This protocol is registered on the PROSPERO international prospective register of systematic reviews (Submitted 15/12/20 ID: 225613) and is written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines (24, 25). The methodology applied to the final systematic review and meta-analysis is derived from, and in line with, the Cochrane Handbook for Systematic Review of Interventions(26) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (27).
Search strategy
The search strategy (Table 1) will be applied to the MEDLINE and Ovid EMBASE databases from inception to 2nd January 2021.
Table 1.
Electronic database search – MEDLINE and Ovid EMBASE
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Concept 1 – Surgery
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AND
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Concept 2 – Micro
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AND
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Concept 3 – STSM
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MeSH term
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Surgery
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Free Tissue Flaps
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Medical Missions
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OR
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Microsurgery
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OR
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Flap*
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OR
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Mission*
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OR
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Free Flap*
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OR
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Humanitarian
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OR
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Free Tissue Transfer
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OR
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Visit*
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OR
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Charit*
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OR
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Trip
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OR
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Outreach
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OR
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Volunt*
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OR
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Non-government*
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OR
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Safari
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OR
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Blitz
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OR
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Camp
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Study selection criteria
Inclusion criteria
All clinical studies reporting outcomes of any microsurgical procedure performed on a short-term reconstructive mission to any low-income or middle-income country (in accordance with the world bank classification(28)) will be eligible for inclusion. Studies that match the inclusion criteria performed in low-resource environments in a high-income country will also be included. Children and adults will be considered. All cases performed using either operating microscope or loupe magnification will be included, as both are successfully reported in resource-limited settings(15). The Population, Intervention, Comparison, Outcome (PICO) model was used to determine study selection criteria (Table 2)(29).
Table 2.
Population, Intervention, Comparison, Outcome (PICO)
Population
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Intervention
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Comparator
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Outcomes
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Patients operated on during STSMs
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Reconstructive surgery by microvascular free tissue transfer
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Data from the UK National Flap Registry(8)
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Rate of complications
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In low- and middle-income countries or low-resource health environments
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Performed during a visiting surgical mission
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Nature of complications
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Children and adults to be included
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This will include both loupes and microscope magnification
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Rate of return to theatre
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Rate of free flap salvage
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Nature of attempted salvage
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Exclusion criteria
Studies that do not provide sufficient data for comparative analysis will be excluded. Where incomplete or absent data is presented in a given study, study authors will be contacted by email on a maximum of two separate occasions, two weeks apart, inviting them to provide further data before being excluded. Data presented from microsurgical units already independently performing microsurgery in low-income or middle-income countries, not on a STSM, will also be excluded.
Study design
Randomised controlled trials (RCTs), cohort, case-control and case series will be considered for inclusion. Pilot searches indicate that the majority of studies will be case series of varying sizes. As such, no limitation regarding study size or clinical follow-up will be made. Case reports, letters, opinion pieces and literature reviews will be excluded. Any unpublished or ongoing prospective clinical trials will also be excluded.
Participants
Children or adults that have undergone microsurgical free tissue transfer during a short-term surgical mission in a low-income and middle-income country. No limitations based on patient demographics, body region or aetiology will be imposed.
Outcomes
Primary outcomes
The primary outcomes are rate of free flap failure and rate of emergency return to theatre for attempted free flap salvage. Return to theatre will be classified as a donor site or anastomotic complication. The time taken to return to theatre, and the rate of successful flap salvage will also be documented where available. Where disclosed, we will record the method of flap salvage attempted.
Secondary outcomes
The secondary outcomes will include complications and any functional or patient reported outcome measures included. Based on previous large case studies of free flaps, complications will be divided into medical and surgical. The surgical group will be further subdivided into intraoperative and post-operative. Complications will be stratified according to the Clavien-Dindo classification(30–32). Finally, if available any assessment of pre-operative fitness will be recorded.
Additional data
In addition to the primary and secondary outcomes, duration of procedure and length of stay will also be recorded where available. In the context of a STSM to a LMIC, this is particularly important. The following will also be extracted: bibliographic data (Title, author, date), study characteristics (design, method of randomisation/allocation, blinding, number of participants, groups/subgroups), mission characteristics (country, length of mission, type of mission/subspecialty, organisation (type and size), type of hospital (e.g. public or private), frequency of missions), patient characteristics (age, sex, indication for surgery, comorbidities, smoking status), intervention characteristics (Operation(s) performed, duration of operation, length of stay, who performed the surgery (local or visiting surgeon), experience level of surgeon who performed anastomosis and raised flap, pre-operative workup), and rate and duration of follow up.
Outcomes will be compared to data available from the multicentre, UK National Flap Registry, published in 2019(8).
Data management and extraction
Abstracts will be screened on the Rayyan systematic review software tool. Full papers will be downloaded as PDFs, and stored locally on Mendeley Desktop. All abstracts included will proceed to full text analysis unless it is immediately apparent following reading of the introduction that they are irrelevant. Data items will be collected in a standardised data collection proforma. For instances of incomplete data, we will contact the corresponding author. If 2 weeks elapse with no response, we will repeat this request once.
Data selection
Screening will be conducted and recorded in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines(27). Abstracts screened according to criteria set out in this protocol by two independent researchers (HdB and UC). In case of disagreements: researchers will meet to discuss disparities; if there are still disagreements, a third author (CH) will make the final decision on inclusion. If abstracts are not available on assessment, the paper will be downloaded in full for analysis.
Risk of bias assessment
Each study will be assessed for risk of bias by two independent reviewers (HdB and UC) according to an appropriate validated tool. Randomised studies will be assessed using the revised Cochrane risk of bias tool for randomized trials (Rob2)(33). Non-randomised studies will be assessed using the ‘Risk of bias in non-randomized studies of interventions’ (ROBINS-I) tool(34).
Quality of studies
Each study will be assessed according to the Oxford Evidence-based Medicine Scales of Evidence 2(35). This data will be tabulated.
Strategy for data analysis and synthesis
Statistical analysis of included studies will be undertaken in Revman 5.4 (Cochrane Collaboration, Oxford, United Kingdom). Patient demographics will be presented using basic descriptive statistics. Complications, free flap failure, emergency return to theatre and successful free flap salvage will be calculated and displayed as rate (%). Data from the first UK National flap registry will be used as a comparator(8). Statistical heterogeneity will be examined by calculating I2 and Cochran’s Q statistic, and interpreted according to Cochrane guidance on determining heterogeneity(26). If I2>50, a random-effects model (DerSimonian and Laird with a logit transformation applied) will be used to calculate relative risk with 95% confidence intervals(36). If I2≤50, a fixed-effects model will be used for relative risk calculations. A p-value of <0.05 will be considered statistically significant. The results of this meta-analysis will be presented in Forest plots. Funnel plots will be used to detect publication bias. If quantitative analysis is inappropriate a narrative synthesis will be performed.
The analysis detailed above will be undertaken for the pooled data. If sufficient data is available, subgroup analysis by region (e.g. head and neck, trunk etc.) will be undertaken.
Confidence in cumulative evidence
The body of evidence underpinning each of the findings will be assessed according to the ‘Grading of Recommendations, Assessment, Development and Evaluations’ (GRADE) approach(37). Using this approach, the authors will express their ‘certainty’ that the body of evidence reflects reality (High, moderate, low, very low).