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The additional benefit of professional fluoride application for children as an adjunct to regular fluoride toothpaste: A systematic review and meta-analysis
No full textObjective: To assess whether professional fluoride application (PFA) used in addition to regular fluoride toothpaste (RFT, ≥ 1,000 ppm) is more effective than RFT alone in children.Materials and Methods: A systematic search was conducted using the PubMed, Embase, Google Scholar and CENTRAL databases. Randomized controlled trials (RCTs) comparing the effectiveness of RFT+PFA and RFT alone were included. Meta-analyses with random-effects models were performed. The certainty of evidence was assessed using the GRADE approach.Results: A total of 2,729 records were identified from electronic and manual searches, which were screened by two reviewers independently and in duplicate. Six RCTs (5,034 participants) were included, of which four had high risk of bias and two had unclear risk of bias. The PFA used in all these trials was fluoride varnish (FV). In meta-analyses, no significant difference was observed between participants receiving FV+RFT and RFT alone of d(m/e)fs increment [mean difference (MD) -0.17, 95% confidence interval (CI) -0.60 to 0.26, P = 0.43, I2 = 38%; 6 trials, 5,034 participants, moderate certainty evidence], incidence of caries [risk ratio (RR) 0.91, 95% CI 0.80 to 1.05, P = 0.21, I2 = 41%; 4 trials, 4,487 participants, moderate certainty evidence], or changes in prevalence of caries (RR 0.89, 95% CI 0.78 to 1.01, P = 0.07, I2 = 0%, 4 trials, 4,189 participants, low certainty evidence).Conclusions: Low to moderate certainty evidence suggests that FV does not have significant additional caries-preventive benefit for children (under 8 years old) when provided as an adjunct to daily tooth brushing with RFT (≥ 1,000 ppm). There is insufficient evidence regarding the additional benefit of other PFA interventions
Chemotherapy for Advanced Gallbladder Cancer (GBC): A Systematic Review and Meta-Analysis
No full textBackground: The benefit from chemotherapy, specifically for patients with gallbladder cancer (GBC), has been poorly explored since GBC is mostly studied jointly with other biliary tract cancers (BTC). Methods: Eligible studies reporting outcome of palliative systemic chemotherapy for advanced GBC were identified through MEDLINE, cross-referencing and conferences (PROSPERO-CRD42019155745). Meta-analysis of proportions and calculation of pooled weighted means were performed. Results: 58 eligible studies (n=1,986 patients); cisplatin/gemcitabine (33% of patients), gemcitabine/oxaliplatin (14%) or gemcitabine monotherapy (9%). Estimated pooled overall radiological response rate(ORR), and pooled weighted mean progression-free (PFS) and overall survivals (OS) were 23.2% (95%-CI 20.0-26.5) (I2: 52.5% (p<0.001)), 4.8 months (95%-CI 4.3-5.2) and 8.3 months (95%CI 7.6-8.9), respectively. Patients with non-GBC BTCs achieved a lower ORR than GBC [odds ratio 0.65 (95% CI, 0.50-0.84)]. Conclusions: GBC benefit from chemotherapy differs from other BTCs, with shorter PFS/OS despite higher ORR; new treatment options are urgently required for management of advanced GBC
TEMPERATURE RESPONSE TO COLD CHALLENGE AND MOBILE PHONE THERMOGRAPHY AS OUTCOME MEASURES FOR SYSTEMIC SCLEROSIS-RELATED RAYNAUD'S PHENOMENON
No full textObjectives Objective outcome measures of systemic sclerosis (SSc)-related Raynaud's phenomenon(RP) are badly needed. Our objectives were to (a) further validate thermographic response to a standard hand cold challenge as an outcome measure by assessing sensitivity to change and (b) explore mobile phone thermography as a feasible, ambulatory tool. Methods Twelve patients with a SSc-spectrum disorder admitted for intravenous iloprost infusions underwent a standard cold challenge before and after one infusion. Thermographic measurements included area under the rewarming curve (AUC) and maximum rewarming temperature (MAX). Before and during another infusion, each patient underwent monitoring of finger skin temperature by two methods: continuous thermocouple recording (the standard method) and mobile phone thermography. Results All cold challenge summary measures (including AUC and MAX) increased after iloprost (most not significantly). However, when the response curves were modelled after averaging across fingers (linear mixed models, three versions), significant change was detected. For example, with Model 1 (no interaction between period and time) temperature was on average 1.67 (95% CI 1.49 to 1.85, p<0.001)OC higher post-iloprost. Mobile phone and thermocouple temperature measurements showed a strong estimated latent correlation (0.88 [95% CI 0.81 to 0.92]). The estimated increases/hour were 0.25 (95% CI 0.05 to 0.45)OC for the thermocouple and 0.36 (0.13 to 0.60)OC for mobile phone thermography. Conclusions Our pilot study suggests that (a) thermographic response to a cold challenge is sensitive to change and (b) mobile phone thermography could bring feasibility to thermographic parameters as outcome measures in later phase, large-scale, community-based clinical trials of RP
Exposure to ambient air pollution during childhood and subsequent risk of self-harm: a national cohort study
No full textA growing body of evidence indicates that exposure to air pollution not only impacts on physical health but is also linked with a deterioration in mental health. We conducted the first study to investigate exposure to ambient particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) and nitrogen dioxide (NO2) during childhood and subsequent self-harm risk. The study cohort included persons born in Denmark between January 1, 1979 and December 31, 2006 (N = 1,424,670), with information on daily exposures to PM2.5 and NO2 at residence from birth to 10th birthday. Follow-up began from 10th birthday until first hospital-presenting self-harm episode, death, or December 31, 2016, whichever came first. Incidence rate ratios estimated by Poisson regression models revealed a dose relationship between increasing PM2.5 exposure and rising self-harm risk. Exposure to 17-19 μg/m3 of PM2.5 on average per day from birth to 10th birthday was associated with a 1.45 fold (95% CI 1.37-1.53) subsequently elevated self-harm risk compared with a mean daily exposure of <13 μg/m3, whilst those exposed to 19 μg/m3 or above on average per day had a 1.59 times (1.45-1.75) elevated risk. Higher mean daily exposure to NO2 during childhood was also linked with increased self-harm risk, but the dose-response relationship observed was less evident than for PM2.5. Covariate adjustment attenuated the associations, but risk remained independently elevated. Although causality cannot be assumed, these novel findings indicate a potential etiological involvement of ambient air pollution in the development of mental ill health.</p
Hepatic Scaling Factors for In Vitro-In Vivo Extrapolation (IVIVE) of Metabolic Drug Clearance in Patients with Colorectal Cancer with Liver Metastasis
No full textIn vitro-in vivo extrapolation (IVIVE) linked with physiologically based pharmacokinetic (PBPK) modelling is used to predict the fates of drugs in patients. Ideally, the IVIVE-PBPK models should incorporate “systems” information accounting for characteristics of the specific target population. There is a paucity of such scaling factors in cancer, particularly microsomal protein per gram of liver (MPPGL) and cytosolic protein per gram of liver (CPPGL). In this study, cancerous and histologically normal liver tissue from 16 patients with colorectal liver metastasis (CRLM) were fractionated to microsomes and cytosol. Protein content was measured in homogenates, microsomes and cytosol. The loss of microsomal protein during fractionation was accounted for using corrections based on NADPH cytochrome P450 reductase activity in different matrices. MPPGL was significantly lower in cancerous tissue (24.8 ± 9.8 mg/g) than histologically normal tissue (39.0 ± 13.8 mg/g). CPPGL in cancerous tissue was 42.1 ± 12.9 mg/g compared with 56.2 ± 16.9 mg/g in normal tissue. No correlations between demographics (sex, age and BMI) and MPPGL or CPPGL were apparent in the data. The generated scaling factors together with assumptions regarding the relative volumes of cancerous versus non-cancerous tissue were used to simulate plasma exposure of drugs with different extraction ratios. The PBPK simulations revealed a substantial difference in drug exposure (AUC), up to 3.3-fold, when using typical scaling factors (healthy population) instead of disease-related parameters in cancer population. These indicate the importance of using population-specific scalars in IVIVE-PBPK for different disease states
Impact of COVID-19 on diagnoses, monitoring and mortality in people with Type 2 diabetes in the UK
No full textPolymer-induced microcolony compaction in early biofilms: a computer simulation study
No full textMicroscopic organisms, such as bacteria, have the ability of colonizing surfaces and developing biofilms that can determine diseases and infections. Most bacteria secrete a significant amount of extracellular polymer substances that are relevant for biofilm stabilization and growth. In this work, we apply computer simulation and perform experiments to investigate the impact of polymer size and concentration on early biofilm formation and growth. We observe as bacterial cells formed loose, disorganized clusters whenever the effect of diffusion exceeded that of cell growth and division. Addition of model polymeric molecules induced particle self-assembly and aggregation to form compact clusters in a polymer size- and concentration-dependent fashion. We also find that large polymer size or concentration lead to the development of intriguing stripe-like and dendritic colonies. The results obtained by Brownian dynamic simulation closely resemble the morphologies that we experimentally observe in biofilms of a Pseudomonas Putida strain with added polymers. The analysis of the Brownian dynamic simulation results suggests the existence of a threshold polymer concentration that distinguishes between two growth regimes. Below this threshold, the main force driving polymer-induced compaction is hindrance of bacterial cell diffusion, while collective effects play a minor role. Above this threshold, especially for large polymers, polymer-induced compaction is a collective phenomenon driven by depletion forces. Well above this concentration threshold, severely limited diffusion drives the formation of filaments and dendritic colonies
Efficacy of intra-articular corticosteroid injections in knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials
No full textIntroduction: Knee osteoarthritis (OA) is a frequent degenerative disease representing an important health and economic burden. Symptomatic medical treatments available include intra-articular (IA) injections of corticosteroids (GC) but their efficacy and safety profile are debated. Methods: We performed a systematic literature review (SLR) and a meta-analysis (MA) of randomized controlled trials (RCTs) assessing the effect of IA GC injections for knee OA. The effect of the interventions on pain and function was extracted from the single studies and pooled standardized mean differences (SMD) are reported. Results: Of 520 studies screened, 23 were included in the SLR and 15 subsequently included in the MA. IA GC showed a trend towards a superior effect compared to control on both pain (SMD -0.61 (95% CI -1.25, 0.03)) and function (SMD -1.02 (95% CI -2.14, 0.10)) in short term follow-up (≤6 weeks), while long term follow-up (≥24 weeks) analysis showed a trend towards superiority of controls (IA HA, IA NSAID, physiotherapy) for pain (SMD 0.68 (95% CI -0.11, 1.47)) and function (SMD 0.88 (95% CI -0.36, 2.12). There were no differences between interventions in medium term (>6 weeks & <24 weeks). Conclusion: In this work, IA GC injections reduced pain and improved function early after administration (≤6 weeks) compared to placebo; while this results was no longer statistically significant with other comparators (IA hyaluronic acid or physiotherapy). Other interventions seem to be more efficient in the long term (≥24 weeks) but this effect was largely driven by single studies with large effect sizes
Assessing the Superhydrophobic Performance of Laser Micropatterned Aluminium Overhead Line Conductor Material
No full textOverhead electric supply lines are subject to water and ice accumulation, causing noise and weight increase, and leading to faults or failures. In this research, micro-textures were laser-ablated on aluminium substrates representative of overhead line conductors to achieve superhydrophobic properties. Samples were then subjected to a range of tests to measure the resilience and durability of such surfaces to conditions experienced byoverhead line conductors. Tests to examine thermal ageing, thermal cycling, UV exposure, long term ambient outdoor environment exposure, and corona exposure testing were conducted and the evolution of surface superhydrophobicity was quantified. A high degree of resilience was observed for most of the testing. The feasibility of manufacturing upscale is discussed in addition to optimising test methods
Ceramic buckling for determining the residual stress in thin films
No full textA new technique for determination of residual stress in thin films and coatings has been presented. The method consists of focused ion beam milling to create a lamella of thin film, followed by analysis of stress driven buckling profile of undercut lamella (beam) to extract residual stress. The residual stresses in crystalline TiN and Al2O3 films, produced by reactive magnetron sputtering and thermal oxidation, respectively, have been successfully determined by this new technique and validated by conventional X-ray diffraction and photoluminescence piezospectroscopy techniques, respectively. This new technique successfully measures and tracks the evolution of residual stress in as-deposited and different thermally cycled amorphous SiAlN films induced by thermal mismatch or relieved via mechanical twinning in interlayer, where diffraction methods are not applicable, thereby evaluating the thermal cycling performance of amorphous SiAlN coatings for protection of Ti at high temperature