Identification of multiple system atrophy mimicking Parkinson's disease or progressive supranuclear palsy.

We studied a subset of patients with autopsy-confirmed multiple system atrophy who presented a clinical picture that closely resembled either Parkinson's disease or progressive supranuclear palsy. These mimics are not captured by the current diagnostic criteria for multiple system atrophy. Among 218 autopsy-proven multiple system atrophy cases reviewed, 177 (81.2%) were clinically diagnosed and pathologically confirmed as multiple system atrophy (i.e. typical cases), while the remaining 41 (18.8%) had received an alternative clinical diagnosis, including Parkinson's disease (i.e. Parkinson's disease mimics; n = 16) and progressive supranuclear palsy (i.e. progressive supranuclear palsy mimics; n = 17). We also reviewed the clinical records of another 105 patients with pathologically confirmed Parkinson's disease or progressive supranuclear palsy, who had received a correct final clinical diagnosis (i.e. Parkinson's disease, n = 35; progressive supranuclear palsy-Richardson syndrome, n = 35; and progressive supranuclear palsy-parkinsonism, n = 35). We investigated 12 red flag features that would support a diagnosis of multiple system atrophy according to the current diagnostic criteria. Compared with typical multiple system atrophy, Parkinson's disease mimics more frequently had a good levodopa response and visual hallucinations. Vertical gaze palsy and apraxia of eyelid opening were more commonly observed in progressive supranuclear palsy mimics. Multiple logistic regression analysis revealed an increased likelihood of having multiple system atrophy [Parkinson's disease mimic versus typical Parkinson's disease, odds ratio (OR): 8.1; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 2.3] if a patient developed any one of seven selected red flag features in the first 10 years of disease. Severe autonomic dysfunction (orthostatic hypotension and/or urinary incontinence with the need for a urinary catheter) was more frequent in clinically atypical multiple system atrophy than other parkinsonian disorders (Parkinson's disease mimic versus typical Parkinson's disease, OR: 4.1; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 8.8). The atypical multiple system atrophy cases more frequently had autonomic dysfunction within 3 years of symptom onset than the pathologically confirmed patients with Parkinson's disease or progressive supranuclear palsy (Parkinson's disease mimic versus typical Parkinson's disease, OR: 4.7; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 2.7). Using all included clinical features and 21 early clinical features within 3 years of symptom onset, we developed decision tree algorithms with combinations of clinical pointers to differentiate clinically atypical cases of multiple system atrophy from Parkinson's disease or progressive supranuclear palsy.

Hippocampal α-synuclein pathology correlates with memory impairment in multiple system atrophy.

Recent post-mortem studies reported 22-37% of patients with multiple system atrophy can develop cognitive impairment. With the aim of identifying associations between cognitive impairment including memory impairment and α-synuclein pathology, 148 consecutive patients with pathologically proven multiple system atrophy were reviewed. Among them, 118 (79.7%) were reported to have had normal cognition in life, whereas the remaining 30 (20.3%) developed cognitive impairment. Twelve of them had pure frontal-subcortical dysfunction, defined as the presence of executive dysfunction, impaired processing speed, personality change, disinhibition or stereotypy; six had pure memory impairment; and 12 had both types of impairment. Semi-quantitative analysis of neuronal cytoplasmic inclusions in the hippocampus and parahippocampus revealed a disease duration-related increase in neuronal cytoplasmic inclusions in the dentate gyrus and cornu ammonis regions 1 and 2 of patients with normal cognition. In contrast, such a correlation with disease duration was not found in patients with cognitive impairment. Compared to the patients with normal cognition, patients with memory impairment (pure memory impairment: n = 6; memory impairment + frontal-subcortical dysfunction: n = 12) had more neuronal cytoplasmic inclusions in the dentate gyrus, cornu ammonis regions 1-4 and entorhinal cortex. In the multiple system atrophy mixed pathological subgroup, which equally affects the striatonigral and olivopontocerebellar systems, patients with the same combination of memory impairment developed more neuronal inclusions in the dentate gyrus, cornu ammonis regions 1, 2 and 4, and the subiculum compared to patients with normal cognition. Using patients with normal cognition (n = 18), frontal-subcortical dysfunction (n = 12) and memory impairment + frontal-subcortical dysfunction (n = 18), we further investigated whether neuronal or glial cytoplasmic inclusions in the prefrontal, temporal and cingulate cortices or the underlying white matter might affect cognitive impairment in patients with multiple system atrophy. We also examined topographic correlates of frontal-subcortical dysfunction with other clinical symptoms. Although no differences in neuronal or glial cytoplasmic inclusions were identified between the groups in the regions examined, frontal release signs were found more commonly when patients developed frontal-subcortical dysfunction, indicating the involvement of the frontal-subcortical circuit in the pathogenesis of frontal-subcortical dysfunction. Here, investigating cognitive impairment in the largest number of pathologically proven multiple system atrophy cases described to date, we provide evidence that neuronal cytoplasmic inclusion burden in the hippocampus and parahippocampus is associated with the occurrence of memory impairment in multiple system atrophy. Further investigation is necessary to identify the underlying pathological basis of frontal-subcortical dysfunction in multiple system atrophy.

Intra-day variation in daily outdoor walking speed among community-dwelling older adults.

BACKGROUND: Walking speed is an important measure associated with health outcomes in older individuals, such as dependency and death. This study aimed to examine whether the walking speed of community-dwelling older adults varies between time periods within a day, as measured outdoors in daily life. We aimed to determine the types of walking speed variations and examine the factors associated with them. METHODS: Daily life outdoor walking speed was measured in 92 participants (average age 71.9 years±5.64) using a GPS smartphone app for 1 month. Average walking speeds for five time periods were analyzed with a linear mixed model. Intra-day walking speed variation patterns were classified by latent class analysis. Factors associated with the class were identified by logistic regression analysis. RESULTS: A statistically significant difference in average walking speed was found between early morning (1.33 m/s), and afternoon (1.27 m/s) and evening (1.26 m/s) (p < 0.01). The intra-day variation in walking speed was attributed to variation in cadence. Two classes were identified: (1) fast walking speed with large variation and (2) slow walking speed with little variation; hypertension and frailty level were associated with the class. CONCLUSION: The results suggest that there is intra-day variation in walking speed in daily life, wherein the speed is the fastest early in the morning and slower in the afternoon and evening. A larger variation in the walking speed was related to the health status without hypertension or frailty. These results suggest that if a person shows less intra-day variation in walking speed, this could be a sign that they are susceptible to hypertension and an increased frailty level.

Impact of cytoreductive nephrectomy in patients with primary metastatic renal cell carcinoma receiving systemic tyrosine kinase inhibitor therapy: A multicenter retrospective study.

OBJECTIVES: To compare overall survival between patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy and those not treated by cytoreductive nephrectomy. METHODS: We retrospectively evaluated 278 patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors between January 2008 and November 2019. Patients were divided into two groups: a cytoreductive nephrectomy group (immediate or deferred cytoreductive nephrectomy) and a group who received systemic tyrosine kinase inhibitor therapies alone without cytoreductive nephrectomy (control group). Overall survival comparisons were made in all patients in the control versus the cytoreductive nephrectomy group, the control versus the immediate cytoreductive nephrectomy group, the control versus the deferred cytoreductive nephrectomy group, and the deferred cytoreductive nephrectomy versus the immediate cytoreductive nephrectomy group. Analyses were weighted using the propensity score-based inverse probability of treatment weighting method to adjust for group imbalances. RESULTS: The median (range) age of the patients was 65 (59-73) years. Of the 278 patients, 132 and 146 were in the control group and the cytoreductive nephrectomy (immediate, n = 107 and deferred, n = 39) group, respectively. A significant difference was noted between the control and cytoreductive nephrectomy groups in age, clinical stage, International Metastatic Renal Cell Carcinoma Database Consortium risk factors, and the number of metastatic sites. Inverse probability of treatment weighting-adjusted Cox regression analysis showed a significant difference in overall survival between the control and the cytoreductive nephrectomy groups and between the control and the immediate or deferred cytoreductive nephrectomy groups. However, there was no significant difference in overall survival between the immediate and the deferred cytoreductive nephrectomy groups. CONCLUSIONS: Our findings suggest that metastatic renal cell carcinoma patients undergoing cytoreductive nephrectomy are more likely to have longer overall survival than those who receive tyrosine kinase inhibitor therapy only.

Improving diagnostic accuracy of multiple system atrophy: a clinicopathological study.

Clinical diagnosis of multiple system atrophy is challenging and many patients with Lewy body disease (i.e. Parkinson's disease or dementia with Lewy bodies) or progressive supranuclear palsy are misdiagnosed as having multiple system atrophy in life. The clinical records of 203 patients with a clinical diagnosis of multiple system atrophy were reviewed to identify diagnostic pitfalls. We also examined 12 features supporting a diagnosis of multiple system atrophy (red flag features: orofacial dystonia, disproportionate antecollis, camptocormia and/or Pisa syndrome, contractures of hands or feet, inspiratory sighs, severe dysphonia, severe dysarthria, snoring, cold hands and feet, pathological laughter and crying, jerky myoclonic postural/action tremor and polyminimyoclonus) and seven disability milestones (frequent falls, use of urinary catheters, wheelchair dependent, unintelligible speech, cognitive impairment, severe dysphagia, residential care). Of 203 cases, 160 (78.8%) were correctly diagnosed in life and had pathologically confirmed multiple system atrophy. The remaining 21.2% (43/203) had alternative pathological diagnoses including Lewy body disease (12.8%; n = 26), progressive supranuclear palsy (6.4%; n = 13), cerebrovascular diseases (1%; n = 2), amyotrophic lateral sclerosis (0.5%; n = 1) and cerebellar degeneration (0.5%; n = 1). More patients with multiple system atrophy developed ataxia, stridor, dysphagia and falls than patients with Lewy body disease; resting tremor, pill-rolling tremor and hallucinations were more frequent in Lewy body disease. Although patients with multiple system atrophy and progressive supranuclear palsy shared several symptoms and signs, ataxia and stridor were more common in multiple system atrophy. Multiple logistic regression analysis revealed increased likelihood of multiple system atrophy versus Lewy body disease and progressive supranuclear palsy if a patient developed orthostatic hypotension or urinary incontinence with the requirement for urinary catheters [multiple system atrophy versus Lewy body disease: odds ratio (OR): 2.0, 95% confidence interval (CI): 1.1-3.7, P = 0.021; multiple system atrophy versus progressive supranuclear palsy: OR: 11.2, 95% CI: 3.2-39.2, P < 0.01]. Furthermore, autonomic dysfunction within the first 3 years from onset can differentiate multiple system atrophy from progressive supranuclear palsy (multiple system atrophy versus progressive supranuclear palsy: OR: 3.4, 95% CI: 1.2-9.7, P = 0.023). Multiple system atrophy patients with predominant parkinsonian signs had a higher number of red flag features than patients with Lewy body disease (OR: 8.8, 95% CI: 3.2-24.2, P < 0.01) and progressive supranuclear palsy (OR: 4.8, 95% CI: 1.7-13.6, P < 0.01). The number of red flag features in multiple system atrophy with predominant cerebellar signs was also higher than in Lewy body disease (OR: 7.0, 95% CI: 2.5-19.5, P < 0.01) and progressive supranuclear palsy (OR: 3.1, 95% CI: 1.1-8.9, P = 0.032). Patients with multiple system atrophy had shorter latency to reach use of urinary catheter and longer latency to residential care than progressive supranuclear palsy patients, whereas patients with Lewy body disease took longer to reach multiple milestones than patients with multiple system atrophy. The present study has highlighted features which should improve the ante-mortem diagnostic accuracy of multiple system atrophy.

Effects and Risks of Heparin Bridging and Different Modes of Interruption/Resumption of Rivaroxaban on Perioperative Complications of Catheter Ablation for Atrial Fibrillation　- Another Analysis of the JACRE-R Registry.

BACKGROUND: The JACRE-R Registry, in which 42 Japanese institutions participated, monitored the efficacy and safety of rivaroxaban in catheter ablation (CA) of atrial fibrillation (AF). In the present analysis, we sought to elucidate the effects and risks of heparin bridging and different patterns of interruption/resumption of rivaroxaban on complications of CA.Methods and Results:We administered rivaroxaban during the perioperative period and recorded the incidence of complications up to 30 days after CA. A total of 1,118 patients were registered; 546 received heparin bridging and 572 did not. The bridging group showed a significantly higher incidence of non-major bleeding than the no-bridging group (4.03% vs. 0.87%; P=0.001). In the group receiving their last dose of rivaroxaban at 8-28 h before CA, neither thromboembolism nor major bleeding was observed during or after CA and the incidence of non-major bleeding was low (4/435, 0.92%). The incidence of non-major bleeding was significantly higher in the group resuming rivaroxaban ≥12 h after CA than in the group resuming <12 h (1.79% vs. 0.27%, P=0.045). CONCLUSIONS: Heparin bridging increased the risk of non-major bleeding perioperatively. It was safe to stop rivaroxaban 8-28 h before the CA procedure, whereas resumption of the drug within 12 h of CA was associated with a lower incidence of non-major bleeding.

Efficacy and Safety of Rivaroxaban and Warfarin in the Perioperative Period of Catheter Ablation for Atrial Fibrillation　- Outcome Analysis From a Prospective Multicenter Registry Study in Japan.

BACKGROUND: Catheter ablation (CA) is a common treatment for atrial fibrillation (AF). Although rivaroxaban is increasingly used as a substitute for warfarin, its safety and efficacy during CA have not been established in Japanese patients. In the present study we explored the efficacy/safety of rivaroxaban during the CA perioperative period.Methods and Results:We prospectively enrolled Japanese AF patients scheduled for CA who had received either rivaroxaban (rivaroxaban cohort, JACRE-R) or warfarin (warfarin cohort, JACRE-W) during the perioperative period. Primary outcome was a composite of thromboembolism and major bleeding within 30 days after CA. In JACRE-R and JACRE-W, 1,118 (median age, 65 years) and 204 patients (median, 69 years) were enrolled from 42 and 22 institutions, respectively. In JACRE-R, the primary outcome occurred in 7 patients (0.6%), comprising thromboembolism in 2 and major bleeding in 5. Non-major bleeding occurred in 27 patients (2.4%), and the incidence was significantly lower in patients without heparin bridging (n=572) than in those with heparin bridging (n=546). In JACRE-W, the primary outcome occurred in 3 patients (1.5%), all of which were major bleeding. After adjustment for patients' characteristics, no significant difference was observed between the JACRE-R and JACRE-W cohorts for the primary outcome. CONCLUSIONS: The rates of thromboembolism and major bleeding events during the AF ablation perioperative period in Japanese patients treated with rivaroxaban was as low as in those treated with warfarin. (Circ J 2016; 80: 2295-2301).

Validation of Risk Scoring System Excluding Female Sex From CHA2DS2-VASc in Japanese Patients With Nonvalvular Atrial Fibrillation ­ Subanalysis of the J-RHYTHM Registry.

BACKGROUND: Because the current Japanese guideline recommends CHADS2 score-based risk stratification in nonvalvular atrial fibrillation (NVAF) patients and does not list female sex as a risk for thromboembolic events, we designed the present study to compare the CHA2DS2-VASc and CHA2DS2-VA scores in the J-RHYTHM Registry. METHODS AND RESULTS: We prospectively assessed the incidence of thromboembolic events for 2 years in 997 NVAF patients without warfarin treatment (age 68±12 years, 294 females). The predictive value of the CHA2DS2-VASc and CHA2DS2-VA scores for thromboembolic events was evaluated by c-statistic difference and net reclassification improvement (NRI). Thromboembolic events occurred in 7/294 females (1.2%/year) and 23/703 males (1.6%/year) (odds ratio 0.72 for female to male, 95% confidence interval (CI) 0.28-1.62, P=0.44). No sex difference was found in patient groups stratified by CHA2DS2-VASc and CHA2DS2-VA scores. There were significant c-statistic difference (0.029, Z=2.3, P=0.02) and NRI (0.11, 95% CI 0.01-0.20, P=0.02), with the CHA2DS2-VA score being superior to the CHA2DS2-VASc score. In patients with CHA2DS2-VASc scores 0 and 1 (n=374), there were markedly significant c-statistic difference (0.053, Z=6.6, P<0.0001) and NRI (0.11, 95% CI 0.07-0.14, P<0.0001), again supporting superiority of CHA2DS2-VA to CHA2DS2-VASc score. CONCLUSIONS: In Japanese NVAF patients, the CHA2DS2-VA score, a risk scoring system excluding female sex from CHA2DS2-VASc, may be more useful in risk stratification for thromboembolic events than CHA2DS2-VASc score, especially in identifying truly low-risk patients.

Role of Acute Physiotherapy in Bilateral Medial Medullary Infarction: A Case Report.

Bilateral medial medullary infarction (BMMI) is a rare stroke syndrome, which frequently has poor clinical outcomes. Reports on physical therapy for BMMI are few because of its poor prognosis. Therefore, this report aims to present a patient who developed BMMI and underwent well-considered rehabilitation. A 67-year-old man presented to our clinic with an acute onset of vomiting and dizziness. Magnetic resonance imaging (MRI) showed no abnormal signal intensity, and the patient was admitted for peripheral dizziness. On day two, he developed quadriplegia, bulbar palsy, and respiratory impairment, such as prolonged apnea. A second MRI revealed a high-intensity lesion in the bilateral medial medulla oblongata. He was diagnosed with BMMI, and rehabilitation treatment was initiated. On day 16, his sputum volume increased, and he could not expectorate effectively due to decreased coughing ability. Therefore, mechanical insufflation-exsufflation (MI-E) was performed to improve his airway clearance. On day 21, he developed aspiration pneumonia (AP), which became severe and led to acute respiratory failure. Nasal airway intubation and oxygen flow of 5 L/minute were initiated. His respiratory function was not seriously aggravated, and recurrent AP was prevented with the application of respiratory physiotherapy procedures, such as postural drainage, in collaboration with other medical staff, and MI-E. On day 60, the patient was transferred to the recovery phase rehabilitation ward. BMMI tends to worsen swallowing disorders progressively and is associated with a high risk of severe AP. Providing physiotherapy in the acute phase is important to reduce the risk of serious illness.

Association Between Anterior Hip Capsule Thickening and Sagittal Pelvic Alignment Among Patients With Developmental Dysplasia of the Hip.

INTRODUCTION: The pathogenesis and pathology of secondary osteoarthritis (OA) of the hip, which is mainly due to developmental dysplasia of the hip (DDH), in Japan are obscure. There are some reports on the thickening of the hip capsule, but the relationship between the thickness of the hip capsule and the pelvic alignment due to hip deformity is not well known. This research investigated whether the capsular thickness of female DDH patients was related to pelvic alignment. METHODS: This single-center cross-sectional study included female patients aged 50-79 years (n=13) who had undergone primary total hip arthroplasty (THA) due to secondary hip OA with a background of DDH. The part of the hip capsule including the iliofemoral ligament was resected and measured directly with a digital caliper. The Sharp angle, center-edge (CE) angle, sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), and lumbar lordosis angle (LLA) were measured with an X-ray image to investigate the relationship between the capsular thickness and the pelvic posture. RESULTS: Pearson's correlation coefficient showed a negative correlation between hip capsular thickness and Sharp angle (r=-0.57, p>0.05). No significant correlation was found between the thickness of the hip capsule and the sagittal X-ray parameters including SS, PT, PI, LLA, and CE angle in the coronal plane. CONCLUSION: The thickness of the hip capsule is moderately associated with the Sharp angle on the coronal plane. The results of this study suggest that the thickness of the joint capsule does not necessarily relate to the degenerative process among patients with DDH and the process can be complex to apply two-dimensional postural indices for the explanation.

Detection of misery perfusion in the cerebral hemisphere with chronic unilateral major cerebral artery steno-occlusive disease using crossed cerebellar hypoperfusion: comparison of brain SPECT and PET imaging.

PURPOSE: In patients with unilateral internal carotid or middle cerebral artery (ICA or MCA) occlusive disease, the degree of crossed cerebellar hypoperfusion that is evident within a few months after the onset of stroke may reflect cerebral metabolic rate of oxygen in the affected cerebral hemisphere relative to that in the contralateral cerebral hemisphere. The aim of the present study was to determine whether the ratio of blood flow asymmetry in the cerebellar hemisphere to blood flow asymmetry in the cerebral hemisphere on positron emission tomography (PET) and single photon emission computed tomography (SPECT) correlates with oxygen extraction fraction (OEF) asymmetry in the cerebral hemisphere on PET in patients with chronic unilateral ICA or MCA occlusive disease and whether this blood flow ratio on SPECT detects misery perfusion in the affected cerebral hemisphere in such patients. METHODS: Brain blood flow and OEF were assessed using (15)O-PET and N-isopropyl-p-[(123)I]iodoamphetamine ((123)I-IMP) SPECT, respectively. All images were anatomically standardized using SPM2. A region of interest (ROI) was automatically placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres using a three-dimensional stereotaxic ROI template, and affected-to-contralateral asymmetry in the MCA territory or contralateral-to-affected asymmetry in the cerebellar hemisphere was calculated. Sixty-three patients with reduced blood flow in the affected cerebral hemisphere on (123)I-IMP SPECT were enrolled in this study. RESULTS: A significant correlation was observed between MCA ROI asymmetry of PET OEF and the ratio of cerebellar hemisphere asymmetry of blood flow to MCA ROI asymmetry of blood flow on PET (r = 0.381, p = 0.0019) or SPECT (r = 0.459, p = 0.0001). The correlation coefficient was higher when reanalyzed in a subgroup of 43 patients undergoing a PET study within 3 months after the last ischemic event (r = 0.541, p = 0.0001 for PET; r = 0.609, p < 0.0001 for SPECT). The blood flow ratio on brain perfusion SPECT in all patients provided 100 % sensitivity and 58 % specificity, with 43 % positive and 100 % negative predictive values for detecting abnormally elevated MCA ROI asymmetry of PET OEF. CONCLUSION: The ratio of blood flow asymmetry in the cerebellar hemisphere to blood flow asymmetry in the cerebral hemisphere on PET and SPECT correlates with PET OEF asymmetry in the cerebral hemisphere, and this blood flow ratio on SPECT detects misery perfusion in the affected cerebral hemisphere.

Interobserver and intraobserver reliability of the classification and diagnosis for ossification of the posterior longitudinal ligament of the cervical spine.

PURPOSE: Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine has been classified into four types by lateral plain radiographs, but the reliability of the classification and of the diagnosis of either cervical OPLL or cervical spondylotic myelopathy (CSM) was unknown. We investigated the interobserver and intraobserver reliability of the classification and diagnosis for OPLL by radiographs and computed tomography (CT) images. METHODS: A total of 16 observers classified each patient's images into five groups; OPLL continuous, segmental, mixed, circumscribed type, or CSM. To evaluate interobserver reliability, the observers first classified only radiograph images, and next both radiographs and CT images. On another day they followed the same procedure to evaluate intraobserver reliability. We also evaluated interobserver and intraobserver reliability of the diagnosis of either cervical OPLL or CSM. RESULTS: Interobserver reliability of the classification with radiographs only showed moderate agreement, but interobserver reliability with both radiographs and CT images showed substantial agreement. Intraobserver of reliability the classification was also improved by additional CT images. Interobserver reliability of the diagnosis with both radiographs and CT images was almost similar to with radiographs only. Intraobserver reliability of the diagnosis was improved by additional CT images. CONCLUSIONS: This study suggested that the reliability of the classification and diagnosis for cervical OPLL was improved by additional CT images. We propose that diagnostic criteria for OPLL include both radiographs and CT images.

Japanese physical therapist's evidence-to-practice gap in knee osteoarthritis clinical practice guidelines: A cross-sectional study.

OBJECTIVE: As management for osteoarthritis, clinical practice guidelines (CPGs) have been published worldwide with the aim of attaining optimal treatment and rehabilitation. However, we suspect a lack of knowledge of and/or adherence to osteoarthritis CPGs in physiotherapists' clinical practice. There may be an evidence-to-practice gap in knee osteoarthritis rehabilitation among Japanese physiotherapists. Therefore, we aimed to measure the level of knowledge and adherence to osteoarthritis CPGs within a cohort of Japanese physiotherapists. METHODS: An online survey was created based on three appropriate and high-quality CPGs. The first two sections comprised 23 statements, and participants responded via a five-point Likert scale ("completely disagree" to "completely agree"). Consensus was defined as ≥70% agreement with a statement. In the second section, participants read clinical scenarios and selected what they considered to be the most appropriate management and interventions. RESULTS: The survey was completed by 558 Japanese physiotherapists. The mean age of the participants included in the analysis was 34.8 years, 61 participants were female (13.7%). Consensus was attained in just 12 out of 23 items (52%). In the second section, none of the physiotherapists were considered to have good knowledge of CPGs, 85.2% were considered to have only partial knowledge, and 14.8% had no knowledge. Familiarity with the CPGs was therefore poor and there was clearly poor adherence to the recommended rehabilitation guidelines. CONCLUSIONS: The level of knowledge and adherence to osteoarthritis CPGs within our cohort was poor, suggesting an evidence-to-practice gap in rehabilitation for knee osteoarthritis among Japanese physiotherapists.

Interpreting Results from Statistical Hypothesis Testing: Understanding the Appropriate P-value.

Clinical research based on epidemiological study designs requires a good understanding of statistical analysis. This paper discusses the common misconceptions of p-values so that researchers and readers of research papers will be able to properly present and understand the results of null hypothesis significance testing (NHST). The p-values calculated by NHST are categorized as three different types: "significant at p <0.05," "significant at p <0.01," or "not significant." If specified, they may be written as p = 0.124. The 95% confidence interval (CI) of the supplementary statistics is presented regardless of the p-value, and the range of the CI is observed and discussed to determine whether the results are clinically valid. The effect size (ES), which is a measure of the magnitude of the effect, is also referenced and discussed. However, the ES should not be overestimated. It is important to examine the actual descriptive statistics and consider them comprehensively as much as possible. A high detection power of 80% or more indicates that NHST with high accuracy was applied. However, even when it falls below 80%, it is important to consider the limitations of the study, because the results are not completely useless.

A Randomized Controlled Trial for the Intervention Effect of Early Exercise Therapy on Axial Pain after Cervical Laminoplasty.

Introduction: Cervical isometric muscle strengthening and cervical range of motion (ROM) training are recommended after laminoplasty (LP). However, their preventive effects on axial pain are unclear. We examined whether neck extension muscle strengthening and cervical ROM training from the early postoperative period effectively suppress postoperative axial pain. Methods: Sixty-one patients undergoing a muscle-preserving LP attached to C2 and C7 for cervical spondylotic myelopathy or ossification of the posterior longitudinal ligament were randomly allocated to the cervical exercise (33 patients) or nonexercize (28 patients) groups. Postoperative cervical collars were not worn in any cases. The cervical exercise group underwent neck extension isometric muscle strengthening and cervical ROM exercises for 3 months starting on postoperative day 2. Changes in axial pain (visual analog scale [VAS]) from baseline at 2 weeks and 3 months after surgery were evaluated as the primary outcome. Cervical muscle strength, cervical ROM, and Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) scores were evaluated as secondary outcomes. Results: Axial pain was significantly exacerbated at 2 weeks after LP compared with before surgery, and then, a significant improvement was observed at 3 months after surgery. No significant interaction was observed between the intervention and nonintervention groups. There was no difference in secondary outcomes between groups. The change in the VAS of axial pain from before surgery to 3 months after surgery showed a greater decreased neck extension muscle strength resulting in severer axial pain. Conclusions: Cervical muscle strengthening and cervical ROM exercise from the early postoperative period did not relieve axial pain at 2 weeks and 3 months after a muscle-preserving LP attached to C2 and C7. No significant difference in neck extension muscle and cervical movement was observed between the intervention and nonintervention groups. Therefore, a muscle-preserving LP attached to C2 and C7 is a good strategy to prevent axial pain in the early postoperative period.Clinical Trials Registration Number: UMIN000040692.

Time in the therapeutic range during warfarin therapy in Japanese patients with non-valvular atrial fibrillation. - A multicenter study of its status and infuential factors-.

BACKGROUND: Time in the therapeutic range (TTR) assesses the appropriateness of international normalized ratio of prothrombin time (PT-INR) control during warfarin therapy. We examined the status of and the factors influencing TTR in Japanese patients with non-valvular atrial fibrillation (AF). METHODS AND RESULTS: We enrolled 501 AF patients (mean age, 70 ± 10 years; males 66%; mean CHADS2 score 2.0 ± 1.2) taking warfarin for ≥ 2 years from 5 prefectures. The PT-INR therapeutic range was set up according to the 2008 Japanese Guideline. TTR was 64 ± 25% for all patients and varied from 56% to 74% with the institution. Time below and above TTR was 31 ± 26% and 5 ± 7%, respectively. TTR was not affected by gender or antiplatelet co-administration. TTR in patients < 70 and ≥ 70 years old was 46 ± 23% and 77 ± 17%, respectively (P < 0.0001). TTR in patients with CHADS2 score ≤ 1 and ≥ 2 was 59 ± 27% and 68 ± 23%, respectively (P < 0.0001). TTR in patients with warfarin doses < 2.0, 2.0-4.9, and ≥ 5.0 mg/day was 72 ± 22%, 63 ± 25% and 48 ± 24%, respectively (all P < 0.001). Multivariate analysis revealed age and warfarin dose as independent predictors of TTR. CONCLUSIONS: TTR is generally high in Japan, although it varies with institutions. Most of the time spent out of therapeutic range is below the range. TTR is influenced by age presumably because of the low range recommendation for elderly patients, and by warfarin dose presumably because of physicians' anxiety about the hemorrhage risk.

Effects of physical activity on quality of life and physical function in postoperative patients with gastrointestinal cancer.

OBJECTIVES: This study was to clarify changes in physical function and quality of life (QOL) for postoperative, and to examine the influence of the amount of physical activity on these variables. METHODS: This study included 29 patients who underwent gastrointestinal cancer surgery. The QOL measurement was used to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for preoperative and 2nd and 4th postoperative weeks. Physical function measured knee extension strength, 4 m walk time, 5 times sit-to-stand test, and 6-minute walk for preoperative and 1st and 2nd postoperative weeks. The amount of physical activity score was based on METs-hours, which is estimated from cumulative physical activity. As basic characteristics were investigated cancer stage, comorbidities and complications, and operative. Statistical analysis was repeated measures analysis of variance was performed to observe postoperative changes in physical function and QOL. Furthermore, stepwise multiple regression analysis was used to the parameters of physical function and QOL affected by the physical activity score were investigated. RESULTS: Physical function decreased postoperatively and generally improved 2nd postoperative week. Though scores on the QOL functional scales improved, some items did not improve sufficiently. Multiple regression analysis showed that physical activity score had an effect on constipation and emotion functioning. CONCLUSIONS: Improvement in symptom scales is not sufficient in a short period of time, and they need to be followed up by increasing the amount of physical activity and promoting instantaneous exercise.

Impact of low iodine density tumor area ratio on the local control of non-small cell lung cancer through stereotactic body radiotherapy.

Lung cancer with low average iodine density measured via contrast-enhanced computed tomography (CT) using dual-energy CT technology has shown a reduced local control rate after stereotactic body radiotherapy (SBRT). The current study therefore investigated the relationship between low iodine density tumor area and its ratio and local recurrence after SBRT. Dual-energy CT was performed on the day before SBRT initiation, with a low iodine density tumor area being defined as that with an iodine density of <1.81 mg cm-3. The low iodine density tumor area, the ratio between the low iodine density tumor area and the entire tumor, and the local recurrence rate were then determined. No correlation was observed between the low iodine density tumor area and the local recurrence rate. However, tumors with a large low iodine density tumor area ratio showed an increased local recurrence rate, with the prognostic accuracy almost similar to that in previous studies using average iodine densities. Our results therefore suggest that the low iodine density tumor area ratio was a useful prognostic index after SBRT, with an accuracy comparable with that of the average iodine density.

Long-term efficacy and safety of anticoagulation after atrial fibrillation ablation: data from the JACRE registry.

BACKGROUND: Catheter ablation (CA) is an important strategy for managing atrial fibrillation (AF). However, long-term anticoagulation strategies and clinical outcomes following CA, including thromboembolism and bleeding, have not yet been elucidated. METHODS: We established a prospective registry, called the JACRE registry, for patients on rivaroxaban or warfarin administration who received CA for AF. The outcomes up to 30 days following the procedure were reported previously. The present study involved longer follow-up of patients enrolled in this registry to evaluate long-term anticoagulation strategies and clinical outcomes. RESULTS: Data of 975 patients (rivaroxaban, n = 823; warfarin, n = 152) were collected from 27 institutes. Patient population had mean age 63.7 ± 10.3 years, 710 (72.8%) males, mean CHA2DS2-VASc score 1.9 ± 1.5, and mean follow-up period 28.7 ± 12.7 months after the index procedure. Anticoagulants were continued in 496 (50.9%) patients during the follow-up. Thromboembolism occurred in 3 patients, hemorrhagic stroke in 5, and major bleeding events in 9 (annualized event rate, 0.13%, 0.22%, and 0.40% per patient-year, respectively). There were no differences in the composite event rate of thromboembolism and International Society on Thrombosis and Haemostasis major bleeding between rivaroxaban and warfarin cohorts (0.53% and 0.55% per patient-year, respectively). CONCLUSIONS: Long-term incidence of thromboembolism was extremely low in patients with AF treated with CA, while that of major bleeding was not especially low. Clinical Trials Registry: UMIN000032829 / UMIN000032830.

Effects of back extensor strengthening exercises on postural alignment, physical function and performance, self-efficacy, and quality of life in Japanese community-dwelling older adults: A controlled clinical trial.

OBJECTIVE: To examine the changes in postural alignment and kyphosis-correlated factors after 6 months of back extensor strengthening exercise in a group of community-dwelling older adults aged ≥65 years. METHODS: We quasi-randomized 29 subjects into an intervention group treated with a back extensor strengthening program and a control group treated with a full-body exercise program. These groups completed 20-30 minutes of exercise directed by a physical therapist one or more times per week and were instructed to exercise at home as well. The participants were assessed prior to and after the intervention using the following criteria: postural alignment of "usual" and "best" posture, physical function, physical performance, self-efficacy, and quality of life. The differences between two factors (group and period) were compared for each of the measurement variables. RESULTS: Subjects who adequately completed the exercises were analyzed. A reduced knee flexion angle was noted in the "best" posture of both groups, as were improved physical function and performance with the exception of one-leg standing time. Verifying the effect size in the post-hoc analysis, the body parts that showed changes to postural alignment after the intervention differed between groups. CONCLUSIONS: Back extensor strengthening exercises improved physical function and performance, but did not improve spinal alignment. The changes due to these interventions were not significantly different from changes observed in the full-body exercise group. However, post-hoc analysis revealed that the effect size of posture change was different, possible indicating that the two groups experienced different changes in the postural alignment.