Risk heterogeneity of bullous pemphigoid among dipeptidyl peptidase-4 inhibitors: A population-based cohort study using Japanese Latter-Stage Elderly Healthcare Database.

AIMS/INTRODUCTION: Although the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and bullous pemphigoid (BP) has begun to be established, some studies have suggested there are risk differences among DPP-4 inhibitors. We conducted a population-based cohort study to examine the risk differences. MATERIALS AND METHODS: Using the claims databases of the Fukuoka Prefecture Wide-Area Association of Latter-Stage Elderly Healthcare between April 1, 2013 and March 31, 2017, we conducted a retrospective cohort study to compare patients receiving one DPP-4 inhibitor with those who were prescribed another antidiabetic drug. The primary outcome was an adjusted hazard ratio (HR) of the development of bullous pemphigoid during a 3-year follow-up. The secondary outcome was the development of BP requiring systemic steroids immediately after the diagnosis. These were estimated using Cox proportional hazards regression models. RESULTS: The study comprised 33,241 patients, of which 0.26% (n = 88) developed bullous pemphigoid during follow-up. The percentages of patients with bullous pemphigoid who required immediate systemic steroid treatment was 0.11% (n = 37). We analyzed four DPP-4 inhibitors: sitagliptin, vildagliptin, alogliptin, and linagliptin. Vildagliptin and linagliptin raised the risk of BP significantly (primary outcome, vildagliptin, HR 2.411 [95% confidence interval (CI) 1.325-4.387], linagliptin, HR 2.550 [95% CI 1.266-5.136], secondary outcome, vildagliptin HR 3.616 [95% CI 1.495-8.745], linagliptin HR 3.556 [95% CI 1.262-10.024]). A statistically significant risk elevation was not observed with sitagliptin and alogliptin (primary outcome, sitagliptin, HR 0.911 [95% CI 0.508-1.635], alogliptin, HR 1.600 [95% CI 0.714-3.584], secondary outcome, sitagliptin, HR 1.192 [95% CI 0.475-2.992], alogliptin, HR 2.007 [95% CI 0.571-7.053]). CONCLUSIONS: Not all the DPP-4 inhibitors could induce bullous pemphigoid significantly. Therefore, the association warrants further investigations before generalization.

Effect of body mass index on vertebral and hip fractures in older people and differences according to sex: a retrospective Japanese cohort study.

OBJECTIVES: The purpose of this study was to investigate the incidence of vertebral and hip fractures in the older people and to clarify the relationship between these fractures and body mass index (BMI) along with the impact of sex differences.DesignThis was a retrospective cohort study.SettingWe used administrative claims data between April 2010 and March 2018. PARTICIPANTS: Older people aged ≥75 years who underwent health examinations in 2010 and were living in the Fukuoka Prefecture, Japan were included in the study. A total of 24 691 participants were included; the mean age was 79.4±4.3 years, 10 853 males and 13 838 females, and an the mean duration of observation was 6.9±1.6 years. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the incidence of vertebral and hip fractures by BMI category (underweight: <18.5 kg/m2, normal weight: 18.5-24.9 kg/m2, overweight and obese: ≥25.0 kg/m2) using a Kaplan-Meier curve in males and females and determined fracture risk by sex using Cox proportional hazards regression analyses. RESULTS: The incidence of vertebral and hip fractures was 16.8% and 6.5%, respectively. The cumulative incidence of vertebral and hip fracture at the last observation (8 years) in each BMI groups (underweight/normal weight/overweight and obese) estimated using the Kaplan-Meier curve was 14.7%/10.4%/9.0% in males and 24.9%/23.0%/21.9% in females, and 6.3%/2.9%/2.4% in males and 14.1%/9.0%/8.1% in females, respectively, and both fractures were significantly higher in underweight groups regardless of sex. Multivariable Cox proportional hazards models showed that underweight was a significant risk factor only in males for vertebral fractures and in both males and females for hip fractures. CONCLUSION: Underweight was associated with fractures in the ageing population, but there was a sex difference in the effect for vertebral fractures.

Influence of Occupational Background on Smoking Prevalence as a Health Inequality Among Employees of Medium- and Small-Sized Companies in Japan.

Tobacco smoking is a major public health problem. In addition, the influence of socioeconomic status on health inequalities has received great attention worldwide. The authors used insurance data of beneficiaries employed in medium- and small-sized Japanese companies to investigate the influence of occupational background on smoking prevalence as a health inequality among workers in Japan. Participants were aged 35-74 years and underwent health examinations in 2015. Smoking prevalence was estimated for each occupational group according to sex, age, and income. Logistic regression analysis was used to assess the association between smoking status and occupational groups. A total of 385,945 participants were included. Overall smoking prevalence was 36.3%, higher than average in Japan. Smoking prevalence was lowest among workers in the education and learning support category; all other occupational groups had significantly high prevalence, with the highest for transport and postal services (odds ratio 2.69, 95% confidence interval 2.53-2.86). There were few differences in smoking prevalence at higher income levels among female participants, but differences were remarkably significant at lower income levels. For health inequalities related to smoking, occupational background was associated with smoking prevalence. In particular, there was high smoking prevalence in workplaces not covered by smoke-free policies. These results also demonstrated differences between the sexes; smoking prevalence among female workers with lower income levels was strongly associated with occupational background whereas there were no large differences among male workers by income. These findings suggest that the government should encourage companies to adopt smoke-free policies in the workplace.

Risk of depressive disorders after tobacco smoking cessation: a retrospective cohort study in Fukuoka, Japan.

OBJECTIVE: We sought to examine the effect of smoking cessation on subsequent development of depressive disorders. DESIGN: This was a retrospective cohort study. METHODS: We used administrative claim and health check data from fiscal years 2010 to 2014, obtained from the largest health insurance association in Fukuoka, Japan. Study participants were between 30 and 69 years old. The end-point outcome was incidence of depressive disorders. Survival analysis and Cox proportional hazards models were conducted. The evaluated potential confounders were sex, age, standard monthly income and psychiatric medical history. RESULTS: The final number of participants was 87 255, with 7841 in the smoking cessation group and 79 414 in the smoking group. The result of survival analysis showed no significant difference in depressive disorders between the two groups. The results of Cox proportional hazards models showed no significant difference by multivariate analysis between participants, including users of smoking cessation medication (HR 1.04, 95% Cl 0.89 to 1.22) and excluding medication use (HR 0.97, 95% Cl 0.82 to 1.15). CONCLUSIONS: The present study showed that there were no significant differences with respect to having depressive disorders between smoking cessation and smoking groups. We also showed that smoking cessation was not related to incidence of depressive disorders among participants, including and excluding users of smoking cessation medication, after adjusting for potential confounders. Although the results have some limitations because of the nature of the study design, our findings will provide helpful information to smokers, health professionals and policy makers for improving smoking cessation.

Efficacy of S-1 monotherapy for older patients with unresectable pancreatic cancer: A retrospective cohort study.

OBJECTIVES: Pancreatic cancer is a fatal malignancy that frequently occurs in older patients. However, limited evidence is available on the effects of chemotherapy on older patients with unresectable pancreatic cancer. Here we explored the efficacy of S-1, an oral fluorouracil drug, compared with gemcitabine, as first-line chemotherapy. MATERIALS AND METHODS: We conducted a retrospective cohort study of patients with unresectable pancreatic cancer aged ≥75 years. For this purpose, we used the claims and master databases of the Fukuoka Prefecture Wide-Area Association of Latter-Stage Elderly Healthcare between April 1, 2010 to March 31, 2017. According to first-line chemotherapy, we divided patients into gemcitabine and S-1 groups to compare three-year survival from the date of diagnosis and time to second-line chemotherapy as a surrogate indicator of progression-free survival. We analyzed the data using multivariate Cox proportional hazards method. RESULTS: The study comprised 680 patients, of which 92.5% (N = 629) died within three years of diagnosis. The S-1 group had a significantly lower risk of death within three years of diagnosis (hazard ratio (HR) 0.695, 95% CI: 0. 588-0. 821, p < .001). There were no significant differences (HR 0.968, 95% CI: 0.708-1.324, p = .838) in time to second-line chemotherapy. Two sensitivity analyses excluding study subjects who received radiation therapy or second-line chemotherapy yielded consistent results (HR 0.746, 95% CI: 0.622-0.895, p = .002, HR 0.628, 95% CI: 0. 509-0.776, p < .001, respectively). CONCLUSION: S-1 can serve as a first-line chemotherapeutic option of patients aged ≥75 years with unresectable pancreatic cancer.

Secondhand Smoke and Streptococcal Infection in Young Children Under Japan's Voluntary Tobacco-Free Policy.

Tobacco-free policy in Japan lags behind those of most developed countries. Evidence is required to promote strong implementation of existing policies. This study aimed to assess whether exposure to secondhand smoke (SHS) influences the incidence of streptococcal infection in young children, to further support the need for effective tobacco-free policies in Japan. This study used medical administrative claim and health check data from the Japan Health Insurance Association Fukuoka branch. Participants were beneficiaries' dependents younger than age 4 years. Exposure was defined as SHS from beneficiaries' smoking, each year during 2011-2014. The outcome was incidence of streptococcal infection, diagnosed with and without laboratory testing. Logistic regression analysis was performed to yield odds ratios (ORs) of associations with the outcome and 95% confidence intervals (CIs). This study included a total of 5743 children. The proportion of all participants with a record of streptococcal infection was 4.2% (n = 244). The results of logistic regression analysis between streptococcal infection and SHS exposure showed a significantly higher association (OR 1.39, 95% CI 1.07-1.80, P < 0.05) if all cases were included and an insignificant association with diagnoses using testing (OR 1.20, 95% Cl 0.80-1.80, P = 0.39). This study showed that 60% of streptococcal infections in young children were diagnosed without testing, and SHS increased this incidence regardless of testing. It reports new findings regarding the effect of SHS on infection in young children to support implementation and promotion of tobacco-free policies by the Japanese government not only in public spaces, but also at home.

Transcatheter Embolization of High-flow Renal Arteriovenous Fistula Using N-butyl Cyanoacrylate Accompanied by Delayed Hydronephrosis.

Renal arteriovenous fistula (AVF) is an uncommon anomaly characterized by the communication between renal arteries and veins. Renal AVFs are often asymptomatic but are occasionally accompanied by hematuria or heart failure. Transcatheter closure with embolization is a safe and effective treatment for renal AVF. We herein report an 87-year-old patient with heart failure due to renal AVF who was treated by transcatheter embolization. She developed bacteremia with hydronephrosis, which is a rare complication following the embolization of renal AVF.

Investigation into the causes of indwelling urethral catheter implementation and its effects on clinical outcomes and health care resources among dementia patients with pneumonia: A retrospective cohort study.

There is a possibility that unnecessary treatments and low-quality medical care, such as inappropriate indwelling urethral catheter use, are being provided to older Japanese individuals.The aim of this study was to investigate contextual effects relating to indwelling urethral catheters in older people with dementia and to clarify the effects of indwelling urethral catheter use on patients' mortality, length of stay (LOS), and health care spending. This retrospective cohort study involved 4501 male and female Japanese participants. Those who were aged 75 or older with dementia and had a primary diagnosis of acute lower respiratory disease with antibiotics administered during hospitalization were eligible for inclusion. Patient mortality, LOS, and total charge during hospitalization were the main study outcomes. This study showed that indwelling urethral catheter use was significantly associated with higher mortality, longer LOS, and higher total charge for hospitalization. The pattern of indwelling urethral catheter use was clustered by care facility level. Physician density was significantly associated with indwelling urethral catheter use; the relationship was not linear but U-shaped, such that the approximate median had the lowest rate of urethral catheter use and this increased gradually toward both lower and higher physician densities. Our study found considerable variation in indwelling urethral catheter use between care facilities in older people with dementia. Additionally, indwelling urethral catheter use was related to poor outcomes. Based on these findings, we consider there to be an urgent need for constructing a framework to measure, report on, and promote the improvement of care quality for older individuals in Japan.

Investigation of the Existence of Supplier-Induced Demand in use of Gastrostomy Among Older Adults: A Retrospective Cohort Study.

The aim of this study is to clarify whether there is small area variation in the use of gastrostomy that is explained by hospital physician density, so as to detect the existence of supplier-induced demand (SID).The study design is a retrospective cohort using claim data of Fukuoka Late Elders' Health Insurance, submitted from 2010 to 2013. Study participants included 51,785 older adults who had been diagnosed with eating difficulties. We designated use of gastrostomy as an event. Multilevel logistic analyses were then used to investigate the existence of SID.After controlling for patient factors, we found significant regional level variance in gastrectomy use (median odds ratio [MOR]: 1.72, 1.37-2.51). Hospital physician density was significantly positively related with gastrostomy (adjusted OR of hospital physician density: 1.75, 1.25-2.45; P < 0.001). MORs were largely reduced for the input variable of hospital physician density.We found that the small area variation in use of gastrostomy among older adults could be explained by hospital physician density, which might indicate the existence of SID.

A Case of IgG4-Related Hypophysitis Presented with Hypopituitarism and Diabetes Insipidus.

Immunoglobulin (Ig) G4-related systemic syndrome is a recently described entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells. Pituitary gland can be involved as hypophysitis. We report a case of a 72-year-old man, who presented with general fatigue and weakness. Laboratory tests revealed diabetes insipidus as well as hypopituitarism including adrenal insufficiency, hypogonadism, and hypothyroidism. His serum IgG4 was elevated. MR images showed enlargement of the pituitary stalk. Multiple nodules in bilateral kidneys were pointed out in the abdominal CT. Histological examination of the nodules showed increased IgG4-positive plasma cells. We diagnosed him with IgG4-related kidney disease and hypophysitis. After treatment with hydrocortisone, his symptoms improved. The follow-up images showed that almost all renal nodules disap-peared and his pituitary stalk was shrinking. Our case appears to be very sensitive to glucocorticoid and suggests the possibility of treating IgG4-related hypophysitis successfully with a lower dose of glucocorticoid.

A case of isolated adrenocorticotropic hormone deficiency: a rare but possible cause of hypercalcemia.

A 52-year-old woman presented with an 8-month history of epigastric pain, nausea, and weight loss. One year before, she was diagnosed with breast cancer. During the postoperative chemotherapy, she developed epigastric pain and nausea. As a result, she gradually lost 12 kg of her body weight. We performed upper gastrointestinal endoscopy, which revealed mild erosive gastritis. After the treatment with a proton pump inhibitor, her symptoms persisted. Before the admission, mild hypercalcemia was pointed out. Fluid replacement didn't improve hypercalcemia. We assessed adrenocortical function, which showed that her serum cortisol and adrenocorticotropic hormone were decreased. Through loading tests, we established diagnosis of isolated adrenocorticotropic hormone deficiency. She was treated with hydrocortisone. Soon after the treatment, her serum calcium level returned to normal and her symptoms improved. In a case of hypercalcemia unresponsive to fluid replacement, we recommend ruling out adrenal insufficiency after excluding more common diseases which induce hypercalcemia.

Case of cytomegalovirus colitis in an immunocompetent patient: a rare cause of abdominal pain and diarrhea in the elderly.

Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients after undergoing organ transplantation or chemotherapy. We report the case of a 60-year-old immunocompetent Japanese woman who presented with abdominal pain and bloody diarrhea. She was initially diagnosed as having ischemic colitis with pseudomembranous colitis on the basis of her symptoms, Clostridium difficile antigen positivity, and colonoscopic findings, which showed ulcer formation from the sigmoid colon to rectum. In spite of bowel rest and administration of metronidazole, her symptoms did not improve. On follow-up colonoscopy, ulcerations remained unchanged. Biopsy of the ulceration revealed CMV-infected cells leading to a diagnosis of CMV colitis. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients. We recommend endoscopic biopsy in a case of refractory abdominal pain and bloody diarrhea.

The mobility of Bach2 nuclear foci is regulated by SUMO-1 modification.

The small ubiquitin-like modifier-1 (SUMO-1) modulates the functions of nuclear proteins by changing their structure and/or subnuclear localization. Several nuclear proteins form dynamic higher order nuclear structures, termed non-chromatin nuclear domains, which are involved in the regulation of nuclear function. However, the role that SUMO modification of the component proteins plays in the regulation of the activity and function of nuclear domains is unclear. Here we demonstrate that nuclear domains formed by Bach2, a transcription repressor, show restricted movement and undergo fusion events upon oxidative stress. Mutation of the SUMO-acceptor lysines in Bach2 alters the behavior of these nuclear foci and results in a decreased frequency of fusion events. We propose that SUMO modification is an important regulatory system for the mobility of the nuclear domains formed by Bach2.