Honey as a topical treatment for wounds

Types of studies

Randomised controlled trials (RCTs) and quasi-randomised controlled trials were included. Quasi-randomised controlled trials are trials which use a quasi-random allocation strategy, such as alternate days, date of birth, or hospital number.

Types of participants

Trials involving participants of any age with an acute or chronic wound were included. For the purposes of this review an acute wound was considered to be any of the following: burns, lacerations or other skin injuries resulting from minor trauma, and minor surgical wounds healing by primary or secondary intention. Chronic wounds were considered to be: skin ulcers of any type, pressure ulcers and infected wounds healing by secondary intention.

Types of interventions

The primary intervention was any formulation of honey topically applied by any means, alone or in combination with other dressings or components, to an acute or chronic wound. Eligible comparison interventions were dressings or other topical agents applied to the wound.

Types of outcome measures

Trials had to provide data on one of the primary outcomes listed below, and the unit of analysis had to be by participant (See "Differences between protocol and review" for further information about unit of analysis issues).

Electronic searches

For the search methods used in the original version of this review see Appendix 1.

For this second update we searched the following databases for reports of eligible randomised controlled trials: 

• The Cochrane Wounds Group Specialised Register (searched 15 October 2014);

• The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 9);

• Ovid MEDLINE (1946 to October Week 1 2014);

• Ovid MEDLINE (In-Process & Other Non-Indexed Citations 13 October, 2014);

• Ovid EMBASE (1974 to 13 October, 2014);

• EBSCO CINAHL (1982 to 15 October, 2014).

The following search strategy was used in CENTRAL and adapted appropriately for other databases: 

#1 MeSH descriptor Skin Ulcer explode all trees
#2 MeSH descriptor Pilonidal Sinus explode all trees
#3 MeSH descriptor Wounds, Penetrating explode all trees
#4 MeSH descriptor Lacerations explode all trees
#5 MeSH descriptor Burns explode all trees
#6 MeSH descriptor Wound Infection explode all trees
#7 MeSH descriptor Surgical Wound Dehiscence explode all trees
#8 MeSH descriptor Bites and Stings explode all trees
#9 MeSH descriptor Cicatrix explode all trees
#10 ((plantar or diabetic or heel* or foot or feet or ischaemic or ischemic or venous or varicose or stasis or arterial or decubitus or pressure or skin or leg or mixed or tropical or rheumatoid or sickle
cell) NEAR/5 (wound* or ulcer*)):ti,ab,kw
#11 (bedsore* or (bed NEXT sore*)):ti,ab,kw
#12 (pilonidal sinus* or pilonidal cyst*):ti,ab,kw
#13 (cavity wound* or sinus wound*):ti,ab,kw
#14 (laceration* or gunshot stab or stabbing or stabbed or bite*):ti,ab,kw
#15 ("burn" or "burns" or "burned" or scald*):ti,ab,kw
#16 (surg* NEAR/5 infection*):ti,ab,kw
#17 (surg* NEAR/5 wound*):ti,ab,kw
#18 (wound* NEAR/5 infection*):ti,ab,kw
#19 (malignant wound* or experimental wound* or traumatic wound*):ti,ab,kw
#20 (infusion site* or donor site* or wound site* or surgical site*):ti,ab,kw
#21 (skin abscess* or skin abcess*):ti,ab,kw
#22 (hypertrophic scar* or keloid*):ti,ab,kw
#23 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR
#12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22)
#24 MeSH descriptor Honey explode all trees
#25 honey:ti,ab,kw
#26 (#24 OR #25)
#27 (#23 AND #26) 

The search strategies for Ovid MEDLINE, Ovid EMBASE and EBSCO CINAHL can be found in Appendix 2. We combined the Ovid MEDLINE search with the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity- and precision-maximizing version (2008 revision) (Lefebvre 2011). The Ovid EMBASE and EBSCO CINAHL searches were combined with the trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN) (SIGN 2008). There were no restrictions with respect to language, date of publication (taking into account searches from the original review) or study setting.

Searching other resources

For the initial review we contacted experts in the field, authors of the included trials and manufacturers of honey products for wound care (Comvita NZ Ltd and MediHoney Australia Pty Ltd), but did not repeat this for updates. The bibliographies of all obtained studies and review articles were searched for potentially eligible trials for both the initial review and the first update. No language or date restrictions were applied to the trials and both published and unpublished trials were sought.

Selection of studies

Two authors (either AJ and NW, or for this update JD and NC) independently examined titles and abstracts of potentially relevant trials. Full text copies of all relevant trials, or trials that might be relevant to the review were obtained. The two review authors independently selected the trials using the inclusion criteria. Disagreements were resolved by discussion.

Data extraction and management

Data were extracted from included trials by one review author and recorded on a standardised form. The extracted data were independently reviewed for accuracy by a second review author and disagreements resolved by discussion. All data have subsequently been verified by a third (MW) and fourth author (NC). If the data from the trial report were inadequate, or ambiguous, additional information was sought from the trial authors. We collected data on the topics listed below:

1. Author; title; source of reference.

2. Study setting.

3. Study design.

4. A priori sample size calculation; sample size.

5. Inclusion/exclusion criteria.

6. Age of participants; sex of participants.

7. Wound type.

8. Intervention and comparison.

9. Outcomes.

10. Withdrawals and reason for withdrawal.

11. Funding source.

12. Co-interventions

Assessment of risk of bias in included studies

For the first update, one review author (SD) assessed each included study using the Cochrane Collaboration tool for assessing risk of bias (Higgins 2011), and this assessment was checked by a second (AJ) review author. For this second update two more pairs of review authors/editors checked risk of bias (either MW and JD or JD and NC) and reviewed by the lead review author (AJ). This tool addresses six specific domains, namely sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other issues, such as extreme baseline imbalance (see Appendix 3 for details of criteria on which the judgement was based). Blinding and completeness of outcome data were assessed for each outcome separately. We completed a risk of bias table for each eligible study and discussed any disagreement amongst all review authors to achieve a consensus.

We present an assessment of risk of bias using a 'risk of bias summary figure', which presents all of the judgements in a cross-tabulation of study by entry. This display of internal validity indicates the weight the reader may give the results of each study.

Data synthesis

Where trials were sufficiently alike in terms of population and comparison interventions, their results were combined. Mean differences (MD) and 95% confidence intervals (95% CI) were reported for continuous outcomes, and risk ratio (RR) and 95% confidence intervals (95% CI) were reported for dichotomous variables. Statistical heterogeneity was tested by comparing Cochran's Q statistic and the chi-squared distribution. Heterogeneity was assumed with P values of less than 0.1 (Higgins 2011). In addition, the I² statistic was used to determine the percentage of variation due to heterogeneity rather than chance (Higgins 2003), and any sources of heterogeneity were explored. Where significant statistical heterogeneity was present, a random-effects model was used when combining trials (Ioannidis 2008).

Included studies

Twenty six trials met the inclusion criteria (please see the Characteristics of included studies) and were available for analysis; eight trials were added in updates (Baghel 2009; Gulati 2014; Kamaratos 2014; Mashood 2006; Memon 2005; Nilforoushzadeh 2007; Robson 2009; Shukrimi 2008), including one trial that was mistakenly excluded in the previous review, but was found in the first update to meet the inclusion criteria on re-screening (Mashood 2006). Another trial was previously wrongly included and has now been excluded in this update (Subrahmanyam 1996c). Three trials are awaiting assessment while attempts are made to contact the authors to request further data (Askarpour 2009; Jan 2012; Maghsoudi 2011).

Ten separate trials were conducted by the same investigator (Subrahmanyam 1991; Subrahmanyam 1993a; Subrahmanyam 1993b; Subrahmanyam 1994; Subrahmanyam 1996a; Subrahmanyam 1996b; Subrahmanyam 1998; Subrahmanyam 1999; Subrahmanyam 2001a; Subrahmanyam 2004) based in India. Important information was missing from the published reports of these studies however some was provided on request.

Fourteen trials recruited participants with acute wounds: 11 with burns (Baghel 2009; Mashood 2006; Memon 2005; Subrahmanyam 1991; Subrahmanyam 1993b; Subrahmanyam 1994; Subrahmanyam 1996a; Subrahmanyam 1996b; Subrahmanyam 1998; Subrahmanyam 1999; Subrahmanyam 2001a), two with minor surgical excisions (Marshall 2005; McIntosh 2006), and one with minor trauma (Ingle 2006). Ten trials recruited participants with chronic wounds including venous leg ulcers (Jull 2008; Gethin 2007), infected surgical wounds (Al Waili 1999), pressure injuries (Weheida 1991), Fournier's gangrene (Subrahmanyam 2004), cutaneous Leishmaniasis (ulcers caused by protozoans injected by sandfly bite) (Nilforoushzadeh 2007), diabetic foot ulcers (Kamaratos 2014; Shukrimi 2008), and a variety of chronic wounds healing by secondary intention though mainly venous leg ulcers (Gulati 2014; Robson 2009). Two trials recruited participants with either chronic or acute wounds (Mphande 2007; Subrahmanyam 1993a).

Eight trials were conducted in community settings or outpatient clinics (Gulati 2014; Kamaratos 2014; Gethin 2007; Ingle 2006; Jull 2008; Marshall 2005; McIntosh 2006; Nilforoushzadeh 2007). The remaining trials were conducted in hospital settings, or a mixed inpatient and outpatient setting (Robson 2009). Eight trials reported recruiting only adults (Al Waili 1999; Gulati 2014; Gethin 2007; Ingle 2006; Jull 2008; Kamaratos 2014; Shukrimi 2008; Subrahmanyam 2004). The remaining trials did not specify an age range (Marshall 2005; McIntosh 2006; Robson 2009), or recruited both children and adults.

Monofloral honey (aloe, jarrah, jamun, jambhul or manuka) was used in ten trials (Gethin 2007; Gulati 2014; Ingle 2006; Jull 2008; Kamaratos 2014; Marshall 2005; McIntosh 2006; Robson 2009; Subrahmanyam 2001a; Subrahmanyam 2004); the type of honey used was not specified in the remaining trials. Honey was delivered as a honey impregnated gauze dressing in six trials (Kamaratos 2014; Mphande 2007; Nilforoushzadeh 2007; Subrahmanyam 1993a; Subrahmanyam 1994; Subrahmanyam 2004); as a honey impregnated alginate dressing in two (Jull 2008; McIntosh 2006); as honey spread between gauze in one trial (Memon 2005) and as topical honey covered with either a film dressing (Ingle 2006; Gulati 2014) or with gauze in the remaining trials. Six trials investigated honey as an adjunct treatment: four included people with venous leg ulcers, and, for these, honey was used as an adjunct to compression (Gethin 2007; Gulati 2014; Jull 2008; Robson 2009). One trial in people with Leishmaniasis gave honey alongside an injection of glucantamine (Nilforoushzadeh 2007). In a further trial, 50% patients receiving honey also received delayed autologous skin grafting, as necessary (Subrahmanyam 1999).

There was a range of comparison treatments in this review, which have been grouped under the broad categories of conventional dressings, silver sulfadiazine (SSD), antiseptics, early excision and atypical dressings. Seven trials compared honey with SSD, and of these, the comparator was a SSD impregnated dressing in four trials (Subrahmanyam 1991; Subrahmanyam 1993b; Subrahmanyam 1998; Subrahmanyam 2001a) and SSD cream in three (Baghel 2009; Mashood 2006; Memon 2005). Two studies compared honey with hydrogel (Gethin 2007; Ingle 2006). In the adjunct trials, the comparators were either other dressings plus compression (Gethin 2007; Gulati 2014; Jull 2008; Robson 2009) or glucantamine injection alone (Nilforoushzadeh 2007). The comparator for the trial giving honey plus delayed skin grafting was early tangential excision and skin grafting (Subrahmanyam 1999).

In view of the clinical diversity of the evidence, this review is organised by wound type, and then by comparison type.

There was a great deal of variation in the outcomes reported by the included studies which makes the drawing of overall conclusions very difficult. Many of the included studies report "mean time to healing" but it was frequently not clear whether every participant's wound had healed during follow up (in which case the mean time with associated SD or 95% confidence interval would be acceptable). However if all wounds in a study do not heal during the period of observation, simple calculation of the mean (or median) time to healing without accounting for censoring is inappropriate since, by definition, this approach excludes people who did not heal during follow up (as they cannot contribute to the numerator). Importantly excluding people who failed to heal from the data excludes treatment failures and will over-estimate treatment success. Time to healing is a type of "time to event" outcome and should be analysed as such using a survival approach which allows people who did not heal to contribute data to the analysis for the period for which they were observed. Only three studies (Jull 2008; Nilforoushzadeh 2007; Robson 2009) analysed time to healing as time to event data. One study (Shukrimi 2008) reported time to readiness for wound closure surgery.

The multiplicity of time points at which healing was reported was a further problem which had not been anticipated in the protocol. We opted to analyse the outcomes for the longest point of follow up shared by several trials of the same comparison (since to extract and analyse all time points risks a Type I error).

Excluded studies

For details on the excluded studies please see Characteristics of excluded studies table. Of the 57 excluded studies, 24 were not RCTs or quasi-RCTs (Abdelatif 2008; Ahmed 2003; Al Waili 2004c; Al Waili 2005; Bose 1982; Dunford 2004; Freeman 2010; Gethin 2005; Lusby 2002; Marshall 2002; Mayer 2014; Misirligou 2003; Moghazy 2010; Molan 2002; Molan 2006; Mwipatayi 2004; Nagane 2004; Robson 2002; Schumacher 2004; Subrahmanyam 1993; Thurnheer 1983; Tostes 1994; Vijaya 2012; Visscher 1996). Seven of the excluded studies were not in wounds (Al Waili 2003; Albietz 2006; Biswal 2003; Johnson 2005; Quadri 1998; Quadri 1999; Somaratne 2012). Three were studies in animal models (Al Waili 2004a; Al Waili 2004b; Subrahmanyam 2001b). Thirteen studies did not report sufficient information on healing (Bangroo 2005; Chokotho 2005; Gad 1988; Heidari 2013; Jeffery 2008; Lund-Nielsen 2011; Mat Lazim 2013; Robson 2012; Rogers 2010; Rucigaj 2006; Saha 2012; Subrahmanyam 2003; Ur-Rehman 2013). Three studies did not evaluate honey (Berchtold 1992; Muller 1985), one evaluated the effect of adding vitamins and polyethylene glycol to honey (Subrahmanyam 1996c) and a further two could not be obtained for assessment (Calderon Espina 1989; Rivero Varona 1999). Four studies had unit of analysis issues, they had randomised, or reported, by wound rather than by the participant. Such unit of randomisation or analysis issues were not considered in the protocol for the review, but we considered that such studies could not contribute usefully to this review. For further discussion on the rationale for this decision see "Differences between protocol and review" (Malik 2010; Okeniyi 2005; Oluwatosin 2000; Yapucu Gunes 2007).

1. Acute wounds

2. Mixed acute and chronic wounds

Two trials (140 participants) each recruited participants with a range of different acute and chronic wounds. Subrahmanyam 1993b recruited 100 participants with burns (50% of the study population), lower limb ulcers caused by trauma, pressure, diabetes, and venous disease, or trophic ulcers and compared honey with SSD. In a quasi-randomised study, Mphande 2007 recruited 40 participants with ulcers, chronic osteomyelitis, abscesses, post-surgical or traumatic wounds; the comparison treatment was sugar dressings.

3. Chronic Wounds

Ten trials (819 participants) evaluated the effects of honey in chronic wounds. Two trials recruited people with venous leg ulcers (Gethin 2007; Jull 2008); one study (Robson 2009) recruited participants with any type of wound healing by secondary intention but most of these were leg ulcers (70%); one study recruited people with a range of chronic wounds though most were venous leg ulcers (Gulati 2014). Two studies recruited people with diabetic foot ulcers (Kamaratos 2014; Shukrimi 2008) and one study for each of the following: ulcers caused by Leishmaniasis (Nilforoushzadeh 2007); pressure injuries (Weheida 1991); infected post-operative wounds (Al Waili 1999), and Fournier's gangrene (Subrahmanyam 2004). Five of these ten studies were added at the first or second update (Gulati 2014; Kamaratos 2014; Nilforoushzadeh 2007; Robson 2009; Shukrimi 2008),

Three trials reported either the mean or median time to healing (Al Waili 1999; Jull 2008), or the mean time to surgical closure (Shukrimi 2008); seven trials reported the proportion of participants with completely healed wounds (Gethin 2007; Gulati 2014; Jull 2008; Kamaratos 2014; Nilforoushzadeh 2007; Robson 2009; Weheida 1991). One trial only reported the outcome, "mean hospital stay", but data on mean time to healing were provided by the author (Subrahmanyam 2004). Given the clinical and methodological heterogeneity between the trials, it was not possible to combine the trials to produce an overall summary statistic for the effect of honey on chronic wounds and instead we consider the evidence by wound type below.

1. Acute wounds

2. Mixed acute and chronic wounds

The rationale for conducting trials in which the participants have either burns or a mix of chronic wounds is unclear. The aetiologies are so different that no matter what the results, the findings will be difficult to interpret and unlikely to influence clinical practice. Overall we found low quality evidence from two studies Mphande 2007; Subrahmanyam 1993b), that on average honey heals a heterogeneous population of acute and chronic wounds more quickly than sugar dressings or SSD. The comparative rates of adverse events and infection are unclear.

3. Chronic wounds

Most of the evidence for the effects of honey on chronic wounds is of low or very low quality. Most trials were small, with comparators that may not be relevant to current practice and at high or unclear risk of bias.

Electronic searches

Searches of the following electronic databases were undertaken:

Cochrane Wounds Group Specialised Register (Searched 27/5/08)
The Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library Issue 2 2008
Ovid MEDLINE - 1950 to May Week 2 2008
Ovid EMBASE - 1980 to 2008 Week 21
Ovid CINAHL - 1982 to May Week 4 2008

The following search strategy was used in the CENTRAL and adapted where appropriate for other databases :

#1 MeSH descriptor Skin Ulcer explode all trees
#2 MeSH descriptor Pilonidal Sinus explode all trees
#3 MeSH descriptor Wounds, Penetrating explode all trees
#4 MeSH descriptor Lacerations explode all trees
#5 MeSH descriptor Burns explode all trees
#6 MeSH descriptor Wound Infection explode all trees
#7 MeSH descriptor Surgical Wound Dehiscence explode all trees
#8 MeSH descriptor Bites and Stings explode all trees
#9 MeSH descriptor Cicatrix explode all trees
#10 ((plantar or diabetic or heel* or foot or feet or ischaemic or ischemic or venous or varicose or stasis or arterial or decubitus or pressure or skin or leg or mixed or tropical or rheumatoid or sickle
cell) NEAR/5 (wound* or ulcer*)):ti,ab,kw
#11 (bedsore* or (bed NEXT sore*)):ti,ab,kw
#12 (pilonidal sinus* or pilonidal cyst*):ti,ab,kw
#13 (cavity wound* or sinus wound*):ti,ab,kw
#14 (laceration* or gunshot stab or stabbing or stabbed or bite*):ti,ab,kw
#15 ("burn" or "burns" or "burned" or scald*):ti,ab,kw
#16 (surg* NEAR/5 infection*):ti,ab,kw
#17 (surg* NEAR/5 wound*):ti,ab,kw
#18 (wound* NEAR/5 infection*):ti,ab,kw
#19 (malignant wound* or experimental wound* or traumatic wound*):ti,ab,kw
#20 (infusion site* or donor site* or wound site* or surgical site*):ti,ab,kw
#21 (skin abscess* or skin abcess*):ti,ab,kw
#22 (hypertrophic scar* or keloid*):ti,ab,kw
#23 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR
#12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22)
#24 MeSH descriptor Honey explode all trees
#25 honey:ti,ab,kw
#26 (#24 OR #25)
#27 (#23 AND #26)

The MEDLINE search was combined with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity- and precision-maximizing version (2008 revision); Ovid format. The EMBASE and CINAHL searches were combined with the trial filters developed by the Scottish Intercollegiate Guidelines Network. Additionally, LILACS (1982 to October 2006), AMED (1985 to October 2006) and Google Scholar were searched using the text word "honey".

Searching other resources

Contact was made with experts in the field, authors of the included trials and manufacturers of honey products for wound care (Comvita NZ Ltd and MediHoney Australia Pty Ltd). The bibliographies of all obtained studies and review articles were searched for potentially eligible trials. No language or date restrictions were applied to the trials and both published and unpublished trials were sought.

Ovid Medline

1 exp Skin Ulcer/ (18230)
2 exp Pilonidal Sinus/ (543)
3 exp Wounds, Penetrating/ (14308)
4 exp Lacerations/ (1423)
5 exp Burns/ (17087)
6 exp Wound Infection/ (14097)
7 exp Surgical Wound Dehiscence/ (2829)
8 exp "Bites and Stings"/ (7739)
9 exp Cicatrix/ (13623)
10 ((plantar or diabetic or heel$ or foot or feet or ischaemic or ischemic or venous or varicose or stasis or arterial or decubitus or pressure or skin or leg or mixed or tropical or rheumatoid or sickle cell) adj5 (wound$ or ulcer$)).ti,ab. (18800)
11 (bedsore$ or bed sore$).ti,ab. (239)
12 (pilonidal sinus$ or pilonidal cyst$).ti,ab. (437)
13 (cavity wound$ or sinus wound$).ti,ab. (37)
14 (laceration$ or gunshot or stab or stabbing or stabbed or bite$).ti,ab. (19976)
15 (burn or burns or burned or scald$).ti,ab. (19171)
16 (surg$ adj5 wound$).ti,ab. (5431)
17 (surg$ adj5 infection$).ti,ab. (8723)
18 (wound adj5 infection$).ti,ab. (10745)
19 (malignant wound$ or experimental wound$ or traumatic wound$).ti,ab. (428)
20 (infusion site$ or donor site$ or wound site$).ti,ab. (7460)
21 (skin abscess$ or skin abcess$).ti,ab. (162)
22 (hypertrophic scar$ or keloid scar$).ti,ab. (1595)
23 or/1-22 (130992)
24 exp Honey/ (1328)
25 honey.ti,ab. (3036)
26 or/24-25 (3160)
27 23 and 26 (249)

Ovid Embase

1 exp Skin Ulcer/ (30058)
2 exp Pilonidal Sinus/ (883)
3 exp Penetrating Trauma/ (5303)
4 exp Laceration/ (4283)
5 exp Skin Abrasion/ (2135)
6 exp Burns/ (25289)
7 exp Wound Infection/ (17999)
8 exp Surgical Wound/ (3060)
9 exp Wound Dehiscence/ (6273)
10 exp Bite Wound/ (340)
11 exp Scar/ (28923)
12 ((plantar or diabetic or heel$ or foot or feet or ischaemic or ischemic or venous or varicose or stasis or arterial or decubitus or pressure or skin or leg or mixed or tropical or rheumatoid or sickle cell) adj5 (wound$ or ulcer$)).ti,ab. (26847)
13 (bedsore$ or bed sore$).ti,ab. (397)
14 (pilonidal sinus$ or pilonidal cyst$).ti,ab. (628)
15 (cavity wound$ or sinus wound$).ti,ab. (50)
16 (laceration$ or gunshot or stab or stabbing or stabbed or bite$).ti,ab. (26569)
17 (burn or burns or burned or scald$).ti,ab. (26981)
18 (surg$ adj5 wound$).ti,ab. (7562)
19 (surg$ adj5 infection$).ti,ab. (12748)
20 (wound adj5 infection$).ti,ab. (15320)
21 (malignant wound$ or experimental wound$ or traumatic wound$).ti,ab. (559)
22 (infusion site$ or donor site$ or wound site$).ti,ab. (9548)
23 (skin abscess$ or skin abcess$).ti,ab. (278)
24 (hypertrophic scar$ or keloid scar$).ti,ab. (2338)
25 or/1-24 (183396)
26 exp Honey/ (2368)
27 honey.ti,ab. (4323)
28 or/26-27 (4693)
29 25 and 28 (337)

EBSCO CINAHL

S29 S25 and S28
S28 S26 or S27
S27 TI honey or AB honey
S26 (MH "Honey")
S25 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11 or S12 or S13 or S14 or S15 or S16 or S17 or S18 or S19 or S20 or S21 or S22 or S23 or S24
S24 TI ( hypertrophic scar* or keloid scar* ) or AB ( hypertrophic scar* or keloid scar* )
S23 TI ( skin abscess* or skin abcess* ) or AB ( skin abscess* or skin abcess* )
S22 TI ( infusion site* or donor site* or wound site* ) or AB ( infusion site* or donor site* or wound site* )
S21 TI ( malignant wound* or experimental wound* or traumatic wound* ) or AB ( malignant wound* or experimental wound* or traumatic wound* )
S20 TI wound* N5 infect* or AB wound* N5 infect*
S19 TI surg* N5 infection* or AB surg* N5 infection*
S18 TI surg* N5 wound* or AB surg* N5 wound*
S17 TI ( burn or burns or burned or scald* ) or AB ( burn or burns or burned or scald* )
S16 TI (laceration* or gunshot or stab or stabbing or stabbed or bite*) or AB (laceration* or gunshot or stab or stabbing or stabbed or bite*)
S15 TI ( cavity wound* or sinus wound* ) or AB ( cavity wound* or sinus wound* )
S14 TI ( pilonidal sinus* or pilonidal cyst* ) or AB ( pilonidal sinus* or pilonidal cyst*)
S13 TI ( bedsore* or bed sore* ) or AB ( bedsore* or bed sore* )
S12 AB ( plantar or diabetic or heel* or foot or feet or ischemia or ischemic or venous or varicose or stasis or arterial or crural or decubitus or pressure or skin or leg or mixed or tropical or rheumatoid or sickle cell ) and AB ulcer*
S11 TI ( plantar or diabetic or heel* or foot or feet or ischemia or ischemic or venous or varicose or stasis or arterial or crural or decubitus or pressure or skin or leg or mixed or tropical or rheumatoid or sickle cell ) and TI ulcer*
S10 (MH "Cicatrix+")
S9 (MH "Bites and Stings+")
S8 (MH "Surgical Wound Dehiscence")
S7 (MH "Surgical Wound")
S6 (MH "Wound Infection+")
S5 (MH "Burns+")
S4 (MH "Tears and Lacerations")
S3 (MH "Wounds, Penetrating+")
S2 (MH "Diabetic Foot")
S1 (MH "Skin Ulcer+")

1.  Was the allocation sequence randomly generated?

2.  Was the treatment allocation adequately concealed?

3.  Blinding was knowledge of the allocated interventions adequately prevented during the study?

4.  Were incomplete outcome data adequately addressed?

5.  Are reports of the study free of suggestion of selective outcome reporting?

6.  Other sources of potential bias:

Summary

Email received from Barry Wolfenson on behalf of Derma Sciences expressing concern at the wording of the Authors' conclusions - as follows:
“There is insufficient evidence to guide clinical practice in other types of wounds, and purchasers should refrain from providing honey dressings for routine use until sufficient evidence of effect is available.”

Reply

Andrew Jull, Author; Nicky Cullum, Coordinating Editor CWG; Sally Bell-Syer Managing Editor CWG.

Thank you for your feedback. this statement has been present in the Authors' conclusions since the review was first published in 2008. However this is a valid point and does contravene Cochrane guidance from the Handbook which states " The primary purpose of the review should be to present information, rather than to offer advice". As a result we have modified this section to read: "There is insufficient evidence to guide clinical practice in other areas, health services may wish to consider avoiding routine use of honey dressings until sufficient evidence of effect is available"

Contributors

Barry J. Wolfenson, Group President, Advanced Wound Care & Drug Development, Derma Sciences.
Andrew Jull, Author; Nicky Cullum, Coordinating Editor CWG; Sally Bell-Syer Managing Editor CWG.

Summary

Email received from Barry Wolfenson, Group President, Advanced Wound Care & Drug Development, Derma Sciences.

Q1. Can you please let me know, regarding the 132 Cochrane Reviews on the topic of Wounds, aside from the one titled “Honey as a topical treatment for wounds”, how many include studies within the review that are authored by authors of the Cochrane Review itself?

Authors response: This is a very general question; you have not identified the 132 reviews you are referring to and we do not routinely record that information outside of the review. However, any included trial which has a trialist who is also an author of the Cochrane review must declare this in the Declaration of Interests section of the review.

Q2. Given that one of your stated core principles is to minimize bias, can you please let me know your organizational guidelines regarding authorship of reviews and whether or not authors should be able to review their own studies? To a lay person, there seems to be quite a potential for conflict here.

Authors response: In the Cochrane Wounds Group we adhere strictly to the policy that if an author of a Cochrane review is also a trialist of an included trial in that same review they must declare this in the Declaration of Interests section of the review. This declaration is also made in the online Declaration of Interests form which has to be completed by all authors before a protocol or a review can be published on the Cochrane Library.

Q3. As reviewers of the Jull et al study (Randomized clinical trial of honey-impregnated dressings for venous leg ulcers), how did you judge the relative bias of the study author’s ad hoc decision to remove incidence of infections from the adverse events table?

Authors response: This question is directly with respect to a trial we conducted, not the systematic review. We did not remove incidence of infections from adverse events. The incidence of infection was analysed separately as specified a priori in the protocol and statistical analysis plan in response to interest in whether honey may prevent infections in venous leg ulcers.

Q4. With regard to the above, the removal of infections from the adverse events section somehow allowed the study authors to also remove the costs associated with hospitalizations associated with those infections from their overall cost of care analysis. However, the other costs associated with hospitalization (not having to do with infection) remained. When the costs associated with hospitalizations due to infection were included in the analysis, the honey arm was less expensive. Only after the costs associated with the additional hospitalizations associated with infection were removed (ad hoc) was the honey arm more expensive. Given that the decision to remove infections was ad hoc, how did you judge the relative bias of the statement by the study authors that the honey arm was likely more expensive?

Authors response: This question is directly with respect to a trial we conducted, not the systematic review. Incidence of infection was included in all the cost analyses. An analysis for sensitivity of the base case (all costs for ulcer treatment) to the small number of patients hospitalized for treatment related to their ulcer was undertaken. We do not know what the exact purpose of the hospitalization was i.e. whether it was related to infection or not, only that it was self-reported by the patients as related to their ulcer. As explained in the paper, the difference was likely due to random variability rather than use of honey or not. The decision to sensitivity test the base case was not ad hoc.

Q5. As reviewers of the Jull et al study, how did you judge the relative bias of the study regarding the author’s conclusion that honey dressings should not be considered for venous leg ulcer healing given that all the primary and secondary endpoints favored the honey arm (although not statistically)? It would seem, based on the results of the study, that honey should be included into the control group of alginate, hydrofiber, hydrocolloid, foam, non-adherent, iodine, and silver-based dressings as dressings that have demonstrated efficacy as adjuvants to compression therapy. Again, given the positive nature of the evidence derived in this study, how did you judge the potential bias within the authors’ conclusion?

Authors response: This question is directly with respect to a trial we conducted, not the systematic review. There were no statistically significant differences between the groups on the primary outcome, nor on any of the secondary outcomes. In fact the results for the blinded verification of healing suggest barely any difference between groups (absolute difference 0.5%, 95%CI -10.6% to 11.3%) on the primary outcome. Routine use of honey dressings is therefore not superior to other dressings for promoting healing compared to usual care. This conclusion does not preclude non-routine use of honey.

Q6. You included a second study in your Cochrane Review to address the management of venous leg ulcers. This second study, by Gethin et al, allowed only those wounds with greater than 50% slough coverage. In the larger Jull et al study of potentially likely to heal venous leg ulcers, the authors stated that the positive results (not statistically significant) favoring honey should be “generalizable” to all venous leg ulcers, regardless of wound bed appearance, unless new data shows otherwise. In the Gethin study, the wounds in both arms had average slough coverage ranging from 78% - 86%, and had average wound areas of 9.9cm² to 10.5cm². However, in the Jull study, there is no notation of slough coverage and the wounds ranged in average area from only 2.6cm² to 2.7cm². Thus, the wound bed appearance was dramatically different between these two studies. If the authors of the Jull study thought it was wise to view different wound bed appearance as indicative of a different patient set, why did you chose to combine results of these two vastly different studies? It should be noted that in the Gethin study on harder-to-heal wounds, even a much smaller number of patients resulted in the honey arm providing statistically significant healing benefit over control. Based on what the authors of the Jull et al study stated, shouldn’t your conclusions from these two studies have been: Honey provides a non-significant healing benefit for routine venous leg ulcers, and provides a significant healing benefit for non-routine venous leg ulcers?

Authors response: The commentator states two studies were “vastly different” but mistakenly compares median ulcer size reported in Jull et al to mean ulcer size reported in Gethin & Cowman, two statistics that are not comparable. The median ulcer area reported in Gethin & Cowman was 5.4 and 4.2 cm2. Ulcer duration is also an important consideration when considering likelihood of healing. The mean duration of ulceration prior to enrolment in the Gethin and Cowman study was 39 weeks and 30 weeks, which was similar to the means in Jull et al (39 and 48 weeks). To suggest therefore that Gethin & Cowman recruited harder-to-heal wounds compared to Jull et al is not accurate. These studies were not dissimilar in terms of populations and there is no evidence to suggest that they were different in terms of wound bed appearance – one trial provided information on this factor, another did not. In the Gethin & Cowman study, the statistically significant difference only emerged in the adjusted analysis. The unadjusted analysis for Gethin and Cowman is presented in the systematic review and shows no significant difference (RR 1.33, 95%CI 0.82 – 2.16).

Q7. Regarding honey versus SSD, why should the results of these studies be disregarded as you suggest due to other studies having shown benefit of hydrocolloids and silicone based dressings over SSD? Does this mean that you recommend that no other studies be done comparing one arm to SSD in the treatment of partial thickness burns?

Authors response: There is evidence that suggests SSD cream applied from time treatment initiated until healing may delay healing. (Thomas SS et al. J Wound Care 1995;4:218-20. Wyatt D et al. J Trauma 1990;30:857-65. Bugmann P et al. Burns 1998;24:609-12.) It appears the issue may be how SSD cream is used, not whether it is used. Our focus in the review was in trying to understand whether honey conferred a benefit. Using an appropriate comparator is pertinent to such an analysis and it is not clear that SSD applied daily from treatment initiation to healing is an appropriate comparator.

Q8. Regarding the above, which do you think is the more commonly used product on partial thickness burns, SSD or hydrocolloids? Are you aware of the commonplace usage on SSD in burn centers? If so, why would you suggest disregarding the results of studies which show a benefit over SSD? If not, and you find this to be true (that SSD is still commonly used in burn centers), would you change your decision to disregard the evidence derived from studies utilizing SSD as a control arm?

Authors response: See above

Q9. Also regarding the honey vs SSD studies, can you provide a more thorough clarification on why the CHIT method employed by the investigator disqualified these studies from your analysis?

Authors response: The use of the chit method did not disqualify any trial from consideration. Authors of trials that did not describe the method for generating the random sequence were approached for further information. The author of 11 trials replied stating the sequence was “manually generated random numbers by the chit method”, without providing any further information about what was meant by this approach with respect to sequence generation. We sought the advice of broadly experienced senior biostatistician who could not infer from this response what method of sequence generation was used. We therefore stated in the Risk of bias tables “method of generation of random sequence not reported. The author informed us that the sequence was generated by the ‘chit method’, but it is not clear what this method is.”

Q10. Of the 6 additional studies cited as rationale for this “updated” Cochrane Review, 5 out of the 6 are positive in favor of honey. Why is only the one negative study included in your updated conclusion? How did the biases of this study, as well as the overall structure of the study, compare with the other 5 studies which were not included in your updated conclusion? Were these differences the reason you only cited the negative study?

Authors response: When a review is updated we run the searches again and assess the resulting output. For this update we identified six additional studies which met the inclusion criteria published in the review, and all six studies were included in the review with the results of those studies presented.

Q11. Would someone be wrong if they stated it appears as though your inclusion of only the one negative study, and lack of inclusion of the 5 positive studies, appears to be “cherry picking”?

Authors response: A systematic review is conducted according to a defined, peer reviewed and published protocol to minimize bias. Any studies which are excluded have to be identified in the Table of Excluded studies and the reasons for the exclusion made clear. I am assuming you are referring to the six additional studies which were included in the last update of this review. All six studies are “included studies”.

Q12. Regarding the one negative study, which was on the treatment of cutaneous Leishmaniasis (a wound resulting from a bite from a sand fly indigenous to the Middle East), the study authors note that further studies should be done using standardized medical grade honeys, such as Leptospermum Scoparium (Manuka Honey). They acknowledge the fact that they used plain local honey could have been the reason for not achieving positive results. Why did you not include this in your conclusions or anywhere in your description of the study?

Authors response: The purpose of the review was to summarise the available evidence, not to restate authors’ interpretations.

Q13. Regarding the negative study on honey vs early excision and grafting of mixed partial and full thickness ulcers, to the best of your knowledge, how many studies do you know that compare one dressing vs this surgical standard and show improved results? Given the rest of the consistently positive results of the other honey studies cited for management of partial thickness burns, do you think the results of the early excision and grafting study suggest that honey would in any way be dangerous to use on partial thickness wounds that do not require early excision and grafting? If so, why?

Authors response: This review does not set out to present results of any dressing when compared with early excision and grafting of mixed partial and full thickness ulcers. Clearly there was sufficient equipoise for a trial to be conducted comparing early excision and grafting versus treatment with honey and delayed grafting as necessary. This trial was therefore included in the review.

Q14. Can you please provide the total numbers of the following: How many studies cited in your review had a statistically significantly positive outcome for the honey arm? How many studies cited in your review had a positive outcome (although not significantly) for the honey arm? How many studies had a negative outcome (although not significantly) for the honey arm? How many studies had a statistically significantly negative outcome for the honey arm?

Authors response: The data extracted from the trials and presented in the results section is provided in the review. Counting the number of statistically significant studies is not a sensible approach to summarising evidence when meta-analysis is possible.

Q15. Given the numbers above, why did you feel that it was important to include in your updated conclusion the following statement; “…purchasers should refrain from providing honey dressings for routine use until sufficient evidence of effect is available”? This statement seems cautionary in its advice. What is the caution that you believe purchasing agents should take into account when considering routine use of honey based dressings?

Authors response: In the light of insufficient evidence a cautionary approach is warranted. Routine use of honey dressings refers to use of honey as a first line dressing.

Q16. Given that Andrew Jull is not only is the author of the key study cited in the Cochrane Review, but that he is also on the editorial board for the wounds group reviewing all Cochrane Reviews on wound care, this question is directed specifically to him in his role as an editor: Due to the lack of well controlled RCTs, the vast majority of Cochrane Reviews on wound dressings / technologies (with the exception of total contact casts) have negative conclusions. The majority of these conclusions all seem to have a “boiler plate” type of statement, basically stating “there is not enough evidence to suggest the use of one product over another.” Given the recent updated conclusion in the review of honey dressings, do you think, if any of the other reviews are similarly “updated” (including those on negative pressure, silver based dressings, alginates, hydrocolloids, foams, etc.), without any meaningful positive results from well controlled studies, do you think that clinicians should similarly be advised to refrain from routine use of those dressings/technologies for routine use until sufficient evidence of effect is available? If not, then why?

Authors response: Andrew Jull is an Editor of the Cochrane Wounds Group; he does not review all Cochrane reviews in wound care and reviews are distributed amongst all the editors and each review is peer reviewed by a number of editors and reviewers. It is not appropriate for the authors of this review to suggest how other authors should write their reviews.

Q17. Why was the statement, “purchasers should refrain from providing honey dressings for routine use until sufficient evidence of effect is available” subsequently changed?

Authors response: This change was in response to feedback received from Barry Wolfenson on behalf of Derma Sciences (14^th June 2013) expressing concern at the wording of the Authors' conclusions - as follows: “There is insufficient evidence to guide clinical practice in other types of wounds, and purchasers should refrain from providing honey dressings for routine use until sufficient evidence of effect is available.” This statement had been present in the Authors' conclusions since the review was first published in 2008. Cochrane guidance from the Handbook states "The primary purpose of the review should be to present information, rather than to offer advice". Having considered the feedback and received the advice of the Cochrane Collaboration, we have modified this section to read: "…There is insufficient evidence to guide clinical practice in other areas, and health services may wish to consider avoiding routine use of honey dressings until sufficient evidence of effect is available". Although the primary purpose of a review is to present information, rather than to offer advice, review authors are invited to interpret the findings of their review in the "implications for practice" section. This section is clearly labelled as "authors' conclusions".

Q18. Do you believe the following statement is intended to provide advice; “…Health services may wish to consider avoiding routine use of honey dressings until sufficient evidence of effect is available”? If not, how do you interpret this statement to not be providing advice on usage?

Authors response: Review authors are invited to interpret the findings of their review in the "implications for practice" section and these are clearly labelled as "authors' conclusions". It seems perfectly reasonable where no compelling evidence of benefit has been identified to suggest that decision makers consider this finding. The use of the terms "consider" and "routine" clearly indicate that this is not intended to be a didactic recommendation, simply something for consideration by decision makers.

Q19. How many times is this type of advice given in any of the other Cochrane Reviews regarding wound dressings? Please only limit your response to those Cochrane Reviews that had negative conclusions, such as on alginates, foams, silver dressings, negative pressure, etc… If the answer is 0 (zero), what do you think is the distinction between the evidence presented for honey-based dressings and the evidence presented for these other dressings/technologies?

Authors response: There is no blueprint for the precise wording of this section, and it is not unusual for Cochrane Reviews to present text that provides guidance that decision makers should consider the absence of high quality evidence of benefit when making treatment decisions.

Q20. Specifically regarding your statement in the Cochrane Review that clinicians may consider refraining from routine use on honey-based dressings, can you please clarify:

20.1 For routine venous leg ulcers: Should clinicians refrain from using honey-based dressings? If so, why?
Authors response: It is reasonable to highlight the apparent failure of routine use honey dressings to deliver such an important outcome as healing rate.

20.2 For chronic/stalled venous leg ulcers: Should clinicians refrain from using honey-based dressings? If so, why?
Authors response: All venous leg ulcers are chronic. The evidence from the trials does not address “stalled” venous ulcers.

20.3 For other routine ulcers such as pressure ulcers: Should clinicians refrain from using honey-based dressings? If so, why?
Authors response: The results of the review demonstrate clear uncertainty in respect of this outcome.

20.4 For other chronic/stalled ulcers such as pressure ulcers: Should clinicians refrain from using honey-based dressings? If so, why?
Authors response: The evidence from the single available trial does not address “stalled” pressure ulcers.

20.5 For partial thickness burns that do not require early excision and grafting: Should clinicians refrain from using honey-based dressings? If so, why?Authors response: The
results of the review demonstrate clear uncertainty in respect of this outcome.

20.6 For any challenging wounds where a clinician would typically use negative pressure, silver-based dressings, iodine-based dressings, alginates, or foams: Should clinicians refrain from using honey-based dressings? If so, why?
Authors response: There were no trials where the wounds were defined as ‘challenging’.

20.7 Do you consider chronic wounds (whether they be venous leg ulcers, diabetic foot ulcers, pressure ulcers, or dehisced surgical wounds) to be “routine”?
Authors response: It is not clear what is meant by “routine” in this context – none of the conditions are uncommon.

20.8 Do you consider partial thickness burns that are treated in a burn center to be “routine”?
Authors response: It is not clear what is meant by “routine” in this context.

Reply

The authors of the review have responded to this feedback giving a point by point response to the questions above.

Contributors

Barry Wolfenson, Group President, Advanced Wound Care & Drug Development, Derma Sciences.
Declaration of interest: I am the President of Advanced Wound Care at Derma Sciences. Thus, I clearly have involvement with an organization with a financial interest in the subject matter of my feedback.

Andrew Jull, Author; Nicky Cullum, Coordinating Editor CWG; Sally Bell-Syer Managing Editor CWG.

Summary

Comment: I strongly support evidence-based practice and was trained as a Cochrane reviewer in 1995. Am concerned that this SR is eroding Cochrane credibility as so many wound care professionals have asked me to clarify issues in it. Please help correct the following errors as quickly and thoroughly as possible:
1. Errors in describing the studies (omission of important facts or perspective),
2. Arbitrary emphasis on non-statistically significant or irrelevant or inappropriate findings in abstract and conclusions
3. Omitting statistically significant RCT healing results favorable to honey in abstract and conclusions
4. Statements in the Authors conclusion and Abstract do not seem to reflect the results reported in the body of the SR
5. Inappropriate recommendations to avoid honey use that usurp clinician's point of care decisions rather than inform them of level of evidence supporting honey use for various indications, which appears no less sufficient than that for many other wound care interventions.
My Cochrane trainers insisted we avoid recommending and simply describe levels of evidence to empower clinical decision making. Has this changed?
To clarify the issues Dr. Janice Beitz and I presented a webinar with more detail on each issue accessible at:
http://www.dermasciences.com/pdf/Scientific-Review-of-Cochrane-Review-Honey-as-Topical-Treatment-for-Wounds-Dr.-Bolton-and-Dr.%20Beitz.pdf
Thank you and the hard working Cochrane Wounds Group for your immediate attention to help uphold Cochrane credibility!

Reply

The authors of the review have considered the feedback and are pleased to report that the review has been fully updated, a new search conducted with two additional studies included. All the data have been checked and the evidence assessed using the GRADE approach and four Summary of Findings Tables added. The Results section has been restructured to bring all outcomes together for each comparison and the conclusions of the review have been slightly amended. This updated review has been peer reviewed.

Contributors

Laura Bolton, Adjunct Associate Professor of Surgery, Rutgers University Medical School.
Declaration of interest: I certify that I consult on evidence-based product development and study design for EuroMed, Derma Sciences and Systagenix, but have never received any corporate funding for honey-related consulting or speaking nor for my part in presenting the Webinar described.

Andrew Jull, Author; Nicky Cullum, Coordinating Editor CWG; Sally Bell-Syer Managing Editor CWG.

Summary

I was concerned to learn of the recent negative review regarding honey and treating wounds. The review did not seem to provide a balance of the available literature. Thank you for considering this comment.

Reply

The authors have carefully considered and incorporated the observations and items of feedback submitted through the “Submit Comments” facility on the Cochrane Library for this review. These comments and the replies from the authors have been retained in this version of the review. This is to enable readers to follow the exchange and to form their own interpretation of the evidence that is now available.

Contributors

Joy Schank, Private Practice, Nurse Practitioner.
I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback.

Andrew Jull, Author; Nicky Cullum, Coordinating Editor CWG; Sally Bell-Syer Managing Editor CWG.

Summary

Dear Editor: As a Certified Wound Specialist, a Doctor of Physical Therapy with a Masters in Healthcare Administration, and a director of both inpatient and outpatient wound care services at Inspira Health Network in New Jersey I have recently read the Cochrane Review “Honey as a Topical Treatment for Wounds” by Jull et al, 2013. A sales representative that does not sell honey products pointed out the conclusion of the Cochrane review to me stating “health services may wish to consider avoiding routine use of honey dressing until sufficient evidence is available”. For many years I have been using honey dressings on a variety of wounds including pressure ulcers, venous leg ulcers, arterial ulcers, surgical wounds and diabetic foot ulcers. I have authored and presented multiple case series at international wound congresses demonstrating my success with the use of these dressings on a variety of wounds. I have treated hundreds of wounds with honey and have found these dressings to be helpful in the healing of these wounds and have never noted any severe adverse reactions. I was extremely surprised to see that the conclusion to “avoid” usage and question how this recommendation can be made when I have not been able to find evidence nor have experienced any negative issues. Upon my concern with the conclusion I then read with great interest the entire published review.
Pertaining to the author’s recommendation to “avoid” usage seems to indicate a safety or efficacy concern. In the AE table published in the review, “ulcer pain” is the only difference in the number of AEs. However, in the review authors’ own study incorporated into the review (HALT study by Jull et al 2007), the authors note that while pain on dressing changes was more frequent in the honey arm, the pain was not severe enough to cause patients to exit the study, suggesting it was well tolerated. This is similar to my own experience, where if a patient does feel pain upon dressing changes, it is short in duration and well tolerated. Additionally, it has been my experience that application of honey helps to reduce the chronic wound pain commonly suffered by venous leg ulcer patients, potentially due to a reduction in inflammation. Thus, I do not see how this could possibly be an issue with regard to use of honey dressings. Can you please clarify what is the reason for authors’ recommendation to avoid usage? There were only four articles out of 25 reviewed that did not favor honey so please clarify what specific concern the authors have that led to that recommendation.
I would like to commend the Editors of the Cochrane Review on providing the health care community with a balanced review of clinical information that is helpful in making decisions regarding the treatment of our patients with new procedures and medical products. Unfortunately, this review is inconsistent with my clinical experience as well as the long established excellence of the Cochrane Review. I believe the authors’ conclusion needs to be made clearer. I did agree with the vast majority of the studies having more favorable results in the honey arms of the study but I would also note that the recommendation itself seems out of place in a Cochrane review, and I was very surprised to find it in the review at all.

Reply

The authors of the review have considered the feedback and are pleased to report that the review has been fully updated, a new search conducted with two additional studies included. All the data have been checked and the evidence assessed using the GRADE approach and four Summary of Findings Tables added. The Results section has been restructured to bring all outcomes together for each comparison and the conclusions of the review have been slightly amended. This updated review has been peer reviewed.

Contributors

Jennifer A. Gardner, PT DPT MHA CWS. Manager, Wound Care Services. Inspira Medical Center Woodbury.
I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback.

Andrew Jull, Author; Nicky Cullum, Coordinating Editor CWG; Sally Bell-Syer Managing Editor CWG.

Summary

Dear Editor in Chief,
I am Burn Surgeon and the Director of one of the largest burn centers in the US, which treats thousands of patients annually. I recently had the pleasure of reviewing your 2013 publication Honey as a topical treatment for wounds (Review) written by Drs. Jull, Walker and Deshpande. While I did enjoy reading the review, I would like to express my concern about the Authors’ Conclusions.
As a clinician who regularly treats patients who have suffered from partial-thickness and full-thickness burns, I do not share the sentiment expressed by the authors that “health services may wish to consider avoiding routine use of honey dressings until sufficient evidence of effect is available.” In my personal experience, communication with other physicians and reviews of available literature, I have found that honey dressings are quite effective, especially where previous treatments have failed to provide benefit.
Additionally, I believe that the authors have put significant weight in their conclusion on one study (Subrahmanyam 1999) which evaluated the use of honey dressings compared to the industry standard for moderate to severe partial-thickness and full-thickness burns. It is my opinion, given the vast amount of supportive literature from this author as well as others, that although the results of this study were not in favor of the use of honey dressings, results should not be used to discredit their use. As early excision and grafting is an established practice, it is my opinion that the author was attempting to evaluate honey as an alternative remedy for more troublesome burn injuries. The fact that the study failed to show positive results in this setting informs an upper limit for defining honey dressings as a standard of care treatment in burns and validates the practice of grafting rather than discrediting the use of honey dressings in less severe clinical scenarios.
It is evident that honey dressings are not a panacea for all wound types and severity, however, the recommendation that the medical community avoid the use of such dressings is confusing as it is not founded by the clinical safety and efficacy evidence (or lack thereof) provided in the review. Therefore, I would ask that you consider revising the aforementioned conclusion.
Thank you for your time and consideration.

Reply

The authors of the review have considered the feedback and are pleased to report that the review has been fully updated, a new search conducted with two additional studies included. All the data have been checked and the evidence assessed using the GRADE approach and four Summary of Findings Tables added. The Results section has been restructured to bring all outcomes together for each comparison and the conclusions of the review have been slightly amended. This updated review has been peer reviewed.

Contributors

Kevin Foster, MD, MBA, FACS. Director Burn Services. The Arizona Burn Center at Maricopa Burn Center Phoenix, Arizona.
I certify that I have the affiliations/involvement as described. I have spoken to the sales force for Medihoney, describing my experience with its use. I received an honorarium and travel expenses.

Andrew Jull, Author; Nicky Cullum, Coordinating Editor CWG; Sally Bell-Syer Managing Editor CWG.

Summary

To the Editors of the Cochrane Collaboration,
After reviewing one of your recent publications, Honey as a topical treatment for wounds (Review), I have become very concerned about some of the language used in the Authors’ Conclusions regarding “avoiding use” of honey dressings.
I am a practicing doctor of osteopathy and Medical Director at Wayne Memorial Wound Care Center in North Carolina. Over 120 patients are seen in our clinic on a weekly basis. I regularly use impregnated honey dressings and honey gel for diabetic, venous and pressure ulcers as well as acute and chronic wounds. I have personally experienced positive patient outcomes and no safety or efficacy issues with this intervention. Additionally I have found honey dressings to be cost efficient to go along with a high patient compliance rate.
In reading the review, the data presented seems to point towards a positive effect of honey, which correlates with my personal experience. For example, in the pressure ulcer study cited (Weheida 1991), the mean time to healing favored honey with statistical significance. Also in the Diabetic foot ulcer study cited (Shukrimi 2008) the endpoint of time to healing also favored honey.
Therefore, it is confusing to see this conclusion and recommendation that “There is insufficient evidence to guide clinical practice in other areas, and health services may wish to consider avoiding routine use of honey dressings until sufficient evidence of effect is available.” It inaccurately gives the reader - especially those who do not read the full review - the impression that this intervention is not safe and efficacious; an impression which is not supported by the data presented or my experience in clinical practice.
It would like to suggest that you consider revising the current conclusion to help readers have a more balanced perspective of the body of evidence supporting honey base wound care.
I appreciate your consideration of this matter.

Reply

The authors of the review have considered the feedback and are pleased to report that the review has been fully updated, a new search conducted with two additional studies included. All the data have been checked and the evidence assessed using the GRADE approach and four Summary of Findings Tables added. The Results section has been restructured to bring all outcomes together for each comparison and the conclusions of the review have been slightly amended. This updated review has been peer reviewed.

Contributors

Dr. Dimitrios Lintzeris, DO, CWS. Medical Director. Wayne Memorial Wound Care Center.
I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback.

Andrew Jull, Author; Nicky Cullum, Coordinating Editor CWG; Sally Bell-Syer Managing Editor CWG.

Summary

Comment: I was handed a copy of the Cochrane Report on medihoney by the Santyl rep in our area. He of course espoused the report's statement that clinicians should cease use of the product as stated in the report. This prompted me to assess carefully tow of the patients which I was overseeing their complex wounds and using medihoney. I can tell you that the wound made outstanding progress with medihoney - in fact remarkable considering both patients were complex and compromised - one with active cancer undergoing radiation and chemontherapy and the other had breast cancer several years before with reconstructive surgery. At no time did they have any failure of their wound care and I have the photos to prove their excellent results. I am appalled at the campaign Smith & Nephew/Healthpoint has directed at medihoney based on the Cochrane Report - a report that is riddled with inconsistencies.

Reply

The authors of the review have considered the feedback and are pleased to report that the review has been fully updated, a new search conducted with two additional studies included. All the data have been checked and the evidence assessed using the GRADE approach and four Summary of Findings Tables added. The Results section has been restructured to bring all outcomes together for each comparison and the conclusions of the review have been slightly amended. This updated review has been peer reviewed.

Contributors

Margarita Simon, MS, FNP-BC, CWCN. wound care consultant. Simon WOund Consulting, PLLC.
I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback.

Andrew Jull, Author; Nicky Cullum, Coordinating Editor CWG; Sally Bell-Syer Managing Editor CWG.

Summary

Comment: The March 2015 update includes a paper by Gethin (2009, J Clin Nursing) which was retracted in July 2014, and thus it should not be included. The unpublished thesis by Gethin (2007) is only available by visiting the library at the Royal College of Surgeons in Dublin. It should be read and the data carefully evaluated if it is to be included, as readers of the review won't easily be able to draw their own independent conclusions.

Reply

Thank you for your comment. We were aware of the article’s retraction and the reason for the retraction. As noted in the review history, review notes, and the references, we used Gethin’s 2007 PhD thesis as a primary source of information for description of the trial, risk of bias assessment, and outcome data on healing rates and infections. It is worth noting that the extracted data for risk of bias assessments, healing rates, and infections is not in dispute. We used Dr Gethin's data as an input into a meta-analysis that produced a summary statistic for the two trials being pooled. Our interpretations are based on our meta-analysis, not any other analyses from primary sources.

Contributors

Herbert B. Slade MD (Email Address: bert.slade@smith-nephew.com).
Affiliation: Univ of North Texas Health Sciences Center, Smith & Nephew. Role: Assoc Clin Prof Pediatrics (UNT), Chief Medical Officer (S&N).
I have modified the conflict of interest statement below to declare my interests:
I am the chief scientific and medical officer of a medical devices company which markets products for wounds.

Andrew Jull, Author.