Medicina (Kaunas). 2024 Jun 23;60(7):1028. doi: 10.3390/medicina60071028.

ABSTRACT

Background and Objectives: Despite high incidences of cognitive impairment with aging, evidence on the prevalence and the seriousness of drug-induced cognitive impairment is limited. This study aims to evaluate the prevalence and the severity of drug-induced cognitive impairment and to investigate the clinical predictors of increased hospitalization risk from serious drug-induced cognitive impairment. Materials and Methods: Adverse drug events (ADEs) regarding drug-induced cognitive impairment reported to the Korean Adverse Event Reporting System Database (KAERS DB) from January 2012 to December 2021 were included (KIDS KAERS DB 2212A0073). The association between the etiologic classes and the reporting serious adverse events (SAEs) was evaluated using disproportionality analysis, and the effect was estimated with reporting odds ratio (ROR). Clinical predictors associated with increased risk of hospitalization from SAEs were identified via multivariate logistic analysis, and the effect was estimated with odds ratio (OR). Results: The most etiologic medication class for drug-induced cognitive impairment ADEs was analgesics, followed by sedative-hypnotics. Anticancer (ROR 57.105, 95% CI 15.174-214.909) and anti-Parkinson agents (ROR 4.057, 95% CI 1.121-14.688) were more likely to report serious drug-induced cognitive impairments. Male sex (OR 19.540, 95% CI 2.440-156.647) and cancer diagnosis (OR 18.115, 95% CI 3.246-101.101) are the major clinical predictors for increased risk of hospitalizations due to serious drug-induced cognitive impairment. Conclusions: This study highlights the significant prevalence and severity of drug-induced cognitive impairment with cancer diagnosis and anticancer agents. However, further large-scaled studies are required because of the potential underreporting of drug-induced cognitive impairments in real practice settings, which is further contributed to by the complexity of multiple contributing factors such as comorbidities.

PMID:39064457 | DOI:10.3390/medicina60071028

Aging Clin Exp Res. 2024 Jul 26;36(1):151. doi: 10.1007/s40520-024-02799-3.

ABSTRACT

Drug-related problems (DRPs) are critical medical issues during transition from hospital to home with high prevalence. The application of a variety of interventional strategies as part of the transitional care has been studied for preventing DRPs. However, it remains challenging for minimizing DRPs in patients, especially in older adults and those with high risk of medication discrepancies after hospital discharge. In this narrative review, we demonstrated that age, specific medications and polypharmacy, as well as some patient-related and system-related factors all contribute to a higher prevalence of transitional DPRs, most of which could be largely prevented by enhancing nurse-led multidisciplinary medication reconciliation. Nurses' contributions during transitional period for preventing DRPs include information collection and evaluation, communication and education, enhancement of medication adherence, as well as coordination among healthcare professionals. We concluded that nurse-led strategies for medication management can be implemented to prevent or solve DRPs during the high-risk transitional period, and subsequently improve patients' satisfaction and health-related outcomes, prevent the unnecessary loss and waste of medical expenditure and resources, and increase the efficiency of the multidisciplinary teamwork during transitional care.

PMID:39060872 | PMC:PMC11282160 | DOI:10.1007/s40520-024-02799-3

Sci Rep. 2024 Jul 25;14(1):17138. doi: 10.1038/s41598-024-67627-0.

ABSTRACT

This study aims to collect and analyze adverse event (AE) reports related to Nusinersen from the FAERS database. The study employed a combination of signal quantification techniques, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), to enhance the accuracy of signal detection and reduce the risk of false positives or negatives. Between the first quarter of 2017 and the third quarter of 2023, the FAERS database collected a total of 11,485,105 drug AE reports, of which 5772 were related to Nusinersen. Through signal mining analysis, 218 preferred term (PT) signals involving 27 system organ classes (SOCs) were identified. The study discovered AEs related to metabolism and nutrition disorders, psychiatric disorders, and cardiac disorders SOCs, which were not mentioned in the product information. Additionally, complications directly related to the intrathecal administration of Nusinersen, such as increased CSF pressure, positive CSF red blood cell count, and AEs related to the method of drug use, such as neuromuscular scoliosis and cerebrospinal fluid reservoir placement, were highlighted. Notably, AEs related to renal function abnormalities, such as abnormal Urine protein/creatinine ratio and protein urine presence, showed higher frequency and signal strength. The findings of this study emphasize the importance of comprehensive safety monitoring in the clinical application of Nusinersen. These results are significant for guiding future clinical practices, improving disease management strategies, and developing safer treatment protocols.

PMID:39060346 | PMC:PMC11282055 | DOI:10.1038/s41598-024-67627-0

Eur J Cancer. 2024 Jul 22;209:114235. doi: 10.1016/j.ejca.2024.114235. Online ahead of print.

ABSTRACT

The use of immune checkpoint inhibitors (ICI) in cancer treatment is expanding, offering promising outcomes but with an important risk of immune-related adverse events (irAEs). These events, stemming from an overstimulated immune system attacking healthy cells, can necessitate immunosuppressant treatment, disrupt treatment courses, and impact patients' quality of life. The analysis of ICI efficacy data has led to a better understanding of the characteristics of responders. Similarly, we are gaining clearer insights into the characteristics of patients who develop irAEs, prompting an increasing emphasis on modifiable factors associated with irAE risk. These factors include lifestyle choices and the composition of the gut microbiome. Despite comprehensive reviews exploring the microbiome's role in therapy efficacy, understanding its connection with immune-related toxicity remains incomplete. While endeavours to identify predictive biomarkers continue, lifestyle modifications emerge as a promising avenue for enhancing treatment outcomes. This review consolidates the current evidence regarding the impact of the gut microbiome on irAE occurrence. Furthermore, it focuses on actionable strategies for mitigating these adverse events, elucidating the evidence supporting dietary adjustments, supplementation, medication management, and physical activity. With the expanding range of indications for ICI therapy, a significant proportion of oncology patients, including those in early disease stages, are now exposed to these treatments. Acknowledging the importance of averting irAEs in this context, our review offers timely insights crucial for addressing the evolving challenges associated with immunotherapy across diverse oncological settings.

PMID:39059186 | DOI:10.1016/j.ejca.2024.114235

Semin Arthritis Rheum. 2024 Jul 15;68:152516. doi: 10.1016/j.semarthrit.2024.152516. Online ahead of print.

ABSTRACT

OBJECTIVES: The pediatric Glucocorticoid Toxicity Index (pGTI) is a new, pediatric-specific tool to quantify glucocorticoid (GC)-related morbidity in children. We evaluated the feasibility and construct validity of retrospective pGTI scoring in patients with pediatric-onset systemic lupus erythematosus (pSLE) and identified risk factors for cumulative toxicity.

METHODS: We conducted a retrospective cohort study of patients with pSLE treated with GCs at two pediatric centers (1999-2023). GC exposure was estimated using interval-averaged oral prednisone-equivalent dose and cumulative prednisone-equivalent dose. We scored change in GC toxicity every 6 months (±2) using a modified pGTI including 7 of 10 domains. We calculated the Cumulative Worsening Score (CWS), a continuous summation of toxicity accrued. Mixed effects linear regression was used to identify factors associated with CWS.

RESULTS: There were 126 patients with pSLE, including 88 with nephritis, with a median of 6 visits/patient. Nearly half (47 %) experienced toxicity in the Blood Pressure domain. Other common toxicities were mood disturbance (25 %), followed by increased body mass index (BMI), striae, and sleep disturbance (21 % each). Decreased growth velocity was observed in 18 %. There was modest correlation between cumulative GC dose and CWS (rho 0.3; p < 0.01). Greater cumulative toxicity was associated with younger age, elevated BMI, and rituximab use at the time of GC initiation, albeit indications for the latter were not captured.

CONCLUSIONS: Patients with pSLE experience a high burden of GC toxicity, particularly related to blood pressure, BMI, sleep, and growth. Standardized, pediatric-specific GC toxicity assessment is feasible in real-world settings and can facilitate evaluation of strategies to reduce morbidity in children requiring chronic GC treatment.

PMID:39059156 | DOI:10.1016/j.semarthrit.2024.152516

Cells. 2024 Jul 19;13(14):1216. doi: 10.3390/cells13141216.

ABSTRACT

BACKGROUND: Solid organ transplantation is hindered by immune-mediated chronic graft dysfunction and the side effects of immunosuppressive therapy. Regulatory T cells (Tregs) are crucial for modulating immune responses post-transplantation; however, the transfer of polyspecific Tregs alone is insufficient to induce allotolerance in rodent models.

METHODS: To enhance the efficacy of adoptive Treg therapy, we investigated different immune interventions in the recipients. By utilizing an immunogenic skin transplant model and existing transplantation medicine reagents, we facilitated the clinical translation of our findings. Specifically, antigen-specific Tregs were used.

RESULTS: Our study demonstrated that combining the available induction therapies with drug-induced T-cell proliferation due to lymphopenia effectively increased the Treg/T effector ratios. This results in significant Treg accumulation within the graft, leading to long-term tolerance after the transfer of antigen-specific Tregs. Importantly, all the animals achieved operational tolerance, which boosted the presence of adoptively transferred Tregs within the graft.

CONCLUSIONS: This protocol offers a means to establish tolerance by utilizing antigen-specific Tregs. These results have promising implications for future trials involving adoptive Treg therapy in organ transplantation.

PMID:39056797 | DOI:10.3390/cells13141216

Digit Health. 2024 Jul 23;10:20552076241253090. doi: 10.1177/20552076241253090. eCollection 2024 Jan-Dec.

ABSTRACT

OBJECTIVE: This study aimed to analyze the effect of Smart Cancer Care program on the quality of life and ease of chemotherapy continuation in cancer patients and the effect of additional tele-management on frequency of use and satisfaction with the Smart Cancer Care program.

METHODS: 'Smart Cancer Care' is a mobile program that allows cancer patients undergoing chemotherapy to report symptoms of adverse events and receive remote management. In this study, patients were randomly assigned to three groups: Group A, who received only classical face-to-face management; Group B, who used the Smart Cancer Care program as addition; and Group C, who used the Smart Cancer Care program and received telephone management. After 12 weeks of follow-up, the effectiveness of using the Smart Cancer Care program was analyzed by examining the quality of life, ease of maintaining chemotherapy, and unplanned hospital visits in each group. The frequency of use and satisfaction with the Smart Cancer Care program were also analyzed.

RESULTS: Cancer patients who used the Smart Cancer Care program had 1.93-fold (1.15-3.25) higher overall quality of life than those who did not. This became 2.33-fold (1.34-4.04) higher when phone care was added. Patients with tele-management were significantly more likely to use the Smart Cancer Care program (odds ratio (OR) = 25.80; 95% confidence interval (CI), 11.28-58.97).

CONCLUSIONS: A mobile self-reported management program has a positive effect on the quality of life of cancer patients undergoing chemotherapy. Tele-management is conducive to active and effective use of this program.

PMID:39055783 | PMC:PMC11271138 | DOI:10.1177/20552076241253090

BMC Cancer. 2024 Jul 25;23(Suppl 1):1256. doi: 10.1186/s12885-023-11213-6.

ABSTRACT

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) levels correlate with poor outcomes in urothelial carcinoma (UC). IDO1 and programmed death-ligand 1 (PD-L1) are often co-expressed. Epacadostat is a potent and highly selective inhibitor of IDO1. In a subgroup analysis of patients with advanced UC participating in a phase I/II study, epacadostat-pembrolizumab treatment produced an objective response rate (ORR) of 35%.

METHODS: ECHO-303/KEYNOTE-698 was a double-blinded, randomized phase III study of adults with metastatic or unresectable locally advanced UC with recurrence or progression following first-line platinum-based chemotherapy. Participants were randomized to epacadostat 100 mg twice daily (BID) plus pembrolizumab or placebo plus pembrolizumab until completion of 35 pembrolizumab infusions, disease progression, or unacceptable toxicity. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors version 1.1.

RESULTS: Target enrollment was 648 patients; enrollment was halted early based on efficacy results from the phase III ECHO-301/KEYNOTE-252 study in metastatic melanoma. Forty-two patients were randomized to each treatment arm. Median duration of follow-up was 62 days in each arm. The investigator-assessed ORR (unconfirmed) was 26.2% (95% CI 16.35-48.11) for epacadostat plus pembrolizumab and 11.9% (95% CI 4.67-29.50) for placebo plus pembrolizumab. Two complete responses were reported, both in the placebo-plus-pembrolizumab arm. Circulating kynurenine levels increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and numerically decreased in the epacadostat-plus-pembrolizumab arm. The safety profile of epacadostat plus pembrolizumab was similar to that of pembrolizumab monotherapy, although a numerically greater proportion of patients in the combination vs. control arm experienced treatment-related grade ≥ 3 adverse events (16.7% vs. 7.3%). One patient in each arm died due to cardiovascular events, which were not deemed drug-related. No new safety concerns were identified for either agent.

CONCLUSIONS: Epacadostat plus pembrolizumab demonstrated anti-tumor activity and was generally tolerable as second-line treatment of patients with unresectable locally advanced or recurrent/progressive metastatic UC. Epacadostat 100 mg BID, when administered with pembrolizumab, did not normalize circulating kynurenine in most patients. Further study of combined IDO1/PD-L1 inhibition in this patient population, particularly with epacadostat doses that result in durable normalization of circulating kynurenine, may be warranted.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT03374488. Registered 12/15/2017.

PMID:39054485 | DOI:10.1186/s12885-023-11213-6

BMC Cancer. 2024 Jul 25;23(Suppl 1):1251. doi: 10.1186/s12885-023-11203-8.

ABSTRACT

BACKGROUND: Pembrolizumab is a first-line therapy for certain patients with advanced/metastatic non-small cell lung cancer (NSCLC). Combining pembrolizumab with other immunotherapies may enhance tumor cell killing and clinical outcomes. Epacadostat is a selective inhibitor of indoleamine 2,3-dioxygenase 1, an immuno-regulatory enzyme involved in tryptophan to kynurenine metabolism that inhibits T cell-mediated immune responses.

METHODS: In this randomized phase II study, patients with metastatic NSCLC expressing high (≥ 50%) programmed death-ligand 1 (PD-L1) levels received pembrolizumab 200 mg every 21 days plus oral epacadostat 100 mg twice daily (combination) or matching placebo (control). The primary objective was objective response rate (ORR); secondary objectives were progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety/tolerability.

RESULTS: 154 patients were randomized (77 per group). Median (range) follow-up was 6.8 months (0.1-11.4) and 7.0 months (0.2-11.9) in the combination and control groups, respectively Confirmed ORR was similar between groups (combination: 32.5%, 95% CI 22.2-44.1; control: 39.0%, 95% CI 28.0-50.8; difference: - 6.5, 95% CI - 21.5 to 8.7; 1-sided P = 0.8000). Median (range) DOR was 6.2 months (1.9 + to 6.5 +) and not reached (1.9 + to 8.6 +) in the combination and control groups, respectively. Although not formally tested, median PFS was 6.7 and 6.2 months for the combination and control groups, respectively, and median OS was not reached in either group. Circulating kynurenine levels increased from C1D1 to C2D1 (P < 0.01) in the control group and decreased from C1D1 to C2D1 (P < 0.01) in the combination group but were not normalized in most patients. The most frequent serious adverse events (AEs) (≥ 2%) were pneumonia (4.0%), anemia (2.7%), atelectasis (2.7%) and pneumonitis (2.7%) in the combination group and pneumonia (3.9%), pneumonitis (2.6%) and hypotension (2.6%) in the control group. Two deaths due to drug-related AEs were reported, both in the control group.

CONCLUSIONS: Addition of epacadostat to pembrolizumab therapy for PD-L1-high metastatic NSCLC was generally well tolerated but did not demonstrate an improved therapeutic effect. Evaluating higher doses of epacadostat that normalize kynurenine levels when given in combination with checkpoint inhibitors may be warranted.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT03322540. Registered 10/26/2017.

PMID:39054476 | DOI:10.1186/s12885-023-11203-8

Mol Genet Metab Rep. 2024 Jul 1;40:101115. doi: 10.1016/j.ymgmr.2024.101115. eCollection 2024 Sep.

ABSTRACT

Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (Phe) metabolism, resulting from the deficient activity of phenylalanine hydroxylase that converts Phe to tyrosine in the liver, leading to elevated levels of Phe. Pegvaliase is an innovative and effective enzyme replacement therapy for reducing Phe concentration, but it has been associated with severe drug-induced hypersensitivity adverse events (HAEs). Limited data is available on the management of these HAEs, thus, we aimed to present a case report of a successful management strategy. The patient was a 28-year-old Caucasian male with classical PKU, who was otherwise healthy. Due to poor metabolic control, the pegvaliase treatment was initiated. The titration phase was uneventful, with transient and mild side effects, localized to the injection site. After the patient was on a maintenance dose of pegvaliase and had no reactions to the drug, we discontinued the H1-antihistamine. In the following days, within minutes after receiving the pegvaliase injection, an acute hypersensitivity reaction occurred that required emergency treatment. H1-antihistamine treatment was reintroduced. Four days after the incident he received pegvaliase under medical supervision and did not experience any symptoms. In conclusion, cautious reintroduction of pegvaliase in a hospital setting can be safely performed after HAE due to the discontinuation of H1-antihistamines. HAEs could be successfully mitigated by scheduling daily antihistamines administration closer to the pegvaliase injection. This approach can enable PKU patients to maintain their access to an effective and quality-of-life-improving therapy.

PMID:39049877 | PMC:PMC11267064 | DOI:10.1016/j.ymgmr.2024.101115

Pharmacol Res Perspect. 2024 Aug;12(4):e1236. doi: 10.1002/prp2.1236.

ABSTRACT

Detailed data on safety associated with drug-drug interactions (DDIs) between Linezolid (LZD) and other antibiotics are limited. The aim of this study was to investigate the safety signals related to these DDIs and to provide a reference for clinically related adverse drug event monitoring. Adverse event (AE) information from 1 January 2004 to 16 June 2022 of the target antibiotics including LZD using alone or in combination with LZD was extracted from the OpenVigil FDA data platform for safety signal analysis. The combined risk ratio model, reporting ratio method, Ω shrinkage measure model, and chi-square statistics model were used to analyze the safety signals related to DDIs. Meanwhile, we evaluated the correlation and the influence of sex and age between the drug(s) and the target AE detected. There were 18991 AEs related to LZD. There were 2293, 1726, 4449, 821, 2431, 1053, and 463 AE reports when LZD was combined with amikacin, voriconazole, meropenem, clarithromycin, levofloxacin, piperacillin-tazobactam, and azithromycin, respectively. Except for azithromycin, there were positive safety signals related to DDIs between LZD and these antibiotics. These DDIs might influence the incidence of 13, 16, 7, 7, 6, and 15 types of AEs, respectively, and is associated with higher reporting rates of AEs compared with use alone. Moreover, sex and age might influence the occurrence of AEs. We found that the combinations of LZD and other antibiotics are related to multiple AEs, such as hepatotoxicity, drug resistance and electrocardiogram QT prolonged, but further research is still required to investigate their underlying mechanisms. This study can provide a new reference for the safety monitoring of LZD combined with other antibiotics in clinical practice.

PMID:39049495 | DOI:10.1002/prp2.1236

Stud Health Technol Inform. 2024 Jul 24;315:398-403. doi: 10.3233/SHTI240177.

ABSTRACT

Frequent transitions of care among patients with cancer increase their risks for medication safety events (MSEs). Patients and families need to become "vigilant partners" in MSE self-reporting when transitioning back home. However, limited evidence is available to guide patient and family engagement in preventing and managing MSEs. This study explored patients' perceptions of using technology for MSE self-reporting by interviewing 41 patients with breast, prostate, lung, or colorectal cancer. The findings revealed that patients with cancer perceived technology as convenient and easy to use to address urgent MSE concerns. However, the lack of access to technology and being unconfident in using technology can be barriers to using technology for MSE reporting. Personalized support is needed to facilitate patients' engagement in MSE self-reporting. Factors identified in the study will further support the user-centered design and development of technology systems that can support patients' needs and expectations for medication safety.

PMID:39049290 | DOI:10.3233/SHTI240177

BMC Psychiatry. 2024 Jul 25;24(1):532. doi: 10.1186/s12888-024-05950-6.

ABSTRACT

BACKGROUND: Adverse events (AEs) are commonly reported in clinical studies using the Medical Dictionary for Regulatory Activities (MedDRA), an international standard for drug safety monitoring. However, the technical language of MedDRA makes it challenging for patients and clinicians to share understanding and therefore to make shared decisions about medical interventions. In this project, people with lived experience of depression and antidepressant treatment worked with clinicians and researchers to co-design an online dictionary of AEs associated with antidepressants, taking into account its ease of use and applicability to real-world settings.

METHODS: Through a pre-defined literature search, we identified MedDRA-coded AEs from randomised controlled trials of antidepressants used in the treatment of depression. In collaboration with the McPin Foundation, four co-design workshops with a lived experience advisory panel (LEAP) and one independent focus group (FG) were conducted to produce user-friendly translations of AE terms. Guiding principles for translation were co-designed with McPin/LEAP members and defined before the finalisation of Clinical Codes (CCs, or non-technical terms to represent specific AE concepts). FG results were thematically analysed using the Framework Method.

RESULTS: Starting from 522 trials identified by the search, 736 MedDRA-coded AE terms were translated into 187 CCs, which balanced key factors identified as important to the LEAP and FG (namely, breadth, specificity, generalisability, patient-understandability and acceptability). Work with the LEAP showed that a user-friendly language of AEs should aim to mitigate stigma, acknowledge the multiple levels of comprehension in 'lay' language and balance the need for semantic accuracy with user-friendliness. Guided by these principles, an online dictionary of AEs was co-designed and made freely available ( https://thesymptomglossary.com ). The digital tool was perceived by the LEAP and FG as a resource which could feasibly improve antidepressant treatment by facilitating the accurate, meaningful expression of preferences about potential harms through a shared decision-making process.

CONCLUSIONS: This dictionary was developed in English around AEs from antidepressants in depression but it can be adapted to different languages and cultural contexts, and can also become a model for other interventions and disorders (i.e., antipsychotics in schizophrenia). Co-designed digital resources may improve the patient experience by helping to deliver personalised information on potential benefits and harms in an evidence-based, preference-sensitive way.

PMID:39049079 | DOI:10.1186/s12888-024-05950-6

J Korean Med Sci. 2024 Jul 22;39(28):e205. doi: 10.3346/jkms.2024.39.e205.

ABSTRACT

BACKGROUND: Older adults are at a higher risk of severe adverse drug events (ADEs) because of multimorbidity, polypharmacy, and lower physiological function. This study aimed to determine whether polypharmacy, defined as the use of ≥ 5 active drug ingredients, was associated with severe ADEs in this population.

METHODS: We used ADE reports from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database, a national spontaneous ADE report system, from 2012 to 2021 to examine and compare the strength of association between polypharmacy and severe ADEs in older adults (≥ 65 years) and younger adults (20-64 years) using disproportionality analysis.

RESULTS: We found a significant association between severe ADEs of cardiac and renal/urinary Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC) with polypharmacy in older adults. Regarding individual-level ADEs included in these MedDRA SOCs, acute cardiac arrest and renal failure were more significantly associated with polypharmacy in older adults compared with younger adults.

CONCLUSION: The addition of new drugs to the regimens of older adults warrants close monitoring of renal and cardiac symptoms.

PMID:39048300 | DOI:10.3346/jkms.2024.39.e205

Eur J Hosp Pharm. 2024 Jul 24:ejhpharm-2024-004250. doi: 10.1136/ejhpharm-2024-004250. Online ahead of print.

NO ABSTRACT

PMID:39048297 | DOI:10.1136/ejhpharm-2024-004250

PLoS One. 2024 Jul 24;19(7):e0307237. doi: 10.1371/journal.pone.0307237. eCollection 2024.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs) represent a significant barrier to achieve optimal treatment outcomes. Cardiovascular drugs, including antihypertensive drugs, lipid-lowering drugs, and antithrombotic drugs, are among the most prescribed medications in the primary care setting.

OBJECTIVES: To estimate the prevalence of cardiovascular drug-related ADRs consultations in United Kingdom (UK) primary care and identify risk factors of these ADRs.

METHODS: This was a cross-sectional study of cardiovascular drug users between 2000-2019 using UK IQVIA Medical Research Data. ADRs consultations were identified using database screening method employing standardised designated codes. The overall and annual age-standardised prevalence was estimated using direct standardisation method using 2019 mid-year UK population. Risk factors of ADRs consultations were estimated using logistic regression model stratified by therapeutic areas.

RESULTS: The standardised prevalence of consultations related to cardiovascular drugs ADRs was 10.60 (95% CI. 10.46, 10.75) per 1000 patients. Patients aged 70-79 years had the highest occurrence of ADRs consultations. The most frequently drug classes implicated in the ADRs consultations were statins (n = 9,993 events, 27.09%), beta-blockers (n = 8,538 events, 23.15%), ACEIs/ARBs (n = 8,345 events, 22.62%), and aspirin (n = 6,482 events, 17.57%). Risk factors of ADRs consultations were previous history of cardiovascular diseases, e.g., myocardial infarction and stroke; advanced age, comorbidities; diabetes and dyslipidaemia; and polypharmacy.

CONCLUSIONS: The burden of cardiovascular drug-related ADRs consultations in primary care was considerable. Statins, beta-blockers, ACEIs/ARBs, and aspirin were the most frequently implicated drug classes. Closer clinical monitoring should be performed for patients affected by the ADRs to mitigate the risk of suboptimal treatment outcomes.

PMID:39046945 | DOI:10.1371/journal.pone.0307237

Trials. 2024 Jul 24;25(1):503. doi: 10.1186/s13063-024-08317-0.

ABSTRACT

BACKGROUND: It is essential that electronic data collection (EDC) systems are both compliant with regulations and the principles of Good Clinical Practice (GCP) to allow for the timely and accurate reporting of data including safety data. For clinical trials of investigational medicinal products (CTIMPs), investigators must immediately report to the sponsor any serious adverse event (SAE) that occurs in a site for which they are responsible. It is therefore expected that sponsors provide systems for timely review and reporting should a SAE be classified as a suspected unexpected serious adverse reaction (SUSAR). Challenges arise when data related to adverse events (AEs) needs to be re-entered for SAEs; this can be prone to error and may delay reporting. Additionally, recognising what has changed from an initial SAE report when an investigator responds to queries raised can cause errors.

METHOD: A multi-disciplinary working group came together from a UK academic clinical trials unit (CTU) to establish if an electronic system could be created in the unit's open-source EDC system-REDCap, to manage SAEs in an efficient way.

RESULTS: A module has been created in REDCap to facilitate electronic SAE reporting: enabling an AE form to automatically trigger an SAE form for any AE which is also a SAE, prepopulating relevant fields of the SAE form, reducing the risk of delay and error when entering data into the SAE form. The system has also been developed with an embedded code to allow for instant visual recognition of any data updated following reporting to allow the sponsor to immediately review and resolve SAEs in a timely manner, complying with UK regulatory reporting. This functionality 'The eSAE Project' is now an active project for all of our new trials where data collection is undertaken using the REDCap system.

CONCLUSION: The eSAE Project coded into REDCap offers a unique way of populating SAE forms with information already entered in the initial AE forms as applicable, coupled with highlighting any updates during the lifetime of the SAE for sponsors to identify any new information that needs to be reassessed to process and report the SAE.

PMID:39044237 | DOI:10.1186/s13063-024-08317-0

Farm Hosp. 2024 Jul 22:S1130-6343(24)00099-0. doi: 10.1016/j.farma.2024.06.003. Online ahead of print.

ABSTRACT

INTRODUCTION: Older patients are more susceptible to medication use, and physiological changes resulting from aging and organic dysfunctions presented by critically ill patients may alter the pharmacokinetic or pharmacodynamic behavior. Thus, critically ill older people present greater vulnerability to the occurrence of pharmacotherapeutic problems.

OBJECTIVE: To evaluate pharmacotherapy and the development of potential adverse drug reactions (ADRs) in older patients admitted to an intensive care unit (ICU).

METHOD: A cohort study was conducted in an ICU for adults of a Brazilian University Hospital during a 12-month period. The patients' pharmacotherapy was evaluated daily, considering the occurrence of ADRs and drug-drug interactions (DDIs), the use of potentially inappropriate medications (PIMs) for older people, and the pharmacotherapy anticholinergic burden (ACB). A trigger tool was used for active search of ADRs, with subsequent causality evaluation. PIM use was evaluated by means of the Beers criteria and the STOPP/START criteria. The ABC scale was employed to estimate ACB. The Micromedex® and Drugs.com® medication databases were employed to evaluate the DDIs.

RESULTS: The sample of this study consisted of 41 patients, with a mean age of 66.8 years old (±5.2). The 22 triggers used assisted in identifying 15 potential ADRs, and 26.8% of the patients developed them. The mean estimated ACB score was 3.0 (±1.8), and the patients used 3.1 (±1.4) and 3.3 (±1.6) PIMs according to the Beers and the STOPP criteria, respectively. A total of 672 DDIs were identified, with a mean of 16.8 (±9.5) DDIs/patient during ICU hospitalization. Our findings show an association between occurrence of ADRs in the ICU and polypharmacy (p=.03) and DDIs (p=.007), corroborating efforts for rational medication use as a preventive strategy.

CONCLUSIONS: Using tools to evaluate the pharmacotherapy for older people in intensive care can assist in the recognition and prevention of pharmacotherapeutic problems, with emphasis on the identification of ADRs through the observation of triggers and subsequent causality analysis.

PMID:39043496 | DOI:10.1016/j.farma.2024.06.003

Curr Cardiol Rep. 2024 Jul 23. doi: 10.1007/s11886-024-02099-2. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: This review explores the cardiovascular toxicity associated with cancer therapies, emphasizing the significance of the growing field of cardio-oncology. It aims to elucidate the mechanisms of cardiotoxicity due to radiotherapy, chemotherapy, and targeted therapies, and to discuss the advancements in human induced pluripotent stem cell technology (hiPSC) for predictive disease modeling.

RECENT FINDINGS: Recent studies have identified several chemotherapeutic agents, including anthracyclines and kinase inhibitors, that significantly increase cardiovascular risks. Advances in hiPSC technology have enabled the differentiation of these cells into cardiovascular lineages, facilitating more accurate modeling of drug-induced cardiotoxicity. Moreover, integrating hiPSCs into clinical trials holds promise for personalized cardiotoxicity assessments, potentially enhancing patient-specific therapeutic strategies. Cardio-oncology bridges oncology and cardiology to mitigate the cardiovascular side-effects of cancer treatments. Despite advancements in predictive models using hiPSCs, challenges persist in accurately replicating adult heart tissue and ensuring reproducibility. Ongoing research is essential for developing personalized therapies that balance effective cancer treatment with minimal cardiovascular harm.

PMID:39042344 | DOI:10.1007/s11886-024-02099-2

Transl Vis Sci Technol. 2024 Jul 1;13(7):17. doi: 10.1167/tvst.13.7.17.

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of bevacizumab-awwb in the off-label treatment of neovascular age-related macular degeneration (n-AMD) and diabetic macular edema (DME).

METHODS: All patients with n-AMD and DME treated in the maintenance phase according to the "treat and extend" strategy, who underwent forced drug substitution from bevacizumab to bevacizumab-awwb from October 2022 to April 2023 at the Tor Vergata Polyclinic in Rome, were evaluated in a retrospective study. The primary outcome was changes in central retinal thickness (CRT) over time following drug substitution. The secondary outcomes were variations in drug durability, best corrected visual acuity (BCVA) and retinal fluid, and the incidence of drug-related local and systemic serious adverse events.

RESULTS: Of 80 eyes of 76 patients with n-AMD and 55 eyes of 44 patients with DME included, before and after drug substitution, the average CRT did not statistically differ; the proportion of patients within time intervals of q8, q12, and q16 was not different; and the mean BCVA remained constant. Of a cumulative 3496 bevacizumab-awwb treatments (2154 for patients with n-AMD and 1342 for patients with DME), no local severe complications were detected. Out of a total of 544 patients (342 affected by n-AMD and 202 affected by DME), no serious adverse events were reported.

CONCLUSIONS: In our cohort of patients with n-AMD and DME in the maintenance phase, bevacizumab-awwb seems to represent a viable and cost-effective intravitreal therapy with comparable efficacy and safety to the originator.

TRANSLATIONAL RELEVANCE: This study provides a preliminary assessment of the efficacy and safety of intravitreal bevacizumab-awwb, which is widely used off-label in retinal vascular diseases.

PMID:39042047 | DOI:10.1167/tvst.13.7.17