Open access

A practical evidence-based approach to management of type 2 diabetes in children and young people (CYP): UK consensus (2024)

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Type of publication:
Journal article

Author(s):
White, Billy; Ng, S M; Agwu, J C; Barrett, T G; Birchmore, N; Kershaw, M; Drew, J; Kavvoura, F; Law, J; Moudiotis, C; Procter, E; Paul, P; Regan, F; Reilly, P; Sachdev, P; *Sakremath, R; Semple, C; Sharples, K; Skae, M; Timmis, A; Williams, E; Wright, N; Soni, A.

Citation:
BMC Medicine. 22(1):144, 2024 Apr 02.

Abstract:
BACKGROUND: Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes. METHODS: Multidisciplinary professionals from The Association of Children's Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. RESULTS AND DISCUSSION: Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events. CONCLUSIONS: This evidence-based guideline aims to provide a practical approach in managing this condition in the UK.

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Association of day-case rates with post COVID-19 recovery of elective laparoscopic cholecystectomy activity across England (2024)

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Type of publication:
Journal article

Author(s):
Ayyaz, F M; Joyner, J; *Cheetham, M; Briggs, Twr; Gray, W K.

Citation:
Annals of the Royal College of Surgeons of England. 2024 Apr 02.

Abstract:
INTRODUCTION: The aim of this study was to investigate the safety of day-case laparoscopic cholecystectomy, and the association between day-case rates and, post the COVID-19 pandemic, recovery of activity to prepandemic levels for integrated care boards (ICBs) in England. METHODS: This was a retrospective observational study of the Hospital Episodes Statistics (HES) data set. Elective laparoscopic
cholecystectomies for the period 1 January 2019 to 31 December 2022 were identified. Activity levels for 2022 were compared with those for the whole of 2019 (baseline). Day-case activity was identified where the length of stay recorded in the HES was zero days. RESULTS: Data were available for 184,252 patients across the 42 ICBs in England, of which 120,408 (65.3%) were day-case procedures. By December
2022, activity levels for the whole of England had returned to 88.2% of prepandemic levels. The South West region stood out as having recovered activity levels to the greatest extent, with activity at 97.3% of
prepandemic levels during 2022. The South West also had the highest postpandemic day-case rate at 74.9% of all patients seen as a day-case during 2022; this compares with an England average of 65.3%. At an ICB level, there was a significant correlation between day-case rates and postpandemic activity levels (r = 0.362, p = 0.019). There was no strong or consistent evidence that day-case surgery had poorer patient outcomes than inpatient surgery. CONCLUSIONS: Recovery of elective laparoscopic cholecystectomy activity has been better in South West England than in other regions. Increasing day-case rates may be important if ICBs in other regions are to increase activity levels up to and beyond prepandemic levels.

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British Oncology Pharmacy Association Delphi Consensus Guidelines: co-infusion of trometamol-containing calcium folinate (Leucovorin) with Systemic Anti-Cancer Treatments (2024)

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Type of publication:
Journal article

Author(s):
Polwart C.; Root T.; Tezcan S.; Meehan S.; Wetherill B.; Waterson C.; *Burnett B.; Chauhan R.; Al-Modaris I.; Walters-Davies R.

Citation:
medRxiv. (no pagination), 2024. Date of Publication: 11 Feb 2024.

Abstract:
Drug stability and compatibility are critical factors influencing cost and logistics of treatment delivery, therapeutic effectiveness, and patient safety. This is particularly significant in the realm of cancer chemotherapeutics, where stability and compatibility studies play a vital role in ensuring rational and safe medicine administration. Oxaliplatin, fluorouracil, and irinotecan, commonly used in various combination for gastrointestinal cancers, are complemented by co-administration of folinic acid in certain protocols. Notably, some folinic acid preparations include trometamol as an excipient, potentially impacting the stability of the chemotherapeutic agents if infused concomitantly. This study seeks to establish guidelines for oncology multidisciplinary teams, addressing potential risks associated with the combination of trometamol-containing folinic acid and chemotherapeutics. To achieve this, a quantitative questionnaire was distributed to members of the British Oncology Pharmacy Association (BOPA) and non-BOPA members through an online survey. Nineteen healthcare professionals with oncology experience, comprising 18 pharmacists and 1 nurse, completed the questionnaires. Each participant rated the validity and clarity of statements on a 5-point scale. The Delphi process concluded after the fourth round, consolidating the findings and recommendations from the multidisciplinary team. Twelve recommendations for safe practice have been made.

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Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance (2024)

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Type of publication:
Journal article

Author(s):
Lauri, Chiara; Noriega-Alvarez, Edel; *Chakravartty, Riddhika M; Gheysens, Olivier; Glaudemans, Andor W J M; Slart, Riemer H J A; Kwee, Thomas C; Lecouvet, Frederic; Panagiotidis, Emmanouil; Zhang-Yin, Jules; Martinez, Jose Luis Lazaro; Lipsky, Benjamin A; Uccioli, Luigi; Signore, Alberto.

Citation:
European Journal of Nuclear Medicine & Molecular Imaging. 2024 Mar 27.

Abstract:
PURPOSE: Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings. METHODS: This working group includes 8 nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), 3 radiologists and 3 clinicians (one diabetologist, one podiatrist and one infectious diseases specialist) selected for their expertise in diabetic foot. The latter members formulated some clinical questions that are not completely covered by current guidelines. These questions were converted into statements and addressed through a systematic analysis of available literature by using the PICO (Population/Problem-Intervention/Indicator-Comparator-Outcome) strategy. Each consensus statement was scored for level of evidence and for recommendation grade, according to the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria. RESULTS: Nine clinical questions were formulated by clinicians and used to provide 7 evidence-based recommendations: (1) A patient with a positive probe-to-bone test, positive plain X-rays and elevated ESR should be treated for presumptive osteomyelitis (OM). (2) Advanced imaging with MRI and WBC scintigraphy, or [18F]FDG PET/CT, should be considered when it is needed to better evaluate the location, extent or severity of the infection, in order to plan more tailored treatment. (3) In a patient with suspected OM, positive PTB test but negative plain X-rays, advanced imaging with MRI or WBC scintigraphy + SPECT/CT, or with [18F]FDG PET/CT, is needed to accurately assess the extent of the infection. (4) There are no evidence-based data to definitively prefer one imaging modality over the others for detecting OM or STI in fore- mid- and hind-foot. MRI is generally the first advanced imaging modality to be performed. In case of equivocal results, radiolabelled WBC imaging or [18F]FDG PET/CT should be used to detect OM or STI. (5) MRI is the method of choice for diagnosing or excluding Charcot neuro-osteoarthropathy; [18F]FDG PET/CT can be used as an alternative. (6) If assessing whether a patient with a Charcot foot has a superimposed infection, however, WBC scintigraphy may be more accurate than [18F]FDG PET/CT in differentiating OM from Charcot arthropathy. (7) Whenever possible, microbiological or histological assessment should be performed to confirm the diagnosis. (8) Consider appealing to an additional imaging modality in a patient with persisting clinical suspicion of infection, but negative imaging. CONCLUSION: These practical recommendations highlight, and should assist clinicians in understanding, the role of imaging in the diagnostic workup of diabetic foot complications.

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Best practice for embryology staffing in HFEA licensed assisted conception centres-guidance from Association of Reproductive & Clinical Scientists (2024)

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Type of publication:
Journal article

Author(s):
*Kasraie, Jason; Kennedy, Hannah

Citation:
Human Fertility. 27(1):2322729, 2024 Dec.

Abstract:
The Association of Reproductive and Clinical Scientists (ARCS) has long promoted the importance of externally accredited training and assessment of scientific staff within assisted conception centres to ensure professional registration and relevant training at all levels. This not only gives scientific staff the opportunity to empower themselves but also acts to ensure assisted conception centres maintain the highest standards of care and quality for patients whilst meeting HFEA requirements for staffing and training. It also provides assurance to patients that treatment is being delivered by highly trained and competent staff. Clinical embryology practice requires intense concentration, with increasingly complex treatment plans and options coupled with the ever-present consequences of clinical error at the forefront of practitioners' minds, exhaustion and burn out are very real risks. Overloading embryology teams is likely to lead to increased error rates and serious incidents. This guideline aims to bring the sector in line with other Clinical Science specialities to optimise patient care, increase safety, reduce risk (including the risk of legal action against centres and individuals), ensure the use of recognised job titles with appropriate levels of remuneration, and provide centres with a template to work towards for appropriate levels of scientific staffing.

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A genome-wide meta-analysis of palmoplantar pustulosis implicates Th2 responses and cigarette smoking in disease pathogenesis (2024)

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Type of publication:
Journal article

Author(s):
Hernandez-Cordero A.; Thomas L.; Smail A.; Lim Z.Q.; Saklatvala J.R.; Chung R.; Curtis C.J.; Baum P.; Visvanathan S.; Burden A.D.; Cooper H.L.; Dunnill G.; Griffiths C.E.M.; Levell N.J.; Parslew R.; Reynolds N.J.; Wahie S.; Warren R.B.; Wright A.; Simpson M.; Hveem K.; Barker J.N.; Dand N.; Loset M.; Smith C.H.; Capon F.; Abraham T.; Ali M.; August S.; Baudry D.; Becher G.; Bewley A.; Brown V.; Cornelius V.; Ghaffar S.; Ingram J.; Kavakleiva S.; *Kelly S.; Khorshid M.; Lachmann H.; Ladoyanni E.; McAteer H.; McKenna J.; Meynell F.; Patel P.; Pink A.; Powell K.; Pushparajah A.; Sinclair C.; Wachsmuth R.;

Citation:
Journal of Allergy and Clinical Immunology. 2024 May 28:S0091-6749(24)00553-0 [epub ahead of print]

Abstract:
Background: Palmoplantar pustulosis (PPP) is an inflammatory skin disorder that mostly affects smokers and manifests with painful pustular eruptions on the palms and soles. While the disease can present with concurrent plaque psoriasis, TNF and IL-17/IL-23 inhibitors show limited efficacy. There is therefore a pressing need to uncover PPP disease drivers and therapeutic targets. Objective(s): To identify genetic determinants of PPP and investigate whether cigarette smoking contributes to disease pathogenesis. Method(s): We performed a genome-wide association meta-analysis of three North-European cohorts (n=1,456 PPP cases and 402,050 controls). We then used the scGWAS program to investigate the cell-type specificity of the resulting association signals. We undertook genetic correlation analyses to examine the similarities between PPP and other immune-mediated diseases. Finally, we applied Mendelian randomization to analyze the causal relationship between cigarette smoking and PPP. Result(s): We found that PPP is not associated with the main genetic determinants of plaque psoriasis. Conversely, we identified genome-wide significant associations with the FCGR3A/FCGR3B and CCHCR1 loci. We also observed 13 suggestive (P<5X10-6) susceptibility regions, including the IL4/IL13 interval. Accordingly, we demonstrated a significant genetic correlation between PPP and Th2-mediated diseases like atopic dermatitis and ulcerative colitis. We also found that genes mapping to PPP-associated intervals were preferentially expressed in dendritic cells and enriched for T-cell activation pathways. Finally, we undertook a Mendelian randomization analysis, which supported a causal role of cigarette smoking in PPP. Conclusion(s): The first genome-wide association study of PPP points to a pathogenic role for deregulated Th2 responses and cigarette smoking.

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Cardiac rehabilitation for children and young people (CardioActive): protocol for a single-blind randomised feasibility and acceptability study of a centre-based cardiac rehabilitation programme versus usual care in 11-16 years with heart conditions (2024)

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Type of publication:
Journal article

Author(s):
Capobianco, Lora; Hann, Mark; McManus, Emma; Peters, Sarah; Doherty, Patrick Joseph; Ciotti, Giovanna; *Murray, Joanne; Wells, Adrian.

Citation:
BMJ Open. 14(2):e077958, 2024 Feb 24.

Abstract:
BACKGROUND: Congenital heart conditions are among the most common non-communicable diseases in children and young people (CYP), affecting 13.9 million CYP globally. While survival rates are increasing, support for young people adjusting to life with a heart condition is lacking. Furthermore, one in three CYP with heart conditions also experiences anxiety, depression or adjustment disorder, for which little support is offered. While adults are offered cardiac rehabilitation (CR) to support their mental and physical health, this is not offered for CYP.One way to overcome this is to evaluate a CR programme comprising exercise with
mental health support (CardioActive; CA) for CYP with heart conditions. The exercise and mental health components are informed by the metacognitive model, which has been shown to be effective in treating anxiety and depression in CYP and associated with improving psychological outcomes in adult CR. METHOD AND ANALYSIS: The study is a single-blind parallel randomised feasibility trial comparing a CR programme (CA) plus usual care against usual care alone with 100 CYP (50 per arm) aged 11-16 diagnosed with a heart condition. CA will include six group exercise, lifestyle and mental health modules. Usual care consists of routine outpatient management. Participants will be assessed at three time points: baseline, 3-month (post-treatment) and 6-month follow-up. Primary outcomes are feasibility and acceptability (ie, referral rates, recruitment and retention rates, attendance at the intervention, rate of return and level of completion of follow-up data). Coprimary symptom outcomes (Strength and Difficulties Questionnaire and Paediatric Quality of Life) and a range of secondary outcomes will be administered at each time point. A nested qualitative study will investigate CYP, parents and healthcare staff views of CR and its components, and staff's experience of delivering CA. Preliminary health economic data will be collected to inform future cost-effectiveness analyses. Descriptive data on study processes and clinical outcomes will be reported. Data analysis will follow intention to treat. Qualitative data will be analysed using thematic analysis and the theoretical framework of acceptability. ETHICS AND DISSEMINATION: Ethical approval was granted on 14 February 2023 by the Greater Manchester East Research Ethics Committee (22/NW/0367). The results will be disseminated through peer-reviewed journals, conference presentations and local dissemination. TRIAL REGISTRATION NUMBER: ISRCTN50031147; NCT05968521.

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A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial (2024)

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Type of publication:
Randomised controlled trial

Author(s):
Smith, Tim A D; West, Catharine M L; Joseph, Nuradh; Lane, Brian; Irlam-Jones, Joely; More, Elisabet; Mistry, Hitesh; Reeves, Kimberley J; Song, Yee Pei; Reardon, Mark; Hoskin, Peter J; Hussain, Syed A; *Denley, Helen; Hall, Emma; Porta, Nuria; Huddart, Robert A; James, Nick D; Choudhury, Ananya.

Citation:
EBioMedicine. 101:105032, 2024 Feb 21.

Abstract:
BACKGROUND: BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. METHODS: RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). PRIMARY ENDPOINT: invasive loco-regional control (ILRC); secondary overall survival. FINDINGS: Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99-1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82-2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99-2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28-1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7-119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07-15.5, p = 0.978) radiotherapy. INTERPRETATION: Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial.

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Rhabdomyolysis Following Prolonged Entrapment on a Fence: A Case Report (2024)

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Type of publication:
Journal article

Author(s):
*Nwaneri, Chukwuemeka; *Aboshehata, Ahmed M; *Marsh, Adrian R.

Citation:
Cureus. 16(1):e51954, 2024 Jan.

Abstract:
It is well documented that prolonged immobilization and heavy alcohol consumption can independently cause rhabdomyolysis; however, entrapment on a fence following alcohol consumption resulting in rhabdomyolysis without prolonged coma or seizures has not been reported. We report a case of a 25-year-old man who, following alcohol consumption, whilst attempting to climb a fence, became entrapped and desperately had to clinch on the fence with both forearms for over three hours, resulting in rhabdomyolysis. This case report highlights the importance of recognizing the potential complications associated with prolonged immobilization and the subsequent management of rhabdomyolysis.

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A UK prospective multicentre decision impact, decision conflict and economic evaluation of the 21-gene assay in women with node+ve, hormone receptor+ve, HER2-ve breast cancer (2024)

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Type of publication:
Journal article

Author(s):
Holt, Simon; Verrill, Mark; *Pettit, Laura; Rigg, Anna; Hickish, Tamas; Archer, Caroline; Dent, Jo; Dillon, Marianne; Nathan, Mark; Barthelmes, Ludger; Rehman, Shazza; Sharaiha, Yousef; Innis, Paige; Sai-Giridhar, Priya; Khawaja, Saira.

Citation:
British Journal of Cancer. 2024 Feb 02.

Abstract:
BACKGROUND: For a tumour profiling test to be of value, it needs to demonstrate that it is changing clinical decisions, improving clinical confidence, and of economic benefit. This trial evaluated the use of the Oncotype DX Breast Recurrence Score R assay against these criteria in 680 women with hormone receptor-positive (HR+), HER2-negative early breast cancer with 1-3 lymph nodes positive (LN+) in the UK National Health Service (NHS). METHODS: Prior to receipt of the Recurrence Score (RS) result, both the physician and the patient were asked to state their preference for or against chemotherapy and their level of confidence on a scale of 1-5. Following receipt of the RS result, the physician and patient were asked to make a final decision regarding chemotherapy and record their post-test level of confidence. RESULTS: Receipt of the RS result led to a 51.5% (95% CI, 47.2-55.8%) reduction in chemotherapy, significantly increased the relative and absolute confidence for both physicians and patients and led to an estimated saving to the NHS of 787 per patient. CONCLUSION: The use of the Oncotype DX assay fulfils the criteria of changing clinical decisions, improving confidence and saving money.

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