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Polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome are common inflammatory rheumatic diseases in the elderly. In this study, we investigated the difference of the therapeutic responses between patients with PMR and RS3PE syndrome. Twenty-four patients with PMR and 12 patients with RS3PE syndrome were treated with initial dosages of 10-20 mg per day oral prednisolone, and the dosages were then tapered. Percentages of patients with negative c-reactive protein (CRP) after 8-week treatment were significantly more in RS3PE syndrome than in PMR. Percentages of patients with relapse during one-year treatment were less likely to be in RS3PE syndrome than in PMR. These differences observed between the two disorders were not associated with the level of initial CRP. There was no significant difference in percentages of patients with prednisolone-free remission after two-year treatment between PMR and RS3PE syndrome. These results indicate that the early response to the treatment is greater in RS3PE syndrome than in PMR. J. Med. Invest. 70 : 145-149, February, 2023.

The popularity of online classes in university education has grown rapidly since the COVID-19 outbreak. This study aims to examine the association between the detailed characteristics/various contexts of students and the evaluation of online classes. An online questionnaire survey administered to third- and fourth-grade medical students of Tokushima University in September 2021-with 101 (42.8%) valid responses-showed the respondents' general impressions, comprehension, convenience, and desire for online classes even after the pandemic ends were significantly higher for the on-demand lectures than for simultaneous online classes. Notably, students who did not do other things while watching video lectures (10.9%) rated on-demand lectures as facilitating significantly higher impression, comprehension, and convenience than those who did other things (89.1%). A multivariate analysis revealed that students who did not do anything else while watching, whose waking time changed slightly, who commuted to school for shorter periods, who were not good at morning lectures, and who watched at high speed rated the video lectures highly. Thus, video lectures are appreciated by students who are committed to learning, which is a positive result for the future of on-demand education. J. Med. Invest. 70 : 483-493, August, 2023.

Geographic maldistribution of physicians is a serious problem in Japan, resulting in a few physicians in remote areas. We distributed questionnaires to 396 medical students at Tokushima University from 2013 to 2016. We examined the intensity of medical students toward medicine in remote areas by using a visual analog scale and investigated what medical specialty they chose after two years of clinical training. The intensity of interest in medicine and the intensity of willingness to contribute to it in remote areas were statistically higher among medical students who intended to choose general medicine. After graduation, only five participants chose to specialize in general medicine. Of the 14 medical students who originally chose general medicine, six chose internal medicine, three chose general medicine, and the others chose surgery, neurosurgery, anesthesiology, orthopedics, or emergency medicine. This study demonstrated that medical students who intend to choose general medicine have a higher intensity of willingness to contribute to medicine in remote areas, indicating that the support program for these students to become general practitioners after graduation increases the number of physicians in remote areas. J. Med. Invest. 70 : 129-134, February, 2023.

In recent years, Japan has promoted home visits to support older adults, with caregivers playing an important role. However, caregivers generally experience a high frequency of anxiety and depression, and the factors associated with these conditions among home visit caregivers remain unknown. To identify the associated factors, we conducted a questionnaire-based cross-sectional study of home visit caregivers in Tokushima Prefecture, Japan. The survey included caregivers' Hospital Anxiety and Depression Scale;sociodemographic items of patients and caregivers;and caregivers' perceptions of the home care environment, patients, and themselves. The questionnaires were sent to 379 caregivers;203 responded (53.6% response rate), of which 173 were valid (85.2% valid response rate). The prevalence of anxiety and depression was 43.9% and 69.4%, respectively. Multiple logistic regression analysis of factors associated with anxiety and depression showed that stable family finances (OR:0.69, 95% CI:0.48-1.00, p=0.049) and stable caregiver health (OR:0.45, 95% CI:0.30-0.68, p<0.001) were associated with anxiety. Further, stable family finances (OR:0.60, 95% CI:0.38-0.93, p=0.022), stable caregiver health (OR:0.49, 95% CI:0.30-0.81, p=0.005), and stable patient condition (OR:0.51, 95% CI:0.29-0.92, p=0.025) were associated with depression. These findings demonstrate that caregiver wellbeing is essential in home care settings. J. Med. Invest. 70 : 443-449, August, 2023.

Background : Rheumatoid arthritis (RA), an autoimmune disease of unknown etiology, is believed to occur as the result of actions of genetic and environmental factors. In this study, we examined the relation of past histories about infectious diseases with the levels anti-citrullinated protein autoantibodies (ACPA) in RA. Methods : Results of a questionnaire about histories of infectious diseases were obtained from 85 patients with RA, and were analyzed. Results : Significantly lower level of ACPA was detected in patients with the history of tonsillitis, otitis media or urinary cystitis than in those without it. There was no difference in the level of ACPA in RA patients between with and without cold / influenza, rubella, chickenpox, herpes labialis or herpes zoster. When RA patients were divided into two groups, high-level and low-level ACPA, multiple logistic regression analysis revealed that the history of otitis media was a significantly independent factor for the low level of ACPA. There was no significant relation between the level of rheumatoid factor and histories of infectious diseases. Conclusion : This study clarified that the past history of otitis media is associated with the low level of ACPA in RA. J. Med. Invest. 67 : 182-188, February, 2020.

[Introduction] The purpose of this study was to investigate the differences in the preference of enteral tube feeding between elderly inhabitants of Mugi town, Tokushima Prefecture, Japan, and their parents in various physical conditions. [Methods] This population-based questionnaire survey studied 300 randomly selected participants aged 65-80 years. Respondents were to consider a situation where eating was difficult, and were questioned on their desire for tube feeding, using a visual analogue scale (VAS) ranging from "do not want tube feeding (0)" to "want tube feeding (100)." [Results] Valid responses of 103 (34.4%) participants were analyzed. Under conditions of being "healthy," "bedridden," "with dementia," and "bedridden and with dementia," the median (IQR) of the VAS values for the desire for tube feeding were 31.8 (3.3 to 83.8), 19.3 (2.4 to 52.3), 5.2 (0.7 to 18.9), 4.0 (0.3 to 15.2) for respondents and 55.2 (11.6 to 92.2), 48.7 (5.5 to 85.5), 9.0 (1.2 to 46.8), 5.1 (0.1 to 36.5) for parents, respectively. The VAS values for the parents were significantly higher (p=0.001, 0.002, 0.001, and 0.01, respectively for the four conditions described) for the same items. [Conclusion] Surrogate decisions made by family members often differ from what the patients would have desired. J. Med. Invest. 66 : 258-263, August, 2019.

Polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome are common inflammatory rheumatic diseases in the elderly. In this study, we investigate predictive factors which correspond to subsequent disease control of PMR and RS3PE syndrome. Twenty four patients, which contained 18 PMR and 6 RS3PE syndrome, were treated with initial dosages of 10-20 mg per day oral prednisolone, and the dosage of prednisolone was then tapered. Significantly higher initial CRP was observed in patients with poor disease control than in those with good disease control afterwards. The number of patients with negative CRP after 4 weeks was significantly more in patients with good disease control after 1 year than in those with poor disease control. Patients were shown to be in good disease control status after 1 year when CRP after 4 weeks became negative even if they had initial high CRP. Our study clarify that to make CRP negative after 4 weeks is associated with subsequent suppression of the disease activity and with decreased dosages of corticosteroids. J. Med. Invest. 66 : 112-118, February, 2019.

We administered a questionnaire to 5 th grade medical students to examine the effect of community-based clinical practice on their attitudes to remote area medicine and their course after the graduation. Data from 192 students were obtained. The intensity of students' attitudes was estimated by using visual analogue scale. The intensities of the interest and a sense of fulfillment in remote area medicine were significantly increased after the practice. A significantly lower level of the intensity to become a generalist than that to become a specialist was seen in the students with low intensity in a sense of fulfillment. The percentages of the students who answered that they can work for 5 years or more in remote area were significantly lower in students with low intensity of a sense of fulfillment than in those with high intensity. A significantly higher percentage in students who worked at a familiar prefecture to them after the graduation was seen in female than in male. This study shows that the community-based practice is meaningful in increasing motivation which desire to work in remote area medicine, and that the motivation may affect their course after the graduation. J. Med. Invest. 64: 210-216, August, 2017.

The terminal elimination half-life (t1/2) of empagliflozin is 13.1 hours. Accordingly, we hypothesized that the administration of empagliflozin every other day might improve glycemic control in patients with type 2 diabetes mellitus, not being inferior to the therapy every day. We investigated the clinical effects and safety of the addition of empagliflozin every day or every other day to type 2 diabetic patients with a poor control in glycemia. Thirteen Japanese patients diagnosed as type 2 diabetes mellitus recruited to this study. Subjects were divided into two groups; one was treatment with 10 mg of empagliflozin every day (Group A), the other was 10 mg of empagliflozin every other day (Group B). The comparable study of multiple clinical indexes between the 2 groups was made before and 8, 16, and 24 weeks after the treatment. After the treatment for 24 weeks, the HbA1c level was decreased both in group A (from 7.5%±1.1% to 6.5%±0.8%) and in group B (from 7.6%±0.8% to 7.2%±0.5%). This pilot trial suggested the possibility of 10-mg every other day administration with empagliflozin for Japanese patients with type 2 diabetes mellitus. J. Med. Invest. 64: 50-57, February, 2017.

In this study, we administered a questionnaire to medical students to evaluate the effect of community-based clinical education on their attitudes to community medicine and medicine in remote area. Questionnaires were given 4 times to all the students from first-year to sixth-year. Of 95 students, 65 students (68.4%) who completed all questionnaires, were used in this study. The intensity of students' attitudes was estimated by using visual analogue scale. The intensity of interest, a sense of fulfillment and passion in medicine of remote area was significantly increased after the community-based practice. On the other hand, the level of understanding in medicine in remote area was increased by the lecture not by the practice. The intensity of desire both to become a generalist and a specialist was significantly increased when the grade went up. Most of sixth-year students desired to have abilities of a generalist and a specialist simultaneously. This study shows that the community-based practice is more meaningful in increasing motivation in medicine in remote area than the lecture, and suggests that it is important to prepare more courses to experience community medicine to increase the number of physicians who desire to work in remote area.

Biological agents represent an important advancement in for the treatment of rheumatoid arthritis (RA), but there is a subset of patients who do not improve despite therapy. This study aimed to determine the efficacy of biological agents for RA and to identify clinical factors that are associated with their response. We studied 98 patients with RA who started an initiating biological agent which was selected from infliximab, etanercept, adalimumab and tociliximab at 4 medical institutions. Etanercept was the most frequently used biological agent followed by infliximab although there was a difference in the selection of the biological agents among medical institutions. We found that etanercept achieved the highest treatment response, remission rate and drug survival rate. A high disease activity in the baseline disease activity score-c-reactive protein (CRP) was shown to be a negative predictor of the treatment response, and high patient global assessment was significantly less likely to achieve a good response. At week 4, decreases in 28 swollen joint counts and CRP were useful as predictors for sustaining the efficacy up to week 48. These data demonstrate that assessments of the disease activity at baseline and the early treatment response may be useful in predicting the efficacy and drug survival rate of biological agents.

Background: Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, has been reported to be associated with interstitial lung disorders, and their high incidence and mortality have become a matter of great concern, especially in Japan. In this study, we investigated the effect of gefitinib on different phases of radiation-induced lung disorders in an experimental model., Methods: The thoraxes of Wistar rats were irradiated on day 1 with a single X-ray dose of 20 Gy, and gefitinib (50 mg/kg/day) was orally administered from day 1 to 14. The rat lungs were harvested on days 15 and 57 and the bronchoalveolar lavage (BAL) was performed., Results: Gefitinib treatment increased the infiltration of inflammatory cells, which produced more pro-inflammatory cytokines (IL-6, IL-1β), in the lungs of the irradiated rats on days 15 and 57, while gefitinib treatment reduced collagen content of the lungs in irradiated rats and decreased proliferation and EGFR expression in the lung fibroblasts from irradiated rats on day 57., Conclusions: In irradiated rats, gefitinib treatment augmented lung inflammation, including inflammatory cell infiltration and pro-inflammatory cytokine expression, while gefitinib treatment attenuated fibrotic lung remodeling due to the inhibition of lung fibroblast proliferation.

The shortage of medical doctors is now a serious social problem in Japan. There are 2.1 physicians per 1000 residents in Japan, fewer than most other OECD countries. Tokushima Prefecture has the second highest population of medical doctors in Japan, but the shortage of medical doctors in rural areas was observed by an uneven distribution. Primary care practice was started in the education of clinical clerkship for 5th grade medical students of our university since July, 2008. They round a variety of hospitals, clinics and facilities for nursing-care during one week in Kaihu county where has a severe problem in the shortage of medical doctors in Tokushima Prefecture. In order to research the efficacy of the primary care practice, we have administered a questionnaire for medical students before and after the lecture and practice, and the intensity was estimated in each student by using visual analogue scale. The results showed that the practice was more meaningful in increasing the intensity for interest and passion for community medicine and medicine in remote area than the lecture. Our data indicate that it is important to prepare more courses to learn primary care and general medicine in our clinical practice system to continue the interest and passion in community medicine.

Systemic lupus erythematosus (SLE) is a chronic disease that is characterized by an undulating course of exacerbations and remissions, and a major determinant of long-term prognosis is organ damage consequent to tissue injury that accompanies disease activity and toxicity of therapy. In this study, we evaluated which patients with SLE will develop an exacerbation and whether factors can be identified to predict the development of an exacerbation. Fifty-seven SLE patients (52 females) were included in this study. The exacerbation of SLE was found in 15 patients (26.3%). A relatively increased incidence of an exacerbation was found in younger SLE patients. An increased percentage of patients who had lupus nephritis at the time of diagnosis of SLE was found in patients with a subsequent exacerbation when compared with that in those without it. Increased incidence of an exacerbation was observed in patients who had decreased number of WBC and platelets, decreased level of C3 and CH50, and the presence positivity of anti-Sm antibodies at the time of the diagnosis. This study suggests that age, renal involvement, and the presence of decreased number of WBC and platelets, decreased level of complements anti-Sm antibodies are predictors of exacerbation.

Polymyositis (PM) and dermatomyositis (DM) are systemic inflammatory disorders affecting skeletal muscles and other organs, and are associated with high morbidity and mortality rates. In this study, we studied the prevalence, clinical features and its comparative outcome of PM/DM, comparing PM and DM. Twenty-three PM/DM patients (9 PM and 14 DM) were included in this study. The complication of interstitial pneumonia (IP) was found in 17 patients (74%). HRCT showed that non-specific interstitial pneumonia pattern was the most common in patterns of lung involvement. Twenty-one patients (91%) with PM/DM received high dose of prednisolone therapy. The percentage of patients who received methylprednisolone (mPSL) pulse and cyclosporin A was higher in DM patients than in PM patients. The percentage of patients who received mPSL pulse and cyclosporin A was higher in later (after Apr 2004) patients than in former (before Mar 2004) patients. Malignant diseases appeared in 3 patients with DM which consisted of breast cancer, epipharyngeal cancer and gastric cancer. We observed 2 deaths in DM patients during the course of therapy; one was due to IP, and the other due to miliary tuberculosis. This study showed that a poorer prognosis was observed in patients with DM when compared with those with PM, and immunosuppressive medications may be implicated at least partially in increased risk of infections and malignancies in PM/DM patients especially DM patients, indicating that patients with PM/DM may require careful monitoring during the clinical course.

Macrophage-derived chemokine (MDC/CCL22) and thymus-and activation-regulated chemokine (TARC/CCL17) are ligands for CC chemokine receptor 4. Recently, TARC has been reported to play a role in the pathogenesis of idiopathic eosinophilic pneumonia (IEP). The purpose of this study was to evaluate the role of MDC in IEP and other interstitial lung diseases (ILDs). MDC and TARC in the bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay in patients with ILDs and healthy volunteers (HV). We also examined the expression of MDC mRNA in alveolar macrophages (AM) by real-time quantitative reverse transcriptase-polymerase chain reaction. Both MDC and TARC were detected only in BALF obtained from IEP patients. The concentration of MDC was higher than that of TARC in all cases. The level of MDC in IEP correlated with that of TARC. AM from IEP patients expressed a significantly higher amount of MDC than that from HV at the levels of protein and mRNA. MDC in BALF from IEP dramatically decreased when patients achieved remission. These findings suggest that MDC, in addition to TARC, might be involved in the pathogenesis of IEP, and AM play a role in the elevation of MDC in IEP.

To determine the significance of proteases in interstitial lung diseases, we examined the activity of cathepsins, thrombin, and aminopeptidase in bronchoalveolar lavage (BAL) fluid from patients with these disorders. Significantly increased activities of cathepsin H and aminopeptidase were detected in BAL fluid from patients with idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), chronic eosinophilic pneumonia (CEP) and hypersensitivity pneumonitis (HP). Significantly higher activity of cathepsin B was found in BAL fluid from patients with CEP. The activity of thrombin was significantly higher in patients with IPF and CEP. In patients with IPF, there were significant correlations between neutrophil number and the activity of cathepsin B, cathepsin H or aminopeptidase. In patients with COP and HP, the activity of the proteases was significantly higher in patients with higher number of lymphocytes than in those with lower number of lymphocytes. The present study suggests that the activity of the proteases is a useful marker in activity of the interstitial lung diseases, and may have a role in the pathogenesis of these disorders.

With the recognition that airway inflammation is present even in patients with mild bronchial asthma, therapy with inhaled corticosteroids is now indicated in various stages of patients. In the present article, we retrospectively examined the prescriptions for inhaled corticosteroids and other drugs for the treatment of outpatients with bronchial asthma at Tokushima University Hospital. We also analyzed asthma control in these patients, in terms of the incidence of emergency consultations and hospitalizations due to asthma exacerbations. To analyze the recent trend, the patients observed from 1998 to 2000 (recent years) were included, and for control purpose, those in 1990 and 1991 (earlier years) were also included. The percentage of patients treated with inhaled corticosteroids remarkably increased in recent years (mean; 81.3%) compared to earlier years (mean; 23.5%). In contrast, the usage of oral corticosteroids, oral xanthine derivatives, beta-adrenergic receptor agonists and anti-allergic agents tended to decrease in the 10 years period. After the introduction in 1995, considerable patients up to 25% have been treated with anti-leukotrienes. Emergency consultations decreased in recent years (mean; 0.18/patient/year) compared to earlier years (mean; 0.79/patient/year). Emergency hospitalizations also decreased in recent years (mean; 0.043/patient/year) compared to earlier years (mean; 0.23/patient/ year). In the present study, spread of inhaled corticosteroid therapy and decline in incidence of emergency consultation and hospitalization were simultaneously observed at Tokushima University Hospital, and the former has, at least in part, a contribution to the latter.