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Background Recruitment to stroke clinical trials is challenging, but consumer registers can facilitate participation. Researchers need to understand the key factors that facilitate trial involvement and improve consumer partnerships to identify what research topics important to stroke and transient ischemic attack (TIA) survivors and their carers. We aimed to examine i) the experience of being involved in a stroke research register, and ii) the priorities for stroke research from the perspective of stroke survivors. Methods Online and paper-based surveys were sent directly to members of a stroke register and disseminated online. Multiple choice questions were reported as counts and percentages and open-ended questions were thematically analysed using Braun and Clarke’s 6-stage process. Results Of 445 survey respondents, 154 (38%) were a member of the Stroke Research Register. The most frequently reported reason for research participation was to help others in the future. Respondents reported they were less likely to take part in research if the research question was not relevant to them, if transport was an issue, or because they lacked time. The most important research problems reported were targeting specific impairments including recovery of movement, fatigue, and aphasia, improvement of mental health services, and increased support for carers. Conclusions Recruitment to trials may be improved by research registers if an inclusive research culture is fostered, in which consumers feel valued as members of a community, have direct and timely access to research findings and the opportunity to be meaningfully involved in research around the problems that consumers find most important.

SummaryThe ATP-sensitive K+channel (KATP) is a key regulator of hormone secretion from pancreatic islet endocrine cells. Using direct measurements of KATPchannel activity in pancreatic β cells and the lesser-studied α cells, from both humans and mice, we demonstrate that a glycolytic metabolon locally controls KATPchannels on the plasma membrane. The two ATP-consuming enzymes of upper glycolysis, glucokinase and phosphofructokinase, generate ADP that activates KATP. Substrate channeling of fructose 1,6-bisphosphate through the enzymes of lower glycolysis fuels pyruvate kinase, which directly consumes the ADP made by phosphofructokinase to raise ATP/ADP and close the channel. We further demonstrate the presence of a plasma membrane NAD+/NADH cycle, whereby lactate dehydrogenase is functionally coupled to glyceraldehyde-3-phosphate dehydrogenase. These studies provide direct electrophysiological evidence of a KATP-controlling glycolytic signaling complex and demonstrate its relevance to islet glucose sensing and excitability.Graphical abstractHoet al. demonstrate that the enzymes of glycolysis, as well as lactate dehydrogenase, form a plasma membrane-associated metabolon with intrinsic ATP/ADP and NAD+/NADH cycles. The subcellular location of this signaling complex allows both ATP-consuming and ATP-producing enzymes to locally control the activity of ATP-sensitive K+channels in pancreatic α and β cells from humans and mice.HighlightsKATPchannels are regulated by a glycolytic metabolon on the plasma membrane.Substrate channeling occurs between the consecutive enzymes of glycolysis.Upper glycolysis produces ADP that is used directly by lower glycolysis to make ATP.LDH and GADPH facilitate a plasma membrane-associated NAD+/NADH redox cycle.

Vedolizumab is a monoclonal antibody used to treat inflammatory bowel disease (IBD). There is little known about the safety and comparative efficacy of this agent in the elderly population. Here, we present data on the safety and comparative efficacy of vedolizumab versus tumor necrosis factor α antagonists (anti-TNF) in elderly patients with IBD. This retrospective cohort study included IBD patients started on vedolizumab or anti-TNF at age 60 or older at a single tertiary IBD center. Safety was evaluated by assessing for the development of serious infection. The comparative needs for IBD-related surgery, IBD-related hospitalization, and drug discontinuation for any reason were obtained. Efficacy was assessed by comparing changes in endoscopic, histologic, and patient-report outcomes. 212 cases were identified—108 patients treated with vedolizumab and 104 patients treated with anti-TNF. There were no significant differences between cohorts in serious infection, surgical intervention, or IBD-hospitalization-free survival (p = NS). Drug discontinuation survival was different between anti-TNF and vedolizumab (p = 0.02) with more patients remaining on vedolizumab at the time of last follow-up (51.9% vs. 25.9%). Endoscopic remission and response rates were higher in the vedolizumab versus anti-TNF group (65.7% vs. 45.2%, p = 0.02; 80.0% vs. 59.3%, p

Background A Functional Medicine program was developed at an inflammatory bowel disease (IBD) center with the goal of integrating strategies to address modifiable lifestyle factors and to complete a 6-week elimination diet under the direction of a trained Functional Medicine dietitian and Functional Medicine providers. Methods From January 2019 to November 2019, patients with controlled, but persistent, symptoms from IBD were offered enrollment. Each of the 5 visits incorporated an educational session focused on nutrition followed by a session focusing on modifiable lifestyle factors. The patients were placed on a supervised 6-week elimination diet. At each visit, patients completed the SIBDQ (Short Inflammatory Bowel Disease Questionnaire), FSS (Fatigue Severity Scale), PSQI (The Pittsburgh Sleep Quality Index), and MSQ (Medical Symptoms Questionnaire). Statistical analysis was performed using the Wilcoxon matched pairs signed-rank test. Results Nineteen patients enrolled (2 men: 1 ulcerative colitis [UC], 1 Crohn’s disease [CD]; 17 women: 3 UC, 14 CD). 15 patients completed all modules. There was improvement in all patient-reported outcomes (PROs) (FSS, P < .001; PSQI, P < .001; SIBDQ, P < .001; MSQ, P < .001). Every patient who completed the last session demonstrated weight loss. Conclusions The psychoemotional roots to immune disease states, particularly IBD, are complicated and often not addressed in traditional care. We are just beginning to understand the impact of nutrition, sleep, stress, movement, and relationships on IBD. In this cohort, utilizing Functional Medicine as an adjunct to traditional care resulted in improvement in all PROs.

Background Prior research demonstrates Crohn’s disease patients often do well in pregnancy; however, less is known about the risk of flare in the postpartum period. Methods A retrospective chart review was conducted at a tertiary care inflammatory bowel disease center. All pregnant women with Crohn’s disease who were followed in the postpartum period, defined as 6 months after delivery, were included. Statistical analysis included χ 2 analysis, Wilcoxon rank sum test, and logistic regression analysis. The primary outcome of interest was rate of flare in the postpartum period. Results There were 105 patients included in the study, with a majority (68%) on biologic medication during pregnancy. Thirty-one patients (30%) had a postpartum flare at a median of 9 weeks (range 2–24 weeks). Twenty-five patients (81%) had their postpartum flare managed in the outpatient setting with medications (only 4 of these patients required prednisone). 6 of 31 patients (19%) were hospitalized at a median of 4 weeks (range 2–26 weeks) after delivery, requiring intravenous corticosteroids or surgery. In multivariable regression, there was no significant increase in risk of postpartum flare with increasing maternal age, flare during pregnancy, or steroid or biologic use during pregnancy. Smoking during pregnancy increased risk of postpartum flare (odds ratio, 16.2 [1.72–152.94], P Conclusion In a cohort of Crohn’s disease patients, 30% experienced a postpartum flare despite being on medical therapy, but most were able to be managed in the outpatient setting.

Background This study evaluated synchronous audiovisual telehealth and audio-only visits for patients with inflammatory bowel disease (IBD) to determine frequency of successful telehealth visits and determine what factors increase the likelihood of completion. Methods Data were collected from March to July 2020 in a tertiary care adult IBD clinic that was transitioned to a fully telehealth model. A protocol for telehealth was implemented. A retrospective analysis was performed using electronic medical record (EMR) data. All patients were scheduled for video telehealth. If this failed, providers attempted to conduct the visit as audio only. Results Between March and July 2020, 2571 telehealth visits were scheduled for adult patients with IBD. Of these, 2498 (99%) were successfully completed by video or phone. Sixty percent were female, and the median age was 41 years. Eighty six percent of the population was white, 8% black, 2% other, and 4% were missing. Seventy-five percent had commercial insurance, 15% had Medicare, 5% had Medicaid, and 5% had other insurance. No significant factors were found for an attempted but completely failed visit. Using a multivariate logistic regression model, increasing age (odds ratio, 1.80; 95% CI, 1.55–2.08; P Conclusions There is a high success rate for telehealth within an IBD population with defined clinic protocols. Certain patient characteristics such as age, race, and health insurance type increase the risk of failure of a video visit.

Physical activity is recommended after stroke. However, the rehabilitation day is largely spent sedentary. Understanding patterns of physical activity across the rehabilitation week may help identify opportunities to improve participation. We aimed to examine: (1) differences between weekday and weekend sedentary time and physical activity, (2) the pattern of 24-h rehabilitation activity. Participants with stroke (n = 29) wore an activity monitor continuously during the final 7-days of inpatient rehabilitation. Linear mixed models (adjusted for waking hours) were performed with activity (sedentary, steps per day, walking time) as the dependent variable, and day type (weekday or weekend) as the independent variable. Patterns of upright time during the 24-h period were determined by averaging daily activity in 60-min intervals and generating a heat map of activity levels as a function of time. Participant mean age was 69 (SD 13) years (52% male) and mean National Institutes of Health Stroke Scale score was 7.0 (SD, 5.5). There was no significant difference in sedentary time between weekdays and weekends. At the weekend, participants spent 8.4 min less time walking (95% CI, -12.1 to -4.6) taking 624 fewer steps/day (95% CI, -951 to -296) than during the week. Activity patterns showed greatest upright time in the morning during the week. Afternoon and evening activities were low on all days. Sedentary time did not change across the 7-day rehabilitation week, but less walking activity occurred on the weekend. There are opportunities for stroke survivors to increase physical activity during afternoons and evenings and on weekend mornings during rehabilitation.

While the pathogenesis of inflammatory bowel disease (IBD) is incompletely understood, disruption of epithelial integrity is suspected to play a prominent role in disease initiation and progression. Currently, there is no convenient way to measure this in vivo. Our aim is to determine whether a mucosal integrity (MI) testing device that has been used to measure MI in the esophagus can also be used to measure barrier function in the colon during colonoscopy. Mucosal integrity testing was measured in patients with IBD (n = 17) and controls (n = 7) during colonoscopy. During the procedure, an MI catheter was passed down the working channel of the colonoscope and placed along the mucosal wall to measure MI in the rectum, left, transverse, and right colon. In patients with IBD, MI measurements and biopsies were taken in areas which appeared inflamed when present. We then determined if there was a significant difference in MI between patients with IBD and controls. MI was significantly higher in the rectum of patients with IBD (CD and UC combined) versus control colons [767 (618–991) vs. 531 (418–604) ohms, P

Purpose: We aimed to understand from the perspective of stroke survivors and their carers (1) factors contributing to sedentary time and physical activity during inpatient rehabilitation and the transition home, and (2) actual and perceived opportunities to reduce sedentary time and increase physical activity. Material and methods: Qualitative study with 7 stroke survivor/carer dyads and 8 stroke survivors. Semi-structured interviews were conducted 2-4 weeks after hospital discharge, audio recorded and transcribed prior to thematic analysis. Results: Stroke survivors were mean age 69 [SD15] years (53% male). Carers were mean age 62 [SD15] years (86% were female). Five themes were identified: (1) Education and guidance about physical activity and sedentary behaviour after stroke is important to build understanding of recovery and secondary prevention, (2) Stroke survivors need clear communication about safety and risk, (3) Return to life participation supports motivation for and engagement in physical activity, 4) Social and professional influences and 5) Opportunities to be physically active. Conclusion: Stroke survivors and their carers need a clearer understanding of the role of physical activity and risks of sedentary time during stroke recovery. Physical activity enablers included consistent communication, building confidence and skills to self-manage activity before discharge. Implications for RehabilitationInpatient rehabilitation and early after discharge may be an important time-point to support stroke survivors to establish long term physical activity behaviours before contact with healthcare professionals reduces.To reduce sedentary behaviour, people need to understand the health benefits of breaking up sedentary time and people who need physical support to stand up will need greater support from health professionals.Being able to imagine a future post-stroke self is important motivation to get up and move. Rehabilitation should help develop a person's vision of their post-stroke self.Managing potential risks in hospital without overly restricting physical activity is important and requires consistent communication from the multi-disciplinary team.Building a person's confidence and skills to self-manage physical activity in the community prior to discharge home may be another key enabler for activity.

BACKGROUND Rehabilitation provided via telehealth offers an alternative to in-person health care consultations. Effective rehabilitation depends on accurate and relevant assessments that reliably measure changes in function over time. The reliability of a suite of relevant assessments to measure the impact of rehabilitation on physical function during a telehealth consultation is unknown. OBJECTIVE We aimed to measure the intra-rater reliability of mobility-focused physical outcome measures delivered via telehealth using Zoom (a commonly used telecommunication platform), and inter-rater reliability comparing telehealth with in-person assessments. METHODS Healthy volunteers were recruited to complete seven mobility-focussed outcome measures in view of a laptop computer under instruction from a remotely-based researcher. Another in-person researcher (providing the benchmark scores) concurrently recorded their scores. The same researchers collected all of the data. Inter- and intra-rater reliability was assessed for Grip Strength, Functional reach test, Five-time Sit to Stand, 3 and 4 meter walks and Timed up-and-go, using intra-class correlation coefficients (ICC) and Bland-Altman plots. These tests were chosen as they cover a wide array of physical mobility, strength and balance constructs that relate to functional daily activities, require little to no assistance from a clinician, can be performed in the limits of a home environment and were likely to be feasible over a telehealth delivery mode. RESULTS Thirty participants (age 36.2±12.5 years, 63% male) completed all assessments. Inter-rater reliability was excellent for Grip Strength (ICC: 0.99) and Functional reach (ICC: 0.99), good for Five-time Sit to Stand (ICC: 0.842) and 4 Meter Walk (ICC: 0.76), moderate for timed up and go (ICC: 0.64), and poor for 3 Meter Walk (ICC: -0.46). Intra-rater reliability for the remote researcher was excellent for Grip Strength (ICC: 0.91), good for Timed up-and-go, 3 Meter Walk, 4 Meter Walk, Functional reach (ICC: 0.84-0.89) and moderate for Five-time Sit to Stand (ICC: 0.67). Although recorded simultaneously, the timing-based assessments were recorded as significantly longer via telehealth for Five-time Sit to Stand (1.2s), Timed up-and-go (1.0s) and 3 Meter Walk (1.3s). CONCLUSIONS High intra-rater reliability of mobility-focused physical outcome assessments measured over telehealth (Zoom) have been demonstrated. Untimed mobility-focussed physical outcome measures have excellent inter-rater reliability between in-person and telehealth measurement. Timed outcome measures recorded approximately one second longer via telehealth, reducing the reliability of shorter duration tests. Small time differences favouring in-person attendance are of a similar magnitude to clinically importance differences, indicating assessments undertaken using telehealth (Zoom) cannot be compared directly with face-to-face delivery. This has implications for clinicians using blended (some face-to-face and some telehealth) assessments.