Adv Ther. 2024 Oct 28. doi: 10.1007/s12325-024-03023-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF), other forms of progressive pulmonary fibrosis (PPF), and systemic sclerosis-associated interstitial lung disease (ILD). We present global post-marketing safety data for nintedanib in these fibrosing ILDs.

METHODS: Data on adverse events in patients with fibrosing ILDs who were treated with nintedanib were collected via spontaneous reporting and solicited reporting in various studies (excluding clinical trials). Data were collected from 15 October 2014 (first regulatory approval) to 15 October 2023. Adverse events were coded using the Medical Dictionary for Regulatory Activities. Cumulative exposure to nintedanib was estimated using sales data.

RESULTS: Cumulative exposure to nintedanib was 380,557 patient-years. Diarrhoea was reported at a rate of 227.5 per 1000 patient-years. Only 2.6% of diarrhoea events were reported as serious. Of 39,788 (33.6%) diarrhoea events with a known time to onset, almost 60% occurred within the first 3 months of treatment. The rate of serious liver enzyme and bilirubin elevations (including drug-induced liver injury) was 4.0 per 1000 patient-years. Bleeding was reported at a rate of 24.2 per 1000 patient-years. Most (81.3%) bleeding events were non-serious. The rates of myocardial infarction, ischaemic stroke, and venous thromboembolism were 3.3, 3.3, and 2.0 per 1000 patient-years, respectively. Gastrointestinal perforation was reported at a rate of 0.9 per 1000 patient-years.

CONCLUSION: Post-marketing safety data on established and potential adverse events associated with nintedanib in patients with fibrosing ILDs, collected over 9 years, demonstrated a safety profile that was similar to that established in clinical trials and provided in the product labels. Education of patients about the adverse events that may be associated with nintedanib, and the effective management of adverse events when they occur, is important to minimise the impact of adverse events and help patients remain on treatment.

PMID:39466587 | DOI:10.1007/s12325-024-03023-4

Hum Vaccin Immunother. 2024 Dec 31;20(1):2387904. doi: 10.1080/21645515.2024.2387904. Epub 2024 Oct 28.

ABSTRACT

The aim of this study was to analyze the incidence and characteristics of adverse events following immunization (AEFI) with post-licensure vaccines used in Hebei province from 2018 to 2020 and to evaluate the safety of vaccines. All information of AEFI was gained from national adverse event following immunization surveillance system (NAEFISS) in Hebei Province from 2018 to 2020. Descriptive epidemiology method was used to analyze the data about AEFI in Hebei province. Reporting rates of AEFI were calculated by sex, age, city, categories of AEFI, severity of AEFI, reaction categories, etc. A total of 35,999 AEFI were reported through NAEFISS, and the average annual rate was 47.64/100,000 doses. The reporting rates of common adverse reactions and rare adverse reactions were 46.37/100,000 doses and 1.05/100,000 doses. The male-to-female ratio was 1.26:1. Most of the AEFI were concentrated in the ≤1 year age group and were reported in the second quarter and third quarter. The majority of AEFI were reported to be recovered or improved, and about 62% of the AEFI occurred within 24 hours after vaccination. Vaccines associated with the highest reporting rate of AEFI were diphtheria, tetanus and acellular pertussis combined vaccine (DTaP, 170.45/100,000 doses). The reporting rate of allergic rash was found to be the highest in the adverse reactions (0.29/100,000 doses). The majority of AEFI cases were common adverse reactions, while serious rare adverse reactions caused by vaccines were extremely uncommon, and all vaccines used in Hebei Province were safe.

PMID:39466071 | DOI:10.1080/21645515.2024.2387904

Neurooncol Adv. 2024 Sep 30;6(1):vdae166. doi: 10.1093/noajnl/vdae166. eCollection 2024 Jan-Dec.

ABSTRACT

BACKGROUND: This phase 1 (NCT04396717) open-label, multicenter study, evaluated Pritumumab, a IgG1 monoclonal antibody, in patients with gliomas and brain metastases. The primary objective was to evaluate the safety and/or tolerability and to identify a recommended phase 2 dose (RP2D) of Pritumumab.

METHODS: Adult patients with recurrent gliomas or brain metastases were enrolled in the dose cohort that was open at the time of their consent. Study treatment consisted of pritumumab administered intravenously weekly on days 1, 8, 15, and 22 in 28-day cycles. Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated.

RESULTS: Fifteen patients received Pritumumab in the recurrent setting. Pritumumab was well tolerated, with no serious adverse events related to Pritumumab reported. The most common drug-related toxicities were constipation and fatigue. There were no dose-limiting toxicities observed, and a maximum tolerable dose was not reached. Thus, the maximum feasible dose and recommended phase 2 dose of Pritumumab was established at 16.2 mg/kg weekly. Out of eleven patients evaluated for efficacy, one patient (9.1%) demonstrated partial response based on response assessment in neuro-oncology criteria, and disease stabilization was seen in 3 patients (27.3%).

CONCLUSIONS: Pritumumab was well tolerated with no DLTs observed up to 16.2 mg/kg weekly. Further studies are warranted to determine clinical benefit in patients.

PMID:39465217 | PMC:PMC11502913 | DOI:10.1093/noajnl/vdae166

Glob Pediatr Health. 2024 Oct 23;11:2333794X241291398. doi: 10.1177/2333794X241291398. eCollection 2024.

NO ABSTRACT

PMID:39464239 | PMC:PMC11503824 | DOI:10.1177/2333794X241291398

Eur J Hosp Pharm. 2024 Oct 26:ejhpharm-2024-004319. doi: 10.1136/ejhpharm-2024-004319. Online ahead of print.

ABSTRACT

OBJECTIVES: There have been cases of cardiotoxicity induced by osimertinib in patients with non-small-cell lung cancer (NSCLC). However, limited data exist for a comprehensive cardiotoxicity profile analysis for osimertinib use in NSCLC patients. The aim of this study was to report the entire profile of cardiotoxicities after the initiation of osimertinib in consecutive patients with estimated glomerular filtration rate (EGFR) mutation at a single health system.

METHODS: The data were retrospectively collected from electronic medical records for all patients who were started on osimertinib for NSCLC at West Virginia University Health System. Prevalence of heart failure (HF), atrial fibrillation, and prolonged QT before and after starting osimertinib were calculated.

RESULTS: This study had 116 participants and the median age was 72 years. The frequency of each new cardiotoxicity was between 6% and 9%, and the overall percentage of patients who had developed any of the four cardiotoxicities while on osimertinib was 19.9%. The median time of follow-up was 477 days and the median time on osimertinib for all patients was 390 days. The strongest risk factor in predicting a new onset cardiac event was hypertension with a hazard ratio (HR) of 6.35 (confidence interval (CI) 1.48 to 27.23, p=0.013) and HR 5.36 (CI 1.23 to 23.39, p=0.025) in univariate and multivariate analysis respectively.

CONCLUSION: Osimertinib appears to be associated with an increase in cardiac abnormalities. Given the association between this medication exposure and the observed cardiac toxicities, use of osimertinib may entail closer cardiac monitoring of electrocardiogram (ECG) and echocardiogram abnormalities.

PMID:39461730 | DOI:10.1136/ejhpharm-2024-004319

Medicina (Kaunas). 2024 Oct 18;60(10):1714. doi: 10.3390/medicina60101714.

ABSTRACT

Background and Objectives: Recent studies suggest that the binary categorization of first-generation antipsychotics (FGAs) as being primarily responsible for extrapyramidal symptoms (EPSs) and second-generation antipsychotics (SGAs) for cardiometabolic abnormalities is an oversimplification. SGAs also demonstrate antagonistic affinity for D2 receptors, indicating their potential to induce EPSs. This study utilized the Korea Adverse Event Reporting System (KAERS) database to explore adverse drug event (ADE) signals related to both FGAs and SGAs. Materials and Methods: Relevant ADE reports from January 2013 to December 2022 were extracted from the KAERS database and analyzed using disproportionality analysis, employing the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) with its 95% lower confidence interval (LCI) indices. Results: Of the initial dataset of 2,890,702 ADE reports, those with insufficient data and duplicates were removed, resulting in a final dataset of 5249 reports for analysis. Aripiprazole, an SGA, showed signals for movement disorders, including EPSs (PRR 4.7, ROR 4.8, IC 2.2), tremors (PRR 5.3, ROR 5.4, IC 2.4), and akathisia (PRR 18.6, ROR 19.3, IC 3.5). Notably, for quetiapine, cardiovascular signals were detected, including increased blood pressure (PRR 2.1, ROR 2.3, IC 0.5), and tachyarrhythmia (PRR 13.9, ROR 14.1, IC 1.8), along with peripheral edema (PRR 2.5, ROR 2.5, IC 0.2). Metabolic abnormalities, such as weight gain and increased appetite, were identified for four SGAs: aripiprazole, olanzapine, quetiapine, and risperidone. Safety signals related to movement disorders were not detectable for FGAs, likely due to the limited number of ADE reports available for analysis. Conclusions: Our study findings support that the distribution of ADEs between FGAs and SGAs is not strictly binary. Aripiprazole, despite being an SGA, showed signals for extrapyramidal movement disorders. Four SGAs (aripiprazole, olanzapine, quetiapine, and risperidone) were linked to metabolic side effects, while quetiapine was associated with cardiovascular safety signals.

PMID:39459501 | DOI:10.3390/medicina60101714

Medicina (Kaunas). 2024 Oct 17;60(10):1705. doi: 10.3390/medicina60101705.

ABSTRACT

Background and Objective: The complexity of antiretroviral therapy (ART) regimens in people living with HIV (PLHIV) poses significant challenges for medication management, impacting adherence and overall health outcomes. The Medication Regimen Complexity Index (MRCI) is a tool that quantifies regimen complexity, yet its correlation with hospitalization rates and adverse drug reactions (ADRs) in PLHIV remains underexplored. Materials and Methods: This prospective study, which was conducted at a government-funded antiretroviral treatment center, investigated the relationships among MRCI scores, hospitalization due to ADRs, and the ADR rates in 285 PLHIV participants over 18 months. Results: The study revealed a significant association between higher baseline MRCI scores and hospitalization due to ADRs, with a threshold MRCI score of 8 indicating increased risk. There was no significant association between average MRCI scores and overall ADR rates or non-ADR-related hospitalizations. Conclusions: These findings emphasize the importance of monitoring medication regimen complexity in PLHIV, particularly in the context of preventing hospitalizations related to ADRs. Further research is needed to understand the multifactorial influences on ADR occurrence and to optimize ART regimens for better patient outcomes.

PMID:39459492 | DOI:10.3390/medicina60101705

Medicina (Kaunas). 2024 Oct 6;60(10):1633. doi: 10.3390/medicina60101633.

ABSTRACT

Background and Objectives: Alzheimer's disease is a global health concern, with a rising prevalence among the elderly. Current pharmacological treatments, including acetylcholinesterase inhibitors (AChEIs) and N-Methyl D-Aspartate (NMDA) receptor antagonists, are associated with adverse events (AEs), particularly in the context of polypharmacy. This study aimed to investigate the relationship between Alzheimer's disease treatment combinations, the number of concomitant medications, and the occurrence of AEs. Materials and Methods: Data from the Japanese Adverse Drug Event Report database, spanning from April 2004 to June 2020, were analyzed. Patients aged 60 and older with Alzheimer's disease treated with AChEIs (donepezil, galantamine, and rivastigmine) or the NMDA receptor antagonist memantine were included. Logistic regression models were employed to assess the association between AEs and Alzheimer's disease drug combinations, as well as the number of concomitant medications. Results: Among 2653 patients, 47.7% were prescribed five or more drugs. The frequency of AEs was 6.4% for bradycardia, 4.6% for pneumonia, 3.6% for altered state of consciousness, 3.5% for seizures, 3.5% for decreased appetite, 3.5% for vomiting, 3.4% for loss of consciousness, 3.4% for fracture, 3.2% for cardiac failure, and 3.0% for falls. The combination of memantine with AChEIs was associated with a higher risk of bradycardia, whereas donepezil alone was linked to a reduced risk of fractures and falls. Polypharmacy was significantly correlated with an increased incidence of AEs, particularly altered state of consciousness, decreased appetite, vomiting, and falls. The adjusted odds ratios for using five or more drugs compared to no drugs was 10.45 for altered state of consciousness, 7.92 for decreased appetite, 4.74 for vomiting, and 5.95 for falls. Conclusions: In the treatment of Alzheimer's disease, the occurrence of AEs is associated with the number of concurrent medications, independently of the known AEs of Alzheimer's disease drugs and their combination patterns.

PMID:39459419 | DOI:10.3390/medicina60101633

Biomedicines. 2024 Sep 24;12(10):2163. doi: 10.3390/biomedicines12102163.

ABSTRACT

Objective: Hypertensionis one of the most common chronic diseases, affecting more than 20% of the population. The side effects experienced due to antihypertensive medications, such as tiredness, muscle pain, and insomnia, are often a significant predictor of poor adherence to therapy. The goal of the current study is to present the frequency, type, seriousness, and severity of adverse drug reactions reported to the BDA via Individual Case Safety Reports (ICSRs) and following differentiation of messages found in more than one patient. Methods: We conducted a retrospective analysis of the reported adverse drug reactions (ADRs) reported in the Bulgarian Drug Agency database after treatment with antihyperlipidemic medicines, angiotensin-converting enzyme (ACE) inhibitors, and sartans for the period 2017-2021. Each ICSR form was observed, and data for suspected medicine and type of adverse reaction was analyzed. Results: The total number of processed notifications for adverse drug reactions (ADRs) included in the database is 142. The highest number of ADRs was reported for ARB (58), followed by antihyperlipidemic medicines (55) and ACE inhibitors (29). Most of the assessed adverse events experienced by more than one patient fall into the probable and related categories based on the Global Introspection method classification. Therefore, they have been investigated and are consistent with exposure in the population. Conclusions: Cardiovascular medicines from the groups of ACE inhibitors, sartans, and statins have a high share of reported ADRs in the BDA system. Some of them are severe and need further investigation.

PMID:39457476 | DOI:10.3390/biomedicines12102163

BMC Health Serv Res. 2024 Oct 25;24(1):1283. doi: 10.1186/s12913-024-11587-8.

ABSTRACT

INTRODUCTION: The majority of metastatic renal cell carcinoma (mRCC) patients receive one or more VEGFR TKI agents, alone or in combination with an immune-oncology (IO) agent or an mTOR inhibitor. To date, the cost of adverse events (AEs) common to VEGFR TKIs has not been quantified. This study estimated the potential impact of differences in VEGFR TKI AE profiles on treatment cost efficiency in the relapsed/refractory (R/R) setting.

METHODS: Patients with documented mRCC who were treated with VEGFR TKI therapies between Jan 2015 and Mar 2021 were identified using EMR. ICD-10 diagnosis codes were used to identify the first occurrence of each class effect AE. Patients were matched to 3rd party insurance claims, and costs associated to TKI AEs within 90 days of index event were captured. Average per patient AE cost data was calculated and applied to published incidence data to estimate regimen-specific AE total cost burden within a hypothetical commercial plan for mRCC patients undergoing treatment in the R/R setting.

RESULTS: The highest total cost for AE management was attributed to lenvatinib and everolimus use at $13,303, followed closely by sunitinib at $13,092. Tivozanib treatment was associated with the lowest total cost of AE management at $7,523, driven by the relatively lower incidence of certain high-cost AEs.

CONCLUSIONS: The estimated costs of managing VEGFR TKI class-effect AEs were lowest with tivozanib, and highest with lenvatinib and everolimus, indicating potentially differential healthcare resource burden by TKI regimen. The use of tivozanib in the 3 L + mRCC setting suggests potential costs offsets when compared to other TKI regimens.

PMID:39456060 | DOI:10.1186/s12913-024-11587-8

BMC Med. 2024 Oct 25;22(1):495. doi: 10.1186/s12916-024-03717-0.

ABSTRACT

BACKGROUND: Pregnant women are significantly underrepresented in clinical trials, yet most of them take medication during pregnancy despite the limited safety data. The objective of this study was to characterize medication use during pregnancy and apply propensity score matching method at scale on patient records to accelerate and prioritize the drug effect signal detection associated with the risk of preterm birth and other adverse pregnancy outcomes.

METHODS: This was a retrospective study on continuously enrolled women who delivered live births between 2013/01/01 and 2022/12/31 (n = 365,075) at Providence St. Joseph Health. Our exposures of interest were all outpatient medications prescribed during pregnancy. We limited our analyses to medication that met the minimal sample size (n = 600). The primary outcome of interest was preterm birth. Secondary outcomes of interest were small for gestational age and low birth weight. We used propensity score matching at scale to evaluate the risk of these adverse pregnancy outcomes associated with drug exposure after adjusting for demographics, pregnancy characteristics, and comorbidities.

RESULTS: The total medication prescription rate increased from 58.5 to 75.3% (P < 0.0001) from 2013 to 2022. The prevalence rate of preterm birth was 7.7%. One hundred seventy-five out of 1329 prenatally prescribed outpatient medications met the minimum sample size. We identified 58 medications statistically significantly associated with the risk of preterm birth (P ≤ 0.1; decreased: 12, increased: 46).

CONCLUSIONS: Most pregnant women are prescribed medication during pregnancy. This highlights the need to utilize existing real-world data to enhance our knowledge of the safety of medications in pregnancy. We narrowed down from 1329 to 58 medications that showed statistically significant association with the risk of preterm birth even after addressing numerous covariates through propensity score matching. This data-driven approach demonstrated that multiple testable hypotheses in pregnancy pharmacology can be prioritized at scale and lays the foundation for application in other pregnancy outcomes.

PMID:39456023 | DOI:10.1186/s12916-024-03717-0

BMC Infect Dis. 2024 Oct 25;24(1):1204. doi: 10.1186/s12879-024-10105-9.

ABSTRACT

BACKGROUND: Older people with HIV (PWH) are at risk of polypharmacy (taking multiple medications). Most medications may be necessary and indicated to manage HIV (e.g., antiretroviral therapy [ART]) and HIV-associated comorbidities. However, some are potentially inappropriate medications (PIMs), defined as causing greater harm than benefit, which leads to medication overload. The objective of this study was to characterize polypharmacy (taking multiple medications) and medication overload (prescription of ≥ 1 PIMs) among older PWH.

METHODS: This retrospective study included older PWH (aged ≥ 50 years old) attending the tertiary care HIV clinic at the McGill University Health Centre (Montreal, Canada), from June 2022-June 2023. Patient characteristics, medications, and select laboratory values (e.g., CD4 count, hemoglobin A1C) were entered into the MedSafer software identifying PIMs and classifying them according to risk of adverse drug event. We measured the prevalence of polypharmacy (≥ 5 medications prescribed, both including and excluding ART) and medication overload (≥ 1 PIMs). Multivariable logistic regression identified factors associated with medication overload.

RESULTS: The study included 100 patients, with a median age of 59 years (IQR = 54-63; range 50-82); 42% female. Polypharmacy affected 89% of patients when including antiretroviral therapy (ART) and 60% when excluding ART. Medication overload was present in 58% of patients, and 37.4% of identified PIMs were classified as high-risk. Polypharmacy was the sole predictor of medication overload.

CONCLUSION: Older PWH are at significant risk of medication overload and receiving higher risk PIMs. Deprescribing PIMs in this population could improve medication appropriateness while reducing the risk of ADEs.

PMID:39455936 | DOI:10.1186/s12879-024-10105-9

Target Oncol. 2024 Oct 26. doi: 10.1007/s11523-024-01107-3. Online ahead of print.

ABSTRACT

BACKGROUND: Oncology research is increasingly adopting new clinical trial models that implement the concept of precision medicine. One of these is the basket clinical trial design. Basket clinical trials allow new treatments to be evaluated across multiple tumor types. Patients recruited to basket clinical trials share certain molecular characteristics of their cancer that are predictive of clinical benefit from the experimental treatment.

OBJECTIVE: Our aim was to describe the risks and benefits of basket clinical trials in oncology.

METHODS: Our study was prospectively registered in PROSPERO (CRD42023406401). We systematically searched PubMed, Embase, and ClinicalTrials.gov for reports of basket clinical trials in oncology published between 1 January, 2001, and 14 June, 2023. We measured the risk by treatment-related adverse events (grades 3, 4, and 5), and the benefit by objective response rate. We also extracted and analyzed data on progression-free survival and overall survival. When possible, data were meta-analyzed.

RESULTS: We included 126 arms of 75 basket clinical trials accounting for 7659 patients. The pooled objective response rate was 18.0% (95% confidence interval [CI] 14.8-21.1). The rate of treatment-related death was 0.7% (95% CI 0.4-1.0), while 30.4% (95% CI 24.2-36.7) of patients experienced grade 3/4 drug-related toxicity. The median progression-free survival was 3.1 months (95% CI 2.6-3.9), and the median overall survival was 8.9 months (95% CI 6.7-10.2).

CONCLUSIONS: Our results provide an empirical basis for communicating about the risks and benefits of basket clinical trials and for refining new models of clinical trials applied in precision medicine.

PMID:39455508 | DOI:10.1007/s11523-024-01107-3

Ann Intensive Care. 2024 Oct 26;14(1):164. doi: 10.1186/s13613-024-01390-3.

ABSTRACT

BACKGROUND: Ciprofol was approved for use in intensive care unit (ICU) patients requiring sedation during mechanical ventilation in July 2022. A pooled post-hoc analysis of phase 2 and phase 3 trials was conducted primarily to explore hypotension-free outcome in ICU patients who required mechanical ventilation and achieved the target light sedation goal at an early stage after being sedated with ciprofol or propofol.

METHODS: All eligible ICU patients who were expected to require sedation for 6-24 h were randomly assigned in a 2:1 ratio to either a ciprofol or propofol group. Ciprofol or propofol was initially infused at loading doses of 0.5 or 1.0 mg/kg followed by maintenance doses of 0.3 or 1.5 mg/kg/h. Ciprofol or propofol dosages were adjusted up or down at rates of 0.05-0.10 mg/kg/h or 0.25-0.50 mg/kg/h, respectively, to achieve the target light sedation (a Richmond Agitation-Sedation Scale of -2 to + 1). The primary post-hoc outcome was the hypotension-free rate in patients who had achieved the target sedation goal after 30-min administration of ciprofol or propofol.

RESULTS: In total, 174 patients were enrolled for pooled post-hoc analysis, of whom 116 and 58 were assigned to the ciprofol and propofol groups, respectively. The hypotension-free rate was significantly higher in patients who achieved the target sedation goal after 30-min administration of ciprofol (93.0% vs. 81.0%, P = 0.018), and especially in the subgroups of males and patients aged < 65 years. Multivariable analysis revealed that ciprofol treatment, a younger age and lower baseline body mass index were independent favorable predictors for a higher hypotension-free rate in patients who achieved the target sedation goal after 30-min of drug administration. Moreover, hypotension-free patients who reached the target sedation level after 30 min had a more favorable short-term prognosis including a lower incidence of drug-related treatment-emergent adverse events, shorter time to extubation and fewer dose adjustments of ciprofol or propofol (all P < 0.05).

CONCLUSION: ICU patients undergoing mechanical ventilation and sedated with ciprofol had significantly lower rate of hypotension during the early phase of achieving light sedation during a 6-24 h period, leading to a more favorable short-term prognosis (within 24 h).

TRIAL REGISTRATION: Phase 2 trial (clinicaltrials.gov, NCT04147416. Registered November 1, 2019, https://classic.

CLINICALTRIALS: gov/ct2/show/NCT04147416 ) and phase 3 trial (clinicaltrials.gov, NCT04620031. Registered November 6, 2020, https://classic.

CLINICALTRIALS: gov/ct2/show/NCT04620031 ).

PMID:39455495 | DOI:10.1186/s13613-024-01390-3

Curr Oncol. 2024 Oct 18;31(10):6356-6383. doi: 10.3390/curroncol31100473.

ABSTRACT

The increased use of immune checkpoint inhibitors (ICIs) across cancer programs has created the need for standardized monitoring and management of immune-related adverse events (irAEs). Delayed recognition without appropriate treatment can have serious and life-threatening consequences. The management of irAEs presents a unique set of challenges that must be addressed at a multidisciplinary level. Although various national and international guidelines and working groups provide high-level recommendations for the management of irAEs, practical guidance is lacking. Furthermore, timely collaboration between specialists requires institutional protocols that enable the early recognition, assessment, and treatment of irAEs. Such protocols should be developed by institution specialists and include algorithms for all healthcare providers involved in the care of patients treated with ICIs. At William Osler Health System in Brampton, Ontario, practical step-by-step multidisciplinary treatment approaches with recommendations for the management of irAEs were developed in collaboration with experts across Canada. Here, we provide an in-depth description of the approaches, outlining baseline investigations prior to the initiation of ICIs, as well as the monitoring and management of irAEs based on symptoms, severity, and involved organ systems. We encourage other centres to adapt and modify our approaches according to their specific needs and requirements.

PMID:39451777 | DOI:10.3390/curroncol31100473

Br J Community Nurs. 2024 Oct 2;29(10):480-486. doi: 10.12968/bjcn.2024.0102.

ABSTRACT

Ageing is associated with an increased risk of adverse drug reactions. This calls for great care and diligent follow up when prescribing medication to older patients. Yet, this is seldom the case and the proportion of older people taking five or more medications has quadrupled from 12% to 49% in the last 20 years. Certain medications are riskier than others. Those with anticholinergic effects are of particular concern. Adverse effects of anticholinergics include dry mouth, nausea, dizziness, fatigue, vomiting, constipation, abdominal pain, urinary retention, blurred vision, tachycardia and neurologic impairment, such as confusion and agitation. Anticholinergic medication can cause daytime drowsiness and cognitive decline, while increasing the risk of fall and can lead to increased mortality. Although anticholinergic medication should be avoided in older people whenever possible, their use has almost doubled in the last 20 years, and those who are most vulnerable to its adverse effects had the greatest increase in use. This article examines why older people are at increased risk of adverse drug reactions and how medication review can enable older persons to take medications regularly, improve quality of life and minimise medication waste.

PMID:39446678 | DOI:10.12968/bjcn.2024.0102

Tunis Med. 2024 Oct 5;102(10):682-689. doi: 10.62438/tunismed.v102i10.4970.

ABSTRACT

Introduction-Aim: The iatrogenic risk in the elderly is a real public health problem due to its frequency and seriousness. Our study aimed to analyze the epidemiological, clinical and chronological aspects of adverse drug reactions occurring in elderly subjects and to identify the incriminated drugs.

METHODS: We carried out a retrospective study of all the observations of adverse drug reactions in elderly subjects, notified to the Clinical Pharmacology department of Monastir over a period of 17 years (2004 - 2020). Drug skin tests were performed according to ENDA recommendations and imputability was analyzed using the French method of Bégaud et al. The drugs have been grouped according to the ATC classification.

RESULTS: Among 545 events occurring in elderly subjects, drug responsibility was retained in 209 patients. They were 106 men and 103 women (gender-ratio=1.03). The average age of the patients was 72.3±6 years. Drug hypersensitivity reactions accounted for 75% of all adverse effects. The majority of these reactions were type IV (delayed). The incriminated drugs were: anti-infectives (47%), drugs for the musculoskeletal system (20%), drugs for the cardiovascular system (17%) and drugs for the central nervous system (5%).

CONCLUSION: Through this study, we noted a predominance of delayed drug hypersensitivity reactions as well as an increased involvement of anti-infectives and allopurinol in the occurrence of adverse effects in the elderly population.

PMID:39441168 | DOI:10.62438/tunismed.v102i10.4970

Farm Comunitarios. 2024 Sep 17;16(4):5-14. doi: 10.33620/FC.2173-9218.(2024).21. eCollection 2024 Oct 15.

ABSTRACT

INTRODUCTION: The Medication Review in the Pharmacotherapeutic Follow-up Service (PFS) seems to be an effective method to study long-term drug safety in the outpatient setting. The adverse drug reactions (ADRs) that are not immediately obvious are difficult to identify and sometimes can be confused with a more common condition. Misdiagnosis by not associating the symptoms of AMR to its pharmacological cause causes its masking and hinders its detection.

OBJECTIVE: Detect in the SFT service the diagnostic errors related to the non-detection of adverse reactions to statins.

MATERIAL AND METHODS: The data obtained from the medication review at the Pharmacotherapeutic Follow-up Service (PFS) were pooled for analysis. The patients who received the service were selected with the "DLGM screening" tool, an acronym "Diagnosis load Generated by Medications", that allows us to describe adverse drug reactions (ADRs), when their symptoms are attributed to a pathology, without considering medication as a possible underlying cause.Only the results of patients over 60 years of age, who after a prolonged period of statin use gradually presented musculoskeletal disorders (MSD) and other symptoms theoretically described as possible ADRs, are shown.

RESULTS: In 66 % of the cases, corresponding to 14 patients out of a total of 21 studied, the physician modified the treatment and in 92% of these cases there was improvement and a decrease of the consumption of analgesics drug, anti-inflammatory and other drugs used to treat ADR symptoms.

CONCLUSION: DLGM screening identified hidden AMRs in 62 % of patients.

PMID:39439866 | PMC:PMC11491921 | DOI:10.33620/FC.2173-9218.(2024).21

Front Immunol. 2024 Oct 8;15:1439231. doi: 10.3389/fimmu.2024.1439231. eCollection 2024.

ABSTRACT

BACKGROUND: Understanding the risk relationship between statin use and immune-related adverse events (irAEs) in patients undergoing immune checkpoint inhibitors (ICIs) therapy is crucial for optimizing oncological management.

OBJECTIVE: This study aimed to investigate whether the use of statins increases the risk of irAEs in patients receiving ICI therapy.

METHODS: This study primarily utilized data from FAERS database. Multivariable logistic regression was the principal method of analysis, and the Benjamini-Hochberg procedure was employed to adjust for multiple hypothesis testing.

RESULTS: In a group of 145,214 patients undergoing ICI therapy, 9,339 reported using statin medications. Multivariable analysis indicated an increased risk of irAEs among statin users (OR 1.199, 95% CI: 1.141-1.261; FDR p < 0.001) in comparison to those not using statins. Notably, increased risks were observed particularly in patients diagnosed with lung, pancreatic, and renal cancers. The link between statin usage and increased irAEs risk remained consistent across various ICIs treatments.

CONCLUSIONS: Statin medication usage is linked to an elevated probability of experiencing irAEs in patients enrolled in ICI therapy. In cancer patients receiving immune checkpoint inhibitors, careful consideration of statin use is essential to avoid potentially increased irAEs risk. These findings provide critical guidance for clinicians in developing treatment strategies that balance therapeutic efficacy and safety in oncological management.

PMID:39439792 | PMC:PMC11493589 | DOI:10.3389/fimmu.2024.1439231

PLoS One. 2024 Oct 22;19(10):e0312481. doi: 10.1371/journal.pone.0312481. eCollection 2024.

ABSTRACT

BACKGROUND: Due to the limitations of clinical trials, some delayed and rare adverse events (AEs) may remain undetected, and safety information can be supplemented through post-market data analysis. This study aims to comprehensively analyze the AEs associated with Relugolix (Orgovyx®) using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Relugolix (Orgovyx®) therapy.

METHODS: Data of Relugolix (Orgovyx®) were collected from the FAERS database covering the period from the fourth quarter of 2020 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), Bayesian analysis confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) to detect positive signals.

RESULTS: Totally, 5,382,189 reports were collected from the FAERS database, 4,397 reports of Relugolix (Orgovyx®) were identified as the 'primary suspected (PS)' AEs. Relugolix (Orgovyx®) induced AEs occurred in 26 organ systems. 58 significant disproportionality preferred terms (PTs) satisfying with the four algorithms were retained at the same time. Unexpected significant AEs such as Pollakiuria, and Prostatic specific antigen increased also occur. The median time of onset was 60 days. The majority of the AEs occurred within the first 30 days after Relugolix (Orgovyx®) initiation.

CONCLUSION: Common AEs included Hot flush, Fatigue, Asthenia, Constipation, and Myalgia. These AEs should be focused on when using the drug to avoid serious consequences. In addition, the study results also suggested that the drug may exist Pollakiuria, Prostatic specific antigen increased and other AEs not mentioned in the manual, to supplement the AEs in the manual. This study is helpful for clinicians and pharmacists to improve their understanding of Relugolix (Orgovyx®) related AEs, and take timely prevention and treatment measures to ensure drug safety for patients.

PMID:39436909 | DOI:10.1371/journal.pone.0312481