Alternative magnetic field exposure suppresses tumor growth via metabolic reprogramming.

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti-cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti-cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF-induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming.

Computational modeling of multiscale collateral blood supply in a whole-brain-scale arterial network.

The cerebral arterial network covering the brain cortex has multiscale anastomosis structures with sparse intermediate anastomoses (O[102] µm in diameter) and dense pial networks (O[101] µm in diameter). Recent studies indicate that collateral blood supply by cerebral arterial anastomoses has an essential role in the prognosis of acute ischemic stroke caused by large vessel occlusion. However, the physiological importance of these multiscale morphological properties-and especially of intermediate anastomoses-is poorly understood because of innate structural complexities. In this study, a computational model of multiscale anastomoses in whole-brain-scale cerebral arterial networks was developed and used to evaluate collateral blood supply by anastomoses during middle cerebral artery occlusion. Morphologically validated cerebral arterial networks were constructed by combining medical imaging data and mathematical modeling. Sparse intermediate anastomoses were assigned between adjacent main arterial branches; the pial arterial network was modeled as a dense network structure. Blood flow distributions in the arterial network during middle cerebral artery occlusion simulations were computed. Collateral blood supply by intermediate anastomoses increased sharply with increasing numbers of anastomoses and provided one-order-higher flow recoveries to the occluded region (15%-30%) compared with simulations using a pial network only, even with a small number of intermediate anastomoses (≤10). These findings demonstrate the importance of sparse intermediate anastomoses, which are generally considered redundant structures in cerebral infarction, and provide insights into the physiological significance of the multiscale properties of arterial anastomoses.

Medication-based profiling of older orthopedic patients: a multicenter cross-sectional study.

BACKGROUND: Managing medication use in older orthopedic patients is imperative to extend their healthy life expectancy in an aging society. However, the actual situation regarding polypharmacy, the intake of potentially inappropriate medications (PIMs), and fall risk-increasing drugs (FRIDs) among older orthopedic patients is not well characterized. This study aimed to investigate the medication-based profiles of older orthopedic patients to highlight the critical points of concern. METHODS: We retrospectively reviewed the clinical data of consecutive patients aged ≥ 65 years who underwent orthopedic surgery at two acute care hospitals between April 2020 and March 2021. The cutoff number of prescribed drugs for polypharmacy was set at 6. According to the specified guidelines, 19 categories of drugs were identified as PIMs, and 10 categories were classified as FRIDs. RESULTS: A total of 995 older patients with orthopedic surgery were assessed, of which 57.4% were diagnosed with polypharmacy, 66.0% were receiving PIMs, and 41.7% were receiving FRIDs. The prevalence of FRID intake did not significantly differ among patients with degenerative spinal disease (n = 316), degenerative disease of extremities (n = 331), and fractures (n = 272). Compared with patients with degenerative disease of the extremities, the multivariable-adjusted prevalence ratios (PRs) of polypharmacy and PIM intake were significantly higher in patients with degenerative spinal disease (1.26 [confidence intervals (CI): 1.11-1.44] and 1.12 [CI: 1.00-1.25]), respectively. Use of antiemetic drugs (adjusted PR, 13.36; 95% CI: 3.14-56.81) and nonsteroidal anti-inflammatory drugs (adjusted PR, 1.37; 95% CI: 1.05-1.78) was significantly higher in patients with degenerative spinal disease. Among patients with degenerative spinal disease, the prevalence of antiemetic drug intake was 8.7% in lumbar spinal patients and 0% in cervical spinal patients. CONCLUSIONS: More than half of the orthopedic patients in this study were affected by polypharmacy, and approximately two-thirds were prescribed some form of PIMs. Patients with degenerative spinal disease showed a significantly higher prevalence of polypharmacy and PIM use compared with other orthopedic diseases. Particular attention should be paid to the high frequency of antiemetic drugs and nonsteroidal anti-inflammatory drugs intake among patients with degenerative lumbar spine conditions.

[New Preoperative Simulations for the Future of Hydrocephalus Surgery].

Ventricular puncture is a basic procedure that neurosurgeons learn in the early stages of their careers and is also performed in ventricular drainage and neuroendoscopic surgery. However, few neurosurgeons are confident in their ability to insert and place a ventricular catheter in the optimal position for ventriculoperitoneal(VP)shunting in a single pass. Even experienced neurosurgical consultants confident in difficult microsurgical procedures are uncomfortable with ventricular catheter placement in VP shunting. Moreover, many neurosurgeons believe that they will never perform a ventricular puncture from the posterior horn of the lateral ventricles. The reason for thinking that ventricular puncture via the anterior horn is safer and more accurate compared with the posterior approach is because the anterior approach can use facial landmarks such as eyes, nose, and ears. However, even with the anterior approach in VP shunting, it is more difficult than with ventricular drainage or neuroendoscopic surgery to achieve accurate placement owing to head rotation, and the success rate has been reported to be as high as 50%. In this article, I introduced "fool proof," which uses preoperative simulation to place a ventricular catheter in the optimal position according to the size and shape of each patient's head and ventricles. The first choice for VP shunting is the right parieto-occipital approach with a posterior horn puncture from Frazier's Point and, for L-P shunting, a paramedian puncture from the 2/3 or 3/4 lumbar interspace.

Uncertainty quantification in cerebral circulation simulations focusing on the collateral flow: Surrogate model approach with machine learning.

Collateral circulation in the circle of Willis (CoW), closely associated with disease mechanisms and treatment outcomes, can be effectively investigated using one-dimensional-zero-dimensional hemodynamic simulations. As the entire cardiovascular system is considered in the simulation, it captures the systemic effects of local arterial changes, thus reproducing collateral circulation that reflects biological phenomena. The simulation facilitates rapid assessment of clinically relevant hemodynamic quantities under patient-specific conditions by incorporating clinical data. During patient-specific simulations, the impact of clinical data uncertainty on the simulated quantities should be quantified to obtain reliable results. However, as uncertainty quantification (UQ) is time-consuming and computationally expensive, its implementation in time-sensitive clinical applications is considered impractical. Therefore, we constructed a surrogate model based on machine learning using simulation data. The model accurately predicts the flow rate and pressure in the CoW in a few milliseconds. This reduced computation time enables the UQ execution with 100 000 predictions in a few minutes on a single CPU core and in less than a minute on a GPU. We performed UQ to predict the risk of cerebral hyperperfusion (CH), a life-threatening condition that can occur after carotid artery stenosis surgery if collateral circulation fails to function appropriately. We predicted the statistics of the postoperative flow rate increase in the CoW, which is a measure of CH, considering the uncertainties of arterial diameters, stenosis parameters, and flow rates measured using the patients' clinical data. A sensitivity analysis was performed to clarify the impact of each uncertain parameter on the flow rate increase. Results indicated that CH occurred when two conditions were satisfied simultaneously: severe stenosis and when arteries of small diameter serve as the collateral pathway to the cerebral artery on the stenosis side. These findings elucidate the biological aspects of cerebral circulation in terms of the relationship between collateral flow and CH.

Aging-related volume changes in the brain and cerebrospinal fluid using artificial intelligence-automated segmentation.

OBJECTIVES: To verify the reliability of the volumes automatically segmented using a new artificial intelligence (AI)-based application and evaluate changes in the brain and CSF volume with healthy aging. METHODS: The intracranial spaces were automatically segmented in the 21 brain subregions and 5 CSF subregions using the AI-based application on the 3D T1-weighted images in healthy volunteers aged > 20 years. Additionally, the automatically segmented volumes of the total ventricles and subarachnoid spaces were compared with the manually segmented volumes of those extracted from 3D T2-weighted images using the intra-class correlation and Bland-Altman analysis. RESULTS: In this study, 133 healthy volunteers aged 21-92 years were included. The mean intra-class correlations between the automatically and manually segmented volumes of the total ventricles and subarachnoid spaces were 0.986 and 0.882, respectively. The increase in the CSF volume was estimated to be approximately 30 mL (2%) per decade from 265 mL (18.7%) in the 20s to 488 mL (33.7%) in ages above 80 years; however, the increase in the volume of total ventricles was approximately 20 mL (< 2%) until the 60s and increased in ages above 60 years. CONCLUSIONS: This study confirmed the reliability of the CSF volumes using the AI-based auto-segmentation application. The intracranial CSF volume increased linearly because of the brain volume reduction with aging; however, the ventricular volume did not change until the age of 60 years and above and then gradually increased. This finding could help elucidate the pathogenesis of chronic hydrocephalus in adults. KEY POINTS: • The brain and CSF spaces were automatically segmented using an artificial intelligence-based application. • The total subarachnoid spaces increased linearly with aging, whereas the total ventricle volume was around 20 mL (< 2%) until the 60s and increased in ages above 60 years. • The cortical gray matter gradually decreases with aging, whereas the subcortical gray matter maintains its volume, and the cerebral white matter increases slightly until the 40s and begins to decrease from the 50s.

Long-term outcomes of delayed clozapine initiation in treatment-resistant schizophrenia: a multicenter retrospective cohort study.

BACKGROUND: Clozapine is the only antipsychotic medication with proven efficacy against treatment-resistant schizophrenia. This multicenter retrospective cohort study aimed to evaluate the impact of a delay in clozapine initiation on long-term outcomes. METHODS: Patients who initiated clozapine treatment between July 2009 and December 2018 were included in this study. According to the length of time from the diagnosis of schizophrenia to clozapine initiation, the patients were categorized into one of three groups: early (≤ 9 years), intermediate (10-19 years), and late (≥ 20 years) initiation. The endpoints were psychiatric rehospitalization and all-cause clozapine discontinuation within 3 years. Hazard ratios (HR) and 95% confidence interval (CI) were estimated using the Fine and Gray method or the Cox proportional hazards model. RESULTS: The incidence rates of rehospitalization within three years, according to the cumulative incidence function, were 32.3% for early, 29.7% for intermediate, and 62.2% for late initiation, respectively. Late initiation had a significantly higher risk of psychiatric rehospitalization than early initiation (HR, 2.94; 95% CI, 1.01- 8.55; P = 0.016 by the Gray's test). The risk of psychiatric rehospitalization was not significantly different between the early and intermediate initiation groups. The incidence rate of all-cause clozapine discontinuation within three years using the Kaplan-Meier method was 13.0% for early, 10.6% for intermediate, and 20.1% for late initiation. The risk of all-cause clozapine discontinuation was not significantly among the groups. The late initiation group had more patients discontinuing because of death due to physical diseases than the other groups. CONCLUSIONS: The study suggests that clozapine should be initiated promptly in patients with treatment-resistant schizophrenia to prevent psychiatric rehospitalization during long-term treatment. Further prospective studies with appropriate consideration of confounding factors and large sample sizes are needed to strengthen the evidence.

Factors Affecting the Comprehension of Outpatients Receiving Cancer Chemotherapy.

Pharmaceutical consultation targeting outpatients at the Fujita Health University Hospital (Japan) provides support to patients undergoing anticancer drug treatment. This study aimed to explore factors that affect the comprehension of cancer chemotherapy among outpatients who received cancer treatment at our hospital. A questionnaire survey was conducted, and comprehension was scored on a scale of 1-5 (1, no comprehension; 5, full comprehension). When factors other than age and sex [the influence of which on comprehension has been reported in previous reports] were noted, differences in comprehension between the questionnaire items were comparatively analyzed according to the presence/absence of the relevant factors. Overall, 536 patients were included. Age (<70 years) and pharmacist interventions were identified as factors contributing to a comprehension score. The levels of comprehension regarding the name of the cancer chemotherapy, content/schedule of the treatment, purposes of the prescribed drugs, and objectives of blood tests were significantly higher in the group that received the pharmaceutical interventions; conversely, the level of comprehension for the self-management of adverse events was significantly lower in this group than in the group that did not receive any pharmaceutical interventions. Age and interventions by the pharmacist affected the comprehension of cancer chemotherapy by patients.

Occurrence of intraocular hemorrhages under monotherapy or combination therapy of antiplatelets and anticoagulants using the Japanese Adverse Drug Event Report database.

Purpose: An intraocular hemorrhage is an adverse event that can lead to visual acuity impairment. Antithrombotic therapy with antiplatelet agents and anticoagulants may increase intraocular hemorrhage. However, since their frequency is low, studies on the risk of intraocular hemorrhage with these drugs, especially under combination therapy, are limited. This study aimed to investigate the occurrence of intraocular hemorrhages under monotherapy and combination therapy with antiplatelets and anticoagulants by analyzing a large pharmacovigilance database. Methods: Intraocular hemorrhage signals with oral antiplatelets and anticoagulants were evaluated by calculating reporting odds ratios and information components using the Japan Adverse Drug Reactions Report database from April 2004 to March 2022. In addition, differences in signals between younger and elderly patients, affecting factors, and time-to-onset from initial antiplatelet and anticoagulant treatments were analyzed. Results: Aspirin, clopidogrel, warfarin, apixaban, and rivaroxaban, but not ticagrelor, ticlopidine, prasugrel, dabigatran, and edoxaban showed intraocular hemorrhage signals under monotherapy. In combination therapy, dual therapy (aspirin + P2Y12 inhibitors, warfarin, direct oral anticoagulants, and P2Y12 inhibitors + warfarin) and triple therapy (aspirin + P2Y12 inhibitors + warfarin) resulted in intraocular hemorrhage signals. Intraocular hemorrhage signals were observed in younger patients receiving monotherapy with aspirin and in elderly patients receiving monotherapy and combination therapy with warfarin. Affecting factors were diabetes mellitus in patients with prasugrel, use of medications for intravitreal injections, and posterior sub-Tenon injections with some antiplatelets and anticoagulants. The median period of intraocular hemorrhage occurrence after starting monotherapy with aspirin, clopidogrel, warfarin, or rivaroxaban was within 90 days. Conclusion: In addition to monotherapy with several antiplatelets and anticoagulants, combination therapy using aspirin, P2Y12 inhibitors, and warfarin has the potential risk of intraocular hemorrhage. Particular attention should be paid to the occurrence of intraocular hemorrhages in younger patients taking aspirin, in elderly patients taking warfarin, and within the first 90 days of antiplatelet and anticoagulant use.

COVID-19 mRNA vaccination is associated with IgA nephropathy: an analysis of the Japanese adverse drug event report database.

Purpose: Coronavirus disease 2019 (COVID-19) mRNA vaccines are used worldwide to prevent severe symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. IgA nephropathy (IgAN) is the most common form of glomerular injury after COVID-19 vaccination; however, because of the low frequency of such events, only a few reports have been published. A large pharmacovigilance database of real-world spontaneous adverse event (AE) reports is essential for evaluating the drug-associated safety signals regarding rare AEs. Herein, we aimed to investigate the frequency of IgAN after the COVID-19 vaccination, using the Japanese Adverse Drug Event Report (JADER) database. Methods: Data on drug-associated AEs reported between April 2004 and May 2022 were obtained from the JADER database on the Pharmaceuticals and Medical Devices Agency website. To evaluate the safety signals for the targeted AEs, reporting odds ratios (RORs), information components (ICs), and their 95% confidence intervals (CIs) were calculated using two-by-two contingency tables. Results: A total of 697,885 cases were included in the analysis. Safety signals were detected for IgAN (ROR: 6.49, 95% CI: 4.38-9.61; IC: 2.27, 95% CI: 1.70-2.83). Of 30 cases for IgAN associated with COVID-19 mRNA vaccines, 16 had information available on time to onset. Of the 16 cases, 11 occurred ≤2 days after vaccination, and two occurred >28 days after vaccination. Conclusion: These results suggest that, compared with other drugs, COVID-19 vaccination is associated with a higher frequency of IgAN. Monitoring of gross hematuria following COVID-19 vaccination should be needed.

Efficacy of surgical treatment on polypharmacy of elderly patients with lumbar spinal canal stenosis: retrospective exploratory research.

BACKGROUND: Polypharmacy is a growing public health problem occurring in all healthcare settings worldwide. Elderly patients with lumbar spinal canal stenosis (LSS) who manifest low back and neuropathic pain and have a high frequency of comorbidity are predicted to take many drugs. However, no studies have reported polypharmacy in elderly patients with LSS. Thus, we aimed to review the polypharmacy among elderly LSS patients with elective surgeries and examine how the surgical treatment reduces the polypharmacy. METHODS: We retrospectively enrolled all the patients aged ≥ 65 years who underwent spinal surgery for LSS between April 2020 and March 2021. The prescribed drugs of participants were directly checked by pharmacists in the outpatient department preoperatively and 6-month and 1-year postoperatively. The baseline characteristics were collected beside the patient-based outcomes including Roland-Morris Disability Questionnaire, Zurich Claudication Questionnaire, and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). The cutoff number of drugs for polypharmacy was defined as 6. The prescription drugs were divided into 9 categories: drugs for neuropsychiatric, cardiovascular, respiratory, digestive, endocrine metabolic, and urinary renal diseases; blood products; pain relief medication; and others. RESULTS: A total of 102 cases were finally analyzed, with a follow-up rate of 78.0%. Of the participants, the preoperative polypharmacy prevalence was 66.7%. The number of drugs 6-month and 1-year postoperatively was significantly less than the preoperative one. The proportions of polypharmacy at 6 months and 1 year after surgery significantly decreased to 57.8% and 55.9%, respectively. When the prescribed drugs were divided into 9 categories, the number of drugs for pain relief and digestive diseases was significantly reduced after surgery. The multi-variable analysis revealed that a higher score in the psychological disorder of JOABPEQ was associated with 3 or more drugs decreased 1-year postoperatively (OR, 2.5; 95% CI: 1.0-6.1). CONCLUSION: Polypharmacy prevalence was high among elderly LSS patients indicated for lumbar spinal surgery. Additionally, our data showed that lumbar spinal surgery was effective in reducing polypharmacy among elderly LSS patients. Finally, the multi-variable analysis indicated that better psychological condition was associated with the reduction of prescribed drugs after lumbar spinal surgery.

Artificial Intelligence Distinguishes Pathological Gait: The Analysis of Markerless Motion Capture Gait Data Acquired by an iOS Application (TDPT-GT).

Distinguishing pathological gait is challenging in neurology because of the difficulty of capturing total body movement and its analysis. We aimed to obtain a convenient recording with an iPhone and establish an algorithm based on deep learning. From May 2021 to November 2022 at Yamagata University Hospital, Shiga University, and Takahata Town, patients with idiopathic normal pressure hydrocephalus (n = 48), Parkinson's disease (n = 21), and other neuromuscular diseases (n = 45) comprised the pathological gait group (n = 114), and the control group consisted of 160 healthy volunteers. iPhone application TDPT-GT captured the subjects walking in a circular path of about 1 meter in diameter, a markerless motion capture system, with an iPhone camera, which generated the three-axis 30 frames per second (fps) relative coordinates of 27 body points. A light gradient boosting machine (Light GBM) with stratified k-fold cross-validation (k = 5) was applied for gait collection for about 1 min per person. The median ability model tested 200 frames of each person's data for its distinction capability, which resulted in the area under a curve of 0.719. The pathological gait captured by the iPhone could be distinguished by artificial intelligence.

Fluctuations in Upper and Lower Body Movement during Walking in Normal Pressure Hydrocephalus and Parkinson's Disease Assessed by Motion Capture with a Smartphone Application, TDPT-GT.

We aimed to capture the fluctuations in the dynamics of body positions and find the characteristics of them in patients with idiopathic normal pressure hydrocephalus (iNPH) and Parkinson's disease (PD). With the motion-capture application (TDPT-GT) generating 30 Hz coordinates at 27 points on the body, walking in a circle 1 m in diameter was recorded for 23 of iNPH, 23 of PD, and 92 controls. For 128 frames of calculated distances from the navel to the other points, after the Fourier transforms, the slopes (the representatives of fractality) were obtained from the graph plotting the power spectral density against the frequency in log-log coordinates. Differences in the average slopes were tested by one-way ANOVA and multiple comparisons between every two groups. A decrease in the absolute slope value indicates a departure from the 1/f noise characteristic observed in healthy variations. Significant differences in the patient groups and controls were found in all body positions, where patients always showed smaller absolute values. Our system could measure the whole body's movement and temporal variations during walking. The impaired fluctuations of body movement in the upper and lower body may contribute to gait and balance disorders in patients.

Quantitative Gait Feature Assessment on Two-Dimensional Body Axis Projection Planes Converted from Three-Dimensional Coordinates Estimated with a Deep Learning Smartphone App.

To assess pathological gaits quantitatively, three-dimensional coordinates estimated with a deep learning model were converted into body axis plane projections. First, 15 healthy volunteers performed four gait patterns; that is, normal, shuffling, short-stepped, and wide-based gaits, with the Three-Dimensional Pose Tracker for Gait Test (TDPT-GT) application. Second, gaits of 47 patients with idiopathic normal pressure hydrocephalus (iNPH) and 92 healthy elderly individuals in the Takahata cohort were assessed with the TDPT-GT. Two-dimensional relative coordinates were calculated from the three-dimensional coordinates by projecting the sagittal, coronal, and axial planes. Indices of the two-dimensional relative coordinates associated with a pathological gait were comprehensively explored. The candidate indices for the shuffling gait were the angle range of the hip joint < 30° and relative vertical amplitude of the heel < 0.1 on the sagittal projection plane. For the short-stepped gait, the angle range of the knee joint < 45° on the sagittal projection plane was a candidate index. The candidate index for the wide-based gait was the leg outward shift > 0.1 on the axial projection plane. In conclusion, the two-dimensional coordinates on the body axis projection planes calculated from the 3D relative coordinates estimated by the TDPT-GT application enabled the quantification of pathological gait features.

A subject-specific assessment of measurement errors and their correction in cerebrospinal fluid velocity maps using 4D flow MRI.

PURPOSE: Phase-contrast MRI (PC-MRI) of cerebrospinal fluid (CSF) velocity is used to evaluate the characteristics of intracranial diseases, such as normal-pressure hydrocephalus (NPH). Nevertheless, PC-MRI has several potential error sources, with eddy-current-based phase offset error being non-negligible in CSF measurement. In this study, we assess the measurement error of CSF velocity maps obtained using 4D flow MRI and evaluate correction methods. METHODS: CSF velocity maps of 10 patients with NPH were acquired using 4D flow MRI (velocity-encoding = 5 cm/s). Distributed phase offset error was estimated for a whole 3D background field by polynomial fitting using robust regression analysis. This estimated phase offset error was then used to correct the CSF velocity maps. The estimated error profiles were compared with those obtained using an existing 2D correction approach involving local background information near the region of interest. RESULTS: The residual standard error of the polynomial fitting against the phase offset error extracted from the measured velocities was within 0.2 cm/s. The spatial dependencies of the phase offset errors showed similar tendencies in all cases, but sufficient differences in these values were found to indicate requirement of velocity correction. Differences of the estimated errors among other correction approaches were in the order of 10-2 cm/s, and the estimated errors were in good agreement with those obtained using existing approaches. CONCLUSION: Our method is capable of estimating the measurement error of CSF velocity maps obtained from 4D flow MRI and provides quantitatively reasonable characteristics for the main CSF profile in the cerebral aqueduct in patients with NPH.

Hospital-Wide Surveillance of Fracture Risk Assessment by Both FRAX and Medication Patterns in Acute Care Hospital.

To identify patients at a high risk for primary and secondary osteoporotic fractures using fracture risk assessments performed using the current method and the proposed method, in an acute care hospital and to identify departments where high-risk patients are admitted. This retrospective study included patients aged 40-90 years who were hospitalized at Fujita Health University Hospital. We collated the clinical data and prescriptions of all study participants. We also gathered data pertaining to risk factors according to Fracture Risk Assessment Tool (FRAX). Of the 1595 patients, the mean number of major osteoporotic fracture risk predicted using FRAX was 11.73%. The department of rheumatology showed the highest fracture risk (18.55 ± 16.81) and had the highest number of patients on medications that resulted in reduced bone mineral density (1.07 ± 0.98 medication). Based on the FRAX, the proportion of patients in the high-risk group in this department was significantly higher compared with those in the remaining departments with respect to glucocorticoid administration, rheumatoid arthritis, and secondary osteoporosis. However, the departments included in the high-risk group were not necessarily the same as the departments included in the top group, based on the administered medications. FRAX score is calculated based on various risk factors; however, only glucocorticoid corresponds to medications. We should focus on medication prescription patterns in addition to FRAX to improve fracture risk assessment in hospital-wide surveillance. Therefore, we recommend the use of FRAX along with the prescribed medications to identify departments that admit high-risk patients.

Efficacy of a Pharmacist Team Clinical Medication Review in Older Adults: A Prospective and Retrospective Observational Study.

Polypharmacy in older adults causes problems such as increased adverse drug reactions, overdose or duplication, and poor medication adherence. We have established a "medication review team" organized by pharmacists. This prospective and retrospective observational study evaluated the effectiveness of the pharmacist-led team-based approach for reducing polypharmacy as compared to the individual pharmacist approach. Data on the individual pharmacist approach were collected retrospectively, but prospectively for the pharmacist-led team approach. The study included patients who were admitted to the nephrology, orthopedic surgery, and psychiatry wards. Characteristics for patient included in each study group were adjusted using the propensity score method. The pharmacist-led team approach had a significantly higher medication change rate compared to that of the individual pharmacist approach (odds ratio (OR), 2.28; 95% confidence interval (CI), 1.21 to 4.46; p = 0.009). The rate of patients with two or more medication discontinuations and the rate of patients with intervention by young clinical pharmacist were also significantly higher in the pharmacist-led team approach (OR, 2.19; 95% CI, 1.06 to 4.74; p = 0.03 and OR, 5.67; 95% CI, 1.22 to 53.15; p = 0.02, respectively). The rate of patients with discontinuation of potentially inappropriate medications was not significantly different between the two groups (OR, 2.07; 95% CI, 0.86 to 5.33; p = 0.11). Our results suggest that it is possible to improve the quality of medication review by conducting team conferences even with only pharmacists.

Development of Smartphone Application for Markerless Three-Dimensional Motion Capture Based on Deep Learning Model.

To quantitatively assess pathological gait, we developed a novel smartphone application for full-body human motion tracking in real time from markerless video-based images using a smartphone monocular camera and deep learning. As training data for deep learning, the original three-dimensional (3D) dataset comprising more than 1 million captured images from the 3D motion of 90 humanoid characters and the two-dimensional dataset of COCO 2017 were prepared. The 3D heatmap offset data consisting of 28 × 28 × 28 blocks with three red-green-blue colors at the 24 key points of the entire body motion were learned using the convolutional neural network, modified ResNet34. At each key point, the hottest spot deviating from the center of the cell was learned using the tanh function. Our new iOS application could detect the relative tri-axial coordinates of the 24 whole-body key points centered on the navel in real time without any markers for motion capture. By using the relative coordinates, the 3D angles of the neck, lumbar, bilateral hip, knee, and ankle joints were estimated. Any human motion could be quantitatively and easily assessed using a new smartphone application named Three-Dimensional Pose Tracker for Gait Test (TDPT-GT) without any body markers or multipoint cameras.

[Mechanisms of Cerebrospinal Fluid Production and Absorption and Ventricular Dilatation in Hydrocephalus].

The concept of cerebrospinal fluid(CSF)production and absorption changed significantly in the early 2010s from "third circulation theory" and "classical bulk flow theory" as follows. First, CSF is mainly produced from the interstitial fluid excreted from the brain; CSF produced by the choroid plexus is important in maintaining homeostasis of the brain. Next, CSF is not absorbed in the venous sinus via the arachnoid granules, but rather in the dural lymphatic vessels. Finally, the ventricles and subarachnoid spaces have several compensatory direct CSF pathways around the attachment of the choroid plexus other than the foramina of Luschka and Magendie. Because of the compensatory direct CSF pathways, the lateral ventricles and the basal cistern are enlarged simultaneously in idiopathic normal pressure hydrocephalus(iNPH). Due to the decrease in brain volume with aging, the average total intracranial CSF volume increases from approximately 150 mL at 20 years to approximately 350 mL at 70 years, and further increases by approximately 50-100 mL to above 400 mL in patients with iNPH. CSF movement is composed of a steady flow produced by the rhythmic wavy movement of motile cilia on the ventricular surface and the dynamic pulsatile flow produced by the pulsation of the cerebral arteries or brain, respiration, and head movement. In general, this pulsatile CSF flow decreases with aging but increases at the opening of the foramen of Magendie and causes the ventricles to expand in iNPH.

The Influence of Intervening on the Pharmaceutical Consultation Targeting Outpatients with Advanced Non-small Cell Lung Cancer Receiving Erlotinib Treatment.

Erlotinib is used to treat advanced non-small-cell lung cancer (NSCLC), the common serious adverse events are skin disorders. The dose intensity of erlotinib should be maintained as much as possible by an appropriate control of adverse events in order to maintain its efficacy. Therefore, the management of these adverse events related to skin disorders would enable a continuous erlotinib treatment without interruption and dose reduction. This study assessed the effect of pharmaceutical consultation in outpatients who received erlotinib. Participants included patients with NSCLC who received erlotinib therapy for more than 6 months between December 2007 and March 2019. The participants were divided into two groups: the intervention group that included patients who received pharmaceutical consultation targeting outpatients by a pharmacist and the nonintervention group that included patients who did not. We retrospectively investigated patient characteristics, treatment regimens, and treatment efficacy. We included a total of 33 patients (18 and 15 patients in the nonintervention and intervention groups, respectively) in this study. The intervention group had a significantly higher median relative dose intensity (RDI) of erlotinib than the nonintervention group (p = 0.0437). In addition, the pharmaceutical consultation targeting outpatients was identified as a factor contributing to the maintenance of RDI ≥90% (p = 0.0269). The present study indicated that there was improvement in RDI with pharmaceutical consultation targeting outpatients with advanced NSCLC.