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)

Thoracic load carriage-induced respiratory muscle fatigue.

We investigated the effect of carrying a 25 kg backpack upon exercise-induced respiratory muscle fatigue, pulmonary function and physiological and perceptual responses to exercise.N/

Military veteran mortality following a survived suicide attempt

<p>Abstract</p> <p>Background</p> <p>Suicide is a global public health problem. Recently in the U.S., much attention has been given to preventing suicide and other premature mortality in veterans returning from Iraq and Afghanistan. A strong predictor of suicide is a past suicide attempt, and suicide attempters have multiple physical and mental comorbidities that put them at risk for additional causes of death. We examined mortality among U.S. military veterans after hospitalization for attempted suicide.</p> <p>Methods</p> <p>A retrospective cohort study was conducted with all military veterans receiving inpatient treatment during 1993-1998 at United States Veterans Affairs (VA) medical facilities following a suicide attempt. Deaths occurring during 1993-2002, the most recent available year at the time, were identified through VA Beneficiary and Records Locator System data and National Death Index data. Mortality data for the general U.S. adult population were also obtained from the National Center for Health Statistics. Comparisons within the veteran cohort, between genders, and against the U.S. population were conducted with descriptive statistics and standardized mortality ratios. The actuarial method was used estimate the proportion of veterans in the cohort we expect would have survived through 2002 had they experienced the same rate of death that occurred over the study period in the U.S. population having the age and sex characteristics.</p> <p>Results</p> <p>During 1993-1998, 10,163 veterans were treated and discharged at a VA medical center after a suicide attempt (mean age = 44 years; 91% male). There was a high prevalence of diagnosed alcohol disorder or abuse (31.8%), drug dependence or abuse (21.8%), psychoses (21.2%), depression (18.5%), and hypertension (14.2%). A total of 1,836 (18.1%) veterans died during follow up (2,941.4/100,000 person years). The cumulative survival probability after 10 years was 78.0% (95% CI = 72.9, 83.1). Hence the 10-year cumulative mortality risk was 22.0%, which was 3.0 times greater than expected. The leading causes overall were heart disease (20.2%), suicide (13.1%), and unintentional injury (12.7%). Whereas suicide was the ninth leading cause of death in the U.S. population overall (1.8%) during the study period, suicide was the leading and second leading cause among women (25.0%) and men (12.7%) in the cohort, respectively.</p> <p>Conclusions</p> <p>Veterans who have attempted suicide face elevated risks of all-cause mortality with suicide being prominent. This represents an important population for prevention activities.</p

Broader Neutralizing Antibodies against H5N1 Viruses Using Prime-Boost Immunization of Hyperglycosylated Hemagglutinin DNA and Virus-Like Particles

BACKGROUND: Highly pathogenic avian influenza (HPAI) H5N1 viruses and their transmission capability from birds to humans have raised global concerns about a potential human pandemic. The inherent nature of antigenic changes in influenza viruses has not been sufficiently taken into account in immunogen designs for broadly protective HPAI H5N1 vaccines. METHODS: We designed a hyperglycosylated HA vaccine using N-linked glycan masking on highly variable sequences in the HA1 globular head. Immunization of these hyperglycosylated HA DNA vaccines followed by a flagellin-containing virus-like particle booster in mice was conducted to evaluate neutralizing antibody responses against various clades of HPAI H5N1 viruses. RESULTS: We introduced nine N-X-S/T motifs in five HA1 regions: 83NNT, 86NNT, 94NFT, 127NSS, 138NRT, 156NTT, 161NRS, 182NDT, and 252NAT according to sequence alignment analyses from 163 HPAI H5N1 human isolates. Although no significant differences of anti-HA total IgG titers were found with these hyperglycosyalted HA compared to the wild-type control, the 83NNT and 127NSS mutants elicited significantly potent cross-clade neutralizing antibodies against HPAI H5N1 viruses. CONCLUSIONS: This finding may have value in terms of novel immunogen design for developing cross-protective H5N1 vaccines

A Transcriptional “Scream” Early Response of E. coli Prey to Predatory Invasion by Bdellovibrio

We have transcriptionally profiled the genes differentially expressed in E. coli prey cells when predatorily attacked by Bdellovibrio bacteriovorus just prior to prey cell killing. This is a brief, approximately 20–25 min period when the prey cell is still alive but contains a Bdellovibrio cell in its periplasm or attached to and penetrating its outer membrane. Total RNA was harvested and labelled 15 min after initiating a semi-synchronous infection with an excess of Bdellovibrio preying upon E. coli and hybridised to a macroarray spotted with all predicted ORFs of E. coli. SAM analysis and t-tests were performed on the resulting data and 126 E. coli genes were found to be significantly differentially regulated by the prey upon attack by Bdellovibrio. The results were confirmed by QRT-PCR. Amongst the prey genes upregulated were a variety of general stress response genes, potentially “selfish” genes within or near prophages and transposable elements, and genes responding to damage in the periplasm and osmotic stress. Essentially, the presence of the invading Bdellovibrio and the resulting damage to the prey cell elicited a small “transcriptional scream”, but seemingly no specific defensive mechanism with which to counter the Bdellovibrio attack. This supports other studies which do not find Bdellovibrio resistance responses in prey, and bodes well for its use as a “living antibiotic”

An Efficient Method of Modeling Material Properties Using a Thermal Diffusion Analogy: An Example Based on Craniofacial Bone

The ability to incorporate detailed geometry into finite element models has allowed researchers to investigate the influence of morphology on performance aspects of skeletal components. This advance has also allowed researchers to explore the effect of different material models, ranging from simple (e.g., isotropic) to complex (e.g., orthotropic), on the response of bone. However, bone's complicated geometry makes it difficult to incorporate complex material models into finite element models of bone. This difficulty is due to variation in the spatial orientation of material properties throughout bone. Our analysis addresses this problem by taking full advantage of a finite element program's ability to solve thermal-structural problems. Using a linear relationship between temperature and modulus, we seeded specific nodes of the finite element model with temperatures. We then used thermal diffusion to propagate the modulus throughout the finite element model. Finally, we solved for the mechanical response of the finite element model to the applied loads and constraints. We found that using the thermal diffusion analogy to control the modulus of bone throughout its structure provides a simple and effective method of spatially varying modulus. Results compare favorably against both experimental data and results from an FE model that incorporated a complex (orthotropic) material model. This method presented will allow researchers the ability to easily incorporate more material property data into their finite element models in an effort to improve the model's accuracy

Oligonucleotide Sequence Motifs as Nucleosome Positioning Signals

To gain a better understanding of the sequence patterns that characterize positioned nucleosomes, we first performed an analysis of the periodicities of the 256 tetranucleotides in a yeast genome-wide library of nucleosomal DNA sequences that was prepared by in vitro reconstitution. The approach entailed the identification and analysis of 24 unique tetranucleotides that were defined by 8 consensus sequences. These consensus sequences were shown to be responsible for most if not all of the tetranucleotide and dinucleotide periodicities displayed by the entire library, demonstrating that the periodicities of dinucleotides that characterize the yeast genome are, in actuality, due primarily to the 8 consensus sequences. A novel combination of experimental and bioinformatic approaches was then used to show that these tetranucleotides are important for preferred formation of nucleosomes at specific sites along DNA in vitro. These results were then compared to tetranucleotide patterns in genome-wide in vivo libraries from yeast and C. elegans in order to assess the contributions of DNA sequence in the control of nucleosome residency in the cell. These comparisons revealed striking similarities in the tetranucleotide occurrence profiles that are likely to be involved in nucleosome positioning in both in vitro and in vivo libraries, suggesting that DNA sequence is an important factor in the control of nucleosome placement in vivo. However, the strengths of the tetranucleotide periodicities were 3–4 fold higher in the in vitro as compared to the in vivo libraries, which implies that DNA sequence plays less of a role in dictating nucleosome positions in vivo. The results of this study have important implications for models of sequence-dependent positioning since they suggest that a defined subset of tetranucleotides is involved in preferred nucleosome occupancy and that these tetranucleotides are the major source of the dinucleotide periodicities that are characteristic of positioned nucleosomes

Transcriptional interaction-assisted identification of dynamic nucleosome positioning

<p>Abstract</p> <p>Background</p> <p>Nucleosomes regulate DNA accessibility and therefore play a central role in transcription control. Computational methods have been developed to predict static nucleosome positions from DNA sequences, but nucleosomes are dynamic in vivo.</p> <p>Results</p> <p>Motivated by our observation that transcriptional interaction is discriminative information for nucleosome occupancy, we developed a novel computational approach to identify dynamic nucleosome positions at promoters by combining transcriptional interaction and genomic sequence information. Our approach successfully identified experimentally determined nucleosome positioning dynamics available in three cellular conditions, and significantly improved the prediction accuracy which is based on sequence information alone. We then applied our approach to various cellular conditions and established a comprehensive landscape of dynamic nucleosome positioning in yeast.</p> <p>Conclusion</p> <p>Analysis of this landscape revealed that the majority of nucleosome positions are maintained during most conditions. However, nucleosome occupancy at most promoters fluctuates with the corresponding gene expression level and is reduced specifically at the phase of peak expression. Further investigation into properties of nucleosome occupancy identified two gene groups associated with distinct modes of nucleosome modulation. Our results suggest that both the intrinsic sequence and regulatory proteins modulate nucleosomes in an altered manner.</p