Measuring the physical activity level and pattern in daily life in persons with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review

Background: A lower activity level and imbalanced activity pattern are frequently observed in persons with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) due to debilitating fatigue and post-exertional malaise (PEM). To provide an optimal treatment strategy, insight into a patient’s current physical activity level and pattern is necessary and identification of reliable and valid measures or scales measuring physical activity level and pattern in this population is warranted.

Objective: To identify measures or scales used to evaluate activity level and/or pattern in patients with CFS/ME and review their psychometric properties.

Methods: A systematic literature search was performed in the electronic databases PubMed and Web of Science until 12 October 2016. First, articles including relevant measures were identified. Secondly, psychometric properties of relevant measurement instruments were extracted and rated based on the COSMIN checklist.

Results: The review was performed and reported according to PRISMA statement. A total of 51 articles and 15 unique measurement instruments were found, but only three instruments have been evaluated in patients with CFS: the Chronic Fatigue Syndrome-Activity Questionnaire (CFS-AQ), Activity Pattern Interview (API) and International Physical Activity Questionnaire-Short Form (IPAQ-SF), all self-report instruments measuring physical activity level.

Conclusions: The IPAQ-SF, CFS-AQ and API are all equally capable of evaluating the physical activity level, but none of these are optimal to use. Although often used as gold standard to capture physical activity patterns, activity monitors have not yet been evaluated in these patients. More research is needed to evaluate the psychometric properties of existing instruments, including activity monitors.     

OligoG CF‐5/20 normalizes cystic fibrosis mucus by chelating calcium

The goal of this study was to determine whether the guluronate (G) rich alginate OligoG CF‐5/20 (OligoG) could detach cystic fibrosis (CF) mucus by calcium chelation, which is also required for normal mucin unfolding. Since bicarbonate secretion is impaired in CF, leading to insufficient mucin unfolding and thereby attached mucus, and since bicarbonate has the ability to bind calcium, we hypothesized that the calcium chelating property of OligoG would lead to detachment of CF mucus. Indeed, OligoG could compete with the N‐terminus of the MUC2 mucin for calcium binding as shown by microscale thermophoresis. Further, effects on mucus thickness and attachment induced by OligoG and other alginate fractions of different length and composition were evaluated in explants of CF mouse ileum mounted in horizontal Ussing‐type chambers. OligoG at 1.5% caused effective detachment of CF mucus and the most potent alginate fraction tested, the poly‐G fraction of about 12 residues, had similar potency compared to OligoG whereas mannuronate‐rich (M) polymers had minimal effect. In conclusion, OligoG binds calcium with appropriate affinity without any overt harmful effect on the tissue and can be exploited for treating mucus stagnation.     

Return to Work in Patients with Chronic Musculoskeletal Pain: Multidisciplinary Intervention Versus Brief Intervention: A Randomized Clinical Trial

Objective: This randomized clinical trial was performed to compare the effect of a new multidisciplinary intervention (MI) programme to a brief intervention (BI) programme on return to work (RTW), fully and partly, at a 12-month and 24-month follow-up in patients on long-term sick leave due to musculoskeletal pain. Methods: Patients (n = 284, mean age 41.3 years, 53.9 % women) who were sick-listed with musculoskeletal pain and referred to a specialist clinic in physical rehabilitation were randomized to MI (n = 141) or BI (n = 143). The MI included the use of a visual educational tool, which facilitated patient-therapist communication and self-management. The MI also applied one more profession, more therapist time and a comprehensive focus on the psychosocial factors, particularly the working conditions, compared to a BI. The main features of the latter are a thorough medical, educational examination, a brief cognitive assessment based on the non-injury model, and a recommendation to return to normal activity as soon as possible. Results: The number of patients with full-time RTW developed similarly in the two groups. The patients receiving MI had a higher probability to partly RTW during the first 7  months of the follow-up compared to the BI-group. Conclusions: There were no differences between the groups on full-time RTW during the 24 months. However, the results indicate that MI hastens the return to work process in long-term sick leave through the increased use of partial sick leave. Trial Registration: http://www.clinicaltrials.gov with the registration number NCT01346423.     

Adjuvant treatment of in-transit melanoma: Narrowing the knowledge gap left by clinical trials

Few clinical trials address efficacy of adjuvant systemic treatment in patients with in-transit melanoma (ITM). This study describes adjuvant systemic therapy of ITM patients beyond clinical trials. In this study, we included stage III adjuvant-treated melanoma patients registered in the nationwide Dutch Melanoma Treatment Registry between July 2018 and December 2020. Patients were divided into three groups: nodal disease only, ITM only and ITM and nodal disease. Recurrence patterns, recurrence-free survival (RFS) and overall survival (OS) at 12-months were analyzed. In our study population of 1037 patients, 66.8% had nodal disease only, 16.7% had ITM only and 16.2% had ITM with nodal disease. RFS at 12-months was comparable in the nodal only and ITM only group (72.2% vs70.1%, P = .97) but lower in ITM and nodal disease patients (57.8%; P = .01, P < .01). Locoregional metastases occurred as first recurrence in 38.9% nodal disease only, 71.9% of ITM-only and 44.0% of ITM and nodal disease patients. Distant recurrences occurred in 42.3%, 18.8% and 36.0%, respectively (P = .02). 12-months OS was not significantly different for nodal disease only patients compared with ITM-only (94.4% vs 97.6%, P = .06) but was significantly higher for ITM-only compared with ITM and nodal disease patients (97.6% vs 91.0%, P < .01). In conclusion, we showed that in the adjuvant setting, RFS rates in ITM-only patients are similar to non-ITM, though better than in ITM and nodal disease patients. Adjuvant-treated ITM-only patients less often experience distant recurrences and have a superior OS compared with ITM and nodal disease patients.     

Ultra-sensitive troponin I is an independent predictor of incident coronary heart disease in the general population

Troponins are sensitive markers of myocardial injury and predictive of cardiovascular events, but conventional assays fail to detect slightly elevated troponins in a considerable proportion of the general population. Using a novel ultrasensitive assay, we explored the relationship of troponin levels with the incidence of coronary heart disease (CHD) in a case-cohort sample (mean age 52.5 ± 0.2 years, 51.5% women) comprising 803 CHD cases and 1942 non-cases. Ultrasensitive troponin I was detectable in 99.9% of available case-cohort samples. In an age- and sex-adjusted model, individuals in the highest quartile of the troponin distribution had a more than threefold increased risk for CHD events compared to those in the bottom quartile [hazard ratio, HR, 3.11; 95% confidence interval (CI) 2.15–4.49]. In a model adjusting for cardiovascular risk factors including C-reactive protein, cystatin C and N-terminal pro brain natriuretic peptide, individuals in the highest troponin I quartile still showed a hazard ratio of 2.58 (95% CI 1.66–4.00) for incident CHD as compared to those in the lowest quartile. Ultrasensitive troponin I was detectable in almost all individuals of a study sample reflecting middle-aged to elderly European general population. Ultrasensitive troponin concentrations exhibit an independent, graded, positive relation with incident CHD.     

Atypical language representation is unfavorable for language abilities following childhood stroke

Brain plasticity has often been quoted as a reason for the more favorable outcome in childhood stroke compared to adult stroke. We investigated the relationship between language abilities and language localization in childhood stroke. Seventeen children and adolescents with left- or right-sided ischemic stroke and 18 healthy controls were tested with a comprehensive neurolinguistic test battery, and the individual neural representation of language was measured with an fMRI language paradigm. Overall, 12 of 17 stroke patients showed language abilities below average, and five patients exhibited impaired language performance. fMRI revealed increased activity in right hemisphere areas homotopic to left hemisphere language regions. In sum, seven stroke patients revealed atypical, i.e. bilateral or right lateralized language representation. Typical left hemispheric language lateralization was associated with better performance in naming and word fluency, whereas increased involvement of right homologues was accompanied by worse language outcome. In contrast, lesion lateralization or lesion volume did not correlate with language outcome or atypical language lateralization. Thus, atypical language lateralization is unfavorable for language outcome, and right homologues do not have the same cognitive capacity, even in young children.     

Erfassung selbst berichteter kardiovaskulärer und metabolischer Erkrankungen in der NAKO Gesundheitsstudie: Methoden und erste Ergebnisse

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Aus der NAKO Gesundheitsstudie, der größten deutschen bevölkerungsbasierten Studie zur Gesundheit, liegen die...     

Delineation of dominant and recessive forms of LZTR1-associated Noonan syndrome

Noonan syndrome (NS) is characterised by distinctive facial features, heart defects, variable degrees of intellectual disability and other phenotypic manifestations. Although the mode of inheritance is typically dominant, recent studies indicate LZTR1 may be associated with both dominant and recessive forms. Seeking to describe the phenotypic characteristics of LZTR1-associated NS, we searched for likely pathogenic variants using two approaches. First, scrutiny of exomes from 9624 patients recruited by the Deciphering Developmental Disorders (DDDs) study uncovered six dominantly-acting mutations (p.R97L; p.Y136C; p.Y136H, p.N145I, p.S244C; p.G248R) of which five arose de novo, and three patients with compound-heterozygous variants (p.R210*/p.V579M; p.R210*/p.D531N; c.1149+1G>T/p.R688C). One patient also had biallelic loss-of-function mutations in NEB, consistent with a composite phenotype. After removing this complex case, analysis of human phenotype ontology terms indicated significant phenotypic similarities (P = 0.0005), supporting a causal role for LZTR1. Second, targeted sequencing of eight unsolved NS-like cases identified biallelic LZTR1 variants in three further subjects (p.W469*/p.Y749C, p.W437*/c.-38T>A and p.A461D/p.I462T). Our study strengthens the association of LZTR1 with NS, with de novo mutations clustering around the KT1-4 domains. Although LZTR1 variants explain ~0.1% of cases across the DDD cohort, the gene is a relatively common cause of unsolved NS cases where recessive inheritance is suspected.