Tag: Unger

Regional distribution of fatiguing illnesses in the United States: a pilot study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating illness with no known cause or effective therapy. Population-based epidemiologic data on CFS prevalence are critical to put CFS in a realistic context for public health officials and others responsible for allocating resources.

METHODS: We conducted a pilot random-digit-dialing survey to estimate the prevalence of fatiguing illnesses in different geographic regions and in urban and rural populations of the United States. This report focuses on 884 of 7,317 respondents 18 to 69 years old. Fatigued (440) and randomly selected non-fatigued (444) respondents completed telephone questionnaires concerning fatigue, other symptoms, and medical history.

RESULTS: We estimated 12,186 per 100,000 persons 18 to 69 years of age suffered from fatigue lasting for at least 6 months (chronic fatigue), and 1,197 per 100,000 described an illness that, though lacking clinical evaluation, met criteria for CFS (CFS-like). Chronic fatigue and CFS-like illness were more common in rural than in urban populations, although the differences were not significant. The prevalence of these fatiguing illnesses did not differ meaningfully among the four regions surveyed, and no significant geographic trends were observed.

CONCLUSIONS: This investigation estimated that nearly 2.2 million American adults suffer from CFS-like illness. The study also suggested the need to focus future investigations of fatigue on populations with lower incomes and less education. There was no evidence for regional differences in the occurrence of fatiguing illnesses.

 

Source: Bierl C, Nisenbaum R, Hoaglin DC, Randall B, Jones AB, Unger ER, Reeves WC. Regional distribution of fatiguing illnesses in the United States: a pilot study. Popul Health Metr. 2004 Feb 4;2(1):1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC356930/ (Full article)

 

Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is defined by symptoms and disability, has no confirmatory physical signs or characteristic laboratory abnormalities, and the etiology and pathophysiology remain unknown. Difficulties with accurate case ascertainment contribute to this ignorance.

METHODS: Experienced investigators from around the world who are involved in CFS research met for a series of three day workshops in 2000, 2001 and 2002 intended to identify the problems in application of the current CFS case definition. The investigators were divided into focus groups and each group was charged with a topic. The investigators in each focus group relied on their own clinical and scientific knowledge, brainstorming within each group and with all investigators when focus group summaries were presented. Relevant literature was selected and reviewed independent of the workshops. The relevant literature was circulated via list-serves and resolved as being relevant by group consensus. Focus group reports were analyzed and compiled into the recommendations presented here.

RESULTS: Ambiguities in the current CFS research definition that contribute to inconsistent case identification were identified. Recommendations for use of the definition, standardization of classification instruments and study design issues are presented that are intended to improve the precision of case ascertainment. The International CFS Study Group also identified ambiguities associated with exclusionary and comorbid conditions and reviewed the standardized, internationally applicable instruments used to measure symptoms, fatigue intensity and associated disability.

CONCLUSION: This paper provides an approach to guide systematic, and hopefully reproducible, application of the current case definition, so that case ascertainment would be more uniform across sites. Ultimately, an operational CFS case definition will need to be based on empirical studies designed to delineate the possibly distinct biological pathways that result in chronic fatigue.

Comment in: Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. [BMC Health Serv Res. 2005]

 

Source: Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER; International Chronic Fatigue Syndrome Study Group. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res. 2003 Dec 31;3(1):25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC317472/ (Full article)

 

Integration of gene expression, clinical, and epidemiologic data to characterize Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) has no diagnostic clinical signs or diagnostic laboratory abnormalities and it is unclear if it represents a single illness. The CFS research case definition recommends stratifying subjects by co-morbid conditions, fatigue level and duration, or functional impairment. But to date, this analysis approach has not yielded any further insight into CFS pathogenesis. This study used the integration of peripheral blood gene expression results with epidemiologic and clinical data to determine whether CFS is a single or heterogeneous illness.

RESULTS: CFS subjects were grouped by several clinical and epidemiological variables thought to be important in defining the illness. Statistical tests and cluster analysis were used to distinguish CFS subjects and identify differentially expressed genes. These genes were identified only when CFS subjects were grouped according to illness onset and the majority of genes were involved in pathways of purine and pyrimidine metabolism, glycolysis, oxidative phosphorylation, and glucose metabolism.

CONCLUSION: These results provide a physiologic basis that suggests CFS is a heterogeneous illness. The differentially expressed genes imply fundamental metabolic perturbations that will be further investigated and illustrates the power of microarray technology for furthering our understanding CFS.

 

Source: Whistler T, Unger ER, Nisenbaum R, Vernon SD. Integration of gene expression, clinical, and epidemiologic data to characterize Chronic Fatigue Syndrome. J Transl Med. 2003 Dec 1;1(1):10. http://www.ncbi.nlm.nih.gov/pubmed/14641939

 

A population-based study of the clinical course of chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) presents a challenge for patients, health care providers, and health insurance groups because of its incapacitating nature, unknown cause, and poorly understood prognosis. We conducted a longitudinal population-based study to characterize the clinical course of CFS.

METHODS: Sixty-five CFS subjects were identified from a random-digit-dialing survey of Wichita, Kansas residents and followed for up to 3 years. We evaluated changes in CFS classification (partial or total remission, alternative medical or psychiatric diagnoses), CFS case-defining criteria, wellness scores, hours of activities and sleep, and treatments used to reduce fatigue. Associations between risk factors and outcomes were determined by use of logistic regression and generalized estimating equations models.

RESULTS: Only 20%-33% of the subjects were classified as having CFS at follow-up, 56.9% ever experienced partial or total remission, 10% sustained total remission, and 23.1% received alternative diagnoses, of which 20% were sleep disorders. Higher fatigue severity scores and total number of symptoms were negatively associated with ever remitting. Duration of illness < or = 2 years was positively associated with sustained remission. Unrefreshing sleep persisted in at least 79% of the subjects across all periods but, as with most of the CFS symptoms, tended to be less frequent over time. The number of activities affected by fatigue decreased over time, while wellness scores increased. At any follow-up, more than 35% of subjects reporting reduced fatigue used complementary and alternative medicine therapies, and of those subjects, at least 50% thought these therapies were responsible for reducing their fatigue.

CONCLUSIONS: The clinical course of CFS was characterized by an intermittent pattern of relapse and remission. Remission rates documented by our population-based study were similar to those reported in clinical studies. Shorter illness duration was a significant predictor of sustained remission, and thus early detection of CFS is of utmost importance. The persistence of sleep complaints and identification of sleep disorders suggest that CFS subjects be evaluated for sleep disturbances, which could be treated.

Comment in: Chronic fatigue and chronic fatigue syndrome in the general population. [Health Qual Life Outcomes. 2003]

 

Source: Nisenbaum R, Jones JF, Unger ER, Reyes M, Reeves WC. A population-based study of the clinical course of chronic fatigue syndrome. Health Qual Life Outcomes. 2003 Oct 3;1:49. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC269990/ (Full article)

 

Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating illness with no known cause or effective therapy. Population-based epidemiologic data on CFS prevalence and incidence are critical to put CFS in a realistic context for public health officials and others responsible for allocating resources and for practicing physicians when examining and caring for patients.

METHODS: We conducted a random digit-dialing survey and clinical examination to estimate the prevalence of CFS in the general population of Wichita, Kan, and a 1-year follow-up telephone interview and clinical examination to estimate the incidence of CFS. The survey included 33 997 households representing 90 316 residents. This report focuses on 7162 respondents aged 18 to 69 years. Fatigued (n = 3528) and randomly selected nonfatigued (n = 3634) respondents completed telephone questionnaires concerning fatigue, other symptoms, and medical history. The clinical examination included the Diagnostic Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, laboratory testing, and a physical examination.

RESULTS: The overall weighted point prevalence of CFS, adjusted for nonresponse, was 235 per 100,000 persons (95% confidence interval, 142-327 per 100,000 persons). The prevalence of CFS was higher among women, 373 per 100,000 persons (95% confidence interval, 210-536 per 100,000 persons), than among men, 83 per 100,000 persons (95% confidence interval, 15-150 per 100,000 persons). Among subjects nonfatigued and fatigued for less than 6 months, the 1-year incidence of CFS was 180 per 100,000 persons (95% confidence interval, 0-466 per 100,000 persons).

CONCLUSIONS: Chronic fatigue syndrome constitutes a major public health problem. Longitudinal follow-up of this cohort will be used to further evaluate the natural history of this illness.

 

Source: Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC. Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Intern Med. 2003 Jul 14;163(13):1530-6. http://www.ncbi.nlm.nih.gov/pubmed/12860574

 

Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating illness lacking consistent anatomic lesions and eluding conventional laboratory diagnosis. Demonstration of the utility of the blood for gene expression profiling and biomarker discovery would have implications into the pathophysiology of CFS. The objective of this study was to determine if gene expression profiles of peripheral blood mononuclear cells (PMBCs) could distinguish between subjects with CFS and healthy controls.

Total RNA from PBMCs of five CFS cases and seventeen controls was labeled and hybridized to 1764 genes on filter arrays. Gene intensity values were analyzed by various classification algorithms and nonparametric statistical methods. The classification algorithms grouped the majority of the CFS cases together, and distinguished them from the healthy controls.

Eight genes were differentially expressed in both an age-matched case-control analysis and when comparing all CFS cases to all controls. Several of the differentially expressed genes are associated with immunologic functions (e.g., CMRF35 antigen, IL-8, HD protein) and implicate immune dysfunction in the pathophysiology of CFS. These results successfully demonstrate the utility of the blood for gene expression profiling to distinguish subjects with CFS from healthy controls and for identifying genes that could serve as CFS biomarkers.

 

Source: Vernon SD, Unger ER, Dimulescu IM, Rajeevan M, Reeves WC. Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome. Dis Markers. 2002;18(4):193-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851413/ (Full article)

 

Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects

Abstract:

BACKGROUND: The association of an infectious agent with chronic fatigue syndrome (CFS) has been difficult and is further complicated by the lack of a known lesion or diseased tissue. Cell-free plasma DNA could serve as a sentinel of infection and disease occurring throughout the body. This type of systemic sample coupled with broad-range amplification of bacterial sequences was used to determine whether a bacterial pathogen was associated with CFS. Plasma DNA from 34 CFS and 55 non-fatigued subjects was assessed to determine plasma DNA concentration and the presence of bacterial 16S ribosomal DNA (rDNA) sequences.

RESULTS: DNA was isolated from 81 (91%) of 89 plasma samples. The 55 non-fatigued subjects had higher plasma DNA concentrations than those with CFS (average 151 versus 91 ng) and more CFS subjects (6/34, 18%) had no detectable plasma DNA than non-fatigued subjects (2/55, 4%), but these differences were not significant. Bacterial sequences were detected in 23 (26%) of 89. Only 4 (14%) CFS subjects had 16S rDNA sequences amplified from plasma compared with 17 (32%) of the non-fatigued (P = 0.03). All but 1 of the 23 16S rDNA amplicon-positive subjects had five or more unique sequences present.

CONCLUSIONS: CFS subjects had slightly lower concentrations or no detectable plasma DNA than non-fatigued subjects. There was a diverse array of 16S rDNA sequences in plasma DNA from both CFS and non-fatigued subjects. There were no unique, previously uncharacterized or predominant 16S rDNA sequences in either CFS or non-fatigued subjects.

 

Source: Vernon SD, Shukla SK, Conradt J, Unger ER, Reeves WC. Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects. BMC Microbiol. 2002 Dec 23;2:39. Epub 2002 Dec 23. http://www.ncbi.nlm.nih.gov/pubmed/12498618