Economics methods in Cochrane systematic reviews of health promotion and public health related interventions.

Peer reviewedPublisher PD

Spectrum of HLA associations: the case of medically refractory pediatric acute lymphoblastic leukemia

Although studies of HLA and disease now date back some 50 years, a principled understanding of that relationship has been slow to emerge. Here, we examine the associations of three HLA loci with medically refractory pediatric acute lymphoblastic leukemia (pALL) patients in a case–control study involving 2,438 cases and 41,750 controls. An analysis of alleles from the class I loci, HLA-A and HLA-B, and the class II locus DRB1 illuminates a spectrum of extremely significant allelic associations conferring both predisposition and protection. Genotypes constructed from predisposing, protective, and neutral allelic categories point to an additive mode of disease causation. For all three loci, genotypes homozygous for predisposing alleles are at highest disease risk while the favorable effect of homozygous protective genotypes is less striking. Analysis of A–B and B–DRB1 haplotypes reveals locus-specific differences in disease effects, while that all three loci influence pALL; the influence of HLA-B is greater than that of HLA-A, and the predisposing effect of DRB1 exceeds that of HLA-B. We propose that the continuum in disease susceptibility suggests a system in which many alleles take part in disease predisposition based on differences in binding affinity to one or a few peptides of exogenous origin. This work provides evidence that an immune response mediated by alleles from several HLA loci plays a critical role in the pathogenesis of pALL, adding to the numerous studies pointing to a role for an infectious origin in pALL

The factorial structure of the mini mental state examination (MMSE) in Japanese dementia patients

<p>Abstract</p> <p>Background</p> <p>The Mini-Mental State Examination (MMSE) is one of the most commonly used instruments in the evaluation of global cognitive status. Few studies have investigated the relationship among its components in terms of factorial structure in Japanese individuals suffering from dementia. The aims of this study were: 1) to analyze the factorial structure of MMSE in Japanese dementia patients, 2) to clarify the MMSE static structure in identifying different cognitive profiles and understanding how these profiles are related to levels of dysfunction in subsets of dementia patients.</p> <p>Methods</p> <p>30,895 consecutive outpatients with dementia were evaluated. The 11 subtests composing the MMSE and the global MMSE score were analyzed. Factor analysis based on principal component analysis with Promax rotation was applied to the data representing the frequency of failures in each subtest as identified by the MMSE.</p> <p>Results</p> <p>Factor analysis identified three factors that explained approximately 44.57% of the total variance. The first factor, immediate memory, essentially constituted a simple index of the reading and writing subtests. The second factor, orientation and delayed recall, expressed the ability to handle new information. The third factor, working memory, was most closely related to the severity of dementia at the time of test administration.</p> <p>Conclusions</p> <p>Japanese dementia patients appear to develop difficulty handling new information in the early stages of their disease. This finding, and our finding that there is a factor associated with disease severity, suggest that understanding the specific factors related to subtest items, which underlie the total MMSE score may be useful to clinicians in planning interventions for Japanese patients in the early stages of dementia.</p

Multiple volcanic episodes of flood basalts caused by thermochemical mantle plumes

The hypothesis that a single mushroom-like mantle plume head can generate a large igneous province within a few million years has been widely accepted(1). The Siberian Traps at the Permian Triassic boundary(2) and the Deccan Traps at the Cretaceous Tertiary boundary(3) were probably erupted within one million years. These large eruptions have been linked to mass extinctions. But recent geochronological data(4-11) reveal more than one pulse of major eruptions with diverse magma flux within several flood basalts extending over tens of million years. This observation indicates that the processes leading to large igneous provinces are more complicated than the purely thermal, single-stage plume model suggests. Here we present numerical experiments to demonstrate that the entrainment of a dense eclogite-derived material at the base of the mantle by thermal plumes can develop secondary instabilities due to the interaction between thermal and compositional buoyancy forces. The characteristic timescales of the development of the secondary instabilities and the variation of the plume strength are compatible with the observations. Such a process may contribute to multiple episodes of large igneous provinces.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62705/1/nature03697.pd

The study protocol of a cluster-randomised controlled trial of family-mediated personalised activities for nursing home residents with dementia

<p>Abstract</p> <p>Background</p> <p>Following admission to a nursing home, the feelings of depression and burden that family carers may experience do not necessarily diminish. Additionally, they may experience feelings of guilt and grief for the loss of a previously close relationship. At the same time, individuals with dementia may develop symptoms of depression and agitation (BPSD) that may be related to changes in family relationships, social interaction and stimulation. Until now, interventions to alleviate carer stress and BPSD have treated carers and relatives separately rather than focusing on maintaining or enhancing their relationships. One-to-one structured activities have been shown to reduce BPSD and also improve the caring experience, but barriers such as a lack of resources impede the implementation of activities in aged care facilities. The current study will investigate the effect of individualised activities based on the Montessori methodology administered by family carers in residential care.</p> <p>Methods/Design</p> <p>We will conduct a cluster-randomised trial to train family carers in conducting personalised one-to-one activities based on the Montessori methodology with their relatives. Montessori activities derive from the principles espoused by Maria Montessori and subsequent educational theorists to promote engagement in learning, namely task breakdown, guided repetition, progression in difficulty from simple to complex, and the careful matching of demands to levels of competence. Persons with dementia living in aged care facilities and frequently visiting family carers will be included in the study. Consented, willing participants will be randomly assigned by facility to a treatment condition using the Montessori approach or a control waiting list condition. We hypothesise that family carers conducting Montessori-based activities will experience improvements in quality of visits and overall relationship with the resident as well as higher self-rated mastery, fewer depressive symptoms, and a better quality of life than carers in the waiting list condition.</p> <p>Discussion</p> <p>We hypothesise that training family carers to deliver personalised activities to their relatives in a residential setting will make visits more satisfying and may consequently improve the quality of life for carers and their relatives. These beneficial effects might also reduce nursing staff burden and thus impact positively on residential facilities.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry - <a href="http://www.anzctr.org.au/ACTRN12611000998943.aspx">ACTRN12611000998943</a></p

Impact of exercise-based cardiac rehabilitation in patients with heart failure (ExTraMATCH II) on mortality and hospitalisation:an individual-patient data meta-analysis of randomised trials

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordAIMS: To undertake an individual patient data (IPD) meta-analysis to assess the impact of exercise-based cardiac rehabilitation (ExCR) in patients with heart failure (HF) on mortality and hospitalisation, and differential effects of ExCR according to patient characteristics: age, sex, ethnicity, New York Heart Association functional class, ischaemic aetiology, ejection fraction, and exercise capacity. METHODS AND RESULTS: Randomised trials of exercise training for at least 3 weeks compared with no exercise control with 6-month follow-up or longer, providing IPD time to event on mortality or hospitalisation (all-cause or HF-specific). IPD were combined into a single dataset. We used Cox proportional hazards models to investigate the effect of ExCR and the interactions between ExCR and participant characteristics. We used both two-stage random effects and one-stage fixed effect models. IPD were obtained from 18 trials including 3912 patients with HF with reduced ejection fraction. Compared to control, there was no statistically significant difference in pooled time to event estimates in favour of ExCR although confidence intervals (CIs) were wide [all-cause mortality: hazard ratio (HR) 0.83, 95% CI 0.67-1.04; HF-specific mortality: HR 0.84, 95% CI 0.49-1.46; all-cause hospitalisation: HR 0.90, 95% CI 0.76-1.06; and HF-specific hospitalisation: HR 0.98, 95% CI 0.72-1.35]. No strong evidence was found of differential intervention effects across patient characteristics. CONCLUSION: Exercise-based cardiac rehabilitation did not have a significant effect on the risk of mortality and hospitalisation in HF with reduced ejection fraction. However, uncertainty around effect estimates precludes drawing definitive conclusions.This work is supported by UK National Institute for Health Research funding (HTA 15/80/30)

Conformational Space and Stability of ETD Charge Reduction Products of Ubiquitin

Owing to its versatility, electron transfer dissociation (ETD) has become one of the most commonly utilized fragmentation techniques in both native and non-native top-down mass spectrometry. However, several competing reactions—primarily different forms of charge reduction—occur under ETD conditions, as evidenced by the distorted isotope patterns usually observed. In this work, we analyze these isotope patterns to compare the stability of nondissociative electron transfer (ETnoD) products, specifically noncovalent c/z fragment complexes, across a range of ubiquitin conformational states. Using ion mobility, we find that more extended states are more prone to fragment release. We obtain evidence that for a given charge state, populations of ubiquitin ions formed either directly by electrospray ionization or through collapse of more extended states upon charge reduction, span a similar range of collision cross-sections. Products of gas-phase collapse are, however, less stabilized towards unfolding than the native conformation, indicating that the ions retain a memory of previous conformational states. Furthermore, this collapse of charge-reduced ions is promoted if the ions are ‘preheated’ using collisional activation, with possible implications for the kinetics of gas-phase compaction

Patient advocacy: barriers and facilitators

BACKGROUND: During the two recent decades, advocacy has been a topic of much debate in the nursing profession. Although advocacy has embraced a crucial role for nurses, its extent is often limited in practice. While a variety of studies have been generated all over the world, barriers and facilitators in the patient advocacy have not been completely identified. This article presents the findings of a study exploring the barriers and facilitators influencing the role of advocacy among Iranian nurses. METHOD: This study was conducted by grounded theory method. Participants were 24 Iranian registered nurses working in a large university hospital in Tehran, Iran. Semi-structured interviews were used for data collection. All interviews were transcribed verbatim and simultaneously Constant comparative analysis was used according to the Strauss and Corbin method. RESULTS: Through data analysis, several main themes emerged to describe the factors that hindered or facilitated patient advocacy. Nurses in this study identified powerlessness, lack of support, law, code of ethics and motivation, limited communication, physicians leading, risk of advocacy, royalty to peers, and insufficient time to interact with patients and families as barriers to advocacy. As for factors that facilitated nurses to act as a patient advocate, it was found that the nature of nurse-patient relationship, recognizing patients' needs, nurses' responsibility, physician as a colleague, and nurses' knowledge and skills could be influential in adopting the advocacy role. CONCLUSION: Participants believed that in this context taking an advocacy role is difficult for nurses due to the barriers mentioned. Therefore, they make decisions and act as a patient's advocate in any situation concerning patient needs and status of barriers and facilitators. In most cases, they can not act at an optimal level; instead they accept only what they can do, which we called 'limited advocacy' in this study. It is concluded that advocacy is contextually complex, and is a controversial and risky component of the nursing practice. Further research is needed to determine the possibility of a correlation between identified barriers/ facilitators and the use of advocacy