Rosane Nisenbaum

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

BackgroundChronic 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.MethodsExperienced 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.ResultsAmbiguities 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.ConclusionThis 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.

Chronic Fatigue Syndrome – A clinically empirical approach to its definition and study

BackgroundThe lack of standardized criteria for defining chronic fatigue syndrome (CFS) has constrained research. The objective of this study was to apply the 1994 CFS criteria by standardized reproducible criteria.MethodsThis population-based case control study enrolled 227 adults identified from the population of Wichita with: (1) CFS (n = 58); (2) non-fatigued controls matched to CFS on sex, race, age and body mass index (n = 55); (3) persons with medically unexplained fatigue not CFS, which we term ISF (n = 59); (4) CFS accompanied by melancholic depression (n = 27); and (5) ISF plus melancholic depression (n = 28). Participants were admitted to a hospital for two days and underwent medical history and physical examination, the Diagnostic Interview Schedule, and laboratory testing to identify medical and psychiatric conditions exclusionary for CFS. Illness classification at the time of the clinical study utilized two algorithms: (1) the same criteria as in the surveillance study; (2) a standardized clinically empirical algorithm based on quantitative assessment of the major domains of CFS (impairment, fatigue, and accompanying symptoms).ResultsOne hundred and sixty-four participants had no exclusionary conditions at the time of this study. Clinically empirical classification identified 43 subjects as CFS, 57 as ISF, and 64 as not ill. There was minimal association between the empirical classification and classification by the surveillance criteria. Subjects empirically classified as CFS had significantly worse impairment (evaluated by the SF-36), more severe fatigue (documented by the multidimensional fatigue inventory), more frequent and severe accompanying symptoms than those with ISF, who in turn had significantly worse scores than the not ill; this was not true for classification by the surveillance algorithm.ConclusionThe empirical definition includes all aspects of CFS specified in the 1994 case definition and identifies persons with CFS in a precise manner that can be readily reproduced by both investigators and clinicians.

Psychometric properties of the CDC Symptom Inventory for assessment of Chronic Fatigue Syndrome

ObjectivesValidated or standardized self-report questionnaires used in research studies and clinical evaluation of chronic fatigue syndrome (CFS) generally focus on the assessment of fatigue. There are relatively few published questionnaires that evaluate case defining and other accompanying symptoms in CFS. This paper introduces the self-report CDC CFS Symptom Inventory and analyzes its psychometric properties.MethodsOne hundred sixty-four subjects (with CFS, other fatiguing illnesses and non fatigued controls) identified from the general population of Wichita, Kansas were enrolled. Evaluation included a physical examination, a standardized psychiatric interview, three previously validated self-report questionnaires measuring fatigue and illness impact (Medical Outcomes Survey Short-Form-36 [MOS SF-36], Multidimensional Fatigue Inventory [MFI], Chalder Fatigue Scale), and the CDC CFS Symptom Inventory. Based on theoretical assumptions and statistical analyses, we developed several different Symptom Inventory scores and evaluated them on their ability to differentiate between participants with CFS and non-fatigued controls.ResultsThe Symptom Inventory had good internal consistency and excellent convergent validity. A Total score (all symptoms), Case Definition score (CFS case defining symptoms) and Short Form score (6 symptoms with minimal correlation) differentiated CFS cases from controls. Furthermore, both the Case Definition and Short Form scores distinguished people with CFS from fatigued subjects who did not meet criteria for CFS.ConclusionThe Symptom Inventory appears to be a reliable and valid instrument to assess symptoms that accompany CFS. It is a positive addition to existing instruments measuring fatigue because it allows other dimensions of the illness to be assessed. Further research is needed to confirm and replicate the current findings in a normative population.

Incidence and Prevalence of Recurrent Respiratory Papillomatosis among Children in Atlanta and Seattle

The incidence and prevalence of recurrent respiratory papillomatosis (RRP) for children aged <18 years were estimated in 2 US cities, Atlanta and Seattle, in 1996. All otolaryngologists in a 24-county area in metropolitan Atlanta (101 physicians) and an 8-county area in metropolitan Seattle (139 physicians) agreed to participate in the study. Medical record chart abstraction was performed only for children with documented current residence in the study area (21 patients in Atlanta and 14 patients in Seattle). The incidence rate for juvenile RRP was 1.11/100,000 population in Atlanta and 0.36/100, 000 in Seattle. The prevalence rate was 2.59/100,000 population in Atlanta and 1.69/100,000 in Seattle. In neither city did prevalences differ significantly when stratified by sex or race. Extrapolation of these estimates to the US population suggests that 80-1500 incident cases and 700-3000 prevalent cases of juvenile RRP will occur in the United States during 1999.

Effect of Scattered-Site Housing Using Rent Supplements and Intensive Case Management on Housing Stability Among Homeless Adults With Mental Illness A Randomized Trial

IMPORTANCE Scattered-site housing with Intensive Case Management (ICM) may be an appropriate and less-costly option for homeless adults with mental illness who do not require the treatment intensity of Assertive Community Treatment. OBJECTIVE To examine the effect of scattered-site housing with ICM services on housing stability and generic quality of life among homeless adults with mental illness and moderate support needs for mental health services. DESIGN, SETTING, AND PARTICIPANTS The At Home/Chez Soi project was an unblinded, randomized trial. From October 2009 to July 2011, participants (N = 1198) were recruited in 4 Canadian cities (Vancouver, Winnipeg, Toronto, and Montreal), randomized to the intervention group (n = 689) or usual care group (n = 509), and followed up for 24 months. INTERVENTIONS The intervention consisted of scattered-site housing (using rent supplements) and off-site ICM services. The usual care group had access to existing housing and support services in their communities. MAIN OUTCOMES AND MEASURES The primary outcome was the percentage of days stably housed during the 24-month period following randomization. The secondary outcome was generic quality of life, assessed by a EuroQoL 5 Dimensions (EQ-5D) health questionnaire. RESULTS During the 24 months after randomization, the adjusted percentage of days stably housed was higher among the intervention group than the usual care group, although adjusted mean differences varied across sites. [table: see text] The mean change in EQ-5D score from baseline to 24 months among the intervention group was not statistically different from the usual care group (60.5 [95%CI, 58.6 to 62.5] at baseline and 67.2 [95%CI, 65.2 to 69.1] at 24 months for the intervention group vs 62.1 [95% CI, 59.9 to 64.4] at baseline and 68.6 [95%CI, 66.3 to 71.0] at 24 months for the usual care group, difference in mean changes, 0.10 [95%CI, −2.92 to 3.13], P=.95). CONCLUSIONS AND RELEVANCE Among homeless adults with mental illness in 4 Canadian cities, scattered site housing with ICM services compared with usual access to existing housing and community services resulted in increased housing stability over 24 months, but did not improve generic quality of life. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN42520374.

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

BackgroundChronic 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.MethodsSixty-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.ResultsOnly 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 ≤ 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.ConclusionsThe 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.

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

BackgroundChronic 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.ResultsCFS 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.ConclusionThese 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.

Factor analysis of symptoms among subjects with unexplained chronic fatigue: what can we learn about chronic fatigue syndrome?

OBJECTIVE Chronic fatigue syndrome (CFS) case definitions agree that fatigue must be unexplained, debilitating and present for at least 6 months, but they differ over accompanying symptoms. Our objective was to compare the 1994 CFS case-defining symptoms with those identified by factor analysis. METHODS We surveyed the Wichita population and measured the occurrence of 21 symptoms in 1391 chronically fatigued subjects who did not report fatigue-associated medical or psychiatric conditions. We used factor analyses to identify symptom dimensions of fatigue and cluster analysis to assign subjects to subgroups. RESULTS Forty-three subjects had CFS. We confirmed three factors: musculoskeletal, infection and cognition-mood-sleep, essentially defined by CFS symptoms. Although factor scores were higher among CFS subjects, CFS and non-CFS distributions overlapped substantially. Three clusters also showed overlap between CFS and non-CFS subjects. CONCLUSION CFS symptomatology is a multidimensional phenomenon overlapping with other unexplained fatiguing syndromes and this must be considered in CFS research.

Longitudinal trends in nutritional status and the relation between lung function and BMI in cystic fibrosis: a population-based cohort study

BACKGROUND A high-calorie diet has been a standard of care in cystic fibrosis (CF) for >3 decades. However, energy requirements may have changed with new treatments and milder genotypes. OBJECTIVES The objectives of this study were to describe longitudinal trends in nutritional status and to evaluate the relation between nutritional status and lung function. DESIGN This longitudinal cohort study included 909 individuals followed at the Adult CF Clinic in Toronto from 1985 to 2011. Nutritional status was classified on the basis of WHO BMI guidelines. Multivariable linear regression with the use of generalized estimating equations was applied to evaluate the relation between BMI and lung function. RESULTS The proportion of underweight individuals decreased from 20.6% before 1990 to 11.1% in the most recent decade, whereas the proportion of overweight and obese subjects increased from 7.0% to 18.4% (P < 0.001). Overweight and obese subjects were older, had better lung function, had milder genotypes, and were more often male and pancreatic sufficient. Multivariable regression analyses showed that within the underweight group, an increase in BMI resulted in improved lung function, whereas this effect was half of that in overweight individuals. The greatest advantage of improved nutrition on lung function was observed in the underweight group and in pancreatic- insufficient patients. CONCLUSIONS Modification to a high-fat diet may be required in some individuals with CF to optimize nutritional health. Higher BMI is associated with improvements in lung function, although the lung function benefit of increasing ones BMI (in kg/m(2)) to >25 is small and needs to be balanced against the known health risks of obesity.

Effect of a low glycaemic index diet on blood glucose in women with gestational hyperglycaemia

AIM The objectives of this pilot study were to determine the feasibility and effect on glycaemic control of a low-glycaemic-index (GI) diet in women with gestational diabetes or impaired glucose tolerance of pregnancy. METHODS participants, recruited from the Diabetes-in-Pregnancy Clinic of an inner-city teaching hospital serving a predominantly non-Caucasian population, were randomized to a low-GI (n=23) or control (n=24) diet and followed from 28 weeks gestation until delivery. Self-monitored-blood-glucose (SMBG), maternal and infant weight were collected from medical charts. Dietary intakes were assessed using diet records and questionnaires. RESULTS diet GI on control (58, 95% CI: 56,60) was significantly higher than on low-GI (49, 95% CI: 47,51; p=0.001). Glycaemic control improved on both diets, but more postprandial glucose values were within target on low-GI (58.4% of n=1891) than control (48.7% of n=1834; p<0.001). SMBG post-breakfast was directly related to pre-pregnancy BMI in the control, but not the low-GI group (BMI*diet interaction; p=0.021). Participants accepted the study foods and were willing to consume them post-intervention. CONCLUSIONS a low-GI diet was feasible and acceptable in this sample and facilitated control of postprandial glucose. A larger study is needed to determine the effect of a low-GI diet on maternal and infant outcomes.