A Pilot Study of the Pharmacogenetics of Ketamine-Induced Emergence Phenomena: A Dissertation

Background: Up to 55% of patients administered ketamine, experience an emergence phenomena (EP) that closely mimics schizophrenia and increases their risk of injury. While genetics accounts for about 50% of severe adverse drug reactions, no studies have investigated genetic association of ketamine-induced EP in healthy patients. Ketamine is metabolized by CYP 2B6 enzymes and CYP 2B^8^ allele significantly alter ketamine metabolism. In addition, ketamine exerts most of its effects by inhibiting the N-methyl-D-aspartate receptor (NMADR), and NMDAR genes (GRIN2B) are associated with learning and memory impairment and schizophrenia. Purpose: To investigate the relationship between CYP2B6*6 and GRIN2B single nucleotide polymorphisms (SNPs) and ketamine-induced emergence phenomena (EP). Methods: This cross-sectional pharmacogenetic study recruited 75 patients having minor orthopedic, hand, foot, anorectal surgeries from two outpatient surgical centers. EP was measured with the Clinician Administered Dissociative State Scale (CADSS). DNA was genotyped using standard Taqman assays and protocols. Genetic association of CYP2B6*6 and GRIN2B (rs1019385 & rs1806191) SNPs and ketamine induced EP occurrence and severity were tested using multivariate logistic and linear regression, adjusting for age, ketamine dose, duration of anesthesia, and time since ketamine administration. Results: Forty-seven patients (63%) received ketamine and were genotyped. Nineteen EP cases were identified (CADSS \u3e 4), leaving 28 non-EP controls. For our population, CADSS has an internal consistency reliability Cronbach’s alpha of 0.82, and could reliably distinguish ketamine from non-ketamine cases. Occurrence and severity of EP were not associated with CYP2B6*6 or GRIN2B (p \u3e 0.1). Models removing genotype and containing age, ketamine dose, duration of v anesthesia, and time since ketamine administration significantly predicted EP occurrence (p = 0.001) and severity (p = 0.007). Presence and severity of EP did not affect patient satisfaction with care. Discussion: Younger age, higher dose and longer duration of anesthesia significantly predicted EP occurrence and severity among our sample. This study provides effect size estimates useful for the design of adequately powered future genetic association studies. The feasibility of recruitment from patients undergoing elective, outpatient surgeries and ease of post-operative EP assessment with CADSS supports our approach. However, the small sample size may have limited about ability to determine significant differences. Conclusion: Fully powered studies are needed to investigate this important phenomena. Determining factors for anesthesia-related EP symptoms may reduce risks and costs associated with this adverse medication effect

The pace of biological aging helps explain the association between insomnia and chronic low back pain

Chronic low back pain (cLBP) is associated with insomnia and advanced age. Emerging evidence suggests that the severity of both sleep disorders (like insomnia) and chronic pain are associated with a faster pace of biological aging. We aimed to determine whether the pace of biological age mediates the relationship between insomnia and the impact of cLBP in a sample of community-dwelling adults ages 19 to 85 years. Participants (49 with no pain, 32 with low-impact pain, and 37 with high-impact pain) completed sociodemographic, pain, insomnia, and short physical performance battery assessments. We calculated the pace of biological aging using DunedinPACE from blood leukocyte DNA. On average, individuals with high-impact cLBP had significantly faster biological aging than those with low-impact and no chronic pain

Pharmacogenetics of Ketamine-Induced Emergence Phenomena: A Pilot Study

BACKGROUND: Up to 55% of patients who are administered ketamine experience an emergence phenomena (EP) that closely mimics schizophrenia and increases their risk of injury; however, to date, no studies have investigated genetic association of ketamine-induced EP in healthy patients. OBJECTIVES: The aim of the study was to investigate the feasibility and sample sizes required to explore the relationship between CYP2B6*6 and GRIN2B single-nucleotide polymorphisms and ketamine-induced EP. METHODS: This cross-sectional, pharmacogenetic candidate, gene pilot study recruited 75 patients having minor elective outpatient surgeries. EP was measured with the Clinician Administered Dissociative State Scale. Genetic association of CYP2B6*6 and GRIN2B (rs1019385 and rs1806191) single-nucleotide polymorphisms and ketamine-induced EP occurrence and severity were tested using logistic and linear regression. RESULTS: Forty-seven patients (63%) received ketamine and were genotyped, and 40% of them experienced EP. Occurrence and severity of EP were not associated with CYP2B6*6 or GRIN2B (p \u3e .10). Exploratory analysis of nongenotype models containing age, ketamine dose, duration of anesthesia, and time from ketamine administration to assessment for EP significantly predicted EP occurrence (p = .001) and severity (p = .007). This pilot study demonstrates feasibility for implementing a pharmacogenetic study in a clinical setting, and we estimate that between 380 and 570 cases will be needed to adequately power future genetic association studies. DISCUSSION: Younger age, higher dose, and longer duration of anesthesia significantly predicted EP occurrence and severity among our pilot sample. Although the small sample size limited our ability to demonstrate significant genotype differences, we generated effect sizes, sample size estimates, and nongenetic covariates information in order to support future pharmacogenetic study design for evaluating this adverse event

Engaging teens and parents in collaborative practice: perspectives on diabetes self-management

PURPOSE: The purpose of this exploratory focus group study was to describe the perspectives of teens and their parents about self-management knowledge, behaviors (including division of labor associated with T1D management), and resources used to manage T1D. The overall goal is to use this information to develop a teen-family transition clinic. METHODS: The self and family management behaviors framework undergirded the separate teen-parent focus groups that were conducted concurrently. Note-based qualitative content analysis was used, resulting in several important messages. RESULTS: From the teens\u27 perspective there was variation in interest in learning more about T1D and management. Those teens who had been diagnosed at a very young age reported not knowing anything else but diabetes, while those diagnosed later developmentally embraced the active learning process. Diabetes camp and peer group support were not seen as beneficial. All the teens were interested in helping others with diabetes. Parents shared the common struggle with transition of self-management, with variation in parenting styles. A small group of parents reported their job as a parent was to make sure their child was self-sufficient in self-management, but felt pressure from the health care providers (HCPs) to physically do the care, defeating the purpose. Parents and teens reported wanting HCPs to be less focused on numbers (blood glucose levels) and more on the whole person. Scheduling appointment changes and long waiting times were reported as problematic by all participants. CONCLUSIONS: Teen and parent perspectives are critical in designing future well-received adolescent-family transition clinics. Development from the ground up with family recommendations may contribute to high-quality health outcomes

Confronting Racism in Pain Research: A Call to Action

Racism is an established health determinant across the world. In this 3-part series, we argue that a disregard of how racism manifests in pain research practices perpetuates pain inequities and slows the progression of the field. Our goal in part-1 is to provide a historical and theoretical background of racism as a foundation for understanding how an antiracism pain research framework - which focuses on the impact of racism, rather than “race,” on pain outcomes - can be incorporated across the continuum of pain research. We also describe cultural humility as a lifelong self-awareness process critical to ending generalizations and successfully applying antiracism research practices through the pain research continuum. In part-2 of the series, we describe research designs that perpetuate racism and provide reframes. Finally, in part-3, we emphasize the implications of an antiracism framework for research dissemination, community-engagement practices and diversity in research teams. Through this series, we invite the pain research community to share our commitment to the active process of antiracism, which involves both self-examination and re-evaluation of research practices shifting our collective work towards eliminating racialized injustices in our approach to pain research

Confronting Racism in All Forms of Pain Research: A Shared Commitment for Engagement, Diversity, and Dissemination

This third paper in the “Confronting Racism in All Forms of Pain Research” series discusses adopting an antiracism framework across all pain research disciplines and highlights the significant benefits of doing so. We build upon the previous call to action and the proposed reframing of study designs articulated in the other papers in the series and seek to confront and eradicate racism through a shared commitment to change current research practices. Specifically, we emphasize the systematic disadvantage created by racialization (ie, the Eurocentric social and political process of ascribing racialized identities to a relationship, social practice, or group) and discuss how engaging communities in partnership can increase the participation of racialized groups in research studies and enrich the knowledge gained. Alongside this critical work, we indicate why diversifying the research environment (ie, research teams, labs, departments, and culture) enriches our scientific discovery and promotes recruitment and retention of participants from racialized groups. Finally, we recommend changes in reporting and dissemination practices so that we do not stigmatize or reproduce oppressive forms of power for racialized groups. Although this shift may be challenging in some cases, the increase in equity, generalizability, and credibility of the data produced will expand our knowledge and reflect the pain experiences of all communities more accurately

Confronting Racism in Pain Research: Reframing Study Designs

This second paper in a 3-part series on antiracism in pain research across the translational spectrum focuses on study design factors. Although objectivity is a cornerstone value of science, subjectivity is embedded in every step of the research process as investigators make choices about who they collaborate with, which research questions they ask, how they recruit participants, which research tools they use, and how they analyze and interpret data. We present theory and evidence from disciplines such as sociology, medical anthropology, statistics, and public health to discuss 4 common study design factors, including 1) the dominant biomedical narrative of pain that restricts funding and exploration of social indicators of pain, 2) low diversity and inclusion in pain research enrollment that restricts generalizability to racialized groups, 3) the use of “race” or “ethnicity” as a statistical variable and proxy for lived experiences (eg, racism, resilience), and 4) limited modeling in preclinical research for the impact of social factors on pain physiology. The information presented in this article is intended to start conversations across stakeholders in the pain field to explore how we can come together to adopt antiracism practices in our work at large to achieve equity for racialized groups

Greater socioenvironmental risk factors and higher chronic pain stage are associated with thinner bilateral temporal lobes

Abstract Introduction: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is evident. Methods: Consistent with the prior study, the sample was comprised of 147 adults (95 women, 52 men), 45–85 years of age, who self‐identified as non‐Hispanic Black (n = 72) and non‐Hispanic White (n = 75), with knee pain with/at risk for osteoarthritis. Measures included demographics, health history, pain questionnaires, cognitive screening, body mass index, individual‐ and community‐level socioenvironmental factors (education, income, household size, marital and insurance status, and area deprivation index), and brain imaging. We computed a summative socioenvironmental risk index. Results: Regression analyses showed that with the inclusion of socioenvironmental factors, the model was significant (p < .001), and sociodemographic (ethnic/race) group differences were not significant (p = .118). Additionally, findings revealed an additive stress load pattern indicating thinner temporal lobe cortices with greater socioenvironmental risk and chronic pain severity (p = .048). Implications: Although individual socioenvironmental factors were not independent predictors, when collectively combined in models, ethnic/race group differences in bilateral temporal lobe structures were not replicated. Further, combined socioenvironmental risk factors and higher chronic pain severity were associated with thinner bilateral temporal lobes