A multimodal physiotherapy programme plus deep water running for improving cancer-related fatigue and quality of life in breast cancer survivors

The aim of the study was to assess the feasibility and effectiveness of aquatic‐based exercise in the form of deep water running ( DWR ) as part of a multimodal physiotherapy programme ( MMPP ) for breast cancer survivors. A controlled clinical trial was conducted in 42 primary breast cancer survivors recruited from community‐based P rimary C are C entres. Patients in the experimental group received a MMPP incorporating DWR , 3 times a week, for an 8‐week period. The control group received a leaflet containing instructions to continue with normal activities. Statistically significant improvements and intergroup effect size were found for the experimental group for P iper F atigue S cale‐ R evised total score ( d = 0.7, P = 0.001), as well as behavioural/severity ( d = 0.6, P = 0.05), affective/meaning ( d = 1.0, P = 0.001) and sensory ( d = 0.3, P = 0.03) domains. Statistically significant differences between the experimental and control groups were also found for general health ( d = 0.5, P < 0.05) and quality of life ( d = 1.3, P < 0.05). All participants attended over 80% of sessions, with no major adverse events reported. The results of this study suggest MMPP incorporating DWR decreases cancer‐related fatigue and improves general health and quality of life in breast cancer survivors. Further, the high level of adherence and lack of adverse events indicate such a programme is safe and feasible.

An individual-based versus group-based exercise and counselling intervention for improving quality of life in breast cancer survivors. A feasibility and efficacy study

Background Cancer and its treatments produce lingering side-effects that undermine the quality of life (QOL) of survivors. Exercise and psycho-therapies increase QOL among survivors, however, research is needed to identify intervention characteristics most associated with such improvements. Objective This research aimed to assess the feasibility of a 9 week individual or group based exercise and counselling program, and to examine if a group based intervention is as effective at improving the QOL of breast cancer survivors as an individual-based intervention. Methods A three group design was implemented to compare the efficacy of a 9 week individual (IEC n = 12) and group based exercise and counselling (GEC n = 14) intervention to a usual care (UsC n = 10) group on QOL of thirty-six breast cancer survivors. Results Across all groups, 90% of participants completed the interventions, with no adverse effects documented. At the completion of the intervention, there was a significant difference between groups for change in global QOL across time (p < 0.023), with IEC improving significantly more (15.0 points) than the UsC group (1.8 points). The effect size was moderate (0.70). Although the GEC improved QOL by almost 10.0 points, this increase did not reach significance. Both increases were above the minimally important difference of 7–8 points. Conclusion These preliminary results suggest a combined exercise and psychological counseling program is both a feasible and acceptable intervention for breast cancer survivors. Whilst both the individual and group interventions improved QOL above the clinically important difference, only the individual based intervention was significant when compared to UsC.

The YOU CALL-WE CALL randomized clinical trial: Impact of a multimodal support intervention after a mild stroke

Background Comparison of a multimodal intervention WE CALL (study initiated phone support/information provision) versus a passive intervention YOU CALL (participant can contact a resource person) in individuals with first mild stroke. Methods and Results This study is a single-blinded randomized clinical trial. Primary outcome includes unplanned use of health services (participant diaries) for adverse events and quality of life (Euroquol-5D, Quality of Life Index). Secondary outcomes include planned use of health services (diaries), mood (Beck Depression Inventory II), and participation (Assessment of Life Habits [LIFE-H]). Blind assessments were done at baseline, 6, and 12 months. A mixed model approach for statistical analysis on an intention-to-treat basis was used where the group factor was intervention type and occasion factor time, with a significance level of 0.01. We enrolled 186 patients (WE=92; YOU=94) with a mean age of 62.5±12.5 years, and 42.5% were women. No significant differences were seen between groups at 6 months for any outcomes with both groups improving from baseline on all measures (effect sizes ranged from 0.25 to 0.7). The only significant change for both groups from 6 months to 1 year (n=139) was in the social domains of the LIFE-H (increment in score, 0.4/9±1.3 [95% confidence interval, 0.1–0.7]; effect size, 0.3). Qualitatively, the WE CALL intervention was perceived as reassuring, increased insight, and problem solving while decreasing anxiety. Only 6 of 94 (6.4%) YOU CALL participants availed themselves of the intervention. Conclusions Although the 2 groups improved equally over time, WE CALL intervention was perceived as helpful, whereas YOU CALL intervention was not used.

The Driver Behaviour Questionnaire as accident predictor: A methodological re-meta-analysis

Problem The Manchester Driver Behaviour Questionnaire (DBQ) is the most commonly used self-report tool in traffic safety research and applied settings. It has been claimed that the violation factor of this instrument predicts accident involvement, which was supported by a previous meta-analysis. However, that analysis did not test for methodological effects, or include contacting researchers to obtain unpublished results. Method The present study re-analysed studies on prediction of accident involvement from DBQ factors, including lapses, and many unpublished effects. Tests of various types of dissemination bias and common method variance were undertaken. Results Outlier analysis showed that some effects were probably not reliable data, but excluding them did not change the results. For correlations between violations and crashes, tendencies for published effects to be larger than unpublished ones and for effects to decrease over time were observed, but were not significant. Also, analysis using the proxy of the mean of accidents in studies indicated that studies where effects for violations are unknown have smaller effect sizes. These differences indicate dissemination bias. Studies using self-reported accidents as dependent variables had much larger effects than those using recorded accident data. Also, zero-order correlations were larger than partial correlations that controlled for exposure. Similarly, violations/accidents effects were strong only when there was also a strong correlation between accidents and exposure. Overall, the true effect is probably very close to zero (r<.07) for violations versus traffic accident involvement, depending upon which systematic tendencies in the data are controlled for. Conclusions: Methodological factors and dissemination bias have inflated the mean effect size of the DBQ in the published literature. Strong evidence of various artefactual effects is apparent. Practical Applications A greater level of care should be taken if the DBQ continues to be used in traffic safety research. Also, validation of self-reports should be more comprehensive in the future, taking into account the possibility of common method variance.

Combining meta- and mega-analytic approaches for multi-site diffusion imaging based genetic studies: From the enigma-DTI working group

Meta-analyses estimate a statistical effect size for a test or an analysis by combining results from multiple studies without necessarily having access to each individual study's raw data. Multi-site meta-analysis is crucial for imaging genetics, as single sites rarely have a sample size large enough to pick up effects of single genetic variants associated with brain measures. However, if raw data can be shared, combining data in a "mega-analysis" is thought to improve power and precision in estimating global effects. As part of an ENIGMA-DTI investigation, we use fractional anisotropy (FA) maps from 5 studies (total N=2, 203 subjects, aged 9-85) to estimate heritability. We combine the studies through meta-and mega-analyses as well as a mixture of the two - combining some cohorts with mega-analysis and meta-analyzing the results with those of the remaining sites. A combination of mega-and meta-approaches may boost power compared to meta-analysis alone.

A genome-wide association study identifies five loci influencing facial morphology in Europeans

Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs) and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes-PRDM16, PAX3, TP63, C5orf50, and COL17A1-in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications.

Identification of genetic variants contributing to the migraine phenotype in different Australian populations

This project aimed to identify novel genetic risk variants associated with migraine in the Norfolk Island population. Statistical analysis and bioinformatics approaches such as polygenic modeling and gene clustering methods were carried out to explore genotypic and expression data from high-throughput techniques. This project had a particular focus on hormonal genes and other genetic variants and identified a modest effect size on the migraine phenotype.

WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ~2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10-9). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10-12, and -0.16 SD per G allele, P = 1.2×10-15, respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10-9), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10-6 and rs2707466: OR = 1.22, P = 7.2×10-6). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16-/- mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10-13<P<5.9×10-4) at both femur and tibia, compared with their wild-type littermates. Natural variation in humans and targeted disruption in mice demonstrate that WNT16 is an important determinant of CBT, BMD, bone strength, and risk of fracture. © 2012 Zheng et al.

Matters Arising: Role of HLA genes in familial spondyloarthropathy

Said-Nahal and colleagues report an intriguing finding of an association with HLA-DR4 independent of B27 in families with ankylosing spondylitis (AS),1 a finding highlighted by an accompanying editorial.2 The approach of studying B27 positive and B27 negative haplotypes may prove powerful in identifying further cis or trans encoded genes involved in AS. However, the reported association of DR4 with AS is quite a surprising finding given that no difference was noted in B27-DR4 haplotype frequencies in patients and ethnically matched healthy controls. Many previous studies have not reported any such association,3–9 including a similar preliminary study by the same authors.10 Although these studies were mainly case-control studies, population stratification is highly unlikely to cause a false negative finding if the effect size of the reported association with DR4 is as high as Said-Nahal and colleagues describe...

Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p<5×10-8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6×10-8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98-1.14; p=0.17), displaying high degree of heterogeneity (I2=57%; Qhet p=0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (p=0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.

An investigation into the effectiveness of sensory modulation in reducing seclusion within an acute mental health unit

In this paper we report the findings from an evaluation of the introduction of sensory modulation (SM) in an acute mental health inpatient unit. It was expected that SM could be used to help settle patients experiencing high levels of disturbance and that as a result, there would be less need for use of more restrictive seclusion practices. The evaluation took place in a hospital in south-east Queensland, Australia. SM was introduced in one acute unit while the other served as a control. The evaluation comprised two studies. In the first study we aimed to determine whether SM reduced the level of disturbance among patients given the opportunity to use it. In the second study we aimed to find out whether the introduction of SM reduced the frequency and duration of seclusion. In study 1, we found that most patients reported marked reduction in disturbance after using SM and there was a very large effect size for the group as a whole. In study 2, we found that frequency of seclusion dropped dramatically in the unit that introduced SM but rose slightly in the unit that did not have access to SM. The change in seclusion rate was highly significant (χ2 = 49.1, df = 1, p < 0.001). Results are discussed, having reference to the limitations inherent in a naturalistic study.

Efficacy and feasibility of a tele-health intervention for acute coronary syndrome patients with depression: Results of the 'MoodCare' randomized controlled trial

Background Depression is common after a cardiac event, yet there remain few approaches to management that are both effective and scalable. Purpose We aimed to evaluate the 6-month efficacy and feasibility of a tele-health program (MoodCare) that integrates depression management into a cardiovascular disease risk reduction program for acute coronary syndrome patients with low mood. Methods A two-arm, parallel, randomized design was used comprising 121 patients admitted to one of six hospitals for acute coronary syndrome. Results Significant treatment effects were observed for Patient Health Questionnaire 9 (PHQ9) depression (mean difference [change] = −1.8; p = 0.025; effect size: d = 0.36) for the overall sample, when compared with usual medical care. Results were more pronounced effects for those with a history of depression (mean difference [change] = −2.7; p = 0.043; effect size: d = 0.65). Conclusions MoodCare was effective for improving depression in acute coronary syndrome patients, producing effect sizes exceeding those of some face-to-face psychotherapeutic interventions and pharmacotherapy. (Trial Registration Number: ACTRN1260900038623.)

Genetic insights into common pathways and complex relationships among iImmune-mediated diseases

Shared aetiopathogenic factors among immune-mediated diseases have long been suggested by their co-familiality and co-occurrence, and molecular support has been provided by analysis of human leukocyte antigen (HLA) haplotypes and genome-wide association studies. The interrelationships can now be better appreciated following the genotyping of large immune disease sample sets on a shared SNP array: the 'Immunochip'. Here, we systematically analyse loci shared among major immune-mediated diseases. This reveals that several diseases share multiple susceptibility loci, but there are many nuances. The most associated variant at a given locus frequently differs and, even when shared, the same allele often has opposite associations. Interestingly, risk alleles conferring the largest effect sizes are usually disease-specific. These factors help to explain why early evidence of extensive 'sharing' is not always reflected in epidemiological overlap. © 2013 Macmillan Publishers Limited. All rights reserved.

Risk analysis of prostate cancer in PRACTICAL, a multinational consortium, using 25 known prostate cancer susceptibility loci

Background Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. Methods We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS).We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived agespecific absolute risks of developing prostate cancer by PRS stratum and family history. Results The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact:We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.

Laatutyöhön sitoutumisen edellytykset ammattikorkeakoulussa

The goal of this research was to establish the necessary conditions under which individuals are prepared to commit themselves to quality assurance work in the organisation of a Polytechnic. The conditions were studied using four main concepts: awareness of quality, commitment to the organisation, leadership and work welfare. First, individuals were asked to describe these four concepts. Then, relationships between the concepts were analysed in order to establish the conditions for the commitment of an individual towards quality assurance work (QA). The study group comprised the entire personnel of Helsinki Polytechnic, of which 341 (44.5%) individuals participated. Mixed methods were used as the methodological base. A questionnaire and interviews were used as the research methods. The data from the interviews were used for the validation of the results, as well as for completing the analysis. The results of these interviews and analyses were integrated using the concurrent nested design method. In addition, the questionnaire was used to separately analyse the impressions and meanings of the awareness of quality and leadership, because, according to the pre-understanding, impressions of phenomena expressed in terms of reality have an influence on the commitment to QA. In addition to statistical figures, principal component analysis was used as a description method. For comparisons between groups, one way variance analysis and effect size analysis were used. For explaining the analysis methods, forward regression analysis and structural modelling were applied. As a result of the research it was found that 51% of the conditions necessary for a commitment to QA were explained by an individual’s experience/belief that QA was a method of development, that QA was possible to participate in and that the meaning of quality included both product and process qualities. If analysed separately, other main concepts (commitment to the organisation, leadership and work welfare) played only a small part in explaining an individual’s commitment. In the context of this research, a structural path model of the main concepts was built. In the model, the concepts were interconnected by paths created as a result of a literature search covering the main concepts, as well as a result of an analysis of the empirical material of this thesis work. The path model explained 46% of the necessary conditions under which individuals are prepared to commit themselves to QA. The most important path for achieving a commitment stemmed from product and system quality emanating from the new goals of the Polytechnic, moved through the individual’s experience that QA is a method of the total development of quality and ended in a commitment to QA. The second most important path stemmed from the individual’s experience of belonging to a supportive work community, moved through the supportive value of the job and through affective commitment to the organisation and ended in a commitment to QA. The third path stemmed from an individual’s experiences in participating in QA, moved through collective system quality and through these to the supportive value of the job to affective commitment to the organisation and ended in a commitment to QA. The final path in the path model stemmed from leadership by empowerment, moved through collective system quality, the supportive value of the job and an affective commitment to the organisation, and again, ended in a commitment to QA. As a result of the research, it was found that the individual’s functional department was an important factor in explaining the differences between groups. Therefore, it was found that understanding the processing of part cultures in the organisation is important when developing QA. Likewise, learning-teaching paradigms proved to be a differentiating factor. Individuals thinking according to the humanistic-constructivistic paradigm showed more commitment to QA than technological-rational thinkers. Also, it was proved that the QA training program did not increase commitment, as the path model demonstrated that those who participated in training showed 34% commitment, whereas those who did not showed 55% commitment. As a summary of the results it can be said that the necessary conditions under which individuals are prepared to commit themselves to QA cannot be treated in a reductionistic way. Instead, the conditions must be treated as one totality, with all the main concepts interacting simultaneously. Also, the theoretical framework of quality must include its dynamic aspect, which means the development of the work of the individual and learning through auditing. In addition, this dynamism includes the reflection of the paradigm of the functions of the individual as well as that of all parts of the organisation. It is important to understand and manage the various ways of thinking and the cultural differences produced by the fragmentation of the organisation. Finally, it seems possible that the path model can be generalised for use in any organisation development project where the personnel should be committed.