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    Uterine artery embolization vs myomectomy for the management of women with uterine leiomyomas: a systematic review and meta-analysis

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    OBJECTIVE: This study aimed to investigate whether uterine artery embolization offers a better quality of life than myomectomy in premenopausal women diagnosed with leiomyomas of the uterus. DATA SOURCES: A literature search was performed using the electronic databases of PubMed and Cochrane Central Register of Controlled Trials from inception to January 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing uterine artery embolization with myomectomy in women of premenopausal age suffering from uterine leiomyomas were considered. METHODS: The primary outcome was quality of life. The secondary outcomes were reintervention rate and timing, successful pregnancy, stillbirth and miscarriage, cesarean delivery on delivery, and perioperative morbidity. Moreover, time-to-event and standard pairwise meta-analyses were performed, as appropriate. The certainty of the evidence was assessed in line with the Grading of Recommendations, Assessment, Development, and Evaluations methodology. RESULTS: A total of 6 randomized controlled trials met our inclusion criteria. The meta-analysis suggested little to no difference in terms of quality of life between uterine artery embolization and myomectomy (standard mean difference, 0.05; 95% confidence interval, -0.38 to 0.48; I(2)=92%; very low certainty of evidence). Sensitivity analysis, including randomized controlled trials, which included solely myomectomy procedures in the control arm, demonstrated better quality of life for women treated with myomectomy (standard mean difference, -0.32; 95% confidence interval, -0.49 to -0.15; I(2)=15%). Concerning reintervention, myomectomy was likely associated with a decreased risk of future reintervention (risk ratio, 0.32; 95% confidence interval, 0.15-0.69; I(2)=60%; low certainty of evidence) and a more prolonged time interval since a potential reintervention because of recurrence than uterine artery embolization (hazard ratio, 0.41; 95% confidence interval, 0.22-0.77; I(2)=77%; low certainty of evidence). No difference was found between the 2 interventions concerning severe perioperative adverse events (relative risk, 4.13; 95% confidence interval, 0.44-39.20; I(2)=0%; low certainty of evidence). CONCLUSION: Uterine artery embolization is likely associated with increased reintervention rates and less time to reintervention compared with myomectomy in premenopausal women diagnosed with uterine leiomyomas. Evidence suggests no difference between the 2 interventions regarding perioperative morbidity. Uterine artery embolization may exert no effect on quality of life and successful pregnancy; however, the evidence is very uncertain.published versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

    CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom

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    BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.Accepted version (6 month embargo), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

    New AI model for neoplasia detection and characterisation in inflammatory bowel disease

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    Published version, accepted version, submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

    Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK

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    BACKGROUND: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting. METHODS: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey. RESULTS: 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD. CONCLUSION: We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting.published versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

    Psychosocial Health Among Young Adults With Kidney Failure: A Longitudinal Follow-up of the SPEAK (Surveying Patients Experiencing Young Adult Kidney Failure) Study

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    RATIONALE & OBJECTIVE: There have been no longitudinal studies examining the evolution of psychosocial health of young adults with kidney failure as they age. We aimed to address this in the Surveying Patients Experiencing Young Adult Kidney Failure-2 (SPEAK-2) study. STUDY DESIGN: 5-year follow-up longitudinal survey of the original SPEAK cohort. SETTING & PARTICIPANTS: 16- to 30-year-olds in the UK receiving kidney replacement therapy (KRT) between 2015 and 2017 who participated in the SPEAK study. EXPOSURE: Kidney failure and KRT modality. OUTCOMES: Psychosocial health and lifestyle behaviors. ANALYTICAL APPROACH: Within-cohort changes in psychosocial health were analyzed using the paired t test, Wilcoxon signed-rank test and McNemar's test. We compared responses to the age-matched population and examined the impact of changes in KRT modality on psychological health using linear regression for continuous outcome variables as well as logistic, ordered logistic and multinomial logistic regression for binary, ordered categorical and unordered categorical variables, respectively. RESULTS: We obtained 158 survey responses; 129 had previously responded to SPEAK. Of these, 90% had a kidney transplant. Compared to the general population, respondents were less likely to be married or have children and were more likely to be living with their parents. Respondents had nearly 15 times greater odds of being unable to work due to health (odds ratio [OR] = 14.41; 95% confidence interval [CI], 8.0-26.01; P < 0.001). Respondents had poorer quality of life and mental wellbeing and were more likely to report psychological problems (OR = 5.37; 95% CI, 3.45-8.35; P < 0.001). A negative association between remaining on or moving to dialysis and psychosocial health was observed, although this was attenuated when controlling for the psychosocial state in SPEAK. LIMITATIONS: Low response rate resulting in imprecise and potentially biased estimates and impact of COVID-19 pandemic while survey was active on psychosocial health. CONCLUSIONS: Young adults with kidney failure have persistent poorer psychosocial health compared to their healthy peers as they age. Our findings also suggest a potential causal relationship between KRT modality and psychosocial health. The psychosocial impact of kidney failure in young adults is implicated in the observed higher risk of transplant loss and death. The Surveying Patients Experiencing Young Adult Kidney Failure (SPEAK) study investigated the psychosocial health of young adults (16-30 years) in the UK receiving kidney replacement therapy and found they had poorer outcomes than the age-matched general population. In this 5-year follow-up study, we observed that as this group matured, they lagged behind their peers in terms of both lifecourse and psychological outcomes. Dialysis recipients had poorer psychosocial health compared to transplant recipients. This emphasizes the lasting impact of kidney failure on young adults' psychosocial health, particularly for those receiving dialysis, highlighting the need for better mental health support and treatment. engUnknownSupports Open Acces

    Progressive unilateral facial asymmetry in a young girl

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    Published version, accepted version (12 months embrago)The article is available via Open Access. Click on the 'Additional link' above to access the full-text

    New year, new beginning? The death of the single institution case series

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    Accepted version (12 month embargo)RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted

    REPAIRS Delphi: A UK and Ireland Consensus Statement on the Management of Infected Arterial Pseudoaneurysms Secondary to Groin Injecting Drug Use

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    OBJECTIVE: Consensus guidelines on the optimal management of infected arterial pseudoaneurysms secondary to groin injecting drug use are lacking. This pathology is a problem in the UK and globally, yet operative management options remain contentious. This study was designed to establish consensus to promote better management of these patients, drawing on the expert experience of those in a location with a high prevalence of illicit drug use. METHODS: A three round modified Delphi was undertaken, systematically surveying consultant vascular surgeons in the UK and Ireland using an online platform. Seventy five vascular surgery units were invited to participate, with one consultant providing the unit consensus practice. Round one responses were thematically analysed to generate statements for round two. These statements were evaluated by participants using a five point Likert scale. Consensus was achieved at a threshold of 70% or more agreement or disagreement. Those statements not reaching consensus were assessed and modified for round three. The results of the Delphi process constituted the consensus statement. RESULTS: Round one received 64 (86%) responses, round two 59 (79%) responses, and round three 62 (83%) responses; 73 (97%) of 75 units contributed. Round two comprised 150 statements and round three 24 statements. Ninety one statements achieved consensus agreement and 15 consensus disagreement. The Delphi statements covered sequential management of these patients from diagnosis and imaging, antibiotics and microbiology, surgical approach, wound management, follow up, and additional considerations. Pre-operative imaging achieved consensus agreement (97%), with computerised tomography angiography being the modality of choice (97%). Ligation and debridement without arterial reconstruction was the preferred approach at initial surgical intervention (89%). Multidisciplinary management, ensuring holistic care and access to substance use services, also gained consensus agreement. CONCLUSION: This comprehensive consensus statement provides a strong insight into the standard of care for these patients.Published version, accepted version (12 months embrago)Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text

    Cost-effectiveness of surgery for degenerative cervical myelopathy in the United Kingdom

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    PURPOSE: Degenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord dysfunction worldwide, for which surgery is the mainstay of treatment. At present, there is limited literature on the costs associated with the surgical management of DCM, and none from the United Kingdom (UK). This study aimed to evaluate the cost-effectiveness of DCM surgery within the National Health Service, UK. MATERIALS AND METHODS: Incidence of DCM was identified from the Hospital Episode Statistics (HES) database for a single year using five ICD-10 diagnostic codes to represent DCM. Health Resource Group (HRG) data was used to estimate the mean incremental surgery (treatment) costs compared to non-surgical care, and the incremental effect (quality adjusted life year (QALY) gain) was based on data from a previous study. A cost per QALY value of <£30,000/QALY (GBP) was considered acceptable and cost-effective, as per the National Institute for Health and Clinical Excellence (NICE) guidance. A sensitivity analysis was undertaken (±5%, ±10% and ±20%) to account for variance in both the cost of admission and QALY gain. RESULTS: The total number of admissions for DCM in 2018 was 4,218. Mean age was 62 years, with 54% of admissions being of working age (18-65 years). The overall estimated cost of admissions for DCM was £38,871,534 for the year. The mean incremental (per patient) cost of surgical management of DCM was estimated to be £9,216 (ranged £2,358 to £9,304), with a QALY gain of 0.64, giving an estimated cost per QALY value of £14,399/QALY. Varying the QALY gain by ±20%, resulted in cost/QALY figures between £12,000 (+20%) and £17,999 (-20%). CONCLUSIONS: Surgery is estimated to be a cost-effective treatment of DCM amongst the UK population.Published version, accepted version (12 month embargo), submitted versionNot hel

    Developmentally dynamic changes in DNA methylation in the human pancreas

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    Development of the human pancreas requires the precise temporal control of gene expression via epigenetic mechanisms and the binding of key transcription factors. We quantified genome-wide patterns of DNA methylation in human fetal pancreatic samples from donors aged 6 to 21 post-conception weeks. We found dramatic changes in DNA methylation across pancreas development, with > 21% of sites characterized as developmental differentially methylated positions (dDMPs) including many annotated to genes associated with monogenic diabetes. An analysis of DNA methylation in postnatal pancreas tissue showed that the dramatic temporal changes in DNA methylation occurring in the developing pancreas are largely limited to the prenatal period. Significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small proportion of sites showing sex-specific DNA methylation trajectories across pancreas development. Pancreas dDMPs were not distributed equally across the genome and were depleted in regulatory domains characterized by open chromatin and the binding of known pancreatic development transcription factors. Finally, we compared our pancreas dDMPs to previous findings from the human brain, identifying evidence for tissue-specific developmental changes in DNA methylation. This study represents the first systematic exploration of DNA methylation patterns during human fetal pancreas development and confirms the prenatal period as a time of major epigenomic plasticity.Published version, accepted versionJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text

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