H-intensity scale score to estimate CSF GluN1 antibody titers with one-time immunostaining using a commercial assay.

Introduction: Anti-NMDA receptor encephalitis is an autoimmune disorder caused by autoantibodies (abs) against the conformational epitope on GluN1 subunits. GluN1-abs have been determined with cell-based assay (CBA) co-expressing GluN1/GluN2 subunits. However, commercial fixed CBA expressing only GluN1 subunit has increasingly been used in clinical practice. The ab titers can be determined with serial dilutions, but its clinical significance remains unclear. We aimed to develop an H-intensity scale (HIS) score to estimate GluN1-ab titers in cerebrospinal fluid (CSF) with one-time immunostaining using both commercial CBA and immunohistochemistry and report its usefulness. "H" is the initial of a patient with high CSF GluN1-ab titers (1:2,048). Methods: We first determined the reliability of CBA in 370 patients with suspected autoimmune encephalitis by comparing the results between commercial CBA and established assay in Dalmau's Lab. Then, we made positive control panels using the patient H's CSF diluted in a fourfold serial dilution method (1:2, 1:8, 1:32, 1:128, 1:512, and 1:2,048). Based on the panels, we scored the intensity of ab reactivity of 79 GluN1-ab-positive patients' CSF (diluted at 1:2) on a scale from 0 to 6 (with ≥1 considered positive). To assess inter-assay reliability, we performed immunostaining twice in 21 patients' CSF. We investigated an association between the score of CSF obtained at diagnosis and the clinical/paraclinical features. Results: The sensitivity and specificity of CBA were 93.7% (95% CI: 86.0-97.3) and 98.6% (95% CI: 96.5-99.5), respectively. Linear regression analysis showed a good agreement between the scores of the first and second assays. Patients with a typical spectrum, need for mechanical ventilation support, autonomic symptoms/central hypoventilation, dyskinesias, speech dysfunction, decreased level of consciousness, preceding headache, ovarian teratoma, and CSF leukocyte count >20 cells/µL had a higher median HIS score than those without, but HIS score was not associated with sex, age at onset, or seizure. HIS score at diagnosis had a significant effect on 1-year functional status. Discussion: The severity of disease and four of the six core symptoms were associated with higher GluN1-ab titers in CSF at diagnosis, which may play a role in poor 1-year functional status. An incomplete phenotype can be attributed to low CSF GluN1-ab titers.

Extended just-noticeable difference for ultralow-luminance displays used in diagnostic imaging.

This study investigates the just-noticeable difference (JND) in luminance below the 0.050c d/m 2 threshold not covered by the DICOM standard in medical imaging displays. A total of 21 healthy young adults were tested using an ultralow-luminance liquid crystal display at a viewing distance of 46 cm. The optotype featured a 4 cycle/deg rectangular wave-like stripe. The average percentage of correct responses for JND indices between -18 and 0 was 70.8%. Using the extended JND based on the Barten model that matches the current JND definition, we confirmed the JND at a very low luminance of 0.0500c d/m 2 or less. These findings suggest the feasibility of further refining the gradation differences in medical imaging displays.

An interactive simulator to deepen the understanding of Guyton's venous return curve.

Mean circulatory filling pressure, venous return curve, and Guyton's graphical analysis are basic concepts in cardiovascular physiology. However, some medical students may not know how to view and interpret or understand them adequately. To deepen students' understanding of the graphical analysis, in place of having to perform live animal experiments, we developed an interactive cardiovascular simulator, as a self-learning tool, as a web application. The minimum closed-loop model consisted of a ventricle, an artery, resistance, and a vein, excluding venous resistance. The simulator consists of three modules: setting (parameters and simulation modes), calculation, and presentation. In the setting module, the user can interactively customize model parameters, compliances, resistance, Emax of the ventricular contractility, total blood volume, and unstressed volume. The hemodynamics are calculated in three phases: filling (late diastole), ejection (systole), and flow (early diastole). In response to the user's settings, the simulator graphically presents the hemodynamics: the pressure-volume relations of the artery, vein, and ventricle, the venous return curves, and the stroke volume curves. The mean filling pressure is calculated at approximately 7 mmHg at the initial setting. The venous return curves, linear and concave, are dependent on the venous compliance. The hemodynamic equilibrium point is marked on the crossing point of venous return curve and the stroke volume curve. Users can interactively do discovery learning, and try and confirm their interests and get their questions answered about hemodynamic concepts by using the simulator.

Asymptomatic acute ischemic lesions in intracerebral hemorrhage: Its frequency, MRI features, and risk factors.

BACKGROUND: Asymptomatic acute ischemic lesions (AIL) may be coincidentally found on brain magnetic resonance imaging (MRI) obtained during the acute phase of intracerebral hemorrhage, but its clinical significance has yet to be determined. The objective of this study is to determine the frequency of asymptomatic AIL, its characteristic features of brain MRI and risk factors in patients with acute intracerebral hemorrhage. METHODS: We retrospectively reviewed the clinical information of 108 patients with intracerebral hemorrhage who underwent brain MRIs within 30 days of hospitalization between April 2013 and January 2018. We determined the frequency of asymptomatic AIL, its brain MRI features, and risk factors. RESULTS: AIL was found in 26 of 108 patients; symptomatic in 2 and asymptomatic in 24 (22.2%). Asymptomatic AIL were small, multiple, mainly distributed to the white matter in the anterior circulation (22/24, 91.7%), and occasionally seen in deep watershed areas (15/24, 62.5%). Only 2 patients had severe major vessel stenosis. Asymptomatic AIL was associated with high mean blood pressure (BP) on admission (> 145 mmHg), excessive drug-induced reduction in mean BP (≥ 55 mmHg), and large hemorrhage (> 31 mL in volume). CONCLUSIONS: Asymptomatic AIL were found in 22.2% of patients with intracerebral hemorrhage within 30 days of hospitalization. Asymptomatic AIL were often small, multiple and occasionally developed in deep watershed areas despite the absence of major vessel stenosis. High mean BP on admission, excessive drug-induced BP reduction, and larger hemorrhage may be a risk factor for development of asymptomatic AIL.

Physical Activity Dose for Hemodialysis Patients: Where to Begin? Results from a Prospective Cohort Study.

OBJECTIVE: Greater physical activity is associated with lower risk of mortality in persons with kidney disease; however, little is known about the appropriate dose of physical activity among hemodialysis patients. Here detected the minimum level of habitual physical activity to help inform interventions aimed at improving outcomes in the dialysis population. DESIGN: The design was prospective cohort study. SUBJECTS: Clinically stable outpatients in a hemodialysis unit from October 2002 to March 2014 were assessed for their eligibility to be included in this 7-year prospective cohort study. We used the Youden index to determine the optimal cutoff points for physical activity. The prognostic effect of physical activity on survival was estimated by Cox proportional hazards regression analysis. The number of steps per nondialysis day was recorded by accelerometer at study entry. MAIN OUTCOME MEASURE: The main outcome measure was all-cause mortality. RESULTS: There were 282 participants who had a mean age of 65 ± 11 years and 45% were female. A total of 56 deaths occurred during the follow-up period (56 months [interquartile range: 29-84 months]). The cutoff value for the physical activity discriminating those at high risk of mortality was 3,752 steps. After adjustment for the effect of confounders, the hazard ratio in the group of <4,000 steps was 2.37 (95% confidence interval: 1.22-4.60, P = .01) compared with the others. CONCLUSIONS: Engaging in physical activity is associated with decreased mortality risk among hemodialysis patients. Our findings of a substantial mortality benefit among those who engage in at least 4,000 steps provide a basis for as a minimum initial recommendation kidney health providers can provide for mobility disability-free hemodialysis patients.

Development of a Smartphone App for Visualizing Heart Sounds and Murmurs.

BACKGROUND: Auscultation is one of the basic techniques for the diagnosis of heart disease. However, the interpretation of heart sounds and murmurs is a highly subjective and difficult skill. OBJECTIVES: To assist the auscultation skill at the bedside, a handy phonocardiogram was developed using a smartphone (Samsung Galaxy J, Android OS 4.4.2) and an external microphone attached to a stethoscope. METHODS AND RESULTS: The Android app used Java classes, "AudioRecord," "AudioTrack," and "View," that recorded sounds, replayed sounds, and plotted sound waves, respectively. Sound waves were visualized in real-time, simultaneously replayed on the smartphone, and saved to WAV files. To confirm the availability of the app, 26 kinds of heart sounds and murmurs sounded on a human patient simulator were recorded using three different methods: a bell-type stethoscope, a diaphragm-type stethoscope, and a direct external microphone without a stethoscope. The recorded waveforms were subjectively confirmed and were found to be similar to the reference waveforms. CONCLUSIONS: The real-time visualization of the sound waves on the smartphone may help novices to readily recognize and learn to distinguish the various heart sounds and murmurs in real-time.

Trial of real-time locating and messaging system with Bluetooth low energy.

BACKGROUND: Hospital real-time location systems (RTLS) are increasing efficiency and reducing operational costs, but room access tags are necessary. OBJECTVE: We developed three iPhone 5 applications for an RTLS and communications using Bluetooth low energy (BLE). METHODS: The applications were: Peripheral device tags, Central beacons, and a Monitor. A Peripheral communicated with a Central using BLE. The Central communicated with a Monitor using sockets on TCP/IP (Transmission Control Protocol/Internet Protocol) via a WLAN (wireless local area network). To determine a BLE threshold level for the received signal strength indicator (RSSI), relationships between signal strength and distance were measured in our laboratory and on the terrace. RESULTS: The BLE RSSI threshold was set at -70 dB, about 10 m. While an individual with a Peripheral moved around in a concrete building, the Peripheral was captured in a few 10-sec units at about 10 m from a Central. The Central and Monitor showed and saved the approach events, location, and Peripheral's nickname sequentially in real time. Remote Centrals also interactively communicate with Peripherals by intermediating through Monitors that found the nickname in the event database. CONCLUSIONS: Trial applications using BLE on iPhones worked well for patient tracking, and messaging in indoor environments.

Development of a comprehensive medical recorder on a cellphone.

Paper medical diaries have effectively been used in chronic diseases for self-management without information and communication technology for many cases. To facilitate self-control in chronic diseases, and observe one's own condition objectively and continuously, we developed a cellphone-based medical recorder (MedData) for patients with chronic diseases. The MedData is based on the Java2 Micro Edition and DoJa-3.5 (NTT DoCoMo, Inc.), and it runs like a scheduler with a calendar, diary, and data entry canvas. The MedData stores laboratory data, such as blood pressure, BUN (blood urea nitrogen), creatinine, Hb A1c (glycosylated hemoglobin), and other pertinent comments, into a cellphone memory. Detailed graphic displays of the data are automatically visualized. The MedData can customize recording events, items, prescriptions, and graphics all on the cellphone. These can then be transferred via an infrared port between a cellphone and a PC.

Estimation of the upper limit of the reference value of the QT interval in rest electrocardiograms in healthy young Japanese men using the bootstrap method.

BACKGROUND: A prolonged QT interval (QT) is associated with cardiac arrhythmia, and methods for identification of QT prolongation are required. METHODS: The relationship between RR and QT was investigated in resting electrocardiograms of 1276 healthy young Japanese men using the bootstrap method. RESULTS: The upper limit of QT (QT(upper limit)) was approximated well by the exponential equation: QT(upper limit) = 435 x RR(0.3409). We also defined an alternative upper limit of QTc(G upper limit) = 435 milliseconds, where QTc(G) was calculated by dividing QT by RR(0.3409). Thirty-two (2.51%) of the 1276 cases exceeded the criterion and were diagnosed as cases of QT prolongation. CONCLUSION: Using this limit, we propose a criterion to discriminate cases with prolonged QT intervals. The accuracy of the estimation of the mean and the upper limit of the reference value of the QT was good within the range of the RR interval from 0.812 to 1.263 s (heart rates from 48 to 74 beats per minute). Our approach for estimation of the exponent of RR differs from the well-known exponential equations proposed by Fridericia, but the exponent of RR in our equation is very close to that of Fridericia.

Development of an alarm sound database and simulator.

OBJECTIVES: The purpose of this study was to develop an interactive software package of alarm sounds to present, recognize and share problems about alarm sounds among medical staff and medical manufactures. METHODS: The alarm sounds were recorded in variable alarm conditions in a WAV file. The alarm conditions were arbitrarily induced by modifying attachments of various medical devices. The software package that integrated an alarm sound database and simulator was used to assess the ability to identify the monitor that sounded the alarm for the medical staff. RESULTS: Eighty alarm sound files (40MB in total) were recorded from 41 medical devices made by 28 companies. There were three pairs of similar alarm sounds that could not easily be distinguished, two alarm sounds which had a different priority, either low or high. The alarm sound database was created in an Excel file (ASDB.xls 170 kB, 40 MB with photos), and included a list of file names that were hyperlinked to alarm sound files. An alarm sound simulator (AlmSS) was constructed with two modules for simultaneously playing alarm sound files and for designing new alarm sounds. The AlmSS was used in the assessing procedure to determine whether 19 clinical engineers could identify 13 alarm sounds only by their distinctive sounds. They were asked to choose from a list of devices and to rate the priority of each alarm. The overall correct identification rate of the alarm sounds was 48%, and six characteristic alarm sounds were correctly recognized by beetween 63% to 100% of the subjects. The overall recognition rate of the alarm sound priority was only 27%. CONCLUSIONS: We have developed an interactive software package of alarm sounds by integrating the database and the alarm sound simulator (URL: http://info.ahs.kitasato-u.ac.jp/tkweb/alarm/asdb.html ). The AlmSS was useful for replaying multiple alarm sounds simultaneously and designing new alarm sounds interactively.

Model of bidirectional modulated parasystole as a mechanism for cyclic bursts of ventricular premature contractions.

Cyclic bursts of ventricular premature contractions (VPC) coming at minute-order intervals have been discerned by analyzing ambulatory ECG recordings, and their mechanism has not been clarified. The present study simulates this phenomenon by constructing a bidirectional modulated parasystole model. With Ts and Te as the intrinsic periods of the sinus and ectopic pacemakers, there are distinct and initial condition-dependent solutions in the model with Ts / Te values close to 1, 1/2, 1/4, etc. Typically, two distinct stable solutions are found existing together around Ts / Te = 1/2. We have verified theoretically the coexistence of different solutions and their dependence on the model parameters. The solution presented switches between those by a premature stimulus and those by fluctuations in the model parameters such as Ts. Patterns of RR intervals were generated by simulation with randomly fluctuating Ts. They included cyclic bursts of bigeminy of the "flat type" and the "dome type" reported by Takayanagi et al. (1999) and other transient types with Wenckebach or reverse Wenckebach rhythm of coupling intervals. This model provides a mathematical representation of the atrioventricular feedback mechanism and enables the modulated parasystole hypothesis to be applied to wider classes of VPCs.