Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

Imitation Learning Errors Are Affected by Visual Cues in Both Performance and Observation Phases.

Mechanisms of action imitation were examined. Previous studies have suggested that success or failure of imitation is determined at the point of observing an action. In other words, cognitive processing after observation is not related to the success of imitation; 20 university students participated in each of three experiments in which they observed a series of object manipulations consisting of four elements (hands, tools, object, and end points) and then imitated the manipulations. In Experiment 1, a specific intially observed element was color coded, and the specific manipulated object at the imitation stage was identically color coded; participants accurately imitated the color coded element. In Experiment 2, a specific element was color coded at the observation but not at the imitation stage, and there were no effects of color coding on imitation. In Experiment 3, participants were verbally instructed to attend to a specific element at the imitation stage, but the verbal instructions had no effect. Thus, the success of imitation may not be determined at the stage of observing an action and color coding can provide a clue for imitation at the imitation stage.

Nutritional counseling regulates interdialytic weight gain and blood pressure in outpatients receiving maintenance hemodialysis.

Maintenance hemodialysis outpatients must limit salt and water intake to maintain electrolyte balance and blood pressure. In Kawashima Hospital, nationally registered dietitians provide hemodialysis patients with monthly nutritional counseling. We investigated whether nutritional counseling affects interdialytic weight gain (IDWG) and blood pressure. We investigated 48 hemodialysis patients whose monthly average IDWG ratio to dry weight exceeded 5.1% and who had not had a long-term hospital admittance of > 1 month. After the 48-month nutritional counseling period, the IDWG ratio had improved in 37 of the patients (77.1%), significantly decreasing from 6.0±0.7 to 5.3±0.9%. Estimated salt and water intake decreased significantly from 13.3±2.7 to 11.8±2.4 g/day and 2528±455 to 2332±410 ml/day, respectively. During the intervention period, normalized protein catabolic rate and body mass index did not change substantially. Pre-hemodialysis systolic and diastolic blood pressures had significantly decreased from 149±19 to 134±18 mmHg, and 82±13 to 75±10 mmHg for 48 months after study initiation, respectively. The dosage of antihypertensive drugs had significantly decreased in the group that experienced improvement in the IDWG ratio. Long-term nutritional counseling by nationally registered dietitians may improve the IDWG ratio and blood pressure of hemodialysis patients by decreasing their salt and water intake. J. Med. Invest. 64: 129-135, February, 2017.

Shortened red blood cell lifespan is related to the dose of erythropoiesis-stimulating agents requirement in patients on hemodialysis.

Renal anemia is an important complication of chronic kidney disease (CKD). One of the most important complications of renal anemia is reduced red blood cell (RBC) lifespan, but there has been little research conducted into the causes of and treatments for this anemia. We measured alveolar carbon monoxide (CO) and then estimated RBC lifespan in patients on hemodialysis (HD). We also examined their requirement for erythropoiesis-stimulating agents (ESA), HD dose, nutrition factors, iron metabolism factor, reticulocyte counts and % reticulocytes. We enrolled 140 patients undergoing intermittent HD; among this group, 31 were not administered ESA and the others were on ESA therapy. Twelve healthy volunteers served as controls. The RBC lifespans in the healthy volunteers and in the HD patients were 128 ± 28 and 89 ± 28 days (mean ± SD), respectively. The RBC lifespan significantly and negatively correlated with ESA requirement (r = -0.489, P < 0.0001) in the HD patients. Other factors suspected to influence the RBC lifespan did not significantly correlate with the RBC lifespan in HD patients, in contrast to the correlation observed for S-Cr, BUN, S-ALB and total cholesterol vs. RBC lifespan. A shortened RBC lifespan seems to rather significantly affect the ESA requirement. Better nutritional status or active HD patients also seem to have longer RBC lifespans and lower ESA requirement.

Physical imitation and verbal description of modeled movements engage different encoding processes.

The present study analyzed the effects of performing a specified sequence of movements in imitation of a model, and examined the characteristics of the encoding involved in the process. Thirty-two college students were presented with a movement model that consisted of five elements and performed imitation tasks in which they either reproduced the movement sequence physically or described it verbally. During the period from the onset of the movement model to the imitation response, participants performed articulation suppression, movement suppression, and spatial suppression tasks, and their effects on the imitation response were analyzed. The results showed that the encoding processes for conversion to movement and to language were different, and that movements associated with articulations or planning of articulations and spatial processing were involved in converting the model to movement. In addition, imitation-specific goal selection was partially supported in movement conversion, but not in language conversion.

Lower value of glycated haemoglobin relative to glycaemic control in diabetic patients with end-stage renal disease not on haemodialysis.

BACKGROUND: Glycated haemoglobin (HbA1c) concentration is lower relative to glyacemic control in diabetic patients on haemodialysis. However, it is unknown as to whether this is also true for diabetic patients with end-stage renal disease but not on haemodialysis. METHODS: Correlations between HbA1c or glycated albumin (GA) and estimated glomerular filtration rate (eGFR) (determined by serum creatinine concentration, sex and age) were investigated in 86 diabetic patients with renal dysfunction not on dialysis. The mean values of HbA1c and of red blood cell (RBC) lifespan were compared among four groups of patients: Group 1 (n = 30, eGFR ≥ 60 mL/min/1.73 m(2)), Group 2 (n = 30, eGFR < 60 mL/min/1.73 m(2) but ≥30 mL/min/1.73 m(2)), Group 3 (n = 13, eGFR < 30 mL/min/1.73 m(2) but ≥15 mL/min/1.73 m(2)) and Group 4 (n = 13, eGFR < 15 mL/min/1.73 m(2) without haemodialysis). RBC lifespan was determined in each subject from the difference between alveolar carbon monoxide (CO) concentration and atmospheric CO concentration. RESULTS: HbA1c was significantly correlated with eGFR (r = 0.37, P = 0.0004), but GA was not. The HbA1c values in Group 3 (6.8 ± 0.6%) and Group 4 (6.3 ± 0.5%) were significantly lower than that in Group 1 (7.4 ± 0.8%), but there was no difference between Group 2 (7.2 ± 0.7%) and Group 1. There was a significant correlation between RBC lifespan and eGFR, and the mean RBC lifespan in Group 3 (96 ± 35 d) and Group 4 (94 ± 30 d) were significantly shorter than that in Group 1 (127 ± 30 d). CONCLUSIONS: Diabetic patients with stage 4 or 5 chronic kidney disease not on haemodialysis had significantly lower values of HbA1c and shorter RBC lifespan compared with diabetic patients without renal dysfunction.

Imitation of modeled manipulation of objects by children and adults.

Prior studies have investigated imitation by extracting a hierarchy of goals from the key elements of action models. The theoretical model is that all ages practice a method of imitation in which goal or target elements are more easily imitated correctly, while nontarget elements are not. The present study compared error responses among 32 children and 32 adults when imitating an action model for manipulating concrete objects constructed of five elements. The results indicated that the elements for which error responses were easily produced and those for which error responses were more difficult to produce were approximately the same in children and adults. It showed that the imitation mechanisms were similar in children and adults. In addition, children had higher omissions and error responses than adults. This result suggests that imitation and differences in working memory capacity may be related.

Children's imitations of movements are goal-directed and context-specific.

Previous research indicates that imitation of gestures in preschool children is goal-directed. A goal may be a salient feature from a presented movement; that goal may be imitated correctly, but other features were ignored, resulting in observable errors. Objects (e.g., a dot on the table) can become the most salient features and presence or absence of objects influences imitation responses. Imitation responses were examined under conditions in which objects could not be used directly as the most salient feature. 60 children (M age = 5:6) were assigned to Gestural, Dot, No-dot, and Un-dot conditions, and they were asked to imitate 20 movements. The type of presented movement and the occurrence of correct, mirror, and error responses were examined. Responses in the Un-dot condition were similar to those in the Dot condition. Error responses in the Un-dot condition were related to age. Children may extract a more abstract feature in a context without visible objects. This ability is associated with a cognitive mechanism developed in preschool years.

Significance of definition and classification of a gesture for study of spontaneous gesture: comment on Chieffi and Ricci's study.

In research on gesture production, including Chieffi and Ricci's 2005 study, the focus has been on the connection between gesture and speech. To investigate spontaneous gestures, the most important points have been the definition and classification of gesture. These points may directly influence the result and its interpretation.

Action models and verbal descriptions in object representations given through gestures by preschool children.

Previous research suggests that young children have difficulty producing pantomimic gestures with imagined objects for which no substitute objects are presented. They frequently substitute specific body parts to represent the object through gestures involved in the action. This study examined whether adults' verbal descriptions or symbolic action models help to produce an imaginary-object gestural response. 53 children (26 4-yr.-olds, and 27 5-yr.-olds) performed gestural tasks in which they were asked to pretend to use common objects, e.g., "pretend to brush your teeth with a toothbrush." They were then given verbal descriptions or action models to perform those same tasks. Analysis indicated that providing verbal descriptions and action models helps to produce an imaginary-object response in 4- and 5-yr.-old children. Action models proved more effective than verbal descriptions among 4-yr.-old children. Results are discussed indicating that each verbal description and action model could be influenced by different mechanisms underlying preschool children's symbol production.