Erratum: Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande [Phys. Rev. Lett. 130, 031802 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.130.031802.

Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande.

We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton×years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross section between 10^{-33}cm^{2} and 10^{-27}cm^{2} for dark matter mass from 1 MeV/c^{2} to 300 MeV/c^{2}.

Effects of polypharmacy on the prevalence of adverse drug events resulting in outpatient visits and hospitalization.

A high proportion of hospitalizations is attributable to the prevalence of adverse drug events. This retrospective study included outpatients and inpatients to determine the prevalence of adverse drug events and if polypharmacy increases it. The prevalence, classification, and causality of adverse drug events were assessed based on medical records, laboratory values, and other data. Multivariate analysis (multiple logistic regression analysis) was performed with the presence or absence of adverse drug events at the time of the visit as the dependent variable and items for which the P-value was <0.25 in the univariate analysis as independent variables. The prevalence of adverse drug events was 13.0%, 10.9%, and 16.0% among all patients, the outpatient group, and the inpatient group, respectively. Multivariate analysis showed that polypharmacy (≥5 drugs) significantly increased the risk of adverse drug events in all patients. The prevalence of adverse drug events significantly increased with each additional drug used. We expect that minimizing the number of medications through moderation of the number of prescription drugs and elimination of polypharmacy will reduce the number of outpatient visits and hospitalizations due to adverse drug events.

Community pharmacy-level factors associated with medical and nursing home facility collaboration in Japan.

The aim of this study was to clarify the community pharmacy-level factors related to experiences of and attitudes toward collaboration with medical and nursing home care facilities. We conducted a postal questionnaire survey of all pharmacies in Gifu, Japan, assessing the experiences and attitudes of supervising pharmacists regarding the following activities related to collaboration between medical facilities and nursing home care facilities: regional care meetings/service adjustment meetings, case discussion conferences, joint workshops/continuing education conferences, community service, information sharing through medical cooperation networks, and pharmacists accompanying physicians on home care visits. The factors significantly related to inter-professional collaboration were the family pharmacist guidance fee and the number of patients offered pharmaceutical care through cooperation with other medical facilities. Items on attitudes toward collaborating with other medical facilities showed similar results. Overall, policies that support inter-professional collaboration to create a foundation, establish mechanisms to facilitate collaboration, and identify collaborative activities that can be carried out at each pharmacy should be developed.

Signal detection of oral drug-induced dementia in chronic kidney disease patients using association rule mining and Bayesian confidence propagation neural network.

Among the mechanisms responsible for cognitive dysfunction in chronic kidney disease (CKD) are albuminuria and oxidative stress. However, there may be other causes not yet identified. In fact, the full relevance of CKD patient drug use and its relationship to dementia has hardly been barely investigated. We identified drugs affecting cognitive function in CKD patients by analyzing the spontaneous reporting system in Japan using Association rule mining (ARM) and Bayesian confidence propagation neural network (BCPNN). The signal detection criterion used were as follows: case ≥ 3, lift > 1, conviction > 1 (ARM) and IC025 >0 (BCPNN). Drugs with more than 20 cases were valaciclovir (lift: 11.21, conviction: 1.28, IC025: 3.12), amantadine (lift: 19.69, conviction: 1.68, IC025: 3.05), nalfurafine (lift: 8.35, conviction: 1.19, IC025: 2.18), pregabalin (lift: 6.05, conviction: 1.12, IC025: 1.78), and acyclovir (lift: 5.89, conviction: 1.12, IC025: 1.68). This study is the first report to use a large-scale medical database to identify drugs related to oral drugs-induced dementia in CKD.

Association between Sarcopenia and Overactive Bladder in Elderly Diabetic Patients.

OBJECTIVES: To determine the association between sarcopenia and overactive bladder (OAB) in elderly diabetic patients using the Japanese version of SARC-F called SARC-F-J. DESIGN: Cross-sectional study. SETTINGS AND PARTICIPANTS: The study included 329 elderly diabetic patients (aged ≥65 years) who regularly visited the outpatient clinic at Community hospital in Japan. MEASUREMENTS: The condition of OAB was evaluated using the OAM symptom score, which involves a self-administered questionnaire, and sarcopenia was evaluated using the self-administered SARC-F-J questionnaire comprising five items. The odds ratio for OAB due to sarcopenia was calculated using multiple logistic regression analysis, with OAB as the dependent variable and sarcopenia as the explanatory variable. RESULTS: A total of 329 patients (186 males, 143 females) were included for analysis in the present study. Of these patients, 22.9% had sarcopenia and 18.7% had OAB. After adjusting the variables, the odds ratio for OAB due to sarcopenia was 4.46 (95% confidence interval [CI], 1.14-17.36, P = 0.031) and 2.09 (95% CI, 0.52-8.26, P = 0.293) for males and females, respectively. CONCLUSION: This study found that sarcopenia was significantly associated with OAB in elderly diabetic male patients based on SARC-F-J. Moreover, the possibility of the development of OAB should be considered during the medical examinations of elderly diabetic male patients with sarcopenia.

Color change in Perlodel® tablets induced by LED lighting - photolysis of bromocriptine mesylate.

Various types of fluorescent lights are found in the dispensing rooms of medical facilities, such as hospitals and pharmacies, in Japan. However, to reduce electric power consumption, it was necessary to evaluate the substitution of fluorescent lighting with light emitting diode (LED) lighting, which has become widespread in recent years. We subjectively evaluated several types of medicines stored under various light sources and found that different color changes were induced in tablets. In this study, we focused on Perlodel ® tablets, containing 2.5 mg bromocriptine mesylate, as an example for the objective evaluation of the differences in the color change of tablets when stored under LED lighting and fluorescent lighting. High-performance liquid chromatography (HPLC) analysis of part of the tablet surface area revealed a change from white to light brown or dark brown after 28 days of irradiation, with a residual concentration of bromocriptine mesylate of 85.5 % under fluorescent lighting, 85.6 % under daylight-color LED lighting, 90.3 % under bulb-color LED lighting, and 99.2 % in the dark. In addition, the ultraviolet (UV)-visible spectral study of the absorbance of a photo-product at 400-550 nm indicated that the color change of the Perlodel® 2.5 mg tablet was caused by photochemical degradation of bromocriptine mesylate. Thus, this analysis of the photochemical changes in drugs stored under different light sources demonstrated the potency of LED lights. Through the objective evaluation of the color change, the cause of the color change was determined; this will allow us to develop a strategy that minimizes possible disadvantages to patients, such as a decrease in treatment efficacy owing to decomposition of the main component or adverse caused by decomposed matter.

Association between dipeptidyl peptidase-4 inhibitors and autoimmune disorders: Data mining of the spontaneous reporting system in Japan.

The main objective of this study is to conduct a disproportionality analysis of adverse events in the Japan Adverse Event Report (JADER) database and evaluate the risk of the DPP-4 inhibitor induced autoimmune disorder, the secondary objective is risk assessment of sex difference and age difference. The proportional reporting ratio (PRR) of frequency-based statistics and Bayesian estimates of the information components (IC) were calculated as a measure of signal detection. Sex difference and age difference were evaluated using signal score calculated from the PRR and the Chi-square. In patients taking DPP-4 inhibitors, 94 reports of autoimmune disorders were detected with both signals; PRR: 4.09, chi-square: 158.26 and IC: 1.66, 95 % confidence interval: 1.32-2.00). For other antidiabetic drugs, no signals were detected. The signal of males was PRR: 4.53, chi-square: 110.91 and signal score: 6.22, the signal of female was PRR: 3.53, chi-square: 47.65 and signal score: 5.12. About age difference, the signal scores were 6.71 for patients over 60 years and 0.56 for patients under 60 years old. This study suggests that the DPP-4 inhibitors, unlike other antidiabetic drugs, were associated with autoimmune disorders. Signals of the DPP-4 inhibitors induced autoimmune disorders were detected in both male and female, but no sex difference was observed, but age difference was observed. Especially attention should be paid to patients over 60 years old.

Relationship Between Initial Renal Function and the Inhibitory Effect of Dipeptidyl Peptidase-4 Inhibitor Treatment on Renal Function Decline.

We retrospectively investigated the renal function index of patients with type 2 diabetes mellitus (T2DM) to examine the influence of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal function between patients up to early nephropathy and after overt nephropathy. Patients with T2DM (>18 years old) who had been prescribed hypoglycemic agents for ≥3 months at Gifu Municipal Hospital between March 2010 and April 2014 were included in the study. Renal function was evaluated as the estimated glomerular filtration rate (eGFR) decline from baseline at 12 months. Patients in the DPP-4 inhibitor-treated and untreated groups with an eGFR ≥60 (358 [58.2 %] and 257 [41.8 %], respectively) and eGFR <60 (115 [60.2 %] and 76 [39.8 %], respectively) were subjected to multiple logistic regression analysis. Among patients with an eGFR ≥60, no significant differences were observed in eGFR decline rates over time. However, among patients with an eGFR <60, significant decreases were observed in eGFR decline rates >10 % (6 months; odds ratio, 0.476; P = 0.043, 12 months; odds ratio, 0.413; P = 0.010). Similar results were obtained for an eGFR decline rate >20 % (12 months; odds ratio, 0.369; P = 0.049). DPP-4 inhibitors are renoprotective in patients with T2DM and an eGFR <60.

Safer Vitrification of Mouse and Human Embryos Using the Novel Cryoroom Vitrification System for Assisted Reproductive Technology.

BACKGROUND: Vitrification is widely used for assisted reproductive technology (ART). Most vitrification devices require the skillful placement of embryos into the carrier and aspiration of excessive vitrification solution. OBJECTIVE: To evaluate the efficacy and safety of the Cryoroom as a vitrification device. MATERIALS AND METHODS: Mouse and human embryos were vitrified with Cryoroom or Cryotop, and the developmental potency was assessed in vitro. Mouse monozygotic twin blastocysts were vitrified with Cryoroom or Cryotop for microarray analysis. RESULTS AND DISCUSSION: In mouse and human embryos, there were no differences between the survival and developmental progress in each device. In silico, the Cryoroom device showed no changes, particularly in DNA methylation after vitrification compared with the Cryotop. These results showed that the form and function of the device may affect the gene expression levels in vitrified embryos. CONCLUSION: The Cryoroom represents a safe and potentially revolutionary vitrification device for ART.

Factors influencing the use of over-the-counter drugs and health foods/supplements.

Over-the-counter (OTC) drugs and health foods/supplements are used as means of self-medication with the aim of preventing diseases and maintaining health. No reports have yet addressed the relationship between healthcare systems and self-medication. Here, we carried out a retrospective survey to identify healthcare system factors affecting OTC drug and health food/supplement usage. Patients hospitalized at Gifu Municipal Hospital between October 1, 2014 and March 31, 2015 were given a survey. The items surveyed were age, gender, disease, alcohol intake/smoking status, insurance classification, and medical pharmaceuticals, OTC drugs, and health foods/supplements used immediately before hospitalization. We performed multiple logistic regression analysis using OTC drugs and health foods/supplements as dependent variables with patient attributes, medical insurance, etc. as independent variables. A total of 5,965 patients were analyzed. OTC users comprised 2.6 % (156 people) of the total. The use of OTC drugs was significantly higher for females and alcohol consumers than in other categories. In contrast, the use of OTC drugs was significantly lower for participants in public expense/medical subsidy programs. Health foods/supplements were used by 4.0 % of all subjects (240 people); their use was significantly higher among females and users of medical pharmaceuticals. On the other hand, the use of health foods/supplements was significantly lower for smokers, users of the latter-stage elderly healthcare system, and users of public expense/medical subsidy programs.

Clinic-level factors associated with collaboration with community pharmacies in Japan.

The aim of this study was to clarify the clinic-level factors related to experiences of and attitudes toward collaboration with community pharmacies. We conducted a postal questionnaire survey of all clinics in Gifu, Japan, assessing the experiences and attitudes of representative clinical staff regarding the following activities in collaboration with community pharmacists: regional care meetings/service adjustment meetings, case study conferences, joint workshops/continuing education conferences, community services, information sharing through medical cooperation networks, and accompanying community pharmacists during home care. The factors significantly related to experiences of joint workshops/continuing education conferences included home care visits (odds ratio [OR] 2.39) and a 100 % out-of-hospital prescription ratio (OR 4.80). In contrast, only home care visits were significantly associated with consideration of information sharing through medical cooperation networks and accompanying community pharmacists during home care (OR 2.06 and 11.91, respectively). Finally, the factors significantly associated with considering implementing case study conferences and joint workshops/continuing education conferences included home care visits (OR 4.64 and 2.98, respectively) and a 100% out-of-hospital prescription ratio (OR 4.64 and 6.38). Overall, having more opportunities to communicate with community pharmacists and other healthcare professionals appeared to facilitate clinics' consideration of collaboration with community pharmacies, along with actual experiences.

A rapid method to screen poisoning causative agents in an acute care hospital in Japan.

WHAT IS KNOWN AND OBJECTIVE: A simple, rapid analysis is required to simultaneously analyse medicinal toxicants in emergency medical care. In this regard, the analysis of blood samples by LC-MS/MS equipped with a spin column, involving a rapid, simple pretreatment, has attracted attention. In this study, sample pretreatment using a Monospin C18 column was performed to screen 11 medicinal toxicants in blood samples by LC-MS/MS. METHODS: Serum samples supplemented with 11 medical toxicants-acetaminophen, salicylic acid, nitrazepam, diphenhydramine, bromvalerylurea, phenobarbital, amitriptyline, risperidone, fenitrothion, malathion and methomyl-were pretreated with the Monospin C18 column according to Pretreatment I and Pretreatment II, followed by LC-MS/MS analysis. RESULTS AND DISCUSSION: All toxicants were not detected by a single pretreatment method but were detected by two pretreatment methods. According to Pretreatment I, 10 medicinal toxicants-excluding salicylic acid-were detected. The recovery rates of all medicinal toxicants, except acetaminophen and methomyl, were greater than or equal to 80%. Salicylic acid was detected by Pretreatment II, with a recovery rate of 57.1%. Although the coefficient of variation was less than that reported in previous methods employing SPE, the recovery rates were better possibly because of the simultaneous adsorption of water- and lipid-soluble substances and evaporation by drying. WHAT IS NEW AND CONCLUSION: As LC-MS/MS analysis using Monospin C18 can simultaneously and rapidly screen several medicinal toxicants present in blood samples, it is expected to be highly suitable for clinical settings.

Economic evaluation of infection control activities.

BACKGROUND: Healthcare-associated infections by drug-resistant bacteria affect a patient's prognosis. Infection control activities at medical institutions in Japan are increasingly focused on the threat from these bacteria. AIM: To undertake a full cost analysis that included the costs of consumables and labour required for infection control activities. METHODS: The cost of infection control activities undertaken by the infection control team (ICT) at Nishimino Kosei Hospital in Japan was surveyed from January 2013 to December 2015. The evaluation index of infection control activities used the meticillin-resistant Staphylococcus aureus detection rate. The cost:effectiveness ratio (CER) of each intervention was calculated. FINDINGS: Consumables and labour costs increased over time, as did the ratio of labour cost to total cost over time. However, the CER of interventions was found to have decreased, from ¥164,177 in 2014 to ¥57,989 in 2015. There were increases not only in the amount of consumables, but also in ICT time, suggesting the possibility of improvements in the economic efficiency of infection control. CONCLUSION: Increasing the amount of consumables and the time input of the ICT could help improve the economic efficiency of infection control. Our research suggests the possibility for improvements in the economic efficiency of infection control.

Liver Failure From Ultra-Short Bowel Syndrome on the Intestinal Transplant Waiting List: A Retrospective Study.

BACKGROUND: Patients with intestinal failure (IF) are candidates for intestinal transplantation (ITx). In Japan, these patients have few opportunities to undergo cadaveric ITx because of low rates of organ donation. The donor criteria and recipient priority for ITx are still unknown. We reviewed our cases of IF to investigate which patients should be prioritized for ITx. METHODS: Patients with IF who were registered as candidates for cadaveric ITx between January 2010 and November 2015 in our institute were included in this retrospective study. Their data were gathered from their charts and analyzed. RESULTS: Five patients were included. Their primary diseases included total colon aganglionosis (n = 1), chronic idiopathic intestinal pseudo-obstruction syndrome (n = 2), superior mesenteric vein embolization (n = 1), and graft loss after ITx (n = 1). Two patients died of liver failure (LF) during the waiting period. The remaining three are now alive and waiting for transplantation. The lengths of the remaining intestine were more than 20 cm in living cases but less than 20 cm in fatal cases. In the fatal cases, they had several episodes of catheter-related blood stream infection, which caused LF and acute renal failure. CONCLUSIONS: We identified two patients with less than 20 cm residual small bowel who died after acute deterioration of liver function. Patients with ultra-short bowel could have a higher risk of LF. Therefore, they should be referred as soon as possible to a specialized hospital where ITx is a choice of treatment for IF.

Risk factors for developing infusion reaction after rituximab administration in patients with B-cell non-Hodgkin's lymphoma.

Rituximab (RTX), a monoclonal antibody against CD20, is known to cause fewer side effects than conventional anti-cancer drugs; however, infusion reaction (IR), which is specific to monoclonal antibody therapy, is frequently triggered by RTX. Therefore, we designed this study to identify risk factors based on clinical test values for developing IR after RTX administration. Eighty-nine patients with B-cell non-Hodgkin's lymphoma who had received RTX for the first time between February 2010 and March 2013, at the Gifu Municipal Hospital were enrolled as subjects. Analysis of data was conducted for 87 patients, after excluding patients whose data were missing. Univariate analysis showed significant differences in the number of patients exhibiting a soluble interleukin-2 receptor (sLL-2R) level > 2,000 U/L and hemoglobin (Hb) < lower standard limit (LSL) between the IR and non-IR groups. Multivariate analysis showed significant differences with respect to slL-2R > 2,000 U/L [odds ratio (OR), 4.463; 95% confidence interval (Cl), 1.262-15.779; P = 0.020], Hb < LSL [OR, 3.568; 95% CI, 1.071-11.890; P = 0.038], and steroid administration [OR, 0.284; 95% Cl, 0.094-0.852; P = 0.025]. Our findings show that sIL-2R > 2,000 U/L, Hb < LSL, and a lack of steroid premedication are risk factors for developing IR following RTX treatment.

Hyponatremia and hypokalemia as risk factors for falls.

BACKGROUND/OBJECTIVES: Fall accidents may reduce an individual's quality of life and ability to perform the activities of daily life, and may delay recovery from illness. Consequently, medical institutions need to take measures to prevent falls. There are various risk factors for falls, including advanced age, illness and medication effects. Although hyponatremia and hypokalemia have been reported to increase the rate of falls, how they affect falls is not fully understood. SUBJECTS/METHODS: We retrospectively examined 2948 patients, ⩾18 years old who had been hospitalized for ⩾3 days at Gifu (Japan) Municipal Hospital between May 2012 and April 2013 to determine the effects of hyponatremia and hypokalemia on the risk of falls. After the patients had been divided into fall and non-fall groups, their data were subjected to univariate and multiple regression analysis to identify significant differences. RESULTS: The univariate analysis results revealed significant differences between the groups in terms of age (⩾65 years); the presence of hyponatremia, hypokalemia, central nervous system disease, cardiovascular disease and/or peripheral nerve/muscular disease; intake of medications that increase the risk of falls; and increased sedative dosage. The multivariate analysis results revealed significant differences between the groups in terms of the presence of hyponatremia (odds ratio (OR), 1.751; 95% confidence interval (CI), 1.020-3.005), hypokalemia (OR, 2.209; 95% CI, 1.280-3.813), central nervous system disease (OR, 2.492; 95% CI, 1.629-3.814) and/or age ⩾65 years (OR, 2.180; 95% CI, 1.242-3.826). CONCLUSIONS: The results indicated that the presence of hyponatremia or hypokalemia increases the risk of falls.

Induction of tissue-specific stem cells by reprogramming factors, and tissue-specific selection.

Although induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells, there are still several unresolved issues related to the use of iPS cells for clinical applications, such as teratoma formation. In this study, we were able to generate tissue-specific stem (induced tissue-specific stem; iTS) cells from the pancreas (iTS-P) or liver (iTS-L) by transient overexpression of reprogramming factors, combined with tissue-specific selection. The generation of iTS cells was easier than that of iPS cells. The iTS-P/iTS-L cells express genetic markers of endoderm and pancreatic/hepatic progenitors and were able to differentiate into insulin-producing cells/hepatocytes more efficiently than ES cells. Subcutaneous transplantation of both types of iTS cells into immunodeficient mice resulted in no teratoma formation. The technology used for the transient overexpression of reprogramming factors and tissue-specific selection may be useful for the generation of other tissue-specific stem cells, and the generation of iTS cells could have important implications for the clinical application of stem cells.

Plasma amino acid profiles are associated with insulin, C-peptide and adiponectin levels in type 2 diabetic patients.

OBJECTIVES: Plasma-free amino acid (PFAA) profiles have been associated with a future risk of developing diabetes or cardiovascular disease in nondiabetic subjects. These PFAA alterations might predominantly result from the metabolic shift caused by insulin resistance and visceral fat deposition. The variety of PFAA profiles within diabetic subjects is not well researched. In this study, we focused on type 2 diabetic subjects and examined the association between PFAA profiles and insulin- and glucose-related variables. METHODS: Fifty-one Japanese subjects diagnosed with type 2 diabetes were recruited from an outpatient clinic. The plasma concentrations of 21 amino acids; glucose-related markers including glucose, hemoglobin A1c (HbA1c), glycoalbumin and 1,5-anhydroglucitol; insulin-related markers including insulin, C-peptide, and the homeostasis model assessment of insulin resistance; and adipocytokines including adiponectin and leptin were determined. The association of PFAA and other metabolic profiles were analyzed, and stratified analyses of the PFAAs and clinical characteristics were performed according to the fasting plasma insulin and HbA1c levels. In addition, the PFAA indices that correlate to visceral fat obesity were evaluated. RESULTS: Although strong correlations between PFAAs and glucose-related markers were not observed, several amino acids (branched-chain amino acids, tryptophan, alanine, tyrosine, glutamate and proline) and PFAA indices that evaluate visceral obesity were highly correlated with insulin-related markers and adiponectin (P<0.001). In the group of diabetic patients with hyperinsulinemia, the amino acid levels were significantly increased, which generally demonstrated good concordance with insulin-related markers and adiponectin levels. CONCLUSIONS: The PFAA profiles in diabetic patients were strongly associated with hyperinsulinemia and hypoadiponectinemia, which might become risk evaluation factors for the development of cardiovascular diseases.