Application of model-informed drug development (MIDD) for dose selection in regulatory submissions for drug approval in Japan.

Model-informed drug development (MIDD) is an approach to improve the efficiency of drug development. To promote awareness and application of MIDD in Japan, the Data Science Expert Committee of the Drug Evaluation Committee in the Japan Pharmaceutical Manufacturers Association established a task force, which surveyed MIDD applications for approved products in Japan. This study aimed to reveal the trends and challenges in the use of MIDD by analyzing the survey results.

Pharmacokinetics, Safety and Tolerability of Single-dose or Multiple-dose Cefiderocol in Hospitalized Pediatric Patients Three Months to Less Than Eighteen Years Old With Infections Treated With Standard-of-care Antibiotics in the PEDI-CEFI Phase 2 Study.

Background: Multidrug-resistant Gram-negative bacterial infections are increasing globally in neonates, infants and children; antibiotic options are limited.

Methods: This international, multicenter, open-label phase 2 study, investigated the pharmacokinetics, safety and tolerability of single-dose and multiple-dose cefiderocol [as a 3-hour infusion (every 8 hours) dosed at 2000 mg for body weight ≥34 kg and at 60 mg/kg for body weight <34 kg], over a range of renal function, in hospitalized pediatric patients with aerobic Gram-negative bacterial infection; multiple-dose patients required standard-of-care systemic antibiotics for 5-14 days. Four cohorts of pediatric patients were enrolled (cohort 1: 12 to <18 years, cohort 2: 6 to <12 years, cohort 3: 2 to <6 years and cohort 4: 3 months to <2 years).

Evaluation and optimization of sample size of neonates and infants for pediatric clinical studies on cefiderocol using a model-based approach.

When planning pediatric clinical trials, optimizing the sample size of neonates/infants is essential because it is difficult to enroll these subjects. In this simulation study, we evaluated the sample size of neonates/infants using a model-based optimal approach for identifying their pharmacokinetics for cefiderocol. We assessed the usefulness of data for estimation performance (accuracy and variance of parameter estimation) from adults and the impact of data from very young subjects, including preterm neonates.

Lipomatous pseudohypertrophy of the pancreas mimicking liposarcoma: A case report.

Lipomatous pseudohypertrophy of the pancreas (LPH) is a rare disease in which the pancreatic parenchyma is replaced with mature adipose tissue. It is an idiopathic condition whose diagnosis is made based on histopathological analyses. Herein, we report the case of a 50-year-old male patient with a lipomatous mass in the head of the pancreas on computed tomography for close examination of a renal tumor.

The usefulness of super-selective arterial spin labeling for postoperative evaluation of pediatric moyamoya disease: technical note.

Moyamoya disease is characterized by progressive internal carotid artery (ICA) occlusion. Extracranial-intracranial bypass surgery is effective, particularly in pediatric patients; imaging plays a crucial role in evaluating intracranial perfusion pre- and post-surgery. Arterial spin labeling (ASL) is a magnetic resonance technique employed for noninvasive, whole-brain perfusion assessment by magnetically labeling inflowing blood.

Effect of Renal Impairment on Pharmacokinetics and Safety of Ensitrelvir, a SARS-CoV-2 3CL Protease Inhibitor.

Introduction: Ensitrelvir, a novel oral inhibitor of 3C-like protease of SARS-CoV-2, shows efficacy and safety in participants with mild to moderate COVID-19. Since urinary recovery of ensitrelvir ranged from 12.9% to 21.

Carrier systems of radiopharmaceuticals and the application in cancer therapy.

Radiopharmaceuticals play a vital role in cancer therapy. The carrier of radiopharmaceuticals can precisely locate and guide radionuclides to the target, where radionuclides kill surrounding tumor cells. Effective application of radiopharmaceuticals depends on the selection of an appropriate carrier.

Shared Reading as a Community of Practice for Overcoming the Generation Gap and Improving Psychological Safety in Rural Family Medicine Education: A Grounded-Theory Approach.

Background A community of practice (CoP) is essential for continuous professional development in family medicine. A CoP in medical education comprises a group of individuals who share common interests and learn and share knowledge, skills, and attitudes. The generation gap between teachers and learners can influence their effective collaboration in family medicine education.

Importance of Inclusive Education in General Medicine Through the Perception of Medical Trainees: A Thematic Analysis.

Background General medical education plays a pivotal role in ensuring holistic care in the context of rapidly aging populations. Japan's demographic trends underscore the significance of general medicine in elevating community care standards. Understanding and catering to the aspirations, perceptions, and ideals of medical students and residents can significantly augment the effectiveness of general medicine education.

Psychological safety and self-regulated learning through near-peer learning for the sustainability of rural community-based medical education: grounded theory approach.

Introduction: Difficulties in improving psychological safety in medical education can be attributed to the hierarchy among medical professionals. Near-peer learning (NPL) can increase learning between students and residents, and improve psychological safety. Rural community-based medical education (CBME) can use an NPL framework to improve psychological safety and compensate for the lack of resources, leading to sustainability.

Predictive Postoperative Inflammatory Response Indicators of Infectious Complications Following Gastrectomy for Gastric Cancer.

Background: Perioperative factors are useful for predicting postoperative infectious complications (PIC) in gastric cancer. Specifically, postoperative inflammatory response indicators (PIRI), [C-reactive protein (CRP) level, body temperature (BT), and white blood cell (WBC) count], are widely used in clinical practice. We investigated predictive factors for PIC, including PIRI, to establish a simple and practical indicator of postoperative complications after gastrectomy.

[Effect of Landiolol for Atrial Fibrillation after Open Heart Surgery].

Purpose: Postoperative atrial fibrillation (POAF) after open heart surgery is common complication. POAF is reported to prolong hospital stay and increase long-term mortality, therefore prevention of POAF is important. It is widely known that beta blocker decrease POAF, and we had used oral beta blocker after open heart surgery.

Radiological Features of T1a Renal Cell Carcinoma on Axial Unenhanced Computed Tomography.

CT has become a commonly used diagnostic procedure in clinical practice, particularly in emergency healthcare delivery. Accordingly, the increase in CT usage has increased the likelihood of incidental detections (ID) of renal cell carcinomas (RCCs). This article discusses key points and limitations associated with the diagnosis and characterization of T1a RCC (≤4 cm in diameter) and shows how to improvise on the differentiation of T1a RCC with unenhanced CT (UE-CT).

Challenges in Help-Seeking Behaviors among Rural Older People Mitigated through Family Physician-Driven Outreach: A Systematic Review.

Help-seeking behaviors (HSBs) refer to approaches taken by individuals towards their health and symptoms, and they are supported by healthcare professionals. Outreach interventions aimed at older people in rural communities can mitigate difficulties in implementing HSBs and help them remain healthy. This systematic review investigated evidence regarding family medicine-involved outreach aimed at HSBs among older individuals in rural areas.

Preoperative Subcutaneous Fat is an Useful Indicator for Learning Totally Extraperitoneal Repair.

Background: Totally extraperitoneal (TEP) repair is a recommended procedure for inguinal hernia repair in European hernia guidelines. However, technical challenges have limited its uptake in Japan, where transabdominal preperitoneal (TAPP) repair is more common. We evaluated the association of preoperative subcutaneous fat area (preSFA) with surgical outcomes and identified factors associated with the difficulty of TEP repair.

Fluorescence in situ hybridization analysis of chromosomal aberrations in mouse splenocytes at one- and two-months after total body exposure to iron-56 (Fe) ion particles or X-rays.

High atomic number and energy (HZE) particles such as iron-56 (Fe) ions are a major contributor to health risks in long-term manned space exploration. The aim of this study is to understand radiation-induced differential genotoxic effects between HZE particles and low linear energy transfer (LET) photons. C57BL/6J Jms female mice of 8 weeks old were exposed to total body irradiation of accelerated Fe-particles with a dose ranging from 0.

Pharmacokinetic Assessment and Treatment Effect of Lusutrombopag in Child-Pugh Class C Patients: Review of Patient Data from Two Clinical Studies and Post-Marketing Surveillance.

Introduction: Patients with thrombocytopenia and chronic liver disease are at increased risk of bleeding during invasive procedures due to low platelet counts. Lusutrombopag, an orally active thrombopoietin receptor agonist, increases platelet count and reduces the need for platelet transfusion in chronic liver disease patients with thrombocytopenia undergoing a planned invasive procedure. The safety of lusutrombopag in patients with Child-Pugh class C chronic liver disease is not known.

Enhanced Effects of Chronic Restraint-Induced Psychological Stress on Total Body Fe-Irradiation-Induced Hematopoietic Toxicity in -Heterozygous Mice.

Humans are exposed to both psychological stress (PS) and radiation in some scenarios such as manned deep-space missions. It is of great concern to verify possible enhanced deleterious effects from such concurrent exposure. Pioneer studies showed that chronic restraint-induced PS (CRIPS) could attenuate functions and increase gamma-ray-induced carcinogenesis in -heterozygous mice while CRIPS did not significantly modify the effects on X-ray-induced hematopoietic toxicity in wild-type mice.

T2 hypointense signal discovered incidentally at the posterior edge of the adenohypophysis on MRI: its prevalence and morphology and their relationship to age.

Purpose: T2 hypointense signal at the posterior edge of the adenohypophysis (T2HSPA) on magnetic resonance imaging (MRI) is incidentally encountered. We aimed to investigate the prevalence and morphology of T2HSPA and their relationship to age.

Methods: A total of 212 cases between 3 and 88 years old were examined.

ARCH Project and the Global Initiatives of Disaster Health Management.

Objective: The prime aim of Project for Strengthening the ASEAN Regional Capacity on Disaster Health Management (ARCH Project) is to strengthen the disaster health management (DHM) capacity in the context of personal level, Emergency Medical Team (EMT), and the regional collaboration. The ARCH Project was implemented with reference to international trends of DHM and seeks to contribute to the development of global standards.

Methods: The project established the Project Working Groups that consisted of representatives of ASEAN Member States (AMS) to develop standard operating procedures (SOP) for international EMT (I-EMT) coordination.