Papers by Sylviane Defres
Case Studies in Neurological Infections of Adults and Children
Case Studies in Neurological Infections of Adults and Children, 2019
Case Studies in Neurological Infections of Adults and Children, 2019
Case Studies in Neurological Infections of Adults and Children, 2019
Journal of Infection, 2007
Journal of Clinical Pathology, 2000
Aims-To explore the role of the Peutz-Jeghers gene (LKB1) in sporadic breast and colon cancers. M... more Aims-To explore the role of the Peutz-Jeghers gene (LKB1) in sporadic breast and colon cancers. Methods-Thirty consecutive sporadic carcinomas of the breast and 23 of the colon were selected. DNA was extracted from paraYn wax embedded tissue and analysed for loss of heterozygosity (LOH) at microsatellite markers D19S886 and D19S565 close to the LKB1 gene. Tumours showing LOH were screened for LKB1 mutations by single strand conformational polymorphism (SSCP). Results-Five breast carcinomas showed LOH (21% and 7% of those informative for D19S886 and D19S565, respectively). Five of the colorectal carcinomas showed LOH (15% and 36% of those informative for D19S886 and D19S565, respectively), with one sample showing allele loss with both markers. Screening of these 10 carcinomas by SSCP identified one migrational shift but sequencing revealed an intronic polymorphism only. Therefore, no coding mutations were found in these carcinomas. Conclusions-These findings suggest that although allele loss at the LKB1 locus occurs relatively frequently in sporadic breast and colon cancers, mutations do not seem to be a feature.
British Journal of Anaesthesia, 2005
The Lancet Respiratory Medicine
BMC Neurology
Background Seizures can occur unpredictably in patients with acute encephalitis syndrome (AES), a... more Background Seizures can occur unpredictably in patients with acute encephalitis syndrome (AES), and many suffer from poor long-term neurological sequelae. Establishing factors associated with acute seizures risk and poor outcomes could support clinical care. We aimed to conduct regional and volumetric analysis of cerebral oedema on magnetic resonance imaging (MRI) in patients with AES. We assessed the relationship of brain oedema with acute seizure activity and long-term neurological outcome. Methods In a multi-centre cohort study, adults and children presenting with an AES were recruited in the UK. The clinical and brain MRI data were retrospectively reviewed. The outcomes variables were inpatient acute seizure activity and neurological disability at six-months post-discharge. A poor outcome was defined as a Glasgow outcome score (GOS) of 1–3. We quantified regional brain oedema on MRI through stereological examination of T2-weighted images using established methodology by independ...
BMJ Neurology Open
ObjectiveIn patients with encephalitis, the development of acute symptomatic seizures is highly v... more ObjectiveIn patients with encephalitis, the development of acute symptomatic seizures is highly variable, but when present is associated with a worse outcome. We aimed to determine the factors associated with seizures in encephalitis and develop a clinical prediction model.MethodsWe analysed 203 patients from 24 English hospitals (2005–2008) (Cohort 1). Outcome measures were seizures prior to and during admission, inpatient seizures and status epilepticus. A binary logistic regression risk model was converted to a clinical score and independently validated on an additional 233 patients from 31 UK hospitals (2013–2016) (Cohort 2).ResultsIn Cohort 1, 121 (60%) patients had a seizure including 103 (51%) with inpatient seizures. Admission Glasgow Coma Scale (GCS) ≤8/15 was predictive of subsequent inpatient seizures (OR (95% CI) 5.55 (2.10 to 14.64), p<0.001), including in those without a history of prior seizures at presentation (OR 6.57 (95% CI 1.37 to 31.5), p=0.025).A clinical mo...
SSRN Electronic Journal, 2021
Background: Neurological COVID-19 disease has been reported widely, but often without using stand... more Background: Neurological COVID-19 disease has been reported widely, but often without using standard case definitions or detailed diagnostic work up. Several meta-analyses, based on such reports, describe the neurological diagnoses but give little information on outcomes and risk factors.Methods: We conducted an individual patient data meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute, and extracted aggregate data from published reports. We analysed features associated with poor outcome (moderate to severe sequelae or death, 3-6, on the modified Rankin scale) using multivariable models. Findings: We identified 381 studies (31 unpublished) describing 4443 patients with COVID-19 and neurological disease: 83 of these provided IPD for 1979 (45%) patients. Encephalopathy (978 [49%]) and cerebrovascular events (506 [26%]), were the most common diagnoses in the IPD database and aggregate data. Respiratory and systemic symptoms preceded neurological features in 93% of patients;one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41] overall), and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-Dimer. Overall, 30-day mortality was 30% (27-32). The hazard of death was reduced for patients in the WHO European region, but increased in low- and lower-middle-income countries. Interpretation: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission. Funding This study was funded by the UK Medical Research Council’s Global Effort on COVID-19 Programme (MR/V033441/1);UK National Institute for Health Research (NIHR)-funded Global Health Research Group on Acute Brain Infections (17/63/110);and the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (NIHR200907), at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (Grant Nos. IS-HPU-1112-10117 and NIHR200907).Declaration of Interests: BS reports a grant from UKRI/DHSC Global Effort on COVID-19 Research (Medical Research Council) and non-financial support from UK National Institute for Health Research Global Health Research Group on Brain Infections. SL and TS are supported by a grant from the EU Zika Preparedness Latin American Network consortium (ZikaPLAN). ZikaPLAN has received funding from the EU's Horizon 2020 research and innovation programme under grant agreement number 734584. LCG reports non-financial support from Pfizer, non-financial support from Gilead. LB reports grants from GlaxoSmithKline, Research England and Wellcome Trust. AMBM reports grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq/Brazil, and São Paulo Research Foundation FAPESP/Brazil. AP reports personal fees from ZAMBON, UCB , BIOMARIN, and ABBvie pharma. TS was an adviser to the GlaxoSmithKline Ebola Vaccine programme, chaired a Siemens Diagnostics clinical advisory board, and advises the WHO Brain Health Unit Forum on Neurology and COVID-19;TS has also previously filed a patent for a test for bacterial meningitis based on a blood test (GB 1606537.7, April 14, 2016), and has grants from the UK Medical Research Council and National Institute for Health Research. All other authors declare no conflict of interest
The experiences of people hospitalised with COVID-19 are under-researched. We designed a COVID-19... more The experiences of people hospitalised with COVID-19 are under-researched. We designed a COVID-19 patient satisfaction survey and collected responses (n=94) during Liverpool's first wave (April-June 2020). Although care was generally rated highly, including among people of BAME background, sleep-quality and communication about medications and discharge-planning were identified as areas for improvement. In response, we implemented an education and training package for healthcare professionals working on COVID-19 wards. During Liverpool's second/third COVID-19 wave, survey responses (n=101) suggested improvement in patient satisfaction across all care domains except discharge-planning and sleep-quality. These UK-first findings are informing local strategies to improve COVID-19 care.
BackgroundThe impact of COVID-19 on physical and mental health, and employment following hospital... more BackgroundThe impact of COVID-19 on physical and mental health, and employment following hospitalisation is poorly understood.MethodsPHOSP-COVID is a multi-centre, UK, observational study of adults discharged from hospital with a clinical diagnosis of COVID-19 involving an assessment between two- and seven-months later including detailed symptom, physiological and biochemical testing. Multivariable logistic regression was performed for patient-perceived recovery with age, sex, ethnicity, body mass index (BMI), co-morbidities, and severity of acute illness as co-variates. Cluster analysis was performed using outcomes for breathlessness, fatigue, mental health, cognition and physical function.FindingsWe report findings of 1077 patients discharged in 2020, from the assessment undertaken a median 5 [IQR4 to 6] months later: 36% female, mean age 58 [SD 13] years, 69% white ethnicity, 27% mechanical ventilation, and 50% had at least two co-morbidities. At follow-up only 29% felt fully rec...
The Lancet Neurology, 2020
Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Access Microbiology, 2020
Background Bacterial meningitis has significant mortality but frontline doctors will see it infre... more Background Bacterial meningitis has significant mortality but frontline doctors will see it infrequently. Therefore, UK guidance on meningitis in adults, with auditable standards, was revised in 2016. We undertook a national audit to assess adherence to the guidelines. Methods Patients with community acquired meningitis were identified through coding or laboratory data. Audit standards, including immediate management, diagnostics and treatment, were evaluated by notes review. Results Notes from 1472 patients with meningitis were reviewed – 309/1472 (21%) had bacterial aetiology, 615/1472 (42%) viral, 548/1472 (37%) unidentified aetiology. Only 50% of patients had blood cultures taken within one hour of admission and just 2% had a lumbar puncture (LP) within the first hour. 27% received antibiotics within one hour. Most patients received ceftriaxone or cefotaxime but only 37% of over-60s received empirical anti-listeria antibiotics. 26% of patients who had antibiotics were given adjunctive steroids. Half had CSF microscopy within two hours of LP. Less than a third had pneumococcal and/or meningococcal PCR on cerebrospinal fluid. Only 44% had an HIV test. 62% had unnecessary neuroimaging before LP. Overall mortality was 3% - 16% in pneumococcal disease and 8% in meningococcal meningitis. There was a trend toward improved survival in patients with pneumococcal meningitis who received dexamethasone [85/96 (88%)] compared to those who did not [57/73 (78%)] (p=0.066). Conclusions Adherence to the meningitis guidelines is inadequate, potentially compromising patient safety. Improvements in guideline dissemination, novel educational resources and clinician and patient engagement are required if we are to increase guideline adherence and improve outcome.
PLOS ONE, 2019
Background Encephalitis, characterised as inflammation of the brain tissue, is an important cause... more Background Encephalitis, characterised as inflammation of the brain tissue, is an important cause of acquired brain injury in children. Objective clinical outcomes vary significantly between affected patients, however they do not always correlate with quality of life as reported by parents. The aim of this study was to explore how parents experience and interpret outcomes in relation to their child who has been affected by encephalitis. Methods Data were derived from in-depth, semi-structured interviews, with 15 parents of 12 children and young people affected by encephalitis. Paediatric cases were identified from the retrospective arm of the research programme 'ENCEPH-UK-Understanding and Improving the Outcome of Encephalitis', and from the prospective UK childhood meningitis and encephalitis cohort study (UK-ChiMES, 2012 to 2016). Data were analysed thematically. Results Parents' perspectives on important outcomes for their child and family changed during the different stages of the encephalitis illness trajectory: from acute illness, recovery and rehabilitation, then reintegration into everyday life. Parents' understanding of their children's overall outcome was informed by their own experiences, involving comparisons PLOS ONE |
Journal of Travel Medicine, 2019
Background Japanese encephalitis (JE), caused by the mosquito-borne JE virus, is a vaccine-preven... more Background Japanese encephalitis (JE), caused by the mosquito-borne JE virus, is a vaccine-preventable disease endemic to much of Asia. Travellers from non-endemic areas are susceptible if they travel to a JE endemic area. Although the risk to travellers of JE is low, the consequences may be severe. Methods Here, we describe three cases of JE in British travellers occurring in 2014–15. In addition, we report, through interviews with survivors and their families, personal experiences of life after JE. Results Three cases of JE were diagnosed in British travellers in 2014/15. One was acquired in Thailand, one in China and one in either Thailand, Laos or Cambodia. All three patients suffered severe, life-threatening illnesses, all were admitted to intensive care units and required medical evacuation back to the UK. One patient suffered a cardiac arrest during the acute stage but made a good recovery. The other two patients remain significantly paralysed and ventilator dependent. All th...
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Papers by Sylviane Defres