J Med Virol. 2024 Nov;96(11):e70055. doi: 10.1002/jmv.70055.

ABSTRACT

Hepatitis B virus reactivation (HBVr) can be a serious clinical complication that has not been fully characterized in terms of the drugs associated with this adverse effect. Leveraging the expansive data available in the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) databases, we conducted a retrospective analysis to identify drugs significantly linked to HBVr using three disproportionality analyses. Our study identified 44 drugs associated with HBVr, of which 35 did not have warnings in their product labels. The majority of these drugs were antineoplastic and immunomodulating agents, with a tendency for early occurrence of HBVr, particularly among antineoplastic agents and systemic corticosteroids. Additionally, entecavir, tenofovir disoproxil and tenofovir alafenamide demonstrated better safety profiles in preventing HBVr. These findings enhance our understanding of the demographic characteristics of patients at risk for HBVr, the drugs that pose a high risk for HBVr, the timing of such events, and the appropriate preventive medications. This knowledge contributes to the development of better prevention and treatment strategies, ultimately optimizing patient outcomes.

PMID:39558790 | DOI:10.1002/jmv.70055

Trials. 2024 Nov 18;25(1):779. doi: 10.1186/s13063-024-08569-w.

ABSTRACT

BACKGROUND: Clinical decision support systems (CDSSs) enable the automated, real-time detection of situations associated with a risk of adverse drug events (ADEs). However, the effectiveness of CDSS in reducing ADEs has yet to be demonstrated. We have chosen to focus on the detection of ADE such as hyperkalemia and/or acute kidney injury (AKI), which are common among hospitalized older adults. The present study's primary objective is to use a CDSS to reduce the number of ADEs (such as AKI and/or hyperkalemia) that occur in hospitalized older adults.

METHODS: This is a multicenter, stepped-wedge, cluster-randomized study involving five hospitals. Each hospital will start with a control period (i.e., routine care, during which each center's CDSS is deactivated) and then switch to an intervention period (during which the CDSS is activated). The intervention will be the use of a CDSS and a strategy for managing and transmitting alerts to clinical pharmacists. The rules concerning AKI and hyperkalemia have been drafted and reviewed by a multidisciplinary group. Each rule created in the CDSS is associated with a standardized procedure, based on a review of the literature. Older patients (aged 65 or over) admitted to a participating general medicine ward, a surgical ward, or obstetrics ward will be eligible for inclusion after the provision of verbal informed consent.

DISCUSSION: This study will assess the effectiveness of the CDSS in reducing the incidence of AKI and hyperkalemia. The implementation of the CDSS can assist clinical pharmacists in their daily work and is expected to prevent ADEs.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05923983. Registered February 02, 2023.

PMID:39558377 | DOI:10.1186/s13063-024-08569-w

Ann Gen Psychiatry. 2024 Nov 18;23(1):47. doi: 10.1186/s12991-024-00530-0.

ABSTRACT

BACKGROUND: Clinical practice suggests that older adults (i.e., ≥ 65 years of age) experience adverse drug reactions (ADRs) more often than younger patients (i.e., < 65 years of age). ADRs such as falls, extrapyramidal symptoms (EPS), metabolic disorders, sedation, and delirium are particularly worrisome and often associated with psychotropic drugs.

METHODS: This observational study investigated the risk for psychotropic drug-related ADRs in older (n = 99,099) and younger adults (n = 363,562) in psychiatric inpatients using data from the German pharmacovigilance program "Arzneimittelsicherheit in der Psychiatrie" (AMSP) from 1993-2016. The aim was to assess whether age influenced the risk of specific ADR types and if certain psychotropic drugs posed particular concerns.

RESULTS: The risk for ADRs did not differ between older and younger patients (relative risk 0.98, 95% confidence interval 0.92-1.05). However, older patients had a higher risk for delirium (2.35, 1.85-2.99), hyponatremia (3.74, 2.85-4.90), and orthostatic syncope (2.37, 1.72-3.26), as well as certain types of EPS, e.g., parkinsonism (1.89, 1.45-2.48) and Pisa-/metronome syndrome (3.61, 2.51-5.18). The risk for other ADRs, such as acute dystonia (0.20, 0.10-0.37), akathisia (0.47, 0.29-0.76), liver dysfunction (0.63, 0.48-0.82), weight gain (0.07, 0.04-0.14), sexual dysfunction (0.03, CI 0.00-0.25), and hyperprolactinemia/galactorrhea (0.05, 0.02-0.17) was significantly lower for older patients. Older patients treated with any type of antidepressant drug (1.33, 1.26-1.40)-especially selective serotonin reuptake inhibitors (1.57, 1.26-1.40) and selective serotonin-norepinephrine reuptake inhibitors (2.03, 1.80-2.29)-and lithium (1.74, 1.52-2.00) had a higher ADR risk than younger patients. Second-generation antipsychotic drugs had a lower (0.74, 0.71-0.77) and low-potency first-generation antipsychotic drugs a higher (1.19, 1.07-1.33) ADR risk in older patients. The risk for ADRs involving multiple drugs was higher in older patients (1.28, 1.22-1.34). ADRs in older patients were 6.4 times more likely to result in death.

CONCLUSIONS: Clinicians and pharmacists should be aware of the types of ADRs and high-risk drugs across age groups and provide appropriate monitoring. Pharmacovigilance is crucial in psychiatric patients of all ages and should not be neglected, even for drugs generally considered "safe".

PMID:39558338 | DOI:10.1186/s12991-024-00530-0

Neoplasma. 2024 Oct;71(5):482-489. doi: 10.4149/neo_2024_240716N299.

ABSTRACT

Effective treatment strategies for second-line therapy in extensive-stage small cell lung cancer (ES-SCLC) are currently lacking. For this reason, we collected and recorded efficacy and safety data from patients with ES-SCLC who had disease progression after first-line treatment and received albumin-bound paclitaxel, anlotinib, and immunotherapy. Preliminary data showed an objective response rate of 37.78%. Median progression-free survival and overall survival were 5 months and 10 months, respectively. Treatment-related adverse events were mostly tolerable. Subgroup analysis indicated that efficacy correlated with the interval from last chemotherapy to treatment initiation and specific drug-related adverse events. Further analysis of immune cell subtypes suggested that the mechanism may involve depletion of immune suppression to activate immune responses synergistically against tumors. With its promising efficacy and manageable adverse effects, this regimen holds potential as a significant option for second-line therapy in ES-SCLC. However, due to the limited sample size, further clinical validation is needed to ascertain its true clinical value.

PMID:39556427 | DOI:10.4149/neo_2024_240716N299

Cureus. 2024 Oct 16;16(10):e71588. doi: 10.7759/cureus.71588. eCollection 2024 Oct.

ABSTRACT

Amphotericin B deoxycholate (AMPH-B) is a polyene macrolide with antifungal activity. Liposomal AMPH-B (L-AMB) was developed to reduce side effects while maintaining antifungal activity. This study was aimed at evaluating and comparing the adverse event profiles of AMPH-B and L-AMB using a spontaneous reporting system. We analyzed the adverse event reports of AMPH-B and L-AMB from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Case report counts of adverse events were generated according to the preferred terms of the Medical Dictionary for Regulatory Activities (MedDRA). Standardized MedDRA queries (SMQs) and system organ classes (SOCs) were used to compare the organ-specific adverse event profiles of AMPH-B and L-AMB. The reporting odds ratio and proportional reporting rate were used to detect pharmacovigilance signals. The FAERS database contains 21,173,818 cases from January 2004 to March 2024. Adverse events were reported in 2438 cases receiving AMPH-B treatment and 3344 cases receiving L-AMB treatment, including 848 and 1591 cases receiving intravenous AMPH-B and L-AMB injections, respectively. The most frequently reported drug-related adverse event in the AMPH-B and L-AMB groups was hypokalemia. SOCs with statistically significant differences were "Inv" (laboratory tests), "Resp" (respiratory, thoracic, and mediastinal disorders), "Genrl" (general and systemic disorders and conditions at the site of administration), "Card" (cardiac disorders), and "Blood" (blood and lymphatic system disorders). No statistically significant difference was observed in the SMQ profile of adverse events in "Renal" (renal and urinary disorders) and "Hepat" (hepatobiliary disorders) between the L-AMB and AMPH-B formulations in this study. Based on real-world data from FAERS, adverse event profiles of AMPH-B and L-AMB were compared. No statistically significant difference was observed in the SMQ profile of adverse events in the renal and hepatic SOCs between the L-AMB and AMPH-B formulations. Our results suggest that L-AMB is more tolerated by the kidneys than AMPH-B.

PMID:39553150 | PMC:PMC11565214 | DOI:10.7759/cureus.71588

Health Expect. 2024 Dec;27(6):e70092. doi: 10.1111/hex.70092.

ABSTRACT

INTRODUCTION: Medication-related problems remain a significant burden despite the availability of various interventions and services in primary care. Involving health care consumers to design interventions or services across health disciplines is becoming more widely used as this type of engagement reportedly leads to more accessible, acceptable and sustainable health services and quality of life. We conducted a scoping review to examine when and how consumers have been involved in the design and development of medication safety interventions or services within the primary care.

METHODS: We searched five key databases (MEDLINE (EBSCOhost), CINAHL (EBSCOhost), PsycINFO (EBSCOhost), Embase (Elsevier) and Cochrane Library (Wiley)) for relevant articles published up to February 2024. Studies were included if they involved adult consumers (≥ 18 years), their families, carers or the wider community as stakeholders. This review only included studies where the aim was to improve safe and effective medication use, delivered exclusively in primary care. To examine consumer involvement approaches and methods we adapted a framework describing the stages of consumer involvement for the data extraction tool.

RESULTS: Overall, 15 studies were included (comprising 24 articles). Codesign, experience-based codesign, coproduction and participatory action research were commonly used approaches. Meetings, interviews, surveys/questionnaires were commonly used methods. Two studies reported consumer involvement across all stages of the research study, and only one study described the consumer experience of being involved in the research process. The impact of consumer involvement on the effectiveness of these services or interventions was mixed.

CONCLUSION: The potential benefits of consumer involvement in the design and development of medication safety interventions or services may not have been fully maximised, given that genuine consumer involvement across all stages of the research study appears uncommon. More transparent and consistent reporting around the description of consumers involved, their experience of being involved and overall impact and quality of consumer participation is needed.

PATIENT OR PUBLIC CONTRIBUTION: This scoping review was undertaken without consumers, patients, service users, caregivers or people with lived experience or members of the public due to resource limitations. This scoping review was undertaken and written by academics, who have undertaken codesign with consumers and stakeholders and also have personal lived experience of medication-related problems.

PMID:39552111 | DOI:10.1111/hex.70092

BMC Geriatr. 2024 Nov 16;24(1):955. doi: 10.1186/s12877-024-05515-y.

ABSTRACT

BACKGROUND: Adverse drug reactions are more prevalent in geriatric patients and are frequently associated with a range of polypharmacy-related issues as well as some physiological aging-related alterations. These affect the pharmacokinetic and pharmacodynamic properties of drugs. This study aimed to assess the magnitude of ADRs and their contributing factors among geriatric patients admitted at Comprehensive Specialized Hospitals of the Amhara Region.

METHODS: A multicenter prospective cohort study was carried out from May 2023 to August 2023 on geriatric patients admitted to four randomly selected comprehensive hospitals in the Amhara region. We used logistic regression to find the factors influencing the occurrence of ADRs. A P value of less than 0.05 was deemed statistically significant.

RESULTS: During the study's follow-up period, 373 patients in total were included. An incidence rate of 31.10% (95% CI: 26.38-35.82) was obtained from the identification of 121 ADRs in total. The organ most frequently affected by ADRs was the gastrointestinal tract (28.92%), followed by the cardiovascular system (19.01%), and the drug class most often implicated in ADRs was antibiotics (21.49%), then anticoagulants (12.40%). ADRs were substantially linked to being overweight (P < 0.001), having been hospitalized in the previous six months (P = 0.000), and hyperpolypharmacy (p = 0.047). 93.39% of all ADRs received the interventions. 85.12% of the adverse drug reactions were successfully resolved.

CONCLUSIONS: This study found that over one-third of older people and individuals admitted to the hospital experienced ADRs. Overweight, hyperpolypharmacy, and patients who had previously been admitted during the preceding six months were significantly linked with the occurrence of ADRs. Improving the drug safety of elderly patients, particularly those who are admitted, should be a greater priority for healthcare professionals.

PMID:39550566 | DOI:10.1186/s12877-024-05515-y

Sci Rep. 2024 Nov 16;14(1):28309. doi: 10.1038/s41598-024-71746-z.

ABSTRACT

Immune checkpoint inhibitors have revolutionized cancer treatment, but they are associated with a range of immune-related adverse events (irAEs), and emerging evidence suggests significant sex differences in the incidence, type, and severity of these toxicities, suggesting an influential factor and understanding sex-related differences in irAEs as crucial for optimizing patient care and improving clinical outcomes. In MOUSEION-07 study, we aimed to assess the association between sex and treatment-related adverse events in cancer patients treated with immunotherapy through a large up-to-date meta-analysis of available clinical trials. The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis. The protocol was registered with PROSPERO no. CRD42024549518. Sixteen studies encompassing a total of 4658 patients were included, and 2133 adverse effects were highlighted. The analysis observed a not statistically significant difference in terms of immune-related adverse events (irAEs) between males and females (Odds Ratio 1.19; CI 0.88-1.63) and revealed the presence of publication bias (β = -2.53; 95% CI = [-4.03; -1.04]; P = 0.006). Sex differences in immunotherapy-related adverse events are a significant factor in cancer treatment, necessitating a personalized approach to patient care. Further research is needed to fully understand the mechanisms driving these differences and to develop optimized strategies for monitoring and managing irAEs in both females and males.

PMID:39550353 | DOI:10.1038/s41598-024-71746-z

Expert Opin Drug Saf. 2024 Nov 16. doi: 10.1080/14740338.2024.2431587. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-induced cystitis (DIC) significantly impacts patient quality of life and treatment outcomes. This study investigates the incidence and characteristics of DIC using data from the FDA Adverse Event Reporting System (FAERS).

METHODS: We reviewed FAERS reports related to cystitis from Q1 2004 to Q1 2024, compiling a list of potential causative drugs. The top 50 drugs with the highest number of cystitis reports were ranked. Statistical disproportionality analyses, including Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), were used to detect unusually high reporting frequencies of cystitis associated with specific drugs.

RESULTS: From 17,703,515 FAERS reports spanning 2004-2024, 36399 involved cystitis. The majority of implicated drugs were antineoplastics. Busulfan, BCG, and mitomycin had the highest ROR and PRR values. Additionally, drugs such as defibrotide sodium, milrinone, and dyazide, which do not have cystitis listed on their labels, were identified, highlighting the need for increased clinical vigilance and awareness.

CONCLUSION: The findings underscore the importance of ongoing pharmacovigilance in identifying and characterizing DIC. Further clinical studies are warranted to validate these associations and to develop strategies for mitigating the risk of DIC, thereby improving patient safety and treatment outcomes.

PMID:39549041 | DOI:10.1080/14740338.2024.2431587

Integr Cancer Ther. 2024 Jan-Dec;23:15347354241297385. doi: 10.1177/15347354241297385.

ABSTRACT

Women with breast cancer (BC) experience multiple symptoms related to neoadjuvant chemotherapy (NAC) treatment that impair their functioning and quality of life (QoL). This study aimed to explore the effect of high-intensity aerobic interval training (HIIT) on quality of life and NAC side effects in women with BC.

METHODS: 56 patients (48.56 (7.84) years, range 35-64 years) diagnosed locally advanced (stage II-III) ER + BC receiving doxorubicin/cyclophosphamide-based NAC were randomly assigned to the HIIT group and a control group (CG) for 6 months. The HIIT group performed 2 to 3 HIIT sessions per week according to the study protocol (4 × 4 minutes at 85%-95% peak heart rate (HR)). The CG followed the standard of care instructions by the oncologists. To assess the QoL participants completed the EORTC QLQ-C30 with the additional BC module of QLQ BR-23. Weekly self-reports on NAC side effects were collected through online survey.

RESULTS: Study data were analyzed for 37 participants (nHIIT = 17, nCON = 20) who reported at least 14 (60%) weeks. HIIT was effective to reduce BC symptom scale outcomes (ES = 0.113, P = .048), and alleviate systemic therapy side effects (ES = 0.154, P = .020) and cancer related symptoms (ES = 0.124, P = .038). The most common side effect participants experienced at least 1 to 4 days/week was pain (average 50.9% and 56.8% for HIIT and CG, respectively), followed by sleep disturbances (average 50.9% and 49.9%, respectively). About 31% in both groups experienced sleep disturbances 5 to 7 days/week. The NAC induced physical, social and fatigue side effects had significantly lower incidence in HIIT group, while psychological side effects were significantly more common in training group.

CONCLUSIONS: HIIT is an effective physical exercise program to maintain higher quality of life and help to reduce some of NAC induced side effects for women with BC.

PMID:39548802 | DOI:10.1177/15347354241297385

BMC Cancer. 2024 Nov 15;24(1):1411. doi: 10.1186/s12885-024-13192-8.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been employed in the adjuvant and metastatic setting of renal cell carcinoma (RCC) treatment. Among ICIs, combined immunotherapy has the highest risk for immune-related adverse events (irAEs). We aimed to document the incidence of irAEs in RCC patients treated with nivolumab and ipilimumab as data from the European population remain limited.

MATERIALS AND METHODS: We analysed data from 88 RCC patients treated with nivolumab + ipilimumab between May 2022 and June 2024 across six high-volume oncology units in Poland. We reviewed irAEs and estimated their impact on survival parameters via univariate and multivariate Cox proportional hazards regression models, along with log-rank tests.

RESULTS: With a median follow-up of 11.3 months, the median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 12.8 months (6.3-19.3). A total of 74 irAEs were recorded in 50 patients. The most frequent events were endocrine (n = 20, 27%), hepatic (n = 15, 17%), general (n = 12, 13.6%), and cutaneous (n = 11, 12.5%). The occurrence of irAEs was associated with a 60% lower risk of disease progression (hazard ratio 0.44, 95% confidence interval 0.2-0.87, p = 0.018) without impacting OS and higher disease control rate (n = 45, 90% vs. n = 24, 63.2%, p = 0.004). In contrast, patients with hepatotoxicity had poorer outcomes, with a 2.6-fold greater risk of death (p = 0.05).

CONCLUSIONS: IrAEs may serve as a predictive factor for the efficacy of the nivolumab + ipilimumab regimen in RCC patients. Special attention is needed for hepatotoxicity, as it can significantly impact survival outcomes.

PMID:39548483 | DOI:10.1186/s12885-024-13192-8

Cancer Immunol Immunother. 2024 Nov 15;74(1):25. doi: 10.1007/s00262-024-03858-4.

ABSTRACT

BACKGROUND: The combination regimen with immune checkpoint inhibitors (ICIs) and other therapies has been widely applied for patients with non-small-cell lung cancer (NSCLC). To date, no literature has systematically addressed the risk of hepatitis associated with the combination therapy. We conducted this pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS).

PATIENTS AND METHODS: A total of 587,016 NSCLC reports were extracted from FAERS database spanning from the first quarter of 2013 to the second quarter of 2023. After filtering duplicate reports, logistic regression model was used to detect safety signals, and multivariable logistic regression model was used to confirm the interaction between ICI and other drugs.

RESULTS: Of the 81,512 patients with NSCLC, 2785 cases developed hepatitis. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with targeted therapy (TT) was the highest 1.64 (95% CI, 1.32-2.02; P < 0.0001) among all therapies, while that of TT and ICI treatment were 1.07 (95% CI, 0.98-1.17; P = 0.1097) and 1.12 (95% CI, 1.03-1.22; P = 0.0111), respectively. The adjusted ROR for the interaction effect was 1.64 (95% CI, 1.32-2.02; P < 0.0001). Furthermore, the adjusted ROR of ICI combined with KRAS-targeted drugs was the highest 3.03 (95% CI, 1.49-5.93; P = 0.0016) among all targeted drugs, with an adjusted ROR of 3.03 (95% CI, 1.49-5.93; P = 0.0016), indicating a meaningful interaction of these two kinds of drugs.

CONCLUSION: We confirmed that combination treatment of ICI and TT is associated with the amplified risk of hepatitis, which is partly due to the interaction between ICI and TT, and the KRAS-targeted drugs may harbor the highest potential for hepatitis induction among TT drugs when combined with ICI. Besides, the combination treatment of ICI- and KRAS-targeted drugs also increases the incidence of colitis, pulmonary embolism and dehydration.

PMID:39546001 | DOI:10.1007/s00262-024-03858-4

BMC Pharmacol Toxicol. 2024 Nov 14;25(1):86. doi: 10.1186/s40360-024-00815-w.

ABSTRACT

BACKGROUND: Beta-blockers are widely used, with continuously updated clinical recommendations. However, their application faces challenges in personalized treatment and safety. The study aimed to investigate the frequency and patterns of prescribing beta-blockers in China and to explore potential adverse event risk signals associated with beta-blockers, providing reference for rational medication use in clinical settings.

METHODS: Prescription data for beta-blockers from January 2018 to June 2023 were extracted through the Hospital Prescription Analysis Collaborative Project in China to analyze clinical usage trends. While adverse drug reaction reports for beta-blockers were obtained from the FDA Adverse Event Reporting System (FAERS) database. The classification and standardization of adverse drug event (ADE) reports were based on the preferred terms (PT) and corresponding system organ classes (SOC) from the Medical Dictionary for Regulatory Activities (MedDRA). Signal detection utilized a proportion imbalance method.

RESULTS: In clinical practice, metoprolol dominated beta-blocker prescriptions in China, accounting for 62.2%. Beta-blockers were primarily prescribed to the elderly (65.7%) and male patients (57.0%). However, off-label use of beta-blockers was relatively widespread. For instance, sotalol was prescribed for hypertension at 18.25%, while esmolol was used for angina and heart failure at rates of 12.94% and 14.98%, respectively. In addition, we identified newly discovered adverse reactions associated with beta-blockers, such as BRASH syndrome (metoprolol: n = 186, ROR = 391.285; carvedilol: n = 72, ROR = 256.459), acute kidney injury (bisoprolol: n = 247, ROR = 5.641), premature baby (labetalol: n = 110, ROR = 91.385), and sleep disorder (propranolol: n = 254, ROR = 10.98).

CONCLUSIONS: Metoprolol led the beta-blocker market in China. Attention was warranted regarding the newly discovered adverse reactions, such as the risk of acute kidney injury with bisoprolol and the potential for BRASH syndrome with metoprolol and carvedilol.

PMID:39543745 | PMC:PMC11566443 | DOI:10.1186/s40360-024-00815-w

Expert Opin Drug Saf. 2024 Nov 15. doi: 10.1080/14740338.2024.2429475. Online ahead of print.

ABSTRACT

OBJECTIVE: This study was designed to conduct data mining through the Food and Drug Administration Adverse Event Reporting System (FAERS) to assess adverse events (AEs) associated with cabozantinib in the treatment of renal cell carcinoma.

METHODS: Reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms were used to detect drug-related AEs signals from reporting data in FAERS database from 2016 to 2024.

RESULTS: A total of 32,129 AE reports identifying cabozantinib as a 'primary suspect' were retrieved from the FAERS database. Among them, there were 21,549 reports of renal cell carcinoma as an indication. AEs induced by cabozantinib were observed in 23 system organ classes (SOCs). 215 AE signals were detected in 16 SOCs after four algorithms were simultaneously met. Among them, signals related to gastrointestinal disorders, general disorders and administration site conditions, and skin and subcutaneous tissue disorders were the most common. Of note, the median time to onset of AEs was 38 days (interquartile range (IQR) 14-116 days).

CONCLUSION: This study provides new insights into the monitoring, surveillance, and management of cabozantinib-related adverse drug reactions and provides a comprehensive long-term post-marketing safety assessment of cabozantinib.

PMID:39545449 | DOI:10.1080/14740338.2024.2429475

Am J Transl Res. 2024 Oct 15;16(10):6052-6063. doi: 10.62347/WBZU4331. eCollection 2024.

ABSTRACT

OBJECTIVE: To investigate and analyze the clinical efficacy and safety of polymyxin B sulfate in the treatment of carbapenem-resistant gram-negative bacteria (CR-GNB) in sepsis; in order to provide reference for the clinical diagnosis, treatment and prognosis evaluation of sepsis.

METHODS: The clinical data of 76 patients with CR-GNB sepsis treated with polymyxin B sulfate combined with an anti-infection regimen in the First Affiliated Hospital of Gannan Medical University from January 2020 to February 2024 were retrospectively studied. To analyze and discuss the clinical characteristics, results of the bacterial culture and drug sensitivity, clinical efficacy and prognosis of CR-GNB patients, efficacy comparison of different doses of polymyxin B sulfate treatment regimens, efficacy comparison of different combination regimens based on polymyxin B sulfate, changes in clinical indexes before and after treatment of polymyxin B sulfate, adverse drug reactions and adverse events of polymyxin B sulfate were investigated.

RESULTS: A total of 76 patients with CR-GNB sepsis were included in this study, with 55 males and 21 females, with an average age of 59.86 years old, 44 of which were (57.89%) were > 60 years old. All patients included in this study were treated with polymyxin B based combination therapy, 49 cases (64.47%) received the two-drug combination regimen, 27 cases (35.53%) received the three-drug or more combination regimen, and all the patients had the above treatment followed by systematic symptomatic supportive treatment. Patients in this study received polymyxin B for an average of (8.6±4.3) days, there were 60 (78.95%) patients with effective clinical treatment, and 49 patients (64.47%) achieved pathogen (bacterial) clearance of infection. Twenty-two cases (28.95%) died within 28 days, 31 cases (40.79%) died within 90 days, and the remaining 23 cases (30.26%) survived. There were statistically significant differences in the therapeutic effective rates and bacterial clearance rates among different courses of treatment or different initial doses of polymyxin B (all P < 0.05). Moreover, there were significant differences in APACHE II score, WBC, NE, HGB, platelet count, albumin, NT-proBNP and CRP before and after polymyxin B treatment (all P < 0.001). In this study, 7 cases (9.21%) developed drug-related kidney injury, which recovered or decreased below the pre-medication level after discontinuation or dose adjustment and infection control. Skin darkening (melanin deposition) occurred in 5 cases (6.58%), and the above patients basically returned to normal several months after withdrawal of the drug, but there was still a certain degree of skin pigmentation. Meanwhile, 3 cases (3.95%) had neurotoxic reactions, mainly manifested as numbness at the extremities, and the neurotoxic symptoms were improved after reducing the dosage. Accordingly, there was no statistically significant difference in the prognosis of CR-GNB sepsis patients between different age and gender groups (all P > 0.05), while the treatment course and dosage of polymyxin B had statistically significant effects on the prognosis of CR-GNB sepsis patients (all P < 0.05).

CONCLUSION: A Polymyxin B sulfate based combination regimen is an effective choice for CR-GNB sepsis, which can maximize the survival and prognosis benefits of sepsis patients.

PMID:39544731 | PMC:PMC11558405 | DOI:10.62347/WBZU4331

BMC Nephrol. 2024 Nov 14;25(1):409. doi: 10.1186/s12882-024-03689-6.

ABSTRACT

BACKGROUND: Karyomegalic interstitial nephritis (KIN) is a rare renal diagnosis associated with both genetic and medication etiologies. The primary gene associated with KIN is the FAN1 gene which encodes a protein responsible for DNA interstrand repair. Common medication triggers of KIN are chemotherapeutic agents, especially those which disrupt DNA structure such as carboplatin. Despite overlap between these mechanisms, it has not clearly been established if medication usage requires an underlying genetic predisposition for triggering KIN or if medications alone are sufficient. This ambiguous pathogenesis can make it difficult to appropriately assess risk of KIN development when starting patients on one of the known KIN-inducing therapies. Additionally, brentuximab vedotin, an antibody-drug conjugate directed against CD30, has not been previously implicated in KIN development.

CASE PRESENTATION: We present a 49-year-old woman previously diagnosed with metastatic Hodgkin's lymphoma who was treated with doxorubicin, bleomycin, vinblastine, and dacarbazine, then 3 cycles of ifosfamide, carboplatin, etoposide, all of which were discontinued due to side effects. Following an episode of acute kidney injury, the serum creatinine was 1.09 mg/dL. She then received 2 doses of brentuximab, the serum creatinine rose, and the drug was discontinued. Kidney biopsy done 2 months after brentuximab and 5 months following ifosfamide therapies showed karyomegalic interstitial nephritis. Genetic evaluation showed no FAN1 gene mutations. The patient was started on pembrolizumab; no steroids were given due to concerns about interference with lymphoma immunotherapy. She remains with stable disease and stable chronic kidney disease.

CONCLUSIONS: This case presents a patient who developed KIN with a progressively rising serum creatinine after ifosfamide, carboplatin and brentuximab treatment. Although ifosfamide and carboplatin have known associations with the development of KIN, this case raises the possibility that brentuximab, which has a different mechanism of action, also may be associated with KIN. Additionally, the genetic findings demonstrate that drug-induced KIN can develop in the absence of FAN1 mutations, a finding not previously reported.

PMID:39543462 | DOI:10.1186/s12882-024-03689-6

Support Care Cancer. 2024 Nov 14;32(12):791. doi: 10.1007/s00520-024-09014-z.

ABSTRACT

PURPOSE: The prevalence of type 2 diabetes mellitus (T2DM) in cancer patients is high. During the medication review process, clinical pharmacists could detect and manage drug-related problems (DRP) to optimize pharmacotherapy but there is a need to standardize pharmacists' interventions (PI) especially for T2DM-related DRP. The present study aims to describe DRP in cancer patients with T2DM undergoing anticancer treatment (AT) and to propose related preliminary guidelines to manage T2DM-related DRP.

METHODS: The study was conducted in one oncology outpatient hospital where a clinical pharmacy team performs medication reviews to detect and manage DRP by performing PI in cancer patients undergoing AT. All the data from November 23rd, 2015 to November 23rd, 2019 were extracted and demographic, clinical, oncological, and biological data were collected and analyzed. Based on these results and a literature review, a working group (2 pharmacists and one diabetologist) was constituted to propose a first set of preliminary guidelines clinical pharmacists that were then reviewed using the Delphi method by an expert panel of oncologists and pharmacists.

RESULTS: A total of 161 T2DM cancer patients were included in the study (19.7% of all cancer patients screened). Overall, 152 DRP (mean 1.67/patient) were detected (49.3% drug interaction) and 152 PI were performed by clinical pharmacists, mainly drug monitoring (48.0) and drug discontinuation (25.7%). Specifically, there was 24 T2DM-related DRP (including 29.2% drug interactions). Twenty-four DRPs were directly related to T2DM status. The five proposed guidelines reached a consensus after revisions and a sixth has been added.

CONCLUSION: DRPs were frequent among cancer patients with T2DM and we hypothesize that the preliminary guidelines should improve the detection of DRPs directly related to T2DM. The implementation of the preliminary guidelines should now be assessed in clinical practice.

PMID:39542931 | DOI:10.1007/s00520-024-09014-z

Antimicrob Agents Chemother. 2024 Nov 14:e0048424. doi: 10.1128/aac.00484-24. Online ahead of print.

ABSTRACT

Invasive aspergillosis (IA) and mucormycosis (IM) cause significant morbidity and mortality in immunocompromised and/or hospitalized patients. Isavuconazonium sulfate, a prodrug of the antifungal triazole isavuconazole, has been approved for treatment of IA and IM in adults; and was recently approved in children. This study describes the outcomes, safety, and pharmacokinetics of isavuconazole for the treatment of proven, probable, or possible IA or IM in children. In this phase 2, open-label, non-comparative study, patients aged 1 to <18 years with at least possible invasive mold disease were enrolled across 10 centers in the US, Spain, and Belgium from 2019 to 2022. Patients received 10 mg/kg isavuconazonium sulfate daily (maximum 372 mg; equivalent to 5.4 mg/kg or 200 mg isavuconazole) for up to 84 (IA) or 180 days (IM). Outcomes included rates of all-cause case fatality, overall response, treatment-emergent adverse events (TEAEs), and pharmacokinetics. Of 31 patients enrolled, 61.3% were 1-<12 years old; 58.1% had underlying hematologic malignancies. The successful overall response rate at the end of treatment was 54.8%. Day 42 all-cause case fatality was 6.5%; 93.5% experienced TEAEs, and two patients discontinued treatment due to drug-related TEAEs. Dosing at 10 mg/kg (maximum dose: 372 mg) met the pre-defined exposure threshold of above the 25th percentile for the area under the concentration-time curve (≥60 mg·h/L). Simulated doses of 15 mg/kg improved drug exposures in patients aged 1-<3 years. Isavuconazole was well tolerated in children, with exposure consistent with adult studies. Successful response was documented in 54.8% of patients.CLINICAL TRIALSThis study is registered at ClinicalTrials.gov as NCT03816176.

PMID:39540734 | DOI:10.1128/aac.00484-24

J Med Life. 2024 Aug;17(8):800-805. doi: 10.25122/jml-2023-0342.

ABSTRACT

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurring periods of inflammation and remission, primarily affecting the colon. The concept of medication-related burden, which refers to the adverse effects experienced by patients due to conventional medical treatments, is relatively new in the field. This study aimed to measure medication-related burden among patients with ulcerative colitis in Iraq. The study was conducted at the Gastroenterology and Hepatology Teaching Hospital, Medical City, Baghdad, Iraq, from December 2022 to May 2023. We used the Arabic version of the Living with Medicines Questionnaire version 3 (LMQ-3) to explore medication-related burdens experienced by patients with UC. Eighty-six patients with ulcerative colitis were included. The mean of the total medication-related burden score was 107.5 ± 20.7. The findings showed that 45.3% of patients with UC had a moderate degree of medication-related burden, followed by minimum burden (44.2%), high burden (5.8%), and no burden (4.7%). The lowest median burden scores emerged in five domains: interactions with healthcare professionals, practical difficulties with medication use, medication side effects, medication effectiveness, and the impact on daily life. Conversely, the highest-burden scores were noted in the cost, concerns about medication use, and autonomy to vary the regimen domains. In multivariate analysis, none of the patient-related variables was independently correlated with the total medication-related burden score. A large proportion of the patients with UC who participated in the current study reported varying degrees of medication-related burden, with the majority having a minimum to moderate medication-related burden.

PMID:39539436 | PMC:PMC11556520 | DOI:10.25122/jml-2023-0342

J Natl Compr Canc Netw. 2024 Nov;22(9):582-592. doi: 10.6004/jnccn.2024.0057.

ABSTRACT

The NCCN Guidelines for the Management of Immunotherapy-Related Toxicities are intended to provide oncology practitioners with guidance on how to manage the wide-ranging and potentially fatal toxicities that may occur with cancer immunotherapy. The guidelines address immune-related adverse events related to immune checkpoint inhibitors, CAR T-cell therapies, and lymphocyte engagers (which include T-cell-engaging bispecific antibodies). These NCCN Guidelines Insights highlight recent guideline updates pertaining to the management of emerging toxicities related to cancer immunotherapy.

PMID:39536465 | DOI:10.6004/jnccn.2024.0057