Perspectives of People with Stroke, Caregivers and Healthcare Professionals on an Adaptive mHealth Intervention for Physical Activity in the Prevention of Secondary Stroke: A Qualitative Study.

Introduction: Engaging in regular physical activity (PA) is associated with lower mortality following stroke, and PA reduces the chance of recurrent stroke. Despite recent guidelines to optimise PA following stroke, people with stroke are known to be less active than their age-matched counterparts. Given the heterogenous nature of stroke, adaptive PA interventions are recommended for people with stroke. Empirical data is lacking on adaptive PA or behavioural change interventions following stroke. Suggested strategies in the prevention of stroke recommend the use of mobile health (mHealth) interventions in the primary prevention of stroke. A structured stakeholder consultation process is key to successful implementation of complex interventions. This paper reports the findings of our consultation process to inform the development of an adaptive mHealth PA. Methods: We used a qualitative study design to explore the perspectives of key stakeholders on the development of an adaptive PA intervention delivered via mHealth post-stroke. Healthcare workers, carers and people with stroke participated in semi-structured one-to-one or focus group interviews. A reflexive thematic analysis was undertaken on transcribed interviews; key themes and sub-themes were developed using coding and summarised by two researchers, then reviewed by the full research team. Results: Twenty-eight stakeholders were interviewed and three main themes were identified; Key feature of a mHealth intervention, delivering a mHealth intervention, Challenges to development and use. There was widespread agreement across stakeholder groups that an adaptive mHealth PA intervention following stroke would be beneficial to people with stroke, following discharge from acute care. Conclusion: Our consultation supports the development of an adaptive PA programme that addresses specific impairments that can hinder exercise participation after stroke.

"I think it was helpful but not as helpful as it could have been" - a qualitative study of the experiences and perspectives of using fitness apps among manual wheelchair users with spinal cord injury.

PURPOSE: To gain knowledge of the experiences and perceptions of using fitness apps by full-time wheelchair users with spinal cord injury (SCI) and to explore experiences and perceptions of using these apps in relation to barriers to and facilitators of physical activity (PA). MATERIALS AND METHODS: A qualitative design was employed. Semi-structured interviews were conducted with ten manual wheelchair users with SCI. Data were analysed using reflexive thematic analysis. RESULTS: Four themes were developed: 1) App functionality and experience, 2) Enhancing motivation, 3) Precursors to engagement and 4) Knowledge gaps. Experience and perception were strongly influenced by app design, particularly the presence or absence of features tailored for wheelchair users. Many apps incorporated the use wearable or mountable sensors. Fitness apps were perceived to increase motivation, although, this had its limitations. Conversely, apps were reported to have limited influence on commonly reported barriers to PA. Furthermore, the data highlighted gaps in knowledge which created barriers to effective app use. CONCLUSIONS: Fitness apps were perceived to increase motivation to engage in PA in manual wheelchair users with SCI. However, more needs to be done to further develop app features for wheelchair users with SCI and to address remaining barriers to engagement.

Fitness apps may provide additional motivation for manual wheelchair users with Spinal Cord Injury (SCI) to increase their levels of physical activity (PA).Fitness apps should be used in conjunction with other supports to enable these individuals to overcome additional barriers to PA.When recommending the use of fitness apps, health and fitness professionals need to consider the unique motivations of each client in order to select an app that best enhances their motivation.A collaborative approach needs to be taken by health and fitness professionals and individuals with SCI to create greater awareness of the benefits and limitations of apps and to advocate the need for more app features tailored for wheelchair users with SCI.

Sequential multiple assignment randomised trial to develop an adaptive mobile health intervention to increase physical activity in people poststroke in the community setting in Ireland: TAPAS trial protocol.

INTRODUCTION: Stroke is the second-leading cause of death and disability globally. Participation in physical activity (PA) is a cornerstone of secondary prevention in stroke care. Given the heterogeneous nature of stroke, PA interventions that are adaptive to individual performance are recommended. Mobile health (mHealth) has been identified as a potential approach to supporting PA poststroke. To this end, we aim to use a Sequential Multiple Assignment Randomised Trial (SMART) design to develop an adaptive, user-informed mHealth intervention to improve PA poststroke. METHODS AND ANALYSIS: The components included in the 12-week intervention are based on empirical evidence and behavioural change theory and will include treatments to increase participation in Structured Exercise and Lifestyle or a combination of both. 117 participants will be randomly assigned to one of the two treatment components. At 6 weeks postinitial randomisation, participants will be classified as responders or non-responders based on participants' change in step count. Non-responders to the initial treatment will be randomly assigned to a different treatment allocation. The primary outcome will be PA (steps/day), feasibility and secondary clinical and cost outcomes will also be included. A SMART design will be used to evaluate the optimum adaptive PA intervention among community-dwelling, ambulatory people poststroke. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Health Service Executive Mid-Western Ethics Committee (REC Ref: 026/2022). The findings will be submitted for publication and presented at relevant national and international academic conferences TRIALS REGISTRATION NUMBER: NCT05606770.

OptiCogs: feasibility of a multicomponent intervention to rehabilitate people with cognitive impairment post-stroke.

BACKGROUND: Stroke is a leading cause of death and disability worldwide. Despite the prevalence and associated burden of cognitive impairment post-stroke, there is uncertainty regarding optimal cognitive rehabilitation for people post-stroke. This study aimed to assess whether a multicomponent intervention, called OptiCogs, is feasible, acceptable, and safe for people with cognitive impairment post-stroke. A secondary aim was to explore changes in cognitive function, fatigue, quality of life, physical function, and occupational performance, from pre-intervention to post-intervention. METHODS: A feasibility study was conducted where people post-stroke with cognitive impairment enrolled in a 6-week multicomponent intervention. The primary outcomes recorded included response rate, recruitment rate, retention rate, adherence to the intervention protocol, adverse events, and acceptability of the intervention to people post-stroke. Secondary outcomes included (i) change in cognitive functioning using the Addenbrooke's Cognitive Examination III, (ii) fatigue using the Fatigue Severity scale, (iii) quality of life using the Stroke Specific Quality of Life scale (iv) physical function using the patient-reported outcomes measurement information system, and (v) patient-reported occupational performance using the Canadian Occupational Performance Measure. The Consolidated Standards of Reporting Trials extension reporting guidelines were followed, for pilot and feasibility studies, to standardize the conduct and reporting of this study. RESULTS: The response rate was 10.9%. Nine eligible participants were enrolled during the 4-month recruitment period, with eight participants completing the entire 6-week intervention, as well as the pre- and post-intervention outcome measures. There were no reported adverse events. Participants were satisfied with the intervention and found it acceptable overall. Results of the secondary outcomes were promising for cognitive function (ACE III, pre: 63.3 ± 23.9 to post: 69 ± 24.6), fatigue (FSS, pre: 52.5 ± 7.3 to post: 45.6 ± 7.2), quality of life (SSQoL, pre: 131.0 ± 26.3 to post: 169.9 ± 15.3), physical function (PROMIS-PF, pre: 15.5 ± 6.3 to post: 15.8 ± 5.3), and occupational performance (COPM performance, pre: 9.3 ± 2.3 to post: 22.9 ± 4.2) and COPM satisfaction, pre: 9.9 ± 2.1 to post: 22.7 ± 3.5). CONCLUSION: Preliminary results suggest low-modest recruitment and high retention rates for the OptiCogs intervention. Changes in cognitive function, fatigue, quality of life, and self-reported occupational performance show improvement from pre- to post-intervention. These potential benefits require further testing in a larger pilot trial. TRIAL REGISTRATION: NCT05414539.

Brief Report: Combination of Osimertinib and Dacomitinib to Mitigate Primary and Acquired Resistance in EGFR-Mutant Lung Adenocarcinomas.

PURPOSE: Primary and acquired resistance to osimertinib remain significant challenges for patients with EGFR-mutant lung cancers. Acquired EGFR alterations such as EGFR T790M or C797S mediate resistance to EGFR tyrosine kinase inhibitors (TKI) and combination therapy with dual EGFR TKIs may prevent or reverse on-target resistance. PATIENTS AND METHODS: We conducted two prospective, phase I/II trials assessing combination osimertinib and dacomitinib to address on-target resistance in the primary and acquired resistance settings. In the initial therapy study, patients received dacomitinib and osimertinib in combination as initial therapy. In the acquired resistance trial, dacomitinib with or without osimertinib was administered to patients with EGFR-mutant lung cancers with disease progression on osimertinib alone and evidence of an acquired EGFR second-site mutation. RESULTS: Cutaneous toxicities occurred in 93% (any grade) of patients and diarrhea in 72% (any grade) with the combination. As initial therapy, the overall response to the combination was 73% [95% confidence interval (CI), 50%-88%]. No acquired secondary alterations in EGFR were observed in any patients at progression. In the acquired resistance setting, the overall response was 14% (95% CI, 1%-58%). CONCLUSIONS: We observed no acquired secondary EGFR alterations with dual inhibition of EGFR as up-front treatment, but this regimen was associated with greater toxicity. The combination was not effective in reversing acquired resistance after development of a second-site acquired EGFR alteration. Our study highlights the need to develop better strategies to address on-target resistance in patients with EGFR-mutant lung cancers.

A Phase 1 Safety Study of Avelumab Plus Stereotactic Body Radiation Therapy in Malignant Pleural Mesothelioma.

Introduction: Single-agent monoclonal antibody therapy against programmed death-ligand 1 (PD-L1) has modest effects in malignant pleural mesothelioma. Radiation therapy can enhance the antitumor effects of immunotherapy. Nevertheless, the safety of combining anti-PD-L1 therapy with stereotactic body radiation therapy (SBRT) is unknown. We present the results of a phase 1 trial to evaluate the safety of the anti-PD-L1 antibody avelumab plus SBRT in patients with malignant pleural mesothelioma. Methods: This was a single-arm, investigator-initiated trial in patients who progressed on prior chemotherapy. Avelumab was delivered every other week, and SBRT was delivered to one lesion in three to five fractions (minimum of 30 Gy) followed by continuation of avelumab up to 24 months or until disease progression. The primary end point of the study was safety on the basis of grade 3+ nonhematologic adverse events (AEs) within 3 months of SBRT. Results: Thirteen assessable patients received a median of seven cycles (range: 2-26 cycles) of avelumab. There were 27 grade 1, 17 grade 2, four grade 3, and no grade 4 or 5 avelumab-related AEs. The most common were infusion-related allergic reactions (n = 6), anorexia or weight loss (n = 6), fatigue (n = 6), thyroid disorders (n = 5), diarrhea (n = 3), and myalgia or arthralgias (n = 3). There were 10 grade 1, four grade 2, one grade 3, and no grade 4 or 5 SBRT-related AEs. The most common were diarrhea (n = 3), chest pain/myalgia (n = 2), fatigue (n = 2), cough (n = 2), dyspnea (n = 2), and nausea/vomiting (n = 2). Conclusions: Combination avelumab plus SBRT seems tolerable on the basis of the prespecified toxicity end points of the first stage of this Simon two-stage design phase 1 study.

Experiences of people with multiple sclerosis participating in a social cognitive behavior change physical activity intervention.

BACKGROUND: Understanding the experiences of people with MS taking part in physical activity interventions is critical to inform future interventions. AIM: The aim was to gain insight into the experiences of people with MS taking part in a behavior change group physical activity intervention with a novel social cognitive theory component. METHODS: A qualitative semi-structured interview format was utilized. Questions focussed on expectations, views and beliefs at being involved in the study, beliefs on physical activity, and subjective evaluation of the trial content and delivery. Seventeen people were interviewed and data were analyzed using thematic analysis. RESULTS: Three themes were generated: psychological and social factors, intervention processes, and MS identity. The acceptance of MS as an identity acted as an initial barrier to exercise, with a more positive, exercise-enabling identity post-intervention. Psychological factors such as self-efficacy and anxiety, as well as social factors such as social support, were found to play an important role in how participants experienced the program. Similarly, intervention processes included support for group-based activities and structure of exercise classes, and were also inter-linked to the other themes. CONCLUSION: It appears that group-based exercise interventions are acceptable and feasible for people with MS. The qualitative findings support previously reported quantitative findings that the Step it Up intervention is effective at promoting physical activity and improving psychological outcomes.

Exploring the perspectives of key stakeholders on the design and delivery of a cognitive rehabilitation intervention for people post-stroke.

PURPOSE: Stroke is a leading cause of death and disability worldwide. Despite the prevalence and associated burden of post-stroke cognitive impairment, there is uncertainty regarding optimum interventions to improve cognitive function in people post-stroke. The aim of this study is to explore the perspectives of key stakeholders on the design and development of a multidisciplinary intervention to rehabilitate cognitive deficits in people post-stroke. MATERIALS AND METHODS: Audio-recorded, semi-structured interviews were employed with people post-stroke, caregivers, healthcare professionals and academics. All transcribed interviews were exported to NVivo software and analysed using reflexive thematic analysis. RESULTS: Thirty interviews were conducted across stakeholder groups including people post-stroke (n = 10), caregivers (n = 5), healthcare professionals (n = 14) and academics (n = 1). Four themes relevant to the design and development of the intervention were identified (i) engagement in the intervention must be meaningful, (ii) the point of readiness to engage, (iii) a familiar but flexible setting is key (iv) pragmatics of intervention delivery. CONCLUSIONS: These findings present new perspectives across stakeholder groups on the design and delivery of an intervention to rehabilitate cognitive deficits in people post-stroke. Taken together with existing quantitative evidence, these findings will inform the development of a feasibility trial, examining patient and process outcomes, to rehabilitate cognitive deficits post-stroke.

Rehabilitation of Cognitive Deficits Poststroke: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Despite the prevalence of cognitive impairment poststroke, there is uncertainty regarding interventions to improve cognitive function poststroke. This systematic review and meta-analysis evaluate the effectiveness of rehabilitation interventions across multiple domains of cognitive function. METHODS: Five databases were searched from inception to August 2019. Eligible studies included randomized controlled trials of rehabilitation interventions for people with stroke when compared with other active interventions or standard care where cognitive function was an outcome. RESULTS: Sixty-four randomized controlled trials (n=4005 participants) were included. Multiple component interventions improved general cognitive functioning (MD, 1.56 [95% CI, 0.69-2.43]) and memory (standardized MD, 0.49 [95% CI, 0.27-0.72]) compared with standard care. Physical activity interventions improved neglect (MD, 13.99 [95% CI, 12.67-15.32]) and balance (MD, 2.97 [95% CI, 0.71-5.23]) compared with active controls. Noninvasive brain stimulation impacted neglect (MD, 20.79 [95% CI, 14.53-27.04) and functional status (MD, 14.02 [95% CI, 8.41-19.62]) compared with active controls. Neither cognitive rehabilitation (MD, 0.37 [95% CI, -0.94 to 1.69]) nor occupational-based interventions (MD, 0.45 [95% CI, -1.33 to 2.23]) had a significant effect on cognitive function compared with standard care. CONCLUSIONS: There is some evidence to support multiple component interventions, physical activity interventions, and noninvasive brain stimulation improving cognitive function poststroke. Findings must be interpreted with caution given the overall moderate to high risk of bias, heterogeneity of interventions, and outcome measures across studies.

Come for Information, Stay for Support: Harnessing the Power of Online Health Communities for Social Connectedness during the COVID-19 Pandemic.

The COVID-19 pandemic created a globally shared stressor that saw a rise in the emphasis on mental and emotional wellbeing. However, historically, these topics were not openly discussed, leaving those struggling without professional support. One powerful tool to bridge the gap and facilitate connectedness during times of isolation is online health communities (OHCs). This study surveyed Health Union OHC members during the pandemic to determine the degree of COVID-19 concern, social isolation, and mental health distress they are facing, as well as to assess where they are receiving information about COVID-19 and what sources of support they desire. The survey was completed in six independent waves between March 2020 and April 2021, and garnered 10,177 total responses. In the United States, OHCs were utilized significantly more during peak lockdown times, and the desire for emotional and/or mental health support increased over time. Open-ended responses demonstrated a strong desire for connection and validation, which are quintessential characteristics of OHCs. Through active moderation utilizing trained moderators, OHCs can provide a powerful, intermediate and safe space where conversations about mental and emotional wellbeing can be normalized and those in need are encouraged to seek additional assistance from healthcare professionals if warranted.

Pattern of disease and response to pembrolizumab in recurrent cervical cancer.

OBJECTIVE: Since the approval of pembrolizumab for advanced or recurrent PD-L1 positive (CPS > 1%) cervical cancer, the clinical characteristics associated with response have remained undefined. We sought to characterize the clinicopathologic features of patients with advanced cervical cancer at our institution who derived durable clinical benefit from treatment with pembrolizumab. METHODS: We conducted a retrospective cohort study of 14 patients with recurrent or metastatic cervical cancer who received pembrolizumab monotherapy from August 2017 to November 2019 and were followed until November 1, 2020. Reviewed clinical data included age, histology, tumor molecular profiling results, stage at diagnosis, treatment history, baseline pattern of metastatic disease at initiation of anti-PD-1 therapy, and outcomes. Treatment response was evaluated by computed tomography using RECIST v1.1 criteria. RESULTS: The objective response rate was 21% (n = 3), including two partial responses and one complete response. Two patients (14%) had stable disease of six months or greater, for an observed durable clinical benefit rate of 36%. When stratified by those who derived clinical benefit, metastatic spread to lung and/or lymph node only at baseline was associated with improved response to pembrolizumab (n = 7, p = 0.02) and associated with significantly improved PFS and OS. Tumor mutational burden was higher in those with durable clinical benefit compared to non-responders (median 12.7 vs. 3.5 mutations/megabase, p = 0.03). CONCLUSIONS: Our findings highlight clinical features that may select for a population most likely to benefit from pembrolizumab monotherapy and underscores the need for identification of additional biomarkers of response.

Erlotinib and Trametinib in Patients With EGFR-Mutant Lung Adenocarcinoma and Acquired Resistance to a Prior Tyrosine Kinase Inhibitor.

Inhibition of the MEK/ERK pathway is critical for Bcl-2-like protein 11 (BIM)-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-induced apoptosis, and dysregulation of this pathway may be a mechanism of acquired resistance. Therefore, MEK inhibition with trametinib and an EGFR TKI may resensitize tumors with acquired resistance. Limited targeted therapies are available after progression on EGFR TKIs, and it is in this setting that we completed a phase I/II study of erlotinib and trametinib. METHODS: Patients with metastatic EGFR-mutant lung adenocarcinoma and acquired resistance to an EGFR TKI received combination erlotinib 75 mg and trametinib 1.5 mg daily until progression or unacceptable side effects. The primary objective was objective response rate determined using RECIST version 1.1. RESULTS: Twenty-three patients were accrued; patients had received a median of two lines of prior TKI therapy (61% prior osimertinib), and 48% had acquired EGFR T790M. We confirmed one partial response (1/23, 4%, 95% CI, 0 to 22). The median progression-free survival was 1.8 months, and the median overall survival was 21 months. Diarrhea (87%), acneiform rash (87%), and fatigue (52%) were the most common treatment-related adverse events. Two patients who had tumor shrinkage both harbored a BRAF fusion. CONCLUSION: Addition of trametinib to erlotinib in the acquired resistance setting in an unselected population is not efficacious. Future studies should focus on targeted therapies in molecularly selected populations. Acquired BRAF fusions in patients with EGFR-sensitizing mutations may be a molecular subset where EGFR and MEK combination therapy could be studied further.

Pilot Study of Dacomitinib for Patients With Metastatic EGFR-Mutant Lung Cancers With Disease Progression After Initial Treatment With Osimertinib.

Patients with EGFR-mutant lung cancer have no approved targeted therapies after disease progression on first-line osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Preclinical studies suggest that tumors with both EGFR-sensitizing alteration and acquired second-site EGFR resistance alterations after treatment with osimertinib retain sensitivity to second-generation EGFR TKIs. We hypothesized that dacomitinib, a pan-human epidermal growth factor receptor TKI, may be effective in this setting. METHODS: In this phase II study, patients who had progressed on first-line osimertinib were treated with dacomitinib 45 mg orally daily until disease progression or intolerability. The primary end point was objective response rate. RESULTS: We enrolled 12 patients. Two partial responses were documented (17% objective response rate; 95% CI, 5 to 45). The median progression-free survival was 1.8 months (95% CI, 1.6 to not reached). One patient with an original sensitizing EGFR G719A mutation and one patient without molecular testing available had partial responses, whereas 0 of the 3 patients with second-site acquired EGFR resistance mutations (two C797S and one G724S) met the response criteria. The patient with EGFR G719A has an ongoing response at 17 months, which exceeds prior time on osimertinib (11 months). CONCLUSION: In the first trial evaluating a second-generation EGFR TKI after first-line third-generation osimertinib, we found that dacomitinib after disease progression on osimertinib has limited benefit.

Telemedicine Use and Health-Related Concerns of Patients With Chronic Conditions During COVID-19: Survey of Members of Online Health Communities.

BACKGROUND: It has been widely communicated that individuals with underlying health conditions are at higher risk of severe disease due to COVID-19 than healthy peers. As social distancing measures continue during the COVID-19 pandemic, experts encourage individuals with underlying conditions to engage in telehealth appointments to maintain continuity of care while minimizing risk exposure. To date, however, little information has been provided regarding telehealth uptake among this high-risk population. OBJECTIVE: The aim of this study is to describe the telehealth use, resource needs, and information sources of individuals with chronic conditions during the COVID-19 pandemic. Secondary objectives include exploring differences in telehealth use by sociodemographic characteristics. METHODS: Data for this study were collected through an electronic survey distributed between May 12-14, 2020, to members of 26 online health communities for individuals with chronic disease. Descriptive statistics were run to explore telehealth use, support needs, and information sources, and z tests were run to assess differences in sociodemographic factors and information and support needs among those who did and did not use telehealth services. RESULTS: Among the 2210 respondents, 1073 (49%) reported engaging in telehealth in the past 4 months. Higher proportions of women engaged in telehealth than men (890/1781, 50% vs 181/424, 43%; P=.007), and a higher proportion of those earning household incomes of more than US $100,000 engaged in telehealth than those earning less than US $30,000 (195/370, 53% vs 241/530 45%; P=.003). Although 59% (133/244) of those younger than 40 years and 54% (263/486) of those aged 40-55 years used telehealth, aging populations were less likely to do so, with only 45% (677/1500) of individuals 56 years or older reporting telehealth use (P<.001 and P=.001, respectively). Patients with cystic fibrosis, lupus, and ankylosing spondylitis recorded the highest proportions of individuals using telehealth when compared to those with other diagnoses. Of the 2210 participants, 1333 (60%) participants either looked up information about the virus online or planned to in the future, and when asked what information or support would be most helpful right now, over half (1151/2210, 52%) responded "understanding how COVID-19 affects people with my health condition." CONCLUSIONS: Nearly half of the study sample reported participating in telehealth in the past 4 months. Future efforts to engage individuals with underlying medical conditions in telehealth should focus on outreach to men, members of lower-income households, and aging populations. These results may help inform and refine future health communications to further engage this at-risk population in telehealth as the pandemic continues.

Perfusion defects on dual-energy CTA in patients with suspected pulmonary embolism correlate with right heart strain and lower survival.

OBJECTIVES: To evaluate the utility of perfusion defects on dual-energy CT angiograms (DECTA) in assessing the clinical severity of pulmonary embolism (PE). METHODS: We retrospectively reviewed 1136 consecutive diagnostic DECTA exams performed on patients with suspected PE between January 2014 and September 2014. Presence and location of obstructive and non-obstructive PE, right ventricular to left ventricular ratio (RV/LV ratio), and inferior vena cava (IVC) backflow were recorded. Iodine maps were reviewed to establish the presence of perfusion defect and its extent was determined through a score-based segmental impaired perfusion. Subsequently, the perfusion defect scores were correlated with clinical parameters including vital signs, electrocardiogram (ECG) abnormalities, echocardiogram findings, troponin, and brain natriuretic peptide (bnp) levels. Clinical information regarding primary cancer diagnosis, oncologic stage, and date of death if applicable was also recorded. RESULTS: Of the 1136 diagnostic iodine maps, 96 of these patients had perfusion defects on iodine maps. After uni- and multivariate analysis, significant correlation was found between the presence of a perfusion defect and RV/LV ratio (p = 0.05), IVC backflow (p = 0.03), elevated troponin (p = 0.03), and right heart dysfunction as determined on an echocardiogram (p = 0.05). The greater the perfusion defect score, the higher the likelihood of IVC backflow (p = 0.005) and obstructive PE (p = 0.002). When adjusted for oncologic stage, patients with a perfusion defect and a higher perfusion defect score had a higher mortality rate (p = 0.005). CONCLUSION: The presence of a perfusion defect correlates with several parameters evaluating PE severity. A perfusion defect and higher perfusion defect score were associated with a lower survival. KEY POINTS: • Detection of perfusion defects on dual-energy CT angiograms and its extent correlates with right heart strain in the setting of pulmonary embolism. • The presence and extent of a perfusion defect in patients with pulmonary embolism are associated with lower survival.

Assessment of Adaptive Engagement and Support Model for People With Chronic Health Conditions in Online Health Communities: Combined Content Analysis.

BACKGROUND: With the pervasiveness of social media, online health communities (OHCs) are an important tool for facilitating information sharing and support among people with chronic health conditions. Importantly, OHCs offer insight into conversations about the lived experiences of people with particular health conditions. Little is known about the aspects of OHCs that are important to maintain safe and productive conversations that support health. OBJECTIVE: This study aimed to assess the provision of social support and the role of active moderation in OHCs developed in accordance with and managed by an adaptive engagement model. This study also aimed to identify key elements of the model that are central to the development, maintenance, and adaptation of OHCs for people with chronic health conditions. METHODS: This study used combined content analysis, a mixed methods approach, to analyze sampled Facebook post comments from 6 OHCs to understand how key aspects of the adaptive engagement model facilitate different types of social support. OHCs included in this study are for people living with multiple sclerosis, migraine, irritable bowel syndrome, rheumatoid arthritis, lung cancer, and prostate cancer. An exploratory approach was used in the analysis, and initial codes were grouped into thematic categories and then confirmed through thematic network analysis using the Dedoose qualitative analysis software tool. Thematic categories were compared for similarities and differences for each of the 6 OHCs and by topic discussed. RESULTS: Data on the reach and engagement of the Facebook posts and the analysis of the sample of 5881 comments demonstrate that people with chronic health conditions want to engage on the web and find value in supporting and sharing their experiences with others. Most comments made in these Facebook posts were expressions of social support for others living with the same health condition (3405/5881, 57.89%). Among the comments with an element of support, those where community members validated the knowledge or experiences of others were most frequent (1587/3405, 46.61%), followed by the expression of empathy and understanding (1089/3405, 31.98%). Even among posts with more factual content, such as insurance coverage issues, user comments still had frequent expressions of support for others (80/213, 37.5%). CONCLUSIONS: The analysis of this OHC adaptive engagement model in action shows that the foundational elements-social support, engagement, and moderation-can effectively be used to provide a rich and dynamic community experience for individuals with chronic health conditions. Social support is demonstrated in a variety of ways, including sharing information or validating information shared by others, expressions of empathy, and sharing encouraging statements with others.

Effect of Osimertinib and Bevacizumab on Progression-Free Survival for Patients With Metastatic EGFR-Mutant Lung Cancers: A Phase 1/2 Single-Group Open-Label Trial.

Importance: The combination of erlotinib and bevacizumab as initial treatment of epidermal growth factor receptor (EGFR [OMIM 131550])-mutant lung cancers improves progression-free survival (PFS) compared with erlotinib alone. Because osimertinib prolongs PFS compared with erlotinib, this trial was designed to study the combination of osimertinib and bevacizumab as first-line treatment. Objectives: To determine the safety and tolerability of osimertinib and bevacizumab combination treatment and assess the 12-month PFS of the combination in patients with metastatic EGFR-mutant lung cancers. Design, Setting, and Particiants: From August 15, 2016, to May 15, 2018, 49 patients with metastatic EGFR-mutant lung cancers were enrolled in this interventional clinical trial, conducted at a single academic cancer center. In the phase 1 portion of the study, a standard 3 + 3 dose de-escalation design was used to determine the maximum tolerated dose of osimertinib and bevacizumab. In the phase 2 portion of the study, patients were treated at the maximum tolerated dose defined in the phase 1 portion. Statistical analysis was performed from August 1 to October 1, 2019. Interventions: All patients received osimertinib, 80 mg daily, and bevacizumab, 15 mg/kg once every 3 weeks. Main Outcomes and Measures: The primary objective of the phase 2 portion of the study was to determine the number of patients receiving the combination of osimertinib and bevacizumab who were progression free at 12 months. Secondary end points included overall response rate, median PFS, overall survival, and definition of the toxic effects of the combination treatment. Results: Among the 49 patients in the study (34 women; median age, 60 years [range, 36-83 years]), PFS at 12 months was 76% (95% CI, 65%-90%). The overall response rate was 80% (95% CI, 67%-91%), and median PFS was 19 months (95% CI, 15-24 months). Of the 6 patients with measurable central nervous system disease, all had a partial or complete central nervous system response. Persistent detection of EGFR-mutant circulating tumor (ct)DNA at 6 weeks was associated with shorter median PFS (clearance at 6 weeks, 16.2 months [95% CI, 13 months to not reached]; and no clearance at 6 weeks, 9.8 months [95% CI, 4 months to not reached]; P = .04) and median overall survival (clearance at 6 weeks, not reached; and no clearance at 6 weeks, 10.1 months [95% CI, 6 months to not reached]; P = .002). Identified mechanisms of resistance included squamous cell transformation (n = 2) pleomorphic transformation (n = 1), and acquired EGFR L718Q (n = 1) and C797S (n = 1) mutations. Conclusions and Relevance: The combination of osimertinib and bevacizumab met the study's prespecified effectiveness end point. Persistent EGFR-mutant circulating tumor DNA at 6 weeks was associated with early progression and shorter survival. A randomized phase 3 study comparing osimertinib and bevacizumab with osimertinib alone is planned. Trial Registration: ClinicalTrials.gov Identifier: NCT02803203.

Association Between Walking Pace and Stroke Incidence: Findings From the UK Biobank Prospective Cohort Study.

Background and Purpose- Stroke incidence in younger and middle-aged people is growing. Despite this, its associations in this subset of the stroke population are unknown, and prevention strategies are not tailored to meet their needs. This study examined the association between self-reported walking pace and incident stroke. Methods- Data from the UK Biobank were used in a prospective population-based study. Three hundred and sixty-three thousand, one hundred and thirty-seven participants aged 37 to 73 years (52% women) were recruited. The associations of self-reported walking pace with stroke incidence over follow-up were investigated using Cox proportional-hazard models. Results- Among 363,137 participants, 2705 (0.7%) participants developed a fatal or nonfatal stroke event over the mean follow-up period of 6.1 years (interquartile range, 5.4-6.7). Slow walking pace was associated with a higher hazard for stroke incidence (hazard ratio [HR], 1.45 [95% CI, 1.26-1.66]; P<0.0001). Stroke incidence was not associated with walking pace among people <65 years of age. However, slow walking pace was associated with a higher risk of stroke among participants aged ≥65 years (HR, 1.42 [95% CI, 1.17-1.72]; P<0.0001). A higher risk for stroke was observed on those with middle (HR, 1.28 [95% CI, 1.01-1.63]; P=0.039) and higher (HR, 1.29 [95% CI, 1.05-1.69]; P=0.012) deprivation levels but not in the least deprived individuals. Similarly, overweight (HR, 1.30 [95% CI, 1.04-1.63]; P=0.019) and obese (HR, 1.33 [95% CI, 1.09-1.63]; P=0.004) but not normal-weight individuals had a higher risk of stroke incidence. Conclusions- Slow walking pace was associated with a higher risk of stroke among participants over 64 years of age in this population-based cohort study. The addition of the measurement of self-reported walking pace to primary care or public health clinical consultations may be a useful screening tool for stroke risk.

Physical fitness training for stroke patients.

BACKGROUND: Levels of physical activity and physical fitness are low after stroke. Interventions to increase physical fitness could reduce mortality and reduce disability through increased function. OBJECTIVES: The primary objectives of this updated review were to determine whether fitness training after stroke reduces death, death or dependence, and disability. The secondary objectives were to determine the effects of training on adverse events, risk factors, physical fitness, mobility, physical function, health status and quality of life, mood, and cognitive function. SEARCH METHODS: In July 2018 we searched the Cochrane Stroke Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, SPORTDiscus, PsycINFO, and four additional databases. We also searched ongoing trials registers and conference proceedings, screened reference lists, and contacted experts in the field. SELECTION CRITERIA: Randomised trials comparing either cardiorespiratory training or resistance training, or both (mixed training), with usual care, no intervention, or a non-exercise intervention in stroke survivors. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed quality and risk of bias, and extracted data. We analysed data using random-effects meta-analyses and assessed the quality of the evidence using the GRADE approach. Diverse outcome measures limited the intended analyses. MAIN RESULTS: We included 75 studies, involving 3017 mostly ambulatory participants, which comprised cardiorespiratory (32 studies, 1631 participants), resistance (20 studies, 779 participants), and mixed training interventions (23 studies, 1207 participants). Death was not influenced by any intervention; risk differences were all 0.00 (low-certainty evidence). There were few deaths overall (19/3017 at end of intervention and 19/1469 at end of follow-up). None of the studies assessed death or dependence as a composite outcome. Disability scores were improved at end of intervention by cardiorespiratory training (standardised mean difference (SMD) 0.52, 95% CI 0.19 to 0.84; 8 studies, 462 participants; P = 0.002; moderate-certainty evidence) and mixed training (SMD 0.23, 95% CI 0.03 to 0.42; 9 studies, 604 participants; P = 0.02; low-certainty evidence). There were too few data to assess the effects of resistance training on disability. Secondary outcomes showed multiple benefits for physical fitness (VO2 peak and strength), mobility (walking speed) and physical function (balance). These physical effects tended to be intervention-specific with the evidence mostly low or moderate certainty. Risk factor data were limited or showed no effects apart from cardiorespiratory fitness (VO2 peak), which increased after cardiorespiratory training (mean difference (MD) 3.40 mL/kg/min, 95% CI 2.98 to 3.83; 9 studies, 438 participants; moderate-certainty evidence). There was no evidence of any serious adverse events. Lack of data prevents conclusions about effects of training on mood, quality of life, and cognition. Lack of data also meant benefits at follow-up (i.e. after training had stopped) were unclear but some mobility benefits did persist. Risk of bias varied across studies but imbalanced amounts of exposure in control and intervention groups was a common issue affecting many comparisons. AUTHORS' CONCLUSIONS: Few deaths overall suggest exercise is a safe intervention but means we cannot determine whether exercise reduces mortality or the chance of death or dependency. Cardiorespiratory training and, to a lesser extent mixed training, reduce disability during or after usual stroke care; this could be mediated by improved mobility and balance. There is sufficient evidence to incorporate cardiorespiratory and mixed training, involving walking, within post-stroke rehabilitation programmes to improve fitness, balance and the speed and capacity of walking. The magnitude of VO2 peak increase after cardiorespiratory training has been suggested to reduce risk of stroke hospitalisation by ˜7%. Cognitive function is under-investigated despite being a key outcome of interest for patients. Further well-designed randomised trials are needed to determine the optimal exercise prescription, the range of benefits and any long-term benefits.