Using Single-Case Experimental Design and Patient-Reported Outcome Measures to Evaluate the Treatment of Cancer-Related Cognitive Impairment in Clinical Practice.

Cancer-related cognitive impairment (CRCI) affects a large proportion of cancer survivors and has significant negative effects on survivor function and quality of life (QOL). Treatments for CRCI are being developed and evaluated. Memory and attention adaptation training (MAAT) is a cognitive-behavioral therapy (CBT) demonstrated to improve CRCI symptoms and QOL in previous research. The aim of this article is to describe a single-case experimental design (SCED) approach to evaluate interventions for CRCI in clinical practice with patient-reported outcome measures (PROs). We illustrate the use of contemporary SCED methods as a means of evaluating MAAT, or any CRCI treatment, once clinically deployed. With the anticipated growth of cancer survivorship and concurrent growth in the number of survivors with CRCI, the treatment implementation and evaluation methods described here can be one way to assess and continually improve CRCI rehabilitative services.

Digital health and telehealth in cancer care: a scoping review of reviews.

The COVID-19 pandemic necessitated remote cancer care delivery via the internet and telephone, rapidly accelerating an already growing care delivery model and associated research. This scoping review of reviews characterised the peer-reviewed literature reviews on digital health and telehealth interventions in cancer published from database inception up to May 1, 2022, from PubMed, Cumulated Index to Nursing and Allied Health Literature, PsycINFO, Cochrane Reviews, and Web of Science. Eligible reviews conducted a systematic literature search. Data were extracted in duplicate via a pre-defined online survey. Following screening, 134 reviews met the eligibility criteria. 77 of those reviews were published since 2020. 128 reviews summarised interventions intended for patients, 18 addressed family caregivers, and five addressed health-care providers. 56 reviews did not target a specific phase of the cancer continuum, whereas 48 reviews tended to address the active treatment phase. 29 reviews included a meta-analysis, with results showing positive effects on quality of life, psychological outcomes, and screening behaviours. 83 reviews did not report intervention implementation outcomes but when reported, 36 reported acceptability, 32 feasibility, and 29 fidelity outcomes. Several notable gaps were identified in these literature reviews on digital health and telehealth in cancer care. No reviews specifically addressed older adults, bereavement, or sustainability of interventions and only two reviews focused on comparing telehealth to in-person interventions. Addressing these gaps with rigorous systematic reviews might help guide continued innovation in remote cancer care, particularly for older adults and bereaved families, and integrate and sustain these interventions within oncology.

Self-reported cognitive impairments and quality of life in patients with gastrointestinal stromal tumor: Results of a multinational survey.

BACKGROUND: Cancer-related cognitive impairment (CRCI) has long-term effects on survivor quality of life, but CRCI research on patients with gastrointestinal stromal tumor (GIST) is lacking. The aims of this study were to investigate CRCI and concomitant quality of life among patients with GIST. METHODS: An online survey was used to assess CRCI in adult patients with GIST using the validated Functional Assessment of Cancer Therapy-Cognitive-v.3. Age, education, demographically indexed IQ, general health, and quality of life factors (e.g., fatigue, emotional distress) were also assessed. The online survey was administered through five international GIST and sarcoma support organizations. RESULTS: Over the 3-month recruitment period, the survey was completed by 485 participants: mean age, 57.80 (SD, 11.51), median 5 years after diagnosis. A majority (63.91%) reported experiencing cognitive symptoms with a significant negative quality of life impact. Controlling for age, patients with GIST ≥5 years after diagnosis reported worse cognitive function than those <5 years after diagnosis (p < .05) but did not differ in educational level or IQ. Whereas longer term survivors were more likely to have been treated with tyrosine kinase inhibitor (TKI) therapies, there was no observed association of TKI therapy with self-reported cognitive impairments. CONCLUSIONS: A majority of GIST patients report cognitive symptoms that have a negative impact on quality of life, with longer term survivors (≥5 years) tending to report more cognitive impairments. Given the success of TKI therapy to substantially increase overall survival of patients with GIST, addressing CRCI in clinical practice may improve long-term GIST survivor function and quality of life.

Health Care Providers' and Professionals' Experiences With Telehealth Oncology Implementation During the COVID-19 Pandemic: A Qualitative Study.

BACKGROUND: Rapid implementation of telehealth for cancer care during COVID-19 required innovative and adaptive solutions among oncology health care providers and professionals (HPPs). OBJECTIVE: The aim of this qualitative study was to explore oncology HPPs' experiences with telehealth implementation during the COVID-19 pandemic. METHODS: This study was conducted at Moffitt Cancer Center (Moffitt), an NCI (National Cancer Institute)-Designated Comprehensive Cancer Center. Prior to COVID-19, Moffitt piloted telehealth visits on a limited basis. After COVID-19, Moffitt rapidly expanded telehealth visits. Telehealth visits included real-time videoconferencing between HPPs and patients and virtual check-ins (ie, brief communication with an HPP by telephone only). We conducted semistructured interviews with 40 oncology HPPs who implemented telehealth during COVID-19. The interviews were recorded, transcribed verbatim, and analyzed for themes using Dedoose software (version 4.12). RESULTS: Approximately half of the 40 participants were physicians (n=22, 55%), and one-quarter of the participants were advanced practice providers (n=10, 25%). Other participants included social workers (n=3, 8%), psychologists (n=2, 5%), dieticians (n=2, 5%), and a pharmacist (n=1, 3%). Five key themes were identified: (1) establishing and maintaining patient-HPP relationships, (2) coordinating care with other HPPs and informal caregivers, (3) adapting in-person assessments for telehealth, (4) developing workflows and allocating resources, and (5) future recommendations. Participants described innovative strategies for implementing telehealth, such as coordinating interdisciplinary visits with multiple HPPs and inviting informal caregivers (eg, spouse) to participate in telehealth visits. Health care workers discussed key challenges, such as workflow integration, lack of physical exam and biometric data, and overcoming the digital divide (eg, telehealth accessibility among patients with communication-related disabilities). Participants recommended policy advocacy to support telehealth (eg, medical licensure policies) and monitoring how telehealth affects patient outcomes and health care delivery. CONCLUSIONS: To support telehealth growth, implementation strategies are needed to ensure that HPPs and patients have the tools necessary to effectively engage in telehealth. At the same time, cancer care organizations will need to engage in advocacy to ensure that policies are supportive of oncology telehealth and develop systems to monitor the impact of telehealth on patient outcomes, health care quality, costs, and equity.

Cognitive behavioral therapy for cancer-related cognitive dysfunction.

PURPOSE OF REVIEW: To provide the reader with an overview of the cognitive-behavioral conceptualization of cancer-related cognitive dysfunction (CRCD) and how cognitive behavioral therapy (CBT) can play an important role in treatment. RECENT FINDINGS: Recent findings show that Memory and Attention Adaptation Training (MAAT), a CBT developed to help cancer survivors develop adaptive skills to improve daily cognitive performance and emotional coping, may be an efficacious treatment of CRCD and can be delivered through videoconference technology to improve survivor access to care. SUMMARY: The etiology of CRCD remains largely undetermined and likely is produced by multiple mechanisms. This can include neuronal death, microvascular damage, inflammatory processes, and psychological factors of perceptions of inadequate cognitive capacity to meet performance demands and related emotional distress. As a result, there are a variety of treatments currently being researched. More research with larger sample sizes, multiple clinicians and multiple sites are needed to confirm efficacy, but CBT approaches such as Memory and Attention Adaptation Training that address multiple psychological factors involved may offer a flexible nonpharmacological approach to CRCD that optimizes quality of life outcomes.

Methylphenidate and Memory and Attention Adaptation Training for Persistent Cognitive Symptoms after Traumatic Brain Injury: A Randomized, Placebo-Controlled Trial.

The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacological enhancement (ie, with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least 4 months before study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after 6 weeks of treatment (post treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (P<0.05) treatment-related improvements in cognitive functioning were found for word-list learning (MAAT/placebo>ABT/placebo), nonverbal learning (MAAT/MPH>MAAT/placebo and MAAT/MPH>ABT/MPH), and auditory working memory and divided attention (MAAT/MPH>ABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI.

A randomized trial of videoconference-delivered cognitive behavioral therapy for survivors of breast cancer with self-reported cognitive dysfunction.

BACKGROUND: Long-term chemotherapy-related cognitive dysfunction (CRCD) affects a large number of cancer survivors. To the authors' knowledge, to date there is no established treatment for this survivorship problem. The authors herein report results of a small randomized controlled trial of a cognitive behavioral therapy (CBT), Memory and Attention Adaptation Training (MAAT), compared with an attention control condition. Both treatments were delivered over a videoconference device. METHODS: A total of 47 survivors of female breast cancer who reported CRCD were randomized to MAAT or supportive therapy and were assessed at baseline, after treatment, and at 2 months of follow-up. Participants completed self-report measures of cognitive symptoms and quality of life and a brief telephone-based neuropsychological assessment. RESULTS: MAAT participants made gains in perceived (self-reported) cognitive impairments (P = .02), and neuropsychological processing speed (P = .03) compared with supportive therapy controls. A large MAAT effect size was observed at the 2-month follow-up with regard to anxiety concerning cognitive problems (Cohen's d for standard differences in effect sizes, 0.90) with medium effects noted in general function, fatigue, and anxiety. Survivors rated MAAT and videoconference delivery with high satisfaction. CONCLUSIONS: MAAT may be an efficacious psychological treatment of CRCD that can be delivered through videoconference technology. This research is important because it helps to identify a treatment option for survivors that also may improve access to survivorship services. Cancer 2016;122:1782-91. © 2016 American Cancer Society.

A cognitive behavioral intervention (HOBSCOTCH) improves quality of life and attention in epilepsy.

OBJECTIVE: Cognitive difficulties in epilepsy are common and add to disability beyond seizures alone. A self-management intervention targeting cognitive dysfunction was developed and assessed for whether it improves quality of life, objective memory, and mood in adults with epilepsy. METHODS: The HOme Based Self-management and COgnitive Training CHanges lives (HOBSCOTCH) program was developed to incorporate (1) psychoeducation, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem solving therapy. Adults aged 18-65 years with epilepsy (n=66) were randomized into 3 groups, to receive 8 weeks of HOBSCOTCH, with (H+) or without (H) additional working memory training on a commercial gaming device, or to a waitlisted control group. The primary outcome was quality of life (Quality of Life in Epilepsy scale, QOLIE-31) with secondary outcomes of objective cognition measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and depression (as measured by PHQ9 and NDDIE). RESULTS: Both intervention arms showed a significant improvement in quality of life, as compared with controls who demonstrated a decline in QOLIE-31 scores. There was significant improvement in objective cognitive performance among the intervention groups, most notably in attention, compared with the waitlisted controls. There was no significant change in depression scores. SIGNIFICANCE: The HOBSCOTCH program significantly improved quality of life and appeared to be an effective intervention to address cognitive dysfunction in adults with epilepsy. Further studies are needed to assess the generalizability and cost-effectiveness of this intervention.

Design and feasibility of a memory intervention with focus on self-management for cognitive impairment in epilepsy.

The aim of this study was to assess the feasibility of a self-management intervention targeting cognitive dysfunction to improve quality of life and reduce memory-related disability in adults with epilepsy. The intervention incorporates (1) education on cognitive function in epilepsy, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem-solving therapy. In addition to the behavioral modification, formal working memory training was conducted by utilizing a commercially available program in a subgroup of patients. Our findings suggest that a self-management intervention targeting cognitive dysfunction was feasible for delivery to a rural population with epilepsy, with 13 of 16 enrolled participants completing the 8-session program. Qualitative data indicate high satisfaction and subjective improvement in cognitive functioning in day-to-day life. These findings provide support for further evaluation of the efficacy of this intervention through a randomized controlled trial.

Development of CBT for chemotherapy-related cognitive change: results of a waitlist control trial.

OBJECTIVE: To evaluate the efficacy of a brief cognitive-behavioral therapy (CBT) that is being developed for management of cognitive dysfunction following chemotherapy among breast cancer survivors. Memory and Attention Adaptation Training (MAAT) is a brief CBT designed to improve the quality of life and function among cancer survivors with post-chemotherapy cognitive complaints. METHODS: An initial, two-group (MAAT versus waitlist, no treatment control), randomized clinical trial (RCT) was conducted. Forty stage I and II female breast cancer survivors (mean age = 50; SD = 6.4) were randomized to conditions and assessed at baseline, post-treatment (8 weeks) and 2-month follow-up assessment points on measures of: (1) self-reported daily cognitive failures; (2) quality of life; and (3) neuropsychological performance. Participants were also assessed for satisfaction with MAAT. RESULTS: With education and IQ as covariates, MAAT participants made significant improvements relative to controls on the spiritual well-being subscale of the quality of life measure and on verbal memory, but statistical significance was not achieved on self-report of daily cognitive complaints. However, moderate-to-large effect sizes were observed on these outcomes. Participants gave MAAT high satisfaction ratings. CONCLUSIONS: Although this initial RCT is a small study, MAAT participants appear to improve on one measure of quality of life and verbal memory performance relative to no treatment controls and rate MAAT with high satisfaction. These data are encouraging and support the continued development and evaluation of MAAT efficacy.

Preserved learning and memory in mice following chemotherapy: 5-Fluorouracil and doxorubicin single agent treatment, doxorubicin-cyclophosphamide combination treatment.

Clinical studies suggest that chemotherapy is associated with long-term cognitive impairment in some patients. A number of underlying mechanisms have been proposed, however, the etiology of chemotherapy-related cognitive dysfunction remains relatively unknown. As part of a multifaceted approach, animal models of chemotherapy induced cognitive impairment are being developed. Thus far, the majority of animal studies have utilized rats, however, mice may prove particularly beneficial in studying genetic risk factors for developing chemotherapy induced cognitive impairment. Thus, C57BL/6J mice were treated once a week for three weeks with saline, doxorubicin and cyclophosphamide (D&C), doxorubicin (Dox), or 5-fluorouracil (5-FU). Recent and remote contextual fear conditioning and novel object recognition (NOR) was assessed. Despite significant toxic effects as assessed by weight loss, the chemotherapy treated mice performed as well as control mice on all task. As are some humans, C57BL/6J mice may be resistant to at least some aspects of chemotherapy induced cognitive decline.

Recent and remote spatial memory in mice treated with cytosine arabinoside.

Clinical studies suggest that chemotherapy is associated with long-term cognitive impairment in some patients. A number of underlying mechanisms have been proposed, however, the etiology of chemotherapy-related cognitive dysfunction remains relatively unknown. As part of a multifaceted approach, animal models of chemotherapy-induced cognitive impairment are being developed. Thus far, the majority of animal studies have utilized a rat model, however, mice may prove particularly beneficial in studying genetic risk factors for developing chemotherapy-induced cognitive impairment. Various chemotherapy agents, including cytosine arabinoside (Ara-C), have been found to impair remote spatial memory in rats in the Morris water maze. The present study evaluated the effects of Ara-C on remote (30 d) spatial memory in mice. In addition, the possibility that time relative to chemotherapy treatment may modulate the effect of chemotherapy on spatial learning and/or recent (1 d) memory was explored. Male C57BL/6J mice received either Ara-C (275 mg/kg i.p. daily for 5 days) or saline. Spatial learning and memory was assessed using the Morris water maze. Half the mice performed a remote (30 d) memory version of the task and the other half performed a recent (1 d) memory version of the task. The experiment was designed such that the probe trial for the recent memory version occurred on the same day relative to chemotherapy treatment as the remote memory version. Despite significant toxic effects as assessed by weight loss, Ara-C treated mice performed as well as control mice during acquisition, recent memory, and remote memory portions of the task. As are some humans, C57BL/6J mice may be resistant to at least some aspects of chemotherapy induced cognitive decline.

Panorama del manejo cognitivo conductual de la disfunción de la memoria asociada a la quimioterapia / An overview of cognitive-behavioral management of memory dysfunction associated with chemotherapy

Objective: This article summarizes current empirical support for Memory and Attention Adaptation Training (MAAT), a cognitive-behavioral treatment program that uses a compensatory strategy approach for management of late cognitive effects of chemotherapy among cancer survivors. A description of MAAT, in addition to other treatment approaches, is presented. Results: Current methods of assessing treatment gains among cancer survivors with cognitive problems who have completed programs such as MAAT need to be expanded. As such, a table of patient reported outcome (PRO) measures that may be better suited for future outcome research is proposed. Conclusions: Identifying outcome measures that accurately assess the clinical targets of MAAT and other behavioral treatments is of prime importance, as certain variables (e.g., quality of life, role strain) are not detected by neuropsychological testing in isolation. The PRO table presented in this article is intended to aid future researchers in identifying measures that can reflect quality of life improvement in response to treatments such as MAAT (AU)

Objetivo: El presente artículo resume el apoyo empírico actual para el Entrenamiento de la Adaptación de la Memoria y la Atención (MAAT), un programa de tratamiento cognitivo-conductual que utiliza un enfoque de estrategia compensatoria para el manejo de los efectos cognitivos tardíos de la quimioterapia en los supervivientes del cáncer. Se presenta una descripción del MAAT, además de otros enfoques de tratamiento. Resultados: Es necesario ampliar los métodos actuales de evaluación de las mejorías del tratamiento en los supervivientes de cáncer con problemas cognitivos que han completado programas como el MAAT. En este sentido, se propone una tabla de medidas de resultado informadas (PRO) por el paciente que puede ser más adecuada para la investigación de resultados futuros. Conclusiones: Identificar medidas de de resultado que evalúen con precisión los objetivos clínicos del MAAT y otros tratamientos conductuales es de vital importancia, ya que algunas variables (ej., calidad de vida, estrés de rol), no son detectados por pruebas neuropsicológicas de modo aislado. La tabla de PRO presentada en este artículo tiene el propósito de ayudar a los futuros investigadores a identificar las medidas que pueden reflejar la mejoría en calidad de vida en respuesta a tratamientos como el MAAT (AU)

Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy.

PURPOSE: Adjuvant chemotherapy has been associated with mild cognitive decline among a subset of breast cancer survivors. Late cognitive effects after chemotherapy can have a deleterious impact on survivor quality of life and functional health; however, the etiology of chemotherapy-related cognitive dysfunction remains unknown. PATIENTS AND METHODS: We present a case of monozygotic twins who are discordant for breast cancer and chemotherapy exposure (ie, one twin contracted breast cancer and underwent chemotherapy, and the other had no breast cancer). As part of a larger study, each was evaluated with standardized, self-report measures of cognitive function, standard neuropsychological tests, and structural and functional magnetic resonance imaging (MRI). RESULTS: Results indicated small differences in neuropsychological test performance but striking contrasts in self-reported cognitive complaints and structural and functional MRI images. Specifically, the twin who underwent chemotherapy had substantially more subjective cognitive complaints, more white matter hyperintensities on MRI, and an expanded spatial extent of brain activation during working memory processing than her nonaffected twin. CONCLUSION: This case illustrates possible physiologic mechanisms that could produce long-term cognitive complaints among chemotherapy recipients and help formulate hypotheses for further empirical study in the area of chemotherapy-associated cognitive dysfunction.

Cognitive-behavioral management of chemotherapy-related cognitive change.

Adjuvant chemotherapy can produce mild cognitive decline among breast cancer survivors which adversely effects function and quality of life. However, no treatment to date has been proposed or developed for this problem despite large numbers of cancer patients who report post-treatment memory dysfunction. This paper presents data from a single arm pilot study of a brief cognitive-behavioral treatment aimed at helping breast cancer survivors manage cognitive dysfunction associated with adjuvant chemotherapy (Memory and Attention Adaptation Training; MAAT). Participants were twenty-nine women who were an average of 8 years post-chemotherapy for stage I and II breast cancer. All had reported complaints regarding memory and attention. Improvements in self-report of cognitive function, quality of life and standard neuropsychological test performance were observed at post-treatment, 2-month and 6-month follow-up. Participants also reported high treatment satisfaction and rated MAAT as helpful in improving ability to compensate for memory problems. Given these results, the treatment appears to be a feasible and practical cognitive-behavioral program that warrants continued evaluation among cancer survivors who experience persistent cognitive dysfunction.

Posttraumatic stress disorder in primary care: prevalence and relationships with physical symptoms and medical utilization.

OBJECTIVE: This study estimates the prevalence of posttraumatic stress disorder (PTSD) and describes the relationships among PTSD status and health indices in a civilian primary care patient sample. METHODS: Participants (N = 232) completed a paper-and-pencil survey of life events, PTSD symptoms, physical symptoms and health functioning. Utilization was assessed from medical records. RESULTS: Nine percent of the participants met the criteria for full PTSD (based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) and another 25% were defined as partial PTSD. The full-PTSD group evidenced higher rates of medical utilization, more intense physical symptoms and poorer health functioning than the no-PTSD group. The partial-PTSD group more closely resembled the full-PTSD group. CONCLUSIONS: This study, although limited by sample size and diagnosis by questionnaire vs. diagnostic interview, suggests research directions for enhancing our understanding of PTSD among civilian primary care patients and for developing appropriate interventions that can be conducted in the primary care setting.

Psychometric update of the Functional Interference Estimate: a brief measure of pain functional interference.

The Functional Interference Estimate (FIE) is a brief, 5-item self-report measure that assesses the degree to which pain interferes with daily functioning. While the FIE has demonstrated reliability and validity with a small normative sample, not much is known about its reliability and validity with a broad sample of individuals with pain. The current study presents FIE score means, variability estimates, reliability and validity data based on a large sample (n = 1,337) of primary care patients who report problematic pain. The FIE has excellent internal consistency and appears to have strong convergent validity with other well-established measures of function (e.g., SF-36 and Dartmouth COOP Charts). Because of its brevity and flexibility, the FIE may be a useful self-report measure of pain functional interference in clinical research on pain.

Cognitive effects of cytotoxic cancer chemotherapy: predisposing risk factors and potential treatments.

Increasing evidence suggests that systemic cancer chemotherapy can have significant long-term effects on cognition, particularly on verbal learning, memory, attention, and speed of information processing. These deficits can be a source of significant distress to survivors. There is much less known about the mechanisms, predisposing vulnerabilities, and treatment of these deficits. We will summarize current knowledge of chemotherapy-associated cognitive deficits. Emerging theories about the role of selected genetic polymorphisms in heightening the vulnerability to chemotherapy-induced cognitive decline will be described.

Low neuropsychologic performance among adult cancer survivors treated with chemotherapy.

Decline in neuropsychologic test performance following adjuvant chemotherapy for various types of cancer has gained much research attention over the past decade. From available data, about one fourth to one third of individuals undergoing systemic chemotherapy exhibit measurable decrements in performance of standard tests of cognitive function. Many cancer survivors report that cognitive problems interfere with function and compromise quality of life. However, these declines appear subtle and there are little available longitudinal data examining pre- to post-treatment cognitive change. Further, there is little available evidence identifying the causes of cognitive decline. This paper reviews current literature on low neuropsychologic performance following systemic chemotherapy and hypotheses on the causes of cognitive symptoms following chemotherapy. Future research directions, with emphasis on longitudinal research design as well as treatment implications, are discussed.

Distinguishing between excessive daytime sleepiness and fatigue: toward improved detection and treatment.

INTRODUCTION: Excessive daytime sleepiness (EDS) and fatigue occur in high percentages in the general population. They are common complaints in primary care and in specialty medicine. Although they may represent distinct or overlapping phenomena, the general medical literature does not normally distinguish between EDS and fatigue. Despite their prevalence, both EDS and fatigue are identified and treated in a relatively small proportion of those affected. The similarity of EDS and fatigue may create diagnostic ambiguity and thereby contribute to under-identification and under-treatment. Fatigue, in particular, is thought to be difficult to manage when it is identified. METHODS: The literature was searched for reviews, meta-analysis and similar levels of papers focused on EDS or fatigue. RESULTS: EDS and fatigue are operationalized in ways that contribute to blurring rather than to distinguishing between them. Existing measures of both EDS and fatigue may also contribute to their misidentification. Effective treatments for both symptoms have been established. Behavioral interventions are effective and underutilized. DISCUSSION: We suggest more precise operationalization of EDS and fatigue, leading to a refinement of existing measures or development of new tools, a structured interview with fatigue and EDS sections in the clinical setting, and more consideration for behavioral interventions.