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Abstract Background Gabapentinoids (GBP) and benzodiazepines (BZ) are commonly prescribed in older adults and their package inserts list edema and vertigo as adverse drug reactions. These adverse drug reactions may be treated with symptomatic drug therapies without discontinuing the culprit drugs or decreasing their dose, thereby initiating a prescribing cascade and often resulting in polypharmacy. Whether prescribing cascades occur in the treatment of edema and dizziness among Japanese patients treated with GBP and BZ has not been investigated, including treatment with mirogabalin, a class drug of GBP marketed in Japan. Objective We aimed to investigate prescribing cascades with GBP-induced and BZ-induced edema and dizziness treated with loop diuretics (LD) and anti-vertigo drugs (AVD), respectively, among older adults. Methods A prescription sequence symmetry analysis design was used to detect signals of prescribing cascades associated with edema and dizziness induced by GBP and BZ (exposure drugs). Loop diuretics and AVD were the outcome drugs used to identify prescribing cascades following the initiation of exposure drugs. The study population consisted of enrollees of a large-scale health claims database provided by DeSC Healthcare, Inc., between April 2014 and March 2021. Subjects eligible for a prescription sequence symmetry analysis were patients aged ≥ 65 years prescribed an outcome drug within 90 days before and after exposure drug initiation. A signal of a prescribing cascade was detected if secular trend-adjusted sequence ratios were statistically significant on comparison of the frequencies of outcome drug initiation before and after exposure drug initiation. Results We identified 2671 patients with prescriptions of a GBP-LD combination, 4009 with a GBP-AVD combination, 8675 with a BZ-LD combination, and 9462 with a BZ-AVD combination. The adjusted sequence ratios for GBP-LD and BZ-LD cascades were significantly larger than one (adjusted sequence ratio [95% confidence interval], 1.69 [1.56–1.83]; 1.35 [1.29–1.41], respectively), indicating positive signals of prescribing cascades. No signal was detected for the GBP-AVD or BZ-AVD cascade (0.89 [0.83–0.94]; 0.90 [0.87–0.94], respectively). The adjusted sequence ratio for the mirogabalin cascade was higher than that for pregabalin (2.23 [1.84–2.71] vs 1.59 [1.46–1.73]). Conclusions Our study provides good evidence that LD-prescribing cascades associated with edema would be a class effect of GBP and BZ. Edema emerging around 1 month after GBP initiation should be carefully differentiated from pathological edema, and undue LD prescription as a prescribing cascade should be avoided.

Electrodeposition-based metal coating techniques are used to manufacture various industrial products and rely on the quantitative control of the physical properties of the coating layers, such as electrical conductivity, surface roughness, and hardness. To clarify the experimental conditions required to realize the desired physical properties of metal coating layers and shed light on the complex mechanism of the involved reactions, we prepared a custom-built experimental dataset (60 conditions) on the surface roughness of electrodeposited thin copper films and submitted it to an open-access data repository. Data-driven analysis revealed that surface roughness is strongly affected by the deposition temperature, current, and interelectrode distance.

Background The current study tested the hypothesis that urinary angiotensinogen (UAGT) and urinary monocyte chemoattractant protein-1 (UMCP-1) levels provide a specific index of intrarenal renin-angiotensin system (RAS) status and the degree of infiltration of macrophages associated with RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis. Methods We measured baseline UAGT and UMCP-1 levels to examine the correlation between glomerular injury in 48 pediatric chronic glomerulonephritis patients before treatment. Furthermore, we performed immunohistochemical analysis of angiotensinogen (AGT) and CD68 in 27 pediatric chronic glomerulonephritis patients treated with RAS blockades and immunosuppressants for 2 years. Finally, we examined the effects of angiotensin II (Ang II) on monocyte chemoattractant protein-1 (MCP-1) expression in cultured human mesangial cells (MCs). Results Baseline UAGT and UMCP-1 levels positively correlated with urinary protein levels, scores for mesangial hypercellularity, rate of crescentic formation, and expression levels of AGT and CD68 in renal tissues (p < 0.05). UAGT and UMCP-1 levels were significantly decreased after RAS blockade and immunosuppressant treatment (p < 0.01), which was accompanied by AGT and CD68 (p < 0.01), as well as the magnitude of glomerular injury. Cultured human MCs showed increased MCP-1 messenger ribonucleic acid and protein levels after Ang II treatment (p < 0.01). Conclusions The data indicates that UAGT and UMCP-1 are useful biomarkers of the degree of glomerular injury during RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis., Author(s): Tomoki Hattori [sup.1] [sup.2] , Keisuke Fujioka [sup.1] , Takashi Nagai [sup.1] , Shuji Kondo [sup.1] , Shoji Kagami [sup.1] , Masahiro Hirayama [sup.2] , Maki Urushihara [sup.1] Author [...]

BackgroundThis study aimed to determine the actual working conditions, including working hours and desired future working styles of hospital pediatricians and obstetricians/gynecologists (OB/GYNs) in Tokushima Prefecture.MethodThis cross-sectional study used a self-administered questionnaire. Pediatricians and OB/GYNs (n = 96) working at 14 hospitals in Tokushima Prefecture were surveyed. The questionnaire included items related to working hours, working status, number of medical institutions, task-shifting/task-sharing status, and preferred work style. Factors associated with work hours were analyzed.ResultsApproximately 40% and 10% of pediatricians and OB/GYNs worked ≥60 h/week and ≥80 h/week, respectively. Their weekly working hours were significantly positively associated with the number of nights and holidays worked and concurrent medical facilities they worked at. Multiple regression models showed that weekly working hours were significantly associated with working at night and day-off duties and the number of working medical institutions being worked at concurrently. Pediatricians and OB/GYNs who worked ≥60 h/week were not implementing a "multiple attending physician system" or "on-call system," and task-shifting/task-sharing was inadequate. A significantly higher proportion of physicians who worked long hours (≥60 h/week or ≥80 h/week) wanted to reduce the number of night and day-off duties and work hours compared with those who did not.ConclusionsThe results of this study suggest that many pediatricians and OB/GYNs work long hours, and it is essential to improve their work environment, including task-shifting/task-sharing. Further enhanced recruitment and retention of hospital pediatricians and OB/GYNs is required. A detailed and large-scale study of pediatricians and OB/GYNs' working environments is essential in the future.

Machine‐learning‐based optimization techniques are widely used for designing complex materials. However, an efficient search for the complex systems, where a combinatorial explosion occurs in the materials search space, is still challenging. Core–shell nanoparticles (CSNPs) are an example of a complex system with a high degree of freedom owing to their complicated structure and multiple constituent materials. In this study, a new black box optimization technique is developed. In this method, the structure of the CSNPs is optimized using an Ising machine and their constituent materials are selected using Bayesian optimization with the optical properties of the materials as the “descriptors”. Aiming for applications to i‐line photolithography, the authors search for CSNPs that are transparent to ultraviolet light of wavelength 355–375 nm and opaque to visible light of wavelength 400–830 nm. The transmittance spectra of the nanoparticles are obtained using a Mie theory calculator. The proposed nanoparticles with the best optical properties have a multilayered structure with a radius of approximately 40 nm and an outer shell composed of either Mg or Pb. The results indicate that a combination of various optimization techniques is more efficient in discovering the better complex materials.

Abstract The prognostic value of minimal/measurable residual disease (MRD) detection in autografts of patients with multiple myeloma (MM) in an autologous stem‐cell transplantation setting has been reported. Next‐generation flow (NGF) cytometry has lower sensitivity (2 × 10−6) to detect MRD than next‐generation sequencing (NGS) (

Purpose: A postoperative pain management strategy for the enhanced recovery after surgery (ERAS) protocol has recently become more important in pediatric surgery and growing attention is being paid to perioperative use of intravenous acetaminophen (IV-A). In laparoscopic extraperitoneal closure (LPEC) procedure, postoperative pain is still occurring and optimal analgesia remains unclear. We aimed to evaluate the efficacy of preoperative IV-A (pIV-A) for postoperative analgesia after LPEC in children. Methods: After approval of the ethics committee of our hospital (#2,018,131), 40 consecutive pediatric patients with unilateral inguinal hernia were randomized into two group (20 each) and received LPEC procedure with pIV-A (group-A) and without (group-C). The pain scale score (PSS), the frequency of the postoperative acetaminophen bolus use (FPAB) and school start day (SSD) were assessed. Results: The PSS and the FPAB are significantly lower in group-A compared to group-C on POD0 and POD1, indicating a significant reduction in pain in group-A at an early stage after the operation. In addition, SSD after LPEC operation was shorter in group-A compared to group-C. Conclusion: Our results suggest that pIV-A for postoperative analgesia after LPEC in children is safe and useful for the ERAS.

This study investigates the development of freestanding thick films (FSFs) of lead-free (Ba,Ca)(Zr,Ti)O3 and the role of grain growth on the electromechanical response. During deposition, room temperature powder aerosol deposition rapidly produces thick films with a nano-grain structure that limits the electromechanical properties. In this study, the films are removed from the substrate using a sacrificial buffering layer to avoid thermal treatment and allow for an initial as-processed state. Following this, FSFs were thermally treated at various annealing temperatures from 800 °C to 1400 °C to induce grain growth, which was characterized with scanning and transmission electron microscopy. X-ray diffraction revealed an increase in the crystallite size consistent with an increase in grain size and a decrease in internal residual stress. The temperature-dependent dielectric behavior and the large-field ferroelectric response were also characterized, revealing significant differences of the FSFs from the bulk properties.

Abstract The stability constants of metal(M)-ligand(L) complexes are industrially important because they affect the quality of the plating film and the efficiency of metal separation. Thus, it is desirable to develop an effective screening method for promising ligands. Although there have been several machine-learning approaches for predicting stability constants, most of them focus only on the first overall stability constant of M-L complexes, and the variety of cations is also limited to less than 20. In this study, two Gaussian process regression models are developed to predict the first overall stability constant and the n-th (n > 1) overall stability constants. Furthermore, the feature relevance is quantitatively evaluated via sensitivity analysis. As a result, the electronegativities of both metal and ligand are found to be the most important factor for predicting the first overall stability constant. Interestingly, the predicted value of the first overall stability constant shows the highest correlation with the n-th overall stability constant of the corresponding M-L pair. Finally, the number of features is optimized using validation data where the ligands are not included in the training data, which indicates high generalizability. This study provides valuable insights and may help accelerate molecular screening and design for various applications.

In situ temperature-dependent crystal structure of lead-free ferroelectric perovskite Ba0.798Ca0.202Zr0.006Ti0.994O3 single crystal was characterized using x-ray diffraction from 170 to 380 K. Three phases were identified at different temperatures of 170, 220, and 298 K, revealing rhombohedral (R3m), orthorhombic (Pmm2), and tetragonal (P4mm) crystal structures, respectively. The change in the bond length and its distortion are reported for both AO12 and BO6 polyhedrons, allowing for the estimation of the spontaneous polarization. The Debye–Waller factor is reported as a function of temperature for A and B-sites. Density-functional theory calculations on the tetragonal phase were performed to obtain information on the distribution of the Ca ions, the local atomic displacements, and the ideal value of the spontaneous polarization of a defect-free crystal at 0 K. We find that Ca prefers to arrange in columnar 2D plates oriented along the tetragonal axis. The Ca ions avoid being next neighbors of Zr; however, the specific arrangement of Ca has only a minor impact on the spontaneous polarization. [ABSTRACT FROM AUTHOR]

Background: Appropriate timing of surgery for neonates with congenital diaphragmatic hernia (CDH) generally has been considered after cardiopulmonary stabilization. However, few reports clearly showed the definition of physiologic stabilization for surgery, while many studies have addressed hours of life for timing of repair. The aim of this study is to elucidate an optimal respiratory condition for repair in CDH. Methods: A retrospective chart review was conducted of 81 isolated CDH patients who were born and treated in three children's hospitals during Jan. 2009 through Sep.2018. To find an optimal respiratory condition for repair, alveolar-arterial oxygen difference (AaDO2) and oxygenation index (OI) right before surgery was investigated, as well as prenatal prognostic factors (observed/expected lung-to-head ratio (o/e LHR) and liver up), patients’ demographics (sex, gestational weeks, birth weight, Apgar scores), and the 30-day survival. Multivariate logistic regression analysis adjusting for the antenatal severity combined with o/e LHR and liver position was performed. Results: Among 81patients, 75 patients underwent surgery. The data of AaDO2 and OI right before surgery were available in 73 patients. Among 73 patients, six died in total, and of those, two out of five with extracorporeal membrane oxygenation (ECMO) died. The 30-day mortality in the subset of the fourth quartile of AaDO2 (≥340 mmHg) was significantly higher (odds Ratio (OR) 9.23 95% confidence interval (CI) 1.18072.11 P = 0.03). While mortality of the fourth quartile of OI (≥8) was also higher, it was marginally significant (OR 6.52 95% CI 0.93–45.59 p = 0.06). Conclusions: AaDO2 less than 340 mmHg could be a useful stabilization index for safe surgery in neonates with CDH.

Aim: Several studies have shown that the progression of proteinuria and renal tissue injury is associated with activation of the intrarenal renin‐angiotensin system (RAS). CCCTC‐binding factor (CTCF) is a DNA‐binding factor that plays an essential role in the regulation of gene expression. In the present study, we aimed to investigate the phenotypic effects of CTCF deficiency in podocytes. Methods: Angiotensin II type 1 receptor blockers (ARBs) were administered to the podocyte‐specific Ctcf knockout mice, and histological and biochemical analyzes were performed. We also investigated the changes in the expression of podocin in podocyte cell cultures with or without stimulation with angiotensin II from glomeruli isolated using magnetic beads from podocyte‐specific Ctcf knockout mice. Results: Mice in which Ctcf was deleted from podocytes developed glomerulopathy and mice developed severe progressive proteinuria, and impaired renal function. Moreover, ARBs suppressed the development of glomerulopathy in podocyte‐specific Ctcf knockout mice. Both real‐time polymerase chain reaction and western blotting showed that podocin expression was decreased in cell cultures stimulated with angiotensin II. Furthermore, RAS components gene expressions in podocyte cell cultures isolated from podocyte‐specific Ctcf knockout mice were significantly increased. Conclusion: These results suggest that RAS is involved in the development of glomerulopathy in podocyte‐specific Ctcf knockout mice. Elucidation of the pathophysiology of podocyte‐specific Ctcf knockout mice may provide new insights into the relationship between podocyte injury and chronic glomerulonephritis. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the actual working conditions, including working hours and desired future working styles of hospital pediatricians and obstetricians/gynecologists (OB/GYNs) in Tokushima Prefecture. Method: This cross-sectional study used a self-administered questionnaire. Pediatricians and OB/GYNs (n = 96) working at 14 hospitals in Tokushima Prefecture were surveyed. The questionnaire included items related to working hours, working status, number of medical institutions, task-shifting/task-sharing status, and preferred work style. Factors associated with work hours were analyzed. Results: Approximately 40% and 10% of pediatricians and OB/GYNs worked ≥60 h/week and ≥80 h/week, respectively. Their weekly working hours were significantly positively associated with the number of nights and holidays worked and concurrent medical facilities they worked at. Multiple regression models showed that weekly working hours were significantly associated with working at night and day-off duties and the number of working medical institutions being worked at concurrently. Pediatricians and OB/GYNs who worked ≥60 h/week were not implementing a "multiple attending physician system" or "on-call system," and task-shifting/task-sharing was inadequate. A significantly higher proportion of physicians who worked long hours (≥60 h/week or ≥80 h/week) wanted to reduce the number of night and day-off duties and work hours compared with those who did not. Conclusions: The results of this study suggest that many pediatricians and OB/GYNs work long hours, and it is essential to improve their work environment, including task-shifting/task-sharing. Further enhanced recruitment and retention of hospital pediatricians and OB/GYNs is required. A detailed and large-scale study of pediatricians and OB/GYNs' working environments is essential in the future. [ABSTRACT FROM AUTHOR]

In this study, we investigated the charged domain wall structure of lead-free piezoceramics (Na0.55K0.45)NbO3 using multiple microscopy techniques. It was found that the oxygen partial pressure during sintering affected the volatilization of A2O (A = Na, K), whereby the resulting vacancies were found to be related to grain sizes. In the polycrystals sintered under the air atmosphere condition, almost all grains show rapid grain growth and complex domain structures containing striped and indefinite shaped domains as revealed by confocal laser microscope and piezoelectric force microscope images. Transmission electron microscopy showed that a part of these domain structures has charged domain walls due to bending the 180° domain walls. The A-site vacancies, such as Na and K, lead to forming large grains and charged domain wall structures. [ABSTRACT FROM AUTHOR]

Clinicians, researchers, regulators, and other decision-makers increasingly rely on evidence from real-world data (RWD), including data routinely accumulating in health and administrative databases. RWD studies often rely on algorithms to operationalize variable definitions. An algorithm is a combination of codes or concepts used to identify persons with a specific health condition or characteristic. Establishing the validity of algorithms is a prerequisite for generating valid study findings that can ultimately inform evidence-based health care. In this paper, we aim to systematize terminology, methods, and practical considerations relevant to the conduct of validation studies of RWD-based algorithms. We discuss measures of algorithm accuracy, gold/reference standards, study size, prioritization of accuracy measures, algorithm portability, and implications for interpretation. Information bias is common in epidemiologic studies, underscoring the importance of transparency in decisions regarding choice and prioritizing measures of algorithm validity. The validity of an algorithm should be judged in the context of a data source, and one size does not fit all. Prioritizing validity measures within a given data source depends on the role of a given variable in the analysis (eligibility criterion, exposure, outcome, or covariate). Validation work should be part of routine maintenance of RWD sources. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

BackgroundDisease/patient registries are underutilized despite their multiple advantages over clinical trials in the clinical evaluation of drugs, such as the capacity for long-term curation, provision of patient outcome data in routine clinical practice, and provision of benchmark data for comparison. Ensuring the fit-for-purpose quality of data generated from such registries is important to informing regulatory decision making. Here, we report the construction of a quality management system aiming to ensure regulatory-grade data quality for a registry of Japanese patients with glaucoma to evaluate long-term patient outcomes.MethodsThe quality management system was established by reference to the risk-based approach in the ICH-E6 (R2) recommendations. The following three-component approach was taken: establishment of governance, computerized system validation (CSV), and implementation of risk assessment and control. Compliance of the system with the recommendations of regulatory guidelines relevant to use of the registry was assessed.ResultsGovernance by academic collaboration was established. This was followed by the development of a total of 15 standard operating procedures, including CSV, data management, monitoring, audit, and management of imaging data. The data management system was constructed based on a data management plan, which specified data/paper flow and data management procedures. The electronic data capture (EDC) system was audited by an external vendor, and configured and validated using the V-model framework as recommended in the GAMP5 guideline. Informed consent, eligibility assessment and major ophthalmology measurements were determined as Critical to Quality (CTQ) factors. A total of 22 risk items were identified and classified into three categories, and operationalized in the form of a risk control plan, which included training sessions and risk-based monitoring. The glaucoma registry addressed most quality recommendations in official guidelines issued by multiple health authorities, although two recommendations were not met.ConclusionsWe established and configured a quality management system for a glaucoma registry to ensure fit-for-purpose data quality for regulatory use, and to curate long-term follow-up data of glaucoma patients in a prospective manner.