Minimum data set to measure rehabilitation needs and health outcome after major trauma : application of an international framework

BACKGROUND: Measurement of long term health outcome after trauma remains non-standardized and ambiguous which limits national and international comparison of burden of injuries. The World Health Organization (WHO) has recommended the application of the International Classification of Function, Disability and Health (ICF) to measure rehabilitation and health outcome worldwide. No previous poly-trauma studies have applied the ICF comprehensively to evaluate outcome after injury. AIM: To apply the ICF categorization in patients with traumatic injuries to identify a minimum data set of important rehabilitation and health outcomes to enable national and international comparison of outcome data. DESIGN: A mixed methods design of patient interviews and an on-line survey. SETTING: An ethnically diverse urban major trauma center in London. POPULATION: Adult patients with major traumatic injuries (poly-trauma) and international health care professionals (HCPs) working in acute and post-acute major trauma settings. METHODS: Mixed methods investigated patients and health care professionals (HCPs) perspectives of important rehabilitation and health outcomes. Qualitative patient data and quantitative HCP data were linked to ICF categories. Combined data were refined to identify a minimum data set of important rehabilitation and health outcome categories. RESULTS: Transcribed patient interview data (N.=32) were linked to 234 (64%) second level ICF categories. Two hundred and fourteen HCPs identified 121 from a possible 140 second level ICF categories (86%) as relevant and important. Patients and HCPs strongly agreed on ICF body structures and body functions categories which include temperament, energy and drive, memory, emotions, pain and repair function of the skin. Conversely, patients prioritised domestic tasks, recreation and work compared to HCP priorities of self-care and mobility. Twenty six environmental factors were identified. Patient and HCP data were refined to recommend a 109 possible ICF categories for a minimum data set. CONCLUSIONS: The comprehensive measurement of health outcomes after trauma is important for patients, health professionals and trauma systems. An internationally applied ICF minimum data set will standardize the language used and concepts measured after major trauma to enable national and international comparison of outcome data

Profiles of Serial Changes in Cardiac Troponin T Concentrations and Outcome in Ambulatory Patients With Chronic Heart Failure

ObjectivesThe purpose of this study was to determine whether different profiles of cardiac troponin T (cTnT) values assessed over time would yield incremental prognostic information on clinically stable outpatients with heart failure (HF).BackgroundcTnT levels were used to estimate prognosis in HF; however, most studies evaluated hospitalized patients using single measurements.MethodsA cohort of 172 New York Heart Association functional class III to IV outpatients was prospectively studied with serial cTnT measurements collected every 3 months over a 2-year period. The primary end point was death or cardiac transplantation, and secondary end points included HF hospitalization.ResultsOf the 172 patients, 22 (13%) died or underwent transplantation during the first year. Therefore, 150 patients were included in the second-year analysis of 3 pre-determined groups: 1) no serial cTnT elevations (defined as <0.01 ng/ml); 2) 1 or more, but not all cTnT values elevated ≥0.01 ng/ml; and 3) all cTnT values elevated during the first year. During the second year, 30 events occurred: 53 patients had persistently normal cTnT levels (<0.01 ng/ml) with 6 primary events (11%); 57 patients had 1 or more but not all cTnT levels elevated with 11 events (19%); 40 patients demonstrated persistently elevated cTnT levels with 13 (33%) primary events (odds ratio: 3.77; 95% confidence interval: 1.28 to 11.07, p = 0.02).ConclusionsElevations in cTnT, even using a low threshold of 0.01 ng/ml, detected during routine clinical follow-up of ambulatory patients with HF, are highly associated with an increased risk of events, particularly with frequent or persistent cTnT elevations of ≥0.01 ng/ml. Therefore, the ability to monitor clinical change through serial cTnT measurements may add to risk assessment in the ambulatory HF population

Improving outcome over time of percutaneous coronary interventions in unstable angina

AbstractOBJECTIVEThis study was performed to evaluate the recent changes in the outcome of coronary interventions in patients with unstable angina (UA).BACKGROUNDAn early invasive strategy has not been shown to be superior to conservative treatment in patients with UA. Earlier studies had utilized older technology. Interventional approaches have changed in the recent past, but to our knowledge, no large studies have addressed the impact of these changes on the outcome of coronary interventions.METHODSWe analyzed the in-hospital and intermediate-term outcome in 7,632 patients with UA who underwent coronary interventions in the last two decades. The study population was divided into three groups: group 1, n = 2,209 who had coronary intervention from 1979 to 1989; group 2, n = 2,212 with interventions from 1990 to 1993; and group 3, n = 3,211 treated from 1994 to 1998.RESULTSGroup 2 and 3 patients were older and sicker compared with group 1 patients. The clinical success improved significantly in group 3 (94.1%) compared with group 2 (87%) and group 1 (76.5%) (p < 0.001). There was a significant reduction in in-hospital mortality, Q-wave myocardial infarction and need for emergency bypass surgery in group 3 compared with the earlier groups. One-year event-free survival was also significantly higher in the recent group compared with the earlier groups: 77% in group 3, 70% in group 2 and 74% in group 1 (p < 0.001). With the use of multivariate models to adjust for clinical and angiographic variables, treatment during the most recent era was found to be independently associated with improved in-hospital and intermediate-term outcomes.CONCLUSIONSThere has been significant improvement in the in-hospital and intermediate-term outcome of coronary interventions in patients with UA in recent years; newer trials comparing conservative and invasive strategies are therefore needed

Histologic Correlates of Angiographic Chronic Total Coronary Artery Occlusions Influence of Occlusion Duration on Neovascular Channel Patterns and Intimal Plaque Composition

AbstractObjectives. Age-related changes in histologic composition and neovascular channel (NC) pattern of angiographic chronic total coronary artery occlusions (CTOs) were studied to define histologic correlates of age-related revascularization profiles and neovascular channel formation.Background. Revascularization of CTOs is frequently characterized by inability to cross or dilate the lesion and a high incidence of reocclusion or restenosis but low periprocedural ischemic complication rates. Little is known about the histopathologic basis of these observations.Methods. Ninety-six angiographic CTOs from autopsy studies in 61 patients who had undergone coronary angiography within 3 months of death were studied. Abrupt plaque rupture was excluded. Occlusion segments were analyzed for 1) histologic composition as a function of lesion age; and 2) NC pattern as a function of lesion age and intimal plaque (IP) composition.Results. Cholesterol and foam cell–laden IP was more frequent in younger lesions (p = 0.0007), whereas fibrocalcific IP increased with CTO age (p = 0.008). IP NCs arose directly from adventitial vasa vasorum and were anatomically and quantitatively related in terms of number and size (p = 0.0001) to the extent of IP cellular inflammation. IP cellular inflammation exceeded that found in the adventitia (p < 0.001) or media (p = 0.0001) across all CTO ages. In CTOs <1 year old, the adventitia was associated with a larger number and size of NCs relative to the IP (p = 0.0006 and p = 0.009), media (p = 0.0001 and p = 0.002) and recanalized lumen (p = 0.0001 and p = 0.001). In CTOs >1 year old, the adventitia and IP NC numbers were similar and exceeded NC numbers found in the media (p = 0.0001) and recanalized lumen (p = 0.0001 and p = 0.003).Conclusions. Angiographic CTO frequently corresponds to less than complete occlusion by histologic criteria. Age-related changes in IP composition from cholesterol laden to fibrocalcific may explain the adverse revascularization profile of older CTOs. IP NC growth derived from the adventitia increases with age and is strongly associated with IP cellular inflammation. IP NC formation may protect against the flow-limiting effects of IP growth.(J Am Coll Cardiol 1997;29:955–63)© 1997 by the American College of Cardiolog

Virus-specific and shared gene expression signatures in immune cells after vaccination in response to influenza and vaccinia stimulation

BackgroundIn the vaccine era, individuals receive multiple vaccines in their lifetime. Host gene expression in response to antigenic stimulation is usually virus-specific; however, identifying shared pathways of host response across a wide spectrum of vaccine pathogens can shed light on the molecular mechanisms/components which can be targeted for the development of broad/universal therapeutics and vaccines.MethodWe isolated PBMCs, monocytes, B cells, and CD8+ T cells from the peripheral blood of healthy donors, who received both seasonal influenza vaccine (within &lt;1 year) and smallpox vaccine (within 1 - 4 years). Each of the purified cell populations was stimulated with either influenza virus or vaccinia virus. Differentially expressed genes (DEGs) relative to unstimulated controls were identified for each in vitro viral infection, as well as for both viral infections (shared DEGs). Pathway enrichment analysis was performed to associate identified DEGs with KEGG/biological pathways.ResultsWe identified 2,906, 3,888, 681, and 446 DEGs in PBMCs, monocytes, B cells, and CD8+ T cells, respectively, in response to influenza stimulation. Meanwhile, 97, 120, 20, and 10 DEGs were identified as gene signatures in PBMCs, monocytes, B cells, and CD8+ T cells, respectively, upon vaccinia stimulation. The majority of DEGs identified in PBMCs were also found in monocytes after either viral stimulation. Of the virus-specific DEGs, 55, 63, and 9 DEGs occurred in common in PBMCs, monocytes, and B cells, respectively, while no DEGs were shared in infected CD8+ T cells after influenza and vaccinia. Gene set enrichment analysis demonstrated that these shared DEGs were over-represented in innate signaling pathways, including cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, Toll-like receptor signaling, RIG-I-like receptor signaling pathways, cytosolic DNA-sensing pathways, and natural killer cell mediated cytotoxicity.ConclusionOur results provide insights into virus-host interactions in different immune cells, as well as host defense mechanisms against viral stimulation. Our data also highlights the role of monocytes as a major cell population driving gene expression in ex vivo PBMCs in response to viral stimulation. The immune response signaling pathways identified in this study may provide specific targets for the development of novel virus-specific therapeutics and improved vaccines for vaccinia and influenza. Although influenza and vaccinia viruses have been selected in this study as pathogen models, this approach could be applicable to other pathogens

The Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH) can measure the impairment, activity limitations and participation restriction constructs from the International Classification of Functioning, Disability and Health (ICF)

Background The International Classification of Functioning, Disability and Health (ICF) model of the consequences of disease identifies three health outcomes, impairment, activity limitations and participation restrictions. However, few orthopaedic health outcome measures were developed with reference to the ICF. This study examined the ability of a valid and frequently used measure of upper limb function, namely the Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH), to operationalise the ICF. Methods Twenty-four judges used the method of Discriminant Content Validation to allocate the 38 items of the DASH to the theoretical definition of one or more ICF outcome. One-sample t-tests classified each item as measuring, impairment, activity limitations, participation restrictions, or a combination thereof. Results The DASH contains items able to measure each of the three ICF outcomes with discriminant validity. The DASH contains five pure impairment items, 19 pure activity limitations items and three participation restriction items. In addition, seven items measured both activity limitations and participation restrictions. Conclusions The DASH can measure the three health outcomes identified by the ICF. Consequently the DASH could be used to examine the impact of trauma and subsequent interventions on each health outcome in the absence of measurement confound

Integration of Immune Cell Populations, mRNA-Seq, and CpG Methylation to Better Predict Humoral Immunity to Influenza Vaccination: Dependence of mRNA-Seq/CpG Methylation on Immune Cell Populations

The development of a humoral immune response to influenza vaccines occurs on a multisystems level. Due to the orchestration required for robust immune responses when multiple genes and their regulatory components across multiple cell types are involved, we examined an influenza vaccination cohort using multiple high-throughput technologies. In this study, we sought a more thorough understanding of how immune cell composition and gene expression relate to each other and contribute to interindividual variation in response to influenza vaccination. We first hypothesized that many of the differentially expressed (DE) genes observed after influenza vaccination result from changes in the composition of participants’ peripheral blood mononuclear cells (PBMCs), which were assessed using flow cytometry. We demonstrated that DE genes in our study are correlated with changes in PBMC composition. We gathered DE genes from 128 other publically available PBMC-based vaccine studies and identified that an average of 57% correlated with specific cell subset levels in our study (permutation used to control false discovery), suggesting that the associations we have identified are likely general features of PBMC-based transcriptomics. Second, we hypothesized that more robust models of vaccine response could be generated by accounting for the interplay between PBMC composition, gene expression, and gene regulation. We employed machine learning to generate predictive models of B-cell ELISPOT response outcomes and hemagglutination inhibition (HAI) antibody titers. The top HAI and B-cell ELISPOT model achieved an area under the receiver operating curve (AUC) of 0.64 and 0.79, respectively, with linear model coefficients of determination of 0.08 and 0.28. For the B-cell ELISPOT outcomes, CpG methylation had the greatest predictive ability, highlighting potentially novel regulatory features important for immune response. B-cell ELISOT models using only PBMC composition had lower performance (AUC = 0.67), but highlighted well-known mechanisms. Our analysis demonstrated that each of the three data sets (cell composition, mRNA-Seq, and DNA methylation) may provide distinct information for the prediction of humoral immune response outcomes. We believe that these findings are important for the interpretation of current omics-based studies and set the stage for a more thorough understanding of interindividual immune responses to influenza vaccination

Technical and biological variance structure in mRNA-Seq data: life in the real world

Abstract Background mRNA expression data from next generation sequencing platforms is obtained in the form of counts per gene or exon. Counts have classically been assumed to follow a Poisson distribution in which the variance is equal to the mean. The Negative Binomial distribution which allows for over-dispersion, i.e., for the variance to be greater than the mean, is commonly used to model count data as well. Results In mRNA-Seq data from 25 subjects, we found technical variation to generally follow a Poisson distribution as has been reported previously and biological variability was over-dispersed relative to the Poisson model. The mean-variance relationship across all genes was quadratic, in keeping with a Negative Binomial (NB) distribution. Over-dispersed Poisson and NB distributional assumptions demonstrated marked improvements in goodness-of-fit (GOF) over the standard Poisson model assumptions, but with evidence of over-fitting in some genes. Modeling of experimental effects improved GOF for high variance genes but increased the over-fitting problem. Conclusions These conclusions will guide development of analytical strategies for accurate modeling of variance structure in these data and sample size determination which in turn will aid in the identification of true biological signals that inform our understanding of biological systems.</p