Standard Versus Family-Based Screening, Brief Intervention, and Referral to Treatment for Adolescent Substance Use in Primary Care: Protocol for a Multisite Randomized Effectiveness Trial.

BACKGROUND: Screening, brief intervention, and referral to treatment for adolescents (SBIRT-A) is widely recommended to promote detection and early intervention for alcohol and other drug (AOD) use in pediatric primary care. Existing SBIRT-A procedures rely almost exclusively on adolescents alone, despite the recognition of caregivers as critical protective factors in adolescent development and AOD use. Moreover, controlled SBIRT-A studies conducted in primary care have yielded inconsistent findings about implementation feasibility and effects on AOD outcomes and overall developmental functioning. There is urgent need to investigate the value of systematically incorporating caregivers in SBIRT-A procedures. OBJECTIVE: This randomized effectiveness trial will advance research and scope on SBIRT-A in primary care by conducting a head-to-head test of 2 conceptually grounded, evidence-informed approaches: a standard adolescent-only approach (SBIRT-A-Standard) versus a more expansive family-based approach (SBIRT-A-Family). The SBIRT-A-Family approach enhances the procedures of the SBIRT-A-Standard approach by screening for AOD risk with both adolescents and caregivers; leveraging multidomain, multireporter AOD risk and protection data to inform case identification and risk categorization; and directly involving caregivers in brief intervention and referral to treatment activities. METHODS: The study will include 2300 adolescents (aged 12-17 y) and their caregivers attending 1 of 3 hospital-affiliated pediatric settings serving diverse patient populations in major urban areas. Study recruitment, screening, randomization, and all SBIRT-A activities will occur during a single pediatric visit. SBIRT-A procedures will be delivered digitally on handheld tablets using patient-facing and provider-facing programming. Primary outcomes (AOD use, co-occurring behavior problems, and parent-adolescent communication about AOD use) and secondary outcomes (adolescent quality of life, adolescent risk factors, and therapy attendance) will be assessed at screening and initial assessment and 3-, 6-, 9-, and 12-month follow-ups. The study is well powered to conduct all planned main and moderator (age, sex, race, ethnicity, and youth AOD risk status) analyses. RESULTS: This study will be conducted over a 5-year period. Provider training was initiated in year 1 (December 2023). Participant recruitment and follow-up data collection began in year 2 (March 2024). We expect the results from this study to be published in early 2027. CONCLUSIONS: SBIRT-A is widely endorsed but currently underused in pediatric primary care settings, and questions remain about optimal approaches and overall effectiveness. In particular, referral to treatment procedures in primary care remains virtually untested among youth. In addition, whereas research strongly supports involving families in interventions for adolescent AOD, SBIRT-A effectiveness trial testing approaches that actively engage family members in primary care are absent. This trial is designed to help fill these research gaps to inform the critical health decision of whether and how to include caregivers in SBIRT-A activities conducted in pediatric primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05964010; https://www.clinicaltrials.gov/study/NCT05964010. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54486.

Launching Relationship-Oriented Behavioral Services for Youth Opioid Use Disorder: Innovations in Medication Decision-Making and Adherence Planning.

This article presents behavioral interventions designed to enhance uptake and retention on medication for opioid use disorder (MOUD) among transition-age youth (16-25 years) enrolled in treatment services. The article describes three relationship-oriented interventions designed to address barriers to MOUD uptake, enhance MOUD adherence planning, and strengthen OUD recovery among youth: Relational Orientation; Medication Education and Decision-making Support, and Family Leadership and Ownership of Adherence to Treatment. These interventions are inter-connected can be delivered flexibly. The article concludes with three case examples that illustrate how these modular interventions can be tailored to meet the needs of diverse client profiles.

Training Community Therapists in Core Elements of CBT and Family Therapy for Adolescent Externalizing Problems.

OBJECTIVE: This pilot study tested pragmatic methods for training therapists in core techniques of two evidence-based interventions (EBIs) for adolescent externalizing problems: cognitive-behavioral therapy (CBT) or family therapy (FT). Training methods were designed to help therapists accurately self-monitor their use of EBIs and increase delivery of EBIs with current clients. The study compared coder training only versus coder training plus fidelity-focused consultation. METHOD: Therapists (N = 42) from seven behavioral health clinics reported on 65 youth clients; four clinics elected to train in CBT and three in FT. Therapists were randomized to either coder training only, consisting of a 25-week observational coder training course (didactic instruction and mock session coding exercises in core EBI techniques); or coder training plus fidelity-focused consultation, consisting of direct-to-therapist fidelity measurement feedback along with fidelity-focused expert consultation. During the 25 weeks of training, therapists submitted self-report data on EBI use along with companion session audiotapes subsequently coded by observational raters. RESULTS: Compared to coder training only, coder training plus fidelity-focused consultation produced superior effects in therapist ability to judge the extensiveness of EBI techniques in online coding sessions, as well as therapist ability to self-rate use of EBI techniques with their own cases. In both conditions, therapists who trained in CBT showed a significant, though modest, increase in real-world delivery of core CBT techniques; this did not occur for FT. CONCLUSIONS: Pragmatic training and consultation methods show promise as viable and effective options for enhancing EBI fidelity monitoring and, for CBT, increasing EBI delivery.

Caregiver Engagement in Outpatient Treatment for Adolescents in Community Settings: Construct and Predictive Validity of Family Therapy Techniques.

Caregiver engagement and participation in community-based outpatient treatment services for adolescents is generally poor, which is problematic given the integral role of caregivers prescribed by evidence-based treatments across orientations. The current study explores the psychometric and predictive properties of a set of caregiver engagement techniques distilled from family therapy, used by community clinicians in routine care. It highlights relational engagement interventions and adds to growing work distilling core elements of family therapy. The study examined caregiver engagement techniques observed in 320 recorded sessions and outcome data from 152 cases treated by 45 therapists participating in one of three randomized trials investigating delivery of family therapy for adolescent behavior problems in community settings. Construct and predictive validity of caregiver engagement coding items were analyzed to understand the degree to which they cohered as a single factor and predicted outcomes in predictable ways. Results demonstrated item reliability and construct validity of a Caregiver Engagement Techniques factor. Greater use of these techniques was associated with decreased adolescent substance use. Unexpected results suggested greater use of techniques was associated with worsening internalizing symptoms and family cohesion per youth-report only. Post-hoc analyses revealed additional complexities in the association between engagement techniques and outcomes. Caregiver engagement practices tested in the current study represent a unified treatment factor that may contribute to positive therapeutic outcomes for adolescents in some clinical domains. Further research is needed to understand predictive effects.

Core Elements of Family Therapy for Adolescent Behavioral Health Problems: Validity Generalization in Community Settings.

OBJECTIVE: The core elements of family therapy for adolescent mental health and substance use problems, originally distilled from high-fidelity sessions conducted by expert clinicians, were tested for validity generalization when delivered by community therapists in routine settings. METHOD: The study sampled recorded sessions from 161 cases participating in one of three treatment pools: implementation trial of Functional Family Therapy (98 sessions/50 cases/22 therapists), adaptation trial of Multisystemic Therapy (115 sessions/59 cases/2 therapists), and naturalistic trial of non-manualized family therapy in usual care (107 sessions/52 cases/21 therapists). Adolescents were identified as 60% male and 40% female with an average age of 15.4 years; 49% were Latinx, 27% White Non-Latinx, 15% African American, 3% another race/ethnicity, 6% race/ethnicity unknown. Session recordings (n = 320) were randomly selected for each case and coded for 21 discrete family therapy techniques. Archived data of one-year clinical outcomes were gathered. RESULTS: Confirmatory factor analyses replicated the factor structure from the original distillation study, retaining all four clinically coherent treatment modules comprised of all 21 techniques: Interactional Change (ICC = .77, Cronbach's α = .81); Relational Reframe (ICC = .75, α = .81); Adolescent Engagement (ICC = .72, α = .78); Relational Emphasis (ICC = .76, α = .80). Exploratory analyses found that greater use of core techniques predicted symptom improvements in one treatment pool. CONCLUSIONS: Core techniques of family therapy distilled from manualized treatments for adolescent behavioral health problems showed strong evidence of validity generalization, and initial evidence of links to client outcomes, in community settings.

Pilot Trial of Online Measurement Training and Feedback in Family Therapy for Adolescent Behavior Problems.

OBJECTIVE: Pragmatic procedures for sustaining high-fidelity delivery of evidence-based interventions are needed to support implementation in usual care. This study tested an online therapist training system, featuring observational coder training and self-report fidelity feedback, to promote self-report acumen and routine use of family therapy (FT) techniques for adolescent behavior problems. METHOD: Therapists (N = 84) from nine substance use and mental health treatment sites reported on 185 adolescent clients. Therapists submitted baseline data on FT technique use with clients, completed a workshop introducing the 32-week training system, and were randomly assigned by site to Core Training versus Core Training + Consultation. Core Training included a therapist coder training course (didactic instruction and mock session coding exercises in 13 FT techniques) and fidelity feedback procedures depicting therapist-report data on FT use. Consultation convened therapists and supervisors for one-hour monthly sessions with an external FT expert. During the 32 weeks of training, therapists submitted self-report data on FT use along with companion session audiotapes subsequently coded by observational raters. RESULTS: Therapist self-report reliability and accuracy both increased substantially during training. Observers reported no increase over time in FT use; therapists self-reported a decrease in FT use, likely an artifact of their improved self-report accuracy. Consultation did not enhance therapist self-report acumen or increase FT use. CONCLUSIONS: Online training methods that improve therapist-report reliability and accuracy for FT use may confer important advantages for treatment planning and fidelity monitoring. More intensive and/or different training interventions appear needed to increase routine FT delivery.

What is the Status of Multi-Informant Treatment Fidelity Research?

OBJECTIVE: The precise measurement of treatment fidelity (quantity and quality in the delivery of treatment strategies in an intervention) is essential for intervention development, evaluation, and implementation. Various informants are used in fidelity assessment (e.g., observers, practitioners [clinicians, teachers], clients), but these informants often do not agree on ratings. This scoping review aims to ascertain the state of science around multi-informant assessment of treatment fidelity. METHOD: A literature search of articles published through December 2021 identified 673 articles. Screening reduced the number of articles to 44, and the final study set included 35 articles. RESULTS: There was substantial variability across studies regarding study design, how fidelity was operationalized, and how reliability was defined and assessed. Most studies evaluated the agreement between independent observers and practitioner-report, though several other informant pairs were assessed. Overall, findings suggest that concordance across fidelity informants was low to moderate, with a few key exceptions. CONCLUSIONS: It is difficult to draw clear conclusions about the degree to which single versus multiple informant assessment is needed to produce an accurate and complete picture of treatment fidelity. The field needs to take steps to determine how to leverage multi-informant assessment to accurately assess treatment fidelity.

Mindfulness Meditation Interventions for Long COVID: Biobehavioral Gene Expression and Neuroimmune Functioning.

Some individuals infected with SARS CoV-2 have developed Post-Acute Sequelae of SARS CoV-2 infection (PASC) or what has been referred to as Long COVID. Efforts are underway to find effective treatment strategies for those with Long COVID. One possible approach involves alternative medical interventions, which have been widely used to treat and manage symptoms of a variety of medical problems including post-viral infections. Meditation has been found to reduce fatigue and unrefreshing sleep, and for those with post-viral infections, it has enhanced immunity, and reduced inflammatory-driven pathogenesis. Our article summarizes the literature on what is known about mindfulness meditation interventions, and reviews evidence on how it may apply to those with Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Evidence is reviewed suggesting effective and sustainable outcomes may be achieved for symptomatology and underlying pathology of post-viral fatigue (PASC and ME/CFS).

Therapist Self-Report of Fidelity to Core Elements of Family Therapy for Adolescent Behavior Problems: Psychometrics of a Pragmatic Quality Indicator Tool.

Therapist-report measures of evidence-based interventions have enormous potential utility as quality indicators in routine care; yet, few such tools have shown strong psychometric properties. This study describes reliability and validity characteristics of a therapist-report measure of family therapy techniques for treating adolescent conduct and substance use problems: Inventory of Therapy Techniques for Core Elements of Family Therapy (ITT-CEFT). Study participants included 31 staff therapists treating 68 adolescent clients in eight community-based mental health and substance use clinics. Therapists submitted ITT-CEFT checklists and companion audio recordings for 189 sessions. The ITT-CEFT contains 13 techniques identified as core elements of three manualized family therapy models that are empirically supported for the target group. Therapists also reported on their use of three motivational interventions, and independent observers coded the submitted recordings. ITT-CEFT factor validity was shown via confirmatory factor analyses of the tool's theoretical structure. Derived modules were: Family Engagement (four items; Cronbach's α = .72); Relational Orientation (five items; α = .74); and Interactional Change (four items; α = .66). Concurrent validity analyses showed fair-to-excellent therapist reliability compared to observer ratings (ICCs range .64-.75); they showed moderate therapist accuracy compared to observer mean scores, reflecting a tendency to overestimate delivery of the techniques. Discriminant validity analyses showed tool differentiation from motivational interventions. Results offer provisional evidence for the feasibility of using the therapist-report ITT-CEFT to anchor quality procedures for family therapy interventions in real-world settings.Trial Registration: The parent clinical trial is registered at www.ClinicalTrials.gov , ID: NCT03342872 (registration date: 11.10.17).

Online Training of Community Therapists in Observational Coding of Family Therapy Techniques: Reliability and Accuracy.

A foundational strategy to promote implementation of evidence-based interventions (EBIs) is providing EBI training to therapists. This study tested an online training system in which therapists practiced observational coding of mock video vignettes demonstrating family therapy techniques for adolescent behavior problems. The study compared therapists ratings to gold-standard scores to measure therapist reliability (consistency across vignettes) and accuracy (approximation to gold scores); tested whether reliability and accuracy improved during training; and tested therapist-level predictors of overall accuracy and change in accuracy over time. Participants were 48 therapists working in nine community behavioral health clinics. The 32-exercise training course provided online instruction (about 15 min/week) in 13 core family therapy techniques representing three modules: Family Engagement, Relational Orientation, Interactional Change. Therapist reliability in rating technique presence (i.e., technique recognition) remained moderate across training; reliability in rating extensiveness of technique delivery (i.e., technique judgment) improved sharply over time, from poor to good. Whereas therapists on average overestimated extensiveness for almost every technique, their tendency to give low-accuracy scores decreased. Therapist accuracy improved significantly over time only for Interactional Change techniques. Baseline digital literacy and submission of self-report checklists on use of the techniques in their own sessions predicted coding accuracy. Training therapists to be more reliable and accurate coders of EBI techniques can potentially yield benefits in increased EBI self-report acumen and EBI use in daily practice. However, training effects may need to improve from those reported here to avail meaningful impact on EBI implementation.Trial Registration: The parent clinical trial is registered at www.ClinicalTrials.gov , ID: NCT03342872 (registration date: 11.10.17).

Late frontal positivity effects in Self-referential Memory: Unique to the Self?

The self-reference effect in memory (SRE), in which stimuli related to self are better remembered than other stimuli, has been studied often in the fMRI literature, but much less with EEG. In two experiments, we investigated how self-referencing modulated event-related potential (ERP) markers of the subsequent memory effect, testing whether the same components that reflect memory success are impacted or whether unique components are modulated by self-referencing. Participants were asked to evaluate whether an adjective accurately described either the self or a given other by making a yes/no key press during EEG recording. Then participants were given a surprise recognition memory test where they judged each adjective as old or new. We observed a main effect of self-relevance on a late positivity at right frontal electrodes. A very similar effect was observed when comparing words subsequently remembered to those that were forgotten. However, no interaction was found between self-relevance and subsequent memory, suggesting the frontal positivity is not exclusive to the SRE, but instead a reflection of deeper encoding that leads to better memory. Thus, this frontal positivity may be a marker of a deeper encoding process that is elicited by self-referencing but not exclusive to the SRE.

Evaluation plan of the 6for6 research skills program for rural and remote physicians.

Overwhelming issues and barriers often prevent rural and remote physicians (RRPs) from pursuing the many socially accountable research questions they encounter on a daily basis. Although research training programs can empower RRPs to rise to these challenges, there is a lack of evidence on how they should be developed and refined. At Memorial University, a faculty development program (FDP) called 6for6 has been helping RRPs surmount their research quagmires and engage in scholarship since 2014. After an initial three-year (2014-17) pilot, we prepared a detailed plan to evaluate the 6for6 research FDP for RRPs and inform future years of delivery. Using a modified Delphi method and participatory action model a group of program team members, stakeholders and evaluation experts developed an evaluation plan including a logic model and an evaluation matrix addressing five key themes. To our knowledge, this is the first evaluation plan for a research-focused FDP targeting RRPs. While this plan was developed specifically for the 6for6 FDP, our approach to its development may be useful to any institution interested in evaluating an FDP with limited resources.

Conceptual framework for telehealth strategies to increase family involvement in treatment and recovery for youth opioid use disorder.

With opioid use at crisis levels, it is imperative to support youth ages with opioid use disorders (OUD) in taking medication and accessing behavioral services over long periods. This article presents a conceptual framework for telehealth strategies that can be adopted to increase family involvement across a four-stage continuum of youth OUD treatment and recovery: Treatment Preparation, Treatment Initiation, Treatment Stabilization, OUD Recovery. It first identifies provider-delivered tele-interventions that can enhance OUD services in each of the four stages, including family outreach, family engagement, family-focused intervention, and family-focused recovery maintenance. It then introduces several types of direct-to-family tele-supports that can be used to supplement provider-delivered interventions. These include both synchronous tele-supports (remote interactions that occur in real time) such as helplines, peer-to-peer coaching, and online support groups; and asynchronous tele-supports (communications that occur without participants being simultaneously present) such as automated text messaging, self-directed internet-based courses, and digital web support.

Randomized Trial of Academic Training and Medication Decision-Making for Adolescents with ADHD in Usual Care.

Objective: This study tested two family-based interventions designed for delivery in usual care: Changing Academic Support in the Home for Adolescents with ADHD (CASH-AA), containing motivational interventions, homework management and schoolwork organization training, and family-school partnership building; and Medication Integration Protocol (MIP), containing ADHD psychoeducation, medication decision-making, and integrated medication management.Method: This study used a cluster randomized design to test CASH-AA + MIP versus CASH-AA Only for adolescents with ADHD in five sites. Therapists (N = 49) were site clinicians randomized to condition. Clients (N = 145) included 72% males; 42% White Non-Hispanic, 37% Hispanic American, 15% African American, and 6% more than one race; average age was 14.8 years. Fidelity data confirmed protocol adherence and between-condition differentiation.Results: One-year improvements were observed across conditions in several outcomes. Overall, CASH-AA + MIP produced greater declines in adolescent-report inattentive symptoms and delinquent acts. Similarly, among non-substance users, CASH-AA + MIP clients attended more treatment sessions. In contrast, among substance users, CASH-AA Only clients showed greater declines in caregiver-report hyperactive symptoms and externalizing.Conclusions: This study provides initial experimental support for family-based ADHD medication decision-making when coupled with academic training in usual care. The treatment protocols, CASH-AA and MIP, showed positive effects in addressing not only ADHD symptoms but also common co-occurring problems, and youth with substance use problems benefitted along with non-using peers.

Giving patients a voice: a participatory evaluation of patient engagement in Newfoundland and Labrador Health Research.

BACKGROUND: Efforts to engage patients as partners in health research have grown and thereby the need for feedback and evaluation. In this pilot evaluation study, we aimed to 1) evaluate patient engagement in health research projects in Newfoundland and Labrador, Canada, and 2) learn more about how to best monitor and evaluate patient engagement. This paper presents the results of our participatory evaluation study and the lessons learned. The evaluation of the projects was driven by questions patients wanted answered. METHODS: We conducted a formative evaluation of patient engagement in health research projects. Projects spanned a variety of topics, target groups, research designs and methods of patient engagement. Participants included principal investigators (n = 6) and their patient partners (n = 14). Furthermore, graduate students (n = 13) working on their own research projects participated. Participants completed an online survey with closed and open-ended questions about their patient engagement efforts, experiences and preliminary outcomes. Patients were involved as co-investigators in the entire evaluation study. We used qualitative methods to evaluate our participatory process. RESULTS: The evaluation study results show that most patients and researchers felt prepared and worked together in various phases of the research process. Both groups felt that the insights and comments of patients influenced research decisions. They believed that patient engagement improved the quality and uptake of research. Students felt less prepared and were less satisfied with their patient engagement experience compared to researchers and their patient partners. Involvement of patient co-investigators in this evaluation resulted in learnings, transparency, validation of findings and increased applicability. Challenges were to select evaluation questions relevant to all stakeholders and to adapt evaluation tools to local needs. CONCLUSIONS: Our findings show that researchers, patient partners and students value patient engagement in health research. Capacity building at the supervisor level in academic institutions is needed to better support students. Sufficient time is also needed to permit observable outcomes. Participatory evaluation may increase the relevance and usefulness of information, but it also raises issues such as who defines and designs the content of evaluation tools. A co-creation process is required to develop appropriate monitoring and evaluation strategies.

Measurement training and feedback system for implementation of evidence-based treatment for adolescent externalizing problems: protocol for a randomized trial of pragmatic clinician training.

BACKGROUND: Innovations in clinical training and support that enhance fidelity to evidence-based treatment (EBT) for adolescent behavior problems are sorely needed. This study will develop an online training system to address this gap: Measurement Training and Feedback System for Implementation (MTFS-I). Using procedures intended to be practical and sustainable, MTFS-I is designed to increase two aspects of therapist behavior that are fundamental to boosting EBT fidelity: therapist self-monitoring of EBT delivery, and therapist utilization of core techniques of EBTs in treatment sessions. This version of MTFS-I focuses on two empirically supported treatment approaches for adolescent conduct and substance use problems: family therapy and cognitive behavioral therapy (CBT). METHODS/DESIGN: MTFS-I expands on conventional measurement feedback systems for client outcomes by adding training in observational coding to promote EBT self-monitoring and focusing on implementation of EBT treatment techniques. It has two primary components. (1) The training component, delivered weekly in two connected parts, involves self-monitored learning modules containing brief clinical descriptions of core EBT techniques and mock session coding exercises based on 5-8 min video segments that illustrate delivery of core techniques. (2) The feedback component summarizes aggregated therapist-reported data on EBT techniques used with their active caseloads. MTFS-I is hosted online and requires approximately 20 min per week to complete for each treatment approach. This randomized trial will first collect data on existing delivery of family therapy and CBT techniques for youth in outpatient behavioral health sites (Baseline phase). It will then randomize site clinicians to two study conditions (Implementation phase): Training Only versus Training + Feedback + Consultation. Therapists will choose whether to train in family therapy, CBT, or both. Study aims will compare clinician performance across study phase and between study conditions on MTFS-I uptake, reliability and accuracy in EBT self-monitoring, and utilization of EBT techniques in treatment sessions (based on observer coding of audiotapes). DISCUSSION: Study contributions to implementation science and considerations of MTFS-I sustainability are discussed. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03722654. Registered on 29 October 2018.

A review and meta-synthesis of qualitative studies on myalgic encephalomyelitis/chronic fatigue syndrome.

OBJECTIVE: To review and synthesize findings across qualitative studies on Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS). METHODS: Articles were systematically reviewed and analyzed within a meta-analytic framework. Analyses included a multi-perspective examination of ME/CFS, as well as a comparative analysis of ME/CFS versus other chronic conditions. RESULTS: Thirty-four qualitative studies on ME/CFS were included. Findings include three substantive thematic areas that focus on: (1) experiences of people with ME/CFS, (2) experiences of physicians, and (3) themes that intersect both of these groups. For patients, illness development influenced identity, reductions in functioning, and coping. Physician-specific themes described lack of awareness about ME/CFS and recommended improvement in educational resources. Intersecting themes expressed issues with diagnosis creating tensions and fueling the stigmatization of ME/CFS. CONCLUSIONS: Findings indicate multilayered, context-specific experiences and ways in which both people with ME/CFS, as well as those involved in their lives (e.g., family or the medical community), interpret this illness. Future qualitative studies should recognize the various facets of the ME/CFS experience, the network members of people with ME/CFS, and the sociocultural environment through which the illness is understood. PRACTICE IMPLICATIONS: Health care professionals can gain unique insight from patient experiences, allowing for more accurate diagnoses and treatment recommendations.

Fatigue Scales and Chronic Fatigue Syndrome: Issues of Sensitivity and Specificity.

Few studies have explored issues of sensitivity and specificity for using the fatigue construct to identify patients meeting chronic fatigue syndrome (CFS) criteria. In this article, we examine the sensitivity and specificity of several fatigue scales that have attempted to define severe fatigue within CFS. Using Receiver Operating Characteristic (ROC) curve analysis, we found most scales and sub-scales had either significant specificity and/or sensitivity problems. However, the post-exertional subscale of the ME/CFS Fatigue Types Questionnaire (Jason, Jessen, et al., 2009) was the most promising in terms of specificity and sensitivity. Among the more traditional fatigue scales, Krupp, LaRocca, Muir-Nash, and Steinberg's (1989) Fatigue Severity Scale had the best ability to differentiate CFS from healthy controls. Selecting questions, scales and cut off points to measure fatigue must be done with extreme care in order to successfully identify CFS cases.

An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Kindling might represent a heuristic model for understanding the etiology of Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS). Kindling occurs when an organism is exposed repeatedly to an initially sub-threshold stimulus resulting in hypersensitivity and spontaneous seizure-like activity. Among patients with ME/CFS, chronically repeated low-intensity stimulation due to an infectious illness might cause kindling of the limbic-hypothalamic-pituitary axis. Kindling might also occur by high-intensity stimulation (e.g., brain trauma) of the limbic-hypothalamic-pituitary axis. Once this system is charged or kindled, it can sustain a high level of arousal with little or no external stimulus and eventually this could lead to hypocortisolism. Seizure activity may spread to adjacent structures of the limbic-hypothalamic-pituitary axis in the brain, which might be responsible for the varied symptoms that occur among patients with ME/CFS. In addition, kindling may also be responsible for high levels of oxidative stress, which has been found in patients with ME/CFS.

Increased HDAC in association with decreased plasma cortisol in older adults with chronic fatigue syndrome.

Hypocortisolism is a frequent finding in individuals with chronic fatigue syndrome (CFS) with other research findings implying potential dysregulation of glucocorticoid signaling. Glucocorticoid signaling is under the influence of several pathways, several of which are of interest in the study of CFS. Oxidative stress and decreased antioxidant capacity are known to disrupt the hypothalamic-pituitary-adrenal (HPA) axis (Epel et al., 2004) and the presence of histone deacetylases (HDAC) could also impact glucocorticoid signaling. The intent of this pilot study was to investigate the relationship among oxidative stress elements, select HDAC's (2/3) and glucocorticoid receptor signaling in an elderly sample with CFS. Findings suggest increased histone deacetylase activity, lower total antioxidant power, in the context of decreased plasma cortisol and increased plasma dehydroepiandrosterone concomitant with decreased expression of the encoding gene for the glucocorticoid receptor. These findings support the presence of HPA axis dysregulation in elderly individuals with CFS.