Cost-effectiveness of an integrated 'fast track' rehabilitation service for multi-trauma patients involving dedicated early rehabilitation intervention programs: design of a prospective, multi-centre, non-randomised clinical trial

Contains fulltext : 79649.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: In conventional multi-trauma care service (CTCS), patients are admitted to hospital via the accident & emergency room. After surgery they are transferred to the IC-unit followed by the general surgery ward. Ensuing treatment takes place in a hospital's outpatient clinic, a rehabilitation centre, a nursing home or the community. Typically, each of the CTCS partners may have its own more or less autonomous treatment perspective. Clinical evidence, however, suggests that an integrated multi-trauma rehabilitation approach ('Supported Fast-track multi-Trauma Rehabilitation Service': SFTRS), featuring: 1) earlier transfer to a specialised trauma rehabilitation unit; 2) earlier start of 'non-weight-bearing' training and multidisciplinary treatment; 3) well-documented treatment protocols; 4) early individual goal-setting; 5) co-ordination of treatment between trauma surgeon and physiatrist, and 6) shorter lengths-of-stay, may be more (cost-)effective.This paper describes the design of a prospective cohort study evaluating the (cost-) effectiveness of SFTRS relative to CTCS. METHODS/DESIGN: The study population includes multi-trauma patients, admitted to one of the participating hospitals, with an Injury Severity Scale score > = 16, complex multiple injuries in several extremities or complex pelvic and/or acetabulum fractures. In a prospective cohort study CTCS and SFTRS will be contrasted. The inclusion period is 19 months. The duration of follow-up is 12 months, with measurements taken at baseline, and at 3,6,9 and 12 months post-injury.Primary outcome measures are 'quality of life' (SF-36) and 'functional health status' (Functional Independence Measure). Secondary outcome measures are the Hospital Anxiety & Depression Scale, the Mini-Mental State Examination as an indicator of cognitive functioning, and the Canadian Occupational Performance Measure measuring the extent to which individual ADL treatment goals are met. Costs will be assessed using the PROductivity and DISease Questionnaire and a cost questionnaire. DISCUSSION: The study will yield results on the efficiency of an adapted care service for multi-trauma patients (SFTRS) featuring earlier (and condensed) involvement of specialised rehabilitation treatment. Results will show whether improved SFTRS logistics, combined with shorter stays in hospital and rehabilitation clinic and specialised early rehabilitation training modules are more (cost-) effective, relative to CTCS. TRIAL REGISTRATION: Current Controlled Trials register (ISRCTN68246661) and Netherlands Trial Register (NTR139)

Women's experiences of ovulation testing: A qualitative analysis

© 2015 Jones et al.Background: The introduction of home digital ovulation tests (OTs) has provided a simple solution for women wishing to optimise the timing of intercourse when trying to conceive. However, despite this, very little is understood about women's experiences of using these tests. Methods: We carried out qualitative, semi-structured telephone interviews with women who were seeking to conceive (not actively undergoing clinical investigation/fertility treatment) from the general UK population. The interviews were conducted following participation in a randomised controlled trial (RCT) in which participants were either provided with digital home OTs to assist in timing intercourse (n = 18) or advised to have intercourse every 2-3 days (n = 18). The interviews were digitally recorded, transcribed and then analysed using Framework analysis to identify the themes. Results: Data saturation was reached after 36 interviews. The use of the OT appeared to elicit 10 key themes, which could be described within the context of three overarching issues: 1) a positive impact (understanding the menstrual cycle, confirming when ovulating, emotional support, improving the relationship), 2) a negative impact (changing sex life and relationship with their partner, the emotional consequences of prolonged use, questions and uncertainty about what their results mean for them) and 3) the experiences of trying to conceive in general (use of clinical guidance and emotional experience). Conclusions: Overall, the use of home OTs were found to affect women's thoughts and feelings in multiple ways during attempts to conceive. Although some women reported a range of negative experiences when using OTs, they also reported similar negative experiences when trying to conceive without using the tests. However, there were many positive themes associated with OT use, including an increased understanding of the menstrual cycle, confirmation of ovulation timing and providing a source of help and support when trying to conceive. Overall, when women are trying to conceive, ensuring they have access to high-quality information, including use of OT, may be of benefit to help address some of the questions and uncertainties that were raised by the participants in this study. Trial registration number: NCT01084304

The Stroke Outcomes Study 2 (SOS2): a prospective, analytic cohort study of depressive symptoms after stroke

<p>Abstract</p> <p>Background</p> <p>Mood disorder is recognised as an important and common problem after stroke but little is known about the longer term effects of mood on functional outcomes. This protocol paper describes the Stroke Outcomes Study 2 (SOS2), a research study conducted in two large acute NHS Trusts in the North of England, which was designed to investigate the impact of early depressive symptoms on outcomes after an acute stroke.</p> <p>Methods and design</p> <p>SOS2 was a prospective cohort study that aimed to recruit patients in the first few weeks after a stroke, and to follow them up at regular intervals for one year thereafter in order to describe the trajectory of psychological symptoms and study their impact on physical functional recovery. Measures of mood and function were completed at baseline (approximately 3 weeks) and at four follow-up time-points: approximately 9, 13, 26 and 52 weeks after the index stroke.</p> <p>Discussion</p> <p>Recruiting patients to research studies soon after an acute stroke is difficult. Mortality following stroke is approximately 30% and in the region of half the patients that survive the initial event are significantly disabled. Together these factors reduced the number of patients available to participate in SOS2 but once recruited to the study the drop-out rate was relatively low. During the recruitment period over 6000 admissions for stroke or query stroke were screened for eligibility. A cohort of 592 study participants was finally achieved.</p

Comparing methods to estimate treatment effects on a continuous outcome in multicentre randomized controlled trials: A simulation study

<p>Abstract</p> <p>Background</p> <p>Multicentre randomized controlled trials (RCTs) routinely use randomization and analysis stratified by centre to control for differences between centres and to improve precision. No consensus has been reached on how to best analyze correlated continuous outcomes in such settings. Our objective was to investigate the properties of commonly used statistical models at various levels of clustering in the context of multicentre RCTs.</p> <p>Methods</p> <p>Assuming no treatment by centre interaction, we compared six methods (ignoring centre effects, including centres as fixed effects, including centres as random effects, generalized estimating equation (GEE), and fixed- and random-effects centre-level analysis) to analyze continuous outcomes in multicentre RCTs using simulations over a wide spectrum of intraclass correlation (ICC) values, and varying numbers of centres and centre size. The performance of models was evaluated in terms of bias, precision, mean squared error of the point estimator of treatment effect, empirical coverage of the 95% confidence interval, and statistical power of the procedure.</p> <p>Results</p> <p>While all methods yielded unbiased estimates of treatment effect, ignoring centres led to inflation of standard error and loss of statistical power when within centre correlation was present. Mixed-effects model was most efficient and attained nominal coverage of 95% and 90% power in almost all scenarios. Fixed-effects model was less precise when the number of centres was large and treatment allocation was subject to chance imbalance within centre. GEE approach underestimated standard error of the treatment effect when the number of centres was small. The two centre-level models led to more variable point estimates and relatively low interval coverage or statistical power depending on whether or not heterogeneity of treatment contrasts was considered in the analysis.</p> <p>Conclusions</p> <p>All six models produced unbiased estimates of treatment effect in the context of multicentre trials. Adjusting for centre as a random intercept led to the most efficient treatment effect estimation across all simulations under the normality assumption, when there was no treatment by centre interaction.</p

Extracellular Superoxide Dismutase Protects Histoplasma Yeast Cells from Host-Derived Oxidative Stress

In order to establish infections within the mammalian host, pathogens must protect themselves against toxic reactive oxygen species produced by phagocytes of the immune system. The fungal pathogen Histoplasma capsulatum infects both neutrophils and macrophages but the mechanisms enabling Histoplasma yeasts to survive in these phagocytes have not been fully elucidated. We show that Histoplasma yeasts produce a superoxide dismutase (Sod3) and direct it to the extracellular environment via N-terminal and C-terminal signals which promote its secretion and association with the yeast cell surface. This localization permits Sod3 to protect yeasts specifically from exogenous superoxide whereas amelioration of endogenous reactive oxygen depends on intracellular dismutases such as Sod1. While infection of resting macrophages by Histoplasma does not stimulate the phagocyte oxidative burst, interaction with polymorphonuclear leukocytes (PMNs) and cytokine-activated macrophages triggers production of reactive oxygen species (ROS). Histoplasma yeasts producing Sod3 survive co-incubation with these phagocytes but yeasts lacking Sod3 are rapidly eliminated through oxidative killing similar to the effect of phagocytes on Candida albicans yeasts. The protection provided by Sod3 against host-derived ROS extends in vivo. Without Sod3, Histoplasma yeasts are attenuated in their ability to establish respiratory infections and are rapidly cleared with the onset of adaptive immunity. The virulence of Sod3-deficient yeasts is restored in murine hosts unable to produce superoxide due to loss of the NADPH-oxidase function. These results demonstrate that phagocyte-produced ROS contributes to the immune response to Histoplasma and that Sod3 facilitates Histoplasma pathogenesis by detoxifying host-derived reactive oxygen thereby enabling Histoplasma survival

Are self-report of disability pension and long-term sickness absence accurate? Comparisons of self-reported interview data with national register data in a Swedish twin cohort

<p>Abstract</p> <p>Background</p> <p>Self-reported disability pension (DP) and sickness absence are commonly used in epidemiological and other studies as a measure of exposure or even as an outcome. The aims were (1) to compare such self-reports with national register information in order to evaluate the validity of self-reported DP and sickness absence, and (2) to estimate the concordance of reporting behaviour in different twin zygosity groups, also by sex.</p> <p>Methods</p> <p>All Swedish twins born 1933-1958 who participated in the Screening Across the Lifespan Twin study (SALT) 1998-2003, were included (31,122 individuals). The self-reported DP and long-term sickness absence (LTSA) at the time of interview was compared to the corresponding register information retrieved from the National Social Insurance Agency by calculating the proportions of agreements, kappa, sensitivity, specificity, concordance rates, and chi-square test, to evaluate construct validity.</p> <p>Results</p> <p>The proportions of overall agreement were 96% and specificity 99% for both DP and LTSA, while the sensitivity was 70% for DP and 45% for LTSA. Kappa estimates were 0.76 for DP, and 0.58 for LTSA. The proportions of positive agreement were 64% for DP and 42% for LTSA. No difference in response style was found between zygosity groups among complete twin pairs for DP and LTSA. Results were similar for women and men and across age. Kappa estimates for DP differed somewhat depending on years of education, 0.68 (college/university) vs. 0.77 (less than 13 years in school) but not for LTSA.</p> <p>Conclusions</p> <p>Self-reported DP data may be very useful in studies when register information is not available, however, register data is preferred especially for LTSA. The same degree of twin similarity was found for truthful self-report of DP and LTSA in both monozygotic and dizygotic twin pairs. Thus, the response style was not influenced by genetic factors. One consequence of this would be that when estimating the relative importance of genetic and environmental effects from twin models, heritability estimates would not be biased.</p

Loss of Nuclear Activity of the FBXO7 Protein in Patients with Parkinsonian-Pyramidal Syndrome (PARK15)

Mutations in the F-box only protein 7 gene (FBXO7) cause PARK15, an autosomal recessive neurodegenerative disease presenting with severe levodopa-responsive parkinsonism and pyramidal disturbances. Understanding the PARK15 pathogenesis might thus provide clues on the mechanisms of maintenance of brain dopaminergic neurons, the same which are lost in Parkinson's disease. The protein(s) encoded by FBXO7 remain very poorly characterized. Here, we show that two protein isoforms are expressed from the FBXO7 gene in normal human cells. The isoform 1 is more abundant, particularly in primary skin fibroblasts. Both isoforms are undetectable in cell lines from the PARK15 patient of an Italian family; the isoform 1 is undetectable and the isoform 2 is severely decreased in the patients from a Dutch PARK15 family. In human cell lines and mouse primary neurons, the endogenous or over-expressed, wild type FBXO7 isoform 1 displays mostly a diffuse nuclear localization. An intact N-terminus is needed for the nuclear FBXO7 localization, as N-terminal modification by PARK15-linked missense mutation, or N-terminus tag leads to cytoplasmic mislocalization. Furthermore, the N-terminus of wild type FBXO7 (but not of mutant FBXO7) is able to confer nuclear localization to profilin (a cytoplasmic protein). Our data also suggest that overexpressed mutant FBXO7 proteins (T22M, R378G and R498X) have decreased stability compared to their wild type counterpart. In human brain, FBXO7 immunoreactivity was highest in the nuclei of neurons throughout the cerebral cortex, intermediate in the globus pallidum and the substantia nigra, and lowest in the hippocampus and cerebellum. In conclusion, the common cellular abnormality found in the PARK15 patients from the Dutch and Italian families is the depletion of the FBXO7 isoform 1, which normally localizes in the cell nucleus. The activity of FBXO7 in the nucleus appears therefore crucial for the maintenance of brain neurons and the pathogenesis of PARK15

Educational intervention improves anticoagulation control in atrial fibrillation patients:the TREAT randomised trial

Background: Stroke prevention in atrial fibrillation (AF), most commonly with warfarin, requires maintenance of a narrow therapeutic target (INR 2.0 to 3.0) and is often poorly controlled in practice. Poor patient-understanding surrounding AF and its’ treatment may contribute to patient’s willingness to adhere to recommendations. Method: A theory-driven intervention, developed using patient interviews and focus groups, consisting of a one-off group session (1-6 patients) utilising an ‘expert-patient’ focussed DVD, educational booklet, self-monitoring diary and worksheet, was compared in a randomised controlled trial (ISRCTN93952605) against usual care, with patient postal follow-ups at 1, 2, 6, and 12-months. Ninety-seven warfarin-naïve AF patients were randomised to intervention (n=46, mean age (SD) 72.0 (8.2), 67.4% men), or usual care (n=51, mean age (SD) 73.7 (8.1), 62.7% men), stratified by age, sex, and recruitment centre. Primary endpoint was time within therapeutic range (TTR); secondary endpoints included knowledge, quality of life, anxiety/depression, beliefs about medication, and illness perceptions. Main findings: Intervention patients had significantly higher TTR than usual care at 6-months (76.2% vs. 71.3%; p=0.035); at 12-months these differences were not significant (76.0% vs. 70.0%; p=0.44). Knowledge increased significantly across time (F (3, 47) = 6.4; p<0.01), but there were no differences between groups (F (1, 47) = 3.3; p = 0.07). At 6-months, knowledge scores predicted TTR (r=0.245; p=0.04). Patients’ scores on subscales representing their perception of the general harm and overuse of medication, as well as the perceived necessity of their AF specific medications predicted TTR at 6- and 12-months. Conclusions: A theory-driven educational intervention significantly improves TTR in AF patients initiating warfarin during the first 6-months. Adverse clinical outcomes may potentially be reduced by improving patients’ understanding of the necessity of warfarin and reducing their perception of treatment harm. Improving education provision for AF patients is essential to ensure efficacious and safe treatment