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Article ; Online: Severe acute hepatitis of unknown aetiology in children-what is known?

Khader, Susan / Foster, Isabel / Dagens, Andrew / Norton, Alice / Sigfrid, Louise

2022 Volume 20, Issue 1, Page(s) 280

Abstract: The ongoing investigations into clusters of children affected by severe acute hepatitis of unknown aetiology have put our global capacity for a coordinated, effective response to the test. The global health community have rapidly convened to share data ... ...

Abstract	The ongoing investigations into clusters of children affected by severe acute hepatitis of unknown aetiology have put our global capacity for a coordinated, effective response to the test. The global health community have rapidly convened to share data and inform the response. In the UK, where most cases were initially identified, a coordinated public health and clinical research response was rapidly initiated. Since then, cases have been reported from other countries, predominantly from higher-income countries. While agencies are keeping an open mind to the cause, the working hypothesis and case notifications raise important questions about our capacity to detect emerging cases in lower-resourced settings with a recognised lack of access to diagnostics even for commonly circulating viruses such as hepatitis A. The limited capability to generate integrated global pathogen surveillance data is a challenge for the outbreak investigations, highlighting an urgent need to strengthen access to diagnostics, with a focus on lower-resourced settings, to improve the capacity to detect emerging diseases to inform care and to improve outcomes and outbreak control.
MeSH term(s)	Acute Disease ; Child ; Disease Outbreaks ; Global Health ; Hepatitis ; Humans ; Public Health
Language	English
Publishing date	2022-07-29
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-022-02471-5
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Article ; Online: The diagnostic accuracy of rapid diagnostic tests for Ebola virus disease: a systematic review.

Dagens, Andrew B / Rojek, Amanda / Sigfrid, Louise / Plüddemann, Annette

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2022 Volume 29, Issue 2, Page(s) 171–181

Abstract: Background: Ebola virus disease (EVD) is a dangerous condition that can cause an epidemic. Several rapid diagnostic tests (RDTs) have been developed to diagnose EVD. These RDTs promise to be quicker and easier to use than the current reference standard ... ...

Abstract	Background: Ebola virus disease (EVD) is a dangerous condition that can cause an epidemic. Several rapid diagnostic tests (RDTs) have been developed to diagnose EVD. These RDTs promise to be quicker and easier to use than the current reference standard diagnostic test, PCR. Objectives: To assess the diagnostic accuracy of RDTs for EVD. Methods: A systematic review of diagnostic accuracy studies. Data sources: The following bibliographic databases were searched from inception to present: MEDLINE (Ovid), Embase, Global Health, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus database, Web of Science, PROSPERO register of Systematic Reviews, and Clinical Trials.Gov. Study eligibility criteria: Diagnostic accuracy studies. Participants: Patients presenting to the Ebola treatment units with symptoms of EVD. Interventions: RDTs; reference standard, RT-PCR. Assessment of risk of bias: Quality Assessment of Diagnostic Accuracy Studies-2 tool. Methods of data synthesis: Summary estimates of diagnostic accuracy study were produced for each device type. Subgroup analyses were performed for RDT type and specimen material. A sensitivity analysis was performed to assess the effect of trial design and bias. Results: We included 15 diagnostic accuracy studies. The summary estimate of sensitivity for lateral flow assays was 86.1% (95% CI, 86-86.2%), with specificity of 97% (95% CI, 96.1-97.9%). The summary estimate for rapid PCR devices was sensitivity of 96.2% (95% CI, 95.3-97.9%), with a specificity of 96.8% (95% CI, 95.3-97.9%). Pre-specified subgroup analyses demonstrated that RDTs were effective on a range of specimen material. Overall, the risk of bias throughout the included studies was low, but it was high in patient selection and uncertain in the flow and timing domains. Conclusions: RDTs possess both high sensitivity and specificity compared with RT-PCR among symptomatic patients presenting to the Ebola treatment units. Our findings support the use of RDTs as a 'rule in' test to expedite treatment and vaccination.
MeSH term(s)	Humans ; Hemorrhagic Fever, Ebola/diagnosis ; Hemorrhagic Fever, Ebola/epidemiology ; Polymerase Chain Reaction ; Rapid Diagnostic Tests ; Sensitivity and Specificity
Language	English
Publishing date	2022-09-23
Publishing country	England
Document type	Journal Article ; Systematic Review
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1016/j.cmi.2022.09.014
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Zs.A 4541: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Severe acute hepatitis of unknown aetiology in children—what is known?

Susan Khader / Isabel Foster / Andrew Dagens / Alice Norton / Louise Sigfrid

BMC Medicine, Vol 20, Iss 1, Pp 1-

2022 Volume 9

Abstract: Abstract The ongoing investigations into clusters of children affected by severe acute hepatitis of unknown aetiology have put our global capacity for a coordinated, effective response to the test. The global health community have rapidly convened to ... ...

Abstract	Abstract The ongoing investigations into clusters of children affected by severe acute hepatitis of unknown aetiology have put our global capacity for a coordinated, effective response to the test. The global health community have rapidly convened to share data and inform the response. In the UK, where most cases were initially identified, a coordinated public health and clinical research response was rapidly initiated. Since then, cases have been reported from other countries, predominantly from higher-income countries. While agencies are keeping an open mind to the cause, the working hypothesis and case notifications raise important questions about our capacity to detect emerging cases in lower-resourced settings with a recognised lack of access to diagnostics even for commonly circulating viruses such as hepatitis A. The limited capability to generate integrated global pathogen surveillance data is a challenge for the outbreak investigations, highlighting an urgent need to strengthen access to diagnostics, with a focus on lower-resourced settings, to improve the capacity to detect emerging diseases to inform care and to improve outcomes and outbreak control.
Keywords	Acute severe hepatitis of unknown origin ; Paediatrics ; Child health ; Preparedness ; Outbreak response ; Global health ; Medicine ; R
Subject code	360
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Acute intermittent porphyria leading to posterior reversible encephalopathy syndrome (PRES): a rare cause of abdominal pain and seizures.

Dagens, Andrew / Gilhooley, Michael James

BMJ case reports

2016 Volume 2016

Abstract: Acute intermittent porphyria (AIP) is an inherited deficiency in the haem biosynthesis pathway. AIP is rare, affecting around 1 in 75 000 people. Acute attacks are characterised by abdominal pain associated with autonomic, neurological and psychiatric ... ...

Abstract	Acute intermittent porphyria (AIP) is an inherited deficiency in the haem biosynthesis pathway. AIP is rare, affecting around 1 in 75 000 people. Acute attacks are characterised by abdominal pain associated with autonomic, neurological and psychiatric symptoms. AIP is rarely associated with posterior reversible encephalopathy syndrome (PRES). PRES is a clinicoradiological condition caused by the failure of the posterior circulation to autoregulate, resulting in cerebral oedema, headaches, nausea and seizures. This association is important because drugs used in the management of seizures may worsen an attack of AIP. This article describes a case of AIP and PRES in a young woman.
MeSH term(s)	Abdominal Pain/etiology ; Adult ; Female ; Humans ; Magnetic Resonance Imaging ; Porphyria, Acute Intermittent/complications ; Porphyria, Acute Intermittent/diagnosis ; Porphyrins/urine ; Posterior Leukoencephalopathy Syndrome/diagnosis ; Posterior Leukoencephalopathy Syndrome/diagnostic imaging ; Seizures/etiology
Chemical Substances	Porphyrins
Language	English
Publishing date	2016-06-08
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2016-215350
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Article ; Online: Trans-Atlantic aeromedical repatriation of multiple COVID-19 patients: a hybrid military-civilian model.

Dagens, Andrew Benjamin / Mckinnon, J / Simpson, R / Calvert, C / Keast, T / Hart, N / Almond, M

BMJ military health

2020 Volume 169, Issue e1, Page(s) e93–e96

Abstract: Here, we report the first known transcontinental aeromedical evacuation of a large number (55) of patients with known and suspected positive COVID-19. These patients were evacuated from Havana, Cuba, to the UK through MOD Boscombe Down as part of ... ...

Abstract	Here, we report the first known transcontinental aeromedical evacuation of a large number (55) of patients with known and suspected positive COVID-19. These patients were evacuated from Havana, Cuba, to the UK through MOD Boscombe Down as part of Operation BROADSHARE, the British military's overseas response to COVID-19. We describe the safe transfer of patients with COVID-19 using a combined military-civilian model. In our view, we have demonstrated that patients with COVID-19 can be aeromedically transferred while ensuring the safety of patients and crew using a hybrid military-civilian model; this report contains lessons for future aeromedical evacuation of patients with COVID-19.
MeSH term(s)	Humans ; Air Ambulances ; Transportation of Patients ; Military Personnel ; COVID-19
Language	English
Publishing date	2020-12-24
Publishing country	England
Document type	Editorial
ZDB-ID	3011686-7
ISSN	2633-3775 ; 2633-3767
ISSN (online)	2633-3775
ISSN	2633-3767
DOI	10.1136/bmjmilitary-2020-001565
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Article ; Online: Scope, quality, and inclusivity of clinical guidelines produced early in the covid-19 pandemic: rapid review.

Dagens, Andrew / Sigfrid, Louise / Cai, Erhui / Lipworth, Sam / Cheng, Vincent / Harris, Eli / Bannister, Peter / Rigby, Ishmeala / Horby, Peter

BMJ (Clinical research ed.)

2020 Volume 369, Page(s) m1936

Abstract: Objective: To appraise the availability, quality, and inclusivity of clinical guidelines produced in the early stage of the coronavirus disease 2019 (covid-19) pandemic.: Design: Rapid review.: Data sources: Ovid Medline, Ovid Embase, Ovid Global ... ...

Abstract	Objective: To appraise the availability, quality, and inclusivity of clinical guidelines produced in the early stage of the coronavirus disease 2019 (covid-19) pandemic. Design: Rapid review. Data sources: Ovid Medline, Ovid Embase, Ovid Global Health, Scopus, Web of Science Core Collection, and WHO Global Index Medicus, searched from inception to 14 Mar 2020. Search strategies applied the CADTH database guidelines search filter, with no limits applied to search results. Further studies were identified through searches of grey literature using the ISARIC network. Inclusion criteria: Clinical guidelines for the management of covid-19, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) produced by international and national scientific organisations and government and non-governmental organisations relating to global health were included, with no exclusions for language. Regional/hospital guidelines were excluded. Only the earliest version of any guideline was included. Quality assessment: Quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. The quality and contents of early covid-19 guidelines were also compared with recent clinical guidelines for MERS and SARS. Results: 2836 studies were identified, of which 2794 were excluded after screening. Forty two guidelines were considered eligible for inclusion, with 18 being specific to covid-19. Overall, the clinical guidelines lacked detail and covered a narrow range of topics. Recommendations varied in relation to, for example, the use of antiviral drugs. The overall quality was poor, particularly in the domains of stakeholder involvement, applicability, and editorial independence. Links between evidence and recommendations were limited. Minimal provision was made for vulnerable groups such as pregnant women, children, and older people. Conclusions: Guidelines available early in the covid-19 pandemic had methodological weaknesses and neglected vulnerable groups such as older people. A framework for development of clinical guidelines during public health emergencies is needed to ensure rigorous methods and the inclusion of vulnerable populations. Systematic review registration: PROSPERO CRD42020167361.
MeSH term(s)	Adrenal Cortex Hormones/therapeutic use ; Antiviral Agents/therapeutic use ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/therapy ; Humans ; Oxygen Inhalation Therapy ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/therapy ; Practice Guidelines as Topic/standards ; SARS-CoV-2 ; Severe Acute Respiratory Syndrome/therapy ; Venous Thromboembolism/prevention & control ; Vulnerable Populations ; World Health Organization
Chemical Substances	Adrenal Cortex Hormones ; Antiviral Agents
Keywords	covid19
Language	English
Publishing date	2020-05-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj.m1936
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Article: Laparoscopic management of a delayed traumatic diaphragmatic rupture complicated by bowel strangulation.

Baldwin, Mathew / Dagens, Andrew / Sgromo, Bruno

Journal of surgical case reports

2014 Volume 2014, Issue 7

Abstract: Traumatic rupture of the diaphragm (TDR) presents diagnostic difficulty, with basic radiological investigations discovering less than half of all cases. As a consequence, complications of diaphragmatic rupture may present long after the initial injury ... ...

Abstract	Traumatic rupture of the diaphragm (TDR) presents diagnostic difficulty, with basic radiological investigations discovering less than half of all cases. As a consequence, complications of diaphragmatic rupture may present long after the initial injury has occurred-the time delay obscuring diagnosis. Once discovered repair is necessary with previous reports advocating open repair. Here, we report a case of traumatic diaphragmatic rupture causing small bowel obstruction 20 years after initial injury. The patient, a young woman, underwent successful laparoscopic assisted diaphragmatic repair with small bowel resection. TDR is an unusual but important differential diagnosis of an acute abdomen. A high index of suspicion is required to avoid delayed diagnosis and increased mortality.
Language	English
Publishing date	2014-07-16
Publishing country	England
Document type	Case Reports
ISSN	2042-8812
ISSN	2042-8812
DOI	10.1093/jscr/rju073
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Article ; Online: Standard of care for viral haemorrhagic fevers (VHFs): a systematic review of clinical management guidelines for high-priority VHFs.

The Lancet. Infectious diseases

2023 Volume 23, Issue 7, Page(s) e240–e252

Abstract: The Sudan virus disease outbreak in Uganda in 2022 showed our vulnerability to viral haemorrhagic fevers (VHFs). Although there are regular outbreaks of VHFs with high morbidity and mortality, which disproportionally affect low-income settings, our ... ...

Abstract	The Sudan virus disease outbreak in Uganda in 2022 showed our vulnerability to viral haemorrhagic fevers (VHFs). Although there are regular outbreaks of VHFs with high morbidity and mortality, which disproportionally affect low-income settings, our understanding of how to treat them remains inadequate. In this systematic review, we aim to explore the availability, scope, standardisation, and quality of clinical management guidelines for VHFs. We identified 32 guidelines, 25 (78%) of which were low quality and did not have supporting evidence and eight (25%) of which had been produced or updated in the past 3 years. Guidance on supportive care and therapeutics had little detail and was sometimes contradictory. Guidelines based on uncertain evidence are a risk to patients, an ethical challenge for clinicians, and a challenge to implementing trials due to heterogeneous standards of care. We recommend a standard living guideline framework to improve the quality, scope, and applicability of guidelines. Furthermore, investments into trials should aim to identify optimal treatment strategies for VHFs and prioritise affordable and scalable interventions to improve outcomes globally.
MeSH term(s)	Humans ; Standard of Care ; Hemorrhagic Fevers, Viral/epidemiology ; Disease Outbreaks ; Uganda/epidemiology
Language	English
Publishing date	2023-02-06
Publishing country	United States
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(22)00874-X
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Article ; Online: Preparing for pandemics: a systematic review of pandemic influenza clinical management guidelines.

Rigby, Ishmeala / Michelen, Melina / Cheng, Vincent / Dagens, Andrew / Dahmash, Dania / Lipworth, Samuel / Harriss, Eli / Cai, Erhui / Balan, Valeria / Oti, Alexandra / Joseph, Reena / Groves, Helen / Hart, Peter / Jacob, Shevin / Blumberg, Lucille / Horby, Peter W / Sigfrid, Louise

BMC medicine

2022 Volume 20, Issue 1, Page(s) 425

Abstract: Background: The COVID-19 pandemic has highlighted the importance of evidence-based clinical decision-making. Clinical management guidelines (CMGs) may help reduce morbidity and mortality by improving the quality of clinical decisions. This systematic ... ...

Abstract	Background: The COVID-19 pandemic has highlighted the importance of evidence-based clinical decision-making. Clinical management guidelines (CMGs) may help reduce morbidity and mortality by improving the quality of clinical decisions. This systematic review aims to evaluate the availability, inclusivity, and quality of pandemic influenza CMGs, to identify gaps that can be addressed to strengthen pandemic preparedness in this area. Methods: Ovid Medline, Ovid Embase, TRIP (Turning Research Into Practice), and Guideline Central were searched systematically from January 2008 to 23rd June 2022, complemented by a grey literature search till 16th June 2022. Pandemic influenza CMGs including supportive care or empirical treatment recommendations were included. Two reviewers independently extracted data from the included studies and assessed their quality using AGREE II (Appraisal of Guidelines for Research & Evaluation). The findings are presented narratively. Results: Forty-eight CMGs were included. They were produced in high- (42%, 20/48), upper-middle- (40%, 19/48), and lower-middle (8%, 4/48) income countries, or by international organisations (10%, 5/48). Most CMGs (81%, 39/48) were over 5 years old. Guidelines included treatment recommendations for children (75%, 36/48), pregnant women (54%, 26/48), people with immunosuppression (33%, 16/48), and older adults (29%, 14/48). Many CMGs were of low quality (median overall score: 3 out of 7 (range 1-7). All recommended oseltamivir; recommendations for other neuraminidase inhibitors and supportive care were limited and at times contradictory. Only 56% (27/48) and 27% (13/48) addressed oxygen and fluid therapy, respectively. Conclusions: Our data highlights the limited availability of up-to-date pandemic influenza CMGs globally. Of those identified, many were limited in scope and quality and several lacked recommendations for specific at-risk populations. Recommendations on supportive care, the mainstay of treatment, were limited and heterogeneous. The most recent guideline highlighted that the evidence-base to support antiviral treatment recommendations is still limited. There is an urgent need for trials into treatment and supportive care strategies including for different risk populations. New evidence should be incorporated into globally accessible guidelines, to benefit patient outcomes. A 'living guideline' framework is recommended and further research into guideline implementation in different resourced settings, particularly low- and middle-income countries.
MeSH term(s)	Child ; Female ; Humans ; Pregnancy ; Aged ; Child, Preschool ; Pandemics ; Influenza, Human/drug therapy ; Influenza, Human/epidemiology ; COVID-19 ; Oseltamivir ; Antiviral Agents/therapeutic use
Chemical Substances	Oseltamivir (20O93L6F9H) ; Antiviral Agents
Language	English
Publishing date	2022-11-07
Publishing country	England
Document type	Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-022-02616-6
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Article ; Online: Accessibility, inclusivity, and implementation of COVID-19 clinical management guidelines early in the pandemic: a global survey

Pilbeam, Caitlin / Malden, Deobrah / Newell, Katherine / Dagens, Andrew / Kennon, Kalynn / Michelen, Melina / Gobat, Nina / Sigfrid, Louise

medRxiv

Abstract: Background: With a rapidly changing evidence base, high-quality clinical management guidelines (CMGs) are key tools for aiding clinical decision making and increasing access to best available evidence-based care. A rapid review of COVID-19 CMGs found ... ...

Abstract	Background: With a rapidly changing evidence base, high-quality clinical management guidelines (CMGs) are key tools for aiding clinical decision making and increasing access to best available evidence-based care. A rapid review of COVID-19 CMGs found that most lacked methodological rigour, overlooked many at-risk populations, and had variations in treatment recommendations. Furthermore, social science literature highlights the complexity of implementing guidelines in local contexts where they were not developed and the resulting potential to compound health inequities. The aim of this study was to evaluate access to, inclusivity of, and implementation of Covid-19 CMGs in different settings. Methods: A cross-sectional survey of clinicians worldwide from 15 June to 20 July 2020, to explore access to and implementation of Covid-19 CMGs and treatment and supportive care recommendations provided. Data on accessibility, inclusivity, and implementation of CMGs. were analyzed by geographic location. Results: Seventy-six clinicians, from 27 countries responded, 82% from high-income countries, 17% from low-middle income countries. Most respondents reported access to Covid-19 CMG and confidence in implementation of these. However, many respondents, particularly from LMICs reported barriers to implementation, including limited access to treatments and equipment. Only 20% of respondents reported having access to CMGs covering care for children, 25% for pregnant women and 50% for older adults (>65 years). Themes emerging were for CMGs to include recommendations for different at-risk populations, and settings, include supportive care guidance, be readily updated as evidence emerges, and CMG implementation supported by training, and access to treatments recommended. Conclusion: Our findings highlight important gaps in Covid-19 CMG development and implementation challenges during a pandemic, particularly affecting different at-risk populations and lower resourced settings. The findings highlight a need for a new, harmonized evidence-based, that is inclusive and adaptable for different context, incorporating implementation support, to improve access in evidence-based care recommendations during an emergency.
Keywords	covid19
Language	English
Publishing date	2021-04-01
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.03.31.21254680
Database	COVID19

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