Recent Submissions

  • Tertiary centre study highlights low inpatient deintensification and risks associated with adverse outcomes in frail people with diabetes

    Aftab, Faseeha; Fazil, Mohamed; Gallagher, Alison; Higgins, Kath; Lwin, Huin; Melson, Eka; Thomas, Anu; Thottungal, Kevin; Tun, HayMar (2024-03)
    Introduction: The community deintensification rates in older people with diabetes are low and hospital admission presents an opportunity for medication review. We audited the inpatient assessment and deintensification rate in people with diabetes and frailty. We also identified factors associated with adverse inpatient outcomes. Methods: A retrospective review of electronic charts was conducted in all people with diabetes and clinical frailty score ≥6 who were discharged from the medical unit in 2022. Data on demographics, comorbidities and background glucose-lowering medications were collected. Results: Six-hundred-and-sixty-five people with diabetes and moderate/severe frailty were included in our analysis. For people with no HbA1c in the last six months preceding admission, only 9.0% had it assessed during inpatient. Deintensification rates were 19.1%. Factors that were associated with adverse inpatient outcomes included inpatient hypoglycaemia, non-White ethnicity, and being overtreated (HbA1c <7.0% [53 mmol/mol] with any glucose-lowering medication). Conclusion: The assessment and deintensification rate in secondary care for people with diabetes and frailty is low. Inpatient hypoglycaemia, non-White ethnicity, and overtreatment are important factors in determining inpatient outcomes highlighting the importance of deintensification and the need for an evidence-based risk stratification tool.
  • Making research everybody's business-innovation to introduce foundation doctors to research

    Brunskill, Nigel; Choudhary, Pratik; Davies, Melanie; Screder, Sally (2024-03-05)
    In order to train a future workforce able to meet the needs of its patients it is vital to ensure that opportunities to engage in research are inbuilt to training programmes. This strategy meets national recommendations recently published by NIHR, RCP and GMC. A nationally funded expansion of 'standard' Foundation programmes offers a unique opportunity to develop innovative new posts which include exposure to clinical research. In NHSE Midlands a pilot Foundation Year two (F2) post in Diabetes Research was implemented in August 2022, embedded into a standard Foundation programme. Subjective evaluation of the post, by F2 doctors and trainers, has been very positive and a further two posts in Research and Innovation commence August 2023 and 2024. These unique and geographically co-located programmes also aim to support the widening participation in medicine agenda. This model could be adapted within any Foundation School.
  • A practical approach to screening for Carbapenemase-Producing Enterobacterales- views of a group of multidisciplinary experts from English hospitals

    Jenkins, David (2024-04-26)
    Introduction: Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges. Methods: A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE. Key findings: Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks. Conclusion: Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources- such as upscaled screening- to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.
  • From bench to bedside- is there a role of IL-17 drugs in rheumatoid arthritis?

    Moorthy, Arumugam (2024-05-02)
    Introduction: IL-17 has been described as a pro-inflammatory cytokine that is relevant in the seronegative spondylarthritides with IL-17 targeted therapies being licensed for their treatment.There is evidence to demonstrate that IL-17 is found in RA joints and contributes to the pro-inflammatory cascade. This results in synovial hyperplasia and osteoclastogenesis thus causing joint destruction and bony erosions. Areas covered: This review article summarizes trials that have studied the use of IL-17 targeted therapies in RA patients who have failed conventional synthetic disease-modifying therapy (C-DMARDS) and biologic DMARDS. Expert opinion: The trials that have studied IL-17 inhibitors in RA patients have only shown a modest improvement in disease activity. In several trials, the primary endpoint was not achieved whilst in others, when comparing with existing licensed biologics for RA, did not demonstrate any superiority.Tissue Necrosis Factor-alpha (TNF-α) likely plays more of a pivotal role in the pathogenesis of RA with IL-17 having a synergistic effect. Therefore, in our opinion, IL-17 inhibitors as an independent therapy for RA are less likely to provide a cost-effective benefit. There may be scope to potentially combine it with TNF-α-inhibitors (TNF-i), but this requires further research especially with the potential concerns related to increased immunosuppression.
  • Glycaemic control and macrovascular and microvascular outcomes: A systematic review and meta-analysis of trials investigating intensive glucose-lowering strategies in people with type 2 diabetes

    Zaccardi, Francesco (2024-06)
    Aim: We aimed to determine the macrovascular and microvascular outcomes of intensive versus standard glucose-lowering strategies in type 2 diabetes (T2D) and investigate the relationships between these outcomes and trial arm glycated haemoglobin (HbA1c) reduction. Materials and methods: In this systematic review and meta-analysis, we identified relevant trials from MEDLINE, Embase, the Cochrane Library, and bibliographies up to August 2023. Macrovascular and microvascular outcomes, along with safety outcomes, were evaluated. Pooled study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and meta-regression was employed to analyse the relationships between outcomes and HbA1c reduction. Results: We included 11 unique RCTs involving 51 469 patients with T2D (intensive therapy, N = 26 691; standard therapy, N = 24 778). Intensive versus standard therapy reduced the risk of non-fatal myocardial infarction (MI) (HR 0.84; 95% CI 0.75-0.94) with no difference in the risk of major adverse cardiovascular events (HR 0.97; 95% CI 0.92-1.03) and other adverse cardiovascular outcomes. Intensive versus standard therapy reduced the risk of retinopathy (HR 0.85; 0.78-0.93), nephropathy (HR 0.71; 0.58-0.87) and composite microvascular outcomes (HR 0.88; 0.77-1.00). Meta-regression analyses showed modest evidence of inverse linear relationships between HbA1c reduction and the outcomes of major adverse cardiovascular events, non-fatal MI, stroke and retinopathy, but these were not statistically significant. Conclusions: In people with T2D, intensive glucose control was associated with a reduced risk of non-fatal MI and several microvascular outcomes, particularly retinopathy and nephropathy. The lack of an effect of intensive glucose-lowering on most macrovascular outcomes calls for a more comprehensive approach to managing cardiovascular risk factors alongside glycaemic control.
  • Fasting and post prandial pancreatic and enteroendocrine hormone levels in obese and non-obese participants

    Meek, Claire (2024-06)
    Circulating insulin levels are known to be increased in people with higher body mass index (BMI) due to effects of adiposity on insulin resistance, whilst gut hormones have a more complex relationship, with fasting peptideYY (PYY) reported to be inversely related to BMI. This study aimed to further explore fasting and post prandial pancreatic and gut hormone concentrations in plasma samples from obese and non-obese participants. Participants with healthy BMI (n=15), overweight BMI (n=29) and obesity (n=161) had samples taken fasting and 30 min post mixed liquid meal for analysis of glucagon-like peptide-1 (GLP-1), PYY, glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon. Data visualiation used linear discriminant analysis for dimensionality reduction, to visualise the data and assess scaling of each hormone. Fasting levels of insulin, GIP and PYY were shown to be key classifiers between the 3 groups on ANCOVA analysis, with an observation of increased GIP levels in overweight, but not obese participants. In non-obese subjects, fasting GIP, PYY and insulin correlated with BMI, whereas in subjects with obesity only the pancreatic hormones glucagon and insulin correlated with BMI. Concentrations of total GLP-1 in the fasting state correlated strongly with glucagon levels, highlighting potential assay cross-reactivities. The study, which included a relatively large number of subjects with severe obesity, supported previous evidence of BMI correlating negatively with fasting PYY and positively with fasting insulin. The observation of increased fasting GIP levels in overweight but not obese participants deserves further validation and mechanistic investigation.
  • Sarcopenia prevalence using handgrip strength or chair stand performance in adults living with type 2 diabetes mellitus

    Davies, Melanie; Hall, Andrew P; Henson, Joseph; Sargeant, Jack (2024-05-01)
    Background: The updated European Working Group on Sarcopenia in Older People (EWGSOP2) recommends handgrip strength (HGS) and the chair stand test (CST) to assess muscle strength, with the CST being a convenient proxy for lower limb strength. However, adiposity may differentially influence these strength criteria and produce discrepant sarcopenia prevalence. Objective: To determine the prevalence of sarcopenia using HGS or the CST, and to investigate the associations between these strength criteria and adiposity in adults with type 2 diabetes mellitus. Methods: The EWGSOP2 definition was used to assess the prevalence of probable (low muscle strength), confirmed (plus low muscle mass) and severe (plus poor physical performance) sarcopenia. Linear regression models were used to study the association between different measures of muscle strength and adiposity. Results: We used data from 732 adults with type 2 diabetes mellitus (35.7% female, aged 64 ± 8 years, body mass index 30.7 ± 5.0 kg/m2). Using the CST compared with HGS produced a higher prevalence of probable (31.7% vs. 7.1%), confirmed (5.6% vs. 1.6%) and severe (1.0% vs. 0.3%) sarcopenia, with poor agreement between strength criteria to identify probable sarcopenia. CST performance, but not HGS, was significantly associated with all measures of adiposity in unadjusted and adjusted models. Conclusions: Higher levels of adiposity may impact CST performance, but not HGS, resulting in a higher prevalence of sarcopenia in adults with type 2 diabetes mellitus. Consideration should be paid to the most appropriate measure of muscle function in this population.
  • Informed consent in balloon Eustachian tuboplasty: a systematic review of possible complications and preventive measures

    Hussain, Syed Zohaib Maroof (2024-05)
    Objective: To systematically identify the complications associated with balloon Eustachian tuboplasty and their frequency of occurrence. This study will also highlight the measures that can be employed to avoid these complications and perform this procedure more safely. Methods: Systematically reviewed relevant papers published until January 2023. Each reference was checked and evaluated for any potential manuscripts. There was no registered protocol; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used. Results: Sixty-nine publications were found, from which 14 publications met our inclusion criteria: 2 randomised clinical trials, 5 retrospective studies, 2 systematic reviews, 2 case series and 3 case reports. Studies with balloon Eustachian tuboplasty procedure only were included, regardless of ethnicity, gender and age. All studies were excluded in which more than one procedure was performed. Conclusion: Balloon Eustachian tuboplasty is a relatively safe procedure with an overall complication risk of 1.66 per cent. Major complication rate was 0.43 per cent. Surgical emphysema was the most common, around 0.40 per cent.
  • Physiological variability during prehospital stroke care: which monitoring and interventions are used?

    Divall, Pip; Ince, Jonathan; Minhas, Jatinder; Robinson, Thompson (2024-04-15)
    Prehospital care is a fundamental component of stroke care that predominantly focuses on shortening the time between diagnosis and reaching definitive stroke management. With growing evidence of the physiological parameters affecting long-term patient outcomes, prehospital clinicians need to consider the balance between rapid transfer and increased physiological-parameter monitoring and intervention. This systematic review explores the existing literature on prehospital physiological monitoring and intervention to modify these parameters in stroke patients. The systematic review was registered on PROSPERO (CRD42022308991) and conducted across four databases with citation cascading. Based on the identified inclusion and exclusion criteria, 19 studies were retained for this review. The studies were classified into two themes: physiological-monitoring intervention and pharmacological-therapy intervention. A total of 14 included studies explored prehospital physiological monitoring. Elevated blood pressure was associated with increased hematoma volume in intracerebral hemorrhage and, in some reports, with increased rates of early neurological deterioration and prehospital neurological deterioration. A reduction in prehospital heart rate variability was associated with unfavorable clinical outcomes. Further, five of the included records investigated the delivery of pharmacological therapy in the prehospital environment for patients presenting with acute stroke. BP-lowering interventions were successfully demonstrated through three trials; however, evidence of their benefit to clinical outcomes is limited. Two studies investigating the use of oxygen and magnesium sulfate as neuroprotective agents did not demonstrate an improvement in patient's outcomes. This systematic review highlights the absence of continuous physiological parameter monitoring, investigates fundamental physiological parameters, and provides recommendations for future work, with the aim of improving stroke patient outcomes.
  • Facilitators and barriers to vaccination uptake in pregnancy: A qualitative systematic review

    Ravindran, Pahalavi (2024-04-19)
    Introduction: Vaccination during pregnancy protects both the mother and the foetus from vaccine-preventable diseases. However, uptake of the recommended vaccines (influenza, pertussis, COVID-19) by pregnant women remains low in Europe and the USA. Understanding the reasons for this is crucial to inform strategies to increase vaccination rates in pregnant women. This qualitative systematic review aimed to identify the barriers and facilitators to vaccination against influenza, pertussis/whooping cough and COVID-19 during pregnancy and identify possible strategies to increase vaccination rates. Methods: We conducted a comprehensive search of electronic databases, including Medline, PsycINFO, CINAHL, Web of Science, WHO database, Embase and grey literature to identify qualitative studies that explored barriers and facilitators to vaccine uptake among pregnant women (PROSPERO CRD42023399488). The search was limited to studies published between 2012 and 2022 conducted in high-income countries with established vaccination programmes during pregnancy. Studies were thematically analysed and underwent quality assessment using the Joanna Briggs Institute validated critical appraisal tool for qualitative research. Results: Out of 2681 articles screened, 28 studies (n = 1573 participants) were eligible for inclusion. Five overarching themes emerged relating to personal, provider and systemic factors. Barriers to vaccine uptake included concerns about vaccine safety and efficacy, lack of knowledge about vaccines' benefits and necessity, fear of adverse effects on the foetus or mother and low perception of disease severity. Facilitators included recommendations from trusted healthcare providers, easy access to vaccination, clear communication on the benefits and safety of vaccination, and positive social influences from family and friends. Strategies for increasing vaccination uptake included strong and proactive vaccine recommendations by trusted healthcare professionals, provision of vaccines during routine antenatal care, and clear and consistent communication about vaccines addressing pregnant women's concerns. Conclusion: This review highlights the need for interventions that address the identified barriers to vaccine uptake among pregnant women. Recommendation from a healthcare provider can play a significant role in promoting vaccine uptake, as can clear risk/benefit communication and convenient access to vaccination. Addressing concerns about vaccine safety and providing accurate information about vaccines is also important.
  • The paradox of haemodialysis: the lived experience of the clocked treatment of chronic illness

    Burton, James O; Hull, Katherine L (2024-03)
    Studies exploring the relationship between time and chronic illness have generally focused on measurable aspects of time, also known as linear time. Linear time follows a predictable, sequential order of past, present and future; measured using a clock and predicated on normative assumptions. Sociological concepts addressing lifecourse disruption following diagnosis of chronic illness have served to enhance the understanding of lived experience. To understand the nuanced relationship between time and chronic illness, however, requires further exploration. Here, we show how the implicit assumptions of linear time meet in tension with the lived experience of chronic illness. We draw on interviews and photovoice work with people with end-stage kidney disease in receipt of in-centre-daytime haemodialysis to show how the clocked treatment of chronic illness disrupts experiences of time. Drawing on concepts of 'crip' and 'chronic' time we argue that clocked treatment and the lived experience of chronic illness converge at a paradox whereby clocked treatment allows for the continuation of linear time yet limits freedom. We use the concept of 'crip time' to challenge the normative assumptions implicit within linear concepts of time and argue that the understanding of chronic illness and its treatment would benefit from a 'cripped' starting point.
  • Daylight photodynamic therapy as a treatment for actinic field change in patients diagnosed with oculocutaneous albinism in sub-Saharan Africa

    Roberts, Elizabeth; Sharp, Andrew; Twigg, Emily (2024-04-23)
    Background: Oculocutaneous albinism (OCA) is a genetically inherited condition, whereby melanin is reduced or absent in the skin. A lack of melanin predisposes people to actinic damage and skin malignancies. In Tanzania, a resource-limited country, the treatment of choice for precancerous skin lesions is cryotherapy. Objectives: To investigate whether daylight photodynamic therapy (dPDT) is a safe and well-tolerated treatment for actinic field change in the OCA population in Tanzania. Methods: Twelve participants with actinic damage were recruited from a Standing Voice skin surveillance clinic and treated with dPDT. Study participants completed tolerability and acceptability questionnaires at day 5 and 3 months after treatment. A dermatologist assessed their clinical response to dPDT at 3 months. Results: dPDT was well-tolerated and acceptable to the majority of patients. Actinic damage was reduced by 25-90%. No skin cancers developed during the treatment. Conclusions: This pilot study suggests that dPDT is a safe and tolerable treatment for actinic damage in people with OCA in Tanzania. Further work is required to compare the efficacy of dPDT against other topical therapies for actinic field change.
  • Real-world study of the concomitant use of biphasic insulin aspart 30/70 with GLP-1 receptor agonist versus first-generation basal insulin with GLP-1 receptor agonist in type 2 diabetes

    Davies, Melanie (2024-05)
    Aims: Combining insulin with a glucagon-like peptide-1 receptor agonist (GLP-1RA) to treat type 2 diabetes (T2D) is common. While many studies have investigated concomitant therapy with basal insulin+GLP-1RA, few have reported on premixed insulin+GLP-1RA. We aimed to address this gap using data from the Clinical Practice Research Datalink Aurum database in England. Methods: This retrospective cohort study with propensity score matching assessed glycaemic levels and other clinical outcomes in people with T2D, comparing biphasic insulin aspart 30/70 (BIAsp 30) + GLP-1RA with basal insulin (insulin detemir/glargine U100) + GLP-1RA (from 2006 to 2021). Results: In total, 4770 eligible people were identified; 1511 had a BIAsp 30 + GLP-1RA regimen and were propensity score-matched to an equal number receiving basal+GLP-1RA. There was no significant difference in glycated haemoglobin (HbA1c) reduction between cohorts at 6 months (p = 0.15), with a decrease of -1.07 (95% CI: -1.16; -0.98) %-points (-11.7 mmol/mol [95% CI: -12.7; -10.7]) in the BIAsp 30 + GLP-1RA cohort, versus -0.97 (95% CI: -1.07; -0.88) %-points (-10.6 mmol/mol [95% CI: -11.7; -9.6]) in the basal+GLP-1RA cohort. Body mass index (BMI) decreased by -0.35 kg/m2 (95% CI: -0.52;-0.18) at 6 months with BIAsp 30 + GLP-1RA, versus -0.72 kg/m2 (95% CI: -0.90;-0.54) with basal+GLP-1RA (p = 0.003). BMI was influenced by the initiation sequence of GLP-1RA in relation to insulin (p < 0.0001). Hypoglycaemia rates were low and not significantly different between cohorts. Conclusions: Combining BIAsp 30 + GLP-1RA provides glycaemic control with no significant difference to that of propensity score-matched people receiving basal insulin+GLP-1RA, with no increase in hypoglycaemia risk or weight gain.
  • Non-pharmacological interventions to improve cardiovascular risk factors in people with diabetic foot disease: A systematic review and meta-analysis

    Davies, Melanie; Webb, David (2024-03)
    Cardiovascular disease (CVD) risk in those with diabetic foot disease is very high. Non-pharmacological interventions may improve this risk, though no previous evidence synthesis has been completed. This systematic review aimed to investigate the impact of non-pharmacological interventions on CVD risk factors in diabetic ulcer disease. Multiple databases and trials registers were searched from inception to December 6th 2023. We included reports of randomised controlled trials investigating the impact of non-pharmacological interventions on cardiovascular risk in those with type 1 or type 2 diabetes and current or previous diabetic foot disease. Twenty studies were included. Extracted data included: study design and setting; participant sociodemographic factors; and change in cardiovascular risk factors. Data were synthesised using random effects meta-analyses and narrative syntheses. Interventions included nutritional supplementation, collaborative care, hyperbaric oxygen therapy, patient education, nurse-led intervention, self-management, family support, relaxation and exercise, over a median duration of 12 weeks. Significant post-intervention changes were observed in fasting plasma glucose, serum insulin levels, insulin sensitivity and resistance, glycated haemoglobin, triglycerides, total cholesterol, low-density lipoprotein-cholesterol and C-reactive protein. No effects were detected in very low- or high-density lipoprotein-cholesterol or body mass index. Non-pharmacological interventions show promise in improving CVD risk in diabetic foot disease.
  • Emergency department discharge practices for children with acute wheeze and asthma: a survey of discharge practice and review of safety netting instructions in the UK and Ireland

    Roland, Damian (2024-04-16)
    Objective: Recovery from acute wheeze and asthma attacks should be supported with safety netting, including treatment advice. We evaluated emergency department (ED) discharge practices for acute childhood wheeze/asthma attacks to describe variation in safety netting and recovery bronchodilator dosing. Design: Two-phase study between June 2020 and September 2021, comprising (1) Departmental discharge practice survey, and (2) Analysis of written discharge instructions for caregivers. Setting: Secondary and tertiary EDs in rural and urban settings, from Paediatric Emergency Research in the UK and Ireland (PERUKI). Main outcome measures: Describe practice and variation in discharge advice, treatment recommendations and safety netting provision. Results: Of 66/71 (93%) participating sites, 62/66 (93.9%) reported providing written safety netting information. 52/66 (78.8%) 'nearly always' assessed inhaler/spacer technique; routine medication review (21/66; 31.8%) and adherence (16/66; 21.4%) were less frequent. In phase II, 61/66 (92.4%) submitted their discharge documents; 50/66 (81.9%) included bronchodilator plans. 11/66 (18.0%) provided Personalised Asthma Action Plans as sole discharge information. 45/50 (90%) provided 'fixed' bronchodilator dosing regimes; dose tapering was common (38/50; 76.0%). Median starting dose was 10 puffs 4 hourly (27/50, 54.0%); median duration was 4 days (29/50, 58.0%). 13/61 (21.3%) did not provide bronchodilator advice for acute deterioration; where provided, 42/48 (87.5%) recommended 10 puffs immediately. Subsequent dosages varied considerably. Common red flags included inability to speak (52/61, 85.2%), inhalers not lasting 4 hours (51/61, 83.6%) and respiratory distress (49/61, 80.3%). Conclusions: There is variation in bronchodilator dosing and safety netting content for recovery following acute wheeze and asthma attacks. This reflects a lack of evidence, affirming need for further multicentre studies regarding bronchodilator recovery strategies and optimal safety netting advice. Keywords: Child Health; Paediatric Emergency Medicine; Paediatrics; Respiratory Medicine.

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