Whole home exercise intervention for depression in older care home residents (the OPERA study) : a process evaluation

Background: The ‘Older People’s Exercise intervention in Residential and nursing Accommodation’ (OPERA) cluster randomised trial evaluated the impact of training for care home staff together with twice-weekly, physiotherapist-led exercise classes on depressive symptoms in care home residents, but found no effect. We report a process evaluation exploring potential explanations for the lack of effect. Methods: The OPERA trial included over 1,000 residents in 78 care homes in the UK. We used a mixed methods approach including quantitative data collected from all homes. In eight case study homes, we carried out repeated periods of observation and interviews with residents, care staff and managers. At the end of the intervention, we held focus groups with OPERA research staff. We reported our first findings before the trial outcome was known. Results: Homes showed large variations in activity at baseline and throughout the trial. Overall attendance rate at the group exercise sessions was low (50%). We considered two issues that might explain the negative outcome: whether the intervention changed the culture of the homes, and whether the residents engaged with the intervention. We found low levels of staff training, few home champions for the intervention and a culture that prioritised protecting residents from harm over encouraging activity. The trial team delivered 3,191 exercise groups but only 36% of participants attended at least 1 group per week and depressed residents attended significantly fewer groups than those who were not depressed. Residents were very frail and therefore most groups only included seated exercises. Conclusions: The intervention did not change the culture of the homes and, in the case study homes, activity levels did not change outside the exercise groups. Residents did not engage in the exercise groups at a sufficient level, and this was particularly true for those with depressive symptoms at baseline. The physical and mental frailty of care home residents may make it impossible to deliver a sufficiently intense exercise intervention to impact on depressive symptoms

Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis

Background. Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. Aim:To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. Patients: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. Methods: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. Results: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (< 2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. Conclusion: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance. Copyright (c) 2006 S. Karger AG, Basel

Alcohol consumption and lifetime change in cognitive ability:a gene × environment interaction study

Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol

Developing a questionnaire to determine the impact of self-management in diabetes: giving people with diabetes a voice

Background The prevalence of diabetes mellitus (DM) is increasing dramatically, placing considerable financial burden on the healthcare budget of each country. Patient self-management is crucial for the control of blood glucose, which largely determines the chances of developing diabetes-related complications. Self-management interventions vary widely, and a method is required for assessing the impact of self-management. This paper describes the development of a questionnaire intended for use to measure the impact of self-management in diabetes. Methods An iterative development process was undertaken to identify the attributes of self-management using 5 steps. First, a literature review was undertaken to identify and understand themes relating to self-management of DM to inform a topic guide. Second, the topic guide was further refined following consultation with a Patient and Public Involvement group. Third, the topic guide was used to inform semi-structured interviews with patients with Type 1 DM (T1DM) and Type 2 DM (T2DM) to identify how self-management of DM affects individuals. Fourth, the research team considered potential attributes alongside health attributes from an existing measure (Diabetes Health Profile, DHP) to produce an instrument reflecting both health and self-management outcomes simultaneously. Finally, a draft instrument was tested in a focus group to determine the wording and acceptability. Results Semi-structured interviews were carried out with 32 patients with T1DM and T2DM. Eight potential attributes were identified: fear/worry/anxiety, guilt, stress, stigma, hassle, control, freedom, and feeling supported. Four of these self-management attributes were selected with four health attributes (mood, worry about hypos (hypoglycaemic episodes), vitality and social limitations) to produce the Health and Self-Management in Diabetes (HASMID v1) questionnaire. Conclusions HASMID v1 is a short questionnaire that contains eight items each with four response levels to measure the impact of self-management in diabetes for both T1DM and T2DM. The measure was developed using a mixed-methods approach that involved semi-structured interviews with people with diabetes. The measure has high face validity. Ongoing research is being undertaken to assess the validity of this questionnaire for measuring the impact of self-management interventions in economic evaluation

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

Strengthening fairness, transparency and accountability in health care priority setting at district level in Tanzania

Health care systems are faced with the challenge of resource scarcity and have insufficient resources to respond to all health problems and target groups simultaneously. Hence, priority setting is an inevitable aspect of every health system. However, priority setting is complex and difficult because the process is frequently influenced by political, institutional and managerial factors that are not considered by conventional priority-setting tools. In a five-year EU-supported project, which started in 2006, ways of strengthening fairness and accountability in priority setting in district health management were studied. This review is based on a PhD thesis that aimed to analyse health care organisation and management systems, and explore the potential and challenges of implementing Accountability for Reasonableness (A4R) approach to priority setting in Tanzania. A qualitative case study in Mbarali district formed the basis of exploring the sociopolitical and institutional contexts within which health care decision making takes place. The study also explores how the A4R intervention was shaped, enabled and constrained by the contexts. Key informant interviews were conducted. Relevant documents were also gathered and group priority-setting processes in the district were observed. The study revealed that, despite the obvious national rhetoric on decentralisation, actual practice in the district involved little community participation. The assumption that devolution to local government promotes transparency, accountability and community participation, is far from reality. The study also found that while the A4R approach was perceived to be helpful in strengthening transparency, accountability and stakeholder engagement, integrating the innovation into the district health system was challenging. This study underscores the idea that greater involvement and accountability among local actors may increase the legitimacy and fairness of priority-setting decisions. A broader and more detailed analysis of health system elements, and socio-cultural context is imperative in fostering sustainability. Additionally, the study stresses the need to deal with power asymmetries among various actors in priority-setting contexts

A General Framework for Formal Tests of Interaction after Exhaustive Search Methods with Applications to MDR and MDR-PDT

The initial presentation of multifactor dimensionality reduction (MDR) featured cross-validation to mitigate over-fitting, computationally efficient searches of the epistatic model space, and variable construction with constructive induction to alleviate the curse of dimensionality. However, the method was unable to differentiate association signals arising from true interactions from those due to independent main effects at individual loci. This issue leads to problems in inference and interpretability for the results from MDR and the family-based compliment the MDR-pedigree disequilibrium test (PDT). A suggestion from previous work was to fit regression models post hoc to specifically evaluate the null hypothesis of no interaction for MDR or MDR-PDT models. We demonstrate with simulation that fitting a regression model on the same data as that analyzed by MDR or MDR-PDT is not a valid test of interaction. This is likely to be true for any other procedure that searches for models, and then performs an uncorrected test for interaction. We also show with simulation that when strong main effects are present and the null hypothesis of no interaction is true, that MDR and MDR-PDT reject at far greater than the nominal rate. We also provide a valid regression-based permutation test procedure that specifically tests the null hypothesis of no interaction, and does not reject the null when only main effects are present. The regression-based permutation test implemented here conducts a valid test of interaction after a search for multilocus models, and can be applied to any method that conducts a search to find a multilocus model representing an interaction

Handgrip performance in relation to self-perceived fatigue, physical functioning and circulating IL-6 in elderly persons without inflammation

BACKGROUND: Low grip strength is recognized as one of the characteristics of frailty, as are systemic inflammation and the sensation of fatigue. Contrary to maximal grip strength, the physical resistance of the muscles to fatigue is not often included in the clinical evaluation of elderly patients. The aim of this study was to investigate if the grip strength and the resistance of the handgrip muscles to fatigue are related to self-perceived fatigue, physical functioning and circulating IL-6 in independently living elderly persons. METHODS: Forty elderly subjects (15 female and 25 male, mean age 75 ± 5 years) were assessed for maximal grip strength, as well as for fatigue resistance and grip work (respectively time and work delivered until grip strength drops to 50% of its maximum during sustained contraction), self perceived fatigue (VAS-Fatigue, Mob-Tiredness scale and the energy & fatigue items of the WHOQOL-100), self rated physical functioning (domain of physical functioning on the MOS short-form) and circulating IL-6. Relationships between handgrip performance and the other outcome measures were assessed. RESULTS: In the male participants, fatigue resistance was negatively related to actual sensation of fatigue (VAS-F, p < .05) and positively to circulating IL-6 (p < .05). When corrected for body weight, the relations of fatigue resistance with self-perceived fatigue became stronger and also apparent in the female. Grip strength and grip work were significantly related with several items of self-perceived fatigue and with physical functioning. These relations became more visible by means of higher correlation coefficients when grip strength and grip work were corrected for body weight. CONCLUSION: Well functioning elderly subjects presenting less handmuscle fatigue resistance and weaker grip strength are more fatigued, experience more tiredness during daily activities and are more bothered by fatigue sensations. Body weight seems to play an important role in the relation of muscle performance to fatigue perception. Elderly patients complaining from fatigue should be physically assessed, both evaluating maximal grip strength and fatigue resistance, allowing the calculation of grip work, which integrates both parameters. Grip work might best reflect the functional capacity resulting from the development of a certain strength level in relation to the time it can be maintained

π+\pi^+ photoproduction on the proton for photon energies from 0.725 to 2.875 GeV

Differential cross sections for the reaction $\gamma p \to n \pi^+$ have been measured with the CEBAF Large Acceptance Spectrometer (CLAS) and a tagged photon beam with energies from 0.725 to 2.875 GeV. Where available, the results obtained here compare well with previously published results for the reaction. Agreement with the SAID and MAID analyses is found below 1 GeV. The present set of cross sections has been incorporated into the SAID database, and exploratory fits have been made up to 2.7 GeV. Resonance couplings have been extracted and compared to previous determinations. With the addition of these cross sections to the world data set, significant changes have occurred in the high-energy behavior of the SAID cross-section predictions and amplitudes.Comment: 18 pages, 10 figure