Development of a core outcome set for orthodontic trials using a mixed-methods approach: Protocol for a multicentre study

© 2017 The Author(s). Background: Orthodontic treatment is commonly undertaken in young people, with over 40% of children in the UK needing treatment and currently one third having treatment, at a cost to the National Health Service in England and Wales of £273 million each year. Most current research about orthodontic care does not consider what patients truly feel about, or want, from treatment, and a diverse range of outcomes is being used with little consistency between studies. This study aims to address these problems, using established methodology to develop a core outcome set for use in future clinical trials of orthodontic interventions in children and young people. Methods/design: This is a mixed-methods study incorporating four distinct stages. The first stage will include a scoping review of the scientific literature to identify primary and secondary outcome measures that have been used in previous orthodontic clinical trials. The second stage will involve qualitative interviews and focus groups with orthodontic patients aged 10 to 16 years to determine what outcomes are important to them. The outcomes elicited from these two stages will inform the third stage of the study in which a long-list of outcomes will be ranked in terms of importance using electronic Delphi surveys involving clinicians and patients. The final stage of the study will involve face-to-face consensus meetings with all stakeholders to discuss and agree on the outcome measures that should be included in the final core outcome set. Discussion: This research will help to inform patients, parents, clinicians and commissioners about outcomes that are important to young people undergoing orthodontic treatment. Adoption of the core outcome set in future clinical trials of orthodontic treatment will make it easier for results to be compared, contrasted and combined. This should translate into improved decision-making by all stakeholders involved. Trial registration: The project has been registered on the Core Outcome Measures in Effectiveness Trials (COMET) website, January 2016

Group-based memory rehabilitation for people with multiple sclerosis: subgroup analysis of the ReMiND trial

Background/Aim: Memory problems are frequently reported in people with multiple sclerosis (MS). These can be debilitating and affect individuals and their families. This sub-group analysis focused on the effectiveness of memory rehabilitation in patients with MS. Methods: Data were extracted from a single blind randomised controlled trial, the ReMiND trial, which also included participants with traumatic brain injury and stroke. Participants were randomly allocated to compensation or restitution treatment programmes, or a self-help control. The programmes were manual-based and comprised two individual and ten group sessions. Outcome measures included assessments of memory, mood and activities of daily living. A total of 39 patients with MS participated in this study (ten males (26%), 29 females (74%); mean±SD age: 48.3±10.8 years). Results: Comparison of groups showed no significant effect of treatment on memory, but there were significant differences between compensation and restitution on self-report symptoms of emotional distress at both 5- (p=0.04) and 7-month (p=0.05) follow-up sessions. The compensation group showed less distress than the restitution group. Conclusions: Individuals with MS who received compensation memory rehabilitation reported significantly less emotional distress than those who received restitution. Further research is needed to explore why self-reported memory problems did not differ between groups

Mechanisms of Class II correction induced by the crown Herbst appliance as a single-phase Class II therapy : 1 year follow-up

Background The objective of this study is to evaluate the skeletal and dentoalveolar effects of the crown Herbst appliance used alone for a single phase of therapy followed by a 1-year observation period. Methods Forty patients (mean age 13.6 ± 1.3 years) with a stable Class I occlusion 1 year following the treatment with the crown Herbst appliance were selected from a prospective sample of 180 consecutively treated Class II patients. No other appliances were used during treatment or during the follow-up period. The dentoskeletal changes were compared with a matched sample of untreated Class II subjects (mean age 13.9 ± 1.6 years). Lateral cephalograms were taken before treatment, after Herbst treatment (1 year), and after 1-year follow-up. Overcorrection was avoided intentionally. Results Treatment produced an increase in mandibular length, a decrease in ANB angle, and a restriction in the vertical growth of posterior maxilla. The maxillary molars moved backward and tipped distally. The lower incisors proclined markedly, and the upper incisors became retroclined. During the follow-up period, the changes primarily were dentoalveolar in nature, with marked rebound of the upper molars and lower incisors, resulting in some increases in overbite and overjet. Conclusions The occlusal correction of Class II malocclusion observed 1 year after the crown Herbst appliance as a single-phase therapy was achieved primary due to the dentoalveolar changes and only limited skeletal change occurred.publishersversionPeer reviewe

Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: a potential regulator of involution

Post-lactational involution of the mammary gland is initiated within days of weaning. Clearing of cells occurs by apoptosis of the milk-secreting luminal cells in the alveoli and through stromal tissue remodeling to return the gland almost completely to its pre-pregnant state. The pathways that specifically target involution of the luminal cells in the alveoli but not the basal and ductal cells are poorly understood. In this study we show in cultured human mammary alveolar structures that the involution process is initiated by fresh media withdrawal, and is characterized by cellular oxidative stress, expression of activated macrophage marker CD68 and finally complete clearing of the luminal but not basal epithelial layer. This process can be simulated by ectopic addition of reactive oxygen species (ROS) in cultures without media withdrawal. Cells isolated from post-involution alveoli were enriched for the CD49f+ mammary stem cell (MaSC) phenotype and were able to reproduce a complete alveolar structure in subcultures without any significant loss in viability. We propose that the ROS produced by accumulated milk breakdown post-weaning may be the mechanism underlying the selective involution of secretory alveolar luminal cells, and that our culture model represents an useful means to investigate this and other mechanisms further

Headwater Influences on Downstream Water Quality

We investigated the influence of riparian and whole watershed land use as a function of stream size on surface water chemistry and assessed regional variation in these relationships. Sixty-eight watersheds in four level III U.S. EPA ecoregions in eastern Kansas were selected as study sites. Riparian land cover and watershed land use were quantified for the entire watershed, and by Strahler order. Multiple regression analyses using riparian land cover classifications as independent variables explained among-site variation in water chemistry parameters, particularly total nitrogen (41%), nitrate (61%), and total phosphorus (63%) concentrations. Whole watershed land use explained slightly less variance, but riparian and whole watershed land use were so tightly correlated that it was difficult to separate their effects. Water chemistry parameters sampled in downstream reaches were most closely correlated with riparian land cover adjacent to the smallest (first-order) streams of watersheds or land use in the entire watershed, with riparian zones immediately upstream of sampling sites offering less explanatory power as stream size increased. Interestingly, headwater effects were evident even at times when these small streams were unlikely to be flowing. Relationships were similar among ecoregions, indicating that land use characteristics were most responsible for water quality variation among watersheds. These findings suggest that nonpoint pollution control strategies should consider the influence of small upland streams and protection of downstream riparian zones alone is not sufficient to protect water quality

Intra-week spatial-temporal patterns of crime

Since its original publication, routine activity theory has proven most instructive for understanding temporal patterns in crime. The most prominent of the temporal crime patterns investigated is seasonality: crime (most often assault) increases during the summer months and decreases once routine activities are less often outside. Despite the rather widespread literature on the seasonality of crime, there is very little research investigating temporal patterns of crime at shorter time intervals such as within the week or even within the day. This paper contributes to this literature through a spatial-temporal analysis of crime patterns for different days of the week. It is found that temporal patterns are present for different days of the week (more crime on weekends, as would be expected) and there is a spatial component to that temporal change. Specifically, aside from robbery and sexual assault at the micro-spatial unit of analysis (street segments) the spatial patterns of crime changed. With regard to the spatial pattern changes, we found that assaults and theft from vehicle had their spatial patterns change in predictable ways on Saturdays: assaults increased in the bar district and theft from vehicles increased in the downtown and recreational car park areas

UK adults' implicit and explicit attitudes towards obesity: a cross-sectional study.

Background: Anti-fat attitudes may lead to stigmatisation of and lowered self-esteem in obese people. Examining anti-fat attitudes is warranted given that there is an association with anti-fat behaviours. Previous studies, mainly outside the UK, have demonstrated that anti-fat attitudes are increasing over time. Methods: The study was cross-sectional with a sample of 2380 participants (74.2 % female; aged 18–65 years). In an online survey participants reported demographic characteristics and completed a range of implicit and explicit measures of obesity related attitudes. Results: Perceptions of obesity were more negative than reported in previously. Main effects indicated more negative perceptions in males, younger respondents and more frequent exercisers. Attitudes about obesity differed in relation to weight category, and in general were more positive in obese than non-obese respondents. Conclusions: This is the first study to demonstrate anti-fat attitudes across different sections of the UK population. As such, this study provides the first indication of the prevalence of anti-fat attitudes in UK adults. Interventions to modify these attitudes could target specific groups of individuals with more negative perceptions as identified here. Future work would be useful that increases understanding of both implicit and explicit attitudes towards obesity

Cutaneous Head and Neck Squamous Cell Carcinoma with Regional Metastases: The Prognostic Importance of Soft Tissue Metastases and Extranodal Spread

Extranodal spread (ENS) is an established adverse prognostic factor in metastatic cutaneous squamous cell carcinoma (cSCC); however, the clinical significance of soft tissue metastases (STM) is unknown. The aim of this study was to evaluate the prognosis of patients with STM from head and neck cSCC, and to compare this with that of node metastases with and without ENS. Patients with cSCC metastatic to the parotid and/or neck treated by primary surgical resection between 1987 and 2007 were included. Metastatic nodes > 3 cm in size were an exclusion criterion. A Cox proportional hazard model was used to determine the effect of STM adjusting for other relevant prognostic factors. The population included 164 patients with a median follow-up of 26 months. There were 8 distant and 37 regional recurrences. There were 22 were cancer-specific deaths, and 29 patients died. STM was a significant predictor of reduced overall (hazard ratio 3.3; 95% confidence interval 1.6-6.4; P = 0.001) and disease-free survival (hazard ratio 2.4; 95% confidence interval 1.4-4.1; P = 0.001) when compared to patients with node disease with or without ENS. After adjusting for covariates, STM and number of involved nodes were significant independent predictors of overall and disease-free survival. In metastatic cSCC of the head and neck, the presence of STM is an independent predictor of reduced survival and is associated with a greater adverse effect than ENS alone

Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells

Glucocorticoids play a pivotal role in the proliferation of osteoblasts, but the underlying mechanism has not been successfully elucidated. In this report, we have investigated the molecular mechanism which elucidates the inhibitory effects of dexamethasone on murine osteoblastic MC3T3-E1 cells. It was found that the inhibitory effects were largely attributed to apoptosis and G1 phase arrest. Both the cell cycle arrest and apoptosis were dependent on glucocorticoid receptor (GR), as they were abolished by GR blocker RU486 pre-treatment and GR interference. G1 phase arrest and apoptosis were accompanied with a p53-dependent up-regulation of p21 and pro-apoptotic genes NOXA and PUMA. We also proved that dexamethasone can’t induce apoptosis and cell cycle arrest when p53 was inhibited by p53 RNA interference. These data demonstrate that proliferation of MC3T3-E1 cell was significantly and directly inhibited by dexamethasone treatment via aberrant GR activation and subsequently P53 activation