OBJECTIVE:Histone deacetylase 1 (HDAC1) exacerbates ventricular remodeling and heart failure by promoting myocardial peroxidative damage. Thus, this study aimed to investigate whether the HDAC1 inhibitor mocetinostat alleviates pathological cardiac hypertrophy via suppressing ferroptosis and to elucidate the potential mechanisms involving the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. METHODS:Primary cardiomyocytes were stimulated with phenylephrine (PE) to induce hypertrophy and ferroptosis in vitro, with or without mocetinostat treatment. The Nrf2 inhibitor ML385 was used to verify pathway specificity. In vivo, a mouse model of pressure-overload-induced cardiac hypertrophy was established using a transverse aortic constriction (TAC)-induced approach. Mocetinostat was administered to evaluate its therapeutic effects. Ferroptosis markers including lipid peroxidation, iron accumulation, and levels of ferroptosis-related proteins, were assessed. The acetylation and nuclear translocation of Nrf2, as well as the expression of the associated downstream targets (Solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), ferroportin, ferritin heavy chain 1 (FTH1), heme oxygenase-1 (HO-1)), were analyzed. RESULTS:Mocetinostat treatment significantly ameliorated PE-induced cardiomyocyte hypertrophy and ferroptosis in vitro and attenuated TAC-induced cardiac hypertrophy and fibrosis in vivo. Mechanistically, mocetinostat facilitated Nrf2 acetylation and promoted Nrf2 nuclear translocation, leading to the transcriptional activation of downstream antioxidant targets and subsequent inhibition of lipid peroxidation. The protective effects of mocetinostat were abrogated by the Nrf2 inhibitor ML385. CONCLUSION:This study demonstrates that mocetinostat attenuates pathological cardiac hypertrophy by inhibiting ferroptosis through activation of the Nrf2 pathway . These findings indicate the potential of mocetinostat as a therapeutic strategy for delaying heart failure progression.
BACKGROUND:Switching from branded to generic extended-release (ER) metoprolol formulations is common practice due to cost considerations. Although generics are approved as bioequivalent, subtle differences in formulation, such as coating composition, may influence drug release under real-life conditions across patients. OBJECTIVE:This study aimed to evaluate potential differences in drug release between the originator product Beloc-Zok 95 mg and randomly selected generic ER metoprolol succinate formulations available on the German market. METHODS:Formulations were assessed under variable, interindividual, physiologically relevant in vitro conditions simulating gastrointestinal transit. RESULTS:All formulations demonstrated controlled drug release; however, the release profiles were not fully overlapping. One generic formulation consistently exhibited slightly slower release across all test scenarios. These findings indicate that minor differences in release behavior can occur even among bioequivalent ER formulations. While such variations are generally clinically negligible, they may contribute to pharmacokinetic and pharmacodynamic differences in sensitive individuals, potentially explaining reported adverse effects such as bradycardia, hypotension, chest pain, or increased blood pressure when switching to generic products. CONCLUSIONS:The results underscore the importance of considering patient-specific variability when switching from branded to generic formulations. Incorporating physiologically relevant in vitro studies combined with physiologically based pharmacokinetic and pharmacodynamic modeling in future research may improve predictions of in vivo performance and support safer therapeutic decisions.
BACKGROUND:β-lactam allergy labels (BALs) are commonly found in patient records but are often inaccurate. This can lead to suboptimal antibiotic selection, increased healthcare costs, and antimicrobial resistance. Most existing risk assessment tools were developed in Western settings and are not applicable in Chinese clinical contexts. This study developed and pilot-tested a pharmacist-led BAL risk assessment tool tailored to the Chinese healthcare environment. METHODS:The study was conducted in three phases: (1) A systematic review of 90 studies to identify key β-lactam allergy risk factors; (2) Grounded theory and text co-occurrence analysis to extract high-risk features and construct the assessment framework; and (3) A pilot implementation in a tertiary hospital to evaluate the tool's feasibility, clinical impact, and patient outcomes using a quasi-experimental design. RESULTS:The final tool comprised eight dimensions, 35 subdimensions, and over 1328 distinct coded nodes. Of the 289 patients involved in the pilot, 18.7% were classified as high risk. Compared with patients with BALs but without high-risk features, those at lower risk had significantly shorter hospital stays (8.5 ± 4.3 vs. 10.6 ± 5.5 days; p < 0.001), reduced hospitalization costs (17,800 ± 6200 vs. 21,000 ± 7500; p = 0.0011), and lower allergy event rates (0% vs. 6.5%; p = 0.002). β-lactam use increased (75.3% vs. 40.3%; p < 0.001), whereas second-line antibiotic use decreased (24.7% vs. 59.7%; p < 0.001). The tool also demonstrated high feasibility, achieving a 100% completion rate and strong adherence among pharmacists. CONCLUSION:This pharmacist-led risk assessment tool has strong potential for accurately identifying high-risk β-lactam allergy patients and optimising antimicrobial stewardship in Chinese hospitals. Further large-scale validation is warranted.
BACKGROUND:Prophylactic opioid rescue therapy is often used to manage cancer-related pain. However, the effect of prophylactic rescue therapy in suppressing increases in breakthrough pain due to body movements has not yet been investigated. Therefore, this study aimed to compare the efficacy and safety of prophylactic rescue therapy before and after administration. METHODS:This multicenter, retrospective survey was conducted in Japan. Participants were patients with cancer who received prophylactic strong opioid rescue therapy for the first time. The primary endpoint was the suppression of an increase in pain, assessed using a Numerical Rating Scale (NRS), before and after administration of prophylactic rescue due to body movement. RESULTS:The overall analysis (193 cases) showed that prophylactic rescue suppressed the increase in the median NRS value by 3.00 (interquartile range: 1.00-4.00, p < 0.001). In addition, subgroup analysis by purpose (meals/bathing/rehabilitation/radiation therapy/others) also showed a significant reduction in the increase in NRS, with all categories exhibiting a decrease of 2.00 or more. CONCLUSIONS:Prophylactic opioid rescue with appropriate patient selection can effectively suppress breakthrough pain caused by body movement.
BACKGROUND:The placenta plays important roles in pregnancy maintenance and fetal development, and chemical-induced functional or structural abnormalities can lead to adverse pregnancy outcomes. However, information on the placental effects of chemicals remains limited. To help address this gap, this study aimed to investigate the effects of two model chemicals, phenytoin and phenobarbital, on syncytialization (the fusion of cytotrophoblasts into multinucleated syncytiotrophoblasts), a critical process in placental development, using the human choriocarcinoma cell line BeWo. METHODS:Phenytoin and phenobarbital, anticonvulsant drugs known to cause major congenital malformations, were each co-treated with forskolin, which promotes syncytialization in BeWo cells, for 48 h. RESULTS:Evaluation of cell fusion showed that phenytoin significantly suppressed forskolin-induced luciferase activity, whereas phenobarbital did not. Enzyme-linked immunosorbent assay showed that the concentration of human chorionic gonadotropin beta (hCGβ) in the cell culture supernatant was decreased in phenytoin-treated syncytialized BeWo cells but increased in phenobarbital-treated cells. Western blotting also showed a similar pattern in the hCG protein expression level. CONCLUSION:Collectively, these results indicate that phenytoin suppresses the process of syncytialization, whereas phenobarbital does not affect cell fusion and instead enhances hCG production.
BACKGROUND:Dexamethasone is typically included in the anti-emetic regimens during the administration of anticancer drugs. However, the incidence and severity of nausea and vomiting in patients receiving anticancer therapy, for whom dexamethasone must be avoided to prevent the recurrence of diabetes mellitus or hepatitis, remain unknown. METHODS:This retrospective, observational study evaluated nausea and vomiting in patients with breast cancer who underwent highly emetogenic chemotherapy, including anthracycline and cyclophosphamide, for breast cancer. In all patients, dexamethasone was completely omitted from the standard antiemetic regimen for reasons such as hepatitis, and only palonosetron and aprepitant were administered. RESULTS:For the 82 evaluated cases, the incidence of nausea was 84.1%, vomiting was 14.6%, and the complete response (CR) rate was 8.5%. In addition, the incidence rate of grade 2 or higher nausea (CTCAE ver. 4) was 47.6%, and the proportion of cases in which anticancer drug doses were reduced in the subsequent course due to nausea and vomiting was 2.4%. Factor analysis showed that treatment regimens, age, drinking history, history of prior chemotherapy, and reasons for omitting dexamethasone had no significant effects on the incidence of chemotherapy-induced nausea and vomiting. CONCLUSIONS:This study confirmed that the antiemetic effect of only administering palonosetron and aprepitant is insufficient for patients receiving highly emetogenic chemotherapy in whom dexamethasone cannot be administered. Prophylactic administration of other antiemetic drugs is necessary to effectively manage nausea and vomiting in patients receiving anticancer therapy who cannot receive dexamethasone.
The aim of this study was to investigate how patient background influences the prolonged effect of midazolam, focusing on factors previously reported and albumin levels. A total of 196 patients aged 18 years and older were admitted to the University Hospital and Matsuyama Shimin Hospital intensive care units between January 2015 and May 2022 and received continuous midazolam infusion for at least 24 h were initially considered. Ultimately, 68 patients meeting the inclusion criteria were analyzed. We collected patient data, including background information, laboratory test values, and usage status of sedatives such as midazolam, from medical records. The primary outcome was the time required to see improvement in the Richmond Agitation-Sedation Scale score after midazolam administration. Factors influencing the duration of midazolam's effects were assessed using the Mann-Whitney U test and logistic regression analysis. The improvement in Richmond Agitation-Sedation Scale scores post-midazolam discontinuation occurred within 48 h for 52 patients (76.4%) and exceeded 48 h for 16 patients (23.5%). Risk factors identified in prior studies, and albumin levels were linked to the prolonged effect of midazolam. Multivariate logistic regression analysis indicated that albumin levels significantly affected the duration of midazolam's effects (odds ratio, 0.61; 95% confidence interval, 0.44-0.85; P < .05). In this study, the serum albumin level was identified as a new factor that enhances and prolongs the action of midazolam. Therefore, sedation in patients with low albumin levels should be performed carefully to avoid the prolongation and potentiation of midazolam action.
Chronopharmaceutic drug delivery systems are designed to align the release of active substances with the body's biological rhythms, offering significant advantages in diseases with time-dependent symptom patterns. Delayed-release tablets are widely used in this field to achieve controlled drug release after a defined lag time, typically by modulating the composition of excipients. However, the reliance on excipient-based control may limit the flexibility and predictability of release profiles. This study is the first in the literature to focus on the mechanistic design of chronopharmaceutical tablets by exploring how physical tablet properties-specifically tablet geometry and compression physics-can independently control delayed drug release, without relying on excipient effects. By systematically varying tablet shape, size, and compression force, we aimed to establish a new formulation approach centered on the physical characteristics of the dosage form. Prednisone was selected as a model drug due to its common use in chronotherapy, where precisely timed drug release is essential to improve therapeutic outcomes. In vitro dissolution studies demonstrated that manipulation of tablet geometry and compression parameters effectively modulated lag time and drug release kinetics, independent of excipient composition. These findings suggest that optimizing the mechanistic properties of tablets provides a valuable strategy for the design of advanced chronopharmaceutical systems, potentially enhancing drug efficacy, patient comfort, and treatment adherence.
Febrile neutropenia is a common complication of hematopoietic stem cell transplantation. Although anti-MRSA agents such as vancomycin and teicoplanin are widely used for treatment, their clinical efficacy and safety during the early post-transplant period remain unclear. In this study, we retrospectively compared the shortterm mortality and safety of vancomycin and teicoplanin in patients with febrile neutropenia during the early post-transplantation period. This study analyzed patients who received vancomycin or teicoplanin injections for febrile neutropenia within 30 days of hematopoietic stem cell transplantation at the National Cancer Center Hospital between January 2014 and December 2016. Blood concentrations, clinical efficacy, and safety were evaluated. The proportion of patients who achieved the effective target concentration in the first measurement was significantly higher in the teicoplanin group than in the vancomycin group (79.2% vs. 35.3%, P < 0.01). The teicoplanin group reached the target concentration more rapidly (3.0 days vs. 4.5 days, P = 0.04). The all-cause mortality within 90 days of initiating anti-MRSA treatment was significantly lower in the teicoplanin group (1.0% vs. 9.8%, P = 0.01), as was the incidence of renal dysfunction (1.0% vs. 27.4%, P < 0.01). In the vancomycin group, renal dysfunction was significantly more frequent after concomitant tazobactam/piperacillin treatment (50.0% vs. 12.9%, P < 0.01). Breakthrough gram-positive cocci infections occurred only in the teicoplanin group (2.0%), with MR- Staphylococcus haemolyticus identified in all cases. Teicoplanin reached effective concentrations more efficiently than vancomycin, with a lower incidence of renal dysfunction and improved short-term outcomes in early post-transplant febrile neutropenia.
Equisetum arvense L., commonly known as horsetail, is the most prominent Equisetum species and a widely used medicinal plant in traditional and herbal medicine. This study presents a comprehensive phytochemical characterisation of various pharmaceutical extracts prepared from field horsetail according to a national pharmacopoeia, including aqueous fermented extracts, oil-based extracts and hydroalcoholic extracts. Polar constituents were analysed using HPLC-DAD-ESI-MS n. GC-MS analyses following silylation were performed to elucidate low-molecular-weight compounds. The results revealed different phytochemical compositions of the E. arvense L. extracts, with distinct profiles of compounds including hydroxycinnamic acids and flavonoids. The results of the GC-MS investigations indicated the presence of an even broader variety of compounds, comprising benzoic acids, fatty acids, sugars, and phytosterols. Additionally, chlorophyll and carotenoid contents were quantified in the oil-based extracts by UV-VIS spectroscopy. This study underlines the significant impact of the respective extraction parameters on the phytochemical profile of the corresponding pharmaceutical extracts and highlights the rich history and continuing importance of this medicinal plant in traditional and complementary medicine.
Background and aim: Studies provide strong evidence for antidiabetic efficacy of certain drugs but adverse events (AEs) and drug-related problems (DRPs) limit their effectiveness. Investigations: Patients with type-2 diabetes mellitus of community pharmacies were invited to participate in a multicenter controlled trial and were randomized either to receive "basic care" (control group, CG) or "advanced pharmaceutical care" (intervention group, IG). In two home visits at t0 (status quo) and t1 ( follow-up after 4-6 weeks), patients were asked about AE/DRP typical for antidiabetics and their adherence. Results: Totally, 130 patients were randomized to CG or IG (median age 73 vs. 67 years, n. s., 32 vs. 27 women, n. s.). At t0, 57 gastrointestinal-AE occurred in 33 patients (CG) vs. 56/31 (IG, n. s.). At t1, 57 "unchanged persisting" gastrointestinal-AE occurred in 32 patients (CG) vs. 25/17 (IG, p=0.006) and 59 "overall persisting" gastrointestinal-AE in 33 patients (CG) vs. 39/25 (IG, n. s.). At t0, 11 hypoglycemic-AE occurred in 9 patients (CG) vs. 13/10 (IG, n. s.). At t1, 10 "unchanged persisting" hypoglycemic-AE occurred in 9 patients (CG) vs. 2/2 (IG, p=0.028) and 10 "overall persisting" hypoglycemic-AE in 9 patients (CG) vs. 5/4 (IG, n. s.). At t0, 135 DRP occurred in 36 patients (CG) vs. 147/43 (IG, n. s.). At t1, 133 DRP occurred in 34 patients (CG) vs. 41/19 (IG, p=0.005). At t0, 58 patients (CG) vs. 50 patients (IG) self-reported to be adherent (n. s.) and at t1, 60 patients (CG) vs. 59 (IG, n. s.). Conclusions: "Advanced pharmaceutical care" decreased the number of "unchanged persisting" gastroenterological- and hypoglycemic-AE and DRP.
Our understanding of pharmacists as Nazi perpetrators remains rather vague. Considerable research has examined the Nazification and transformation of German pharmaceutical research, practice, and education between 1933 and 1945. The names of several SS pharmacists who served in concentration camps are also known. Yet little is known about their actual practices and their concrete involvement in medical crimes. What tasks did pharmacists perform in the concentration camps, what scope of action did they have, and in which perpetrator networks were they embedded? This article addresses these questions through the biographical example of Herbert Siggelkow (1906-1976), chief pharmacist of the concentration camps. Drawing on extensive archival records, we reconstruct the biography of Siggelkow, who, already as a grammar school student, had joined a völkisch-nationalist paramilitary association and, in 1932, the Nazi Party and the SS. We then analyze his responsibilities, individual scope of action, and involvement in medical crimes across the various settings of his service in the Waffen-SS and within the concentration camp system. As camp pharmacist at Dachau and Sachsenhausen and as chief pharmacist of the concentration camp medical service, Siggelkow shared responsibility for both the individual and the structural medical neglect of inmates. In fact, he was among the very few who had precise knowledge of the extent of medical shortages throughout the entire camp system. Through the distribution of poisons, he facilitated the systematic killing of sick and incapacitated prisoners by injection, while the provision of drugs and equipment for the camp research stations sustained the criminal practice of coerced human experimentation. We demonstrate that, over the course of his service, Siggelkow operated within markedly varying but generally limited scopes of action. While he had initially used his individual latitude clearly to the detriment of prisoners, his demeanor shifted markedly as hopes of a German victory waned. However, as part of a multi-professional perpetrator network, he bore substantial co-responsibility for atrocious medical crimes committed in the camps.
Purpose: Pemetrexed causes renal impairment. However, few studies have investigated the risk factors associated with pemetrexed-induced renal impairment. This study aimed to investigate the incidence of nephrotoxicity in patients receiving pemetrexed in combination with carboplatin and to identify the associated risk factors. Methods: This single-center retrospective study included patients with lung cancer (including malignant mesothelioma) who underwent pemetrexed-based treatment between May 2019 and August 2022. Nephrotoxicity incidence was evaluated according to the Kidney Disease Improving Global Outcomes diagnostic criteria, and risk factors for nephrotoxicity during pemetrexed treatment were identified using logistic regression analysis. Results: Renal impairment occurred in 17 of 108 patients (15.7 %), with many experiencing irreversible renal function decline after its onset. The risk factors for nephrotoxicity during pemetrexed-based treatment were identified as the total number of cycles (≥ 10) (odds ratio: 7.94, p < 0.01) and its combination with any two non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs), or diuretics (odds ratio: 6.30, p < 0.01). Conclusion: Patients receiving pemetrexed treatment are at risk of developing renal impairment, with risk potentially increasing with the number of treatment cycles and concomitant use of NSAIDs, ACEIs/ARBs, or diuretics. However, further studies are required to confirm these findings.
Background and aim: To implement Clinical Pharmaceutical Services (CPS) in routine hospital care with limited resources, their use should be prioritized. We present an objectifiable approach to planning development particularly for pharmaceutical staff. Investigations: We designed a Human Resource Development Score (HRD): HRD=P-([I+F]/2) with P: prioritization score of CPS assessed by a pharmaceutical expert panel; I: intensity score of CPS currently offered in routine care; F: frequency score of CPS offered; all scores ranged from 0[min]4[max]. An HRD<0 indicates a future decrease, HRD=0 no change and HRD>0 a desirable increase in the pharmaceutical staff development. To obtain an estimated future development (ΔHRD), we multiplied HRD as a weighting factor by the proportion of current or evaluated for the start of the respective CPS pharmaceutical staff positions (n, median per hospital pharmacy) as follows: ΔHRD=HRD*n. We calculated the ΔHRD in 155 of 162 CPS for which all required data were available. Results: In the "Top-5 categories to be increased", the pharmaceutical staff positions (n) and the Human Resource Development (ΔHRD=HRD*n) were as follows (median per hospital pharmacy): 1. "Interfaces"/"Closed-loop concepts" (n: 1.850; ΔHRD: +7.400), 2. "Progress-management"/"Interdisciplinary ward-rounds" (2.000; +2.000), 3. "Progress-management"/"Nursing ward-rounds" (1.000; +2.000). 4. "Interfaces"/"Electronic-prescription and knowledge-support" (0.300; +1.200), 5. "Progress-management"/"Ward-rounds for high-risk-patients" (1.100; +1.100). The most relevant categories whose resources could potentially be decreased to support other CPS were assessed as: "Indication-related (non-patient-related) drug analysis" (0.500; -0.250) and "Oncology consultations" (0.275; -0.275). Conclusions: With the help of a weighted Human Resource Development Score based on an expert panel, proposals for Human Resource Development in CPS were calculated.
Creatine and taurine are frequently found together in sports supplements due to their performance-enhancing and metabolic benefits. However, discrepancies between label claims and actual content have raised concerns about product quality, regulatory compliance, and possible health impacts. Accurate quantification of these compounds is therefore essential. Liquid chromatography mass spectrometry (LC-MS/MS) is widely used for its ability to detect and quantify compounds with high sensitivity and specificity. Therefore, in a previous study, an LC-MS/MS method was developed and validated for the simultaneous quantification of creatine and taurine in sports supplements. While accurate and sensitive, its somewhat cumbersome sample preparation step makes it less suitable for a commercial setting, where typically large numbers of samples must be analysed for quality control purposes. In this study, we report the first application of quantitative nuclear magnetic resonance (qNMR) for the simultaneous quantification of creatine and taurine in sports supplements, offering a simpler alternative for quality control. A qNMR method was developed, validated, and applied to commercial sports supplements, and the results were compared to label claims. All validation parameters fell well within acceptable limits, and sample analysis revealed deviations from label claims of up to +65.97% for creatine and +141.52% for taurine. Batch-to-batch variation of the products showed better consistency with variability only as high as 8.49%. Overall, this study confirms qNMR as a reliable method demonstrating specificity, precision, accuracy, and suitability for quantitative analysis. Although high-field NMR systems remain more commonly used, the method developed here is directly transferable to modern cryogen-free benchtop NMR instruments. Benchtop NMR significantly reduces operational costs and complexity, and may arguably become a valuable, reliable, and affordable tool in quality control laboratories.
Since many years, immunoglobulin G (IgG) substitution has been used to treat patients with primary immunodeficiencies (PID) to reduce the number of infections and the burden of disease. Nevertheless, many patients continue to suffer from persisting infections. In this SINUS study, a patient questionnaire consisting of 21 questions was used to assess the current situation in patients with PID. Of the 160 patients included, most showed a persistent tendency to infections (N=140, 87.5%). During the last 12 month, most of the patients suffered from upper and lower respiratory tract infections such as sinusitis (N=85, 60.7%), bronchitis (N=88, 62.9%), and pneumonia (N=10, 7.1%). Yet the presence of persistent infections was not inversely correlated with patient satisfaction. Therefore, the treating physicians need to carefully evaluate the infection history and additional therapeutic approaches are required for satisfying improvement in the patient's infection control. Patients are open to explore new ways to achieve this goal.
Off-label drug prescribing in pediatric populations is a common practice worldwide due to the limited availability of approved formulations and clinical data for children. While often necessary, it raises concerns regarding safety, efficacy, and ethical considerations. Pharmacists play a key role in ensuring the safe use of off-label drugs; however, their perspectives in low-resource settings like Kosovo remain under-investigated. A cross-sectional, questionnaire-based survey was conducted among 296 community pharmacists across Kosovo between December 2024 and January 2025. The 27-item structured survey collected demographic data and assessed pharmacists' familiarity, practices, and perspectives on pediatric off-label use. Data were analyzed using IBM SPSS 22.0. Of the pharmacists surveyed, 49% reported moderate familiarity with pediatric off-label use, and 79% had not received formal training. Nearly all participants (99%) had encountered off-label prescriptions, most commonly involving anti-infectives and respiratory medications. Although 98% acknowledged that off-label use is sometimes necessary, many expressed concerns about safety and effectiveness. Only 21% had observed adverse drug reactions, while 96% reported no treatment failures. Communication with prescribers was rated as good by 49% of respondents, though 71% emphasized the need for stronger interdisciplinary collaboration. This study provides the first national insight into community pharmacists' perspectives on pediatric off-label prescribing in Kosovo. The findings highlight the urgent need for targeted pharmacist education, the development of standardized national guidelines, and enhanced collaboration between pharmacists and prescribers to improve medication safety in pediatric patients.
Zolbetuximab, a monoclonal antibody against claudin-18.2 (CLDN18.2), improves outcomes in CLDN18.2-positive gastric cancer, but gastrointestinal adverse events-especially nausea and vomiting-are frequently reported. Using PMDA-JADER (April 2004-March 2025), we identified individual case safety reports (ICSRs) listing zolbetuximab as a suspected drug and defined the outcome with MedDRA-concordant preferred terms (nausea, vomiting, nausea and vomiting, retching). Within zolbetuximab reports, binary logistic regression with sex (male reference) and age (<60 years reference) showed higher adjusted odds in females (aOR 3.07; 95% CI 1.45-6.51; p=0.003) and lower odds in patients ≥60 years (aOR 0.25; 95% CI 0.10-0.61; p=0.002); model calibration was acceptable (Hosmer-Lemeshow p=1.000). Disproportionality analysis yielded a markedly elevated reporting odds ratio (ROR) for zolbetuximab versus all other reports (ROR 85.40; 95% CI 62.58-116.53), whereas immune checkpoint inhibitors showed no signal. These measures reflect reporting disproportionality within a spontaneous-reporting system and should not be interpreted as incidence or causality. These exploratory findings support proactive, guideline-based antiemetic strategies-particularly for younger female patients-and warrant prospective confirmation.
Introduction: Carnitine is essential for mitochondrial fatty acid transport and energy production. Tube-fed patients with severe motor and intellectual disabilities (SMID) receiving carnitine-free enteral nutrition are at increased risk of carnitine deficiency. Famotidine, used to treat gastroesophageal reflux disease (GERD), inhibits carnitine transport in vitro, but its clinical impact remains unclear. This study investigated the effect of famotidine on blood carnitine concentrations and L-carnitine supplementation requirements in tube-fed patients with SMID. Methods: A retrospective observational study including patients receiving exclusive enteral nutrition and L-carnitine supplementation was conducted at the Tokyo Metropolitan Tobu Medical Center. Blood carnitine level and L-carnitine dose were compared between famotidine users and non-users. Results: Among 25 subjects (45 data points), famotidine users required significantly higher L-carnitine doses to maintain normal free carnitine levels than did non-users (22.0 ± 4.0 mg/kg/day vs. 13.0 ± 2.8 mg/kg/day, respectively [p = 0.024]). A correlation between L-carnitine dose and free carnitine level was observed only among non-users of famotidine (correlation coefficient: 0.352). Additionally, 36.8% of famotidine users exhibited persistently low free carnitine levels despite supplementation, compared to 3.9% of non-users. Conclusion: Famotidine use was associated with increased L-carnitine supplementation requirements, likely due to impaired renal carnitine reabsorption. Routine monitoring of famotidine-treated patients may help prevent L-carnitine deficiency. Further studies should assess possible long-term effects and explore alternative GERD treatments that have minimal impact on carnitine metabolism. Expanding insurance coverage for carnitine testing could improve early detection and intervention.
This study aimed to evaluate the temporal effect of a serum creatinine (SCr) correction intervention in critically ill patients with daily muscle wasting. A total of 5,355 critical care days in 574 patients with creatinine clearance (Clcr) and glomerular filtration rate (GFR) measured and estimated simultaneously were included. The primary endpoint was the difference in accuracy over time of the estimated Clcr/GFR relative to the measured Clcr. The CG equation was used to estimate Clcr, and the MDRD and CKD-EPI-equations were used to estimate GFR. Estimated Clcr(round-up)/GFR(round-up) indicates the estimated Clcr/GFR calculated using the rounded up value if SCr was <0.6 mg/dL. Bias was analyzed using Bland-Altman analysis, correlation using Spearman's rank correlation coefficient, and accuracy using percentage within 30% of the measured Clcr (P30). The CKD-EPI equation showed a large underestimation bias in the early period, whereas the CG and MDRD equations indicated large overestimation biases in the later period. Round-up correction increased the underestimation bias in the early period of the CG(round-up) and MDRD(round-up) equations, but decreased the overestimation bias in the later period. The limits of agreements for the CG(round-up) and MDRD(round-up) equations were narrower, although not consistently acceptable. The correlations were stronger for the CG(round-up) and MDRD(round-up) equations. Accuracy did not improve with the corrective intervention. Conclusion: SCr round-up correction increased the underestimation of kidney function in the early phase, but mitigated overestimation in the later phase. The limits of agreement remained unacceptable, and the accuracy did not improve.
