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.

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.

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.

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.

Assessment of ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome): A Case Study for Health Care Providers.

INTRODUCTION: Over a million adults in the U.S. are affected by chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME). A debilitating illness, ME/CFS is accompanied by profound fatigue that is not relieved by rest and affects daily activities. Symptoms include postexertional malaise, cognitive problems, unrefreshing sleep, and pain. This course provides tools to teach medical, physician assistant, and nursing students to recognize, diagnose, and manage patients with ME/CFS. METHODS: The student is expected to view the provider-to-provider video and the PowerPoint slide curriculum, which describe the steps for evaluation. The video depicts two physicians conferring about ME/CFS and addresses the challenges of making a diagnosis. The slide curriculum shows the different ME/CFS symptoms and case definitions and how to apply them using a case study. Medical, physician assistant, and nursing students were recruited to evaluate the course and viewed it either online or in a campus education center. RESULTS: Results showed that students met learning objectives and showed increases from pre- to posttest evaluation in their understanding of the difficulties of diagnosing ME/CFS and managing the illness. In addition to knowledge, student attitudes towards ME/CFS changed, with more empathy towards patients and the awareness that ME/CFS requires frequent communication and reevaluation of patients' symptoms. DISCUSSION: Strategies of how to manage ME/CFS for the patient and manage time constraints during visits with ME/CFS patients are discussed.

Utilization of two web-based continuing education courses evaluated by Markov chain model.

OBJECTIVES: To evaluate the web structure of two web-based continuing education courses, identify problems and assess the effects of web site modifications. DESIGN: Markov chain models were built from 2008 web usage data to evaluate the courses' web structure and navigation patterns. The web site was then modified to resolve identified design issues and the improvement in user activity over the subsequent 12 months was quantitatively evaluated. MEASUREMENTS: Web navigation paths were collected between 2008 and 2010. The probability of navigating from one web page to another was analyzed. RESULTS: The continuing education courses' sequential structure design was clearly reflected in the resulting actual web usage models, and none of the skip transitions provided was heavily used. The web navigation patterns of the two different continuing education courses were similar. Two possible design flaws were identified and fixed in only one of the two courses. Over the following 12 months, the drop-out rate in the modified course significantly decreased from 41% to 35%, but remained unchanged in the unmodified course. The web improvement effects were further verified via a second-order Markov chain model. CONCLUSIONS: The results imply that differences in web content have less impact than web structure design on how learners navigate through continuing education courses. Evaluation of user navigation can help identify web design flaws and guide modifications. This study showed that Markov chain models provide a valuable tool to evaluate web-based education courses. Both the results and techniques in this study would be very useful for public health education and research specialists.

Surveillance of certain health behaviors and conditions among states and selected local areas --- Behavioral Risk Factor Surveillance System, United States, 2009.

PROBLEM: Chronic diseases and conditions (e.g., heart disease, cancer, stroke, and diabetes) are the leading causes of death in the United States. Controlling health risk behaviors and conditions (e.g., smoking, physical inactivity, poor diet, excessive drinking, and obesity) and using preventive health-care services (e.g., physical examination, vaccination, screening for high blood pressure and high cholesterol, consumption of fruits and vegetables, and participation in regular leisure-time physical activity) can reduce morbidity and mortality from chronic diseases. REPORTING PERIOD: January 2009--December 2009. DESCRIPTION OF THE SYSTEM: The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing state-based random-digit--dialed telephone survey of noninstitutionalized adults aged ≥18 years residing in the United States. BRFSS collects data on health risk behaviors and conditions, chronic diseases and conditions, access to health care, and use of preventative health services and practices related to the leading causes of death and disabilities in the United States. This report presents results for 2009 for all 50 states, the District of Columbia, the Commonwealth of Puerto Rico, Guam, the U.S. Virgin Islands, 180 metropolitan and micropolitan statistical areas (MMSAs), and 283 selected counties. RESULTS: In 2009, the estimated prevalence of general health status, use of preventive health-care services, health risk behaviors and conditions, chronic diseases, and health impairments and disabilities varied substantially by state and territory, MMSA, and county. The following is a summary of results listed by BRFSS question topics. Each set of proportions refers to the range of estimated prevalence for the disease, condition, or behavior, as reported by the survey respondent. Adults who reported having fair or poor health: 10.1%--30.9% for states and territories, 7.9%--25.8% for MMSAs, and 4.5%--26.1% for counties. Adults with health-care coverage: 71.4%--94.7% for states and territories, 52.7%--96.3% for MMSAs, and 52.7%--97.6% for counties. Annual routine physical checkup among adults aged ≥18 years: 55.8%--79.3% for states and territories, 51.8%--80.7% for MMSAs, and 49.2%--83.5% for counties. Annual influenza vaccination among adults aged ≥65 years: 26.8%--76.8% for states and territories, 55.4%--81.4% for MMSAs, and 50.5%--83.5% for counties. Pneumococcal vaccination among adults aged ≥65 years: 19.1%--73.9% for states and territories, 52.9%--81.3% for MMSAs, and 41.9%--82.0% for counties. Adults who had their cholesterol checked within the preceding 5 years: 67.5%--85.3% for states and territories, 58.2%--88.8% for MMSAs, and 58.2%--92.4% for counties. Adults who consumed at least five servings of fruits and vegetables per day: 14.6%--31.5% for states and territories, 12.6%--33.0% for MMSAs, and 13.4%--34.9% for counties. Adults who engaged in moderate or vigorous physical activity: 28.0%--60.7% for states and territories, 34.6%--64.9% for MMSAs, and 33.6%--67.3% for counties. Adults who engaged in only vigorous physical activity: 13.7%--40.1% for states and territories, 13.8%--43.3% for MMSAs, and 14.2%--50.0% for counties. Current cigarette smoking among adults: 6.4%--25.6% for states and territories, 5.7%--29.0% for MMSAs, and 5.6%--29.8% for counties. Binge drinking among adults: 6.8%--23.9% for states and territories, 3.5%--23.2% for MMSAs, and 3.4%--26.3% for counties. Heavy drinking among adults: 1.9%--8.1% for states and territories, 1.0%--11.1% for MMSAs, and 0.9%--11.1% for counties. Adults who reported no leisure-time physical activity: 15.8%--45.6% for states and territories, 13.3%--40.2% for MMSAs, and 10.5%--40.2% for counties. Adults aged ≥18 years who were overweight: 31.6%--38.7% for states and territories, 28.7%--44.1% for MMSAs, and 25.6%--46.7% for counties. Adults aged ≥20 years who were obese: 19.7%--36.0% for states and territories, 15.4%--43.6% for MMSAs, and 13.8%--45.7% for counties. Adults aged ≥18 years who did not get enough rest or sleep: 34.3%--52.6% for states and territories, 28.2%--54.8% for MMSAs, and 24.5%--55.6% for counties. Adults who had received a high blood pressure diagnosis: 22.1%--38.5% for states and territories, 18.8%--43.9% for MMSAs, and 17.2%--43.6% for counties. Adults who had a high blood cholesterol diagnosis: 24.9%--42.2% for states and territories, 27.5%--47.8% for MMSAs, and 26.7%--51.4% for counties. Adults who had received a diagnosis of coronary heart disease: 2.5%--10.3% for states and territories, 2.6%--11.6% for MMSAs, and 1.6%--12.3% for counties. Adults who had received a stroke diagnosis: 1.4%--3.9% for states and territories, 0.8%--5.9% for MMSAs, and 0.8%--6.6% for counties. Adults who had received a diabetes diagnosis: 5.8%--12.9% for states and territories, 2.8%--15.4% for MMSAs, and 2.8%--14.7% for counties. Adults who had received a cancer diagnosis: 3.0%--12.6% for states and territories, 5.8%--15.1% for MMSAs, and 3.9%--16.2% for counties. Adults who had asthma: 4.4%--11.1% for states and territories, and 3.2%--15.3% for MMSAs, and 3.2%--15.7% for counties. Adults who had arthritis: 10.7%--35.6% for states and territories, 16.2%--36.0% for MMSAs, and 12.6%--39.4% for counties. Adults with activity limitation associated with physical, mental, or emotional problems: 10.2%--27.1% for states and territories, 13.1%--33.7% for MMSAs, and 10.4%--36.1% for counties. Adults who required special equipment because of health problems: 3.6%--10.2% for states and territories, 3.4%--11.5% for MMSAs, and 1.7%--13.0% for counties. INTERPRETATION: The findings in this report indicate substantial variations in self-rated general health status, health-care coverage, use of preventive health-care services, health risk behaviors and health conditions, cardiovascular conditions, other chronic diseases, and health impairments and disabilities among U.S. adults at the state and territory, MMSA, and county levels. The findings show that Healthy People 2010 objectives had not been met in many areas by 2009, which underscores the continued need for surveillance of general health status, use of preventive health-care services, health risk behaviors and conditions, chronic diseases, and health impairment and disability. PUBLIC HEALTH ACTION: Data on health risk behaviors, chronic health conditions, preventive care practices, and chronic diseases are used to develop health promotion activities, intervention programs, and health policies at the state, city, and county levels.. The overarching goals of Healthy People 2010 are to increase quality and years of healthy life and to eliminate health disparities. Local and state health departments and federal agencies should continue to use BRFSS data to identify populations at high risk for certain health risk behaviors and conditions, cardiovascular conditions, and other chronic diseases and to evaluate the use of preventive health-care services. In addition, BRFSS data can be used to direct, implement, monitor, and evaluate public health programs and policies that can lead to a reduction in morbidity and mortality.

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.

Web usage data as a means of evaluating public health messaging and outreach.

BACKGROUND: The Internet is increasingly utilized by researchers, health care providers, and the public to seek medical information. The Internet also provides a powerful tool for public health messaging. Understanding the needs of the intended audience and how they use websites is critical for website developers to provide better services to the intended users. OBJECTIVE: The aim of the study was to examine the utilization of the chronic fatigue syndrome (CFS) website at the Centers for Disease Control and Prevention (CDC). We evaluated (1) CFS website utilization, (2) outcomes of a CDC CFS public awareness campaign, and (3) user behavior related to public awareness campaign materials and CFS continuing medical education courses. METHODS: To describe and evaluate Web utilization, we collected Web usage data over an 18-month period and extracted page views, visits, referring domains, and geographic locations. We used page views as the primary measure for the CFS awareness outreach effort. We utilized market basket analysis and Markov chain model techniques to describe user behavior related to utilization of campaign materials and continuing medical education courses. RESULTS: The CDC CFS website received 3,647,736 views from more than 50 countries over the 18-month period and was the 33rd most popular CDC website. States with formal CFS programs had higher visiting density, such as Washington, DC; Georgia; and New Jersey. Most visits (71%) were from Web search engines, with 16% from non-search-engine sites and 12% from visitors who had bookmarked the site. The public awareness campaign was associated with a sharp increase and subsequent quick drop in Web traffic. Following the campaign, user interest shifted from information targeting consumer basic knowledge to information for health care professionals. The market basket analysis showed that visitors preferred the 60-second radio clip public service announcement over the 30-second one. Markov chain model results revealed that most visitors took the online continuing education courses in sequential order and were less likely to drop out after they reached the Introduction pages of the courses. CONCLUSIONS: The utilization of the CFS website reflects a high level of interest in the illness by visitors to the site. The high utilization shows the website to be an important online resource for people seeking basic information about CFS and for those looking for professional health care and research information. Public health programs should consider analytic methods to further public health by understanding the characteristics of those seeking information and by evaluating the outcomes of public health campaigns. The website was an effective means to provide health information about CFS and serves as an important public health tool for community outreach.