Reliability and validity of the Japanese version of the Chemotherapy-induced Alopecia Distress Scale.

BACKGROUND: The Chemotherapy-induced Alopecia Distress Scale (CADS) is a patient-reported outcome measure for assessing distress associated with Chemotherapy-induced alopecia (CIA). This study aimed to confirm the psychometric validity of the Japanese version of the CADS (CADS-J). METHODS: A total of 132 patients with breast cancer who developed CIA were asked to complete the CADS-J twice at 2 week intervals to confirm test-retest reliability. The body image domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) breast cancer-specific module, the self-esteem scale from the Rosenberg Self-Esteem Scale, and the emotional domain of the EORTC QLQ Core 30 were used to confirm the convergent validity of the CADS-J. The overall quality of life and physical domains of the EORTC QLQ Core 30 were used to confirm the discriminant validity of the CADS-J. RESULTS: In total, 125 participants provided valid responses. The mean age was 52.2 years. The overall Cronbach's alpha for the CADS-J was 0.903. The intraclass correlation coefficients of the first and second responses were r = 0.874, r = 0.952, r = 0.911, and r = 0.959 for the physical domain, emotional domain, activity domain, and relationship domain, respectively. In terms of convergent validity, the total CADS-J score was moderately correlated with body image (r = - 0.63), self-esteem (r = - 0.48), and the emotional domain (r = - 0.61). Regarding discriminant validity, the total CADS-J score was weakly correlated with the overall quality of life (r = - 0.34) and physical domain (r = - 0.24). CONCLUSIONS: The CADS-J is psychometrically reliable and valid for evaluating the distress caused by CIA. It is expected to be used in daily practice and as an endpoint in various studies.

Visualization of droplets and aerosols in simulated dental treatments to clarify the effectiveness of oral suction devices.

PURPOSE: The hazards of aerosols generated during dental treatments are poorly understood. This study aimed to establish visualization methods, discover conditions for droplets/aerosols generated in simulating dental treatments and identify the conditions for effective suction methods. METHODS: The spreading area was evaluated via image analysis of the droplets/aerosols generated by a dental air turbine on a mannequin using a light emitting diode (LED) light source and high-speed camera. The effects of different bur types and treatment sites, reduction effect of intra-oral suction (IOS) and extra-oral suction (EOS) devices, and effect of EOS installation conditions were evaluated. RESULTS: Regarding the bur types, a bud-shaped bur on the air turbine generated the most droplets/aerosols compared with round-shaped, round end-tapered, or needle-tapered burs. Regarding the treatment site, the area of droplets/aerosols produced by an air turbine from the palatal plane of the anterior maxillary teeth was significantly higher. The generated droplet/aerosol area was reduced by 92.1% by using IOS alone and 97.8% by combining IOS and EOS. EOS most effectively aspirated droplets/aerosols when placed close (10 cm) to the mouth in the vertical direction (0°). CONCLUSIONS: The droplets/aerosols generated by an air turbine could be visualized using an LED light and a high-speed camera in simulating dental treatments. The bur shape and position of the dental air turbine considerably influenced droplet/aerosol diffusion. The combined use of IOS and EOS at a proper position (close and perpendicular to the mouth) facilitated effective diffusion prevention to protect the dental-care environment.

Significant increase in the prevalence of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus, particularly the USA300 variant ΨUSA300, in the Japanese community.

IMPORTANCE: USA300 is an MRSA clone producing PVL, a toxin associated with SSTIs. ΨUSA300 is a USA300 variant recently identified in Japan by Takadama et al. (15). Here, we found that the prevalence rate of PVL-positive MRSA in S. aureus was elevated in the Japanese community, and ΨUSA300 accounted for most of them. ΨUSA300 strains have been isolated from several areas in Japan and were associated with deep-seated SSTIs. This study highlighted the emerging threat posed by ΨUSA300 in Japan.

Long-term Observation in Patients with Duchenne Muscular Dystrophy with Early Introduction of a Standing Program Using Knee-ankle-foot Orthoses.

Objectives: This study investigated the outcomes of the early introduction of a standing program for patients with Duchenne muscular dystrophy (DMD). Methods: This was a retrospective observational study of 41 outpatients with DMD aged 15-20 years. We introduced the standing program using knee-ankle-foot orthoses (KAFO) to slow the progression of scoliosis when ankle dorsiflexion became less than 0° in the ambulatory period. Results: Thirty-two patients with DMD were offered the standing program with KAFO; 12 continued the program until the age of 15 years (complete group) and 20 discontinued the program before the age of 15 years (incomplete group). The non-standing program group included 9 patients. The standing program with KAFO was significantly associated with the Cobb angle at the age of 15 years after adjustment for the duration of corticosteroid use and DMD mutation type (P=0.0004). At the age of 15 years, significant correlations were found between the ankle dorsiflexion range of motion (ROM) and non-ambulatory period (P=0.0010), non-ambulatory period and Cobb angle (P<0.0001), Cobb angle and percent predicted forced vital capacity (P=0.0004), and ankle dorsiflexion ROM and Cobb angle (P=0.0066). In the complete group, the age at ambulation loss (log-rank P=0.0015), scoliosis progression (log-rank P=0.0032), and pulmonary dysfunction (log-rank P=0.0006) were significantly higher than in the non-standing program group. Conclusions: The early introduction of a standing program for DMD patients may prolong the ambulation period and slow the progression of scoliosis and pulmonary dysfunction.

Oral health status of pregnant women in the Republic of Kiribati.

Prenatal dental examinations were performed from June 2012 to May 2013 in the Republic of Kiribati as a Japan International Cooperation Agency support program. We analyzed the examination data and compared it with Japanese data retrospectively to clarify the oral health condition of pregnant women in the Republic of Kiribati. We recorded the DMF index, gingival status, and calculus attachment, analyzed data of 512 pregnant women. We also compared the city and the rural group data. The average number of present teeth, decayed teeth, missing teeth and filled teeth was 26.9, 2.5, 1.1, 0.2, respectively. Pregnant Kiribati women had significantly more decayed teeth and fewer filled teeth, more severe periodontal condition, more calculus deposition, and more severe gingival swelling than pregnant Japanese women. No significant difference was found in missing and filled teeth, but pregnant women in the city group had significantly more decayed teeth and tooth stumps than those in the rural group. Our findings indicate that pregnant women in Kiribati have more decayed teeth, more missing teeth, fewer filled teeth, and more severe periodontal problems than their counterparts in Japan. Additionally, the oral health status of pregnant women in Kiribati could be subject to regional variations. J. Med. Invest. 70 : 110-114, February, 2023.

Effectiveness of PET/CT and VATS for detecting and treating internal mammary lymph node metastasis: a case series.

OBJECTIVE: We occasionally observed internal mammary lymph node metastases of breast cancer in a clinical setting. However, unlike a standard treatment in axillary metastasis, surgical resection for internal mammary lymph node metastasis is not prevalent because of unclear safety and benefits. Thus, we aimed to evaluate the diagnostic ability and clinical outcomes of positron emission tomography/computed tomography and video-assisted thoracoscopic surgery. METHODS: We retrospectively investigated 34 patients with breast cancer with abnormal 18F-fluorodeoxyglucose uptake in internal mammary lymph nodes, at a single centre, between January 2015 and June 2022 and identified 11 female patients (mean age ± SD, 51.5 ± 12.9 years) who underwent video-assisted thoracoscopic surgery resection. Positron emission tomography/computed tomography was used to determine the clinical stage. We reviewed the surgical pathology of eleven and two patients who underwent direct-view internal mammary lymph node resection to calculate the positive predictive value of positron emission tomography/computed tomography. RESULTS: Ipsilateral fluorodeoxyglucose accumulation was observed, with an average maximum standardized uptake value of 8.9 (range, 3.1-24.0). No perioperative complications occurred, and all patients who underwent video-assisted thoracoscopic surgery alone were discharged from the hospital on post-operative day 2 or 3. The estimated positive predictive value was 80%. All patients were alive, and seven of nine patients with metastasis were relapse-free, at a mean follow-up period of 17.9 months (range, 1-51). However, two patients had recurrence at 16 and 14 months after surgery for internal mammary lymph node relapse. CONCLUSIONS: Radiotherapy is the standard treatment for suspected internal mammary lymph node metastasis detected using positron emission tomography/computed tomography; however, we could safely perform minimally invasive video-assisted thoracoscopic surgery resection, leading to a definite pathological diagnosis.

High-accuracy prediction of axillary lymph node metastasis in invasive lobular carcinoma using focal cortical thickening on magnetic resonance imaging.

BACKGROUND: Invasive lobular carcinoma (ILC) grows diffusely in a single-cell fashion, sometimes presenting only subtle changes in preoperative imaging; therefore, axillary lymph node (ALN) metastases of ILC are difficult to detect using magnetic resonance imaging (MRI). Preoperative underestimation of nodal burden occurs more frequently in ILC than in invasive ductal carcinoma (IDC), however, the morphological assessment for metastatic ALNs of ILC have not fully been investigated. We hypothesized that the high false-negative rate in ILC is caused by the discrepancy in the MRI findings of ALN metastases between ILC and IDC and aimed to identify the MRI finding with a strong correlation with ALN metastasis of ILC. METHOD: This retrospective analysis included 120 female patients (mean ± standard deviation age, 57.2 ± 11.2 years) who underwent upfront surgery for ILC at a single center between April 2011 and June 2022. Of the 120 patients, 35 (29%) had ALN metastasis. Using logistic regression, we constructed prediction models based on MRI findings: primary tumor size, focal cortical thickening (FCT), cortical thickness, long-axis diameter (LAD), and loss of hilum (LOH). RESULTS: The area under the curves were 0.917 (95% confidence interval [CI] 0.869-0.968), 0.827 (95% CI 0.758-0.896), 0.754 (95% CI 0.671-0.837), and 0.621 (95% CI 0.531-0.711) for the FCT, cortical thickness, LAD, and LOH models, respectively. CONCLUSIONS: FCT may be the most relevant MRI finding for ALN metastasis of ILC, and although its prediction model may lead to less underestimation of the nodal burden, rigorous external validation is required.

A 19-Year Study of Dental Needlestick and Sharps Injuries in Japan.

BACKGROUND: Needlestick and sharps injuries (NSIs) are serious problems for dental health care workers (DHCWs) because they are at risk for occupational blood-borne infections. In this study, risk factors for NSIs in DHCWs at Tohoku University Hospital (TUH) in Japan over 19 years were analysed. METHODS: NSI data of DHCWs at TUH from April 2002 to March 2020 were collected from the Exposure Prevention Information Network (EPINet) and statistically analysed. RESULTS: A total of 195 NSIs occurred during the 19-year study period. Approximately 58.5% of NSIs occurred in DHCWs with less than 5 years of experience. Injection needles were the most frequent cause of NSIs (19.0%) followed by suture needles (13.3%) and ultrasonic scaler chips (12.8%). Needle injuries occurred mainly on the left hand, whereas ultrasonic scaler chip and bur injuries occurred on the right hand and other body parts whilst DHCWs were placing the instruments back on the dental unit hanging holder without removing the sharps. NSIs from other instruments primarily occurred on both hands and foot insteps during cleanup. No case of occupational blood-borne infection caused by NSIs was observed during the study period at TUH. CONCLUSIONS: NSIs occurred in DHCWs with less experience, and there were associations between the instruments, timing of use, and NSI site. EPINet was considered a valuable tool for monitoring NSIs in order to develop future strategies for minimising NSIs.

Solitary fibrous tumor of male breast: A case report and literature review.

BACKGROUND: Solitary fibrous tumors (SFT) are uncommon mesenchymal neoplasms which can arise in any anatomical location. Pleural SFTs have been most frequently documented; however, breast SFT is an exceedingly rare entity and seldom present in male breast, with only 8 previously reported cases. Recently, STAT6 immunostaining was considered to be a definitive marker of SFT, however, no case of the male breast SFT showing STAT6 positivity preoperatively has been reported. METHODS AND RESULTS: We describe a case of breast SFT in a 73-year-old male patient with a 12-month history of a palpable breast mass. The only associated clinical symptom was bilateral gynecomastia. An ultrasound scan examination revealed an oval, well-circumscribed and hypoechoic mass with hypervascularity. A core-needle biopsy was performed, and microscopic examination with immunohistochemistry confirmed the diagnosis of SFT. He underwent a complete surgical resection with clear margins, and there were no signs of high cellularity, remarkable mitotic activity, pleomorphism, hemorrhage or necrosis. CONCLUSION: A perioperative immunohistochemical evaluation for diffuse and intense nuclear expression of STAT6 was helpful to distinguish SFT from myofibroblastoma. We, herein, describe the first case of SFT in a male breast, confirmed by STAT6 immunostaining positivity. We also conducted a literature review of all previous cases of breast SFTs.

Clinical prediction model based on 18F-FDG PET/CT plus contrast-enhanced MRI for axillary lymph node macrometastasis.

Purpose: Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) are useful for detecting axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC); however, there is limited clinical evidence to demonstrate the effectiveness of the combination of PET/CT plus MRI. Further axillary surgery is not recommended against ALN micrometastasis (lesion ≤2 mm) seen in sentinel lymph nodes, especially for patients who received proper adjuvant therapy. We aimed to evaluate the efficacy of a prediction model based on PET/CT plus MRI for ALN macrometastasis (lesion >2 mm) and explore the possibility of risk stratification of patients using the preoperative PET/CT plus MRI and biopsy findings. Materials and methods: We retrospectively investigated 361 female patients (370 axillae; mean age, 56 years ± 12 [standard deviation]) who underwent surgery for primary IDC at a single center between April 2017 and March 2020. We constructed a prediction model with logistic regression. Patients were divided into low-risk and high-risk groups using a simple integer risk score, and the false negative rate for ALN macrometastasis was calculated to assess the validity. Internal validation was also achieved using a 5-fold cross-validation. Results: The PET/CT plus MRI model included five predictor variables: maximum standardized uptake value of primary tumor and ALN, primary tumor size, ALN cortical thickness, and histological grade. In the derivation (296 axillae) and validation (74 axillae) cohorts, 54% and 61% of patients, respectively, were classified as low-risk, with a false-negative rate of 11%. Five-fold cross-validation yielded an accuracy of 0.875. Conclusions: Our findings demonstrate the validity of the PET/CT plus MRI prediction model for ALN macrometastases. This model may aid the preoperative identification of low-risk patients for ALN macrometastasis and provide helpful information for PET/MRI interpretation.

Effectiveness of third vaccine dose for coronavirus disease 2019 during the Omicron variant pandemic: a prospective observational study in Japan.

The administration of a third booster dose of messenger ribonucleic acid (mRNA) vaccines against coronavirus disease 2019 (COVID-19) has progressed worldwide. Since January 2022, Japan has faced a nationwide outbreak caused by the Omicron variant, which occurred simultaneously with the progression of mass vaccination with the third booster dose. Therefore, this study evaluated the effectiveness of the third dose of vaccine by reverse transcription-polymerase chain reaction (RT-PCR) test using nasopharyngeal swab samples from adults aged ≥ 18 years tested after having close contact with COVID-19 cases between January and May 2022. Participants who completed only one dose were excluded from the study. Among the 928 enrolled participants, 139 had never been vaccinated, 609 had completed two doses, 180 had completed three doses before the swab test, and the overall RT-PCR test positivity rate in each group was 48.9%, 46.0%, and 32.2%, respectively. The vaccine effectiveness of the third dose to prevent infection after close contact was approximately 40% (95% confidence interval: 20-60%), which was the highest at 10-70 days after receiving the third dose. In conclusion, the effectiveness of the three-dose mRNA COVID-19 vaccine after close contact during the Omicron outbreak is approximately 40%.

COVID-19-Related Symptoms during the SARS-CoV-2 Omicron (B.1.1.529) Variant Surge in Japan.

The exact profiles of the clinical symptoms related to the SARS-CoV-2 Omicron variant (B.1.1.529) remain largely uncertain. Therefore, this study aimed to clarify the clinical manifestations of infection with this variant. We enrolled individuals who were tested by quantitative nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) test at a large screening center in a city of Japan during the B.1.1.529 Omicron variant wave between January and May 2022, after contact with COVID-19 patients. Swab tests were planned to be performed approximately 4-5 days after contact. The presence of COVID-19-related symptoms was assessed at the swab test site. Among the 2,507 enrolled individuals, 943 (37.6%) were RT-PCR test-positive and 1,564 (62.4%) were test-negative. Among the 943 PCR test-positive participants, the prevalence of the symptoms was as follows: 47.3% with cough, 32.9% with sore throat, 18.4% with fatigability, 12.7% with fever of ≥ 37.5℃, 9.9% with dyspnea, 2.1% with dysosmia, and 1.4% with dysgeusia. The prevalence of cough, sore throat, dyspnea, and fatigability was higher among adults aged ≥ 18 years than among children and adolescents. The prevalence of dysosmia and dysgeusia remarkably decreased during the Omicron wave (1-3%) compared to during the pre-Omicron variant waves (15-25%). In summary, common COVID-19-related symptoms during the Omicron variant wave included cough and sore throat, followed by fatigability, fever, and dyspnea. The prevalence of most of these symptoms was higher in adults than in non-adults. The prevalence of dysosmia and dysgeusia remarkably decreased with the Omicron variant than with pre-Omicron variants.

Effectiveness of mRNA COVID-19 Vaccines in Japan during the Nationwide Pandemic of the Delta Variant.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remained a major global health concern in 2021. To suppress the spread of infection, mass vaccinations have been performed across countries worldwide. In Japan, vaccinations of the first and second doses for most of the nation were performed during the nationwide outbreak of the B.1.617.2 (Delta) variant with the L452R spike protein mutation, and the effectiveness of the vaccinations to suppress the spread of COVID-19 among the people in Japan remains uncertain. In this study, adults aged ≥18 years, who were in contact with patients with COVID-19 and underwent nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) tests during August and September 2021 at a mass screening test center in Japan, were enrolled. In this period, more than 95% of the COVID-19 infections were reportedly caused by the Delta variant. As a result, a total of 784 adults with recent contact history, including 231 (29.5%) RT-PCR test-positive cases, were enrolled. The test positivity rate was lower in individuals who had been vaccinated twice than in unvaccinated individuals (12.5% vs. 39.0%, p < 0.0001), with the risk ratio of 0.32 (95% confidence interval 0.23-0.46). The vaccine effectiveness was the highest between 7-90 days after the second vaccine dose. In conclusion, two doses of mRNA COVID-19 vaccines effectively suppressed transmission in Japan during the nationwide pandemic of the Delta variant, estimated to have prevented 50-80% of the infection.

Effects of a novel selective PPARα modulator, statin, sodium-glucose cotransporter 2 inhibitor, and combinatorial therapy on the liver and vasculature of medaka nonalcoholic steatohepatitis model.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a disease entity with an increasing incidence, with involvement of several metabolic pathways. Various organs, including the liver, kidneys, and the vasculature, are damaged in NASH, indicating the urgent need to develop a standard therapy. Therefore, this study was conducted to investigate the effects of drugs targeting various metabolic pathways and their combinations on a high-fat diet (HFD)-induced NASH medaka model. METHODS: To investigate the effects of drugs on vascular structures, the NASH animal model was developed using the fli::GFP transgenic medaka fed with HFD at 20 mg/fish daily. The physiological changes, histological changes in the liver, vascular structures in the fin, and serum biochemical markers were evaluated in a time-dependent manner after treatment with selective peroxisome proliferator-activated receptor α modulator (pemafibrate), statin (pitavastatin), sodium-glucose cotransporter 2 inhibitor (tofogliflozin), and their combinations. Furthermore, to determine the mechanisms underlying the effects, whole transcriptome sequencing was conducted using medaka liver samples. RESULTS: Histological analyses revealed significant suppression of fat accumulation and fibrotic changes in the liver after treatment with drugs and their combinations. The expression levels of steatosis- and fibrosis-related genes were modified by the treatments. Moreover, the HFD-induced vascular damages in the fin exhibited milder changes after treatment with the drugs. CONCLUSION: The effects of treating various metabolic pathways on the medaka body, liver, and vascular structures of the NASH medaka model were evidenced. Moreover, to our knowledge, this study is the first to report whole genome sequence and gene expression evaluation of medaka livers, which could be helpful in clarifying the molecular mechanisms of drugs.

Japanese university students' longing for an idealized France and encounters with global English in Europe.

Japanese college students' akogare (meaning "longing") for an idealized West has conventionally been researched and discussed under the assumption that the West is synonymous with Anglophone countries and that an encounter with the West is categorically an international experience. The present study provides new insights by exploring Japanese college students' longing for an idealized France through a content analysis of blogs and reflective entries written by students during or after participating in a French study abroad program. The analysis reveals that Japanese students from prestigious universities display a high level of satisfaction irrespective of how well they are able to use French. This finding, which is intertwined with the nature of fun-oriented study abroad programs, is also related to the widespread use of English in Europe. The linguistic discovery reminds students of the overriding global status of English vis-à-vis French as a regional language. The study provides future research directions and pedagogical implication in light of (1) increasingly fierce competition for the securement of language course takers, which drives the institutional reproduction of language ideologies and the implementation of fun study abroad programs, and (2) the long-term effectiveness of such ideology-driven survival strategies amid the changing popularity of foreign languages in Japan and elsewhere.

COVID-19 Transmission at Schools in Japan.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health concern in 2021. However, the risk of attending schools during the pandemic remains unevaluated. This study estimated the secondary transmission rate at schools using the results of a real-time reverse transcription-polymerase chain reaction (RT-PCR) screening test performed between July 2020 and April 2021, before starting the nationwide mass vaccination. A total of 1,924 students (20 RT-PCR-positive; 1.0%) from 52 schools or preschools were evaluated, together with 1,379 non-adults (95 RT-PCR-positive; 6.9%) exposed to SARS-CoV-2 in non-school environments. Assuming that the infectious index cases were asymptomatic and the transmission at schools followed a Bernoulli process, we estimated the probability of transmission after each contact at school as approximately 0.005 (0.5% per contact) with the current infection prevention measures at schools in Japan (i.e., hand hygiene, physical distancing, wearing masks, and effective ventilation). Furthermore, assuming that all children are capable of carrying the infection, then contact between an index case and 20-30 students per day at schools would yield the expected value for secondary cases of ≥ 1.0, during the 10 days of the infectious period. In conclusion, with the current infection prevention measures at schools in Japan, secondary transmission at schools would occur in approximately every 200 contacts. When considering this rate, compliance with the current infection prevention measures at schools and early detection and quarantine of the index cases would be effective in preventing the spread of COVID-19 at schools.

Risk of delayed bleeding after hot snare polypectomy and endoscopic mucosal resection in the colorectum with continuation of anticoagulants.

BACKGROUND: Current guidelines recommend the temporary discontinuation of anticoagulants before colonoscopic polypectomy, but the effect of this practice on reducing the risk of delayed bleeding after hot snare polypectomy (HSP) and endoscopic mucosal resection (EMR) remains unclear. Our aim was to assess the impact of anticoagulants on the risk of colorectal delayed bleeding after HSP and EMR, and evaluate the necessity of drug withdrawal. METHODS: We reviewed the clinical data of patients with colorectal polyps using antithrombotic drugs who underwent HSP and/or EMR between January 2016 and September 2020 at Nagaoka Red Cross Hospital. After excluding antiplatelet users, patients were classified into those who continued anticoagulants [continuation group: 50 patients (93 lesions)] and those who discontinued anticoagulants [discontinuation group: 87 patients (190 lesions)]. RESULTS: Delayed bleeding occurred in 12 lesions, and there was no significant difference in the incidence rates between the continuation and the discontinuation groups (3.2% vs. 4.7%; P=0.756). Logistic regression analysis showed that continued use of anticoagulants was not a significant risk factor for delayed bleeding compared to anticoagulant discontinuation (odds ratio, 0.670; 95% CI, 0.177-2.537; P=0.556). There was no significant difference in the incidence rate and risk of delayed bleeding, regardless of the length of the anticoagulant withdrawal period. CONCLUSIONS: Continued use of anticoagulants, compared to their discontinuation, did not increase the risk of colorectal delayed bleeding after HSP and EMR. Our results suggest that current guideline recommendations for anticoagulant withdrawal before colonoscopic polypectomy may be reconsidered. TRIAL REGISTRATION: UMIN000040449.

Hard-to-heal wound treatment medical devices: clinical trial protocol in Japan.

In consultation with academia and the Pharmaceuticals and Medical Devices Agency (PMDA), we have developed guidance for drafting protocols for clinical trials concerning medical devices for the healing of hard-to-heal wounds without ischaemia. The guidance summarises the validity of single-arm trials for hard-to-heal wounds, the definition of hard-to-heal wounds without ischaemia, methods of patient enrolment and clinical endpoints. This review focuses on the logical thinking process that was used when establishing the guidance for improving the efficiency of clinical trials concerning medical devices for hard-to-heal wounds. We particularly focused on the feasibility of conducting single-arm trials and also tried to clarify the definition of hard-to-heal wounds. If the feasibility of randomised control trials is low, conducting single-arm trials should be considered for the benefit of patients. In addition, hard-to-heal wounds were defined as meeting the following two conditions: wounds with a wound area reduction <50% at four weeks despite appropriate standards of care; and wounds which cannot be closed by a relatively simple procedure (for example, suture, skin graft and small flaps). Medical devices for hard-to-heal wound healing are classified into two types: (1) devices for promoting re-epithelialisation; and (2) devices for improving the wound bed. For medical devices for promoting re-epithelialisation, we suggest setting complete wound closure, percent wound area reduction or distance moved by the wound edge as the primary endpoint in single-arm trials for hard-to-heal wounds. For medical devices for improving the wound bed, we suggest setting the period in which wounds can be closed by secondary intention or a simple procedure, such as the primary endpoint.

Cybernic treatment with wearable cyborg Hybrid Assistive Limb (HAL) improves ambulatory function in patients with slowly progressive rare neuromuscular diseases: a multicentre, randomised, controlled crossover trial for efficacy and safety (NCY-3001).

BACKGROUND: Rare neuromuscular diseases such as spinal muscular atrophy, spinal bulbar muscular atrophy, muscular dystrophy, Charcot-Marie-Tooth disease, distal myopathy, sporadic inclusion body myositis, congenital myopathy, and amyotrophic lateral sclerosis lead to incurable amyotrophy and consequent loss of ambulation. Thus far, no therapeutic approaches have been successful in recovering the ambulatory ability. Thus, the aim of this trial was to evaluate the efficacy and safety of cybernic treatment with a wearable cyborg Hybrid Assistive Limb (HAL, Lower Limb Type) in improving the ambulatory function in those patients. RESULTS: We conducted an open-label, randomised, controlled crossover trial to test HAL at nine hospitals between March 6, 2013 and August 8, 2014. Eligible patients were older than 18 years and had a diagnosis of neuromuscular disease as specified above. They were unable to walk for 10 m independently and had neither respiratory failure nor rapid deterioration in gait. The primary endpoint was the distance passed during a two-minute walk test (2MWT). The secondary endpoints were walking speed, cadence, and step length during the 10-m walk test (10MWT), muscle strength by manual muscle testing (MMT), and a series of functional measures. Adverse events and failures/problems/errors with HAL were also evaluated. Thirty patients were randomly assigned to groups A or B, with each group of 15 receiving both treatments in a crossover design. The efficacy of a 40-min walking program performed nine times was compared between HAL plus a hoist and a hoist only. The final analysis included 13 and 11 patients in groups A and B, respectively. Cybernic treatment with HAL resulted in a 10.066% significantly improved distance in 2MWT (95% confidence interval, 0.667-19.464; p = 0.0369) compared with the hoist only treatment. Among the secondary endpoints, the total scores of MMT and cadence at 10MWT were the only ones that showed significant improvement. The only adverse effects were slight to mild myalgia, back pain, and contact skin troubles, which were easily remedied. CONCLUSIONS: HAL is a new treatment device for walking exercise, proven to be more effective than the conventional method in patients with incurable neuromuscular diseases. TRIAL REGISTRATION: JMACTR, JMA-IIA00156.

Discriminatory Value of Self-reported Olfactory Dysfunction in the Prediction of Coronavirus Disease 2019.

Objective Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), remains the world's largest public health concern in 2021. A history of close contact with infectious patients is a factor that predicts a positive SARS-CoV-2 test result. Meanwhile, the precise predictive value of symptoms suggestive of COVID-19 has not been fully elucidated. This study aimed to clarify the predictive and discriminatory value of each clinical symptom suggestive of COVID-19. Methods This study enrolled participants who were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction using a nasopharyngeal swab between November 2020 and January 2021. All enrolled patients were evaluated for data regarding the presence and closeness of contact with infectious patients and comprehensive clinical features (i.e., fever, cough, dyspnea, fatigue, dysosmia, and dysgeusia). Results Among the 1,744 tested participants, 144 tested positive for SARS-CoV-2. In the test-positive group, self-reported cough, fatigue, dysosmia, and dysgeusia were significant predictors of COVID-19, independent from a history of close contact. In particular, the presence of dysosmia was the strongest predictor of COVID-19 in both univariate and multivariate analyses. Among the 42 patients with self-reported dysosmia, 25 (59.5%) were SARS-CoV-2 test-positive. Self-reported dysosmia was reported by 25 (17.4%) of the 144 patients who tested positive for SARS-CoV-2, and 15 (60.0%) of the 25 COVID-19 patients with dysosmia had accompanying dysgeusia. Conclusion The presence of dysosmia was reported by 10-25% of patients with COVID-19, and is a significant predictor of COVID-19 infection, independent from a history of close contact.