Topical fluoride as a cause of dental fluorosis in children.

This is an update of a review first published in 2010. Use of topical fluoride has become more common over time. Excessive fluoride consumption from topical fluorides in young children could potentially lead to dental fluorosis in permanent teeth. To describe the relationship between the use of topical fluorides in young children and the risk of developing dental fluorosis in permanent teeth. We carried out electronic searches of the Cochrane Oral Health Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and two trials registers. We searched the reference lists of relevant articles. The latest search date was 28 July 2022. We included randomized controlled trials (RCTs), quasi-RCTs, cohort studies, case-control studies, and cross-sectional surveys comparing fluoride toothpaste, mouth rinses, gels, foams, paint-on solutions, and varnishes to a different fluoride therapy, placebo, or no intervention. Upon the introduction of topical fluorides, the target population was children under six years of age. We used standard methodological procedures expected by Cochrane and used GRADE to assess the certainty of the evidence. The primary outcome measure was the percentage prevalence of fluorosis in the permanent teeth. Two authors extracted data from all included studies. In cases where both adjusted and unadjusted risk ratios or odds ratios were reported, we used the adjusted value in the meta-analysis. We included 43 studies: three RCTs, four cohort studies, 10 case-control studies, and 26 cross-sectional surveys. We judged all three RCTs, one cohort study, one case-control study, and six cross-sectional studies to have some concerns for risk of bias. We judged all other observational studies to be at high risk of bias. We grouped the studies into five comparisons. Comparison 1. Age at which children started toothbrushing with fluoride toothpaste Two cohort studies (260 children) provided very uncertain evidence regarding the association between children starting to use fluoride toothpaste for brushing at or before 12 months versus after 12 months and the development of fluorosis (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.81 to 1.18; very low-certainty evidence). Similarly, evidence from one cohort study (3939 children) and two cross-sectional studies (1484 children) provided very uncertain evidence regarding the association between children starting to use fluoride toothpaste for brushing before or after the age of 24 months (RR 0.83, 95% CI 0.61 to 1.13; very low-certainty evidence) or before or after four years (odds ratio (OR) 1.60, 95% CI 0.77 to 3.35; very low-certainty evidence), respectively. Comparison 2. Frequency of toothbrushing with fluoride toothpaste Two case-control studies (258 children) provided very uncertain evidence regarding the association between children brushing less than twice per day versus twice or more per day and the development of fluorosis (OR 1.63, 95% CI 0.81 to 3.28; very low-certainty evidence). Two cross-sectional surveys (1693 children) demonstrated that brushing less than once per day versus once or more per day may be associated with a decrease in the development of fluorosis in children (OR 0.62, 95% CI 0.53 to 0.74; low-certainty evidence). Comparison 3. Amount of fluoride toothpaste used for toothbrushing Two case-control studies (258 children) provided very uncertain evidence regarding the association between children using less than half a brush of toothpaste, versus half or more of the brush, and the development of fluorosis (OR 0.77, 95% CI 0.41 to 1.46; very low-certainty evidence). The evidence from cross-sectional surveys was also very uncertain (OR 0.92, 95% CI 0.66 to 1.28; 3 studies, 2037 children; very low-certainty evidence). Comparison 4. Fluoride concentration in toothpaste There was evidence from two RCTs (1968 children) that lower fluoride concentration in the toothpaste used by children under six years of age likely reduces the risk of developing fluorosis: 550 parts per million (ppm) fluoride versus 1000 ppm (RR 0.75, 95% CI 0.57 to 0.99; moderate-certainty evidence); 440 ppm fluoride versus 1450 ppm (RR 0.72, 95% CI 0.58 to 0.89; moderate-certainty evidence). The age at which the toothbrushing commenced was 24 months and 12 months, respectively. Two case-control studies (258 children) provided very uncertain evidence regarding the association between fluoride concentrations under 1000 ppm, versus concentrations of 1000 ppm or above, and the development of fluorosis (OR 0.89, 95% CI 0.52 to 1.52; very low-certainty evidence). Comparison 5. Age at which topical fluoride varnish was applied There was evidence from one RCT (123 children) that there may be little to no difference between a fluoride varnish application before four years, versus no application, and the development of fluorosis (RR 0.77, 95% CI 0.45 to 1.31; low-certainty evidence). There was low-certainty evidence from two cross-sectional surveys (982 children) that the application of topical fluoride varnish before four years of age may be associated with the development of fluorosis in children (OR 2.18, 95% CI 1.46 to 3.25). Most evidence identified mild fluorosis as a potential adverse outcome of using topical fluoride at an early age. There is low- to very low-certainty and inconclusive evidence on the risk of having fluorosis in permanent teeth for: when a child starts receiving topical fluoride varnish application; toothbrushing with fluoride toothpaste; the amount of toothpaste used by the child; and the frequency of toothbrushing. Moderate-certainty evidence from RCTs showed that children who brushed with 1000 ppm or more fluoride toothpaste from one to two years of age until five to six years of age probably had an increased chance of developing dental fluorosis in permanent teeth. It is unethical to propose new RCTs to assess the development of dental fluorosis. However, future RCTs focusing on dental caries prevention could record children's exposure to topical fluoride sources in early life and evaluate the dental fluorosis in their permanent teeth as a long-term outcome. In the absence of these studies and methods, further research in this area will come from observational studies. Attention needs to be given to the choice of study design, bearing in mind that prospective controlled studies will be less susceptible to bias than retrospective and uncontrolled studies.

Wong MCM ，Zhang R ，Luo BW ，Glenny AM ，Worthington HV ，Lo ECM ... -  《Cochrane Database of Systematic Reviews》

Water fluoridation for the prevention of dental caries.

Dental caries is a major public health problem in most industrialised countries, affecting 60% to 90% of school children. Community water fluoridation (CWF) is currently practised in about 25 countries; health authorities consider it to be a key strategy for preventing dental caries. CWF is of interest to health professionals, policymakers and the public. This is an update of a Cochrane review first published in 2015, focusing on contemporary evidence about the effects of CWF on dental caries. To evaluate the effects of initiation or cessation of CWF programmes for the prevention of dental caries. To evaluate the association of water fluoridation (artificial or natural) with dental fluorosis. We searched CENTRAL, MEDLINE, Embase and four other databases up to 16 August 2023. We also searched two clinical trials registers and conducted backward citation searches. We included populations of all ages. For our first objective (effects of initiation or cessation of CWF programmes on dental caries), we included prospective controlled studies comparing populations receiving fluoridated water with those receiving non-fluoridated or naturally low-fluoridated water. To evaluate change in caries status, studies measured caries both within three years of a change in fluoridation status and at the end of study follow-up. For our second objective (association of water fluoridation with dental fluorosis), we included any study design, with concurrent control, comparing populations exposed to different water fluoride concentrations. In this update, we did not search for or include new evidence for this objective. We used standard methodological procedures expected by Cochrane. For our first objective, we included the following outcomes as change from baseline: decayed, missing or filled teeth ('dmft' for primary and 'DMFT' for permanent teeth); decayed, missing or filled tooth surfaces ('dmfs' for primary and 'DMFS' for permanent teeth); proportion of caries-free participants for both primary and permanent dentition; adverse events. We stratified the results of the meta-analyses according to whether data were collected before or after the widespread use of fluoride toothpaste in 1975. For our second objective, we included dental fluorosis (of aesthetic concern, or any level of fluorosis), and any other adverse events reported by the included studies. We included 157 studies. All used non-randomised designs. Given the inherent risks of bias in these designs, particularly related to management of confounding factors and blinding of outcome assessors, we downgraded the certainty of all evidence for these risks. We downgraded some evidence for imprecision, inconsistency or both. Evidence from older studies may not be applicable to contemporary societies, and we downgraded older evidence for indirectness. Water fluoridation initiation (21 studies) Based on contemporary evidence (after 1975), the initiation of CWF may lead to a slightly greater change in dmft over time (mean difference (MD) 0.24, 95% confidence interval (CI) -0.03 to 0.52; P = 0.09; 2 studies, 2908 children; low-certainty evidence). This equates to a difference in dmft of approximately one-quarter of a tooth in favour of CWF; this effect estimate includes the possibility of benefit and no benefit. Contemporary evidence (after 1975) was also available for change in DMFT (4 studies, 2856 children) and change in DMFS (1 study, 343 children); we were very uncertain of these findings. CWF may lead to a slightly greater change over time in the proportion of caries-free children with primary dentition (MD -0.04, 95% CI -0.09 to 0.01; P = 0.12; 2 studies, 2908 children), and permanent dentition (MD -0.03, 95% CI -0.07 to 0.01; P = 0.14; 2 studies, 2348 children). These low-certainty findings (a 4 percentage point difference and 3 percentage point difference for primary and permanent dentition, respectively) favoured CWF. These effect estimates include the possibility of benefit and no benefit. No contemporary data were available for adverse effects. Because of very low-certainty evidence, we were unsure of the size of effects of CWF when using older evidence (from 1975 or earlier) on all outcomes: change in dmft (5 studies, 5709 children), change in DMFT (3 studies, 5623 children), change in proportion of caries-free children with primary dentition (5 studies, 6278 children) or permanent dentition (4 studies, 6219 children), or adverse effects (2 studies, 7800 children). Only one study, conducted after 1975, reported disparities according to socioeconomic status, with no evidence that deprivation influenced the relationship between water exposure and caries status. Water fluoridation cessation (1 study) Because of very low-certainty evidence, we could not determine if the cessation of CWF affected DMFS (1 study conducted after 1975; 2994 children). Data were not available for other review outcomes for this comparison. Association of water fluoridation with dental fluorosis (135 studies) The previous version of this review found low-certainty evidence that fluoridated water may be associated with dental fluorosis. With a fluoride level of 0.7 parts per million (ppm), approximately 12% of participants had fluorosis of aesthetic concern (95% CI 8% to 17%; 40 studies, 59,630 participants), and approximately 40% had fluorosis of any level (95% CI 35% to 44%; 90 studies, 180,530 participants). Because of very low-certainty evidence, we were unsure of other adverse effects (including skeletal fluorosis, bone fractures and skeletal maturity; 5 studies, incomplete participant numbers). Contemporary studies indicate that initiation of CWF may lead to a slightly greater reduction in dmft and may lead to a slightly greater increase in the proportion of caries-free children, but with smaller effect sizes than pre-1975 studies. There is insufficient evidence to determine the effect of cessation of CWF on caries and whether water fluoridation results in a change in disparities in caries according to socioeconomic status. We found no eligible studies that report caries outcomes in adults. The implementation or cessation of CWF requires careful consideration of this current evidence, in the broader context of a population's oral health, diet and consumption of tap water, movement or migration, and the availability and uptake of other caries-prevention strategies. Acceptability, cost-effectiveness and feasibility of the implementation and monitoring of a CWF programme should also be taken into account.

Iheozor-Ejiofor Z ，Walsh T ，Lewis SR ，Riley P ，Boyers D ，Clarkson JE ，Worthington HV ，Glenny AM ，O'Malley L ... -  《Cochrane Database of Systematic Reviews》

Topical silver diamine fluoride (SDF) for preventing and managing dental caries in children and adults.

Dental caries is the world's most prevalent disease. Untreated caries can cause pain and negatively impact psychosocial health, functioning, and nutrition. It is important to identify cost-effective, easy-to-use agents, which can prevent or arrest caries. This review evaluates silver diamine fluoride (SDF). To assess the effects of silver diamine fluoride for preventing and managing caries in primary and permanent teeth (coronal and root caries) compared to any other intervention including placebo or no treatment. We searched CENTRAL, MEDLINE, Embase, Cochrane Oral Health's Trial Register and two clinical trials registers in June 2023. We included randomised controlled trials (RCTs), with parallel-group or split-mouth design, in children and adults (with or without carious lesions) that compared SDF with placebo or no treatment; different frequencies, concentrations or duration of SDF; or any other intervention. We used standard methodological procedures expected by Cochrane, and GRADE to assess the certainty of the evidence. We collected data for primary caries prevention (change in caries increment), arrest of carious lesions, secondary prevention of caries (lesions do not progress from initial classification), adverse effects, dental pain or sensitivity, and aesthetics at the end of study follow-up. We included 29 RCTs (13,036 participants; 12,020 children, 1016 older adults). We summarise outcome data for the five most clinically relevant comparisons. All studies included high risks of bias, and some findings were imprecise (e.g. because of small sample sizes). SDF versus placebo or no treatment (14 studies; 2695 children, 905 older adults) Compared to placebo or no treatment, SDF may help prevent new caries in the primary dentition (1 study, 373 participants), or on the coronal surfaces of permanent dentition (1 study, 373 participants) but the evidence is very uncertain. SDF likely prevents new root caries (mean difference (MD) -0.79 surfaces, 95% confidence interval (CI) -1.40 to -0.17; 3 studies, 439 participants; moderate-certainty evidence). SDF may help arrest caries in the primary dentition (MD 0.86 surfaces, 95% CI 0.39 to 1.33; 2 studies, 841 participants; low-certainty evidence) and the permanent dentition (coronal: 1 study, 373 participants; root: 1 study, 158 participants) but the evidence is very uncertain. The evidence is very uncertain for secondary prevention of caries (primary dentition: 1 study, 128 participants; permanent dentition (coronal): 1 study, 663 participants), for adverse effects (5 studies, 1299 participants), and aesthetics (1 study, 43 participants). Different approaches to SDF application (5 studies, 1808 children) Studies compared different frequencies or intervals of application, different concentrations of SDF, and different durations of treatment. Some studies included multiple comparisons of different approaches. Because of the different approaches, we could not combine findings from these studies. Due to very low-certainty evidence, we were unsure whether any approach to SDF application was better than another for caries arrest (4 studies, including 8 comparisons of different approaches, 1360 participants); secondary prevention of caries (1 study, 203 participants), or led to differences in adverse effects (3 studies, 1121 children) or aesthetics (1 study, 119 children). SDF versus fluoride varnish (8 studies, 2868 children, 223 older adults) Compared to flouride varnish, SDF may result in little or no difference to the prevention of new caries in the primary dentition (MD 0.00, 95% CI -0.26 to 0.26; 1 study, 434 participants; low-certainty evidence). The evidence is very uncertain for this outcome measure in the permanent dentition (coronal: 1 study, 237 participants; root: 1 study, 100 participants; very low-certainty evidence). Due to very low-certainty evidence, we were unsure whether or not there were any differences between flouride varnish (applied weekly for three applications) and SDF for caries arrest and secondary prevention of caries in the primary dentition (1 study, 309 participants). Similarly, we were unsure of adverse effects (3 studies, 980 children), dental pain or sensitivity (1 study, 62 children), or aesthetics (1 study, 263 children). SDF versus sealants and resin infiltration (2 studies, 343 children) Very low-certainty evidence in this comparison meant we were unsure if either treatment was better than the other for primary prevention of caries in permanent dentition (coronal: 1 study, 242 participants), or adverse effects (2 studies, 336 participants). SDF versus atraumatic restorative treatment (ART) with glass ionomer cement (GIC) or GI material (4 studies, 610 children) Very low-certainty evidence in this comparison meant we were unsure if either treatment was better than the other at arresting caries in the primary dentition (1 study, 143 participants). We were also unsure whether there were any differences between treatments in adverse effects (3 studies, 482 participants), dental pain or sensitivity (1 study, 234 participants), or aesthetics (2 studies, 248 participants). In the primary dentition, evidence remains uncertain whether SDF prevents new caries or progression of existing caries compared to placebo or no treatment, but it may offer benefit over placebo or no treatment in caries arrest. Compared to placebo or no treatment, SDF probably also helps prevent new root caries. However, the evidence is uncertain for other caries outcome measures in this dentition and in all caries outcomes for coronal surfaces of permanent dentition. Compared to flouride varnish, SDF may offer little or no benefit in preventing new caries in the primary dentition, but the evidence is very uncertain for other caries outcome measures in the primary dentition and for preventing new caries in the permanent dentition. We were unable to establish whether one SDF treatment approach was better than another, or how SDF compared to other treatments, because of very low-certainty evidence. The impact of SDF staining of teeth was poorly reported and the evidence for adverse effects is very uncertain. Additional well-conducted studies are needed. These should measure the impact of staining and be analysed to take account of clustering issues within participants.

Worthington HV ，Lewis SR ，Glenny AM ，Huang SS ，Innes NP ，O'Malley L ，Riley P ，Walsh T ，Wong MCM ，Clarkson JE ，Veitz-Keenan A ... -  《Cochrane Database of Systematic Reviews》

Antioxidants for female subfertility.

M.G. Showell, R. Mackenzie‐Proctor, V. Jordan, and R.J. Hart, “Antioxidants for Female Subfertility,” Cochrane Database of Systematic Reviews, no. 8 (2020): CD007807, https://doi.org/10.1002/14651858.CD007807.pub4 This Editorial Note is for the above article, published online on August 27, 2020, in Cochrane Library (cochranelibrary.com), and has been issued by the Publisher, John Wiley & Sons Ltd, in agreement with Cochrane. The Editorial note has been agreed due to concerns discovered by the Cochrane managing editor regarding the retraction of six studies in the Review (Badawy et al. 2006, 10.1016/j.fertnstert.2006.02.097; El Refaeey et al. 2014, 10.1016/j.rbmo.2014.03.011; El Sharkwy & Abd El Aziz 2019a, https://doi.org/10.1002/ijgo.12902; Gerli et al. 2007, https://doi.org/10.26355/eurrev_202309_33752, full text: https://europepmc.org/article/MED/18074942; Ismail et al. 2014, http://dx.doi.org/10.1016/j.ejogrb.2014.06.008; Hashemi et al. 2017, https://doi.org/10.1080/14767058.2017.1372413). In addition, expressions of concern have been published for two studies (Jamilian et al. 2018, https://doi.org/10.1007/s12011-017-1236-3; Zadeh Modarres 2018, https://doi.org/10.1007/s12011-017-1148-2). The retracted studies will be moved to the Excluded Studies table, and their impact on the review findings will be investigated and acted on accordingly in a future update. Initial checks indicate that removal of the six retracted studies did not make an appreciable difference to the results. Likewise, the studies for which Expressions of Concern were issued will be moved to the Awaiting classification table; they did not report any review outcomes, so removal will have no impact on the review findings. A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility. To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women. We searched the following databases (from their inception to September 2019), with no language or date restriction: Cochrane Gynaecology and Fertility Group (CGFG) specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of relevant studies and searched the trial registers. We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility. We used standard methodological procedures expected by Cochrane. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events. We included 63 trials involving 7760 women. Investigators compared oral antioxidants, including: combinations of antioxidants, N-acetylcysteine, melatonin, L-arginine, myo-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant. Only 27 of the 63 included trials reported funding sources. Due to the very low-quality of the evidence we are uncertain whether antioxidants improve live birth rate compared with placebo or no treatment/standard treatment (odds ratio (OR) 1.81, 95% confidence interval (CI) 1.36 to 2.43; P < 0.001, I2 = 29%; 13 RCTs, 1227 women). This suggests that among subfertile women with an expected live birth rate of 19%, the rate among women using antioxidants would be between 24% and 36%. Low-quality evidence suggests that antioxidants may improve clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.65, 95% CI 1.43 to 1.89; P < 0.001, I2 = 63%; 35 RCTs, 5165 women). This suggests that among subfertile women with an expected clinical pregnancy rate of 19%, the rate among women using antioxidants would be between 25% and 30%. Heterogeneity was moderately high. Overall 28 trials reported on various adverse events in the meta-analysis. The evidence suggests that the use of antioxidants makes no difference between the groups in rates of miscarriage (OR 1.13, 95% CI 0.82 to 1.55; P = 0.46, I2 = 0%; 24 RCTs, 3229 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI 0.63 to 1.56; P = 0.99, I2 = 0%; 9 RCTs, 1886 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10; P = 0.47, I2 = 0%; 3 RCTs, 343 women; low-quality evidence). Low-quality evidence showed that there was also no difference between the groups in rates of ectopic pregnancy (OR 1.40, 95% CI 0.27 to 7.20; P = 0.69, I2 = 0%; 4 RCTs, 404 women). In the antioxidant versus antioxidant comparison, low-quality evidence shows no difference in a lower dose of melatonin being associated with an increased live-birth rate compared with higher-dose melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). This suggests that among subfertile women with an expected live-birth rate of 24%, the rate among women using a lower dose of melatonin compared to a higher dose would be between 12% and 40%. Similarly with clinical pregnancy, there was no evidence of a difference between the groups in rates between a lower and a higher dose of melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). Three trials reported on miscarriage in the antioxidant versus antioxidant comparison (two used doses of melatonin and one compared N-acetylcysteine versus L-carnitine). There were no miscarriages in either melatonin trial. Multiple pregnancy and gastrointestinal disturbances were not reported, and ectopic pregnancy was reported by only one trial, with no events. The study comparing N-acetylcysteine with L-carnitine did not report live birth rate. Very low-quality evidence shows no evidence of a difference in clinical pregnancy (OR 0.81, 95% CI 0.33 to 2.00; 1 RCT, 164 women; low-quality evidence). Low quality evidence shows no difference in miscarriage (OR 1.54, 95% CI 0.42 to 5.67; 1 RCT, 164 women; low-quality evidence). The study did not report multiple pregnancy, gastrointestinal disturbances or ectopic pregnancy. The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency. In this review, there was low- to very low-quality evidence to show that taking an antioxidant may benefit subfertile women. Overall, there is no evidence of increased risk of miscarriage, multiple births, gastrointestinal effects or ectopic pregnancies, but evidence was of very low quality. At this time, there is limited evidence in support of supplemental oral antioxidants for subfertile women.

Showell MG ，Mackenzie-Proctor R ，Jordan V ，Hart RJ ... -  《Cochrane Database of Systematic Reviews》

Interventions to prevent surgical site infection in adults undergoing cardiac surgery.

Surgical site infection (SSI) is a common type of hospital-acquired infection and affects up to a third of patients following surgical procedures. It is associated with significant mortality and morbidity. In the United Kingdom alone, it is estimated to add another £30 million to the cost of adult cardiac surgery. Although generic guidance for SSI prevention exists, this is not specific to adult cardiac surgery. Furthermore, many of the risk factors for SSI are prevalent within the cardiac surgery population. Despite this, there is currently no standard of care for SSI prevention in adults undergoing cardiac surgery throughout the preoperative, intraoperative and postoperative periods of care, with variations in practice existing throughout from risk stratification, decontamination strategies and surveillance. Primary objective: to assess the clinical effectiveness of pre-, intra-, and postoperative interventions in the prevention of cardiac SSI. (i) to evaluate the effects of SSI prevention interventions on morbidity, mortality, and resource use; (ii) to evaluate the effects of SSI prevention care bundles on morbidity, mortality, and resource use. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (Ovid, from inception) and Embase (Ovid, from inception) on 31 May 2021. gov and the WHO International Clinical Trials Registry Platform (ICTRP) were also searched for ongoing or unpublished trials on 21 May 2021. No language restrictions were imposed. We included RCTs evaluating interventions to reduce SSI in adults (≥ 18 years of age) who have undergone any cardiac surgery. We followed the methods as per our published Cochrane protocol. Our primary outcome was surgical site infection. Our secondary outcomes were all-cause mortality, reoperation for SSI, hospital length of stay, hospital readmissions for SSI, healthcare costs and cost-effectiveness, quality of life (QoL), and adverse effects. We used the GRADE approach to assess the certainty of evidence. A total of 118 studies involving 51,854 participants were included. Twenty-two interventions to reduce SSI in adults undergoing cardiac surgery were identified. The risk of bias was judged to be high in the majority of studies. There was heterogeneity in the study populations and interventions; consequently, meta-analysis was not appropriate for many of the comparisons and these are presented as narrative summaries. We focused our reporting of findings on four comparisons deemed to be of great clinical relevance by all review authors. Decolonisation versus no decolonisation Pooled data from three studies (n = 1564) using preoperative topical oral/nasal decontamination in all patients demonstrated an uncertain direction of treatment effect in relation to total SSI (RR 0.98, 95% CI 0.70 to 1.36; I2 = 0%; very low-certainty evidence). A single study reported that decolonisation likely results in little to no difference in superficial SSI (RR 1.35, 95% CI 0.84 to 2.15; moderate-certainty evidence) and a reduction in deep SSI (RR 0.36, 95% CI 0.17 to 0.77; high-certainty evidence). The evidence on all-cause mortality from three studies (n = 1564) is very uncertain (RR 0.66, 95% CI 0.24 to 1.84; I2 = 49%; very low-certainty evidence). A single study (n = 954) demonstrated that decolonisation may result in little to no difference in hospital readmission for SSI (RR 0.80, 95% CI 0.44 to 1.45; low-certainty evidence). A single study (n = 954) reported one case of temporary discolouration of teeth in the decolonisation arm (low-certainty-evidence. Reoperation for SSI was not reported. Tight glucose control versus standard glucose control Pooled data from seven studies (n = 880) showed that tight glucose control may reduce total SSI, but the evidence is very uncertain (RR 0.41, 95% CI 0.19 to 0.85; I2 = 29%; numbers need to treat to benefit (NNTB) = 13; very-low certainty evidence). Pooled data from seven studies (n = 3334) showed tight glucose control may reduce all-cause mortality, but the evidence is very uncertain (RR 0.61, 95% CI 0.41 to 0.91; I2 = 0%; very low-certainty evidence). Based on four studies (n = 2793), there may be little to no difference in episodes of hypoglycaemia between tight control vs. standard control, but the evidence is very uncertain (RR 2.12, 95% CI 0.51 to 8.76; I2 = 72%; very low-certainty evidence). No studies reported superficial/deep SSI, reoperation for SSI, or hospital readmission for SSI. Negative pressure wound therapy (NPWT) versus standard dressings NPWT was assessed in two studies (n = 144) and it may reduce total SSI, but the evidence is very uncertain (RR 0.17, 95% CI 0.03 to 0.97; I2 = 0%; NNTB = 10; very low-certainty evidence). A single study (n = 80) reported reoperation for SSI. The relative effect could not be estimated. The certainty of evidence was judged to be very low. No studies reported superficial/deep SSI, all-cause mortality, hospital readmission for SSI, or adverse effects. Topical antimicrobials versus no topical antimicrobials Five studies (n = 5382) evaluated topical gentamicin sponge, which may reduce total SSI (RR 0.62, 95% CI 0.46 to 0.84; I2 = 48%; NNTB = 32), superficial SSI (RR 0.60, 95% CI 0.37 to 0.98; I2 = 69%), and deep SSI (RR 0.67, 95% CI 0.47 to 0.96; I2 = 5%; low-certainty evidence. Four studies (n = 4662) demonstrated that topical gentamicin sponge may result in little to no difference in all-cause mortality, but the evidence is very uncertain (RR 0.96, 95% CI 0.65 to 1.42; I2 = 0%; very low-certainty evidence). Reoperation for SSI, hospital readmission for SSI, and adverse effects were not reported in any included studies. This review provides the broadest and most recent review of the current evidence base for interventions to reduce SSI in adults undergoing cardiac surgery. Twenty-one interventions were identified across the perioperative period. Evidence is of low to very low certainty primarily due to significant heterogeneity in how interventions were implemented and the definitions of SSI used. Knowledge gaps have been identified across a number of practices that should represent key areas for future research. Efforts to standardise SSI outcome reporting are warranted.

Cardiothoracic Interdisciplinary Research Network ，Rogers LJ ，Vaja R ，Bleetman D ，Ali JM ，Rochon M ，Sanders J ，Tanner J ，Lamagni TL ，Talukder S ，Quijano-Campos JC ，Lai F ，Loubani M ，Murphy GJ ... -  《Cochrane Database of Systematic Reviews》