Tumor-immune signatures of treatment resistance to brentuximab vedotin with ipilimumab and/or nivolumab in Hodgkin lymphoma.

PURPOSE: To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin Lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA-4 and PD1. PATIENTS AND METHODS: Phase 1/2, multicenter, open-label, trial NCT01896999 enrolled patients with refractory or relapsed HL (R/R HL) after one or more lines of therapy, with adequate performance status and organ function. Using peripheral blood, we assessed soluble proteins, cell composition, T cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. RESULTS: NCT01896999 reported high (>75%) overall objective response rates with brentuximab-vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed durable increase in soluble PD-1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV+N and BV+I+N) compared with BV+I (p<0.05). Non-responders and patients with short progression free-survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine-deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (p<0.05). CONCLUSIONS: The results suggest a circulating tumor-immune-derived signature of BV±I+N treatment resistance that may be useful for patient stratification in combination checkpoint therapy.

Multi-omics Analysis Reveals Immune Features Associated with Immunotherapy Benefit in Patients with Squamous Cell Lung Cancer from Phase III Lung-MAP S1400I Trial.

PURPOSE: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need. EXPERIMENTAL DESIGN: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink. RESULTS: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivo+ipi. Immune cell density and closer proximity of CD8+GZB+ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression. CONCLUSIONS: The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC.

How should we treat painful sensitivity in the hand? An international e-Delphi study.

BACKGROUND: Evidence synthesis suggests allodynia resulting from neuropathic pain has few interventions with clear effectiveness. As research continues to build this needed evidence base, expert consensus recommendations can address the conflicting approaches within current hand therapy practice. PURPOSE: This study aimed to develop consensus recommendations for the clinical management of allodynia from an international panel of hand therapists. STUDY DESIGN: This was an international e-Delphi survey study. METHODS: We recruited international hand rehabilitation experts to participate in an e-Delphi survey. Consensus was defined as 75% or more of participants agreeing with a recommendation, and at least 3 rounds of consensus building were anticipated. Experts were identified from 21 countries, and clinical vignettes describing a spectrum of patients with painful sensitivity in the hand were provided to elicit treatment recommendations. Initial recommendations were summarized, and consensus sought for clinical practice recommendations. RESULTS: Sixty-eight participants were invited, with 44 more added through peer nominations. Fifty-four participants from 19 countries completed the initial survey and were invited to participate in all subsequent rounds. Over 900 treatment suggestions were provided from the initial vignettes across domains, including sensory, physical, and functional interventions, education, and cortical representation techniques: 46 ultimately reached consensus. However, important discrepancies in justification (eg, why allodynia should be covered) and implementation of techniques (eg, desensitization, sensory reeducation) were identified as the consensus exercise progressed. CONCLUSIONS: Experts recommend individually tailored programs to treat allodynia using a variety of physical/movement, sensory-based, and "top-down" approaches; this is highly aligned with contemporary theories, such as the Neuromatrix Model of Pain. However, consensus was not reached on the justification and implementation of some of these approaches, reflecting the lack of a taxonomy and supporting evidence for tactile stimulation approaches in the current literature. Trials directly comparing the effectiveness of these approaches are needed.

Evaluation of virtual problem-based tutorials in healthcare professional education.

PURPOSE: To explore student and tutor perspectives on the learning efficacy of virtual, compared to in-person, problem-based tutorial (PBT) in occupational therapy, physiotherapy, and speech-language pathology health professional programs. MATERIALS AND METHODS: This was a quality improvement study using a cross sectional survey at a single institution. Separate student and tutor surveys were disseminated online. Students received the survey at two timepoints, tutors received the survey at one timepoint. Descriptive statistics summarized quantitative survey questions. Chi-squared or Fischer's Exact analyses explored differences between in-person and virtual PBT. Exploratory analyses determined if associations amongst programs and/or between cohorts existed on variables of interest. Open-ended survey questions were analyzed using content analysis. RESULTS: A total of 241 students and 85 tutors completed the survey. Results demonstrate most students and tutors were satisfied with the use of virtual tutorials (77%; 89% respectively) and felt that they were effective in exploring content within the PBT course. However, students in the most recent cohort rated virtual tutorials more highly (p = 0.01). CONCLUSIONS: Virtual modes of PBT were successful in achieving course objectives and led to high satisfaction in users. Health professional programs can use this information when designing virtual problem-based tutorial courses in the post-pandemic era.

Problem-based learning (PBL) involves the active engagement of students in self-directed learning where learning gaps are identified, and information is retrieved and critically appraised to apply clinical reasoning to healthcare decisions.Traditionally, the PBL process has been implemented in-person through the use of small group tutorial with six to eight students and a tutor, however, the COVID-19 pandemic led to a quick transition to virtual tutorials.This study found that virtual modes of conducting PBL tutorial were successful in achieving course objectives and both students and tutors were satisfied with using virtual means to achieve course objectives in three professional rehabilitation programs (Occupational Therapy, Physiotherapy, Speech Language Pathology).Health professional programs in rehabilitation can use this information when designing courses using PBL processes in the future, and clinicians can use this information when considering the use of virtual means for care and for collaboration between professionals in various healthcare settings.

How should we define and assess painful sensitivity in the hand? An international e-Delphi study.

BACKGROUND: Painful sensitivity in the hand is commonly seen with neuropathic pain, interfering with daily activities including rehabilitation. However, there are currently several terms used to describe the problem and a lack of guidance on what assessments should be used. PURPOSE: To gather expert opinion a) identifying current and common terminology used in hand therapy, b) developing a consensus definition of hypersensitivity, and c) developing consensus guidance on how to best assess allodynia. STUDY DESIGN: International e-Delphi survey study. METHODS: We conducted an e-Delphi consensus study drawing on international experts in hand rehabilitation. We planned up to four rounds of consensus-seeking, defining consensus as 75% or more of participants agreeing with a definition or recommendation. Experts were identified from 21 countries, with the nomination of other experts encouraged for 'snowball sampling'. The first round included clinical vignettes describing 'painful sensitivity of the hand' and asked participants to describe how they would assess each case. Definitions for hypersensitivity, tactile hyperesthesia, and allodynia were also requested. RESULTS: We invited 68 participants: 44 more were added through nominations. Sixty-three agreed to participate and were sent the round one survey; 54 participants from 19 countries completed this survey and were invited to participate in all subsequent rounds. No two definitions of hypersensitivity were the same, while 87% of the definitions for allodynia and 78% for tactile hyperesthesia were concordant with a published taxonomy. Over 700 assessment items were proposed in round one: ultimately 38 items representing eight distinct constructs reached a consensus for assessing allodynia. CONCLUSIONS: Therapists definitions were consistent with an existing taxonomy for allodynia. Although hypersensitivity conceptualizations varied regarding the qualities of stimulus and response, a working definition was reached. Recommended assessments were relatively consistent internationally, holistic, and reflected a potential link between allodynia and central sensitization.

What mobility factors are critical to include in a comprehensive mobility discharge assessment framework for older adults transitioning from hospital-to-home in the community? An international e-Delphi study.

PURPOSE: To prioritize and achieve consensus on mobility determinant factors [cognitive, financial, environmental, personal, physical, psychological, social] considered critical to include in the COmprehensive Mobility Discharge Assessment Framework (COMDAF) for older adults transitioning from hospital-to-home. MATERIALS AND METHODS: We conducted a three-round modified e-Delphi process with 60 international experts (seven older adults, nine family caregivers, 24 clinicians, and 20 researchers) from nine countries with universal or near-universal health coverage. Expert members rated 91 factors identified from scoping reviews using a 9-point scale: not important (1-3), important (4-6), and critical (7-9). RESULT: A total of 41 of 91 factors (45.1%) met the a-priori consensus criterion after three rounds: five cognitive, five environmental, two personal, 19 physical, six psychological, and six social factors. No financial factors reached a consensus. The older adult steering committee member recommended the addition of two environmental factors, resulting in 43 mobility factors included in the COMDAF. CONCLUSIONS: We advanced a comprehensive mobility framework by developing, through consensus, 43 mobility factors to be assessed as part of a COMDAF. However, its use in hospital-to-home may not be feasible. Therefore, future research will determine the core mobility factors for COMDAF and which measurement instruments best measure these factors. RELEVANCE: An interdisciplinary discharge rehabilitation team can utilize the COMDAF during hospital-to-home transition.Implications for rehabilitationMobility assessment following a hospital discharge is a complex process requiring an interdisciplinary discharge rehabilitation team.This study provided a comprehensive list of 91 factors across all seven mobility determinants (cognitive, environmental, financial, personal, physical, psychological, and social) for clinicians in other care settings to use as a starting point to determine which mobility factor should be assessed during older adults' hospital-to-home transition.This international e-Delphi study identified 43 factors within mobility determinants (cognitive, environmental, personal, physical, psychological, and social) to be included in a Comprehensive Mobility Discharge Assessment Framework to assess older adults' mobility during the hospital to home transition.Using these 43 factors, clinicians can identify which assessment tool is best suited to assess the factors while reflecting on the logistics and feasibility; this is the next phase of this project.

Understanding the Experience and Impacts of Brain Fog in Chronic Pain: A Scoping Review.

Introduction: Approximately 15% to 40% of persons with chronic pain as a primary disorder experience brain fog. Prior research has investigated the etiology of "brain fog" in conditions in which pain presents as a key feature (e.g., fibromyalgia). However, it remains understudied in the context of chronic 10 musculoskeletal pain. Following current scoping review guidelines, we obtained stakeholder input from patient and health care professionals (HCPs) to define this phenomenon. Specific aims of this review were to (1) identify factors contributing to brain fog, (2) identify the functional correlates of brain fog and assessments used to measure them, and (3) establish a definition of brain fog that can be employed by researchers and HCPs to advance research and care. Methods: A scoping review was conducted using recommendations of the Joanna Briggs Institute methodology of scoping reviews and the Levac et al methodology. Embase, Cinahl, PsycINFO, and Medline was searched to identify relevant sources. Findings were verified with patient and healthcare professionals. Results: We identified four 15 key features of brain fog: perceived variability, subjective cognitive dysfunction, participation limitations, and changes in functional activities. We developed a model of brain fog illustrating the overlapping categories of contributors to brain fog in chronic musculoskeletal pain: (1) neuroanatomical and neurophysiological, (2) mental health/emotional, and (3) environmental/lifestyle. Conclusion: The results of this scoping review conclude that the inconsistency in research regarding brain fog in 20 chronic musculoskeletal pain is obstructing a clear understanding of the phenomenon and therefore may be impeding persons with chronic pain and brain fog from receiving optimal care.

Introduction: Environ 15 % à 40 % des personnes souffrant de douleur chronique en tant que trouble primaire ressentent un brouillard cérébral. Des recherches antérieures ont étudié l'étiologie du « brouillard cérébral ¼ dans des affections dans lesquelles la douleur se présente comme une caractéristique clé (par exemple, la fibromyalgie). Cependant, elle reste sous-étudiée dans le contexte de la douleur musculo-squelettiques chronique. Conformément aux lignes directrices actuelles en matière d'examen de la portée, nous avons obtenu les commentaires des parties prenantes provenant de patients et de professionnels de la santé (PS) pour définir ce phénomène. Les objectifs spécifiques de cet examen étaient de (1) déterminer les facteurs contribuant au brouillard cérébral, (2) déterminer les corrélats fonctionnels du brouillard cérébral et les évaluations utilisées pour les mesurer, et (3) établir une définition du brouillard cérébral qui peut être utilisée par les chercheurs et les professionnels de la santé pour faire progresser la recherche et les soins.Méthodes: Un examen de la portée a été mené en utilisant les recommandations de la méthodologie pour les examens de la portée de l'Institut Joanna Briggs et de la méthodologie de Levac et al. Des recherches ont été effectuées dans Embase, Cinahl, PsycINFO et Medline pour réertorier les sources pertinentes. Les résultats ont été vérifiés auprès des patients et des professionnels de la santé.Résultats: Nous avons recensé quatre caractéristiques clés du brouillard cérébral : la variabilité perçue, le dysfonctionnement cognitif subjectif, les limites à la participation et les changements dans les activités fonctionnelles. Nous avons élaboré un modèle de brouillard cérébral illustrant les catégories se de facteurs contributeurs au brouillard cérébral dans le système musculo-squelettique chronique Douleur qui se chevauchent : (1) neuroanatomique et neurophysiologique, (2) santé mentale/émotionnelle, et (3) environnement/mode de vie.Conclusion: Les résultats de cet examen de la portée concluent que l'incohérence de la recherche en ce qui concerne le brouillard cérébral dans la douleur musculo-squelettique chronique ne permet pas d'avoir une compréhension claire du phénomène et peut donc empêcher les personnes souffrant de douleur chronique et de brouillard cérébral de recevoir des soins optimaux.

A Scoping Review of Personal, Financial, and Environmental Determinants of Mobility Among Older Adults.

OBJECTIVE: To synthesize available evidence of factors comprising the personal, financial, and environmental mobility determinants and their association with older adults' self-reported and performance-based mobility outcomes. DATA SOURCES: PubMed, EMBASE, PsychINFO, Web of Science, AgeLine, Sociological Abstract, Allied and Complementary Medicine Database, and Cumulative Index to Nursing and Allied Health Literature databases search for articles published from January 2000 to December 2021. STUDY SECTION: Using predefined inclusion and exclusion criteria, multiple reviewers independently screened 27,293 retrieved citations from databases, of which 422 articles underwent full-text screening, and 300 articles were extracted. DATA EXTRACTION: The 300 articles' information, including study design, sample characteristics including sample size, mean age and sex, factors within each determinant, and their associations with mobility outcomes, were extracted. DATA SYNTHESIS: Because of the heterogeneity of the reported associations, we followed Barnett et al's study protocol and reported associations between factors and mobility outcomes by analyses rather than by article to account for multiple associations generated in 1 article. Qualitative data were synthesized using content analysis. A total of 300 articles were included with 269 quantitative, 22 qualitative, and 9 mixed-method articles representing personal (n=80), and financial (n=1), environmental (n=98), more than 1 factor (n=121). The 278 quantitative and mixed-method articles reported 1270 analyses; 596 (46.9%) were positively and 220 (17.3%) were negatively associated with mobility outcomes among older adults. Personal (65.2%), financial (64.6%), and environmental factors (62.9%) were associated with mobility outcomes, mainly in the expected direction with few exceptions in environmental factors. CONCLUSIONS: Gaps exist in understanding the effect of some environmental factors (eg, number and type of street connections) and the role of gender on older adults' walking outcomes. We have provided a comprehensive list of factors with each determinant, allowing the creation of core outcome set for a specific context, population, or other forms of mobility, for example, driving.

Circulating proteins to predict COVID-19 severity.

Predicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4701 circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict COVID-19 severity in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different COVID-19 severity were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of COVID-19 severity. Further research is needed to understand how to incorporate protein measurement into clinical care.

The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals.

INTRODUCTION: Severe COVID-19 leads to important changes in circulating immune-related proteins. To date it has been difficult to understand their temporal relationship and identify cytokines that are drivers of severe COVID-19 outcomes and underlie differences in outcomes between sexes. Here, we measured 147 immune-related proteins during acute COVID-19 to investigate these questions. METHODS: We measured circulating protein abundances using the SOMAscan nucleic acid aptamer panel in two large independent hospital-based COVID-19 cohorts in Canada and the United States. We fit generalized additive models with cubic splines from the start of symptom onset to identify protein levels over the first 14 days of infection which were different between severe cases and controls, adjusting for age and sex. Severe cases were defined as individuals with COVID-19 requiring invasive or non-invasive mechanical respiratory support. RESULTS: 580 individuals were included in the analysis. Mean subject age was 64.3 (sd 18.1), and 47% were male. Of the 147 proteins, 69 showed a significant difference between cases and controls (p < 3.4 × 10-4). Three clusters were formed by 108 highly correlated proteins that replicated in both cohorts, making it difficult to determine which proteins have a true causal effect on severe COVID-19. Six proteins showed sex differences in levels over time, of which 3 were also associated with severe COVID-19: CCL26, IL1RL2, and IL3RA, providing insights to better understand the marked differences in outcomes by sex. CONCLUSIONS: Severe COVID-19 is associated with large changes in 69 immune-related proteins. Further, five proteins were associated with sex differences in outcomes. These results provide direct insights into immune-related proteins that are strongly influenced by severe COVID-19 infection.

Rapid, scalable assessment of SARS-CoV-2 cellular immunity by whole-blood PCR.

Fast, high-throughput methods for measuring the level and duration of protective immune responses to SARS-CoV-2 are needed to anticipate the risk of breakthrough infections. Here we report the development of two quantitative PCR assays for SARS-CoV-2-specific T cell activation. The assays are rapid, internally normalized and probe-based: qTACT requires RNA extraction and dqTACT avoids sample preparation steps. Both assays rely on the quantification of CXCL10 messenger RNA, a chemokine whose expression is strongly correlated with activation of antigen-specific T cells. On restimulation of whole-blood cells with SARS-CoV-2 viral antigens, viral-specific T cells secrete IFN-γ, which stimulates monocytes to produce CXCL10. CXCL10 mRNA can thus serve as a proxy to quantify cellular immunity. Our assays may allow large-scale monitoring of the magnitude and duration of functional T cell immunity to SARS-CoV-2, thus helping to prioritize revaccination strategies in vulnerable populations.

Cognitive, psychological and social factors associated with older adults' mobility: a scoping review of self-report and performance-based measures.

Although many factors have been associated with mobility among older adults, there is paucity of research that explores the complexity of factors that influence mobility. This review aims to synthesise the available evidence for factors comprising the cognitive, psychological, and social mobility determinants and their associations with mobility self-reported and performance-based outcomes in older adults (60 years). We followed Arksey and O'Malley's five stages of a scoping review and searched PubMed, EMBASE, PsychINFO, Web of Science, AgeLine, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature and Sociological Abstract databases. Reviewers in pairs independently conducted title, abstract, full-text screening and data extraction. We reported associations by analyses rather than articles because articles reported multiple associations for factors and several mobility outcomes. Associations were categorised as significantly positive, negative, or not significant. We included 183 peer-reviewed articles published in 27 countries, most of which were cross-sectional studies and conducted among community-dwelling older adults. The 183 articles reported 630 analyses, of which 381 (60.5%) were significantly associated with mobility outcomes in the expected direction. For example, older adults with higher cognitive functioning such as better executive functioning had better mobility outcomes (e.g., faster gait speed), and those with poor psychological outcomes, such as depressive symptoms, or social outcomes such as reduced social network, had poorer mobility outcomes (e.g., slower gait speed) compared to their counterparts. Studies exploring the association between cognitive factors, personality (a psychological factor) and self-reported mobility outcomes (e.g., walking for transportation or driving), and social factors and performance-based mobility outcomes in older adults are limited. Understanding the additive relationships between cognitive, psychological, and social factors highlights the complexity of older adults' mobility across different forms of mobility, including independence, use of assistive devices, transportation, and driving.

Survey of Physiotherapy Practice in Ontario Cardiac Surgery Intensive Care Units.

Purpose: This article describes current physiotherapy practice for critically ill adult patients requiring prolonged stays in critical care (> 3 d) after complicated cardiac surgery in Ontario. Method: We distributed an electronic, self-administered 52-item survey to 35 critical care physiotherapists who treat adult cardiac surgery patients at 11 cardiac surgical sites. Pilot testing and clinical sensibility testing were conducted beforehand. Participants were sent four email reminders. Results: The response rate was 80% (28/35). The median reported number of cardiac surgeries performed per week was 30 (interquartile range [IQR] 10), with a median number of 14.5 (IQR 4) cardiac surgery beds per site. Typical reported caseloads ranged from 6 to 10 patients per day per therapist, and 93% reported that they had initiated physiotherapy with patients once they were clinically stable in the intensive care unit. Of 28 treatments, range of motion exercises (27; 96.4%), airway clearance techniques (26; 92.9%), and sitting at the edge of the bed (25; 89.3%) were the most common. Intra-aortic balloon pump and extracorporeal membrane oxygenation appeared to limit physiotherapy practice. Use of outcome measures was limited. Conclusions: Physiotherapists provide a variety of interventions to critically ill cardiac surgery patients. Further evaluation of the limited use of outcome measures in the cardiac surgical intensive care unit is warranted.

Objectif : décrire la pratique actuelle de la physiothérapie auprès des patients adultes gravement malades de l'Ontario qui doivent séjourner plus de trois jours en soins intensifs après une opération cardiaque complexe. Méthodologie : distribution d'un sondage électronique autoadministré de 52 questions à 35 physiothérapeutes en soins intensifs qui soignent des patients après une opération cardiaque dans 11 établissements de chirurgie cardiaque. Les chercheurs ont procédé à des essais pilotes et à des tests de sensibilité clinique auparavant. Les participants ont reçu quatre rappels par courriel. Résultats : le taux de réponse s'élevait à 80 % (28 sur 35). Selon la médiane, 30 (plage interquartile [PIQ] de 10) chirurgies cardiaques étaient effectuées par semaine, pour une médiane de 14,5 (PIQ de 4) lits en chirurgie cardiaque par établissement. La charge de travail habituelle se situait entre six et dix patients par thérapeute par jour, et 93 % ont déclaré entreprendre la physiothérapie avec les patients dont l'état s'était stabilisé à l'unité de soins intensifs. Sur 28 traitements, les plus courants étaient des exercices d'amplitude (27 sur 28, 96,4 %), des techniques de dégagement des voies respiratoires (26 sur 28, 92,9 %) et la capacité de s'asseoir au bord du lit (25 sur 28, 89,3 %). Le ballon de contrepulsion intra-aortique et l'oxygénation par membrane extracorporelle semblaient limiter la pratique de la physiothérapie. L'utilisation des mesures de résultats cliniques était limitée. Conclusion : les physiothérapeutes proposent diverses interventions aux patients gravement malades après une opération cardiaque. Une évaluation plus approfondie du recours limité aux mesures de résultats cliniques à l'unité de soins intensifs de cardiologie s'impose.

Exploring patient perspectives of barriers and facilitators to participating in hospital-based stroke rehabilitation.

BACKGROUND: Patient participation is recognized as an important element of rehabilitation. However, few studies have used a qualitative lens to specifically examine factors influencing patient participation in stroke rehabilitation. AIM: The purpose of this study was to investigate patient perspectives of barriers and facilitators to participating in hospital-based stroke rehabilitation. METHODS: Semi-structured interviews were conducted with 11 patients, with confirmed diagnoses of stroke, recruited from three separate rehabilitation settings. Analysis of the interviews was guided by a process of interpretive description to identify key barriers and facilitators to participation in stroke rehabilitation. RESULTS: Four main themes and corresponding sub-themes were constructed concerning participation in rehabilitation: (i) Environmental Factors, (ii) Components of Therapy, (iii) Physical and Emotional Well-Being, and (iv) Personal Motivators. An exploratory model of personalized rehabilitation emerged, integrating the themes emerging from the data. DISCUSSION: Personalized rehabilitation can be considered in comparison to person-centred care principles. The barriers and enablers experienced by patients in this study contribute to the existing knowledge of the patient experience of stroke rehabilitation and may be used to inform clinical practices and future research.Implications for RehabilitationThe surrounding environments can facilitate participation in rehabilitation using strategies to reduce noise and disruption and also by encouraging social interactions among patients.Increasing the frequency and consistency of communication with patients about rehabilitation goals and progress could enhance participation.Designing interventions to include activities that are meaningful and focused on the resumption of valued life roles is key to participation.Therapy intensity, time spent sedentary, and the emotional impact of stroke are aspects of rehabilitation patient's feel are neglected.

The experiences of cardiac surgery critical care clinicians with in-bed cycling in adult patients undergoing complex cardiac surgery.

PURPOSE: In-bed cycling is a novel modality that permits the early initiation of rehabilitation in the intensive care unit. We explored clinicians' experiences and perceptions of in-bed cycling with critically ill cardiac surgery patients. MATERIALS AND METHODS: We used an interpretive description methodology. All critical care clinicians who had been present for at least 2 cycling sessions were eligible. Data were collected using semi-structured, audio-recorded, face-to-face interviews transcribed verbatim. Content analysis was used to identify themes. RESULTS: Nine clinicians were interviewed. Our sample was predominantly female (77.8%) with a median [IQR] age of 40 [21.5] years. Critical care experience ranged from <5 years to ≥30 years. Acceptability was influenced by previous cycling experiences, identifying the "ideal" patient, and the timing of cycling within a patient's recovery. Facilitators included striving towards a common goal and feeling confident in the method. Barriers included inadequate staffing, bike size, and the time to deliver cycling. CONCLUSIONS: Clinicians supported the use of in-bed cycling. Concerns included appropriate patient selection and timing of the intervention. Teamwork was integral to successful cycling. Strategies to overcome the identified barriers may assist with successful cycling implementation in other critical care environments.IMPLICATIONS FOR REHABILITATIONIn-bed cycling is a relatively novel rehabilitation modality that can help initiate physical rehabilitation earlier in a patient's recovery and reduce the iatrogenic effects of prolonged admissions to an intensive care unit.Clinicians found in-bed cycling to be an acceptable intervention with a population of critically ill cardiac surgery patients.Teamwork and interprofessional communication are important considerations for successful uptake of a relatively new rehabilitation modality.Identified barriers to in-bed cycling can assist with developing strategies to encourage cycling uptake in similar critical care environments.

Experiences of inpatient rehabilitation from the perspective of persons with acquired brain injury.

BACKGROUND: Perspectives of individuals with acquired brain injury (ABI) regarding inpatient rehabilitation experiences can inform patient-centered care; however, these voices are under-represented in the literature. PURPOSE: To explore the experiences, needs, and preferences of patients from an ABI inpatient rehabilitation program in Ontario. METHODS: Using an interpretive description approach, we interviewed 12 participants and analyzed the transcripts inductively to generate themes. FINDINGS: We identified three major themes: (1) Life Rerouted - participants felt their lives diverted due to ABI, with rehabilitation seen as a way to return to pre-injury life, (2) Autonomy within Rehab highlighted the perceived importance of personal autonomy in decision-making within rehabilitation, and (3) Life (and Recovery) Go On reflected an ongoing recovery process after discharge - leading to mixed emotions. An overall message, "re-establishing personal identity is important to the recovery process," reflected theories of biographical disruption and relational autonomy. IMPLICATIONS: Our findings provide a patient perspective for clinicians and administrators to consider. We found that ABI was significantly disruptive to personal identity - resulting in tensions in autonomy while attempting to reclaim a sense of identity. We suggest counseling services and strategies supporting post-injury adjustment, along with ways for rehabilitation professionals to enhance patient autonomy where possible.Implications for rehabilitationSustaining an ABI can significantly disrupt personal identity and sense of autonomy - especially as persons occupy the role of "patient" while in inpatient rehabilitation.Psychological support is recommended to address the impacts of ABI on patients' sense of identity, as well as on family members.Strategies of support might include, providing formal psychotherapy, as well as creating opportunities for patients and family members to discuss the changes they are experiencing, and to establish their personal narratives (e.g., through writing or art) or peer mentorship programs between discharged and current patients.Clinicians can enhance patient autonomy by increasing opportunities for communication with patients about choice; educating patients and family members on the rehabilitation team's decision-making process, and other methods that increase communication and provide consistent up-to-date information to patients and their family members.

CardiO Cycle: a pilot feasibility study of in-bed cycling in critically ill patients post cardiac surgery.

BACKGROUND: In-bed cycling is a novel modality for the initiation of early mobilization in the intensive care unit. No study has investigated its use in the critically ill, off-track post cardiac surgery population. Before conducting an effectiveness trial, feasibility data are needed. The aim of this study was to determine the feasibility of in-bed cycling in a population of off-track cardiac surgery patients. METHODS: We conducted a prospective feasibility study in a 16-bed adult cardiac surgery intensive care unit in Ontario, Canada. Previously ambulatory adults (≥ 18 years) who were mechanically ventilated for ≥ 72 h were enrolled within 3 to 7 days post cardiac surgery. Twenty minutes of in-bed cycling was delivered by ICU physiotherapists 5 days/week. The primary outcome, feasibility, was the percent of patient-cycling sessions that occurred when cycling was appropriate. The secondary outcome was cycling safety, measured as cycling discontinuation due to predetermined adverse events. RESULTS: We screened 2074 patients, 29 met eligibility criteria, and 23 (92%) consented. Patients were male (78.26%) with a median [IQR] age of 76 [11] years, underwent isolated coronary bypass (39.1%), and had a median EuroScore II of 5.4 [7.8]. The mean (SD) time post-surgery to start of cycling was 5.9 (1.4) days. Patients were cycled on 80.5% (136/169) of eligible days, with limited physiotherapy staffing accounting for 48.5% of the missed patient-cycling sessions. During 136 sessions of cycling, 3 adverse events occurred in 3 individual patients. The incidence of an adverse event was 2.2 per 100 patient-cycling sessions (95% CI 0.50, 6.4). CONCLUSIONS: In-bed cycling with critically ill cardiac surgery patients is feasible with adequate physiotherapy staffing and appears to be safe. Future studies are needed to determine the effectiveness of this intervention in a larger sample. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov ( NCT02976415 ). Registered November 29, 2016.

Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and multiple organ involvement in individuals under 21 years following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To identify genes, pathways and cell types driving MIS-C, we sequenced the blood transcriptomes of MIS-C cases, pediatric cases of coronavirus disease 2019, and healthy controls. We define a MIS-C transcriptional signature partially shared with the transcriptional response to SARS-CoV-2 infection and with the signature of Kawasaki disease, a clinically similar condition. By projecting the MIS-C signature onto a co-expression network, we identified disease gene modules and found genes downregulated in MIS-C clustered in a module enriched for the transcriptional signatures of exhausted CD8 + T-cells and CD56 dim CD57 + NK cells. Bayesian network analyses revealed nine key regulators of this module, including TBX21 , a central coordinator of exhausted CD8 + T-cell differentiation. Together, these findings suggest dysregulated cytotoxic lymphocyte response to SARS-Cov-2 infection in MIS-C.