Neuropsychiatric Complications of Efavirenz Therapy: Suggestions for a New Research Paradigm

Literature supports a relationship between attachment style and emotional regulation (Panfile & Laible, 2012; Waters, Virmani, Thompson, Meyer, & Jochem, 2010; Mikulincer, & Shaver, 2005; Cassidy, 1994). Research also indicates that emotional regulation is linked to cognitive and behavioral regulation (Garner & Waajid, 2012; Denham, Bassett, Way, Mincic, Zinsser, & Graling, 2012; Tarullo, Obradovic, & Gunnar, 2009; Ramani, Brownell, & Campbell, 2010; Raver, Garner, & Smith-Donald, 2007). However, existing literature surrounding attachment theory and various components of self-regulation is limited. The paucity of information available and lack of consensus about the definition of cognitive and behavioral regulation make them difficult constructs to examine. Furthermore, a relationship between attachment status and salient self-regulation abilities has never been studied individually. Insecurely attached infants have a harder time achieving emotional, behavioral and cognitive regulation when compared to their secure counterparts. This study examines the relationship between attachment status and self-regulation at preschool age by analyzing data from the Early Childhood Longitudinal Study -Birth Cohort. The Early Childhood Longitudinal Study-Birth Cohort is the most recent longitudinal data set that captures socio-emotional as well as physical development in a variety of caregiver settings for young children (Sparks, 2009; Kotelchuck, 2009; Paulson, Keef, & Leiferman, 2009). Attachment was measured using the Toddler Attachment Sort-45 (Bimler & Kirkland, 2002; Kirkland, Bimler, Drawneek, McKim, Schölmerich, & Axel, 2004). Emotional, behavioral, and cognitive elements of self-regulation at preschool age were measured in Early Care and Education Provider interviews that incorporated elements of socio-emotional development in the context of the environment. The final sample contained 2,650 children. Results indicated that self-regulation is significantly related to attachment status at preschool age. Securely attached preschoolers have overall higher self-regulation scores in most domains than insecurely attached preschoolers. Analysis of Covariance between self-regulation types and attachment style revealed significant relationships between secure attachment and high levels of emotional, behavioral, and cognitive regulation. Furthermore, pair wise comparisons revealed that ambivalent attached preschoolers have low levels of emotional self-regulation when compared to their secure and avoidant attached counterparts. Pairwise comparisons between attachment groups and self-regulation measures also revealed that avoidant attached infants experience low levels of cognitive regulation. The implications of these results are addressed in the discussion.

The terms 'adverse drug effects' and 'adverse drug reactions' are commonly used interchangeably, but they have different implications. Adverse drug reactions arise when a compound (e.g. a drug or metabolite, a contaminant or adulterant) is distributed in the same place as a body tissue (e.g. a receptor, enzyme, or ion channel), and the encounter results in an adverse effect (a physiological or pathological change), which results in a clinically appreciable adverse reaction. Both the adverse effect and the adverse reaction have manifestations by which they can be recognized: adverse effects are usually detected by laboratory tests (e.g. biochemical, haematological, immunological, radiological, pathological) or by clinical investigations (e.g. endoscopy, cardiac catheterization), and adverse reactions by their clinical manifestations (symptoms and/or signs). This distinction suggests five scenarios: (i) adverse reactions can result directly from adverse effects; (ii) adverse effects may not lead to appreciable adverse reactions; (iii) adverse reactions can occur without preceding adverse effects; (iv) adverse effects and reactions may be dissociated; and (v) adverse effects and reactions can together constitute syndromes. Defining an adverse drug reaction as "an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product" suggests a definition of an adverse drug effect: "a potentially harmful effect resulting from an intervention related to the use of a medicinal product, which constitutes a hazard and may or may not be associated with a clinically appreciable adverse reaction and/or an abnormal laboratory test or clinical investigation, as a marker of an adverse reaction."

No abstract available.

Troubles de l’humeur et prophylaxie antipaludique (méfloquine) : à propos de deux cas

Adolescent cognitive and behavioral regulation is influenced by multidimensional and multidirectional processes within and across biological and contextual systems that shift throughout development. Key among these influences are distal processes such as early life socioeconomic position (SEP), and proximal processes such as pubertal development, but questions remain concerning how links between SEP, pubertal development, and cognitive and behavioral regulation accumulate and unfold over adolescence. In the current study, and in line with Dr. John Schulenberg's foundational work, direct associations between SEP, puberty, and adolescent cognitive and behavioral regulation were examined; then pubertal timing and tempo were considered as moderators and mediators of links between SEP and adolescent cognitive and behavioral regulation. Data were drawn from the NICHD Study of Early Child Care and Youth Development, a longitudinal study of 970 youth (52% male; 80% White, 13% Black, and 7% another race/ethnicity). Cognitive and behavioral regulation was measured using direct assessments of working memory, planning, risky decision‐making, and impulse control at age 15. SEP included maternal education and family income‐to‐needs and was averaged from birth to 54 months old; estimates of pubertal timing and tempo were derived using logistic growth curve models from age 9 to age 15. SEP was directly associated with cognitive and behavioral regulation. Pubertal development tended to moderate those links, but rarely mediated them. Specifically, socioeconomic disadvantage along with earlier timing or faster tempo tended to be associated with worse cognitive and behavioral regulation. Overall, findings suggest that pubertal timing and tempo may exacerbate existing environmental constraints.

Depressive Symptoms Predict Increased Incidence of Neuropsychiatric Side Effects in Patients Treated with Efavirenz

Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial. The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital. We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment. Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests. A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response. A psychiatric history was a strong risk factor for depression, anxiety and other psychiatric disorders during treatment. Neuropsychiatric adverse effects during interferon-based treatments in patients with chronic hepatitis C were common but mostly mild or moderate. Early detection and accurate multidisciplinary management avoided treatment discontinuation, ensuring adherence and attaining sustained viral response. The identified risk factors could be used to determine patients eligible for interferon-free combinations, thus optimizing health system economics.

Frequency of Allergic or Hematologic Adverse Reactions to Ticlopidine Among Patients With Allergic or Hematologic Adverse Reactions to Clopidogrel

A variety of newer antiepileptic drugs (AEDs) are now available for treating patients with epilepsy in addition to the 'conventional' drugs that have been available throughout a large part of the last century. Since these drugs act to suppress the pathological neuronal hyperexcitability that constitutes the final substrate in many seizure disorders, it is not surprising that they are prone to causing adverse reactions that affect the CNS.Information on adverse effects of the older AEDs has been mainly observational. Equally, whilst the newer drugs have been more systematically studied, their long-term adverse effects are not clearly known. This is illustrated by the relatively late emergence of the knowledge of visual field constriction in the case of vigabatrin, which only became known after several hundred thousand patient-years of use. However, older drugs continue to be studied and there has been more recent comment on the possible effect of valproate (valproic acid) on cognition following exposure to this drug in utero.With most AEDs, there are mainly dose-related adverse effects that could be considered generic, such as sedation, drowsiness, incoordination, nausea and fatigue. Careful dose titration with small initial doses can reduce the likelihood of these adverse effects occurring. Adverse effects such as paraesthesiae are more commonly reported with drugs such as topiramate and zonisamide that have carbonic anhydrase activity. Weight loss and anorexia can also be peculiar to these drugs. Neuropsychiatric adverse effects are reported with a variety of AEDs and may not be dose related. Some drugs, such as carbamazepine when used to treat primary generalized epilepsy, can exacerbate certain seizure types. Rare adverse effects such as hyperammonaemia with valproate are drug specific. There are relatively very few head-to-head comparisons of AEDs and limited information is available in this regard.In this review, we discuss the available literature and provide a comprehensive summary of adverse drug reactions of AEDs affecting the CNS.

BackgroundThe JoyPop™ smartphone app is a digital intervention designed to enhance day-to-day resilience in youth, particularly those exposed to traumatogenic events [adverse childhood experiences (ACEs)]. Processes of adaptation that foster resilience in response to high stress include affect, cognitive, and behavioral regulation, and social interaction. Digital interventions have application for youth and those who provide them support, including social work trainees navigating the stressors of university studies concurrent with practice internships. Research on resilience-enhancing apps is needed to understand the underlying mechanisms by which change occurs and who is most likely to benefit from these interventions.MethodsSocial work student participants (N = 91) were invited to use the JoyPop app two times daily for 28 days. Baseline ACE exposure and change-over-time in affect regulation, stress responsivity, and social support were evaluated after 2 and 4 weeks of app use with t-tests and generalized estimating equation (GEE) modeling.ResultsParticipants identified predominantly as cisgender women of European descent, mean age 26 years (SD = 6.78), 70% undergraduates, and reported consistent daily app use (Mean days = 26.9, SD = 1.90). Self-reported baseline ACE exposure was high (30% ≥ 5+). We tested change-over-time with generalized estimating equation and saw improvement in affect regulation in the Abbreviated Dysregulation Inventory scale (β = −3.38, p = <.001), and subscales of behavioral (β = −1.63, p = <.001), affect (β = −3.24, p = <.001), and cognitive regulation (β = 1.50, p = .009). Perceived stress decreased with app use (β = −2.65, p = <.001) and even more so for participants with reported exposure to more than 4 ACEs (β = −3.786, p = .030).ConclusionsThe exploratory findings from our pilot study suggest that consistent use of the app may enhance multidimensional resilience amongst university students who self-report higher than average levels of baseline traumatogenic exposures. Our findings support an approach modeling resilience as a complex, dynamic, multicomponent process supported by resources within and between individuals. Further testing of the mechanisms of adaptation in response to high stress that enhance resilience and identification of the JoyPop™ app features that influence this change is needed to validate that daily app use could help youth with experiences of past and current high stress to better regulate their affect, reduce stress reactivity, and increase resilience.

Individual differences in self-regulation have been a topic of increased empirical research. However, few investigations have been conducted on how sub-components of self-regulation differentially predict education outcomes over time. We examined cognitive and behavior regulation as predictors of middle-school students’ (n = 127) long-term academic achievement. It has been previously reported that behavior regulation, not cognitive regulation, predicts state standardized test scores in the first year (Modrek et al. 2019). However, here we show that after two years, this pattern flips in that cognitive regulation, not behavior regulation, predicts state standardized test scores for both math and English. We analyzed the mediating role of learning using structural equation modeling, suggesting the differing roles of self-regulation in education where certain facets may or may not affect students’ long-term outcomes.

A strict gluten-free diet is the only treatment for celiac disease (CD), yet dietary adherence can be challenging for youth and may be impacted by the youth’s executive functioning and attentional abilities. This study aimed to investigate whether attention and executive functioning (EF) were associated with dietary adherence in children with CD. Parents of 34 children (child age M(SD) = 13.01(3.88), 56% female) from a multidisciplinary CD clinic completed ratings of attention and EF and dietary adherence. Parent-reported adherence was negatively correlated with behavioral regulation (r = -.52, p < .01, r 2 = .27, 95% confidence interval (CI) [−.73, −.22]) and cognitive regulation (r = -.48, p < .01, r 2 = .23, 95% CI [−.71, −.17]), with an interaction by age (p = .01, adjusted R 2 = .35, B = −0.15, 95% CI [−0.29, −0.07]) for behavior regulation. Youth who were rated as less adherent by their parents were rated as having more problems with behavioral (e.g. inhibition and self-monitoring) and cognitive regulation (e.g. planning, organization), and adolescents with lower parent-rated adherence were rated as having more problems with behavioral regulation in particular. Executive functioning deficits are an important treatment consideration for CD, particularly during adolescence.

Consumer reporting of adverse drug reactions: Systems that allow patients to report side effects of the drugs they are taking have yielded valuable information for improving drugs safety and health care.

Objective: Levetiracetam is commonly used in malignant glioma populations because of its efficacy, limited drug-drug interactions and adverse effects. Although, there has been growing evidence of adverse neuropsychiatric side effects from levetiracetam; however, such evidence in malignant brain tumor settings is limited. Hence, we hypothesized that malignant glioma patients exposed to levetiracetam would also experience more adverse neuropsychiatric effects compared to patients not receiving this medication.Material and Methods: A retrospective cohort analysis was conducted in 150 high grade malignant glioma patients at our Cleveland Clinic Cancer Center; from 2013-2014, comparing the accumulative adverse neuropsychiatric outcomes between patients who received levetiracetam and patients who did not (n=108 and 42, respectively). A sub-analysis of each specific neuropsychiatric side effect between these two groups was performed.Results: Patients with malignant glioma receiving levetiracetam had increased risk of developing neuropsychiatric adverse effects compared to the non-levetiracetam group (odds ratio=2.08, p-value=0.040, 95% confidence interval=1.00-4.36). After adjusting for confounding factors, past psychiatric history and the interaction between seizure and levetiracetam use was significantly associated with neuropsychiatric problems. Delirium, psychosis, and irritability were more common in the levetiracetam group, and likely led to more psychiatric referrals, starting of psychotropic medications, and vitamin B6 use.Conclusion: Incidence of neuropsychiatric presentations in malignant glioma patients was higher in the levetiracetam exposed group than the non-exposed group. The changes, or emergence of new neuropsychiatric behaviors should prompt clinicians to search for possible causes; including levetiracetam adverse effects, so they can be managed accordingly.

Adaptability has been recently proposed as cognitive, behavioural, and emotional regulation assisting individuals to effectively respond to change, uncertainty and novelty. Given students with attention-deficit/hyperactivity disorder (ADHD) have known impairments with regulatory functions, they may be at particular disadvantage as they seek to navigate change, uncertainty, and novelty in their academic lives. This discussion summarises current research of adaptability as relevant to students with ADHD, presents preliminary exploration of data that suggests evidence for the difficulties students with ADHD face with regards to adaptability (particularly in regards to cognitive and behavioural regulation), and concludes with suggestions for counselling, psychological, and educational practices aimed at enhancing the adaptability of students with ADHD.