ELABORACIÓN DE PROTOTIPOS

4.3.1

Criteria for considering studies for this review

Trials eligible for this review were all randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical record numbers, date of birth or other predictable methods) looking at the effect of prophylactic antimicrobials, topical antiseptics, medicated dressings and non-medicated dressings on the incidence of infectious complications among haemodialysis patients with CVC.

4.3.1.2 Types of participants

Inclusion criteria

• Adults and children with End Stage Kidney Disease (ESKD) who had, or were about to commence, either short-term or maintenance haemodialysis using tunnelled or non-tunnelled CVCs as vascular access.

• Children were defined as up to the age of 18 years of age or as defined by the eligible trial.

Exclusion criteria

• Adults and children whose vascular access for haemodialysis included antimicrobial-impregnated CVC or CVC using locking solutions, which have antimicrobial properties. These interventions are the focus of another Cochrane Review, ‘Antimicrobial lock solutions for preventing catheter- related infections in haemodialysis’ (Arechabala et al. 2013).

• Adults and children with ESKD whose CVC was used for purposes other than haemodialysis.

4.3.1.3 Types of interventions

Studies containing the following comparisons were eligible for the review: • Skin cleansers versus no skin cleansers.

• Skin cleansing using different cleaning solutions. • Different cleaning techniques.

• Antibiotics versus no antibiotics.

• Antibiotics using different modes of administration oral/intravenous/topical. • Antibiotics using different dosages.

• Antibiotics using different durations. • Antibiotics using different starting points.

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• Topical antimicrobial versus no topical antimicrobial. • Topical antimicrobial using different durations. • Different topical antimicrobial agents.

• Different non-medicated topical dressings. • Different medicated dressings.

• Non-medicated and medicated dressings. • Different frequencies of dressing changes. • Different health care staff who inserted CVC. • Different insertion techniques.

• Different health care staff accessing CVC. • Different techniques used to access CVC.

Studies describing intranasal application of mupirocin in haemodialysis patients were not considered and are included in a Cochrane Review on mupirocin ointment for preventing S. aureus infections in nasal carriers (Van Rijen et al. 2008).

The following definitions were used:

• Antimicrobials are any agents capable of destroying or inhibiting the growth of micro-organisms (NKF K/DOQI 2006a).

• Skin cleansers such as antiseptic agents help in the physical removal of foreign materials such as dirt, micro-organisms, and dead cells.

• Antiseptics are any agents capable of preventing infection by inhibiting the growth of micro-organisms. These agents are routinely thought of as topical agents for application to the skin (NKF K/DOQI 2006a).

4.3.1.4 Types of outcome measures

The following outcomes were to be assessed. Primary outcomes

• Incidence and type of infectious complication. • Patient mortality.

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Secondary outcomes

• Time to development of infection. • Episodes of hospitalisation. • Patient morbidity.

• Quality of life.

4.3.2

Search methods for identification of studies

The following sources were used to identify relevant studies.

4.3.2.1 Electronic searches included

1. The Cochrane Renal Group’s Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library. CENTRAL and the Renal Group’s Specialised Register contain the hand searched results of conference proceedings from general and speciality meetings. This searching is an ongoing activity across The Cochrane Collaboration and is both retrospective and prospective (Master List 2009). Therefore, conference proceedings were not specifically searched separately for this review. The Cochrane Renal Group’s Module in The Cochrane Library provides the most up-to-date list of conference proceedings searched by that Group (Renal Group 2009 et al. 2009). 2. MEDLINE, using the optimally sensitive strategy developed for The

Cochrane Collaboration for the identification of RCTs (Lefebvre et al.

2008) with a specific search strategy developed with input from the Cochrane Renal Group’s Trial Search Coordinator.

3. EMBASE, using a search strategy adapted from that developed for The Cochrane Collaboration for the identification of RCTs (Lefebvre et al.

2008) together with a specific search strategy developed with input from the Cochrane Renal Group’s Trial Search Co-ordinator.

See Appendix 4.1for electronic search strategies.

4.3.2.2 Searching other resources included

1. Reference lists of nephrology textbooks, review articles and relevant studies.

2. Correspondence seeking information about unpublished or incomplete studies to investigators known to be involved in previous studies.

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4.3.3

Data collection & analysis

The search strategy was used to obtain titles and abstracts of studies that might be relevant to the review. These titles and abstracts were screened independently by me and another colleague. Studies that were not applicable to the inclusion criteria for this review were discarded, but studies and reviews that might include relevant data or information on studies were retained initially. Retrieved abstracts and, if necessary the full text, of these reports were independently assessed to determine which studies satisfied the inclusion criteria.

4.3.3.2 Data extraction & management

My colleague and I both carried out data extraction independently, using standard data extraction forms. It was planned that studies reported in languages other than English would be translated before assessment. Where more than one publication of a study was found, reports were grouped together and the most recent or most complete dataset was used for the review. Any discrepancy between published versions is highlighted. Any further information required from the original author was requested through written or electronic correspondence and any relevant information obtained in this manner was included in the review. Disagreements between the two reviewers were resolved in consultation with the Cochrane Renal Group.

4.3.3.3 Assessment of risk of bias in included studies

My colleague and I independently assessed the quality of studies to be included without blinding to authorship or journal, using the checklist developed for the Cochrane Renal Group. Disagreements were resolved by discussion with the Cochrane Renal Group. The quality items assessed were allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow-up.

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4.3.3.4 Quality checklist

The following quality categories were used: Allocation concealment

• Adequate (A) - Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study;

• Unclear (B) - Randomisation stated, but no information on method used is available;

• Inadequate (C) - Method of randomisation used such as alternate medical record numbers or unsealed envelopes; any information in the study that indicated that investigators or participants could influence intervention group.

Blinding

• Blinding of investigators: Yes/no/not stated; • Blinding of participants: Yes/no/not stated; • Blinding of outcome assessor: Yes/no/not stated; • Blinding of data analysis: Yes/no/not stated.

These groups are considered not blinded if the treatment group could be identified for more than 20% of participants because of treatment side effects.

Intention-to-treat

• Yes: Specifically reported by authors that intention-to-treat analysis was undertaken and this was confirmed on study assessment;

• Yes: Not stated but confirmed on study assessment;

• No: Not reported and lack of intention-to-treat analysis 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);

• No: Stated but not confirmed upon study assessment; • Not stated.

Completeness of follow-up

• Percentage of randomised (or quasi-randomised) participants excluded or lost to follow-up.

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4.3.3.5 Measures of treatment effect

For dichotomous outcomes (mortality, presence of infection), results are presented as risk ratios (RR) with 95% confidence intervals (CI). It was planned that if continuous scales were used to measure the effects of treatment (e.g. catheter survival), the mean difference (MD) would be used, or the standardised mean difference (SMD) if different scales were used.

4.3.3.6 Assessment of heterogeneity

Heterogeneity was analysed using a Chi² test on N-1 degrees of freedom, with a P-value of 0.05 used for statistical significance, and with the I² test (Higgins

et al. 2003). I² values of 25%, 50% and 75% correspond to low, medium and high levels of heterogeneity.

4.3.3.7 Data synthesis

Data were pooled using the random-effects model, but the fixed effect model was also analysed to ensure robustness of the model chosen and susceptibility to outliers.

4.3.3.8 Subgroup analysis & investigation of heterogeneity

Subgroup analysis was used to explore possible sources of heterogeneity (e.g. participants, interventions and study quality). Heterogeneity among participants could be related to age and renal pathology. Heterogeneity in treatments could be related to prior agent(s) used and the agent, dose and duration of therapy. It was planned that adverse effects would be tabulated and assessed with descriptive techniques, because they are likely to differ between the agents.