Treatment of cryptogenic new-onset refractory status epilepticus (C-NORSE) with tocilizumab: A case report.

A 35-year-old woman with no prior history of epilepsy developed status epilepticus (SE), which was highly resistant to multiple antiseizure medications and sedatives. The etiology of SE was not identified despite extensive investigation, and the patient was diagnosed with cryptogenic new-onset refractory status epilepticus (C-NORSE). Although first-line immunotherapies such as high-dose corticosteroids and plasma exchange were ineffective, the patient manifested a resolution of SE after the administration of tocilizumab, which inhibits interleukin-6. Non-antibody-mediated inflammation has been hypothesized to be a probable pathophysiology of C-NORSE in recent studies, and tocilizumab may be a plausible second-line treatment.

Multiple electrolytes imbalances in a patient with inflammatory bowel disease associated with vitamin D deficiency: a case report.

BACKGROUND: Inflammatory bowel disease involves chronic inflammation and ulceration, primarily Crohn's disease and ulcerative colitis. The prevalence of inflammatory bowel disease is rising in industrialized countries. We describe the case of a patient with inflammatory bowel disease and multiple electrolyte disturbances that emphasize the link between a vitamin D deficiency and electrolyte imbalances. CASE: An 86-year-old Japanese man with severe hypocalcemia, hypophosphatemia, hypokalemia, and hypomagnesemia was referred to the gastroenterology and hepatology department our university hospital for severe diarrhea and abdominal pain. Based on clinical symptoms and biochemical and endoscopic findings, Crohn's disease, intestinal Behçet's disease, and intestinal tuberculosis were considered as differential diagnoses, but a final diagnosis was not reached. Prednisolone, azathioprine, and metronidazole were administered, and no apparent electrolyte abnormality was observed at the patient's admission to our hospital. On the 80th hospital day, marked hypocalcemia, hypophosphatemia, hypokalemia, and hypomagnesemia were noted and prolonged, despite daily supplementation with Ca and inorganic P. At his consultation with our department, we observed decreased fractional excretion of Ca, tubular reabsorption of phosphate, fractional excretion of K, and fractional excretion of Mg, suggesting the depletion of vitamin D and extrarenal wasting of K and Mg. The patient's serum Ca and inorganic P were quickly elevated in response to treatment with an active form of vitamin D, and his serum levels of K and Mg were restored to the normal range by an intravenous administration of K and Mg. A vitamin D deficiency is not rare in inflammatory bowel disease and is caused primarily by the decreased intestinal absorption of vitamin D. In the management of electrolyte imbalances in patients with inflammatory bowel disease, clinicians must consider the possible development of vitamin D deficiency-related disorders. CONCLUSION: Vitamin D deficiency in entero-Behçet's disease leads to severe hypocalcemia and hypophosphatemia, highlighting the importance of awareness in management.

A retrospective study on tolvaptan prescription in clinical practice in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) using the Japanese claims database.

We aimed to survey the status of tolvaptan administration in routine clinical practice since the approval of a novel indication for treating syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in Japan. Data from a population of 3,152 patients aged ≥18 years and diagnosed with SIADH between July 1, 2020 and June 30, 2021 were extracted from a Japanese database. Tolvaptan was administered to 586 patients while 2,566 patients were followed up without tolvaptan. In the tolvaptan-treated group, the standard initial doses were 3.75 mg and 7.5 mg in 290 (49.5%) and 250 (42.7%) patients, respectively. The dose was increased in 112 (38.6%) and 71 (28.4%) and decreased in 8 (2.8%) and 46 (18.4%) of patients with 3.75 and 7.5 mg initial doses, respectively. Of the total 586 SIADH patients treated with tolvaptan, serum sodium concentrations were analyzed in 60 patients. In both treatment groups of 3.75 and 7.5 mg initial doses, the serum sodium concentration was elevated from the second day of treatment and reached 135 mEq/L on the fourth day, which was maintained for 2 weeks. Rapid correction of hyponatremia (>10 mEq/L increase in serum sodium concentration over 1 day or >18 mEq/L increase over 2 days) occurred in 26.7% patients with a 7.5 mg initial dose (4 of 15 patients) but not in the patients with a 3.75 mg initial dose (n = 16), suggesting that an initial dose of 3.75 mg of tolvaptan may be a better choice for the safe and proper correction of hyponatremia.

Impact of tolvaptan add-on treatment on patients with heart failure requiring long-term congestion management: A retrospective cohort study using a medical claim database in Japan.

BACKGROUND: The impact of tolvaptan on the long-term outcomes of patients with heart failure (HF) remains inconclusive. We evaluated patients requiring long-term congestion management for the time to rehospitalization for HF (HF rehospitalization), the time to in-hospital death and explored the factors that may influence the outcomes. METHODS: Using data (April 2008 to September 2019) from a medical claims database, patients with HF prescribed tolvaptan (tolvaptan cohort) and those prescribed loop diuretics before tolvaptan was introduced to the hospital (furosemide cohort) were compared. Patients with HF who experienced ≥2 HF hospitalizations and ≥1 tolvaptan or loop diuretic prescription during and after HF hospitalization were included. Data of patients with serum creatinine and estimated glomerular filtration rate were analyzed for time to HF rehospitalization and in-hospital death within 1 year after the second discharge and factors that may influence the outcomes. RESULTS: Among the 1931 and 631 tolvaptan and furosemide cohort patients, respectively, time to HF rehospitalization was not significantly different (p = 0.0921); time to in-hospital death was significantly longer in the tolvaptan cohort than in the furosemide cohort (p = 0.0005). Age, serum sodium, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were identified as factors for both outcomes (p < 0.05). CONCLUSIONS: Tolvaptan did not significantly affect time to HF rehospitalization. However, further worsening of the condition leading to death may be delayed, and time to in-hospital death may be prolonged in patients treated with tolvaptan, indicating its usefulness for long-term congestion management.

Pressure cells for in situ neutron total scattering: time and real-space resolution during deuterium absorption.

In situ gas-loading sample holders for two-dimensionally arranged detectors in time-of-flight neutron total scattering experiments have been developed to investigate atomic arrangements during deuterium absorption using time and real-space resolution. A single-crystal sapphire container was developed that allows conditions of 473 K and 10 MPa hydrogen gas pressure. High-resolution transient measurements detected deuterium absorption by palladium that proceeded within a few seconds. A double-layered container with thick- and thin-walled vanadium allowed conditions of 423 K and 10 MPa hydrogen gas pressure. The deuterium occupation sites of a lanthanum-nickel-aluminium alloy are discussed in detail on the basis of real-space high-resolution data obtained from in situ neutron scattering measurements and reverse Monte Carlo structural modeling.

Educational Program Using Robots for Preventing Cognitive Decline of Elderly Persons.

An expected surge of dementia patients in Japan indicates a pressing need to establish countermeasures. As described herein, by developing an educational program for elderly people using robots, we performed a demonstration experiment. Results revealed that involvement of elderly people with robots enhances their enjoyment, indicating a future direction of cognitive decline prevention education for elderly people.

Economic Evaluations of Interventions to Optimize Medication Use in Older Adults with Polypharmacy and Multimorbidity: A Systematic Review.

PURPOSE: To conduct a systematic review of the economic impact of interventions intended at optimizing medication use in older adults with multimorbidity and polypharmacy. METHODS: We searched Ovid-Medline, Embase, CINAHL, Ageline, Cochrane, and Web of Science, for articles published between 2004 and 2020 that studied older adults with multimorbidity and polypharmacy. The intervention studied had to be aimed at optimizing medication use and present results on costs. RESULTS: Out of 3,871 studies identified by the search strategy, eleven studies were included. The interventions involved different provider types, with a majority described as a multidisciplinary team involving a pharmacist and a general practitioner, in the decision-making process. Interventions were generally associated with a reduction in medication expenditure. The benefits of the intervention in terms of clinical outcomes remain limited. Five studies were cost-benefit analyses, which had a net benefit that was either null or positive. Cost-utility and cost-effectiveness analyses resulted in incremental cost-effectiveness ratios that were generally within the willingness-to-pay thresholds of the countries in which the studies were conducted. However, the quality of the studies was generally low. Omission of key cost elements of economic evaluations, including intervention cost and payer perspective, limited interpretability. CONCLUSION: Interventions to optimize medication use may provide benefits that outweigh their implementation costs, but the evidence remains limited. There is a need to identify and address barriers to the scaling-up of such interventions, starting with the current incentive structures for pharmacists, physicians, and patients.

SUR1, newly expressed in astrocytes, mediates neuropathic pain in a mouse model of peripheral nerve injury.

BACKGROUND: Neuropathic pain following peripheral nerve injury (PNI) is linked to neuroinflammation in the spinal cord marked by astrocyte activation and upregulation of interleukin 6 (IL-6), chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 1 (CXCL1), with inhibition of each individually being beneficial in pain models. METHODS: Wild type (WT) mice and mice with global or pGfap-cre- or pGFAP-cre/ERT2-driven Abcc8/SUR1 deletion or global Trpm4 deletion underwent unilateral sciatic nerve cuffing. WT mice received prophylactic (starting on post-operative day [pod]-0) or therapeutic (starting on pod-21) administration of the SUR1 antagonist, glibenclamide (10 µg IP) daily. We measured mechanical and thermal sensitivity using von Frey filaments and an automated Hargreaves method. Spinal cord tissues were evaluated for SUR1-TRPM4, IL-6, CCL2 and CXCL1. RESULTS: Sciatic nerve cuffing in WT mice resulted in pain behaviors (mechanical allodynia, thermal hyperalgesia) and newly upregulated SUR1-TRPM4 in dorsal horn astrocytes. Global and pGfap-cre-driven Abcc8 deletion and global Trpm4 deletion prevented development of pain behaviors. In mice with Abcc8 deletion regulated by pGFAP-cre/ERT2, after pain behaviors were established, delayed silencing of Abcc8 by tamoxifen resulted in gradual improvement over the next 14 days. After PNI, leakage of the blood-spinal barrier allowed entry of glibenclamide into the affected dorsal horn. Daily repeated administration of glibenclamide, both prophylactically and after allodynia was established, prevented or reduced allodynia. The salutary effects of glibenclamide on pain behaviors correlated with reduced expression of IL-6, CCL2 and CXCL1 by dorsal horn astrocytes. CONCLUSION: SUR1-TRPM4 may represent a novel non-addicting target for neuropathic pain.

Unveiling Nanoscale Compositional and Structural Heterogeneities of Highly Textured Mg0.7Ti0.3Hy Thin Films.

Thin films often exhibit fascinating properties, but the understanding of the underlying mechanism behind such properties is not simple. This is partially because of the limited structural information available. The hurdle in obtaining such information is especially high for textured thin films such as Mg-rich MgxTi1-x, a promising switchable smart coating material. Although these metastable thin films are seen as solid solution alloys by conventional crystallographic methods, their hydrogen-induced optical transition is hardly understood by a solid solution model. In this study, we collect atomic pair distribution function (PDF) data for a Mg0.7Ti0.3Hy thin film in situ on hydrogenation and successfully resolve TiH2 clusters of an average size of 30 Å embedded in the Mg matrix. This supports the chemically segregated model previously proposed for this system. We also observe the emergence of a previously unknown intermediate face-centered tetragonal phase during hydrogenation of the Mg matrix. This phase appears between Mg and MgH2 to reduce lattice mismatch, thereby preventing pulverization and facilitating rapid hydrogen uptake. This work may shed new light on the hydrogen-induced properties of Mg-rich MgxTi1-x thin films.

Metallurgical Synthesis of Mg2FexSi1-x Hydride: Destabilization of Mg2FeH6 Nanostructured in Templated Mg2Si.

Magnesium-based transition-metal hydrides are attractive hydrogen energy materials because of their relatively high gravimetric and volumetric hydrogen storage capacities combined with low material costs. However, most of them are too stable to release the hydrogen under moderate conditions. Here we synthesize the hydride of Mg2FexSi1-x, which consists of Mg2FeH6 and Mg2Si with the same cubic structure. For silicon-rich hydrides (x < 0.5), mostly the Mg2Si phase is observed by X-ray diffraction, and Mössbauer spectroscopy indicates the formation of an octahedral FeH6 unit. Transmission electron microscopy measurements indicate that Mg2FeH6 domains are nanometer-sized and embedded in a Mg2Si matrix. This synthesized metallographic structure leads to distortion of the Mg2FeH6 lattice, resulting in thermal destabilization. Our results indicate that nanometer-sized magnesium-based transition-metal hydrides can be formed into a matrix-forced organization induced by the hydrogenation of nonequilibrium Mg-Fe-Si composites. In this way, the thermodynamics of hydrogen absorption and desorption can be tuned, which allows for the development of lightweight and inexpensive hydrogen storage materials.

Development of a Practical Course to Assist Elementary School Students in Acquiring the Ability to Support for Elderly People with Dementia.

Support for elderly people with dementia is required in the community. Many elementary school students are taking dementia kids supporter training courses, but it is difficult to nurture the ability to correctly understand and respond to dementia. By using multiple information communication technologies, we developed a practical program with concrete response method to convey knowledge on supporting of elderly people with dementia.

Barriers and Strategies for Specialty Care Access through Federally Qualified Health Centers: A Scoping Review.

Federally qualified health centers (FQHCs) provide health care to vulnerable patients with limited resources. We conducted a scoping review on barriers to specialized care and strategies implemented by FQHCs. We searched PubMed, CINAHL, Health Business FULLTEXT, and Web of Science databases. Barriers and success measures were categorized based on the Donabedian framework of structure-process-outcome. We conducted a thematic analysis of identified strategies using Arksey and O'Malley's framework for scoping reviews. Across 19 articles, the most common patient-level barriers were cost and insurance status. The most common system-level barriers were wait time and office accessibility. Six themes emerged from the analysis of strategies, identified across 46 articles: 1) virtual consults, 2) substitution, 3) referral coordinators, 4) network-building, 5) on-site specialty care, and 6) algorithmic screening. Strategies to increase specialty care access via FQHCs do not necessarily align with the most commonly documented barriers. Instead, strategies are highly dependent on clinic context.

Structural Variation of Self-Organized Mg Hydride Nanoclusters in Immiscible Ti Matrix by Hydrogenation.

Hydrogenation of nonequilibrium alloys may form nanometer-sized metal hydride clusters, depending on the alloy compositions and hydrogenation conditions. Here in the Ti-rich compositions of the immiscible Mg-Ti system MgH2 clusters are embedded in a Ti-H matrix. Our previous works have indicated that the interface energy between the two metal hydrides reduces the stability of MgH2. The aim of our study is to obtain the structural information on the nanometer-sized clusters. Indeed, MgD2 clusters embedded in a face-centered-cubic (FCC) Ti-D matrix is found in Mg0.25Ti0.75D1.65 by means of 2H magic angle spinning nuclear magnetic resonance (MAS NMR). The atomic pair distribution function (PDF) analysis of neutron total scattering data suggests that the MgD2 clusters have an orthorhombic structure, which is different from a rutile-type body-centered-tetragonal (BCT) structure of α-MgD2 observed in the Mg-rich compositions. Our results suggest that we can tune the thermodynamics of hydrogen absorption and desorption in Mg-H using the interface energy effect and accompanying stress-induced structural change, which contributes to the substantial development of lightweight and inexpensive hydrogen storage materials.

Protein Energy Wasting and Sarcopenia in Dialysis Patients.

As the aging of the population progresses in Japan, the nutritional problems in dialysis patients are being highlighted. Frailty is a clinical concept including body weight loss, muscle weakness, fatigability, decreased walking speed, and decreased physical activity, which means an intermediate concept between healthy subjects and disability subjects, indicating that their activities of daily living are not decreased but they cannot smoothly perform housework or exercise. Morbidity of dialysis patients is known to be high, and mortality of dialysis patients with frailty is 3 times higher. Sarcopenia is one of the principal reasons for or triggers of frailty. It is a disease setting showing decreased muscle volume and quality associated with decreased physical function or quality of life. Recent mean age at dialysis therapy induction is getting near to 70 years old in Japan. Japanese dialysis patients who are elderly and present organ failure would have a double risk for sarcopenia. Patients with advanced stages of CKD are generally given protein diet, and it has been reported that a low protein intake in dialysis patients would be a significant risk for developing sarcopenia and increasing mortality. Recently, the focus has been on protein energy wasting (PEW) - an underlying disease condition in sarcopenia or frailty. PEW is an energy wasting condition occurring in dialysis patients, and the cause of PEW is principally decreased food intake and increased catabolism. It has recently been revealed that decreased protein intake would be a risk factor for increased mortality in dialysis patients. The incidence of PEW in dialysis patients is reported to be 14%. To avoid sarcopenia and PEW leading to frailty, we should pay much more attention to an appropriate protein and calorie intake rather than restriction in dialysis patients.

Development of Teaching Materials of Dementia by Incorporating a Communications Robot for Schoolchildren Who Are Dementia Supporters.

In this study, we aimed to teach elementary school students how to practically deal with elderly people with dementia and developed and evaluated teaching materials using a communication robot called Pepper. The teaching material used the robot to model representative symptoms seen in elderly people with dementia in a realistic context. We applied the two principles of Merrill's first principle and the ARCS model to achieve learning objectives and sustain learning motivation. Furthermore, to verify the effectiveness of the teaching materials, we conducted a questionnaire survey on five experts in community welfare. As a result, it was speculated that by using Pepper, motivation for learning increases and learning can be effectively accomplished. In the future, we aim to introduce the function to the teaching materials based on the evaluation and introduce it to kids' dementia supporter training course.

Development of e-Learning System for Nurses to Learn Medical English and Chinese Conversation.

Globalization has brought an increase of non-Japanese residents in Japan; it has been urgent for nurses to improve conversational skills. We designed and developed an e-learning system for nurses to learn medical English and Chinese conversation. The teaching materials were created as a video including conversations in a hospital in English and in Chinese between a patient and a nurse. Subtitles are shown and read out twice in English and Chinese and once in Japanese.

Best surgical technique and outcomes for large macular holes: retrospective multicentre study in Japan.

The purpose of this study was to compare the surgical outcomes of vitrectomy with conventional internal limiting membrane (C-ILM) peeling to that with the inverted ILM (I-ILM) flap technique for large macular holes (MHs). This was a retrospective chart review of consecutive cases with a large MH at nine hospitals in Japan. Among the 1342 eyes, 165 eyes of 165 cases met the inclusion criteria. The results for medium-large MHs with a diameter 400-550 µm were compared to that of eyes with an extra-large MH with a diameter >550 µm. In addition, the results of C-ILM peeling were compared to that of the I-ILM technique. In medium-large MHs, the closure rate was 95.2% (59/62) by C-ILM peeling and 100% (19/19) by the I-ILM technique. In extra-large MHs, the closure rate was 88.4% (38/43) by C-ILM peeling and 100% (41/41) by I-ILM. Although the difference between the two methods was not significant, the I-ILM technique was successful in 100% of the cases. Multiple logistic regression analysis showed the best-corrected visual acuity (BCVA) at 6 months was significantly associated with the preoperative BCVA, MH size, age and sex of the patient. Analyses of the eyes with extra-large MHs show that the surgical success is high, and the I-ILM technique is more effective for closure in eyes with extra-large MHs.

The Usefulness of the Electric Textbooks at Nursing Practicam by Analyzing the Usage Logs of the Terminal Tablet.

We conducted assessment tests for clinical training, analyzing the usage of the electronic textbooks and the tablet functions from the log information of the terminal tablets. Results revealed that usage of the terminal tablet and digital nursing dictionary (ver. 2), by which users can enjoy free access to electric textbooks during clinical training, was effective as learning support.

Melting of Pb Charge Glass and Simultaneous Pb-Cr Charge Transfer in PbCrO3 as the Origin of Volume Collapse.

A metal to insulator transition in integer or half integer charge systems can be regarded as crystallization of charges. The insulating state tends to have a glassy nature when randomness or geometrical frustration exists. We report that the charge glass state is realized in a perovskite compound PbCrO3, which has been known for almost 50 years, without any obvious inhomogeneity or triangular arrangement in the charge system. PbCrO3 has a valence state of Pb(2+)(0.5)Pb(4+)(0.5)Cr(3+)O3 with Pb(2+)-Pb(4+) correlation length of three lattice-spacings at ambient condition. A pressure induced melting of charge glass and simultaneous Pb-Cr charge transfer causes an insulator to metal transition and ∼10% volume collapse.