Oral alkalinizing supplementation suppressed intrarenal reactive oxidative stress in mild-stage chronic kidney disease: a randomized cohort study.

BACKGROUND: The beneficial effects of oral supplements with alkalinizing agents in patients with chronic kidney disease (CKD) have been limited to the severe stages. We investigated whether two types of supplements, sodium bicarbonate (SB) and potassium citrate/sodium citrate (PCSC), could maintain renal function in patients with mild-stage CKD. METHODS: This was a single-center, open-labeled, randomized cohort trial. Study participants with CKD stages G2, G3a, and G3b were enrolled between March 2013 and January 2019 and randomly assigned by stratification according to age, sex, estimated glomerular filtration rate (eGFR), and diabetes. They were followed up for 6 months (short-term study) for the primary endpoints and extended to 2 years (long-term study) for the secondary endpoints. Supplementary doses were adjusted to achieve an early morning urinary pH of 6.8-7.2. We observed renal dysfunction or new-onset cerebrovascular disease and evaluated urinary surrogate markers for renal injury. RESULTS: Overall, 101 participants were registered and allocated to three groups: standard (n = 32), SB (n = 34), and PCSC (n = 35). Two patients in the standard group attained the primary endpoints (renal stones and overt proteinuria) but were not statistically significant. There was one patient in the standard reduced eGFR during the long-term study (p = 0.042 by ANOVA). SB increased proteinuria (p = 0.0139, baseline vs. 6 months), whereas PCSC significantly reduced proteinuria (p = 0.0061, baseline vs. 1 year, or p = 0.0186, vs. 2 years) and urinary excretion of 8-hydroxy-2'-deoxyguanosine (p = 0.0481, baseline vs. 6 months). CONCLUSION: This study is the first to report supplementation of PCSC reduced intrarenal oxidative stress in patients with mild-stage CKD.

Predictors for the Development of Hypoxia or Prolonged Acute Symptoms among Non-Hospitalized Mild-to-Moderate Patients with Coronavirus Disease 2019.

The coronavirus disease 2019 (COVID-19) pandemic remains a global public health concern. The clinical course and risk of developing severe illness among patients with COVID-19 who are at low-risk of severe COVID-19 remain uncertain. This retrospective cohort study from an isolation facility for low-risk COVID-19 patients in Japan evaluated the potential risks for severe disease with hypoxia (SpO2 ≤ 93%) or experiencing prolonged isolation period longer than 14 days with persistent acute symptoms. The study was performed before the spread of the alpha variant in the country and before the start of a nationwide mass vaccination campaign against COVID-19. Among the 929 participants with reliable outcome data regarding the development of hypoxia, 63 (6.8%) developed severe disease with hypoxia during their stays at the facility. Higher age [adjusted odds ratio (aOR), 1.08; 95% confidence interval (CI), 1.06-1.10] and male sex (aOR, 4.70; 95% CI, 2.39-9.22) were associated with this outcome. As for the experience of prolonged isolation period, higher age (aOR, 1.02; 95% CI, 1.01-1.04), atopic diseases (aOR, 1.69, 95% CI, 1.09-2.64), presence of cough at onset (aOR, 1.64; 95% CI, 1.09-2.48), and prescription of oral antibiotics before positive test results for COVID-19 (aOR, 2.37; 95% CI, 1.33-4.22) were associated with this outcome. In summary, 5-10% of low-risk COVID-19 patients later develop hypoxia. Older age and male sex were associated with both the development of hypoxia and prolonged acute symptoms. The unnecessary prescription of antibiotics before COVID-19 diagnosis may prolong COVID-19 symptoms.

Refractory Chest Pain in Mild to Moderate Coronavirus Disease 2019 Successfully Treated with Saikanto, a Japanese Traditional Medicine.

Coronavirus disease 2019 (COVID-19) causes a variety of pain symptoms in the acute phase. Severe chest pain suddenly occurs even without abnormalities on examination and is sometimes refractory to analgesics. Such pain is a clinical concern in care facilities with limited resources, and this is the first report on the use of saikanto for its treatment. In Miyagi Prefecture, Japan, COVID-19 patients with mild symptoms were admitted to a hotel that operated as an isolation facility, and their symptoms were observed. In this article, we report four cases in which chest pain comorbid with mild to moderate COVID-19 was successfully treated with saikanto, a traditional Japanese (Kampo) medicine. The patients presented with chest pain and underwent medical examination at the facility. Two patients had severe chest pain refractory to acetaminophen. Critical cardiopulmonary diseases were ruled out in all the patients, and three patients had features of pneumonia on chest radiograph. Medications, including saikanto, were administered to the patients. The patients' chest pain and other symptoms improved 1-4 days after the administration of saikanto, and they left the care facility without hospitalization. The cause of the chest pain experienced by these patients is unclear, but we speculate that it could be minimal pleural inflammation or neuropathy. Previous pharmacological studies have suggested anti-inflammatory and analgesic properties of the crude drugs that constitute saikanto. This case report suggests that saikanto could be a treatment option for chest pain refractory to analgesics in patients with mild to moderate COVID-19.

Response to Glucocorticoid Therapy in Patients with Mild to Moderate Coronavirus Disease 2019 at a Japanese Care Facility.

The fifth wave of the coronavirus disease 2019 (COVID-19) pandemic caused by delta variant infection depleted medical resources, and the Japanese government announced glucocorticoid use for outpatients. An appropriate outpatient-glucocorticoid treatment for COVID-19 has not been established; therefore, we created treatment manuals with indications for glucocorticoid administration in a care facility adequately equipped to manage patients with mild to moderate COVID-19. Thirty-eight patients (24 males, 14 females; mean age 40.5 ± 11.8 years) were treated with glucocorticoids from August 1 to October 1, 2021 [COVID-19 staging, mild (n = 1), moderate I (n = 19), and moderate II (n = 18)]. Patients were treated with 6.6 mg/day d.i.v. or 6 mg/day p.o. dexamethasone, or 20-30 mg/day p.o. prednisolone. The median (25th-75th percentile) number of days from the date of onset to glucocorticoid administration was 8.0 days (7.0-11.25 days). While 24 patients were hospitalized, the condition of 14 improved without hospitalization. The median number of days from glucocorticoid administration to hospitalization was 1.0 day (range, 1.0-1.0 day). In the non-hospitalized patients, the median number of days of glucocorticoid administration was 5.0 days (5.0-5.25 days). The mean number of days from glucocorticoid administration to discharge from the care facility for non-hospitalized patients was 8.4 ± 3.3 days. The adverse reactions among non-hospitalized patients included insomnia (n = 1) and mild liver dysfunction (n = 3). The present method of glucocorticoid administration can be safely used for patients with COVID-19 in care facilities.

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.

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.

Clinical trial monitoring effectiveness: Remote risk-based monitoring versus on-site monitoring with 100% source data verification.

BACKGROUND/AIMS: Traditional on-site monitoring of clinical trials via frequent site visits and 100% source data verification is cost-consuming, and it still cannot guarantee data quality effectively. Depending on the types and designs of clinical trials, an alternative would be combining several monitoring methods, such as risk-based monitoring and remote monitoring. However, there is insufficient evidence of its effectiveness. This research compared the effectiveness of risk-based monitoring with a remote monitoring system with that of traditional on-site monitoring. METHODS: With a cloud-based remote monitoring system called beagle View®, we created a remote risk-based monitoring methodology that focused only on critical data and processes. We selected a randomized controlled trial conducted at Tohoku University Hospital and randomly sampled 11 subjects whose case report forms had already been reviewed by data managers. Critical data and processes were verified retrospectively by remote risk-based monitoring; later, all data and processes were confirmed by on-site monitoring. We compared the ability of remote risk-based monitoring to detect critical data and process errors with that of on-site monitoring with 100% source data verification, including an examination of clinical trial staff workload and potential cost savings. RESULTS: Of the total data points (n = 5617), 19.7% (n = 1105, 95% confidence interval = 18.7-20.7) were identified as critical. The error rates of critical data detected by on-site monitoring, remote risk-based monitoring, and data review by data managers were 7.6% (n = 84, 95% CI = 6.2-9.3), 7.6% (n = 84, 95% confidence interval = 6.2-9.3), and 3.9% (n = 43, 95% confidence interval = 2.9-5.2), respectively. The total number of critical process errors detected by on-site monitoring was 14. Of these 14, 92.9% (n = 13, 95% confidence interval = 68.5-98.7) and 42.9% (n = 6, 95% confidence interval = 21.4-67.4) of critical process errors were detected by remote risk-based monitoring and data review by data managers, respectively. The mean time clinical trial staff spent dealing with remote risk-based monitoring was 9.9 ± 5.3 (mean ± SD) min per visit per subject. Our calculations show that remote risk-based monitoring saved between 9 and 41 on-site monitoring visits, corresponding to a cost of between US$13,500 and US$61,500 per trial site. CONCLUSION: Remote risk-based monitoring was able to detect critical data and process errors as well as on-site monitoring with 100% source data verification, saving travel time and monitoring costs. Remote risk-based monitoring offers an effective alternative to traditional on-site monitoring of clinical trials.

Retrospective study revealed that Zn relate to improvement of swallowing function in the older adults.

BACKGROUND: Zinc is an essential micronutrient for maintaining biological activity. The level of zinc in the blood is known to decrease with age, especially in those over 75 years of age. In older adults patients with impaired functional status, aspiration pneumonia based on dysphagia often becomes problematic. However, the relationship between zinc deficiency and swallowing function has not been studied before. METHODS: A total of 52 older adults subjects (15 males and 37 females) living in a nursing home were enrolled for this study. At the time of enrollment, data of gender, age, body weight, serum zinc levels, serum albumin levels, and the time in a simple 2-step swallowing provocation test (S-SPT) were collected. In patients with serum zinc levels < 60 µg/dL, we initiated 2 months of oral zinc supplementation therapy with a 34 mg/day zinc load. Those who underwent zinc supplementation were re-evaluated after the treatment period and serum zinc levels and S-SPT time were measured. RESULTS: At the time of enrollment, serum zinc level was significantly correlated with serum albumin levels (Pearson's R = 0.58, p < 0.0001) and time in the S-SPT (Spearman's rho = - 0.32, p = 0.0219). Twenty-five of the 52 patients had zinc deficiency with a serum zinc level < 60 µg/dL. After 2 months of oral zinc supplementation, both serum zinc levels (p < 0.0001) and time in the S-SPT (p = 0.04) significantly improved. Meanwhile, serum albumin level (p = 0.48) or body weight (p = 0.07) did not significantly change following zinc supplementation. Zinc supplementation significantly improved swallowing function, especially in the older adults who had comorbid dysphagia and zinc deficiency. CONCLUSIONS: Zinc deficiency is associated with compromised swallowing function in older adults patients with impaired general functions. Oral zinc supplementation can alleviate dysphagia in older adults patients with zinc deficiency even though this is a retrospective study. Further study will be needed to confirm this positive effect.

Treatment of COVID-19-Related Olfactory Disorder Promoted by Kakkontokasenkyushin'i: A Case Series.

Olfactory disorders are one of the characteristic symptoms of the coronavirus disease of 2019 (COVID-19), which causes infection and inflammation of the upper and lower respiratory tract. To our knowledge, there are no treatments for COVID-19-related olfactory disorder. Here, we report five olfactory disorder cases in COVID-19, treated using the Japanese traditional (Kampo) medicine, kakkontokasenkyushin'i. We treated five patients with mild COVID-19 at an isolation facility using Kampo medicine, depending on their symptoms. Patients with the olfactory disorder presented with a blocked nose, nasal discharge or taste impairment. Physical examination using Kampo medicine showed similar findings, such as a red tongue with red spots and sublingual vein congestion, which presented as blood stasis and inflammation; thus, we prescribed the Kampo medicine, kakkontokasenkyushin'i. After administration, the numeric rating scale scores of the smell impairment improved within 3 days from 9 to 3 in case 1, from 10 to 0 in case 2, from 9 to 0 in case 3, from 5 to 0 in case 4, and from 9 to 0 within 5 days in case 5. Following the treatment, other common cold symptoms were also alleviated. Kakkontokasenkyushin'i can be used for treating nasal congestion, rhinitis, and inflammation in the nasal mucosa. The olfactory disorder in COVID-19 has been reportedly associated with inflammation and congestion, especially in the olfactory bulb and olfactory cleft. Kakkontokasenkyushin'i may be one of the treatment alternatives for the olfactory disorder with rhinitis in patients with COVID-19.

Predictors of SARS-CoV-2 Positivity Based on RT-PCR Swab Tests at a Drive-Through Outpatient Clinic for COVID-19 Screening in Japan.

In response to the COVID-19 pandemic caused by SARS-CoV-2 in 2020, we conducted drive-through nasopharyngeal swab testing for COVID-19 in Sendai city, Japan, since April 2020. All tested individuals were judged in advance by public health centers for the necessity of undergoing the test with possible contact history and/or symptoms suggestive of COVID-19. In this study, to identify the predictors of SARS-CoV-2 test positivity for more efficient and evidenced selection of suspected individuals, we enrolled 3,540 consecutive individuals, tested in the first 7 months of the testing program, with data regarding to the history of close contact with COVID-19 patients, including those involved in cluster outbreaks. This cohort included 284 foreign students (257 males and 27 females) from a vocational school involved in the largest cluster outbreak in the area. Close contact history was present in 952 (26.9%) of the participants. The reverse transcription-polymerase chain reaction (RT-PCR) test results showed that 164 participants (4.6%) were positive and 3,376 participants (95.4%) were negative for the SARS-CoV-2 nucleocapsid gene (N2). In the univariate and multivariate analyses, history of close contact with COVID-19 patients, higher age, cough symptoms, and non-native ethnicity were predictors for SARS-CoV-2 test positivity. However, the significance of age and foreign nationality disappeared or declined upon excluding the foreign students from the aforementioned largest cluster outbreak. In conclusion, a history of close contact with COVID-19 patients and the presence of cough symptoms are significant predictors of SARS-CoV-2 test positivity.

Impacts of Natural Environmental Factors and Prevalence of Airway Symptoms on the Local Spread of COVID-19: A Time-Series Analysis in Regional COVID-19 Epidemics.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the world's largest public health concern in 2021. This study evaluated the associations of the prevalence of airway symptoms among the tested individuals and data regarding the natural environmental factors with the weekly number of newly diagnosed COVID-19 patients in Sendai City (Nt). For the derivatives of the screening test results, data from individuals with a contact history who underwent nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) testing between July 2020 and April 2021 (6,156 participants, including 550 test-positive patients) were used. The value of Nt correlated with the weekly RT-PCR test-positive rate after close contact, prevalence of cough symptoms in test-positive individuals or in test-negative individuals, lower air temperature, lower air humidity, and higher wind speed. The weekly test-positive rate correlated with lower air humidity and higher wind speed. In cross-correlation analyses, natural environmental factors correlated with the regional epidemic status on a scale of months, whereas the airway symptoms among non-COVID-19 population affected on a scale of weeks. When applying an autoregression model to the serial data of Nt, large-scale movements of people were suggested to be another factor to influence the local epidemics on a scale of days. In conclusion, the prevalence of cough symptoms in the local population, lower air humidity or higher wind speed, and large-scale movements of people in the locality would jointly influence the local epidemic status of COVID-19.

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.

Genome-wide association study identifies new loci for albuminuria in the Japanese population.

BACKGROUND: Urinary albumin excretion (UAE) is a risk factor for cardiovascular diseases, metabolic syndrome, chronic kidney disease, etc. Only a few genome-wide association studies (GWAS) for UAE have been conducted in the European population, but not in the Asian population. Here we conducted GWAS and identified several candidate genes harboring single nucleotide polymorphisms (SNPs) responsible for UAE in the Japanese population. METHODS: We conducted GWAS for UAE in 7805 individuals of Asian ancestry from health-survey data collected by Tohoku Medical Megabank Organization (ToMMo) and Iwate Tohoku Medical Megabank Organization (IMM). The SNP genotype data were obtained with a SNP microarray. After imputation using a haplotype panel consisting of 2000 genome sequencing, 4,962,728 SNP markers were used for the GWAS. RESULTS: Eighteen SNPs at 14 loci (GRM7, EXOC1/NMU, LPA, STEAP1B/RAPGEF5, SEMA3D, PRKAG2, TRIQK, SERTM1, TPT1-AS1, OR5AU1, TSHR, FMN1/RYR3, COPRS, and BRD1) were associated with UAE in the Japanese individuals. A locus with particularly strong associations was observed on TSHR, chromosome 14 [rs116622332 (p = 3.99 × 10-10)]. CONCLUSION: In this study, we successfully identified UAE-associated variant loci in the Japanese population. Further study is required to confirm this association.

Reno-protective effects of oral alkalizing agents in chronic kidney disease with aciduria: protocol for a randomized cohort study.

BACKGROUND: Aciduria caused by urinary excretion of acidic metabolic wastes produced in daily life is known to be augmented in patients with chronic kidney disease (CKD). To evaluate the reno-protective effect of oral alkalizing agents for the improvement of metabolic acidosis and neutralization of intratubular pH in the patients with mild stages of CKD. Also, to identify reno-protective surrogate markers in the serum and urine that can closely associate the effect of urine alkalization. METHODS: In this single-centered, open-labeled, randomized cohort study, patients with CKD stages G2, G3a and G3b, who visited and were treated at Tohoku University Hospital during the enrollment period were registered. We administered sodium bicarbonate or sodium-potassium citrate as the oral alkalinizing agents. A total of 150 patients with CKD will be randomly allocated into the following three groups: sodium bicarbonate, sodium-potassium citrate and standard therapy group without any alkalinizing agents. The data of performance status, venous blood test, spot urine test, venous blood-gas test, electrocardiogram, renal arterial ultrasonography and chest X-ray will be collected at 0, 6, 12 and 24 weeks (short-term study) from starting the interventions. These data will be also collected at 1 and 2 years (long-term study). The samples of plasma and serum and early-morning urine at every visit will be acquired for the analysis of renal function and surrogate uremic biomarkers. The recruitment for this cohort study terminated in March, 2018, and the follow-up period for all the enrolled subjects will be terminated in December, 2020. The primary endpoint will be the development of originally-defined significant renal dysfunction or the occurrence of any cerebrovascular disease in the short-term study. The secondary endpoint will be the same endpoints as in the long-term study, or the patients with significant changes in the suggested the surrogate biomarkers. DISCUSSION: The findings of this study will address the importance of taking oral alkalizing agents in the patients with early stages of CKD, furthermore they could address any new surrogate biomarkers that can be useful from early stage CKD. TRIAL REGISTRATION: Registered Report Identifier: UMIN000010059 and jRCT021180043. The trial registration number; 150. Date of registration; 2013/02/26.

Importance of Barium Swallow Test and Chest CT Scan for Correct Diagnosis of Achalasia in the Primary Care Setting.

Esophageal achalasia is a disease characterized by the impaired esophageal peristalsis and non-relaxation of the lower esophageal sphincter muscle with unknown causes. Clinical manifestation of the disease is nonspecific (e.g., weight loss, vomiting, and persistent cough); namely, early diagnosis of the disease is often difficult. Delayed diagnosis of the disease is known to impair the patients' quality of life. Identifying the diagnostic factors that could cause diagnostic delay is needed. In this study, we collected data from 38 patients with achalasia and searched for diagnostic factors associated with delayed diagnosis (i.e., ≥ 6 months from the first hospital visit to diagnosis). The enrolled patients, diagnosed with achalasia based on esophageal manometry findings, had undergone surgical myotomy. As a result, the diagnosis of achalasia was likely to be delayed when the physician who had first contacted the patient did not perform a barium swallow test (p < 0.0001) or chest CT scan (p < 0.01) in a timely fashion. Among the patients with a delayed diagnosis (n = 15), none underwent a barium swallow test or chest CT within 6 months from their first hospital visit. The estimated sensitivities of diagnostic examinations for achalasia based on the enrolled 38 patients were higher than 80% for the barium swallow test and chest CT scan, but only 50-81% for endoscopy. To avoid the delayed diagnosis of achalasia, performing a barium swallow test or chest CT scan in a timely fashion, in addition to routine endoscopy, appears to be highly important.

Application of Large Electronic Medical Database for Detecting Undiagnosed Patients in the General Population.

Clinical application of accumulated medical big data is a hot topic in medical informatics. Not only for suggesting possible diagnoses in each individual, large medical database can be possibly used for detecting undiagnosed patients in the general population. In this study, we tried to develop a computerized system of detecting overlooked undiagnosed patients with rare chronic diseases in the community population by utilizing the uniformed national medical insurance record database. A cumulative total of 489,823 hospital visits at one tertiary medical center were collected for this project. As the target disease, we selected esophagogastric junction outflow obstruction (EGJOO), including achalasia, which is known to be easily overlooked without performing a barium swallow test. Patient selection software automatically picked out 17,814 individuals with the given suspected diagnoses that could be misdiagnosed in patients with the target disease, from which the software further picked out 526 individuals who underwent upper endoscopy but did not undergo barium swallow test. Of them, the hospital medical records suggested that 39 people still suffered from prolonged symptoms lasting for more than 6 months after the first hospital visit. Among them, 16 individuals agreed to undergo the barium swallow test. One of them was confirmed to suffer from EGJOO, possibly based on some undiagnosed connective tissue diseases. An automated computerized detection system with uniform big medical data would realize more efficient and less expensive screening system for undiagnosed chronic diseases in the general population based on symptoms and previously performed examinations in each individual.

Low frequency of cervicocranial artery involvement in Japanese with renal artery fibromuscular dysplasia compared with that of Caucasians.

BACKGROUND: Fibromuscular dysplasia (FMD), which usually affects the renal artery, also affects the carotid, vertebral, and intracranial arteries. Previous studies have shown a high prevalence of concomitant renal artery and cervicocranial lesions in FMD patients. However, the analyzed subjects were mostly Caucasians in Western countries. METHOD: We performed a retrospective analysis to examine the prevalence of cervicocranial vascular lesions in Japanese FMD patients with renal artery involvement at a single institution. The presence of cervicocranial lesions was evaluated by Doppler echography and magnetic resonance angiography. We compared this prevalence with that reported in the literature. RESULT: Thirty-one Japanese FMD patients with renal artery lesions were studied. The mean age was 30 ± 12 years, 71% were women, and 16% were smokers; all patients were Asians and had hypertension. Multifocal, tubular, and unifocal types of renal lesions were found in 52, 35, and 13% of patients, respectively. Bilateral renal lesions were found in 13% of patients. None of the patients had a cervical vascular lesion associated with FMD. Only two patients (8%) had a lesion in the intracranial artery, of which one was a known case of moyamoya disease. CONCLUSION: These findings suggest that cervical artery involvement and intracranial artery involvement are not common in renal FMD patients in Japan, which is in contrast to the data reported for Caucasian patients in Western countries. Ethnic differences could influence the occurrence of cervicocranial lesions. A study with a larger sample size should be performed to validate these findings.

Improving the Quality of Postgraduate Education in Traditional Japanese Kampo Medicine for Junior Residents: An Exploratory Survey Conducted in Five Institutions in the Tohoku Area.

Traditional Japanese (Kampo) medicine has been widely applied in general medicine in Japan. In 2001, the model core curriculum for Japanese medical education was revised to include Kampo medicine. Since 2007, all 80 Japanese medical schools have incorporated it within their programs. However, postgraduate training or instruction of Kampo medicine has not been recognized as a goal for the clinical training of junior residents by Japan's Ministry of Health, Labour and Welfare; little is known about postgraduate Kampo medicine education. This exploratory study investigated attitudes about Kampo medicine among junior residents in Japanese postgraduate training programs. A questionnaire survey was administered to junior residents at five institutions in the Tohoku area of Japan. Questions evaluated residents' experiences of prescribing Kampo medicines and their expectations for postgraduate Kampo education and training. As a result, 121 residents responded (response rate = 74%). About 96% of participants had previously received Kampo medicine education at their pre-graduate medical schools and 64% had prescribed Kampo medications. Specifically, daikenchuto was prescribed to prevent ileus and constipation after abdominal surgery and yokukansan was prescribed to treat delirium in the elderly. Residents received on-the-job instruction by attending doctors. Over 70% of participants indicated that there was a need for postgraduate Kampo medicine education opportunities and expected lectures and instruction on how to use it to treat common diseases. In conclusion, we have revealed that junior residents require Kampo medicine education in Japanese postgraduate training programs. The programs for comprehensive pre-graduate and postgraduate Kampo education are expected.

Questionnaire-Based Development of an Educational Program of Traditional Japanese Kampo Medicine.

Traditional Japanese Kampo medicine has been widely used in clinical practice in Japan. Though it is a compulsory subject in Japanese medical schools, a standard educational program in Kampo medicine does not exist. Tohoku University has incorporated Kampo medicine into clinical education via didactic lectures since 2003; however, student evaluations have been lower for Kampo than for all other clinical specialties. We administered a questionnaire about a Kampo medicine course for fifth-year students from 2009 to 2012 and developed an educational program based on feedback obtained. The questionnaire consisted of nine questions (a clear training plan; opportunities for learning, practice, and patient contact; acquisition of medical knowledge and physical examination; learning professionalism; understanding the specialty; overall assessment) that were rated on a 5-point Likert scale along with open-ended questions about the course's strengths and weaknesses. The students responded to the questionnaire after clinical practice in Kampo medicine and other clinical specialty courses. Scores for Kampo medicine and the average of other clinical specialties were compared. All 389 students who participated in Kampo clinical practice answered the questionnaire. In 2009, scores for Kampo medicine for nine questions were lower than for the average of the other clinical specialties. After curriculum reformation involving hands-on training in 2012, all scores except "opportunities to learn about clinical cases" and "opportunities to practice involvement" were higher than the average of all other clinical specialties. In conclusion, we have successfully developed a Kampo medicine educational program for our university through this survey study.