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Abstract Background A randomised clinical trial titled the Carer End of Life Planning Intervention (CELPI) in people dying with dementia evaluated the effect of carer education and support about palliative care on care recipient outcomes. We present a pre-planned qualitative analysis of data collected during the CELPI trial in which needs of carers randomised to the study intervention group were assessed using a novel instrument (Carer Needs Directed Assessment in Dementia (CANDID). This tool aimed to identify carers’ perceptions of their own and their care-recipients’ needs and is an important step in identifying support provision for dementia-specific, palliative cares services upon hospital discharge. Methods The CANDID tool was designed to identify the needs and experiences of primary carers and of their care recipients during the last twelve months of the care recipient’s life. The tool consisted of 33 open-ended questions evaluating: symptom management, emergency contacts, advance care planning, carer’s perception of the care recipient’s future needs, carer’s current needs, and a proposed current and future care plan. The researcher’s philosophical assumption of interpretative phenomenology informed the study and approach to data collection and analysis. Qualitative data collected during interviews using this tool were thematically analysed in five steps: compiling, disassembling, reassembling, interpreting and concluding. An interpretation of participants’ reality emerged from their common experiences and the subjective meanings assigned to actions attached to the phenomena studied. Results Thirty carer participants were included. Analysis identified three major themes: Carers’ perceived stressors, systemic barriers to care provision, and future planning. Issues identified included barriers to accessing supports, carer health and division between roles, financial burden, familial conflicts, adquate care in hospital and aged care facilities, concern about future needs, and end-of-life discussions. Conclusion The CANDID tool enabled an evaluation of carer needs and concerns. Identifying those needs may inform a referral to palliative care services where the level of management required may be benenficial for both the person living with dementia and their primary carer. Trial Registration Australian Clinical Trials Registration: (ACTRN12619001187134).

Abstract Purpose To investigate the effect of IV fluid resuscitation on endothelial glycocalyx (EG) shedding and activation of the vascular endothelium and inflammation. Materials and methods A planned biomarker sub-study of the REFRESH trial in which emergency department (ED) patients) with suspected sepsis and hypotension were randomised to a restricted fluid/early vasopressor regimen or IV fluid resuscitation with later vasopressors if required (usual care). Blood samples were collected at randomisation (T0) and at 3 h (T3), 6 h (T6)- and 24 h (T24) for measurement of a range of biomarkers if EG shedding, endothelial cell activation and inflammation. Results Blood samples were obtained in 95 of 99 enrolled patients (46 usual care, 49 restricted fluid). Differences in the change in biomarker over time between the groups were observed for Hyaluronan (2.2-fold from T3 to T24, p = 0.03), SYN-4 (1.5-fold from T3 to T24, P = 0.01) and IL-6 (2.5-fold from T0 to T3, p = 0.03). No difference over time was observed between groups for the other biomarkers. Conclusions A consistent signal across a range of biomarkers of EG shedding or of endothelial activation or inflammation was not demonstrated. This could be explained by pre-existing EG shedding or overlap between the fluid volumes administered in the two groups in this clinical trial. Trial registration Australia New Zealand Clinical Trials Registry ACTRN126160000006448 Registered 12 January 2016.

Abstract Endothelial glycocalyx (EG) shedding is associated with septic shock and described following intravenous (IV) fluid administration. To investigate the possible impact of IV fluids on the pathobiology of septic shock we investigated associations between biomarkers of EG shedding and endothelial cell activation, and relationships with IV fluid volume. Serum samples were obtained on admission (T0) and at 24 h (T24) in patients undergoing haemodynamic resuscitation for suspected septic shock in the emergency department. Biomarkers of EG shedding—Syndecan-1 (Syn-1), Syndecan-4 (Syn-4), Hyaluronan, endothelial activation—Endothelin-1 (ET-1), Angiopoeitin-2 (Ang-2), Vascular Endothelial Growth Factor Receptor-1(VEGF-1) and leucocyte activation/inflammation—Resistin, Neutrophil Gelatinase Associated Lipocalin (NGAL) and a marker of cardiac stretch—Pro-Atrial Natriuretic Peptide (Pro-ANP) were compared to the total IV fluid volume administered using Tobit regression. Data on 86 patients (52 male) with a mean age of 60 (SD 18) years were included. The mean fluid volume administered to T24 was 4038 ml (SD 2507 ml). No significant association between fluid volume and Pro-ANP or any of the biomarkers were observed. Syn-1 and Syn-4 were significantly correlated with each other (Spearman Rho 0.43, p

IntroductionNatural language processing (NLP) uses various computational methods to analyse and understand human language, and has been applied to data acquired at Emergency Department (ED) triage to predict various outcomes. The objective of this scoping review is to evaluate how NLP has been applied to data acquired at ED triage, assess if NLP based models outperform humans or current risk stratification techniques when predicting outcomes, and assess if incorporating free-text improve predictive performance of models when compared to predictive models that use only structured data.MethodsAll English language peer-reviewed research that applied an NLP technique to free-text obtained at ED triage was eligible for inclusion. We excluded studies focusing solely on disease surveillance, and studies that used information obtained after triage. We searched the electronic databases MEDLINE, Embase, Cochrane Database of Systematic Reviews, Web of Science, and Scopus for medical subject headings and text keywords related to NLP and triage. Databases were last searched on 01/01/2022. Risk of bias in studies was assessed using the Prediction model Risk of Bias Assessment Tool (PROBAST). Due to the high level of heterogeneity between studies and high risk of bias, a metanalysis was not conducted. Instead, a narrative synthesis is provided.ResultsIn total, 3730 studies were screened, and 20 studies were included. The population size varied greatly between studies ranging from 1.8 million patients to 598 triage notes. The most common outcomes assessed were prediction of triage score, prediction of admission, and prediction of critical illness. NLP models achieved high accuracy in predicting need for admission, triage score, critical illness, and mapping free-text chief complaints to structured fields. Incorporating both structured data and free-text data improved results when compared to models that used only structured data. However, the majority of studies (80%) were assessed to have a high risk of bias, and only one study reported the deployment of an NLP model into clinical practice.ConclusionUnstructured free-text triage notes have been used by NLP models to predict clinically relevant outcomes. However, the majority of studies have a high risk of bias, most research is retrospective, and there are few examples of implementation into clinical practice. Future work is needed to prospectively assess if applying NLP to data acquired at ED triage improves ED outcomes when compared to usual clinical practice.

Abstract Objective Mechanisms underlying the anaphylactic reaction in humans are not fully understood. Here, we aimed at improving our understanding of anaphylaxis by investigating gene expression changes. Methods Microarray data set GSE69063 was analysed, describing emergency department (ED) patients with severe anaphylaxis (n = 12), moderate anaphylaxis (n = 6), sepsis (n = 20) and trauma (n = 11). Samples were taken at ED presentation (T0) and 1 h later (T1). Healthy controls were age and sex matched to ED patient groups. Gene expression changes were determined using limma, and pathway analysis applied. Differentially expressed genes were validated in an independent cohort of anaphylaxis patients (n = 31) and matched healthy controls (n = 10), using quantitative reverse transcription‐polymerase chain reaction. Results Platelet aggregation was dysregulated in severe anaphylaxis at T0, but not in moderate anaphylaxis, sepsis or trauma. Dysregulation was not observed in patients who received adrenaline before T0. Seven genes (GATA1 (adjusted P‐value = 5.57 × 10−4), TLN1 (adjusted P‐value = 9.40 × 10−4), GP1BA (adjusted P‐value = 2.15 × 10−2), SELP (adjusted P‐value = 2.29 × 10−2), MPL (adjusted P‐value = 1.20 × 10−2), F13A1 (adjusted P‐value = 1.39 × 10−2) and SPARC (adjusted P‐value = 4.06 × 10−2)) were significantly downregulated in severe anaphylaxis patients who did not receive adrenaline before ED arrival, compared with healthy controls. One gene (TLN1 (adjusted P‐value = 1.29 × 10−2)) was significantly downregulated in moderate anaphylaxis patients who did not receive adrenaline before ED arrival, compared with healthy controls. Conclusion Downregulation of genes involved in platelet aggregation and activation is a unique feature of the early anaphylactic reaction not previously reported and may be associated with reaction severity.

Background: People with intellectual disabilities living in group homes often have complex health needs, are high health service users and need support from their service provider to access health services. In Australia, little is known about the types and amounts of these supports. Methods: A case study was conducted on a large Western Australian disability provider of group homes to 160 people with intellectual disability. Over an 18-month period, including during the COVID-19 pandemic, the study quantified health service use in hospital- and community-based settings, ways by which the person was supported to access health care and the impact on other people supported by the provider. Economic costs of supporting access to health services were estimated. Findings: Overall, the disability provider supported 160 people in accessing health services an average of 23 times each (n = 3617, median = 20, interquartile range = 10-33) over the 18 months. Support included staff attending with the person (96%), following up with guardian/decision-maker (50%), additional resourcing via overtime or staff backfills (6%) and transport (94%). The average cost of supporting one health visit was estimated at $78.51 AUD (2021). Impact on the person's household included loss of opportunity for housemates (30%), reduced supervision within the home (79%) and longer timeframes to complete care needs (32%). The impact of COVID-19 restrictions saw a reduction in allied and mental health service use that did not return to prepandemic levels following the cessation of restrictions. Primary care, specialist, outpatient, pathology and emergency service use was also lower in the postrestriction period compared to the prepandemic period. Conclusions: For people living in group homes, the disability provider plays an essential role in supporting health service access, primarily through the provision of support staff and transport. The change in health service utilisation following the COVID-19 restriction period indicates that altered health system priorities can potentially exacerbate access inequality for people with intellectual disability.

Abstract Background RESPOND is a telephone-based falls prevention program for older people who present to a hospital emergency department (ED) with a fall. A randomised controlled trial (RCT) found RESPOND to be effective at reducing the rate of falls and fractures, compared with usual care, but not fall injuries or hospitalisations. This process evaluation aimed to determine whether RESPOND was implemented as planned, and identify implementation barriers and facilitators. Methods A mixed-methods evaluation was conducted alongside the RCT. Evaluation participants were the RESPOND intervention group (n = 263) and the clinicians delivering RESPOND (n = 7). Evaluation data were collected from participant recruitment and intervention records, hospital administrative records, audio-recordings of intervention sessions, and participant questionnaires. The Rochester Participatory Decision-Making Scale (RPAD) was used to evaluate person-centredness (score range 0 (worst) - 9 (best)). Process factors were compared with pre-specified criteria to determine implementation fidelity. Six focus groups were held with participants (n = 41), and interviews were conducted with RESPOND clinicians (n = 6). Quantitative data were analysed descriptively and qualitative data thematically. Barriers and facilitators to implementation were mapped to the ‘Capability, Opportunity, Motivation – Behaviour’ (COM-B) behaviour change framework. Results RESPOND was implemented at a lower dose than the planned 10 h over 6 months, with a median (IQR) of 2.9 h (2.1, 4). The majority (76%) of participants received their first intervention session within 1 month of hospital discharge with a median (IQR) of 18 (12, 30) days. Clinicians delivered the program in a person-centred manner with a median (IQR) RPAD score of 7 (6.5, 7.5) and 87% of questionnaire respondents were satisfied with the program. The reports from participants and clinicians suggested that implementation was facilitated by the use of positive and personally relevant health messages. Complex health and social issues were the main barriers to implementation. Conclusions RESPOND, which was previously shown to reduce falls and fractures in the main trial analysis, was found to be delivered in a timely and person-centred manner, at a substantially lower dose, using fewer resource than anticipated. Trial registration This study was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614000336684 (27 March 2014).

Introduction Mild traumatic brain injury (mTBI) is a complex injury with heterogeneous physical, cognitive, emotional and functional outcomes. Many who sustain mTBI recover within 2 weeks of injury; however, approximately 10%–20% of individuals experience mTBI symptoms beyond this ‘typical’ recovery timeframe, known as persistent post-concussion symptoms (PPCS). Despite increasing interest in PPCS, uncertainty remains regarding its prevalence in community-based populations and the extent to which poor recovery may be identified using early predictive markers.Objective (1) Establish a research dataset of people who have experienced mTBI and document their recovery trajectories; (2) Evaluate a broad range of novel and established prognostic factors for inclusion in a predictive model for PPCS.Methods and analysis The Concussion Recovery Study (CREST) is a prospective, longitudinal observational cohort study conducted in Perth, Western Australia. CREST is recruiting adults aged 18–65 from medical and community-based settings with acute diagnosis of mTBI. CREST will create a state-wide research dataset of mTBI cases, with data being collected in two phases. Phase I collates data on demographics, medical background, lifestyle habits, nature of injury and acute mTBI symptomatology. In Phase II, participants undergo neuropsychological evaluation, exercise tolerance and vestibular/ocular motor screening, MRI, quantitative electroencephalography and blood-based biomarker assessment. Follow-up is conducted via telephone interview at 1, 3, 6 and 12 months after injury. Primary outcome measures are presence of PPCS and quality of life, as measured by the Post-Concussion Symptom Scale and the Quality of Life after Brain Injury questionnaires, respectively. Multivariate modelling will examine the prognostic value of promising factors.Ethics and dissemination Human Research Ethics Committees of Royal Perth Hospital (#RGS0000003024), Curtin University (HRE2019-0209), Ramsay Health Care (#2009) and St John of God Health Care (#1628) have approved this study protocol. Findings will be published in peer-reviewed journals and presented at scientific conferences.Trial registration number ACTRN12619001226190.

Introduction Delirium is a dangerous syndrome of acute brain dysfunction that is common in the emergency department (ED), especially among the geriatric population. Most systematic reviews of interventions for delirium prevention and treatment have focused on inpatient settings. Best practices of effective delirium care in ED settings have not been established. The primary objective of this study is to identify pharmacologic and non-pharmacologic interventions as applied by physicians, nursing staff, pharmacists and other ED personnel to prevent incident delirium and to shorten the severity and duration of prevalent delirium in a geriatric population within the ED.Methods and analysis Searches using subject headings and keywords will be conducted from database inception through June 2020 in MEDLINE, EMBASE, Web of Science, PsychINFO, CINAHL, ProQuest Dissertations and Theses Global and Cochrane CENTRAL as well as grey literature. Database searches will not be limited by date or language. Two reviewers will identify studies describing any interventions for delirium prevention and/or treatment in the ED. Disagreements will be settled by a third reviewer. Pooled data analysis will be performed where possible using Review Manager. Risk ratios and weighted difference of means will be used for incidence of delirium and other binary outcomes related to delirium, delirium severity or duration of symptoms, along with 95% CIs. Heterogeneity will be measured by calculating I2, and a forest plot will be created. If significant heterogeneity is identified, metaregression is planned using OpenMeta to identify possible sources of heterogeneity.Ethics and dissemination This is a systematic review of previously conducted research; accordingly, it does not constitute human subjects research needing ethics review. This review will be prepared as a manuscript and submitted for publication to a peer-reviewed journal, and the results will be presented at conferences.PROSPERO trial registration number CRD42020169654.

Abstract Background Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified. Methods/design The REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support ‘free days’ to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups. Discussion This is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking a large, international, multicentre trial with sufficient power to assess clinical outcomes. The embedded biomarker study aims to provide mechanistic plausibility for a larger trial by defining the effects of fluid volume on markers of systemic inflammation and the vascular endothelium. Trial registration Australia and New Zealand Clinical Trials Registry, ID: ACTRN12616000006448. Registered on 12 January 2016.

Abstract Background Health literacy is an important concept associated with participation in preventive health initiatives, such as falls prevention programs. A comprehensive health literacy measurement tool, appropriate for this population, is required. The aim of this study was to evaluate the measurement properties of the Health Literacy Questionnaire (HLQ) in a cohort of older adults who presented to a hospital emergency department (ED) after a fall. Methods Older adults who presented to an ED after a fall had their health literacy assessed using the HLQ (n = 433). Data were collected as part of a multi-centre randomised controlled trial of a falls prevention program. Measurement properties of the HLQ were assessed using Rasch analysis. Results All nine scales of the HLQ were unidimensional, with good internal consistency reliability. No item bias was found for most items (43 of 44). A degree of overall misfit to the Rasch model was evident for six of the nine HLQ scales. The majority of misfit indicated content overlap between some items and does not compromise measurement. A measurement gap was identified for this cohort at mid to high HLQ score. Conclusions The HLQ demonstrated good measurement properties in a cohort of older adults who presented to an ED after a fall. The summation of the HLQ items within each scale, providing unbiased information on nine separate areas of health literacy, is supported. Clinicians, researchers and policy makers may have confidence using the HLQ scale scores to gain information about health literacy in older people presenting to the ED after a fall. Trial registration This study was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614000336684 (27 March 2014).

BackgroundFalls are a leading reason for older people presenting to the emergency department (ED), and many experience further falls. Little evidence exists to guide secondary prevention in this population. This randomised controlled trial (RCT) investigated whether a 6-month telephone-based patient-centred program-RESPOND-had an effect on falls and fall injuries in older people presenting to the ED after a fall.Methods and findingsCommunity-dwelling people aged 60-90 years presenting to the ED with a fall and planned for discharge home within 72 hours were recruited from two EDs in Australia. Participants were enrolled if they could walk without hands-on assistance, use a telephone, and were free of cognitive impairment (Mini-Mental State Examination > 23). Recruitment occurred between 1 April 2014 and 29 June 2015. Participants were randomised to receive either RESPOND (intervention) or usual care (control). RESPOND comprised (1) home-based risk assessment; (2) 6 months telephone-based education, coaching, goal setting, and support for evidence-based risk factor management; and (3) linkages to existing services. Primary outcomes were falls and fall injuries in the 12-month follow-up. Secondary outcomes included ED presentations, hospital admissions, fractures, death, falls risk, falls efficacy, and quality of life. Assessors blind to group allocation collected outcome data via postal calendars, telephone follow-up, and hospital records. There were 430 people in the primary outcome analysis-217 randomised to RESPOND and 213 to control. The mean age of participants was 73 years; 55% were female. Falls per person-year were 1.15 in the RESPOND group and 1.83 in the control (incidence rate ratio [IRR] 0.65 [95% CI 0.43-0.99]; P = 0.042). There was no significant difference in fall injuries (IRR 0.81 [0.51-1.29]; P = 0.374). The rate of fractures was significantly lower in the RESPOND group compared with the control (0.05 versus 0.12; IRR 0.37 [95% CI 0.15-0.91]; P = 0.03), but there were no significant differences in other secondary outcomes between groups: ED presentations, hospitalisations or falls risk, falls efficacy, and quality of life. There were two deaths in the RESPOND group and one in the control group. No adverse events or unintended harm were reported. Limitations of this study were the high number of dropouts (n = 93); possible underreporting of falls, fall injuries, and hospitalisations across both groups; and the relatively small number of fracture events.ConclusionsIn this study, providing a telephone-based, patient-centred falls prevention program reduced falls but not fall injuries, in older people presenting to the ED with a fall. Among secondary outcomes, only fractures reduced. Adopting patient-centred strategies into routine clinical practice for falls prevention could offer an opportunity to improve outcomes and reduce falls in patients attending the ED.Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12614000336684).

Background: Persisting post-concussion symptoms (PPCS) is a complex, multifaceted condition in which individuals continue to experience the symptoms of mild traumatic brain injury (mTBI; concussion) beyond the timeframe that it typically takes to recover. Currently, there is no way of knowing which individuals may develop this condition. Method: Patients presenting to a hospital emergency department (ED) within 48 h of sustaining a mTBI underwent neuropsychological assessment and demographic, injury-related information and blood samples were collected. Concentrations of blood-based biomarkers neuron specific enolase, neurofilament protein-light, and glial fibrillary acidic protein were assessed, and a subset of patients also underwent diffusion tensor−magnetic resonance imaging; both relative to healthy controls. Individuals were classified as having PPCS if they reported a score of 25 or higher on the Rivermead Postconcussion Symptoms Questionnaire at ~28 days post-injury. Univariate exact logistic regression was performed to identify measures that may be predictive of PPCS. Neuroimaging data were examined for differences in fractional anisotropy (FA) and mean diffusivity in regions of interest. Results: Of n = 36 individuals, three (8.33%) were classified as having PPCS. Increased performance on the Repeatable Battery for the Assessment of Neuropsychological Status Update Total Score (OR = 0.81, 95% CI: 0.61−0.95, p = 0.004), Immediate Memory (OR = 0.79, 95% CI: 0.56−0.94, p = 0.001), and Attention (OR = 0.86, 95% CI: 0.71−0.97, p = 0.007) indices, as well as faster completion of the Trails Making Test B (OR = 1.06, 95% CI: 1.00−1.12, p = 0.032) at ED presentation were associated with a statistically significant decreased odds of an individual being classified as having PPCS. There was no significant association between blood-based biomarkers and PPCS in this small sample, although glial fibrillary acidic protein (GFAP) was significantly increased in individuals with mTBI relative to healthy controls. Furthermore, relative to healthy age and sex-matched controls (n = 8), individuals with mTBI (n = 14) had higher levels of FA within the left inferior frontal occipital fasciculus (t (18.06) = −3.01, p = 0.008). Conclusion: Performance on neuropsychological measures may be useful for predicting PPCS, but further investigation is required to elucidate the utility of this and other potential predictors.

ObjectivePeople with schizophrenia face an increased risk of premature death from chronic diseases and injury. This study describes the trajectory of acute care health service use in the last year of life for people with schizophrenia and how this varied with receipt of community-based specialist palliative care and morbidity burden.MethodA population-based retrospective matched cohort study of people who died from 01/01/2009 to 31/12/2013 with and without schizophrenia in Western Australia. Hospital inpatient, emergency department, death and community-based care data collections were linked at the person level. Rates of emergency department presentations and hospital admissions over the last year of life were estimated.ResultsOf the 63508 decedents, 1196 (1.9%) had a lifetime history of schizophrenia. After adjusting for confounders and averaging over the last year of life there was no difference in the overall rate of ED presentation between decedents with schizophrenia and the matched cohort (HR 1.09; 95%CI 0.99-1.19). However, amongst the subset of decedents with cancer, choking or intentional self-harm recorded on their death certificate, those with schizophrenia presented to ED more often. Males with schizophrenia had the highest rates of emergency department use in the last year of life. Rates of hospital admission for decedents with schizophrenia were on average half (HR 0.53, 95%CI 0.44-0.65) that of the matched cohort although this varied by cause of death. Of all decedents with cancer, 27.5% of people with schizophrenia accessed community-based specialist palliative care compared to 40.4% of the matched cohort (pConclusionIn the last year of life, people with schizophrenia were less likely to be admitted to hospital and access community-based speciality palliative care, but more likely to attend emergency departments if male. Community-based specialist palliative care was associated with increased rates of hospital admissions.

Community-based palliative care is known to be associated with reduced acute care health service use. Our objective was to investigate how reduced acute care hospital use in the last year of life varied temporally and by patient factors.A retrospective cohort study of the last year of life of 12,763 Western Australians who died from cancer or one of seven non-cancer conditions. Outcome measures were rates of hospital admissions and mean length of hospital stays. Multivariate analyses involved time-to-event and population averaged log-link gamma models.There were 28,939 acute care overnight hospital admissions recorded in the last year of life, an average of 2.3 (SD 2.2) per decedent and a mean length of stay of 9.2 (SD 10.3) days. Overall, the rate of hospital admissions was reduced 34% (95%CI 1-66) and the mean length of stay reduced 6% (95%CI 2-10) during periods of time decedents received community-based palliative care compared to periods of time not receiving this care. Decedents aged

BACKGROUND:Accurately assessing changes in the quality of life of older people living permanently in nursing homes is important. The multi-attribute utility instrument most commonly used and recommended to assess health-related quality of life in the nursing home population is the three-level EuroQol EQ-5D-3L. To date, there have been no studies using the Health Utilities Index Mark III (HUI3). The purpose of this study was to compare the level of agreement and sensitivity to change of the EQ-5D-3L and HUI3 in a nursing home population. METHODS:EQ-5D-3L and HUI3 scores were measured as part of a cluster randomised controlled trial of nurse led care coordination in a nursing home population in Perth, Western Australia at baseline and 6-month follow up. RESULTS:Both measures were completed for 199 residents at baseline and 177 at 6-month follow-up. Mean baseline utility scores for EQ-5D-3L (0.45; 95% CI 0.41-0.49) and HUI3 (0.15; 95% CI 0.10-0.20) were significantly different (Wilcoxon signed rank test, p

To identify biomarkers which distinguish severe sepsis/septic shock from uncomplicated sepsis in the Emergency Department (ED).Patients with sepsis underwent serial blood sampling, including arrival in the ED and up to three subsequent time points over the first 24 hours. Messenger RNA (mRNA) levels of 13 genes representing arms of the innate immune response, organ dysfunction or shock were measured in peripheral blood leucocytes using quantitative PCR, and compared with healthy controls. Serum protein concentrations of targets differentially expressed between uncomplicated sepsis and severe sepsis/septic shock were then measured at each time point and compared between the two patient groups.Of 27 participants (median age 66 years, (IQR 35, 78)), 10 had uncomplicated sepsis and 17 had sepsis with organ failure (14 septic shock; 3 had other sepsis-related organ failures). At the time of first sample collection in the ED, gene expression of Interleukin (IL)-10 and Neutrophil Gelatinase Associated Lipocalin (NGAL) were significantly higher in severe sepsis than uncomplicated sepsis. Expression did not significantly change over time for any target gene. Serum concentrations of IL-6, IL-8, IL-10, NGAL and Resistin were significantly higher in severe sepsis than uncomplicated sepsis at the time of first sample collection in the ED, but only IL-8, NGAL and Resistin were consistently higher in severe sepsis compared to uncomplicated sepsis at all time points up to 24 h after presentation.These mediators, produced by both damaged tissues and circulating leukocytes, may have important roles in the development of severe sepsis. Further work will determine whether they have any value, in addition to clinical risk parameters, for the early identification of patients that will subsequently deteriorate and/or have a higher risk of death.

BACKGROUND: Systemic spread of immune activation and mediator release is required for the development of anaphylaxis in humans. We hypothesized that peripheral blood leukocyte (PBL) activation plays a key role. OBJECTIVE: To characterize PBL genomic responses during acute anaphylaxis. METHODS: PBL samples were collected at three timepoints from six patients presenting to the Emergency Department (ED) with acute anaphylaxis and six healthy controls. Gene expression patterns were profiled on microarrays, differentially expressed genes were identified, and network analysis was employed to explore underlying mechanisms. RESULTS: Patients presented with moderately severe anaphylaxis after oral aspirin (2), peanut (2), bee sting (1) and unknown cause (1). Two genes were differentially expressed in patients compared to controls at ED arrival, 67 genes at 1 hour post-arrival and 2,801 genes at 3 hours post-arrival. Network analysis demonstrated that three inflammatory modules were upregulated during anaphylaxis. Notably, these modules contained multiple hub genes, which are known to play a central role in the regulation of innate inflammatory responses. Bioinformatics analyses showed that the data were enriched for LPS-like and TNF activation signatures. CONCLUSION: PBL genomic responses during human anaphylaxis are characterized by dynamic expression of innate inflammatory modules. Upregulation of these modules was observed in patients with different reaction triggers. Our findings indicate a role for innate immune pathways in the pathogenesis of human anaphylaxis, and the hub genes identified in this study represent logical candidates for follow-up studies.