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.

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.

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.

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.

Results of a voter registration project at 2 family medicine residency clinics in the Bronx, New York.

PURPOSE: Federally qualified health centers provide care to medically underserved populations, the same individuals often underrepresented in the electoral process. These centers are unique venues to access patients for voter registration services. METHODS: We undertook a clinician-led, nonpartisan voter registration drive within 2 university-affiliated federally qualified health centers in the Bronx, New York. Patients were approached by voter registration volunteers in clinic waiting areas during a 12-week period. RESULTS: Volunteers directly engaged with 304 patients. Of the 128 patients who were eligible and not currently registered, 114 (89%) registered to vote through this project. This number corresponded to 38% of all patients engaged. Sixty-five percent of new registrants were aged younger than 40 years. CONCLUSIONS: This project was successful in registering clinic patients to vote. Clinics are not only health centers, but also powerful vehicles for bringing a voice to civically disenfranchised communities.

An Examination of the Usefulness of a Human Resource Development Tool of New Visiting Nurses.

Japan's aging rate is among the highest in the world these days. Consequently, home-visiting nursing stations ("stations") are increasing rapidly, but visiting nurses do not remain working at them for long. We developed a human resource promotional tool using spreadsheet software (Excel®; Microsoft Corp.) to support the education of newly appointed nurses working at the stations. Through this research we report findings of an examination concerning the usefulness of this tool on a trial basis. The results show that use of the tool led to increased motivation and decreased educational needs, a visualization of the skills acquired by newcomer nurses had an impact on their motivation to learn along with learning effectiveness.

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.

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.

Control of the orientation and photoinduced phase transitions of macrocyclic azobenzene.

Photoinduced phase transitions caused by photochromic reactions bring about a change in the state of matter at constant temperature. Herein, we report the photoinduced phase transitions of crystals of a photoresponsive macrocyclic compound bearing two azobenzene groups (1) at room temperature on irradiation with UV (365 nm) and visible (436 nm) light. The trans/trans isomer undergoes photoinduced phase transitions (crystal-isotropic phase-crystal) on UV light irradiation. The photochemically generated crystal exhibited reversible phase transitions between the crystal and the mesophase on UV and visible light irradiation. The molecular order of the randomly oriented crystals could be increased by irradiating with linearly polarized visible light, and the value of the order parameter was determined to be -0.84. Heating enhances the thermal cis-to-trans isomerization and subsequent cooling returned crystals of the trans/trans isomer.

In situ XRD study of La2Ni7H(x) during hydrogen absorption-desorption.

Structural changes of La2Ni7H(x) during the first and second absorption-desorption processes along the P-C isotherm were investigated by in situ X-ray diffraction (XRD). Orthorhombic (Pbcn) and monoclinic (C2/c) hydrides coexisted in the first absorption plateau, but only a monoclinic (C2/c) hydride was observed in the first desorption plateau. Phase transformation of La2Ni7H(x) was irreversible between the first as well as the second absorption-desorption process. The lattice parameters and expansion of the La2Ni4 and LaNi5 cells during the absorption-desorption process were refined using the Rietveld method. The lattice parameters a and b of the orthorhombic hydride (Pbcn) decreased, while the lattice parameter c increased with increasing hydrogen content in the first absorption. During the first absorption, the volume of the orthorhombic La2Ni4 cell expanded by more than 50%, while the expansion of the LaNi5 cell was below 10%. The monoclinic La2Ni4 cell expanded to approximately four times the size of the LaNi5 cell in the first absorption. The lattice parameters a, b, and c of the monoclinic hydride (C2/c) decreased with decreasing hydrogen content in the first desorption. These La2Ni4 and LaNi5 cells contracted isotropically in the first desorption.

Increased pituitary volume in subjects at risk for psychosis and patients with first-episode schizophrenia.

AIM: Enlarged pituitary gland has been reported in schizophrenia, possibly reflecting hypothalamic-pituitary-adrenal hyperactivity. The aim of the present study was to examine whether individuals at risk of psychosis also have similar changes. METHODS: Magnetic resonance imaging was used to examine the pituitary volume in 22 individuals with at-risk mental state (ARMS; 11 male, 11 female), 64 first-episode patients with schizophrenia (FESz; 37 male, 27 female), and 86 healthy controls. The control subjects were divided into age- and gender-matched controls for ARMS (11 male, 11 female) and FESz (37 male, 27 female). RESULTS: Both the ARMS and FESz groups had a larger pituitary volume compared with matched controls, but no difference was found between the ARMS and FESz subjects. There was no association between the pituitary volume and clinical variables (symptommeasures at scanning, daily dosage or duration of antipsychotic medication) in either clinical group. The pituitary volume did not differ significantly between the ARMS individuals who later developed schizophrenia (n = 5) and those who did not (n = 17). The pituitary volume was larger in women than in men for all diagnostic groups. CONCLUSION: The finding of increased pituitary volume in both ARMS and FESz subjects may reflect a common vulnerability to stress in early psychosis. Further work in a larger ARMS sample is required to examine the possible relationship between pituitary volume and emergence of psychosis.

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.

High-energy 'composite' layered manganese-rich cathode materials via controlling Li2MnO3 phase activation for lithium-ion batteries.

The 'composite' layered materials for lithium-ion batteries have recently attracted great attention owing to their large discharge capacities. Here, the 0.5Li(2)MnO(3)·0.5LiMn(0.42)Ni(0.42)Co(0.16)O(2)'composite' layered manganese-rich material is prepared and characterized by the synchrotron X-ray powder diffraction (SXPD). The relationship between its electrochemical performance and its 'composite' components, the Li(2)MnO(3) phase activation process during cycling and the cycle stability of this material at room temperature are elucidated based on its kinetic controlled electrochemical properties, dQ/dV curves and Raman scattering spectroscopies associated with different initial charge-discharge current densities (5 mA g(-1), 20 mA g(-1) and 50 mA g(-1)), cut-off voltages (4.6 V and 4.8 V) and cycle numbers (50 cycles and 150 cycles). Furthermore, its reaction pathways are tracked via a firstly introduced integrated compositional phase diagram of four components, Li(2)MnO(3), LiMn(0.42)Ni(0.42)Co(0.16)O(2), MO(2) (M = Mn(1-α-ß)Ni(α)Co(ß); 0 ≤α≤ 5/12, 0 ≤ß≤ 1/6) and LiMnO(2), which turns out to be a very important guiding tool for understanding and utilizing this 'composite' material.

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.

Synthesis and crystal structure of a Pr5Ni19 superlattice alloy and its hydrogen absorption-desorption property.

The intermetallic compound Pr(5)Ni(19), which is not shown in the Pr-Ni binary phase diagram, was synthesized, and the crystal structure was investigated by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Two superlattice reflections with the Sm(5)Co(19)-type structure (002 and 004) and the Pr(5)Co(19)-type structure (003 and 006) were observed in the 2θ region between 2° and 15° in the XRD pattern using Cu Kα radiation. Rietveld refinement provided the goodness-of-fit parameter S = 6.7 for the Pr(5)Co(19)-type (3R) structure model and S = 1.7 for the Sm(5)Co(19)-type (2H) structure model, indicating that the synthesized compound has a Sm(5)Co(19) structure. The refined lattice parameters were a = 0.50010(9) nm and c = 3.2420(4) nm. The high-resolution TEM image also clearly revealed that the crystal structure of Pr(5)Ni(19) is of the Sm(5)Co(19) type, which agrees with the results from Rietveld refinement of the XRD data. The P-C isotherm of Pr(5)Ni(19) in the first absorption was clearly different from that in the first desorption. A single plateau in absorption and three plateaus in desorption were observed. The maximum hydrogen storage capacity of the first cycle reached 1.1 H/M, and that of the second cycle was 0.8 H/M. The 0.3 H/M of hydrogen remained in the metal lattice after the first desorption process.

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.

Phase transformation and crystal structure of La(2)Ni(7)H(x) studied by in situ X-ray diffraction.

The phase transformation of La(2)Ni(7) during hydrogenation was investigated by in situ X-ray diffraction. We found two hydride phases, La(2)Ni(7)H(7.1) (phase I) and La(2)Ni(7)H(10.8) (phase II), during the first absorption cycle. The metal sublattice of phase I was orthorhombic (space group Pbcn) with lattice parameters a = 0.50128(6) nm, b = 0.8702(1) nm, and c = 3.0377(1) nm. The sublattice for phase II was monoclinic (space group C2/c) with lattice parameters a = 0.51641(9) nm, b = 0.8960(1) nm, c = 3.1289(1) nm, and ß = 90.17(1)°. The lattice parameter c increased with the hydrogen content, while a and b decreased in the formation of phase I from the alloy. Phase transformation from phase I to phase II was accompanied by isotropic expansion. The La(2)Ni(4) and LaNi(5) subunit expanded by 48.9% and 6.0% in volume, respectively, during hydrogenation to phase I. They expanded an additional 14% and 5.8%, respectively, in the formation of phase II. The obtained volume expansion suggested different hydrogen distribution in the La(2)Ni(4) and LaNi(5) subunit during hydrogenation.