Evaluating the effect of metabolic traits on oral and oropharyngeal cancer risk using Mendelian randomization.

A recent World Health Organization report states that at least 40% of all cancer cases may be preventable, with smoking, alcohol consumption, and obesity identified as three of the most important modifiable lifestyle factors. Given the significant decline in smoking rates, particularly within developed countries, other potentially modifiable risk factors for head and neck cancer warrant investigation. Obesity and related metabolic disorders such as type 2 diabetes (T2D) and hypertension have been associated with head and neck cancer risk in multiple observational studies. However, adiposity has also been correlated with smoking, with bias, confounding or reverse causality possibly explaining these findings. To overcome the challenges of observational studies, we conducted two-sample Mendelian randomization (inverse variance weighted [IVW] method) using genetic variants which were robustly associated with adiposity, glycaemic and blood pressure traits in genome-wide association studies (GWAS). Outcome data were taken from the largest available GWAS of 6034 oral and oropharyngeal cases, with 6585 controls. We found limited evidence of a causal effect of genetically proxied body mass index (BMI; OR IVW = 0.89, 95% CI 0.72-1.09, p = 0.26 per 1 standard deviation in BMI [4.81kg/m2]) on oral and oropharyngeal cancer risk. Similarly, there was limited evidence for related traits including T2D and hypertension. Small effects cannot be excluded given the lack of power to detect them in currently available GWAS.

Oral and maxillofacial injuries from electric scooters in Bristol: a retrospective observational study.

The 'Voi' (Voi Technology) electric scooter (e-scooter) pilot scheme was initiated in Southwest England on 29 October 2020.The aim of this study was to describe the patient demographic and patterns of oral and maxillofacial injuries related to the use of e-scooters in the Bristol area, to target public safety interventions at high-risk groups. Data were collected retrospectively from patients attending the Bristol Royal Infirmary Emergency Department (ED) over a six-month period. A total of 42 patients attending the ED had the search term 'scooter' in their initial presenting complaint.The majority of patients (n = 35) were discharged without follow up, with only three requiring admission to oral and maxillofacial surgery. Overall trauma injuries related to e-scooters increased incrementally over the study period.Only two patients were reported to be wearing a helmet at the time of injury, versus one fifth not wearing one. More worryingly, 33% of injured users were intoxicated.The majority of injured patients appeared to be young males (n = 33, median age 26 years). Understanding the local epidemiology of e-scooter injuries will help authorities target public safety interventions at high-risk groups. The results of this study will be shared with the West of England Combined Authority, to improve future e-scooter policy-making and safety implementation in this region.

Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization.

BACKGROUND: Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. We aimed to evaluate the causal effect of sexual behaviour on the risk of OPC using Mendelian randomization (MR). METHODS: Genetic variants robustly associated with age at first sex (AFS) and the number of sexual partners (NSP) were used to perform both univariable and multivariable MR analyses with summary data on 2641 OPC cases and 6585 controls, obtained from the largest available genome-wide association studies (GWAS). Given the potential for genetic pleiotropy, we performed a number of sensitivity analyses: (i) MR methods to account for horizontal pleiotropy, (ii) MR of sexual behaviours on positive (cervical cancer and seropositivity for Chlamydia trachomatis) and negative control outcomes (lung and oral cancer), (iii) Causal Analysis Using Summary Effect estimates (CAUSE), to account for correlated and uncorrelated horizontal pleiotropic effects, (iv) multivariable MR analysis to account for the effects of smoking, alcohol, risk tolerance and educational attainment. RESULTS: In univariable MR, we found evidence supportive of an effect of both later AFS (IVW OR = 0.4, 95%CI (0.3, 0.7), per standard deviation (SD), p = < 0.001) and increasing NSP (IVW OR = 2.2, 95%CI (1.3, 3.8) per SD, p = < 0.001) on OPC risk. These effects were largely robust to sensitivity analyses accounting for horizontal pleiotropy. However, negative control analysis suggested potential violation of the core MR assumptions and subsequent CAUSE analysis implicated pleiotropy of the genetic instruments used to proxy sexual behaviours. Finally, there was some attenuation of the univariable MR results in the multivariable models (AFS IVW OR = 0.7, 95%CI (0.4, 1.2), p = 0.21; NSP IVW OR = 0.9, 95%CI (0.5 1.7), p = 0.76). CONCLUSIONS: Despite using genetic variants strongly related sexual behaviour traits in large-scale GWAS, we found evidence for correlated pleiotropy. This emphasizes a need for multivariable approaches and the triangulation of evidence when performing MR of complex behavioural traits.

Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: main results of a cluster preference randomised controlled trial.

PURPOSE: The patient concerns inventory (PCI) is a prompt list allowing head and neck cancer (HNC) patients to discuss issues that otherwise might be overlooked. This trial evaluated the effectiveness of using the PCI at routine outpatient clinics for one year after treatment on health-related QOL (HRQOL). METHODS: A pragmatic cluster preference randomised control trial with 15 consultants, 8 'using' and 7 'not using' the PCI intervention. Patients treated with curative intent (all sites, disease stages, treatments) were eligible. RESULTS: Consultants saw a median (inter-quartile range) 16 (13-26) patients, with 140 PCI and 148 control patients. Of the pre-specified outcomes, the 12-month results for the mean University of Washington Quality of Life (UW-QOLv4) social-emotional subscale score suggested a small clinical effect of intervention of 4.6 units (95% CI 0.2, 9.0), p = 0.04 after full adjustment for pre-stated case-mix. Results for UW-QOLv4 overall quality of life being less than good at 12 months (primary outcome) also favoured the PCI with a risk ratio of 0.83 (95% CI 0.66, 1.06) and absolute risk 4.8% (- 2.9%, 12.9%) but without achieving statistical significance. Other non-a-priori analyses, including all 12 UWQOL domains and at consultant level also suggested better HRQOL with PCI. Consultation times were unaffected and the number of items selected decreased over time. CONCLUSION: This novel trial supports the integration of the PCI approach into routine consultations as a simple low-cost means of benefiting HNC patients. It adds to a growing body of evidence supporting the use of patient prompt lists more generally.

Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: baseline results in a cluster preference randomised controlled trial.

PURPOSE: The main aim of this paper is to present baseline demographic and clinical characteristics and HRQOL in the two groups of the Patient Concerns Inventory (PCI) trial. The baseline PCI data will also be described. METHODS: This is a pragmatic cluster preference randomised control trial with 15 consultant clusters from two sites either 'using' (n = 8) or 'not using' (n = 7) the PCI at a clinic for all of their trial patients. The PCI is a 56-item prompt list that helps patients raise concerns that otherwise might be missed. Eligibility was head and neck cancer patients treated with curative intent (all sites, stage of disease, treatments). RESULTS: From 511 patients first identified as eligible when screening for the multi-disciplinary tumour board meetings, 288 attended a first routine outpatient baseline study clinic after completion of their treatment, median (IQR) of 103 (71-162) days. At baseline, the two trial groups were similar in demographic and clinical characteristics as well as in HRQOL measures apart from differences in tumour location, tumour staging and mode of treatment. These exceptions were cluster (consultant) related to Maxillofacial and ENT consultants seeing different types of cases. Consultation times were similar, with PCI group times taking about 1 min longer on average (95% CL for the difference between means was from - 0.7 to + 2.2 min). CONCLUSION: Using the PCI in routine post-treatment head and neck cancer clinics do not elongate consultations. Recruitment has finished but 12-month follow-up is still ongoing.

Epigenetic prediction of complex traits and mortality in a cohort of individuals with oropharyngeal cancer.

BACKGROUND: DNA methylation (DNAm) variation is an established predictor for several traits. In the context of oropharyngeal cancer (OPC), where 5-year survival is ~ 65%, DNA methylation may act as a prognostic biomarker. We examined the accuracy of DNA methylation biomarkers of 4 complex exposure traits (alcohol consumption, body mass index [BMI], educational attainment and smoking status) in predicting all-cause mortality in people with OPC. RESULTS: DNAm predictors of alcohol consumption, BMI, educational attainment and smoking status were applied to 364 individuals with OPC in the Head and Neck 5000 cohort (HN5000; 19.6% of total OPC cases in the study), followed up for median 3.9 years; inter-quartile range (IQR) 3.3 to 5.2 years (time-to-event-death or censor). The proportion of phenotypic variance explained in each trait was as follows: 16.5% for alcohol consumption, 22.7% for BMI, 0.4% for educational attainment and 51.1% for smoking. We then assessed the relationship between each DNAm predictor and all-cause mortality using Cox proportional-hazard regression analysis. DNAm prediction of smoking was most consistently associated with mortality risk (hazard ratio [HR], 1.38 per standard deviation (SD) increase in smoking DNAm score; 95% confidence interval [CI] 1.04 to 1.83; P 0.025, in a model adjusted for demographic, lifestyle, health and biological variables). Finally, we examined the accuracy of each DNAm predictor of mortality. DNAm predictors explained similar levels of variance in mortality to self-reported phenotypes. Receiver operator characteristic (ROC) curves for the DNAm predictors showed a moderate discrimination of alcohol consumption (area under the curve [AUC] 0.63), BMI (AUC 0.61) and smoking (AUC 0.70) when predicting mortality. The DNAm predictor for education showed poor discrimination (AUC 0.57). Z tests comparing AUCs between self-reported phenotype ROC curves and DNAm score ROC curves did not show evidence for difference between the two (alcohol consumption P 0.41, BMI P 0.62, educational attainment P 0.49, smoking P 0.19). CONCLUSIONS: In the context of a clinical cohort of individuals with OPC, DNAm predictors for smoking, alcohol consumption, educational attainment and BMI exhibit similar predictive values for all-cause mortality compared to self-reported data. These findings may have translational utility in prognostic model development, particularly where phenotypic data are not available.

Human disease/clinical medical sciences in dentistry: Current state and future development of undergraduate assessments in the UK and Ireland.

INTRODUCTION: The United Kingdom and Ireland teachers of Human Disease/Clinical Medical Science for Dentistry (HD/CMSD) group continue to work together and most recently collaborated to review current and future assessments. MATERIALS AND METHODS: The first part of the review of assessments in HD/CMSD took place at a face-to-face meeting with presentations from delegates on assessments in their home institutions. The second and larger part comprised an online survey where all eighteen schools in the UK and Ireland participated. RESULTS: All schools had some element of formative assessment, and the majority had a stand-alone summative assessment at the end of the HD/CMSD teaching block. Most schools had a written paper and practical elements to their assessments, most commonly a combination of a multiple-choice type question combined with an objective structured clinical examination (OSCE). There was a trend towards the use of single best answer (SBA) questions and a willingness amongst participants to share a question bank. All schools incorporated elements of HD/CMSD in their final examinations. DISCUSSION AND CONCLUSION: This collaboration promoted the sharing of developments in assessment for HD/CMSD and demonstrated a willingness to cooperate between institutions. Assessment in HD/CMSD in the UK and Ireland continues to be refined by those responsible for its content and delivery, and assessment methods are progressing following evidence-based best practice.

Examining the causal association between 25-hydroxyvitamin D and caries in children and adults: a two-sample Mendelian randomization approach.

Background: Prior observational studies have reported that higher levels of vitamin D are associated with decreased caries risk in children. However, these studies are prone to bias and confounding so do not provide causal inference. Genetic variants associated with a risk factor of interest can be used as proxies, in a Mendelian randomization (MR) analysis, to test for causal association with an outcome. The objective was to estimate the causal association between serum 25-hydroxyvitamin D (25(OH)D) (the commonly measured vitamin D metabolite in blood) and dental caries using a MR approach which estimates the causal effect of an exposure on an outcome. Methods: A total of 79 genetic variants reliably associated with 25(OH)D were identified from genome-wide association studies and used as a proxy measure of 25(OH)D. The association of this proxy measure with three outcome measures was tested; specifically: caries in primary teeth (n=17,035, aged 3-12 years), caries in permanent teeth in childhood and adolescence (n=13,386, aged 6-18 years), and caries severity in adulthood proxied by decayed, missing and filled tooth surfaces (DMFS) counts (n=26,792, aged 18-93 years). Results: The estimated causal effect of a one standard deviation increase in natural log-transformed 25(OH)D could be summarized as an odds ratio of 1.06 (95%CI: 0.81, 1.31; P=0.66) for caries in primary teeth and 1.00 (95%CI: 0.76, 1.23; P=0.97) for caries in permanent teeth in childhood and adolescence. In adults, the estimated casual effect of a one standard deviation increase in natural log-transformed 25(OH)D was 0.31 fewer affected tooth surfaces (95%CI: from 1.81 fewer DMFS to 1.19 more DMFS; P=0.68) Conclusions: The MR-derived effect estimates for these three measures are small in magnitude with wide confidence intervals and do not provide evidence against the null hypothesis of no effect.

Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci.

Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alter the odds of developing non-specific mouth ulcers and replicate these in an independent cohort (n = 355,744) (lead variant after meta-analysis: rs76830965, near IL12A, OR 0.72 (95% CI: 0.71, 0.73); P = 4.4e-483). Additional effect estimates from three independent cohorts with more specific phenotyping and specific study characteristics support many of these findings. In silico functional analyses provide evidence for a role of T cell regulation in the aetiology of mouth ulcers. These results provide novel insight into the pathogenesis of a common, important condition.

Solution Stability of Poloxamer 188 Under Stress Conditions.

Poloxamer 188 (P188) is a triblock copolymer of the form polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO). The center PPO block is hydrophobic, and the side PEO blocks are hydrophilic, resulting in surface-active properties. P188 has been used in the pharmaceutical industry as an excipient in various formulations and drug delivery systems. Although the chemical stability of P188 in the solid state has been reported, there are very few reports detailing the solution state stability. In this study, we report the solution state stability of P188 conducted to evaluate the effects of P188 concentration, temperature, pH and buffer type, and trace metals on chemical stability. The degradation chemistry of P188 and identification of degradation products was studied using various analytical techniques (ultraviolet, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry). The degradation of P188 in solution was found to be strongly dependent on temperature, P188 concentration, and buffer type. For the first time, we report that in histidine buffer, oxidation of both P188 and histidine may occur at pharmaceutically relevant conditions. We observed degradation of both histidine and P188 as well as species formed from the mutual interactions of the degradation products from the 2 types of molecules.

Consortium-based genome-wide meta-analysis for childhood dental caries traits.

Prior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from nine contributing centres. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage and the results were combined using fixed-effects meta-analysis. Analysis included up to 19 003 individuals (7530 affected) for primary teeth and 13 353 individuals (5875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth [intronic within ALLC, odds ratio (OR) 0.85, effect allele frequency (EAF) 0.60, P 4.13e-8] and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, P 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low [h2 of 1% (95% CI: 0%: 7%) and 6% (95% CI 0%: 13%) for primary and permanent dentitions, respectively] compared with corresponding within-study estimates [h2 of 28% (95% CI: 9%: 48%) and 17% (95% CI: 2%: 31%)] or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.

Depressive symptoms in relation to overall survival in people with head and neck cancer: A longitudinal cohort study.

OBJECTIVE: The objective of the study is to investigate the relation between pretreatment depressive symptoms (DS) and the course of DS during the first year after cancer diagnosis, and overall survival among people with head and neck cancer (HNC). METHODS: Data from the Head and Neck 5000 prospective clinical cohort study were used. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) pretreatment, at 4 and 12-month follow-up. Also, socio-demographic, clinical, lifestyle, and mortality data were collected. The association between before start of treatment DS (HADS-depression > 7) and course (never DS, recovered from DS, or persistent/recurrent/late DS at 12-month follow-up) and survival was investigated using Cox regression. Unadjusted and adjusted analyses were performed. RESULTS: In total, 384 of the 2144 persons (18%) reported pretreatment DS. Regarding DS course, 63% never had DS, 16% recovered, and 20% had persistent/recurrent/late DS. People with pretreatment DS had a higher risk of earlier death than people without DS (hazard ratio (HR) = 1.65; 95% confidence interval (CI) 1.33-2.05), but this decreased after correcting for socio-demographic, clinical, and lifestyle-related factors (HR = 1.21; 95% CI 0.97-1.52). Regarding the course of DS, people with persistent/recurrent/late DS had a higher risk of earlier death (HR = 2.04; 95% CI 1.36-3.05), while people who recovered had a comparable risk (HR = 1.12; 95% CI 0.66-1.90) as the reference group who never experienced DS. After correcting for socio-demographic and clinical factors, people with persistent/recurrent/late DS still had a higher risk of earlier death (HR = 1.66; 95% CI 1.09-2.53). CONCLUSIONS: Pretreatment DS and persistent/recurrent/late DS were associated with worse survival among people with HNC.

Tooth loss is a complex measure of oral disease: Determinants and methodological considerations.

OBJECTIVES: Counts of missing teeth or measures of incident tooth loss are gaining attention as a simple way to measure dental status in large population studies. We explore the meaning of these metrics and how missing teeth might influence other measures of dental status. METHODS: An observational study was performed in 2 contrasting adult populations. In total, 62 522 adult participants were available with clinically assessed caries and periodontal indices from the Swedish arm of the Gene-Lifestyle Interactions and Dental Endpoints Study (GLIDE) and the Korea National Health and Nutrition Examination Survey (KNHANES) in the Republic of Korea. Longitudinal measures of tooth loss were available for 28 244 participants in GLIDE with median follow-up of 10.6 years. RESULTS: In longitudinal analysis, hazard for tooth loss was associated with baseline dental status (previous tooth loss, periodontal status and caries status) and socio-demographic variables (age, smoking status and highest educational level). Analysis of cross-sectional data suggested that indices of caries exposure were not independent of periodontal status. The strength and direction of association varied between groups, even for measures specifically intended to avoid measuring tooth loss. Individuals with impaired periodontal health (community periodontal index [CPI] 3 or higher in any sextant) had higher standardized decayed and filled surfaces (DFS; number of DFS divided by total number of tooth surfaces) in GLIDE (incidence risk ratio [IRR] 1.05 [95% CI: 1.04, 1.07], but lower standardized DFS in KNHANES (IRR: 0.95 [0.92, 0.98]) than individuals with better periodontal health (CPI <3 in all sextants). CONCLUSIONS: Incident tooth loss is a complex measure of dental disease, with multiple determinants. The relative importance of dental caries and periodontal disease as drivers of tooth loss differs between age groups. Measures of dental caries exposure are associated with periodontal status in the studied populations, and these associations can be population-specific. Consideration of the study-specific properties of these metrics may be required for valid inference in large population studies.

Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: a cluster preference randomized controlled trial.

BACKGROUND: The consequences of treatment for Head and Neck cancer (HNC) patients has profound detrimental impacts such as impaired QOL, emotional distress, delayed recovery and frequent use of healthcare. The aim of this trial is to determine if the routine use of the Patients Concerns Inventory (PCI) package in review clinics during the first year following treatment can improve overall quality of life, reduce the social-emotional impact of cancer and reduce levels of distress. Furthermore, we aim to describe the economic costs and benefits of using the PCI. METHODS: This will be a cluster preference randomised control trial with consultants either 'using' or 'not using' the PCI package at clinic. It will involve two centres Leeds and Liverpool. 416 eligible patients from at least 10 consultant clusters are required to show a clinically meaningful difference in the primary outcome. The primary outcome is the percentage of participants with less than good overall quality of life at the final one-year clinic as measured by the University of Washington QOL questionnaire version 4 (UWQOLv4). Secondary outcomes at one-year are the mean social-emotional subscale (UWQOLv4) score, Distress Thermometer (DT) score ≥ 4, and key health economic measures (QALY-EQ-5D-5 L; CSRI). DISCUSSION: This trial will provide knowledge on the effectiveness of a consultation intervention package based around the PCI used at routine follow-up clinics following treatment of head and neck cancer with curative intent. If this intervention is (cost) effective for patients, the next step will be to promote wider use of this approach as standard care in clinical practice. TRIAL REGISTRATION: 32,382. Clinical Trials Identifier, NCT03086629 . PROTOCOL: Version 3.0, 1st July 2017.

Tobacco smoking and alcohol drinking at diagnosis of head and neck cancer and all-cause mortality: Results from head and neck 5000, a prospective observational cohort of people with head and neck cancer.

Tobacco smoking and alcohol consumption are well-established risk factors for head and neck cancer. The prognostic role of smoking and alcohol intake at diagnosis have been less well studied. We analysed 1,393 people prospectively enrolled into the Head and Neck 5000 study (oral cavity cancer, n=403; oropharyngeal cancer, n=660; laryngeal cancer, n=330) and followed up for a median of 3.5 years. The primary outcome was all-cause mortality. We used Cox proportional hazard models to derive minimally adjusted (age and gender) and fully adjusted (age, gender, ethnicity, stage, comorbidity, body mass index, HPV status, treatment, education, deprivation index, income, marital status, and either smoking or alcohol use) mortality hazard ratios (HR) for the effects of smoking status and alcohol intake at diagnosis. Models were stratified by cancer site, stage and HPV status. The fully-adjusted HR for current versus never-smokers was 1.7 overall (95% confidence interval [CI] 1.1, 2.6). In stratified analyses, associations of smoking with mortality were observed for oropharyngeal and laryngeal cancers (fully adjusted HRs for current smokers: 1.8 (95% CI=0.9, 3.40 and 2.3 (95% CI=0.8, 6.4)). We found no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non-drinkers (HR=1.2 (95% CI=0.9, 1.6)). There was no strong evidence that HPV status or tumour stage modified the association of smoking with survival. Smoking status at the time of a head and neck cancer diagnosis influenced all-cause mortality in models adjusted for important prognostic factors.

Assessing the causal association between 25-hydroxyvitamin D and the risk of oral and oropharyngeal cancer using Mendelian randomization.

Circulating 25-hydroxyvitamin D (25OHD) is an appealing potential intervention for cancer risk and has been associated with oral and oropharyngeal cancer risk but evidence is inconsistent. The availability of genetic variants, uncorrelated with known confounders, but predictive of 25OHD and genetic data in a large oral and oropharyngeal cancer collaboration aids causal inference when assessing this association. A total of 5,133 oral and oropharyngeal cancer cases and 5,984 controls with genetic data were included in the study. Participants were based in Europe, North America and South America and were part of the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Five genetic variants reliably associated with circulating 25OHD were used to create a relative genetic measure of 25OHD. In the absence of measured 25OHD, two-sample Mendelian randomization using individual level outcome data were used to estimate causal odds ratios (OR) for cancer case status per standard deviation increase in log25OHD. Analyses were replicated in an independent population-based cohort (UK Biobank). In the GAME-ON study, there was little evidence of a causal association between circulating 25OHD and oral cancer (OR = 0.86 [0.68;1.09], p = 0.22), oropharyngeal cancer (OR = 1.28 [0.72;2.26], p = 0.40) or when sites were combined (OR = 1.01 [0.74;1.40], p = 0.93). Replication in UK Biobank and pooled estimates produced similar results. Our study suggests that a clinically relevant protective effect of 25OHD on oral and oropharyngeal cancer risk is unlikely and supplementation of the general population with 25OHD is unlikely to be beneficial in preventing these cancers.

Change in alcohol and tobacco consumption after a diagnosis of head and neck cancer: Findings from Head and Neck 5000.

BACKGROUND: Tobacco and alcohol consumption are risk factors for developing head and neck cancer, and continuation postdiagnosis can adversely affect prognosis. We explored changes to these behaviors after a head and neck cancer diagnosis. METHODS: Demographic and clinical data were collected from 973 people newly diagnosed with oral cavity, oropharyngeal, or laryngeal cancer. Tobacco and alcohol consumption were additionally collected 4 and 12 months later. RESULTS: The prevalence of high alcohol consumption reduced from 54.3% at diagnosis to 41.4% at 12 months, and smoking reduced from 21.0% to 11.7%. Changes in behavior were dynamic, for example, 44% of smokers at 12 months were not smoking at diagnosis or 4 months. Several factors were associated with alcohol consumption, whereas only tumor site and comorbidities were associated with smoking. CONCLUSION: A diagnosis of head and neck cancer can result in important changes in alcohol consumption and smoking prevalence. However, these changes are dynamic in the first year after diagnosis.

Core information sets for informed consent to surgical interventions: baseline information of importance to patients and clinicians.

BACKGROUND: Consent remains a crucial, yet challenging, cornerstone of clinical practice. The ethical, legal and professional understandings of this construct have evolved away from a doctor-centred act to a patient-centred process that encompasses the patient's values, beliefs and goals. This alignment of consent with the philosophy of shared decision-making was affirmed in a recent high-profile Supreme Court ruling in England. The communication of information is central to this model of health care delivery but it can be difficult for doctors to gauge the information needs of the individual patient. The aim of this paper is to describe 'core information sets' which are defined as a minimum set of consensus-derived information about a given procedure to be discussed with all patients. Importantly, they are intended to catalyse discussion of subjective importance to individuals. MAIN BODY: The model described in this paper applies health services research and Delphi consensus-building methods to an idea orginally proposed 30 years ago. The hypothesis is that, first, large amounts of potentially-important information are distilled down to discrete information domains. These are then, secondly, rated by key stakeholders in multiple iterations, so that core information of agreed importance can be defined. We argue that this scientific approach is key to identifying information important to all stakeholders, which may otherwise be communicated poorly or omitted from discussions entirely. Our methods apply systematic review, qualitative, survey and consensus-building techniques to define this 'core information'. We propose that such information addresses the 'reasonable patient' standard for information disclosure but, more importantly, can serve as a spring board for high-value discussion of importance to the individual patient. CONCLUSION: The application of established research methods can define information of core importance to informed consent. Further work will establish how best to incorporate this model in routine practice.

The Olympic legacy: Journal metrics in sports medicine and dentistry.

Systematic analysis of integral aspects within sport enables improvement in performance. One key aspect is the management and prevention of injuries. Bibliometrics is a systematic method for evaluating research output. It may be expected that the quantity and quality of sports injury research over time may strongly correlate with the timing of the Olympic games. This study was conducted to determine the effect of the Olympic legacy on academic sports medicine and evidence to prevent injuries of the face and teeth. A literature search within the PubMed database was undertaken to identify the quantity of literature published annually between 1996 and 2015 in the fields of sports injuries and injury prevention. The top 5 journals publishing in each field were then identified and the change in their impact factor (IF) was investigated. It was seen that, since 1996, there has been an overall increase in the quantity of literature published regarding sports injuries and prevention of sports injuries of 209% and 217%, respectively. Publications regarding facial injuries and dental injuries within sport show an increase of 114% and 71%, respectively. There was an increase in IF since 2000 in almost every journal investigated. A strong, positive correlation is seen among journals publishing on the prevention of sports injuries, showing a median IF increase of 2.8198. No statistical significance was found between Olympic years and the number of publications. Hence, there has been a gradual increase in both the quality and quantity of publications regarding sports injuries since 1996. However, there appears to be no immediate added effect of the "Olympic legacy" following each Olympic games on the quantity or quality of publications in these fields.

Serum from human burn victims impairs myogenesis and protein synthesis in primary myoblasts.

The pathophysiological response to a severe burn injury involves a robust increase in circulating inflammatory/endocrine factors and a hypermetabolic state, both of which contribute to prolonged skeletal muscle atrophy. In order to characterize the role of circulating factors in muscle atrophy following a burn injury, human skeletal muscle satellite cells were grown in culture and differentiated to myoblasts/myotubes in media containing serum from burn patients or healthy, age, and sex-matched controls. While incubation in burn serum did not affect NFκB signaling, cells incubated in burn serum displayed a transient increase in STAT3 phosphorlyation (Tyr705) after 48 h of treatment with burn serum (≈ + 70%; P < 0.01), with these levels returning to normal by 96 h. Muscle cells differentiated in burn serum displayed reduced myogenic fusion signaling (phospho-STAT6 (Tyr641), ≈-75%; ADAM12, ≈-20%; both P < 0.01), and reduced levels of myogenin (≈-75%; P < 0.05). Concomitantly, myotubes differentiated in burn serum demonstrated impaired myogenesis (assessed by number of nuclei/myotube). Incubation in burn serum for 96 h did not increase proteolytic signaling (assessed via caspase-3 and ubiquitin levels), but reduced anabolic signaling [p-p70S6k (Ser421/Thr424), -30%; p-rpS6 (Ser240/244), ≈-50%] and impaired protein synthesis (-24%) (P < 0.05). This resulted in a loss of total protein content (-18%) and reduced cell size (-33%) (P < 0.05). Overall, incubation of human muscle cells in serum from burn patients results in impaired myogenesis and reduced myotube size, indicating that circulating factors may play a significant role in muscle loss and impaired muscle recovery following burn injury.