Royal Devon and Exeter Research Repository
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Parameters affecting outcomes of transumbilical and periumbilical median incisions in ovarian cancer patients
No full textunknownThis article is freely available online. Click on the 'Additional Link' above to access the full-text via the publisher's site
Successful treatment of ureteral-stent-related fungal ball using fluconazole instillation through a nephrostomy tube
No full textThe kidneys are the most common solid organ to be infected by Candida sp. And may occur due to hematogenous spread, ascending infection, or with the presence of stent and nephrostomy tubes. Evidence for treatment is limited to case reports. We successfully cleared a candida infection of a ureteric stent in a 35-year-old diabetic gentleman by instilling 300 mg of fluconazole in 500 mL of normal saline over 8 hours once daily for 7 days via the nephrostomy tube.Published version, accepted version, submitted versionSupports Open Acces
Increased rates of chronic physical health conditions across all organ systems in autistic adolescents and adults
No full textBACKGROUND: The poorer physical health of autistic adults compared to non-autistic adults has been highlighted by several epidemiological studies. However, research has so far been limited to specific geographical areas and has primarily focused on young autistic individuals (aged 35 years and younger). Recent studies indicate a higher rate of mortality in autistic people, as well as poorer quality of self-reported healthcare interactions. This study aims to determine, first, whether autistic people experience greater levels of non-communicable health conditions and second, whether these are explained by differences in demographics (i.e. sex, country of residence, ethnicity, education level), alcohol use, smoking, body mass index (BMI), or family history of medical conditions. METHOD: We employed a cross-sectional, convenience-sampling study via an anonymous, online survey of autistic and non-autistic adults (n = 2305, mean age = 41.6, 65.9% female, 49% autistic). The survey asked participants to self-report information about their demographics, autism diagnosis, diet, exercise, sleep, sexual health, substance use, personal medical history, and family medical history (for all first-degree, biological relatives). Binomial logistic regression across four iterative models of increasing complexity was applied to assess rates of physical health conditions. The Benjamini-Hochberg correction was used to account for multiple testing, and only physical health conditions that achieved at least 1% endorsement within the overall sample (n > 22) were included in the analysis to reduce risk of Type I errors. We also used novel network analysis methods to test whether there are increased levels of multimorbidity between autistic and non-autistic people. RESULTS: There were significantly elevated rates of non-communicable conditions across all organ systems in autistic people, including gastrointestinal, neurological, endocrine, visual, ear/nose/throat, skin, liver and kidney, and haematological conditions. We confirmed previous findings by showing highly significant differences in rates of neurological and gastrointestinal symptoms (p < 0.0001). In addition, we established in the largest sample to date that Ehler-Danlos Syndrome (EDS) was more likely to occur among autistic females compared to non-autistic females. Finally, we found a higher prevalence of Coeliac's disease among autistic individuals compared to non-autistic individuals after controlling for sex, ethnicity, country of residence, alcohol use, smoking, and BMI, but these results became non-significant after accounting for family history. LIMITATIONS: Our study is biased towards females, white individuals, highly educated people, and UK residents, likely due to sampling biases. Our self-report study design may also exclude those who lack access to computers, or those with intellectual disability. Our network analysis is also limited in size. CONCLUSIONS: This study provides evidence of widespread, physical health comorbidity that spans nearly all major organ systems in autistic adults compared to non-autistic adults, using both binary logistic regression and network models. Healthcare professionals must be made aware of the range of co-occurring physical health conditions that may be more common among autistic people. However, our findings also point towards potential avenues requiring further exploration, such as the association of autism with both Coeliac's disease and EDS.Published versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Artificial intelligence as a diagnostic aid in cross-sectional radiological imaging of surgical pathology in the abdominopelvic cavity: a systematic review
No full textOBJECTIVES: There is emerging use of artificial intelligence (AI) models to aid diagnostic imaging. This review examined and critically appraised the application of AI models to identify surgical pathology from radiological images of the abdominopelvic cavity, to identify current limitations and inform future research. DESIGN: Systematic review. DATA SOURCES: Systematic database searches (Medline, EMBASE, Cochrane Central Register of Controlled Trials) were performed. Date limitations (January 2012 to July 2021) were applied. ELIGIBILITY CRITERIA: Primary research studies were considered for eligibility using the PIRT (participants, index test(s), reference standard and target condition) framework. Only publications in the English language were eligible for inclusion in the review. DATA EXTRACTION AND SYNTHESIS: Study characteristics, descriptions of AI models and outcomes assessing diagnostic performance were extracted by independent reviewers. A narrative synthesis was performed in accordance with the Synthesis Without Meta-analysis guidelines. Risk of bias was assessed (Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2)). RESULTS: Fifteen retrospective studies were included. Studies were diverse in surgical specialty, the intention of the AI applications and the models used. AI training and test sets comprised a median of 130 (range: 5-2440) and 37 (range: 10-1045) patients, respectively. Diagnostic performance of models varied (range: 70%-95% sensitivity, 53%-98% specificity). Only four studies compared the AI model with human performance. Reporting of studies was unstandardised and often lacking in detail. Most studies (n=14) were judged as having overall high risk of bias with concerns regarding applicability. CONCLUSIONS: AI application in this field is diverse. Adherence to reporting guidelines is warranted. With finite healthcare resources, future endeavours may benefit from targeting areas where radiological expertise is in high demand to provide greater efficiency in clinical care. Translation to clinical practice and adoption of a multidisciplinary approach should be of high priority. PROSPERO REGISTRATION NUMBER: CRD42021237249.Published version, accepted version, submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Biallelic NUDT2 variants defective in mRNA decapping cause a neurodevelopmental disease
No full textDysfunctional RNA processing caused by genetic defects in RNA processing enzymes has a profound impact on the nervous system, resulting in neurodevelopmental conditions. We characterized a recessive neurological disorder in 18 children and young adults from 10 independent families typified by intellectual disability, motor developmental delay, and gait disturbance. In some patients peripheral neuropathy, corpus callosum abnormalities, and progressive basal ganglia deposits were present. The disorder is associated with rare variants in NUDT2, a mRNA decapping and Ap4A hydrolysing enzyme, including novel missense and in-frame deletion variants. We show that these NUDT2 variants lead to a marked loss of enzymatic activity, strongly implicating loss of NUDT2 function as the cause of the disorder. NUDT2-deficient patient fibroblasts exhibit a markedly altered transcriptome, accompanied by changes in mRNA half-life and stability. Amongst the most up-regulated mRNAs in NUDT2-deficient cells, we identified host response and interferon-responsive genes. Importantly, add-back experiments using an Ap4A hydrolase defective in mRNA decapping highlighted loss of NUDT2 decapping as the activity implicated in altered mRNA homeostasis. Our results confirm that reduction or loss of NUDT2 hydrolase activity is associated with a neurological disease, highlighting the importance of a physiologically balanced mRNA processing machinery for neuronal development and homeostasis.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
Considerations for peripheral blood transport and storage during large-scale multicentre metabolome research
No full textPublished version, accepted version, submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
How to critically appraise a systematic review: an aide for the reader and reviewer
No full textThe number of published systematic reviews has soared rapidly in recent years. Sadly, the quality of most systematic reviews in dermatology is substandard. With the continued increase in exposure to systematic reviews, and their potential to influence clinical practice, we sought to describe a sequence of useful tips for the busy clinician reader to determine study quality and clinical utility. Important factors to consider when assessing systematic reviews include: determining the motivation to performing the study, establishing if the study protocol was prepublished, assessing quality of reporting using the PRISMA checklist, assessing study quality using the AMSTAR 2 critical appraisal checklist, assessing for evidence of spin, and summarizing the main strengths and limitations of the study to determine if it could change clinical practice. Having a set of heuristics to consider when reading systematic reviews serves to save time, enabling assessment of quality in a structured way, and come to a prompt conclusion of the merits of a review article in order to inform the care of dermatology patients.Published version, accepted version (12 month 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
Contralateral breast cancer risk in irradiated breast cancer patients with a germline-BRCA1/2 pathogenic variant
No full textBACKGROUND: Radiation-induced secondary breast cancer may be a concern after radiotherapy for primary breast cancer (PBC), especially in young germline (g)BRCA-associated breast cancer patients with already high contralateral breast cancer (CBC) risk and potentially increased genetic susceptibility to radiation. AIM: To investigate whether adjuvant radiotherapy for PBC increases the risk of CBC in gBRCA1/2-associated BC patients. METHODS: gBRCA1/2 pathogenic variant carriers diagnosed with PBC were selected from the prospective International BRCA1/2 Carrier Cohort Study. We used multivariable Cox proportional hazards models to investigate the association between radiotherapy (yes versus no) and CBC risk. We further stratified for BRCA status and PBC age (40 years). Statistical significance tests were two-sided. RESULTS: Of 3,602 eligible patients, 2,297 (64%) received adjuvant radiotherapy. Median follow-up was 9.6 years. The radiotherapy group had more stage III PBC patients compared to the non-radiotherapy group (15% versus 3%, p < 0.001), received more often chemotherapy (81% vs. 70%, p < 0.001) and endocrine therapy (50% vs. 35%, p < 0.001). The radiotherapy group had an increased CBC risk compared to the non-radiotherapy group (adjusted HR: 1.44, 95% CI: 1.12-1.86). Statistical significance was observed in gBRCA2 (HR: 1.77, 95% CI: 1.13-2.77), but not in gBRCA1 pathogenic variant carriers (HR: 1.29, 95% CI: 0.93-1.77; p-value for interaction, 0.39). In the combined gBRCA1/2 group, patients irradiated below and above age 40 at PBC diagnosis showed similar risks (HR: 1.38, 95% CI: 0.93-2.04 and HR: 1.56, 95% CI: 1.11-2.19, respectively). DISCUSSION/CONCLUSION: Radiotherapy regimens minimizing contralateral breast dose should be considered in gBRCA1/2 pathogenic variant carriers.Accepted version (12 month embargo), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Impact of Frailty on the Development of Proximal Junctional Failure: Does Frailty Supersede Achieving Optimal Realignment?
No full textBACKGROUND: Patients undergoing surgery for adult spinal deformity (ASD) are often elderly, frail, and at elevated risk of adverse events perioperatively, with proximal junctional failure (PJF) occurring relatively frequently. Currently, the specific role of frailty in potentiating this outcome is poorly defined. PURPOSE: To determine if the benefits of optimal realignment in ASD, with respect to the development of PJF, can be offset by increasing frailty. STUDY DESIGN: Retrospective cohort. METHODS: Operative ASD patients (scoliosis >20°, SVA>5 cm, PT>25°, or TK>60°) fused to pelvis or below with available baseline (BL) and 2-year (2Y) radiographic and HRQL data were included. The Miller Frailty Index (FI) was used to stratify patients into 2 categories: Not Frail (FI 3). Proximal Junctional Failure (PJF) was defined using the Lafage criteria. Matched" and "unmatched" refers to ideal age-adjusted alignment post-operatively. Multivariable regression determined impact of frailty on development of PJF. RESULTS: 284 ASD patients met inclusion criteria (62.2yrs±9.9, 81%F, BMI: 27.5 kg/m2±5.3, ASD-FI: 3.4±1.5, CCI: 1.7±1.6). 43% of patients were characterized as Not Frail (NF) and 57% were characterized as Frail (F). PJF development was lower in the NF group compared to the F group, (7% vs. 18%; P=0.002). F patients had 3.2X higher risk of PJF development compared to NF patients (OR: 3.2, 95% CI: 1.3-7.3, P=0.009). Controlling for baseline factors, F unmatched patients had a higher degree of PJF (OR: 1.4, 95% CI:1.02-1.8, P=0.03), however, with prophylaxis there was no increased risk. Adjusted analysis shows F patients when matched post-operatively in PI-LL had no significantly higher risk of PJF. CONCLUSIONS: An increasingly frail state is significantly associated with the development of PJF after corrective surgery for ASD. Optimal realignment may mitigate the impact of frailty on eventual PJF. Prophylaxis should be considered in frail patients who do not reach ideal alignment goals."UnknownNot hel
Patient Experience of Systemic Sclerosis-Related Calcinosis: An International Study Informing Clinical Trials, Practice, and the Development of the Mawdsley Calcinosis Questionnaire
No full textSystemic sclerosis (SSc) -related calcinosis can be a debilitating, constantly painful, poorly understood vascular complication of calcium hydroxyapatite deposition in soft tissue structures that affects approximately 40% of both limited and diffuse cutaneous SSc subtypes. This publication describes the iterative and multitiered international qualitative investigations that yielded remarkable insights into natural history, daily experience, and complications of SSc-calcinosis providing pivotal information for health management. Patient-driven question development and field testing, according to Food and Drug Administration guidance, propelled the development of a patient-reported outcome measure for SSc-calcinosis, the Mawdsley Calcinosis Questionnaire.Published version, accepted version (12 month embargo)Not hel