Mild traumatic brain injury recovery: a growth curve modelling analysis over 2 years.

BACKGROUND: An improved understanding of the trajectory of recovery after mild traumatic brain injury is important to be able to understand individual patient outcomes, for longitudinal patient care and to aid the design of clinical trials. OBJECTIVE: To explore changes in health, well-being and cognition over the 2 years following mTBI using latent growth curve (LGC) modelling. METHODS: Sixty-one adults with mTBI presenting to a UK Major Trauma Centre completed comprehensive longitudinal assessment at up to five time points after injury: 2 weeks, 3 months, 6 months, 1 year and 2 years. RESULTS: Persisting problems were seen with neurological symptoms, cognitive issues and poor quality of life measures including 28% reporting incomplete recovery on the Glasgow Outcome Score Extended at 2 years. Harmful drinking, depression, psychological distress, disability, episodic memory and working memory did not improve significantly over the 2 years following injury. For other measures, including the Rivermead Post-Concussion Symptoms and Quality of Life after Brain Injury (QOLIBRI), LGC analysis revealed significant improvement over time with recovery tending to plateau at 3-6 months. INTERPRETATION: Significant impairment may persist as late as 2 years after mTBI despite some recovery over time. Longitudinal analyses which make use of all available data indicate that recovery from mTBI occurs over a longer timescale than is commonly believed. These findings point to the need for long-term management of mTBI targeting individuals with persisting impairment.

Influence of Concomitant Extracranial Injury on Functional and Cognitive Recovery From Mild Versus Moderateto Severe Traumatic Brain Injury.

OBJECTIVE: To determine the effect of extracranial injury (ECI) on 6-month outcome in patients with mild traumatic brain injury (TBI) versus moderate-to-severe TBI. PARTICIPANTS/SETTING: Patients with TBI (n = 135) or isolated orthopedic injury (n = 25) admitted to a UK major trauma center and healthy volunteers (n = 99). DESIGN: Case-control observational study. MAIN MEASURES: Primary outcomes: (a) Glasgow Outcome Scale Extended (GOSE), (b) depression, (c) quality of life (QOL), and (d) cognitive impairment including verbal fluency, episodic memory, short-term recognition memory, working memory, sustained attention, and attentional flexibility. RESULTS: Outcome was influenced by both TBI severity and concomitant ECI. The influence of ECI was restricted to mild TBI; GOSE, QOL, and depression outcomes were significantly poorer following moderate-to-severe TBI than after isolated mild TBI (but not relative to mild TBI plus ECI). Cognitive impairment was driven solely by TBI severity. General health, bodily pain, semantic verbal fluency, spatial recognition memory, working memory span, and attentional flexibility were unaffected by TBI severity and additional ECI. CONCLUSION: The presence of concomitant ECI ought to be considered alongside brain injury severity when characterizing the functional and neurocognitive effects of TBI, with each presenting challenges to recovery.

Prospective Study of a Novel, Radiation-Free, Reduced-Intensity Bone Marrow Transplantation Platform for Primary Immunodeficiency Diseases.

Allogeneic blood or marrow transplantation (BMT) is a potentially curative therapy for patients with primary immunodeficiency (PID). Safe and effective reduced-intensity conditioning (RIC) approaches that are associated with low toxicity, use alternative donors, and afford good immune reconstitution are needed to advance the field. Twenty PID patients, ranging in age from 4 to 58 years, were treated on a prospective clinical trial of a novel, radiation-free and serotherapy-free RIC, T-cell-replete BMT approach using pentostatin, low-dose cyclophosphamide, and busulfan for conditioning with post-transplantation cyclophosphamide-based graft-versus-host-disease (GVHD) prophylaxis. This was a high-risk cohort with a median hematopoietic cell transplantation comorbidity index of 3. With median follow-up of survivors of 1.9 years, 1-year overall survival was 90% and grade III to IV acute GVHD-free, graft-failure-free survival was 80% at day +180. Graft failure incidence was 10%. Split chimerism was frequently observed at early post-BMT timepoints, with a lower percentage of donor T cells, which gradually increased by day +60. The cumulative incidences of grade II to IV and grade III to IV acute GVHD (aGVHD) were 15% and 5%, respectively. All aGVHD was steroid responsive. No patients developed chronic GVHD. Few significant organ toxicities were observed. Evidence of phenotype reversal was observed for all engrafted patients, even those with significantly mixed chimerism (n = 2) or with unknown underlying genetic defect (n = 3). All 6 patients with pre-BMT malignancies or lymphoproliferative disorders remain in remission. Most patients have discontinued immunoglobulin replacement. All survivors are off immunosuppression for GVHD prophylaxis or treatment. This novel RIC BMT approach for patients with PID has yielded promising results, even for high-risk patients.

Outcomes of Related and Unrelated Donor Searches Among Patients with Primary Immunodeficiency Diseases Referred for Allogeneic Hematopoietic Cell Transplantation.

Patients with primary immunodeficiencies (PIDs) are potentially cured by allogeneic hematopoietic cell transplantation (HCT). The spectrum of PIDs has expanded greatly beyond those that present in infancy or are diagnosed on newborn screening and require urgent, preemptive HCT. Many PID diagnoses are now made later in life, and the role of HCT is only considered for severe disease manifestations; in these cases, the kinetics and goals of a donor search may be different than for severe combined immunodeficiency. Across all PIDs, related donor searches have the additional selection factor of the inherited disease, and such searches may yield more limited options than searches for patients with hematologic malignancies; thus, unrelated donor options often become more critical in these patients. We retrospectively evaluated the outcomes of donor searches among patents with PIDs referred for HCT at the National Institutes of Health, where the minimum patient age for evaluation is 3 years and where donor options include matched sibling donors or matched related donors, HLA-haploidentical (haplo), or 7-8/8 HLA matched unrelated donors (mMUDs/MUDs). Patient (n = 161) and donor demographics, MUD search results, HLA typing, pedigrees, mutation testing, and donor selection data were collected. The National Marrow Donor Program HapLogic 8/8 HLA match algorithm was used to predict the likelihood of a successful MUD search and categorized as very good, good, fair, poor, very poor, or futile per the Memorial Sloan Kettering Cancer Center (MSKCC) Search Prognosis method. There were significant differences by PID mode of inheritance in patient age, disposition (receipt of HCT or not), donor source, and donor relatedness. A related or unrelated donor option could be identified for 94% of patients. Of living first-degree relatives (median, 3; range, 0 to 12 per patient), a median of 1 donor remained for autosomal dominant and X-linked (XL) diseases after HLA typing, mutation testing, and other exclusions, and a median of 2 donors remained for autosomal recessive (AR) diseases. Among patients with a PID of known mode of inheritance (n = 142), the best related donor was haplo for 99 (70%) patients, with 56 (39%) haplos age 40 years or older and 5 (4%) second-degree haplos; 13 (9%) had no family donor options. The best related donor was a heterozygote/asymptomatic carrier of the PID mutation in 36 (49%) patients with AR or XL disease (n = 73). Among patients with MUD search performed (n = 139), 53 (38%) had very poor/futile 8/8 MUD searches, including 6 (32%) of those with unknown PID mutation and therefore no family donor options. The MSKCC Search Prognosis was less favorable for those of non-European ancestry compared with European ancestry (P = .002). Most patients of Hispanic or African ancestry had very poor/futile MUD searches, 71% and 63%, respectively. No HCT recipients with very poor/futile MUD searches (n = 38) received 8/8 MUD grafts. Alternative donor options, including haplo and unrelated donors, are critical to enable HCT for patients with PIDs. MUD search success remains low for those of non-European ancestry, and this is of particular concern for patients with PIDs caused by an unknown genetic defect. Among patients with PIDs, related donor options are reduced and haplos age 40 years and older and/or mutation carriers are often the best family option.

Neurocognitive testing in the emergency department: A potential assessment tool for mild traumatic brain injury.

OBJECTIVE: Despite mild traumatic brain injury (mTBI) accounting for 80% of head injury diagnoses, recognition of individuals at risk of cognitive dysfunction remains a challenge in the acute setting. The objective of this study was to evaluate the feasibility and potential role for computerised cognitive testing as part of a complete ED head injury assessment. METHODS: mTBI patients (n = 36) who incurred a head injury within 24 h of presentation to the ED were compared to trauma controls (n = 20) and healthy controls (n = 20) on tests assessing reaction time, speed and attention, episodic memory, working memory and executive functioning. Testing occurred during their visit to the ED at a mean of 12 h post-injury for mTBI and 9.4 h for trauma controls. These tasks were part of the Cambridge Neuropsychological Test Automated Battery iPad application. Healthy controls were tested in both a quiet environment and the ED to investigate the potential effects of noise and distraction on neurocognitive function. RESULTS: Reaction time was significantly slower in the mTBI group compared to trauma patients (P = 0.015) and healthy controls (P = 0.011), and deficits were also seen in working memory compared to healthy controls (P ≤ 0.001) and in executive functioning (P = 0.021 and P < 0.001) compared to trauma and healthy controls. Performances in the control group did not differ between testing environments. CONCLUSION: Computerised neurocognitive testing in the ED is feasible and can be utilised to detect deficits in cognitive performance in the mTBI population as part of a routine head injury assessment.

Neural correlates of visual memory in patients with diffuse axonal injury.

PRIMARY OBJECTIVE: To investigate the neural substrates of visual memory in a sample of patients with traumatic brain injury (TBI). We hypothesized that patients with decreased grey and white matter volume in frontal and parietal cortices as well as medial temporal and occipital lobes would perform poorly on the tests of visual memory analysed. METHODS AND PROCEDURES: 39 patients and 53 controls were assessed on tests of visual memory and learning from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Patients with TBI were scanned with magnetic resonance imaging (MRI). Partial correlations and multiple regression analyses were used to examine relationships between cognitive variables and MRI volumetric findings. This study complements and extends previous studies by performing volumetric comparisons on a variety of resolution levels, from whole brain to voxel-based level analysis. MAIN OUTCOMES AND RESULTS: Patients with TBI performed significantly worse than controls in all the tasks assessed. Performance was associated with wide-spread reductions in grey and white matter volume of several cortical and subcortical structures as well as with cerebrospinal fluid space enlargement in accordance with previous studies of memory in patients with TBI and cognitive models suggesting that memory problems involve the alteration of multiple systems. CONCLUSIONS: Our results propose that compromised visual memory in patients with TBI is related to a distributed pattern of volume loss in regions mediating memory and attentional processing.

Involvement of Spearman's g in conceptualisation versus execution of complex tasks.

Strong correlations between measures of fluid intelligence (or Spearman's g) and working memory are widely reported in the literature, but there is considerable controversy concerning the nature of underlying mechanisms driving this relationship. In the four experiments presented here we consider the role of response conflict and task complexity in the context of real-time task execution demands (Experiments 1-3) and also address recent evidence that g confers an advantage at the level of task conceptualisation rather than (or in addition to) task execution (Experiment 4). We observed increased sensitivity of measured fluid intelligence to task performance in the presence (vs. the absence) of response conflict, and this relationship remained when task complexity was reduced. Performance-g correlations were also observed in the absence of response conflict, but only in the context of high task complexity. Further, we present evidence that differences in conceptualisation or 'modelling' of task instructions prior to execution had an important mediating effect on observed correlations, but only when the task encompassed a strong element of response inhibition. Our results suggest that individual differences in ability reflect, in large part, variability in the efficiency with which the relational complexity of task constraints are held in mind. It follows that fluid intelligence may support successful task execution through the construction of effective action plans via optimal allocation of limited resources.

Health Care Transition Experiences of Young Adults With Cerebral Palsy.

Health care transition (HCT) describes the purposeful, planned movement of adolescents from child to adult-orientated care. The purpose of this qualitative study is to uncover the meaning of transition to adult-centered care as experienced by young adults with cerebral palsy (YA-CP) through the research question: What are the lived experiences of young adults with cerebral palsy transitioning from pediatric to adult healthcare? Six females and 3 males, aged 19-25 years of age, who identified as carrying the diagnosis of cerebral palsy without cognitive impairment, were interviewed. Giorgi's (1985) method for analysis of phenomenology was the framework for the study and guided the phenomenological reduction. The meaning of the lived experiences of YA-CPs transition to adult health care is expert novices with evidence and experience-based expectations, negotiating new systems interdependently and accepting less than was expected. More information and support is needed for the YA-CP during transition to ensure a well-organized move to appropriate adult-oriented health care that is considerate of the lifelong impact of the disorder. The nurses' role as advocate, mentor and guide can optimize the individual's response to the transition process.

A constipation assessment scale for use in pediatric oncology.

Constipation is prevalent in pediatric oncology patients because of treatment with vinca alkaloids and/or narcotics and lifestyle changes secondary to disease process. Sequelae of constipation include anorexia, nausea, vomiting, abdominal pain, emergency department visits, and a decrease in quality of life. There are no reliable instruments to measure constipation in children. A pilot study (N = 21) evaluating the presence and severity of constipation and the reliability and validity of a modified version of the adult Constipation Assessment Scale (CAS) in children with cancer was conducted. Patients receiving weekly vinca alkaloids and/or narcotics = 2 times per day were recruited. Initial bowel function assessments included standardized nursing and nutrition assessments, history/physical review, and baseline CAS score repeated at 1 hour to assess test-retest reliability. Subsequent assessments included CAS administered 3 times per week and daily patient bowel diaries. Test-retest reliability was evident (r = .93; P = .000). Acceptable construct validity was indicated by a difference in mean CAS scores (t = 4.4, P <.001). Patients reported difficulty with CAS questions and response selections. Symptoms asked on CAS were often not viewed as a problem.