Co-Designed Cardiac Rehabilitation for the Secondary Prevention of Stroke (CARESS): A Pilot Program Evaluation.

Structured health system-based programs, such as cardiac rehabilitation, may reduce the risk of recurrent stroke. This study aimed to co-design and evaluate a structured program of rehabilitation, developed based on insights from focus groups involving stroke survivors and health professionals. Conducted in Tasmania, Australia in 2019, the 7-week program comprised one hour of group exercise and one hour of education each week. Functional capacity (6 min walk test), fatigue, symptoms of depression (Patient Health Questionnaire), and lifestyle were assessed pre- and post-program, with a historical control group for comparison. Propensity score matching determined the average treatment effect (ATE) of the program. Key themes from the co-design focus groups included the need for coordinated care, improved psychosocial management, and including carers and peers in programs. Of the 23 people approached, 10 participants (70% men, mean age 67.4 ± 8.6 years) completed the program without adverse events. ATE analysis revealed improvements in functional capacity (139 m, 95% CI 44, 234) and fatigue (-5 units, 95% CI -9, -1), with a small improvement in symptoms of depression (-0.8 units, 95% CI -1.8, 0.2) compared to controls. The co-designed program demonstrated feasibility, acceptability, and positive outcomes, suggesting its potential to support stroke survivors.

Single-Center Incidence and Patterns of Stroke in Early Renal Anhydramnios After Serial Amnioinfusions.

The Renal Anhydramnios Fetal Therapy (RAFT) trial is a study of serial amnioinfusions to prevent lethal neonatal pulmonary hypoplasia from early renal anhydramnios. Infant neurologic outcomes were not originally evaluated. We describe the high incidence of stroke observed among infants in the treatment arm of the trial at our center.

The diagnostic accuracy of a shock advisory algorithm in automated external defibrillators in the presence of real-world artifacts.

BACKGROUND: The current standards for shock advisory algorithms in AEDs require performance testing on artifact-free ECGs. However, AED analysis in the real world is more challenging due to potential artifacts from various sources (e.g., patient handling, and electromagnetic interference). This retrospective data analysis reports the real-world performance and behavior of a shock advisory algorithm used in three AED models with the presence of artifacts. METHODS: ECG rhythm analyses recorded during the use of three AED models (HS1, FRx and FR3) were reviewed. The shock recommendations made in the AEDs were compared to the expert annotations of reviewers. The effects of real-world artifacts and the handling by the algorithm were analyzed. RESULTS: Among the 3,941 analyses, 619 were annotated as shockable rhythms, and 2,912 were non-shockable. The overall sensitivity and specificity were 97.1% (601/619), and 99.9% (2,908/2,912), respectively. Artifacts were detected by the algorithm in 23.3% (918/3,941) of the analysis periods. The algorithm performance for the analysis periods with artifacts detected was 95.2% (80/84) for sensitivity and 100.0% (687/687) for specificity. In the remaining analysis periods with no artifacts detected, the sensitivity was 97.4% (521/535), and specificity was 99.8% (2,221/2,225). CONCLUSIONS: The performance of this shock advisory algorithm during real-world resuscitations with or without artifacts, exceeded AHA recommendations and the requirements in international standards. The high sensitivity and specificity demonstrate the effectiveness and safety of this algorithm in all three AED models.

Diazobutanone-assisted isobaric labelling of phospholipids and sulfated glycolipids enables multiplexed quantitative lipidomics using tandem mass spectrometry.

Mass spectrometry-based quantitative lipidomics is an emerging field aiming to uncover the intricate relationships between lipidomes and disease development. However, quantifying lipidomes comprehensively in a high-throughput manner remains challenging owing to the diverse lipid structures. Here we propose a diazobutanone-assisted isobaric labelling strategy as a rapid and robust platform for multiplexed quantitative lipidomics across a broad range of lipid classes, including various phospholipids and glycolipids. The diazobutanone reagent is designed to conjugate with phosphodiester or sulfate groups, while accommodating various functional groups on different lipid classes, enabling subsequent isobaric labelling for high-throughput multiplexed quantitation. Our method demonstrates excellent performance in terms of labelling efficiency, detection sensitivity, quantitative accuracy and broad applicability to various biological samples. Finally, we performed a six-plex quantification analysis of lipid extracts from lean and obese mouse livers. In total, we identified and quantified 246 phospholipids in a high-throughput manner, revealing lipidomic changes that may be associated with obesity in mice.

The Comorbidity of Patient-Reported Crohn's Disease Activity and Depression: The Role of Health Behavior Mediators.

Background: Longitudinal research reveals a unidirectional relationship between a nonsomatic symptom of depression, a negative view of the self, and later reported Crohn's disease (CD) activity. We evaluated whether health behaviors mediated this association using a longitudinal design. Methods: We studied 3304 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, a symptom-specific index of depression, and measures of physical activity, smoking, and sleep quality. Crohn's disease status and the cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We specified single-mediator and multiple-mediator models to elucidate the depression-disease activity relationship. Results: Among 2395 females and 909 males, we found a significant mediation effect for activity level (P < .001) after adjusting for age, sex, and body mass index. There was no evidence that sleep quality and smoking are significant single mediators. When we considered multiple mediation models, smoking and less activity partially mediate the depression-CD association. Conclusions: Smoking and lower levels of physical activity are potential mediators of the unidirectional association between a nonsomatic symptom of depression-a negative view of the self-and patient-reported CD activity. Evaluating and treating specific symptoms of depression may reduce the frequency of CD exacerbations.

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

RATIONALE: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities. METHODS: We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts. We identified four priority areas: (1) best measurement tools for research, (2) clinical identification of fatigue and potentially modifiable causes, (3) promising interventions and recommendations for future trials, and (4) possible biological mechanisms of fatigue. Cross-cutting themes were aphasia and the voice of people with lived experience. Working parties were formed and structured consensus building processes were followed. RESULTS: We present 20 recommendations covering outcome measures for research, development, and testing of new interventions and priority areas for future research on the biology of post-stroke fatigue. We developed and recommend the use of the Stroke Fatigue Clinical Assessment Tool. CONCLUSIONS: By synthesizing current knowledge in post-stroke fatigue across clinical and pre-clinical fields, our work provides a roadmap for future research into post-stroke fatigue.

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

RATIONALE: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities. METHODS: We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts. We identified four priority areas: (1) best measurement tools for research, (2) clinical identification of fatigue and potentially modifiable causes, (3) promising interventions and recommendations for future trials, and (4) possible biological mechanisms of fatigue. Cross-cutting themes were aphasia and the voice of people with lived experience. Working parties were formed and structured consensus building processes were followed. RESULTS: We present 20 recommendations covering outcome measures for research, development, and testing of new interventions and priority areas for future research on the biology of post-stroke fatigue. We developed and recommend the use of the Stroke Fatigue Clinical Assessment Tool. CONCLUSIONS: By synthesizing current knowledge in post-stroke fatigue across clinical and pre-clinical fields, our work provides a roadmap for future research into post-stroke fatigue.

Mechanisms of Post-Stroke Fatigue: A Follow-Up From the Third Stroke Recovery and Rehabilitation Roundtable.

BACKGROUND: Post-stroke fatigue (PSF) is a significant and highly prevalent symptom, whose mechanisms are poorly understood. The third Stroke Recovery and Rehabilitation Roundtable paper on PSF focussed primarily on defining and measuring PSF while mechanisms were briefly discussed. This companion paper to the main paper is aimed at elaborating possible mechanisms of PSF. METHODS: This paper reviews the available evidence that potentially explains the pathophysiology of PSF and draws parallels from fatigue literature in other conditions. We start by proposing a case for phenotyping PSF based on structural, functional, and behavioral characteristics of PSF. This is followed by discussion of a potentially significant role of early inflammation in the development of fatigue, specifically the impact of low-grade inflammation and its long-term systemic effects resulting in PSF. Of the many neurotransmitter systems in the brain, the dopaminergic systems have the most evidence for a role in PSF, along with a role in sensorimotor processing. Sensorimotor neural network dynamics are compromised as highlighted by evidence from both neurostimulation and neuromodulation studies. The double-edged sword effect of exercise on PSF provides further insight into how PSF might emerge and the importance of carefully titrating interventional paradigms. CONCLUSION: The paper concludes by synthesizing the presented evidence into a unifying model of fatigue which distinguishes between factors that pre-dispose, precipitate, and perpetuate PSF. This framework will help guide new research into the biological mechanisms of PSF which is a necessary prerequisite for developing treatments to mitigate the debilitating effects of post-stroke fatigue.

A Specialized Epithelial Cell Type Regulating Mucosal Immunity and Driving Human Crohn's Disease.

Crohn's disease (CD) is a complex chronic inflammatory disorder that may affect any part of gastrointestinal tract with extra-intestinal manifestations and associated immune dysregulation. To characterize heterogeneity in CD, we profiled single-cell transcriptomics of 170 samples from 65 CD patients and 18 non-inflammatory bowel disease (IBD) controls in both the terminal ileum (TI) and ascending colon (AC). Analysis of 202,359 cells identified a novel epithelial cell type in both TI and AC, featuring high expression of LCN2, NOS2, and DUOX2, and thus is named LND. LND cells, confirmed by high-resolution in-situ RNA imaging, were rarely found in non-IBD controls, but expanded significantly in active CD. Compared to other epithelial cells, genes defining LND cells were enriched in antimicrobial response and immunoregulation. Moreover, multiplexed protein imaging demonstrated that LND cell abundance was associated with immune infiltration. Cross-talk between LND and immune cells was explored by ligand-receptor interactions and further evidenced by their spatial colocalization. LND cells showed significant enrichment of expression specificity of IBD/CD susceptibility genes, revealing its role in immunopathogenesis of CD. Investigating lineage relationships of epithelial cells detected two LND cell subpopulations with different origins and developmental potential, early and late LND. The ratio of the late to early LND cells was related to anti-TNF response. These findings emphasize the pathogenic role of the specialized LND cell type in both Crohn's ileitis and Crohn's colitis and identify novel biomarkers associated with disease activity and treatment response.

Maternal and Neonatal Outcomes in Vedolizumab and Ustekinumab Exposed Pregnancies: Results from the PIANO registry.

BACKGROUND: Pregnancy outcomes in inflammatory bowel disease (IBD) patients with quiescent disease are similar to the general population. Data from the Pregnancy Inflammatory bowel disease And Neonatal Outcomes (PIANO) registry have demonstrated the safety of anti-tumor necrosis factor alpha (TNFs) agents and thiopurines in pregnancy. The objective of this study was to provide information from the PIANO registry on maternal and fetal outcomes in patients exposed to the newer biologics ustekinumab (UST) and vedolizumab (VDZ). METHODS: In this multicenter prospective observational study, we included pregnant women with singleton pregnancies and a diagnosis of IBD. Questionnaires were administered to women at study intake, each subsequent trimester, delivery, and at 4, 9, and 12 months after birth. Bivariate analyses were utilized to determine the independent effects of specific drug classes on outcomes. The exposure cohorts were VDZ, UST, anti-TNFs, immunomodulators, and combination with anti-TNFs and immunomodulators. All were compared to no exposure and to biologics/immunomodulators. RESULTS: There were 1669 completed pregnancies with 1610 live births. Maternal mean age was 32.1 (SD 4.6) years at delivery with 66 VDZ and 47 UST exposed. Women on UST were more likely to have Crohn's disease. There was no increased risk of spontaneous abortion, small for gestational age, low birth weight, neonatal intensive care unit stay, congenital malformations, or intrauterine growth restriction with in utero VDZ or UST exposure. The rate of preterm birth was lower (0.0%) for UST-exposed as compared to other groups including VDZ (13.8%), anti-TNF (8.2%), combination therapy (14.2%), immunomodulator (12.3%), and unexposed (9.7%)(p = 0.03). Rates of serious infections at birth, 4 months, and within the first 12 months of life were comparable among all groups. Nonserious infections were lower at 12 months in UST exposed pregnancies. There was no increased risk signal for placental complications in the VDZ cohort. UST infant concentrations at birth were increased whereas VDZ concentrations were overall decreased compared to maternal serum drug concentration. CONCLUSION: This analysis of UST and VDZ exposure during pregnancy suggests no increase in complications compared to TNFs, immunomodulators and combination TNFs/immunomodulators. No signal was found for increased placental events with either therapy. Continuation of UST and VDZ throughout pregnancy is recommended.

Exploring post-stroke fatigue from the perspective of stroke survivors: what strategies help? A qualitative study.

PURPOSE: Post-stroke fatigue is a research priority for stroke survivors and health professionals but there is limited evidence to guide management. We aimed to explore (1) the experience of post-stroke fatigue from the perspective of stroke survivors and their caregivers and (2) fatigue management strategies that are used. MATERIALS AND METHODS: This was a qualitative study using semi-structured interviews. People with self-reported post-stroke fatigue and caregivers were recruited using maximum variation sampling. Analysis was done via the framework approach. RESULTS: We recruited 17 stroke survivors, nine male (53%), most under 65 years (n = 12, 76%), and greater than 1-year post-stroke (n = 16, 94%, range 10-months to 22-years). One-third of participants self-reported having aphasia (n = 5, 36%). We also recruited eight caregivers, most of whom were female (n = 7, 88%). We identified four themes: (1) fatigue is unexpected after stroke and symptoms vary; (2) the individual experience of fatigue is complex, influenced by multifactorial and biopsychosocial factors; (3) learning to adapt and accept fatigue; and (4) Strategies to manage fatigue and personal approaches to rest. CONCLUSIONS: Post-stroke fatigue experience varies presenting cognitively, physically, and psychologically according to a complex interplay of biopsychosocial factors and personal triggers. Self-management strategies are individualised and include organisation, medications, lifestyle modifications, and peer support.Implications for rehabilitationPost-stroke fatigue is a complex individual experience involving biopsychosocial factors, and stroke survivors need assistance to identify their triggers and support from family, peers, and the stroke community to live well with fatigue.Fatigue is not commonly discussed by health professionals and stroke survivors need simple, practical advice over the long-term to reduce fear and distress.There are a range of strategies that may be helpful. Stroke survivors may benefit from adopting problem-solving approaches, trial pacing, lifestyle modifications and planning, and find forms of rest that work for them.

Effects of Using Websites on Physical Activity and Diet Quality for Adults Living With Chronic Health Conditions: Systematic Review and Meta-Analysis.

BACKGROUND: Adults with chronic health conditions need support to manage modifiable risk factors such as physical inactivity and poor diet. Disease-specific websites with health information on physical activity and diet quality may be effective in supporting adults in managing their chronic illnesses. OBJECTIVE: The primary aim of this review was to determine whether using websites with health information can lead to improvements in physical activity levels or diet quality in adults with chronic health conditions. METHODS: Randomized controlled trials evaluating the effectiveness of website use on levels of physical activity or diet quality in adults with chronic health conditions were included. MEDLINE, Embase, CINAHL, and the Physiotherapy Evidence Database were searched from the earliest available record until February 2023. Data for outcomes measuring physical activity levels; diet quality; and, where reported, self-efficacy and quality of life were independently extracted by 2 reviewers. The risk of bias was assessed using the Physiotherapy Evidence Database scale, and the overall certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Where values were presented as the same unit of measure, postintervention scores were pooled for meta-analysis to yield an overall mean difference (MD). A standardized MD (SMD) was calculated for the pooled data in which different units for the same outcome were used. Individual trial data were described in cases where the data of trials could not be pooled. RESULTS: A total of 29 trials (N=6418 participants) across 8 different disease groups with intervention periods ranging from 4 weeks to 12 months were included in the analysis. There was moderate-certainty evidence that using websites with health information increased levels of moderate to vigorous physical activity (MD=39 min/wk, 95% CI 18.60-58.47), quality of life (SMD=0.36, 95% CI 0.12-0.59), and self-efficacy (SMD=0.26, 95% CI 0.05-0.48) and high-certainty evidence for reduction in processed meat consumption (MD=1.1 portions/wk, 95% CI 0.70-1.58) when compared with usual care. No differences were detected in other measures of diet quality. There was no increased benefit for website users who were offered additional support. CONCLUSIONS: The use of websites for risk factor management has the potential to improve physical activity levels, quality of life, and self-efficacy as well as reduce processed meat consumption for adults living with chronic health conditions when compared with usual care. However, it remains unclear whether using websites leads to meaningful and long-lasting behavior change. TRIAL REGISTRATION: PROSPERO CRD42021283168; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283168.

Pearls & Oy-sters: Epilepsy Is a Key Feature of Pediatric-Onset Huntington Disease.

Pediatric-onset Huntington disease (PoHD) presents differently from adult-onset disease. Children typically exhibit regression in school performance, psychiatric features such as inattention, and oral motor dysfunction. Unlike adult-onset HD, in which seizures occur at approximately the rate of the general public, at least half of children with HD develop epilepsy, and seizures can be a presenting feature of PoHD. Here we present the case of a 10-year-old boy with a history of language delay, motor regression, oral motor dysfunction, and tremor who presented with a first lifetime seizure. Given a family history of Huntington disease in his father, PoHD was considered, and a pathogenic allele with 88 repeats was confirmed in the child. As symptoms progressed, history alone could not differentiate abnormal movements from seizures. Continuous video electroencephalography helped to demonstrate epileptic myoclonic jerks and guide treatment.

Characterization of non-cardiac arrest PulsePoint activations in public and private settings.

BACKGROUND: Geospatial smartphone application alert systems are used in some communities to crowdsource community response for out-of-hospital cardiac arrest (OHCA). Although the clinical focus of this strategy is OHCA, dispatch identification of OHCA is imperfect so that activation may occur for the non-arrest patient. The frequency and clinical profile of such non-arrest patients has not been well-investigated. METHODS: We undertook a prospective 3-year cohort investigation of patients for whom a smartphone geospatial application was activated for suspected OHCA in four United States communities (total population ~1 million). The current investigation evaluates those patients with an activation for suspected OHCA who did not experience cardiac arrest. The volunteer response cohort included off-duty, volunteer public safety personnel (verified responders) notified regardless of location (public or private) and laypersons notified to public locations. The study linked the smartphone application information with the EMS records to report the frequency, condition type, and EMS treatment for these non-arrest patients. RESULTS: Of 1779 calls where volunteers were activated, 756 had suffered OHCA, resulting in 1023 non-arrest patients for study evaluation. The most common EMS assessments were syncope (15.9%, n=163), altered mental status (15.5%, n=159), seizure (14.3%, n=146), overdose (13.0%, n=133), and choking (10.5%, n=107). The assessment distribution was similar for private and public locations. Overall, the most common EMS interventions included placement of an intravenous line (43.1%, n=441), 12-Lead ECG(27.9%, n=285), naloxone treatment (9.8%, n=100), airway or ventilation assistance (8.7%, n=89), and oxygen administration (6.6%, n=68). CONCLUSIONS: More than half of patients activated for suspected OHCA had conditions other than cardiac arrest. A subset of these conditions may benefit from earlier care that could be provided by both layperson and public safety volunteers if they were appropriately trained and equipped.

A plasma membrane-associated glycolytic metabolon is functionally coupled to KATP channels in pancreatic α and ß cells from humans and mice.

The ATP-sensitive K+ (KATP) channel is a key regulator of hormone secretion from pancreatic islet endocrine cells. Using direct measurements of KATP channel activity in pancreatic ß cells and the lesser-studied α cells, from both humans and mice, we provide evidence that a glycolytic metabolon locally controls KATP channels 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 show the presence of a plasma membrane-associated 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.

The gut microbiome-Does stool represent right?

Many stool-based gut microbiome studies have highlighted the importance of the microbiome. However, we hypothesized that stool is a poor proxy for the inner-colonic microbiome and that studying stool samples may be inadequate to capture the true inner-colonic microbiome. To test this hypothesis, we conducted prospective clinical studies with up to 20 patients undergoing an FDA-cleared gravity-fed colonic lavage without oral purgative pre-consumption. The objective of this study was to present the analysis of inner-colonic microbiota obtained non-invasively during the lavage and how these results differ from stool samples. The inner-colonic samples represented the descending, transverse, and ascending colon. All samples were analyzed for 16S rRNA and shotgun metagenomic sequences. The taxonomic, phylogenetic, and biosynthetic gene cluster analyses showed a distinctive biogeographic gradient and revealed differences between the sample types, especially in the proximal colon. The high percentage of unique information found only in the inner-colonic effluent highlights the importance of these samples and likewise the importance of collecting them using a method that can preserve these distinctive signatures. We proposed that these samples are imperative for developing future biomarkers, targeted therapeutics, and personalized medicine.

A patient education intervention improved rates of successful video visits during rapid implementation of telehealth.

INTRODUCTION: The need to rapidly implement telehealth at large scale during the COVID-19 pandemic led to many patients using telehealth for the first time. We assessed the effect of structured pre-visit preparatory telephone calls on success of telehealth visits and examined risk factors for unsuccessful visits. METHODS: A retrospective cohort study was carried out of 45,803 adult patients scheduled for a total of 64,447 telehealth appointments between March and July 2020 at an academic medical center. A subset of patients received a structured pre-visit phone call. Demographic factors and inclusion of a pre-visit call were analysed by logistic regression. Primary outcomes were non-completion of any visit and completion of phone-only versus audio-visual telehealth visits. RESULTS: A pre-visit telephone call to a subset of patients significantly increased the likelihood of a successful telehealth visit (OR 0.54; 95% CI: 0.48-0.60). Patients aged 18-30 years, those with non-commercial insurance or those of Black race were more likely to have incomplete visits. Compared to age 18-30, increasing age increased likelihood of a failed video visit: 31-50 years (OR 1.31; 95% CI: 1.13-1.51), 51-70 years (OR 2.98; 2.60-3.42) and >70 years (OR 4.16; 3.58-4.82). Those with non-commercial insurance and those of Black race (OR 1.8; 95% CI 1.67-1.92) were more likely to have a failed video visit. DISCUSSION: A structured pre-call to patients improved the likelihood of a successful video visit during widespread adoption of telehealth. Structured pre-calls to patients may be an important tool to help reduce gaps in utilization among groups.