National Health Service Wales

Treatment-resistant depression (TRD) is a common phenomenon and a considerable clinical challenge; recently, esketamine in conjunction with an oral antidepressant (AD) has emerged as a potential treatment for TRD. Several studies have shown the efficacy of esketamine in improving depressive symptoms. This prospective study aims to explore the long-term effects of esketamine therapy on subjective quality of life (QoL) and general status of adults with TRD. The study was an observational, prospective and multicenter study comprising a total of 18 TRD patients treated with Esketamine-Nasal Spray ESK-NS. Anamnestic data and psychometric assessments were collected at baseline (T0) and at follow-ups at 1 month (T1), 3 months (T2), and 6 months (T3). Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF), Sheehan Disability Scale (SDS), and Personal and Social Performance Scale (PSP) showed a statistically significant amelioration in QoL and functioning for all 3 scales, with progressive improvements at 1, 3, and 6 months. Montgomery-Asberg Depression Rating Scale (MADRS) scores decreased from a baseline score of 39.2 to 28.7 on T1, 20.9 on T2, and 15.9 on T3, respectively. Correlation analyses showed statistical significance between changes at 6 months between MADRS and QLES and between MADRS and SDS, but not between MADRS and PSP. Significant improvement in QoL was observed among patients with TRD treated with ESK-NS; ESK-NS in combination with an oral AD appears to offer meaningful benefit as a treatment option for patients with TRD who generally have substantial QoL and functioning limitations as a result of their depressive illness.

ObjectivesTo develop and validate a bilingual experience survey for use in any NHS healthcare setting, to support service improvement.DesignA prospective mixed-methods study.SettingAny healthcare setting in NHS Wales including primary, secondary, urgent and planned care.ParticipantsAn opportunistic sample of people with experience of using local healthcare services. Qualitative interviews and focus groups were held to develop a draft survey. These were followed by online data collection from a wide participant sample for statistical validation. The tool was translated and linguistically validated following recognised methods. Patient engagement leads were involved to ensure the tool met their needs.ResultsWe conducted and analysed five focus groups and four interviews, consisting of 33 people in total. 12 draft questions were developed related to key aspects of patient experience. A series of online surveys were conducted to test the draft questions, with 769 responses received. Data were analysed to assess completion rates, intra-rater reliability, internal consistency and convergent validity. One question had both sub-par intrarater reliability and poor convergent validity, and despite attempts to improve the wording, it failed to meet minimum requirements of validity and was subsequently removed. The final validated People’s Experience Survey (PES) was subsequently translated into Welsh and validated with service users.ConclusionsThe PES is a reliable and valid tool, suitable for use in any healthcare setting. The robust processes that have been undertaken ensure that the questions included are available bilingually to collect reliable, meaningful data to support service improvement work.

The advent of genetic technologies requires consideration of neo-microbes. Attention must first be given to mirror life-forms that exhibit chirality discordant to that prevalent in nature. It is important to understand the merits and challenges faced by “contra-lateralized” organisms. The hypothesis here is that such organisms would suffer almost insuperable disadvantages. Their energy transduction mechanisms would result in ATP hydrolysis. They would be vulnerable to both innate achiral and acquired bi-chiral host immunity, but their defense and virulence mechanisms would exhibit heterodox chirality and thus be ineffectual. They would be savagely out-competed by commensals. It is hypothesized that the greatest utility and threat is from “ambidextrous” species that exhibit chiral chimerism/chiral duality. Different functions would be executed by effectors of varying chirality which may be inducible or facultative. Such microbiota would show predominantly conventional biochemical “lateralization”. However, few strategic functions would exhibit non-conformative chirality. One of the most significant dangers and potential benefits is the sheer unpredictability of the host response to counter-chiral antigens/molecules. Some synthetic enantiomers are an order of magnitude more active than their stereoisomer. Exceptional hazards thus lie in chiral chimeras that may elicit a hyper-exuberant immune reaction and shield themselves from that immune response by deploying a “cloaking” device in the form of a contra-chiral cell wall. As proof of this principle, cancer, which frequently overwhelms hosts, shows biochemical ambidexterity with bio-affinity for both L-glucose and D-glucose uptake and potentially also exploits D-amino acids for protein synthesis. Intriguingly, organisms of varying sophistication exhibit varying degrees of chiral duality. Hetero-chiral D-alanine and L-galactose derivates (fucose) and conjugate enzymes, for example, are bio-molecular protagonists. Extreme caution is required with such stereo-diverse agents, especially given that their chiral plasticity would be transmissible via plasmids or recombination, unlike obligate “mirror” species. However, effective regulation is fraught with obstacles as non-canonical chiral and bi-chiral enzymes and molecules already exist in nature, serving roles germane to species’ survival. The fundamental question is whether there is a need for a critical threshold for the heterochiral metabolic enrichment of organisms beyond which a tangible hazard subsists.

The gut microbiota is a modulator of cardiometabolic disease. Circulating imidazole propionate (ImP) is a microbiota-derived proatherogenic amino acid metabolite modulating the inflammatory response of myeloid cells, endothelial function and glucose metabolism. This study examined the prognostic value of ImP in patients with coronary artery disease (CAD). Circulating ImP levels were measured in independent prospective cohorts of patients with acute coronary syndrome (ACS, Switzerland n=4937, Germany n=1497) and chronic coronary syndrome (CCS, Germany n=701). Major adverse cardiovascular events (MACE), defined as the first occurrence of a composite of death, nonfatal myocardial infarction, or nonfatal stroke after admission, were the primary endpoint. Cox models, accounting for established risk factors including the gut-derived cardiovascular risk factor trimethylamine N-oxide (TMAO), were used to evaluate the predictive value of ImP. Circulating ImP was associated with more advanced CAD and with cardiometabolic characteristics including diabetes and elevated high-sensitivity C-reactive protein. High ImP was an independent predictor of MACE (Swiss ACS cohort: hazard ratio [HR] per log2 increase 1.22, 95% confidence interval [CI] 1.10-1.35, P<0.001; German ACS cohort: HR 2.34, 95% CI 1.46-3.76, P<0.001; German CCS cohort: HR 1.32, 95% CI 1.13-1.53, P<0.001) and of mortality (Swiss ACS cohort: HR 1.34, 95% CI 1.17-1.54, P<0.001; German ACS cohort: HR 2.38, 95% CI 1.48-3.82, P<0.001; German CCS cohort: HR 1.50, 95% CI 1.14-1.98, P=0.004) after adjustment for established risk factors. ImP provided predictive value beyond TMAO (Swiss ACS cohort: HR 1.30, 95% CI 1.05-1.61, P=0.014; German CCS cohort: HR 1.31, 95% CI 1.11-1.53, P=0.001). Gut microbiota-derived ImP predicted MACE in patients with CAD independently of traditional risk factors and holds promise as a therapeutic target. ImP may refine risk stratification for personalised secondary prevention strategies.

Abstract Aims To improve the standard of care for the increasingly frail and co-morbid vascular surgery patient population in Hairmyres Hospital. This was by introducing a Peri-operative care of the Older Person undergoing Surgery (POPS) service. This is an evidence-based intervention which involves consultant geriatrician input to conduct complex geriatric assessments to help improve outcomes in older surgical patients. A POPS service is yet to be introduced into a vascular surgery department in Scotland. Methods The vascular department opted to sacrifice the salary of one consultant vascular surgeon in favour of the provision of daily consultant geriatrician input. FY1 surveys before and after the introduction of the service were carried out to observe the effect of the service on patient care and FY1 experiences. Data on the effect of the service on length of stay, admissions to ICU and in-phase reports will continue to be studied over time. Results When compared to FY1 experiences before the POPS service, there was shown to be an increase in FY1 support, an increase in patient safety and better management of delirium, polypharmacy and diabetes after the introduction of the POPS service. Early data shows a decrease in length of stay in over 60s which is not yet statistically significant. Conclusion The introduction of the POPS service to the vascular department in Hairmyres Hospital has improved patient safety and the standard of care. The effects of the POPS service will need to be studied further over time, but initial outcomes are very encouraging.