Scoping Review Protocol
1.0 TITLE
A scoping review of the use of ultrasound in dengue
2.0 PROTOCOL INFORMATION
2.1 Contact Person
Neelesh Dewan (ndewan@umn.edu)
2.2 Authors
Mr Neelesh Dewan, Doris Duke Charitable Foundation, University of Minnesota, US.
Dr Christian Messu, Universidad del Valle, Colombia.
Dr Melissa Eelkema, Hennepin Country Medical Center, US.
Dr Iñigo Prieto, Universidad del Valle, Colombia.
Ms Caitlin Bakker, Health Sciences Libraries, University of Minnesota, US.
Dr Prof Lyda Osorio, Epidemiology and Population Health Research Group, School of Public Health,
Universidad del Valle, Colombia.
Dr Jonathan Kirsch, Medical School, University of Minnesota, US.
2.3 Organizational Affiliation of the Review
Universidad del Valle (Univalle), https://www.univalle.edu.co/
Hennepin County Medical Center, https://www.hennepinhealthcare.org/
University of Minnesota, https://www.umn.edu
2.4 Dates
Anticipated Start Date: 07 January 2019
Anticipated Completion Date: 10 May 2019
2.5 Funding Sources
Doris Duke Charitable Foundation
Center for Global Health and Social Responsibility
2.6 Conflicts of Interest
There are no known conflicts of interest
2.7 Countries
United States, Colombia
3.0 BACKGROUND
3.1 Review Question
How has ultrasound been used in dengue?
3.2 Review Objectives
The objective of this review is to identify and map the available evidence and knowledge gaps for the
use of ultrasound in dengue. This review is being undertaken concurrently with a study examining the
utility and feasibility of ultrasound performed by primary care physicians at point-of-care in dengue in
Cali, Colombia.
4.0 METHODS
We will limit to human participants in the context of dengue fever, particularly the detection of dengue
using ultrasound. This use can be in ambulatory or hospitalized settings. Ultrasound in the context of
dengue is most often utilized for detection of signs of plasma leakage. These signs can manifest as
pleural effusion, pericardial effusion, pericholecystic fluid, gallbladder wall thickening, ascites as
detected by fluid accumulation in the hepatorenal, splenorenal, or pelvic recesses, and presumably
inferior vena cava collapsibility suggesting depleted intravascular volume and/or pulmonary B-lines
suggesting interstitial pulmonary edema. There are no restrictions on the types of study design eligible
for inclusion. However, articles that do not present original data, such as editorials or opinion pieces,
will not be included.
We will search the following electronic bibliographic databases: MEDLINE via PubMed and Ovid,
Cochrane Library (Wiley), EMBASE via Ovid, Global Index Medicus, ClinicalTrials.gov, WHO ICTRP,
WHOLIS, opengrey.eu, and Scopus. The search strategy will include only terms relating to two key
concepts: 1) dengue and, 2) ultrasound. Search terms will be adapted for use according to respective
bibliographic databases. A combination of natural language and controlled vocabulary will be utilized
and reported in accordance with MECIR and PRISMA-ScR guidelines. There will be no language
restrictions or restrictions based on study design. There will be no date restriction as we would like to
document when the reporting on ultrasound in dengue began and how it progressed over time.
Additional studies identified in the reference lists of retrieved literature and relevant to the review
question will also be sought. The searches will be re-run just before the final analyses and further
studies retrieved for inclusion. Contacting dengue clinical researchers directly as to ongoing projects will
also be considered.
5.0 DATA COLLECTION AND ANALYSIS
5.1 Selection of Studies
Titles and abstracts of studies retrieved using the search strategy and those from additional sources will
be screened independently by two to three review authors to identify studies that potentially meet
inclusion criteria. Duplicates will be removed before a pilot round of screening. In the pilot round,
screeners will be assigned random selected references and asked to decide whether they meet inclusion
or exclusion criteria and why. The pilot will be conducted using a standardized Excel (Microsoft
Corporation, Richmond, WA, USA) form or Rayyan, a web and mobile app for systematic reviews. Each
screener will be blinded to others’ inputted data. Screeners will then meet to discuss their justifications
to reach a common understanding of how inclusion criteria shall be applied. Any disagreement between
them over the eligibility of particular studies will be resolved through discussion with an additional
reviewer. The full text of potentially eligible studies will be retrieved and independently assessed for
eligibility by one to two review team member(s) using the same process (i.e. following a pilot round with
other reviewers to establish consensus). Reasons for exclusion will be detailed and presented as a flow
diagram according the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension
for Scoping Reviews (PRISMA-ScR).
5.2 Quality Assessment
One to two study author(s) will assess the risk of bias using University of Bristol’s QUADAS-2 tool. We
will consider the following domains, as applicable:
 Patient selection: was a consecutive or random sample of patients enrolled? Was a casecontrol design avoided? Did the study avoid inappropriate exclusions?
 Index test(s): were the index test results interpreted without knowledge of the results of the
reference standard? If a threshold was used, was it pre-specified?
 Reference standard: is the reference standard likely to correctly classify the target condition?
Were the reference standard results interpreted without knowledge of the results of the
index test?
 Flow and timing: was there an appropriate interval between index test(s) and reference
standard? Did all patients receive a reference standard? Did patients receive the same
reference standard? Were all patients included in the analysis?
 Each domain will be rated as “low risk,” “high risk,” or “unclear risk” of “risk of bias” or of
“applicability concerns” according to the suggested use of QUADAS-2.
5.3 Data Extraction and Charting
Retrieved literature will be collected into Rayyan. Extracted data will include STARD 2015 essential items
for reporting diagnostic accuracy studies, QUADAS-2 results for assessment of bias (risk of bias [patient
selection, index test, reference standard, flow and timing], applicability concerns [patient selection,
index tests, reference standard]), and the following: study ID, title, year of publication, type of study
(prospective, retrospective, blinded or open, comparison group, case report, gold standard
confirmation), setting ( study country, language, hospitalization, outpatient, intensive care unit,
predominantly urban), demographics (percent male, average age, children included, pregnant women
included, race/ethnicity), study eligibility criteria, method of identifying eligible subjects (lab
confirmation, clinical/symptoms, combination), disease severity, probable dengue criteria
(nausea/vomiting, rash, aches and pains, tourniquet test positive), warning signs criteria (abdominal
pain, persistent vomiting, clinical fluid accumulation, mucosal bleed, lethargy, hepatomegaly,
hematocrit increase with platelet decrease), criteria for severe dengue (impaired consciousness,
hepatitis, severe organ failure, severe bleeding, shock, respiratory distress with fluid accumulation,
number of subjects, sampling method (consecutive, random, convenience), illness phase (day of
measurement in illness), competing diagnoses, dengue confirmation method (clinical/symptoms, 1997
or 2009 WHO diagnostic criteria, lab confirmation, combination), ultrasound equipment, ultrasound
user, time interval (fever to ultrasound timing), ultrasound findings ([qualitative/quantitative, cutoff
points] gallbladder edema/wall thickening, pericardial effusion, ascites, pleural effusion, hepatomegaly,
splenomegaly, inferior vena cava collapsibility, pulmonary B-lines, normal findings), gold standard for
ultrasound findings (radiologist, non-radiologist, labs (platelets, hematocrit, lactate, AST/ALT), outcome
measurements with confidence intervals (sensitivity, specificity, positive predictive value/negative
predictive value, likelihood ratio, kappa index, concordance/agreement, other), adverse events, and
mortality. One to two review author(s) will extract full-text data independently, discrepancies will be
identified and resolved through discussion with another review author if necessary. Extracted data will
be collected and organized in an Excel data extraction grid. Missing data will be requested from study
authors.
5.4 Strategies for Synthesis
A narrative (descriptive) synthesis will be provided. The synthesis will be structured (generally) around
target population characteristics, time of intervention, findings, and outcomes. We will provide
summaries of intervention effects and outcome measures. Results will undergo appraisal for bias and
compilation to map available evidence and existing knowledge gaps. We will explore different types of
participants by sex, average age, race/ethnicity, disease severity, and setting (country, hospitalized,
outpatient, intensive care unit, predominantly urban). If the necessary data are available, subgroup
analyses will be done for non-severe cases and patients at point-of-care. A narrative approach to the
different types of participants, intervention, settings, and types of studies will be employed.