Post-Traumatic Stress Disorder after Civilian Traumatic Brain Injury: A Systematic Review and Meta-Analysis of Prevalence Rates

Post-traumatic stress disorder (PTSD) is a commonly diagnosed psychiatric disorder following traumatic brain injury (TBI). Much research on PTSD and TBI has focused on military conflict settings. Less is known about PTSD in civilian TBI. We conducted a systematic review and meta-analysis on the prevalence of PTSD after mild and moderate/severe TBI in civilian populations. We further aimed to explore the influence of methodological quality and assessment methods. A systematic literature search was performed on studies reporting on PTSD in civilian TBI, excluding studies on military populations. The risk of bias was assessed using the MORE (Methodological evaluation of Observational REsearch) checklist. Meta-analysis was conducted for overall prevalence rates for PTSD with sensitivity analyses for the severity of TBI. Fifty-two studies were included, of which 31 were graded as low risk of bias. Prevalence rates of PTSD in low risk of bias studies varied widely (2.6–36%) with a pooled prevalence rate of 15.6%. Pooled prevalence rates of PTSD for mild TBI (13.5%, 95% confidence interval [CI]: 11.7–15.3; I2 = 2%) did not differ from moderate/severe TBI (11.8, 95% CI: 7.5–16.1; I2 = 63%). Similar rates were reported in studies using different approaches and times of assessment. Although most studies that compared participants with TBI with trauma patients and healthy controls found no difference in prevalence rates of PTSD, a meta-analysis across studies revealed a higher prevalence of PTSD in patients with TBI (odds ratio [OR]: 1.73, 95% CI: 1.21–2.47). This review highlights variability between studies and emphasizes the need for higher-quality studies. Further research is warranted to determine risk factors for the development of PTSD after TBI

Genetic Influences on Patient-Oriented Outcomes in Traumatic Brain Injury: A Living Systematic Review of Non-Apolipoprotein E Single-Nucleotide Polymorphisms

There is a growing literature on the impact of genetic variation on outcome in traumatic brain injury (TBI). Whereas a substantial proportion of these publications have focused on the apolipoprotein E (APOE) gene, several have explored the influence of other polymorphisms.We undertook a systematic review of the impact of single-nucleotide polymorphisms (SNPs) in non–apolipoprotein E (non-APOE) genes associated with patient outcomes in adult TBI). We searched EMBASE, MEDLINE, CINAHL, and gray literature from inception to the beginning of August 2017 for studies of genetic variance in relation to patient outcomes in adult TBI. Sixty-eight articles were deemed eligible for inclusion into the systematic review. The SNPs described were in the following categories: neurotransmitter (NT) in 23, cytokine in nine, brain-derived neurotrophic factor (BDNF) in 12, mitochondrial genes in three, and miscellaneous SNPs in 21. All studies were based on small patient cohorts and suffered from potential bias. A range of SNPs associated with genes coding for monoamine NTs, BDNF, cytokines, and mitochondrial proteins have been reported to be associated with variation in global, neuropsychiatric, and behavioral outcomes. An analysis of the tissue, cellular, and subcellular location of the genes that harbored the SNPs studied showed that they could be clustered into blood–brain barrier associated, neuroprotective/regulatory, and neuropsychiatric/degenerative groups. Several small studies report that various NT, cytokine, and BDNF-related SNPs are associated with variations in global outcome at 6–12 months post-TBI. The association of these SNPs with neuropsychiatric and behavioral outcomes is less clear. A definitiv

The European Brain Injury Consortium survey of head injuries

To provide a picture of contemporary practice, a survey was carried out of severely and moderately head injured patients admitted to 67 'neuro' centres in 12 European countries. 1,005 adult head injuries were recruited over a three month period. Sixty items of information on demography, clinical features, investigations, management and early complications were captured on a simple, two-page questionnaire and, information on outcome at six months on a third page. The median age of the subjects was 38 years, 74% were male and 51% injured in road traffic accidents; 57% of patients were transferred to the 'neuro' centre from another hospital. Assessment of clinical responsiveness was limited by the use of sedation and intubation and information from four early time points (pre-hospital, arrival at the Accident and Emergency department, post-resuscitation, and arrival at the 'neuro' unit) was combined to stratify the subjects as severe (58%), moderate (17%) or intermediate (19%). In 48% of patients classified the CT scan showed features of a 'mass lesion' and in 40% showed a subarachnoid haemorrhage. Fifty-five centres provided the data on outcome for 94% of the cases recruited in these centres six months after injury. 31% died, 3% were vegetative, 16% severely disabled, 20% moderately disabled and 31% had made a good recovery. Comparison of the data from different parts of Europe showed differences in the frequency of secondary transfer, cause of injury, occurrence of major extracranial injury, CT scan findings, intracranial operation, clinical severity of injury and utilisation of the components of intensive care and the occurrence of a favourable outcome, although the latter difference was not statistically significant when variations in the initial severity of injury were taken into account. The findings in the present survey are compared with newly analysed information for three previous large series: the International Data Bank involving the UK, the Netherlands and the USA, the North American Traumatic Coma Data Bank, and data from four centres in the UK. The comparisons showed substantial similarities and also differences that may reflect variations in policy for admission of the head injury to 'neuro' units, and evolution in methods of assessment, investigation and management. The effects of these differences on outcome requires further, rigorous prospective study

The temporal pattern of immune and inflammatory proteins prior to a recurrent coronary event in post-acute coronary syndrome patients

Purpose: We assessed the temporal pattern of 29 immune and inflammatory proteins in post-acute coronary syndrome (ACS) patients, prior to the development of recurrent ACS. Methods: High-frequency blood sampling was performed in 844 patients admitted for ACS during one-year follow-up. We conducted a case-control study on the 45 patients who experienced reACS (cases) and two matched event-free patients (controls) per case. Olink Proteomics’ immunoassay was used to obtain serum levels of the 29 proteins, expressed in an arbitrary unit on the log2-scale (Normalized Protein eXpression, NPX). Linear mixed-effects models were applied to examine the temporal pattern of the proteins, and to illustrate differences between cases and controls. Results: Mean age was 66 ± 12 years and 80% were men. Cases and controls had similar baseline clinical characteristics. During the first 30 days, and after multiple testing correction, cases had significantly higher serum levels of CXCL1 (difference of 1.00 NPX, p ¼ 0.002), CD84 (difference of 0.64 NPX, p ¼ 0.002) and TNFRSF10A (difference of 0.41 NPX, p < 0.001) than controls. After 30 days, serum levels of all 29 proteins were similar in cases and controls. In particular, no increase was observed prior to reACS. Conclusions: Among 29 immune and inflammatory proteins, CXCL1, CD84 and TNFRSF10A were associated with early reACS after initial ACS-admission

Pre-injury Comorbidities Are Associated With Functional Impairment and Post-concussive Symptoms at 3-and 6-Months After Mild Traumatic Brain Injury: A TRACK-TBI Study

Introduction: Over 70% of traumatic brain injuries (TBI) are classified as mild (mTBI), which present heterogeneously. Associations between pre-injury comorbidities and outcomes are not well-understood, and understanding their status as risk factors may improve mTBI management and prognostication. Methods: mTBI subjects (GCS 13–15) from TRACK-TBI Pilot completing 3- and 6-month functional [Glasgow Outcome Scale-Extended (GOSE)] and post-concussive outcomes [Acute Concussion Evaluation (ACE) physical/cognitive/sleep/emotional subdomains] were extracted. Pre-injury comorbidities >10% incidence were included in regressions for functional disability (GOSE ≤ 6) and post-concussive symptoms by subdomain. Odds ratios (OR) and mean differences (B) were reported. Significance was assessed at p < 0.0083 (Bonferroni correction). Results: In 260 subjects sustaining blunt mTBI, mean age was 44.0-years and 70.4% were male. Baseline comorbidities >10% incidence included psychiatric-30.0%, cardiac (hypertension)-23.8%, cardiac (structural/valvular/ischemic)-20.4%, gastrointestinal15.8%, pulmonary-15.0%, and headache/migraine-11.5%. At 3- and 6-months separately, 30.8% had GOSE ≤ 6. At 3-months, psychiatric (GOSE ≤ 6: OR = 2.75, 95% CI [1.44–5.27]; ACE-physical: B = 1.06 [0.38–1.73]; ACE-cognitive: B = 0.72 [0.26–1.17]; ACE-sleep: B = 0.46 [0.17–0.75]; ACE-emotional: B = 0.64 [0.25–1.03]), headache/migraine (GOSE ≤ 6: OR = 4.10 [1.67–10.07]; ACE-sleep: B = 0.57 [0.15–1.00]; ACE-emotional: B = 0.92 [0.35–1.49]), and gastrointestinal history (ACE-physical: B = 1.25 [0.41–2.10]) were multivariable predictors of worse outcomes. At 6-months, psychiatric (GOSE ≤ 6: OR = 2.57 [1.38–4.77]; ACE-physical: B = 1.38 [0.68–2.09]; ACE-cognitive: B = 0.74 [0.28–1.20]; ACE-sleep: B = 0.51 [0.20–0.83]; ACE-emotional: B = 0.93 [0.53–1.33]), and headache/migraine history (ACE-physical: B = 1.81 [0.79–2.84]) predicted worse outcomes. Conclusions: Pre-injury psychiat

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH)

STUDY QUESTION: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratchin

Additive Conjoint Measurement for Multiattribute Utility

This paper shows that the role of risky alternatives can be greatly reduced in the clicitation procedures of multiattribute utility. This reduction can be achieved by invoking methods from additive conjoint measurement; it is desirable because risky choices involve more cognitive problems, thus more biases and unreliability, than riskless ones. Existing results of multiattribute utility are generalized to obtain a complete axiomatization of the new clicitation procedure. The approach has been developed in a medical decision analysis project to advise on the choice between surgery and radiotherapy for laryngeal cancer