Analysis of the association between salivary proteins and oral mucositis in patients with head and neck cancer undergoing IMRT: a longitudinal study.

INTRODUCTION: This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and neck tumours treated with intensity-modulated-radiotherapy (IMRT). METHODS: Saliva samples/clinical data were obtained from 40 head and neck cancer patients treated at Guy's Hospital before -IMRT(T0) and after-IMRT (T1 = 6 m, T2 = 12 m) (ethics approval/consent). Salivary flow rate, total protein concentration, and secretion rate were determined from saliva samples and compared with pre-treatment values. OM was assessed, total/specific salivary proteins, including mucin 5B and 7, IgA, cystatin-S, albumin, and α-amylase, were quantified. RESULTS: 95% patients experienced OM during IMRT, with 33 subjects reaching grade 2&3. At T1, there was a significant reduction in salivary flow rate, total protein secretion rate, α-amylase and cystatin-S compared to baseline. Remarkably IMRT did not significantly alter mucin 5B and 7, or the IgA secretion rate at any time point. At T1, all the analyzed proteins were associated with the OM outcomes. In addition, there was a significant inverse correlation between IgA concentration at T0 and the severity of OM during IMRT. CONCLUSION: This study revealed significant associations between several salivary proteins and OM in patients with head and neck cancer undergoing IMRT. Further longitudinal studies are needed to confirm these results. CLINICAL SIGNIFICANCE: The study contributes to the understanding of certain salivary proteins association with OM. This could be the first step towards identifying potential salivary markers that could offer perspectives for personalized medicine approaches to improve their quality of life (QoL). RESEARCH QUESTION: What is the association between salivary proteins and the occurrence and severity of OM in head and neck cancer patients? AIM: To assess the association between salivary protein composition with the clinical onset/severity of oral mucositis (OM) in head and neck cancer patients treated with intensity modulated radiotherapy. NULL HYPOTHESIS: There is no association between salivary proteins and onset/severity of OM in HNC patients.

Cell Tracking Profiler - a user-driven analysis framework for evaluating 4D live-cell imaging data.

Accurate measurements of cell morphology and behaviour are fundamentally important for understanding how disease, molecules and drugs affect cell function in vivo Here, by using muscle stem cell (muSC) responses to injury in zebrafish as our biological paradigm, we established a 'ground truth' for muSC behaviour. This revealed that segmentation and tracking algorithms from commonly used programs are error-prone, leading us to develop a fast semi-automated image analysis pipeline that allows user-defined parameters for segmentation and correction of cell tracking. Cell Tracking Profiler (CTP) is a package that runs two existing programs, HK Means and Phagosight within the Icy image analysis suite, to enable user-managed cell tracking from 3D time-lapse datasets to provide measures of cell shape and movement. We demonstrate how CTP can be used to reveal changes to cell behaviour of muSCs in response to manipulation of the cell cytoskeleton by small-molecule inhibitors. CTP and the associated tools we have developed for analysis of outputs thus provide a powerful framework for analysing complex cell behaviour in vivo from 4D datasets that are not amenable to straightforward analysis.

Management of compromised first permanent molars in a cohort of UK paediatric patients referred to hospital-based services.

BACKGROUND: There are diverse opinions among dentists about managing compromised first permanent molars (cFPMs) in children and a perceived lack of guidance to help them evaluate prognosis. AIM: To evaluate the current management of cFPM in children referred to a UK hospital centre and to report the severity of the affected teeth. DESIGN: A service evaluation was undertaken, based on case records of medically fit children (6-11 years) referred to for the management of cFPMs. The presence of hypomineralisation, post-eruptive breakdown and the proposed care plans were recorded. Radiographic signs of severity were scored using the ICDAS index (intra/inter-rater kappa 0.96/0.82). RESULTS: From 349 records screened over a 4-month period, 249 met the selection criteria. Almost 81% were planned to have extraction of at least one cFPM, whereas 19.3% were managed without extraction. More than half of the extraction cases (n = 105) had radiographic radiolucencies not exceeding the middle third of dentine in the worst-affected FPM. At the time of extraction, the mean age of the patients was 9.8 years (±0.9). GA was used in 196 (97.5%) cases, and 40.8% had not received previous treatment in any of their cFPMs. CONCLUSION: Potentially restorable cFPMs in children is, most of the time, in a cohort of UK patients referred for tier 3 services, being managed by timed extractions under general anasethesia.

Refocusing dental care: A risk-based preventative oral health programme for dentate older people in UK care homes.

BACKGROUND: There is strong evidence for managing the risk of dental caries, notably dose-dependent use of fluoride based on risk. Specific guidance is lacking on higher fluoride use in older people in care homes and prevention is often omitted from dental care plans. OBJECTIVES: To introduce a risk-based preventative approach to existing routine dental care for older people in care homes. METHODS: Three mixed residential and nursing care homes for the frail and elder (>65 years) were selected to participate. All residents were risk assessed based on dependency, dentition status and self-care abilities and consequently placed on the appropriate evidence-based intervention (2800 ppm high dose fluoride toothpaste and/or quarterly fluoride varnish placement). Full mouth ICDAS dental examinations were completed at baseline, 6 months and 12 months. RESULTS: At baseline, 127 risk assessments were completed in which most dentate residents (58.2%, n = 74) were assessed as Risk Level 2/3 (mod/high) whilst edentulous residents were all Risk Level 1 (low) (41.7%, n = 53). Only 13 (26.5%) of the 49 eligible residents completed the 12-month preventative programme. There was a significant difference in root caries (P < .0001), with 17 (51.5%) root lesions changing from active at baseline to arrested at 12 months. CONCLUSIONS: The findings provide early indication of fluoride efficacy, especially on root caries in this vulnerable group, and highlight the challenges of delivering programme's in these complex, changing environments.

Validation of the Lyon classification for GORD diagnosis: acid exposure time assessed by prolonged wireless pH monitoring in healthy controls and patients with erosive oesophagitis.

OBJECTIVE: Acid exposure time (AET) from ambulatory pH studies and reflux oesophagitis are independent measurements used by the Lyon classification to diagnose GORD. This study aimed to validate AET reference ranges and diagnostic thresholds by analysis of 96-hour wireless pH studies from healthy, asymptomatic controls (HCs) and patients with and without oesophagitis. DESIGN: HC and consecutive patients referred for wireless pH studies (off acid suppressants for >7 days) underwent 96-hour pH studies at two tertiary referral centres. Erosive oesophagitis was categorised by the Los Angeles (LA) classification. Linear regression and receiver operating curve (ROC) analysis were performed to define optimal diagnostic cut-offs. RESULTS: Prolonged, 96-hour pH studies were completed in 39 HCs (age 28 (18-53) years, 72% female) and 944 patients (age 46 (16-85) years, 65% female), of whom 136 (14.5%) had reflux oesophagitis. Median AET in HC was 1.3% (upper 95th percentile 4.6%) for any study day and 2.6% (upper 95th percentile 6.9%) for the worst day (24-hour period) during the study. ROC analysis for average AET differentiated HC from patients with moderate-to-severe oesophagitis (LA BCD; sensitivity 87%, specificity 95%, positive predictive value (PPV) 59%, negative predictive value 99% for a cut-off AET of 4.3%; area under the receiver operating curve 0.95). Specificity was higher, but PPV was substantially lower for severe oesophagitis (LA CD). 'Worst-day' analysis provided similar results; however, day-to-day variability was high. CONCLUSION: Diagnostic thresholds for average AET were identified that accurately discriminate between HCs and patients with erosive oesophagitis. The findings provide conditional support for diagnostic criteria for GORD proposed by the Lyon Consensus.

A systematic review and meta-analysis of the role of sugar-free chewing gum on Streptococcus mutans.

BACKGROUND: Preventive strategies targeting Streptococcus mutans may be effective in reducing the global burden of caries. The aim of the current systematic review of published literature was to determine the difference in level of Streptococcus mutans in adults and children who chew sugar-free gum (SFG), compared with those who did not chew gum, who chewed a control gum or received alternatives such as probiotics or fluoride varnish. METHODS: Systematic review (PROSPERO registration No. CRD42018094676) of controlled trials with adult and child participants where chewing of SFG was the main intervention. Databases searched (1 Jan 1946 to 31 August 2020): MEDLINE, EMBASE, PsycINFO, Scopus, Web of Science, Allied and Complimentary Medicine Database, Cochrane Central Register of Controlled Trials (CENTRAL), Open Grey, PROSPERO and the Cochrane library of systematic reviews. 'Search terms included Medical Subject Headings, and free text to cover the following range of constructs: chewing gum, sugar free, oral health, caries, xerostomia, periodontal disease. Data extraction and Risk of Bias assessment was undertaken by three researchers using a modified version of the Cochrane RoB tool (version 1). Data synthesis was conducted using meta-analysis in STATA. RESULTS: Thirteen studies of SFG with micro-organisms as outcomes were identified. The use of SFG significantly reduced the load of Streptococcus mutans (effect size - 0.42; 95% CI - 0.60 to - 0.25) compared to all controls. In seven of the 13 studies the confidence intervals of the effect size estimate included zero, suggesting no effect of the intervention. Twelve trials used xylitol gum only as the basis of the intervention; xylitol gum significantly reduced the load of Streptococcus mutans (effect size - 0.46; 95% CI - 0.64 to - 0.28) in comparison to all controls. There was a moderate level of heterogeneity across the included studies. No adverse effects were recorded. CONCLUSION: Chewing SFG reduces the load of Streptococcus mutans in the oral cavity in comparison to non-chewing controls. Considering the degree of variability in the effect and the moderate quality of the trials included, there is a need for future research exploring the use SFG as a preventive measure for reducing the cariogenic oral bacterial load.

Ethnically diverse urban transmission networks of Neisseria gonorrhoeae without evidence of HIV serosorting.

OBJECTIVE: We aimed to characterise gonorrhoea transmission patterns in a diverse urban population by linking genomic, epidemiological and antimicrobial susceptibility data. METHODS: Neisseria gonorrhoeae isolates from patients attending sexual health clinics at Barts Health NHS Trust, London, UK, during an 11-month period underwent whole-genome sequencing and antimicrobial susceptibility testing. We combined laboratory and patient data to investigate the transmission network structure. RESULTS: One hundred and fifty-eight isolates from 158 patients were available with associated descriptive data. One hundred and twenty-nine (82%) patients identified as male and 25 (16%) as female; four (3%) records lacked gender information. Self-described ethnicities were: 51 (32%) English/Welsh/Scottish; 33 (21%) white, other; 23 (15%) black British/black African/black, other; 12 (8%) Caribbean; 9 (6%) South Asian; 6 (4%) mixed ethnicity; and 10 (6%) other; data were missing for 14 (9%). Self-reported sexual orientations were 82 (52%) men who have sex with men (MSM); 49 (31%) heterosexual; 2 (1%) bisexual; data were missing for 25 individuals. Twenty-two (14%) patients were HIV positive. Whole-genome sequence data were generated for 151 isolates, which linked 75 (50%) patients to at least one other case. Using sequencing data, we found no evidence of transmission networks related to specific ethnic groups (p=0.64) or of HIV serosorting (p=0.35). Of 82 MSM/bisexual patients with sequencing data, 45 (55%) belonged to clusters of ≥2 cases, compared with 16/44 (36%) heterosexuals with sequencing data (p=0.06). CONCLUSION: We demonstrate links between 50% of patients in transmission networks using a relatively small sample in a large cosmopolitan city. We found no evidence of HIV serosorting. Our results do not support assortative selectivity as an explanation for differences in gonorrhoea incidence between ethnic groups.

Epidemiology of Hepatitis E in England and Wales: A 10-Year Retrospective Surveillance Study, 2008-2017.

Indigenous, foodborne transmission of hepatitis E virus genotype 3 (HEV G3) has become recognized as an emerging problem in industrialized countries. Although mostly asymptomatic, HEV G3 infection has a range of outcomes, including mild illness, severe acute hepatitis, and, of particular concern, chronic progressive hepatitis in immunocompromised patients. Public Health England has monitored cases of acute HEV infection in England and Wales since 2003. Between 2010 and 2017, enhanced surveillance using 2 linked laboratory databases and questionnaires on clinical features and risk factors was conducted. There was a year-on-year increase in the number of infections from 2008 (183) through 2016 (1243). Then, in 2017, the number of infections declined (to 912). As reported previously, HEV G3 group 2 (also known as "G3 abcdhij") is the predominant cause of acute infections, and older men are most at risk. Consumption of pork and pork products was significantly higher among patients than in the general population, but other previously reported associations, such as consumption of shellfish, were not observed. Ongoing surveillance is required to monitor future trends and changes in the epidemiology of the virus. The changing methods of animal husbandry and processing and distribution of animal products needs to be further investigated.

Absence of Persistent Hepatitis E Virus Infection in Antibody-Deficient Patients Is Associated With Transfer of Antigen-Neutralizing Antibodies From Immunoglobulin Products.

Background: Persistent hepatitis E virus (HEV) infection is described in a number of immunosuppressive conditions. We aimed to determine the risk of persistent HEV infection in patients with primary or secondary antibody deficiency. Methods: Two hundred forty-five antibody-deficient patients receiving regular immunoglobulin replacement therapy were tested for HEV RNA and anti-HEV immunoglobulin G (IgG). Immunoglobulin products and plasma specimens obtained from 9 antibody-deficient patients before and after intravenous immunoglobulin (IVIG) therapy, 5 recently treated patients with persistent HEV infection, and 5 healthy patients recovered from acute HEV infection were analyzed for anti-HEV IgG and for antibody reacting with HEV antigen. Results: No antibody-deficient patient had detectable plasma HEV RNA. Anti-HEV IgG was detected in 38.8% of patients. All 10 immunoglobulin products tested contained anti-HEV capable of neutralizing HEV antigen. Plasma samples collected following IVIG infusion therapy demonstrated a higher anti-HEV IgG level and neutralizing activity, compared with samples collected before IVIG therapy. Neutralizing activity was similar to that in healthy patients with recent acute HEV infection. Conclusion: The risk of persistent HEV infection in patients with antibody deficiency appears extremely low. This may be due to passive seroprotection afforded by the ubiquitous presence of anti-HEV in immunoglobulin replacement products.

Clinical evaluation of tumour-infiltrating lymphocytes as a prognostic factor in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma.

Clinical evaluation of tumour-infiltrating lymphocytes as a prognostic factor in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma AIMS: The majority of patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OpSCC) have favourable survival outcomes, but a significant minority of individuals will die of their disease. There are currently no definitive criteria with which to identify HPV-associated OpSCC patients with poor outcomes. Recent reports suggest that quantitative evaluation of T-cell subpopulations in OpSCC may be of prognostic value, but the methods used have limited utility in a clinical diagnostic setting. We therefore sought to determine the clinical prognostic utility of tumour-infiltrating lymphocyte (TIL) evaluation in patients with HPV-associated OpSCC within the context of a diagnostic histopathology setting. METHODS AND RESULTS: Representative diagnostic haematoxylin and eosin (H&E)-stained slides from 232 consecutive HPV-associated OpSCC patients were classified as containing a high (TILHi ; diffuse, lymphocytes in >80% of tumour and stroma), moderate (TILMod ; patchy, present in 20-80% of tumour and stroma) or low (TILLo ; sparse or absent, present in <20% of tumour and stroma) TILs. Interobserver reliability was assessed, and TIL category was then correlated with overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses showed statistically significant differences in OS and DFS estimates when TILHi and TILMod patients were compared with TILLo patients (P < 0.0001 for TILHi versus TILLo ; P < 0.0001 for TILMod versus TILLo ). Statistical significance was retained when TILHi and TILMod patients were grouped into a single category (TILHi ) and compared with TILLo patients (P < 0.0001). CONCLUSION: We demonstrate the prognostic utility of TILs in patients with HPV-associated OpSCC in clinical practice. A binary system classifying HPV-associated OpSCC into TILHi and TILLo on the basis of routine H&E staining stratifies patients into those with potentially favourable and unfavourable survival outcomes, respectively.

Promoting breast cancer awareness in older women during the seasonal flu vaccination campaign.

BACKGROUND:: older women are at high risk of presenting with breast cancer when it has reached a late stage, which may be partly because of poor breast cancer awareness. AIM:: the aim of this project was to implement and evaluate a new way of delivering the Promoting Early Presentation (PEP) Intervention during flu vaccination appointments in primary care. The PEP Intervention is a 1-minute intervention, accompanied by a booklet and delivered by primary care health professionals to provide older women with the knowledge, confidence and skills to present promptly on discovering symptoms of breast cancer. METHOD:: health professionals delivered the PEP Intervention to older women at six general practices in south London. The authors measured changes in breast cancer awareness after the intervention and interviewed practice staff about their experiences of using it. FINDINGS:: knowledge of breast symptoms and breast checking was greater in women aged 70 years and above after the implementation than before. Health professionals' found it acceptable and feasible to implement. CONCLUSION:: this intervention is a novel way of increasing breast cancer awareness in older women, which could contribute to earlier presentation and diagnosis of breast cancer in the UK.

Uptake and impact of vaccinating primary school-age children against influenza: experiences of a live attenuated influenza vaccine programme, England, 2015/16.

The 2015/16 influenza season was the third season of the introduction of an intra-nasally administered live attenuated influenza vaccine (LAIV) for children in England. All children aged 2‒6 years were offered LAIV, and in addition, a series of geographically discrete areas piloted vaccinating school-age children 7‒11 years old. Influenza A(H1N1)pdm09 was the dominant circulating strain during 2015/16 followed by influenza B. We measured influenza vaccine uptake and the overall and indirect effect of vaccinating children of primary school -age, by comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot and non-pilot areas in England. Uptake of 57.9% (range: 43.6-72.0) was achieved in the five pilot areas for children aged 5‒11 years. In pilot areas, cumulative emergency department respiratory attendances, influenza-confirmed hospitalisations and intensive care unit admissions were consistently lower, albeit mostly non-significantly, in targeted and non-targeted age groups compared with non-pilot areas. Effect sizes were less for adults and more severe endpoints. Vaccination of healthy primary school-age children with LAIV at moderately high levels continues to be associated with population-level reductions in influenza-related respiratory illness. Further work to evaluate the population-level impact of the programme is required.

Uptake and effectiveness of influenza vaccine in those aged 65 years and older in the United Kingdom, influenza seasons 2010/11 to 2016/17.

BackgroundIn 2016/17, seasonal influenza vaccine was less effective in those aged 65 years and older in the United Kingdom. We describe the uptake, influenza-associated mortality and adjusted vaccine effectiveness (aVE) in this age group over influenza seasons 2010/11-2016/17. Methods: Vaccine uptake in 2016/17 and five previous seasons were measured using a sentinel general practitioners cohort in England; the test-negative case-control design was used to estimate pooled aVE by subtype and age group against laboratory-confirmed influenza in primary care from 2010-2017. Results: Vaccine uptake was 64% in 65-69-year-olds, 74% in 70-74-year-olds and 80% in those aged 75 and older. Overall aVE was 32.5% (95% CI: 11.6 to 48.5); aVE by sub-type was 60.8% (95% CI: 33.9 to 76.7) and 50.0% (95% CI: 21.6 to 68.1) against influenza A(H1N1)pdm09 and influenza B, respectively, but only 5.6% (95% CI: - 39.2 to 35.9) against A(H3N2). Against all laboratory-confirmed influenza aVE was 45.2% (95% CI: 25.1 to 60.0) in 65-74 year olds; - 26.2% (95% CI: - 149.3 to 36.0) in 75-84 year olds and - 3.2% (95% CI: - 237.8 to 68.5) in those aged 85 years and older. Influenza-attributable mortality was highest in seasons dominated by A(H3N2). Conclusions: Vaccine uptake with non-adjuvanted, normal-dose vaccines remained high, with evidence of effectiveness against influenza A(H1N1)pdm09 and B, though poor against A(H3N2), particularly in those aged 75 years and older. Forthcoming availability of newly licensed vaccines with wider use of antivirals can potentially further improve prevention and control of influenza in this group.

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.

BACKGROUND: Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. METHODS: In this randomised controlled trial, we recruited postmenopausal women aged 50-74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. FINDINGS: Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202,638 women: 50,640 (25·0%) to MMS, 50,639 (25·0%) to USS, and 101,359 (50·0%) to no screening. 202,546 (>99·9%) women were eligible for analysis: 50,624 (>99·9%) women in the MMS group, 50,623 (>99·9%) in the USS group, and 101,299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345,570 MMS and 327,775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0-12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p=0·10) with MMS and 11% (-7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (-20 to 31) in years 0-7 and 23% (1-46) in years 7-14, and in the USS group, of 2% (-27 to 26) in years 0-7 and 21% (-2 to 42) in years 7-14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favour of MMS. INTERPRETATION: Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7-14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening. FUNDING: Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal.

Which symptoms are linked to a delayed presentation among melanoma patients? A retrospective study.

BACKGROUND: The incidence of melanoma is rising. Early detection is associated with a more favourable outcome. The factors that influence the timing of a patient's presentation for medical assessment are not fully understood. The aims of the study were to measure the nature and duration of melanoma symptoms in a group of patients diagnosed with melanoma within the preceding 18 months and to identify the symptoms and barriers associated with a delay in presentation. METHODS: A questionnaire was distributed to a random sample of 200 of the 963 melanoma patients who had participated in the Cancer Patient Experience Survey 2010 and were known to be alive 1 year later. Data were collected on symptoms, duration of symptoms prior to presentation and the reasons for not attending a doctor sooner. RESULTS: A total of 159 patients responded to the questionnaire; 74 (47%) were men; mean age was 62 (range 24-90) years. Of the 149 patients who reported a symptom, 40 (27%) had a delayed presentation (i.e. >3 months). A mole growing bigger was the most common symptom and reporting this symptom was significantly associated with a delayed presentation (odds ratio (OR) 2.04, 95% confidence interval (95% CI) 1.14-5.08). Patients aged ≥65 years were less likely to report a barrier to presentation and were less likely to delay than those under 40, although this was of borderline statistical significance (OR 0.28, 95% CI 0.08-1.00). CONCLUSIONS: This study highlights that an enlarging mole is a significant symptom influencing the timing of presentation. Increasing public awareness of the signs of melanoma and of the importance of early presentation is desirable. Health professionals should take advantage of the opportunity to educate patients on such symptoms and signs where feasible. Further exploration of the barriers to presentation in younger people should be considered.

Live attenuated influenza vaccine effectiveness against hospitalisation due to laboratory-confirmed influenza in children two to six years of age in England in the 2015/16 season.

The United Kingdom is introducing a universal annual influenza vaccination programme for children. Live attenuated influenza vaccine (LAIV) effectiveness (VE) against laboratory-confirmed influenza hospitalisation in 2 to 6 year-olds in England was measured in 2015/16 using the screening method. VE adjusted for age, geography and month was 54.5% (95% confidence interval (CI): 31.5% to 68.4%) for all influenza types combined; 48.3% (95% CI: 16.9% to 67.8%) for A(H1N1)pdm09 and 70.6% (95% CI: 33.2% to 87.1%) for B. The findings support on-going programme roll-out.

End-of-season influenza vaccine effectiveness in adults and children, United Kingdom, 2016/17.

IntroductionThe United Kingdom is in the fourth season of introducing a universal childhood influenza vaccine programme. The 2016/17 season saw early influenza A(H3N2) virus circulation with care home outbreaks and increased excess mortality particularly in those 65 years or older. Virus characterisation data indicated emergence of genetic clusters within the A(H3N2) 3C.2a group which the 2016/17 vaccine strain belonged to. Methods: The test-negative case-control (TNCC) design was used to estimate vaccine effectiveness (VE) against laboratory confirmed influenza in primary care. Results: Adjusted end-of-season vaccine effectiveness (aVE) estimates were 39.8% (95% confidence interval (CI): 23.1 to 52.8) against all influenza and 40.6% (95% CI: 19.0 to 56.3) in 18-64-year-olds, but no significant aVE in ≥ 65-year-olds. aVE was 65.8% (95% CI: 30.3 to 83.2) for 2-17-year-olds receiving quadrivalent live attenuated influenza vaccine. Discussion: The findings continue to provide support for the ongoing roll-out of the paediatric vaccine programme, with a need for ongoing evaluation. The importance of effective interventions to protect the ≥ 65-year-olds remains.

Ethnic differences in cancer symptom awareness and barriers to seeking medical help in England.

BACKGROUND: Ethnic differences in cancer symptom awareness and barriers to seeking medical help in the English population are not fully understood. We aimed to quantify these differences, to help develop more effective health campaigns, tailored to the needs of different ethnic groups. METHODS: Using a large national data set (n=38 492) of cross-sectional surveys that used the Cancer Research UK Cancer Awareness Measure, we examined how cancer symptom awareness and barriers varied by ethnicity, controlling for socio-economic position, age and gender. Data were analysed using multivariable logistic regression. RESULTS: Awareness of cancer symptoms was lower in minority ethnic groups than White participants, with the lowest awareness observed among Bangladeshis and Black Africans. Ethnic minorities were more likely than White British to report barriers to help-seeking. South Asians reported the highest emotional barriers, such as lack of confidence to talk to the doctor, and practical barriers, such as worry about many other things. The Irish were more likely than the White British to report practical barriers, such as being too busy to visit a doctor. White British participants were more likely than any other ethnic group to report that they would feel worried about wasting the doctor's time. Overall, Black Africans had the lowest barriers. All differences were statistically significant (P<0.01 level), after controlling for confounders. CONCLUSIONS: Our findings suggest the need for culturally sensitive and targeted health campaigns, focused on improving recognition of cancer symptoms among ethnic minorities. Campaigns should tackle the specific barriers prevalent in each ethnic group.

Effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 mid-season results.

In 2015/16, the influenza season in the United Kingdom was dominated by influenza A(H1N1)pdm09 circulation. Virus characterisation indicated the emergence of genetic clusters, with the majority antigenically similar to the current influenza A(H1N1)pdm09 vaccine strain. Mid-season vaccine effectiveness (VE) estimates show an adjusted VE of 41.5% (95% confidence interval (CI): 3.0-64.7) against influenza-confirmed primary care consultations and of 49.1% (95% CI: 9.3-71.5) against influenza A(H1N1)pdm09. These estimates show levels of protection similar to the 2010/11 season, when this strain was first used in the seasonal vaccine.

Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results.

The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season's adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0-61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6-64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1-68.6) against influenza B. In 2-17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6-94.3) against influenza B and 41.5% (95% CI: -8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17.