Fundamental differences in patterns of retinal ageing between primates and mice

Photoreceptors have high metabolic demands and age rapidly, undermining visual function. We base our understanding mainly on ageing mice where elevated inflammation, extracellular deposition, including that of amyloid beta, and rod and cone photoreceptor loss occur, but cones are not lost in ageing primate although their function declines, revealing that primate and mouse age differently. We examine ageing primate retinae and show elevated stress but low inflammation. However, aged primates have a >70% reduction in adenosine triphosphate (ATP) and a decrease in cytochrome c oxidase. There is a shift in cone mitochondrial positioning and glycolytic activity increases. Bruch’s membrane thickens but unlike in mice, amyloid beta is absent. Hence, reduced ATP may explain cone functional decline in ageing but their retained presence offers the possibility of functional restoration if they can be fuelled appropriately to restore cellular function. This is important because as humans we largely depend on cone function to see and are rarely fully dark adapted. Presence of limited aged inflammation and amyloid beta deposition question some of the therapeutic approaches taken to resolve problems of retinal ageing in humans and the possible lack of success in clinical trials in macular degeneration that have targeted inflammatory agents

Investigating the effects of frailty on six-month outcomes in older trauma patients admitted to UK major trauma centres: a multi-centre follow up study.

BACKGROUND: Pre-injury frailty is associated with adverse in-hospital outcomes in older trauma patients, but the association with longer term survival and recovery is unclear. We aimed to investigate post discharge survival and health-related quality of life (HRQoL) in older frail patients at six months after Major Trauma Centre (MTC) admission. METHODS: This was a multi-centre study of patients aged ≥ 65 years admitted to five MTCs. Data were collected via questionnaire at hospital discharge and six months later. The primary outcome was patient-reported HRQoL at follow up using Euroqol EQ5D-5 L visual analogue scale (VAS). Secondary outcomes included health status according to EQ5D dimensions and care requirements at follow up. Multivariable linear regression analysis was conducted to evaluate the association between predictor variables and EQ-5D-5 L VAS at follow up. RESULTS: Fifty-four patients died in the follow up period, of which two-third (64%) had been categorised as frail pre-injury, compared to 21 (16%) of the 133 survivors. There was no difference in self-reported HRQoL between frail and not-frail patients at discharge (Mean EQ-VAS: Frail 55.8 vs. Not-frail 64.1, p = 0.137) however at follow-up HRQoL had improved for the not-frail group but deteriorated for frail patients (Mean EQ-VAS: Frail: 50.0 vs. Not-frail: 65.8, p = 0.009). There was a two-fold increase in poor quality of life at six months (VAS ≤ 50) for frail patients (Frail: 65% vs. Not-frail: 30% p < 0.009). Frailty (β-13.741 [95% CI -25.377, 2.105], p = 0.02), increased age (β -1.064 [95% CI [-1.705, -0.423] p = 0.00) and non-home discharge (β -12.017 [95% CI [118.403, 207.203], p = 0.04) were associated with worse HRQoL at follow up. Requirements for professional carers increased five-fold in frail patients at follow-up (Frail: 25% vs. Not-frail: 4%, p = 0.01). CONCLUSIONS: Frailty is associated with increased mortality post trauma discharge and frail older trauma survivors had worse HRQoL and increased care needs at six months post-discharge. Pre-injury frailty is a predictor of poor longer-term HRQoL after trauma and recognition should enable early specialist pathways and discharge planning

435 THE IMPACT OF COMPREHENSIVE GERIATRIC ASSESSMENT IN THE OUTCOMES OF OLDER ACUTE NEUROSURGICAL PATIENTS

Abstract Introduction As the population ages, an increasing proportion of the neurosurgical caseload is comprised of older patients. This trend is reinforced by technical advances and anaesthetic considerations within the field, allowing a higher proportion of patients eligible for surgery. Comprehensive geriatric assessment (CGA) is the gold standard clinical approach for evaluating older patients. Peri-operative care of older people (POPS) has provided strong evidence that CGA services can result in fewer post-operative complications. However, this evidence stems largely from trauma and orthopaedic surgery. Currently, there is little evidence of the impact CGA has on older neurosurgical patients. The study aimed to investigate whether CGA for older neurosurgical patients improved outcomes such as thirty-day mortality and length of stay. Methods A control group was established by collecting retrospective data for all acute neurosurgical patients over the age of 65. This was then compared with an intervention group who received CGA in the form of regular geriatric consultant reviews. 49 patients were recruited into each group. Results Analysis showed that the interventional group had a significantly higher mean age and level of frailty. They also had more confirmed complications with a significant difference in the diagnosis of pneumonia (p = 0.05) and hyponatremia (p = 0.015). Despite this, the thirty-day mortality was lower and average length of stay was on average two days shorter compared to the control group, although this did not reach statistical significance (p = 0.701). The study showed that more patients who received a CGA were discharged home (p = 0.209). Conclusion Our findings suggest that CGA input for older neurosurgical patients improves outcomes and should be incorporated routinely into neurosurgical clinical pathways. </jats:sec

A retrospective cohort study of risk factors and outcomes in older patients admitted to an inner-city geriatric unit in London during first peak of COVID-19 pandemic.

PURPOSE: Compared to younger patients, coronavirus disease 2019 (COVID-19) clinical presentation in older people can be more heterogeneous and fatal. We aim to describe a cohort of older adults admitted in an inner-city London hospital during the first peak of the pandemic. METHODS: A retrospective observational study that enrolled older adults consecutively admitted into two geriatric wards with suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We collected socio-demographic data, comorbidities, symptoms at presentation and/or during admission, biochemical and radiological data and outcomes at 28 days. RESULTS: One hundred twenty-four patients were included, and 75% were > 80 years old. 19.5% of COVID-19 cases were judged to be hospital-acquired. More than half presented or developed typical symptoms, respiratory failure or fatigue. 46.8% were diagnosed with delirium, 24.2% with falls and dysphagia was present in 13.7%. The mortality rate was 29.8% and was higher among males, those > 80 years, patients with a higher grade of frailty, a history of dementia or chronic kidney disease, as well as those diagnosed with respiratory failure, acute kidney injury or hypernatremia. Independent predictors of mortality were male sex, age > 80 years, respiratory failure and hypernatremia. CONCLUSION: We have described a cohort of patients with SARS-CoV-2 infection in the first UK peak of the global pandemic. We found that these patients had significant frailty with multiple comorbidities. There was a high mortality and increased dependency and greater social care need in survivors

Surgical versus non-surgical management of lateral compression type-1 pelvic fracture in adults 60 years and older: the L1FE RCT.

BACKGROUND: Lateral compression type-1 pelvic fractures are a common fragility fracture in older adults. Patients who do not mobilise due to ongoing pain are at greater risk of immobility-related complications. Standard treatment in the United Kingdom is provision of pain relief and early mobilisation, unlike fragility hip fractures, which are usually treated surgically based on evidence that early surgery is associated with better outcomes. Currently there is no evidence on whether patients with lateral compression type-1 fragility fractures would have a better recovery with surgery than non-surgical management. OBJECTIVES: To assess the clinical and cost effectiveness of surgical fixation with internal fixation device compared to non-surgical management of lateral compression type-1 fragility fractures in older adults. DESIGN: Pragmatic, randomised controlled superiority trial, with 12-month internal pilot; target sample size was 600 participants. Participants were randomised between surgical and non-surgical management (1 : 1 allocation ratio). An economic evaluation was planned. SETTING: UK Major Trauma Centres. PARTICIPANTS: Patients aged 60 years or older with a lateral compression type-1 pelvic fracture, arising from a low-energy fall and unable to mobilise independently to a distance of 3 m and back due to pelvic pain 72 hours after injury. INTERVENTIONS: Internal fixation device surgical fixation and non-surgical management. Participants, surgeons and outcome assessors were not blinded to treatment allocation. MAIN OUTCOME MEASURES: Primary outcome - average patient health-related quality of life, over 6 months, assessed by the EuroQol-5 Dimensions, five-level version utility score. Secondary outcomes (over the 6 months following injury) - self-rated health, physical function, mental health, pain, delirium, displacement of pelvis, mortality, complications and adverse events, and resource use data for the economic evaluation. RESULTS: The trial closed early, at the end of the internal pilot, due to low recruitment. The internal pilot was undertaken in two separate phases because of a pause in recruitment due to the coronavirus disease 2019 pandemic. The planned statistical and health economic analyses were not conducted. Outcome data were summarised descriptively. Eleven sites opened for recruitment for a combined total of 92 months. Three-hundred and sixteen patients were assessed for eligibility, of whom 43 were eligible (13.6%). The main reason for ineligibility was that the patient was able to mobilise independently to 3 m and back (n = 161). Of the 43 eligible participants, 36 (83.7%) were approached for consent, of whom 11 (30.6%) provided consent. The most common reason for eligible patients not consenting to take part was that they were unwilling to be randomised to a treatment (n = 10). There were 11 participants, 5 randomised to surgical management with internal fixation device and 6 to non-surgical management. The average age of participants was 83.0 years (interquartile range 76.0, 89.0) and the EuroQol-5 Dimensions, five-level version utility score at 6 months post randomisation (n = 8) was 0.32 (standard deviation 0.37). A limitation of the trial was that study objectives were not addressed due to poor recruitment. CONCLUSIONS: It was not feasible to recruit to this trial in the current context. Further research to understand the treatment and recovery pathways of this group of patients, along with their outcomes, would be needed prior to undertaking a future trial. FUTURE WORK: Exploration of equipoise across different healthcare professional groups. Investigate longer-term patient outcomes. TRIAL REGISTRATION: This trial is registered as ISRCTN16478561. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/167/57) and is published in full in Health Technology Assessment; Vol. 28, No. 15. See the NIHR Funding and Awards website for further award information