Prevention of orthodontic enamel demineralization: a systematic review with meta‐analyses

Aim of this systematic review was to assess the efficacy of preventive interventions against the development of white spot lesions (WSLs) during fixed appliance orthodontic treatment. Nine databases were searched without limitations in September 2018 for randomized trials. Study selection, data extraction and risk of bias assessment were done independently in duplicate. Random-effects meta-analyses of mean differences (MDs) or relative risks (RRs) with their 95% confidence intervals (CIs) were conducted, followed by sensitivity analyses, and the GRADE analysis of the evidence quality. A total of 24 papers (23 trials) were included, assessing preventive measures applied either around orthodontic brackets (21 trials; 1427 patients; mean age 14.4 years) or molar bands (2 trials; 46 patients; age/sex not reported). Active patient reminders were associated with reduced WSL incidence on patient level compared to no reminder (3 trials; 190 patients; RR: 0.4; 95% CI: 0.31-0.64; Number Needed to Treat [NNT]: 3 patients), flat surface sealants were associated with reduced WSL incidence on tooth level than no sealant (5 trials; 2784 teeth; RR: 0.8; 95% CI: 0.63-0.95; NNT: 33 teeth), and fluoride varnish was associated with reduced WSL severity on tooth level (2 trials; 1160 teeth; MD: -0.32 points; 95% CI: -0.44 to -0.21 points). However, the quality of evidence was low according to GRADE, due to risk of bias. Some evidence indicates that active patient reminders and flat surface sealants or fluoride varnish around orthodontic brackets might be associated with reduced WSL burden, but further research is needed. Keywords: adverse effects; clinical trials; dental caries; evidence-based medicine; fixed appliances; systematic review

Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium–glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication

Cardiac magnetic resonance for ventricular arrhythmias: a systematic review and meta-analysis

Background: Cardiac magnetic resonance (CMR) allows comprehensive myocardial tissue characterisation, revealing areas of myocardial inflammation or fibrosis that may predispose to ventricular arrhythmias (VAs). With this study, we aimed to estimate the prevalence of structural heart disease (SHD) and decipher the prognostic implications of CMR in selected patients presenting with significant VAs. Methods: Electronic databases were searched for studies enrolling adult patients that underwent CMR for diagnostic or prognostic purposes in the setting of significant VAs. A random effects model meta-analysis of proportions was performed to estimate the prevalence of SHD. HRs were pooled together in order to evaluate the prognostic value of CMR. Results: The prevalence of SHD was reported in 18 studies. In all-comers with significant VAs, the pooled rate of SHD post-CMR evaluation was 39% (24% in the subgroup of premature ventricular contractions and/or non-sustained ventricular tachycardia vs 63% in the subgroup of more complex VAs). A change in diagnosis after use of CMR ranged from 21% to 66% with a pooled average of 35% (29%–41%). A non-ischaemic cardiomyopathy was the most frequently identified SHD (56%), followed by ischaemic heart disease (21%) and hypertrophic cardiomyopathy (5%). After pooling together data from six studies, we found that the presence of late gadolinium enhancement was associated with increased risk of major adverse outcomes in patients with significant VAs (pooled HR: 1.79; 95% CI 1.33 to 2.42). Conclusion: CMR is a valuable tool in the diagnostic and prognostic evaluation of patients with VAs. CMR should be considered early after initial evaluation in the diagnostic algorithm for VAs of unclear aetiology as this strategy may also define prognosis and improve risk stratification

Effects of Imatinib Mesylate (Gleevec) on Human Islet NF-kappaB Activation and Chemokine Production In Vitro

Imatinib Mesylate (Gleevec) is a drug that potently counteracts diabetes both in humans and in animal models for human diabetes. We have previously reported that this compound in human pancreatic islets stimulates NF-κB signaling and islet cell survival. The aim of this study was to investigate control of NF-κB post-translational modifications exerted by Imatinib and whether any such effects are associated with altered islet gene expression and chemokine production in vitro.Human islets were either left untreated or treated with Imatinib for different timepoints. IκB-α and NF-κB p65 phosphorylation and methylation were assessed by immunoblot analysis. Islet gene expression was assessed using a commercial Pathway Finder microarray kit and RT-PCR. Islet chemokine production was determined by flow cytometric bead array analysis.Human islet IκB-α and Ser276-p65 phosphorylation were increased by a 20 minute Imatinib exposure. Methylation of p65 at position Lys221 was increased after 60 min of Imatinib exposure and persisted for 3 hours. Microarray analysis of islets exposed to Imatinib for 4 hours revealed increased expression of the inflammatory genes IL-4R, TCF5, DR5, I-TRAF, I-CAM, HSP27 and IL-8. The islet release of IL-8 was augmented in islets cultured over night in the presence of Imatinib. Following 30 hours of Imatinib exposure, the cytokine-induced IκB-α and STAT1 phosphorylation was abolished and diminished, respectively. The cytokine-induced release of the chemokines MIG and IP10 was lower in islets exposed to Imatinib for 30 hours.Imatinib by itself promotes a modest activation of NF-κB. However, a prolonged exposure of human islets to Imatinib is associated with a dampened response to cytokines. It is possible that Imatinib induces NF-κB preconditioning of islet cells leading to lowered cytokine sensitivity and a mitigated islet inflammation

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe