Aims: Conduct a systematic review of case reports and case series regarding the development of acute abdomen following vaccination with COVID-19, to describe in detail the possible association, the clinical and demographic characteristics. Methods: Case report studies and case series regarding the development of acute abdomen following COVID-19 vaccination were included. Systematic review studies, literature, letters to the editor, brief comments, etc. were excluded. PubMed, Scopus, EMBASE, and Web of Science databases were searched until June 15, 2023. The Joanna Brigs Institute tool was used to assess risk of bias and study quality. Descriptive data were expressed as frequency, median, mean, and standard deviation. Results: Seventeen clinical case studies were identified and 17 patients with acute abdomen associated with COVID-19 vaccination were evaluated, including: acute appendicitis (n=3), acute pancreatitis (n=9), diverticulitis (n=1), cholecystitis (n=2) and colitis (n=2). The most associated COVID-19 vaccine was Pfizer-BioNTech (mRNA) with 64.71 %. The majority of cases acute abdomen was after the first dose (52.94 %). All patients responded objectively to medical (88.34 %) and surgical (11.76 %) treatment and were discharged within a few weeks. There were no cases of death. Conclusions: Acute abdomen is a rare complication of great interest in the medical and surgical practice of COVID-19 vaccination, our study reviewed based on a small sample of patients, therefore it is recommended to conduct future observational studies and fully elucidate the mechanisms by which this association occurs.

Epithelial ovarian cancer is a disease with the highest mortality rate among gynecological tumors. After years of studies, despite targeted drugs and immunotherapies have been developing, their therapeutic effects are still not ideal. Statins, as lipid-lowering medicines, have many findings beyond expectation in the fight against cancer, and have shown promisingly positive results in clinical trials. Actually, statins cannot be used as a monotherapy to achieve complete remission due to its efficacy established, but for its great potential lying in effects about synergism and sensibilization with other drugs, and even the reduction of side effects of anti-cancer treatment. This review summarizes the evidence and potential of combining statins with first-line chemotherapy, bevacizumab, PARP inhibitors and immunotherapy drugs in the pharmacotherapy of ovarian cancer, and proposes hypothesises about new combination therapies based on the current mechanisms and theories, to provide a new perspective to further experimental research and clinical trials.

Objective: To explore the scope of antimicrobial stewardship activities based on the point prevalence study of antimicrobials among hospitalized patients in a tertiary-level care hospital in the UAE. Methods: A single-center cross-sectional prevalence study was conducted among inpatients admitted to a tertiary care hospital using the European Surveillance of Antimicrobial Consumption tool in February 2023. Antimicrobials used against bacteria only were surveyed. All patients admitted to the selected departments at 8 AM on the day of the survey were included. Data were described in numbers and percentages. Results: Among 136 patients admitted at the time of the study, 87 received antimicrobials, representing a prevalence of 64%. A total of 144 antimicrobial prescriptions were prescribed in 87 patients. The majority of the antimicrobials were administered parenterally (n=122, 84.7%), and over 60% (n=53) of the patients on antimicrobials received two antimicrobials. The majority of antimicrobials used for therapy were empiric in nature (n=68, 89.5%). Over half of the patients receiving antimicrobials for surgical prophylaxis were prescribed antimicrobials for two or more days. More than 60% of the antimicrobial orders were adherent to the hospital guidelines. Conclusion: The point prevalence of the use of antimicrobials is high, which highlights the need for more efficient and targeted stewardship efforts in improving adherence with the hospital guidelines. Wide usage of broadspectrum antimicrobials is observed.

Aims: This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation. Methods: This retrospective observational study enrolled a total of 234 lung transplant recipients. TAC trough levels (C0) were collected for 3 intervals: 0–3 months, 3–12 months, and 12–24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed. Patients were further divided into groups based on the C0 cut-off value of 8 ng/mL and IPV cut-off value of 30%. Cox proportional hazards regression models were used to explore the potential impact of C0 and IPV on outcomes of interests, including donor-specific antibodies (DSA), chronic lung allograft dysfunction (CLAD) and mortality. Results: The influence of CYP3A5*3 polymorphism was only significant for C0 and IPV during the first 3 months. Low C0 (< 8 ng/mL) at 3–12 months increased the risk of DSA (hazard ratio [HR] 2.820, 95% confidence interval [CI] 1.093–7.276) and mortality (HR 2.220, 95% CI 1.162–4.243), while High IPV (>=30%) during this period was associated with an increased risk of mortality (HR 2.100, 95% CI 1.120–3.937). Patients with Low C0/High IPV combination had significantly higher risks for DSA (HR 4.534, 95% CI 1.326–15.507) and survival (HR 4.205, 95% CI 1.739–10.168), surpassing the predictive power provided by C0 or IPV alone. Conclusion: A combination of Low C0/High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation.

Semaglutide is a Glucagon Like Peptide GLP agonist, Semaglutide has been shown to be effective in inducing weight loss in patients with obesity. Studies have shown that the infusion of GLP 1 results in reduced gastrointestinal emptying and an increased rate of fasting and postprandial gastric volumes, resulting in a decrease in hepatic glycemia. Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, Semaglutide affects the brain’s hunger control centers, causing a reduction in food intake and an increased feeling of fullness, that is helpful in people who are struggling to lose weight. Multiple trials have shown that introduction of Semaglutide in regime helps with weight loss in patients of PCOD and is also effective in management of insulin resistance and lowering high levels of VLDL, LDL and triglycerides. Possible introduction of Semaglutide in the treatment of PCOD and obesity should be considered.

Aim: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large inter-individual variability was found in its pharmacokinetics, and how to handle a delayed or missed dose of INH remains unclear. This study aimed to develop a population pharmacokinetics (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for non-adherent patients. Methods: A nonlinear mixed-effects modeling was used to analyze the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. A two-compartment model well described the PPK of INH. Results: N-acetyltransferase 2 (NAT2) genotype and body weight were identified as significant factors on INH PK. Monte Carlo simulations determined optimal dosage regimens for patients with different NAT2 genotype and body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. On delaying a INH dose exceed 12 h, only need to take the next single dose normally. Conclusion: PPK modeling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

Omeprazole is a proton pump inhibitor (PPI) that is indicated for gastroduodenal ulcer, gastroesophageal reflux and hypersecretory states. It has an excellent safety profile with a low incidence of adverse effects. We report an Omeprazole-induced urticaria in a patient and emphasize the role of allergological work-up to point out the culprit drug and in exploring cross-reactivity. A 56-year-old man with a history of Biermer anemia treated by vitamin B12. He has asthma and no other illnesses, allergic diseases or reactions, especially to drugs. He was treated with Omeprazole, for abdominal discomfort. Four hours after the first dose, the patient developed urticarial lesions with annular erythematous wheals localized on the trunk and upper limbs. There was neither angioedema nor respiratory and hemodynamic symptoms. An acute generalized urticaria to omeprazole was suspected. Four weeks later, Skin prick test than intradermal tests (IDT) to omeprazole were performed on the patient’s forearm. They revealed respectively a negative and a positive result. To assess cross-reactivity to other PPIs in our patient, we subsequently performed prick test to lansoprazole and IDT to esomeprazole, and pantoprazole that were negative at 20-min reading. Moreover, graded oral provocation test with these drugs were carried out with negative result. In conclusion we add to the medical literature a case report of omeprazole-induced urticaria without a cross reactivity and point out the usefulness and safety of skin and provocation testing in diagnosing this drug reaction and in the assessment of cross-reactivity between PPIs. KEYWORDS: omeprazole, urticaria, cross-reactivity, selective hypersensitivity

Aims: There is no specific guidance on optimal clozapine plasma concentrations in older people. This study aimed to test the hypothesis that therapeutic plasma clozapine concentrations would be lower in patients with an onset of psychosis after 60 years, compared to those with an earlier onset of schizophrenia (EOS) and to investigate the relationship between pharmacokinetic indices and side effects. Methods: Data were extracted from anonymised healthcare records for clozapine treated patients aged over 55 years. Median plasma clozapine and norclozapine concentrations (Cclozapine, Cnorclozapine) were compared across diagnostic groups. Mixed-effects models were used to investigate the relationship between pharmacokinetic biomarkers and side effects. Results: Of the 481 patients (4519 samples, median 6 per person), 430 (89.4%) were diagnosed with EOS. Cclozapine and Cnorclozapine in those with Parkinson’s disease psychosis (0.17mgL-1, 0.08mgL-1) were lower than those with EOS (0.41mgL-1, 0.19mgL-1), dementia-related psychosis (0.40mgL-1, 0.24mgL-1) and very late-onset schizophrenia-like psychosis (0.42mgL-1, 0.17mgL-1). Cclozapine was associated with higher corrected QT interval (QTc), whilst Cclozapine and Cnorclozapine were associated with higher neutrophil counts and body mass index, but not with clinical thresholds for neutropenia, obesity, QTc prolongation, or with sedation. Conclusions: Our findings suggest that, compared to EOS, therapeutic plasma clozapine concentrations are lower in Parkinson’s disease psychosis but not in other forms of later onset psychosis. Interpretation was limited by the relatively young age of the sample and the small number of samples associated with side effects. Prospective studies are needed to further explore optimal dosing specifically in older people.

Background: Nilotinib is a leukemia drug that can treat imatinib tolerance. During the drug trial, some adverse reactions of nilotinib have been proposed, and some articles have mentioned that nilotinib may have cardiovascular-related ADR signals. However, there is no systematic and comprehensive analysis of the potential ADR of nilotinib. AIM: The purpose of this study is to use the FDA adverse event reporting system (FAERS) database to detect the potential adverse event signals of nilotinib. Method: Data from the first quarter of 2015 to the fourth quarter of 2022 were selected for analysis from in the FAERS database. Use the preferred term in the Management activity Medical Dictionary (version 24.0) to extract cases of adverse events. The reported odds ratio (ROR) and information component (IC) methods based on statistical shrinkage transformation were used for disproportional analysis. Results: There were 24,451 adverse events associated with nilotinib in 11,190,626 records.A total of 529 positive signals of adverse reactions were found in taking nilotinib. Peripheral arterial occlusive disease (〖ROR〗_025=41.74 〖IC〗_025=5.36), Arteriosclerosis(〖ROR〗_025=33.49 〖IC〗_025=5.04), Intermittent claudication (〖ROR〗_025=32.12 〖IC〗_025=4.96), Splenitis (〖ROR〗_025=29.18 〖IC〗_025=4.79), Peripheral vascular disorder (〖ROR〗_025=27.00 〖IC〗_025=4.72), Peripheral artery stenosis (〖ROR〗_025=26.95 〖IC〗_025=4.96), Carotid artery stenosis (〖ROR〗_025=22.94 〖IC〗_025=4.48) had the strongest signal intensities. Conclusion: This study found that patients with leukemia taking nilotinib may have adverse reactions such as arteriovenous adverse reactions, myocardial infarction, splenitis, intermittent claudication and so on. KEYWORDS Disproportionate analysis, Nilotinib, FAERS database, pharmacovigilance study, CML

Objective: Based on the discovery and summary of adverse drug reactions of nucleotide analogues against herpes virus drugs, this study aims to analyze the situations of ADRs in the real world, put forward reasonable drug use recommendations, refine the rules of use, and formulate necessary alternative strategies to provide protection against herpes virus infection, and provide guidance and reference for the rational and individualized use of clinical drugs. Methods: All ADRs data of the drugs from the Q1 of 2004 to the Q4 of 2022 were obtained from the FDA Adverse Event Reporting System database. Duplicate reports, reports with uncertain information, and other reports containing abnormal information were excluded from the obtained data, and the data with more than 3 reports were selected. Apply the ROR, PRR and BCPNN in the disproportionality analysis for data mining . Results: All data from the Q1 of 2004 to the Q4 of 2022 were screened from the FAERS database. For ADEs with high frequency SOC level, we found that several important signals, including ADEs of ACV, GCV and VACV, simultaneously involved the following SOC systems: kidney and urinary system diseases, nervous system disease, skin and subcutaneous tissue diseases and mental diseases. Conclusion: Analysis of the FAERS database suggests that in addition to paying attention to efficacy, drug administration should be individualized according to the specific condition and potential risk of disease.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first appeared in Wuhan, China in 2019. Soon after, it was declared a pandemic by the World Health Organization (WHO). The health crisis imposed by a new virus and its rapid spread worldwide prompted the fast development of vaccines. For the first time in human history, two vaccines based on recombinant genetic material technology were approved for human use. These mRNA vaccines were applied in massive immunization programs around the world, followed by other vaccines based on more traditional approaches. Even though all vaccines were tested in clinical trials prior to their general administration, serious adverse events, usually of very low incidence, were mostly identified after application of millions of doses. Probing a direct correlation (the cause-effect paradigm) between vaccination and the appearance of adverse effects has proven challenging. This review focuses on anaphylaxis, myocarditis, vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome and transverse myelitis reported in the context of COVID-19 vaccination. We highlight their symptoms and laboratory tests required for an adequate diagnosis, and briefly outline the recommended treatments. The aim of the present work is to increase awareness among healthcare personal about these serious adverse events that may arise post-vaccination. Regardless of the ongoing discussion about the safety of COVID-19 vaccination, these adverse effects must be identified promptly and treated effectively to reduce the risk of complications.

Aim: This retrospective study aimed to determine whether different renal function estimation formulas affect the incidence of venous thromboembolism (VTE) and bleeding when anticoagulant dosages are determined. Methods: The study included patients who underwent lower-limb orthopedic surgery and were treated with anticoagulants between January 2017 and March 2020 at Yaizu City Hospital. The appropriateness of anticoagulant dosing was assessed using creatinine clearance (CCr), estimated glomerular filtration rate (eGFR), and de-indexed eGFR without correction for body surface area, and the incidence of VTE and bleeding was compared among the different renal function estimation formulas. Results: The median values for body surface area, CCr, eGFR, and de-indexed eGFR were 1.40m2, 56.0mL/min, 73.0mL/min/1.73m2, and 60.9mL/min, respectively. There was no significant difference in the incidence of VTE among the different renal function estimation formulas. However, when the threshold for dose reduction or contraindication was determined by eGFR rather than CCr, the incidence of bleeding was significantly higher in the group that was overdosed in CCr (6.0% vs 25.7% p<0.05). Similarly, when the threshold for dose reduction or contraindication was determined by de-indexed eGFR rather than CCr, the incidence of bleeding was significantly higher in the group that was overdosed in CCr (7.5% vs 28.6% p<0.05). Conclusion: It is necessary to set the dosage of anticoagulants based on CCr for patients with a small body surface area in the field of orthopedics to avoid the risk of bleeding.

Background: The purpose of pharmacovigilance is the timely detection and identification of harmful drug-related reactions in the clinical application of drugs to reduce the risk of their clinical use. Macitentan has been on the market for close to 10 years, during which time several clinical studies have reported adverse events associated with macitentan outside of the drug description and uploaded them into the U.S. Food and Drug Administration’s (FDA) Adverse Event Reporting System.Aim: This study aimed to promote the safe use of macitentan by mining and analyzing the adverse event signals of macitentan in the FAERS database.Method： The proportionate disequilibrium method was used to mine and analyze the FAERS database for macitentan-related adverse events. Preferred Terms of ADR reports were categorized by System Organ Class (SOC) based on the Medical Dictionary for Regulatory Activities. Results： A total of 32,607 macitentan adverse events were retrieved, and after exclusion by the methodology developed in this study, a total of 253 positive signals for AEs were obtained, and it was found that macitentan may have potential new adverse reactions such as blood potassium decreased(ROR [95% CI]= 3.51[3.10-3.98]), respiratory failure(ROR [95% CI]=4.06[3.77-4.39]), epistaxis(ROR [95% CI]=2.50[2.29-2.73]), and other potential adverse reactions in addition to the adverse reactions that have already been reported in the specification.Conclusion: Clinical attention is recommended for the new adverse drug reactions to macitentan detected in this study.

Advanced therapy medicinal products (ATMPs) are becoming the new kid on the block for the treatment of a variety of indications with promising results. Academic centres have often been at the forefront of basic research, preclinical phases, and translational studies for the clinical development of ATMPs for several approved drugs. Despite the academic contribution to the basic and clinical research of ATMPs, undertaking a full product development process is extraordinarily challenging and demanding for academic institutions. Meeting regulatory requirements is probably the most challenging aspect for academic development, considering the limited experience and resources compared with pharmaceutical companies. The aim of this review is to present and discuss the key aspects to be considered when developing novel ATMPs from an academic perspective, based on our own experience. Emphasis is placed on understanding the regulatory requirements during the early phases of the drug development process, particularly for the preparation of a Clinical Trial Application. In general, academic centres do not possess experience in product-related documentation (such as the Investigational Medicinal Product Dossier), and therefore, early interaction with regulators is crucial to understand their requirements and receive guidance to comply with them. Tips are provided on how to manage quality, non-clinical, clinical, and risk and benefit documentation, based on our own experience and challenges. We believe this review will contribute to providing key regulatory knowledge to academic and clinical environments with the purpose of smoothing the regulatory path of ATMPs.

Amphotericin B is a broad-spectrum antifungal agent that is used in the treatment of systemic fungal infections. We describe the case of a 62-year-old female patient with recent aneurysmal subarachnoid hemorrhage who was treated for suspected ventriculitis and a fungal coinfection. Instead of liposomal amphotericin B (L-AmB), 465 mg (5 mg/kg) amphotericin B deoxycholate (DOC) was inadvertently administered, leading to refractory shock with multiple organ failure and requiring mechanical ventilation. Since an overdose of amphotericin B can lead to fatal consequences and has a half-life of 15 days, plasmapheresis was started. The serum concentration decreased from 1.32 µg/mL to 0.62 µg/mL before plasmapheresis, demonstrating a mean half-life of 49 hours. After two plasmapheresis sessions, the serum concentration further dropped to 0.26 µg/mL, demonstrating a mean half-life of 17 hours. In contrast, the third plasmapheresis session had no effect on serum concentration. The patient made a full recovery, potentially facilitated by enhanced amphotericin B elimination through plasmapheresis. Positive outcomes were previously reported in two adult patients treated with plasmapheresis. However, other reports without plasmapheresis described fatal outcomes in adult patients, albeit with a twofold overdose compared to the two patients successfully treated with plasmapheresis. Moreover, plasmapheresis itself carries risks such as hypocalcemia, metabolic alkalosis, and coagulation deficits. Consequently, the role of plasmapheresis in amphotericin B overdose is still debated.

Aims: To compare the outcomes of real-world Japanese patients with nonvalvular atrial fibrillation who are ineligible for phase III trials of direct oral anticoagulants with those of eligible patients. Methods: In retrospective cohort design, consecutively registered patients with nonvalvular atrial fibrillation who had taken warfarin were followed up and assessed eligibility of patients for phase III trials of direct oral anticoagulants. The effects of the ineligibility of patients on outcomes were estimated using Cox proportional hazards models to calculate the hazard ratio (HR) and 95% confidence interval. Results: We registered 7826 Japanese patients with nonvalvular atrial fibrillation from 71 hospitals. Nearly half (48.2%, n=3772) of these patients were ineligible for phase III trials of direct oral anticoagulants, mainly because of low CHADS2 scores (26.4%), renal dysfunction (9.5%), anemia (6.4%), and chronic treatment with nonsteroidal anti-inflammatories (4.0%). After excluding patients with a CHADS2 score <2 (n=2064, 26.4%) from total ineligible patients, the remaining ineligible patients (n=1708) exhibited significantly greater risks of major bleeding (unadjusted hazard ratio 2.00, 95% confidence interval 1.63–2.44, p<0.0001), stroke/systemic embolism (unadjusted hazard ratio 1.53, 95% confidence interval 1.17–1.98, p=0.0016), and all-cause mortality (unadjusted hazard ratio 2.84, 95% confidence interval 2.36–3.43, p<0.0001) compared to the eligible patients. Conclusions: The benefits and risks of direct oral anticoagulants suggested by phase III trials may not necessarily apply to patients ineligible for Phase III trials. This gap between evidence and practice is an issue in the real-world safety and efficacy of anticoagulants.

Aim: Multi-compartment medication compliance aids (MCAs) aim to support medication adherence and administration. Many older people have their medications supplied in a pharmacy-filled MCA (pMCA), despite growing evidence of increased risks of medication-related harm and inappropriate prescribing practices. Little is known about patients’ perspectives on the various MCAs and their impact. The aim was to determine patient views on pMCAs. Methods: A questionnaire-survey of adults over 65 years old, who use, have declined or discontinued a pMCA. Participants were recruited from inpatient, outpatient and community settings in central London. 88 participants were recruited. Responses were analysed using thematic analysis. Results: 61 participants used, 5 had discontinued and 22 had declined a pMCA. Those not using a pMCA often self-filled an MCA of their choice. Participants’ views on pMCAs fell into three themes: Polypharmacy and medication supply systems; Autonomy and independence; and Design of products. The majority of those using pMCAs would not revert to original medication packaging. For some, the convenience of the aid in managing polypharmacy overrode the loss of autonomy. Those who had stopped or declined pMCAs highlighted the importance of control and knowledge of their medications. The environmental impact of the devices caused concern across all groups. Conclusion: Whether self-filled or pharmacy-filled, MCAs were deemed useful in supporting adherence. An individualised approach to medication rationalisation would reduce the burden of polypharmacy and potentially the need for any form of MCA. Redesign of pMCAs and systems surrounding their use would be beneficial at an individual and global level.

Cyclophosphamide (Cy) is a prodrug that is mainly bioactivated by the cytochrome enzyme CYP2B6. Several other enzymes are also involved in its bioactivation and affect its kinetics. Previous studies have shown the effect of the enzymes’ genetic polymorphisms on Cy kinetics and its clinical outcome. These results were controversial primarily because of the involvement of several interacting enzymes in the Cy metabolic pathway, which can be also affected by several clinical factors as well as other drugs interactions. In this article, we present the effect of CYP2B6 polymorphisms on Cy kinetics since it is the main bioactivating enzyme, as well as discussing all previously reported enzymes and clinical factors that can alter Cy efficacy. Additionally, we present explanations for key Cy side effects due to its extrahepatic bioactivation. Finally, we discuss the role of busulphan in conditioning regimens in the Cy metabolic pathway as a clinical example of drug-drug interactions involving several enzymes. By the end of this article, our aim is to have provided a conclusive summary of Cy pharmacogenomics and the effect of its kinetics. The use of these findings in new strategies for Cy personalized patient dose adjustment will certainly help in optimizing the Cy dose and in improving the clinical outcome.

Aim. To estimate the effect of the reduced-function polymorphism SLCO1B1 c.521T>C on the renal graft function (estimated glomerular filtration rate, eGFR) over 12 months in patients treated with mycophenolic acid (MPA). Methods. Consecutive eligible adults (≥16 years of age) engrafted over a 6-year period who received MPA as a part of maintenance immunosuppression were assessed for eGFR on 9 occasions over 12 post-transplant months. The SLCO1B1 c.521C>T variant allele carriers (treated) and wild-type subjects (controls) were balanced on a range of demographic, medical, and genetic variables at baseline, and the development of eGFR (slope) was estimated with further adjustment for time-varying covariates. A subset of patients were assessed for exposure to MPA 5-7 days after the transplantation. Results. The adjusted eGFR slopes from day 1 to day 28 (peak), and from day 28 to day 365 were practically identical in treated (n=86) and control (n=168) patients (GMR=0.99, 95%CI 0.92-1.06, and GMR=0.98, 0.94-1.01, respectively). The rates of adverse renal outcomes and possible MPA-related adverse effects were low, and similar in treated and controls (adjusted RR=0.94, 0.49-1.84 and RR=1.08, 0.74-1.58, respectively). The pharmacokinetic substudy did not signal that treated and control patients differed with respect to MPA clearance, peak, trough or total exposure, overall (treated n=23, control n=45), if cotreated with cyclosporine (n=17 vs. n=26) or with tacrolimus (n=8 vs. n=17). Discussion. In patients treated with MPA, variant allele SLCO1B1 c.521T>C has no effect on the 12-month renal graft function. It does not seem to affect exposure to- and safety of MPA.

Aim: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have been reported to manifest controversial relationships with cancer, and recent focus concerning the tumorigenic effect of ACEIs mainly falls on lung cancer. We compared ACEIs with ARBs for their impact on the risk and prognosis of lung cancer and non-lung cancers, respectively. Methods: A meta-analysis was performed to explore the impact of ACEIs on the risk of lung cancer and non-lung cancers, while a systematic review was performed to further analyze ACEIs’ influence on the prognosis of lung cancer. Terms concerning ACEIs and cancer were searched, and 10 cohort studies were included for risk analysis, while 5 cohort studies were included for analyzing the prognosis of lung cancer. Results: Initial pooled result revealed that ACEIs prescription is associated with an observed increase on the risk of lung cancer (RR 1.28, 95% CI 1.02-1.61), colorectal cancer (RR 1.46, 95% CI 1.13-1.87) and hepatic cancer (RR 2.00, 95% CI 1.01-3.94) when compared with ARBs, but further sensitivity analyses suggested the results unsolid, thus neither the development of lung cancer nor non-lung cancers could be proved associated with ACEIs prescription. However, systematic review suggested that ACEIs prescription is associated with an improved lung cancer prognosis. Conclusion: There has been no adequate evidence to demonstrate that ACEIs are associated with a higher incidence of lung cancer or non-lung cancers, but an improved prognosis of lung cancer was observed in patients taking ACEIs. Large-scale RCTs are needed and underlying mechanisms need further exploration.

Abstract: Purpose: Fundus fluorescein angiography (FFA) is usually done when the patient is on an empty stomach. In case, if the patient is not, their FFA is rescheduled for the next day to avoid the risk of complications. The purpose of this study was to compare the complications in patients who had undergone an FFA procedure on an empty stomach to those who had breakfast immediately before the procedure. Methods: In this study, 210 participants underwent FFA, of which 104 were fasting, and 106 had breakfast just before their procedure. In these two populations, we compare the immediate and post-procedure complications. Result: Patients who had FFA on an empty stomach were more likely to experience nausea and vomiting (11.32% vs 7.69%), skin allergies (1.89% vs 1.92%), and unconsciousness (0.94% vs 2.88%). In either the fasting or control groups, no complications were statistically significant (P>0.05). Conclusion: FFA is generally a safe procedure, however, previous studies have observed increased adverse events with people on empty stomachs. In individuals with various systemic disorders and diets, our study found no increase in adverse effects. Consequently, FFA shouldn’t be postponed in these individuals who are not on a diet or who have systemic co-morbidities.

There may be significant histopathological overlap between Epstein–Barr virus (EBV) -positive diffuse large B cell lymphoma (DLBCL) and other diagnoses, including angioimmunoblastic T-cell lymphoma (AITL). Herein, we report a rare case of EBV-positive AITL developing two years after the initial diagnosis of EBV-positive DLBCL. Histone deacetylase (HDAC) inhibitor, chidamide, in combination with COEP (cyclophosphamide, vindesine, etoposide, prednisone) were administrated to treat AITL, which appeared to prolong the survival of patient. Next-generation sequencing (NGS) was used to study the possible mechanisms by which this patient developed AITL after DLBCL. NGS revealed that TET2 mutated in both DLBCL and AITL. When EBV-positive DLBCL patients with the TET2 mutation, it is necessary to beware of lymphoma recurrence and note that it may be completely different from the previous type. Our case suggests that chidamide plus COEP may be a treatment option for AITL after DLBCL and may prolong patient survival, but this requires a larger sample size to confirm.

Aim: As the non-vitamin K antagonist oral anticoagulant (NOAC) most recently approved in China, data pertaining to clinical edoxaban use are still scarce. This study investigated the prevalence of and contemporary trends in edoxaban prescription among Chinese patients as well as factors associated with its inappropriate use in a multi-center registry of patients treated in real-world clinical practice. Methods: This real-world, prospective, multicenter, and non-interventional study included 1005 inpatients treated with edoxaban. According to National Medical Products Administration and European Heart Rhythm Association guidelines, edoxaban therapy was determined to be appropriate or inappropriate in each case. Results: The median patient age was 70.0 years (interquartile range, 61.0–78.0 years), and 46.3% were women. Overall, 456 (45.4%) patients received inappropriate edoxaban therapy, and common issues included an inappropriately low (183, 18.2%) or high (73, 7.3%) dosage, wrong drug selection (109, 10.8%), unreasonable off-label use (49, 4.9%), incorrect administration timing (16, 1.6%), and contraindication due to other medications (27, 2.7%). Several factors (e.g., age, weight, kidney function, anemia, and bleeding history) were associated with an increased risk of inappropriate edoxaban therapy, whereas factors associated with cardiovascular specialties (e.g., hospitalized in cardiovascular department and dronedarone or amiodarone use) decreased this risk. Conclusion: In this real-world study, 45.4% of patients received an inappropriate treatment with edoxaban. Multiple clinical characteristics can help identify patients who should receive edoxaban. Further development and implantation of educational activities and management strategies are needed to ensure the correct use of edoxaban.

Artificial intelligence (AI) will impact many aspects of clinical pharmacology including drug discovery and development, clinical trials, personalised medicine, pharmacogenomics, pharmacovigilance and clinical toxicology. The rapid progress of AI in healthcare means clinical pharmacologists should have an understanding of AI and its implementation into clinical practice. As with any new therapy or health technology, it is imperative that AI tools are subject to robust and stringent evaluation to ensure that they enhance clinical practice in a safe and equitable manner. This review serves as an introduction to AI for the clinical pharmacologist, highlighting current applications, aspects of model development and issues surrounding evaluation and deployment. The aim of this article is to empower clinical pharmacologists to embrace and lead on the safe and effective use of AI within healthcare.