Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults.

Cannabidiol (CBD) is a dietary supplement with numerous purported health benefits and an expanding commercial market. Commercially available CBD preparations range from tinctures, oils, and powders, to foods and beverages. Despite widespread use, information regarding bioavailability of these formulations is limited. The purpose of this study was to test the bioavailability of two oral formulations of CBD in humans and explore their potential acute anti-inflammatory activity. We conducted a pilot randomized, parallel arm, double-blind study in 10 healthy adults to determine differences in pharmacokinetics of commercially available water and lipid-soluble CBD powders. Participants consumed a single 30 mg dose, which is within the range of typical commercial supplement doses, and blood samples were collected over 6 hr and analyzed for CBD concentrations. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and T = 90 min, cultured and stimulated with bacterial lipopolysaccharide (LPS) to induce an inflammatory response. Cell supernatants were assayed for IL-10 and TNF, markers of inflammation, using enzyme-linked immunosorbent assays. The water-soluble powder had Cmax = 2.82 ng/ml, Tmax = 90 min, and was approximately ×4.5 more bioavailable than the lipid-soluble form. TNF was decreased in LPS-stimulated PBMCs collected 90 min after CBD exposure relative to cells collected at baseline. This study provides pilot data for designing and powering future studies to establish the anti-inflammatory potential and bioavailability of a larger variety of commercial CBD products consumed by humans.

A systematic review of recommended modifications of CBT for people with cognitive impairments following brain injury.

Due to diverse cognitive, emotional and interpersonal changes that can follow brain injury, psychological therapies often need to be adapted to suit the complex needs of this population. The aims of the study were to synthesise published recommendations for therapy modifications following brain injury from non-progressive traumatic, vascular, or metabolic causes and to determine how often such modifications have been applied to cognitive behavioural therapy (CBT) for post-injury emotional adjustment problems. A systematic review and narrative synthesis of therapy modifications recommended in review articles and reported in intervention studies was undertaken. Database and manual searches identified 688 unique papers of which eight review articles and 16 intervention studies met inclusion criteria. The review articles were thematically analysed and a checklist of commonly recommended modifications composed. The checklist items clustered under themes of: therapeutic education and formulation; attention; communication; memory; and executive functioning. When this checklist was applied to the intervention studies, memory aids and an emphasis on socialising patients to the CBT model were most frequently reported as adaptations. It was concluded that the inconsistent reporting of psychological therapy adaptations for people with brain injury is a barrier to developing effective and replicable therapies. We present a comprehensive account of potential modifications that should be used to guide future research and practice.

Evaluation of Sleep Disorders in Patients With Severe Traumatic Brain Injury During Rehabilitation.

OBJECTIVE: To explore the presence and types of sleep disorders in chronic patients with severe traumatic brain injury (TBI) undergoing inpatient rehabilitation using formal diagnostic criteria based on the International Classification of Sleep Disorders, 2nd edition. DESIGN: Cross-sectional study. SETTING: Inpatient brain injury rehabilitation units. PARTICIPANTS: Chronic inpatients with severe TBI (N=30) were evaluated during rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants wore an actiwatch for 7 days and completed self-report measures on sleep, mood, fatigue, pain, and daytime sleepiness. RESULTS: Twenty participants (67%) had a sleep-wake cycle disturbance, of which 15 (50%) met diagnostic criteria for a sleep disorder. Diagnosed sleep disorders in the sample were insomnia (26.7%), posttraumatic hypersomnia (6.7%), delayed sleep phase syndrome (10%), irregular sleep-wake pattern disorder (3.3%), and periodic limb movement disorder (3.3%). Sleep quality was estimated by senior clinical staff as interfering with rehabilitation in 36.6% of the sample. Poor sleep quality was associated with greater anxiety, fatigue, and daytime sleepiness. CONCLUSIONS: Consistent with previous studies, the present study showed high levels of sleep-wake cycle disturbances in patients with severe TBI undergoing rehabilitation, which were associated with anxiety, fatigue, and daytime sleepiness. These findings highlight the importance of assessing and treating sleep problems in patients with TBI undergoing rehabilitation.

Mortality from Head Injury over Four Decades in Scotland.

Although the causes of head injury, the population at risk, and approaches to prevention and treatment are continually evolving, there is little information about how these are reflected in patterns of mortality over time. We used population-based comprehensive data uniquely available in Scotland to investigate changes in the total numbers of deaths from 1974 to 2012, as well as the rates of head injury death, from different causes, overall and in relation to age and gender. Total mortality fell from an annual average of 503 to 339 with a corresponding annual decrease in rate from 9.6 to 6.4 per 100,000 population, the decline substantially occurring between 1974 and 1990. Deaths in children fell strikingly, but rose in older people. Deaths in males fell to a greater extent than females, but remained at a higher rate overall. Initially, a transport accident accounted for most deaths, but these fell by 80%, from 325 per year to 65 per year over the 39-year period. Deaths from falling and all other causes did not decline, coming to outnumber transport accident deaths by 1998, which accounts for the overall absence of change in total mortality in recent years. In order to reduce mortality in the future, more-effective measures to prevent falls are needed and these strategies will vary in younger adults (where alcohol is often a factor), as well as in older adults where infirmity can be a cause. In addition, measures to sustain reductions in transport accidents need to be maintained and further developed.

Head injury and mortality in the homeless.

Risk factors for head injury are also risk factors for becoming homeless but there is little research on this vulnerable group, who can be neglected by health services that specialize in acquired brain injury. This study investigates the prevalence of admissions to hospital with a head injury in the homeless and associations with later mortality. It compares homeless people with and without a record of hospitalized head injury (HHI) and the Glasgow population. Data were obtained from a U.K. National Health Service strategy to enhance care of the homeless. This included development and production of local registers of homeless people. In Glasgow, the initiative took place over a seven-year period (2004-2010) and comprised 40 general practitioner (family practice) services in the locality of 55 homeless hostels. The register was linked to hospital admissions with head injury recorded in Scottish Medical Records and to the General Register of Scotland, which records deaths. A total of 1590 homeless people was registered in general practitioner (family doctor) returns. The prevalence of admission to hospital with head injury in the homeless over a 30-year period (13.5%) was 5.4 times higher than in the Glasgow population. In the homeless with HHI, 33.6% died in the seven-year census period, compared with 13.9% in the homeless with no hospitalized HI (NHHI). The standardized mortality ratio for HHI (4.51) was more than twice that for NHHI (2.08). The standardized mortality ratio for HHI aged 15-34 (17.54) was particularly high. These findings suggest that HHI is common in the homeless relative to the general population and is a risk factor for late mortality in the homeless population.

The epidemiology of hospital treated traumatic brain injury in Scotland.

BACKGROUND: Traumatic Brain Injury (TBI) is an important global public health problem made all the more important by the increased likelihood of disability following a hospital admission for TBI. Understanding those groups most at risk will help inform interventions designed to prevent causes of TBI, such as falls prevention measures. This study identifies the rate of hospitalisation episodes of TBI in Scotland, explores causes of TBI admissions, and trends in hospitalisation episodes by age and gender over a twelve year period using routinely collected hospital data. METHODS: A retrospective analysis of routine hospital episode data identified records relating to TBI for the twelve years between 1998 and 2009. Descriptive and joinpoint regression analysis were used, average annual percentage changes (AAPC) and annual percentage change (APC) in rates were calculated. RESULTS: Between 1998 and 2009 there were 208,195 recorded episodes of continuous hospital care in Scotland as a result of TBI. Almost half (47%) of all TBIs were the result of falls, with marked peaks observed in the very young and the oldest groups. The AAPC of hospitalization episode rates over the study period for boys and girls aged 0-14 were -4.9% (95% CI -3.5 to-6.3) and -4.7% (95% CI -2.6 to -6.8) respectively. This reduction was not observed in older age groups. In women aged 65 and over there was an APC of 3.9% (95% CI 1.2 to 6.6) between 2004 and 2009. CONCLUSIONS: Hospitalisation for TBI is relatively common in Scotland. The rise in the age-adjusted rate of hospitalisation episodes observed in older people indicates that reduction of TBI should be a public health priority in countries with an ageing population. Public health interventions such as falls prevention measures are well advised and evaluations of such interventions should consider including TBI hospitalisation as an alternative or supplementary outcome measure to fractured neck of femur. Further research is needed to advance understanding of the associations of risk factors with increased incidence of TBI hospital episodes in the elderly population.

Pediatric sleep difficulties after moderate-severe traumatic brain injury.

The objective of this study is to systematically investigate sleep following moderate-severe pediatric traumatic brain injury (TBI). School-aged children with moderate-severe TBI identified via hospital records were invited to participate, along with a school-age sibling. Subjective reports and objective actigraphy correlates of sleep were recorded: Children's Sleep Habits Questionnaire (CSHQ), Sleep Self-Report questionnaire (SSR), and 5-night actigraphy. TBI participants (n = 15) and their siblings (n = 15) participated. Significantly more sleep problems were parent-reported (CSHQ: p = 0.003; d = 1.57), self-reported (SSR: p = 0.003; d = 1.40), and actigraph-recorded in the TBI group (sleep efficiency: p = 0.003; d = 1.23; sleep latency: p = 0.018; d = 0.94). There was no evidence of circadian rhythm disorders, and daytime napping was not prevalent. Moderate-severe pediatric TBI was associated with sleep inefficiency in the form of sleep onset and maintenance problems. This preliminary study indicates that clinicians should be aware of sleep difficulties following pediatric TBI, and their potential associations with cognitive and behavioral problems in a group already at educational and psychosocial risk.

The Glasgow Outcome at Discharge Scale: an inpatient assessment of disability after brain injury.

This study assesses the validity and reliability of the Glasgow Outcome at Discharge Scale (GODS), which is a tool that is designed to assess disability after brain injury in an inpatient setting. It is derived from the Glasgow Outcome Scale-Extended (GOS-E), which assesses disability in the community after brain injury. Inter-rater reliability on the GODS is high (quadratic-weighted kappa 0.982; 95% confidence interval [CI] 0.968, 0.996) as is concurrent validity with the Disability Rating Scale (DRS) (Spearman correlation -0.728; 95% CI -0.819, -0.601). The GODS is significantly associated with physical and fatigue subscales of the short form (SF)-36 in hospital. In terms of predictive validity the GODS is highly associated with the GOS-E after discharge (Spearman correlation 0.512; 95% CI 0.281, 0.687), with the DRS, and with physical, fatigue, and social subscales of the SF-36. The GODS is recommended as an assessment tool for disability after brain injury pre-discharge and can be used in conjunction with the GOS-E to monitor disability between hospital and the community.

Disability in young people and adults after head injury: 12-14 year follow-up of a prospective cohort.

BACKGROUND: There is a need to establish how long term outcome evolves after head injury (HI) and factors related to this, to inform opportunities for intervention. OBJECTIVE: To determine late outcome in adults 12-14 years after hospital admission for HI and to examine relationships between injury, early and late factors, and disability. METHODS: A prospective cohort with HI, whose outcome was reported previously at 1 and 5-7 years after injury, were followed up after 12-14 years. Participants were assessed using structured and validated measures of disability (Glasgow Outcome Scale-Extended), psychological well being, alcohol use and health status. RESULTS: Of 219 survivors followed-up at 5-7 years, 34 (15.5%) had died by 12-14 years. Disability remained common in survivors at 12-14 years (51%), as found at 1 and 5-7 years (53%). For those disabled at 1 year, outcome was poor, with 80% dead or disabled at 12-14 years. Older age at injury, a premorbid history of brain illness or physical disability and post-injury low self-esteem and stress were associated with disability at 12-14 years. Disability changed between 5-7 and 12-14 years in 55% of survivors, improving in 23%. Late changes in disability between 5-7 and 12-14 years were associated with self-perceptions of locus of control as being 'powerful others' at 5-7 years. CONCLUSIONS: Disability is common 12-14 years after hospital admission with a HI. For some there is a dynamic process of change in disability over time that is associated with self-perceptions of control that could be a target for intervention based research.

PTSD, attention bias, and heart rate after severe brain injury.

Does "partial" posttraumatic stress disorder (PTSD) occur after head injury? The authors found that attention bias to trauma-related threat stimuli and higher heart rate during trauma interview were not associated with PTSD symptom severity in 42 participants with severe head injury. They found no evidence for "partial" PTSD.

Accuracy in scoring vignettes using the mini mental state examination and the short orientation memory concentration test.

OBJECTIVE: To compare the accuracy in scoring of vignettes of 2 cognitive screening tests-the Mini Mental State Examination (MMSE) and the Short Orientation Memory Concentration Test (S-OMC). DESIGN: Within group comparison. SETTING: Academic institution. PARTICIPANTS: A total of 74 student nurses. METHOD: Participants received instruction on the scoring of each test and were then asked to score 6 videotaped clinical vignettes. MAIN OUTCOME MEASURES: Scores allocated by participants on the vignettes for the MMSE and S-OMC. RESULTS: The proportion of participants assigning the correct total score to the vignettes was low (MMSE 53.2%, S-OMC 66.7%), and the difference in accuracy between tests was significant (P = .005). The total scores that were assigned resulted in misclassification across all 4 caseness cutoffs within each test (MMSE 0.9%-5.9%; S-OMC 1.4%-2.7%). The differences in correct caseness placement between the 2 tests were significant only for the moderate impairment cutoff, where the S-OMC achieved greater correct caseness placement. CONCLUSIONS: The high proportion of scoring mistakes overall has implications for the use of both the tests in routine clinical practice but in particular for the MMSE. An increased awareness is needed in clinical settings and among tests developers, of the likelihood of, and implications arising from, variations in scoring accuracy. In the current study, the S-OMC was scored more accurately than the MMSE.

Quality of life in children with acquired brain injury: parent perspectives 1-5 years after injury.

PRIMARY OBJECTIVE: To obtain parental ratings of children's quality of life, cognitive, emotional and behavioural functioning, as well as ratings of service provision, following traumatic brain injury (TBI). RESEARCH DESIGN: A retrospective, cross-sectional study. METHODS AND PROCEDURES: Parents of 47 children with mild or moderate-severe TBI completed standardized questionnaires evaluating quality of life (PedsQL 4.0) and cognitive, emotional and behavioural functioning (Strengths and Difficulties Questionnaire). Data collected was compared with published normative data for these scales. Views regarding parental experiences of care and their ratings of service provision were also obtained. RESULTS: Quality of life was significantly lower in 13-times as many children with TBI than expected from the normative population. Parents reported that more than 43% of children with TBI had cognitive, emotional and behavioural difficulties that impacted on their daily life. Whilst high levels of social deprivation were found, this did not fully explain the significantly raised levels of difficulties. Another factor associated with this poor outcome was the absence of systematic, routine follow-up or intervention. CONCLUSIONS: Parents frequently reported poor quality of life and cognitive, emotional and behavioural problems in their children following TBI. These preliminary findings indicate that children, after TBI, are at risk of developing persistent clinical problems and require follow-up beyond the acute period of their recovery.

Diagnosis and epidemiological studies of human metapneumovirus using real-time PCR.

BACKGROUND: Human metapneumovirus (hMPV) is prevalent in children, the elderly and immunocompromised individuals, but available epidemiological data is limited. OBJECTIVES: (1) To develop and validate a real-time PCR method for hMPV diagnosis. (2) To determine the percentage of hMPV in respiratory specimens from the community and its association with outbreaks in our geographic area. (3) To provide epidemiological data in terms of age distribution, seasonality and co-infections. STUDY DESIGN: A real-time PCR assay was designed for detection of hMPV lineages A and B. Prospective testing for hMPV over a 22-month period was then undertaken. RESULTS: The real-time PCR was sensitive and specific for detection of both lineages of hMPV. hMPV was detected in 9.5% (n=8239) of the specimens and 25% of the outbreaks (n=100) tested. The hMPV-positive patients ranged in age from 18 days to 99 years with a median age of 24 months. The number of positive samples peaked during the winter months of December, January and February. A high rate of co-infections was noted in the samples tested. CONCLUSIONS: hMPV is common in the community and is associated with outbreaks. Including hMPV in routine testing improves etiological diagnosis of acute respiratory infections.

Knowledge and expectation of postconcussion symptoms in the general population.

OBJECTIVE: Beliefs about mild traumatic brain injury (MTBI) may affect complaints and their persistence. This study investigates the relationships between knowledge, experience, and expectation in the general population. METHODS: One hundred seventy-one people reported symptoms expected from vignettes about MTBI, depression, posttraumatic stress disorder (PTSD), and orthopedic injury. Then they completed a postconcussional syndrome (PCS) checklist about these vignettes and about personal symptoms. RESULTS: The ability to generate symptoms from vignettes was poor for PCS, depression, and PTSD, and was greatly improved using a PCS checklist, probably by symptom guessing. No postconcussion symptoms were associated specifically with MTBI. Those with more personal symptoms expected more symptoms. Past experience of MTBI did not improve symptom knowledge. Beliefs about the 'undesirability' of conditions were associated with expected outcomes. CONCLUSIONS: People know little about PCS. Expectations about MTBI are influenced by psychological factors that are relevant if we consider information given in hospitals. Symptom overlap means that psychological conditions such as depression may be misdiagnosed as PCS, and checklists should not be used for diagnosis.