BACKGROUND: Over 3000 infants suffer a brain injury around the time of birth every year in England. Although these injuries can have important implications for children and their families, our understanding of how these injuries affect children\'s lives is limited.
METHODS: The aim of the CHERuB study (Childhood Health and Educational outcomes afteR perinatal Brain injury) is to investigate longitudinal childhood health and educational outcomes after perinatal brain injury through the creation of a population-matched cohort study. This study will use the Department of Health and Social Care definition of perinatal brain injury which includes infants with intracranial haemorrhage, preterm white matter injury, hypoxic ischaemic encephalopathy, perinatal stroke, central nervous system infections, seizures and kernicterus. All children born with a perinatal brain injury in England between 2008 and 2019 will be included (n=54 176) and two matched comparator groups of infants without brain injury will be created: a preterm control group identified from the National Neonatal Research Data Set and a term/late preterm control group identified using birth records. The national health, education and social care records of these infants will be linked to ascertain their longitudinal childhood outcomes between 2008 and 2023. This cohort will include approximately 170 000 children. The associations between perinatal brain injuries and survival without neurosensory impairment, neurodevelopmental impairments, chronic health conditions and mental health conditions throughout childhood will be examined using regression methods and time-to-event analyses.
BACKGROUND: This study has West London Research Ethics Committee and Confidential Advisory Group approval (20/LO/1023 and 22/CAG/0068 issued 20/10/2022). Findings will be published in open-access journals and publicised via the CHERuB study website, social media accounts and our charity partners.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of disability, with annual global incidence estimated as 69 million people. Survivors can experience long-term visual changes, altered mental state, neurological deficits and long-term effects that may be associated with mental illness. TBI is prevalent in military personnel due to gunshot wounds, and blast injury. This study aims to evaluate the relationship between evolving visual, biochemical and mental health changes in both military veterans and civilians, suffering from TBI, and detect preliminary indicators of prognosis for TBI recovery, and quality-of-life outcomes.
METHODS: UNTANGLE is a 24-month prospective observational pilot study recruiting three patient groups: civilians with acute moderate-severe TBI, military veterans with diagnosis of a previous TBI and a control group of civilians or veterans with no history of a previous TBI. Patients will undergo visual, biochemical and mental health assessments, as well as patient-reported quality of life outcome measures over the course of a 1-year follow-up period.
BACKGROUND: Ethical approval has been obtained from the Health Research Authority and Health and Care Research Wales with a REC reference number of 23/NW/0203. The results of the study will be presented at scientific meetings and published in peer-reviewed journals, including both civilian and military-related publications. We will also present our findings at national and international meetings of learnt neuroscience and neuropsychiatry and military societies. We anticipate that our pilot study will inform a larger study on the long-term outcomes of TBI and quality of life, specific to military veterans, such that potential interventions may be accessed as quickly as possible.
BACKGROUND: ISRCTN13276511.

OBJECTIVE: Decompressive craniectomy is occasionally performed as a life-saving neurosurgical intervention in patients with acute severe brain injury to reduce refractory intracranial hypertension. Subsequently, cranioplasty (CP) is performed to repair the skull defect. In the meantime, patients are living without cranial bone protection, and little is known about their daily life. This study accordingly explored daily life among patients living without cranial bone protection after decompressive craniectomy while awaiting CP.
METHODS: A multiple-case study examined six purposively sampled patients, patients\' family members, and healthcare staff. The participants were interviewed and the data were analyzed using qualitative content analysis.
RESULTS: The cross-case analysis identified five categories: \"Adapting to new ways of living,\" \"Constant awareness of the absence of cranial bone protection,\" \"Managing daily life requires available staff with adequate qualifications,\" \"Impact of daily life depends on the degree of recovery,\" and \"Daily life stuck in limbo while awaiting cranioplasty.\" The patients living without cranial bone protection coped with daily life by developing new habits and routines, but the absence of cranial bone protection also entailed inconveniences and limitations, particularly among the patients with greater independence in their everyday living. Time spent awaiting CP was experienced as being in limbo, and uncertainty regarding planning was perceived as frustrating.
CONCLUSIONS: The results indicate a vulnerable group of patients with brain damage and communication impairments struggling to find new routines during a waiting period experienced as being in limbo. Making this period safe and reducing some problems in daily life for those living without cranial bone protection calls for a person-centered approach to care involving providing contact information for the correct healthcare institution and individually planned scheduling for CP.

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OBJECTIVE: Care partners\' involvement is a key feature of the Cognitive Orientation to daily Occupational Performance (CO-OP) approach that can enhance rehabilitation outcomes and promote the generalization and transfer of strategies and skills to everyday life. Gaining insight into care partners\' experience with their child\'s CO-OP intervention is critical to understanding how to enhance care partners\' involvement.
OBJECTIVE: To gain insight into the experience of care partners whose child with acquired brain injury (ABI) participated in CO-OP intervention.
METHODS: A qualitative descriptive research design was used. Semistructured interviews were conducted at three time points (immediate postintervention and at 2 and 6 mo postintervention).
METHODS: Two rehabilitation centers.
METHODS: Thirteen care partners of 12 children or youth with severe ABI.
RESULTS: Three themes emerged from the analysis of 33 interviews: (1) The child is an active agent in their therapy, (2) the care partner is the keystone who helps solidify the elements of CO-OP, and (3) CO-OP mastery requires time and practice, and its use evolves over time.
CONCLUSIONS: These themes highlight the progressive nature of proficiency in CO-OP for both care partners and children. This was evident not only in the children\'s improvement in task performance, but also in their ability to problem solve. Care partners\' role in supporting the CO-OP approach also unfolds over time as their confidence in their child\'s problem-solving abilities, and in their own ability to adequately provide guidance, increases. Engagement seems to be central in facilitating this progression for both children and their care partners. Plain-Language Summary: This is the first study to provide insights into the involvement of care partners in the Cognitive Orientation to daily Occupational Performance (CO-OP) approach for children and youth with executive function deficits after acquired brain injury. This is also the first study to explore the evolution of care partners\' experiences over time. Involving care partners is a key feature of the CO-OP. Understanding care partners\' experiences with their child\'s CO-OP intervention can improve a child\'s rehabilitation outcomes. The study found that care partners\' role in supporting their child\'s CO-OP approach improved over time as their confidence in their child\'s problem-solving abilities increased. The care partners\' own ability to adequately provide guidance to their child also increased over time. Engagement seems to be central in facilitating this progression for both children and their care partners. It is hoped that occupational therapists will consider the findings of this study to better support care partners in implementing the CO-OP approach with their child in their real-life context.

UNASSIGNED: The findings regarding the prognosis of prolonged disorders of consciousness (PDOC) vary widely among different studies. This study aims to investigate the mortality, consciousness recovery and disabilities of patients with PDOC after brain injury.
UNASSIGNED: A total of 204 patients with PDOC were included in a longitudinal cohort study, including 129 males and 75 females. There were 112 cases of traumatic brain injury (TBI), 62 cases of cerebral hemorrhage (CH), 13 cases of cerebral infarction (CI) and 17 cases of ischemic hypoxic encephalopathy (IHE). The status of consciousness at 1, 2, 3, 6, 12, 18, 24, 36, 48 months of the disease course was assessed or followed up using the Revised Coma Recovery Scale (CRS-R). If the patients were conscious, the disability Rating Scale (DRS) was also performed. The prognosis of different PDOC including coma, vegetative state (VS) and minimal conscious state (MCS) was analyzed. The survival patients were screened for variables and included in multivariate binary Logistic regression to screen the factors affecting the recovery of consciousness.
UNASSIGNED: The mortality rates at 12, 24, 36, and 48 months were 10.7, 23.4, 38.9, and 68.4%, respectively. The median time of death was 18 months (8.75, 29). The probability of MCS regaining consciousness was higher than VS (p < 0.05), with the degree of disability left lower than VS (p < 0.05). There was no significant difference between MCS- and MCS+ groups in terms of the probability of regaining consciousness, the extent of residual disability, and mortality rates (p > 0.05). The mortality rate of coma was higher than that of other PDOC (p < 0.05). The mortality rate of MCS was lower than that of VS, but the difference was not statistically significant (p > 0.05). The probability of consciousness recovery after TBI was the highest and the mortality rate was the lowest. The possibility of consciousness recovery in IHE was the least, and the mortality rate of CI was the highest. The cause of brain injury and initial CRS-R score were the factors affecting the consciousness recovery of patients (p < 0.05).
UNASSIGNED: The prognosis of MCS is more favorable than VS, with comparable outcomes between MCS- and MCS+, while comatose patients was the poorest. TBI has the best prognosis and IHE has the worst prognosis.

BACKGROUND: People with acquired brain injury (ABI) may experience concurrent conditions such as, mental health and substance use concerns, that require specialized care. There are services that aim to support people with ABI and these conditions separately; however, little is known about the facilitators and barriers of these services. Therefore, the purpose of this study was to engage stakeholders to investigate the facilitators and barriers of healthcare services for ABI and concurrent issues.
METHODS: Semi-structured focus groups were conducted in-person and virtually with people with ABI, caregivers, healthcare professionals, and policy makers during a one-day event in British Columbia, Canada. Manifest content analysis was used with a constructivist perspective to analyze data.
RESULTS: 90 participants (including 34 people with ABI) provided insights during 15 simultaneous focus groups. Three categories were identified: (1) complexity of ABI, (2) supports, (3) structure of care. Complexity of ABI outlined the ongoing basic needs after ABI and highlighted the need for public awareness of ABI. Supports outlined healthcare professional and community-based supports. Structure of care described people with ABI needing to meet criteria for support, experiences of navigating through the system and necessity of integrated services.
CONCLUSIONS: These findings highlight the facilitators and barriers of healthcare services for ABI and concurrent conditions and provide insights into the changes that may be needed. Doing so can improve the accessibility and quality of ABI healthcare services.

BACKGROUND: Patients with severe acute brain injury have a high risk of a poor clinical outcome due to primary and secondary brain injury. Ketamine reportedly inhibits cortical spreading depolarization, an electrophysiological phenomenon that has been associated with secondary brain injury, making ketamine potentially attractive for patients with severe acute brain injury. The aim of this systematic review is to explore the current literature regarding ketamine for patients with severe acute brain injury.
METHODS: We systematically searched international databases for randomized clinical trials comparing ketamine by any regimen versus placebo, no intervention, or any control drug for patients with severe acute brain injury. Two authors independently reviewed and selected trials for inclusion, extracted data, assessed risk of bias, and performed analysis using Review Manager and Trial Sequential Analysis. Evidence certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation. The primary outcomes were the proportion of participants with an unfavorable functional outcome, the proportion of participants with one or more serious adverse events, and quality of life.
RESULTS: We identified five randomized trials comparing ketamine versus sufentanil, fentanyl, other sedatives, or saline (total N = 149 participants). All outcomes were at overall high risk of bias. The proportions of participants with one or more serious adverse events did not differ between ketamine and sufentanil or fentanyl (relative risk 1.45, 95% confidence interval 0.81-2.58; very low certainty). Trial sequential analysis showed that further trials are needed.
CONCLUSIONS: The level of evidence regarding the effects of ketamine on functional outcome and serious adverse events in patients with severe acute brain injury is very low. Ketamine may markedly, modestly, or not at all affect these outcomes. Large randomized clinical trials at low risk of bias are needed.

BACKGROUND: Early mobilization benefits critically ill patients, but concerns persist, especially in neurologic intensive care unit patients with acute brain injuries. This study assesses early mobility\'s impact on cerebrovascular autoregulation (CA) and systemic hemodynamics.
METHODS: This single-center retrospective study focused on adult neurologic intensive care unit patients undergoing passive cycle ergometry. Data were collected from December 2020 to April 2022. Physical therapists conducted sessions using a standardized protocol, monitoring mean arterial blood pressure (MAP) and intracranial pressure (ICP). The Pressure Reactivity Index (PRx) was calculated as a measure of CA. Statistical analysis included mixed models and repeated measures ANOVA.
RESULTS: Eleven patients undergoing continuous physiologic monitoring and early mobility were included, primarily with subarachnoid hemorrhage or intracranial hemorrhage. Median time to protocol initiation was 4 days, with two patients discontinuing due to hemodynamic disturbances. Over a total of 11-hours of neuromonitoring data, passive cycling demonstrated a significant reduction in heart rate (HR), MAP, and ICP across different rotations per minute (RPM) settings compared to baseline. No significant alterations in PRx or cerebral perfusion pressure (CPP) were noted at various RPM levels. However, a significant difference in PRx emerged between patients who completed the protocol and those who did not, particularly at 10 RPM.
CONCLUSIONS: This study offers preliminary insights into the impact of early mobility on CA in acute brain injured patients. While passive cycling demonstrates promise in preserving cerebral hemodynamics, its tolerability may not be uniform across all brain-injured patients. These findings highlight the need to determine optimal early mobilization timing and intensity in this population, emphasizing the necessity for larger prospective studies to validate these findings and inform clinical practice.
UNASSIGNED: This manuscript complies with all instructions to the authors. All coauthors meet the authorship requirements and have reviewed and approved the contents of the manuscript. The manuscript has not been published totally or partly, accepted for publication, or under editorial review for publication elsewhere. We have no conflicts of interest to disclose. STROBE checklist was reviewed prior to the submission of this paper. The manuscript adheres to ethical guidelines and was approved by Cleveland Clinic\'s institutional research board for retrospective study. There is no funding to disclose for this study.

BACKGROUND: Socioeconomic inequalities in cognitive impairment may partly act through structural brain damage and reduced connectivity. This study investigated the extent to which the association of early-life socioeconomic position (SEP) with later-life cognitive functioning is mediated by later-life SEP, and whether the associations of SEP with later-life cognitive functioning can be explained by structural brain damage and connectivity.
METHODS: We used cross-sectional data from the Dutch population-based Maastricht Study (n = 4,839; mean age 59.2 ± 8.7 years, 49.8% women). Early-life SEP was assessed by self-reported poverty during childhood and parental education. Later-life SEP included education, occupation, and current household income. Participants underwent cognitive testing and 3-T magnetic resonance imaging to measure volumes of white matter hyperintensities, grey matter, white matter, cerebrospinal fluid, and structural connectivity. Multiple linear regression analyses tested the associations between SEP, markers of structural brain damage and connectivity, and cognitive functioning. Mediation was tested using structural equation modeling.
RESULTS: Although there were direct associations between both indicators of SEP and later-life cognitive functioning, a large part of the association between early-life SEP and later-life cognitive functioning was explained by later-life SEP (72.2%). The extent to which structural brain damage or connectivity acted as mediators between SEP and cognitive functioning was small (up to 5.9%).
CONCLUSIONS: We observed substantial SEP differences in later-life cognitive functioning. Associations of structural brain damage and connectivity with cognitive functioning were relatively small, and only marginally explained the SEP gradients in cognitive functioning.