Efficacy and safety of remote cardiac rehabilitation in the recovery phase of cardiovascular diseases (RecRCR study): A multicenter, nonrandomized, and interventional trial in Japan.

Backgrounds: Remote cardiac rehabilitation has proven useful in patients with cardiovascular disease; however, the methodology had not been fully validated. This study aimed to investigate the efficacy and safety of remote cardiac rehabilitation (RCR) with real-time monitoring and an ergometer using a bidirectional communication tool during the recovery phase of cardiovascular diseases. Methods: This multicenter, nonrandomized, interventional study was conducted at 29 institutions across Japan and enrolled patients with cardiovascular diseases who met indications for cardiac rehabilitation (CR) after receiving in-hospital treatment. The RCR group exercised at home using an ergometer and was monitored in real-time using interactive video and monitoring tools for 2-3 months. Educational instructions were provided concurrently through e-learning approaches. The safety of the RCR protocol and the improvement in peak oxygen consumption (VO2) were compared with those of the historical control group that participated in center-based CR. Results: Fifty-three patients from the RCR group were compared with 103 historical controls having similar background characteristics. No patients in RCR experienced significant cardiovascular complications while engaging in exercise sessions. After 2-3 months of RCR, the peak VO2 improved significantly, and the increases in the RCR group did not exhibit any significant differences compared to those in the historical controls. During follow-up, the proportion of patients whose exercise capacity increased by 10% or more was also evaluated; this finding did not indicate a statistically significant distinction between the groups. Conclusions: RCR during the recovery phase of cardiovascular diseases proved equally efficient and safe as center-based CR.

Hospital-Level Variation in Cardiac Rehabilitation After Myocardial Infarction in Japan During Fiscal Years 2014-2015 Using the National Database.

Background: Cardiac rehabilitation (CR) is an evidence-based medical service for patients with acute myocardial infarction (AMI); however, its implementation is inadequate. We investigated the provision status and equality of CR by hospitals in Japan using a comprehensive nationwide claims database. Methods and Results: We analyzed data from the National Database of Health Insurance Claims and Specific Health Checkups in Japan for the period April 2014-March 2016. We identified patients aged ≥20 years with postintervention AMI. We calculated hospital-level proportions of inpatient and outpatient CR participation. The equality of hospital-level proportions of inpatient and outpatient CR participation was evaluated using the Gini coefficient. We included 35,298 patients from 813 hospitals for the analysis of inpatients and 33,328 patients from 799 hospitals for the analysis of outpatients. The median hospital-level proportions of inpatient and outpatient CR participation were 73.3% and 1.8%, respectively. The distribution of inpatient CR participation was bimodal; the Gini coefficients of inpatient and outpatient CR participation were 0.37 and 0.73, respectively. Although there were statistically significant differences in the hospital-level proportion of CR participation for several hospital factors, CR certification status for reimbursement was the only visually evident factor affecting the distribution of CR participation. Conclusions: The distributions of inpatient and outpatient CR participation by hospitals were suboptimal. Further research is warranted to determine future strategies.

Outcomes After Intensive Rehabilitation for Mechanically Ventilated Patients: A Nationwide Retrospective Cohort Study.

OBJECTIVE: To examine the effects of intensive rehabilitation on mortality and liberation from mechanical ventilation among patients with mechanical ventilation in intensive care units. DESIGN: Retrospective cohort study using the Diagnosis Procedure Combination inpatient database. SETTING: Patients discharged from acute care hospitals from April 2010 to March 2016. PARTICIPANTS: Patients (N=46,438) aged 20 years and older who were admitted to intensive care units and who started rehabilitation within 3 days of starting mechanical ventilation. INTERVENTION: Intensive rehabilitation in intensive care unit in the first 5 days after admission. Amount of rehabilitation was defined as the average number of units per day in the first 5 days after admission and was dichotomized as intensive (≥1.0 unit/d) or nonintensive (<1.0 unit/d) rehabilitation. MAIN OUTCOME MEASURES: The primary outcome was in-hospital mortality. The secondary outcome was liberation from mechanical ventilation. RESULTS: We identified 29,982 eligible patients, including intensive (n=7745) and nonintensive (n=22,237) rehabilitation groups. In the propensity score-matched analysis, the intensive rehabilitation group had significantly lower in-hospital mortality (risk difference: -3.4%; 95% CI, -4.9% to -1.9%) and a higher proportion of liberation from mechanical ventilation (subdistribution hazard ratio, 1.08; 95% CI, 1.03-1.13) compared with the nonintensive rehabilitation group. CONCLUSIONS: Patients receiving a higher amount of rehabilitation in intensive care units were less likely to die and more likely to be liberated from mechanical ventilation.

Cost-Effectiveness of Cardiac Rehabilitation in Patients with Coronary Artery Disease: A Meta-Analysis.

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 (<50,000 USD/QALY, CR is costlier but more effective than UC), respectively. Therefore, there were 2 dominant and 3 effective results. CONCLUSIONS: While there are some limitations, primarily regarding data sources, our results suggest that CR is potentially cost-effective.

Peak exercise stroke volume effects on cognitive impairment in community-dwelling people with preserved ejection fraction.

AIMS: The association of vascular dysfunction and amyloid beta deposition attracted attentions for its relationship with cognitive decline. Previous studies show the correlation between the declined cardiac function and the cognitive impairment. In the present study, we analysed the association between cognitive functions and cardiac parameters in community-dwelling people with preserved ejection fraction without heart failure. METHODS AND RESULTS: Subjects were 108 Japanese community-dwelling middle-aged and older adults with preserved ejection fraction (25 men and 83 women; mean age 74.7 years). Cardiac functional parameters at rest were assessed with B-type natriuretic peptide and echocardiography. The cardiopulmonary exercise test was used to test these parameters during exercise. Cognitive function was assessed with the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Other indices were assessed biochemically, physiologically, and physically. There were significant correlations between MoCA-J score and age (r = -0.388), peak oxygen uptake (VO2 , r = 0.201), peak VO2 /heart rate (HR, r = 0.243), peak VO2 /weight (r = 0.244), peak metabolic equivalents (r = 0.244), usual walking speed (r = -0.200), and the Timed Up and Go test (r = -0.230). Multiple linear regression analysis showed peak VO2 /HR was an independent determinant of MoCA-J score after adjusting for potential confounders (B = 0.424). After 6 months of exercise training with 64 subjects, we found that the per cent change of peak VO2 /HR was related to the per cent change of MoCA-J score (r = 0.296). CONCLUSIONS: These results suggested that peak VO2 /HR (an index of stroke volume at peak exercise) might be associated with cognitive impairment based on the vascular cascade hypothesis.

Japanese version of the Montreal Cognitive Assessment cut-off score to clarify improvement of mild cognitive impairment after exercise training in community-dwelling older adults.

AIM: Physical exercise improves cognitive function in people with mild cognitive impairment (MCI). However, information about whether the degree of MCI before exercise training affects improvement in cognitive function is lacking. Therefore, we aimed to investigate the cut-off value in a MCI screening tool that predicts reversal to normal cognitive function after exercise training in older adults with MCI. METHODS: Participants included 112 Japanese community-dwelling older adult outpatients (37 men, 75 women; mean age 76.3 years). We administered the Japanese version of the Montreal Cognitive Assessment (MoCA-J) before and after exercise training. MCI was defined as a MoCA-J score <26. All participants underwent exercise training 2 days per week for 6 months, according to American Heart Association guidelines. RESULTS: The prevalence of MCI was 65.2%. After exercise training, 46.6% of participants with MCI reversed to normal cognitive function. The MoCA-J cut-off score to predict cognitive function potentially reversible to normal was 23, with receiver operating characteristic analysis showing an area under the curve of 0.80, sensitivity of 79.4% and specificity of 69.2%. Multiple logistic regression analysis to predict non-MCI after exercise training showed that MoCA-J score ≥23 (OR 6.9, P < .001), female sex (OR 3.4, P = .04) and age (OR 0.9, P = .04) were independent determinants. CONCLUSIONS: The MoCA-J cut-off score of 23 might be useful to predict cognitive function that is potentially reversible to normal among community-dwelling Japanese older adults with MCI. Geriatr Gerontol Int 2018; 18: 833-838.

Association Between Early Rehabilitation and Mobility Status in Elderly Inpatients with Heart Failure: A Nationwide Retrospective Cohort Study.

OBJECTIVE: We set out to examine the effectiveness of early rehabilitation for maintaining mobility status during hospitalization in elderly patients with heart failure. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database, we retrospectively examined the eligibility of 527,440 consecutive patients aged ≥60 years who were diagnosed with heart failure with New York Heart Association class ≥ II at admission between July 2010 and March 2014. Of the 146,735 eligible subjects, 39,357 underwent early rehabilitation and 107,378 underwent non-early rehabilitation. Early rehabilitation was defined as rehabilitation starting within 3 days after admission. A multivariable logistic regression analysis and an instrumental variable analysis were carried out to examine the association of early rehabilitation with changes in mobility status during hospitalization. RESULTS: The proportion of heart failure patients with maintained or improved mobility status during hospitalization was higher in the early rehabilitation group. Multivariable logistic regression analysis revealed that the early rehabilitation group had a significantly higher proportion with maintained or improved mobility status (odds ratio, 1.32; 95% confidence interval, 1.21-1.43; P<0.001). The instrumental variable analysis showed that early rehabilitation was associated with an increased proportion of patients with maintained or improved mobility status (risk difference, 0.8%; 95% confidence interval, 0.4%-1.1%; P<0.001). CONCLUSIONS: The present study suggests that early rehabilitation is associated with an increase in the proportion of patients with maintained or improved mobility status compared with non-early rehabilitation in elderly inpatients with heart failure.

Relationship between skeletal muscle mass and cardiac function during exercise in community-dwelling older adults.

AIMS: This study aimed to investigate the relationship between skeletal muscle mass and cardiac functional parameters in older adults during cardiopulmonary exercise testing (CPET). METHODS AND RESULTS: Sixty-three Japanese community-dwelling older adults were enrolled (20 men and 43 women; mean age 80 years, range 65-97 years). Cardiac functional parameters during exercise were assessed using CPET. Skeletal muscle mass index (SMI) was calculated by dividing the appendicular lean mass (measured using dual-energy X-ray absorptiometry) by height in metres squared. Subjects were divided into two groups: men with SMI ≥ 7.0 kg/m2 and women with SMI ≥ 5.4 kg/m2 (non-sarcopenic group); or men with SMI < 7.0 kg/m2 and women with SMI < 5.4 kg/m2 (sarcopenic group). There were significant positive correlations between SMI and peak oxygen uptake (VO2 ) (r = 0.631, P < 0.001), and between SMI and peak VO2 /heart rate (HR) (r = 0.683, P < 0.001). However, only peak VO2 /HR significantly differed between groups in both sexes. Multiple linear regression analyses with peak VO2 /HR as a dependent variable showed that SMI was the only independent determinant after adjusting for potential confounders. After 4 month follow-up of 47 participants, there was still a significant positive correlation between SMI and peak VO2 /HR (r = 0.567, P < 0.001), and between percent change of SMI and percent change of peak VO2 /HR (r = 0.305, P < 0.05). CONCLUSIONS: Peak VO2 /HR, an index of stroke volume at peak exercise, was associated with SMI. This indicates that skeletal muscle mass might affect cardiac function during exercise.

Femoral muscle mass relates to physical frailty components in community-dwelling older people.

AIM: To examine the relationship between lower limb muscle (femoral muscle, calf muscle) mass and exercise capacity, and frailty components in community-dwelling older people. METHODS: Participants included 121 community-dwelling individuals. There were 42 men and 79 women, and the mean age was 77.7 years (range 56-97 years). Appendicular skeletal muscle mass was determined using dual-energy X-ray absorptiometry, and the skeletal muscle index was calculated using the following formula: appendicular skeletal muscle / body height2 . Femoral muscle mass and calf muscle mass were determined, respectively, by dividing the femoral bone and tibial bone at the knee joint space. A symptom-limited cardiopulmonary exercise testing was carried out and peak oxygen uptake was measured. Functional exercise performance was evaluated using the handgrip strength measurement, comfortable walking speed, and the Timed Up and Go test. All patients gave written, informed consent before data collection. RESULTS: Peak oxygen uptake correlated positively with the skeletal muscle index (r = 0.491). Only femoral muscle mass that was corrected with the whole body muscle mass was positively correlated with peak oxygen uptake (r = 0.473), handgrip strength (r = 0.382), comfortable walking speed (r = 0.427), and the Timed Up and Go test (r = 0.379). Calf muscle mass that was corrected with the whole-body muscle mass showed no correlation with exercise capacity and frailty components. A similar tendency was observed in both men and women. CONCLUSIONS: Femoral muscle mass influenced exercise capacity and physical frail components compared with calf muscle mass. These results suggest the importance of the femoral muscle in physical frailty. Geriatr Gerontol Int 2017; 17: 1636-1641.

Impact of Rehabilitation on Outcomes in Patients With Ischemic Stroke: A Nationwide Retrospective Cohort Study in Japan.

BACKGROUND AND PURPOSE: We aimed to examine the concurrent effects of timing and intensity of rehabilitation on improving activities of daily living (ADL) among patients with ischemic stroke. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database, we retrospectively analyzed consecutive patients with ischemic stroke at admission who received rehabilitation (n=100 719) from April 2012 to March 2014. Early rehabilitation was defined as that starting within 3 days after admission. The average rehabilitation intensity per day was calculated as the total units of rehabilitation during hospitalization divided by the length of hospital stay. A multivariable logistic regression analysis with multiple imputation and an instrumental variable analysis were performed to examine the association of early and intensive rehabilitation with the proportion of improved ADL score. RESULTS: The proportion of improved ADL score was higher in the early and intensive rehabilitation group. The multivariable logistic regression analysis showed that significant improvements in ADL were observed for early rehabilitation (odds ratio: 1.08; 95% confidence interval: 1.04-1.13; P<0.01) and intensive rehabilitation of >5.0 U/d (odds ratio: 1.87; 95% confidence interval: 1.69-2.07; P<0.01). The instrumental variable analysis showed that an increased proportion of improved ADL was associated with early rehabilitation (risk difference: 2.8%; 95% confidence interval: 2.0-3.4%; P<0.001) and intensive rehabilitation (risk difference: 5.6%; 95% confidence interval: 4.6-6.6%; P<0.001). CONCLUSIONS: The present results suggested that early and intensive rehabilitation improved ADL during hospitalization in patients with ischemic stroke.

Effect of early rehabilitation on activities of daily living in patients with aspiration pneumonia.

AIM: To assess the effect of early rehabilitation on improving activities of daily living (ADL) in elderly patients with aspiration pneumonia. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database, we retrospectively analyzed consecutive patients with aspiration pneumonia at admission who received early rehabilitation (n = 48 201) or did not receive any rehabilitation (n = 64 357) from July 2010 to March 2013. Early rehabilitation was defined as any type of physical rehabilitation initiated within 7 days after admission. The proportions of improved ADL scores from admission to discharge were compared between the early rehabilitation group and the non-rehabilitation group using a multivariable logistic regression analysis and instrumental variable analysis. RESULTS: The proportion of improved ADL scores was higher in the early rehabilitation group than in the non-rehabilitation group (25.4% vs 33.9%; P < 0.001). The multivariable logistic regression analysis showed that the early rehabilitation group exhibited significant improvement in ADL (odds ratio 1.57; 95% confidence interval 1.50-1.64; P < 0.001). The instrumental variable analysis showed that early rehabilitation was associated with increased proportion of improved ADL (risk difference 8.2%; 95% confidence interval 6.9-9.5%; P < 0.001). CONCLUSIONS: The present results suggest that early rehabilitation might improve ADL during hospitalization in patients with aspiration pneumonia. Geriatr Gerontol Int 2016; 16: 1181-1187.

Comparison of recombinant protein expression in a baculovirus system in insect cells (Sf9) and silkworm.

Using a hybrid baculovirus system, we compared the expression of 45 recombinant proteins from six categories using two models: silkworm (larvae and pupae) and an Sf9 cell line. A total of 45 proteins were successfully expressed; preparation of hybrid baculovirus was unsuccessful for one protein, and two proteins were not expressed. A similar pattern of expression was seen in both silkworm and Sf9 cells, with double and multiple bands found in immunoblotting of the precipitate of both hosts. Degraded proteins were seen only in the silkworm system (particularly in the larvae). Production was more efficient in silkworms; a single silkworm produced about 70 times more protein than 10(6) Sf9 cells in 2 ml of culture medium.

The Dock tag, an affinity tool for the purification of recombinant proteins, based on the interaction between dockerin and cohesin domains from Clostridium josui cellulosome.

Highly specific dockerin-cohesin interaction intrinsically involved in the cellulosome formation in Clostridium josui was applied for the construction of an affinity tag purification system. Amino acid substitutions were introduced into the dockerin domain of C. josui Cel8A at positions 11, 12, 44, and 45 and mutant dockerin domains were examined for their ability as an affinity tag: mutant dockerin-tagged proteins were adsorbed onto a cohesin (Coh2)-coupled Sepharose in the presence of Ca(2+) and desorbed from the protein and Coh2-Sepharose complex by the addition of a chelating agent, EGTA. Single-step purification tests showed that substitution of glycine or serine for isoleucine at position 45 markedly improved the recovery of the recombinant proteins from the proteins and Coh2-Sepharose complex. Surface plasmon resonance analysis of the interaction between the I45G mutant and Coh2 indicated that the mutation decreased binding rate and increased dissociation rate, resulting in decrease in dissociation constant. When model proteins such as JNK3, MAP2K3, IL-8, and pro-IL-18 were expressed as I45G dockerin-tagged proteins in the baculovirus expression system and purified by the single-step purification, purity of all the I45G dockerin-tagged proteins tested was higher than 90%. Furthermore, insertion of a thrombin cleavage site between the dockerin tag and target proteins enabled rapid removal of the tag from the target proteins by thrombin protease. This system, named the Dock tag purification system, can be widely utilized and contributes to various fields in academic and application researches.

Congenital anomaly of the external iliac artery: a case report.

A 51-year-old man was admitted with acute ischemic pain in the left leg. An angiogram demonstrated a well-developed left internal iliac artery that appeared to be continuous with the left common femoral artery, but no left external iliac artery. The left superficial and proximal deep femoral arteries were obstructed with thrombi. At surgery it was revealed that the distal end of the left common iliac artery was continuous with the dilated left internal iliac artery, forming the continuation with the left common femoral artery in the pelvic cavity. The left external iliac artery was absent between the common iliac and femoral arteries.