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Obstetrics and Gynecology Sep 2017To assess the efficacy of vaginal cleansing before cesarean delivery in reducing postoperative endometritis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the efficacy of vaginal cleansing before cesarean delivery in reducing postoperative endometritis.
DATA SOURCES
MEDLINE, Ovid, EMBASE, Scopus, Clinicaltrials.gov, and Cochrane Library were searched from their inception to January 2017.
METHODS OF STUDY SELECTION
Selection criteria included all randomized controlled trials comparing vaginal cleansing (ie, intervention group) with a control group (ie, either placebo or no intervention) in women undergoing cesarean delivery. Any method of vaginal cleansing with any type of antiseptic solution was included. The primary outcome was the incidence of endometritis. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of relative risk (RR) with 95% CI.
TABULATION, INTEGRATION, AND RESULTS
Sixteen trials (4,837 women) on vaginal cleansing immediately before cesarean delivery were identified as relevant and included in the review. In most of the included studies, 10% povidone-iodine was used as an intervention. The most common way to perform the vaginal cleansing was the use of a sponge stick for approximately 30 seconds. Women who received vaginal cleansing before cesarean delivery had a significantly lower incidence of endometritis (4.5% compared with 8.8%; RR 0.52, 95% CI 0.37-0.72; 15 studies, 4,726 participants) and of postoperative fever (9.4% compared with 14.9%; RR 0.65, 95% CI 0.50-0.86; 11 studies, 4,098 participants) compared with the control group. In the planned subgroup analyses, the reduction in the incidence of endometritis with vaginal cleansing was limited to women in labor before cesarean delivery (8.1% compared with 13.8%; RR 0.52, 95% CI 0.28-0.97; four studies, 440 participants) or those with ruptured membranes (4.3% compared with 20.1%; RR 0.23, 95% CI 0.10-0.52; three studies, 272 participants).
CONCLUSION
Vaginal cleansing immediately before cesarean delivery in women in labor and in women with ruptured membranes reduces the risk of postoperative endometritis. Because it is generally inexpensive and a simple intervention, we recommend preoperative vaginal preparation before cesarean delivery in these women with sponge stick preparation of povidone-iodine 10% for at least 30 seconds. More data are needed to assess whether this intervention may be also useful for cesarean deliveries performed in women not in labor and for those without ruptured membranes.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO International prospective register of systematic reviews, https://www.crd.york.ac.uk/PROSPERO/, CRD42017054843.
Topics: Administration, Intravaginal; Anti-Infective Agents, Local; Cesarean Section; Female; Humans; Povidone-Iodine; Pregnancy; Preoperative Care; Randomized Controlled Trials as Topic; Surgical Wound Infection; Vagina
PubMed: 28796683
DOI: 10.1097/AOG.0000000000002167 -
The Lancet. Infectious Diseases Aug 2022WHO and the UK's National Institute for Health and Care Excellence recommend alcoholic chlorhexidine skin preparation and triclosan-coated sutures to prevent surgical... (Meta-Analysis)
Meta-Analysis
Alcoholic chlorhexidine skin preparation or triclosan-coated sutures to reduce surgical site infection: a systematic review and meta-analysis of high-quality randomised controlled trials.
BACKGROUND
WHO and the UK's National Institute for Health and Care Excellence recommend alcoholic chlorhexidine skin preparation and triclosan-coated sutures to prevent surgical site infections (SSIs). Existing meta-analyses that include studies at high risk of bias, combined with the recent publication of large, randomised trials, justify an updated meta-analysis of high-quality randomised controlled trials (RCTs). We aimed to test the rates of SSI according to skin preparation solutions (ie, alcoholic chlorhexidine vs aqueous povidone-iodine) and types of sutures (ie, coated vs uncoated).
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, Embase, Pubmed, and Cochrane Library databases, with no language restrictions, to identify high-quality RCTs testing either alcoholic chlorhexidine skin preparation (vs aqueous povidone-iodine) or triclosan-coated sutures (vs uncoated sutures), or both, published from database inception to Sept 1, 2021. Patients who received clean-contaminated, contaminated, or dirty surgery were included. We predefined the characteristics of a high-quality trial through an expert consensus process to develop an enhanced Cochrane risk of bias-2 tool specifically for RCTs with a primary outcome of SSI. Data were extracted from published reports. Meta-analysis was performed using a random-effects model and heterogeneity was assessed using the I statistic. This systematic review and meta-analysis was prospectively registered in PROSPERO, CRD42021267220.
FINDINGS
Of 942 studies identified, 933 were excluded. Four high-quality RCTs (n=7467 patients) were included that tested alcoholic chlorhexidine. No significant difference in SSI rates was noted between alcoholic chlorhexidine and aqueous povidone-iodine (17·9% [667 of 3723 patients] vs 19·8% [740 of 3744 patients]; odds ratio 0·84 [95% CI 0·65-1·06]; p=0·21, I=53·1%). Five high-quality RCTs were included that tested triclosan-coated sutures (n=8619 patients), with no significant difference noted between triclosan-coated and uncoated sutures (16·8% [733 of 4360 patients] vs 18·4% [784 of 4259 patients]; OR 0·90 [95% CI 0·74-1·09]; p=0·29, I=36·4%).
INTERPRETATION
Contrary to previous meta-analyses, this study did not show a benefit from either alcoholic chlorhexidine skin preparation or triclosan-coated sutures, both of which are more expensive than other readily available alternatives. Global and national guidance should be reconsidered to remove recommendations for their routine use.
FUNDING
National Institute for Health Research (NIHR) Global Health Research Unit.
Topics: Anti-Infective Agents, Local; Chlorhexidine; Humans; Povidone-Iodine; Randomized Controlled Trials as Topic; Surgical Wound Infection; Sutures; Triclosan
PubMed: 35644158
DOI: 10.1016/S1473-3099(22)00133-5 -
The Journal of Hospital Infection Mar 2017Catheter-associated urinary tract infections (CAUTIs) are among the most common healthcare-associated infections. Antiseptic cleaning of the meatal area before and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Catheter-associated urinary tract infections (CAUTIs) are among the most common healthcare-associated infections. Antiseptic cleaning of the meatal area before and during catheter use may reduce the risk of CAUTIs.
AIM
To undertake a systematic review of the literature and meta-analysis of studies investigating the effectiveness of antiseptic cleaning before urinary catheter insertion and during catheter use for prevention of CAUTIs.
METHODS
Electronic databases were searched to identify randomized controlled trials. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and compared across intervention and control groups using DerSimonian-Laird random-effects model. Subgroup analyses were performed. Heterogeneity was estimated using the I statistic.
FINDINGS
In total, 2665 potential papers were identified; of these, 14 studies were eligible for inclusion. There was no difference in the incidence of CAUTIs when comparing antiseptic and non-antiseptic agents (pooled OR 0.90, 95% CI 0.73-1.10; P=0.31), or when comparing different agents: povidone-iodine vs routine care; povidone-iodine vs soap and water; chlorhexidine vs water; povidone-iodine vs saline; povidone-iodine vs water; and green soap and water vs routine care (P>0.05 for all). Comparison of an antibacterial agent with routine care indicated near significance (P=0.06). There was no evidence of heterogeneity (I=0%; P>0.05). Subgroup analyses showed no difference in the incidence of CAUTIs in terms of country, setting, risk of bias, sex and frequency of administration.
CONCLUSIONS
There were no differences in CAUTI rates, although methodological issues hamper generalizability of this finding. Antibacterial agents may prove to be significant in a well-conducted study. The present results provide good evidence to inform infection control guidelines in catheter management.
Topics: Anti-Infective Agents, Local; Antisepsis; Catheter-Related Infections; Catheterization; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Urinary Tract Infections
PubMed: 27986361
DOI: 10.1016/j.jhin.2016.10.025 -
American Journal of Obstetrics &... Aug 2023Precesarean vaginal antisepsis can benefit pregnant women with ruptured membranes. However, in the general population, recent trials have shown mixed results in reducing... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Precesarean vaginal antisepsis can benefit pregnant women with ruptured membranes. However, in the general population, recent trials have shown mixed results in reducing postoperative infections. This study aimed to systematically review clinical trials and summarize the most suitable vaginal preparations for cesarean delivery in preventing postoperative infection.
DATA SOURCES
We searched PubMed, Web of Science, Cochrane Library, SinoMed databases, and the ClinicalTrials.gov clinical trials registry for randomized controlled trials and conference presentations (past 20 years, 2003-2022). Reference lists of previous meta-analyses were searched manually. In addition, we conducted subgroup analysis on the basis of whether the studies were conducted in developed or developing countries, whether the membranes were ruptured, and whether patients were in labor.
STUDY ELIGIBILITY CRITERIA
We included randomized controlled trials comparing vaginal preparation methods for the prevention of postcesarean infection with each other or with negative controls.
METHODS
Two reviewers independently extracted data and assessed the risk of bias and the certainty of the evidence. The effectiveness of prevention strategies was assessed by frequentist-based network meta-analysis models. The outcomes were endometritis, postoperative fever, and wound infection.
RESULTS
A total of 23 trials including 10,026 cesarean delivery patients were included in this study. Vaginal preparation methods included 19 iodine-based disinfectants (1%, 5%, and 10% povidone-iodine; 0.4% and 0.5% iodophor) and 4 guanidine-based disinfectants (0.05% and 0.20% chlorhexidine acetate; 1% and 4% chlorhexidine gluconate). Overall, vaginal preparation significantly reduced the risks of endometritis (3.4% vs 8.1%; risk ratio, 0.41 [0.32-0.52]), postoperative fever (7.1% vs 11.4%; risk ratio, 0.58 [0.45-0.74]), and wound infection (4.1% vs 5.4%; risk ratio, 0.73 [0.59-0.90]). With regard to disinfectant type, iodine-based disinfectants (risk ratio, 0.45 [0.35-0.57]) and guanidine-based disinfectants (risk ratio, 0.22 [0.12-0.40]) significantly reduced the risk of endometritis, and iodine-based disinfectants reduced the risk of postoperative fever (risk ratio, 0.58 [0.44-0.77]) and wound infection (risk ratio, 0.75 [0.60-0.94]). With regard to disinfectant concentration, 1% povidone-iodine was most likely to simultaneously reduce the risks of endometritis, postoperative fever, and wound infection.
CONCLUSION
Preoperative vaginal preparation can significantly reduce the risk of postcesarean infectious diseases (endometritis, postoperative fever, and wound infection); 1% povidone-iodine has particularly outstanding effects.
Topics: Humans; Female; Pregnancy; Povidone-Iodine; Anti-Infective Agents, Local; Surgical Wound Infection; Endometritis; Network Meta-Analysis; Iodine; Disinfectants; Communicable Diseases
PubMed: 37178722
DOI: 10.1016/j.ajogmf.2023.100990 -
Therapeutic Advances in Infectious... 2021Cleaning is a major control component for outbreaks of infection. However, for the SARS-CoV-2 pandemic, there is limited specific guidance regarding the proper... (Review)
Review
BACKGROUND
Cleaning is a major control component for outbreaks of infection. However, for the SARS-CoV-2 pandemic, there is limited specific guidance regarding the proper disinfection methods that should be used.
METHODS
We conducted a systematic review of the literature on cleaning, disinfection or decontamination methods in the prevention of SARS-CoV-2.
RESULTS
A total of 27 studies were included, reporting a variety of methods with which the effectiveness of interventions were assessed. Virus was inoculated onto different types of material including masks, nasopharyngeal swabs, serum, laboratory plates and simulated saliva, tears or nasal fluid and then interventions were applied in an attempt to eliminate the virus including chemical, ultraviolet (UV) light irradiation, and heat and humidity. At body temperature (37°C) there is evidence that the virus will not be detectable after 2 days but this can be reduced to non-detection at 30 min at 56°C, 15 min at 65°C and 2 min at 98°C. Different experimental methods testing UV light have shown that it can inactivate the virus. Light of 254-365 nm has been used, including simulated sunlight. Many chemical agents including bleach, hand sanitiser, hand wash, soap, ethanol, isopropanol, guandinium thiocynate/t-octylphenoxypolyethoxyethanol, formaldehyde, povidone-iodine, 0.05% chlorhexidine, 0.1% benzalkonium chloride, acidic electrolysed water, Clyraguard copper iodine complex and hydrogen peroxide vapour have been shown to disinfect SARS-CoV-2.
CONCLUSIONS
Heating, UV light irradiation and chemicals can be used to inactivate SARS-CoV-2 but there is insufficient evidence to support one measure over others in clinical practice.
PubMed: 33796289
DOI: 10.1177/2049936121998548 -
Infectious Disorders Drug Targets 2022Puerperal infection is used to describe any bacterial infection of the reproductive tract after delivery. Identifying the factors affecting postpartum infections can...
BACKGROUND
Puerperal infection is used to describe any bacterial infection of the reproductive tract after delivery. Identifying the factors affecting postpartum infections can reduce the risk and complications of such factors and postpartum maternal mortality.
OBJECTIVE
This structured study was designed to evaluate factors affecting postpartum infections.
METHODS
In this study, after selecting Scopus, PubMed, SID, and Web of Science electronic databases, all observational studies (cohort and case-control) available and published in Farsi and English to investigate factors affecting postpartum infections were searched. The search was performed using the terms postpartum, infection, wound infection, puerperium, reason, risk factor, and their equivalent Persian words from 2010 to November 2019 regardless of publication status.
RESULTS
Out of the 3227 studies obtained, 19 were reviewed after removing irrelevant articles, duplicates (shared in databases), and animal samples. Age, level of education, delivery method, presence of episiotomy, anemia due to postpartum hemorrhage, interventions and manipulations during childbirth, prenatal hygiene, Povidone Iodine usage before delivery to wash the vagina, antibiotic prevention, increased labor duration, obesity, and the presence of bacteria were common symptoms affecting postpartum infection.
CONCLUSION
In this study, the factors affecting postpartum infection have been identified, some of which are avoidable. Identifying these factors helps reduce postpartum infections and their complications.
Topics: Case-Control Studies; Female; Humans; Observational Studies as Topic; Postpartum Period; Pregnancy; Puerperal Infection
PubMed: 34844548
DOI: 10.2174/1871526521666211129100519 -
Evidence-based Dentistry May 2022Objective To conduct a living systematic review of the clinical evidence about the effect of different mouthrinses on the viral load of SARS-CoV-2 in the saliva of... (Review)
Review
Objective To conduct a living systematic review of the clinical evidence about the effect of different mouthrinses on the viral load of SARS-CoV-2 in the saliva of infected patients.Methods This study was reported using the PRISMA guidelines. An electronic search was conducted in seven databases and preprint repositories. We included human clinical trials that evaluated the effect of mouthrinses with antiseptic substances on the viral load of SARS-CoV-2 in the saliva of children or adults, who tested positive for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction (RT-PCR). The risk of bias was assessed using the ROBINS-I tool. PROSPERO registration number: CRD42021240561.Results Five studies were included (n = 66 participants). Study participants underwent oral rinses with hydrogen peroxide (H2O2) at 1%, povidone-iodine (PI) at 0.5% or 1%, chlorhexidine gluconate (CHX) at 0.2% or 0.12%, cetylpyridinium chloride (CPC) at 0.075%, and Linolasept. Only one study included a control group with sterile water. Three of the studies identified a reduction in viral load in saliva after the use of mouthrinses with PI (up to three hours), CHX (up to four hours), or Linolasept mouthwash (up to six hours). One study reported a statistically significant reduction after the use of mouthrinses with CPC or PI vs water (up to six hours) and one study reported a non-significant reduction in viral load after the use of HO rinses.Conclusions According to the present systematic review, the effect of mouthrinses on SARS-CoV-2 viral load in the saliva of COVID-19 patients remains uncertain. Evidence from well-designed randomised clinical trials is required for further and more objective evaluation of this effect.
PubMed: 35610479
DOI: 10.1038/s41432-022-0253-z -
The Cochrane Database of Systematic... Sep 2014The risk of maternal mortality and morbidity (particularly postoperative infection) is higher for caesarean section than for vaginal birth. With the increasing rate of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The risk of maternal mortality and morbidity (particularly postoperative infection) is higher for caesarean section than for vaginal birth. With the increasing rate of caesarean section, it is important that the risks to the mother are minimised as far as possible. This review focuses on different forms and methods for preoperative skin preparation to prevent infection.
OBJECTIVES
To compare the effects of different agent forms and methods of preoperative skin preparation for preventing postcaesarean infection.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (26 June 2014) and the reference lists of all included studies and review articles.
SELECTION CRITERIA
Randomised and quasi-randomised trials, including cluster-randomised trials, evaluating any type of preoperative skin preparation agents, forms and methods of application for caesarean section.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed all potential studies for inclusion, assessed risk of bias and extracted the data using a predesigned form. Data were checked for accuracy.
MAIN RESULTS
We included six trials with a total of 1522 women. No difference was found in the primary outcomes of either wound infection or endometritis. Two trials of 1294 women, compared drape with no drape (one trial using iodine and the other using chlorhexidine) and found no significant difference in wound infection (risk ratio (RR) 1.29; 95% confidence interval (CI) 0.97 to 1.71). One trial of 79 women comparing alcohol scrub and iodophor drape with iodophor scrub without drape reported no wound infection in either group. One trial of 50 women comparing parachlorometaxylenol plus iodine with iodine alone reported no significant difference in wound infection (RR 0.33; 95% CI 0.04 to 2.99).Two trials reported endometritis, one trial comparing alcohol scrub and iodophor drape with iodophor scrub only found no significant difference (RR 1.62; 95% CI 0.29 to 9.16). The other trial of 50 women comparing parachlorometaxylenol plus iodine with iodine alone reported no significant difference in endometritis (RR 0.88; 95% CI 0.56 to 1.38). One trial of 60 women comparing chlorhexidine gluconate with povidone-iodine reported significant lower rates of bacterial growth at 18 hours after caesarean section (RR 0.23, 95% CI 0.07 to 0.70). No difference was found in the secondary outcome of either length of stay or reduction of skin bacteria colony count. No trial reported other maternal outcomes, i.e. maternal mortality, repeat surgery and re-admission resulting from infection. One trial, which was only available as an abstract, investigated the effect of skin preparation on neonatal adverse events and found cord blood iodine concentration to be significantly higher in the iodine group.Most of the risk of bias in the included studies was unclear in selection bias and attrition bias. The quality of the evidence using GRADE was low for wound infection comparing drape versus no drape, one-minute alcohol scrub with iodophor drape versus five-minute iodophor scrub without drape, and parachlorometaxylenol with iodine versus iodine alone. The quality of the evidence for wound infection comparing chlorhexidine gluconate with povidone-iodine was very low.
AUTHORS' CONCLUSIONS
This review found that chlorhexidine gluconate compared with iodine alone was associated with lower rates of bacterial growth at 18 hours after caesarean section. However, this outcome was judged as very low quality of evidence. Little evidence is available from the included randomised controlled trials to evaluate different agent forms, concentrations and methods of skin preparation for preventing infection following caesarean section. Therefore, it is not yet clear what sort of skin preparation may be most efficient for preventing postcaesarean wound and surgical site infection.There is a need for high-quality, properly designed randomised controlled trials with larger sample sizes in this field. High priority questions include comparing types of antiseptic (especially iodine versus chlorhexidine), the timing and duration of applying the antiseptic (especially previous night versus day of surgery, and application methods (scrubbing, swabbing and draping).
Topics: Adult; Anti-Infective Agents, Local; Bandages; Cesarean Section; Chlorhexidine; Endometritis; Ethanol; Female; Humans; Iodine; Iodophors; Pregnancy; Randomized Controlled Trials as Topic; Surgical Wound Infection; Xylenes
PubMed: 25229700
DOI: 10.1002/14651858.CD007462.pub3 -
BMC Pediatrics Jul 2022Surgical site infections (SSIs) in children represent a common and serious postoperative complication. Surgical skin preparation is an essential preventive measure in...
BACKGROUND
Surgical site infections (SSIs) in children represent a common and serious postoperative complication. Surgical skin preparation is an essential preventive measure in every surgical procedure. The most commonly used antiseptic agents for surgical skin preparation are chlorhexidine gluconate and iodophors in alcohol-based solutions. In adult patients the use of chlorhexidine-containing antiseptic solutions for preoperative skin preparation has been advocated to reduce SSI rates. Our objective was to conduct a systematic literature review on use of antiseptic agents for surgical skin preparation in children less than 16 years of age.
METHODS
A systematic review of MEDLINE, EMBASE, CINAHL and CENTRAL was performed using both MeSH and free text terms and using the relevant Cochrane filter to identify full text randomized trials (RCTs) and comparative observational studies. Interventions of interest were the choice of main agent in antiseptic solutions (chlorhexidine/povidone-iodine/alcohol) compared with each other or with other antiseptic agents. Primary outcome was the reported rate of surgical site infections.
RESULTS
In total 8 studies were included in the review; 2 RCTs and 6 observational studies. Observational studies generally did not primarily investigate the association of different antiseptics with subsequent SSI. The identified randomised controlled trials included only 61 children in total, and were of low quality. Consequently, we did not conduct a formal meta-analysis. Since the publication of a comprehensive systematic review of perioperative measures for the prevention of SSI in 2016, no randomized controlled trials comparing antiseptic agents for surgical skin preparation in paediatric surgery have been conducted.
CONCLUSION
Robust evidence on the optimal skin antisepsis to reduce SSIs in children is lacking. Direct extrapolation of effects from trials involving adults is not appropriate as physiologic characteristics and risk factors for SSIs differ between adults and children. It is therefore essential to conduct high quality RCT investigating interventions to identify optimal measures to reduce SSI rates in children.
TRIAL REGISTRATION
Prospero registration ( CRD42020166193 ).
Topics: Adult; Anti-Infective Agents, Local; Child; Chlorhexidine; Humans; Povidone-Iodine; Preoperative Care; Surgical Wound Infection
PubMed: 35902844
DOI: 10.1186/s12887-022-03502-z -
Surgical Infections 2017Surgical site infections (SSIs) are one of the most common hospital-acquired infections. To reduce SSIs, prophylactic intra-operative wound irrigation (pIOWI) has been... (Meta-Analysis)
Meta-Analysis Review
Systematic Review and Meta-Analysis of Randomized Controlled Trials Evaluating Prophylactic Intra-Operative Wound Irrigation for the Prevention of Surgical Site Infections.
BACKGROUND
Surgical site infections (SSIs) are one of the most common hospital-acquired infections. To reduce SSIs, prophylactic intra-operative wound irrigation (pIOWI) has been advocated, although the results to date are equivocal. To develop recommendations for the new World Health Organization (WHO) SSI prevention guidelines, a systematic literature review and a meta-analysis were conducted on the effectiveness of pIOWI using different agents as a means of reducing SSI.
METHODS
The PUBMED, Embase, CENTRAL, CINAHL, and WHO databases were searched. Randomized controlled trials (RCTs) comparing either pIOWI with no pIOWI or with pIOWI using different solutions and techniques were retrieved with SSI as the primary outcome. Meta-analyses were performed, and odds ratios (OR) and the mean difference with 95% confidence intervals (CI) were extracted and pooled with a random effects model.
RESULTS
Twenty-one studies were suitable for analysis, and a distinction was made between intra-peritoneal, mediastinal, and incisional wound irrigation. A low quality of evidence demonstrated a statistically significant benefit for incisional wound irrigation with an aqueous povidone-iodine (PVP-I) solution in clean and clean contaminated wounds (OR 0.31; 95% CI 0.13-0.73; p = 0.007); 50 fewer SSIs per 1,000 procedures (from 19 fewer to 64 fewer)). Antibiotic irrigation had no significant effect in reducing SSIs (OR 1.16; 95% CI 0.64-2.12; p = 0.63).
CONCLUSION
Low-quality evidence suggests considering the use of prophylactic incisional wound irrigation to prevent SSI with an aqueous povidone-iodine solution. Antibiotic irrigation does not show a benefit and therefore is discouraged.
Topics: Humans; Randomized Controlled Trials as Topic; Surgical Wound Infection; Therapeutic Irrigation
PubMed: 28448203
DOI: 10.1089/sur.2016.272