Differences in Adverse Drug Events Among Pediatric Patients With and Without Cancer: Sub-Analysis of a Retrospective Cohort Study

Objectives: This study investigated the differences in the incidence and severity of adverse drug events (ADEs) in pediatric patients with and without cancer. Methods: We used data from the Japan Adverse Drug Events Study for pediatrics, a cohort study enrolling pediatric inpatients at two tertiary care teaching hospitals in Japan. ADEs were identified by on-site review of all medical charts, incident reports, and prescription queries by pharmacists. Two independent physicians reviewed all potential ADEs and classified ADEs in terms of severity and class of causative medication. We compared the incidence and characteristics of ADEs between pediatric cancer patients and non-cancer patients. Results: We enrolled 1189 patients during the study period, 27 with cancer and 1162 without cancer. We identified 480 ADEs in 234 patients (20%): 191 ADEs among 21 cancer patients and 289 ADEs among 213 non-cancer patients (7.1 per patient vs. 0.25 per patient, respectively; p < 0.0001). The most common medications associated with ADEs in cancer patients were antitumor agents; in contrast, medications associated with fatal or life-threatening ADEs in cancer patients were most often sedatives (25%) and blood products (25%). Medications associated with fatal or life-threatening ADEs among non-cancer patients were most often sedatives (15%). The percentages of fatal or life-threatening ADEs in cancer patients and non-cancer patients were 2.1 and 4.5%, respectively. Conclusions: Pediatric patients with cancer have a higher risk for ADEs. Although the overall severity was similar between patients with and without cancer, the most common classes of causative medication and medications associated with a higher rate of severe ADEs differed. Application of this information may help minimize the impact of ADEs in pediatric patients

JunB regulates homeostasis and suppressive functions of effector regulatory T cells

Foxp3-expressing CD4(+) regulatory T (Treg) cells need to differentiate into effector Treg (eTreg) cells to maintain immune homeostasis. T-cell receptor (TCR)-dependent induction of the transcription factor IRF4 is essential for eTreg differentiation, but how IRF4 activity is regulated in Treg cells is still unclear. Here we show that the AP-1 transcription factor, JunB, is expressed in eTreg cells and promotes an IRF4-dependent transcription program. Mice lacking JunB in Treg cells develop multi-organ autoimmunity, concomitant with aberrant activation of T helper cells. JunB promotes expression of Treg effector molecules, such as ICOS and CTLA4, in BATF-dependent and BATF-independent manners, and is also required for homeostasis and suppressive functions of eTreg. Mechanistically, JunB facilitates the accumulation of IRF4 at a subset of IRF4 target sites, including those located near Icos and Ctla4. Thus, JunB is a critical regulator of IRF4-dependent Treg effector programs, highlighting important functions for AP-1 in Treg-mediated immune homeostasis

Results of All ITER TF Full-Size Joint Sample Tests in Japan

Nine toroidal field (TF) coils have been developed in Japan for the international thermonuclear experimental reactor (ITER). The joint resistance of TF coil should satisfy the requirement of smaller than 3 nano-ohm at 2 T of external magnetic field and 68 kA of transport current. Full-size joint sample (FSJS) tests were performed for joint development and for TF coil manufacture, as part of the process control. 11 FSJS tests are conducted in total. FSJS tests were conducted with assistance from a test faculty in the National Institute for Fusion Science as reported in a previous paper. All FSJS tests successfully satisfied the requirement of resistance less than 3 nΩ at 2 T. Additionally, the TF coil joints are subjected to cyclic electromagnetic force and warm-up/cool-down during the ITER operation. The authors investigated the joint performance for the abovementioned influence. The results showed no degradation in the joint resistance. Thus, the TF joint developed in Japan was qualified successfully

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

The result of ITER TF coil double-pancake heat treatment in Japan

ITER TFコイル製作におけるDP熱処理成果及び超伝導線サンプルの臨界電流測定結果について報告する。27th International Conference on Magnet Technology (MT27

Completion of the First ITER Toroidal Field Coil in Japan

ITER TFコイルは18機1セットが真空容器周りに配置されることで均一な磁場を発生させて、真空容器内にプラズマを閉じ込める役割を果たす。それぞれのTFコイルの磁場特性はコイル内部の導体中心位置(CCL)に対し、公差を設けることで担保されており、そのTFコイルを精度よく18機配置することでTFコイルシステム全体の磁場要求を担保している。これらの要求を達成するには、一体化作業中の巻線部の位置調整および管理、また、コイル容器の溶接変形の制御などの課題があった。著者らは、試作試験や構造解析を通してこれらの課題を解決し、製作手法を確立した。その結果、世界初のITER TFコイルは要求を達成したうえで完成した。本講演では確立された一体化製作技術の内容と共にその技術を適用したITER TFコイル初号機の完成について報告する。28th IAEA Fusion Energy Conference (FEC-2020