Therapeutic options for neurocardiogenic syncope: a meta-analysis of randomised trials with and without blinding.

BACKGROUND: Neurocardiogenic syncope is a common condition with significant associated psychological and physical morbidity. The effectiveness of therapeutic options for neurocardiogenic syncope beyond placebo remains uncertain. METHODS: The primary endpoint was the risk ratio (RR) of spontaneously recurring syncope following any therapeutic intervention. We also examined the effect of blinding on treatment efficacy. We identified all randomised trials which evaluated the effect of any pharmacological, device-based or supportive intervention on patients with a history of syncope. A systematic search was conducted on Medline, Embase, PubMed databases and Cochrane Central Register for Controlled Trials from 1950 to 25 April 2023. Event rates, their RRs and 95% CIs were calculated, and a random-effects meta-analysis was conducted for each intervention. Data analysis was performed in R using RStudio. RESULTS: We identified 47 eligible trials randomising 3518 patients. Blinded trials assessing syncope recurrence were neutral for beta blockers, fludrocortisone and conventional dual-chamber pacing but were favourable for selective serotonin reuptake inhibitors (SSRIs) (RR 0.40, 95% CI 0.26 to 0.63, p<0.001), midodrine (RR 0.70, 95% CI 0.53 to 0.94, p=0.016) and closed-loop stimulation (CLS) pacing (RR 0.15, 95% CI 0.07 to 0.35, p<0.001). Unblinded trials reported significant benefits for all therapy categories other than beta blockers and consistently showed larger benefits than blinded trials. CONCLUSIONS: Under blinded conditions, SSRIs, midodrine and CLS pacing significantly reduced syncope recurrence. Future trials for syncope should be blinded to avoid overestimating treatment effects. PROSPERO REGISTRATION NUMBER: CRD42022330148.

Prospective association of occupational and leisure-time physical activity with orthostatic blood pressure changes in older adults.

Orthostatic hypotension (OH) is common in older people. We examined the influence of self-reported occupational-related physical activity (PA) and leisure-time physical exercise (PE) on orthostatic response in a sample of older people over a 2 year period. Supine and orthostatic systolic blood pressure (sBP), diastolic blood pressure (dBP), and mean blood pressure (mBP) were assessed in response to Active Stand (AS) test in 205 older subjects (> 60 years old) at baseline and 2-year follow-up. OH was found in 24 subjects (11.71%) at baseline and 20 subjects (9.76%) after 2 years, with a significant degree of variability in the occurrence of OH after 2 years. Twenty-two subjects who had OH at baseline were free of it after 2 years, two subjects had persistent OH at baseline and after 2 years. After 2 years, adults with occupational PA showed no significant decrease of blood pressure in response to AS test, while lack of undertaking an occupation-related PA was significantly related with a greater decrease in sBP and mBP in response to AS testing in the 1st min. Occupation-related PA and leisure-time-related PE were related to an increase in the response of BP on AS in change between baseline and after 2 years. High between-subjects variance in OH over 2 years was noted. Occupations that involved continuous physical activity and leisure-time physical exercise in middle age were both protective for BP decline on orthostatic stress test within 2 years.

Using home monitoring technology to study the effects of traumatic brain injury in older multimorbid adults.

Internet of things (IOT) based in-home monitoring systems can passively collect high temporal resolution data in the community, offering valuable insight into the impact of health conditions on patients' day-to-day lives. We used this technology to monitor activity and sleep patterns in older adults recently discharged after traumatic brain injury (TBI). The demographics of TBI are changing, and it is now a leading cause of hospitalisation in older adults. However, research in this population is minimal. We present three cases, showcasing the potential of in-home monitoring systems in understanding and managing early recovery in older adults following TBI.

Using home monitoring technology to study the effects of traumatic brain injury on older multimorbid adults: protocol for a feasibility study.

INTRODUCTION: The prevalence of traumatic brain injury (TBI) among older adults is increasing exponentially. The sequelae can be severe in older adults and interact with age-related conditions such as multimorbidity. Despite this, TBI research in older adults is sparse. Minder, an in-home monitoring system developed by the UK Dementia Research Institute Centre for Care Research and Technology, uses infrared sensors and a bed mat to passively collect sleep and activity data. Similar systems have been used to monitor the health of older adults living with dementia. We will assess the feasibility of using this system to study changes in the health status of older adults in the early period post-TBI. METHODS AND ANALYSIS: The study will recruit 15 inpatients (>60 years) with a moderate-severe TBI, who will have their daily activity and sleep patterns monitored using passive and wearable sensors over 6 months. Participants will report on their health during weekly calls, which will be used to validate sensor data. Physical, functional and cognitive assessments will be conducted across the duration of the study. Activity levels and sleep patterns derived from sensor data will be calculated and visualised using activity maps. Within-participant analysis will be performed to determine if participants are deviating from their own routines. We will apply machine learning approaches to activity and sleep data to assess whether the changes in these data can predict clinical events. Qualitative analysis of interviews conducted with participants, carers and clinical staff will assess acceptability and utility of the system. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the London-Camberwell St Giles Research Ethics Committee (REC) (REC number: 17/LO/2066). Results will be submitted for publication in peer-reviewed journals, presented at conferences and inform the design of a larger trial assessing recovery after TBI.

Autoimmunity in Long Covid and POTS.

Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these are common, multi-system constitutional features such as fatigue, malaise and skin rashes which can signify generalized immune dysregulation. At the same time, multiple autoantibodies are identified in both Covid-related autonomic disorders and non-Covid autonomic disorders, implying a possible underlying autoimmune pathology. The lack of specificity of these findings precludes direct interpretations of cause and association, but their prevalence with its supporting evidence is compelling.

Long COVID: mechanisms, risk factors and recovery.

NEW FINDINGS: What is the topic of this review? The emerging condition of long COVID, its epidemiology, pathophysiological impacts on patients of different backgrounds, physiological mechanisms emerging as explanations of the condition, and treatment strategies being trialled. The review leads from a Physiological Society online conference on this topic. What advances does it highlight? Progress in understanding the pathophysiology and cellular mechanisms underlying Long COVID and potential therapeutic and management strategies. ABSTRACT: Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS-CoV-2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery. This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post-viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post-viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance - namely the military and elite athletes. The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID-related changes in physiology - including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve. We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro-clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations. Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.

Neuroinflammation is independently associated with brain network dysfunction in Alzheimer's disease.

Brain network dysfunction is increasingly recognised in Alzheimer's disease (AD). However, the causes of brain connectivity disruption are still poorly understood. Recently, neuroinflammation has been identified as an important factor in AD pathogenesis. Microglia participate in the construction and maintenance of healthy neuronal networks, but pro-inflammatory microglia can also damage these circuits. We hypothesised that microglial activation is independently associated with brain connectivity disruption in AD. We performed a cross-sectional multimodal imaging study and interrogated the relationship between imaging biomarkers of neuroinflammation, Aß deposition, brain connectivity and cognition. 42 participants (12 Aß-positive MCI, 14 Aß-positive AD and 16 Aß-negative healthy controls) were recruited. Participants had 11C-PBR28 and 18F-flutemetamol PET to quantify Aß deposition and microglial activation, T1-weighted, diffusion tensor and resting-state functional MRI to assess structural network and functional network. 11C-PBR28 uptake, structural network integrity and functional network orgnisation were compared across diagnostic groups and the relationship between neuroinflammation and brain network was tested in 26 Aß-positive patients. Increased 11C-PBR28 uptake, decreased FA, network small-worldness and local efficiency were observed in AD patients. Cortical 11C-PBR28 uptake correlated negatively with structural integrity (standardised ß = -0.375, p = 0.037) and network local efficiency (standardised ß = -0.468, p < 0.001), independent of cortical thickness and Aß deposition, while Aß was not. Network structural integrity, small-worldness and local efficiency, and cortical thickness were positively associated with cognition. Our findings suggest cortical neuroinflammation coincide with structural and functional network disruption independent of Aß and cortical atrophy. These findings link the brain connectivity change and pathological process in Alzheimer's disease, and suggest a pathway from neuroinflammation to systemic brain dysfunction.

Acute Sarcopenia after Elective and Emergency Surgery.

Sarcopenia is an increasingly recognised condition of loss of muscle mass and function. The European Working Group on Sarcopenia in Older People 2 (EWSOP2) updated their definition in 2018, emphasising the importance of low muscle strength in diagnosis. Acute sarcopenia has been arbitrarily defined as sarcopenia lasting less than 6 months. This review highlights the pathophysiology involved in muscle wasting following surgery, focussing on hormonal factors, inflammation, microRNAs, and oxidative stress. Biomarkers such as GDF-15, IGF-1 and various microRNAs may predict post-surgical muscle loss. The impact of existing sarcopenia on various types of surgery and incident muscle wasting following surgery is also described. The gaps in research found include the need for longitudinal studies looking in changes in muscle strength and quantity following surgery. Further work is needed to examine if biomarkers are replicated in other surgery to consolidate existing theories on the pathophysiology of muscle wasting.

New horizons in the ageing autonomic nervous system: orthostatic hypotension and supine hypertension.

Blood pressure regulation is an automatic, moment-by-moment buffering of the blood pressure in response to physiological changes such as orthostasis, exercise and haemorrhage. This finely orchestrated reflex is called the baroreflex. It is a regulated arc of afferent, central and efferent arms. Multiple physiological changes occur with ageing that can disrupt this reflex, making blood pressure regulation less effective. In addition, multiple changes can occur with ageing-related diseases such as neurodegeneration, atherosclerosis, deconditioning and polypharmacy. These changes commonly result in orthostatic hypotension, hypertension or both, and are consistently associated with multiple adverse outcomes. In this article, we discuss the healthy baroreflex, and physiological and pathophysiological reasons for impaired baroreflex function in older people. We discuss why the common clinical manifestations of orthostatic hypotension and concomitant supine hypertension occur, and strategies for balancing these conflicting priorities. Finally, we discuss strategies for treating them, outlining our practice alongside consensus and expert guidance.

Cytokine changes in cerebrospinal fluid following vascular surgery on the thoracic aorta.

There is growing evidence that surgery can drive an inflammatory response in the brain. However, the mechanisms behind this response are incompletely understood. Here, we investigate the hypotheses that 1. Cerebrospinal fluid (CSF) cytokines increase after vascular surgery and 2. That these changes in CSF cytokines are interrelated. Patients undergoing either open or endovascular elective surgery of the thoracic aorta were invited to participate in this study. Cerebrospinal fluid samples were taken before surgery and on the first post-operative day. These were analysed for the presence of ten cytokines by immunoassay to examine for post-operative changes in cytokine levels. After surgery, there were significant increases in six out of the ten measured CSF cytokines (IL-1ß, 2, 6, 8, 10 and 13). This included changes in both putative pro-inflammatory (IL-1ß, 6 and 8) and putative anti-inflammatory (IL-2, 10 and 13) cytokines. The greatest increases occurred in IL-6 and IL-8, which showed a 63-fold and a 31-fold increase respectively. There was strong intercorrelation between CSF cytokines after the operation. Following surgery on the thoracic aorta, there was a marked increase in CSF cytokines, consistent with a potential role in neuroinflammation. The ten measured cytokines showed intercorrelation after the operation, indicating that a balance between multiple pro- and anti-inflammatory cytokines may be present.

Putative Involvement of Cytokine Modulation in the Development of Perioperative Neurocognitive Disorders.

Following surgery, local cytokine-driven inflammation occurs, as part of the normal healing process. Cytokines in the central nervous system such as IL-6 and IL-8 may also be elevated. These cytokine changes likely contribute to neuroinflammation, but the complex mechanisms through which this occurs are incompletely understood. It may be that perioperative changes in pro- and anti-inflammatory cytokines have a role in the development of perioperative neurocognitive disorders (PND), such as post-operative delirium (POD). This review considers the current evidence regarding perioperative cytokine changes in the blood and cerebrospinal fluid (CSF), as well as considering the potential for cytokine-altering therapies to prevent and treat PND.

Consent for orthopaedic trauma surgery during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has brought a series of new challenges to the management of surgical patients. The consent process relies on a foundation of open and non-coerced discussion between clinician and patient, which includes all the potential risks of surgery. This must be updated to incorporate the additional risks of surgery during the pandemic including infection with the SARS-CoV-2 and increased risks of complications with the potential requirement for intensive care support. AIM: The aim of this multi-cycle quality improvement project was to ensure all patients were fully informed of the risks of developing COVID-19 and the possible need for intensive care unit (ICU) support. METHODS: We investigated the quality of the consent process for patients undergoing surgery for trauma at our major trauma centre. Our baseline data collection included a review of all orthopaedic trauma consent forms over a 4-week period in March 2020. We subsequently undertook three further Plan-Do-Study-Act (PDSA) cycles over separate 4-week periods. First, in June 2020, after education measures and presentation of baseline data, second in July 2020 after further education and regular digital reminders were sent to staff, and third in September 2021 after the implementation of an electronic consent form. RESULTS: At baseline, only 2.6% of consent forms mentioned the risk of COVID-19 and none mentioned the risk of requiring ITU support. Through three PDSA cycles this increased to 97% of cases where consent forms displayed the additional risks of COVID-19 and the potential need for ITU admission. CONCLUSION: Our quality improvement project improved the informed consent procedure at our trust. By incorporating these additional risks into the template of an electronic consent form, we hope to achieve sustained improvement in practice.

Cytokine changes in cerebrospinal fluid and plasma after emergency orthopaedic surgery.

Neuroinflammation after surgery and its contribution to peri-operative neurocognitive disorders (PND) is not well understood. Studying the association between central and peripheral cytokines and neuroinflammation is a prelude to the development of treatments for PND. Here, we investigate the hypotheses that there is a greater cytokine response in cerebrospinal fluid (CSF) than plasma after orthopaedic surgery, and that plasma cytokine levels are directly related to CSF cytokine levels, indicating that plasma cytokine levels may have potential as biomarkers of neuroinflammation. Patients admitted with a fractured neck of femur were invited to participate in this study. Participants had a spinal catheter inserted just prior to induction of anaesthesia. Samples of blood and CSF were taken before, immediately after, and on the first day following emergency surgery. The catheter was then removed. Samples were analysed for the presence of ten cytokines by immunoassay. A spinal catheter was successfully inserted in 11 participants during the 18-month study period. Five plasma cytokines (IL-4, IL-6, IL-10, IL-12p70 and IL-13) rose significantly following surgery, whereas all ten CSF cytokines rose significantly (IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IFN-γ and TNF-α) (adjusted-p < 0.05). Central (CSF) cytokine levels were consistently higher than their peripheral (plasma) counterparts after surgery, with some patients having a particularly marked neuroinflammatory response. The greatest increases occurred in IL-8 in CSF and IL-6 in plasma. There were significant, strong positive correlations between several of the measured cytokines in the CSF after surgery, but far fewer in plasma. There was no significant correlation between cytokine levels in the plasma and CSF at each of the three time points. To our knowledge, this is the first study to analyse paired samples of plasma and CSF for cytokine levels before and after emergency orthopaedic surgery. This study demonstrates that following surgery for a fractured neck of femur, there is a far greater rise in cytokines in the CSF compared to plasma. The lack of correlation between peripheral and central cytokines suggests measurement of peripheral cytokines are not necessarily related to which patients may have a large neuroinflammatory response.

BLANKETS: a toasty tool to improve social history documentation for our older patients.

A thorough social history is an important component of all medical clerkings and is particularly crucial when admitting an older patient. Standards exist to guide the social history content but are rarely referenced in practice. This quality improvement project conceived and implemented the novel BLANKETS (Bladder and bowels, Legal arrangements, Activities of daily living, Neurology (cognition), Kit (dentures, hearing or visual aids), EtOH and smoking, Trips, walking aids and exercise tolerance, Setup at home) tool for social history documentation, derived from existing standards, at a specialist medical inpatient hospital setting. Over a 15-week period with two cycles of intervention involving 125 patients in total, there was good staff engagement and overall improvement in social history documentation with 194/403 (48.1%) vs 199/545 (36.5%) criteria met overall and on average 6.3/13 vs 4.7/13 criteria documented for each patient. The social history BLANKETS tool is a memorable acronym to prompt clerking doctors to take a thorough and focused social history which is intrinsic to determining appropriate rehabilitation goals for effective discharge planning and setting appropriate ceiling of care decisions.

Teaching geriatric medicine through gamification: a tool for enhancing postgraduate education in geriatric medicine.

BACKGROUND: Polypharmacy is becoming increasingly common and all doctors must be prepared to manage it competently. AIMS: The aim of this project is to evaluate the feasibility and use of a novel gamification-based teaching intervention on polypharmacy among doctors undergoing advanced geriatric training. Among others, one of the learning goals for the students was to be able to describe the adherence to medication. METHODS: Electronic questionnaire sent to students of the third session "evidence-based medicine in geriatrics" of advanced postgraduate course in geriatrics of the European Academy for Medicine of Ageing. RESULTS: Most students reported issues with forgetting doses and remembering sufficiently to establish a medication routine due to busy schedules as well as social influences around medication taking. Reflecting on the challenges of the game, most students reported that their own prescribing practice was likely to change. DISCUSSION AND CONCLUSION: The current model of learning appears to be a feasible approach for postgraduate medical education or in other areas of healthcare such as nursing or physiotherapy. Learning through action and reflection promotes deeper thinking and can lead to behavioral change, in this case thus enhancing the attitudes and understanding regarding pharmacological issues associated with ageing. Recommendations for future research in medical education about medication adherence are outlined.

Delirium in older inpatients with COVID-19: impact on service provision.

Delirium is a common clinical manifestation of SARS-CoV-2 (COVID-19) in older inpatients. We assessed the prevalence of delirium in inpatients aged over 65 years with confirmed COVID-19 infection to identify its clinical correlations and association with in-hospital mortality and admission duration. Data were extracted retrospectively from electronic health records. The prevalence of delirium was found to be 23.9% (158 out of 662 patients). Factors associated with delirium included older age, dementia (including cases of suspected dementia), frailty and concurrent infection. Delirium was not associated with higher mortality. Admission duration was approximately 1.5 times longer in patients who experienced delirium (median 14 days; interquartile range (IQR) 8-30) compared with those who did not (median 9 days; IQR 5-17; p<0.001). We confirmed that delirium is common in older inpatients with COVID-19 and has significant implications for patient care and planning services and rehabilitation.

A new reality: Bedside geriatric teaching in an age of remote learning.

Population ageing poses many challenges in the landscape of general medicine. One of these is the requirement for more geriatricians to minimise future strain on healthcare systems. Previous studies have identified that, while demand for geriatricians is on the rise, interest among medical students for a career in geriatrics falls behind. We utilised a new augmented reality technology (the Microsoft HoloLens 2) to deliver students a remote bedside teaching experience. Features of this teaching included bi-directional communication, exposure to physical signs, and use of holograms around the patient bedside as a teaching aid. Given its convenience, scope and engagement potential, this educational tool has potential to be used effectively throughout medical training.

Geriatrician-led care model in frail cardiology patients reduces re-admissions.

BACKGROUND: As the population admitted under cardiology is likely to become frailer, a geriatrician-led model of post-procedural care similar to that used in orthopaedic surgery may be beneficial. METHODS: In 2016, a new geriatrician-led ward was created in Hammersmith Hospital where frail cardiology patients could be transferred post-treatment. Using diagnostic coding, patients over the age of 65 years between 01 April and the 31 August for both 2016 and 2019 were identified, and data collected retrospectively from electronic patient records. An anonymised staff survey was completed following the introduction of the new service. RESULTS: Patients discharged from the geriatrician-led ward had fewer re-admissions than both cardiology-led wards in 2019 (chi-squared 5.46; p=0.02), and overall re-admissions in 2016 (chi-squared 4.34; p=0.037). The majority of surveyed respondents felt that this level of geriatrician input was useful. CONCLUSION: Geriatrician-led post-procedural care in cardiology reduced 30-day re-admissions in an elderly cohort.

"Be Careful What You Swallow": A Case Series of Swallow Syncope.

Swallow (deglutition) syncope is a rare form of neurally mediated cardioinhibitory reflex syncope occurring during swallowing. Patients may present to clinicians across multiple disciplines, so high awareness and careful evaluation are essential. We report 3 such individuals, describing our strategies in diagnosis, investigation and treatment, particularly focusing on conservative management. (Level of Difficulty: Intermediate.).