Cancer-related fatigue:Predictors and effects of rehabilitation

Background. The aims of the study were to examine the effects of a multidimensional rehabilitation program on cancer-related fatigue, to examine concurrent predictors of fatigue, and to investigate whether change in fatigue over time was associated with change in predictors. Methods. Sample: 72 cancer survivors with different diagnoses. Setting: rehabilitation center. Intervention: 15-week rehabilitation program. Measures: Fatigue (Multidimensional Fatigue Inventory), demographic and disease/treatment-related variables, body composition (bioelectrical impedance), exercise capacity (symptom-limited bicycle ergometry), muscle force (handheld dynamometry), physical and psychological symptom distress (Rotterdam Symptom Check List), experienced physical and psychological functioning (RAND-36), and self-efficacy (General-Self-Efficacy Scale, Dutch version). Measurements were performed before (T0) and after rehabilitation (T1). Results. At T1 (n = 56), significant improvements in fatigue were found, with effect sizes varying from -0.35 to -0.78. At TO, the different dimensions of fatigue were predicted by different physical and psychological variables. Explained variance of change in fatigue varied from 42%-58% and was associated with pre-existing fatigue and with change in physical functioning, role functioning due to physical problems, psychological functioning, and physical symptoms distress. Conclusions. Within this selected group of patients we found that (a) rehabilitation is effective in reducing fatigue, (b) both physical and psychological parameters predicted different dimensions of fatigue at baseline, and (c) change in fatigue was mainly associated with change in physical parameters

Переходная зона между шельфом и континентальным склоном северной части Чёрного моря. Ландшафтный подход

На основе данных, полученных с применением обитаемых подводных аппаратов, рассмотрена проблема положения бровки шельфа как важной структурно фациальной границы морского бассейна. Описана ландшафтная фациальная зональность в диапазоне глубин 70–220 м в северной части Черного моря. Выявлено, что смена фаций в переходной зоне между шельфом и материковым склоном от бровки шельфа до глубины около 200 м находится в тесной связи с усилением гипоксии до полной аноксии.На основі даних, отриманих із застосуванням підводних апаратів, розглянуто проблему положення бровки шельфу як важливої структурно фаціальної межі морського басейну. Описано ландшафтну фаціальну зональність в діапазоні глибин 70–20 м у північній частині Чорного моря. Виявлено, що зміна фацій у перехідній зоні між шельфом і материковим схилом від бровки шельфу до глибини близько 200 м тісно пов’язана із збільшенням гіпоксії до повної аноксії.The problem of continental shelf break position as an important structural – facial marine basin boundary discussed on the basis of manned submersibles’ data. The range and setting of Northern Black Sea facial zones in the depths interval 70 220m are described. It’s found that the facial changes are related closely with hypoxia increasing to complete anoxia from the shelf break to the depth of about 200 m

Defining frequent attendance in general practice

Background: General practitioners (GPs) or researchers sometimes need to identify frequent attenders (FAs) in order to screen them for unidentified problems and to test specific interventions. We wanted to assess different methods for selecting FAs to identify the most feasible and effective one for use in a general (group) practice. Methods: In the second Dutch National Survey of General Practice, data were collected on 375 899 persons registered with 104 practices. Frequent attendance is defined as the top 3% and 10% of enlisted patients in each one-year age-sex group measured during the study year. We used these two selections as our reference standard. We also selected the top 3% and 10% FAs (90 and 97 percentile) based on four selection methods of diminishing preciseness. We compared the test characteristics of these four methods. Results: Of all enlisted patients, 24 % did not consult the practice during the study year. The mean number of contacts in the top 10% FAs increased in men from 5.8 (age 15-24 years) to 17.5 (age 64-75 years) and in women from 9.7 to 19.8. In the top 3% of FAs, contacts increased in men from 9.2 to 24.5 and in women from 14 to 27.8. The selection of FAs becomes more precise when smaller age classes are used. All selection methods show acceptable results (kappa 0.849 - 0.942) except the three group method. Conclusion: To correctly identify frequent attenders in general practice, we recommend dividing patients into at least three age groups per se

Targeting exercise interventions to patients with cancer in need:An individual patient data meta-analysis

Background: Exercise effects in cancer patients often appear modest, possibly because interventions rarely target patients most in need. This study investigated the moderator effects of baseline values on the exercise outcomes of fatigue, aerobic fitness, muscle strength, quality of life (QoL), and self-reported physical function (PF) in cancer patients during and post-treatment. Methods: Individual patient data from 34 randomized exercise trials (n = 4519) were pooled. Linear mixed-effect models were used to study moderator effects of baseline values on exercise intervention outcomes and to determine whether these moderator effects differed by intervention timing (during vs post-treatment). All statistical tests were two-sided. Results: Moderator effects of baseline fatigue and PF were consistent across intervention timing, with greater effects in patients with worse fatigue (Pinteraction = .05) and worse PF (Pinteraction = .003). Moderator effects of baseline aerobic fitness, muscle strength, and QoL differed by intervention timing. During treatment, effects on aerobic fitness were greater for patients with better baseline aerobic fitness (Pinteraction = .002). Post-treatment, effects on upper (Pinteraction < .001) and lower (Pinteraction = .01) body muscle strength and QoL (Pinteraction < .001) were greater in patients with worse baseline values. Conclusion: Although exercise should be encouraged for most cancer patients during and post-treatments, targeting specific subgroups may be especially beneficial and cost effective. For fatigue and PF, interventions during and post-treatment should target patients with high fatigue and low PF. During treatment, patients experience benefit for muscle strength and QoL regardless of baseline values; however, only patients with low baseline values benefit post-treatment. For aerobic fitness, patients with low baseline values do not appear to benefit from exercise during treatment

Effects and moderators of exercise on quality of life and physical function in patients with cancer:An individual patient data meta-analysis of 34 RCTs

This individual patient data meta-analysis aimed to evaluate the effects of exercise on quality of life (QoL) and physical function (PF) in patients with cancer, and to identify moderator effects of demographic (age, sex, marital status, education), clinical (body mass index, cancer type, presence of metastasis), intervention-related (intervention timing, delivery mode and duration, and type of control group), and exercise-related (exercise frequency, intensity, type, time) characteristics. Relevant published and unpublished studies were identified in September 2012 via PubMed, EMBASE, PsycINFO, and CINAHL, reference checking and personal communications. Principle investigators of all 69 eligible trials were requested to share IPD from their study. IPD from 34 randomised controlled trials (n=4,519 patients) that evaluated the effects of exercise compared to a usual care, wait-list or attention control group on QoL and PF in adult patients with cancer were retrieved and pooled. Linear mixed-effect models were used to evaluate the effects of the exercise on post-intervention outcome values (z-score) adjusting for baseline values. Moderator effects were studies by testing interactions. Exercise significantly improved QoL (β=0.15, 95%CI=0.10;0.20) and PF (β=0.18,95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (βdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (βdifference_in_effect=0.10, 95%CI=0.01;0.20) were significantly larger for supervised than unsupervised interventions. In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment. Although effect sizes are small, there is consistent empirical evidence to support implementation of exercise as part of cancer care

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation