Evaluation of randomized controlled trials on complementary and alternative medicine

OBJECTIVES: Use of complementary and alternative medicine (CAM) is growing in all Western countries. The goal of this study was to evaluate quality of randomized controlled trials (RCTs) of CAM interventions for specific diagnoses to inform clinical decision making. METHODS: MEDLINE and related databases were searched for CAM RCTs. Visual review was done of bibliographies, meta-analyses, and CAM journals. Inclusion criteria for review and scoring were blinded RCT, specified diagnosis and intervention, complete study published between January 1, 1966 and July 31, 1998 in an English-language, peer-reviewed journal. Two reviewers independently scored each study. RESULTS: More than 5,000 trials were found, but only 258 met all study inclusion criteria. The main cause for rejection (> 90%) was that the study was not an RCT or had no blinding. Mean score across 95 diagnosis/intervention categories was 44.7 (S.D. +/- 14.3) on a 100-point scale. Ordinary least-squares regression found date of publication, biostatistician as author or consultant, published in one of five widely read English-language medical journals and diagnosis/intervention category of hypertension/relaxation as significant predictors of higher scores. CONCLUSIONS: The overall quality of evidence for CAM RCTs is poor but improving slowly over time, about the same as that of biomedicine. Thus, most services are provided without good evidence of benefit.     

Behavioural interventions for the prevention of sexually transmitted infections in young people aged 13-19 years: a systematic review

We systematically reviewed school-based skills building behavioural interventions for the prevention of sexually transmitted infections. References were sought from 15 electronic resources, bibliographies of systematic reviews/included studies and experts. Two authors independently extracted data and quality-assessed studies. Fifteen randomized controlled trials (RCTs), conducted in the United States, Africa or Europe, met the inclusion criteria. They were heterogeneous in terms of intervention length, content, intensity and providers. Data from 12 RCTs passed quality assessment criteria and provided evidence of positive changes in non-behavioural outcomes (e.g. knowledge and self-efficacy). Intervention effects on behavioural outcomes, such as condom use, were generally limited and did not demonstrate a negative impact (e.g. earlier sexual initiation). Beneficial effect on at least one, but never all behavioural outcomes assessed was reported by about half the studies, but this was sometimes limited to a participant subgroup. Sexual health education for young people is important as it increases knowledge upon which to make decisions about sexual behaviour. However, a number of factors may limit intervention impact on behavioural outcomes. Further research could draw on one of the more effective studies reviewed and could explore the effectiveness of 'booster' sessions as young people move from adolescence to young adulthood.     

A systematic review of omega-3 fatty acids and osteoporosis

Some epidemiological evidence suggests that diets high in omega 3 fatty acids (n-3 FAs) may be beneficial for skeletal health. The aim of this systematic review was to determine if randomized controlled trials (RCTs) support a positive effect of n-3 FAs on osteoporosis. A systematic search was performed in PubMed and EMBASE databases. We included RCTs with skeletal outcomes conducted in adults or children (> = 1 year old) using n-3 FA fortified foods, diets or supplements alone or in combination with other vitamins/minerals, versus placebo. Primary outcomes were incident fracture at any site and bone mineral density (BMD) in g/cm2. Secondary outcomes included bone formation or resorption markers and bone turnover regulators. A total of 10 RCTs met inclusion criteria. Effect sizes with 95 % confidence intervals were estimated to compare studies across various treatments and outcome measures. No pooled analysis was completed due to heterogeneity of studies and small sample sizes. No RCTs included fracture as an outcome. Four studies reported significant favorable effects of n-3 FA on BMD or bone turnover markers. Of these, three delivered n-3 FA in combination with high calcium foods or supplements. Five studies reported no differences in outcomes between n-3 FA intervention and control groups; one study included insufficient data for effect size estimation. Strong conclusions regarding n-3 FAs and bone disease are limited due to the small number and modest sample sizes of RCTs, however, it appears that any potential benefit of n-3 FA on skeletal health may be enhanced by concurrent administration of calcium.     

Chronic Fatigue Syndrome: a survey of GPs' attitudes and knowledge

BACKGROUND: GPs need evidence and guidance to help them diagnose and manage Chronic Fatigue Syndrome (CFS)/ME appropriately. OBJECTIVES: The aim of this survey was to obtain baseline data and identify the factors associated with GPs' attitudes to and knowledge of CFS/ME. The attitude of GPs to the condition is an important indicator of likely prognosis. METHODS: A postal questionnaire was sent to 1054 GPs served by Taunton, Bristol and Gloucester laboratories. GPs' attitudes to nine statements about CFS/ME were assessed and the factors associated with positive or negative responses were determined. Knowledge of the clinical features was also assessed. RESULTS: 811 GPs (77%) returned the questionnaire. 48% of GPs did not feel confident with making a diagnosis of CFS/ME and 41% did not feel confident in treatment. 72% of GPs accepted CFS/ME as a recognisable clinical entity and those GPs had significantly more positive attitudes. Three other key factors that were significantly, positively associated with GPs' attitudes were knowing someone socially with CFS/ME, being male and seeing more patients with the condition in the last year. CONCLUSION: Despite the publication of guidance for GPs on CFS/ME, confidence with making a diagnosis and management was found to be low. Educational initiatives and guidance for GPs should stress the importance of accepting CFS/ME as a recognisable clinical entity, as this is linked to having a positive attitude and could lead to improved confidence to make a diagnosis and treat CFS/ME patients.     

‘A life I can cope with’. An alternative model of cognitive behavioural therapy (CBT) for CFS/ME

ObjectivesThis study aimed to explore the experience of cognitive behavioural therapy (CBT) aimed at better management of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), rather than increasing activity.DesignThis was a qualitative study using grounded theory analysis.MethodsSemi‐structured interviews were conducted with 13 adults who had engaged in CBT at a specialist CFS/ME service in which CBT is aimed at improved management of the condition.ResultsA model was produced in which participants felt more able to cope with CFS/ME. Reduced fatigue did not seem to be a necessary precondition to managing. This has implications for CBT for CFS/ME.ConclusionsSpecialist CBT for CFS/ME may result in improved coping and reduced distress, independently of changes in fatigue.Patient or Public ContributionThe researcher met with a representative from the university''s service user advisory group (SAGE), who had lived experience of CFS/ME. They commented on possible questions for the interview topic guide and provided advice on ways in which ethical issues specific to CFS/ME could be considered, for example, prevention of harm during interviews. Second, for quality assurance as part of respondent validation, a proposed draft of the grounded theory was discussed with participants.     

Effectiveness of nutritional and exercise interventions to improve body composition and muscle strength or function in sarcopenic obese older adults: A systematic review

Although sarcopenic obesity (SO) poses a major public health concern, a robust approach for the optimization of body composition and strength/function in SO has not yet been established. The purpose of this systematic review was to assess the effectiveness of nutritional (focusing on energy and protein modulation) and exercise interventions, either individually or combined, on body composition and strength/function in older adults with SO. MEDLINE, the Cochrane Central Register of Controlled Trials, CINAHL and SPORTDiscus were searched. Main inclusion criteria comprised sarcopenia as defined by the European Working Group on Sarcopenia in Older People (EWGSOP) and obesity defined as % body fat ≥40% (women) and ≥28% (men). Randomized controlled trials (RCTs), randomized controlled crossover trials and controlled clinical trials with older adults (mean age ≥65 years) following a nutritional regimen and/or an exercise training program were considered. Out of 109 full text articles identified, only two RCTs (61 participants) met the inclusion criteria. One study was a nutritional intervention adding 15 g protein·day⁻¹ (via cheese consumption) to the participants' habitual diet. The second study was a high-speed circuit resistance training intervention. Body composition did not change significantly in either of the studies. However, the exercise intervention improved significantly muscle strength and physical function. Although this review was limited by the small number of eligible studies, it provides evidence for the potential benefits of exercise and highlights the necessity for future research to develop effective interventions including dietary and exercise regimens to combat sarcopenic obesity.     

A systematic review describing the prognosis of chronic fatigue syndrome

AIM: To perform a systematic review of studies describing the prognosis of chronic fatigue (CF) and chronic fatigue syndrome (CFS) and to identify occupational outcomes from such studies. METHOD: A literature search was used to identify all studies describing the clinical follow-up of patients following a diagnosis of CF or CFS. The prognosis is described in terms of the proportion of individuals improved during the period of follow-up. Return to work, other medical illnesses and death as outcomes are also considered, as are variables which may influence prognosis. RESULTS: Twenty-eight articles met the inclusion criteria and, for the 14 studies of subjects meeting operational criteria for CFS, the median full recovery rate was 5% (range 0-31%) and the median proportion of patients who improved during follow-up was 39.5% (range 8-63%). Less fatigue severity at baseline, a sense of control over symptoms and not attributing illness to a physical cause were all associated with a good outcome. Return to work at follow-up ranged from 8 to 30% in the three studies that considered this outcome. CONCLUSIONS: Full recovery from untreated CFS is rare. The prognosis for an improvement in symptoms is less gloomy. This review looks at the course of CF/CFS without systematic intervention. However, there is increasing evidence for the effectiveness of cognitive behavioural and graded exercise therapies. Medical retirement should be postponed until a trial of such treatment has been given.     

Interventions to Reduce Anticholinergic Burden in Adults Aged 65 and Older: A Systematic Review

IntroductionOlder age is associated with multimorbidity and polypharmacy with high anticholinergic burden (ACB). High ACB is linked to adverse events such as poor physical functioning, dementia, cardiovascular disease, and falls. Interventions are needed to reduce this burden.Aims/ObjectivesThe aim was to systematically review the literature to identify and describe studies of clinical and cost-effectiveness of interventions designed to reduce ACB in adults (≥65 years) on polypharmacy regimes, compared with usual care. The objective was to answer the following questions: What are the contents of the interventions? Were these interventions clinically effective? Were these interventions cost effective?.Design, setting, and participantsSystematic review of interventions to reduce anticholinergic burden in adults aged 65 and older in any clinical setting.MethodsEligible papers reported primary or secondary research describing any type of intervention including systematic reviews, randomized controlled trials (RCTs), controlled clinical trials, or nonrandomized pre-post intervention studies (PPIs) published in English from January 2010 to February 2019. Databases searched included CINAHL, Ovid MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials (CENTRAL).ResultsThe search yielded 5862 records. Eight studies (4 RCTs, 4 PPIs) conducted in hospital (4), community (2), nursing homes (1), and retirement villages (1) met the inclusion criteria. Pharmacists, either individually or as part of a team, provided the intervention in the majority of studies (6/8). Most (7/8) involved individual patient medication review followed by feedback to the prescriber. Two of the 4 RCTs and all non-RCTs reported a decrease in ACB following the intervention. No study reported cost outcome.Conclusions/ImplicationsPharmacists may be well placed to implement an ACB reduction intervention. This is the first systematic review of interventions to reduce ACB in older adults, and it highlights the need for development and testing of high-quality pragmatic clinical and cost-effectiveness trials in community and specific patient populations at high risk of harm from ACB.[PROSPERO registration: CRD42018089764].     

Effects of technology-based interventions on dietary intake or anthropometrics among adolescents and adults in South Asia – A systematic review of intervention studies

IntroductionMobile technology has been increasingly used as part of dietary interventions, but the effects of such interventions have not been systematically evaluated in the South Asian context. The systematic review aimed to determine the effects of technology-based interventions on dietary intake or anthropometrics among adolescents and adults in South Asia. Methods: Five electronic databases were searched (PubMed, Scopus, Web of Science, Global Health Library and Health Technology Assessment). Studies published in English between 1st January 2011 and 31st December 2021were included. Interventions that evaluated the effects of dietary interventions using technology on dietary outcomes and anthropometrics in adolescents or adults in the age group of 13–44 years (or a broader age group) from South Asia were eligible for inclusion. The risk of bias was assessed using the Cochrane Risk-of-bias 2 tool and ROBINS-I tool. A narrative synthesis was conducted.ResultsTwenty-one studies met the inclusion criteria (20,667 participants). Eleven of the 17 randomised controlled trials (RCTs) had a high overall risk of bias. The four non-randomised intervention studies had a serious or critical overall risk of bias. When including studies with low risk or some concern for bias, the interventions had a beneficial effect on at least one dietary outcome in four of the six RCTs that measured changes in diet, and no effect on the anthropometric outcomes in the six RCTs that measured changes in anthropometric outcomes.DiscussionTechnology-based dietary interventions have had some positive effects on dietary intake, but no effects on anthropometry in South Asia. More evidence is needed as the overall risk of bias was high in a majority of the studies.     

The Influence of Mindful Eating and/or Intuitive Eating Approaches on Dietary Intake: A Systematic Review

BackgroundStimuli that promote eating in the absence of the physiological need for food are pervasive and can facilitate excessive energy intake. The practices of mindful eating (ME) and intuitive eating (IE) have been developed to minimize external drivers of energy intake by helping individuals emphasize the sensory properties of foods and internal indicators of hunger and fullness.ObjectiveTo enhance understanding about the effect of ME and IE interventions on dietary intake, this systematic review included randomized trials of ME and IE interventions that examined dietary intake, defined as energy intake or diet quality, in adults of varying weight status without a diagnosis of an eating disorder.MethodsThe selection of literature followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review process, in which PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and PsycINFO databases were searched for studies published between January 1980 and November 2019. Studies were included if they met the following criteria: randomized trial design in which 1 arm was an intervention with an ME or IE component and there was at least 1 control or active comparison arm; enrolled participants were of a healthy weight or with overweight or obesity and reported not having an eating disorder (ie, anorexia, bulimia nervosa, or binge eating disorder) or other health conditions in which dietary restrictions were applied; were at least 18 years of age; and outcomes of energy intake or diet quality were reported at baseline and post intervention. The modified Downs and Black checklist was used to assess risk of bias for each study that met inclusion criteria.ResultsA total of 13 studies, including 8 investigating ME interventions and 5 investigating IE interventions, represented in 14 articles, were included in the review. Seven of the 9 articles reporting on energy intake did not find significant group differences. Eight of the 12 articles reporting on diet quality did not find significant group differences. The mean bias assessment score was 13.6 out of 28, indicating poor quality.ConclusionsLittle evidence suggests that ME and IE interventions influence energy intake or diet quality. To draw strong conclusions about the effect of ME and IE on dietary intake, future research using study designs of high rigor are needed.     

Contrasting case definitions for chronic fatigue syndrome, Myalgic Encephalomyelitis/chronic fatigue syndrome and myalgic encephalomyelitis

This article uses data from patients recruited using the 1994 case definition of chronic fatigue syndrome (CFS) to contrast those meeting criteria for the Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) Canadian case definition with those that did not meet these criteria. The study also contrasts those meeting criteria for Myalgic Encephalomyelitis (ME) based on criteria from Ramsay and other theorists with those that did not meet the ME criteria. The ME/CFS case definition criteria identified a subset of patients with more functional impairments and physical, mental, and cognitive problems than the subset not meeting these criteria. The ME subset had more functional impairments, and more severe physical and cognitive symptoms than the subset not meeting ME criteria. When applied to a population meeting the 1994 CFS case definition, both ME/CFS and ME criteria appear to select a more severe subset of patients.     

Effectiveness of monetary incentives in modifying dietary behavior:a review of randomized, controlled trials

To review research evidence on the effectiveness of monetary incentives in modifying dietary behavior, we conducted a systematic review of randomized, controlled trials (RCTs) identified from electronic bibliographic databases and reference lists of retrieved relevant articles. Studies eligible for inclusion met the following criteria: RCT comparing a form of monetary incentive with a comparative intervention or control; incentives were a central component of the study intervention and their effect was able to be disaggregated from other intervention components; study participants were community-based; and outcome variables included anthropometric or dietary assessment measures. Data were extracted on study populations, setting, interventions, outcome variables, trial duration, and follow-up. Appraisal of trial methodological quality was undertaken based on comparability of baseline characteristics, randomization method, allocation concealment, blinding, follow-up, and use of intention-to-treat analysis. Four RCTs were identified as meeting the inclusion criteria. All four trials demonstrated a positive effect of monetary incentives on food purchases, food consumption, or weight loss. However, the trials had some methodological limitations including small sample sizes and short durations. In addition, no studies to date have assessed effects according to socioeconomic or ethnic group or measured the cost-effectiveness of such schemes. Monetary incentives are a promising strategy to modify dietary behavior, but more research is needed to address the gaps in evidence. In particular, larger, long-term RCTs are needed with population groups at high risk of nutrition-related diseases.     

The financial and psychological impacts on mothers of children with chronic fatigue syndrome (CFS/ME)

Background Paediatric chronic fatigue syndrome or myalgic encephalopathy (CFS/ME) is relatively common and children can be severely affected attending little or no school for extended periods. There are no studies quantifying the financial impact of having a child with CFS/ME and there is little information of the impact on parental mood. Methods Forty mothers of children with CFS/ME from a regional specialist CFS/ME service completed inventories to assess their psychological well‐being (Hospital Anxiety and Depression Scale, General Health Questionnaire‐12) loss of earnings and increased expenditure. In addition, eight mothers took part in a semi‐structured qualitative interview. Results Most parents of children with CFS/ME experience loss of monthly income (mean =£247) and increase in monthly expenditure (mean =£206). Twenty‐eight (72%) mothers were above the cut‐off for the General Health Questionnaire‐12 compared with 20% in the healthy population (95% CI 55, 85, P < 0.001) suggesting they probably have a mental health problem. This may be explained by the qualitative interviews where mothers described five areas contributing to poor parental health: lack of understanding from others; marital tension; concern about their child's distress; concern about the impact on siblings and emotional distress causing physical symptoms. Conclusions The majority of families of children with CFS/ME experience decreased income and increased expenditure with a marked impact on maternal psychological health. Clinicians need to be aware of this to provide appropriate support to families who care for children with CFS/ME.     

Brief interventions to prevent sexually transmitted infections suitable for in-service use: A systematic review

BackgroundSexually transmitted infections (STIs) are more common in young people and men who have sex with men (MSM) and effective in-service interventions are needed.MethodsA systematic review of randomized controlled trials (RCTs) of waiting-room-delivered, self-delivered and brief healthcare-provider-delivered interventions designed to reduce STIs, increase use of home-based STI testing, or reduce STI-risk behavior was conducted. Six databases were searched between January 2000 and October 2014.Results17,916 articles were screened. 23 RCTs of interventions for young people met our inclusion criteria. Significant STI reductions were found in four RCTs of interventions using brief one-to-one counselling (2 RCTs), video (1 RCT) and a STI home-testing kit (1 RCT). Increase in STI test uptake was found in five studies using video (1 RCT), one-to-one counselling (1 RCT), home test kit (2 RCTs) and a web-based intervention (1 RCT). Reduction in STI-risk behavior was found in seven RCTs of interventions using digital online (web-based) and offline (computer software) (3 RCTs), printed materials (1 RCT) and video (3 RCTs). Ten RCTs of interventions for MSM met our inclusion criteria. Three tested for STI reductions but none found significant differences between intervention and control groups. Increased STI test uptake was found in two studies using brief one-to-one counselling (1 RCT) and an online web-based intervention (1 RCT). Reduction in STI-risk behavior was found in six studies using digital online (web-based) interventions (4 RCTs) and brief one-to-one counselling (2 RCTs).ConclusionA small number of interventions which could be used, or adapted for use, in sexual health clinics were found to be effective in reducing STIs among young people and in promoting self-reported STI-risk behavior change in MSM.     

Assessing the Physiological Effects of Traditional Regional Diets Targeting the Prevention of Cardiovascular Disease: A Systematic Review of Randomized Controlled Trials Implementing Mediterranean,New Nordic,Japanese, Atlantic,Persian and Mexican Dietary Interventions

Traditional regional diets are considered as sustainable dietary patterns, while many have been examined with regard to their health benefits. The aim of the present systematic review was to aggerate all evidence on the physiological effects of regional diets among adults at high risk for cardiovascular disease (CVD). Three databases were searched for randomized controlled trials (RCTs) implementing any regional diet (Mediterranean (MedD), Persian, Southern European Atlantic, Japanese, Chinese, new Nordic, or other) while examining cardiovascular risk factors among adults at increased risk. Primary outcomes included anthropometric indices and secondary outcomes involved blood lipid concentrations, glucose metabolism, inflammation and other markers of CVD progression. Twenty RCTs fulfilled the study’s criteria and were included in the qualitative synthesis, with the majority implementing a MedD. Adherence to most of the regional diets induced a reduction in the BW and anthropometric indices of the participants. The majority of RCTs with blood pressure endpoints failed to note a significant reduction in the intervention compared to the comparator arm, with the exception of some new Nordic and MedD ones. Despite the interventions, inflammation markers remained unchanged except for CRP, which was reduced in the intervention groups of one new Nordic, the older Japanese, and the Atlantic diet RCTs. With regard to blood lipids, regional diet interventions either failed to induce significant differences or improved selective blood lipid markers of the participants adhering to the experimental regional diet arms. Finally, in the majority of RCTs glucose metabolism failed to improve. The body of evidence examining the effect of regional dietary patterns on CVD risk among high-risk populations, while employing an RCT design, appears to be limited, with the exception of the MedD. More research is required to advocate for the efficacy of most regional diets with regard to CVD.     

Should structural interventions be evaluated using RCTs? The case of HIV prevention

Structural interventions addressing macro-social determinants of risk have been suggested as potentially important adjuncts to biomedical and behavioural interventions for the prevention of HIV and other diseases. A few interventions of this type have been evaluated using randomised controlled trials (RCTs), the most rigorous design to evaluate the effects of biomedical and behavioural interventions. The appropriateness of applying RCTs to structural interventions is however debated. This paper considers whether issues of ethics, feasibility and utility preclude the use of RCTs in evaluations of structural interventions for HIV prevention. We conclude there is nothing particular to this category of interventions prohibiting use of RCTs. However, we suggest that RCTs may prove unacceptable, unfeasible or not useful in certain circumstances, such as where an intervention brings important benefits other than HIV prevention (such as increased income); where leaders of clusters do not allow decisions about macro-social policies to be determined randomly; where the unit of social organization addressed by an intervention is so large that recruitment of adequate numbers of clusters is impossible; and where the period required to trial interventions extends beyond practical decision-making time-scales. In such cases, alternative evaluative designs must be assessed for their ability to provide evidence of intervention effectiveness.     

Interventions for reducing loneliness: An umbrella review of intervention studies

Loneliness is a common phenomenon associated with several negative health outcomes. Current knowledge regarding interventions for reducing loneliness in randomised controlled trials (RCTs) is conflicting. The aim of the present work is to provide an overview of interventions to reduce loneliness, using an umbrella review of previously published systematic reviews and meta-analyses. We searched major databases from database inception to 31 March 2020 for RCTs comparing active versus non-active interventions for reducing loneliness. For each intervention, random-effects summary effect size and 95% confidence intervals (CIs) were calculated. For significant outcomes (p-value < 0.05), the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool was used, grading the evidence from very low to high. From 211 studies initially evaluated, seven meta-analyses for seven different types of interventions were included (median number of RCTs: 8; median number of participants: 600). Three interventions were statistically significant for reducing loneliness, that is, meditation/mindfulness, social cognitive training and social support. When applying GRADE criteria, meditation/mindfulness (mean difference, MD = −6.03; 95% CI: −9.33 to −2.73; very low strength of the evidence), social cognitive training (8 RCTs; SMD = −0.49; 95% CI: −0.84 to −0.13; very low strength of the evidence) and social support (9 RCTs; SMD = −0.13; 95% CI: −0.25 to −0.01; low strength of the evidence) significantly decreased the perception of loneliness. In conclusion, three intervention types may be utilised for reducing loneliness, but they are supported by a low/very low certainty of evidence indicating the need for future large-scale RCTs to further investigate the efficacy of interventions for reducing loneliness.     

Variability in diagnostic criteria for chronic fatigue syndrome may result in substantial differences in patterns of symptoms and disability

Chronic fatigue syndrome (CFS) is an illness that involves severe, prolonged exhaustion as well as neurologic, immunologic, and endocrine system pathology. Because the pathogenesis of CFS has yet to be determined, case definitions have relied on clinical observation in classifying signs and symptoms for diagnosis. The current investigation examined differences between CFS as defined by Fukuda and colleagues and a set of criteria that has been stipulated for myalgic encephalomyelitis (ME). Dependent measures included psychiatric comorbidity, symptom frequency, symptom severity, and functional impairment. The ME and Fukuda et al. (1994) CFS criteria were compared with a group having chronic fatigue due to psychiatric reasons. Significant differences occurred primarily with neurologic, neuropsychiatric, fatigue/weakness, and rheumatological symptoms. These findings suggest that it might be inappropriate to synthesize results from studies of this illness that use different definitions to select study populations.