Relationships between Walking Speed and Lower Extremity Muscle Quality and Strength in Elderly Females

The link between walking speed, rectus femoris (RF) muscle quality [echo intensity (EI)], and maximal and rapid strength in older adults is not well understood. PURPOSE: To examine the relationships between walking speed, RF EI, and maximal and rapid isometric torque characteristics of the leg extensors in elderly females. METHODS: Twenty elderly females (age = 67 ± 4 years; height = 159 ± 6 cm; mass = 68 ± 7 kg) underwent one diagnostic ultrasound assessment followed by three isometric maximal voluntary contractions (MVC) of the leg extensors and a 6-min walk test. RF EI was measured on the right leg using a portable B-mode ultrasound imaging device and linear-array probe. Walking speed was determined as the average speed during the 6-min walk test. For each MVC, participants sat in an upright position and were instructed to push “as hard and fast as possible” against a load cell for 3-4 s. Isometric MVC peak torque (PT) was determined as the highest mean 500 ms epoch during the entire 3-4 s MVC plateau. Peak rate of torque development (RTD) was calculated during each MVC as the highest slope value for any 50 ms epoch that occurred over the initial 200 ms of the torque-time curve. Pearson correlation coefficients (r) were used to examine the relationships between walking speed, EI, PT, and RTD. A partial correlation was used to examine the relationship between walking speed and RTD when controlling for EI. RESULTS: Mean ± SD values were 1.55 ± 0.23 m/s for walking speed, 144.16 ± 19.48 AU for EI, 107.62 ± 23.79 Nm for PT, and 872.35 ± 365.16 Nm/s for RTD. There were significant relationships between walking speed and RTD (r = 0.451; P = 0.046) and EI (r = -0.497; P = 0.026). There was a significant negative relationship between EI and RTD (r = -0.469; P = 0.037). No significant relationships were observed between PT and walking speed (r = 0.394; P = 0.085) or EI (r = -0.413; P = 0.071). With EI as a control variable, there was no significant relationship between walking speed and RTD (r = 0.285; P = 0.238). CONCLUSION: We found a significant positive relationship between walking speed and RTD of the leg extensors in elderly females. Although the reason for this is uncertain, partial correlation analysis suggested that this relationship may be explained by the variance shared (collinearity) between walking speed and RF EI. From a functional standpoint, an age-related decrease in RTD due to its apparent collinearity with RF EI, may significantly impact the quality of life among older adults by impairing their ability to perform important time-dependent movement tasks (i.e., walking fast to catch the bus or train, quickly crossing the street to avoid oncoming traffic, etc.). Consequently, given the influence of EI on RTD, it is possible that training programs used to improve muscle quality may also be used to help improve rapid strength, which could be beneficial for increasing walking speed as well as a multitude of other functional performance abilities in the elderly

Sex-related Differences in Maximal and Rapid Hamstrings to Quadriceps Strength Capacities

The balance between leg flexor and extensor strength, which is typically assessed using the hamstrings to quadriceps (H/Q) strength ratio, has been implicated as an important factor in the kneejoint stability of younger populations. Sex differences in hamstrings and quadriceps maximal and rapid strength are commonly reported between young men and women; however, few studies have investigated the influence of sex on maximal and rapid strength H/Q ratios. PURPOSE: To examine sex-related differences in maximal and rapid strength H/Q ratios between college-aged men and women. METHODS: Ten physically-active men (age = 23 ± 3 years; height = 177 ± 5 cm; mass = 82 ± 8 kg) and 10 physically-active women (age = 22 ± 3 years; height = 165 ± 9 cm; mass = 66 ± 7 kg) performed three isometric maximal voluntary contractions (MVCs) of the leg extensors and flexors on a calibrated isokinetic dynamometer. For each MVC, participants sat in an upright position and were instructed to extend or flex the leg “as hard and fast as possible”for 3-4 seconds. Maximal and rapid isometric H/Q strength ratios were determined by taking the quotients between leg flexor and extensor peak torque (PT H/Q) and rate of torque development(RTD H/Q). Independent samples t-tests were used to compare demographic characteristics and PT and RTD H/Q ratios between the men and women. RESULTS: The men were taller (P = 0.002) and weighed more (P \u3c 0.001) than the women. The women exhibited a lower RTD H/Q ratio (women = 0.44 ± 0.08; men = 0.54 ± 0.11; P= 0.027) than the men; however, there was no significant difference between the men and women for PT H/Q (women = 0.55 ± 0.09; men = 0.57 ± 0.11; P= 0.576). CONCLUSION: These findings demonstrated that the rapid strength H/Q ratio was significantly lower in the women than the men, while no difference was observed for the maximal strength H/Q ratio. Because a deficit in hamstrings to quadriceps rapid strength may decrease one’s ability to stabilize the knee joint during explosive-type activities, it is possible that the sex difference in RTD H/Q ratio found in the present study may be a significant contributor to the high prevalence of knee-related injuries that are often observed in physically-active women. As such, lower-extremity muscle strengthening programs with an emphasis on explosive power training (particularly for the hamstrings muscles) may be warranted as a preventative measure for women who are highly susceptible to physical-activity induced injuries involving the knee

Relationships between Functional Performance and Quadriceps Muscle Size and Quality in Healthy Older Women

Ultrasound assessments of quadriceps cross-sectional area (CSA) and echo intensity (EI) are commonly used to evaluate lower-body muscle size and quality in older adults. It has been hypothesized that muscle CSA and EI of the quadriceps may be important predictors of functional performances such as gait speed and vertical jump power. However, limited data exist regarding how these parameters associate with performance during a timed up-and-go (TUG) task. PURPOSE: The purpose of this study was to examine the relationships between TUG performance and muscle CSA and EI of the quadriceps in older women. METHODS: Twenty healthy older women (mean ± SD; age = 67 ± 4 years; body mass = 68 ± 7 kg; height = 159 ± 6 cm) volunteered to participate in this study. TUG performance was measured as the time (sec) taken to rise from a chair, walk three meters, return, and sit down. Panoramic ultrasound images of the vastus lateralis (VL) and rectus femoris (RF) were obtained on the right thigh to determine CSA and EI for each muscle. The CSAs (cm2) for the VL and RF were added together and normalized to body mass (kg) to provide a relative measure of quadriceps CSA (cm2/kg). Quadricep EI (AU) was determined as the average of the EIs for the VL and RF. Pearson correlation coefficients (r) were used to examine the relationships between TUG performance and quadriceps CSA and EI. RESULTS: TUG performance (mean ± SD) was 8.25 ± 1.39 sec, CSA was 0.22 ± 0.04 cm2/kg, and EI was 137.37 ± 23.43 AU. There was a significant positive relationship between TUG and EI (r = 0.509; P = 0.022) and a significant negative relationship between TUG and CSA (r = -0.546; P = 0.013).CONCLUSION: The present findings of significant relationships between TUG and CSA and EI suggest that muscle size and quality of the quadriceps may be characteristics relevant to mobility in older adults. Researchers and practitioners may use these findings as ultrasound screening tools to help predict the TUG performance capacities of older populations. Additionally, these findings highlight the importance of developing training programs aimed at increasing quadriceps muscle size and quality, as these changes may be beneficial for improving TUG as well as a multitude of other functional performance abilities in older adults

Feasibility and acceptability of electronic symptom surveillance with clinician feedback using the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Danish prostate cancer patients

Abstract Background The aim was to examine the feasibility, acceptability and clinical utility of electronic symptom surveillance with clinician feedback using a subset of items drawn from the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a cancer treatment setting. Methods Danish-speaking men with castration-resistant metastatic prostate cancer receiving treatment at the Department of Oncology, Rigshospitalet, Copenhagen between March 9, 2015 and June 8, 2015 were invited to participate (n = 63 eligible). Participants completed the PRO-CTCAE questionnaire on tablet computers using AmbuFlex software at each treatment visit in the outpatient clinic. In total, 22 symptomatic toxicities (41 PRO-CTCAE items), corresponding to the symptomatic adverse-events profile associated with the regimens commonly used for prostate cancer treatment (Docetaxel, Cabazitaxel, Abiraterone, Alpharadin), were selected. Participants’ PRO-CTCAE responses were presented graphically to their treating oncologists via an AmbuFlex dashboard, for real-time use to enhance the patient-clinician dialogue that occurs during the consultation prior to each treatment cycle. Technical and clinical barriers and acceptability were evaluated through semi-structured interviews with both patients and oncologists. Patients receiving active treatment at the end of the study period completed an evaluation questionnaire. Results Fifty-four out of sixty-three (86%) eligible patients were enrolled. The PRO-CTCAE questionnaire was completed a total of 168 times by 54 participants (median number per patient was 3, range 1–5). Eight surveys were missed, resulting in a compliance rate of 97%. At the end of the study period, 35 patients (65%) were still receiving active treatment and completed the evaluation questionnaire. Patients reported that their PRO-CTCAE responses served as a communication tool. Oncologists stated that the availability of the PRO-CTCAE self-reports during the consultation improved patient-clinician communication about side effects. Conclusion Electronic capture of symptomatic toxicities using PRO-CTCAE and the submission of self-reports to clinicians prior to consultation were feasible among metastatic prostate cancer patients receiving chemotherapy in an outpatient setting, and this procedure was acceptable to both patients and clinicians. Continued research, including a cluster-randomized trial, will evaluate the effects of submitting patients’ PRO-CTCAE results to clinicians prior to consultation on the quality of side-effects management and resultant clinical outcomes

Evaluation of pedometry as a patient-centered outcome in patients undergoing hematopoietic cell transplant (HCT): A comparison of pedometry and patient-reports of symptoms, health, and quality of life.

Aims We evaluated pedometry as a novel patient-centered outcome because it enables passive continuous assessment of activity and may provide information about the consequences of symptomatic toxicity complementary to self-report. Methods Adult patients undergoing hematopoietic cell transplant (HCT) wore pedometers and completed PRO assessments during transplant hospitalization (4 weeks) and 4 weeks post-discharge. Patient reports of symptomatic treatment toxicities (single items from PROCTCAE, http://healthcaredelivery.cancer.gov/pro-ctcae) and symptoms, physical health, mental health, and quality of life (PROMIS Global-10, http://nih.promis.org), assessed weekly with 7-day recall on Likert scales, were compared individually with pedometry data, summarized as average daily steps per week, using linear mixed models. Results Thirty-two patients [mean age 55 (SD = 14), 63 % male, 84 % white, 56 % autologous, 43 % allogeneic] completed a mean 4.6 (SD = 1.5, range 1–8) evaluable assessments. Regression model coefficients (β) indicated within-person decrements in average daily steps were associated with increases in pain (β = -852; 852 fewer steps per unit increase in pain score, p<0.001), fatigue (β = -886, p<0.001), vomiting (β = -518, p<0.01), shaking/chills (β = -587, p<0.01), diarrhea (β = -719, p<0.001), shortness of breath (β = -1018, p<0.05), reduction in carrying out social activities (β = 705, p<0.01) or physical activities (β = 618, p<0.01), and global physical health (β = 101, p<0.001), but not global mental health or quality of life. Conclusions In this small sample of HCT recipients, more severe symptoms, impaired physical health, and restrictions in the performance of usual daily activities were associated with statistically significant decrements in objectively measured daily steps. Pedometry may be a valuable outcome measure and validation anchor in clinical research

Comparison of Patient- and Practitioner-Reported Toxic Effects Associated With Chemoradiotherapy for Head and Neck Cancer

Agreement between patient- and practitioner-reported toxic effects during chemoradiotherapy for head and neck cancer is unknown. To compare patient-reported symptom severity and practitioner-reported toxic effects among patients receiving chemoradiotherapy for head and neck cancer. Forty-four patients participating in a phase 2 trial of deintensified chemoradiotherapy for oropharyngeal carcinoma were included in the present study (conducted from February 8, 2012, to March 2, 2015). Most treatment (radiotherapy, 60 Gy, with concurrent weekly administration of cisplatin, 30 mg/m2) was administered at academic medical centers. Included patients had no prior head and neck cancers, were 18 years or older, and had a smoking history of 10 pack-years or less or more than 10 pack-years but 30 pack-years or less and abstinent for the past 5 years. Cancer status was untreated human papillomavirus or p16-positive squamous cell carcinoma of the oropharynx or unknown head and neck primary site; and cancer staging was category T0 to T3, category N0 to N2c, M0, and Eastern Cooperative Oncology Group performance status 0 to 1. Baseline, weekly, and posttreatment toxic effects were assessed by physicians or nurse practitioners using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Patient-reported symptom severity was measured using the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE). Descriptive statistics were used to characterize raw agreement between CTCAE grades and PRO-CTCAE severity ratings. Baseline, weekly, and posttreatment toxic effects assessed using CTCAE, version 4.0, and PRO-CTCAE. Raw agreement indices between patient-reported toxic effects, including symptom frequency, severity, and interference with daily activities (score range, 0 [none] to 4 [very severe]), and practitioner-measured toxic effects, including swallowing, oral pain, and hoarseness (score range, 1 [mild] to 5 [death]). Of the 44 patients included in the analysis (39 men, 5 women; mean [SD] age, 61 [8.4] years), there were 327 analyzable pairs of CTCAE and PRO-CTCAE symptom surveys and no treatment delays due to toxic effects. Patient-reported and practitioner-reported symptom severity agreement was high at baseline when most symptoms were absent but declined throughout treatment as toxic effects increased. Most disagreement was due to lower severity of toxic effects reported by practitioners (eg, from 45% agreement at baseline to 27% at the final week of treatment for pain). This was particularly noted for domains that are not easily evaluated by physical examination, such as anxiety and fatigue (eg, severity of fatigue decreased from 43% at baseline to 12% in the final week of treatment). Practitioner-reported toxic effects are lower than patient self-reports during head and neck chemoradiotherapy. The inclusion of patient-reported symptomatic toxic effects provides information that can potentially enhance clinical management and improve data quality in clinical trials

Evaluation of different recall periods for the US National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Aims—The U.S. National Cancer Institute recently developed the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). PRO-CTCAE is a library of questions for clinical trial participants to self-report symptomatic adverse events (e.g., nausea). The objective of this study is to inform evidence-based selection of a recall period when PRO-CTCAE is included in a trial. We evaluated differences between 1-week, 2-week, 3-week, and 4-week recall periods, using daily reporting as the reference. Methods—English-speaking patients with cancer receiving chemotherapy and/or radiotherapy were enrolled at four U.S. cancer centers and affiliated community clinics. Participants completed 27 PRO-CTCAE items electronically daily for 28 days, and then weekly over 4 weeks, using 1-week, 2-week, 3-week, and 4-week recall periods. For each recall period, mean differences, effect sizes, and intraclass correlation coefficients were calculated to evaluate agreement between the maximum of daily ratings and the corresponding ratings obtained using longer recall periods (e.g., maximum of daily scores over 7 days vs. 1-week recall). Analyses were repeated using the average of daily scores within each recall period rather than the maximum of daily scores. Results—127 subjects completed questionnaires (57% male; median age 57). The median of the 27 mean differences in scores on the PRO-CTCAE 5-point response scale comparing the maximum daily versus the longer recall period (and corresponding effect size), was −0.20 (−0.20) for 1-week recall; −0.36 (−0.31) for 2-week recall; −0.45 (−0.39) for 3-week recall; and −0.47 (−0.40) for 4-week recall. The median intraclass correlation across 27 items between the maximum of daily ratings and the corresponding longer recall ratings for 1-week recall was 0.70 (range: 0.54–0.82); 2-week recall: 0.74 (range: 0.58–0.83); 3-week recall: 0.72 (range: 0.61–0.84); and 4-week recall: 0.72 (range: 0.64–0.86). Similar results were observed for all analyses using the average of daily scores rather than the maximum of daily scores. Conclusions—1-week recall corresponds best to daily reporting. Although intraclass correlations remain stable over time, there are small but progressively larger differences between daily and longer recall periods at 2, 3, and 4 weeks, respectively. The preferred recall period for the PRO-CTCAE is the past 7 days, although investigators may opt for recall periods of 2, 3, or 4 weeks with an understanding that there may be some information loss

A literature synthesis of symptom prevalence and severity in persons receiving active cancer treatment

Patients with cancer experience acute and chronic symptoms caused by their underlying disease or by the treatment. While numerous studies have examined the impact of various treatments on symptoms experienced by cancer patients, there are inconsistencies regarding the symptoms measured and reported in treatment trials. This article presents a systematic review of the research literature of the prevalence and severity of symptoms in patients undergoing cancer treatment

PD-1 Inhibitory Receptor Downregulates Asparaginyl Endopeptidase and Maintains Foxp3 Transcription Factor Stability in Induced Regulatory T Cells

CD4+ T cell differentiation into multiple T helper (Th) cell lineages is critical for optimal adaptive immune responses. This report identifies an intrinsic mechanism by which programmed death-1 receptor (PD-1) signaling imparted regulatory phenotype to Foxp3+ Th1 cells (denoted as Tbet+iTregPDL1 cells) and inducible regulatory T (iTreg) cells. Tbet+iTregPDL1 cells prevented inflammation in murine models of experimental colitis and experimental graft versus host disease (GvHD). Programmed death ligand-1 (PDL-1) binding to PD-1 imparted regulatory function to Tbet+iTregPDL1 cells and iTreg cells by specifically downregulating endo-lysosomal protease asparaginyl endopeptidase (AEP). AEP regulated Foxp3 stability and blocking AEP imparted regulatory function in Tbet+iTreg cells. Also, Aep−/− iTreg cells significantly inhibited GvHD and maintained Foxp3 expression. PD-1-mediated Foxp3 maintenance in Tbet+ Th1 cells occurred both in tumor infiltrating lymphocytes (TILs) and during chronic viral infection. Collectively, this report has identified an intrinsic function for PD-1 in maintaining Foxp3 through proteolytic pathway.Bio-organic Synthesi

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PROCTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

Purpose—To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials—Patients enrolled in Trial XXXX (XXXX) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly x4 during treatment; 12-weeks post-treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Results—Among 226 study sites participating in Trial XXXX, 100% completed 35-minute PROCTCAE training for clinical research associates (CRAs); 80 sites enrolled patients of which 34 (43%) required tablet computers to be provided. All 152 patients in Trial XXXX agreed to selfreport using the PRO-CTCAE (median age 66; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range 30–240), and median time for CRAs to teach a patient to self-report was 10 minutes (range 2–60). Compliance was high, particularly during active treatment when patients self-reported at 86% of expected time points, although compliance was lower post-treatment (72%). Common reasons for non-compliance were institutional errors such as forgetting to provide computers to participants; patients missing clinic visits; internet connectivity; and patients feeling “too sick”. Conclusions—Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic adverse events at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between-visits, and by employing central compliance monitoring. These approaches are being incorporated into ongoing studies