Natural killer cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a multi-site clinical assessment of ME/CFS (MCAM) sub-study.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by substantial reduction in function accompanied by profound unexplained fatigue not significantly relieved by rest, post-exertional malaise, and other symptoms. Reduced natural killer (NK) cell count and cytotoxicity has been investigated as a biomarker for ME/CFS, but few clinical laboratories offer the test and multi-site verification studies have not been conducted. METHODS: We determined NK cell counts and cytotoxicity in 174 (65%) ME/CFS, 86 (32%) healthy control (HC) and 10 (3.7%) participants with other fatigue associated conditions (ill control [IC]) from the Multi-Site Clinical Assessment of ME/CFS (MCAM) study using an assay validated for samples shipped overnight instead of testing on day of venipuncture. RESULTS: We found a large variation in percent cytotoxicity [mean and (IQR) for ME/CFS and HC respectively, 34.1% (IQR 22.4-44.3%) and 33.6% (IQR 22.9-43.7%)] and no statistically significant differences between patients with ME/CFS and HC (p-value = 0.79). Analysis stratified on illness domain measured with standardized questionnaires did not identify an association of NK cytotoxicity with domain scores. Among all participants, NK cytotoxicity was not associated with survey results of physical and mental well-being, or health factors such as history of infection, obesity, smoking, and co-morbid conditions. CONCLUSION: These results indicate this assay is not ready for clinical implementation and studies are needed to further explore immune parameters that may be involved in the pathophysiology of ME/CFS.

Feasibility Assessment of a School Nurse-Led Approach Using Chronic Absenteeism to Establish the School-Based Active Surveillance Process.

This article shares what was learned from the feasibility assessment of a nurse-led school-based active surveillance (SBAS) pilot to track chronic absenteeism using myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as an exemplar. This pilot encompassed a 3-year period with training and feedback from school nurses (SNs) on data collection and ME/CFS. SNs found that the SBAS process helped them effectively identifying undiagnosed conditions. The assessment revealed the importance of focusing outreach efforts and establishing relationships with the school leadership in developing health policies and programs in the school setting. The pilot data were used to develop a manual to guide SNs for the SBAS process. This can be viewed as a model for SNs in establishing a surveillance to identify and track conditions like ME/CFS. With overlapping symptoms of Long COVID to ME/CFS, this assessment may provide insights for additional efforts to understand the impact of Long COVID on students' education.

Physiological assessment of orthostatic intolerance in chronic fatigue syndrome.

BACKGROUND: Orthostatic intolerance-OI is common in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-ME/CFS. We used a 10-min passive vertical lean test as orthostatic challenge-OC and measured changes in vitals and end tidal CO2 (eTCO2). An abnormal physiologic response to OC was identified in 60% of the 63 patients evaluated from one to three times over several years. Hypocapnia, either resting or induced by OC, was the most frequent abnormality, followed by postural orthostatic tachycardia. OBJECTIVE: Evaluate the physiologic response of patients with ME/CFS to a standardized OC. DESIGN: Respiratory and heart rate, blood pressure and eTCO2 were recorded twice at the end of 10-min supine rest and then every minute during the 10-min lean. Hypocapnia was eTCO2 ≤ 32 mmHg. Orthostatic tachycardia was heart rate increase ≥ 30 beats per minute compared with resting or ≥ 120 BPM. Orthostatic hypotension was decreased systolic pressure ≥ 20 mmHg from baseline. Tachypnea was respiratory rate of  ≥ 20 breaths per minute-either supine or leaning. Questionnaire data on symptom severity, quality of life and mood were collected at visit #2. PATIENTS: 63 consecutive patients fulfilling the 1994 case definition for CFS underwent lean testing at first visit and then annually at visit 2 (n = 48) and 3 (n = 29). MEASURES: Supine hypocapnia; orthostatic tachycardia, hypocapnia or hypotension. RESULTS: The majority of ME/CFS patients (60.3%, 38/63) had an abnormality detected during a lean test at any visit (51%, 50% and 45% at visits 1, 2 and 3, respectively). Hypocapnia at rest or induced by OC was more common and more likely to persist than postural orthostatic tachycardia. Anxiety scores did not differ between those with and without hypocapnia. CONCLUSIONS: The 10-min lean test is useful in evaluation of OI in patients with ME/CFS. The most frequent abnormality, hypocapnia, would be missed without capnography.

Assessing sleep and pain among adults with myalgic encephalomyelitis/chronic fatigue syndrome: psychometric evaluation of the PROMIS® sleep and pain short forms.

PURPOSE: To evaluate the psychometric properties of the patient-reported outcome measurement information system® (PROMIS) short forms for assessing sleep disturbance, sleep-related impairment, pain interference, and pain behavior, among adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). METHODS: Data came from the Multi-Site ME/CFS study conducted between 2012 and 2020 at seven ME/CFS specialty clinics across the USA. Baseline and follow-up data from ME/CFS and healthy control (HC) groups were used to examine ceiling/floor effects, internal consistency reliability, differential item functioning (DIF), known-groups validity, and responsiveness. RESULTS: A total of 945 participants completed the baseline assessment (602 ME/CFS and 338 HC) and 441 ME/CFS also completed the follow-up. The baseline mean T-scores of PROMIS sleep and pain measures ranged from 57.68 to 62.40, about one standard deviation above the national norm (T-score = 50). All four measures showed high internal consistency (ω = 0.92 to 0.97) and no substantial floor/ceiling effects. No DIF was detected by age or sex. Known-groups comparisons among ME/CFS groups with low, medium, and high functional impairment showed significant small-sized differences in scores (η2 = 0.01 to 0.05) for the two sleep measures and small-to-medium-sized differences (η2 = 0.01 to 0.15) for the two pain measures. ME/CFS participants had significantly worse scores than HC (η2 = 0.35 to 0.45) for all four measures. Given the non-interventional nature of the study, responsiveness was evaluated as sensitivity to change over time and the pain interference measure showed an acceptable sensitivity. CONCLUSION: The PROMIS sleep and pain measures demonstrated satisfactory psychometric properties supporting their use in ME/CFS research and clinical practice.

Extracting medication information from unstructured public health data: a demonstration on data from population-based and tertiary-based samples.

BACKGROUND: Unstructured data from clinical epidemiological studies can be valuable and easy to obtain. However, it requires further extraction and processing for data analysis. Doing this manually is labor-intensive, slow and subject to error. In this study, we propose an automation framework for extracting and processing unstructured data. METHODS: The proposed automation framework consisted of two natural language processing (NLP) based tools for unstructured text data for medications and reasons for medication use. We first checked spelling using a spell-check program trained on publicly available knowledge sources and then applied NLP techniques. We mapped medication names into generic names using vocabulary from publicly available knowledge sources. We used WHO's Anatomical Therapeutic Chemical (ATC) classification system to map generic medication names to medication classes. We processed the reasons for medication with the Lancaster stemmer method and then grouped and mapped to disease classes based on organ systems. Finally, we demonstrated this automation framework on two data sources for Mylagic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): tertiary-based (n = 378) and population-based (n = 664) samples. RESULTS: A total of 8681 raw medication records were used for this demonstration. The 1266 distinct medication names (omitting supplements) were condensed to 89 ATC classification system categories. The 1432 distinct raw reasons for medication use were condensed to 65 categories via NLP. Compared to completion of the entire process manually, our automation process reduced the number of the terms requiring manual labor for mapping by 84.4% for medications and 59.4% for reasons for medication use. Additionally, this process improved the precision of the mapped results. CONCLUSIONS: Our automation framework demonstrates the usefulness of NLP strategies even when there is no established mapping database. For a less established database (e.g., reasons for medication use), the method is easily modifiable as new knowledge sources for mapping are introduced. The capability to condense large features into interpretable ones will be valuable for subsequent analytical studies involving techniques such as machine learning and data mining.

Psychometric properties of the PROMIS® Fatigue Short Form 7a among adults with myalgic encephalomyelitis/chronic fatigue syndrome.

PURPOSE: To evaluate the psychometric properties of the Patient-Reported Outcome Measurement Information System® Fatigue Short Form 7a (PROMIS F-SF) among people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). METHODS: Analyses were conducted using data from the Multi-Site Clinical Assessment of ME/CFS study, which recruited participants from seven ME/CFS specialty clinics across the US. Baseline and follow-up data from ME/CFS participants and healthy controls were used. Ceiling/Floor effects, internal consistency reliability, differential item functioning (DIF), known-groups validity, and responsiveness were examined. RESULTS: The final sample comprised 549 ME/CFS participants at baseline, 386 of whom also had follow-up. At baseline, the sample mean of PROMIS F-SF T-score was 68.6 (US general population mean T-score of 50 and standard deviation of 10). The PROMIS F-SF demonstrated good internal consistency reliability (Cronbach's α = 0.84) and minimal floor/ceiling effects. No DIF was detected by age or sex for any item. This instrument also showed good known-groups validity with medium-to-large effect sizes (η2 = 0.08-0.69), with a monotonic increase of the fatigue T-score across ME/CFS participant groups with low, medium, and high functional impairment as measured by three different variables (p < 0.01), and with significantly higher fatigue T-scores among ME/CFS participants than healthy controls (p < 0.0001). Acceptable responsiveness was found with small-to-medium effect sizes (Guyatt's Responsiveness Statistic = 0.28-0.54). CONCLUSIONS: Study findings support the reliability and validity of PROMIS F-SF as a measure of fatigue for ME/CFS and lend support to the drug development tool submission for qualifying this measure to evaluate therapeutic effect in ME/CFS clinical trials.

Association of chronic fatigue syndrome with premature telomere attrition.

BACKGROUND: Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a severely debilitating condition of unknown etiology. The symptoms and risk factors of ME/CFS share features of accelerated aging implicated in several diseases. Using telomere length as a marker, this study was performed to test the hypothesis that ME/CFS is associated with accelerated aging. METHODS: Participant (n = 639) data came from the follow-up time point of the Georgia CFS surveillance study. Using the 1994 CFS Research Case Definition with questionnaire-based subscale thresholds for fatigue, function, and symptoms, participants were classified into four illness groups: CFS if all criteria were met (n = 64), CFS-X if CFS with exclusionary conditions (n = 77), ISF (insufficient symptoms/fatigue) if only some criteria were met regardless of exclusionary conditions (n = 302), and NF (non-fatigued) if no criteria and no exclusionary conditions (n = 196). Relative telomere length (T/S ratio) was measured using DNA from whole blood and real-time PCR. General linear models were used to estimate the association of illness groups or T/S ratio with demographics, biological measures and covariates with significance set at p < 0.05. RESULTS: The mean T/S ratio differed significantly by illness group (p = 0.0017); the T/S ratios in CFS (0.90 ± 0.03) and ISF (0.94 ± 0.02) were each significantly lower than in NF (1.06 ± 0.04). Differences in T/S ratio by illness groups remained significant after adjustment for covariates of age, sex, body mass index, waist-hip ratio, post-exertional malaise and education attainment. Telomere length was shorter by 635, 254 and 424 base pairs in CFS, CFS-X and ISF, respectively, compared to NF. This shorter telomere length translates to roughly 10.1-20.5, 4.0-8.2 and 6.6-13.7 years of additional aging in CFS, CFS-X and ISF compared to NF respectively. Further, stratified analyses based on age and sex demonstrated that the association of ME/CFS with short telomeres is largely moderated by female subjects < 45 years old. CONCLUSIONS: This study found a significant association of ME/CFS with premature telomere attrition that is largely moderated by female subjects < 45 years old. Our results indicate that ME/CFS could be included in the list of conditions associated with accelerated aging. Further work is needed to evaluate the functional significance of accelerated aging in ME/CFS.

Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM): Design and Implementation of a Prospective/Retrospective Rolling Cohort Study.

In the Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM), we relied on expert clinician diagnoses to enroll patients from 7 specialty clinics in the United States in order to perform a systematic collection of data on measures of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Healthy persons and those with other illnesses that share some features with ME/CFS were enrolled in comparison groups. The major objectives were to: 1) use standardized questionnaires to measure illness domains of ME/CFS and to evaluate patient heterogeneity overall and between clinics; 2) describe the course of illness, identify the measures that best correlate with meaningful clinical differences, and assess the performances of questionnaires as patient/person-reported outcome measures; 3) describe prescribed medications, orders for laboratory and other tests, and management tools used by expert clinicians to care for persons with ME/CFS; 4) collect biospecimens for future hypothesis testing and for evaluation of morning cortisol profiles; and 5) identify measures that best distinguish persons with ME/CFS from those in the comparison groups and detect subgroups of persons with ME/CFS who may have different underlying causes. Enrollment began in 2012 and is planned to continue in multiple stages through 2017. We present the MCAM methods in detail, along with an initial description of the 471 patients with ME/CFS who were enrolled in stage 1.

Heterogeneity in Measures of Illness among Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Explained by Clinical Practice: A Study in Seven U.S. Specialty Clinics.

Background: One of the goals of the Multi-site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM) study was to evaluate whether clinicians experienced in diagnosing and caring for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) recognized the same clinical entity. Methods: We enrolled participants from seven specialty clinics in the United States. We used baseline data (n = 465) on standardized questions measuring general clinical characteristics, functional impairment, post-exertional malaise, fatigue, sleep, neurocognitive/autonomic symptoms, pain, and other symptoms to evaluate whether patient characteristics differed by clinic. Results: We found few statistically significant and no clinically significant differences between clinics in their patients' standardized measures of ME/CFS symptoms and function. Strikingly, patients in each clinic sample and overall showed a wide distribution in all scores and measures. Conclusions: Illness heterogeneity may be an inherent feature of ME/CFS. Presenting research data in scatter plots or histograms will help clarify the challenge. Relying on case-control study designs without subgrouping or stratification of ME/CFS illness characteristics may limit the reproducibility of research findings and could obscure underlying mechanisms.

Mental illness in metropolitan, urban and rural Georgia populations.

BACKGROUND: Mental illness represents an important public health problem. Local-level data concerning mental illness in different populations (e.g., socio-demographics and residence--metropolitan/urban/rural) provides the evidence-base for public health authorities to plan, implement and evaluate control programs. This paper describes prevalence and covariates of psychiatric conditions in Georgia populations in three defined geographic areas. METHODS: Data came from the Georgia population-based random-digit-dialing study investigating unwellness and chronic fatigue syndrome (CFS) in Georgia populations of three defined geographic areas (metropolitan, urban, and rural). Respondents were screened for symptoms of fatigue, sleep, cognition, and pain at household screening interviews, and a randomly selected sample completed detailed individual phone interviews. Based on the detailed phone interviews, we conducted one-day clinical evaluations of 292 detailed interview participants classified as unwell with a probable CFS (i.e. CFS-like; a functional somatic syndrome), 268 classified as other unwell, and 223 well (matched to CFS-like). Clinical evaluation included psychiatric classification by means of the Structured Clinical Interview for DSM (SCID). To derive prevalence estimates we used sample weighting to account for the complexity of the multistage sampling design. We used 2- and 3-way table analyses to examine socio-demographic and urbanicity specific associations and multiple logistic regression to calculate adjusted odds ratios. RESULTS: Anxiety and mood disorders were the most common psychiatric conditions. Nineteen percent of participants suffered a current anxiety disorder, 18% a mood disorder and 10% had two or more conditions. There was a significant linear trend in occurrence of anxiety or mood disorders from well to CFS-like. The most common anxiety disorders were post-traumatic stress disorder (PTSD) (6.6%) and generalized anxiety disorder (GAD) (5.8%). Logistic regression showed that lower education and female sex contributed significantly to risk for both PTSD and GAD. In addition, rural/urban residence and Hispanic ethnicity were associated with PTSD. We defined moderate to severe depression as Major Depressive Disorder or a Zung score>60 and logistic regression found lower education to be significantly associated but sex, age and urbanicity were not. CONCLUSIONS: Overall occurrence of anxiety and mood disorders in Georgia mirrored national findings. However, PTSD and GAD occurred at twice the published national rates (3.6 and 2.7%, respectively). State and local prevalence and associations with education, sex and urbanicity comprise important considerations for developing control programs. The increased prevalence of anxiety and mood disorders in people with a functional somatic syndrome (or CFS-like illness) is important for primary care providers, who should consider additional psychiatric screening or referral of individuals presenting with somatoform symptoms.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Adults: United States, 2021-2022.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after activity, and other symptoms (1). It affects all age, sex, and racial and ethnic groups and costs the U.S. economy about $18-$51 billion annually (2-5). This report describes the percentage of adults who had ME/CFS at the time of interview by selected demographic and geographic characteristics based on data from the 2021-2022 National Health Interview Survey (NHIS).

Long COVID in Children: United States, 2022.

While most individuals who contract COVID-19 feel better within a few weeks, others have new, returning, or ongoing symptoms that they did not have before COVID-19, which is often referred to as Long COVID (1). This report describes the percentage of children ages 0-17 years who ever had Long COVID or had Long COVID at the time of interview (currently have Long COVID) based on parent-reported data from the 2022 National Health Interview Survey (NHIS). Long COVID was defined as the presence of symptoms for at least 3 months after having COVID-19 among those who received either a positive test or a doctor's diagnosis of COVID-19.

A technology-enabled multi-disciplinary team-based care model for the management of Long COVID and other fatiguing illnesses within a federally qualified health center: protocol for a two-arm, single-blind, pragmatic, quality improvement professional cluster randomized controlled trial.

BACKGROUND: The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions. METHODS: We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts. DISCUSSION: We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021.

Cardiopulmonary, metabolic, and perceptual responses during exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Multi-site Clinical Assessment of ME/CFS (MCAM) sub-study.

BACKGROUND: Cardiopulmonary exercise testing has demonstrated clinical utility in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, to what extent exercise responses are independent of, or confounded by, aerobic fitness remains unclear. PURPOSE: To characterize and compare exercise responses in ME/CFS and controls with and without matching for aerobic fitness. METHODS: As part of the Multi-site Clinical Assessment of ME/CFS (MCAM) study, 403 participants (n = 214 ME/CFS; n = 189 controls), across six ME/CFS clinics, completed ramped cycle ergometry to volitional exhaustion. Metabolic, heart rate (HR), and ratings of perceived exertion (RPE) were measured. Ventilatory equivalent ([Formula: see text], [Formula: see text]), metrics of ventilatory efficiency, and chronotropic incompetence (CI) were calculated. Exercise variables were compared using Hedges' g effect size with 95% confidence intervals. Differences in cardiopulmonary and perceptual features during exercise were analyzed using linear mixed effects models with repeated measures for relative exercise intensity (20-100% peak [Formula: see text]). Subgroup analyses were conducted for 198 participants (99 ME/CFS; 99 controls) matched for age (±5 years) and peak [Formula: see text] (~1 ml/kg/min-1). RESULTS: Ninety percent of tests (n = 194 ME/CFS, n = 169 controls) met standard criteria for peak effort. ME/CFS responses during exercise (20-100% peak [Formula: see text]) were significantly lower for ventilation, breathing frequency, HR, measures of efficiency, and CI and significantly higher for [Formula: see text], [Formula: see text] and RPE (p<0.05adjusted). For the fitness-matched subgroup, differences remained for breathing frequency, [Formula: see text], [Formula: see text], and RPE (p<0.05adjusted), and higher tidal volumes were identified for ME/CFS (p<0.05adjusted). Exercise responses at the gas exchange threshold, peak, and for measures of ventilatory efficiency (e.g., [Formula: see text]) were generally reflective of those seen throughout exercise (i.e., 20-100%). CONCLUSION: Compared to fitness-matched controls, cardiopulmonary responses to exercise in ME/CFS are characterized by inefficient exercise ventilation and augmented perception of effort. These data highlight the importance of distinguishing confounding fitness effects to identify responses that may be more specifically associated with ME/CFS.

Association of Initial SARS-CoV-2 Test Positivity With Patient-Reported Well-being 3 Months After a Symptomatic Illness.

Importance: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use. Objective: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection. Design, Setting, and Participants: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form-Cognitive Function 8a scale, for which population-normed T scores were reported. Exposures: SARS-CoV-2 status (positive or negative test result) at enrollment. Main Outcomes and Measures: Mean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis. Results: Among 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19-positive group and 147 of 275 participants (53.5%) in the COVID-19-negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19-positive group vs the COVID-19-negative group only for social participation (ß = 3.32; 95% CI, 1.84-4.80; P < .001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19-positive group were concentrated among participants aged 18 to 34 years (eg, social participation: ß = 3.90; 95% CI, 1.75-6.05; P < .001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: ß = 4.16; 95% CI, 2.12-6.20; P < .001). Conclusions and Relevance: In this study, participants in both the COVID-19-positive and COVID-19-negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19.

The economic impact of chronic fatigue syndrome in Georgia: direct and indirect costs.

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating chronic illness affecting at least 4 million people in the United States. Understanding its cost improves decisions regarding resource allocation that may be directed towards treatment and cure, and guides the evaluation of clinical and community interventions designed to reduce the burden of disease. METHODS: This research estimated direct and indirect costs of CFS and the impact on educational attainment using a population-based, case-control study between September 2004 and July 2005, Georgia, USA. Participants completed a clinical evaluation to confirm CFS, identify other illnesses, and report on socioeconomic factors. We estimated the effect of CFS on direct medical costs (inpatient hospitalizations, provider visits, prescription medication spending, other medical supplies and services) and loss in productivity (employment and earnings) with a stratified sample (n = 500) from metropolitan, urban, and rural Georgia. We adjusted medical costs and earnings for confounders (age, sex, race/ethnicity, education, and geographic strata) using econometric models and weighted estimates to reflect response-rate adjusted sampling rates. RESULTS: Individuals with CFS had mean annual direct medical costs of $5,683. After adjusting for confounding factors, CFS accounted for $3,286 of these costs (p < 0.01), which were driven by increased provider visits and prescription medication use. Nearly one-quarter of these expenses were paid directly out-of pocket by those with CFS. Individuals with CFS reported mean annual household income of $23,076. After adjustment, CFS accounted for $8,554 annually in lost household earnings (p < 0.01). Lower educational attainment accounted for 19% of the reduction in earnings associated with CFS. CONCLUSIONS: Study results indicate that chronic fatigue syndrome may lead to substantial increases in healthcare costs and decreases in individual earnings. Studies have estimated up to 2.5% of non-elderly adults may suffer from CFS. In Georgia, a state with roughly 5.5 million people age 18-59, illness could account for $452 million in total healthcare expenditures and $1.2 billion of lost productivity.

Personality features and personality disorders in chronic fatigue syndrome: a population-based study.

BACKGROUND: Chronic fatigue syndrome (CFS) presents unique diagnostic and management challenges. Personality may be a risk factor for CFS and may contribute to the maintenance of the illness. METHODS: 501 study participants were identified from the general population of Georgia: 113 people with CFS, 264 with unexplained unwellness but not CFS (insufficient fatigue, ISF) and 124 well controls. We used the Personality Diagnostic Questionnaire, 4th edition, to evaluate DSM-IV personality disorders. We used the NEO Five-Factor Inventory to assess personality features (neuroticism, extraversion, openness, agreeableness and conscientiousness). The Multidimensional Fatigue Inventory measured 5 dimensions of fatigue, and the Medical Outcomes Survey Short Form 36 measured 8 dimensions of functional impairment. RESULTS: Twenty-nine percent of the CFS cases had at least 1 personality disorder, compared to 28% of the ISF cases and 7% of the well controls. The prevalence of paranoid, schizoid, avoidant, obsessive-compulsive and depressive personality disorders were significantly higher in CFS and ISF compared to the well controls. The CFS cases had significantly higher scores on neuroticism, and significantly lower scores on extraversion than those with ISF or the well controls. Personality features were correlated with selected composite characteristics of fatigue. CONCLUSIONS: Our results suggest that CFS is associated with an increased prevalence of maladaptive personality features and personality disorders. This might be associated with being noncompliant with treatment suggestions, displaying unhealthy behavioral strategies and lacking a stable social environment. Since maladaptive personality is not specific to CFS, it might be associated with illness per se rather than with a specific condition.

Association of childhood trauma with cognitive function in healthy adults: a pilot study.

BACKGROUND: Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults. METHODS: In this pilot study, we investigated the relationship between childhood trauma exposure and cognitive function in 47 healthy adults, who were identified as part of a larger study from the general population in Wichita, KS. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Wide-Range-Achievement-Test (WRAT-3) to examine cognitive function and individual achievement. Type and severity of childhood trauma was assessed by the Childhood Trauma Questionnaire (CTQ). Data were analyzed using multiple linear regression on CANTAB measures with primary predictors (CTQ scales) and potential confounders (age, sex, education, income). RESULTS: Specific CTQ scales were significantly associated with measures of cognitive function. Emotional abuse was associated with impaired spatial working memory performance. Physical neglect correlated with impaired spatial working memory and pattern recognition memory. Sexual abuse and physical neglect were negatively associated with WRAT-3 scores. However, the association did not reach the significance level of p < 0.01. CONCLUSIONS: Our results suggest that physical neglect and emotional abuse might be associated with memory deficits in adulthood, which in turn might pose a risk factor for the development of psychopathology.

U.S. healthcare providers' knowledge, attitudes, beliefs, and perceptions concerning Chronic Fatigue Syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating illness with particular difficulties for healthcare providers because there are no diagnostic signs or laboratory tests and because management aims to merely improve symptoms. Further complicating management, healthcare providers' awareness concerning CFS has not been rigorously assessed. The present study aimed to ascertain United States (U.S.) healthcare providers' awareness of CFS and to assess their knowledge, attitudes, and beliefs (KAB) related to diagnosis and management of the illness. This information forms the foundation for developing CFS educational strategies. METHODS: We combined convenience and probability samples to measure CFS KAB among healthcare providers. In the convenience sample, 1,255 healthcare providers (81% response rate) from 13 professional conferences completed a 12-item form. Descriptive statistics were reported for 9 KAB item responses and chi-square tests were performed for examining their association with giving a diagnosis of CFS. We used principal component analysis to construct multidimensional subscales and perform a general linear model to examine factors associated with subscales. The probability sample involved data on 15 CFS-specific questions from 2006 and 2007 DocStyles web-based panel surveys collected from 2,750 physicians (average response rate 55%). We calculated descriptive and chi-square statistics. The significance was set at two-tailed with the alpha level of 0.05. RESULTS: Healthcare providers in both samples were aware of CFS and exhibited a high level of knowledge. Overall, 96% of respondents in the DocStyles (probability) sample had heard about CFS. Healthcare providers in the conference (convenience) sample demonstrated good KAB scores; physicians' scores were highest on KAB scales and lowest in perception. Nurses' scores were lowest in knowledge. More than 40% of physicians reported ever giving a CFS diagnosis and in the DocStyles (probability) sample more than 80% of physicians correctly identified CFS symptoms. Physicians reported professional journals, the Internet, and continuing education programs as the top 3 sources from which they obtain CFS information. CONCLUSIONS: Findings from these combined samples fill a gap in the evidence-base of U.S. healthcare providers' and knowledge, attitudes, and beliefs concerning CFS. Importantly, respondents in both samples expressed similar knowledge, attitudes, beliefs and perceptions. Awareness was high and negative attitudes were low. The primary areas for future education should address diagnosis and management of CFS and should be delivered through those venues providers indicated they primarily use. Data from this study provide a benchmark for evaluation the success of these future efforts.

Hypersomnolence and sleep-related complaints in metropolitan, urban, and rural Georgia.

Persistent daytime hypersomnolence is associated with significant morbidity and mortality, but its prevalence in the population has been poorly documented. This study sought to characterize the prevalence of persistent daytime hypersomnolence, difficulties initiating and maintaining sleep, unrefreshing sleep, snoring, and the presence of physician-diagnosed sleep disorders in metropolitan, urban, and rural US Georgia populations. Between September 2004 and July 2005, a total of 6,530 randomly selected well and unwell adults, identified by screening interviews of 10,837 households (contacted by random digit dialing), completed a detailed phone interview. Sixteen percent reported persistent problems staying awake during the day; 26% reported persistent problems falling asleep at night; 31% experienced problems sleeping through the night; 34% were bothered by unrefreshing sleep; and 33% reported that they snored. In spite of the high occurrence of reported persistent sleep problems, only 10% of the survey participants reported having been diagnosed with a sleep disorder. These study findings highlight the need for increased public and clinician awareness with respect to proactively identifying signs and symptoms of sleep disorders, a better understanding of their adverse impact upon morbidity and mortality, and their negative impact upon socioeconomic and academic potential.