• Core outcomes and factors influencing the experience of care for children with severe acute exacerbations of asthma: a qualitative study

  Roland, Damian (2023-11)

  Objective: To identify the outcomes considered important, and factors influencing the patient experience, for parents and caregivers of children presenting to hospital with a severe acute exacerbation of asthma. This work contributes to the outcome-identification process in developing a core outcome set (COS) for future clinical trials in children with severe acute asthma. Design: A qualitative study involving semistructured interviews with parents and caregivers of children who presented to hospital with a severe acute exacerbation of asthma. Setting: Hospitals in 12 countries associated with the global Pediatric Emergency Research Networks, including high-income and middle-income countries. Interviews were conducted face-to-face, by teleconference/video-call, or by phone. Findings: Overall, there were 54 interviews with parents and caregivers; 2 interviews also involved the child. Hospital length of stay, intensive care unit or high-dependency unit (HDU) admission, and treatment costs were highlighted as important outcomes influencing the patient and family experience. Other potential clinical trial outcomes included work of breathing, speed of recovery and side effects. In addition, the patient and family experience was impacted by decision-making leading up to seeking hospital care, transit to hospital, waiting times and the use of intravenous treatment. Satisfaction of care was related to communication with clinicians and frequent reassessment. Conclusions: This study provides insight into the outcomes that parents and caregivers believe to be the most important to be considered in the process of developing a COS for the treatment of acute severe exacerbations of asthma.
• The impact of pre-operative mental health on outcomes of foot and ankle surgery: A scoping review

  Haq, Ibrahim I; Bhatia, Maneesh (2023-11-08)

  Background: Evidence suggests that certain groups of orthopaedic patients have an increased prevalence of mental health disorders than the general population. This scoping review aims to evaluate the effect of pre-operative mental health on outcomes of foot and ankle surgery. Methods: A literature search was performed in four databases. Studies investigating a relationship between preoperative mental health and postoperative patient reported outcome measures (PROMs), complications, readmissions or reoperations were included. Results: Of the 19 studies investigating the effect of preoperative mental health on PROMs, 16 (84.2%) reported a significant relationship between poorer preoperative mental health and inferior postoperative PROMs. Poorer mental health was associated with an increased rate of complications, readmissions and/or reoperations in four studies. Conclusions: Poorer preoperative mental health is associated with significantly inferior outcomes following foot and ankle surgery. Clinicians should evaluate mental health to stratify likely outcomes and aid in the management of patient expectations. Level of evidence: Level IV: Scoping review of Level II-IV studies.
• Evaluating niraparib versus active symptom control in patients with previously treated mesothelioma (NERO): a study protocol for a multicentre, randomised, two-arm, open-label phase II trial in UK secondary care centres

  Fennell, Dean; Darlison, Liz; Dulloo, Sean; Poile, Charlotte (2023-11-22)

  Background: Malignant mesothelioma is a rapidly lethal cancer that has been increasing at an epidemic rate over the last three decades. Targeted therapies for mesothelioma have been lacking. A previous study called MiST1 (NCT03654833), evaluated the efficacy of Poly (ADP-ribose) polymerase (PARP) inhibition in mesothelioma. This study met its primary endpoint with 15% of patients having durable responses exceeding 1 year. Therefore, there is a need to evaluate PARP inhibitors in relapsed mesothelioma patients, where options are limited. Niraparib is the PARP inhibitor used in NERO. Methods: NERO is a multicentre, two-arm, open-label UK randomised phase II trial designed to evaluate the efficacy of PARP inhibition in relapsed mesothelioma. 84 patients are being recruited. NERO is not restricted by line of therapy; however, eligible participants must have been treated with an approved platinum based systemic therapy. Participants will be randomised 2:1, stratified according to histology and response to prior platinum-based chemotherapy, to receive either active symptom control (ASC) and niraparib or ASC alone, for up to 24 weeks. Participants will be treated until disease progression, withdrawal, death or development of significant treatment limiting toxicity. Participants randomised to niraparib will receive 200 or 300 mg daily in a 3-weekly cycle. The primary endpoint is progression-free survival, where progression is determined by modified Response Evaluation Criteria in Solid Tumors (mRECIST) or RECIST 1.1; investigator reported progression; or death from any cause, whichever comes first. Secondary endpoints include overall survival, best overall response, 12-week and 24 week disease control, duration of response, treatment compliance and safety/tolerability. If NERO shows niraparib to be safe and biologically effective, it may lead to future late phase randomised controlled trials in relapsed mesothelioma. Ethics and dissemination: The study received ethical approval from London-Hampstead Research Ethics Committee on 06-May-2022 (22/LO/0281). Data from all centres will be analysed together and published as soon as possible. Trial registration number: ISCRTN16171129; NCT05455424.
• Baseline haemoglobin variability by measurement technique in pregnant people on the day of childbirth

  McMahon, O (2023-11-21)

  Point-of-care haemoglobin measurement devices may play an important role in the antenatal detection of anaemia in pregnant people and may be useful in guiding blood transfusion during resuscitation in obstetric haemorrhage. We compared baseline haemoglobin variability of venous and capillary HemoCue® haemoglobin, and Masimo® Rad-67 Pulse CO-Oximeter haemoglobin with laboratory haemoglobin in people on the day of their planned vaginal birth. A total of 180 people undergoing planned vaginal birth were enrolled in this prospective observational study. Laboratory haemoglobin was compared with HemoCue and Masimo Rad-67 Pulse CO-Oximeter measurements using Bland-Altman analysis, calculating mean difference (bias) and limits of agreement. Five (2.8%) people had anaemia (haemoglobin < 110 g.l-1 ). Laboratory haemoglobin and HemoCue venous haemoglobin comparison showed an acceptable bias (SD) 0.7 (7.54) g.l-1 (95%CI -0.43-1.79), with limits of agreement -14.10-15.46 g.l-1 and acceptable agreement range of 29.6 g.l-1 . Laboratory and HemoCue capillary haemoglobin comparison showed an unacceptable bias (SD) 13.3 (14.12) g.l-1 (95%CI 11.17-15.34), with limits of agreement - 14.42-40.93 g.l-1 and unacceptable agreement range of 55.3 g.l-1 . Laboratory and Masimo haemoglobin comparison showed an unacceptable bias (SD) -14.0 (11.15) g.l-1 (95%CI -15.63 to -12.34), with limits of agreement to -35.85 to 7.87 g.l-1 and acceptable agreement range of 43.7 g.l-1 . Venous HemoCue, with its acceptable bias and limits of agreement, should be applied more widely in the antenatal setting to detect, manage and risk stratify pregnant people with anaemia. HemoCue capillary measurement under-estimated haemoglobin and Masimo haemoglobin measurement over-estimated, limiting their clinical use. Serial studies are needed to determine if the accuracy of venous HemoCue haemoglobin measurement is sustained in other obstetric settings.
• Screening for tuberculosis infection and effectiveness of preventive treatment among people living with HIV in low-incidence settings: a systematic review and meta-analysis

  Pareek, Manish (2023-10-12)

  To determine the yield of screening for latent tuberculosis infection (LTBI) among people living with HIV (PLHIV) in low tuberculosis (TB) incidence countries (<10 TB cases per 100.000 persons), we performed a systematic review and meta-analysis to assess prevalence and predictive factors of LTBI, rate of TB progression, effect of TB preventive treatment (TPT), and numbers needed to screen. Pubmed and Cochrane Library were searched for studies reporting primary data, excluding studies on active or pediatric TB. We extracted LTBI cases, odds ratios, and TB incidences; pooled estimates using a random-effects model; and used the Newcastle-Ottawa scale for bias. In 51 studies with 65.930 PLHIV, 12% (95% CI 10-14) had a positive LTBI test, which was strongly associated with origin from a TB-endemic country (OR 4.7) and exposure to TB (OR 2.9). Without TPT (10,629 PLHIV), TB incidence was 28/1000 person years (PY; 95% CI 12-45) for LTBI-test positive versus 4/1000 PY (95% CI 0-7) for LTBI-test negative individuals. Among 625 PLHIV (1644 PY) receiving TPT, 15 developed TB (6/1000 PY). An estimated 20 LTBI-positive individuals would need TPT to prevent one case of TB, and numbers needed to screen to detect LTBI or prevent active TB varied according to a priori risk of LTBI. The relatively high prevalence of LTBI among PLHIV and the strong correlation with origin from a TB-endemic country support risk-stratified LTBI screening strategies for PLHIV in low-incidence countries and treating those who test positive.
• Evaluation of a COVID-19 fundamental nursing care guideline versus usual care: The COVID-NURSE cluster randomized controlled trial

  Singh, Sally J (2023-11-20)

  Aim: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness. Design: Parallel two-arm, cluster-level randomized controlled trial. Methods: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses. Results: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570-572 (98.1%-98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the 'other' ethnicity subgroup. Conclusion: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care. Implications for the profession and/or patient care: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required. Impact: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care. Reporting method: CONSORT and CONSERVE. Patient or public contribution: Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings.
• Robotic-assisted surgery in high-risk surgical patients with endometrial cancer

  Moss, Esther (2023-11-04)

  Many patients diagnosed with an endometrial cancer are at high-risk for surgery due to factors such as advanced age, raised body mass index or frailty. Minimally-invasive surgery, in particular robotic-assisted, is increasingly used in the surgical management of endometrial cancer however, there are a lack of clinical trials investigating outcomes in high-risk patient populations. This article will review the current evidence and identify areas of uncertainty where future research is needed.
• No clinical advantage with customized individually made implants over conventional off-the-shelf implants in total knee arthroplasty: a systematic review and meta-analysis

  Aujla, Randeep (2023-11-18)

  Introduction: Total knee arthroplasty (TKA) can be performed with either conventional off-the-shelf (OTS) or customized individually-made (CIM) implants. The evidence for CIM implants is limited and variable, and the aim of this review was to compare clinical and radiological outcomes between CIM and OTS implants. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Studies reporting on clinical, radiological, or alignment outcomes for CIM and OTS implants were selected. The studies were appraised using the Methodical index for non-randomized studies tool. Results: Twenty-three studies fulfilled the inclusion criteria. The studies comprised 2856 CIM and 1877 OTS TKAs. Revision rate was higher with CIM (5.9%) compared to OTS (3.7%) implants [OR 1.23(95% CI 0.69-2.18)]. Manipulation under anesthesia (MUA) was higher in CIM (2.2%) compared to OTS (1.1%) group [OR 2.95(95% CI 0.95-9.13)] and complications rate was higher in CIM (5%) vs. OTS (4.5%) [OR 1.45(95% CI 0.53-3.96)] but neither reached statistical significance. Length of stay was significantly shorter in CIM group 2.9 days vs. 3.5 days [MD - 0.51(95% CI - 0.82 to - 0.20)]. Knee Society Score showed no difference between CIM and OTS groups for Knee 90.5 vs. 90.6 [MD - 0.27(95% CI - 4.27 to 3.73)] and Function 86.1 vs. 83.1 [MD 1.51(95% CI - 3.69 to 6.70)]. Conclusion: CIM implants in TKA have theoretical benefits over OTS prostheses. However, in this present review, CIM implants were associated with higher revisions, MUA, and overall complication rates. There was no difference in outcome score and CIM implants did not improve overall target alignment; however, more CIM TKAs were found to be in the HKA target zone compared to OTS TKAs. The findings of this review do not support the general utilization of CIM over OTS implants in TKA.
• Clinical Frailty Scale at presentation to the emergency department: interrater reliability and use of algorithm-assisted assessment

  Banerjee, Jay (2023-11-16)

  Purpose: The Clinical Frailty Scale (CFS) allows health care providers to quickly stratify older patients, to support clinical decision-making. However, few studies have evaluated the CFS interrater reliability (IRR) in Emergency Departments (EDs), and the freely available smartphone application for CFS assessment was never tested for reliability. This study aimed to evaluate the interrater reliability of the Clinical Frailty Scale (CFS) ratings between experienced and unexperienced staff (ED clinicians and a study team (ST) of medical students supported by a smartphone application to assess the CFS), and to determine the feasibility of CFS assignment in patients aged 65 or older at triage. Methods: Cross-sectional study using consecutive sampling of ED patients aged 65 or older. We compared assessments by ED clinicians (Triage Clinicians (TC) and geriatric ED trained nurses (geriED-TN)) and a study team (ST) of medical students using a smartphone application for CFS scoring. The study is registered on Clinicaltrials.gov (NCT05400707). Results: We included 1349 patients aged 65 and older. Quadratic-weighted kappa values for ordinal CFS levels showed a good IRR between TC and ST (ϰ = 0.73, 95% CI 0.69-0.76), similarly to that between TC and geriED-TN (ϰ = 0.75, 95% CI 0.66-0.82) and between the ST and geriED-TN (ϰ = 0.74, 95% CI 0.63-0.81). A CFS rating was assigned to 972 (70.2%) patients at triage. Conclusion: We found good IRR in the assessment of frailty with the CFS in different ED providers and a team using a smartphone application to support rating. A CFS assessment occurred in more than two-thirds (70.2%) of patients at triage.
• Lack of regional pathways impact on surgical delay: analysis of the Orthopaedic Trauma Hospital Outcomes-Patient Operative Delays (ORTHOPOD) study

  Nichols, Jennifer; Wildin, Clare (2023-08-22)

  Introduction: Current practice following injury within the United Kingdom is to receive surgery, at the institution of first contact regardless of ability to provide timely intervention and inconsiderate of neighbouring hospital resource and capacity. This can lead to a mismatch of demand and capacity, delayed surgery and stress within hospital systems, particularly with regards to elective services. We demonstrate through a multicentre, multinational study, the impact of this at scale. Methodology: ORTHOPOD data collection period was between 22/08/2022 and 16/10/2022 and consisted of two arms. Arm 1 captured orthopaedic trauma caseload and capacity in terms of sessions available per centre and patients awaiting surgery per centre per given week. Arm 2 recorded patient and injury demographics, time of decision making, outpatient and inpatient timeframes as well as time to surgery. Hand and spine cases were excluded. For this regional comparison, regional trauma networks with a minimum of four centres enroled onto the ORTHOPOD study were exclusively analysed. Results: Following analysis of 11,202 patient episodes across 30 hospitals we found no movement of any patient between hospitals to enable prompt surgery. There is no current system to move patients, between regional centres despite clear discrepancies in workload per capacity across the United Kingdom. Many patients wait for days for surgery when simple transfer to a neighbouring hospital (within 10 miles in many instances) would result in prompt care within national guidelines. Conclusion: Most trauma patients in the United Kingdom are managed exclusively at the place of first presentation, with no consideration of alternative pathways to local hospitals that may, at that time, offer increased operative capacity and a shorter waiting time. There is no oversight of trauma workload per capacity at neighbouring hospitals within a regional trauma network. This leads to a marked disparity in waiting time to surgery, and subsequently it can be inferred but not proven, poorer patient experience and outcomes. This inevitably leads to a strain on the overall trauma system and across several centres can impact on elective surgery recovery. We propose the consideration of inter-regional network collaboration, aligned with the Major Trauma System.
• Geographical variation in underlying social deprivation, cardiovascular and other comorbidities in patients with potentially curable cancers in England: results from a national registry dataset analysis

  Adlam, D (2023-12)

  Aims: To describe the prevalence of cardiovascular disease (CVD), multiple comorbidities and social deprivation in patients with a potentially curable cancer in 20 English Cancer Alliances. Materials and methods: This National Registry Dataset Analysis used national cancer registry data and CVD databases to describe rates of CVD, comorbidities and social deprivation in patients diagnosed with a potentially curable malignancy (stage I-III breast cancer, stage I-III colon cancer, stage I-III rectal cancer, stage I-III prostate cancer, stage I-IIIA non-small cell lung cancer, stage I-IV diffuse large B-cell lymphoma, stage I-IV Hodgkin lymphoma) between 2013 and 2018. Outcome measures included observation of CVD prevalence, other comorbidities (evaluated by the Charlson Comorbidity Index) and deprivation (using the Index of Multiple Deprivation) according to tumour site and allocation to Cancer Alliance. Patients were allocated to CVD prevalence tertiles (minimum: <33.3rd percentile; middle: 33.3rd to 66.6th percentile; maximum: >66.6th percentile). Results: In total, 634 240 patients with a potentially curable malignancy were eligible. The total CVD prevalence for all cancer sites varied between 13.4% (CVD n = 2058; 95% confidence interval 12.8, 13.9) and 19.6% (CVD n = 7818; 95% confidence interval 19.2, 20.0) between Cancer Alliances. CVD prevalence showed regional variation both for male (16-26%) and female patients (8-16%) towards higher CVD prevalence in northern Cancer Alliances. Similar variation was observed for social deprivation, with the proportion of cancer patients being identified as most deprived varying between 3.3% and 32.2%, depending on Cancer Alliance. The variation between Cancer Alliance for total comorbidities was much smaller. Conclusion: Social deprivation, CVD and other comorbidities in patients with a potentially curable malignancy in England show significant regional variations, which may partly contribute to differences observed in treatments and outcomes.
• A repurposing programme evaluating repurposing transdermal oestradiol patches for the treatment of prostate cancer within the PATCH and STAMPEDE Trials: current results and adapting trial design

  Kockelbergh, Roger (2023-11-08)

  Aims: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. Materials and methods: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. Results: to date: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. Future: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.
• Standardized clinical annotation of digital histopathology slides at the point of diagnosis

  Hero, Emily (2023-11)

  As digital pathology replaces conventional glass slide microscopy as a means of reporting cellular pathology samples, the annotation of digital pathology whole slide images is rapidly becoming part of a pathologist's regular practice. Currently, there is no recognizable organization of these annotations, and as a result, pathologists adopt an arbitrary approach to defining regions of interest, leading to irregularity and inconsistency and limiting the downstream efficient use of this valuable effort. In this study, we propose a Standardized Annotation Reporting Style for digital whole slide images. We formed a list of 167 commonly annotated entities (under 12 specialty subcategories) based on review of Royal College of Pathologists and College of American Pathologists documents, feedback from reporting pathologists in our NHS department, and experience in developing annotation dictionaries for PathLAKE research projects. Each entity was assigned a suitable annotation shape, SNOMED CT (SNOMED International) code, and unique color. Additionally, as an example of how the approach could be expanded to specific tumor types, all lung tumors in the fifth World Health Organization of thoracic tumors 2021 were included. The proposed standardization of annotations increases their utility, making them identifiable at low power and searchable across and between cases. This would aid pathologists reporting and reviewing cases and enable annotations to be used for research. This structured approach could serve as the basis for an industry standard and be easily adopted to ensure maximum functionality and efficiency in the use of annotations made during routine clinical examination of digital slides.
• Sustaining interventions in care homes initiated by quality improvement projects: a qualitative study

  Banerjee, Jaydip (2023-11)

  Introduction: Inadequate and varied quality of care in care homes has led to a proliferation of quality improvement (QI) projects. This study examined the sustainability of interventions initiated by such projects. Method: This qualitative study explored the sustainability of seven interventions initiated by three QI projects between 2016 and 2018 in UK care homes and explored the perceived influences to the sustainability of interventions. QI projects were followed up in 2019. Staff leading QI projects (n=9) and care home (n=21, from 13 care homes) and healthcare (n=2) staff took part in semi-structured interviews. Interventions were classified as sustained if the intervention was continued at the point of the study. Thematic analysis of interview data was performed, drawing on the Consolidated Framework for Sustainability (CFS), a 40-construct model of sustainability of interventions. Results: Three interventions were sustained and four interventions were not. Seven themes described perceptions around what influenced sustainability: monitoring outcomes and regular check-in; access to replacement intervention materials; staff willingness to dedicate time and effort towards interventions; continuity of staff and thorough handover/inductions in place for new staff; ongoing communication and awareness raising; perceived effectiveness; and addressing care home priorities. All study themes fell within 18 of the 40 CFS constructs. Discussion: Our findings resonate with the CFS and are also consistent with implementation theories, suggesting sustainability is best addressed during implementation rather than treated as a separate process which follows implementation. Commissioning and funding QI projects should address these considerations early on, during implementation.
• Does patient-reported bath ankylosing spondylitis disease activity index correlate with inflammatory back pain and extra-articular manifestations in axial spondyloarthropathy?

  Moorthy, Arumugam; Byravan, Swetha (2023-09-26)
• Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans

  Athithan, Lavanya; Brady, Emer; Davies, Melanie J; Gulsin, Guarav S; Henson, Joseph; McCann, Gerry; Parke, Kelly (2023-10-06)

  Background: South Asians (SA) constitute a quarter of the global population and are disproportionally affected by both type 2 diabetes (T2D) and heart failure. There remains limited data of the acceptability and efficacy of low-energy meal replacement plans to induce remission of T2D in SA. Objectives: The objective of this exploratory secondary analysis of the DIASTOLIC study was to determine if there was a differential uptake, glycometabolic and cardiovascular response to a low-energy meal replacement plan (MRP) between SA and White European (WE) people with T2D. Methods: Obese adults with T2D without symptomatic cardiovascular disease were allocated a low-energy (~810 kcal/day) MRP as part of the DIASTOLIC study (NCT02590822). Comprehensive multiparametric cardiovascular magnetic resonance imaging, echocardiography, cardiopulmonary exercise testing and metabolic profiling were undertaken at baseline and 12 weeks. A comparison of change at 12 weeks between groups with baseline adjustment was undertaken. Results: Fifteen WE and 12 SAs were allocated the MRP. All WE participants completed the MRP versus 8/12 (66%) SAs. The degree of concentric left ventricular remodelling was similar between ethnicities. Despite similar weight loss and reduction in liver fat percentage, SA had a lower reduction in Homeostatic Model Assessment for Insulin Resistance [-5.7 (95% CI: -7.3, -4.2) versus -8.6 (-9.7, -7.6), p = 0.005] and visceral adiposity compared to WE [-0.43% (-0.61, -0.25) versus -0.80% (-0.91, -0.68), p = 0.002]. Exercise capacity increased in WE with no change observed in SA. There was a trend towards more reverse remodelling in WE compared to SAs. Conclusions: Compliance to the MRP was lower in SA versus WE. Overall, those completing the MRP saw improvements in weight, body composition and indices of glycaemic control irrespective of ethnicity. Whilst improvements in VAT and insulin resistance appear to be dampened in SA versus WE, given the small sample, larger studies are required to confirm or challenge this potential ethnic disparity.
• Achromatopsia-visual cortex stability and plasticity in the absence of functional cones

  McLean, Rebecca (2023-10-03)

  Purpose: Achromatopsia is a rare inherited disorder rendering retinal cone photoreceptors nonfunctional. As a consequence, the sizable foveal representation in the visual cortex is congenitally deprived of visual input, which prompts a fundamental question: is the cortical representation of the central visual field in patients with achromatopsia remapped to take up processing of paracentral inputs? Such remapping might interfere with gene therapeutic treatments aimed at restoring cone function. Methods: We conducted a multicenter study to explore the nature and plasticity of vision in the absence of functional cones in a cohort of 17 individuals affected by autosomal recessive achromatopsia and confirmed biallelic disease-causing CNGA3 or CNGB3 mutations. Specifically, we tested the hypothesis of foveal remapping in human achromatopsia. For this purpose, we applied two independent functional magnetic resonance imaging (fMRI)-based mapping approaches, i.e. conventional phase-encoded eccentricity and population receptive field mapping, to separate data sets. Results: Both fMRI approaches produced the same result in the group comparison of achromatopsia versus healthy controls: sizable remapping of the representation of the central visual field in the primary visual cortex was not apparent. Conclusions: Remapping of the cortical representation of the central visual field is not a general feature in achromatopsia. It is concluded that plasticity of the human primary visual cortex is less pronounced than previously assumed. A pretherapeutic imaging workup is proposed to optimize interventions.
• Predictive factors for subjective vertigo following cochlear implantation: a regional multicenter cohort study of 395 patients

  Mair, Manish (2023-10-19)

  Introduction: Cochlear implantation (CI) is generally accepted as having a low rate of postoperative complications, but between 9.3% and 13% of cases experience vertigo postoperatively. This study aimed to examine patient, surgical, and device factors contributing toward the risk of postoperative vertigo. Methodology: A retrospective review was conducted of adult patients who underwent cochlear implant in a regional area of New South Wales from 2007 to 2018. A total of 395 cochlear implant cases were included in the final study. Results: The overall incidence of vertigo at 3 months of follow-up was 7.1% (n = 28/395). No difference was identified in this study between rates of postoperative vertigo between device factors, including implant make (Cochlear vs. Med-El), electrode shape (perimodiolar vs. straight), and electrode model. No significant difference was found also for surgical factors such as the number of electrode rings inserted, side of implantation, or surgical approach of tympanic ramp (round window insertion vs. cochleostomy).A higher percentage of patients with preoperative vertigo experienced vertigo postoperatively (18.4%, n = 7/38), compared with the population without preoperative vertigo (6.0%, n = 21/352) (p = 0.005). Patients with previous mastoid surgery also reported a higher rate of postoperative vertigo (20%, n = 9/45) compared with those who had not had mastoid surgery (5.43%, n = 19/350) (p = 0.006). The mean age of patients experiencing postoperative vertigo was higher than the population without postoperative symptoms (67 vs. 63). Conclusion: This study of a large multicenter population outlines that patient factors are more critical than surgical or device factors when considering risk factors for vertigo post-cochlear implant.
• Impact of changing from autopsy to post-mortem CT in an entire HM Coroner region due to a shortage of available pathologists

  Robinson, C; Morgan, B (2023-11)

  A significant problem facing routine medicolegal coroner-referred autopsies is a shortfall of pathologists prepared to perform them. This was particularly acute in Lancashire, where the coroner decided to initiate a service that relied on post-mortem computed tomography (PMCT). This involved training anatomical pathology technologists (APTs) to perform external examinations, radiographers to perform scans, and radiologists to interpret them. The service started in 2018 and now examines over 1,500 cases per year. This study outlines the PMCT process using NHS staff, with CT equipment and logistics managed by the commercial sector. It compares the demographics and outcomes of PM investigations for two 6-month periods: the autopsy service prior to 2018, and then the PMCT service. These data were then compared with previous UK PMCT data. Referrals for adult non-suspicious deaths were made in 913 cases of which 793 (87%) had PMCT between 01/10/2018 and 31/03/2019. Fifty-six cases had autopsy after PMCT, so 81% of cases potentially avoided autopsy. The PMCT service did not delay release of bodies to the next-of-kin. Comparing the cause of death given shows no difference in the proportions of natural and unnatural deaths. There was an increase in diagnosis of coronary artery disease for PMCT, with less respiratory diagnoses, a feature not previously demonstrated. These data suggest PMCT is a practical solution for potentially failing autopsy services. By necessity, this involves changes in diagnoses, as PMCT and autopsy have different strengths and weakness, but the ability to pick up unnatural death appears unaffected.
• Effect of delay in treatment intensification in people with type 2 diabetes and suboptimal glycaemia after basal insulin initiation: A real-world observational study

  Davies, Melanie J; Webb, David R; Zaccardi, Francesco (2023-10-19)

  Aim: Despite global recommendations for type 2 diabetes mellitus treatment to maintain optimal glycaemic targets, a significant proportion of people remain in suboptimal glycaemic control. Our objective was to investigate the impact of intensification delay after basal insulin (BI) initiation on long-term complications in people with suboptimal glycaemia. Materials and methods: We conducted a retrospective cohort study in individuals with type 2 diabetes mellitus initiated on BI. Those with suboptimal glycaemia (glycated haemoglobin ≥7% or ≥53 mmol/mol) within 12 months of BI initiation were divided into early (treatment intensified within 5 years), or late (≥5 years) intensification groups. We estimated the age-stratified risks of micro- and macrovascular complications among these groups compared with those with optimal glycaemia (glycated haemoglobin <7%). Results: Of the 13 916 people with suboptimal glycaemia, 52.5% (n = 7304) did not receive any treatment intensification. In those aged <65 years, compared with the optimal glycaemia group late intensification was associated with a 56% higher risk of macrovascular complications (adjusted hazard ratio 1.56; 95% confidence intervals 1.08, 2.26). In elderly people (≥65 years), late intensification was associated with a higher risk of cardiovascular-related death (1.62; 1.03, 2.54) and a lower risk of microvascular complications (0.26; 0.08, 0.83). Conclusions: Those who had late intensification were at an increased risk of cardiovascular death if they were ≥65 years and an increased risk of macrovascular complications if they were <65 years. These findings highlight the critical need for earlier intensification of treatment and adopting personalized treatment strategies to improve patient outcomes.

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