Improvements in Between-Vendor MRI Harmonization of Renal T2 Mapping using Stimulated Echo Compensation.

BACKGROUND: T2 mapping is valuable to evaluate pathophysiology in kidney disease. However, variations in T2 relaxation time measurements across MR scanners and vendors may occur requiring additional correction. PURPOSE: To harmonize renal T2 measurements between MR vendor platforms, and use an extended-phase-graph-based fitting method ("StimFit") to correct stimulated echoes and reduce between-vendor variations. STUDY TYPE: Prospective. SUBJECTS: 8 healthy "travelling" volunteers (37.5% female, 32 ± 6 years) imaged on four MRI systems across three vendors at four sites, 10 healthy volunteers (50% female, 32 ± 8 years) scanned multiple times on a given MR scanner for repeatability evaluation. ISMRM/NIST system phantom scanned for evaluation of T2 accuracy. FIELD STRENGTH/SEQUENCE: 3T, multiecho spin-echo sequence. ASSESSMENT: T2 images fit using conventional monoexponential fitting and "StimFit." Mean absolute percentage error (MAPE) of phantom measurements with reference T2 values. Average cortex and medulla T2 values compared between MR vendors, with masks obtained from T2 -weighted images and T1 maps. Full-width-at-half-maximum (FWHM) T2 distributions to evaluate local homogeneity of measurements. STATISTICAL TESTS: Coefficient of variation (CV), linear mixed-effects model, analysis of variance, student's t-tests, Bland-Altman plots, P-value <0.05 considered statistically significant. RESULTS: In the ISMRM/NIST phantom, "StimFit" reduced the MAPE from 4.9%, 9.1%, 24.4%, and 18.1% for the four sites (three vendors) to 3.3%, 3.0%, 6.6%, and 4.1%, respectively. In vivo, there was a significant difference in kidney T2 measurements between vendors using a monoexponential fit, but not with "StimFit" (P = 0.86 and 0.92, cortex and medulla, respectively). The intervendor CVs of T2 measures were reduced from 8.0% to 2.6% (cortex) and 7.1% to 2.8% (medulla) with StimFit, resulting in no significant differences for the CVs of intravendor repeat acquisitions (P = 0.13 and 0.05). "StimFit" significantly reduced the FWHM of T2 distributions in the cortex and whole kidney. DATA CONCLUSION: Stimulated-echo correction reduces renal T2 variation across MR vendor platforms. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

A semi-structured interview to capture manual wheelchair use for mobility activities among individuals with spinal cord injury in real-life situations: development and content validity of the Wheelchair Mobility Activity Log (WC-MAL).

STUDY DESIGN: Mixed-method approach. OBJECTIVES: To develop and assess the content validity of a semi-structured interview that captures the lived experience of using a manual wheelchair among individuals with SCI in the real world, the Wheelchair Mobility Activity Log (WC-MAL). SETTING: SCIR-Group (UDESC)/Brazil. METHODS: Developing the WC-MAL comprised five steps: (1) defining the construct-based on the International Classification of Functioning, Disability and Health (ICF); (2) identifying relevant activities from other assessment instruments and interviews with the end-users (14 Individuals with SCI and 13 rehabilitation professionals); (3) Selecting the items - activities were linked to ICF codes and grouped into sets; (4) developing the scoring scales based on interviews with the end-users; and, (5) evaluating content validity in accordance with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). The content validity ratio (CVR) for each item and scale and the overall instrument content validity index (CVI) were calculated. RESULTS: From an initial draft of 295 activities identified, a set of 222 activities was linked to the ICF domain of "Mobility (d4)" and further refined to generate the 23 items in the WC-MAL. Three scales were developed to assess Frequency (how often), Performance (how well), and Assistance (assistance needed) levels. The items and scales showed a CVR superior to the critical value established (≥0.64). The general CVI value was 0.96. CONCLUSION: The WC-MAL is a promising clinical instrument with adequate content validity to assess the spontaneous use of the manual wheelchair in the real world among individuals with SCI.

Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI.

BACKGROUND: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool. PURPOSE: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies. STUDY TYPE: Systematic consensus process using a modified Delphi method. POPULATION: Not applicable. SEQUENCE FIELD/STRENGTH: Renal fast gradient echo-based 2D PC-MRI. ASSESSMENT: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4-10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated. STATISTICAL TESTS: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60-74% agreement among the experts. RESULTS: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting. DATA CONCLUSION: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Reliability and Validity of the Lower Extremity Motor Activity Log for Measuring Real-World Leg Use in Adults With Multiple Sclerosis.

OBJECTIVES: To determine the test-retest reliability and validity of the Lower Extremity Motor Activity Log (LE-MAL) for assessing LE use in the community in adults with multiple sclerosis (MS). DESIGN: Prospective analysis of measures conducted by trained examiners. SETTING: Participants were evaluated by telephone on several measures of LE use. PARTICIPANTS: Adults with MS (N=43). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The LE-MAL has 3 subscales (Assistance, Functional Performance, and Confidence). It was administered twice, at least 2 weeks apart. The Multiple Sclerosis Walking Scale (MSWS-12), Patient Determined Disease Steps (PDDS), and Mobility Scale were only administered during the first call. RESULTS: The test-retest reliability of the composite and the 3 subscale LE-MAL scores were high (intraclass correlation, >0.94). The composite and subscale LE-MAL scores were strongly correlated with the MSWS-12, PDDS, and Mobility Scale scores (r=-0.56 to -0.77; P<.001). CONCLUSION: This initial study suggests that the LE-MAL reliably and validly measures LE use in the community in adults with MS.

Consensus-based technical recommendations for clinical translation of renal T1 and T2 mapping MRI.

To develop technical recommendations on the acquisition and post-processing of renal longitudinal (T1) and transverse (T2) relaxation time mapping. A multidisciplinary panel consisting of 18 experts in the field of renal T1 and T2 mapping participated in a consensus project, which was initiated by the European Cooperation in Science and Technology Action PARENCHIMA CA16103. Consensus recommendations were formulated using a two-step modified Delphi method. The first survey consisted of 56 items on T1 mapping, of which 4 reached the pre-defined consensus threshold of 75% or higher. The second survey was expanded to include both T1 and T2 mapping, and consisted of 54 items of which 32 reached consensus. Recommendations based were formulated on hardware, patient preparation, acquisition, analysis and reporting. Consensus-based technical recommendations for renal T1 and T2 mapping were formulated. However, there was considerable lack of consensus for renal T1 and particularly renal T2 mapping, to some extent surprising considering the long history of relaxometry in MRI, highlighting key knowledge gaps that require further work. This paper should be regarded as a first step in a long-term evidence-based iterative process towards ever increasing harmonization of scan protocols across sites, to ultimately facilitate clinical implementation.

Protocol for a Randomized Controlled Trial of CI Therapy for Rehabilitation of Upper Extremity Motor Deficit: The Bringing Rehabilitation to American Veterans Everywhere Project.

Constraint-induced movement therapy (CI therapy) has been shown to reduce disability for individuals with upper extremity (UE) hemiparesis following different neurologic injuries. This article describes the study design and methodological considerations of the Bringing Rehabilitation to American Veterans Everywhere (BRAVE) Project, a randomized controlled trial of CI therapy to improve the motor deficit of participants with chronic and subacute traumatic brain injury. Our CI therapy protocol comprises 4 major components: (1) intensive training of the more-affected UE for target of 3 hour/day for 10 consecutive weekdays, (2) a behavioral technique termed shaping during training, (3) a "transfer package," 0.5 hour/day, of behavioral techniques to transfer therapeutic gains from the treatment setting to the life situation, and (4) prolonged restraint of use of the UE not being trained. The primary endpoint is posttreatment change on the Motor Activity Log, which assesses the use of the more-affected arm outside the laboratory in everyday life situations. Data from a number of secondary outcome measures are also being collected and can be categorized as physical, genomic, biologic, fitness, cognitive/behavioral, quality of life, and neuroimaging measures.

Development of MR quantified pancreatic fat deposition as a cancer risk biomarker.

BACKGROUND: Excess body adiposity is associated with increased risk of pancreatic cancer, and in animal models excess intra-pancreatic fat is a driver of pancreatic carcinogenesis. Within a programme to evaluate pancreatic fat and PC risk in humans, we assessed whether MR-quantified pancreatic fat fraction (PFF) was 'fit for purpose' as an imaging biomarker. METHODS: We determined PFF using MR spectroscopy (MRS) and MR chemical shift imaging (CS-MR), in two groups. In Group I, we determined accuracy of MR-derived PFF with histological digital fat quantification in 12 patients undergoing pancreatic resection. In a second study, we assessed reproducibility in 15 volunteers (Group IIa), and extended to 43 volunteers (Group IIa & IIb) to relate PFF with MR-derived hepatic fat fraction (HFF), body mass index (BMI), and waist circumference (WC) using linear regression models. We assessed intra- and inter-observer, and between imaging modality levels of agreement using Bland-Altman plots. RESULTS: In Group I patients, we found strong levels of agreement between MRS and CS-MR derived PFF and digitally quantified fat on histology (rho: 0.781 and 0.672 respectively). In Group IIa, there was poor reproducibility in initial assessments. We refined our protocols to account for 3D dimensionality of the pancreas, and found substantially improved intra-observer agreements. In Group II, HFF and WC were significantly correlated with PFF (p values < 0.05). INTERPRETATION: Both CS-MR and MRS (after accounting for pancreatic 3D dimensionality) were 'fit for purpose' to determine PFF and might add information on cancer prediction independent from measures of general body adiposity.

Apparent diffusion coefficient is highly reproducible on preclinical imaging systems: Evidence from a seven-center multivendor study.

PURPOSE: To evaluate between-site agreement of apparent diffusion coefficient (ADC) measurements in preclinical magnetic resonance imaging (MRI) systems. MATERIALS AND METHODS: A miniaturized thermally stable ice-water phantom was devised. ADC (mean and interquartile range) was measured over several days, on 4.7T, 7T, and 9.4T Bruker, Agilent, and Magnex small-animal MRI systems using a common protocol across seven sites. Day-to-day repeatability was expressed as percent variation of mean ADC between acquisitions. Cross-site reproducibility was expressed as 1.96 × standard deviation of percent deviation of ADC values. RESULTS: ADC measurements were equivalent across all seven sites with a cross-site ADC reproducibility of 6.3%. Mean day-to-day repeatability of ADC measurements was 2.3%, and no site was identified as presenting different measurements than others (analysis of variance [ANOVA] P = 0.02, post-hoc test n.s.). Between-slice ADC variability was negligible and similar between sites (P = 0.15). Mean within-region-of-interest ADC variability was 5.5%, with one site presenting a significantly greater variation than the others (P = 0.0013). CONCLUSION: Absolute ADC values in preclinical studies are comparable between sites and equipment, provided standardized protocols are employed.

Acute Sodium Ingestion Before Exercise Increases Voluntary Water Consumption Resulting In Preexercise Hyperhydration and Improvement in Exercise Performance in the Heat.

Dehydration has been shown to hinder performance of sustained exercise in the heat. Consuming fluids before exercise can result in hyperhydration, delay the onset of dehydration during exercise and improve exercise performance. However, humans normally drink only in response to thirst, which does not result in hyperhydration. Thirst and voluntary fluid consumption have been shown to increase following oral ingestion or infusion of sodium into the bloodstream. We measured the effects of acute sodium ingestion on voluntary water consumption and retention during a 2-hr hydration period before exercise. Subjects then performed a 60-min submaximal dehydration ride (DR) followed immediately by a 200 kJ performance time trial (PTT) in a warm (30 °C) environment. Water consumption and retention during the hydration period was greater following sodium ingestion (1380 ± 580 mL consumed, 821 ± 367 ml retained) compared with placebo (815 ± 483 ml consumed, 244 ± 402 mL retained) and no treatment (782 ± 454 ml consumed, 148 ± 289 mL retained). Dehydration levels following the DR were significantly less after sodium ingestion (0.7 ± 0.6%) compared with placebo (1.3 ± 0.7%) and no treatment (1.6 ± 0.4%). Time to complete the PTT was significantly less following sodium consumption (773 ± 158 s) compared with placebo (851 ± 156 s) and no treatment (872 ± 190 s). These results suggest that voluntary hyperhydration can be induced by acute consumption of sodium and has a favorable effect on hydration status and performance during subsequent exercise in the heat.

Effects of resistance exercise timing on sleep architecture and nocturnal blood pressure.

Short sleep duration and poor quality of sleep have been associated with health risks including cardiovascular disease, diabetes, and obesity. Prior research has suggested that regular aerobic exercise improves the quality of sleep; however, less is known regarding resistance exercise (RE) and how RE may affect sleep architecture. The purpose of this study was to investigate the acute effects of timing of RE on sleep architecture and nocturnal blood pressure. College-aged subjects engaged in 5 laboratory visits. Visits 1 (C) and 2 provided a non-RE control day and established the 10-repetition maximum on each of 9 RE machines, respectively. During visits 3-5, the subjects reported at 0700 hours (7A), 1300 hours (1P), and 1900 hours (7P) in a randomized order to perform 30 minutes of RE. Ambulatory blood pressure and sleep-monitoring devices were worn during sleep after C, 7A, 1P, and 7P. Time to fall asleep was significantly different between RE conditions 7A and 1P and between 7A and 7P. All exercise conditions exhibited significantly fewer times woken than the non-RE control day, with 7P resulting in significantly less time awake after initially falling asleep as compared with C. Although timing of RE does not seem to statistically impact sleep stages or nocturnal blood pressure, these data indicate that engaging in RE at any time of the day may improve quality of sleep as compared with no RE. Resistance exercise may offer additional benefits regarding the ability to fall asleep and stay asleep to populations with osteoporosis, sarcopenia, anxiety, or depression.

A novel deep learning method for large-scale analysis of bone marrow adiposity using UK Biobank Dixon MRI data.

Background: Bone marrow adipose tissue (BMAT) represents > 10% fat mass in healthy humans and can be measured by magnetic resonance imaging (MRI) as the bone marrow fat fraction (BMFF). Human MRI studies have identified several diseases associated with BMFF but have been relatively small scale. Population-scale studies therefore have huge potential to reveal BMAT's true clinical relevance. The UK Biobank (UKBB) is undertaking MRI of 100,000 participants, providing the ideal opportunity for such advances. Objective: To establish deep learning for high-throughput multi-site BMFF analysis from UKBB MRI data. Materials and methods: We studied males and females aged 60-69. Bone marrow (BM) segmentation was automated using a new lightweight attention-based 3D U-Net convolutional neural network that improved segmentation of small structures from large volumetric data. Using manual segmentations from 61-64 subjects, the models were trained to segment four BM regions of interest: the spine (thoracic and lumbar vertebrae), femoral head, total hip and femoral diaphysis. Models were tested using a further 10-12 datasets per region and validated using datasets from 729 UKBB participants. BMFF was then quantified and pathophysiological characteristics assessed, including site- and sex-dependent differences and the relationships with age, BMI, bone mineral density, peripheral adiposity, and osteoporosis. Results: Model accuracy matched or exceeded that for conventional U-Nets, yielding Dice scores of 91.2% (spine), 94.5% (femoral head), 91.2% (total hip) and 86.6% (femoral diaphysis). One case of severe scoliosis prevented segmentation of the spine, while one case of Non-Hodgkin Lymphoma prevented segmentation of the spine, femoral head and total hip because of T2 signal depletion; however, successful segmentation was not disrupted by any other pathophysiological variables. The resulting BMFF measurements confirmed expected relationships between BMFF and age, sex and bone density, and identified new site- and sex-specific characteristics. Conclusions: We have established a new deep learning method for accurate segmentation of small structures from large volumetric data, allowing high-throughput multi-site BMFF measurement in the UKBB. Our findings reveal new pathophysiological insights, highlighting the potential of BMFF as a novel clinical biomarker. Applying our method across the full UKBB cohort will help to reveal the impact of BMAT on human health and disease.

Method for enhancing real-world use of a more affected arm in chronic stroke: transfer package of constraint-induced movement therapy.

BACKGROUND AND PURPOSE: Constraint-induced movement therapy is a set of treatments for rehabilitating motor function after central nervous system damage. We assessed the roles of its 2 main components. METHODS: A 2 × 2 factorial components analysis with random assignment was conducted. The 2 factors were type of training and presence/absence of a set of techniques to facilitate transfer of therapeutic gains from the laboratory to the life situation (Transfer Package; TP). Participants (N=40) were outpatients ≥ 1-year after stroke with hemiparesis. The different treatments, which in each case targeted the more affected arm, lasted 3.5 hours/d for 10 weekdays. Spontaneous use of the more affected arm in daily life and maximum motor capacity of that arm in the laboratory were assessed with the Motor Activity Log and the Wolf Motor Function Test, respectively. RESULTS: Use of the TP, regardless of the type of training received, resulted in Motor Activity Log gains that were 2.4 times as large as the gains in its absence (P<0.01). These clinical results parallel previously reported effects of the TP on neuroplastic change. Both the TP and training by shaping enhanced gains on the Wolf Motor Function Test (P<0.05). The Motor Activity Log gains were retained without loss 1 year after treatment. An additional substudy (N=10) showed that a single component of the TP, weekly telephone contact with participants for 1 month after treatment, doubled Motor Activity Log scores at 6-month follow-up. CONCLUSIONS: The TP is a method for enhancing both spontaneous use of a more affected arm after chronic stroke and its maximum motor capacity. Shaping enhances the latter.

R1 and R2 * changes in the human placenta in response to maternal oxygen challenge.

PURPOSE: Pregnancy complications such as preeclampsia and fetal growth restriction are sometimes thought to be caused by placental abnormalities associated with reduced oxygenation. Oxygen-enhanced MRI (R1 contrast) and BOLD MRI (R2 * contrast) have the potential to noninvasively investigate this oxygen environment at a range of gestational ages. METHODS: Scanning was carried out at 1.5 T under maternal air and oxygen breathing in a single placental slice in 14 healthy pregnant subjects of gestational ages 21-37 weeks. We report R1 changes using a respiratory-triggered inversion recovery-turbo spin-echo sequence, which is sensitive to changes in PO2 , and R2 * changes using a breathhold multiple gradient-recalled echo sequence sensitive to changes in oxygen saturation. RESULTS: Significant R1 increases (P < 0.005, paired t-test) and R2 * decreases (P < 0.0001, paired t-test) between air and oxygen breathing were demonstrated. ΔR1 decreased with gestational age (P < 0.0005, r = -0.835, Pearson correlation test). No significant effect of gestational age on R2 * change was observed. CONCLUSION: The results demonstrate the feasibility of non-invasive investigation of placental oxygenation using MRI and the sensitivity of R1 oxygen-enhanced MRI to gestational age. The techniques have the potential to provide unique noninvasive biomarkers in compromised pregnancies.

Dehydration and acute weight gain in mixed martial arts fighters before competition.

The purpose of this study was to characterize the magnitude of acute weight gain (AWG) and dehydration in mixed martial arts (MMA) fighters before competition. Urinary measures of hydration status and body mass were determined approximately 24 hours before and then again approximately 2 hours before competition in 40 MMA fighters (mean ± SE, age: 25.2 ± 0.65 years, height: 1.77 ± 0.01 m, body mass: 75.8 ± 1.5 kg). The AWG was defined as the amount of body weight the fighters gained in the approximately 22-hour period between the official weigh-in and the actual competition. On average, the MMA fighters gained 3.40 ± 2.2 kg or 4.4% of their body weight in the approximately 22-hour period before competition. Urine specific gravity significantly decreased (p < 0.001) from 1.028 ± 0.001 to 1.020 ± 0.001 during the approximately 22-hour rehydration period. Results demonstrated that 39% of the MMA fighters presented with a Usg of >1.021 immediately before competition indicating significant or serious dehydration. The MMA fighters undergo significant dehydration and fluctuations in body mass (4.4% avg.) in the 24-hour period before competition. Urinary measures of hydration status indicate that a significant proportion of MMA fighters are not successfully rehydrating before competition and subsequently are competing in a dehydrated state. Weight management guidelines to prevent acute dehydration in MMA fighters are warranted to prevent unnecessary adverse health events secondary to dehydration.

Brain hemispheric structural efficiency and interconnectivity rightward asymmetry in human and nonhuman primates.

Evidence for interregional structural asymmetries has been previously reported for brain anatomic regions supporting well-described functional lateralization. Here, we aimed to investigate whether the two brain hemispheres demonstrate dissimilar general structural attributes implying different principles on information flow management. Common left hemisphere/right hemisphere structural network properties are estimated and compared for right-handed healthy human subjects and a nonhuman primate, by means of 3 different diffusion-weighted magnetic resonance imaging fiber tractography algorithms and a graph theory framework. In both the human and the nonhuman primate, the data support the conclusion that, in terms of the graph framework, the right hemisphere is significantly more efficient and interconnected than the left hemisphere, whereas the left hemisphere presents more central or indispensable regions for the whole-brain structural network than the right hemisphere. From our point of view, in terms of functional principles, this pattern could be related with the fact that the left hemisphere has a leading role for highly demanding specific process, such as language and motor actions, which may require dedicated specialized networks, whereas the right hemisphere has a leading role for more general process, such as integration tasks, which may require a more general level of interconnection.

Behavior Change Interventions for Health Promotion in Physical Therapist Research and Practice: An Integrative Approach.

There is an increasing focus on health promotion in physical therapist research and practice. A clinical model (Health-Focused Physical Therapy Model) was developed for identifying major steps in the delivery of health promotion focusing on adoption of healthy lifestyle behaviors. One of the primary steps within this model is the design and delivery of behavior change interventions. Such interventions involve coordinated sets of activities that target change in a specific pattern of unhealthy behavior (eg, physical inactivity, smoking). This Perspective contends that the science and practice of behavior change interventions can be significantly advanced in the field of physical therapy (implementation science) through the integration of behavior change frameworks and techniques within the context of an experimental medicine approach for health behavior change. This perspective presents the integration of the Theoretical Domains Framework, the Behavior Change Wheel, including the Capability Opportunity Motivation-Behavior core system, and the Behavior Change Technique Taxonomy as a comprehensive approach for designing and delivering behavior change interventions in physical therapy. An experimental medicine approach is described, outlining a 4-step process in the design, delivery, and evaluation of behavior change interventions that can be applied to health promotion in physical therapist research and practice. The proposed integrative approach can advance public health and health promotion through healthy lifestyle behavior change in the field of physical therapy.

Effects of lactate consumption on blood bicarbonate levels and performance during high-intensity exercise.

The authors sought to determine the effects of oral lactate consumption on blood bicarbonate (HCO(3)-) levels, pH levels, and performance during high-intensity exercise on a cycle ergometer. Subjects (N = 11) were trained male and female cyclists. Time to exhaustion (TTE) and total work were measured during high-intensity exercise bouts 80 min after the consumption of 120 mg/kg body mass of lactate (L), an equal volume of placebo (PL), or no treatment (NT). Blood HCO(3)- increased significantly after ingestion of lactate (p < .05) but was not affected in PL or NT (p > .05). No changes in pH were observed as a result of treatment. TTE and total work during the performance test increased significantly by 17% in L compared with PL and NT (p = .02). No significant differences in TTE and total work were seen between the PL and NT protocols (p = .85). The authors conclude that consuming 120 mg/kg body mass of lactate increases HCO(3)- levels and increases exercise performance during high-intensity cycling ergometry to exhaustion.

Tele-rehabilitation of upper-extremity hemiparesis after stroke: Proof-of-concept randomized controlled trial of in-home Constraint-Induced Movement therapy.

BACKGROUND: Although Constraint-Induced Movement therapy (CIMT) has been deemed efficacious for adults with persistent, mild-to-moderate, post-stroke upper-extremity hemiparesis, CIMT is not available on a widespread clinical basis. Impediments include its cost and travel to multiple therapy appointments. To overcome these barriers, we developed an automated, tele-health form of CIMT. OBJECTIVE: Determine whether in-home, tele-health CIMT has outcomes as good as in-clinic, face-to-face CIMT in adults ≥1-year post-stroke with mild-to-moderate upper-extremity hemiparesis. METHODS: Twenty-four stroke patients with chronic upper-arm extremity hemiparesis were randomly assigned to tele-health CIMT (Tele-AutoCITE) or in-lab CIMT. All received 35 hours of treatment. In the tele-health group, an automated, upper-extremity workstation with built-in sensors and video cameras was set-up in participants' homes. Internet-based audio-visual and data links permitted supervision of treatment by a trainer in the lab. RESULTS: Ten patients in each group completed treatment. All twenty, on average, showed very large improvements immediately afterwards in everyday use of the more-affected arm (mean change on Motor Activity Log Arm Use scale = 2.5 points, p < 0.001, d' = 3.1). After one-year, a large improvement from baseline was still present (mean change = 1.8, p < 0.001, d' = 2). Post-treatment outcomes in the tele-health group were not inferior to those in the in-lab group. Neither were participants' perceptions of satisfaction with and difficulty of the interventions. Although everyday arm use was similar in the two groups after one-year (mean difference = -0.1, 95% CI = -1.3-1.0), reductions in the precision of the estimates of this parameter due to drop-out over follow-up did not permit ruling out that the tele-health group had an inferior long-term outcome. CONCLUSIONS: This proof-of-concept study suggests that Tele-AutoCITE produces immediate benefits that are equivalent to those after in-lab CIMT in stroke survivors with chronic upper-arm extremity hemiparesis. Cost savings possible with this tele-health approach remain to be evaluated.

Study protocol: a multicentre, open-label, parallel-group, phase 2, randomised controlled trial of autologous macrophage therapy for liver cirrhosis (MATCH).

INTRODUCTION: Liver cirrhosis is a growing global healthcare challenge. Cirrhosis is characterised by severe liver fibrosis, organ dysfunction and complications related to portal hypertension. There are no licensed antifibrotic or proregenerative medicines and liver transplantation is a scarce resource. Hepatic macrophages can promote both liver fibrogenesis and fibrosis regression. The safety and feasibility of peripheral infusion of ex vivo matured autologous monocyte-derived macrophages in patients with compensated cirrhosis has been demonstrated. METHODS AND ANALYSIS: The efficacy of autologous macrophage therapy, compared with standard medical care, will be investigated in a cohort of adult patients with compensated cirrhosis in a multicentre, open-label, parallel-group, phase 2, randomised controlled trial. The primary outcome is the change in Model for End-Stage Liver Disease score at 90 days. The trial will provide the first high-quality examination of the efficacy of autologous macrophage therapy in improving liver function, non-invasive fibrosis markers and other clinical outcomes in patients with compensated cirrhosis. ETHICS AND DISSEMINATION: The trial will be conducted according to the ethical principles of the Declaration of Helsinki 2013 and has been approved by Scotland A Research Ethics Committee (reference 15/SS/0121), National Health Service Lothian Research and Development department and the Medicine and Health Care Regulatory Agency-UK. Final results will be presented in peer-reviewed journals and at relevant conferences. TRIAL REGISTRATION NUMBERS: ISRCTN10368050 and EudraCT; reference 2015-000963-15.

The EXCITE stroke trial: comparing early and delayed constraint-induced movement therapy.

BACKGROUND AND PURPOSE: Although constraint-induced movement therapy (CIMT) has been shown to improve upper extremity function in stroke survivors at both early and late stages after stroke, the comparison between participants within the same cohort but receiving the intervention at different time points has not been undertaken. Therefore, the purpose of this study was to compare functional improvements between stroke participants randomized to receive this intervention within 3 to 9 months (early group) to participants randomized on recruitment to receive the identical intervention 15 to 21 months after stroke (delayed group). METHODS: Two weeks of CIMT was delivered to participants immediately after randomization (early group) or 1 year later (delayed group). Evaluators blinded to group designation administered primary (Wolf Motor Function Test, Motor Activity Log) and secondary (Stroke Impact Scale) outcome measures among the 106 early participants and 86 delayed participants before delivery of CIMT, 2 weeks thereafter, and 4, 8, and 12 months later. RESULTS: Although both groups showed significant improvements from pretreatment to 12 months after treatment, the earlier CIMT group showed greater improvement than the delayed CIMT group in Wolf Motor Function Test Performance Time and the Motor Activity Log (P<0.0001), as well as in Stroke Impact Scale Hand and Activities domains (P<0.0009 and 0.0214, respectively). Early and delayed group comparison of scores on these measures 24 months after enrollment showed no statistically significant differences between groups. CONCLUSIONS: CIMT can be delivered to eligible patients 3 to 9 months or 15 to 21 months after stroke. Both patient groups achieved approximately the same level of significant arm motor function 24 months after enrollment. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00057018.