Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

BACKGROUND The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. METHODS AND FINDINGS The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose-response relationship and specificity), we found that more than half the relevant studies supported a causal association with Zika virus infection. For GBS, we included 36 items, of which more than half the relevant studies supported a causal association in seven of ten dimensions (all except dose-response relationship, specificity, and animal experimental evidence). Articles identified nonsystematically from May 30 to July 29, 2016 strengthened the review findings. The expert panel concluded that (a) the most likely explanation of available evidence from outbreaks of Zika virus infection and clusters of microcephaly is that Zika virus infection during pregnancy is a cause of congenital brain abnormalities including microcephaly, and (b) the most likely explanation of available evidence from outbreaks of Zika virus infection and GBS is that Zika virus infection is a trigger of GBS. The expert panel recognised that Zika virus alone may not be sufficient to cause either congenital brain abnormalities or GBS but agreed that the evidence was sufficient to recommend increased public health measures. Weaknesses are the limited assessment of the role of dengue virus and other possible cofactors, the small number of comparative epidemiological studies, and the difficulty in keeping the review up to date with the pace of publication of new research. CONCLUSIONS Rapid and systematic reviews with frequent updating and open dissemination are now needed both for appraisal of the evidence about Zika virus infection and for the next public health threats that will emerge. This systematic review found sufficient evidence to say that Zika virus is a cause of congenital abnormalities and is a trigger of GBS

Impact of Trauma System Structure on Injury Outcomes : A Systematic Review and Meta-Analysis

The effectiveness of trauma systems in decreasing injury mortality and morbidity has been well demonstrated. However, little is known about which components contribute to their effectiveness. We aimed to systematically review the evidence of the impact of trauma system components on clinically important injury outcomes. We searched MEDLINE, EMBASE, Cochrane CENTRAL, and BIOSIS/Web of Knowledge, gray literature and trauma association Web sites to identify studies evaluating the association between at least one trauma system component and injury outcome. We calculated pooled effect estimates using inverse-variance random-effects models. We evaluated quality of evidence using GRADE criteria. We screened 15,974 records, retaining 41 studies for qualitative synthesis and 19 for meta-analysis. Two recommended trauma system components were associated with reduced odds of mortality: inclusive design (odds ratio [OR] = 0.72 [0.65-0.80]) and helicopter transport (OR = 0.70 [0.55-0.88]). Pre-Hospital Advanced Trauma Life Support was associated with a significant reduction in hospital days (mean difference [MD] = 5.7 [4.4-7.0]) but a nonsignificant reduction in mortality (OR = 0.78 [0.44-1.39]). Population density of surgeons was associated with a nonsignificant decrease in mortality (MD = 0.58 [-0.22 to 1.39]). Trauma system maturity was associated with a significant reduction in mortality (OR = 0.76 [0.68-0.85]). Quality of evidence was low or very low for mortality and healthcare utilization. This review offers low-quality evidence for the effectiveness of an inclusive design and trauma system maturity and very-low-quality evidence for helicopter transport in reducing injury mortality. Further research should evaluate other recommended components of trauma systems and non-fatal outcomes and explore the impact of system component interactions.Peer reviewe

Common issues raised during the quality assurance process of WHO guidelines: a cross-sectional study

Abstract Background In 2007, WHO established the Guidelines Review Committee (GRC) to ensure that WHO guidelines adhere to the highest international standards. The GRC reviews guideline proposals and final guidelines. The objectives of this study were to examine the rates of and reasons for conditional approval and non-approval of documents submitted for the first time to the GRC, and calculate the time intervals and numbers of submissions to achieve approval for documents conditionally approved or not approved at first submission. Methods All initial submissions to the GRC between 2014 and 2017 were examined. Data were extracted from the GRC’s records of written comments and discussions. Results Of a total of 85 proposals and 88 final guidelines, 32 (37.6%) proposals and 37 (42.0%) final guidelines were conditionally approved, and 15 (17.6%) proposals and 28 (31.8%) final guidelines were not. For both conditionally approved and not approved proposals, the most frequent reasons were suboptimal composition or inadequate description of the guideline contributor groups (in all proposals), followed by inadequate formulation of key questions (in 90.6% of conditionally approved proposals and all not approved proposals). For both conditionally approved and not approved final guidelines, the most frequent reasons were problems with recommendations (in all final guidelines), followed by inappropriate methods for evidence retrieval or an inadequate description thereof (in all conditionally approved final guidelines and 75.0% of not approved final guidelines). The median time to achieve approval was 2 months for proposals and 1–2 months for final guidelines. The median number of submissions was 2 for proposals and 2–2.5 for final guidelines. Conclusion The GRC implements a rigorous quality assurance process and identifies problems with a significant percentage of initial submissions. WHO needs to continuously evaluate its guideline development processes to inform effective quality improvement measures and optimise the quality of its guidelines

Correction: An evaluation of emergency guidelines issued by the World Health Organization in response to four infectious disease outbreaks.

[This corrects the article DOI: 10.1371/journal.pone.0198125.]

An evaluation of emergency guidelines issued by the World Health Organization in response to four infectious disease outbreaks.

BACKGROUND:The production of high-quality guidelines in response to public health emergencies poses challenges for the World Health Organization (WHO). The urgent need for guidance and the paucity of structured scientific data on emerging diseases hinder the formulation of evidence-informed recommendations using standard methods and procedures. OBJECTIVES:In the context of the response to recent public health emergencies, this project aimed to describe the information products produced by WHO and assess the quality and trustworthiness of a subset of these products classified as guidelines. METHODS:We selected four recent infectious disease emergencies: outbreaks of avian influenza A-H1N1 virus (2009) and H7N9 virus (2013), Middle East respiratory syndrome coronavirus (MERS-CoV) (2013), and Ebola virus disease (EVD) (2014 to 2016). We analyzed the development and publication processes and evaluated the quality of emergency guidelines using AGREE-II. RESULTS:We included 175 information products of which 87 were guidelines. These products demonstrated variable adherence to WHO publication requirements including the listing of external contributors, management of declarations of interest, and entry into WHO's public database of publications. For guidelines, the methods for development were incompletely reported; WHO's quality assurance process was rarely used; systematic or other evidence reviews were infrequently referenced; external peer review was not performed; and they scored poorly with AGREE II, particularly for rigour of development and editorial independence. CONCLUSIONS:Our study suggests that WHO guidelines produced in the context of a public health emergency can be improved upon, helping to assure the trustworthiness and utility of WHO information products in future emergencies

Guideline development processes in recent public health emergencies.

<p>Guideline development processes in recent public health emergencies.</p

AGREE II scaled domain scores of guidelines developed for H1N1, H7N9, MERS-CoV and EVD.

<p>EVD, Ebola virus disease; MERS-CoV, Middle East Respiratory Syndrome Coronavirus. The AGREE II domains are displayed along the horizontal axis. The data points are the median, interquartile range, and minimum and maximum standardized scores based on the scores of the two reviewers for each domain and outbreak.</p

Ebola virus disease information products and timing of the epidemic.

<p>EVD, Ebola virus disease.</p