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 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》

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》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

Conservative, physical and surgical interventions for managing faecal incontinence and constipation in adults with central neurological diseases.

People with central neurological disease or injury have a much higher risk of both faecal incontinence (FI) and constipation than the general population. There is often a fine line between the two symptoms, with management intended to ameliorate one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical, with a limited research base. The review is relevant to individuals with any disease directly and chronically affecting the central nervous system (post-traumatic, degenerative, ischaemic or neoplastic), such as multiple sclerosis, spinal cord injury, cerebrovascular disease, Parkinson's disease and Alzheimer's disease. This is an update of a Cochrane Review first published in 2001 and subsequently updated in 2003, 2006 and 2014. To assess the effects of conservative, physical and surgical interventions for managing FI and constipation in people with a neurological disease or injury affecting the central nervous system. We searched the Cochrane Incontinence Specialised Register (searched 27 March 2023), which includes searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP as well as handsearching of journals and conference proceedings; and all reference lists of relevant articles. We included randomised, quasi-randomised (where allocation is not strictly random), cross-over and cluster-randomised trials evaluating any type of conservative, physical or surgical intervention against placebo, usual care or no intervention for the management of FI and constipation in people with central neurological disease or injury. At least two review authors independently assessed the risk of bias in eligible trials using Cochrane's 'Risk of bias' tool and independently extracted data from the included trials using a range of prespecified outcome measures. We produced summary of findings tables for our main outcome measures and assessed the certainty of the evidence using GRADE. We included 25 studies with 1598 participants. The studies were generally at high risk of bias due to lack of blinding of participants and personnel to the intervention. Half of the included studies were also at high risk of bias in terms of selective reporting. Outcomes were often reported heterogeneously across studies, making it difficult to pool data. We did not find enough evidence to be able to analyse the effects of interventions on individual central neurological diseases. Additionally, very few studies reported on the primary outcomes of self-reported improvement in FI or constipation, or Neurogenic Bowel Dysfunction Score. Conservative interventions compared with usual care, no active treatment or placebo Thirteen studies assessed this comparison. The interventions included assessment-based nursing, holistic nursing, probiotics, psyllium, faecal microbiota transplantation, and a stepwise protocol of increasingly invasive evacuation methods. Conservative interventions may result in a large improvement in faecal incontinence (standardised mean difference (SMD) -1.85, 95% confidence interval (CI) -3.47 to -0.23; 3 studies; n = 410; low-certainty evidence). We interpreted SMD ≥ 0.80 as a large effect. It was not possible to pool all data from studies that assessed improvement in constipation, but the evidence suggested that conservative interventions may improve constipation symptoms (data not pooled; 8 studies; n = 612; low-certainty evidence). Conservative interventions may lead to a reduction in mean time taken on bowel care (data not pooled; 5 studies; n = 526; low-certainty evidence). The evidence is uncertain about the effects of conservative interventions on condition-specific quality of life and adverse events. Neurogenic Bowel Dysfunction Score was not reported. Physical therapy compared with usual care, no active treatment or placebo Twelve studies assessed this comparison. The interventions included massage therapy, standing, osteopathic manipulative treatment, electrical stimulation, transanal irrigation, and conventional physical therapy with visceral mobilisation. Physical therapies may make little to no difference to self-reported faecal continence assessed using the St Mark's Faecal Incontinence Score, where the minimally important difference is five, or the Cleveland Constipation Score (MD -2.60, 95% CI -4.91 to -0.29; 3 studies; n = 155; low-certainty evidence). Physical therapies may result in a moderate improvement in constipation symptoms (SMD -0.62, 95% CI -1.10 to -0.14; 9 studies; n = 431; low-certainty evidence). We interpreted SMD ≥ 0.5 as a moderate effect. However, physical therapies may make little to no difference in Neurogenic Bowel Dysfunction Score as the minimally important difference for this tool is 3 (MD -1.94, 95% CI -3.36 to -0.51; 7 studies; n = 358; low-certainty evidence). We are very uncertain about the effects of physical therapies on the time spent on bowel care, condition-specific quality of life and adverse effects (all very low-certainty evidence). Surgical interventions compared with usual care, no active treatment or placebo No studies were found for surgical interventions that met the inclusion criteria for this review. There remains little research on this common and, for patients, very significant issue of bowel management. The available evidence is almost uniformly of low methodological quality. The clinical significance of some of the research findings presented here is difficult to interpret, not least because each intervention has only been addressed in individual trials, against control rather than compared against each other, and the interventions are very different from each other. Understanding whether there is a clinically-meaningful difference from the results of available trials is largely hampered by the lack of uniform outcome measures. This is due to an absence of core outcome sets, and development of these needs to be a research priority to allow studies to be compared directly. Some studies used validated constipation, incontinence or condition-specific measures; however, others used unvalidated analogue scales to report effectiveness. Some studies did not use any patient-reported outcomes and focused on physiological outcome measures, which is of relatively limited significance in terms of clinical implementation. There was evidence in favour of some conservative interventions, but these findings need to be confirmed by larger, well-designed controlled trials, which should include evaluation of the acceptability of the intervention to patients and the effect on their quality of life.

Todd CL ，Johnson EE ，Stewart F ，Wallace SA ，Bryant A ，Woodward S ，Norton C ... -  《Cochrane Database of Systematic Reviews》