Do functional walk tests reflect cardiorespiratory fitness in sub-acute stroke?

BACKGROUND AND PURPOSE: The Six-Minute Walk Test (6MWT) has been employed as a measure of functional capacity, but its relationship to cardiorespiratory fitness in stroke is not well established. Gait speed measured over short distances is commonly used as an index of walking competency following stroke. We evaluated the relationship between the 6MWT, aerobic fitness (VO(2)peak) and walking competency in sub-acute stroke. METHODS: Thirty-six individuals (mean age ± SD, 64.6 ± 14.4 years; time post-stroke 16.2 ± 13.3 days) were evaluated using the 6MWT (distance, speed, heart rate), a maximal exercise test (VO(2)peak, heart rate, exercise test duration), and walking competency using a five meter walk (speed, symmetry ratio). Correlation analyses were used to examine the relationships between these outcomes. RESULTS: There was a strong correlation between the 6MWT and five meter walk velocity for preferred (r = 0.79) and fast (r = 0.82) speed (p < 0.001). On average, the 6MWT speed was faster than the preferred gait speed (94.9 cm/s vs. 83.8 cm/s, p = 0.003), but slower than the fast-paced walk (115.1 cm/s, p < 0.001). There was significant though more moderate association between 6MWT distance and VO(2)peak (r = 0.56, p < 0.001) and exercise test duration (r = 0.60, p < 0.001). CONCLUSION: The speed selected during the 6MWT was strongly related to the velocities selected during the five meter walk distance (intermediate to the selected preferred and fast speeds). Although the 6MWT may be challenging to the cardiorespiratory system, it appears to be more strongly influenced by potential limits to walking speed rather than cardiorespiratory capacity. As a result, this test is not, by itself, an adequate measure of aerobic fitness early after stroke

Analysis of a microscopic stochastic model of microtubule dynamic instability

A novel theoretical model of dynamic instability of a system of linear (1D) microtubules (MTs) in a bounded domain is introduced for studying the role of a cell edge in vivo and analyzing the effect of competition for a limited amount of tubulin. The model differs from earlier models in that the evolution of MTs is based on the rates of single unit (e.g., a heterodimer per protofilament) transformations, in contrast to postulating effective rates/frequencies of larger-scale changes, extracted, e.g., from the length history plots of MTs. Spontaneous GTP hydrolysis with finite rate after polymerization is assumed, and theoretical estimates of an effective catastrophe frequency as well as other parameters characterizing MT length distributions and cap size are derived. We implement a simple cap model which does not include vectorial hydrolysis. We demonstrate that our theoretical predictions, such as steady state concentration of free tubulin, and parameters of MT length distributions, are in agreement with the numerical simulations. The present model establishes a quantitative link between microscopic parameters governing the dynamics of MTs and macroscopic characteristics of MTs in a closed system. Lastly, we use a computational Monte Carlo model to provide an explanation for non-exponential MT length distributions observed in experiments. In particular, we show that appearance of such non-exponential distributions in the experiments can occur because the true steady state has not been reached, and/or due to the presence of a cell edge.Comment: 14 pages, 7 figure

Higher intensity walking improves global cognition during inpatient rehabilitation: A secondary analysis of a randomized control trial

Cognitive deficits are common poststroke. Cognitive rehabilitation is typically used to improve cognitive deficits. It is unknown whether higher doses of exercise to promote motor recovery influence cognitive outcomes. Our recent trial, Determining Optimal Post-Stroke Exercise (DOSE), shows more than double the steps and aerobic minutes can be achieved during inpatient rehabilitation versus usual care, and translates to improved long-term walking outcomes. Thus, the secondary analysis aim was to determine the effect of the DOSE protocol on cognitive outcomes over 1-year poststroke. The DOSE protocol progressively increased step number and aerobic minutes during inpatient stroke rehabilitation over 20 sessions. The Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), and Trail Making Test B were completed at baseline, post-intervention, and 6- and 12-months poststroke, administered using standardized guidelines. Using the DOSE data, we used mixed-effect spline regression to model participants\u27 trajectories of cognitive recovery, controlling for relevant covariates. Participants (Usual Car

What matters to program partners when implementing a community-based exercise program for people post-stroke? A theory-based qualitative study and cost analysis

BackgroundCommunity-based exercise programs integrating a healthcare-community partnership (CBEP-HCP) can facilitate lifelong exercise participation for people post-stroke. Understanding the process of implementation from multiple perspectives can inform strategies to promote program sustainability.PurposeTo explore stakeholders' experiences with undertaking first-time implementation of a group, task-oriented CBEP-HCP for people post-stroke and describe associated personnel and travel costs.MethodsWe conducted a descriptive qualitative study within a pilot randomized controlled trial. In three cities, trained fitness instructors delivered a 12-week CBEP-HCP targeting balance and mobility limitations to people post-stroke at a recreation centre with support from a healthcare partner. Healthcare and recreation managers and personnel at each site participated in semi-structured interviews or focus groups by telephone post-intervention. Interviews and data analysis were guided by the Consolidated Framework of Implementation Research and Theoretical Domains Framework, for managers and program providers, respectively. We estimated personnel and travel costs associated with implementing the program.ResultsTwenty individuals from three sites (4 recreation and 3 healthcare managers, 7 fitness instructors, 3 healthcare partners, and 3 volunteers) participated. We identified two themes related to the decision to partner and implement the program: (1) Program quality and packaging, and cost-benefit comparisons influenced managers' decisions to partner and implement the CBEP-HCP, and (2) Previous experiences and beliefs about program benefits influenced staff decisions to become instructors. We identified two additional themes related to experiences with training and program delivery: (1) Program staff with previous experience and training faced initial role-based challenges that resolved with program delivery, and (2) Organizational capacity to manage program resource requirements influenced managers' decisions to continue the program. Participants identified recommendations related to partnership formation, staff/volunteer selection, training, and delivery of program activities. Costs (in CAD) for first-time program implementation were: healthcare partner ($680); fitness coordinators and instructors ($3,153); and participant transportation (personal vehicle: $283; public transit:$110).ConclusionDuring first-time implementation of a CBEP-HCP, healthcare and hospital managers focused on cost, resource requirements, and the added-value of the program, while instructors and healthcare partners focused on their preparedness for the role and their ability to manage individuals with balance and mobility limitations. Trial Registration: ClinicalTrials.gov, NCT03122626. Registered April 17, 2017—Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT0312262

The re-professionalization of the police in England and Wales

In this article contemporary police claims to professional status are analysed and related to a new structure of police regulation in England and Wales. It is argued that the notion of the police as a profession is not new and, unlike police and academic commentary, analysis of this subject, should draw on sociological understandings of professions. The wider policy context within which claims to professionalisation are made is also considered. It is argued that a new, loosely-coupled system of regulation has been developed in England and Wales. Policing’s professional body, the College of Policing, is central to this regulatory framework that has placed government at a distance from constabularies and police representative associations. Finally, some of the consequences of the hybrid system are considered and benefits of the framework of analysis proposed are discussed

A deterministic oscillatory model of microtubule growth and shrinkage for differential actions of short chain fatty acids.

Short chain fatty acids (SCFA), principally acetate, propionate, butyrate and valerate, are produced in pharmacologically relevant concentrations by the gut microbiome. Investigations indicate that they exert beneficial effects on colon epithelia. There is increasing interest in whether different SCFAs have distinct functions which may be exploited for prevention or treatment of colonic diseases including colorectal cancer (CRC), inflammatory bowel disease and obesity. Based on experimental evidence, we hypothesised that odd-chain SCFAs may possess anti-mitotic capabilities in colon cancer cells by disrupting microtubule (MT) structural integrity via dysregulation of β-tubulin isotypes. MT dynamic instability is an essential characteristic of MT cellular activity. We report a minimal deterministic model that takes a novel approach to explore the hypothesised pathway by triggering spontaneous oscillations to represent MT dynamic behaviour. The dynamicity parameters in silico were compared to those reported in vitro. Simulations of untreated and butyrate (even-chain length) treated cells reflected MT behaviour in interphase or untreated control cells. The propionate and valerate (odd-chain length) simulations displayed increased catastrophe frequencies and longer periods of MT-fibre shrinkage. Their enhanced dynamicity was dissimilar to that observed in mitotic cells, but parallel to that induced by MT-destabilisation treatments. Antimicrotubule drugs act through upward or downward modulation of MT dynamic instability. Our computational modelling suggests that metabolic engineering of the microbiome may facilitate managing CRC risk by predicting outcomes of SCFA treatments in combination with AMDs

Implementation of increased physical therapy intensity for improving walking after stroke: Walk 'n Watch protocol for a multi-site stepped-wedge cluster randomized controlled trial

Clinical practice guidelines support structured, progressive protocols for improving walking after stroke. Yet, practice is slow to change, evidenced by the little amount of walking activity in stroke rehabilitation units. Our recent study (n=75) found that a structured, progressive protocol integrated with typical daily physical therapy improved walking and quality of life measures over usual care. Research therapists progressed the intensity of exercise by using heart rate and step counters worn by the participants with stroke during therapy. To have the greatest impact, our next step is to undertake an implementation trial to change practice across stroke units where we enable the entire unit to use the protocol as part of standard of care. What is the effect of introducing structured, progressive exercise (termed the Walk 'n Watch protocol) to standard of care on the primary outcome of walking in adult participants with stroke over the hospital inpatient rehabilitation period? Secondary outcomes will be evaluated and include quality of life.Methods and sample size estimates: This national, multisite clinical trial will randomize 12 sites using a stepped-wedge design where each site will be randomized to deliver Usual Care initially for 4, 8, 12 or 16-months (three sites for each duration). Then, each site will switch to the Walk 'n Watch phase for the remaining duration of a total 20-month enrolment period. Each participant will be exposed to only one of Usual Care or Walk 'n Watch. The trial will enrol a total of 195 participants with stroke to achieve a power of 80% with a Type I error rate of 5%, allowing for 20% dropout. Participants will be medically stable adults post-stroke and able to take 5 steps with a maximum physical assistance from one therapist. The Walk 'n Watch protocol focuses on completing a minimum of 30-minutes of weight-bearing, walking-related activities (at the physical therapists' discretion) that progressively increases in intensity informed by activity trackers measuring heart rate and step number.Study outcome(s): The primary outcome will be the change in walking endurance, measured by the Six-Minute Walk Test, from Baseline (T1) to 4-weeks (T2). This change will be compared across Usual Care and Walk 'n Watch phases using a linear mixed-effects model. Additional physical, cognitive, and quality of life outcomes will be measured at T1, T2, and 12-months post-stroke (T3) by a blinded assessor. The implementation stepped-wedge cluster-randomized trial enables the protocol to be tested under real-world conditions, involving all clinicians on the unit. It will result in all sites and all clinicians on the unit to gain expertise in protocol delivery. Hence, a deliberate outcome of the trial is facilitating changes in best practice to improve outcomes for participants with stroke in the trial, and for the many participants with stroke admitted after the trial ends

Blood pressure trajectory of inpatient stroke rehabilitation patients from the Determining Optimal Post-Stroke Exercise (DOSE) trial over the first 12 months post-stroke

BackgroundHigh blood pressure (BP) is the primary risk factor for recurrent strokes. Despite established clinical guidelines, some stroke survivors exhibit uncontrolled BP over the first 12 months post-stroke. Furthermore, research on BP trajectories in stroke survivors admitted to inpatient rehabilitation hospitals is limited. Exercise is recommended to reduce BP after stroke. However, the effect of high repetition gait training at aerobic intensities (&gt;40% heart rate reserve; HRR) during inpatient rehabilitation on BP is unclear. We aimed to determine the effect of an aerobic gait training intervention on BP trajectory over the first 12 months post-stroke.MethodsThis is a secondary analysis of the Determining Optimal Post-Stroke Exercise (DOSE) trial. Participants with stroke admitted to inpatient rehabilitation hospitals were recruited and randomized to usual care (n = 24), DOSE1 (n = 25; &gt;2,000 steps, 40–60% HRR for &gt;30 min/session, 20 sessions over 4 weeks), or DOSE2 (n = 25; additional DOSE1 session/day) groups. Resting BP [systolic (SBP) and diastolic (DBP)] was measured at baseline (inpatient rehabilitation admission), post-intervention (near inpatient discharge), 6- and 12-month post-stroke. Linear mixed-effects models were used to examine the effects of group and time (weeks post-stroke) on SBP, DBP and hypertension (≥140/90 mmHg; ≥130/80 mmHg, if diabetic), controlling for age, stroke type, and baseline history of hypertension.ResultsNo effect of intervention group on SBP, DBP, or hypertension was observed. BP increased from baseline to 12-month post-stroke for SBP (from [mean ± standard deviation] 121.8 ± 15.0 to 131.8 ± 17.8 mmHg) and for DBP (74.4 ± 9.8 to 78.5 ± 10.1 mmHg). The proportion of hypertensive participants increased from 20.8% (n = 15/72) to 32.8% (n = 19/58). These increases in BP were statistically significant: an effect [estimation (95%CI), value of p] of time was observed on SBP [0.19 (0.12–0.26) mmHg/week, p &lt; 0.001], DBP [0.09 (0.05–0.14) mmHg/week, p &lt; 0.001], and hypertension [OR (95%CI): 1.03 (1.01–1.05), p = 0.010]. A baseline history of hypertension was associated with higher SBP by 13.45 (8.73–18.17) mmHg, higher DBP by 5.57 (2.02–9.12) mmHg, and 42.22 (6.60–270.08) times the odds of being hypertensive at each timepoint, compared to those without.ConclusionBlood pressure increased after inpatient rehabilitation over the first 12 months post-stroke, especially among those with a history of hypertension. The 4-week aerobic gait training intervention did not influence this trajectory

Monitoring guidance for patients with hypophosphatasia treated with asfotase alfa.

Hypophosphatasia (HPP) is a rare, inherited, systemic, metabolic disorder caused by autosomal recessive mutations or a single dominant-negative mutation in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). The disease is associated with a broad range of signs, symptoms, and complications, including impaired skeletal mineralization, altered calcium and phosphate metabolism, recurrent fractures, pain, respiratory problems, impaired growth and mobility, premature tooth loss, developmental delay, and seizures. Asfotase alfa is a human, recombinant enzyme replacement therapy that is approved in many countries for the treatment of patients with HPP. To address the unmet need for guidance in the monitoring of patients receiving asfotase alfa, an international panel of physicians with experience in diagnosing and managing HPP convened in May 2016 to discuss treatment monitoring parameters. The panel discussions focused on recommendations for assessing and monitoring patients after the decision to treat with asfotase alfa had been made and did not include recommendations for whom to treat. Based on the consensus of panel members, this review provides guidance on the monitoring of patients with HPP during treatment with asfotase alfa, including recommendations for laboratory, efficacy, and safety assessments and the frequency with which these should be performed during the course of treatment. Recommended assessments are based on patient age and include regular monitoring of biochemistry, skeletal radiographs, respiratory function, growth, pain, mobility and motor function, and quality of life. Because of the systemic presentation of HPP, a coordinated, multidisciplinary, team-based, patient-focused approach is recommended in the management of patients receiving asfotase alfa. Monitoring of efficacy and safety outcomes must be tailored to the individual patient, depending on medical history, clinical manifestations, availability of resources in the clinical setting, and the clinician's professional judgment

Maternal common mental disorders and infant development in Ethiopia : the P-MaMiE Birth Cohort

Background: Chronicity and severity of early exposure to maternal common mental disorders (CMD) has been associated with poorer infant development in high-income countries. In low- and middle-income countries (LAMICs), perinatal CMD is inconsistently associated with infant development, but the impact of severity and persistence has not been examined. Methods: A nested population-based cohort of 258 pregnant women was identified from the Perinatal Maternal Mental Disorder in Ethiopia (P-MaMiE) study, and 194 (75.2%) were successfully followed up until the infants were 12 months of age. Maternal CMD was measured in pregnancy and at two and 12 months postnatal using the WHO Self-Reporting Questionnaire, validated for use in this setting. Infant outcomes were evaluated using the Bayley Scales of Infant Development. Results: Antenatal maternal CMD symptoms were associated with poorer infant motor development ( β ^ -0.20; 95% CI: -0.37 to -0.03), but this became non-significant after adjusting for confounders. Postnatal CMD symptoms were not associated with any domain of infant development. There was evidence of a dose-response relationship between the number of time-points at which the mother had high levels of CMD symptoms (SRQ ≥ 6) and impaired infant motor development ( β ^ = -0.80; 95%CI -2.24, 0.65 for ante- or postnatal CMD only, β ^ = -4.19; 95%CI -8.60, 0.21 for ante- and postnatal CMD, compared to no CMD; test-for-trend χ213.08(1), p < 0.001). Although this association became non-significant in the fully adjusted model, the β ^ coefficients were unchanged indicating that the relationship was not confounded. In multivariable analyses, lower socio-economic status and lower infant weight-for-age were associated with significantly lower scores on both motor and cognitive developmental scales. Maternal experience of physical violence was significantly associated with impaired cognitive development. Conclusions: The study supports the hypothesis that it is the accumulation of risk exposures across time rather than early exposure to maternal CMD per se that is more likely to affect child development. Further investigation of the impact of chronicity of maternal CMD upon child development in LAMICs is indicated. In the Ethiopian setting, poverty, interpersonal violence and infant undernutrition should be targets for interventions to reduce the loss of child developmental potential.Peer Reviewe