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1.
Br J Surg ; 111(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38198154

RESUMO

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.


Assuntos
Processamento de Linguagem Natural , Neoplasias Cutâneas , Humanos , Estudos Retrospectivos , Neoplasias Cutâneas/cirurgia , Equipe de Assistência ao Paciente , Internet
2.
Epilepsia ; 65(5): 1394-1405, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38441332

RESUMO

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.


Assuntos
COVID-19 , Epilepsia , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , COVID-19/epidemiologia , COVID-19/mortalidade , Epilepsia/epidemiologia , Epilepsia/mortalidade , Feminino , Masculino , Estudos Retrospectivos , Idoso , Adolescente , Criança , Adulto , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto Jovem , País de Gales/epidemiologia , Pré-Escolar , Estado Epiléptico/mortalidade , Estado Epiléptico/epidemiologia , Hospitalização/estatística & dados numéricos , Lactente , Pandemias , Serviço Hospitalar de Emergência/estatística & dados numéricos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/mortalidade , Idoso de 80 Anos ou mais
3.
Epilepsia ; 65(5): 1383-1393, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38441374

RESUMO

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.


Assuntos
COVID-19 , Epilepsia , Hospitalização , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Feminino , Masculino , Hospitalização/estatística & dados numéricos , Epilepsia/epidemiologia , Epilepsia/mortalidade , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , País de Gales/epidemiologia , Adulto Jovem , Fatores de Risco , Adolescente , Estudos de Coortes , Idoso de 80 Anos ou mais , Comorbidade , SARS-CoV-2
4.
Artigo em Inglês | MEDLINE | ID: mdl-38961704

RESUMO

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.

5.
Epilepsia ; 64(11): 3099-3108, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37643892

RESUMO

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.


Assuntos
Epilepsia , Adulto , Humanos , Feminino , Masculino , Sequenciamento do Exoma , Epilepsia/tratamento farmacológico , Epilepsia/genética , Convulsões/tratamento farmacológico , Atenção à Saúde , Armazenamento e Recuperação da Informação , Anticonvulsivantes/uso terapêutico
6.
Br J Dermatol ; 185(1): 147-152, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33393080

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/genética , Humanos , Estresse Oxidativo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Neoplasias Cutâneas/genética , Esfingolipídeos
7.
Br J Dermatol ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270220

RESUMO

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.

8.
Epilepsy Behav ; 111: 107196, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32554230

RESUMO

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.


Assuntos
Análise de Dados , Epilepsia/cirurgia , Aceitação pelo Paciente de Cuidados de Saúde , Medidas de Resultados Relatados pelo Paciente , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Epilepsia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , País de Gales/epidemiologia , Adulto Jovem
9.
J Eur Acad Dermatol Venereol ; 33 Suppl 8: 57-60, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31833603

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Cutâneas/terapia , Carcinoma de Células Escamosas/patologia , Humanos , Terapia de Imunossupressão , Estadiamento de Neoplasias , Neoplasias Cutâneas/patologia
11.
J Neurol Neurosurg Psychiatry ; 89(7): 736-740, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29588327

RESUMO

OBJECTIVE: Small prospective studies have identified that children exposed to valproate in utero have poorer scores on cognitive testing. We wanted to identify whether children exposed to antiepileptic drugs (AEDs) in utero have poorer school performance. METHODS: We used anonymised, linked, routinely collected healthcare records to identify children born to mothers with epilepsy. We linked these children to their national attainment Key Stage 1 (KS1) tests in mathematics, language and science at the age of 7 and compared them with matched children born to mothers without epilepsy, and with the national KS1 results. We used the core subject indicator (CSI) as an outcome measure (the proportion of children achieving a minimum standard in all subjects) and the results in individual subjects. RESULTS: We identified 440 children born to mothers with epilepsy with available KS1 results. Compared with a matched control group, fewer children with mothers being prescribed sodium valproate during pregnancy achieved the national minimum standard in CSI (-12.7% less than the control group), mathematics (-12.1%), language (-10.4%) and in science (-12.2%). Even fewer children with mothers being prescribed multiple AEDs during pregnancy achieved a national minimum standard: CSI (by -20.7% less than the control group), mathematics (-21.9%), language (-19.3%) and science (-19.4%). We did not observe any significant difference in children whose mothers were prescribed carbamazepine or were not taking an AED when compared with the control group. CONCLUSIONS: In utero exposure to AEDs in combination, or sodium valproate alone, is associated with a significant decrease in attainment in national educational tests for 7-year-old children compared with both a matched control group and the all-Wales national average. These results give further support to the cognitive and developmental effects of in utero exposure to sodium valproate as well as multiple AEDs, which should be balanced against the need for effective seizure control for women during pregnancy.


Assuntos
Anticonvulsivantes/uso terapêutico , Filho de Pais com Deficiência/psicologia , Escolaridade , Epilepsia/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estudos de Casos e Controles , Criança , Desenvolvimento Infantil , Feminino , Humanos , Masculino , Gravidez , Reino Unido
12.
Br J Dermatol ; 177(5): 1225-1233, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29086412

RESUMO

Although tremendous progress has been made in recent years in skin cancer care for organ transplant recipients, significant gaps remain in data-driven clinical guidelines, particularly for the treatment and prevention of cutaneous squamous cell carcinoma (cSCC), the most common malignancy among this population. In this review, we aim to summarize current knowledge around the management of cSCC and highlight the most significant gaps in knowledge that continue to pose challenges in the delivery of skin cancer care for organ transplant recipients. We suggest future directions for research that will bridge existing gaps and establish evidence-driven guidelines for primary prevention, screening and treatment of cSCC in this high-risk patient population.


Assuntos
Carcinoma de Células Escamosas/terapia , Transplante de Órgãos/efeitos adversos , Neoplasias Cutâneas/terapia , Transplantados , Antimetabólitos Antineoplásicos/uso terapêutico , Capecitabina/uso terapêutico , Carcinoma de Células Escamosas/prevenção & controle , Comportamentos Relacionados com a Saúde , Humanos , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Imunossupressores/efeitos adversos , Ceratoacantoma/prevenção & controle , Ceratoacantoma/terapia , Metástase Neoplásica , Niacinamida/uso terapêutico , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Transtornos de Fotossensibilidade/prevenção & controle , Transtornos de Fotossensibilidade/terapia , Qualidade de Vida , Radioterapia Adjuvante , Retinoides/uso terapêutico , Neoplasias Cutâneas/prevenção & controle , Luz Solar/efeitos adversos , Complexo Vitamínico B/uso terapêutico
13.
Br J Dermatol ; 177(4): 1066-1073, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28456133

RESUMO

BACKGROUND: Variants at the oculocutaneous albinism 2 (OCA2)/HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2) locus have been associated with pigmentation phenotypes and risk of developing several types of skin cancer. OBJECTIVES: To evaluate OCA2/HERC2 locus variants for their impact on time to develop cutaneous squamous cell carcinoma (cSCC) in organ transplant recipients (OTRs) who are at elevated risk of developing cSCC. METHODS: Participants were solid OTRs ascertained from two centres (n = 125 and 261) with an average of 13·1 years of follow-up post-transplant. DNA was available for genotyping for all participants, in addition to medical records and questionnaire data. The Ohio State University study had a case-control design with prospective follow-up, and the University of California San Francisco study was a national cross-sectional survey with retrospective chart review. RESULTS: OCA2 variants rs12913832 and rs916977 were significantly associated with time to first cSCC post-transplant. OTRs homozygous for the brown-eye alleles of rs916977 (GG) and rs12913832 (AA) had significant delays of time to first cSCC post-transplant compared with individuals homozygous for the blue-eye alleles (hazard ratio 0·34, P < 0·001 and hazard ratio 0·54, P = 0·012, respectively). Both variants were highly associated with eye colour in the combined studies (P < 0·001). CONCLUSIONS: This study is the first to show an association between OCA2/HERC2 variants and time to first cSCC post-transplant. This may impact dermatological screening recommendations for high-risk populations.


Assuntos
Carcinoma de Células Escamosas/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Proteínas de Membrana Transportadoras/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Criança , Estudos Transversais , Cor de Olho/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos , Complicações Pós-Operatórias/genética , Estudos Retrospectivos , Fatores de Risco , Transplantados , Ubiquitina-Proteína Ligases , Adulto Jovem
14.
Br J Dermatol ; 177(5): 1202-1207, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28952162

RESUMO

Long-term iatrogenic immunosuppression increases the risk of cutaneous malignancies in organ transplant recipients (OTRs), particularly the keratinocyte cancers basal cell carcinoma and cutaneous squamous cell carcinoma (cSCC). cSCC is the most common malignancy in OTRs, with the risk increased to over 65-fold in transplanted patients relative to the general population. There have been very few risk prediction tools developed for accurate determination of the risk of developing keratinocyte cancers in the OTR population. This review summarizes the prediction tools developed to date, and outlines future directions for developing more accurate prediction models that are clinically useful for the transplant physician and dermatologist.


Assuntos
Carcinoma Basocelular/prevenção & controle , Carcinoma de Células Escamosas/prevenção & controle , Queratinócitos , Transplante de Órgãos/efeitos adversos , Neoplasias Cutâneas/prevenção & controle , Carcinoma Basocelular/etiologia , Carcinoma de Células Escamosas/etiologia , Detecção Precoce de Câncer , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Masculino , Medição de Risco/métodos , Fatores de Risco , Neoplasias Cutâneas/etiologia
15.
Am J Transplant ; 16(2): 407-13, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26820755

RESUMO

Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma.


Assuntos
Carcinoma de Célula de Merkel/cirurgia , Carcinoma de Células Escamosas/cirurgia , Melanoma/cirurgia , Transplante de Órgãos , Guias de Prática Clínica como Assunto , Neoplasias Cutâneas/cirurgia , Humanos , Agências Internacionais , Prognóstico , Melanoma Maligno Cutâneo
16.
Am J Transplant ; 16(1): 262-70, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26372838

RESUMO

Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients.


Assuntos
Aspergilose/induzido quimicamente , Aspergillus/efeitos dos fármacos , Carcinoma de Células Escamosas/induzido quimicamente , Rejeição de Enxerto/induzido quimicamente , Transplante de Pulmão/efeitos adversos , Neoplasias Cutâneas/induzido quimicamente , Voriconazol/efeitos adversos , Adolescente , Adulto , Idoso , Antifúngicos , Aspergilose/epidemiologia , Aspergilose/microbiologia , Carcinoma de Células Escamosas/epidemiologia , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Transplantados , Adulto Jovem
17.
Br J Dermatol ; 173(2): 544-6, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25702621

RESUMO

Basal cell carcinoma (BCC), the most common cancer in the U.S.A., is treated primarily with local excision. In some cases, lesion size, location or extent prevent complete resection. Locally advanced BCC responds to systemic therapy with the Hedgehog pathway inhibitor vismodegib, but withdrawal of treatment may result in disease relapse. Here we present a case of locally advanced auricular BCC treated with induction vismodegib and radiation, resulting in durable local control and an acceptable level of acute toxicity.


Assuntos
Carcinoma Basocelular/radioterapia , Neoplasias da Orelha/radioterapia , Proteínas Hedgehog/antagonistas & inibidores , Neoplasias Cutâneas/radioterapia , Anilidas/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Terapia Combinada , Neoplasias da Orelha/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Piridinas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico
19.
Epilepsia ; 56(4): 585-91, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25873180

RESUMO

OBJECTIVE: To investigate whether the link between epilepsy and deprivation is due to factors associated with deprivation (social causation) or factors associated with a diagnosis of epilepsy (social drift). METHODS: We reviewed electronic primary health care records from 2004 to 2010, identifying prevalent and incident cases of epilepsy and recording linked deprivation scores. Logistic and Poisson regression models were used to calculate odds ratios and incidence rate ratios. The change in deprivation was measured 10 years after the initial diagnosis of epilepsy for a cohort of people. RESULTS: Between 2004 and 2010, 8.1 million patient-years of records were reviewed. Epilepsy prevalence and incidence were significantly associated with deprivation. Epilepsy prevalence ranged from 1.13% (1.07-1.19%) in the most deprived decile to 0.49% (0.45-0.53%) in the least deprived decile (adjusted odds ratio 0.92, p < 0.001). Epilepsy incidence ranged from 40/100,000 per year in the most deprived decile to 19/100,000 per year in the least deprived decile (adjusted incidence rate ratio 0.94, p < 0.001). There was no statistically significant change in deprivation index decile 10 years after a new diagnosis of epilepsy (mean difference -0.04, p = 0.85). SIGNIFICANCE: Epilepsy prevalence and incidence are strongly associated with deprivation; the deprivation score remains unchanged 10 years after a diagnosis of epilepsy. These findings suggest that increasing rates of epilepsy in deprived areas are more likely explained by social causation than by social drift. The nature of the association between incident epilepsy and social deprivation needs further exploration.


Assuntos
Coleta de Dados , Registros Eletrônicos de Saúde , Epilepsia/diagnóstico , Epilepsia/psicologia , Necessidades e Demandas de Serviços de Saúde , Carência Psicossocial , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , País de Gales/epidemiologia , Adulto Jovem
20.
Transpl Infect Dis ; 17(1): 14-20, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25620387

RESUMO

BACKGROUND: Fungal infections remain a substantial cause of mortality in lung transplant (LTx) recipients, yet no comprehensive consensus guidelines have been established for antifungal prophylaxis and treatment of Aspergillus infection in these patients. METHODS: A cross-sectional study surveyed the directors from 27 of 64 (45.5%) active LTx centers in the United States to examine clinical practice variations in Aspergillus prophylaxis and treatment of colonization and invasive aspergillosis (IA) in LTx recipients. RESULTS: Antifungal prophylaxis increased from 52.3% in 2011 to 77.8% in 2013, with the most common agent being inhaled amphotericin B (61.9%), followed by oral voriconazole (51.9%). A total of 74.1% of centers treat Aspergillus airway colonization, with 80.0% of centers using oral voriconazole. All centers treat IA, with 92.6% using oral voriconazole. The duration of Aspergillus prophylaxis and treatment of colonization or IA varied widely across centers from 3 months to >1 year. A total of 51.9% of centers reported internal practice variations in the treatment of IA. Factors guiding treatment decisions included microbiologic culture and sensitivity (74.1%), ease of administration (59.3%), interaction with other medications (55.5%), side effect profile (51.8%), and center guidelines (48.1%). Although 85.2% of LTx centers recommended routine skin cancer screening for LTx recipients, only 44.4% of LTx centers reported having a dedicated transplant dermatologist. CONCLUSION: Most active US LTx centers currently employ antifungal prophylaxis and treat Aspergillus colonization and IA, although choice of agent, route of administration, and duration of therapy across and within centers continue to differ substantially. The number of transplant dermatologists available among US LTx centers is limited. Overall, a strong need exists for more comprehensive consensus guidelines to direct antifungal prophylaxis and treatment of Aspergillus infection in LTx recipients.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Aspergilose/prevenção & controle , Aspergillus/efeitos dos fármacos , Transplante de Pulmão/efeitos adversos , Voriconazol/uso terapêutico , Estudos Transversais , Humanos , Profilaxia Pré-Exposição , Inquéritos e Questionários , Estados Unidos
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