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1.
Artículo en Inglés | MEDLINE | ID: mdl-38961704

RESUMEN

BACKGROUND: There is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision-making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas. OBJECTIVE: To generate a consensual and operational classification of cSCCs. METHOD: Unsupervised independent clustering of 248 cases of cSCCs considered difficult-to-treat. Eighteen international experts from different specialties classified these cases into what they considered homogeneous clusters useful for management, each with freedom regarding clustering criteria. Convergences and divergences between clustering were analysed using a similarity matrix, the K-mean approach and the average silhouette method. Mathematical modelling was used to look for the best consensual clustering. The operability of the derived classification was validated on 23 new practitioners. RESULTS: Despite the high heterogeneity of the clinical cases, a mathematical consensus was observed. It was best represented by a partition into five clusters, which appeared a posteriori to describe different clinical scenarios. Applicability of this classification was shown by a good concordance (94%) in the allocation of cases between the new practitioners and the 18 experts. An additional group of easy-to-treat cSCC was included, resulting in a six-group final classification: easy-to-treat/complex to treat due to tumour and/or patient characteristics/multiple/locally advanced/regional disease/visceral metastases. CONCLUSION: Given the methodology based on the convergence of unguided intuitive clustering of cases by experts, this new classification is relevant for clinical practice. It does not compete with staging systems, but they may complement each other, whether the objective is to select the best therapeutic approach in tumour boards or to design homogeneous groups for trials.

2.
Epilepsia ; 65(5): 1394-1405, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38441332

RESUMEN

OBJECTIVE: This study was undertaken to characterize changes in health care utilization and mortality for people with epilepsy (PWE) during the COVID-19 pandemic. METHODS: We performed a retrospective study using linked, individual-level, population-scale anonymized health data from the Secure Anonymised Information Linkage databank. We identified PWE living in Wales during the study "pandemic period" (January 1, 2020-June 30, 2021) and during a "prepandemic" period (January 1, 2016-December 31, 2019). We compared prepandemic health care utilization, status epilepticus, and mortality rates with corresponding pandemic rates for PWE and people without epilepsy (PWOE). We performed subgroup analyses on children (<18 years old), older people (>65 years old), those with intellectual disability, and those living in the most deprived areas. We used Poisson models to calculate adjusted rate ratios (RRs). RESULTS: We identified 27 279 PWE who had significantly higher rates of hospital (50.3 visits/1000 patient months), emergency department (55.7), and outpatient attendance (172.4) when compared to PWOE (corresponding figures: 25.7, 25.2, and 87.0) in the prepandemic period. Hospital and epilepsy-related hospital admissions, and emergency department and outpatient attendances all reduced significantly for PWE (and all subgroups) during the pandemic period. RRs [95% confidence intervals (CIs)] for pandemic versus prepandemic periods were .70 [.69-.72], .77 [.73-.81], .78 [.77-.79], and .80 [.79-.81]. The corresponding rates also reduced for PWOE. New epilepsy diagnosis rates decreased during the pandemic compared with the prepandemic period (2.3/100 000/month cf. 3.1/100 000/month, RR = .73, 95% CI = .68-.78). Both all-cause deaths and deaths with epilepsy recorded on the death certificate increased for PWE during the pandemic (RR = 1.07, 95% CI = .997-1.145 and RR = 2.44, 95% CI = 2.12-2.81). When removing COVID deaths, RRs were .88 (95% CI = .81-.95) and 1.29 (95% CI = 1.08-1.53). Status epilepticus rates did not change significantly during the pandemic (RR = .95, 95% CI = .78-1.15). SIGNIFICANCE: All-cause non-COVID deaths did not increase but non-COVID deaths associated with epilepsy did increase for PWE during the COVID-19 pandemic. The longer term effects of the decrease in new epilepsy diagnoses and health care utilization and increase in deaths associated with epilepsy need further research.


Asunto(s)
COVID-19 , Epilepsia , Aceptación de la Atención de Salud , Humanos , COVID-19/epidemiología , COVID-19/mortalidad , Epilepsia/epidemiología , Epilepsia/mortalidad , Femenino , Masculino , Estudios Retrospectivos , Anciano , Adolescente , Niño , Adulto , Aceptación de la Atención de Salud/estadística & datos numéricos , Persona de Mediana Edad , Adulto Joven , Gales/epidemiología , Preescolar , Estado Epiléptico/mortalidad , Estado Epiléptico/epidemiología , Hospitalización/estadística & datos numéricos , Lactante , Pandemias , Servicio de Urgencia en Hospital/estadística & datos numéricos , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/mortalidad , Anciano de 80 o más Años
3.
Epilepsia ; 65(5): 1383-1393, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38441374

RESUMEN

OBJECTIVE: People with epilepsy (PWE) may be at an increased risk of severe COVID-19. It is important to characterize this risk to inform PWE and for future health and care planning. We assessed whether PWE were at higher risk of being hospitalized with, or dying from, COVID-19. METHODS: We performed a retrospective cohort study using linked, population-scale, anonymized electronic health records from the SAIL (Secure Anonymised Information Linkage) databank. This includes hospital admission and demographic data for the complete Welsh population (3.1 million) and primary care records for 86% of the population. We identified 27 279 PWE living in Wales during the study period (March 1, 2020 to June 30, 2021). Controls were identified using exact 5:1 matching (sex, age, and socioeconomic status). We defined COVID-19 deaths as having International Classification of Diseases, 10th Revision (ICD-10) codes for COVID-19 on death certificates or occurring within 28 days of a positive SARS-CoV-2 polymerase chain reaction (PCR) test. COVID-19 hospitalizations were defined as having a COVID-19 ICD-10 code for the reason for admission or occurring within 28 days of a positive SARS-CoV-2 PCR test. We recorded COVID-19 vaccinations and comorbidities known to increase the risk of COVID-19 hospitalization and death. We used Cox proportional hazard models to calculate hazard ratios. RESULTS: There were 158 (.58%) COVID-19 deaths and 933 (3.4%) COVID-19 hospitalizations in PWE, and 370 (.27%) deaths and 1871 (1.4%) hospitalizations in controls. Hazard ratios for COVID-19 death and hospitalization in PWE compared to controls were 2.15 (95% confidence interval [CI] = 1.78-2.59) and 2.15 (95% CI = 1.94-2.37), respectively. Adjusted hazard ratios (adjusted for comorbidities) for death and hospitalization were 1.32 (95% CI = 1.08-1.62) and 1.60 (95% CI = 1.44-1.78). SIGNIFICANCE: PWE are at increased risk of being hospitalized with, and dying from, COVID-19 when compared to age-, sex-, and deprivation-matched controls, even when adjusting for comorbidities. This may have implications for prioritizing future COVID-19 treatments and vaccinations for PWE.


Asunto(s)
COVID-19 , Epilepsia , Hospitalización , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , Femenino , Masculino , Hospitalización/estadística & datos numéricos , Epilepsia/epidemiología , Epilepsia/mortalidad , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Anciano , Gales/epidemiología , Adulto Joven , Factores de Riesgo , Adolescente , Estudios de Cohortes , Anciano de 80 o más Años , Comorbilidad , SARS-CoV-2
4.
Br J Surg ; 111(1)2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38198154

RESUMEN

BACKGROUND: Cancer multidisciplinary team (MDT) meetings are under intense pressure to reform given the rapidly rising incidence of cancer and national mandates for protocolized streaming of cases. The aim of this study was to validate a natural language processing (NLP)-based web platform to automate evidence-based MDT decisions for skin cancer with basal cell carcinoma as a use case. METHODS: A novel and validated NLP information extraction model was used to extract perioperative tumour and surgical factors from histopathology reports. A web application with a bespoke application programming interface used data from this model to provide an automated clinical decision support system, mapped to national guidelines and generating a patient letter to communicate ongoing management. Performance was assessed against retrospectively derived recommendations by two independent and blinded expert clinicians. RESULTS: There were 893 patients (1045 lesions) used to internally validate the model. High accuracy was observed when compared against human predictions, with an overall value of 0.92. Across all classifiers the virtual skin MDT was highly specific (0.96), while sensitivity was lower (0.72). CONCLUSION: This study demonstrates the feasibility of a fully automated, virtual, web-based service model to host the skin MDT with good system performance. This platform could be used to support clinical decision-making during MDTs as 'human in the loop' approach to aid protocolized streaming. Future prospective studies are needed to validate the model in tumour types where guidelines are more complex.


Asunto(s)
Procesamiento de Lenguaje Natural , Neoplasias Cutáneas , Humanos , Estudios Retrospectivos , Neoplasias Cutáneas/cirugía , Grupo de Atención al Paciente , Internet
5.
J Plast Reconstr Aesthet Surg ; 88: 443-451, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38091687

RESUMEN

INTRODUCTION: Data supporting the current British Association of Dermatologists guidelines for the management of basal cell carcinoma (BCC) are based on historic studies and do not consider the updated Royal College of Pathologists (RCPath) histological reporting standards. The aim of this study was to use natural language processing (NLP)-derived data and undertake a multivariate analysis with updated RCPath standards, providing a contemporary update on the excision margins required to achieve histological clearance in BCC. METHODS: A validated NLP information extraction model was used to perform a rapid multi-centre, pan-specialty, consecutive retrospective analysis of BCCs, managed with surgical excision using a pre-determined clinical margin, over a 17-year period (2004-2021) at Swansea Bay University Health Board. Logistic regression assessed the relationship between the peripheral and deep margins and histological clearance. RESULTS: We ran our NLP algorithm on 34,955 BCCs. Out of the 1447 BCCs that met the inclusion criteria, the peripheral margin clearance was not influenced by the BCC risk level (p = 0.670). A clinical peripheral margin of 6 mm achieved a 95% histological clearance rate (95% confidence interval [CI], 0.93-0.98). Tumour thickness inversely affected deep-margin histological clearance (OR 0.720, 95% CI, 0.525-0.991, p < 0.05). Depth level 2 had a 97% probability of achieving deep-margin histological clearance across all tumour thicknesses. CONCLUSION: Updated RCPath reporting standards minimally impact the peripheral margin histological clearance in BCC. Larger clinical peripheral margins than those indicated by current guidelines may be necessary to achieve excision rates of ≥95%. These findings emphasise the need for continuous reassessment of clinical standards to enhance patient care.


Asunto(s)
Carcinoma Basocelular , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Estudios Retrospectivos , Patólogos , Procesamiento de Lenguaje Natural , Universidades , Carcinoma Basocelular/cirugía , Carcinoma Basocelular/patología , Márgenes de Escisión , Análisis Multivariante
6.
BMJ Open ; 13(12): e077185, 2023 12 30.
Artículo en Inglés | MEDLINE | ID: mdl-38159963

RESUMEN

OBJECTIVES: The Health & Her app provides menopausal women with a means of monitoring their symptoms, symptom triggers and menstrual periods, and enables them to engage in a variety of digital activities designed to promote well-being. This study aimed to examine whether sustained weekly engagement with the app is associated with improvements in menopausal symptoms. DESIGN: A pre-post longitudinal cohort study. SETTING: Analysed data collected from Health & Her app users. PARTICIPANTS: 1900 women who provided symptom data via the app across a 2-month period. PRIMARY AND SECONDARY OUTCOME MEASURES: Symptom changes from baseline to 2 months was the outcome measure. A linear mixed effects model explored whether levels of weekly app engagement influenced symptom changes. Secondary analyses explored whether app-usage factors such as total number of days spent logging symptoms, reporting triggers, reporting menstrual periods and using in-app activities were independently predictive of symptom changes from baseline. Covariates included hormone replacement therapy use, hormonal contraceptive use, present comorbidities, age and dietary supplement use. RESULTS: Findings demonstrated that greater engagement with the Health & Her app for 2 months was associated with greater reductions in symptoms over time. Daily use of in-app activities and logging symptoms and menstrual periods were each independently associated with symptom reductions. CONCLUSIONS: This study demonstrated that greater weekly engagement with the app was associated with greater reductions in symptoms. It is recommended that women be made aware of menopause-specific apps, such as that provided by Health & Her, to support them to manage their symptoms.


Asunto(s)
Aplicaciones Móviles , Humanos , Femenino , Estudios Longitudinales , Estudios de Cohortes , Menopausia , Terapia de Reemplazo de Hormonas
7.
Epilepsia ; 64(11): 3099-3108, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37643892

RESUMEN

OBJECTIVE: This study was undertaken to develop a novel pathway linking genetic data with routinely collected data for people with epilepsy, and to analyze the influence of rare, deleterious genetic variants on epilepsy outcomes. METHODS: We linked whole-exome sequencing (WES) data with routinely collected primary and secondary care data and natural language processing (NLP)-derived seizure frequency information for people with epilepsy within the Secure Anonymised Information Linkage Databank. The study participants were adults who had consented to participate in the Swansea Neurology Biobank, Wales, between 2016 and 2018. DNA sequencing was carried out as part of the Epi25 collaboration. For each individual, we calculated the total number and cumulative burden of rare and predicted deleterious genetic variants and the total of rare and deleterious variants in epilepsy and drug metabolism genes. We compared these measures with the following outcomes: (1) no unscheduled hospital admissions versus unscheduled admissions for epilepsy, (2) antiseizure medication (ASM) monotherapy versus polytherapy, and (3) at least 1 year of seizure freedom versus <1 year of seizure freedom. RESULTS: We linked genetic data for 107 individuals with epilepsy (52% female) to electronic health records. Twenty-six percent had unscheduled hospital admissions, and 70% were prescribed ASM polytherapy. Seizure frequency information was linked for 100 individuals, and 10 were seizure-free. There was no significant difference between the outcome groups in terms of the exome-wide and gene-based burden of rare and deleterious genetic variants. SIGNIFICANCE: We successfully uploaded, annotated, and linked genetic sequence data and NLP-derived seizure frequency data to anonymized health care records in this proof-of-concept study. We did not detect a genetic influence on real-world epilepsy outcomes, but our study was limited by a small sample size. Future studies will require larger (WES) data to establish genetic variant contribution to epilepsy outcomes.


Asunto(s)
Epilepsia , Adulto , Humanos , Femenino , Masculino , Secuenciación del Exoma , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Convulsiones/tratamiento farmacológico , Atención a la Salud , Almacenamiento y Recuperación de la Información , Anticonvulsivantes/uso terapéutico
9.
Front Surg ; 9: 870494, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36439548

RESUMEN

Introduction: Routinely collected healthcare data are a powerful research resource, but often lack detailed disease-specific information that is collected in clinical free text such as histopathology reports. We aim to use natural Language Processing (NLP) techniques to extract detailed clinical and pathological information from histopathology reports to enrich routinely collected data. Methods: We used the general architecture for text engineering (GATE) framework to build an NLP information extraction system using rule-based techniques. During validation, we deployed our rule-based NLP pipeline on 200 previously unseen, de-identified and pseudonymised basal cell carcinoma (BCC) histopathological reports from Swansea Bay University Health Board, Wales, UK. The results of our algorithm were compared with gold standard human annotation by two independent and blinded expert clinicians involved in skin cancer care. Results: We identified 11,224 items of information with a mean precision, recall, and F1 score of 86.0% (95% CI: 75.1-96.9), 84.2% (95% CI: 72.8-96.1), and 84.5% (95% CI: 73.0-95.1), respectively. The difference between clinician annotator F1 scores was 7.9% in comparison with 15.5% between the NLP pipeline and the gold standard corpus. Cohen's Kappa score on annotated tokens was 0.85. Conclusion: Using an NLP rule-based approach for named entity recognition in BCC, we have been able to develop and validate a pipeline with a potential application in improving the quality of cancer registry data, supporting service planning, and enhancing the quality of routinely collected data for research.

10.
Postgrad Med ; 134(8): 718-731, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35984648

RESUMEN

INTRODUCTION: Studies regarding patients who have underwent colectomy reported contradictory post-surgical complications based on their living areas. Due to the conflicting data surrounding whether rural or urban hospitals have lower postoperative complication rates, we have performed a systematic review and meta-analysis with the aim of understanding and assessing the evidence that has already been found. METHODS: The online databases PubMed, MEDLINE, EMBASE, SCOPUS, and CINAHL were searched for our literature review. We included papers with data on the postoperative complication rates for patients who had undergone colectomies. The patients were stratified based on the location status of the hospital, i.e. rural or urban. Data analysis was performed in Cochrane's Review Manager 5.41 software. RESULTS: A total of 921 studies were identified in the initial search; the inclusion and exclusion criteria refined the search results in 11 studies for review. The primary outcomes analyzed were mortality rate, length of stay and total complication rate. This review found that rural hospitals had either equal or lower inpatient postoperative mortality rates in comparison to urban hospitals for patients who had undergone colectomies. However, rural hospitals had a longer length of stay (mean length of stay in rural hospitals was 6.7 days and in urban hospitals was 4.9 days). It is important to note that the Australian hospitals had a mean length of stay of 13.5 days, which was almost double that of rural hospitals in America. The unadjusted rate of total complication was 26.51% in rural hospitals. CONCLUSIONS: Rural hospitals overall have equivalent postoperative complication rates to urban hospitals and can provide sufficient postoperative patient care.


Asunto(s)
Colectomía , Hospitales Rurales , Humanos , Tiempo de Internación , Australia , Colectomía/métodos , Complicaciones Posoperatorias/epidemiología
11.
Skin Health Dis ; 2(2): e95, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35677930

RESUMEN

Background: Renal transplant recipients (RTRs) are at increased risk of keratinocyte cancer (KC), especially cutaneous squamous cell carcinoma (cSCC). Previous studies identified a genetic variant of the Methylenetetrahydrofolate Reductase (MTHFR) gene, C677T, which conferred a risk for diagnosis of cSCC in Irish RTRs. Objective: We sought to find further genetic variation in MTHFR and overlap genes that may be associated with a diagnosis of KC in RTRs. Methods: Genotyping of a combined RTR population (n = 821) from two centres, Ireland (n = 546) and the USA (n = 275), was performed. This included 290 RTRs with KC and 444 without. Eleven single nucleotide polymorphisms (SNPs) in the MTHFR gene and seven in the overlap gene MTHFR Chloride transport protein 6 (CLCN6) were evaluated and association explored by time to event analysis (from transplant to first KC) using Cox proportional hazards model. Results: Polymorphism at MTHFR CLCN6 (rs9651118) was significantly associated with KC in RTRs (HR 1.50, 95% CI 1.17-1.91, p < 0.00061) and cSCC (HR 1.63, 95% CI 1.14-2.34, p = 0.007). A separate SNP, MTHFR C677T, was also significantly associated with KC in the Irish population (HR 1.31, 95% CI 1.05-1.63, p = 0.016), but not American RTRs. Conclusions: We report the association of a SNP in the MTHFR overlap gene, CLCN6 and KC in a combined RTR population. While the exact function of CLCN6 is not known, it is proposed to be involved in folate availability. Future applications could include incorporation in a polygenic risk score for KC in RTRs to help identify those at increased risk beyond traditional risk factor assessment.

12.
Seizure ; 94: 39-42, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34864250

RESUMEN

PURPOSE: The COVID-19 pandemic has increased mortality worldwide and those with chronic conditions may have been disproportionally affected. However, it is unknown whether the pandemic has changed mortality rates for people with epilepsy. We aimed to compare mortality rates in people with epilepsy in Wales during the pandemic with pre-pandemic rates. METHODS: We performed a retrospective study using individual-level linked population-scale anonymised electronic health records. We identified deaths in people with epilepsy (DPWE), i.e. those with a diagnosis of epilepsy, and deaths associated with epilepsy (DAE), where epilepsy was recorded as a cause of death on death certificates. We compared death rates in 2020 with average rates in 2015-2019 using Poisson models to calculate death rate ratios. RESULTS: There were 188 DAE and 628 DPWE in Wales in 2020 (death rates: 7.7/100,000/year and 25.7/100,000/year). The average rates for DAE and DPWE from 2015 to 2019 were 5.8/100,000/year and 23.8/100,000/year, respectively. Death rate ratios (2020 compared to 2015-2019) for DAE were 1.34 (95%CI 1.14-1.57, p<0.001) and for DPWE were 1.08 (0.99-1.17, p = 0.09). The death rate ratios for non-COVID deaths (deaths without COVID mentioned on death certificates) for DAE were 1.17 (0.99-1.39, p = 0.06) and for DPWE were 0.96 (0.87-1.05, p = 0.37). CONCLUSIONS: The significant increase in DAE in Wales during 2020 could be explained by the direct effect of COVID-19 infection. Non-COVID-19 deaths have not increased significantly but further work is needed to assess the longer-term impact.


Asunto(s)
COVID-19 , Epilepsia , Causas de Muerte , Epilepsia/epidemiología , Humanos , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , Gales/epidemiología
13.
Eur Geriatr Med ; 12(5): 1045-1055, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34081314

RESUMEN

AIMS: To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards. METHODS: A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care. The outcome measures were the proportion of patients who developed hospital-acquired pneumonia during hospitalisation, and mean time from randomization to the next hospitalisation due to respiratory infections in 1 year. RESULTS: A total of 123 participants (median age, 85; 43.1% male) were randomized, (n = 59) to intervention group and (n = 64) to control group. The multi-component interventions did not significantly reduce the incidence of hospital-acquired pneumonia but did increase the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). Implementation of multi-component interventions increased diagnoses of oropharyngeal dysphagia (35.6% vs. 20.3%; P < 0.001) and improved the influenza (54.5% vs 17.2%; P < 0.001) and pneumococcal vaccination rates (52.5% vs. 20.3%; P < 0.001). CONCLUSIONS: The nosocomial pneumonia multi-component intervention did not significantly reduce the incidence of hospital-acquired pneumonia during hospitalisation but reduce subsequent hospitalisations for respiratory infections. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, NCT04347395.


Asunto(s)
COVID-19 , Infección Hospitalaria , Neumonía Asociada a la Atención Médica , Anciano , Anciano de 80 o más Años , Infección Hospitalaria/epidemiología , Femenino , Neumonía Asociada a la Atención Médica/epidemiología , Humanos , Masculino , SARS-CoV-2 , Resultado del Tratamiento
14.
Br J Dermatol ; 185(1): 147-152, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33393080

RESUMEN

BACKGROUND: Ceramide kinase-like protein (CERKL) was originally described in retinal tissue. CERKL has been shown to protect cells from oxidative stress, and mutations in CERKL underlie the inherited disease retinitis pigmentosa. CERKL expression maintains cellular sphingolipids via an unknown mechanism. OBJECTIVES: To determine whether CERKL is expressed in epidermis and cutaneous squamous cell carcinoma (cSCC) and whether CERKL expression affects cSCC sphingolipid metabolism and susceptibility to oxidative stress. METHODS: CERKL expression was determined by RNA-Seq, quantitative polymerase chain reaction and immunohistochemistry. CERKL was knocked down in cSCC cells using small interfering RNA. Sphingolipid content was analysed by liquid chromatography-mass spectrometry. Oxidative stress was induced by treatment with H2 O2 , and apoptosis was measured using flow cytometry to determine annexin V binding. RESULTS: CERKL mRNA and protein are highly expressed in actinic keratosis and cSCC in comparison with normal epidermis. CERKL is also expressed in metabolically active epithelial cells in normal hair bulbs and sebaceous glands. CERKL knockdown in cultured cSCC cells reduces cellular sphingolipid content and enhances susceptibility to oxidative stress. CONCLUSIONS: These findings suggest that CERKL may be important in cSCC progression and could lead to novel strategies for prevention and treatment of cSCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Carcinoma de Células Escamosas/genética , Humanos , Estrés Oxidativo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Neoplasias Cutáneas/genética , Esfingolípidos
15.
Br J Dermatol ; 2020 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-33270220

RESUMEN

BACKGROUND: Ceramide Kinase-Like Protein (CERKL) was originally described in retinal tissue. CERKL has been shown to protect cells from oxidative stress, and mutations in CERKL underlie the inherited disease, retinitis pigmentosa. CERKL expression maintains cellular sphingolipids via an unknown mechanism. OBJECTIVES: To determine whether CERKL is expressed in epidermis and cutaneous squamous cell carcinoma (cSCC) and whether CERKL expression affects cSCC sphingolipid metabolism and susceptibility to oxidative stress. METHODS: CERKL expression was determined by RNA-Seq, qPCR and immunohistochemistry. CERKL was knocked down in cSCC cells using siRNA. Sphingolipid content was analyzed by liquid chromatography-mass spectrometry (LC-MS). Oxidative stress was induced by treatment with H2 O2 , and apoptosis was measured using flow cytometry to determine annexin v binding. RESULTS: CERKL mRNA and protein are highly expressed in actinic keratosis and cSCC in comparison with normal epidermis. CERKL also is expressed in metabolically active epithelial cells in normal hair bulbs and sebaceous glands. CERKL knockdown in cultured cSCC cells reduces cellular sphingolipid content and enhances susceptibility to oxidative stress. CONCLUSIONS: These findings suggest that CERKL may be important in cSCC progression and could lead to novel strategies for prevention and treatment of cSCC.

16.
Epilepsy Behav ; 111: 107196, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32554230

RESUMEN

OBJECTIVE: The objective of the study was to assess the long-term outcomes of epilepsy surgery between 1995 and 2015 in South Wales, UK, linking case note review, postal questionnaire, and routinely collected healthcare data. METHOD: We identified patients from a departmental database and collected outcome data from patient case notes, a postal questionnaire, and the QOLIE-31-P and linked with Welsh routinely collected data in the Secure Anonymised Information Linkage (SAIL) databank. RESULTS: Fifty-seven patients were included. Median age at surgery was 34 years (11-70), median: 24 years (2-56) after onset of habitual seizures. Median follow-up was 7 years (2-19). Twenty-eight (49%) patients were free from disabling seizures (Engel Class 1), 9 (16%) experienced rare disabling seizures (Class 2), 13 (23%) had worthwhile improvements (Class 3), and 7 (12%) had no improvement (Class 4). There was a 30% mean reduction in total antiepileptic drug (AED) load at five years postsurgery. Thirty-eight (66.7%) patients experienced tonic-clonic seizures presurgery verses 8 (14%) at last review. Seizure-free patients self-reported a greater overall quality of life (QOL; QOLIE-31-P) when compared with those not achieving seizure freedom. Seizure-free individuals scored a mean of 67.6/100 (100 is best), whereas those with continuing seizures scored 46.0/100 (p < 0.006). There was a significant decrease in the median rate of hospital admissions for any cause after epilepsy surgery (9.8 days per 1000 patient days before surgery compared with 3.9 after p < 0.005). SIGNIFICANCE: Epilepsy surgery was associated with significant improvements in seizures, a reduced AED load, and an improved QOL that closely correlated with seizure outcomes and reduced hospital admission rates following surgery. Despite this, there was a long delay from onset of habitual seizures to surgery. The importance of long-term follow-up is emphasized in terms of evolving medical needs and health and social care outcomes.


Asunto(s)
Análisis de Datos , Epilepsia/cirugía , Aceptación de la Atención de Salud , Medición de Resultados Informados por el Paciente , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Niño , Estudios de Cohortes , Epilepsia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Gales/epidemiología , Adulto Joven
18.
J Eur Acad Dermatol Venereol ; 33 Suppl 8: 57-60, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31833603

RESUMEN

Immunosuppression, both iatrogenic and disease-related, is associated with a greatly increased incidence of cutaneous SCC (cSCC) and with aggressive cSCC and worse disease outcomes. Consequently, rapid access to skin cancer services and prudent surgical choices, such as circumferential margin assessment, is essential when treating advanced cSCC in an immunosuppressed patient. For high-risk cancers and control of cSCC multiplicity, additional strategies should be actively considered within the multidisciplinary clinical care team. These include minimization or revision of immunosuppressive medications, systemic chemoprevention (including retinoids, nicotinamide, capecitabine) and adjuvant therapies such as radiotherapy. Unfortunately, there is a relative paucity of good evidence for many of these treatments in the immunosuppressed. Systemic treatments for metastatic cSCC are often contraindicated in organ transplant recipients, notably checkpoint inhibitor immunotherapy. There are also toxicity concerns with some conventional chemotherapies and EGFR inhibitors. Until recently, clinical trials have largely excluded immunosuppressed individuals. Development of more effective treatment for advanced cSCC in this high-risk group and prospective clinical trials are now research priorities.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Neoplasias Cutáneas/terapia , Carcinoma de Células Escamosas/patología , Humanos , Terapia de Inmunosupresión , Estadificación de Neoplasias , Neoplasias Cutáneas/patología
20.
BMJ Open ; 9(4): e023232, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30940752

RESUMEN

OBJECTIVE: Routinely collected healthcare data are a powerful research resource but often lack detailed disease-specific information that is collected in clinical free text, for example, clinic letters. We aim to use natural language processing techniques to extract detailed clinical information from epilepsy clinic letters to enrich routinely collected data. DESIGN: We used the general architecture for text engineering (GATE) framework to build an information extraction system, ExECT (extraction of epilepsy clinical text), combining rule-based and statistical techniques. We extracted nine categories of epilepsy information in addition to clinic date and date of birth across 200 clinic letters. We compared the results of our algorithm with a manual review of the letters by an epilepsy clinician. SETTING: De-identified and pseudonymised epilepsy clinic letters from a Health Board serving half a million residents in Wales, UK. RESULTS: We identified 1925 items of information with overall precision, recall and F1 score of 91.4%, 81.4% and 86.1%, respectively. Precision and recall for epilepsy-specific categories were: epilepsy diagnosis (88.1%, 89.0%), epilepsy type (89.8%, 79.8%), focal seizures (96.2%, 69.7%), generalised seizures (88.8%, 52.3%), seizure frequency (86.3%-53.6%), medication (96.1%, 94.0%), CT (55.6%, 58.8%), MRI (82.4%, 68.8%) and electroencephalogram (81.5%, 75.3%). CONCLUSIONS: We have built an automated clinical text extraction system that can accurately extract epilepsy information from free text in clinic letters. This can enhance routinely collected data for research in the UK. The information extracted with ExECT such as epilepsy type, seizure frequency and neurological investigations are often missing from routinely collected data. We propose that our algorithm can bridge this data gap enabling further epilepsy research opportunities. While many of the rules in our pipeline were tailored to extract epilepsy specific information, our methods can be applied to other diseases and also can be used in clinical practice to record patient information in a structured manner.


Asunto(s)
Epilepsia/clasificación , Almacenamiento y Recuperación de la Información , Registros Médicos , Procesamiento de Lenguaje Natural , Convulsiones/clasificación , Algoritmos , Electroencefalografía , Registros Electrónicos de Salud , Epilepsia/diagnóstico , Humanos , Imagen por Resonancia Magnética , Convulsiones/diagnóstico , Gales
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