Comment on the manuscript 'Disproportionality analysis of cardiac adverse events associated with sorafenib using Spontaneous Reporting Database in Japanese'
Temporal effects of empirical round-up of serum creatinine on the accuracy of estimated kidney function after critical illness
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.
Prediction of cabazitaxel-induced severe neutropenia based on dose-to-albumin ratio and evaluation of clinical utility
Cabazitaxel is a highly protein-bound drug that has been associated with the development of severe neutropenia, and decreased albumin (Alb) levels may contribute to this phenomenon. For some highly protein-bound drugs, adjustment of drug concentration according to Alb levels is performed in clinical practice. On the other hand, in the case of cabazitaxel, a decrease in Alb levels may lead to an increased proportion of unbound drug at the same dose, which could potentially raise the risk of developing severe neutropenia. Therefore, in this study, we investigated the usefulness of a novel index, the cabazitaxel dose divided by the Alb level (Dose/Alb), as a more accurate predictor of severe neutropenia in patients with metastatic castration-resistant prostate cancer receiving cabazitaxel. Thirty-nine patients were divided into two groups: 14 patients with grade 3-4 neutropenia and 25 with grade 0-2 neutropenia. Dose/Alb at the initiation of cabazitaxel was significantly higher in the grade 3-4 neutropenia group than in the grade 0-2 group ( = 0.013). Logistic regression analysis revealed that Dose/Alb was associated with the development of grade 3-4 neutropenia (odds ratio = 1.70, = 0.021). Receiver operating characteristic analysis identified a cutoff value of 10.5 mg/g/dL; 75.0% of patients with Dose/Alb > 10.5 mg/g/dL developed grade 3-4 neutropenia, versus 18.5% with Dose/Alb ≤ 10.5 mg/g/dL ( < 0.01). The present study shows that a Dose/Alb-based prediction method may be able to predict the risk of developing grade 3-4 neutropenia at the time of the first dose of cabazitaxel.
Effectiveness of polypharmacy measures consisting of a pharmacist check followed by a multidisciplinary team review in patients with poly-pharmacy admitted to a neurology ward
Patients with neurological disease are at high risk of polypharmacy. We previously reported that a countermeasure against polypharmacy which combined a pharmacist check followed by a multidisciplinary team review was useful for diabetes patients with polypharmacy. We evaluated this polypharmacy countermeasure in neurology patients with polypharmacy admitted to our neurological ward. A single-center, retrospective observational study was conducted at Gifu University Hospital. Study participants included neurology patients taking six or more drugs on admission to the neurology ward between June 2021 and April 2023. Of 435 patients admitted to the neurology ward, 24.4% (106/435) [≥65 years old, 28.3% (79/276) patients; < 65 years old, 16.7% (27/159) patients] were taking six or more drugs at admission. Prescription content was optimized in 62 patients, and a total of 212 drugs were discontinued. The median number of medications significantly decreased from 9.0 (interquartile range, 7-10) at admission to 8.0 (interquartile range, 6.25-10) at discharge (p < 0.001). On multivariate analysis, the number of drugs taken on admission and length of hospital stay were significant factors which contributed to drug reduction, while concomitant use of immunosuppressive drugs was a significant factor in increasing the number of drugs. This countermeasure for polypharmacy, which combined a pharmacist check followed by a multidisciplinary team review, was useful in older and non-older patients with polypharmacy on a neurology ward.
Impact of famotidine on blood carnitine levels and L-carnitine supplementation dose in tube-fed patients with severe motor and intellectual disabilities
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 , 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. 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. 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. 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.
Metformin and the molecular pathways of aging: Searching for the modern elixir of life
Metformin, a well-established antidiabetic drug, has recently gained attention in geroscience for its potential to modulate key aging-related pathways. This review aims to summarize current knowledge regarding metformin's mechanisms of action beyond glycemic control, with emphasis on its influence on molecular hallmarks of aging and its potential as a geroprotective agent. A comprehensive literature review was conducted using scientific databases to synthesize findings from , , and clinical studies investigating the effects of metformin on aging-related processes. Particular attention was given to studies elucidating the drug's biochemical pathways and its role in age-associated diseases. Evidence indicates that metformin affects several hallmarks of aging, including mitochondrial dysfunction, oxidative stress, chronic inflammation, and cellular senescence. Mechanistically, activation of adenosine monophosphate-activated protein kinase (AMPK) and inhibition of mitochondrial Complex I are central to its systemic actions. These effects contribute to improved metabolic regulation, reduced production of reactive oxygen species, and enhanced autophagy. Additionally, metformin has shown protective effects in age-related disorders such as cardiovascular disease, neurodegeneration, and cancer. Its long-standing clinical use, low toxicity, and cost-effectiveness further support its relevance in aging research.
Effects of blood and brain midazolam concentrations on prolonged sedation in rats with low albumin levels
Midazolam is a short-acting benzodiazepine widely used for sedation; however, its duration of action can be prolonged by various factors including hypoalbuminemia. Previous behavioral studies in rats with low albumin levels reported reduced muscle strength and spontaneous locomotion, but the relationship between hypoalbuminemia and midazolam pharmacokinetics remains unclear. This study investigated whether prolonged midazolam sedation in hypoalbuminemia correlates with unbound and brain midazolam concentrations. Low-albumin rats were generated using protein-controlled diets for 30 days. Midazolam (5 mg/kg, i. p.) was administered and total blood and brain concentrations were determined by high-performance liquid chromatography 10 and 60 minutes after administration. Compared to controls, low albumin rats showed significantly higher total blood concentrations at 60 minutes (0.27 ± 0.02 vs 0.12 ± 0.02 μg/mL) and brain concentrations (0.21 ± 0.02 vs 0.10 ± 0.03 μg/mL). Unbound concentrations remained below quantification limits due to ultrafiltration adsorption. Pharmacokinetic analysis revealed prolonged half-life and decreased clearance in low-albumin rats. These findings suggest that hypoalbuminemia prolonged midazolam actions through sustained blood and brain concentrations, likely due to increased initial unbound drug levels that rapidly distribute to the brain before accumulating in peripheral tissues. Clinicians should exercise caution when administering midazolam to patients with hypoalbuminemia.
bark and quinine as psychiatric treatments in Portugal, 1700-1900
bark and its main medicinal derivative - quinine - are known antimalarials. Until the 20 century, medicines with bark or quinine were the only effective treatment for malaria used on a large-scale. However, bark and quinine were also used in other diseases. Regarding psychiatric uses, in Britain, bark was recommended in mania (17 th century) and nervous diseases (18 th century). Nevertheless, the full scope of bark and quinine's proposed activity in psychiatric disorders has not been assessed. We aimed to investigate references to bark and quinine's use and recommendation in psychiatric diseases and symptoms in Portugal, published in the 18 and 19 centuries. For this purpose, we reviewed Portuguese medical and pharmaceutical literature from this period. Our sources included books (namely pharmacopoeias) and periodical publications. We found 27 bark or quinine medicines recommended in the treatment of psychiatric diseases and symptoms in Portugal. Those diseases included hysteria, hypochondria, and nervous diseases. bark and quinine medicines were also advised in psychiatric symptoms such as anxiety-induced palpitations, melancholia, or hypochondriac or hysterical symptoms. For most of these medicines - 17 out of 27 - the authors mention their efficacy in clinical practice. Consequently, our research suggests that, in 18 and 19 -century Portugal, bark and quinine medicines were a therapeutic option in various psychiatric conditions. Therefore, it is possible that bark and quinine had additional therapeutic indications that remain unknown.
Glycyrrhizic acid inhibited inflammatory response in LPS-stimulated microglial BV2 cells via MAPK, Akt and NF-κB signaling pathways
Activation of microglia plays a pivotal role in the pathogenesis of neuroinflammation-mediated neurodegenerative diseases. Glycyrrhizic acid (GA), a principal triterpenoid saponin in , has been reported to exhibit a range of biological activities. Nevertheless, the function of GA in microglia activation remains unclear. In this study, the effects and mechanisms of GA on the inflammatory response were investigated in the lipopolysaccharides (LPS)-stimulated microglial BV2 cells. BV2 cells were treated with GA (0, 20 and 50 μM), followed by stimulation with LPS (1 μg/mL). The results demonstrated that GA significantly inhibited the expression of tumor necrosis factor-α (TNF-α ) and interleukin-1β (IL-1β) at the mRNA and protein levels induced by LPS. Furthermore, the release of reactive oxygen species (ROS) and the migration of microglia were suppressed by GA in LPS-stimulated BV2 cells. In addition, GA reduced the activation of mitogen-activated protein kinases (MAPKs) and the phosphorylation of Akt. GA also inhibited the phosphorylation of Iκ Bα kinase (IKK) and p65, and blocked the nuclear translocation of p65 protein. The findings indicate that GA inhibited the inflammatory response in LPS-stimulated microglial BV2 cells through the suppression of MAPK, Akt, and nuclear factor-κ B (NF-κ B) signaling pathways, suggesting that GA may serve as a potential therapeutic approach for the treatment of neuroinflammation-associated neurodegenerative diseases.
Formulation development and optimization of artemether-lumefantrine self-nanoemulsifying drug delivery systems
Poor aqueous solubility may decrease the absorption and oral bioavailability of lipophilic drugs. In the current study, artemether (ART) and lumefantrine (LMF) o/w self-nano emulsifying drug delivery system (SNEDDS) formulations were prepared. Equilibrium solubility studies were conducted and pseudo-ternary phase diagrams were constructed to identify excipients with the best solubilizing capacity for ART and LMF. They were subsequently used to manufacture and optimize SNEDDS using experimental designs, which were then characterized. Solubility and emulsification studies revealed that ART and LMF are highly soluble in oleic acid (OA). Cremophor EL (CEL) and Transcutol HP (THP) were selected as surfactant and co-surfactant. The addition of Capryol™ 90 (C90) increased the region of nano-emulsion formation without evidence of precipitation of ART and LMF. Compatibility studies revealed no prominent or significant incompatibilities between the drugs and selected excipients. The optimized formulation was stable as dispersions with nano-sized droplets and a loading capacity >99 % for both ART and LMF and a release >95% within 15 min for both drugs, reflecting a significant increase in the rate and extent of dissolution compared to that of the pure drug.
Adverse events associated with mesalazine in the real-world: A comprehensive pharmacovigilance analysis of the FAERS and JADER databases
We conducted a pharmacovigilance analysis of mesalazine-related adverse events (AEs) in the realworld using the America's FAERS and Japan's JADER databases. We extracted reports of mesalazine-associated AEs from FAERS and JADER spanning the first quarter of 2004 to the third quarter of 2024. In the disproportionality analysis, we applied the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma-Poisson shrinker (MGPS) algorithms for signal detection. The time to onset of AEs was assessed using Kaplan-Meier curves and the Weibull distribution test. The analysis encompassed 40,265 AEs reports from FAERS and 4,330 from JADER. Mesalazine-related preferred terms (PTs) mapped to 27 System Organ Classes (SOCs) in FAERS and 25 SOCs in JADER. Gastrointestinal disorders emerged as the most frequently reported SOC in both databases. Three SOCs demonstrated significant signal strength across both datasets: (1) gastrointestinal disorders, (2) general disorders and administration site conditions, and (3) respiratory, thoracic, and mediastinal disorders. Common AEs including diarrhœa, pancreatitis, gastroenteritis, asmyopericarditis, proctitis ulcerative, and glutamate dehydrogenase level abnormal aligned with established drug labeling. Notably, novel pharmacovigilance signals were detected for organizing pneumonia (FAERS: n = 113, ROR = 35.21, 95%CI 29.21-42.46; JADER: n = 32, ROR = 7.90, 5.56-11.22) and eosinophilic pneumonia (FAERS: n = 77, ROR = 41.25, 32.87-51.76; JADER: n = 179, ROR = 57.69, 49.26-67.56), both requiring urgent clinical attention. AEs mainly occurred within 30 days (58.36%) with a median onset of 17 days, and the median onset time of female patients (12 days) was shorter than male patients (25 days). This pharmacovigilance study provides clinically significant evidence regarding safety-associated adverse events (AEs) of mesalazine in real-world settings. The detection of novel safety signals, particularly organizing pneumonia and eosinophilic pneumonia, highlights the necessity for enhanced post-marketing surveillance through longitudinal AE monitoring. Our findings contribute to the evolving safety profile of mesalazine and warrant further clinical investigations to validate their clinical relevance and establish causal relationships.
The influence of the third and fourth generation of combined oral contraceptives on hematological and hemostasis parameters
: Combined oral contraceptives (COC) represent an effective form of fertility control, with numerous potential side effects. The aim was to monitor the difference in hematological and hemostatic parameters in users and nonusers of oral contraceptives. : A descriptive study included 121 subjects, classified as 72 oral contraceptive users and 49 nonusers. Participants were recruited by randomization from the Institute for Student Health Care in Novi Sad. : There was no difference in age and body mass index between the groups. The frequency of smoking was higher in the nonusers compared to users (36% vs. 19%; χ =0.039). No significant difference in hematological parameters when comparing the groups was noted. Activated partial thromboplastin time (aPTT) and prothrombin time (PT) were significantly shorter in the users compared to nonusers (24.69 ± 1.83 s vs. 25.78 ± 2.85 s; p = 0.011 and 9.72 ± 2.16 s vs. 10.50 ± 1.93 s vs. p = 0.045, respectively). Significant differences in area under the curve (AUC) for endogenous thrombin potential (ETP) and the time required to reach the maximum thrombin level (ETP-) were noticed when comparing oral contraceptive users and the control group (111.40 ± 28.14 % vs. 93.32 ± 17.03 %; p = 0.02, and 69.85 ± 11.15 vs. 80.78 ± 14.87 s, p = 0.02, respectively). There was no difference in fibrinogen and D-dimer concentrations, while antithrombin and von Willebrand factor were lower in the control group, without statistical significance. Conclusion: The use of oral contraceptives of the third and fourth generation leads to changes in the hemostasis functionality in terms of the shortening of aPTT and PT, and an increase in ETP, thus potentially enabling the identification of women with the increased venous thrombosis risk.
Disproportionality analysis of cardiac adverse events associated with sorafenib using Spontaneous Reporting Database in Japanese
This study was conducted to examine the disproportionality, times to onset, incidence rates, and outcomes of sorafenib-associated cardiac AEs, using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and May 2023. Data on cardiac AEs were extracted and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs). We analyzed 2,230,863 reports and identified 8,374 reports of AEs associated with sorafenib, including 318 cardiac AEs. Signals were detected for seven cardiac AEs: hypertension, cardiac failure congestive, myocardial infarction, acute myocardial infarction, angina pectoris, myocardial ischaemia, and angina unstable. Among these, fatal outcomes were observed for cardiac failure congestive, myocardial infarction, acute myocardial infarction, and myocardial ischaemia. Histograms of median times to onset for the seven detected cardiac AE signals showed that AEs occurred at a median of 9-159 days after sorafenib administration. Weibull distributions showed that the incidence of all these AEs occurred constantly throughout the exposure period (random failure type). In conclusion, we focused on cardiac AEs associated with sorafenib as post-marketing AEs. Some cases could experience serious outcomes after sorafenib administration. Patients should be monitored for signs of onset for these AEs not only at the start of administration, but also over an extended period.
Therapeutic potential of basil ( L.) aqueous extract: Impact on glycemia and oxidative stress in normoglycemic and diabetic rats
The prevention of nutrition-related diseases holds paramount significance for human well-being. Sweet basil ( L., Lamiaceae) emerges as a noteworthy candidate due to its robust antioxidant properties attributed to a high concentration of phenolic and flavonoid compounds, promising potential health benefits for humans. Notably, bile acids and their derivatives exert influence on the metabolic effects of both conventional and herbal drugs. The aim of this study was to examine the effects of administering an aqueous basil extract for seven days on glycemia and antioxidant activity in both healthy and diabetic animals, either alone or in combination with a bile acid derivative. The experimental design involved normoglycemic and diabetic Wistar rats subjected to a seven-day regimen of saline and basil water extract. Hyperglycemia was induced using alloxan. Following the treatment period, animals were euthanized by cardiopuncture, and serum analyses were conducted to assess fasting blood glucose levels and biochemical parameters. Additional assessments included oral glucose tolerance tests and antioxidative stress enzyme assays. The findings showed a significant hypoglycemic effect of the aqueous basil extract in both normoglycemic and diabetic animals. The extract also decreased lipid peroxidation and increased the activity of antioxidant enzymes. Basil extract treatment displayed protective effects on glycemia in both normoglycemic and diabetic animals, indicating considerable antioxidant potential. These effects were evident through increased antioxidant enzyme activity and decreased lipid peroxidation, affirming the beneficial impact of aqueous basil extract on health parameters.
Pharmacokinetic study of two sulfamethoxazole-phytochemical antimicrobial conjugates in mice
Antimicrobial resistance (AMR) has emerged to be a big threat to both human and animal health. Along the tighter control on antibiotic use, developing novel therapeutic agents and approaches is crucial for combating AMR. We recently designed and synthesized several antibiotic-phytochemical conjugates which exhibited potent antimicrobial activities. To understand their pharmacological behavior and obtain a guideline for further drug development, we undertook a pharmacokinetic study on sulfamethoxazole-gallate and sulfamethoxazole-caffeate. C was determined to be 842 ± 544 ng/mL at dose of 1500 mg/kg and 733 ± 477 ng/mL at dose of 2000 mg/kg for sulfamethoxazole-gallate and 211 ± 100 at a dose of 150 mg/kg and 755 ± 705 ng/mL at dose of 300 mg/kg for sulfamethoxazole-caffeate. T was 1 h for sulfamethoxazole-gallate under both doses and 0.5 h for sulfamethoxazole-caffeate under both doses. Since C was significantly lower than the MIC for both conjugates, more formulations and administration routes such as IV injection will be investigated in our future studies.
Direct comparison of the effects of first- and second-generation H -receptor blockers on motor functions in mice
Histamine H1 receptor (H1R) antagonists are widely used to treat allergic reactions; however, their effects on the central nervous system can impair motor functions. This study investigated the impact of first-generation (diphenhydramine and -chlorpheniramine) and second-generation (epinastine, ketotifen, bepotastine, and levocetirizine) H1R antagonists on motor functions in mice using activity wheel, balance beam, inclined screen, and rotarod tests. First-generation H1R antagonists significantly impaired motor functions, with diphenhydramine exerting stronger effects than those of -chlorpheniramine. Among the second-generation agents, bepotastine and levocetirizine had minimal effects on all motor functions, whereas epinastine and ketotifen suppressed spontaneous movement, similar to first-generation H1R antagonists but had little effects on balance, postural stability, and coordinated movement. These findings provide valuable insights into the differential effects of first- and second-generation H1R antagonists on motor functions. These results highlight the importance of understanding individual profiles of H1R antagonists to minimize adverse effects, ensure patient safety, and improve quality of life.
Coumarins attenuate intestinal motility by inhibiting TMEM16A
Transmembrane 16A (TMEM16A) is highly expressed in interstitial cells of Cajal (ICC) and participates in ICC-mediated rhythmic contractile activity of intestinal smooth muscle. TMEM16A is also expressed in epithelium of intestine with a minor contributor to transepithelial fluid secretion, while other unidentified Ca -activated Cl - channels (unCaCCs) are mainly responsible for this physiological process. TMEM16A/CaCCs dysfunction can lead to disorders of intestinal motility and transepithelial fluid secretion. TMEM16A/CaCCs regulators are important tools to identify unCaCCs and study the physiopathological functions related to TMEM16A/CaCCs. In the present study, coumarins were identified as TMEM16A inhibitors in a concentration- and time-dependent manner in TMEM16A-expressed Fischer rat thyroid (FRT) epithelial cells. Coumarins attenuated intestinal motility by inhibiting TMEM16A and . Coumarins inhibited CaCCs-mediated Cl currents induced by ATP in T84 and HT-29 cells or by carbachol (CCh) in mouse colonic mucosa with reduction of ATP-induced increase of cytoplasmic Ca concentration in HT-29 cells. Coumarins inhibited basolateral Ca -activated K channels without affecting Na + /K + -ATPase activity in mouse colonic mucosa. Coumarins did not show inhibition of cystic fibrosis transmembrane conductance regulator (CFTR), but mild activation of CFTR-mediated Cl - currents under the low concentration forskolin (FSK) in CFTR-expressed FRT cells, while coumarins did not activate CFTR-mediated Cl- currents in mouse colonic mucosa. This study was the first to demonstrate that coumarins attenuate intestinal motility by inhibiting TMEM16A, which may provide a strategy for clinical drug intervention aimed at reducing secretory diarrhea.
Development and validation of a fast LC-MS/MS method for the quantitation of creatine and taurine in sports supplements
Sports supplements containing a combination of creatine and taurine have seen a dramatic rise in popularity. However, adequate analytical techniques for the quantification of these metabolites in tissue samples and supplements are essential. Liquid chromatography mass spectrometry offers a selective and sensitive alternative but to date, no method has been reported for the quantification of both compounds in combination. The main objective was to develop and validate a fast analytical method using LC-MS/MS and to test its suitability on seven commercial sports supplements. An isocratic method with a run time of 2.5 min using a hydrophilic interaction liquid chromatography column and multiple reaction monitoring transitions was developed and validated for linearity, precision, LOD and LOQ, ruggedness and recovery. Spiking experiments on seven commercial samples were conducted to test for possible ion enhancement/suppression. All validation parameters fell well within acceptable limits and the spiking recoveries of the commercial samples all fell between 81-116%. The seven products revealed large discrepancies between the measured values by as much as +99.66% for creatine and as low as -83.81% for taurine as compared to the label claims. These discrepancies highlight the importance of quality control, as inaccurate labelling could lead to unintentional overdosing, which may cause gastric issues and, in severe cases, kidney problems.
Pilot of a joint bed-side teaching course for medical and pharmacy university students
: Interprofessional education of medical and pharmacy students may improve competence-based university teaching. : We developed a joint bed-side teaching to improve patient-related competencies in identifying drug-related problems in hospitalized patients at a university cardiology department. Students were randomly allocated in mixed teams of medical and pharmacy students (1:3). The concept consisted of four parts: (i) kick-off session (day 1), (ii) file analysis and bed-side patient interview (day 2), (iii) medication analysis (free time management), and (iv) presentation of the acquired results (day 3). Expectations and competencies, predefined in 10 categories and 10 assessment levels (0-none to 10-maximum), were evaluated before and after the course (degree of fulfillment of the expectations reported after the course). : Overall, 12 students participated, eight of whom were female. Median age was 23 years (Q25/Q75: 22/24). The median time at university was 8 semesters (Q25/Q75: 7/9). The competencies were assessed by the students before and after the course in the following categories: Competencies in "Treatment of diseases" (median rating before/after the course: 6/7; n.s.), "Diagnostics of diseases" (4.5/5; n.s.), "Future physician-pharmacist cooperation" (6/8; p=0.005), "Interaction with patients" (6.5/7; n.s.), "Cardiology" (5/7; p=0.012), "Interprofessional student communication" (6.5/9; p=0.005), "Dealing with patient-oriented questions" (6.5/8; n.s.), "Future professional life" (5/7.5; p=0.012), "Practical problem solving" (6/7; p=0.027), "Scientific work" (6/7.5; n.s.). Expectations before the course were highest (median of 10) in the categories "Future physician-pharmacist cooperation", "Dealing with patient-oriented questions", "Future professional life", and "Practical problem solving". The highest levels of expectation fulfilment were reported after the course for the categories "Future physician-pharmacist cooperation" and "Interprofessional student-communication". In the free text, interprofessional collaboration was frequently mentioned as a particularly positive aspect of the course. : A pilot joint bed-side teaching course for medical and pharmacy students was feasible and an early interprofessional collaboration during medical and pharmacy studies may improve several competencies particularily regarding competencies in physician-pharmacist cooperation and in interprofessional student communication.
Methylenetetrahydrofolate reductase () C677T and A1298C polymorphisms are associated with major depressive disorder in the Saudi patients attending Erada complex for mental health and Erada services - Jeddah, Saudi Arabia
: Major Depressive Disorder (MDD) is a prevalent and debilitating mental disorder that has been linked to hyperhomocysteinemia and folate deficiency. These conditions are influenced by the methylenetetrahydrofolate reductase () gene, which plays a crucial role in converting homocysteine to methionine and is essential for folate metabolism and neurotransmitter synthesis, including serotonin. : This study explored the association between and polymorphisms among Saudi MDD patients attending the Erada Complex for Mental Health and Erada Services outpatient clinic in Jeddah, Saudi Arabia. : The study involved 87 MDD patients and 87 control subjects. Saliva samples were collected, and genomic DNA was extracted. Polymerase chain reaction-restriction fragment length polymorphism was used to detect gene polymorphisms. : A significant difference was observed in the distribution of genotype frequencies for and polymorphisms between MDD patients and controls in the Saudi cohort (: = 0.001; : = 0.01) Risk analysis indicated that individuals with the mutant TT genotype of the polymorphism (Odd Ratio (OR) = 6.80, CI 95% = 1.47-31.36, = 0.01) and the mutant CC genotype of the polymorphism (OR = 2.64, CI 95% = 1.36-5.13, P = 0.004) are more common in MDD patients, suggesting a higher risk for depression. Gender-specific analyses showed that the TT genotype significantly increases the risk of MDD in males compared to females. : These findings underscore the significant impact of genetic factors, particularly the association of polymorphisms with MDD. The results highlight the importance of personalized treatment approaches considering individual genetic profiles.
Quantification of ivermectin in veterinary products consumed off-label as a treatment for COVID-19
The COVID-19 pandemic caused global pandemonium, and due to an unprecedented global response, the popularity and use of (veterinary) ivermectin, amongst many other conceivable 'treatments', experienced a meteoric rise. Ivermectin is a macrocyclic lactone compound belonging to the avermectin drug class and is a registered medicine in many countries, although the most common use is as veterinary medicine. In this study, a fast HPLC method was developed and validated for the quantification of ivermectin in veterinary products that were used off-label by a substantial number of people during COVID-19. Locally used veterinary products were collected as well as commercial products acquired and were tested using the newly developed method. The ivermectin content was compared to the products' label claims and it was found that all products tested contained ivermectin within acceptable limits. However, the use of veterinary products is strongly discouraged due to high dosages and administration regimens that were tested in animals and can lead to serious adverse events in humans. The presence of untested excipients and secondary actives, such as clorsulon, which can cause unknown (long-term) health impacts in humans, further adds credence to this warning.
