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.

     

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.     

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.     

Prevalence and Risk Factors of Urinary Incontinence Among Jordanian Women: Impact on Their Life

We estimate the prevalence and type of urinary incontinence (UI), possible associated risk factors, and the impact of UI on women's social and psychological well-being. The sample consisted of women attending a family medicine clinic at Jordan University Hospital (JUH) who answered a self-administered questionnaire. More than one-third of the sample reported the presence of UI. Stress type was the most frequently reported risk factor, followed by mixed incontinence, then urge. Age, diabetes, chronic cough, parity, and hysterectomy were positively associated with the presence of UI. Incontinence caused low self-esteem in more than half of the women who experienced it.     

In vitro synergism of a water insoluble fraction of Uncaria tomentosa combined with fluconazole and terbinafine against resistant non-Candida albicans isolates

Context: Uncaria tomentosa D.C. (Rubiaceae) has several biological activities, including activity against resistant Candida strains. The synergistic interaction with terbinafine or fluconazole can be an important alternative to overcome this resistance.

Objectives: The potential synergy between a water insoluble fraction (WIF) from Uncaria tomentosa bark and the antifungals terbinafine (TRB) and fluconazole (FLZ) against non-Candida albicans resistant strains was investigated.

Materials and methods: TRB and FLZ, alone and combined with WIF, were tested by the checkerboard procedure using the micro-dilution technique against seven isolates of Candida glabrata and C. krusei. The molecular interactions occurring outside the cell wall were evaluated by scanning electron microscopy, Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) analysis.

Results: The checkerboard inhibitory assay demonstrated synergy for WIF:TRB and WIF:FLZ combinations, respectively. The best synergistic cell damage was demonstrated unequivocally for the associations of WIF and TRB (1.95:4.0?μg/mL) and WIF and FLZ (1.95:8.0?μg/mL). The comparison of the FT-IR spectra of the antifungal alone, and in combination with WIF, allows recognizing clear differences in 3000, 1600, 1400, and 700–800?cm^?1 bands. Additionally, modifications on TRB and FLZ thermograms were clearly noticed after their combination with WIF.

Conclusions: DSC and infrared analysis demonstrated intermolecular interactions between WIF and either TRB or FLZ. Hence, quite likely the synergistic effect is related to interaction events occurring outside the cell wall between antifungal and cat’s claw proanthocyanidins. A direct action on the cell wall is suggested, without connection with the ABC efflux pump mechanism.     

Solubility of E2050 at various pH: a case in which apparent solubility is affected by the amount of excess solid

The solubility of E2050, supplied as a dihydrochloride salt, in aqueous solutions at different pHs was studied. Two pK(a)s controlling the equilibrium between the various protonated species were determined. The solubility-pH profile of E2050 is expected to be high in acidic solutions because protonated species are formed and to be low in alkaline conditions due to the formation of hydrophobic free base. The solubility is also affected by chloride ion, a common ion for this drug substance. Two solubility products (K(sp)) were determined corresponding to the solubility of di-HCl salt and mono-HCl salt. Based on the pK(a)s (3.10 and 7.71), the solubility products with chloride (2.92 and 3.77 as corresponding pK(sp)), and the solubility of free base (2 x 10(-5) M), the solubility in solutions with different pH and different levels of chloride ion can be predicted. The prediction of the solubility change during the dilution of E2050 parenteral formulations by saline was also demonstrated. Furthermore, the present study presents an interesting example in which an apparent solubility can be different if varying (excess) amounts of salt are added to the solution. In this case, excess chloride ion suppresses the solubility in the pH region where mono-HCl salt controls the solubility.     

Introduction: Progress and issues in drug treatment courts

The first drug treatment court began in Miami, Florida in 1989, in direct response to the backlog of court cases for drug possession and trafficking. By mid-2001, there were 700 operational drug treatment courts and 400 more in the planning stages in the United States. In addition to providing an overview of the growth and development of drug treatment courts in the United States, this special issue examines their development in Australia, Canada, and the United Kingdom. The primary focus is the evaluation research conducted to date, which identifies some of the critical unresolved issues facing drug treatment courts.     

Screening for statin-related toxicity: the yield of transaminase and creatine kinase measurements in a primary care setting

BACKGROUND: Recommendations for monitoring levels of transaminases (alanine aminotransferase and aspartate aminotransferase) and of creatine kinase (CK) in patients taking 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) vary and are not based on data from clinical practice. We performed a study to determine the yield of routine screening of aminotransferase and CK levels among patients taking statins. METHODS: We performed a retrospective review of a primary care practice's computerized medical record. A computerized search identified all patients with a statin on their medication list and gave their alanine aminotransferase, aspartate aminotransferase, and CK values for 1998. We reviewed the records of all patients for whom these values were significantly or moderately abnormal to determine the values' relationship to statin therapy and outcomes. RESULTS: During the year of the study, 1014 (85%) of the 1194 patients who had a statin on their medication list had at least 1 monitoring test performed. Of these 1014 patients, 10 (1.0%) had a significant elevation and 5 (0.5%) a moderate elevation of transaminase levels, but none of these abnormalities appeared to be related to statin use. Moreover, 6 (0.9%) patients had at least 1 significantly abnormal CK value but it did not appear to be attributable to a statin; and of the 14 (2.1%) patients who had a moderate CK elevation, it was potentially due to a statin in only 2. There were no documented adverse sequelae associated with these abnormal results. CONCLUSIONS: In this study of statin use in a primary care practice, routine monitoring revealed no cases of significantly or moderately abnormal transaminase values attributable to statins. No significantly abnormal and only 2 moderately abnormal CK values were potentially attributable to statin use. This study questions the usefulness of routine measurement of transaminase and CK levels in all patients taking statins.