BackgroundDental caries is the most common disease of childhood. The NHS guidelines promote preventative care in dental practices, particularly for young children. However, the cost-effectiveness of this policy has not been established.ObjectiveTo measure the effects and costs of a composite fluoride intervention designed to prevent caries in young children attending dental services.DesignThe study was a two-arm, parallel-group, randomised controlled trial, with an allocation ratio of 1 : 1. Randomisation was by clinical trials unit, using randomised permuted blocks. Children/families were not blinded; however, outcome assessment was blinded to group assessment.SettingThe study took place in 22 NHS dental practices in Northern Ireland, UK.ParticipantsThe study participants were children aged 2–3 years, who were caries free at baseline.InterventionsThe intervention was composite in nature, comprising a varnish containing 22,600 parts per million (p.p.m.) fluoride, a toothbrush and a 50-ml tube of toothpaste containing 1450 p.p.m. fluoride; plus standardised, evidence-based prevention advice provided at 6-monthly intervals over 3 years. The control group received the prevention advice alone.Main outcome measuresThe primary outcome measure was conversion from caries-free to caries-active states. Secondary outcome measures were the number of decayed, missing or filled tooth surfaces in primary dentition (dmfs) in caries-active children, the number of episodes of pain, the number of extracted teeth and the costs of care. Adverse reactions (ARs) were recorded.ResultsA total of 1248 children (624 randomised to each group) were recruited and 1096 (549 in the intervention group and 547 in the control group) were included in the final analyses. A total of 87% of the intervention children and 85% of control children attended every 6-month visit (p = 0.77). In total, 187 (34%) children in the intervention group converted to caries active, compared with 213 (39%) in the control group [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.64 to 1.04;p = 0.11]. The mean number of tooth surfaces affected by caries was 7.2 in the intervention group, compared with 9.6 in the control group (p = 0.007). There was no significant difference in the number of episodes of pain between groups (p = 0.81). However, 164 out of the total of 400 (41%) children who converted to caries active reported toothache, compared with 62 out of 696 (9%) caries-free children (OR 7.1 95% CI 5.1 to 9.9;p < 0.001). There was no statistically significant difference in the number of teeth extracted in caries-active children (p = 0.95). Ten children in the intervention group had ARs of a minor nature. The average direct dental care cost was £155.74 for the intervention group and £48.21 for the control group over 3 years (p < 0.05). The mean cost per carious surface avoided over the 3 years was estimated at £251.00.LimitationsThe usual limitations of a trial such as generalisability and understanding the underlying reasons for the outcomes apply. There is no mean willingness-to-pay threshold available to enable assessment of value for money.ConclusionsA statistically significant effect could not be demonstrated for the primary outcome. Once caries develop, pain is likely. There was a statistically significant difference in dmfs in caries-active children in favour of the intervention. Although adequately powered, the effect size of the intervention was small and of questionable clinical and economic benefit.Future workFuture work should assess the caries prevention effects of interventions to reduce sugar consumption at the population and individual levels. Interventions designed to arrest the disease once it is established need to be developed and tested in practice.Trial registrationCurrent Controlled Trials ISRCTN36180119 and EudraCT 2009-010725-39.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 71. See the NIHR Journals Library website for further project information.

Abstract:Background: Two-arm parallel group randomized controlled trial to measure the cost-effectiveness of caries prevention in caries-free children aged 2-3 years attending general practice.Methods: The setting was 22 dental practices in Northern Ireland. Participants were centrally randomized into intervention: 22,600 ppm fluoride varnish; toothbrush; 50 ml tube of 1,450 ppm fluoride toothpaste; and standardised prevention advice, and control: advice-only, both provided at 6-monthly intervals during 3-year follow-up. The primary outcome measure was conversion from caries-free to caries-active states assessed by calibrated and blinded examiners; secondary outcome measures included dmfs, pain and extraction. Cumulative costs were related to each of the trial's outcomes in a series of incremental cost effectiveness ratios (ICERs). Sensitivity analyses examined the impact of using dentist's time as measured by observation rather than that reported by the dentist. The costs of applying topical fluoride were also estimated assuming the work was undertaken by dental nurses or hygienists rather than dentists. AbstractBackground: Two-arm parallel group randomized controlled trial to measure the cost-effectiveness of caries prevention in caries-free children aged 2-3 years attending general practice.Methods: The setting was 22 dental practices in Northern Ireland.Participants were centrally randomized into intervention: 22,600 ppm fluoride varnish; toothbrush; 50 ml tube of 1,450 ppm fluoride toothpaste;and standardised prevention advice, and control: advice-only, both provided at 6-monthly intervals during 3-year follow-up. The primary outcome measure was conversion from caries-free to caries-active states assessed by calibrated and blinded examiners; secondary outcome measures included dmfs, pain and extraction. Cumulative costs were related to each of the trial's outcomes in a series of incremental cost effectiveness ratios (ICERs). Sensitivity analyses examined the impact of using dentist's time as measured by observation rather than that reported by the dentist. The costs of applying topical fluoride were also estimated assuming the work was undertaken by dental nurses or hygienists rather than dentists.Results: A total of 1248 children (624 randomised to each group) were recruited and 1096 (549 in the intervention group and 547 in the control group) were included in the final analyses.

Abstract:Background: We conducted a parallel group randomised controlled trial of children initially aged 2-3 years who were caries free, to prevent the children becoming caries active over the subsequent 36 months.Methods: The setting was 22 dental practices in Northern Ireland and children were randomly assigned by a Clinical Trials Unit (using computer generated random numbers, with allocation concealed from the dental practice until child was recruited) to the intervention (22,600 ppm fluoride varnish, toothbrush, 50 ml tube of 1,450 ppm fluoride toothpaste and standardised, evidence-based prevention advice), or advice-only control, at 6-monthly intervals. The primary outcome measure was conversion from caries-free to caries-active states. Secondary outcome measures were dmfs in caries active children, number of episodes of pain, number of extracted teeth. Adverse reactions were recorded. Calibrated external examiners, blinded to the child's study group, assessed the status of the children at baseline and after 3 years. Results: 1248 children (624 randomised to each group) were recruited and 1,096 (549 intervention, 547 control) were included in the final analyses. 87% of intervention and 86% of control children attended every 6-month visit (P=0.77). 187 (34%) of intervention group converted to caries-active compared to 213 (39%) in control (OR 0.81, 95%CI 0.64 to 1.04; P=0.11). Mean dmfs of those with caries in intervention group was 7.2 compared to 9.6 in control group (P=0.007). There was no significant difference in the number of episodes of pain between groups, (P=0.81) or in the number of teeth extracted in caries-active children (P=0.95). Ten children in the intervention group had adverse reactions of a minor nature.Conclusion: This well conducted trial failed to demonstrate that the intervention kept children caries free, however there was evidence that once children get caries it slowed down its progression. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Methods: The setting was 22 dental practices in Northern Ireland and children were randomly assigned by a Clinical Trials Unit (using computer generated random numbers, with allocation concealed from the dental practice until child was recruited)to the intervention (22,600 ppm fluoride varnish, toothbrush, 50 ml tube of 1,450 ppm fluoride toothpaste and standardised, evidence-based prevention advice), or adviceonly control, at 6-monthly intervals. The primary outcome measure was conversion from caries-free to caries-active states. Secondary outcome measures were dmfs in caries active children, number of episodes of pain, number of extracted teeth.Adv...

BackgroundAtopic eczema (AE) is characterized by skin barrier and immune dysfunction. Null mutations in filaggrin (FLG), a key epidermal barrier protein, strongly predispose to AE; however, the precise role of FLG deficiency in AE pathogenesis remains incompletely understood.ObjectivesWe sought to identify global proteomic changes downstream of FLG deficiency in human epidermal living skin–equivalent (LSE) models and validate findings in skin of patients with AE.MethodsDifferentially expressed proteins from paired control (nontargeting control short hairpin RNA [shNT]) and FLG knockdown (FLG knockdown short hairpin RNA [shFLG]) LSEs were identified by means of proteomic analysis (liquid chromatography–mass spectrometry) and Ingenuity Pathway Analysis. Expression of key targets was validated in independent LSE samples (quantitative RT-PCR and Western blotting) and in normal and AE skin biopsy specimens (immunofluorescence).ResultsProteomic analysis identified 17 (P ≤ .05) differentially expressed proteins after FLG knockdown, including kallikrein-7 (KLK7; 2.2-fold), cyclophilin A (PPIA; 0.9-fold), and cofilin-1 (CFL1, 1.3-fold). Differential protein expression was confirmed in shNT/shFLG LSEs; however, only KLK7 was transcriptionally dysregulated. Molecular pathways overrepresented after FLG knockdown included inflammation, protease activity, cell structure, and stress. Furthermore, KLK7 (1.8-fold) and PPIA (0.65-fold) proteins were differentially expressed in lesional biopsy specimens from patients with AE relative to normal skin.ConclusionsFor the first time, we show that loss of FLG in the absence of inflammation is sufficient to alter the expression level of proteins relevant to the pathogenesis of AE. These include proteins regulating inflammatory, proteolytic, and cytoskeletal functions. We identify PPIA as a novel protein with levels that are decreased in clinically active AE skin and show that the characteristic upregulation of KLK7 expression in patients with AE occurs downstream of FLG loss. Importantly, we highlight disconnect between the epidermal proteome and transcriptome, emphasizing the utility of global proteomic studies.

School dental screening was capable of stimulating dental attendance. The strong effect among the lowest socio-economic group shows that school dental screening may be used to decrease dental health inequalities.

BackgroundMass spectrometry imaging (MSI) is a powerful tool for the study of intact tissue sections. Here, its application to the study of the distribution of lipids in sections of reconstructed living skin equivalents during their development and maturation is described.MethodsLiving skin equivalent (LSE) samples were obtained at 14 days development, re-suspended in maintenance medium and incubated for 24 h after delivery. The medium was then changed, the LSE re-incubated and samples taken at 4, 6 and 24 h time points. Mass spectra and mass spectral images were recorded from 12 μm sections of the LSE taken at each time point for comparison using matrix assisted laser desorption ionisation mass spectrometry.ResultsA large number of lipid species were identified in the LSE via accurate mass-measurement MS and MSMS experiments carried out directly on the tissue sections. MS images acquired at a spatial resolution of 50 μm × 50 μm showed the distribution of identified lipids within the developing LSE and changes in their distribution with time. In particular development of an epidermal layer was observable as a compaction of the distribution of phosphatidylcholine species.ConclusionsMSI can be used to study changes in lipid composition in LSE. Determination of the changes in lipid distribution during the maturation of the LSE will assist in the identification of treatment responses in future investigations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0089-z) contains supplementary material, which is available to authorized users.

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Established treatments for psoriasis are generally based on antiproliferative, anti-inflammatory, or differentiation-modifying activity, or a combination of these effects. New agents for the treatment of psoriasis could be identified by high-throughput screening (HTS) of large compound libraries using keratinocyte proliferation models. Although several new proliferation assays have been developed, the radioactive [(3)H]-thymidine incorporation assay is still considered to be the gold standard for the evaluation of keratinocyte proliferation in vitro. In this study, we compare a number of simple, and reliable, colorimetric (MTT, NRU, SRB, and CVS), and fluorimetric (CAM and AB) methods with the [(3)H]-thymidine incorporation assay for the measurement of keratinocyte proliferation in the exponential growth phase in 96-well formats. The concentrations that induced 50% growth inhibition (GI(50)) were determined by each assay for the established antipsoriatics, dithranol, and methotrexate. Strong correlations were observed between the percentage growth inhibitions determined by the radioactive and the colorimetric assays, with no significant differences (P > 0.05) between their GI(50) values. The colorimetric assays are thus suitable alternatives to the radioactive assay for quantifying keratinocyte growth inhibition. We have also validated the use of the HaCaT cell line as a representative of the hyperproliferative psoriatic epidermis, in the preclinical screening of experimental anti-psoriatic agents.