Masqueraders Around Disaster: Clinical Features of Scrub Typhus in Fukushima, Japan.

Background: Scrub typhus (ST) is endemic in Fukushima, with the largest number of cases reported in Japan from 2009 to 2010. Although ST is highly treatable, its atypical clinical presentation impedes diagnosis, causing delays in treatment. Methods: We review the clinical features of ST in adults from 2008 to 2017 at Ohta Nishinouchi General Hospital in Fukushima, Japan. Results: Fifty-five cases (serotype Karp 24, Irie/Kawasaki 21, Hirano/Kuroki 10) of ST were confirmed via serology based on elevated immunoglobulin (Ig)M and IgG and polymerase chain reaction positivity of eschar samples. The mean age was 69 years, and 64% were female. The case fatality rate was 1.8% (1/55). Approximately 70% of cases (38/55) were not diagnosed as ST upon the initial clinic visit. Inappropriate use of antibiotics was identified in 22% of cases (12/55). In terms of atypical clinical features, 1 or more of the manifestations, fever, rash, and eschar, was absent in 31% of cases (17/55). Approximately 11% of cases presented without eschar (6/55; Karp 1, Irie/Kawasaki 1, Hirano/Kuroki 4). Moreover, severe complications were observed with shock and disseminated intravascular coagulation in 7% of cases (4/55), Thus, while 53% of cases presented with the typical triad (29/55), unusual complications and atypical features occurred in 40% (22/55). Conclusions: Diagnosis of ST becomes clinically challenging in the absence of typical features. In Fukushima, an endemic area of ST, an atypical presentation involving multisystem disease is common.

Systemic Lupus Erythematosus and Antiphospholipid Syndrome Accompanied by Mixed-Type Autoimmune Hemolytic Anemia.

Systemic lupus erythematosus (SLE) is an autoimmune disease that leads to a wide spectrum of clinical and immunological abnormalities. Hematologic abnormalities are an important manifestation of SLE. The incidence of autoimmune hemolytic anemia (AIHA) has been reported in approximately 10% of patients with SLE. Among them, mixed-type AIHA, which is caused by warm autoantibodies and cold hemagglutinin, is relatively rarely reported. We report the case of a 72-year-old woman, who was admitted to our hospital due to shortness of breath, jaundice, and severe anemia, with SLE and antiphospholipid syndrome (APS) complicated by mixed-type AIHA. Laboratory data revealed severe hemolytic anemia (low hemoglobin, high indirect bilirubin, and high lactate dehydrogenase levels), low complement levels, and the presence of antinuclear antibodies and lupus anticoagulant. Imaging results revealed pleural effusion and pulmonary embolisms, and echocardiogram revealed high estimated right ventricular pressure. She was diagnosed with SLE and APS complicated by mixed-type AIHA based on positive direct antiglobulin and cold agglutinin tests (thermal amplitude ≥30°C). As mixed-type AIHA is a severe and chronic condition, she was administered potent treatments with immunosuppressants. However, because she was a carrier of human T-cell leukemia virus type-1, only a moderate amount of prednisolone was administered. She refused to take warfarin. Fortunately, her symptoms and laboratory abnormalities improved after prednisolone administration, and no relapse occurred after tapering the prednisolone dose. Although mixed-type AIHA is characterized by fewer clinical symptoms than cold agglutinin disease, hemolytic anemia is more severe and chronic. Therefore, it is important to confirm the presence of cold agglutinins, which are active at ≥30°C in patients with SLE and warm AIHA. In addition, it is important to consider that AIHA is associated with thromboembolism, and patients with lupus anticoagulant or anticardiolipin antibodies having a history of AIHA are at a high risk of developing thrombosis.

Association of Low-Normal Free T4 Levels With Future Major Depression Development.

Context: Hyperthyroidism and overt and subclinical hypothyroidism are associated with major depression; however, the association of major depression across the spectrum of thyroid function within the normal range is unknown. Objective: We investigated whether higher or lower levels of free thyroxine (T4) and thyrotropin (TSH) within the normal range are associated with major depression. Methods: This was a retrospective cohort study of 66 960 participants with normal thyroid function who visited for health checkups (St. Luke's International Hospital, 2005-2018). The primary outcome was the development of major depression during the follow-up period. Participants were divided into 3 equal groups based on baseline free T4 or TSH values (low-, middle-, or high-normal), and the incidence of major depression was compared using the Cox proportional hazard model after adjusting for potential covariates. Results: During the median follow-up of 1883 days, 1363 (2.0%) patients developed major depression. The low-normal free T4 group had a significantly higher risk of major depression (adjusted HR 1.15; 95% CI, 1.01-1.31), but not the high-normal free T4 group or TSH groups. The association between low-normal free T4 and the development of major depression was maintained, rather more obvious, upon exclusion of participants whose thyroid hormone levels became abnormal during follow-up compared with data from all participants (adjusted HR 1.24; 95% CI, 1.07-1.43). Conclusion: In this cohort, low-normal free T4 was associated with an increased risk of future major depression, even if subsequent hormone levels were maintained within the normal range. The magnitude of the impact of low-normal free T4 was relatively mild.

The Effect of Shiatsu Therapy on Sleep Quality in Patients With Low Back Pain: A Secondary Analysis.

The aim of this study is to investigate the efficacy of shiatsu therapy for chronic low back pain and sleep disturbance. We conducted a secondary analysis of the randomized trial at a large academic hospital in Tokyo. Patients with chronic low back pain were included. Patients were randomly assigned to either shiatsu therapy in addition to standard care or standard care only by computer randomization. Our primary outcome was improvement of the global Pittsburgh Sleep Quality Index (PSQI) score, and the secondary outcomes were improvement in each component of the PSQI at weeks 4 and 8. We included a total of 59 patients. The mean age was 67.8 (SD: 13.5) years, and 21 patients (35.6%) were male. The global PSQI scores improved in the intervention group at week 4 (adjusted ß coefficient: 1.16, 95% confidence interval: 0.10-2.21) and week 8 (adjusted ß coefficient: 1.82, 95% confidence interval: 0.74-2.90). In terms of each component of the PSQI, sleep efficiency (component 4) and sleep disturbance (component 5) were improved, but use of sleep medication (component 5) worsened in the intervention group compared with the control group in several models. Shiatsu therapy in addition to standard therapy for chronic low back pain may improve sleep quality after intervention.

Slight religiosity associated with a lower incidence of any fracture among healthy people in a multireligious country.

BACKGROUND: The aim of this study was to evaluate the association between the degree of religiosity and subsequent fractures and a decrease in bone mineral density in a Japanese population. METHODS: We conducted a retrospective longitudinal study at St. Luke's International Hospital in Tokyo, Japan, from 2005 to 2018. All participants who underwent voluntary health check-ups were included. Our outcomes were any fractures and the change in T-score from baseline to each visit. We compared these outcomes by the self-reported degree of religiosity (not at all; slightly; somewhat; very) and adjusted for potential confounders. RESULTS: A total of 65,898 participants were included in our study. Their mean age was 46.2(SD:12.2) years, and 33,014(50.1%) were male. During a median follow-up of 2,500 days (interquartile range (IQR):987-3,970), 2,753(4.2%) experienced fractures, and their mean delta T-score was -0.03%(SD:18.3). In multivariable longitudinal analyses, the slightly religious group had a statistically lower adjusted odds ratio (AOR) for a fracture than the nonreligious group(AOR:0.81,95% confidence interval(CI):0.71 to 0.92). CONCLUSIONS: We demonstrated that slightly religious people, but not somewhat or very religious people, had a lower incidence of fracture than nonreligious individuals, although the T-scores were similar regardless of the degree of religiosity.

Impact of a continuous quality improvement program on contrast-induced nephropathy in outpatients with chronic kidney disease: an interrupted time-series study.

BACKGROUND: Contrast-induced nephropathy (CIN) caused by exposure to radioactive contrast media can cause acute kidney injury in patients with chronic kidney disease (CKD). We developed a multifaceted approach in a CIN-quality improvement (QI) program based on a shorter saline hydration protocol for the prevention of CIN in outpatients and assessed the effect of our CIN-QI program on decreasing both the incidence rate of CIN and overall use of contrast agents in patients undergoing contrast-enhanced computed tomography (CT). METHODS: We conducted a multi-center prospective interrupted time-series study from 2006 to 2018 investigating the efficacy of a CIN-QI program in preventing CIN among outpatients with CKD. An automatic medical record system alert was implemented to instruct physicians to consult a nephrologist and administer prophylactic hydration and follow-up when ordering contrast-enhanced imaging in patients with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2. The primary outcomes were the rates of prophylactic hydration and follow-up kidney function assessment, and the incidence of CIN for eligible patients. The usage rate of contrast-enhanced CT was also examined. RESULTS: A total of 95 594 patients who underwent contrast-enhanced CT were included in the study. The annual prophylactic hydration rate before the CIN-QI program ranged from 2.0% to 23.2% but increased to 59.2%-75.2% during the CIN-QI program (P < .001). The annual rate of follow-up kidney function testing also improved from 18.6%-25.8% to 34.1%-42.5% after implementation of the CIN-QI program (P < .001). The rate of CIN significantly declined in level by 10.0% at the start of the CIN-QI program (P = .002) and in trend by 2.9%/year (P < .001). The number of contrast-enhanced CT orders showed a positive level change in patients with advanced CKD, who were the CIN-QI program target group of patients with eGFR <45 mL/min/1.73 m2, at the start of the implementation of the CIN-QI program. After implementing the CIN-QI program, the number of contrast-enhanced CT orders showed a negative trend change across all patients, which decreased from -1.4%/year to -10.0%/year for patients with advanced CKD. CONCLUSION: The multifaceted approach in the CIN-QI program may be associated with the decreased incidence of CIN and increased rates of prophylactic hydration and follow-up kidney function testing.

Low Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) Ratio Associated with Increased Cardiovascular Disease and its Risk Factors in Healthy Japanese Population.

AIMS: This study aimed to evaluate the association between aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and cardiovascular disease, and risk factors in a healthy Japanese population. METHODS: A retrospective cohort study was conducted at St. Luke's International Hospital, Tokyo, Japan, between 2005 and 2018. We included all participants who visited the hospital for voluntary health checkups. Our primary outcome was the development of cardiovascular disease, and the secondary outcomes were cardiovascular risk factors. We grouped the participants into quartiles (Qs) according to their baseline AST/ ALT ratios and examined the outcomes of patients in each group. RESULTS: 87,740 participants were included in this study. The mean age of the participants was 44.9 years [standard deviation (SD): 12.1], and 43,191 (49.2%) were men. The mean AST and ALT levels were 21.7 IU/L (SD 10.0) and 22.4 IU/L (SD 16.5), respectively, resulting in a mean AST/ALT ratio of 1.1 (0.4). During the median follow-up of 1,829 days (interquartile range 756-3,470), 1,493 (1.7%) participants developed cardiovascular disease, 831 (1%) experienced ischemic heart disease, and 723 (0.8%) experienced strokes. Those in the Q1 AST/ALT ratio group had significantly higher hazard ratios compared to those in the Q3 AST/ ALT ratio group [adjusted hazard ratio (HR)=1.32, 95% confidence interval (CI): 1.12-1.56 for cardiovascular disease; HR=1.36, 95%CI: 1.09-1.68 for ischemic heart disease; HR=1.28, 95%CI: 1.00-1.65 for stroke]. However, those belonging to the Q4 or Q5 AST/ALT ratio groups was not statistically different for primary outcomes compared to the Q3 AST/ALT ratio group. In contrast, the adjusted HRs for all secondary outcomes decreased in a dose-dependent manner as the AST/ALT ratio increased. CONCLUSIONS: A Q1 AST/ALT ratio was associated with an increased risk of cardiovascular disease compared to the Q3 AST/ALT ratio in the Japanese population, which is in contrast with the Western population. In our study, Q4 or Q5 AST/ALT ratios were not associated with cardiovascular disease compared to the Q3 AST/ ALT ratio. As for cardiovascular risk factors, the risk decreased as the AST/ALT ratio increased.

Longitudinal relationship between long sleep duration and future kidney function decline.

Background: Evidence linking chronic kidney disease (CKD) and sleep duration is inconsistent. This study examined whether sleep duration is associated with a long-term risk of kidney function decline. Methods: This retrospective, longitudinal cohort study included 82 001 participants who visited a primary care centre in Japan. Participants were categorized into CKD risk groups and sleep duration categories according to their self-reported average nightly sleep duration. The relationship between average nightly sleep duration and the incidence of composite renal outcome comprised a ≥40% reduction in estimated glomerular filtration rate (eGFR) from baseline and a decline in eGFR to <15 mL/min/1.73 m² was evaluated. Results: The mean age and eGFR (±standard deviation) of the patient cohort were 45.8 (±12.4) years and 81.8 (±15.4) mL/min/1.73 m², respectively. A total of 41 891 participants (51.1%) were women. During the median follow-up of 5.1 years [interquartile range 2.2-9.6], 4214 (5.1%) participants achieved the composite renal outcome. Only the long and very long sleep durations (≥8 h/night) were associated with an increased incidence of the composite renal outcome compared with the reference duration (7 h/night) [adjusted odds ratio (OR) 1.22 and 1.44; 95% confidence interval (CI) 1.09-1.36 and 1.13-1.84, for long and very long sleep durations, respectively]. Furthermore, this association was significant for both long and very long sleep durations in the low CKD risk group but only for long sleep duration in the intermediate CKD risk group. The results of the sex-specific analysis showed that men had a decreased risk of achieving the composite renal outcome (OR 0.91; 95% CI 0.79-1.06), while there was an increased risk for women (OR 1.14; 95% CI 1.02-1.28). Conclusions: Average sleep durations ≥8 h/night were associated with an increased incidence of poor renal outcomes over time. However, a longitudinal cohort study is required to confirm whether sleep duration can prevent poor renal outcomes.

Longitudinal effects of one-leg standing time on neuropathy outcomes in association with glycemic control in non-elderly patients with type 2 diabetes.

AIMS/INTRODUCTION: Diabetic neuropathy leads to postural instability. This study compared longitudinal changes in neuropathy outcomes relative to long-term glycemic control in patients aged <60 years with uncontrolled type 2 diabetes with and without a short one-leg standing time (OLST <60 s). MATERIALS AND METHODS: In this retrospective study, 58 hospitalized patients with type 2 diabetes (glycated hemoglobin [HbA1c] >7.0%; aged 17-59 years), who underwent re-evaluation of neuropathic sensory symptoms, ankle reflexes and nerve conduction attributes, and cardiac autonomic function (R-R interval), >1 year after discharge were divided into OLST <60 and ≥60 s groups. Patients were followed up every 2-3 months for HbA1c levels for up to 8 years. Neuropathy outcomes relative to OLST and HbA1c levels at baseline and over follow up were compared. RESULTS: Additional development of sensory symptoms (one patient) and abnormal ankle reflexes (five patients) were identified during follow up, and decreased peripheral and cardiac autonomic function at both baseline and follow up, only in patients with OLST <60 s. Mean HbA1c levels were significantly higher in patients with OLST <60 s versus ≥60 s (7.8 ± 0.9% vs 7.2 ± 1.2%; P = 0.022). Better glycemic control during follow up was associated with better neuropathy outcomes only in patients with OLST ≥60 s. CONCLUSION: Non-elderly type 2 diabetes patients with OLST <60 s and decreased peripheral nerve function at baseline are at increased risk for intractable diabetic neuropathy. Better glycemic control alone might not improve neuropathy outcomes in these patients.

Both increased and decreased sleep duration over time are associated with subsequent cancer development.

PURPOSE: Changes in sleep duration have been reported to correlate with lifestyle-related diseases in humans. However, equivalent studies regarding the effects of sleep on cancer progression are lacking. This study aimed to determine whether or not increase or decrease in sleep duration over time is associated with subsequent cancer development. METHODS: A large-scale, retrospective cohort study was conducted at a preventive medicine health center at a general community hospital in Tokyo, Japan. All participants who underwent health checkups at the hospital between January 2005 and December 2018 were included. The primary study outcome was development of any type of cancer according to the slope of sleep duration over the study period. The Cox proportional hazard model was used to adjust the outcomes based on potential covariates. RESULTS: Of 15,025 participants, 7,692 (51.2%) were men. The mean age (standard deviation) was 66.0 (7.5) years. During a median follow-up of 2,588 (interquartile range: 1,583-3,695) days, 1,396 (9.3%) participants developed cancer of any type. Compared to hazard ratio in the stable sleep duration group (- 0.1 to + 0.1 h/day in 1 year), both greatly decreased (less than - 0.2 h/day in 1 year; hazard ratio (HR), 2.13; 95% confidence interval (CI), 1.72-2.62) and increased (more than + 0.2 h/day in 1 year; HR, 2.55; 95% CI 2.14-3.04) groups showed significantly higher hazard ratio for the development of any type of cancer. CONCLUSION: Both increased and decreased sleep duration over time are associated with subsequent cancer development.

Aspartate aminotransferase/alanine aminotransferase ratio and subsequent cancer development.

BACKGROUND: We aimed to evaluate the association between the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and subsequent development of any type of cancer in an apparently healthy population. METHODS: We conducted a retrospective cohort study at St. Luke's International Hospital, Tokyo, Japan between 2005 and 2018. All participants who visited for voluntary health checkups were included. We divided the participants into different quintiles based on the baseline AST/ALT ratios and examined the outcomes. RESULTS: A total of 85,658 participants were included. The mean age was 44.7 years (standard deviation 12.0) at baseline, and 42,913 (50.1%) of them were men. During a median follow-up of 61.6 months, 4701 (5.5%) participants developed some type of cancer. Compared with the middle AST/ALT ratio group, no other groups had similar adjusted hazard ratios (HR) for the development of any type of cancer in both men and women. When stratified by alcohol consumption, very high (adjusted HR 1.36; 95% CI 1.13-1.63) and high (adjusted HR 1.26; 95% CI 1.05-1.50) AST/ALT ratio groups among men who were regular drinkers had increased adjusted HRs for any type of cancer development, but the very high AST/ALT ratio group among men who were abstainers (adjusted HR 0.64; 95% CI 0.42-0.97) and very low AST/ALT ratio group among men who were occasional drinkers (adjusted HR 0.69; 95% CI 0.48-0.98) had lower adjusted HRs compared with the middle AST/ALT ratio group. Among women, regardless of alcohol consumption, adjusted HR for any type of cancer development was similar across all AST/ALT ratio groups. CONCLUSION: People with higher AST/ALT ratios tended to have a higher risk of developing any type of cancer among men who were regular drinkers, but this risk was lower among men who were abstainers. Among women, regardless of alcohol consumption, there was no association between the development of any type of cancer and AST/ALT ratio.

Frequency of tooth brushing as a predictive factor for future kidney function decline.

BACKGROUND: Tooth brushing is important for maintaining oral health and preventing periodontal diseases (PDs), which commonly arise in patients with chronic kidney disease (CKD). However, the association between tooth brushing frequency and kidney function decline remains unclear. METHODS: We conducted a retrospective longitudinal study at St Luke's International Hospital, Japan, and participants who underwent health examinations at the Centre for Preventive Medicine from 2005 to 2011 were included. Participants' tooth brushing frequencies were assessed; multivariate analyses were conducted using a generalized estimating equation to evaluate the association between tooth brushing frequency and a composite renal outcome-composed of a 25% estimated glomerular filtration rate (eGFR) reduction, an eGFR of < 15 mL/min/1.73 m2, and a requirement for regular dialysis-after adjusting for potential covariates. We also stratified participants by baseline CKD risk category to perform sub-analyses. RESULTS: Overall, 76,472 participants were included (mean age of 45.9 years) and 38,233 (50%) were male. During follow-up, 8219 participants (10.8%) experienced composite renal outcomes. Brushing teeth at least once to twice a day was associated with significantly lower incidences of composite renal outcomes than brushing teeth less frequently (adjusted odds ratio [OR] 0.26; 95% confidence interval [CI] 0.24-0.28 for once to twice a day; adjusted OR 0.65; 95% CI 0.62-0.69 for after every meal). In our sub-analyses, brushing at least once to twice a day related to a decreased likelihood of composite renal outcomes; however, this effect was only observed within the low and moderate baseline risk groups. CONCLUSION: Frequent tooth brushing benefits oral health and may be associated with slower kidney function decline, which could have implications for other systemic diseases. However, a longitudinal cohort study is required to confirm whether tooth brushing and overall oral health can haver a role in improving  renal outcomes.

Long-term outcome of targeted therapy for low back pain in elderly degenerative lumbar scoliosis.

PURPOSE: Treatment of low back pain (LBP) associated with elderly degenerative lumbar scoliosis (DLS) remains controversial. We have developed percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI) targeting to the intervertebral vacuum as a minimally invasive surgery. The present study compared the long-term clinical outcomes of PIPI to that of nonoperative treatment. METHODS: Patients with de novo DLS, aged ≥ 65 years, who had LBP with visual analog scale (VAS) of ≥ 50 for ≥ 6 months with intervertebral vacuum on computed tomography and bone marrow edema (BME) on magnetic resonance imaging were included. The clinical outcomes were evaluated using VAS and the Oswestry Disability Index (ODI) at baseline, 1, 6, 12, 24 months, and at the final follow-up. The course of BME was also evaluated. RESULTS: One hundred and one patients underwent PIPI and 61 received nonoperative treatment. The mean follow-up duration after PIPI and nonoperative treatment was 63.7 ± 32.4 and 43.9 ± 20.9 months, respectively. VAS and ODI after PIPI were significantly improved compared to post-nonoperative treatment. BME decreased substantially in the PIPI group and it was significantly correlated with VAS and ODI improvement. Following PIPI, LBP recurred in 28 patients (35%). LBP recurrence was identified at the same level of PIPI in 10 patients, at the adjacent level of PIPI in 11 patients, and at the non-adjacent level of PIPI in seven patients. Eighteen patients underwent additional PIPIs, and both VAS and ODI were significantly improved after additional PIPIs. CONCLUSION: Bone marrow lesions of the endplate are strongly associated with the presence of LBP. PIPI can be considered as an effective, safe and repeatable treatment for LBP in elderly DLS patients.

Effect of antiplatelet agent number, types, and pre-endoscopic management on post-polypectomy bleeding: validation of endoscopy guidelines.

BACKGROUND: It remains unclear whether type of antiplatelet (AP) therapy, AP combination therapy, and AP continuing or switching strategy affect the risk of post-polypectomy bleeding (PPB). In this study, we sought to elucidate this risk. METHODS: We analyzed 1050 patients who underwent colonoscopic polypectomy: 525 AP users and 525 controls matched for age, sex, comorbidities, concomitant non-steroidal anti-inflammatory drugs use, and polyp characteristics who did not receive antithrombotics. PPB risk was evaluated by AP number, type, and continuing or switching strategies during the peri-endoscopic period. RESULTS: In multivariate analysis, bleeding risk increased significantly as the number of AP agents used increased (monotherapy, adjusted odds ratio [aOR], 3.7; dual antiplatelet therapy (DAPT), 4.6; triple antiplatelet therapy (TAPT), 11.1) compared with controls. With monotherapy, significantly increased PPB risk was found for aspirin (aOR 4.3), thienopyridine (aOR 6.3), and cilostazol (aOR 5.9), but not for eicosapentaenoic acid or other APs (beraprost, limaprost, sarpogrelate, dilazep, or dipyridamole). With DAPT, significantly increased PPB risk was found for combination aspirin plus cilostazol, but not aspirin plus other APs. Bleeding rates for continuing monotherapy were 4.3% for aspirin and 0% for thienopyridine, cilostazol, and other APs, respectively. CONCLUSIONS: Analysis of this large polypectomy dataset showed that the use of low-dose aspirin, thienopyridine, or cilostazol and a combination of these is associated with increased PPB risk. Although PPB risk was high with DAPT or TAPT, PPB rate in any antiplatelet monotherapy even with a continuing strategy was low at < 5%.

Incisura angularis belongs to fundic or transitional gland regions in Helicobacter pylori-naïve normal stomach: Sub-analysis of the prospective multi-center study.

OBJECTIVE: Incisura angularis is one of the important parts for evaluating mucosal atrophy and cancer risk. We determined the type of mucosa at incisura angularis in Helicobacter pylori-naïve normal stomach. METHODS: Subjects aged 40 years or older who underwent esophagogastroduodenoscopy for dyspepsia or a routine health checkup were recruited in 24 facilities between March 2008 and February 2009. Serum antibody to H. pylori was measured. Endoscopic atrophy was evaluated according to Updated Kimura-Takemoto classification. Five biopsy specimens were taken from the incisura angularis and greater and lesser curvatures of the antrum and corpus. These specimens were histologically classified as fundic, pyloric or transitional. H. pylori-naïve normal stomach was defined with the strictest criterion among various combinations of histological, endoscopic and serum findings. We determined histological type of mucosa at incisura angularis in H. pylori-naïve normal stomach. RESULTS: A total of 270 subjects (122 men, mean 64.6 yo) were analyzed. The strictest criterion consists of serum antibody ≤ 3.0 U/mL, endoscopic atrophy C-1 and histological grade 0 in all of the five items in Updated Sydney System. The numbers having fundic, transitional and pyloric mucosa at incisura angularis under the strictest criterion were 13 (50%), 13 (50%) and 0, respectively. The probability that the type of mucosa at incisura angularis would be pyloric was almost zero (97.5% confidence interval 0-0.132). CONCLUSIONS: Incisura angularis of the stomach may not belong to pyloric, but fundic or transitional mucosa in H. pylori-naïve normal stomach. UMIN000018218.

Association of self-reported religiosity with the development of major depression in multireligious country Japan.

AIM: In Western Christian countries, religiosity is generally believed to be associated with a lower risk for depression, which is supported by epidemiological evidence. However, the association between religiosity and depression in multireligious countries is unknown. The objective was to evaluate the association between religiosity and subsequent depression in a multireligious population. METHODS: A longitudinal study was conducted in a large hospital in Tokyo, Japan, from 2005 to 2018. All participants who underwent health check-ups without a prior history of depression or depression at baseline were included. Our outcome was development of major depressive disorder (MDD), which was compared according to the degree of religiosity, adjusting for potential confounders. RESULTS: Among 67 723 adult participants, those who were more religious tended to be older, female, married, and to have healthier habits but also more medical comorbidities at baseline. During a median follow-up of 2528 days, 1911 (2.8%) participants developed MDD. Compared to the reference group, religious group participants tended to have higher odds ratios (OR) for developing MDD in a dose-dependent manner. Among them, the extremely religious group (OR, 1.51; 95% confidence interval [CI], 1.28-1.78) and the moderately religious group (OR, 1.30; 95% CI, 1.14-1.49) were statistically associated with increased development of MDD compared to the not-religious-at-all group. Those who had increased their religiosity from baseline had statistically lower development of MDD (OR, 0.85; 95% CI, 0.75-0.97) compared to those who remained in the same degree of religiosity from baseline. CONCLUSION: Religiosity was associated with future MDD in a dose-dependent manner in a multireligious population, which was in the opposite direction from that seen in previous Western longitudinal studies.

Frequency of daily tooth brushing and subsequent cardiovascular events.

OBJECTIVE: Although previous studies have shown an inverse association between the frequency of daily tooth brushing and cardiovascular risk factors, research on cardiovascular events is limited. This study aimed to evaluate the association between the frequency of daily tooth brushing and subsequent cardiovascular events. METHODS AND RESULTS: A retrospective longitudinal study was conducted at a hospital in Tokyo, Japan. We included all participants who underwent health check-ups from 2005 to 2011 and followed up to 2018. Our outcomes were the development of cardiovascular events. Outcomes were compared by the frequency of daily tooth brushing with a generalized estimating equation, adjusting for potential confounders. A total of 71 221 participants were included. The mean age was 45.6 years and 50.3% were male. During a median follow-up of 2061 (interquartile range: 933-3311) days, 1905 participants developed cardiovascular events. The adjusted odds ratios (ORs) of cardiovascular events increased in a dose-dependent manner as the frequency of tooth brushing decreased. Even those who brushed their teeth once in a day had a higher adjusted OR of stroke (1.22; 95% confidence interval, 1.01-1.48) than did those who brushed after every meal. CONCLUSIONS: Frequent tooth brushing was inversely associated with subsequent cardiovascular events in a dose-dependent manner. Even brushing one's teeth once a day may be related to an increased likelihood of stroke than brushing one's teeth after every meal. Less frequent tooth brushing may be considered to be a marker for subsequent cardiovascular disease and coronary heart disease, rather than a risk factor.

Association of One-Leg Standing Time with Discontinuation of Injectable Medications During Hospitalization Among Patients with Type 2 Diabetes.

INTRODUCTION: Persons with type 2 diabetes (T2D) are known to experience impaired physical ability even at the early stages of the disease. However, less attention has been paid to increasing physical ability than to increasing physical activity in the treatment of T2D. The aim of this study was to assess whether improved physical ability parameters are associated with the discontinuation of injectable medications once glycemic targets have been achieved among inpatients with inadequately controlled T2D across a wide range of ages. METHODS: Forty-three patients with glycated hemoglobin levels of ≥ 7.5% (58 mmol/mol) aged between 19 and 82 years who received insulin, glucagon-like peptide-1 receptor agonists or both at admission were enrolled in the study. Muscle strength for knee extension, one-leg standing time with eyes open test(OLST), whole-body reaction time and maximal oxygen uptake were assessed as parameters of physical ability. RESULTS: At admission, patients who during hospitalization discontinued injectable medications (n = 29; Discontinued group) had a shorter duration of diabetes, lower fat mass and higher skeletal muscle mass and performed better on all of the physical ability test parameters than those who continued on injectable medications during hospitalization (n = 14; Continued group). At discharge, patients in the Discontinued group had achieved better glycemic control than those in the Continued group, as indicated by lower mean plasma glucose levels according to the 7-point profile. Stepwise logistic regression analysis that included those variables that were significantly different between the Continued group and the Discontinued group, with the aim to identify candidate(s) of explanatory variables, revealed that only OLST was significantly associated with the discontinuation of injectable medication. Patients with an OLST of ≥ 60 s were more likely to discontinue injectable medication than those with an OLST of < 60 s (odds ratio 18.9; 95% confidence interval 2.0-178.8; p = 0.011). CONCLUSIONS: Among inpatients with inadequately controlled T2D diabetes, longer OLST appear to be associated with discontinuing injectable medications during hospitalization. OLST could possibly be useful as a novel patient factor to consider in de-intensifying injectable medication.

The association of repeatedly measured low-density lipoprotein cholesterol and all-cause mortality and cardiovascular disease in dyslipidemic patients: A longitudinal study.

BACKGROUND AND AIMS: This study aimed to evaluate the association between very low levels of low-density lipoprotein (LDL) cholesterol and subsequent clinical outcomes among dyslipidemic patients. METHODS: A retrospective longitudinal study was conducted at a large teaching hospital in Tokyo, Japan, from 2005 to 2018. We included all dyslipidemic adult patients who were followed up at the department of endocrinology. The primary outcome was all-cause mortality and the secondary outcome was cardiovascular disease. We compared the development of these outcomes according to LDL cholesterol categories through longitudinal analyses adjusting for potential confounders. RESULTS: We included total of 4485 dyslipidemic patients. The mean patient age (standard deviation) was 58.4 (12.2) years, and 2286 patients were men. During a median follow-up of 5.3 (interquartile range 2.2-9.6) years, 252 (5.7%) patients died (25[0.6%] were cardiovascular deaths) and 912 (20.3%) patients developed cardiovascular diseases. Multivariable longitudinal analyses showed that the very low LDL cholesterol group (<60 mg/dl) had significantly higher all-cause mortality than the normal LDL cholesterol group (100-140 mg/dl) (odds ratio[OR] 1.96, 95%confidence interval [CI]:1.22-3.16). Among high-risk patients for atherosclerotic cardiovascular disease (ASCVD), very low LDL cholesterol was significantly associated with increased all-cause mortality (OR 2.61, 95%CI: 1.12-6.10) but decreased incidence of cardiovascular disease (OR 0.47, 95%CI: 0.23-0.93). CONCLUSIONS: Very low LDL cholesterol is associated with increased all-cause mortality but not statistically associated with cardiovascular disease incidence among dyslipidemic patients, regardless of risk. When patients were stratified according to ASCVD risk, this association was more obvious among high-risk patients.

Development of malignancies and changes in time-dependent hemoglobin A1c among a nondiabetic population: longitudinal analysis.

BACKGROUND: The fluctuation of hemoglobin A1c (HbA1c) and changes in health habits over time was not considered in previous studies. The aim of this study was to evaluate the time-sequenced association between malignancy incidence and HbA1c with a longitudinal study design using repeated measurements of HbA1c. METHODS: A retrospective longitudinal study was conducted at a large teaching hospital in Tokyo, Japan, from 2005 to 2016. All participants who underwent voluntary health check-ups at the hospital were included. Our outcomes were the development of malignancy. We compared these outcomes using HbA1c categories. Longitudinal analyses were conducted with a mixed effects model in which time-dependent HbA1c measurements were applied to consider fluctuations in HbA1c levels, adjusted for covariates. RESULTS: A total of 77,385 nondiabetic participants were included in the study; the mean age was 44.7 and 49.4% of participants were male. During a median follow-up of 1588 (interquartile range 730-2946) days, 4506 (5.8%) participants developed malignancies. The relationship between future malignancies and HbA1c was U-shaped; both the lower HbA1c groups (OR 1.31, 95% CI 1.17-1.46 for < 5.0%) and the higher HbA1c group (OR 1.87, 95% CI 1.03-3.39 for ≥ 7.5%) had significantly higher odds ratios compared to the 5.5-5.9%. The lowest HbA1c was associated with higher odds of breast cancer (OR 1.5, 95% CI 1.21-1.86) and female genital cancer (OR 1.57, 95% CI 1.04-2.37). CONCLUSIONS: Our study found a U-shaped association between HbA1c and future malignancies among nondiabetic people but did not find additional risk at the prediabetic level. Low HbA1c may be associated with the incidence of breast cancer and female genital cancer.