Christopher K. T. Farmer

National Institute for Health and Care Excellence (NICE) and National Clinical Guideline for Stroke 2023 (NCGFS23) guidelines recommend specialist TIA clinic assessment within 24 hours of symptom onset of suspected TIA. There is limited evaluation of TIA clinic services in the United Kingdom (UK) and Republic of Ireland (ROI). This study aims to assess attendee characteristics, NICE/NCGFS23 adherence, and clinical outcomes across the UK and ROI.DelAys in TIA Evaluation and Service (DATES) is a prospective national audit and service evaluation delivered through an established collaborative (The Neurology and Neurosurgery Interest Group (NANSIG)). All UK and ROI outpatient rapid-access TIA clinics are eligible. All index suspected TIA presentations will be included, irrespective of final diagnosis. Centres will register as an audit/service evaluation without altering routine practice. Data will be collected electronically, with blinded independent validation. The primary outcome is adherence to the NICE/NCGFS23 recommended 24-hour target. Secondary outcomes include presenting symptoms, diagnosis, investigations, treatment, and onward referral.DATES is anticipated to be the largest prospective study presenting in-depth evaluation of UK/ROI TIA clinic attendances. Our results will provide real-world data on TIA pathways and potentially improve existing services.

Continuous glucose monitoring (CGM) has transformed diabetes management, offering real-time and dynamic insights into glucose variability and addressing the limitations of traditional glucose assessment methods. Kidney transplantation, the most common solid organ transplant, carries a considerable burden of post-transplant diabetes mellitus (PTDM), which is linked to increased cardiovascular events, graft dysfunction, and increased mortality. This review explores the role of CGM in kidney transplant recipients, particularly its impact on glycemic profiles and its predictive value for post-transplant diabetes mellitus (PTDM). At the time of this review, CGM had not yet been incorporated into standard transplant care protocols. Evidence shows that perioperative CGM outperforms traditional tests in identifying frequent hyperglycemia and glycemic variability in the first weeks after transplantation, enabling enhanced glycemic control and improving the recipient’s clinical outcome. Studies demonstrate higher glucose variability in kidney only recipients compared to other organ recipients, and in type 2 diabetes patients compared to those with PTDM. Poor perioperative glycemic control and glycemic variability detected by CGM have been linked to acute rejection and reduced graft survival. CGM-derived metrics outperform conventional glucose measures in predicting PTDM. CGM metric thresholds within the first month post-transplant achieved sensitivities above 85% and specificities up to 83% for PTDM risk. CGM-guided adjustment of immunosuppressants and steroid dosing have been shown to reduce hyperglycemia and variability. Comparative studies indicate that glycosylated hemoglobin A1c correlates poorly with CGM in the early post-transplant period, often misclassifying patients as normoglycemic. CGM appears to offer clinically relevant insights for the early detection, prediction, and management of dysglycemia in kidney transplant recipients.

Objectives The aim of this study was to determine the feasibility of delivering personalised isometric exercise (IE) for people with stage 1 hypertension. Is it feasible to deliver an isometric wall squat intervention in the National Health Service and what sample size is required to conduct an appropriately powered effectiveness randomised controlled trial (RCT)? Design Randomised controlled open-label multicentre feasibility study of IE compared with standard care in unmedicated people with stage 1 hypertension. Setting Initially, the study aimed to recruit through primary care, but this process coincided with the advent of the COVID-19 pandemic. Therefore, we shifted focus to direct-to-public advertising and delivery in secondary care. Participants People with unmedicated stage 1 hypertension aged over 18 able to perform IE were included. Patients were excluded if average home systolic blood pressure (sBP) Primary and secondary outcome measures We assessed deliverability, attrition, adherence and variance in blood pressure (BP) change. Results IE was found to be easily deliverable to all participants. At 6 months, 34% had withdrawn. Of those who completed IE, 85% of their sessions were at the correct intensity, meeting our retention criterion for success. Variance in BP change was 14.4 mm Hg. The study was not powered to show a difference in BP between groups; however, BP reductions were seen in the intervention group at all study time points compared with baseline. There were no adverse events related to study participation. Conclusions We met our a priori recruitment criteria which allowed us to calculate a sample size (n=542) for a full RCT. The results demonstrate good acceptability and adherence rates to the treatment protocol. Our results show a signal towards a consistent sBP reduction in the IE group compared with baseline. Trial registration number NCT04936022 (https://classic.clinicaltrials.gov/ct2/show/NCT04936022?cond=isometric+exercise&draw=2&rank=7); registry identifier: ISRCTN 13472393.

Objectives: We aimed to explore sex-specific differences in resting blood pressure (BP) reduction and associated cardiovascular adaptations following isometric exercise training (IET). Methods: 100 sedentary adults with normal to high-normal systolic BP volunteered for the study. Participants either performed home-based lower-body IET in the form of a wall squat three times a week for 4 weeks (each session comprised 4×2 min bouts) or were allocated to the control group. Cardiovascular variables, including BP, cardiac output, total peripheral resistance, stroke volume and heart rate variability (HRV), were measured at rest preintervention and postintervention. Results: Following 4 weeks of IET, there were no significant differences in resting systolic BP and diastolic BP between females (122.1±6.9 and 80.0±8.3 mm Hg) and males (119.6±7.2 and 77.4±8.6 mm Hg). However, female participants had a greater cardiac autonomic response following training, evidenced by a lower low-frequency to high-frequency HRV ratio (F: 1.38±1.27 and M: 2.1±1.5, p=0.004) and decreased and elevated low-frequency normalised units (F: 50.3%±16.2% and M: 60.9%±16.9%, p=0.015) and high-frequency normalised units (F: 49.7%±16.2% and M: 39.1%±16.9%, p=0.015), respectively. Conclusions: While resting BP reductions were comparable between female and male participants, there was a greater autonomic response and a higher incidence of clinically important BP reductions in females, which could indicate a greater cardioprotective effect following IET. These findings highlight the importance of considering sex differences in the prescription and evaluation of exercise interventions for hypertension management.

Pharmacological interventions targeting the biological processes of ageing hold significant potential to extend healthspan and promote longevity. This, to our knowledge, is the first study that uses Machine Learning models trained specifically on mouse lifespan data (from DrugAge) to predict lifespan-extending compounds. The use of mammalian data significantly elevates translational relevance compared to previously available models trained predominately on C. elegans data. Our most successful Random Forest classifiers were trained on direct drug-target annotations, including Gene Ontology, UniProt Keywords, pathways (KEGG, Reactome, Wiki) and protein domains (InterPro), whereas models trained on gene expression (LINCS) and chemical substructures (PubChem) underperformed. Models trained on male datasets performed better than those trained on mixed-sex and female datasets, with the latter suffering from severe class imbalance due to much fewer positive-class instances. Notably, features related to G-protein coupled receptors, especially receptors for neurotransmitters, metabolic hormones and sex hormones, were identified as strong predictors of lifespan extension. We used ensemble classifiers comprised of top models to screen compounds from DrugBank, highlighting novel candidates for longevity studies. Major clusters of compounds with the highest predicted longevity-promoting effects target IGF1 and insulin receptors, beta adrenergic receptors, carbonic anhydrases, dopamine and serotonin receptors, voltage-gated potassium and calcium channels, sodium-dependent dopamine, serotonin and noradrenalin transporters, muscarinic acetylcholine receptors and adenosine receptors. We tested 22 predicted compounds in C. elegans and found that 6 of them significantly extended median lifespan: dihydroergotamine, mianserin, bromocriptine, voxtalisib, bms-754807 and solifenacine. We have also created a public web server with our top performing classifier ensembles: https://www.cs.kent.ac.uk/projects/lodprime/ Our study not only provides an important contribution to the longevity pharmacology field but also informs research on the fundamental mechanisms of ageing.

BACKGROUND Hypertension affects 1 in 4 adults and increases the risk of CV disease. Management aims to reduce blood pressure to a level that minimises risk; however, up to 50% of people fail to achieve blood pressure targets often due to insufficient treatment or poor adherence. Exercise has a role to play in the management of hypertension. The impact of isometric exercise on hypertension in healthcare settings is poorly understood. METHODS Randomized controlled open label multicentre feasibility study of isometric exercise compared to standard care in unmedicated hypertensives. Participants received an individualized isometric wall squat prescription and performed 4 x 2-minute bouts thrice weekly for 6-months. We assessed recruitment, deliverability, attrition, adherence, and variance in blood pressure change. RESULTS 41 participants (56 ⁺/- 15 years), 59% women, were randomized. Isometric exercise was found to be easily deliverable to all participants. At 6-months 34% withdrew, of those who completed isometric exercise 87% of their sessions were at the correct intensity. Variance in blood pressure change was 14.4 mmHg. The study was not powered to show a difference in blood pressure between groups, however blood pressure reductions were seen in the intervention group at all study time points compared to baseline. CONCLUSIONS The results have allowed us to calculate a sample size (n=542) for a full randomised controlled trial. The results demonstrate good acceptability and adherence rates to the treatment protocol. Our results show a signal towards a consistent systolic blood pressure reduction in the isometric exercise group compared to baseline. REGISTRATION Trial number: NCT04936022 https://classic.clinicaltrials.gov/ct2/show/NCT04936022?cond=isometric+exercise&draw=2&rank=7 Registry Identifier ISRCTN 13472393

Digital technology and artificial intelligence (AI) use in health care is increasing, and it potentially offers significant patient benefit, such as independence, improved care and health care at home. Workforce benefits are apparent, for example, releasing time to see patients. However, are ethical and moral dilemmas of such technologies sufficiently unpacked by patients and understood by clinicians? A person living with dementia, and carers of people with dementia, alongside academics and clinicians, designed a public engagement World Café event for 20 people living with dementia and their carers. This process is described, as are reflections on a World Café approach to generate knowledge on a lesser explored topic. Working with a graphic recorder at the event proved a dynamic and engaging way of visually displaying feedback, served as an aide memoire and generated further discussion. Three feedback themes are highlighted: (1) trust; (2) continuity of care; and (3) support and independence. The event’s subsequent evaluation and impact, including a presentation to the House of Lords All-Party Parliamentary Group on Artificial Intelligence, are described. In conclusion, a suitable World Café approach enables people with dementia and their carers to voice exceptionally useful insights into a topic that already affects, or is very likely to, affect them.

Until the law in the United Kingdom (UK) changed in May 2016 so called “legal highs” or “new psychoactive substances” were freely available in high street shops across the UK. Following prohibition these drugs are still easily purchased illegally via the internet. We report a case of a patient who self-administered 3-fluorophenmetrazine intravenously with catastrophic consequences. Adverse effects were almost immediate with symptoms of malaise and tachycardia. Two days post administration he was transferred to the intensive therapy unit with acute kidney injury and irreversible four limb ischaemia. He required a period of renal replacement therapy and bilateral lower limb amputation. This case highlights the fact that new psychoactive substances have many unintended adverse effect which have not been previously described. Multiple routes of administration are used by people taking these agents including intravenously. Medical practitioners should always consider ingestion of new psychoactive substances in the differential diagnosis of acutely ill patients.

Acute kidney injury (AKI) is characterised by a rapid deterioration in kidney function, and can be identified by examining the rate of change in a patient's estimated glomerular filtration rate (eGFR) signal. Due to the potentially irreversible nature of the damage AKI episodes cause to renal function, their detection plays a significant role in predicting a kidney's effectiveness. Although algorithms for the detection of AKI are available for patients under constant monitoring, e.g. inpatients, their applicability to primary care settings is less clear as the eGFR signal often contains large lapses in time between measurements. However, waiting for hospital admittance before AKI is undesirable, as detecting AKI early can help to mitigate the degradation of kidney function and the associated increase in morbidity and mortality. Traditionally, a clinician in a primary care setting would manually identify AKI episodes from direct observation of eGFR signals. While this approach may work for individual patients, the time consuming nature of it precludes quick large-scale monitoring. We therefore present two alternative automated approaches for detecting AKI: as the outlier points when using Gaussian process regression and using a novel technique we entitle Surrey AKI detection algorithm (SAKIDA). Using SAKIDA, we can identify the number of AKI episodes a patient experiences with an accuracy of 70%, when evaluated against the performance of human experts.