Association between multimorbidity and utilization of medical and long-term care among older adults in a rural mountainous area in Japan.

Objective: With the accelerated population aging, multimorbidity has become an important healthcare issue. However, few studies have examined multimorbidity and its impact on the use of medical and long-term care services in Japan. Therefore, this study aimed to examine the association between multimorbidity and the use of medical and long-term care services among older adults living in the depopulated mountainous areas of Japan. Patients and Methods: A cross-sectional study was conducted using insurance claims data from late-stage medical insurance and long-term care insurance (April 2017 to March 2018) for older adults ≥75 years residing in a mountainous area in the Tottori prefecture. In addition to the descriptive analysis, multiple generalized linear regressions with family gamma and log-link functions were used to examine the association between the number of morbidities and total annual medical and long-term care expenditures. Results: A total of 970 participants ≥75 years were included in the analysis. Participants who had two or more morbidities constituted 86.5% of the total sample. Furthermore, participants with mental disorders were found to have more comorbidities. The number of comorbidities is associated with higher medical and long-term care expenditures. Conclusion: Multimorbidity was dominant among late-stage older adults living in depopulated mountainous areas of Japan, and the number of morbidities was associated with higher economic costs of medical and long-term care services. Mitigating the impact of multimorbidity among older adults in depopulated regions of Japan is an urgent challenge. Future research should investigate the degree and effectiveness of social protections for vulnerable older adults living in remote areas.

Comparison of Recommendations Made by Committee Members with and without Financial Conflict of Interest on Japanese Guideline of Treatment of Hyperuricemia and Gout, Third Edition.

Clinical practice guidelines (CPGs) consist of clinical questions (CQs) and corresponding recommendations. Considering the estimation of body of evidence, patients' opinions, and medical economics, recommendations can vary depending on the votes of the committee members of CPGs. Taking this into consideration, concerns have already been raised on how financial conflict of interest (COI) potentially influences recommendations. In this study, we developed the third edition of guideline for the management of hyperuricemia and gout. This CPG was composed of seven CQs and recommendations. The direction and strength of the recommendations were determined by votes. There are three CQs. Individual questions asked whether uric acid-lowering-agents (ULAs) could be applied to hyperuricemic patients with chronic kidney disease (CKD) (CQ A), hypertension (CQ B), or heart failure (CQ C) to prevent organ damage. We examined whether the absence (18 members) or presence (8 members) of COIs of committee members could influence the votes. In total, 26 committee members with and without COI have equally determined the direction and strength of recommendations. In CQ A, members without financial COIs and those with financial COI selected conditional recommendation for the use of ULAs in patients with CKD (without COI, 17/18; with COI, 7/8). In CQ B, members without financial COIs and those with financial COI selected conditional recommendation against the use of ULAs in hypertensive patients (without COI, 14/18; with COI, 5/8). In CQ C, members without financial COIs and those with financial COIs have selected conditional recommendation against the use of ULAs in patients suffering from heart failure (without COI, 15/18; with COI, 4/8). We found that members with financial COIs have determined their recommendations in the same direction and strength as those without financial COIs.

Late-Onset Intracranial Hemorrhage Presenting as Refractory Hyponatremia: A Case Report.

Here, we report a case of refractory hyponatremia and delayed intracranial hemorrhage following a head injury. A 70-year-old male patient was admitted with complaints of left chest pain and light-headedness after a fall. Hyponatremia recurred despite the correction with intravenous saline. Head computed tomography revealed a chronic subdural hematoma. The subsequent introduction of tolvaptan improved hyponatremia and disorientation. Delayed intracranial hemorrhage is a differential cause of refractory hyponatremia after head contusion. This case is clinically relevant because (i) the diagnostic delay of late-onset intracranial hemorrhage is common but fatal, and (ii) refractory hyponatremia can be a hint of late-onset intracranial hemorrhage.

The Effectiveness of the Multiple-Attending-Physicians System Compared With the Single Attending-Physician System in Inpatient Setting: A Mixed-Method Study.

OBJECTIVES: Medical facilities have been required to effectively utilize insufficient human resources in many countries. Therefore, we qualitatively and quantitively compared physicians' working burden, and assessed advantages and disadvantages of the single- and the multiple-attending physicians systems in inpatient care. METHODS: In this cross-sectional study, we extracted electronic health record of patients from a hospital in Japan from April 2017 to October 2018 to compare anonymous statistical data between the single-attending and multiple-attending-physicians system. Then, we conducted a questionnaire survey for all physicians of single and multiple-attending systems, asking about their physical and psychiatric workload, and their reasons and comments on their working styles. RESULTS: The average length of hospital stay was significantly shorter in the multiple-attending system than in the single-attending system, while patients' age, gender, and diagnoses were similar. From the questionnaire survey, no significant difference was found in all categories although physical burden in multiple-attending system tended to be lower than that in single-attending system. Advantages of multiple-attending system extracted from qualitative analysis are (1) improvement of physicians' quality of life (QOL), (2) lifelong-learning effect, and (3) improving the quality of medical care, while disadvantages were (1) risk of miscommunications, (2) conflicting treatment policies among physicians, and (3) patients' concern. CONCLUSIONS: The multiple-attending physician system in the inpatient setting can reduce the average length of stay for patients and also reduce the physical burden on physicians without compromising their clinical performance.

Effects of Using a Video-Sharing Application on Multidisciplinary Staff During Pre-discharge Home Assessment Visits for Elderly Hospitalized Patients.

Background: Pre-discharge home assessment visits for elderly hospitalized patients are conducted by the hospital staff to ensure a smooth transition to home care and are effective in preventing falls and reducing the rehospitalization rates. However, the effect of an application that enables the viewing of videos of the patient's home activities during the pre-discharge visit on the multidisciplinary professionals who provide services to the patient has not yet been fully clarified. Methods: Multidisciplinary professionals at 23 facilities located in western Tottori Prefecture who used a video-sharing application (Patto-Mie Net) were invited to be interview participants. Those who agreed were interviewed about the usefulness of the application in their work and its effect on multidisciplinary collaboration. A verbatim transcript was made, and thematic analysis was conducted using the qualitative analysis software NVivo. Results: Twenty-eight people participated in the interviews, including nurses, care managers, rehabilitation specialists, care workers, and other social care professions. Fourteen themes and five categories were generated from the analysis: comprehensive information visualization and transferability, identification of changes over time and prognostic prediction, promoting multidisciplinary collaboration, patient and family reality, and disadvantages and concerns. Conclusion: The use of an application that allows video-sharing of a patient's home movement status during a pre-discharge visit has revealed a variety of benefits for multiple professionals in hospitals and other facilities. In particular, the results were characterized by the psychological closeness between multiple professionals, promotion of interprofessional communication, and sharing of reality, including the psychosocial background of the patient and family.

Characterization of Urate Metabolism and Complications of Patients with Renal Hypouricemia.

Objective Both renal hypouricemia (RHU) and gout are associated with renal dysfunction and urolithiasis. The difference in renal complications associated with RHU and gout, however, has not been studied. We characterized the urate metabolism and complications of patients with RHU and compared them with patients with gout. Methods Eighteen patients with RHU who had a serum uric acid (SUA) level <2 mg/dL (10 men and 8 women), 44 patients with gout (44 men) and 16 normouricemic patients (4 men and 12 women) were included. The blood and urinary biochemical data were evaluated. A genetic analysis of uric acid transporter 1 (URAT1) was also conducted in 15 cases with RHU. Results The SUA level of RHU was 0.9±0.5/mg/dL, and the Uur/Ucr and Cur/Ccr were 0.56±0.14% and 45.7±18.0%, respectively. A genetic analysis of URAT1 in 15 RHU patients showed that 13 harbored a URAT1 gene mutation, whereas 2 harbored the wild-type gene. The SUA level was significantly lower in RHU patients (n=11) than in either gout patients (n=44) or normouricemic patients (n=16). This reduction was accompanied by the elevation of Cua/Ccr. Urinary beta 2-microglobulin levels were higher in RHU patients than in gout or normouricemia patients. Cua/Ccr correlated with normalized urinary beta 2-microglobulin levels. The prevalence of urolithiasis was 18.2% in RHU cases and 6.8% in gout cases. A homozygous URAT1 mutation was associated with urolithiasis. Conclusion Besides urolithiasis, RHU can be associated with tubular dysfunction, such as elevated urinary beta 2-microglobulin levels.

A Case of Weight Gain and Edema With Difficulty in Moving Legs Due to Intravascular Large B-cell Lymphoma Diagnosed by Skin Biopsy.

We report a case of intravascular large B-cell lymphoma (IVL) with spinal cord involvement. A 76-year-old woman was referred to our department due to generalized edema and weight gain. She also had difficulty moving her legs. She had no superficial lymphadenopathy upon examination. Her laboratory tests showed a markedly elevated blood lactate dehydrogenase (LDH) level. Although heart failure or interstitial lung disease was initially suspected, she was diagnosed with IVL by skin biopsy. An MRI revealed spinal cord involvement. Post-hospitalization, she began rituximab-combined chemotherapy. In this case, we considered that the spinal cord involvement of the lymphoma caused the neurogenic bladder and leg weakness. IVL often infiltrates the central nervous system and presents with neurological symptoms, including neurogenic bladder. Therefore, imaging studies should be planned to search for the involvement of the central nervous system in lymphoma if accompanied by neurological symptoms. In addition, in patients with a markedly elevated LDH or soluble interleukin-2 receptor level without lymphadenopathy, IVL should be suspected, and consultation with hematologists should be considered.

Xanthinuria Type 1 with a Novel Mutation in Xanthine Dehydrogenase and a Normal Endothelial Function.

Whether or not extremely low levels of serum uric acid (SUA) in xanthinuria are associated with impairment of the endothelial function and exercise-induced acute kidney injury (EIAKI) is unclear. A 59-year-old woman without EIAKI or urolithiasis had undetectable levels of UA in serum and urine and elevated levels of hypoxanthine and xanthine in urine. A genetic analysis revealed homozygous mutations in the XDH gene [c.1585 C>T (p. Gln529*)]. Flow-mediated dilation was within the normal range. This is the first report of a case with extremely low levels of SUA, xanthinuria with novel mutations of xanthine dehydrogenase (XDH) and a normal endothelial function.

Lactobacillus gasseri PA-3 reduces serum uric acid levels in patients with marginal hyperuricemia.

Several studies have reported that Lactobacillus gasseri PA-3 reduces the level of serum uric acid (SUA) in patients with hyperuricemia. However, it remains unknown how PA-3 affects uric acid metabolism. In the present study, we examined effects of PA-3-containing yoghurt on uric acid metabolism in patients with marginal hyperuricemia. Sixteen patients with SUA > 357 µmol/L (marginal hyperuricemia) were enrolled. PA-3-containing yoghurt was administered for 8 weeks. Uric acid metabolism was evaluated just before and 8 weeks after the administration and at 4 weeks after the administration ended (post-administration). SUA levels after the administration were significantly lower than that before the administration and remained low at post-administration. Urinary uric acid concentration (Uur) after the administration were significantly lower than that before the administration. However, post-administration Uur levels were comparable to those before the administration. Therefore, PA-3-containing yoghurt significantly reduced the levels of SUA and Uur in patients with marginal hyperuricemia.

Hsp70 promotes maturation of uromodulin mutants that cause familial juvenile hyperuricemic nephropathy and suppresses cellular damage.

BACKGROUND: Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder caused by mutations in UMOD. Here we studied effects of genetic expression and pharmacological induction of Hsp70 on the UMOD mutants C112Y and C217G. METHODS: We expressed wild type (WT), C112Y and C217G in HEK293 cells and studied their maturation and cellular damage using western blot and flow cytometry. RESULTS: Expression of C112Y or C217G increased pro-apoptotic proteins, decreased anti-apoptotic proteins, and induced cellular apoptosis as examined by annexin V staining and flow cytometry. Overexpression of Hsp70 or administration of an Hsp70 inducer geranylgeranylacetone (GGA) promoted maturation of the mutant proteins, increased their secreted forms, normalized the levels of pro- and anti-apoptotic proteins and suppressed apoptosis. CONCLUSION: These findings indicated that Hsp70 enhanced maturation of C112Y and C217G and reduced cellular apoptosis, suggesting that Hsp70 induction might be of a therapeutic value for treatment of FJHN.

Anorexia in a hemodialysis patient due to pneumatosis intestinalis: A case report.

We report a case of pneumatosis intestinalis (PI) in a hemodialysis patient who presented with anorexia and nausea. Anorexia with postprandial nausea can be caused by gastrointestinal diseases, with one of the rare causes being PI. PI may occur in hemodialysis patients, but it is rarely reported. We experienced a case of benign PI in a hemodialysis patient, for whom the conservative treatment with antibiotics improved the patient's clinical symptoms. In patients with PI, it is important to rule out potentially life-threatening complications, such as the presence of hepatic intraportal gas on CT scan.

Pretreatment with cilnidipine attenuates hypoxia/reoxygenation injury in HL-1 cardiomyocytes through enhanced NO production and action potential shortening.

Myocardial ischemia/reperfusion injury worsens in the absence of nitric oxide synthase (NOS). Cilnidipine, a Ca2+ channel blocker, has been reported to activate endothelial NOS (eNOS) and increases nitric oxide (NO) in vascular endothelial cells. We examined whether pretreatment with cilnidipine could attenuate cardiac cell deaths including apoptosis caused by hypoxia/reoxygenation (H/R) injury. HL-1 mouse atrial myocytes as well as H9c2 rat ventricular cells were exposed to H/R, and cell viability was evaluated by an autoanalyzer and flow cytometry; eNOS expression, NO production, and electrophysiological properties were also evaluated by western blotting, colorimetry, and patch clamping, respectively, in the absence and presence of cilnidipine. Cilnidipine enhanced phosphorylation of eNOS and NO production in a concentration-dependent manner, which was abolished by siRNAs against eNOS or an Hsp90 inhibitor, geldanamycin. Pretreatment with cilnidipine attenuated cell deaths including apoptosis during H/R; this effect was reproduced by an NO donor and a xanthine oxidase inhibitor. The NOS inhibitor L-NAME abolished the protective action of cilnidipine. Pretreatment with cilnidipine also attenuated H9c2 cell death during H/R. Additional cilnidipine treatment during H/R did not significantly enhance its protective action. There was no significant difference in the protective effect of cilnidipine under normal and high Ca2+ conditions. Action potential duration (APD) of HL-1 cells was shortened by cilnidipine, with this shortening augmented after H/R. L-NAME attenuated the APD shortening caused by cilnidipine. These findings indicate that cilnidipine enhances NO production, shortens APD in part by L-type Ca2+ channel block, and thereby prevents HL-1 cell deaths during H/R.

Influence of a community-based approach to improve risk factors of lifestyle diseases by Japanese public health nurses: A case-control study.

BACKGROUND AND OBJECTIVES: It is important to examine the roles of specific health check-up and specific health guidance in individuals at high risk of common lifestyle diseases, but evaluation based on a stratified analysis of people undergoing a health check-up has not been adequately performed. In this study, we examined the effects of providing specific health guidance to individuals considered at high risk for a lifestyle disease after specific health check-ups. METHOD: Subjects who underwent a specific health check-up in 2012 were assigned to either a group that received health guidance from public health nurses over three years (n = 393) or a control group (n = 109). Clinical findings of both groups were analysed to evaluate the correlation between their changes and health guidance. RESULTS: A significant decrease was observed in blood pressure, and lipid and glucose levels only in the health guidance group. Multiple regression analysis revealed that health guidance was the explanatory variable of serum lipid improvement. DISCUSSION: Continued support by Japanese public health nurses through health guidance closely related to the subject's lifestyle over three years may lead to a comprehensive reduction in the risk of lifestyle diseases.

ß-Adrenergic Blocker, Carvedilol, Abolishes Ameliorating Actions of Adipose-Derived Stem Cell Sheets on Cardiac Dysfunction and Remodeling After Myocardial Infarction.

BACKGROUND: Treatment of myocardial infarction (MI) includes inhibition of the sympathetic nervous system (SNS). Cell-based therapy using adipose-derived stem cells (ASCs) has emerged as a novel therapeutic approach to treat heart failure in MI. The purpose of this study was to determine whether a combination of ASC transplantation and SNS inhibition synergistically improves cardiac functions after MI.Methods and Results:ASCs were isolated from fat tissues of Lewis rats. In in vitro studies using cultured ASC cells, mRNA levels of angiogenic factors under normoxia or hypoxia, and the effects of norepinephrine and a ß-blocker, carvedilol, on the mRNA levels were determined. Hypoxia increased vascular endothelial growth factor (VEGF) mRNA in ASCs. Norepinephrine further increased VEGF mRNA; this effect was unaffected by carvedilol. VEGF promoted VEGF receptor phosphorylation and tube formation of human umbilical vein endothelial cells, which were inhibited by carvedilol. In in vivo studies using a rat MI model, transplanted ASC sheets improved contractile functions of MI hearts; they also facilitated neovascularization and suppressed fibrosis after MI. These beneficial effects of ASC sheets were abolished by carvedilol. The effects of ASC sheets and carvedilol on MI heart functions were confirmed by Langendorff perfusion experiments using isolated hearts. CONCLUSIONS: ASC sheets prevented cardiac dysfunctions and remodeling after MI in a rat model via VEGF secretion. Inhibition of VEGF effects by carvedilol abolished their beneficial effects.

Clinical practice guideline for renal hypouricemia (1st edition).

Renal hypouricemia (RHUC) is a disease caused by dysfunction of renal urate reabsorption transporters; however, diagnostic guidance and guidelines for RHUC have been lacking, partly due to the low evidence level of studies on RHUC. This review describes a world-first clinical practice guideline (CPG) and its first version in English for this condition. It was developed following the "MINDS Manual for Guideline Development" methodology, which prioritizes evidence-based medicine. It was published in Japanese in 2017 and later translated into English. The primary goal of this CPG is to clarify the criteria for diagnosing RHUC; another aim is to work towards a consensus on clinical decision-making. One of the CPG's unique points is that it contains textbook descriptions at the expert consensus level, in addition to two clinical questions and recommendations derived from a systematic review of the literature. The guidance shown in this CPG makes it easy to diagnose RHUC from simple blood and urine tests. This CPG contains almost all of the clinical foci of RHUC: epidemiology, pathophysiology, diagnostic guidance, clinical examinations, differential diagnosis, and complications, including exercise-induced acute kidney injury and urolithiasis. A CPG summary as well as a clinical algorithm to assist healthcare providers with a quick reference and notes from an athlete for both physicians and patients are included. We hope that this CPG will help healthcare providers and patients to make clinical decisions, and that it will promote further research on RHUC.

Small Bowel Obstruction Due to Mochi (Rice Cake): A Case Report and Review of the Literature.

A 66-year-old man presented at our emergency department with severe intermittent abdominal pain. His history revealed that he had eaten several mochi (rice cakes) without sufficiently chewing them before swallowing. Following computed tomography that showed a high value, he was diagnosed with an obstruction caused by mochi. Although mochi obstruction can sometimes improve with conservative treatment, this case required laparotomy. Medical literature in English on small bowel obstruction due to mochi is rare, but fortunately in this case we were able to collect complete laboratory and imaging data. Furthermore, due to the surgical findings, we could clearly diagnose the pathophysiology of mochi obstruction. Here we describe a case of small bowel obstruction due to mochi, and review the literature to determine the characteristics of intestinal obstruction caused by it.

Education for Community-based Family Medicine: A Social Need in the Real World.

One of the most critical social problems in Japan is the remarkable increase in the aging population. Elderly patients with a variety of complications and issues other than biomedical problems such as dementia and life support with nursing care have been also increasing. Ever since the Japanese economy started to decline after the economic bubble burst of 1991 and the Lehman Brothers bankruptcy in 2008, how we can resolve health problems of the elderly at a lower cost has become one of our most challenging social issues. On the other hand, the appropriate supply of medical and welfare resources is also a fundamental problem. The disparity of physician distribution leads to a marked lack of medical services especially in remote and rural areas of Japan. The government has been attempting to recruit physicians into rural areas through a regional quota system. Based on this background, the medical field pays a great amount of attention to community-based family medicine (CBFM). CBFM requires basic knowledge of community health and family medicine. The main people involved in CBFM are expected to be a new type of general practitioner that cares for residents in targeted communities. To improve the performance of CBFM doctors, we need to establish a better CBFM education system and assess it appropriately when needed. Here, we review the background of CBFM development and propose an effective education system.

Prevalence and complications of hypouricemia in a general population: A large-scale cross-sectional study in Japan.

BACKGROUNDS: Hypouricemia was reported as a risk factor for exercise-induced acute renal injury (EIAKI) and urinary stones. However, the prevalence of kidney diseases among hypouricemic subjects has not been evaluated. This study was conducted to clarify the prevalence of hypouricemia and the association of hypouricemia with kidney diseases by using a large-scale Japanese population data. METHODS: This study is a retrospective cross-sectional study at the Center for Preventive Medicine, St. Luke's International Hospital, Tokyo, Japan, and Sanin Rousai Hospital, Yonago, Japan. We analyzed the medical records of 90,143 Japanese subjects at the center in St. Luke's International Hospital, Tokyo, and 4,837 subjects in Sanin Rousai Hospital, Yonago, who underwent annual regular health check-up between January 2004 and June 2010. We defined hypouricemia as serum uric acid level of ≤2.0 mg/dL. We checked the medical history of all the study subjects and compared the rates of complications including urinary stones and kidney diseases among those with or without hypouricemia. RESULTS: The prevalence of hypouricemia was 0.19% in St. Luke's International Hospital, Tokyo, and 0.58% in Sanin Rousai Hospital, Yonago. The prevalence of hypouricemia in women was larger than that in men both in Tokyo (0.31% vs 0.068%, p<0.001) and in Yonago (1.237% vs 0.318%, p<0.001). Among 172 hypouricemic subjects (30 men), the rates of previous urinary stones and kidney diseases (including nephritis/nephrosis) were 1.2% (3.3% men, 0.7% women) and 2.3% (10% men, 0.7% women), respectively. Hypouricemic men had a 9-fold higher rate of previously having kidney diseases compared to non-hypouricemic men (p<0.001). However, the rates of other diseases including urinary stones were not significantly different between the two groups. CONCLUSIONS: Hypouricemia was associated with a history of kidney disease especially in men.