Cyanoacrylate microbial sealants for skin preparation prior to surgery
Appendices
Appendix 1. Definitions of Degree of Contamination of the Surgical Site
| Type of wound | Description |
| Clean wound | Non‐infective operative wounds in which no inflammation is encountered, and neither the respiratory, alimentary, genitourinary tract nor the oro‐pharyngeal cavity is entered. In addition these cases are elective, primarily closed, and drained with closed drainage system when required. |
| Clean‐Contaminated wound | These are operative wounds in which respiratory, alimentary, genital or urinary tract is entered under controlled conditions and without unusual contamination. Specifically, operations involving the biliary tract, appendix, vagina and oropharynx are included in this category, provided no evidence of infection or major break in sterile technique is encountered. |
| Contaminated wound | These include fresh, accidental wounds, operations with major breaks in sterile technique or gross spillage from the gastrointestinal tract, and incisions in which acute, non‐purulent inflammation is encountered. |
| Dirty wound | These include old traumatic wounds with retained devitalised tissue and those that involve existing clinical infection or perforated viscera. This definition suggests that organisms causing post‐operative infection were present in the operative field before the operation. |
Appendix 2. Criteria for a judgment of 'yes' for the sources of bias
1. Was the allocation sequence randomly generated?
Yes, low risk of bias
A random (unpredictable) assignment sequence.
Examples of adequate methods of sequence generation are computer‐generated random sequence, coin toss (for studies with two groups), rolling a dice (for studies with two or more groups), drawing of balls of different colours, dealing previously shuffled cards.
No, high risk of bias
‐ Quasi‐randomised approach: Examples of inadequate methods are: alternation, birth date, social insurance/security number, date in which they are invited to participate in the study, and hospital registration number
‐ Non‐random approaches: Allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.
Unclear
Insufficient information about the sequence generation process to permit judgement
2. Was the treatment allocation adequately concealed?
Yes, low risk of bias
Assignment must be generated independently by a person not responsible for determining the eligibility of the participants. This person has no information about the persons included in the trial and has no influence on the assignment sequence or on the decision about whether the person is eligible to enter the trial. Examples of adequate methods of allocation concealment are: Central allocation, including telephone, web‐based, and pharmacy controlled, randomization; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes.
No, high risk of bias
Examples of inadequate methods of allocation concealment are: alternate medical record numbers, unsealed envelopes; date of birth; case record number; alternation or rotation; an open list of random numbers any information in the study that indicated that investigators or participants could influence the intervention group.
Unclear
Randomisation stated but no information on method of allocation used is available.
3. Blinding was knowledge of the allocated interventions adequately prevented during the study?
Was the participant blinded to the intervention?
Yes, low risk of bias
The treatment and control groups are indistinguishable for the participants and outcome assessors or if the participant and outcome assessor were described as blinded and the method of blinding was described.
No, high risk of bias
Blinding of study participants attempted, but likely that the blinding could have been broken; participants were not blinded, and the non blinding of others likely to introduce bias.
Unclear
Was the care provider blinded to the intervention?
Yes, low risk of bias
The treatment and control groups are indistinguishable for the care/treatment providers or if the care provider was described as blinded and the method of blinding was described.
No, high risk of bias
Blinding of care/treatment providers attempted, but likely that the blinding could have been broken; care/treatment providers were not blinded, and the nonblinding of others likely to introduce bias.
Unclear
Was the outcome assessor blinded to the intervention?
Yes, low risk of bias
Adequacy of blinding should be assessed for the primary outcomes. The outcome assessor was described as blinded and the method of blinding was described.
No, high risk of bias
No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding
Unclear
4. Were incomplete outcome data adequately addressed?
Was the drop‐out rate described and acceptable?
The number of participants who were included in the study but did not complete the observation period or were not included in the analysis must be described and reasons given.
Yes, low risk of bias
If the percentage of withdrawals and drop‐outs does not exceed 20% for short‐term follow‐up and 30% for long‐term follow‐up and does not lead to substantial bias. (N.B. these percentages are arbitrary, not supported by literature);
No missing outcome data;
Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias);
Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups;
Missing data have been imputed using appropriate methods.
No, high risk of bias
Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups;
Unclear
Were all randomised participants analysed in the group to which they were allocated? (ITT analysis)
Yes, low risk of bias
Specifically reported by authors that ITT was undertaken and this was confirmed on study assessment, or not stated but evident from study assessment that all randomised participants are reported/analysed in the group they were allocated to for the most important time point of outcome measurement (minus missing values) irrespective of non‐compliance and co‐interventions.
No, high risk of bias
Lack of ITT confirmed on study assessment (patients who were randomised were not included in the analysis because they did not receive the study intervention, they withdrew from the study or were not included because of protocol violation) regardless of whether ITT reported or not.
‘As‐treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.
Unclear
Described as ITT analysis, but unable to confirm on study assessment, or not reported and unable to confirm by study assessment.
5. Are reports of the study free of suggestion of selective outcome reporting?
Yes, low risk of bias
If all the results from all pre‐specified outcomes have been adequately reported in the published report of the trial. This information is either obtained by comparing the protocol and the final trial report, or in the absence of the protocol, assessing that the published report includes enough information to make this judgment. Alternatively a judgement could be made if the trial report lists the outcomes of interest in the methods of the trial and then reports all these outcomes in the results section of the trial report.
No, high risk of bias
Not all of the study’s pre‐specified primary outcomes have been reported;
One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not prespecified;
One or more reported primary outcomes were not pre‐specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect);
One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta‐analysis;
The study report fails to include results for a key outcome that would be expected to have been reported for such a study.
Unclear
6. Other sources of potential bias:
Was the trial sponsored by a manufacturer who potentially had an interest in the results?
Trials that state they received funding from a manufacturer or company with a direct interest int he intervention or trialists funded or employed by a manufacturer or company with a direct interest in the intervention.
Was the trial stopped early?
Was the trial stopped early due to some data‐dependent process (including a formal stopping rule).
Fraud?
Has there been a claim that the trial results were fraudulent?
Were co‐interventions avoided or similar?
There were no co‐interventions or there were co‐interventions but they were similar between the treatment and control groups.
