Brain Injury Screening Tool (BIST): test-retest reliability in a community adult sample.

OBJECTIVE: To determine the test-retest reliability of the Brain Injury Screening Tool (BIST), which was designed to support the initial assessment of mild traumatic brain injury (mTBI) across a variety of contexts, including primary and secondary care. DESIGN: Test-retest design over a 2-week period. SETTING: Community based. PARTICIPANTS: Sixty-eight adults (aged 18-58 years) who had not experienced an mTBI within the last 5 years and completed the BIST on two different occasions. MEASURES: Participants were invited to complete the 15-item BIST symptom scale and the Depression, Anxiety and Stress Scale (DASS-21) online at two time-points (baseline and 2 weeks later). To account for large variations in mood affecting symptom reporting, change scores on the subscales of the DASS-21 were calculated, and outliers were removed from the analysis. RESULTS: The BIST total symptom score and subscale scores (physical-emotional, cognitive and vestibular) demonstrated moderate to good test-retest reliability with intraclass correlation coefficients ranging between 0.51 and 0.83. There were no meaningful differences between symptom reporting on the total scale or subscales of the BIST between time1 and time2 at the p<0.05 level when calculated using related samples Wilcoxon signed-rank tests. CONCLUSION: The BIST showed evidence of good stability of symptom reporting within a non-injured, community adult sample. This increases confidence that changes observed in symptom reporting in an injured sample are related to actual symptom change rather than measurement error and supports the use of the symptom scale to monitor recovery over time. Further research is needed to explore reliability of the BIST within those aged <16 years.

Rasch analysis of the Brain Injury Screening Tool (BIST) in mild traumatic brain injury.

OBJECTIVE: To evaluate the psychometric properties of the Brain Injury Screening Tool (BIST) symptom scale in a sample of people with a mild Traumatic Brain Injury (mTBI) through Rasch analysis, and to obtain an interval level measurement score for potential clinical use. MATERIALS AND METHODS: Data were obtained from 114 adults aged over 16 years, who had experienced at least one mTBI in the past 10 years. Participants were recruited via social media, concussion clinics and sports organisations over a 4-month period between May and September 2020. Participants were asked to compete the symptom scale of the BIST tool via an anonymous online questionnaire. Internal construct validity, dimensionality, person separation index, and differential item functioning of the BIST were examined with Rasch analysis. RESULTS: BIST in its original form produced a satisfactory item-trait interaction, and good reliability, but was found to be multi-dimensional. Rasch analysis of the full scale with three domains as subtests resulted in acceptable model fit (χ2(6) =3.8, p >  0.05), with good reliability (Person Separation Index = 0.84), and uni-dimensionality. Differential Item Functioning (DIF) analysis displayed no significant DIF effects for sex or age revealing that people responded consistently and similarly to the individual BIST items based on severity of symptom burden. CONCLUSIONS: The 15-item symptom scale of the BIST tool is a psychometrically sound measure of symptom burden following mTBI. The findings provide support for use of both total and sub scale scores for clinical use. Ordinal to interval score conversions are recommended for use when using the scores for research purposes in mTBI.

Traumatic brain injuries in New Zealand: National Insurance (Accident Compensation Corporation) claims from 2012 to 2016.

AIM: To provide epidemiological data and related costs to the national health insurance scheme for traumatic brain injury (TBI) in New Zealand. METHOD: A retrospective analytical review utilising detailed descriptive minor and moderate-to-severe epidemiological TBI data obtained from the Accident Compensation Corporation (ACC) for 2012-2016. Injuries were analysed by three levels of increasing severity: moderate, moderate-to-serious (MSC) and severe claims categories. RESULTS: Over the January 2012 to December 2016 period there were 97,955 claims for TBI costing ACC $1,450,643,667 [equivalent to £$743,417,120]. Falls accounted for nearly half (41.7%, 8262), and over a quarter (39.9%; $67,626,000 [£34,662,176]) of the moderate claims for TBI. Motor vehicle accidents recorded the highest percentage (36.5%), total costs ($610,978,229 [£313,170,000]) and highest mean cost per-moderate claim per-year ($47,372 ±â€¯$2401 [£24,282 ±â€¯£1231]) for MSC TBI claims. This was similar for severe claims where motor vehicles accidents accounted for 56% of the total serious claims, 65.1% of the costs with a mean cost per-serious claim of $64,913 ±â€¯4331 [£32,759 ±â€¯£2186] per-year. CONCLUSION: There were 97,955 TBI injury claims lodged over the duration of the study with 36% (n = 35,304) classified as MSC. The incidence of total TBI in New Zealand was 432 per 100,000 population, and 155 per 100,000 for MSC TBI claims. Despite the growing number of studies reporting on the effects of sports-related TBI, there is a paucity of studies reporting on the longitudinal effects of TBI in falls, assaults and motor vehicle accidents. Further research is warranted into the assessment and management of intimate partner violence and child abuse victims for TBI's.

Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning.

Gene therapy is a promising treatment option for monogenic diseases, but success has been seen in only a handful of studies thus far. We now document successful reconstitution of immune function in a child with the adenosine deaminase (ADA)-deficient form of severe combined immunodeficiency (SCID) following hematopoietic stem cell (HSC) gene therapy. An ADA-SCID child who showed a poor response to PEG-ADA enzyme replacement was enrolled into the clinical study. Following cessation of enzyme replacement therapy, autologous CD34(+) HSCs were transduced with an ADA-expressing gammaretroviral vector. Gene-modified cells were reinfused following one dose of preconditioning chemotherapy. Two years after the procedure, immunological and biochemical correction has been maintained with progressive increase in lymphocyte numbers, reinitiation of thymopoiesis, and systemic detoxification of ADA metabolites. Sustained vector marking with detection of polyclonal vector integration sites in multiple cell lineages and detection of ADA activity in red blood cells suggests transduction of early hematopoietic progenitors. No serious side effects were seen either as a result of the conditioning procedure or due to retroviral insertion. Gene therapy is an effective treatment option for the treatment of ADA-SCID.

Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen.

The optimal approach to stem cell transplantation in children with immunodeficiency who lack a matched family donor is controversial. Unrelated donor stem cell transplantation gives equivalent outcome to mismatched family donor stem cell transplantation in severe combined immunodeficiency, whereas unrelated donors may be preferable in non-severe combined immunodeficiency children. However, unrelated donor stem cell transplantation with conventional conditioning regimens has been associated with significant treatment-related toxicity, particularly in non-severe combined immunodeficiency patients with preexisting organ dysfunction. We report the outcome of a series of 33 consecutive unrelated donor transplantations performed at our center in children with primary immunodeficiency using a reduced-intensity conditioning regimen between 1998 and 2001. We have compared these outcomes with a retrospective control cohort of 19 patients who underwent transplantation with myeloablative conditioning between 1994 and 1998. All children in both groups had primary engraftment. There was no statistical difference in the speed of immune reconstitution or incidence of graft-versus-host disease between the 2 groups. Overall survival was significantly better in the reduced-intensity conditioning group: 31 (94%) of 33 patients survived, compared with 10 (53%) of 19 in the myeloablative conditioning group (P = .014). We conclude that the reduced-intensity conditioning regimen results in improved survival and reduced transplantation-related mortality compared with myeloablative conditioning in high-risk patients undergoing unrelated donor transplantation.

Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector.

BACKGROUND: X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the common cytokine-receptor gamma chain (gamma(c)), resulting in disruption of development of T lymphocytes and natural-killer cells. B-lymphocyte function is also intrinsically compromised. Allogeneic bone-marrow transplantation is successful if HLA-matched family donors are available, but HLA-mismatched procedures are associated with substantial morbidity and mortality. We investigated the application of somatic gene therapy by use of a gibbon-ape-leukaemia-virus pseudotyped gammaretroviral vector. METHODS: Four children with SCID-X1 were enrolled. Autologous CD34-positive haemopoietic bone-marrow stem cells were transduced ex vivo and returned to the patients without preceding cytoreductive chemotherapy. The patients were monitored for integration and expression of the gamma(c) vector and for functional immunological recovery. FINDINGS: All patients have shown substantial improvements in clinical and immunological features, and prophylactic medication could be withdrawn in two. No serious adverse events have been recorded. T cells responded normally to mitogenic and antigenic stimuli, and the T-cell-receptor (TCR) repertoire was highly diverse. Where assessable, humoral immunity, in terms of antibody production, was also restored and associated with increasing rates of somatic mutation in immunoglobulin genes. INTERPRETATION: Gene therapy for SCID-X1 is a highly effective strategy for restoration of functional cellular and humoral immunity.