Search

Abstract The risk of virus transmission via the touching of contaminated masks has long been assumed by infection control teams. Yet, robust evidence to support this belief has been lacking. This risk was investigated in a laboratory setting by measuring the amount of viable influenza virus successfully transferred from artificially contaminated medical (surgical) mask surfaces to a human finger used to swipe their outer surface under various experimental conditions. Despite being exposed to high levels of virus contamination on the masks, very little or no viable virus was successfully transferred from the mask to the finger in these experiments.

Abstract Background With improved prognosis after lung transplantation (LTx), improving health-related quality of life (HRQL) in patients who have undergone LTx is a key goal. Although HRQL is improved significantly after transplantation, it is poorer than that in ordinary healthy people. However, the factors associated with poor HRQL remain unclear. This cross-sectional study aimed to identify the factors associated with poor HRQL in patients who have undergone LTx. Methods Between December 2018 and May 2022, 80 patients who had undergone LTx completed St. George’s Respiratory Questionnaire (SGRQ) as a disease-specific quality of life measure, the Short Form-12 (SF-12) as a generic quality of life measure, and modified Medical Research Council (mMRC) scale of dyspnea. The groups were assigned according to the median SGRQ-total score and the Japanese population standard for SF-12, and those with good HRQL were compared with those with poor HRQL. Independent factors were evaluated using multivariate analysis. Results With regard to the SGRQ, there were significant differences in the forced expiratory volume in 1 s (FEV1) (P = 0.041), use of bronchodilators (P = 0.026), 6-min walk distance (6MWD) (P

Abstract Background Lung transplant (LTX) can provide a survival benefit and improve physical function for selected patients with advanced pulmonary disease. Sarcopenia is a systemic muscle-failure that can be found in a variety of life stages and disabilities. In this study, we follow the evolution of each variable defined in sarcopenia and the outcomes in LTX recipients with post-transplant sarcopenia. Methods Patients who underwent LTX at Tohoku University Hospital between 2013 and 2018 were consecutively included in the retrospective cohort study, with follow-up to 2019. Sarcopenia was defined by low muscle mass (the cross-sectional area (CSA) of erector spinae muscle (ESM) in thoracic CT with a threshold

Abstract Background The prevalence of osteopenia and osteoporosis is higher in patients with chronic kidney disease than that in the general population. Although physical exercise prevents bone loss in hemodialysis (HD) patients, previous studies have not focused on peritoneal dialysis (PD) patients. Therefore, we aimed to evaluate the effects of home-based exercise on bone mineral density (BMD) in patients with PD. Methods Stable outpatients undergoing PD were randomly assigned to the intervention group (n = 26; male, 20; median age, 66 years) or usual-care group (n = 27; male, 21; median age, 64 years). Patients in the intervention group performed home-based exercises (resistance exercise, stretching, and aerobic exercise such as walking) for 6 months, whereas those in the usual-care group performed stretching and their usual physical activity. Based on dual X-ray absorptiometry, the primary outcomes were the BMD data of the lumbar spine and proximal femoral neck. Secondary outcomes included physical function and physical activity. Pre- and post-intervention values were compared. Results There was no significant within-group change in the BMD of the lumbar spine, femoral neck, and hip after 6 months of the exercise program. The intervention group had significantly improved 30-s chair-stand test, 6-min walk test, and physical activity results. Conclusions Home-based exercises in patients with PD did not improve BMD at any of the sites evaluated. Improvement in physical function and physical activity may reduce the risk of falls in patients with PD. Trial registration UMIN Clinical Trials Registry, UMIN000041678 . Registered September 4, 2020; retrospectively registered.

Abstract Swimming is an extremely popular sport around the world. The streamlined body position is a crucial and foundational position for swimmers. Since the density of lungs is low, the center of buoyancy is always on the cranial side and the center of gravity is always on the caudal side. It has been reported that the greater the distance between the centers of buoyancy and gravity, the swimmer’s legs will sink more. This is disadvantageous to swimming performance. However, the way to reduce the distance between the centers of buoyancy and gravity is yet to be elucidated. Here we show that swimmers with high gliding performance exhibit different abdominal cavity shapes in the streamlined body position, which causes cranial movement of the abdominal organs. This movement can reduce the distance between the centers of buoyancy and gravity, prevent the legs from sinking, and have a positive effect on gliding performance.

Objectives Delirium is an important prognostic factor in postoperative patients undergoing cardiovascular surgery and intervention, including transcatheter aortic valve implantation (TAVI). However, delirium after transcatheter aortic valve implantation (DAT) is difficult to predict and its pathophysiology is still unclear. We aimed to investigate whether preoperative cerebral blood flow (CBF) is associated with DAT and, if so, whether CBF measurement is useful for predicting DAT. Methods We evaluated CBF in 50 consecutive patients before TAVI (84.7±4.5 yrs., 36 females) using 99mTc ethyl cysteinate dimer single-photon emission computed tomography. Preoperative CBF of the DAT group (N = 12) was compared with that of the non-DAT group (N = 38) using whole brain voxel-wise analysis with SPM12 and region of interest-based analysis with the easy-Z score imaging system. Multivariable logistic regression analysis with the presence of DAT was used to create its prediction model. Results The whole brain analysis showed that preoperative CBF in the insula was lower in the DAT than in the non-DAT group (PConclusions These results suggest that preoperative CBF in the insula is associated with DAT and may be useful for its prediction.

In patients with chronic kidney disease, exercise training with moderate intensity protects renal function and improves mortality. However, the mechanisms of the renal protective effects of exercise training in chronic kidney disease have not been clarified. This study investigated the effects of exercise training on renal NADPH oxidative and xanthine oxidase, which are major sources of reactive oxygen species, in rats with chronic renal failure. Six-week-old, male Sprague–Dawley rats were divided into the sham operation, 5/6 nephrectomy (Nx)+ sedentary, and Nx+ exercise training groups. The Nx+ exercise training group underwent treadmill running. After 12 weeks, systolic blood pressure, renal function, malondialdehyde, renal NADPH oxidase, and xanthine oxidase were examined. Nx induced hypertension, proteinuria, and renal dysfunction, and exercise training attenuated these disorders. Although the plasma levels of malondialdehyde were not different among the group, urinary levels were increased by Nx and decreased by exercise training. Renal activity and expression of NADPH oxidase and xanthine oxidase were increased by Nx and decreased by exercise training. These results indicate that exercise training attenuates hypertension and renal dysfunction and ameliorates NADPH oxidase and xanthine oxidase in rats with chronic renal failure, suggesting that the reduction of reactive oxygen species generation may be involved in the renal protective effects of exercise training.

Abstract In recent years, a concept of renal rehabilitation has become widely known among nephrology specialists, dialysis specialists, kidney transplantation specialists, rehabilitation specialists, nutrition specialists, guideline specialists, nurses, physiotherapists, and representatives of patients. Therefore, in order to make it clear the definition, methods, and effectiveness of renal rehabilitation in Japan, we launched Renal Rehabilitation Guideline Preparation Committee in 2016 as a part of works in the Japanese Society of Renal Rehabilitation, and created a guideline in accordance to the “Minds Handbook for Clinical Practice Guideline Development 2014”. Here, we report systematic reviews and recommendations of exercise therapies in patients with kidney diseases based on the guideline preparation committee works. Six recommendations for the condition of each kidney disorder, groups addressing nephritis/nephrosis, chronic kidney diseases, dialysis therapy, and kidney transplantation were created. All the recommendation grades were determined by a consensus conference participated in by representatives of patients and various professionals. The purpose of this report is to provide an evidence-based, best practice summary to optimize the quality, safety and efficacy, and availability of renal rehabilitation service, and to provide care for maximum patient prognosis, quality of life, and satisfaction.

Background: Abdominal aortic aneurysm (AAA) and peripheral artery disease (PAD) are associated with vascular endothelial dysfunction. To date, flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation (NMD) have been used to evaluate vascular function. Recently, parameters of time-course analysis have been proposed as useful evaluations for arteriosclerotic diseases. In this study, the correlation between the parameters of time-course analysis, to the degree of vascular endothelial damage in AAA and PAD, together with their applicability as a vascular function test, was investigated. Methods: Brachial artery vasoreactivity was assessed in male patients with AAA (n = 150) and PAD (n = 50). The percentage change in peak diameters (ΔFMD and ΔNMD), the time to diameter change, the time to peak diameter from the diameter change, the blood flow decay time constant, the area under the curve (AUC), the maximum dilation rate and the extended time constant were measured. Results: Among the groups of aneurysm diameter in AAA, the FMD-AUC was highly different (p = .01), while the ΔFMD was not significantly different (p = .36). Among the Fontaine stages in PAD, the FMD-AUC was inversely associated with severity (p = .01) although the ΔFMD was not significantly different (p = .71). Among the Fontaine stages, the NMD-AUC was also inversely associated with severity (p = .03) although the ΔNMD was not significantly different (p = .11). Conclusion: This study suggests that FMD-AUC and NMD-AUC are useful for estimating vascular endothelial and vascular smooth muscle dysfunction, serving as supplementary markers for the diagnosis and evaluation of PAD and AAA.

ObjectivesWe developed the Adachi Rehabilitation Programme (ARP), a community rehabilitation program. Under the supervision of professional caregivers, older adults cleaned and planted flowers in the park and they walked and shopped in the community. We examined the effects of ARP on individuals receiving small-group multifunctional at-home care at community facilities.MethodsThis was a multi-centre controlled trial at thirteen small multifunctional at-home care facilities in Adachi, Tokyo. The primary outcomes of the study were daily step counts and timed up & go (TUG). Secondary outcomes included gait speed, step length, Barthel Index for Activities of Daily Living, Functional Independence Measure, Mini-Mental State Examination (MMSE) and EuroQOL 5 Dimension.ResultsNinety-six individuals at thirteen small multifunctional at-home care facilities were recruited for participation in December 2017. They were allocated to intervention (38) and control (40) groups. The average daily step count of the control group decreased from 852 to 727, but it increased by approximately 650 steps, from 990 to 1635, for the intervention group. Average TUG decreased from 16.1 s to 14.0 s and MMSE score increased from 15.9 to 16.3 for the intervention group, but a significant interaction was not found. On non-intervention home days, the daily step counts of the intervention group increased significantly from 908 steps to 1485 steps, while those of the control group decreased from 865 steps to 722 steps.ConclusionsARP may have effectively increased the physical activity of older adults under long-term care by increasing motivation and changing behaviour.

Objective: This study elucidated the effects of exercise training on physical activity, 6-min walk distance, and all-cause hospitalization rates in patients with chronic heart failure, and evaluated factors contributing to changes in physical activity. Design: Prospective cohort observational study. Patients and methods: Patients (n =62) who completed an exercise training programme after implantable cardioverter-defibrillator or cardiac resynchronization therapy treatment between May 2017 and May 2018 were included. Patients exercised for 20–50 min 3–5 times weekly for 3 months and were assigned to the active (≥ 10 min/day) or non-active (

Both exercise training (Ex) and superoxide dismutase (SOD) mimetic tempol have antihypertensive and renal protective effects in rodent models of several hypertensions. We recently reported that Ex increases nitric oxide (NO) production and the expression levels of endothelial and neuronal NO synthase (eNOS and nNOS) in the kidney and aorta of the spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY). We also found that endogenous hydrogen peroxide (H2O2) upregulates the expression levels of eNOS and nNOS in SHR. To elucidate the mechanism of the Ex-upregulated NO system in the kidney, we examined the additive effect of Ex and tempol on the renal NO system in SHR and WKY. Our data showed that, in SHR, both Ex and tempol increase the levels of H2O2 and nitrate/nitrite (NOx) in plasma and urine. We also observed an increased renal NOS activity and upregulated expression levels of eNOS and nNOS with decreased NADPH oxidase activity. The effects of the combination of Ex and tempol on these variables were cumulate in SHR. On the other hand, we found that Ex increases these variables with increased renal NADPH oxidase activity, but tempol did not change these variables or affect the Ex-induced upregulation in the activity and expression of NOS in WKY. The SOD activity in the kidney and aorta was activated by tempol only in SHR, but not in WKY; whereas Ex increased SOD activity only in the aorta in both SHR and WKY. These results indicate that Ex-induced endogenous H2O2 produced in the blood vessel and other organs outside of the kidney may be carried to the kidney by blood flow and stimulates the NO system in the kidney.

Abstract Background Decreased physical activity in hemodialysis (HD) patients causes various structural, metabolic, and functional abnormalities due to uremic changes in skeletal muscles. Electrical stimulation (ES) of the lower limbs was found to be effective in patients with cardiac insufficiency for exercise tolerance. This study compared the effects of ES and variable load ergometers on the lower limbs in HD patients. Methods We performed a prospective, double-center, open-label, randomized controlled trial. Eligible patients were aged over 65 years, had end-stage renal disease, and underwent maintenance HD. The primary endpoint was muscle power, and the secondary endpoints included changes in dialysis efficiency, serum phosphorus, and inflammatory markers. Thirty HD outpatients were randomly assigned to the following groups: exercise (EX), ES, or control (SED). In EX and ES groups, patients were instructed to exercise twice a week for 12 weeks, depending on their physical capabilities. The safety and efficacy of aerobic training and ES during HD were confirmed when a sudden decrease in blood pressure or any other side effects did not occur. A repeated measures analysis of variance was performed as the principal method to evaluate time (baseline vs. 12 weeks) and group (EX vs. ES vs. SED) comparisons for the experimental outcomes. Results The efficiency of HD significantly increased in the ES and EX groups (p ≤ 0.02). Moreover, the ES group experienced a significant increase in muscle power (p = 0.01) and the weight bearing index (p = 0.04) and a significant decrease in serum phosphorus level (p = 0.04) and tumor necrosis factor-alpha (TNF-α) level (p = 0.04) from baseline to 12 weeks. Furthermore, there was a significant increase in serum TNF-α level (p ≤ 0.03) over time in both the EX and SED groups. Conclusion The safety and efficacy of aerobic training and ES during HD were confirmed when a sudden decrease in blood pressure or any other side effects did not occur. Therefore, ES may improve the patient’s condition, similar to lower limb exercises, and ES should be considered as an option for rehabilitation programs in HD patients. Trial registration UMIN Clinical Trials Registry (UMIN-CTR R 000032202); retrospectively registered on April 11, 2018

BackgroundCombined renal dysfunction worsens the subsequent prognosis in patients after acute myocardial infarction (AMI). Therefore, establishing a therapeutic modality to maintain or improve renal function in AMI patients is necessary. This study aimed to elucidate the association between physical activity level and change in renal function in such patients.DesignProspective and observational study.MethodsWe enrolled 41 patients (35 men; average age, 67.5 ± 12.6 years) after AMI onset. Blood biochemistry, urinalysis, and physical function tests were conducted at discharge and 3 months after discharge. Renal function was evaluated based on cystatin C based-estimated glomerular filtration rate (eGFRcys). The number of steps was recorded for 3 months post-discharge. Generalized estimating equations (GEE) was used to test the association between physical activity level and within-patient changes in eGFRcys.ResultsPatients were stratified into low (n = 21; number of steps, 2335 ± 1219 steps/day) and high groups (n = 20; number of steps, 7102 ± 2365 steps/day). eGFRcys significantly increased from baseline to after 3 months in the high group (76.5 ± 13.8 to 83.2 ± 16.0 mL/min/1.73 m2, q = 0.004), whereas no significant change was observed in the low group (65.1 ± 15.9 to 62.2 ± 20.2 mL/min/1.73 m2, q = 0.125). Result of GEE adjusted for potential confounding variables showed a significant positive association between physical activity level and within-patient changes in eGFRcys (p = 0.003). Changes in eGFRcys was -2.9 mL/min/1.73 m2 among low group versus +6.7 mL/min/1.73 m2 among high group.ConclusionsPhysical activity level was positively associated with changes in renal function, demonstrating that high physical activity may suppress renal function decline in patients after AMI.

Background. Medical costs associated with cardiovascular disease are increasing considerably worldwide; therefore, an efficacious, cost-effective therapy which allows the effective use of medical resources is vital. There have been few economic evaluations of cardiac rehabilitation (CR), especially meta-analyses of medical cost versus patient outcome. Methods. The target population in this meta-analysis included convalescent and comprehensive CR patients with coronary artery disease (CAD), the status most commonly observed postmyocardial infarction (MI). Here, we evaluated medical costs, quality-adjusted life year (QALY), cost-effectiveness, mortality, and life year (LY). Regarding cost-effectiveness analysis, we analyzed medical costs per QALY, medical costs per LY, and the incremental cost-utility ratio (ICUR). We then examined the differences in effects for the 2 treatment arms (CR vs. usual care (UC)) using the risk ratio (RR) and standardized mean difference (SMD). Results. We reviewed 59 studies and identified 5 studies that matched our selection criteria. In total, 122,485 patients were included in the analysis. Meta-analysis results revealed that the CR arm significantly improved QALY (SMD: −1.78; 95% confidence interval (CI): −2.69, −0.87) compared with UC. Although medical costs tended to be higher in the CR arm compared to the UC arm (SMD: 0.02; 95% CI: −0.08, 0.13), cost/QALY was significantly improved in the CR arm compared with the UC arm (SMD: −0.31; 95% CI: −0.53, −0.09). The ICURs for the studies (4 RCTs and 1 model analysis) were as follows: −48,327.6 USD/QALY; −5,193.8 USD/QALY (dominant, CR is cheaper and more effective than UC); and 4,048.0 USD/QALY, 17,209.4 USD/QALY, and 26,888.7 USD/QALY (

Aims: This study aimed to investigate the effect of 6-month physical exercise with a multicomponent cognitive program (MCP) on the cognitive function of older adults with moderate to severe Alzheimer's disease (AD). Methods: We included 33 participants with AD in a 6-month randomized controlled trial. The intervention group participated in physical exercise and received a MCP. The control group received only the MCP. Before and after the intervention, cognitive outcomes were assessed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Mini-Mental State Examination, and the Clock Drawing Test. Physical performance was evaluated by exercise time, the number of pedal rotation, total load, grip strength, and the Berg Balance Scale (BBS). Results: In all cognitive measures, there were no significant improvements between the two groups after 6 months in the baseline value-adjusted primary analysis. However, the ADAS-cog score was significantly lower between the two groups in secondary analysis adjusted for baseline value, age, sex, and education years. All physical outcomes were significantly higher in the intervention group except for total load compared with baseline measurements. Conclusion: This study indicates that it is possible to improve cognitive function in older adults with moderate to severe AD through 6-month physical exercise with a multicomponent cognitive intervention.

Music and exercise can both affect autonomic nervous system activity. However, the effects of the combination of music and exercise on autonomic activity are poorly understood. Additionally, it remains unknown whether music affects post-exercise orthostatic tolerance. The aim of this study was to evaluate the effects of music on autonomic nervous system activity in orthostatic tolerance after exercise. Twenty-six healthy graduate students participated in four sessions in a random order on four separate days: a sedentary session, a music session, a bicycling session, and a bicycling with music session. Participants were asked to listen to their favorite music and to exercise on a cycle ergometer. We evaluated autonomic nervous system activity before and after each session using frequency analysis of heart rate variability. High frequency power, an index of parasympathetic nervous system activity, was significantly increased in the music session. Heart rate was increased, and high frequency power was decreased, in the bicycling session. There was no significant difference in high frequency power before and after the bicycling with music session, although heart rate was significantly increased. Additionally, both music and exercise did not significantly affect heart rate, systolic blood pressure or also heart rate variability indices in the orthostatic test. These data suggest that music increased parasympathetic activity and attenuated the exercise-induced decrease in parasympathetic activity without altering the orthostatic tolerance after exercise. Therefore, music may be an effective approach for improving post-exercise parasympathetic reactivation, resulting in a faster recovery and a reduction in cardiac stress after exercise.

Early detection and intervention for dysphagia is important in patients with congestive heart failure (CHF). However, previous studies have focused on how many patients with dysphagia develop CHF. Studies focusing on the comorbidity of dysphagia in patients with CHF are rare. Additionally, risk factors for dysphagia in patients with CHF are unclear. Thus, the aim of this study was to clarify risk factors for dysphagia in patients with acute exacerbation of CHF. A total of 105 patients, who were admitted with acute exacerbation of CHF, were enrolled. Clinical interviews, blood chemistry analysis, electrocardiography, echocardiography, Mini-Mental State Examination (MMSE), exercise tolerance tests, phonatory function tests, and evaluation of activities of daily living (ADL) and nutrition were conducted on admission. After attending physicians permitted the drinking of water, swallowing screening tests were performed. Patients were divided into a dysphagia group (DG) or a non-dysphagia group (non-DG) based on Functional Oral Intake Scale level. Among the 105 patients, 38 had dysphagia. A greater number of patients had history of aspiration pneumonia and dementia, and there was a higher age, N-terminal pro-B-type natriuretic peptide level in the DG compared with the non-DG. MMSE scores, exercise tolerance, phonatory function, status of ADL, nutrition, albumin, and transthyretin were lower in the DG compared with the non-DG. In multivariate analysis, after adjusting for age and sex, MMSE, BI score, and transthyretin was independently associated with dysphagia. Comorbidity of dysphagia was 36.1% in patients with acute exacerbation of CHF, and cognitive dysfunction and malnutrition may be an independent predictor of dysphagia.

Morbidity and mortality from aspiration pneumonia continues to be a major health problem in the elderly. A swallowing disorder, such as a delayed triggering of the swallowing reflex, exists in patients with aspiration pneumonia. We found that the swallowing reflex in elderly people was temperature-sensitive. The swallowing reflex was delayed when the temperature of the food was close to body temperature. The actual swallowing time shortened when the temperature difference increases. The improvement of swallowing reflex by temperature stimuli could be mediated by the temperature-sensitive transient receptor potential (TRP) channel. The administration of a pastille with capsaicin as an agonist stimulus of TRPV1, a warm-temperature receptor, decreased the delay in swallowing reflex. Food with menthol, an agonist of TRPM8, a cold-temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimulation such as black pepper was useful to improve the swallowing reflex for people with low activity of daily living (ADL) levels or with decreased consciousness. Oral care also shortened the latent time of swallowing reflex presumably due to stimulating the nociception of the oral cavity. A combination of these sensory stimuli may improve the swallowing disorders and prevent aspiration pneumonia. Keywords:: elderly, olfactory stimulation, swallowing reflex, drug delivery system, aspiration pneumonia

Exercise training is known to exert multiple beneficial effects including renal protection in type 2 diabetes mellitus and obesity. However, the mechanisms regulating these actions remain unclear. The present study evaluated the effects of chronic running exercise on the early stage of diabetic nephropathy, focusing on nitric oxide synthase (NOS), oxidative stress and glycation in the kidneys of Zucker diabetic fatty (ZDF) rats. Male ZDF rats (6 weeks old) underwent forced treadmill exercise for 8 weeks (Ex-ZDF). Sedentary ZDF (Sed-ZDF) and Zucker lean (Sed-ZL) rats served as controls. Exercise attenuated hyperglycemia (plasma glucose; 242 ± 43 mg/dL in Sed-ZDF and 115 ± 5 mg/dL in Ex-ZDF) with increased insulin secretion (plasma insulin; 2.3 ± 0.7 and 5.3 ± 0.9 ng/mL), reduced albumin excretion (urine albumin; 492 ± 70 and 176 ± 11 mg/g creatinine) and normalized creatinine clearance (9.7 ± 1.4 and 4.5 ± 0.8 mL/min per body weight) in ZDF rats. Endothelial (e) and neuronal (n) NOS expression in kidneys of Sed-ZDF rats were lower compared with Sed-ZL rats (p

Chronic heart failure is increasingly prevalent worldwide and is associated with significant morbidity and mortality. The Cochrane review demonstrated that cardiac rehabilitation (CR) resulted in improvements in QOL and a reduction in long-term mortality. Chronic kidney disease (CKD) is another worldwide public health problem. This review focuses on the importance and efficacy of rehabilitation for CKD patients as a new target of CR. Patients with CKD on hemodialysis (HD) have a high mortality rate, with cardiovascular diseases, such as chronic heart failure. A new systematic review and meta-analysis of randomized controlled trials reported that exercise-based renal rehabilitation improved aerobic capacity, muscular functioning, cardiovascular function, walking capacity, and QOL in CKD patients with HD. Moreover, exercise training may have renal protective effects, not only in some animal models of pre-HD CKD, but also in pre-HD CKD patients. Exercise therapy could be an effective clinical strategy in improving renal function, lowering the need for renal replacement therapy, such as HD, and reducing renal transplant risk in pre-HD CKD patients. This led the Ministry of Health, Labor and Welfare of Japan to extend renal rehabilitation partial coverage to stage 4 pre-HD CKD patients for the first time in the world in 2016.