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Esclerose Múltipla , Transtornos da Motilidade Ocular , Troca Plasmática , Humanos , Troca Plasmática/métodos , Esclerose Múltipla/complicações , Esclerose Múltipla/terapia , Esclerose Múltipla/tratamento farmacológico , Transtornos da Motilidade Ocular/etiologia , Transtornos da Motilidade Ocular/fisiopatologia , Transtornos da Motilidade Ocular/terapia , Feminino , Criança , Masculino , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Isolated tumefactive demyelinating lesions (≥2 cm) may be difficult to distinguish from contrast-enhancing brain tumors, central nervous system infections, and (rarely) tissue dysgenesis, which may all occur with increased signal on T2-weighted images. Establishing an accurate diagnosis is essential for management, and we delineate our single-center experience. METHODS: We performed a retrospective review of medical records, imaging, and biopsy specimens for patients under 18 years presenting with isolated tumefactive demyelination over a 10-year period. RESULTS: Ten children (eight female) met inclusion criteria, with a median age of 14.1 years. Lesions were most likely to involve the thalamus (six of 10), brainstem (five of 10), basal ganglia (four of 10), or corpus callosum (four of 10). Eighty percent had perilesional edema at presentation, and 60% had midline shift. Biopsies demonstrated demyelination with perivascular lymphocytic infiltration and axonal damage ranging from mild to severe. All patients were initially treated with high-dose corticosteroids, and eight of 10 required additional medical therapies such as intravenous immunoglobulin, plasmapheresis, cyclophosphamide, or rituximab. Increased intracranial pressure was managed aggressively with two of 10 patients requiring decompressive craniectomies. Clinical outcomes varied. CONCLUSIONS: Solitary tumefactive demyelinating lesions are rare, and aggressive management of inflammation and increased intracranial pressure is essential. Biopsy is helpful to evaluate for other diagnoses on the differential and maximize therapies. Treatment beyond initial therapy with corticosteroids is often required. Isolated tumefactive demyelinating lesions are uncommon; multicenter natural history studies are needed to better delineate differential diagnoses and optimal therapies.
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Doenças Desmielinizantes , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Adolescente , Estudos Retrospectivos , Doenças Desmielinizantes/diagnóstico por imagem , Doenças Desmielinizantes/patologia , Criança , Pré-Escolar , Encéfalo/diagnóstico por imagem , Encéfalo/patologiaRESUMO
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common but potentially severe adverse event associated with chimeric antigen receptor T-cell (CART) therapy characterized by the development of acute neurologic symptoms following CART infusion. ICANS encompasses a wide clinical spectrum typified by mild to severe encephalopathy, seizures and/or cerebral edema. As more patients have been treated with CART new ICANS phenomenology has emerged. We present the clinical course of five children who developed acute onset of quadriparesis or paraparesis associated with abnormal brain and/or spine neuroimaging after infusion of CD19 or CD22-directed CART, adverse events not previously reported in children. Orthogonal data from autopsy studies, cerebrospinal fluid (CSF) flow cytometry and CSF proteomics/cytokine profiling demonstrated chronic white matter destruction, but a notable lack of inflammatory pathologic changes and cell populations. Instead, children with quadriparesis or paraparesis post-CART therapy had lower levels of pro-inflammatory cytokines such as interferon gamma (IFNï§), CCL17, CCL23, and CXCL10 than those who did not develop quadriparesis or paraparesis. Taken together, these findings imply a non-inflammatory source of this newly described ICANS phenomenon in children. The pathophysiology of some neurologic symptoms following CART may therefore have a more complex etiology than exclusive T-cell activation and excessive cytokine production.
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In vitro preclinical testing of chimeric antigen receptor (CAR) T cells is mostly carried out in monolayer cell cultures. However, alternative strategies are needed to take into account the complexity and the effects of the tumor microenvironment. Here, we describe the modulation of CAR T-cell activity by malignant cells and fibroblasts in human three-dimensional (3D) in vitro cell models of increasing complexity. In models combining mucin-1 (MUC1) and TnMUC1 CAR T cells with human high-grade serous ovarian cancer cell spheroids, malignant cell-intrinsic resistance to CAR T-cell killing was due to defective death receptor signaling involving TNFα. Adding primary human fibroblasts to spheroids unexpectedly increased the ability of CAR T cells to kill resistant malignant cells as CCL2 produced by fibroblasts activated CCR2/4+ CAR T cells. However, culturing malignant cells and fibroblasts in collagen gels engendered production of a dense extracellular matrix that impeded CAR T-cell activity in a TGFß-dependent manner. A vascularized microfluidic device was developed that allowed CAR T cells to flow through the vessels and penetrate the gels in a more physiological way, killing malignant cells in a TNFα-dependent manner. Complex 3D human cell models may provide an efficient way of screening multiple cytotoxic human immune cell constructs while also enabling evaluation of mechanisms of resistance involving cell-cell and cell-matrix interactions, thus accelerating preclinical research on cytotoxic immune cell therapies in solid tumors. Significance: Three-dimensional in vitro models of increasing complexity uncover mechanisms of resistance to CAR T cells in solid tumors, which could help accelerate development of improved CAR T-cell constructs.
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Imunoterapia Adotiva , Neoplasias Ovarianas , Receptores de Antígenos Quiméricos , Esferoides Celulares , Linfócitos T , Microambiente Tumoral , Humanos , Feminino , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Imunoterapia Adotiva/métodos , Microambiente Tumoral/imunologia , Esferoides Celulares/imunologia , Linfócitos T/imunologia , Fibroblastos/imunologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Linhagem Celular TumoralRESUMO
BACKGROUND: Serious illness is characterised by uncertainty, particularly in older age groups. Uncertainty may be experienced by patients, family carers, and health professionals about a broad variety of issues. There are many evidence gaps regarding the experience and management of uncertainty. AIM: We aimed to identify priority research areas concerning uncertainty in serious illness, to ensure that future research better meets the needs of those affected by uncertainty and reduce research inefficiencies. METHODS: Rapid prioritisation workshop comprising five focus groups to identify research areas, followed by a ranking exercise to prioritise them. Participants were healthcare professionals caring for those with serious illnesses including geriatrics, palliative care, intensive care; researchers; patient/carer representatives, and policymakers. Descriptive analysis of ranking data and qualitative framework analysis of focus group transcripts was undertaken. RESULTS: Thirty-four participants took part; 67% female, mean age 47 (range 33-67). The highest priority was communication of uncertainty, ranked first by 15 participants (overall ranking score 1.59/3). Subsequent priorities were: 2) How to cope with uncertainty; 3) healthcare professional education/training; 4) Optimising clinical approaches to uncertainty; and 5) exploring in-depth experiences of uncertainty. Research questions regarding optimal management of uncertainty were given higher priority than questions about experiences of uncertainty and its impact. CONCLUSIONS: These co-produced, clinically-focused research priorities map out key evidence gaps concerning uncertainty in serious illness. Managing uncertainty is the most pressing issue, and researchers should prioritise how to optimally manage uncertainty in order to reduce distress, unlock decision paralysis and improve illness and care experience.
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Pesquisadores , Pesquisa , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Consenso , Incerteza , ComunicaçãoRESUMO
BACKGROUND: The anticipatory prescribing of injectable medications is recommended practice in controlling distressing symptoms in the last days of life. A 2017 systematic review found practice and guidance was based on inadequate evidence. Since then, there has been considerable additional research, warranting a new review. AIM: To review the evidence published since 2017 concerning anticipatory prescribing of injectable medications for adults at the end-of-life in the community, to inform practice and guidance. DESIGN: Systematic review and narrative synthesis. METHODS: Nine literature databases were searched from May 2017 to March 2022, alongside reference, citation and journal hand-searches. Gough's Weight of Evidence framework was used to appraise included studies. RESULTS: Twenty-eight papers were included in the synthesis. Evidence published since 2017 shows that standardised prescribing of four medications for anticipated symptoms is commonplace in the UK; evidence of practices in other countries is limited. There is limited data on how often medications are administered in the community. Prescriptions are 'accepted' by family caregivers despite inadequate explanations and they generally appreciate having access to medications. Robust evidence of the clinical and cost-effectiveness of anticipatory prescribing remains absent. CONCLUSION: The evidence underpinning anticipatory prescribing practice and policy remains based primarily on healthcare professionals' perceptions that the intervention is reassuring, provides effective, timely symptom relief in the community and prevents crisis hospital admissions. There is still inadequate evidence regarding optimal medications and dose ranges, and the effectiveness of these prescriptions. Patient and family caregiver experiences of anticipatory prescriptions warrant urgent investigation. PROSPERO REGISTRATION: CRD42016052108.
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Cuidados Paliativos na Terminalidade da Vida , Assistência Terminal , Humanos , CuidadoresRESUMO
BACKGROUND: Acute flaccid myelitis (AFM) presents with acute onset of flaccid paralysis with involvement of the gray matter on magnetic resonance imaging (MRI) of the spinal cord. Studies have reported brain MRI abnormalities, but the characteristics have not been fully defined. In this multicenter study, we assessed the acute features and evolution of brain MRI abnormalities in AFM. METHODS: We reviewed brain MRIs of patients with AFM who presented to four referral hospitals between 2012 and 2018. Cases met established criteria for AFM. We analyzed the initial and follow-up brain MRIs. Areas were divided into supratentorial, infratentorial, and subdivisions within those regions. RESULTS: A total of 66 patients were included. Brain MRI abnormalities were present in 34 (52%). Infratentorial abnormalities were more common, occurring in 33 (97%) cases with the dorsal pons being the most frequently affected area (88%). Abnormalities were also present in the medulla (74%), cerebellum (41%), and midbrain (38%). Nine subjects (26%) exhibited both supratentorial and infratentorial abnormalities, whereas isolated supratentorial changes were present in only one (3%). Contrast-enhancing abnormalities were encountered in 9% of cases and meningeal involvement in 6%. On follow-up, most abnormalities, 20 of 24 (83%), were stable, improving, or had resolved. CONCLUSIONS: Brain MRI abnormalities occur in about half of the cases of AFM and commonly resolve with time. Dorsal pontine involvement is a characteristic MRI feature, whereas isolated supratentorial abnormalities are rare. Clinicians should consider that brain imaging abnormalities do not exclude a diagnosis of AFM in patients with typical presentations.
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Encefalopatias , Malformações do Sistema Nervoso , Doenças Neuromusculares , Humanos , Imageamento por Ressonância Magnética , Doenças Neuromusculares/diagnóstico por imagem , Cerebelo , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: In March 2020, New Zealand was plunged into its first nationwide lockdown to halt the spread of COVID-19. Our team rapidly adapted our existing chatbot platform to create Aroha, a well-being chatbot intended to address the stress experienced by young people aged 13 to 24 years in the early phase of the pandemic. Aroha was made available nationally within 2 weeks of the lockdown and continued to be available throughout 2020. OBJECTIVE: In this study, we aimed to evaluate the acceptability and relevance of the chatbot format and Aroha's content in young adults and to identify areas for improvement. METHODS: We conducted qualitative in-depth and semistructured interviews with young adults as well as in situ demonstrations of Aroha to elicit immediate feedback. Interviews were recorded, transcribed, and analyzed using thematic analysis assisted by NVivo (version 12; QSR International). RESULTS: A total of 15 young adults (age in years: median 20; mean 20.07, SD 3.17; female students: n=13, 87%; male students: n=2, 13%; all tertiary students) were interviewed in person. Participants spoke of the challenges of living during the lockdown, including social isolation, loss of motivation, and the demands of remote work or study, although some were able to find silver linings. Aroha was well liked for sounding like a "real person" and peer with its friendly local "Kiwi" communication style, rather than an authoritative adult or counselor. The chatbot was praised for including content that went beyond traditional mental health advice. Participants particularly enjoyed the modules on gratitude, being active, anger management, job seeking, and how to deal with alcohol and drugs. Aroha was described as being more accessible than traditional mental health counseling and resources. It was an appealing option for those who did not want to talk to someone in person for fear of the stigma associated with mental health. However, participants disliked the software bugs. They also wanted a more sophisticated conversational interface where they could express themselves and "vent" in free text. There were several suggestions for making Aroha more relevant to a diverse range of users, including developing content on navigating relationships and diverse chatbot avatars. CONCLUSIONS: Chatbots are an acceptable format for scaling up the delivery of public mental health and well-being-enhancing strategies. We make the following recommendations for others interested in designing and rolling out mental health chatbots to better support young people: make the chatbot relatable to its target audience by working with them to develop an authentic and relevant communication style; consider including holistic health and lifestyle content beyond traditional "mental health" support; and focus on developing features that make users feel heard, understood, and empowered.
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BACKGROUND: Up to 6 years after the 2011 Christchurch earthquakes, approximately one-third of parents in the Christchurch region reported difficulties managing the continuously high levels of distress their children were experiencing. In response, an app named Kakano was co-designed with parents to help them better support their children's mental health. OBJECTIVE: The objective of this study was to evaluate the acceptability, feasibility, and effectiveness of Kakano, a mobile parenting app to increase parental confidence in supporting children struggling with their mental health. METHODS: A cluster-randomized delayed access controlled trial was carried out in the Christchurch region between July 2019 and January 2020. Parents were recruited through schools and block randomized to receive immediate or delayed access to Kakano. Participants were given access to the Kakano app for 4 weeks and encouraged to use it weekly. Web-based pre- and postintervention measurements were undertaken. RESULTS: A total of 231 participants enrolled in the Kakano trial, with 205 (88.7%) participants completing baseline measures and being randomized (101 in the intervention group and 104 in the delayed access control group). Of these, 41 (20%) provided full outcome data, of which 19 (18.2%) were for delayed access and 21 (20.8%) were for the immediate Kakano intervention. Among those retained in the trial, there was a significant difference in the mean change between groups favoring Kakano in the brief parenting assessment (F1,39=7, P=.012) but not in the Short Warwick-Edinburgh Mental Well-being Scale (F1,39=2.9, P=.099), parenting self-efficacy (F1,39=0.1, P=.805), family cohesion (F1,39=0.4, P=.538), or parenting sense of confidence (F1,40=0.6, P=.457). Waitlisted participants who completed the app after the waitlist period showed similar trends for the outcome measures with significant changes in the brief assessment of parenting and the Short Warwick-Edinburgh Mental Well-being Scale. No relationship between the level of app usage and outcome was found. Although the app was designed with parents, the low rate of completion of the trial was disappointing. CONCLUSIONS: Kakano is an app co-designed with parents to help manage their children's mental health. There was a high rate of attrition, as is often seen in digital health interventions. However, for those who did complete the intervention, there was some indication of improved parental well-being and self-assessed parenting. Preliminary indications from this trial show that Kakano has promising acceptability, feasibility, and effectiveness, but further investigation is warranted. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12619001040156; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377824&isReview=true.
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Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare disorder that causes significant neurodevelopmental sequelae in children. Approximately half of pediatric OMAS cases are paraneoplastic, typically associated with localized neuroblastic tumors. Since early persistence or relapse of OMAS symptoms is common even after tumor resection, OMAS relapses may not routinely prompt reevaluation for recurrent tumors. We report a 12-year-old girl with neuroblastic tumor recurrence associated with OMAS relapse a decade after initial treatment. Providers should be aware of tumor recurrence as a trigger for distant OMAS relapse, raising intriguing questions about the role of immune surveillance and control of neuroblastic tumors.
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Síndrome de Opsoclonia-Mioclonia , Feminino , Humanos , Criança , Síndrome de Opsoclonia-Mioclonia/etiologia , Síndrome de Opsoclonia-Mioclonia/terapia , Recidiva Local de Neoplasia , Ataxia/terapia , Ataxia/complicaçõesRESUMO
BACKGROUND: Before the COVID-19 pandemic, adolescents with type 1 diabetes (T1D) had already experienced far greater rates of psychological distress than their peers. With the pandemic further challenging mental health and increasing the barriers to maintaining optimal diabetes self-management, it is vital that this population has access to remotely deliverable, evidence-based interventions to improve psychological and diabetes outcomes. Chatbots, defined as digital conversational agents, offer these unique advantages, as well as the ability to engage in empathetic and personalized conversations 24-7. Building on previous work developing a self-compassion program for adolescents with T1D, a self-compassion chatbot (COMPASS) was developed for adolescents with T1D to address these concerns. However, the acceptability and potential clinical usability of a chatbot to deliver self-compassion coping tools to adolescents with T1D remained unknown. OBJECTIVE: This qualitative study was designed to evaluate the acceptability and potential clinical utility of COMPASS among adolescents aged 12 to 16 years with T1D and diabetes health care professionals. METHODS: Potential adolescent participants were recruited from previous participant lists, and on the web and in-clinic study flyers, whereas health care professionals were recruited via clinic emails and from diabetes research special interest groups. Qualitative Zoom (Zoom Video Communications, Inc) interviews exploring views on COMPASS were conducted with 19 adolescents (in 4 focus groups) and 11 diabetes health care professionals (in 2 focus groups and 6 individual interviews) from March 2022 to April 2022. Transcripts were analyzed using directed content analysis to examine the features and content of greatest importance to both groups. RESULTS: Adolescents were broadly representative of the youth population living with T1D in Aotearoa (11/19, 58% female; 13/19, 68% Aotearoa New Zealand European; and 2/19, 11% Maori). Health care professionals represented a range of disciplines, including diabetes nurse specialists (3/11, 27%), health psychologists (3/11, 27%), dieticians (3/11, 27%), and endocrinologists (2/11, 18%). The findings offer insight into what adolescents with T1D and their health care professionals see as the shared advantages of COMPASS and desired future additions, such as personalization (mentioned by all 19 adolescents), self-management support (mentioned by 13/19, 68% of adolescents), clinical utility (mentioned by all 11 health care professionals), and breadth and flexibility of tools (mentioned by 10/11, 91% of health care professionals). CONCLUSIONS: Early data suggest that COMPASS is acceptable, is relevant to common difficulties, and has clinical utility during the COVID-19 pandemic. However, shared desired features among both groups, including problem-solving and integration with diabetes technology to support self-management; creating a safe peer-to-peer sense of community; and broadening the representation of cultures, lived experience stories, and diabetes challenges, could further improve the potential of the chatbot. On the basis of these findings, COMPASS is currently being improved to be tested in a feasibility study.
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This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society, the international scientific organization studying chromosome 22q11.2 differences and related conditions, recruited expert clinicians worldwide to revise the original 2011 pediatric clinical practice guidelines in a stepwise process: (1) a systematic literature search (1992-2021), (2) study selection and data extraction by clinical experts from 9 different countries, covering 24 subspecialties, and (3) creation of a draft consensus document based on the literature and expert opinion, which was further shaped by survey results from family support organizations regarding perceived needs. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text reviews, including 1545 meeting criteria for potential relevance to clinical care of children and adolescents. Informed by the available literature, recommendations were formulated. Given evidence base limitations, multidisciplinary recommendations represent consensus statements of good practice for this evolving field. These recommendations provide contemporary guidance for evaluation, surveillance, and management of the many 22q11.2DS-associated physical, cognitive, behavioral, and psychiatric morbidities while addressing important genetic counseling and psychosocial issues.
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Síndrome de DiGeorge , Adolescente , Humanos , Criança , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/terapia , Aconselhamento Genético , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition. STUDY DESIGN: This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition. RESULTS: In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001). CONCLUSIONS: Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge.
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Viroses do Sistema Nervoso Central , Infecções por Enterovirus , Mielite , Doenças Neuromusculares , Criança , Humanos , Mielite/diagnóstico , Mielite/terapia , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/terapia , Viroses do Sistema Nervoso Central/diagnóstico , Viroses do Sistema Nervoso Central/terapia , Estudos Retrospectivos , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/terapiaRESUMO
STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The purpose of the study was to compare early complication, morbidity and mortality risks associated with fusion surgery crossing the cervico-thoracic junction in patients aged over 80 years undergoing combined anterior and posterior approach versus a posterior-only approach. METHODS: We retrospectively identified octogenarian patients with myelopathy who underwent fusion crossing the cervico-thoracic junction. Patient demographics, Nurick score, surgical characteristics, complications, hospital course, early outcome and 90-day mortality were collected. Comorbidities were classified using the age-adjusted Charlson Comorbidity Index (AACCI). Radiographic measurements for deformity correction included the C2-C7 sagittal Cobb angle, C2-7 sagittal vertical axis and T1 slope pre- and postoperatively. RESULTS: Out of 8,521 surgically treated patients, 12 octogenarian patients had a combined anterior and posterior approach (AP group) and 14 were treated from posterior-only (P group). Mean age was 81.4 ± 1.2 and 82.5 ± 2.7 years, respectively. There was no significant difference in Nurick scores between the groups (P > 0.05). The major complication risk in the AP group was significantly higher, requiring PEG tube placement due to severe dysphagia in 4 patients (33%) compared to none in the P group. A greater improvement in cervical lordosis could be achieved through a combined approach. The 90-day mortality risk was 8% for the AP group and 0% for the P group. CONCLUSIONS: A combined anterior and posterior approach is associated with a significantly higher major complication rate and can result in severe dysphagia requiring PEG tube placement in one-third of patients over 80 years of age.
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OBJECTIVES: We developed a group-based program (My Healthy Brain, MHB) to engage older adults at-risk for dementia in healthy lifestyles. We report on a two-part study to adapt MHB by incorporating mindfulness skills, using mobile health technology to monitor and reinforce behaviors, and delivering it via live video. METHODS: Participants were older adults (age ≥ 60) with subjective cognitive decline (SCD) and at least one lifestyle risk factor. In Aim 1 (n = 11, 2 groups), we conducted focus groups to obtain qualitative feedback on proposed adaptations. In Aim 2 (n = 10), we conducted a virtual open pilot with exit interviews to explore the feasibility and outcomes of the adapted MHB. RESULTS: Thematic analysis revealed: (1) barriers and facilitators to healthy lifestyles, (2) positive impressions of MHB, (3) interest in mindfulness skills, and (4) openness to study technologies. MHB met a-priori feasibility benchmarks and was associated with improvements in cognition, lifestyle (e.g. physical function), and proposed mechanisms (e.g. mindfulness). Exit interviews confirmed high feasibility and satisfaction. CONCLUSION: The integration of mindfulness, live video, and mobile health technologies was feasible and promising for improving healthier lifestyles. The results inform the next feasibility RCT of MHB to prepare for efficacy testing.Supplemental data for this article is available online at http://dx.doi.org/10.1080/13607863.2022.2032600.
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Demência , Atenção Plena , Humanos , Idoso , Atenção Plena/métodos , Estudos de Viabilidade , Estilo de Vida , Fatores de Risco , Demência/prevenção & controleRESUMO
Importance: The administration of a high fraction of oxygen following return of spontaneous circulation in out-of-hospital cardiac arrest may increase reperfusion brain injury. Objective: To determine whether targeting a lower oxygen saturation in the early phase of postresuscitation care for out-of-hospital cardiac arrest improves survival at hospital discharge. Design, Setting, and Participants: This multicenter, parallel-group, randomized clinical trial included unconscious adults with return of spontaneous circulation and a peripheral oxygen saturation (Spo2) of at least 95% while receiving 100% oxygen. The trial was conducted in 2 emergency medical services and 15 hospitals in Victoria and South Australia, Australia, between December 11, 2017, and August 11, 2020, with data collection from ambulance and hospital medical records (final follow-up date, August 25, 2021). The trial enrolled 428 of a planned 1416 patients. Interventions: Patients were randomized by paramedics to receive oxygen titration to achieve an oxygen saturation of either 90% to 94% (intervention; n = 216) or 98% to 100% (standard care; n = 212) until arrival in the intensive care unit. Main Outcomes and Measures: The primary outcome was survival to hospital discharge. There were 9 secondary outcomes collected, including hypoxic episodes (Spo2 <90%) and prespecified serious adverse events, which included hypoxia with rearrest. Results: The trial was stopped early due to the COVID-19 pandemic. Of the 428 patients who were randomized, 425 were included in the primary analysis (median age, 65.5 years; 100 [23.5%] women) and all completed the trial. Overall, 82 of 214 patients (38.3%) in the intervention group survived to hospital discharge compared with 101 of 211 (47.9%) in the standard care group (difference, -9.6% [95% CI, -18.9% to -0.2%]; unadjusted odds ratio, 0.68 [95% CI, 0.46-1.00]; P = .05). Of the 9 prespecified secondary outcomes collected during hospital stay, 8 showed no significant difference. A hypoxic episode prior to intensive care was observed in 31.3% (n = 67) of participants in the intervention group and 16.1% (n = 34) in the standard care group (difference, 15.2% [95% CI, 7.2%-23.1%]; OR, 2.37 [95% CI, 1.49-3.79]; P < .001). Conclusions and Relevance: Among patients achieving return of spontaneous circulation after out-of-hospital cardiac arrest, targeting an oxygen saturation of 90% to 94%, compared with 98% to 100%, until admission to the intensive care unit did not significantly improve survival to hospital discharge. Although the trial is limited by early termination due to the COVID-19 pandemic, the findings do not support use of an oxygen saturation target of 90% to 94% in the out-of-hospital setting after resuscitation from cardiac arrest. Trial Registration: ClinicalTrials.gov Identifier: NCT03138005.
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COVID-19 , Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Feminino , Idoso , Masculino , Parada Cardíaca Extra-Hospitalar/mortalidade , Alta do Paciente , Oxigênio , Pandemias , Saturação de Oxigênio , Oxigenoterapia , Hospitais , VitóriaRESUMO
BACKGROUND: The number of young people in New Zealand (Aotearoa) who experience mental health challenges is increasing. As those in Aotearoa went into the initial COVID-19 lockdown, an ongoing digital mental health project was adapted and underwent rapid content authoring to create the Aroha chatbot. This dynamic digital support was designed with and for young people to help manage pandemic-related worry. OBJECTIVE: Aroha was developed to provide practical evidence-based tools for anxiety management using cognitive behavioral therapy and positive psychology. The chatbot included practical ideas to maintain social and cultural connection, and to stay active and well. METHODS: Stay-at-home orders under Aotearoa's lockdown commenced on March 20, 2020. By leveraging previously developed chatbot technology and broader existing online trial infrastructure, the Aroha chatbot was launched promptly on April 7, 2020. Dissemination of the chatbot for an open trial was via a URL, and feedback on the experience of the lockdown and the experience of Aroha was gathered via online questionnaires and a focus group, and from community members. RESULTS: In the 2 weeks following the launch of the chatbot, there were 393 registrations, and 238 users logged into the chatbot, of whom 127 were in the target age range (13-24 years). Feedback guided iterative and responsive content authoring to suit the dynamic situation and motivated engineering to dynamically detect and react to a range of conversational intents. CONCLUSIONS: The experience of the implementation of the Aroha chatbot highlights the feasibility of providing timely event-specific digital mental health support and the technology requirements for a flexible and enabling chatbot architectural framework.
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COVID-19 , Transtornos Mentais , Adolescente , Humanos , Adulto Jovem , Controle de Doenças Transmissíveis , COVID-19/epidemiologia , COVID-19/prevenção & controle , Nova Zelândia/epidemiologia , Pandemias , Transtornos Mentais/prevenção & controleRESUMO
OBJECTIVES: uncertainty pervades the complex illness trajectories experienced by older adults with multimorbidity. Uncertainty is experienced by older people, their informal carers and professionals providing care, yet is incompletely understood. We aimed to identify and synthesise systematically the experience of uncertainty in advanced multimorbidity from patient, carer and professional perspectives. DESIGN: systematic literature review of published and grey qualitative literature from 9 databases (Prospero CRD 42021227480). PARTICIPANTS: older people with advanced multimorbidity, and informal carers/professionals providing care to this group. Exclusion criteria: early multimorbidity, insufficient focus on uncertainty. ANALYSIS: weight-of-evidence assessment was used to appraise included articles. We undertook thematic synthesis of multi-perspective experiences and response to uncertainty. RESULTS: from 4,738 unique search results, we included 44 articles relating to 40 studies. 22 focused on patient experiences of uncertainty (n = 460), 15 on carer experiences (n = 197), and 19 on health professional experiences (n = 490), with 10 exploring multiple perspectives. We identified a shared experience of 'Total Uncertainty' across five domains: 'appraising and managing multiple illnesses'; 'fragmented care and communication'; 'feeling overwhelmed'; 'uncertainty of others' and 'continual change'. Participants responded to uncertainty by either active (addressing, avoiding) or passive (accepting) means. CONCLUSIONS: the novel concept of 'Total Uncertainty' represents a step change in our understanding of illness experience in advanced multimorbidity. Patients, carers and health professionals experienced uncertainty in similar domains, suggesting a shared understanding is feasible. The domains of total uncertainty form a useful organising framework for health professionals caring for older adults with multimorbidity.