Rapidly progressive cognitive impairment resulting in heavy psychosocial burden in a patient with Fabry disease undergoing hemodialysis: a case report.

BACKGROUND: Long-term enzyme replacement therapy (ERT) may improve prognosis in the patients with Fabry disease (FD), however, detail psychosocial burden has not been focused on long life expectancy. We experienced a male case of FD under ERT, he was placed on hemodialysis and presented rapidly progressive cognitive function. CASE PRESENTATION: A 51-year-old male patient with FD has been receiving ERT from age of 38 years. Hemodialysis was initiated at the age of 47 years. The patient experienced several attacks of cerebral infarction, and brain images demonstrated wide-spread asymptomatic ischemic lesions. His behavior became problematic at the age of 51 years. He often exhibited restlessness during hemodialysis sessions and failure to communicate effectively. The patient experienced impairment of attention and executive function, topographical disorientation, and amnesia. Consequently, it was necessary for medical staff and family members to monitor his behavior for safe extracorporeal circulation and daily life activities. Annual standardized neuropsychiatric testing revealed worsening of cognitive performance. CONCLUSIONS: Despite treating with long-term ERT, it is necessary to determine the psychosocial burden derived from the progression of cognitive impairment in patients with FD undergoing hemodialysis.

Ethnicity and IgA nephropathy: worldwide differences in epidemiology, timing of diagnosis, clinical manifestations, management and prognosis.

Immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis, is one of the major causes of end-stage renal disease. Significant variances in epidemiology, clinical manifestation, timing of diagnosis, management and renal prognosis of IgAN have been reported worldwide. The incidence of IgAN is the most frequent in Asia, followed by Europe, and lower in Africa. Moreover, Asian patients show more frequent acute lesions in renal histology and present poorer renal outcomes compared with Caucasians. The comorbidities also show the difference between Asians and Caucasians. Although the frequency of gross hematuria with upper respiratory tract infection is not different, comorbidities with gastrointestinal diseases are reported to be higher in Europe. Recently, genetic studies for variant ethnic patients revealed widely ranging genetic risks in each ethnicity. A genetic risk score is most elevated in Asians, intermediate in Europeans and lowest in Africans, consistent with the disease prevalence of IgAN globally. Ethnic variance might be highly affected by the difference in genetic background. However, it is also essential to mention that the different timing of diagnosis due to variant urinary screening systems and the indication for renal biopsy in different countries may also contribute to these variances. The management of IgAN also varies internationally. Currently, several novel therapies based on the pathogenesis of IgAN are being assessed and are expected to become available soon. Further understanding the ethnic variance of IgAN might help establish individualized care for this disease. Here, we review the issues of ethnic heterogeneities of IgAN.

Improved Assessment of Soil Nonextractable Residues of the Pyrethroid Insecticide Cyphenothrin.

The metabolic fate of pyrethroid insecticide cyphenothrin (1) [(RS)-α-cyano-3-phenoxybenzyl (1RS)-cis-trans-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate] in soils was investigated using 14C-labeled (1R)-cis/trans isomers at the cyclopropane ring. Both isomers degraded with half-lives of 19.0-47.4 days, and 48.9-56.0% and 27.5-38.7% of the applied radioactivity (AR) were mineralized to CO2 and incorporated into nonextractable residues (NER), respectively, after 120 days at 20 °C. NER analyses revealed 37.5-42.2% (cis-1) and 44.9-54.1% (trans-1) of each residue at 30/120 days were comprised of 14C-amino acids (AAs) as microbial products. Assuming that 50% of microbial biomass is AAs, it was estimated that 11.3-22.9%AR (cis-1, 75.0-84.4% of NER) and 13.9-30.4%AR (trans-1, 89.8-108.2% of NER) were nonhazardous biogenic NER (bio-NER), while type I/II xenobiotic NER (xeno-NER) characterized by silylation was insignificant at 0.9-1.0%/2.8-3.3%AR (cis-1). Detailed 14C-AA quantitation indicated a high relevance of the tricarboxylic acid cycle and pyruvate pathway during bio-NER formation, offering new insights into the microbial assimilation of the chrysanthemic moiety.

Cost Analysis of Screening for IgA Nephropathy Using Novel Biomarkers.

OBJECTIVES: IgA nephropathy (IgAN) is the most common primary chronic glomerulonephritis and a major cause of end-stage kidney disease worldwide. Novel biomarkers, including the aberrantly glycosylated IgA1 and glycan-specific antibodies, could be useful in the diagnosis of IgAN. The aim of this study was to assess the cost analysis of IgAN screening using novel biomarkers in addition to the conventional screening compared with conventional screening alone. METHODS: To estimate the medical expense of each strategy related to renal disease for 40 years, we developed an analytical decision model. The decision tree started at "40 years of age with first-time hematuria." It simulated 2 clinical strategies: IgAN screening using the novel biomarkers (group N) and conventional screening (group C). The analysis results were presented as medical expenses from a societal perspective. Discounting was not conducted. RESULTS: The expected medical expense per person for 40 years was ¥31.2 million (~$291 000) in group N and ¥33.4 million (~$312 000) in group C; hence, expense in group N was lower by ¥2.2 million (~$21 000). In group N, the expected value of IgAN increased by 5.67% points (N 48.44%, C 42.77%) and that of dialysis introduction decreased by 0.85% points (N 19.06%, C 19.91%). In the sensitivity analysis, expenses could be reduced in almost all cases except when renal biopsy using conventional screening was performed at the rate of 73% or higher. CONCLUSION: Screening for IgAN using novel biomarkers would reduce renal disease-related expenses.

Relationship between use of sleep medication and accidental falls during hospitalization.

Falls are common in elderly patients, and prevention of fall is important for safety and for reduction of health care costs. Sleep medications are among many potential causes of fall. In this study, we examined relationship of sleep medication with fall from January 2017 to December 2017. 726 falls occurred in 442 patients, and the average age at the time of fall was 60.7 ± 23.8 years. Fall was most common in patients with neurological disease, followed by gastroenterological, ophthalmological, respiratory, and orthopedic conditions. Sleep medication was used in 223 falls (31%). Fall occurred at all times of day, but with a different distribution in patients with and without use of sleep medication. Thus, the rate of falls from 22:00 to 6:00 was significantly higher in patients using sleep medication (62% vs. 18%, p<0.01). There was also a significantly higher rate of multiple falls in patient using sleep medication (p<0.01). Zolpidem (25%, n=63), a non-benzodiazepine, was the most frequently used sleep medication, followed by brotizolam (16%, n=41) and etizolam (13%, n=32), which are both benzodiazepines. Multiple falls from 22:00 to 6:00 occurred significantly more frequently in patients using ≥2 types of sleep medications compared to one (53% vs. 17%, p<0.01). Taking multiple sleeping pills makes it easier to fall, and even drugs with a short half-life, which are considered to be safe, can cause falls at night in elderly patients. The results of this study show that careful selection of sleep medications is required to prevent fall in elderly patients.

Use of Anti-Dementia Drugs Reduces the Risk of Potentially Inappropriate Medications: A Secondary Analysis of a Nationwide Survey of Prescribing Pharmacies.

AIMS: As the number of older people with dementia increases, safe pharmacotherapy in this population has attracted attention in recent years. The aims of this study were to clarify the prescribing patterns in older patients who were prescribed anti-dementia drugs and to investigate the association of potentially inappropriate medications (PIMs) with the use of anti-dementia drugs. METHODS: Adults aged ≥65 years, who were prescribed anti-dementia drugs at 585 pharmacies across Japan (N = 7,953), were surveyed. The percentage of prescriptions of anti-dementia drugs and the effect of those prescriptions on PIMs were investigated. RESULTS: Prescriptions of anti-dementia drugs were found in 4.4% of the entire study population. A multiple logistic regression analysis revealed that the use of anti-dementia drugs reduced the risk of prescribing psychotropic drugs, which represented PIMs, and that a combination of anti-dementia drugs (e.g., cholineesterase inhibitor with memantine) may reduce the risk of prescribing PIMs compared with monotherapy. CONCLUSION: The use of anti-dementia drugs was associated with fewer prescriptions of drugs considered as PIMs.

Emergent initiation of dialysis is related to an increase in both mortality and medical costs.

The number of patients with end-stage renal disease (ESRD) has been increasing, with dialysis treatment being a serious economic problem. To date, no report in Japan considered medical costs spent at the initiation of dialysis treatment, although some reports in other countries described high medical costs in the first year. This study focused on patient status at the time of initiation of dialysis and examined how it affects prognosis and the medical costs. As a result, all patients dying within 4 months experienced emergent dialysis initiation. Emergent dialysis initiation and high medical costs were risk factors for death within 2 years. High C-reactive protein levels and emergent dialysis initiation were associated with increasing medical costs. Acute kidney injury (AKI) contributed most to emergent dialysis initiation followed by stroke, diabetes, heart failure, and short-term care by nephrologists. Therefore, emergent dialysis initiation was a contributing factor to both death and increasing medical costs. To avoid the requirement for emergent dialysis initiation, patients with ESRD should be referred to nephrologists earlier. Furthermore, ESRD patients with clinical histories of AKI, stroke, diabetes, or heart failure should be observed carefully and provided pre-planned initiation of dialysis.

Improving treatment decisions using personalized risk assessment from the International IgA Nephropathy Prediction Tool.

Immunosuppression in IgA nephropathy (IgAN) should be reserved for patients at high-risk of disease progression, which KDIGO guidelines determine based solely on proteinuria 1g or more/day. To investigate if treatment decisions can be more accurately accomplished using individualized risk from the International IgAN Prediction Tool, we simulated allocation of a hypothetical immunosuppression therapy in an international cohort of adults with IgAN. Two decision rules for treatment were applied based on proteinuria of 1g or more/day or predicted risk from the Prediction Tool above a threshold probability. An appropriate decision was defined as immunosuppression allocated to patients experiencing the primary outcome (50% decline in eGFR or ESKD) and withheld otherwise. The net benefit and net reduction in treatment are the proportion of patients appropriately allocated to receive or withhold immunosuppression, adjusted for the harm from inappropriate decisions, calculated for all threshold probabilities from 0-100%. Of 3299 patients followed for 5.1 years, 522 (15.8%) experienced the primary outcome. Treatment allocation based solely on proteinuria of 1g or more/day had a negative net benefit (was harmful) because immunosuppression was increasingly allocated to patients without progressive disease. Compared to using proteinuria, treatment allocation using the Prediction Tool had a larger net benefit up to 23.4% (95% confidence interval 21.5-25.2%) and a larger net reduction in treatment up to 35.1% (32.3-37.8%). Thus, allocation of immunosuppression to high-risk patients with IgAN can be substantially improved using the Prediction Tool compared to using proteinuria.

An analysis of the current condition of the medical insurance system in Japan.

The social security system, including the national health insurance system, in Japan has been maintained at a world-class level since 1974. However, an increase in the number of elderly people, and a decrease in the working generation, caused by a declining birthrate, represents a serious issue for the system both in the present and future. This report analyzes the key problems in the current insurance system and also considers how they can be handled in the future.

Relationship between blood coagulability and sense of burden among caregivers of patients with dementia.

AIM: This study aimed to examine the relationship between blood coagulability and sense of burden among caregivers of patients with senile dementia of the Alzheimer type. METHODS: A cross-sectional study was carried out involving healthy older caregivers who lived with their patients with senile dementia of the Alzheimer type. We evaluated the Zarit Burden Interview score, levels of von Willebrand factor antigen, D-dimer, thrombin-antithrombin III complex, tissue plasminogen activator/plasminogen activator inhibitor type 1 complex, number of chronic diseases, body mass index and number of medications. A linear regression model was used to estimate adjusted associations. RESULTS: Thrombin-antithrombin III complex levels were higher in female caregivers than in male caregivers (P = 0.07). Headaches were significantly more frequent in female caregivers than in male caregivers, as assessed by a visual analog scale (P < 0.01). The number of chronic diseases and body mass index were positively associated with levels of tissue plasminogen activator/plasminogen activator inhibitor type 1 complex (P < 0.05). Similarly, the number of medications was positively associated with levels of D-dimer (P < 0.05). However, the Zarit Burden Interview score was not associated with blood coagulability (P > 0.05). CONCLUSIONS: The present study found that the number of chronic diseases and body mass index were associated with blood coagulability, and that female caregivers were more prone to headaches and higher blood coagulability than male caregivers. These findings highlight the essential nature of health management during caregiving. The impact of caregiver burden on blood coagulability is likely to differ depending on the long-term or short-term psychological stress associated with caregiving conditions. Geriatr Gerontol Int 2019; 19: 804-808.

Polypharmacy and gait speed in individuals with mild cognitive impairment.

AIM: Polypharmacy has been reported to be associated with poor outcomes, including falls and frailty, in older populations. Past studies have found that slower walking speed is a good predictor of progression to frank dementia in mild cognitive impairment (MCI). Some studies of the general population reported that polypharmacy was associated with slower gait speed; however, it remains to be elucidated whether polypharmacy affects gait speed even in individuals with MCI, who already have some deterioration in gait compared with cognitively preserved individuals. The current study explored the association between the number of medications and gait speed in older adults with MCI who have a Clinical Dementia Rating score of 0.5. METHODS: A total of 128 individuals with MCI were included in the present study. The participants were divided into three groups according to the number of medications they were taking: up to four medications was non-polypharmacy; five to nine medications was polypharmacy; and ≥10 medications was hyperpolypharmacy. The background characteristics were compared by analysis of variance for numerical numbers, and by χ2 analysis for categorical factors. Multiple regression and logistic analysis were applied to investigate the association between gait speed and polypharmacy status or number of medications. RESULTS: Gait speed was significantly negatively associated with hyperpolypharmacy status and the number of medications. Slow gait speed (<1 m/s) was also significantly associated with polypharmacy status and the number of medications. CONCLUSIONS: We found that polypharmacy was associated with slow gait speed in older adults with MCI. Geriatr Gerontol Int 2019; 19: 730-735.

Characteristics of falls in orthopedic patients during hospitalization.

Falls are common in elderly patients and comprise 20-30% of all incident reports in hospitals. The current study examined falls in orthopedic patients among 212,617 inpatients admitted to our hospital from April 2012 to March 2017, using a prospective database in the hospital event reporting system. The risk of fall was evaluated using a fall assessment scoresheet at admission and during hospitalization, based on which patients were divided into risk grades 1, 2 and 3. Fall leading to fracture or a life-threatening injury was defined as an adverse event. The number of falls during the study period was 3,925, including 230 in orthopedic patients. Fall cases occurred at all times, but adverse events were significantly more common from 1-7 a.m. (67% vs. 24%, p<0.01). Patients hospitalized for orthopedic surgery had significantly higher fall rates compared to all other patients (3.12% vs. 1.80%, p<0.01), and were older (65.8 vs. 61.4 years, p<0.05) and more frequently >80 years old (23.4% vs. 17.9%, p<0.05). There was a significant difference in fall incidence between risk grades 2 and 3 for patients hospitalized for non-orthopedic surgery, but not for patients hospitalized for orthopedic surgery. We conclude that fall can occur in orthopedic patients with a low predicted risk of fall, and particularly for older patients. This may indicate that frequent specialized fall assessment is desirable after orthopedic surgery.

Incidence and characteristics of accidental falls in hospitalizations.

Aging of the patient population has led to increased occurrence of accidental falls in acute care settings. The aim of this study is to survey the annual occurrence of falls in a university hospital, and to examine procedures to prevent fall. A total of 49,059 inpatients were admitted to our hospital from April 2015 to March 2016. A fall assessment scale was developed to estimate the risk of fall at admission. Data on falls were obtained from the hospital incident reporting system. There were fall-related incidents in 826 patients (1.7%). Most falls occurred in hospital rooms (67%). Adverse events occurred in 101 patients who fell (12%) and were significantly more frequent in patients aged ≥80 years old and in those wearing slippers. The incidence of falls was also significantly higher in patients in the highest risk group. These results support the validity of the risk assessment scale for predicting accidental falls in an acute treatment setting. The findings also clarify the demographic and environmental factors and consequences associated with fall. These results of the study could provide important information for designing effective interventions to prevent fall in elderly patients.

Effects of leisure activities at home on perceived care burden and the endocrine system of caregivers of dementia patients: a randomized controlled study.

BACKGROUND: Psychological stress associated with caregiving is thought to underlie the high incidence of hypertension, ischemic heart disease, and mortality, as well as reduced immune function, among caregivers of dementia patients. Here, we examined the effects of periodic leisure activities performed by caregivers of dementia patients with care recipients at home on perceived care burden and levels of stress hormones. METHODS: Participants were 42 caregivers aged ≥ 65 years of patients diagnosed with Alzheimer's dementia. They were randomly assigned to intervention and non-intervention groups. The intervention group underwent a leisure activity program (30 min/3 times/week for 24 weeks) with the care recipient, and the control group underwent normal care activities. RESULTS: The Zarit Burden Interview (ZBI) score, a subjective indicator of care burden, significantly decreased after intervention in the intervention group (p < 0.05), whereas no difference was observed in the control group. No significant changes were observed in adrenaline, noradrenaline, dopamine, and cortisol levels in both groups. CONCLUSIONS: The lack of changes in stress hormone levels despite a decrease in subjective care burden in the intervention group might be explained by the effects of the chosen leisure activity on the neuroendocrine system. Our findings suggest that periodic leisure activities can reduce perceived care burden among caregivers of dementia patients. However, in order to evaluate accurately the effects of leisure activities of the present study, long-term follow-up of both caregivers and care recipients is necessary. The Nagoya University Department of Medicine Ethics Committee Clinical Trials Registry Number is 1290.

Paradigm shift in activity assessment of IgA nephropathy - optimizing the next generation of diagnostic and therapeutic maneuvers via glycan targeting.

INTRODUCTION: IgA nephropathy (IgAN) is the most common glomerular disease and has a poor prognosis. Appropriate therapeutic strategies are not currently available due to the lack of information regarding IgAN pathogenesis and the absence of appropriate tools to assess disease activity in IgAN, a long-term chronic disease. However, recent evidence revealed that aberrantly glycosylated serum IgA1, mostly galactose-deficient IgA1 (Gd-IgA1) and immune complexes (ICs) with autoantibodies against glycan-containing epitopes on Gd-IgA1 are essential effector molecules. AREAS COVERED: Assessing disease activity by urinalysis/renal biopsy has some limitations, resulting in conflicts regarding the efficacy of possible IgAN-specific therapies. We summarize the characteristics and molecular basis of Gd-IgA1 and related ICs, their clinical application for activity assessment and early diagnosis, and discuss glycan as a potent target of therapeutic agents based on glycan engineering in IgAN. EXPERT OPINION: Recently, Gd-IgA1 and related ICs have shown clinical value for disease activity assessment and IgAN diagnosis. This suggests a paradigm shift in IgAN treatment thus allowing development of appropriate clinical trials of patients with IgAN stages and objective evaluation of the efficacy of future treatments. Early screening and diagnosis may increase therapeutic options, including quantitative regulation of nephritogenic Gd-IgA1 using therapeutic antibodies and selective depletion of Gd-IgA1-producing cells via glycan engineering.

Usefulness of contrast-enhanced ultrasonography using Sonazoid for the assessment of therapeutic response to percutaneous radiofrequency ablation for hepatocellular carcinoma.

AIM: Accurate assessment of the coagulated area is imperative to achieve an excellent outcome from percutaneous radiofrequency ablation (PRFA) for the treatment of hepatocellular carcinoma (HCC). We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) with the contrast-enhancing agent Sonazoid for precisely assessing the therapeutic effect of PRFA for HCC. METHODS: We enrolled 87 consecutive patients with solitary naïve HCC of less than 3 cm in diameter. PRFA treatment was performed with a 17-G cool-tip needle, and CEUS was performed to assess the ablative margin 3 h after the procedure, when the coagulated tumor outline was easiest to discern. The treatment was repeated until an ablative margin greater than 5 mm was confirmed. After CEUS assessment of the therapeutic response, the patients were followed to investigate local tumor recurrence. RESULTS: In 78 patients (89.7%), the outline of the coagulated tumors could be recognized by ultrasonography, and CEUS assessment of the ablative margin was successful. The remaining nine patients were assessed by computed tomography. The 5-year cumulative survival rate after the assessment of the treatment response with CEUS was 58.4%, and the 4-year cumulative total recurrence rate was 72.3%. The 5-year cumulative local tumor recurrence rate was very low (2.3%). CONCLUSION: The assessment with CEUS at 3 h after the PRFA procedure was successful in the majority of the patients, and it yielded a very low rate of local recurrence.

Diagnosis and activity assessment of immunoglobulin A nephropathy: current perspectives on noninvasive testing with aberrantly glycosylated immunoglobulin A-related biomarkers.

Immunoglobulin (Ig) A nephropathy (IgAN) is the most common form of glomerular disease worldwide and is associated with a poor prognosis. Thus, development of a curative treatment and strategies for early diagnosis and treatment are urgently needed. Pathological analysis of renal biopsy is the gold standard for the diagnosis and assessment of disease activity; however, immediate and frequent assessment based on biopsy specimens is difficult. Therefore, a simple and safe alternative is desirable. On the other hand, it is now widely accepted that multi-hit steps, including production of aberrantly glycosylated serum IgA1 (first hit), and IgG or IgA autoantibodies that recognize glycan containing epitopes on glycosylated serum IgA1 (second hit) and their subsequent immune complex formation (third hit) and glomerular deposition (fourth hit), are required for continued progression of IgAN. Although the prognostic and predictive values of several markers have been discussed elsewhere, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of glycosylated serum IgA1 and related IgA immune complex. In addition, we confirmed a significant correlation between serum levels of these essential effector molecules and disease activity after treatment, suggesting that each can be considered as a practical surrogate marker of therapeutic effects in this slowly progressive disease. Such a noninvasive diagnostic and activity assessment method using these disease-oriented specific biomarkers may be useful in the early diagnosis of and intervention in IgAN, with appropriate indication for treatment, and thus aid in the future development and dissemination of specific and curative treatments.