The association between adverse childhood experiences and adult traumatic brain injury/concussion: a scoping review

Background: Adverse childhood experiences are significant risk factors for physical and mental illnesses in adulthood. Traumatic brain injury/concussion is a challenging condition where pre-injury factors may affect recovery. The association between childhood adversity and traumatic brain injury/concussion has not been previously reviewed. The research question addressed is: What is known from the existing literature about the association between adverse childhood experiences and traumatic brain injury/concussion in adults?

Methods: All original studies of any type published in English since 2007 on adverse childhood experiences and traumatic brain injury/concussion outcomes were included. The literature search was conducted in multiple electronic databases. Arksey and O’Malley and Levac et al.’s scoping review frameworks were used. Two reviewers independently completed screening and data abstraction.

Results: The review yielded six observational studies. Included studies were limited to incarcerated or homeless samples, and individuals at high-risk of or with mental illnesses. Across studies, methods for childhood adversity and traumatic brain injury/concussion assessment were heterogeneous.

Discussion: A positive association between adverse childhood experiences and traumatic brain injury occurrence was identified. The review highlights the importance of screening and treatment of adverse childhood experiences. Future research should extend to the general population and implications on injury recovery.

• Implications for rehabilitation

• Exposure to adverse childhood experiences is associated with increased risk of traumatic brain injury.

• Specific types of adverse childhood experiences associated with risk of traumatic brain injury include childhood physical abuse, psychological abuse, household member incarceration, and household member drug abuse.

• Clinicians and researchers should inquire about adverse childhood experiences in all people with traumatic brain injury as pre-injury health conditions can affect recovery.

     

Evaluating the long-term impact of faculty development programs on MCQ item analysis

Abstract

Purpose: Evaluating the long-term impact of faculty development programs (FDPs) can help monitor the effectiveness of the program and identify areas for development. This study examined long-term differences in confidence, knowledge, behaviors, and policies of faculty members who attended FDPs on multiple choice question (MCQ) item analysis and faculty members who did not attend the FDPs.

Methods: A cross-sectional study design was used, by administering a 24-item survey to a representative sample (simple random selection) of 61 faculty members at King Abdulaziz University Faculty of Medicine.

Results: Among respondents, 34% did not attend FDPs; 53% attended 1–3 FDPs; and 13% attended more than 3 FDPs on MCQ item analysis. Results showed that faculty knowledge on elements of MCQ item analysis was significantly greater (p?=?.01) for members who attended the FDPs. Faculty who attended FDPs on MCQ item analysis were twice more likely to conduct item analysis in general (p?=?.020) and four times more likely to conduct item analysis for more than 70% of module examinations (p?=?.005).

Conclusion: FDPs focused on MCQ item analysis can yield systematic changes on faculty confidence, knowledge, and behaviors. Moreover, FDPs also need support from the department and need sustained strategic support to ensure continued effectiveness.     

Effect of cenobamate on the single‐dose pharmacokinetics of multiple cytochrome P450 probes using a cocktail approach in healthy subjects

This study was designed to evaluate the effects of cenobamate, an antiseizure medication for focal seizures, on the pharmacokinetics of cytochrome P450 probes (bupropion, CYP2B6; midazolam, CYP3A4/5; warfarin, CYP2C9; and omeprazole, CYP2C19) in healthy subjects. Probes were administered alone on days 1 (bupropion) and 7 (midazolam/warfarin/omeprazole), and with cenobamate 100 mg/day on day 69 (midazolam) and cenobamate 200 mg/day on days 99 (bupropion) and 105 (midazolam/warfarin/omeprazole). No significant interaction was concluded if 90% confidence intervals (CIs) for geometric mean ratios (GMRs) for area under the curve (AUC) and maximum concentration of CYP substrates and/or their metabolites were within the no‐effect interval (0.80–1.25). When co‐administered with cenobamate 100 mg/day, AUC from time of administration up to the time of the last quantifiable concentration (AUC_0–last) GMR (90% CIs) for midazolam was 0.734 (0.647–0.832). When co‐administered with cenobamate 200 mg/day, AUC_0–last GMRs (90% CI) for midazolam, bupropion, S‐warfarin, and omeprazole were 0.277 (0.238–0.323), 0.615 (0.522–0.724), 1.14 (1.10–1.18), and 2.07 (1.44–2.98), respectively. Co‐administration of cenobamate with midazolam and bupropion probes led to values that were outside and below the no effect boundary, indicating that cenobamate induces the CYP3A4/5 and CYP2B6 enzymes. Co‐administration of cenobamate led to omeprazole values which were outside and above the no‐effect boundary, but with high variability, suggesting that cenobamate may moderately inhibit CYP2C19 activity. No effect on CYP2C9 was observed with the cenobamate and warfarin combination. Co‐administration of cenobamate with these probes drugs was well‐tolerated. In this study, 200 mg/day cenobamate moderately induced CYP3A4/5 (dose‐dependently; 100 mg/day was a weak inducer), was a weak inducer of CYP2B6, moderately inhibited CYP2C19, and had a negligible effect on CYP2C9.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Drug‐drug interactions are a challenging aspect of managing epilepsy because many antiseizure medications (ASMs) induce or inhibit CYP450 enzymes, which are commonly involved in drug metabolism of many ASMs. Previous studies suggest that cenobamate, a US Food and Drug Administration (FDA)‐approved ASM for the treatment of adults with focal seizures, may affect the activity of certain CYP450 enzymes.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study was designed to determine the effects of cenobamate on the pharmacokinetics of drugs known to affect the activity of these CYP450 enzymes, known as probe drugs. These probe drugs include bupropion, (CYP2B6), midazolam (CYP3A4/5), warfarin (CYP2C9), and omeprazole (CYP2C19).

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

The results of this study indicate that cenobamate induces CYP2B6 activity, exhibits a dose‐dependent induction of CYP3A4/5 activity, inhibits CYP2C19 activity, and has a negligible effect on CYP2C9 activity.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

These findings suggest that dose adjustments may be required when agents metabolized through these CYP450 pathways are used in conjunction with cenobamate.     

Widely Metastatic Squamous Cell Carcinoma Originating from Malignant Transformation of Hypertrophic Lichen Planus in a 24‐Year‐Old Woman: Case Report and Review of the Literature

Hypertrophic lichen planus (HLP) is a T‐cell‐mediated process typically presenting with hypertrophic or verrucous plaques on the lower limbs. We report the case of a 24‐year‐old woman with a history of HLP since age 3 years presenting with rapid malignant transformation of one lesion into a large squamous cell carcinoma (SCC). Subsequent examination revealed progressive, widespread metastatic involvement, and the patient ultimately died from her disease. SCC associated with HLP is rare, with a review of the literature revealing fewer than 50 cases. This case highlights the need to be aware of suspicious changes in HLP and to educate patients as to when to be reevaluated.     

Detection of simulated multiple sclerosis lesions on T2-weighted and FLAIR images of the brain: observer performance

PURPOSE: To determine observer performance in the detection of multiple sclerosis (MS) lesions on magnetic resonance (MR) images of the brain and to assess the dependence of observer performance on lesion size, parenchymal location, pulse sequence, and supratentorial versus infratentorial level. MATERIALS AND METHODS: This HIPAA-compliant protocol was approved by the institutional review board, and previously acquired MR data from a healthy volunteer and a patient with MS were used to derive parameter maps, with waiver of informed consent. Parameter maps and image simulator software were used to generate 320 phantom brain images with simulated supratentorial and infratentorial MS lesions. Images were displayed with T2-weighting or fluid-attenuated inversion recovery (FLAIR) contrast. Four readers independently evaluated the images, rating lesions on a five-point certainty scale. Observer performance was measured by using the area under the alternative free-response receiver operating characteristic curve (A(1)), and significance was determined with the z test. RESULTS: Pooled A(1) scores were significantly better for FLAIR imaging (0.96 +/- 0.01 [standard error]) than for T2-weighted MR imaging (0.89 +/- 0.04) supratentorially (P = .05) but were similar for FLAIR imaging (0.90 +/- 0.06) and T2-weighted MR imaging (0.88 +/- 0.05) infratentorially. A(1) scores for cortical, deep white matter, and periventricular lesions were 0.93 +/- 0.05, 0.97 +/- 0.02, and 0.89 +/- 0.04, respectively, for FLAIR imaging and 0.77 +/- 0.06, 0.99 +/- 0.01, and 0.89 +/- 0.05, respectively, for T2-weighted MR imaging. FLAIR scores were significantly higher than T2-weighted scores for cortical lesions. Linear correlation was found between A(1) and lesion size (r = 0.5). CONCLUSION: Supratentorially, performance was better with FLAIR imaging than with T2-weighted MR imaging. Infratentorially, performance was moderate with both modalities. Observers did better with FLAIR imaging in the detection of cortical lesions, and performance improved with increasing lesion size.     

Depression, anxiety and pain in children with juvenile idiopathic arthritis (JIA).

The aim of this study was to assess relations among depression, anxiety and pain in children with juvenile idiopathic arthritis (JIA). Pain was measured with the visual analogue scale (VAS), and depression and anxiety with depression and anxiety subscales from the Trauma Symptom Checklist for Children (TSC-C). Pain perception was significantly correlated with depression scores.     

Leptin favors Th17/Treg cell subsets imbalance associated with allergic asthma severity

BackgroundObesity has often been associated with severe allergic asthma (AA). Here, we analyzed the frequency of different circulating CD4⁺T‐cell subsets from lean, overweight and obese AA patients.MethodsMononuclear cells from peripheral blood were obtained from 60 AA patients and the frequency of different CD4⁺T‐cell subsets and type 1 regulatory B cells (Br1) was determined by cytometry. The effect of obese‐related leptin dose on cytokine production and Treg cell function in AA‐derived CD4⁺ T cell cultures was evaluated by ELISA and 3H thymidine uptake, respectively. Leptin levels were quantified in the plasma by ELISA. According to the BMI, patients were stratified as lean, overweight and obese.ResultsAA severity, mainly among obese patients, was associated with an expansion of hybrid Th2/Th17 and Th17‐like cells rather than classic Th2‐like cells. On the other hand, the frequencies of Th1‐like, Br1 cells and regulatory CD4⁺ T‐cell subsets were lower in patients with severe AA. While percentages of the hybrid Th2/Th17 phenotype and Th17‐like cells positively correlated with leptin levels, the frequencies of regulatory CD4⁺ T‐cell subsets and Br1 cells negatively correlated with this adipokine. Interestingly, the obesity‐related leptin dose not only elevated Th2 and Th17 cytokine levels, but also directly reduced the Treg function in CD4⁺ T cell cultures from lean AA patients.ConclusionIn summary, our results indicated that obesity might increase AA severity by favoring the expansion of Th17‐like and Th2/Th17 cells and decreasing regulatory CD4⁺T cell subsets, being adverse effects probably mediated by leptin overproduction.     

Trajectories and stability of self‐reported short sleep duration from adolescence to adulthood

The trajectories and stability of self‐reported sleep duration recorded at ages 13, 15, and 23 years on reported sleep duration at age 30 years among 1105 students (55% male) who participated in the Norwegian Longitudinal Health and Behaviour Study were examined. Questionnaire data were used to obtain demographic and sleep variables. Dichotomised short sleep duration was based on normative values and set as ≤8.5 h (age 13 years), ≤8 h (age 15 years) and ≤7 h (ages 23 and 30 years). Results indicated a significant overall reduction in total sleep duration (h per night) across age groups. Sleep duration (continuous) at age 15 and 23 years (whole group) was moderately but positively correlated with sleep duration at age 30 years (P < 0.01). When split by sex, at age 15 years, this association was present among females only (P < 0.01); however, at age 23 years, this association was present in both male and females (both P < 0.001). Categorical short sleep at age 23 years (whole group) was associated with short sleep at age 30 years (unadjusted odds ratio = 3.67, 95% confidence interval 2.36–5.69). Following sex stratification, this effect was significant for both males (unadjusted odds ratio = 3.77, 95% confidence interval: 2.22–6.42) and females (unadjusted odds ratio = 2.71, 95% confidence interval: 1.46–5.04). No associations were noted for categorical short sleep at ages 13 or 15 years, and subsequent short sleep at 30 years. Habitual short sleep duration during middle adulthood is not sustained from the time of early adolescence. Rather, these trends appear to be formed during early adulthood.