlighting the urgent need for more high-quality research.

TRIAL REGISTRATION: PROSPERO number CRD42023494924.

PMID:39407167 | DOI:10.1186/s12877-024-05449-5

J Cyst Fibros. 2024 Oct 14:S1569-1993(24)01788-0. doi: 10.1016/j.jcf.2024.09.020. Online ahead of print.

ABSTRACT

BACKGROUND: A highly effective therapy involving elexacaftor, tezacaftor, and ivacaftor (ETI) for cystic fibrosis (CF) patients has recently raised safety concerns regarding potential psychiatric disorders. The manuscript reports cases of suicide attempts in patients receiving ETI and investigates putative causality using the WHO spontaneous reporting database.

METHODS: First, four cases of suicide attempts/self-injury are described. Second, a disproportionality analysis was conducted using spontaneous reports collected in Vigibase through the standardised MedDRA Query (narrow version) "Suicide/Self-injury" and ETI exposure. Reporting Odds Ratio (ROR) was calculated for the main and subgroup (i/suicide attempt, ii/suicidal ideation) analyses. Sensitivity analyses were performed with variations in exposure, to ivacaftor/lumacaftor to assess the intrinsic psychiatric risk of CF patients, and paracetamol as a positive control for suicide attempt and a negative one for suicidal ideation. Exposure to reduced-dose ETI was studied to evaluate the dose-gradient effect.

RESULTS: Four cases of suicide attempt/self-injury occurred 3 to 13 months after ETI initiation in CF patients and were reported to the Bordeaux Pharmacovigilance centre. Aside, in Vigibase, ETI is associated with an increased likelihood of reporting suicidal behaviour (ROR 2.5, 95 % CI[2.1; 2.8]). A signal of disproportionate reporting was found for the subgroup of suicide attempts (1.4, 95 % CI[1.2; 1.8]), unlike ivacaftor/lumacaftor, which was associated only with the risk of reporting suicidal ideation. Significant ROR values were also found for reduced-dose ETI for all psychiatric effects studied except suicide attempt.

CONCLUSIONS: ETI exposure is related with increased reporting of suicidal behaviour. A potential dose-dependent effect merits further investigation.

PMID:39406576 | DOI:10.1016/j.jcf.2024.09.020

Ter Arkh. 2024 Sep 14;96(8):836-845. doi: 10.26442/00403660.2024.08.202841.

ABSTRACT

The global market for herbal medicines is valued at $83 billion and continues to expand rapidly. Plant extracts, widely used due to their safety and minimal side effects, play a significant role in supporting liver function. The treatment of liver diseases, including hepatitis of various etiologies, alcoholic and non-alcoholic fatty liver disease, and cirrhosis, involves the use of effective hepatoprotective drugs. Plant extracts provide antioxidant and immunomodulatory pharmacological effects that contribute to the maintenance of liver function. The aim of this review was to analyze the mechanisms underlying the hepatoprotective effects of various herbal extracts included in the formulation of DIPANA®, focusing on their antioxidant and immunomodulatory properties. Additionally, the review aimed to present clinical study results supporting their efficacy in treating of various liver diseases. The analysis was based on available literature data and clinical studies on the use of DIPANA®. The reviewed herbal extracts and their combination (DIPANA®) demonstrate efficacy in experimental models of liver damage and clinical studies involving patients with liver diseases, including alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and functional disorders of the gallbladder. This drug exhibits hepatoprotective, choleretic, relaxing effects and is well-tolerated by patients.

PMID:39404730 | DOI:10.26442/00403660.2024.08.202841

Heliyon. 2024 Sep 26;10(19):e38561. doi: 10.1016/j.heliyon.2024.e38561. eCollection 2024 Oct 15.

ABSTRACT

BACKGROUND: Drug-induced dry mouth is an adverse reaction that can significantly affect the quality of life and mental state of patients. In this study, we aimed to identify the most common drugs associated with dry mouth using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.

METHODS: We accessed data from the FAERS database between the first quarter of 2004 and the first quarter of 2024. The Medical Dictionary for Regulatory Activities was used to identify reports of dry mouth, and disproportionality analyses (reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker) were performed to examine the risk signals for dry mouth and its causative drugs.

RESULTS: A total of 75,899 adverse event reports were related to dry mouth. Tiotropium bromide monohydrate (2080 cases) was associated with the majority of dry mouth cases. Disproportionality analysis revealed that the top five drugs with the highest reporting odds ratio (ROR) were darifenacin, solifenacin succinate, fesoterodine fumarate, tolterodine tartrate, and niraparib. Moreover, eight of the top 19 drugs that caused dry mouth were not identified as having major side effects in the package inserts.

CONCLUSION: Tiotropium bromide monohydrate was the most frequently reported drug for dry mouth, whereas darifenacin had the highest ROR. Collectively, our findings emphasize the necessity for improved recognition and management of drug-induced dry mouth, particularly for medications not adequately flagged for this side effect in their labels.

PMID:39403528 | PMC:PMC11472086 | DOI:10.1016/j.heliyon.2024.e38561

Hum Vaccin Immunother. 2024 Dec 31;20(1):2412388. doi: 10.1080/21645515.2024.2412388. Epub 2024 Oct 15.

ABSTRACT

Vaccine co-administration can efficiently increase vaccination uptake and timely immunization. This study aimed to evaluate the safety of the enterovirus 71 (EV71) vaccine administered alone or concurrently with other vaccines in infants 6-11 months. A total of 3,769 EV71 vaccine doses were administered to children in the active surveillance area, of which 1,909 were administered concurrently with other vaccines and 1,860 doses were administered alone. Active surveillance was conducted to observe adverse events (AEs) within 0-7 and ≥8 days after vaccination and to determine the incidence of reported AEs. The overall AE incidence was 2.12% (95% CI: 1.66%-2.58%), with 1.56% (95% CI:1.00%-2.12%) for the EV71 vaccine alone and 2.67% (95% CI: 1.95%-3.40%) for simultaneous administration of the EV71 vaccine and other vaccines (x2 = 5.612, p = .018). The solicited local AE incidence was 1.00% (95% CI: 0.55%-1.44%) in the EV71 vaccine co-administration group and 0.59% (95% CI: 0.24%-0.94%) in the EV71 vaccine alone group (x2 = 1.946, p = .018). The solicited systemic AE incidence was 1.68% (95% CI: 1.10%-2.25%) and 0.86% (95% CI: 0.44%-1.28%) in the EV71 vaccine co-administered and EV71 vaccine alone groups, respectively (x2 = 4.990, p = .025). No serious vaccine-related AEs were reported. Fever was the most common AE; no difference was observed in the incidence rate of fever between the two groups (x2 = 3.467, p = .063). Overall, AE incidence following EV71 vaccination alone or concurrently with other vaccines was acceptable; concurrent vaccination did not increase AE risk or severity.

PMID:39402977 | DOI:10.1080/21645515.2024.2412388

Sci Rep. 2024 Oct 14;14(1):24045. doi: 10.1038/s41598-024-71169-w.

ABSTRACT

The Comprehensive In-vitro Proarrhythmia Assay (CiPA) initiative aims to refine the assessment of drug-induced torsades de pointes (TdP) risk, utilizing computational models to predict cardiac drug toxicity. Despite advancements in machine learning applications for this purpose, the specific contribution of in-silico biomarkers to toxicity risk levels has yet to be thoroughly elucidated. This study addresses this gap by implementing explainable artificial intelligence (XAI) to illuminate the impact of individual biomarkers in drug toxicity prediction. We employed the Markov chain Monte Carlo method to generate a detailed dataset for 28 drugs, from which twelve in-silico biomarkers of 12 drugs were computed to train various machine learning models, including Artificial Neural Networks (ANN), Support Vector Machines (SVM), Random Forests (RF), XGBoost, K-Nearest Neighbors (KNN), and Radial Basis Function (RBF) networks. Our study's innovation is leveraging XAI, mainly through the SHAP (SHapley Additive exPlanations) method, to dissect and quantify the contributions of biomarkers across these models. Furthermore, the model performance was evaluated using the test set from 16 drugs. We found that the ANN model coupled with the eleven most influential in-silico biomarkers namely dVm dt repol , dVm dt max , APD 90 , APD 50 , APD tri , CaD 90 , CaD 50 , Ca tri , Ca Diastole , q I n w a r d , a n d q N e t showed the highest classification performance among all classifiers with Area Under the Curve (AUC) scores of 0.92 for predicting high-risk, 0.83 for intermediate-risk, and 0.98 for low-risk drugs. We also found that the optimal in silico biomarkers selected based on SHAP analysis may be different for various classification models. However, we also found that the biomarker selection only sometimes improved the performance; therefore, evaluating various classifiers is still essential to obtain the desired classification performance. Our proposed method could provide a systematic way to assess the best classifier with the optimal in-silico biomarkers for predicting the TdP risk of drugs, thereby advancing the field of cardiac safety evaluations.

PMID:39402077 | DOI:10.1038/s41598-024-71169-w

Expert Opin Drug Saf. 2024 Oct 14. doi: 10.1080/14740338.2024.2416933. Online ahead of print.

ABSTRACT

BACKGROUND: Myocarditis is a rare but potentially life-threatening inflammation of the heart muscle that can be caused by various drugs. This study aimed to comprehensively evaluate the risk of drug-induced myocarditis using data from the FDA Adverse Event Reporting System (FAERS) database.

METHODS: We queried the FAERS database for reports of myocarditis from Q1 2004 to Q4 2023. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were calculated to detect disproportionality signals for drugs associated with myocarditis.

RESULTS: A total of 8,212 myocarditis-related reports were identified in the FAERS database. The most frequently reported drugs were clozapine (N = 1269), followed by nivolumab (N = 621), pembrolizumab (N = 358), mesalazine (252), and olanzapine (N = 191). Disproportionality analysis revealed strong signals for the top 50 drugs, including mesalazine (ROR 48.01, 95% CI 42.29-54.49), cemiplimab (ROR 38.84, 95% CI 26.71-56.47), clozapine (ROR 35.21, 95% CI 33.13-37.39), nivolumab (ROR 23.21, 95% CI 21.38-25.2), atezolizumab (ROR 20.75, 95% CI 17.91-24.05) and pembrolizumab (ROR 19.90, 95% CI 17.89-22.13).

CONCLUSIONS: Our findings suggest a potential risk of drug-induced myocarditis associated with various medications. Close monitoring for signs and symptoms of myocarditis is crucial, especially in patients with risk factors or those receiving these drugs. Further investigations are warranted to establish causality and identify risk factors.

PMID:39400122 | DOI:10.1080/14740338.2024.2416933

Cureus. 2024 Sep 13;16(9):e69330. doi: 10.7759/cureus.69330. eCollection 2024 Sep.

ABSTRACT

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare multisystem autoimmune disease resulting from necrotizing inflammation of small vessels. Genetic predisposition and environmental factors are typically associated with its presentation, though rarely a drug-induced form has been reported. Here, we present a case of a 73-year-old female with a history of hypertension and chronic kidney disease who presented with acute kidney injury secondary to hydralazine-induced ANCA vasculitis. This report aims to highlight the rare association of hydralazine with vasculitis and the importance of pursuing a full initial workup in patients with acute kidney injury.

PMID:39398788 | PMC:PMC11471049 | DOI:10.7759/cureus.69330

Hum Vaccin Immunother. 2024 Dec 31;20(1):2411824. doi: 10.1080/21645515.2024.2411824. Epub 2024 Oct 13.

ABSTRACT

Hepatitis B vaccination is the most effective means of interrupting HBV transmission. Although the hepatitis B vaccine is very effective and safe, adverse events following immunization do occur and need to be reported so that problems can be identified and appropriate corrective action can be taken. Most of the research on AEFI focuses on the safety observation of newly used vaccines, and there are few long-term studies on AEFI of the hepatitis B vaccine. This study retrospectively analyzes the reporting rate, clinical symptoms, and onset time of AEFI of the hepatitis B vaccine in Quzhou from 2011 to 2023, and compares the differences in AEFI reporting rates between different types of hepatitis B vaccines, different vaccination ages, and different doses. The surveillance results show that from 2011 to 2023, the AEFI reporting rate of hepatitis B Vaccines in Quzhou was 17.55/100,000 doses. 98.73% of reported AEFI were non-serious. The types of AEFI reported were vaccine product-related reactions, immunization anxiety-related reactions, and coincidental events. 94.12% of vaccine product-related reactions occurred within 3 days, and the main symptoms were fever, local reactions at the injection site, and rash. The AEFI reporting rate of the CHO vaccine was higher than that of the yeast vaccines, and the probability of AEFI in children under 1 year of age receiving the hepatitis B vaccine was higher in the latter dose than in the previous dose. The 13-year-long AEFI surveillance provides reliable evidence of the safety of the hepatitis B vaccine.

PMID:39396824 | DOI:10.1080/21645515.2024.2411824

Lancet Gastroenterol Hepatol. 2024 Oct 10:S2468-1253(24)00246-2. doi: 10.1016/S2468-1253(24)00246-2. Online ahead of print.

ABSTRACT

BACKGROUND: Denifanstat, an oral fatty acid synthase (FASN) inhibitor, blocks de-novo lipogenesis, a key pathway driving progressive lipotoxicity, inflammation, and fibrosis in metabolic dysfunction-associated steatohepatitis (MASH). This study aimed to examine the safety and efficacy of denifanstat for improving liver histology in individuals with MASH and moderate to advanced fibrosis.

METHODS: This multicentre, double-blind, randomised, placebo-controlled, phase 2b trial was conducted at 100 clinical sites in the USA, Canada, and Poland. After a screening period of up to 90 days, participants aged 18 years and older with biopsy-confirmed MASH and stage F2 or F3 fibrosis were randomly assigned (2:1) to receive either 50 mg oral denifanstat or placebo once per day for 52 weeks. Participants were dynamically allocated to treatment groups via a centrally administered interactive web-based response system and stratified by type 2 diabetes, region, and fibrosis stage. Investigators, patients, and the sponsor were masked to group allocation until database lock. The primary efficacy endpoints were a 2-point or greater improvement in non-alcoholic fatty liver disease activity score (NAS) without a worsening of fibrosis or MASH resolution with a 2-point or greater improvement in NAS without a worsening of fibrosis at week 52, assessed by intention to treat. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04906421, and is closed for enrolment.

FINDINGS: Of the 1087 individuals screened between June 2, 2021, and June 28, 2022, 168 eligible participants were randomly assigned to receive a dose of 50 mg denifanstat once per day (n=112) or placebo (n=56). All 168 participants (100 female, 68 male) received at least one dose of study treatment. In the ITT population, 42 (38%) of 112 participants in the denifanstat group had a 2-point or greater improvement in NAS without a worsening of fibrosis versus nine (16%) of 56 participants in the placebo group (common risk difference 21·0%, 95% CI 8·1-33·9; p=0·0035). 29 (26%) of 112 participants in the denifanstat group showed MASH resolution with a 2-point or greater improvement in NAS without a worsening of fibrosis compared with six (11%) of 56 participants in the placebo group (common risk difference 13·0%, 0·7-25·3; p=0·0173). The most common treatment-emergent adverse events were COVID-19 (19 [17%] of 112 in the denifanstat group vs six [11%] of 56) in the placebo group, dry eye symptoms (ten [9%] of 112 vs eight [14%] of 56), and alopecia (21 [19%] of 112 vs two [4%] of 56). All adverse events considered to be related to the study drug were of grade 1 or grade 2. None of the serious adverse events (13 [12%] of 112 participants in the denifanstat group vs three [5%] of 56 in the placebo group) were considered drug-related.

INTERPRETATION: Treatment with denifanstat resulted in statistically significant and clinically meaningful improvements in disease activity, MASH resolution, and fibrosis. The results of this phase 2b trial support the advancement of denifanstat to phase 3 development.

FUNDING: Sagimet Biosciences.

PMID:39396529 | DOI:10.1016/S2468-1253(24)00246-2

Crit Rev Oncol Hematol. 2024 Oct 10:104527. doi: 10.1016/j.critrevonc.2024.104527. Online ahead of print.

ABSTRACT

Antibody-drug conjugates (ADCs) are revolutionizing metastatic breast cancer treatment, resulting in a better prognosis and a higher safety profile than chemotherapy. Nevertheless, treatment-related adverse events (TRAE) have been extensively documented. We searched five databases for articles published up to December 2023 and conducted a meta-analysis on 23 clinical trials to estimate TRAE prevalence related to currently approved ADCs. The prevalence of the most common TRAEs ranged from 12% to 33%, depending on the ADC type and study design. Gastrointestinal disorders were highly prevalent during Trastuzumab Deruxtecan, general disorders were extremely common during Trastuzumab Emtansine, and blood system disorders and gastrointestinal disorders were the most prevalent during Sacituzumab Govitecan. This study provides an estimate of ADC-related TRAEs for each treatment based on study design. Despite each ADC having specific toxicities, gastrointestinal symptoms were highly prevalent in all treatments. This study lays the groundwork for developing personalized risk-stratified care pathways.

PMID:39395623 | DOI:10.1016/j.critrevonc.2024.104527

Am J Health Syst Pharm. 2024 Oct 12:zxae301. doi: 10.1093/ajhp/zxae301. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: Trauma video review (TVR) involves reviewing video recordings of team-based trauma response to evaluate team performance, identify improvement opportunities, and assess procedures, but the feasibility of using TVR to gather medication-related information is unknown. We aimed to assess the feasibility of using TVR for data collection of medication-related variables for research and quality improvement by comparing and describing differences between TVR and electronic medical record (EMR) review.

METHODS: This was an observational study of level I/II trauma patients treated between November 2022 and March 2023. Patients with video recording started within 1 minute of arrival, at least 1 medication administered, and with pharmacist participation in care were included. The number of variables able to be collected by TVR or EMR review were compared and reported in the categories of medication administration, indicators of adverse drug events (ADEs), medication errors, and communication. The numbers and types of discrepancies between data collection modalities were quantified and described. Agreement between TVR and EMR review was assessed and reported as an intraclass correlation coefficient (ICC).

RESULTS: Twenty-five patients were included; 758 and 1,011 variables collected by TVR and EMR review, respectively. In total, 689 variables were collected by both methods, and data collection modalities matched exactly in 4 of 25 patients (16%); ICC, 0.677 (moderate level of agreement). There were 46 (6.7%) discrepancies; 84% involved communication related variables. TVR missed more variables than EMR review, mostly medication errors and inability to assess ADEs but captured more communication-related variables.

CONCLUSION: TVR and EMR review together offer a greater source of medication-related information for data collection compared to either alone. EMR review collected medication administration, ADE, and medication errors variables more often than TVR and TVR was better able to collect communication-related variables. When designing studies/quality improvement efforts related to medication use during trauma resuscitation (e.g., pharmacist impact on time to administration), combined data collection modalities should be used, when available.

PMID:39394903 | DOI:10.1093/ajhp/zxae301

Immunotherapy. 2024;16(16-17):1069-1078. doi: 10.1080/1750743X.2024.2409617. Epub 2024 Oct 11.

ABSTRACT

Aim: Immune-checkpoint inhibitors (ICIs) have revolutionized treatment of metastatic head and neck squamous cell carcinomas (HNSCCs). Our goal was to assess for an association between immune-related adverse events (irAEs) and clinical outcomes for patients on ICIs.Methods: We analyzed a cohort of 110 HNSCC patients who received ICI therapy at the University of Virginia.Results: On review, 48% of our patients experienced an irAE with the most common events being hypothyroidism (30%), dermatitis (14%) and hepatitis (11%). Women were more likely to experience irAEs. Treatment interruption/discontinuation occurred in 43% patients with irAEs. Development of irAEs was associated with superior objective response rate (68 vs. 39%, p = 0.009), with a greater rate of CR (17 vs. 5%) and PR (32 vs. 16%). Twelve patients underwent ICI re-treatment following irAE, with 17% attaining a complete disease response, 25% attaining a partial response, 33% achieving stable disease and 25% experiencing disease progression with ICI resumption.Conclusion: Development of irAE was associated with superior objective response rate, with a greater rate of CR and PR. ICI re-treatment following irAE was feasible in a significant proportion of patients and can be attempted in carefully selected patients, given the dearth of second-line therapies for these patients.

PMID:39392156 | DOI:10.1080/1750743X.2024.2409617

BMC Med. 2024 Oct 11;22(1):450. doi: 10.1186/s12916-024-03621-7.

ABSTRACT

BACKGROUND: Trial registration aims to address potential bias from selective or non-reporting of findings, and therefore has a vital role in promoting transparency and accountability of clinical research. In this study, we aim to investigate the influence of trial registration on estimated harm effects in randomized controlled trials of medication interventions.

METHODS: We searched PubMed for systematic reviews and meta-analyses of randomized trials on medication harms indexed between January 1, 2015, and January 1, 2020. To be included in the analyses, eligible meta-analyses should have at least five randomized trials with distinct registration statuses (i.e., prospectively registered, retrospectively registered, and non-registered) and 2 by 2 table data for adverse events for each trial. To control for potential confounding, trials in each meta-analysis were analyzed within confounder-harmonized groups (e.g., dosage) identified using the Directed Acyclic Graph method. The harm estimates arising from the trials with different registration statuses were compared within the confounder-harmonized groups using hierarchical linear regression. Results are shown as ratio of odds ratio (OR) and 95% confidence interval (CI).

RESULTS: The dataset consists of 629 meta-analyses of harms with 10,069 trials. Of these trials, 74.3% were registered, and 23.9% were not registered, and for those registered, 70.6% were prospectively registered, while 26.3% were retrospectively registered. In comparison to prospectively registered trials, both non-registered trials (ratio of OR = 0.82, 95%CI 0.68 to 0.98, P = 0.03) and retrospectively registered trials (ratio of OR = 0.75, 95%CI 0.66 to 0.86, P < 0.01) had lower OR for harms based on 69 and 126 confounders-harmonized groups. The OR of harms did not differ between retrospectively registered and non-registered trials (ratio of OR = 1.02, 95%CI 0.85 to 1.23, P = 0.83) based on 76 confounders-harmonized groups.

CONCLUSIONS: Medication-related harms may be understated in non-registered trials, and there was no obvious evidence that retrospective registration had a demonstrable benefit in reducing such selective or absent reporting. Prospective registration is highly recommended for future trials.

PMID:39394146 | PMC:PMC11470660 | DOI:10.1186/s12916-024-03621-7

BMC Pediatr. 2024 Oct 11;24(1):652. doi: 10.1186/s12887-024-05128-9.

ABSTRACT

BACKGROUND: Drug-drug interactions (DDIs) are associated with increased or decreased adverse effects and decreased or decreased therapeutic effects. Hospitalized pediatric patients are exposed to a number of potential DDIs (pDDIs). There are limited studies on pDDIs among pediatric patients in Ethiopia. This study was aimed to evaluate the pDDIs and associated factors among hospitalized pediatric patients in Adigrat general hospital, Tigrai, northern Ethiopia.

METHODS: A retrospective cross-sectional study was carried out among hospitalized pediatric patients in Adigrat general hospital from 01 July 2020 to 31 August 2020. A simple random sampling technique was used to select medical charts. Micromedex 2.0 database was used to screen pDDIs. Data was analyzed using statistical package for social science version 21 and a P-value of ≤ 0.05 was considered statistically significant.

RESULTS: Of the total 146 patients studied, 100 (68.5%) were exposed for at least one pDDI. A total of 158 pDDIs consisting of 33 distinct interacting drug pairs were identified. About 19.3% of the patients had at least one major pDDI, 6.7% at least one moderate and 68.9% at least one minor pDDIs. On the other hand, 63.3% of the total pDDIs were minor and 25.9% major while 3. 8% were contraindicated pDDIs with 15.2% fair and 81.6% good level of documentation. The overall mean duration of pDDIs exposure was about 4.9 (1-23) days. The frequently occurring potential clinical consequences of pDDIs comprised increased risk of QT-interval prolongation (10.1%), theophylline toxicity (5.1%), antiepileptic toxicity (5.1%) and formation of ceftriaxone calcium precipitates (3.8%). Infant/toddler age group (adjusted odds ratio [AOR] = 31.961, 95% CI: 1.117-914.528), number of diseases (AOR = 0.255, 95% CI: 0.069-0.939) and polypharmacy (AOR = 0.276, 95% CI: 0.091-0.838) were associated with pDDIs exposures.

CONCLUSIONS: A large number of pediatric patients were exposed to a various pDDIs. Age, number of diseases and polypharmacy predicted for the occurrence of pDDIs. Besides, the major severity pDDIs encounted frequently in the current study can potentially lead to a life threatening cardio-vascular toxicicty from QT-interval prolongation. Clinicians should be vigilant to pDDIs to prevent potential clinical consequences of pDDIs. Moreover, computerized drug interaction screening and clincal pharmacy services should be practiced to improve patients' safety.

PMID:39394093 | PMC:PMC11468254 | DOI:10.1186/s12887-024-05128-9

J Alzheimers Dis. 2024;101(4):1107-1120. doi: 10.3233/JAD-240575.

ABSTRACT

BACKGROUND: Older adults with dementia who are on polypharmacy are more vulnerable to the use of potentially inappropriate medications (PIM), which can significantly increase the risk of adverse events and drug-related problems (DRPs).

OBJECTIVE: This systematic review and meta-analysis were conducted to map the prevalence of PIM use, polypharmacy, and hyper-polypharmacy among older adults with cognitive impairment or dementia attending memory clinics.

METHODS: Ovid MEDLINE, Ovid EMBASE, Scopus, Cochrane Library, EBSCOhost CINAHL, and Ovid International Pharmaceutical Abstracts (IPA) were systematically searched from inception to April 22, 2024. Observational studies assessing the PIMs use among older adults with CI or dementia were screened. A random- effects meta-analysis was conducted to pool the prevalence estimates.

RESULTS: Of 5,787 identified citations, 11 studies including 4,571 participants from 8 countries were included. Among all the included studies the pooled prevalence of PIM use was 38% (95% confidence interval (CIn): 27- 50%), highlighting a notable range from 20% to 78%. The analysis identified anticholinergics, benzodiazepines, and non-benzodiazepine sedatives as the most common PIMs. Subgroup analysis revealed a higher pooled prevalence of PIM in the USA (39%; 95% CIn: 10- 78, I2 (%) = 98, 3 studies) and Australia (36%, 95% CIn: 12- 70, I2 (%) = 96, 2 Studies). Additionally, pooled prevalence of polypharmacy and hyper-polypharmacy was reported as (60%; 95% CIn: 46- 73, I2 (%) = 95, 3 studies), and (The prevalence of hyper-polypharmacy was 17.6%; 1 study) respectively.

CONCLUSIONS: The definition of PIMs significantly impacts study results, often more than geographical variations. The variability in criteria and tools like the Beers or Screening Tool of Older Persons' Prescriptions (STOPP) criteria across studies and regions leads to differing prevalence rates.

PMID:39392603 | DOI:10.3233/JAD-240575

iScience. 2024 Sep 10;27(10):110916. doi: 10.1016/j.isci.2024.110916. eCollection 2024 Oct 18.

ABSTRACT

Genetic ancestry plays a major role in pharmacogenomics, and a deeper understanding of the genetic diversity among individuals holds immerse promise for reshaping personalized medicine. In this pivotal study, we have conducted a large-scale genomic analysis of 1,136 pharmacogenomic variants employing machine learning algorithms on 3,714 individuals from publicly available datasets to assess the risk proximity of experiencing drug-related adverse events. Our findings indicate that Admixed Americans and Europeans have demonstrated a higher risk of experiencing drug toxicity, whereas individuals with East Asian ancestry and, to a lesser extent, Oceanians displayed a lower risk proximity. Polygenic risk scores for drug-gene interactions did not necessarily follow similar assumptions, reflecting distinct genetic patterns and population-specific differences that vary depending on the drug class. Overall, our results provide evidence that genetic ancestry is a pivotal factor in population pharmacogenomics and should be further exploited to strengthen even more personalized drug therapy.

PMID:39391720 | PMC:PMC11465127 | DOI:10.1016/j.isci.2024.110916

Bull Emerg Trauma. 2024;12(3):103-110. doi: 10.30476/beat.2024.102203.1503.

ABSTRACT

OBJECTIVE: The present study aimed to evaluate the clinical benefits and drawbacks of administering ECMO/ECLS therapies to drug-intoxicated patients.

METHODS: From inception until April 30, 2024, an extensive search was performed on four main databases: PubMed, Web of Science, Cochrane Library, and EMBASE. There was no restriction on the search period. Only the studies that reported survival to hospital discharge rates, adverse events, and the utilization of ECMO/ECLS in the treatment of intoxicated patients were included. On the other hand, articles that did not report adverse events or hospital discharge rates as outcomes, as well as studies published in languages other than English, were excluded. The evaluated outcomes were the rate of survival to hospital discharge rate and the incidence of adverse events associated with ECMO therapy. The Newcastle Ottawa scale was employed to appraise each study to determine its methodological quality. The Comprehensive Meta-Analysis (CMA) software (version 3.0) for statistical analysis was used, with the random effects model (due to high heterogeneity among the studies) and a 95% confidence interval.

RESULTS: From a total search of 2216 search results, only 10 studies were included. The pooled analysis from 10 studies indicated that ECMO therapies among drug-overdosed/poisoned patients were associated with a significant survival to hospital discharge rate of 65.6% ([95% CI: 51.5%-77.4%], p=0.030). However, the outcomes were highly heterogeneous (I2=83.47%), which could be attributed to the use of several medicines by different studies. In contrast, ECMO therapies among drug-overdosed patients were associated with a significant incidence rate of adverse events of 23.1% ([95% CI: 12.3%-39.2%], p=0.002). However, the pooled analysis had a significant heterogeneity (I2=70.27%).

CONCLUSION: Despite various health complications, extracorporeal membrane treatment enhanced survival to hospital discharge with good neurological outcomes. Hence, it was a viable, effective, and feasible alternative for managing drug-induced intoxication in patients.

PMID:39391356 | PMC:PMC11462113 | DOI:10.30476/beat.2024.102203.1503