The profile and follow-up of patients who attend the Emergency Department following a fall.

UNLABELLED: Falls in the older population are associated with increased morbidity and mortality especially in the absence of risk reduction measures. The study aims were to compare the characteristics of older people who present to the Emergency Department (ED) following a fall with the general older ED population and examine referral patterns following ED discharge. Face-to-face interviews were carried out with 306 people aged 65 years or older. Data was collected on demographic, socio-economic, health and social support factors. Descriptive and inferential statistics (Pearson chi-square test or independent t-test) were used to compare the falls and non-falls group. Falls occurred in 17% (53/306) of the study population and 43% sustained an injury requiring medical intervention. Patients in the falls group were significantly more likely to be female (68%), older (79 years (SD 6.6)) and living alone (59%). The physical and mental health profile of the falls and non-falls group was similar with 30-40% of people in both groups experiencing moderate to severe physical health impairment. A third of the falls group was discharged from the ED without evidence of referrals. CONCLUSION: The older population that present to the ED following a fall requires comprehensive risk factor assessment especially physical function and referrals that include falls prevention. Implications for staff: ED staff need to examine current practice within their ED in relation to falls assessment, management and referral pathways.

How different are older people discharged from emergency departments compared with those admitted to hospital?

OBJECTIVE: To compare the characteristics of older people presenting to the emergency department (ED) and admitted to hospital with those discharged directly from the ED and identify factors independently associated with hospital admission. DESIGN: This is a cross-sectional survey of 306 community dwelling people aged 65 years or older presenting to two hospital EDs. A structured questionnaire and ED records were used to collect patient demographics, socioeconomic, physical, cognitive and social network information. STATISTICS: The profile of admitted and discharged patients was compared using the χ statistic. Logistic regression was used to identify factors independently associated with hospital admission. Odds ratios (OR) and 95% confidence intervals (CI) are presented. RESULTS: The analysis involved 306 patients, 158 admitted and 148 discharged home. There was no significant difference in demographic, socioeconomic, cognitive and social networks between the groups. Factors independently associated with hospital admission in the multivariate model were as follows: prior hospital admission OR 6.16 (95% CI 2.61, 14.50), Manchester Triage category 1-2 OR 5.01 (95% CI 1.19, 21.10), low-energy levels OR 3.97 (95% CI 1.32, 11.9) and presenting with cardiac OR 3.59 (95% CI 1.05, 12.3), neurological OR 4.47 (95% CI 1.21, 16.5) or respiratory-related conditions OR 11.2 (95% CI 2.41, 51.9). Among the cohort of discharged patients, 20-30% shared similar physical and mental health characteristics to admitted patients. CONCLUSION: In this elderly population, health-related variables were the only independent factors associated with hospital admission. Approximately 30% of patients discharged home from ED had similar risk profiles to admitted patients.

The role of health and non-health-related factors in repeat emergency department visits in an elderly urban population.

INTRODUCTION: Patients aged 65 years or older account for a growing proportion of emergency department (ED) repeat attendances. This study aimed to identify health and non-health factors associated with repeat ED attendance, defined as one or more visits in the previous 6 months in patients aged 65 years or older, and to examine the interaction between social and health factors. METHODS: 306 patients were interviewed. Demographic, socioeconomic, physical, mental health and post-ED referrals were examined. Logistic regression was used to identify factors independently associated with a repeat ED visit, OR and 95% CI are presented. Log likelihood ratio tests were used to test for interactions. RESULTS: ED revisits were reported by 37% of this elderly population. Independent risk factors for a repeat ED visit were previous hospital admission OR 3.78 (95% CI 2.53 to 5.65), anxiety OR 1.13 (95% CI 1.04 to 1.22), being part of a vulnerable social network OR 2.32 (95% CI 1.12 to 4.81), whereas a unit increase in physical inability as measured by the Nottingham Health Profile had a week association OR 1.01 (95% CI 1.00 to 1.02). There were no significant interactions between social networks and the other health-related variables (p>0.05). In patients directly discharged from ED, 48% (71/148) had no documented referrals made to community services, of which 18% (27/148) were repeat ED attendees. CONCLUSION: ED act as an important safety net for older people regardless of economic or demographic backgrounds. Appropriate assessment and referral are an essential part of this safety role.

Novel mitochondrial substrates of omi indicate a new regulatory role in neurodegenerative disorders.

The mitochondrial protease OMI (also known as HtrA2) has been implicated in Parkinson's Disease (PD) and deletion or protease domain point mutations have shown profound neuropathologies in mice. A beneficial role by OMI, in preserving cell viability, is assumed to occur via the avoidance of dysfunctional protein turnover. However relatively few substrates for mitochondrial Omi are known. Here we report our identification of three novel mitochondrial substrates that impact metabolism and ATP production. Using a dual proteomic approach we have identified three interactors based upon ability to bind to OMI, and/or to persist in the proteome after OMI activity has been selectively inhibited. One candidate, the chaperone HSPA8, was common to each independent study. Two others (PDHB subunit and IDH3A subunit) did not appear to bind to OMI, however persisted in the mito-proteome when OMI was inhibited. Pyruvate dehydrogenase (PDH) and isocitrate dehydrogenase (IDH) are two key Kreb's cycle enzymes that catalyse oxidative decarboxylation control points in mitochondrial respiration. We verified both PDHB and IDH3A co-immunoprecipitate with HSPA8 and after elution, were degraded by recombinant HtrA2 in vitro. Additionally our gene expression studies, using rotenone (an inhibitor of Complex I) showed Omi expression was silenced when pdhb and idh3a were increased when a sub-lethal dose was applied. However higher dose treatment caused increased Omi expression and decreased levels of pdhb and idh3a transcripts. This implicates mitochondrial OMI in a novel mechanism relating to metabolism.

Mitochondrial oxidative stress causes hyperphosphorylation of tau.

Age-related neurodegenerative disease has been mechanistically linked with mitochondrial dysfunction via damage from reactive oxygen species produced within the cell. We determined whether increased mitochondrial oxidative stress could modulate or regulate two of the key neurochemical hallmarks of Alzheimer's disease (AD): tau phosphorylation, and beta-amyloid deposition. Mice lacking superoxide dismutase 2 (SOD2) die within the first week of life, and develop a complex heterogeneous phenotype arising from mitochondrial dysfunction and oxidative stress. Treatment of these mice with catalytic antioxidants increases their lifespan and rescues the peripheral phenotypes, while uncovering central nervous system pathology. We examined sod2 null mice differentially treated with high and low doses of a catalytic antioxidant and observed striking elevations in the levels of tau phosphorylation (at Ser-396 and other phospho-epitopes of tau) in the low-dose antioxidant treated mice at AD-associated residues. This hyperphosphorylation of tau was prevented with an increased dose of the antioxidant, previously reported to be sufficient to prevent neuropathology. We then genetically combined a well-characterized mouse model of AD (Tg2576) with heterozygous sod2 knockout mice to study the interactions between mitochondrial oxidative stress and cerebral Ass load. We found that mitochondrial SOD2 deficiency exacerbates amyloid burden and significantly reduces metal levels in the brain, while increasing levels of Ser-396 phosphorylated tau. These findings mechanistically link mitochondrial oxidative stress with the pathological features of AD.

Effects of progesterone on neurologic and morphologic outcome following diffuse traumatic brain injury in rats.

Previous studies have identified that progesterone may be neuroprotective following traumatic brain injury (TBI). However, most of these have utilized models of TBI that produce a focal lesion or a significant ischemic component, neither of which is necessarily present in diffuse TBI. The current study uses a model of diffuse TBI in rats to examine the effects of progesterone on morphological changes and functional outcome following TBI. Male and ovariectomized female rats were subject to severe impact-acceleration injury under halothane anesthesia. After injury, animals were given a physiological, subcutaneous dose of progesterone (1.67 mg/kg) or equal volume of vehicle (sesame oil) daily throughout a 9-day neurologic assessment period where functional outcome was assessed using the rotarod and Barnes maze tests. There was a similar post-injury performance of male and ovariectomized female animals. Post-injury administration of progesterone improved the motor and cognitive performance of ovariectomized and male animals compared to vehicle-treated controls. Morphological differences between these animals, such as dark cell change, caspase-3 and APP immunoreactivity, were also investigated. Progesterone-treated males showed comparatively less dead or dying neurons, and marked attenuation of caspase-3 immunoreactivity. Both ovariectomized female and male animals treated with progesterone showed a profound reduction in axonal injury (seen via diminished APP immunoreactivity) when compared to controls. We conclude that physiological concentrations of progesterone administered after diffuse TBI confers beneficial effects on morphologic and functional outcome in both ovariectomized female and male animals.

Superoxide dismutases and their impact upon human health.

Superoxide dismutases (SOD), a group of metal-containing enzymes, have a vital anti-oxidant role in human health, conferred by their scavenging of one of the reactive oxygen species, superoxide anion. Three types of SODs are known in humans, with the most abundant being cytosolic SOD1, identified by its Cu, Zn-containing prosthetic group. The presence of these metals and the coordination to certain amino acids are essential for function. SODs are among the first line of defense in the detoxification of products resulting from oxidative stress. Here, we describe the importance of SOD function, and the need for coordination with other ROS-scavenging enzymes in this pathway of detoxification. The impact of metal-deficient diets (copper or zinc) or incorrect metal ion incorporation (copper chaperone for SOD) onto nascent SOD, are also examined. Finally, human pathologies associated with either SOD dysfunction or decreased activity are discussed with current progress on the development of novel therapies.