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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease usually presenting after infection. Emerging evidence supports that energy metabolism is affected in ME/CFS, but a unifying metabolic phenotype has not been firmly established. We performed global metabolomics, lipidomics, and hormone measurements, and we used exploratory data analyses to compare serum from 83 patients with ME/CFS and 35 healthy controls. Some changes were common in the patient group, and these were compatible with effects of elevated energy strain and altered utilization of fatty acids and amino acids as catabolic fuels. In addition, a set of heterogeneous effects reflected specific changes in 3 subsets of patients, and 2 of these expressed characteristic contexts of deregulated energy metabolism. The biological relevance of these metabolic phenotypes (metabotypes) was supported by clinical data and independent blood analyses. In summary, we report a map of common and context-dependent metabolic changes in ME/CFS, and some of them presented possible associations with clinical patient profiles. We suggest that elevated energy strain may result from exertion-triggered tissue hypoxia and lead to systemic metabolic adaptation and compensation. Through various mechanisms, such metabolic dysfunction represents a likely mediator of key symptoms in ME/CFS and possibly a target for supportive intervention.

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Background: Previous phase 2 trials indicated benefit from B-lymphocyte depletion in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Objective: To evaluate the effect of the monoclonal anti-CD20 antibody rituximab versus placebo in patients with ME/CFS. Design: Randomized, placebo-controlled, double-blind, multicenter trial. (ClinicalTrials.gov: NCT02229942). Setting: 4 university hospitals and 1 general hospital in Norway. Patients: 151 patients aged 18 to 65 years who had ME/CFS according to Canadian consensus criteria and had had the disease for 2 to 15 years. Intervention: Treatment induction with 2 infusions of rituximab, 500 mg/m2 of body surface area, 2 weeks apart, followed by 4 maintenance infusions with a fixed dose of 500 mg at 3, 6, 9, and 12 months (n = 77), or placebo (n = 74). Measurements: Primary outcomes were overall response rate (fatigue score ≥4.5 for ≥8 consecutive weeks) and repeated measurements of fatigue score over 24 months. Secondary outcomes included repeated measurements of self-reported function over 24 months, components of the Short Form-36 Health Survey and Fatigue Severity Scale over 24 months, and changes from baseline to 18 months in these measures and physical activity level. Between-group differences in outcome measures over time were assessed by general linear models for repeated measures. Results: Overall response rates were 35.1% in the placebo group and 26.0% in the rituximab group (difference, 9.2 percentage points [95% CI, -5.5 to 23.3 percentage points]; P = 0.22). The treatment groups did not differ in fatigue score over 24 months (difference in average score, 0.02 [CI, -0.27 to 0.31]; P = 0.80) or any of the secondary end points. Twenty patients (26.0%) in the rituximab group and 14 (18.9%) in the placebo group had serious adverse events. Limitation: Self-reported primary outcome measures and possible recall bias. Conclusion: B-cell depletion using several infusions of rituximab over 12 months was not associated with clinical improvement in patients with ME/CFS. Primary Funding Source: The Norwegian Research Council, Norwegian Regional Health Trusts, Kavli Trust, MEandYou Foundation, and Norwegian ME Association.

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Myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is a debilitating disease of unknown etiology, with hallmark symptoms including postexertional malaise and poor recovery. Metabolic dysfunction is a plausible contributing factor. We hypothesized that changes in serum amino acids may disclose specific defects in energy metabolism in ME/CFS. Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients. The amino acid pattern suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells from both sexes. Myoblasts grown in presence of serum from patients with severe ME/CFS showed metabolic adaptations, including increased mitochondrial respiration and excessive lactate secretion. The amino acid changes could not be explained by symptom severity, disease duration, age, BMI, or physical activity level among patients. These findings are in agreement with the clinical disease presentation of ME/CFS, with inadequate ATP generation by oxidative phosphorylation and excessive lactate generation upon exertion.

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BACKGROUND & AIMS: Mortality among patients with chronic heart failure (CHF) is still high despite progress in medical and surgical treatment. The patients' nutritional condition may play an important role, and needs further investigation. The aim of this study was to evaluate whether nutritional risk in hospitalized patients with CHF was associated with three-year mortality. METHODS: A prospective study was conducted in 131 hospitalized Norwegian patients with CHF. Nutritional screening was performed using Nutritional Risk Screening (NRS-2002). The primary clinical outcome was death from any cause. RESULTS: The prevalence of nutritional risk was 57% (NRS-2002 score ≥ 3). The overall mortality rate was 52.6% within three-year follow up. More patients at nutritional risk (N = 51) died compared to patients not at nutritional risk (N = 18) (P < 0.001). In adjusted analyses patients at nutritional risk had more than five-time higher odds (OR 5.85; 95% CI 2.10-16.24) to die before three-year follow-up than those not at nutritional risk. In adjusted Cox multivariate analysis, the nutritional risk was associated with increased mortality (HR 2.78; 95% CI 1.53-5.03). Furthermore, in adjusted analysis components in NRS-2002 were associated with mortality, i.e. nutritional status (HR 1.82; 95% CI 1.03-3.22), severity of disease (NYHA-class IV) (HR 1.78; 95% CI 1.00-3.16) and age (≥ 70 year) (HR 3.24; 95% CI 1.48-7.10). CONCLUSION: Nutritional risk as defined by NRS-2002 in hospitalized patients with CHF was significantly associated with long term mortality.

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BACKGROUND & AIMS: Malnutrition is an important issue in patient outcome. Screening tools to find risk patients need to be evaluated. This study looks at the validity and reliability of nutritional risk screening (named NRS-2002) in hospitalized patients with chronic heart failure. METHODS: In this cross-sectional study nutritional screening was performed using NRS-2002 in 131 patients with chronic heart failure. The predictive validity was evaluated in relation to whether NRS-2002 predicted the incidence of complications and length of hospital stay. NRS-2002's ability to locate nutritional risk in patients with edema was evaluated. The inter-rater reliability was measured between three investigators screening 45 patients each. RESULTS: The prevalence of nutritional risk was 57%. The incidence of complications and the median length of hospital stay were significantly higher in patients at nutritional risk compared to patients not at nutritional risk. Only the component of severity of disease in NRS-2002 and not the component of the nutritional status was associated with increased length of hospital stay in multivariate analysis. Patients with edema were classified correctly regarding nutritional risk status by NRS-2002 in all but one occasion. The inter-rater reliability was documented, kappa >0.60. CONCLUSION: NRS-2002 was a reliable screening tool in an in-patient sample with chronic heart failure. The validity of NRS-2002 needs further investigation in a larger sample of hospitalized patients with chronic heart failure.

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BACKGROUND: We conducted a systematic review of evidence from randomized controlled trials to answer the following research question: What are the relative effects of different classes of antihypertensive drugs in reducing the incidence of cardiovascular disease outcomes for healthy people at risk of cardiovascular disease? METHODS: We searched MEDLINE, EMBASE, AMED (up to February 2011) and CENTRAL (up to May 2009), and reference lists in recent systematic reviews. Titles and abstracts were assessed for relevance and those potentially fulfilling our inclusion criteria were then assessed in full text. Two reviewers made independent assessments at each step. We selected the following main outcomes: total mortality, myocardial infarction and stroke. We also report on angina, heart failure and incidence of diabetes. We conducted a multiple treatments meta-analysis using random-effects models. We assessed the quality of the evidence using the GRADE-instrument. RESULTS: We included 25 trials. Overall, the results were mixed, with few significant differences, and with no drug-class standing out as superior across multiple outcomes. The only significant finding for total mortality based on moderate to high quality evidence was that beta-blockers (atenolol) were inferior to angiotensin receptor blockers (ARB) (relative risk (RR) 1.14; 95% credibility interval (CrI) 1.02 to 1.28). Angiotensin converting enzyme (ACE)-inhibitors came out inferior to calcium-channel blockers (CCB) regarding stroke-risk (RR 1.19; 1.03 to 1.38), but superior regarding risk of heart failure (RR 0.82; 0.69 to 0.94), both based on moderate quality evidence. Diuretics reduced the risk of myocardial infarction compared to beta-blockers (RR 0.82; 0.68 to 0.98), and lowered the risk of heart failure compared to CCB (RR 0.73; 0.62 to 0.84), beta-blockers (RR 0.73; 0.54 to 0.96), and alpha-blockers (RR 0.51; 0.40 to 0.64). The risk of diabetes increased with diuretics compared to ACE-inhibitors (RR 1.43; 1.12 to 1.83) and CCB (RR 1.27; 1.05 to 1.57). CONCLUSION: Based on the available evidence, there seems to be little or no difference between commonly used blood pressure lowering medications for primary prevention of cardiovascular disease. Beta-blockers (atenolol) and alpha-blockers may not be first-choice drugs as they were the only drug-classes that were not significantly superior to any other, for any outcomes. Review registration: CRD database ("PROSPERO") CRD42011001066.

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AIM: To evaluate the Communication Strategies Scale (CSS) in an adult Norwegian sample with hearing loss. SUBJECTS AND METHODS: Of 474 invited patients, a total of 337 consecutive adults admitted to the outpatient Unit of Audiology, ENT Department of a university hospital answered the CSS of the Communication Profile for the Hearing Impaired. The inventory assesses the use of three specific coping strategies; Maladaptive Behaviour, Verbal and Nonverbal Communication Strategies. The psychometric evaluation included construct validity by corrected item-total correlation, the internal consistency reliability by coefficient alpha (Cronbach's) and standard error of the measurement (SEM). Internal structure was evaluated by factor analyses using principal factors followed by a varimax rotation. RESULTS: CSS showed good psychometric properties with acceptable and good internal consistency reliability for the subscales. The internal structure of the entire scale gave main loadings at 24 of 25 items at the same factor as the original one. CONCLUSION: CSS may well be used as a clinical tool in the routine assessment of maladaptive and adaptive communication strategies in an unselected adult population of hearing impaired outpatients.

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