Prevalence and predictors of direct discharge home following hospitalization of patients with serious adverse events managed by the rapid response system in Japan: a multicenter, retrospective, observational study

Aim: The rapid response system (RRS) is an in-hospital medical safety system. To date, not much is known about patient disposition after RRS activation, especially discharge home. This study aimed to investigate the prevalence, characteristics, and outcomes of patients with adverse events who required RRS activation. Methods: Retrospective data from the In-Hospital Emergency Registry in Japan collected from April 2016 to November 2020 were eligible for our analysis. We divided patients into Home Discharge, Transfer, and Death groups. The primary outcome was the prevalence of direct discharge home, and independently associated factors were determined using multivariable logistic regression. Results: We enrolled 2,043 patients who met the inclusion criteria. The prevalence of discharge home was 45.7%; 934 patients were included in the Home Discharge group. Age (adjusted odds ratio [AOR] 0.96; 95% confidence interval [CI], 0.95-0.97), malignancy (AOR 0.69; 95% CI, 0.48-0.99), oxygen administration before RRS (AOR 0.49; 95% CI, 0.36-0.66), cerebral performance category score on admission (AOR 0.38; 95% CI, 0.26-0.56), do not attempt resuscitation order before RRS (AOR 0.17; 95% CI, 0.10-0.29), RRS call for respiratory failure (AOR 0.50; 95% CI, 0.34-0.72), RRS call for stroke (AOR 0.12; 95% CI, 0.03-0.37), and intubation (AOR 0.20; 95% CI, 0.12-0.34) were independently negative, and RRS call for anaphylaxis (AOR 15.3; 95% CI, 2.72-86.3) was positively associated with discharge home. Conclusion: Less than half of the in-hospital patients under RRS activation could discharge home. Patients' conditions before RRS activation, disorders requiring RRS activation, and intubation were factors that affected direct discharge home

Phamacogenomics of Clozapine-Induced Agranulocytosis

Background: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. Methods: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. Results: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10−9, odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10−8, OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10−5, OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. Conclusions: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated

Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders

Intracellular trafficking of receptor proteins is essential for neurons to detect various extracellular factors during the formation and refinement of neural circuits. However, the precise mechanisms underlying the trafficking of neurotrophin receptors to synapses remain elusive. Here, we demonstrate that a brain-enriched sorting nexin, ARHGAP33, is a new type of regulator for the intracellular trafficking of TrkB, a high-affinity receptor for brain-derived neurotrophic factor. ARHGAP33 knockout (KO) mice exhibit reduced expression of synaptic TrkB, impaired spine development and neuropsychiatric disorder-related behavioural abnormalities. These deficits are rescued by specific pharmacological enhancement of TrkB signalling in ARHGAP33 KO mice. Mechanistically, ARHGAP33 interacts with SORT1 to cooperatively regulate TrkB trafficking. Human ARHGAP33 is associated with brain phenotypes and reduced SORT1 expression is found in patients with schizophrenia. We propose that ARHGAP33/SORT1-mediated TrkB trafficking is essential for synapse development and that the dysfunction of this mechanism may be a new molecular pathology of neuropsychiatric disorders

Reliability and validity of the patient disability-oriented diagnostic nomenclature system for prosthetic dentistry

Purpose: The Japan Prosthodontic Society (JPS) has proposed a new diagnostic nomenclature system (DNS), based on pathogenesis and etiology, to facilitate and improve prosthodontic treatment. This systemspecifies patient disability and the causative factor (i.e. ‘‘B (disability) caused by A (causative factor)’’). The purpose of this study was to examine the reliability and validity of this DNS. Study selection: The JPS Clinical Guideline Committee assessed mock patient charts and formulated disease names using the new DNS. Fifty validators, comprising prosthodontic specialists and dental residents, made diagnoses using the same patient charts. Reliability was evaluated as the consistency of the disease names among the validators, and validity was evaluated using the concordance rate of the disease names with the reference disease names. Results: Krippendorff’s α was 0.378 among all validators, 0.370 among prosthodontic specialists, and 0.401 among dental hospital residents. Krippendorff’s α for 10 validators (3 specialists and 7 residents) with higher concordance rates was 0.524. Two validators (1 specialist and 1 resident) with the highest concordance rates had a Krippendorff’s α of 0.648. Common disease names had higher concordance rates, while uncommon disease names showed lower concordance rates. These rates did not show correlation with clinical experience of the validator or time taken to devise the disease name. Conclusions: High reliability was not found among all validators; however, validators with higher concordance rates showed better reliability. Furthermore, common disease names had higher concordance rates. These findings indicate that the new DNS for prosthodontic dentistry exhibits clinically acceptable reliability and validity

A case of lip edema caused by the accidental ingestion of a bar of soap

Abstract The most common symptom following the accidental ingestion of a soap is lip edema. Although most cases are asymptomatic or exhibit mild symptoms, in some cases, aspiration pneumonia, oropharyngeal edema, and bronchial obstruction may be fatal

Clinical characteristics of pyogenic spondylitis and psoas abscess at a tertiary care hospital: a retrospective cohort study

Abstract Background Psoas abscess and pyogenic spondylitis are intractable diseases that require long-term treatment, but the clinical characteristics and causative organisms have not been fully investigated. Herein, we describe the clinical characteristics of these diseases and evaluate the factors associated with in-hospital mortality and the presence of gram-negative rods as causative microorganisms. Methods All patients diagnosed with pyogenic spondylitis or psoas abscesses at a tertiary hospital were included. We retrieved the clinical data (age, sex, outcome, length of hospital stay, disease, bacteria, medication, comorbidities, and treatment status), vital signs (blood pressure, heart rate, and body temperature), and laboratory test results (blood cell count, liver function, renal function, electrolytes, blood sugar, and C-reactive protein) of all patients. The outcomes were in-hospital deaths and positive cultures of gram-negative rods. Results We analyzed 126 patients consisting of 69 (55%) men with a population mean age of 72 years. Seventy-two patients had pyogenic spondylitis and 54 had psoas abscesses. Eleven patients (8.3%) died during admission. The causative bacteria were gram-positive cocci in 63 patients (50%) and gram-negative bacteria in 19 patients (15%). The multivariate logistic model showed that blood urea nitrogen (BUN) (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02–1.06) and cardiovascular diseases (OR 7.02, 95% CI 1.55–31.8) were associated with in-hospital mortality. Platelets less than 150,000/μL (OR 3.14, 95% CI 1.02–9.65) and higher aspartic aminotransferase (OR 1.02, 95% CI 1.00–1.03) were associated with gram-negative rods. Conclusions Patients with suspected psoas abscesses or pyogenic spondylitis having a high BUN level and a history of cardiovascular diseases have a higher risk of mortality

Radiation-induced nitric oxide mitigates tumor hypoxia and radioresistance in a murine SCCVII tumor model

Tumor hypoxia, which occurs mainly as a result of inadequate tissue perfusion in solid tumors, is a well-known challenge for successful radiotherapy. Recent evidence suggests that ionizing radiation (IR) upregulates nitric oxide (NO) production and that IR-induced NO has the potential to increase intratumoral circulation. However, the kinetics of NO production and the responsible isoforms for NO synthase in tumors exposed to IR remain unclear. In this study, we aimed to elucidate the mechanism by which IR stimulates NO production in tumors and the effect of IR-induced NO on tumor radiosensitivity. Hoechst33342 perfusion assay and electron spin resonance oxymetry showed that IR increased tissue perfusion and pO(2) in tumor tissue. Immunohistochemical analysis using two different hypoxic probes showed that IR decreased hypoxic regions in tumors; treatment with a nitric oxide synthase (NOS) inhibitor, L-NAME, abrogated the effects of IR. Moreover, IR increased endothelial NOS (eNOS) activity without affecting its mRNA or protein expression levels in SCCVII-transplanted tumors. Tumor growth delay assay showed that L-NAME decreased the anti-tumor effect of fractionated radiation (10 Gy x 2). These results suggested that IR increased eNOS activity and subsequent tissue perfusion in tumors. Increases in intratumoral circulation simultaneously decreased tumor hypoxia. As a result, IR-induced NO increased tumor radiosensitivity. Our study provides a new insight into the NO-dependent mechanism for efficient fractionated radiotherapy. (C) 2013 Elsevier Inc. All rights reserved