Standard of care for viral haemorrhagic fevers (VHFs): a systematic review of clinical management guidelines for high-priority VHFs.

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.

Preparing for pandemics: a systematic review of pandemic influenza clinical management guidelines.

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.

An evaluation of global Chikungunya clinical management guidelines: A systematic review.

Background: Chikungunya virus (CHIKV) has expanded its geographical reach in recent decades and is an emerging global health threat. CHIKV can cause significant morbidity and lead to chronic, debilitating arthritis/arthralgia in up to 40% of infected individuals. Prevention, early identification, and clinical management are key for improving outcomes. The aim of this review is to evaluate the quality, availability, inclusivity, and scope of evidence-based clinical management guidelines (CMG) for CHIKV globally. Methods: We conducted a systematic review. Six databases were searched from Jan 1, 1989, to 14 Oct 2021 and grey literature until Sept 16, 2021, for CHIKV guidelines providing supportive care and treatment recommendations. Quality was assessed using the appraisal of Guidelines for Research and Evaluation tool. Findings are presented in a narrative synthesis. PROSPERO registration: CRD42020167361. Findings: 28 CMGs were included; 54% (15/28) were produced more than 5 years ago, and most were of low-quality (median score 2 out of 7 (range 1-7)). There were variations in the CMGs' guidance on the management of different at-risk populations, long-term sequelae, and the prevention of disease transmission. While 54% (15/28) of CMGs recommended hospitalisation for severe cases, only 39% (11/28) provided guidance for severe disease management. Further, 46% (13/28) advocated for steroids in the chronic phase, but 18% (5/28) advised against its use. Interpretation: There was a lack of high-quality CMGs that provided supportive care and treatment guidance, which may impact patient care and outcomes. It is essential that existing guidelines are updated and adapted to provide detailed evidence-based treatment guidelines for different at-risk populations. This study also highlights a need for more research into the management of the acute and chronic phases of CHIKV infection to inform evidence-based care. Funding: The UK Foreign, Commonwealth and Development Office, Wellcome Trust [215091/Z/18/Z] and the Bill & Melinda Gates Foundation [OPP1209135].

Availability, scope and quality of monkeypox clinical management guidelines globally: a systematic review.

BACKGROUND: Monkeypox (MPX) is an important human Orthopoxvirus infection. There has been an increase in MPX cases and outbreaks in endemic and non-endemic regions in recent decades. We appraised the availability, scope, quality and inclusivity of clinical management guidelines for MPX globally. METHODS: For this systematic review, we searched six databases from inception until 14 October 2021, augmented by a grey literature search until 17 May 2022. MPX guidelines providing treatment and supportive care recommendations were included, with no exclusions for language. Two reviewers assessed the guidelines. Quality was assessed using the Appraisal of Guidelines for Research and Evaluation II tool. RESULTS: Of 2026 records screened, 14 guidelines were included. Overall, most guidelines were of low-quality with a median score of 2 out of 7 (range: 1-7), lacked detail and covered a narrow range of topics. Most guidelines focused on adults, five (36%) provided some advice for children, three (21%) for pregnant women and three (21%) for people living with HIV. Treatment guidance was mostly limited to advice on antivirals; seven guidelines advised cidofovir (four specified for severe MPX only); 29% (4/14) tecovirimat, and 7% (1/14) brincidofovir. Only one guideline provided recommendations on supportive care and treatment of complications. All guidelines recommended vaccination as post-exposure prophylaxis (PEP). Three guidelines advised on vaccinia immune globulin as PEP for severe cases in people with immunosuppression. CONCLUSION: Our results highlight a lack of evidence-based clinical management guidelines for MPX globally. There is a clear and urgent need for research into treatment and prophylaxis including for different risk populations. The current outbreak provides an opportunity to accelerate this research through coordinated high-quality studies. New evidence should be incorporated into globally accessible guidelines, to benefit patient and epidemic outcomes. A 'living guideline' framework is recommended. PROSPERO REGISTRATION NUMBER: CRD42020167361.

Scope, quality, and inclusivity of clinical guidelines produced early in the covid-19 pandemic: rapid review.

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.

Serum miR-21 expression in human esophageal squamous cell carcinomas.

To investigate the relationship between serum miRNA-21 (miR-21) expression in esophageal squamous cell carcinomas (ESCCs) and their clinicopathologic features, a 1:1 matched case-control study including 21 patients with ESCC and 21 age- and gender-matched healthy controls was carried out. Serum specimens were taken from all subjects. Total RNA was extracted and the stem-loop real time polymerase chain reaction was used to measure serum miR-21 in both groups. Clinical parameters were assessed to determine associations with serum miR-21 concentrations. Serum miR-21 expression in ESCC samples was significantly higher than in paired cancer-free samples (P <0.05). Metastasis was associated with mir-21 expression in serum (P <0.05), ESCC patients with metastasis having 8.4-fold higher serum miR-21 concentrations than healthy controls. There were no statistically significant associations between miR-21 expression and clinicopathologic parameters, such as gender (P >0.05), age (P >0.05), tumor location (P >0.05), cell differentiation (P >0.05), TNM staging (P >0.05), whether chemo/radiotherapy had been administered (P >0.05), or whether surgery had been performed (P >0.05). These findings suggest that the detection of microRNA-21 in serum might serve as a new tumor biomarker in diagnosis and assessment of prognosis of ESCCs.

Prognostic value of vascular endothelial growth factor expression in patients with esophageal cancer: a systematic review and meta-analysis.

BACKGROUND: VEGF is a prime mediator of tumorigenesis and metastasis. Various studies assessing the prognostic value of VEGF in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the evidence on the suitability of VEGF to predict patients' survival. METHODS: Searches were applied to PubMed and EMBASE until December 31, 2011, without language restrictions. Studies were assessed for quality using REMARK (Reporting recommendations for tumor MARKer prognostic studies). Data were collected comparing overall survival in patients with high VEGF level with those with low level. We conducted a systematic review of 31 studies (n = 2,387 patients) and completed a meta-analysis of 30 studies (n = 2,345 patients) that correlated VEGF levels with overall survival. Data were synthesized with HRs. RESULTS: The estimated risk of death was 1.82-fold greater in patients with high VEGF expression [95% confidence interval (CI), 1.58-2.08]. The heterogeneity was not significant (P = 0.130) between studies. High VEGF expression was associated with worse survival in esophageal squamous cell carcinoma (HR, 1.81; 95% CI, 1.57-2.10) and there was no significance in between-study heterogeneity (P = 0.185). Data collected were not sufficient to determine the prognostic value of VEGF in patients with esophageal adenocarcinoma. CONCLUSIONS: In this meta-analysis, elevated VEGF expression was associated with poor survival in patients with esophageal cancer but not esophageal adenocarcinoma. IMPACT: These results support further investigation of VEGF expression for predicting poor survival in patients with esophageal carcinoma and may have implications for treatments directed at inhibiting VEGF-mediated angiogenesis.

Neoadjuvant chemotherapy for resectable esophageal carcinoma: a meta-analysis of randomized clinical trials.

Neoadjuvant chemotherapy for resectable esophageal carcinoma has been a focus of study, but no agreement has been reached on clinical randomized controlled trials and relevant systematic evaluation. The purpose of this study was to perform a meta-analysis on published randomized controlled trials (RCTs) that compared neoadjuvant chemotherapy and surgery with surgery alone for resectable esophageal carcinoma. Medline and manual searches was conducted in PubMed, ASCO (American Society of Clinical Oncology) meeting summary, Embase, the Cochrane Library (up to October 2010), Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database. The selection contents were to identify all published and unpublished RCTs that compared neoadjuvant chemotherapy and surgery with surgery alone for resectable esophageal carcinoma. Sixteen RCTs which included 2,594 patients were selected. The risk ratio (RR) (95% confidence interval [CI]; P value), expressed as neoadjuvant chemotherapy and surgery versus surgery alone (treatment versus control), was 1.02 (0.95, 1.10; P=0.54) for 1-year survival, 1.29 (1.13, 1.47; P=0.0001) for 3-year survival, 1.31 (1.13, 1.51; P=0.0003) for 5-year survival, 1.00 (0.95, 1.04; P= 0.85) for rate of resection and 0.89 (0.64, 1.23; P=0.48) for operative mortality. The results showed that neoadjuvant chemotherapy for resectable esophageal carcinoma can raise the overall survival rate of patients with esophageal carcinoma, but it does not affect treatment-related mortality.