J Gastroenterol Hepatol. 2024 Sep 3. doi: 10.1111/jgh.16730. Online ahead of print.

ABSTRACT

There is increasing evidence that cannabidiol (CBD) use is associated with clinically significant liver enzyme (LE) elevations and drug-induced liver injury (DILI). The proportion of LE elevations and DILI events reported in the literature meet the Council for International Organizations of Medical Sciences' (CIOMS) classification of a common adverse drug reaction. However, these potential adverse events are unknown to many clinicians and may be overlooked. The increasing use of CBD for both medical and non-medical use necessitates clear direction in the diagnosis and management of CBD-associated hepatotoxicity. To our knowledge, no such clinical guidance currently exists. For people presenting with elevated LEs, CBD use should be screened for and be considered in the differential diagnosis. This narrative review will provide clinicians with guidance in the prevention, detection, and management of CBD-related hepatotoxicity.

PMID:39228144 | DOI:10.1111/jgh.16730

Eur J Hosp Pharm. 2024 Sep 3:ejhpharm-2024-004131. doi: 10.1136/ejhpharm-2024-004131. Online ahead of print.

ABSTRACT

OBJECTIVES: Adverse drug reactions (ADRs) are among the leading standalone causes of morbidity and hospitalisation and contribute substantially to an increase in healthcare expenditure. Repeat ADR events, although difficult to quantify, are a recognised problem that lead to preventable suffering for the patient. The current approaches for the prevention of ADR recurrence in low/middle-income countries range from inefficient to non-existent. There is very little literature that focuses on the preventability of ADRs in such settings. This study aimed to develop the ADR Alert Card, an economical innovation designed as a stop gap in preventing ADR recurrence, and to evaluate its utility by validating the system through input from medical professionals.

METHODS: The ADR Alert Card was validated and registered with the Copyrights Office of the Government of India. To obtain the opinion of healthcare professionals and gauge the status quo in prevention of ADR recurrence, we conducted an online descriptive cross-sectional study over a period of 6 months.

RESULTS: The survey received 218 responses. Demographics varied, ranging across different healthcare specialties and years of experience. Our study found that existing practice in ADR recurrence prevention was inadequate, and most healthcare workers were unaware of an alternative approach. Unique solutions were provided by the respondents, with the majority favouring a card format for preventing recurrence.

CONCLUSIONS: After being introduced to the ADR Alert Card, there was an overwhelming consensus on the utility and practicality of this card in preventing ADR recurrence.

PMID:39227143 | DOI:10.1136/ejhpharm-2024-004131

Expert Opin Drug Saf. 2024 Sep 2. doi: 10.1080/14740338.2024.2399094. Online ahead of print.

ABSTRACT

BACKGROUND: In the United States clozapine was first approved for treatment-resistant schizophrenia and then for suicidality in schizophrenia psychoses. Systematic reviews support clozapine's anti-suicidal effect, but the forensic literature stresses its lethality during overdoses.

RESEARCH DESIGN AND METHODS: Clozapine reports to the international pharmacovigilance database (VigiBase) were analyzed for suicidal ideation, suicide attempts, intentional overdose, and completed suicides from introduction to 1 January 2024. VigiBase uses the information component (IC) as a disproportionality analysis.

RESULTS: The clozapine ICs (range: other antipsychotics) were: 1) suicidal ideation IC = 0.570 with IC025 = 0.454 to IC975 = 0.680 (IC = 3.568 for aripiprazole and 1.729 for risperidone), 2) suicide attempt IC = 1.428 with IC025 = 1.323 to IC975 = 1.529 (IC = 4.150 for quetiapine and 2.968 for risperidone), 3) intentional overdose: IC = 0.995 with IC025 = 0.864 to IC975 = 1.120 (IC = 4.080 for quetiapine and 1.957 for aripiprazole), and 4) completed suicide IC = 1.133 with IC025 = 1.026 to IC975 = 1.235 (IC = 4.648 for quetiapine and 2.160 for risperidone). In summary, all clozapine ICs were significantly lower. We found 2391 clozapine-treated patients on the suicidality spectrum (627 cases with suicidal ideation, 752 with suicide attempt, 488 with intentional overdose and 731 with completed suicide) but many were taking other antipsychotics. The most frequent reporting countries were the United States, the United Kingdom, and Croatia.

CONCLUSION: This pharmacovigilance study, with all its inherent limitations, provides independent proof, not overlapping with prior literature, that clozapine may have specific strong anti-suicidal effects that do not appear to be present in other antipsychotics. Further VigiBase studies are needed to compare the lethality of an intentional overdose of clozapine (14.3%) with other antipsychotics.

PMID:39223773 | DOI:10.1080/14740338.2024.2399094

Cureus. 2024 Aug 1;16(8):e65945. doi: 10.7759/cureus.65945. eCollection 2024 Aug.

ABSTRACT

Trimethoprim-sulfamethoxazole (TMP-SMX), a widely used antibiotic, is associated with both predictable dose-dependent side effects and rare, idiosyncratic adverse reactions. Here, we report the case of a previously healthy, non-G6PD-deficient, 27-year-old male who developed three idiosyncratic reactions: severe thrombocytopenia, aseptic meningitis, and hepatitis concurrently following TMP-SMX administration. The Naranjo adverse reaction probability score was 7, implying TMP-SMX as the probable cause of the clinical presentation. After a comprehensive workup to rule out alternate etiologies, we have established TMP-SMX as the culprit. Our case highlights the importance of early recognition of TMP-SMX-induced rare adverse events for appropriate management to mitigate long-term sequelae and ensure favorable patient outcomes.

PMID:39221287 | PMC:PMC11365456 | DOI:10.7759/cureus.65945

Epilepsy Behav. 2024 Aug 30;159:109989. doi: 10.1016/j.yebeh.2024.109989. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate long-term efficacy, safety, and tolerability, including behavior and executive functioning, during adjunctive lacosamide (LCM) treatment in pediatric patients (≥1 month to <18 years of age) with focal-onset or generalized seizures enrolled in 2 open-label, long-term follow-up trials.

METHODS: Two open-label extension trials (SP848: NCT00938912; EP0034: NCT01964560) were conducted in pediatric patients who had participated in previous trials of adjunctive LCM (SP0847/NCT00938431; SP0966/NCT01969851; EP0060/NCT02710890; SP0967/NCT02477839; SP0969/NCT01921205); SP848 also directly enrolled eligible pediatric patients who had not previously participated in a clinical trial of LCM. Outcomes included retention, efficacy, and safety/tolerability. Patient improvement was assessed with Clinician's and Caregiver's Global Impression of Change scale. Behavior and emotional function was assessed with Achenbach Child Behavior Checklist (CBCL) and executive functioning was assessed with Behavior Rating Inventory of Executive Function® (BRIEF).

RESULTS: The pooled dataset from both trials included 905 patients (851 in the focal-onset seizure population and 47 in the generalized seizure population). In the overall population, Kaplan-Meier-estimated 1-year retention was 80 %. From baseline to the end of the treatment period, patients in the focal-onset seizure population had a median percent reduction in focal-onset seizure frequency per 28 days of 60.4 %, 55.4 % of patients were 50 % responders, and 40.8 % of patients were 75 % responders. In patients with ≥12 months of LCM treatment, ≥12 month seizure freedom during the LCM treatment period was achieved by 29.9 % of patients in the focal-onset seizure population (median duration of first ≥12-month seizure-free interval: 641 days) and 24.4 % of patients in the generalized seizure population (median duration of first ≥12-month seizure-free interval: 665 days). Improvement during LCM treatment was reported in >75 % of patients by both physicians and caregivers. Treatment-emergent adverse events (TEAEs) were reported by 749 (82.8 %) patients, most commonly pyrexia (18.9 %), upper respiratory tract infection (18.6 %), nasopharyngitis (16.2 %), vomiting (15.7 %), and somnolence (11.8 %). The most common drug-related TEAEs were somnolence (8.5 %), dizziness (7.6 %), and vomiting (5.4 %). Behavioral and emotional function was generally stable in patients 1.5-5 years of age and slightly improved in patients ≥6 years of age, and executive functioning was stable in patients <5 years of age and generally slightly improved in patients 5-18 years of age.

CONCLUSIONS: In this analysis of a large patient pool from 2 open-label trials, long-term adjunctive LCM was efficacious and generally well tolerated in children with epilepsy and focal-onset or generalized seizures. Behavior and executive functioning were generally stable without observable worsening during long-term adjunctive LCM treatment.

PMID:39216464 | DOI:10.1016/j.yebeh.2024.109989

Trials. 2024 Aug 31;25(1):573. doi: 10.1186/s13063-024-08418-w.

ABSTRACT

BACKGROUND: Randomised controlled trials (RCTs) are typically designed to determine beneficial intervention effects. In addition, an important aspect of every trial is to collect data on any potential harmful effects, with the aim of ensuring that the benefit-risk balance is appropriate. The language used by trialists to describe these potential harmful effects is inconsistent. In pharmacological trials, researchers collect adverse events; when a causal relationship is suspected adverse events are further classified as adverse reactions. Academic researchers have moved to collectively refer to these as harm outcomes; the pharmaceutical industry refer to these events as safety outcomes. In trials of complex interventions, phrases such as unintended consequences or effects are used. With the inconsistent use of terminology by researchers and the potential benefits to be gained from harmonising communications, we sought public opinion on terminology used to describe harmful effects and how these outcomes are communicated in the scientific literature, as well as in public facing material on medications.

METHODS: We held two in-person public involvement meetings with public partners, in London and Aberdeen in 2023. Both meetings followed a pre-specified format. We provided a background to the topic including the information researchers collect on potential harms in clinical trials and shared examples on how this information gets presented in practice. We then discussed public partners' perspectives on terminology used and communication of intervention harm in academic journals and in public facing materials. A summary of these discussions and the main topics raised by public partners are presented.

RESULTS: Public partners endorsed the use of different terms for different situations, preferring the use of 'side-effect' across all contexts and reserving the use of 'harm' to indicate more severe events. Generally, public partners were happy with the type of information presented in public facing materials but discussions revealed that presentation of information on public NHS websites led to misconceptions about harm.

CONCLUSION: This work provides a starting point on preferred terminology by patients and the public to describe potential harmful intervention effects. Whilst researchers have tried to seek agreement, public partners endorsed use of different terms for different situations. We highlight some key areas for improvement in public facing materials that are necessary to avoid miscommunication and incorrect perception of harm.

PMID:39215336 | DOI:10.1186/s13063-024-08418-w

Medicine (Baltimore). 2024 Aug 30;103(35):e39347. doi: 10.1097/MD.0000000000039347.

ABSTRACT

OBJECTIVE: To determine the clinical benefit of monotherapy with AKT inhibitors in patients diagnosed with triple-negative breast cancer (TNBC).

METHODS: A systematic search was conducted in PubMed, Embase, and Cochrane Library for articles reporting treatment with AKT inhibitors in TNBC. The primary endpoint was progression-free survival and overall survival (OS). Secondary endpoints included the clinical benefit rate (CBR, included the proportion of patients with complete response, partial response, and stable disease), overall response rate (ORR, included the proportion of patients with complete response and partial response), all drug-related adverse events (AEs), and ≥3 grade drug-related grade AE.

RESULTS: We included 723 patients from 5 studies and observed a pooled progression-free survival of 0.80 (95% CI: 0.62-1.02; The Grading of Recommendations, Assessment, Development, and Evaluations [GRADE] assessment: moderate certainty) and OS of 0.7 (95% CI: 0.50-0.99; GRADE assessment: high certainty) in TNBC patients treated with AKT inhibitors. Regarding clinical benefit rate and overall response rate were 1.21 (95% CI 0.85-1.73; GRADE assessment: moderate certainty) and 1.26 (95% CI 0.91-1.73; GRADE assessment: low certainty). Only OS had a statistical difference. For the odd ratio of all grade AE and ≥3 grade AE in the therapeutic process was counted and pooled, 4.34 (95% CI 1.33-14.14; GRADE assessment: moderate certainty) and 1.76 (95% CI 1.28-2.41; GRADE assessment: moderate certainty), respectively.

CONCLUSIONS: AKT inhibitors showed slightly better efficacy in the treatment of TNBC. However, further studies are needed to evaluate its long-term safety and optimal regimen, and caution should be exercised in patients with coexisting gastrointestinal disorders. The clinical characteristics of the patients and the choice of drugs should be considered on an individual basis.

PMID:39213250 | DOI:10.1097/MD.0000000000039347

Pharmacoepidemiol Drug Saf. 2024 Sep;33(9):e70003. doi: 10.1002/pds.70003.

ABSTRACT

PURPOSE: Removing medicines from market may benefit public health by preventing adverse drug reactions (ADRs), which should be quantified. This study's aim was to identify a model to quantify the impact of medicines' marketing authorisation (MA) withdrawal and revocation in terms of preventing morbidity and mortality.

METHODS: MA withdrawals and revocations for safety reasons in France, Germany and/or the United Kingdom between July 2012 and December 2016 were identified for prescription medicines. Annual exposure was estimated for each medicine, using IQVIA Medical Research Data (IMRD)-France, IMRD-Germany and IMRD-UK primary care electronic health record databases. European Medicines Agency records provided reasons for regulatory action for each medicine. Absolute risks of ADRs which led to MA withdrawal were estimated for patients exposed to each medicine by systematic review of quantitative research. Public health impact, expressed as annual number of ADRs avoided, was estimated by modelling exposure and ADR risk.

RESULTS: Four MA withdrawals and two revocations met study inclusion criteria. Each product's usage decreased following MA withdrawal or revocation. Absolute risk for ADRs was 0.1%-41.25%. To estimate impact of each withdrawal or revocation, its average annual exposure within each IMRD population was multiplied by the absolute risk to give the crude number of ADRs prevented annually due to regulatory action.

CONCLUSIONS: This model quantifies the public health impact of MA withdrawal and revocation in terms of serious morbidity, resulting from eliminated or reduced usage of medicines. This method can be applied to products in other settings to quantify the impact of other pharmacovigilance actions.

PMID:39212104 | DOI:10.1002/pds.70003

JMIR Public Health Surveill. 2024 Aug 29;10:e63808. doi: 10.2196/63808.

ABSTRACT

BACKGROUND: Herbal medicines (HMs) are extensively used by consumers/patients worldwide. However, their safety profiles are often poorly reported and characterized. Previous studies have documented adverse events (AEs) associated with HMs, such as hepatotoxicity, renal failure, and allergic reactions. However, the prevalence rate of AEs related to HMs has been reported to be low. To date, no systematic review and meta-analysis has comprehensively analyzed the AEs of HMs using published data acquired from pharmacovigilance (PV) databases.

OBJECTIVE: This study aimed to (1) estimate the reporting rate of the AEs of HMs using PV databases and (2) assess the detailed data provided in AE reports.

METHODS: In this systematic review and meta-analysis, MEDLINE/PubMed, SCOPUS, EMBASE, and CINAHL were systematically searched for relevant studies (until December 2023). The DerSimonian-Laird random effects model was used for pooling the data, and subgroup analyses, the meta-regression model, and sensitivity analysis were used to explore the source of heterogeneity. Crombie's checklist was used to evaluate the risk of bias (ROB) of the included studies.

RESULTS: In total, 26 studies met the eligibility criteria. The reporting rate of the AEs of HMs ranged considerably, from 0.03% to 29.84%, with a median overall pooled estimate of 1.42% (IQR 1.12%-1.72%). Subgroup analyses combined with the meta-regression model revealed that the reporting rate of the AEs of HMs was associated with the source of the reporter (P=.01). None of the included studies provided full details of suspected herbal products, only the main ingredients were disclosed, and other potentially harmful components were not listed.

CONCLUSIONS: This systematic review and meta-analysis highlighted risks related to HMs, with a wide range of reporting rates, depending on the source of the reporter. Continuous efforts are necessary to standardize consumer reporting systems in terms of the reporting form, education, and follow-up strategy to improve data quality assurance, aiming to enhance the reliability and utility of PV data for monitoring the safety of HMs. Achieving effective monitoring and reporting of these AEs necessitates collaborative efforts from diverse stakeholders, including patients/consumers, manufacturers, physicians, complementary practitioners, sellers/distributors, and health authorities.

TRIAL REGISTRATION: PROSPERO (Prospective International Register of Systematic Reviews) CRD42021276492.

PMID:39208414 | DOI:10.2196/63808

PLoS One. 2024 Aug 29;19(8):e0309362. doi: 10.1371/journal.pone.0309362. eCollection 2024.

ABSTRACT

BACKGROUND: Drug, medicament, and biological substance poisoning, adverse effects, and underdosing are significant public health concerns. Gaining insight into the patterns and trends in hospitalizations caused by these occurrences is essential for the development of preventative initiatives, optimization of treatment regimens, and improvement of patient safety. The aim of this study is to examine the trend of hospitalisation related to poisoning by, adverse effect of and underdosing of drugs, medicaments and biological substances in Australia between 1998 and 2019.

METHODS: This is an ecological descriptive study that examined hospitalisation related to poisoning by, adverse effect of and underdosing of drugs, medicaments and biological substances in Australia between 1998 and 2019. A nationwide hospital admissions database was used for this study.

RESULTS: Between 1998 and 2019, a total of 683,869 hospital admission episodes were recorded in Australia. The overall annual number of hospital admissions for various reasons increased by 20.5% from 29,854 in 1998 to 35,960 in 2019, representing a decrease in hospital admission rate of 10.6% [from 158.69 (95% CI 156.90-160.49) in 1998 to 141.91 (95% CI 140.44-143.37) in 2019 per 100,000 persons, trend test, p<0.05]. Overnight-stay admissions accounted for 69.2% of the total number of hospital admissions, and 30.8% were same-day admissions. Rates of same-day hospital admission decreased by 13.3% [from 50.55 (95%CI 49.54-51.57) in 1998 to 43.81 (95%CI 43.00-44.63) in 2019 per 100,000 persons]. Rates of overnight-stay hospital admission decreased by 11.1% [from 108.14 (95%CI 106.66-109.63) in 1998 to 96.17 (95%CI 94.96-97.38) in 2019 per 100,000 persons]. Admissions related to antiepileptic, sedative-hypnotic and antiparkinsonism drugs was the most prevalent hospital admissions type accounting for 26.8%. Females were responsible for 418,751 hospital admission episodes, representing 61.5% of the total number of hospital admission.

CONCLUSION: This study found that while the overall annual number of admissions increased, the rate of admission decreased over the same period. The most common reasons for admissions were antiepileptic, sedative-hypnotic, and anti-parkinsonism drugs. The study also noted increases in admissions related to anaesthetics, therapeutic gases, hormones, and their synthetic substitutes. These findings suggest a concerning rise in the suboptimal use of these medications. In order to combat the increasing incidence of this type of admissions, it is imperative to strengthen public awareness initiatives on medicine safety and abuse.

PMID:39208193 | DOI:10.1371/journal.pone.0309362

Clin Endosc. 2024 Aug 29. doi: 10.5946/ce.2024.003. Online ahead of print.

ABSTRACT

The use of immune checkpoint inhibitors (ICIs) for the treatment of various malignancies is increasing. Immune-related adverse events can occur after ICI administration, with gastrointestinal adverse events constituting a significant proportion of these events. When ICI-related diarrhea/colitis is suspected, endoscopic evaluation is recommended to differentiate it from other etiologies and assess the severity of colitis. The distribution of intestinal inflammation in ICI-related colitis demonstrates a high frequency of extensive colitis (23-86%). However, isolated right-sided colitis (3-8%) and ileitis (2-16%) are less prevalent. Endoscopic findings vary and predominantly encompass features indicative of inflammatory bowel disease, including aphthae, ulcers, diffuse or patchy erythema, mucosal edema, loss of vascular pattern, and friability. The presence of ulcers and extensive intestinal inflammation are associated with a reduced response to treatment. Microscopic inflammation can be observed even in endoscopically normal mucosa, underscoring the need for biopsies of seemingly normal mucosa. Histological findings present with acute/chronic inflammation and occasionally exhibit characteristics observed in inflammatory bowel disease, microscopic colitis, or ischemic colitis. The first-line therapeutic choice for ICI-related diarrhea/colitis with a common terminology criteria for adverse events grade of 2 or above is corticosteroids, whereas infliximab and vedolizumab are recommended for refractory cases.

PMID:39206499 | DOI:10.5946/ce.2024.003

Glob Pediatr Health. 2024 Aug 27;11:2333794X241273171. doi: 10.1177/2333794X241273171. eCollection 2024.

ABSTRACT

Objective. Children's vulnerability to drug-related side effects has been highlighted in several studies. However, there is no consensus on the risk factors associated with these side effects. This study aimed to investigate risk factors associated with drug-related side effects in children. Methods. This scoping review was conducted across multiple databases. The search strategy was created with a focus on drug-related side effects, as they are more predictable based on the pre-determined risk factors. Data were collected, and reported narratively. Results. The demographic, health, hospital, and drug-related risk factors may cause drug-related side effects in children. Among them, low age, sex, polypharmacy, length of hospitalization, and medications used for comorbidities may increase the risk. Conclusion. While most of the risk factors might be similar in adults and children, their impact might be different in these 2 groups. Therefore, future studies should identify more details about the impact of the risk factors in children.

PMID:39205860 | PMC:PMC11350535 | DOI:10.1177/2333794X241273171

Liver Int. 2024 Sep;44(9):2469-2476. doi: 10.1111/liv.16014. Epub 2024 Jun 22.

ABSTRACT

BACKGROUND & AIMS: The benefits of prophylactic antibiotics in patients with alcohol-associated hepatitis (AH) receiving steroids remain unclear. We aimed to assess the clinical impact of prophylactic antibiotics in AH patients receiving steroids.

METHODS: We systematically reviewed four electronic databases from inception to 30 November 2023. Pooled estimates were analysed using random-effects models. The primary outcome was 90-day survival. Secondary outcomes included infection at days 30 and 90 days, hepatorenal syndrome (HRS), acute kidney injury (AKI), hepatic encephalopathy (HE) and drug-related adverse events (AE). Trial sequential analyses were performed for the primary outcome of 90-day mortality.

RESULTS: We screened 419 articles and included six eligible studies (four RCTs and two matched cohort studies) with a total of 510 patients. Compared to standard medical treatment (SMT), prophylactic antibiotics were associated with a lower risk of infection at 30 days (OR: 0.35, 95%CI: 0.20-0.59, I 2 = 0%), infection at 90 days (OR: 0.26, 95%CI: 0.10-0.67, I 2 = 0%) and a lower rate of HE (OR: 0.32, 95%CI: 0.12-0.87, I 2 = 0%). However, prophylactic antibiotics did not improve 90-day survival, sepsis-related mortality, HRS, or AKI. The risks of drug-related AE and fungal infections were similar in patients with AH who received prophylactic antibiotics or SMT. Using trial sequential analysis, the minimum sample size required to detect a 15% relative risk reduction in 90 days mortality with prophylactic antibiotics was 1171.

CONCLUSIONS: In hospitalized AH patients receiving steroid therapy, prophylactic antibiotics reduced the risk of infection and HE, but did not improve survival or prevent AKI compared to SMT.

PMID:39205440 | DOI:10.1111/liv.16014

Pharmaceuticals (Basel). 2024 Aug 22;17(8):1099. doi: 10.3390/ph17081099.

ABSTRACT

Specific drugs are well known to have the capacity to induce Parkinson-like symptoms. Parkinson-like events are side effects that may persist for an extended period even after drug administration is discontinued. Although these events can be triggered by various drugs, the mechanisms underlying their diverse symptoms remain largely unclear. To investigate this, we used the Japanese Adverse Drug Event Reporting Database, which is maintained by the Pharmaceuticals and Medical Devices Agency, to analyze the risk factors associated with Parkinson-like events along with the associated drug trends and characteristics. Our findings indicate that similar to Parkinson's disease, age-related differences affect the onset of these reported events, with older individuals being more susceptible. Hierarchical clustering and principal component analysis revealed that the mechanisms triggering these Parkinson-like events are consistent across reports, suggesting a common underlying cause. However, even with a consistent mechanism, the side effects can vary depending on the site of action. These insights underline the importance of the swift identification of the drugs suspected of causing these events and the implementation of measures to reduce their side effects.

PMID:39204204 | DOI:10.3390/ph17081099

J Clin Med. 2024 Aug 18;13(16):4869. doi: 10.3390/jcm13164869.

ABSTRACT

Introduction: Adverse drug reactions are a significant problem in modern society, stemming from the increase in prescribed medications, over-the-counter drugs, and overall polypharmacy. Glomerular disorders are one of the frequently reported renal conditions associated with medication use. VigiBase is a significant tool for evaluating events associated with drug use, and, to the authors' knowledge, no study has yet assessed this database to identify the primary medications associated with glomerular disorders. Materials and Methods: We collected data from VigiBase for 54 years and evaluated data based on global frequencies, disproportionality (IC025 values), nephrotoxic potential, and physiopathological mechanisms. Results: Over the evaluation period, 33.932.051 spontaneous notifications of adverse drug reactions reported in VigiBase were assessed, from which 106.775 notifications of drug-associated glomerular disorders were extracted. The isolated medications were classified as 'potential nephrotoxins' (47.0%), with 40% of the medications lacking scientific references to report any association with the development of glomerular disorders. Among the evaluated medications, Inotersen (IC025 of 8.3), Penicillamine (IC025 6.8), Bevacizumab (IC025 5.9) and Lenvatinib (IC025 5.4) were identified as having the strongest association with these glomerular disorders. For medications classified as 'non-nephrotoxic', a high disproportionality index was observed, suggesting drugs that might be considered as new potential nephrotoxins. Conclusions: Drug-induced glomerular disorders were significantly associated with medications that had no established nephrotoxic role but demonstrated a high disproportionality index in VigiBase. These newly alleged nephrotoxic drugs warrant further evaluation in dedicated studies to assess their true nephrotoxic potential.

PMID:39201010 | DOI:10.3390/jcm13164869

Korean J Radiol. 2024 Sep;25(9):824-832. doi: 10.3348/kjr.2024.0248.

ABSTRACT

OBJECTIVE: To determine the preventive effect of changing gadolinium-based contrast agents (GBCAs) to reduce the recurrence of GBCA-associated acute adverse drug reactions (ADRs).

MATERIALS AND METHODS: This retrospective, observational, single-center study-conducted between January 2016 and December 2021-included 238743 consecutive GBCA-enhanced MRI examinations. We focused on a subgroup of patients who experienced acute GBCA-associated ADRs during any of these examinations and subsequently underwent follow-up GBCA-enhanced MRI examinations up until July 2023. The follow-up examinations involved either the same (non-change group) or different (change group) GBCAs compared to the ones that initially caused the acute ADR. Baseline participant characteristics, generic profile of the GBCAs, administration of premedication, history of prior ADR to iodinated contrast media, and symptoms of GBCA-associated acute ADRs were retrospectively analyzed. Multivariable logistic regression with generalized estimating equations and propensity score matching were used.

RESULTS: A total of 1042 instances of acute ADRs (0.44%; 95% confidence interval [CI]: 0.41%-0.46%) were reported. Three-hundred and seventy-three patients underwent GBCA-enhanced MRI examinations after experiencing GBCA-associated acute ADRs within the study period; 31.9% (119/373) reexperienced acute ADRs at any of the follow-up examinations. The ADR recurrence was significantly lower in the GBCA change group than in the non-change group according to multivariable logistic regression (adjusted odds ratio [OR]: 0.35; 95% CI: 0.13-0.90; P = 0.03) and analysis with propensity score matching (14.3% [6/42] vs. 36.9% [31/84], respectively; OR: 0.32, 95% CI: 0.11-0.94; P = 0.04). A history of an ADR to iodinated contrast media (OR: 1.14, 95% CI: 0.68-1.90; P = 0.62) and premedication (adjusted OR: 2.09, 95% CI: 0.93-4.68; P = 0.07) were not significantly associated with GBCA-associated acute ADR recurrence. A separate analysis for recurrent allergic-like hypersensitivity reactions demonstrated similar results (adjusted OR: 0.20, 95% CI: 0.06-0.65; P < 0.01).

CONCLUSION: Changing GBCAs may reduce the risk of GBCA-associated acute ADR recurrence.

PMID:39197827 | DOI:10.3348/kjr.2024.0248

J Gerontol Nurs. 2024 Sep;50(9):7-11. doi: 10.3928/00989134-20240809-03. Epub 2024 Sep 1.

ABSTRACT

PURPOSE: To define prescribing cascades (PCs) and provide tools to identify PCs, including the most common PCs described in the literature. PCs lead to the accumulation of medications prescribed to older adults, disproportionately affecting those who often have additional health care complexities, such as multiple chronic conditions and multiple transitions of care.

METHOD: Review of recent research efforts to identify and describe evolving clinical practice interventions to detect and reverse PCs.

RESULTS: Clinicians can contribute to mitigating PCs through better understanding of how PCs occur in practice. Armed with this knowledge, clinical team members can implement proposed strategies and techniques to engage in primary and secondary prevention of PCs.

CONCLUSION: Ultimately, PCs are a culprit of preventable medication harm. Several tools are presented, which are initiated through maintaining a high index of suspicion for PCs in the evaluation of a new symptom presentation by older patients. [Journal of Gerontological Nursing, 50(9), 7-11.].

PMID:39194326 | DOI:10.3928/00989134-20240809-03

J Pharm Health Care Sci. 2024 Aug 27;10(1):52. doi: 10.1186/s40780-024-00373-7.

ABSTRACT

BACKGROUND: Interstitial lung disease (ILD) is one of the most common fatal immune-related adverse events (irAEs). ILD development adversely affects the continuation of anticancer drug therapy, including immune checkpoint inhibitor (ICI) therapy and prognosis. There are no established useful clinical indicators for the early detection of ILD. Furthermore, the factors that lead the attending physician to suspect ICI-induced ILD (ICI-ILD) remain unclear. This study aimed to investigate the ICI-ILD detection based on subjective symptoms and their relationship with disease severity in patients receiving anti-PD-1/PD-L1 antibody.

METHODS: This was a retrospective observational study. We enrolled the patients who received anti-PD-1/PD-L1 antibody at Kyoto University Hospital between September 2014 and April 2021. Patients who developed ICI-ILD were stratified into two distinct groups based on factors that triggered the suspicion of ILD development. The "Subjective symptoms" group was defined as patients in whom ILD was detected based on subjective symptoms. Conversely, the "Routine examinations" group was defined as patients in whom ILD was suspected based on scheduled routine examinations. The severity of ILD in each group was assessed and its association with changes in the respiratory symptoms was examined.

RESULTS: Of 926 patients who received anti-PD-1/PD-L1 antibody, 51 patients (5.5%) developed ICI-ILD. The incidence of ICI-ILD in patients with lung cancer was significantly higher than that in patients with other cancers (P < 0.001). Among the patients with ICI-ILD, 27 patients (52.9%) were classified into the "Subjective symptoms" group. The "Subjective symptoms" group exhibited a significantly higher proportion of Grade 3-5 ICI-ILD cases than the "Routine examinations" group (76.2% vs. 23.8%, P = 0.010). At the last visit, before the suspected onset of ILD, 21 of the 27 patients (77.8%) had no symptoms or no change in the respiratory symptoms.

CONCLUSION: Subjective symptoms triggered the suspicion of Grade 3-5 ICI-ILD. Enhanced monitoring and patient education could be essential for the early detection of ICI-ILD because ILD may develop rapidly. Our findings might help to manage ICI-ILD in clinical practice.

PMID:39192314 | DOI:10.1186/s40780-024-00373-7

J Transl Med. 2024 Aug 27;22(1):789. doi: 10.1186/s12967-024-05439-6.

ABSTRACT

BACKGROUND: Kidneys are at risk from drug-induced toxicity, with a significant proportion of acute kidney injury (AKI) linked to medications, particularly cisplatin. Existing cytoprotective drugs for cisplatin-AKI carry side effects, prompting a search for better biological therapies. Mesenchymal Stem Cells (MSCs) are under consideration given their regenerative properties, yet their clinical application has not achieved their full potential, mainly due to variability in the source of MSC tested. In addition, translating treatments from rodent models to humans remains challenging due to a lack of standardized dosing and understanding potential differential responses to cisplatin between animal strains.

METHOD: In the current study, we performed a time-course analysis of the effect of cisplatin across different mouse strains and evaluated gender related differences to create a robust preclinical model that could then be used to explore the therapeutic efficacy of different sources of MSCs for their ability to reverse AKI.

RESULT: Our data indicated that different mouse strains produce differential responses to the same cisplatin dosing regimen. Despite this, we did not observe any gender-related bias towards cisplatin nephrotoxicity. Furthermore, our time-course analysis identified that cisplatin-induced inflammation was driven by a strong CXCL1 response, which was used as a putative biomarker to evaluate the comparative therapeutic efficacy of different MSC sources in reversing AKI. Our data indicates that UC-MSCs have a stronger anti-inflammatory effect compared to BM-MSCs and AD-MSCs, which helped to ameliorate cisplatin-AKI.

CONCLUSION: Overall, our data underscores the importance of using an optimized preclinical model of cisplatin-AKI to test different therapies. We identified CXCL1 as a potential biomarker of cisplatin-AKI and identified the superior efficacy of UC-MSCs in mitigating cisplatin-AKI.

PMID:39192240 | DOI:10.1186/s12967-024-05439-6

In Vivo. 2024 Sep-Oct;38(5):2098-2106. doi: 10.21873/invivo.13671.

ABSTRACT

BACKGROUND/AIM: Genomic variants can predispose individuals to adverse drug effects (ADEs), implying the potential for personalised therapy based on genetic data to prevent them. However, existing pharmacogenomic databases lack a comprehensive list of such variants due to irregular updates and incomplete literature coverage. To facilitate the assessment of the feasibility of using pharmacogenetic testing on a larger scale and identify existing gaps in the literature, this study sought to compile a comprehensive list of genomic variants associated with ADEs, with a focus on serious ADEs.

PATIENTS AND METHODS: To identify relevant pharmacogenetic studies within randomised controlled trials (RCTs), post-hoc studies of RCTs and meta-analyses, two literature searches were performed across multiple databases. The compiled list of variants associated with ADEs was refined to create a set of variant-drug pairs significantly associated with serious ADEs.

RESULTS: We identified 254 RCTs/post-hoc studies and 207 meta-analyses investigating variants associated with ADEs. Among the 254 RCTs/post-hoc studies identified, 24 meta-analyses were conducted. Among these, only G6PD A- showed a significant association with severe anaemia in patients receiving artemisinin-based treatment for malaria.

CONCLUSION: This systematic review provides a comprehensive list of variants associated with ADEs and a set of variant-drug pairs significantly associated with serious ADEs. These resources serve as valuable references for regulatory agencies, researchers, and healthcare professionals. This study, however, underscores the need for improved indexing and standardised definitions of ADE seriousness in the literature.

PMID:39187310 | DOI:10.21873/invivo.13671