Now showing items 1-20 of 7681

    • Associations of Muscle Strength with Central Aspects of Pain: Data from the Knee Pain and Related Health in the Community (KPIC) Cohort.

      Walsh, David A (Journal of Personalized Medicine, 2023-09)
      Knee pain is associated with lower muscle strength, and both contribute to disability. Peripheral and central neurological mechanisms contribute to OA pain. Understanding the relative contributions of pain mechanisms to muscle strength might help future treatments. The Knee Pain and related health In the Community (KPIC) cohort provided baseline and year 1 data from people with early knee pain (n = 219) for longitudinal analyses. A cross-sectional analysis was performed with baseline data from people with established knee pain (n = 103) and comparative data from people without knee pain (n = 98). Quadriceps and handgrip strength indicated local and general muscle weakness, respectively. The indices of peripheral nociceptive drive were knee radiographic and ultrasound scores. The indices associated with central pain mechanisms were Pressure Pain detection Threshold (PPT) distal to the knee, and a validated self-report Central Aspects of Pain Factor (CAPF). The associations were explored using correlation and multivariable regression. Weaker quadriceps strength was associated with both high CAPF and low PPT at baseline. Year 1 quadriceps weakness was predicted by higher baseline CAPF (β = -0.28 (95% CI: -0.55, -0.01), p = 0.040). Weaker baseline and year 1 handgrip strength was also associated with higher baseline CAPF. Weaker baseline quadriceps strength was associated with radiographic scores in bivariate but not adjusted analyses. Quadriceps strength was not significantly associated with total ultrasound scores. Central pain mechanisms might contribute to muscle weakness, both locally and remote from the knee.
    • Traumatic injuries of the immature hip and pelvis.

      Gnap, Rose (Current Opinion in Pediatrics, 2023-10)
      PURPOSE OF REVIEW: The pelvis and hip account for 0.3--4% of fractures of the immature skeleton, and generally result from high energy trauma. These fractures range in severity from apophyseal avulsions to complete disruptions of the pelvic ring. The purpose of this article is to review the presentation, diagnosis, treatment and complications of these injuries in order to inform clinicians involved in their management. There is a lack of evidence-based management protocols for fractures of the immature pelvis largely due to their rarity and lack of robust scientific literature on the topic. RECENT FINDINGS: Computed tomography/MRI is essential as up to 30% of pelvis and 70% of acetabular fractures are not identified on initial radiographs. A sub-optimal outcome is common in unstable fractures treated conservatively and adequate reduction and surgical stabilization is often required to avoid long-term morbidity. SUMMARY: A coordinated approach involves resuscitation and temporary stabilization with planned definitive fixation. It is generally accepted that these injures should be managed in paediatric trauma centres. Whilst injuries vary in pattern and severity, we present an overview that considers the evaluation and treatment of the paediatric patient with pelvic and hip fractures to ensure that these injuries are identified promptly and treated by surgeons familiar with contemporary management algorithms.
    • The utility of volumetric MRI in assessment of volume changes in ventral diencephalon in autistic children.

      Mahmoud, Hassan Ali Ahmed (Egyptian Journal of Radiology and Nuclear Medicine, 2023-10)
      Abstract Background Autism spectrum disorder (ASD) is a neurobehavioural disorder, characterized by abnormal affiliative and socio-emotional responses which are generally regulated by certain neuropeptides in the hypothalamus (an anatomic component of the ventral diencephalon (VD)). The use of volumetric MRI for studying VD volume change could provide a novel approach for identification of structural brain changes in ASD; this could assist in understanding the pathophysiology of ASD and would reflect on treatment strategies. The aim of the current work was to investigate the role of MRI volumetric analysis of the ventral diencephalon in young children diagnosed with autism spectrum disorder. Methods Fifty children diagnosed with ASD underwent volumetric brain analysis, on a fully automated MRI brain volumetry system (volBrain), with voxel-based morphometry of various segmental structures of the brain including the VD, using vol2Brain 1.0 pipeline software analysis suite. Results There were 48 out of 50 children who demonstrated abnormal VD volume which was found below the normal limits compared with reference standard normalized volume. All cases were normocephalic demonstrating normal intra-cranial cavity volumes. Forty out of fifty cases showed increased total volume of grey matter, and eighteen out of fifty cases showed increased total volume of white matter. Regarding the amygdala and hippocampus, there were only two cases (4.0%) which showed slightly increased relative volume of the total amygdala, and two other cases (4.0%) demonstrated increased relative volume of the total hippocampus. Comparison between the autistic patients and normal references revealed a significant difference regarding the VD volume and total volume of grey matter, whereas no significant differences were found regarding the white matter amygdala and hippocampus. Conclusions Based on the consistent significant volume decrease in the ventral diencephalon in patients with childhood autism, this study concluded that volumetric MRI analysis could be useful for diagnosis of childhood spectrum disorder and could be utilized as a reliable screening method in the clinically vague cases. Further study with a larger sample size including more age groups is recommended for more validation of the results.
    • 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 (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.
    • Scoping review: Evidence for long-term follow-up and monitoring in shoulder and elbow arthroplasty

      Tambe, Amol
      AIMS: Long-term follow-up and monitoring of asymptomatic shoulder and elbow arthroplasty remains contentious, with a wide spectrum of non-evidence-based mechanisms used. This scoping review aims to outline related evidence, thereby informing research requirements. METHODS: Studies relevant to shoulder and elbow arthroplasty follow-up, surveillance and time-related failure were included. The review included randomised controlled trials, systematic reviews and economic studies indexed in MEDLINE, Embase, Cochrane CDSR and Cochrane CENTRAL since 1 January 2012. In addition, all registry studies, follow-up studies, cohort studies and case reports indexed in MEDLINE since 1 January 2020 were included. The screening was undertaken by two reviewers. Key characteristics of each study were described, alongside a narrative review. RESULTS: Twenty-one articles were included. We were unable to identify evidence that long-term follow-up and monitoring of asymptomatic shoulder and elbow arthroplasty identifies failure or leads to a revision that is of reduced patient morbidity and cost. In addition, no evidence was apparent to inform whether patients will self-present with a failing implant. Several surveillance mechanisms were identified. CONCLUSION: This scoping review highlights the paucity of evidence related to long-term follow-up and monitoring of shoulder and elbow arthroplasty, and the need for high-quality data to inform the development of evidence-based care pathways.
    • Feedback control in hemodialysis

      Randhay, Ashveer; Eldehni, Mohamed; Selby, Nicholas
      A number of systems of feedback control during dialysis have been developed, which have the shared characteristic of prospectively measuring physiological parameters and then automatically altering dialysis parameters in real time according to a pre-specified dialysis prescription. These include feedback systems aimed at reducing intradialytic hypotension based on relative blood volume monitoring linked to adjustments in ultrafiltration and dialysate conductivity, and blood temperature monitoring linked to alterations in dialysate temperature. Feedback systems also exist that manipulate sodium balance during dialysis by assessing and adjusting dialysate conductivity. In this review article, we discuss the rationale for automated feedback systems during dialysis, describe how the different feedback systems work, and provide a review of the current evidence on their clinical effectiveness.
    • 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.
    • The Role of NLRP3 Inflammasome in Obesity and PCOS—A Systematic Review and Meta-Analysis

      Atalah Alenezi, Salih; Snell, Lindsay; Aboeldalyl, Shaimaa; Amer, Saad
      Inflammasomes have recently been implicated in the pathogenesis of several chronic inflammatory disorders, such as diabetes and obesity. The aim of this meta-analysis was to investigate the possible role of the NLRP3 inflammasome in obesity and polycystic ovarian syndrome (PCOS). A comprehensive search of electronic databases was conducted to identify studies investigating NLRP3 its related components (Caspase 1, ASC and IL-1β) in adipose tissue and/or blood from obese individuals compared to non-obese controls. Another search was conducted for studies investigating NLRP3 in PCOS women and animal models. The ssearched databases included Medline, EMBASE, Cochrane Library, PubMed,, the EU Clinical Trials Register and the WHO International Clinical Trials Register. The quality and risk of bias for the included articles were assessed using the modified Newcastle–Ottawa scale. Data were extracted and pooled using RevMan software for the calculation of the standardized mean difference (SMD) and 95% confidence interval (CI). Twelve eligible studies were included in the obesity systematic review and nine in the PCOS review. Of the obesity studies, nine (n = 270) were included in the meta-analysis, which showed a significantly higher adipose tissue NLRP3 gene expression in obese (n = 186) versus non-obese (n = 84) participants (SMD 1.07; 95% CI, 0.27, 1.87). Pooled analysis of adipose tissue IL-1β data from four studies showed significantly higher IL-1β gene expression levels in adipose tissue from 88 obese participants versus 39 non-obese controls (SMD 0.56; 95% CI, 0.13, 0.99). Meta-analysis of adipose tissue ASC data from four studies showed a significantly higher level in obese (n = 109) versus non-obese (n = 42) individuals (SMD 0.91, 95% CI, 0.30, 1.52). Of the nine PCOS articles, three were human (n = 185) and six were animal studies utilizing PCOS rat/mouse models. All studies apart from one article consistently showed upregulated NLRP3 and its components in PCOS women and animal models. In conclusion, obesity and PCOS seem to be associated with upregulated expression of NLRP3 inflammasome components. Further research is required to validate these findings and to elucidate the role of NLRP3 in obesity and PCOS.
    • 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.