Royal Devon and Exeter Research Repository
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Questioning the role of HIPEC in patients with granulosa cell ovarian tumours
No full textJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo
A practical evidence-based approach to management of type 2 diabetes in children and young people (CYP): UK consensus
No full textBACKGROUND: 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.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
A Systematic Review of Systematic Reviews on the Use of Aromatase Inhibitors for the Treatment of Endometriosis: The Evidence to Date
No full textEndometriosis is a chronic gynecologic condition that affects around 6-10% of reproductive age women. This clinical entity is characterized with pelvic pain, dysmenorrhea, dyspareunia, and infertility which are the most often presenting symptoms. Aromatase P450 is the key enzyme for ovarian estrogen biosynthesis and there is evidence that endometriotic lesions express aromatase and are able to synthesize their own estrogens. Aromatase inhibitors (AIs) are potent drugs that suppress the estrogen synthesis via suppression of aromatase. We performed a systematic review of systematic reviews and narrative reviews on the use of aromatase inhibitors in the medical management of endometriosis. We searched: PubMed (1950-2022), Google Scholar (2004-2022), Cochrane Library (2010-2022) and Researchgate (2010-2022). The search included the following medical subject headings (MeSH) or keywords: Aromatase Inhibitors" AND "Endometriosis" AND "Systematic reviews" OR "Systematic review" AND "Reviews" OR "Reviews" AND "Endometriosis". The electronic database search yielded initially 12,106 studies from the different databases. Further assessment of the studies resulted in exclusion of (n = 12,015) studies due to duplicates and irrelevance; Finally, 24 studies were selected for inclusion, 5 were Systematic reviews and 19 were Narrative reviews. The 5 systematic reviews were assessed by AMSTAR-2 criteria and were found to have low quality. Narrative reviews were assessed with SANRA criteria and were found to have high-quality aromatase inhibitors are potent drugs that can manage the endometriosis-related symptoms in cases where initial medical management has failed to show positive results. However, their use is limited by the adverse effects that are linked with menopausal symptoms. aromatase inhibitors can be administered as an alternative treatment in patients. Future studies with randomized design are required to reach safer conclusions and further investigation. These studies should define the therapeutic dose, new add-back therapy modalities. Future directions should examine the most-appropriate way of administration and the duration of therapy."Published version, accepted version, submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Improved fistula plug outcome depends on the type of plug: a single-centre retrospective study
No full textAIM: Fistula-in-ano is a common condition that is potentially difficult to treat. In recent years 'sphincter-sparing' procedures have increased in popularity due to the lower rates of reported complications, such as incontinence. One such treatment is the fistula plug, which has seen varied success compared with other techniques. There are currently several plugs on the market and it is possible that difference in outcomes could be linked to the type of plug used. The aim of this study was to compare healing and complication rates between two fistula plugs in a single tertiary referral centre in the UK. METHOD: We conducted a single-centre retrospective analysis of all patients over the age of 18 years who underwent elective fistula plug insertion, with two different fistula plugs over a 13-year period. RESULTS: A total of 113 patients underwent fistula plug insertion (plug A n = 90; plug B n = 23). Plug B had been on the market for the final 4 years of the study period, hence the differing patient numbers. There was no difference in patient demographics, fistula type or aetiology of the fistula between the two plugs. Plug B had a significantly higher fistula healing rate compared with plug A (56.5% vs. 12.2%; p < 0.005). A quarter of all patients experienced a complication, 93% being those who had fistula plug A inserted. The most common complication was extrusion of the plug within 72 h of insertion. CONCLUSION: This study demonstrated significantly different outcomes according to the type of fistula plug used. Whilst current randomized controlled trials have not found a significant difference in healing rates when comparing one type of fistula plug to other treatment modalities, this study suggests that plug type may influence efficacy.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
Achieving Target Cemented Femoral Stem Anteversion Using a 3-Dimensional Model
No full textBACKGROUND: Total hip arthroplasty aims to provide patients with a pain-free and stable hip joint through optimization of biomechanics such as femoral anteversion. There are studies evaluating the limits of cementless stem version, however, none assessing the range of version achieved by a cemented collarless stem. A computed tomography (CT)-based study was performed, utilizing a contemporary robotic planning platform to assess the amount of rotation afforded by a cemented collarless stem, whilst maintaining native biomechanics. METHODS: The study utilized 36 cadaveric hips. All had CT scans of the pelvis and hip joints. The CT scans were then loaded into a contemporary robotic planning platform. A stem that restored the patients native femoral offset was selected and positioned in the virtual femur. The stem was rotated while checking for cortical contact at the level of the neck cut. Cortical contact was regarded as the rotation limit, assessed in both anteversion and retroversion. Target range for stem anteversion was 10°-20°. Failure to achieve target version triggered a sequence of adjustments to simulate surgical decisions. RESULTS: Native femoral offset and target version range was obtained in 29 of 36 (80.5%) cases. Following an adjustment sequence, 4 further stems achieved target anteversion with a compromise in offset of 2.3 mm. Overall 33 of 36 (91.7%) stems achieved the target anteversion range of 10°-20°. CONCLUSIONS: Target femoral stem anteversion can be achieved using a cemented, collarless stem in a CT-based 3-dimensional model in 80.5% of hips. With a small compromise in offset (mean 2.3 mm), this can be increased to 91.7%.UnknownThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Widespread genomic influences on phenotype in Dravet syndrome, a 'monogenic' condition
No full textDravet syndrome is an archetypal rare severe epilepsy, considered 'monogenic', typically caused by loss-of-function SCN1A variants. Despite a recognizable core phenotype, its marked phenotypic heterogeneity is incompletely explained by differences in the causal SCN1A variant or clinical factors. In 34 adults with SCN1A-related Dravet syndrome, we show additional genomic variation beyond SCN1A contributes to phenotype and its diversity, with an excess of rare variants in epilepsy-related genes as a set and examples of blended phenotypes, including one individual with an ultra-rare DEPDC5 variant and focal cortical dysplasia. The polygenic risk score for intelligence was lower, and for longevity, higher, in Dravet syndrome than in epilepsy controls. The causal, major-effect, SCN1A variant may need to act against a broadly compromised genomic background to generate the full Dravet syndrome phenotype, whilst genomic resilience may help to ameliorate the risk of premature mortality in adult Dravet syndrome survivors.Published version, accepted version (12 month embargo), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Patient preference for second- and third-line therapies in type 2 diabetes: a prespecified secondary endpoint of the TriMaster study
No full textPatient preference is very important for medication selection in chronic medical conditions, like type 2 diabetes, where there are many different drugs available. Patient preference balances potential efficacy with potential side effects. As both aspects of drug response can vary markedly between individuals, this decision could be informed by the patient personally experiencing the alternative medications, as occurs in a crossover trial. In the TriMaster (NCT02653209, ISRCTN12039221), randomized double-blind, three-way crossover trial patients received three different second- or third-line once-daily type 2 diabetes glucose-lowering drugs (pioglitazone 30 mg, sitagliptin 100 mg and canagliflozin 100 mg). As part of a prespecified secondary endpoint, we examined patients' drug preference after they had tried all three drugs. In total, 448 participants were treated with all three drugs which overall showed similar glycemic control (HbA1c on pioglitazone 59.5 sitagliptin 59.9, canagliflozin 60.5 mmol mol(-1), P = 0.19). In total, 115 patients (25%) preferred pioglitazone, 158 patients (35%) sitagliptin and 175 patients (38%) canagliflozin. The drug preferred by individual patients was associated with a lower HbA1c (mean: 4.6; 95% CI: 3.9, 5.3) mmol mol(-1) lower versus nonpreferred) and fewer side effects (mean: 0.50; 95% CI: 0.35, 0.64) fewer side effects versus nonpreferred). Allocating therapy based on the individually preferred drugs, rather than allocating all patients the overall most preferred drug (canagliflozin), would result in more patients achieving the lowest HbA1c for them (70% versus 30%) and the fewest side effects (67% versus 50%). When precision approaches do not predict a clear optimal therapy for an individual, allowing patients to try potential suitable medications before they choose long-term therapy could be a practical alternative to optimizing treatment for type 2 diabetes.Accepted version (6 months embargo), submitted versionRD&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
Essential heating and wiping time for preventing of laparoscopic lens fogging
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Moving forward together: collaborative landscapes of research in idiopathic inflammatory myopathies and calcinosis
No full textPublished version, accepted version (12 month embargo), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III)
No full textBACKGROUND: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. METHODS: Prospective observational multicentre study. All new referrals with diagnosis of GO within September-December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. RESULTS: Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0-350) vs 6 (0-552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). CONCLUSION: GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.UnknownRD&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