Clinical Effectiveness of REGN-COV2 in Patients with COVID-19 in Japan:A Retrospective Cohort Study with a Bayesian Inference

Background@#Neutralizing antibody cocktail therapy, REGN-COV2, is promising in preventing a severe form of coronavirus disease 2019 (COVID-19), but its effectiveness in Japan has not been fully investigated. @*Materials and Methods@#To evaluate the effectiveness of REGN-COV2, clinical data of 20 patients with COVID-19 who received REGN-COV2 was compared with the control by matching age and sex. The primary outcome was the time from the onset to defervescence, the duration of hospitalization, and oxygen requirement. A sensitivity analysis using Bayesian analysis was also conducted. @*Results@#The time to defervescence was significantly shorter in the treatment group (5.25 vs. 7.95 days, P = 0.02), and so was the duration of hospitalization (7.115 vs. 11.45, P = 0.0009). However, the oxygen therapy requirement did not differ between the two groups (15% vs. 35%, P = 0.27). For Bayesian analysis, the median posterior probability of the time to defervescence since the symptom onset on the REGN-COV2 group was 5.28 days [95% credible interval (CrI): 4.28 - 6.31 days], compared with the control of 7.99 days (95% CrI: 6.81 - 9.24 days). The posterior probability of the duration of the hospitalization on the REGN-COV2 group was 7.17 days (95% CrI: 5.99 - 8.24 days), compared with the control of 11.54 days (95% CrI: 10.28 - 13.14 days). The posterior probability of the oxygen requirement on the REGN-COV2 group was 18% (95% CrI: 3 - 33%), compared with the control of 36% (95% CrI: 16 - 54%). @*Conclusion@#REGN-COV2 may be effective in early defervescence and shorter hospitalization. Its effectiveness for preventing a severe form of infection needs to be evaluated by further studies.

Two Cases of Chronic Cough Successfully Treated with Kumibinroto / 日本東洋医学雑誌

Cough-variant asthma is the most common cause of chronic cough. It may progress to classic asthma and therefore requires adequate treatment intervention. We experienced two cases of cough-variant asthma that was refractory to standard drug therapy but improved after additional administration of kumibinroto. In Case 1, the patient was a 46-year-old woman receiving hormone therapy after breast cancer surgery. She developed cough-variant asthma 5 years ago, and though she has received drug therapy, the symptoms aggravated. Cough continued to appear at night without improvement of asthma symptoms. However, the symptoms improved with subsequent administration of kumibinroto. In Case 2, the patient was a 47-year-old woman who developed cough-variant asthma after childbirth, which repeatedly worsened and improved. The cough-variant asthma aggravated after change of workplace and did not improve with drug therapy. However, asthma symptoms improved with oral administration of kumibinroto and hangekobokuto, and subsequent administration of kumibinroto alone. In both patients, the asthma was seasonal. These cases suggest that kumibinroto administration may contribute to the improvement of cough-variant asthma.

Hybrid Educational Activities between TBL And PBL Program (HEAT APP) for Cambodian Medical Students and Postgraduate Trainees. A Novel Approach in an Asian Setting / 医学教育

<p> Cooperative, active learning such as Problem-Based Learning, or PBL, and Team-Based Learning, or TBL, is gaining popularity in medical education in Asian countries. Cambodia has been exposed to few, if any, such educational methodologies. Here, the author conducted a week of Hybrid Educational Activities between TBL And PBL Program (HEAT APP) with Cambodian medical students and postgraduate trainees. Further practices and studies will clarify the real value in this specific setting.</p>

The applicability of "Bushido" to Professionalism, and the "Eyes of Others" / 医学教育

<p>　There was a debate on the applicability of "Bushido" to professionalism among Japanese physicians. Regardless of the historical aspects upon the writing of "Bushido" by Inazo Nitobe, "Bushido" can be applicable to professionalism. This conclusion leads to the fact that one cannot avoid the fundamental discussion on the influence of the "Eyes of Others" when evaluating the professionalism of each physician. This suggests that the evaluation, a concept in the field of education regarded as "given" , is essentially an obstacle when it comes to the matter of education for professionalism.</p>

The reform of faculty development workshop at Kobe University Hospital: To be more independent and proactive / 医学教育

Introduction: Kobe University Hospital’s faculty development workshop was unattractive, and people attended it passively.<br>Methods: We attempted to improve the workshop so that faculty would want to attend it independently and proactively. In this report we summarize the changes in the workshop and report the results of questionnaires administered before （2008） and after （2012） the change.<br>Results: Overall contents of the faculty development workshop became more open, and such practices as the Kawakita Jiro method stopped being used. Overall scores for participant satisfaction improved significantly from 2008 to 2012, but the duration of the workshop did not change significantly.<br>Discussion: We improved the quality of the faculty development workshop and increased participant satisfaction. We should continue to improve the workshop through proper assessment.

<b>Development of A Decision Making Model for the Management of Influenza. A Proposal of Diagnostic Policy </b><b>Based on Phenomena and Therapeutics. </b> / 日本東洋医学雑誌

The management of influenza has dramatically changed since the introduction of the rapid influenza diagnostic test, or RIDT, and neuraminidase inhibitors (NI). However, it is still far from optimal due to low RIDT sensitivity and problems involving NI such as side effects and the potential emergence of resistant virus.Therefore, we developed a decision-making model for the management of influenza, which includes Kampo medicines in its strategies. First, the severity of patients is evaluated. If a patient is judged at severe or high-risk, intravenous NI would be the main component of treatment. If a patient has neither a severe condition nor is at high-risk, the patient would be asked to choose either NI or Kampo medicine. In the former, RIDT would be used if pretest probability was less than 50%, but it would not be used if it was more than 50%, based on the lack of influence on the post-test probability. For the latter, RIDT would be not used in general as Kampo targets “phenomena”, not the virus <i>per se</i>. This model enables us to optimize the use of RIDT by appropriately selecting patients based on the characteristics of RIDT, and by avoiding unnecessary tests and their misinterpretation.

Gingyo Gedokusan vs Oseltamivir for the Treatment of Uncomplicated Influenza and Influenza-like illness : An Open-label Prospective Study / General Medicine

<b>Background:</b> Gingyo-gedoku-san (GGGS) is an herbal medicine approved for upper respiratory infections in Japan. We conducted an open-label, multi-center, prospective trial, comparing GGGS with oseltamivir in patients with influenza and influenza-like illness (ILI) as a pilot study.<br><b>Methods:</b> Subjects were healthy persons aged between 16 and 40, and were enrolled from January 12, 2010 to March 24, 2011. Fifteen patients were enrolled in this trial (8 and 7 for GGGS and oseltamivir, respectively). RT-PCR was positive for pandemic influenza A (H1N1) in 10 patients. The patients were provided with either GGGS or oseltamivir for 5 days. The primary outcome was mortality and/or hospitalization 7 days after the initial diagnosis. Body temperature and other clinical characteristics were also evaluated.<br><b>Results:</b> All patients recovered from illness without complication or hospitalization. The mean time to resolve symptoms for the GGGS and oseltamivir groups was 3.9 days and 3.3 days, respectively (p=0.43). The GGGS group appeared to have a smaller symptom score AUC than the oseltamivir group, (p=0.26). Time to recover activity level appeared to be shorter in the GGGS group (p=0.10), with shorter time to recover health status (p=0.02). Sub-group analysis on patients with positive PCR showed similar results between the two groups.<br><b>Conclusion:</b> GGGS was associated with symptom improvements resembling oseltamivir for both influenza and ILI. Randomized controlled trials involving larger sample sizes are needed to confirm these results.

<b>A Case of Intestinal Spirochete Infection Treated with </b><b>Daikenchuto Extract</b> / 日本東洋医学雑誌

Intestinal spirochetosis is a rare gastrointestinal infection caused by <i>Brachyspira</i>. Clinical manifestations vary, ranging from asymptomatic infection to gastrointestinal bleeding, diarrhea, or abdominal pain. Antimicrobial medications such as metronidazole are routinely given, but their clinical efficacy has not determined with any precision. We report a case of intestinal spirochetosis treated with daikenchuto extract with literature reviews. Treatment of intestinal spirochetosis can be difficult, and use of daikenchuto extract may be an option especially for patients with symptoms such as chronic diarrhea, abdominal distention, or change in flatus.

Case of Recurrent Fever With Apparent Response to Antibiotic: Overcoming "CRP dependency" / General Medicine

A 23-year old female was referred to our clinic for intermittent fever occurring over a period of eight years. Every time she developed fever, blood examination revealed elevated leukocytes and C-reactive protein (CRP). Antibiotics were always given based on elevated CRP with apparent improvement. However, the pattern of periodicity with absence of symptoms in between suggested periodic fever syndrome, particularly Familial Mediterranean Fever (FMF), which was later confirmed by mutation analysis. In Japan there is a tendency to use antibiotics solely based on "elevated CRP"; however, careful review of patient history is essential to identify FMF while avoiding the use of unnecessary antibiotics.