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.

Migration and differentiation of muscle stem cells are coupled by RhoA signalling during regeneration.

Skeletal muscle is highly regenerative and is mediated by a population of migratory adult muscle stem cells (muSCs). Effective muscle regeneration requires a spatio-temporally regulated response of the muSC population to generate sufficient muscle progenitor cells that then differentiate at the appropriate time. The relationship between muSC migration and cell fate is poorly understood and it is not clear how forces experienced by migrating cells affect cell behaviour. We have used zebrafish to understand the relationship between muSC cell adhesion, behaviour and fate in vivo. Imaging of pax7-expressing muSCs as they respond to focal injuries in trunk muscle reveals that they migrate by protrusive-based means. By carefully characterizing their behaviour in response to injury we find that they employ an adhesion-dependent mode of migration that is regulated by the RhoA kinase ROCK. Impaired ROCK activity results in reduced expression of cell cycle genes and increased differentiation in regenerating muscle. This correlates with changes to focal adhesion dynamics and migration, revealing that ROCK inhibition alters the interaction of muSCs to their local environment. We propose that muSC migration and differentiation are coupled processes that respond to changes in force from the environment mediated by RhoA signalling.

Epidemiological Impact of the Pediatric Live Attenuated Influenza Vaccine (LAIV) Program on Group A Streptococcus (GAS) Infection in England.

Background: Influenza is known to predispose to secondary bacterial infections including invasive group A streptococcal (iGAS) disease. The universal pediatric live attenuated influenza vaccine (LAIV) program introduced in England from the 2013/2014 influenza season was implemented incrementally, introducing cohorts of children annually to 2-16 years of coverage. Additionally, from the beginning of the program, discrete pilot areas offered LAIV vaccination to all primary school-age children, allowing for a unique comparison of infection rates between pilot and nonpilot areas during the program rollout. Methods: Cumulative incidence rate ratios (IRRs) of GAS infections (all), scarlet fever (SF), and iGAS infection within each season by age group were compared for pilot and nonpilot areas using Poisson regression. The overall effect of the pilot program in the pre- (2010/2011-2012/2013 seasons) and postintroduction (2013/2014-2016/2017 seasons) periods was assessed using negative binomial regression by comparing changes in incidence between pilot/nonpilot areas (ratio of IRR [rIRR]). Results: Reductions in IRRs of GAS and SF were observed within most post-LAIV program seasons, among the age groups 2-4 and 5-10 years. Significant reductions were seen among 5-10 years (rIRR, 0.57; 95% CI, 0.45-0.71; P < .001), 2-4 years (rIRR, 0.62; 95% CI, 0.43-0.90; P = .011), and 11-16 years (rIRR, 0.63; 95% CI, 0.43-0.90; P = .018) for GAS infections when assessing the overall effect of the program. Conclusions: Our findings suggest that vaccination with LAIV may be associated with a reduced risk of GAS infection and support attaining high uptake of childhood influenza vaccination.

An intercountry comparison of the impact of the paediatric live attenuated influenza vaccine (LAIV) programme across the UK and the Republic of Ireland (ROI), 2010 to 2017.

Background: The universal paediatric live attenuated influenza vaccine (LAIV) programme commenced in the United Kingdom (UK) in 2013/2014. Since 2014/2015, all pre-school and primary school children in Scotland and Northern Ireland have been offered the vaccine. England and Wales incrementally introduced the programme with additional school age cohorts being vaccinated each season. The Republic of Ireland (ROI) had no universal paediatric programme before 2017. We evaluated the potential population impact of vaccinating primary school-aged children across the five countries up to the 2016/2017 influenza season. Methods: We compared rates of primary care influenza-like illness (ILI) consultations, confirmed influenza intensive care unit (ICU) admissions, and all-cause excess mortality using standardised methods. To further quantify the impact, a scoring system was developed where each weekly rate/z-score was scored and summed across each influenza season according to the weekly respective threshold experienced in each country. Results: Results highlight ILI consultation rates in the four seasons' post-programme, breached baseline thresholds once or not at all in Scotland and Northern Ireland; in three out of the four seasons in England and Wales; and in all four seasons in ROI. No differences were observed in the seasons' post-programme introduction between countries in rates of ICU and excess mortality, although reductions in influenza-related mortality were seen. The scoring system also reflected similar results overall. Conclusions: Findings of this study suggest that LAIV vaccination of primary school age children is associated with population-level benefits, particularly in reducing infection incidence in primary care.

A Systematic Review and Meta-Analysis of the Role of Sugar-Free Chewing Gum on Plaque Quantity in the Oral Cavity.

Background: The aim of this systematic review of published literature was to answer the research question, "What is the difference in the level of plaque quantity, in adults and children who chew sugar-free gum (SFG), compared with those who do not chew SFG, who do not chew gum, or who use alternatives such as probiotics or fluoride varnish?". Methods: The systematic review [registered on PROSPERO 2018 (CRD42018094676)] included studies on adults and children with chewing of SFG as the main intervention, where "sugar" referred to monosaccharides and disaccharides. Included studies were in English and corresponded to primary research published between 1946 and 2020. The search conducted spanned all relevant databases using both Medical Subject Headings (MESH) and free text with combinations of "chewing gum," "sugar-free," "caries," "xerostomia," "periodontal disease." Results: Eight articles included plaque quantity as part of their outcomes. Meta-analysis showed that SFG significantly reduced plaque quantity (effect size-0.778; 95% CI-1.167 to-0.39). The correlation between the baseline and the end of study data was assumed to be 0.95 for the control and 0.65 for the SFG group. A sensitivity analysis was conducted with the pre- to post-test correlation, set at 0.95 for the SFG group. This gave an effect size of-1.098 (95% CI-1.539 to-0.656) with I 2 = 89.73%. When looking more specifically at xylitol gum, the results of the meta-analysis showed that it significantly reduced plaque quantity (effect size-0.743; 95% CI-1.148 to-0.338). There was a high degree of heterogeneity between studies with I 2 = 86.0%. Conclusion: There is some evidence that chewing sugar-free gum, in particular xylitol SFG, reduces the quantity of plaque in the oral cavity in comparison to non SFG chewing or no chewing controls. Further research with improved design, lengthier timeframes and higher number of participants should be considered. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=94676.

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.

Uptake and impact of vaccinating primary school children against influenza: Experiences in the fourth season of the live attenuated influenza vaccination programme, England, 2016/2017.

BACKGROUND: In the 2016/2017 influenza season, England was in its fourth season of the roll-out of a live-attenuated influenza vaccine (LAIV) targeted at healthy children aged two to less than 17 years. For the first time, all healthy children aged 2 to 8 years were offered LAIV at national level in 2016/2017. Since the commencement of the programme in 2013/2014, a series of geographically discrete pilot areas have been in place where quadrivalent LAIV was also offered to all school age children. In 2016/2017, these were children aged 8 to 11 years, other than those targeted by the national programme. METHODS: We evaluated the overall and indirect impact of vaccinating primary school age children, on the population of England, by measuring vaccine uptake levels and comparing cumulative disease incidence through various influenza surveillance schemes, in targeted and non-targeted age groups in pilot and non-pilot areas in 2016/2017. RESULTS: Our findings indicate that cumulative primary care influenza-like consultations, primary and secondary care swab positivity, influenza confirmed hospitalisations and emergency department attendances in pilot areas were overall lower than those observed in non-pilot areas; however, significant differences were not always observed in both targeted and non-targeted age groups. Excess mortality was higher in pilot areas compared with non-pilot areas. CONCLUSIONS: These results are similar to earlier seasons of the programme indicating the importance and continuing support of vaccinating all primary school children with LAIV to reduce influenza related illness across the population, although further work is needed to understand the differences in excess mortality.

Third molar development in a London population of White British and Black British or other Black ethnicity.

Population differences in dental development between Black and White ethnic groups have been debated but not previously studied in the UK. Using inappropriate data for dental age estimation (DAE) could lead to erroneous results and injustice. Data were collected from dental panoramic radiographs of 5590 subjects aged 6-24 years in a teaching hospital archive. Demirjian stages were determined for left-sided teeth and third molars and data collected regarding hypodontia and third molar agenesis. Third molar development in self-assigned Black British, including other self-assigned Black ethnicity, was compared with that of self-assigned White British subjects. Data were compared for males and females in the two ethnic groups using T-tests for Demirjian Stages A-G of third molar development and Mann-Whitney tests for Stage H once a cut-off age at the maximum age for Stage G had been imposed. Third molar development occurred earlier in subjects of Black ancestry compared to those of White ancestry. While both ethnic groups showed large age ranges for every third molar stage, in female subjects these generally occurred at least 1.5 years earlier, and in males at least one year earlier. Hypodontia and third molar agenesis were more prevalent in White British, but the ethnic difference in third molar development persisted in subjects with complete dentitions. This is a large study that confirms ethnic differences in a London population, emphasises the difficulties of establishing the 18-year-old threshold using DAE, and confirms the risk of overestimating the age of individuals of Black ethnicity using White ethnic reference data.

Impact of the childhood influenza vaccine programme on antibiotic prescribing rates in primary care in England.

Vaccines are a key part of the global strategy to tackle antimicrobial resistance (AMR) since prevention of infection should reduce antibiotic use. England commenced national rollout of a live attenuated influenza vaccine (LAIV) programme for children aged 2-3 years together with a series of geographically discrete pilot areas for primary school age children in 2013 extending to older children in subsequent seasons. We investigated vaccine programme impact on community antibiotic prescribing rates. Antibiotic prescribing incidence rates for respiratory (RTI) and urinary tract infections (UTI; controls) were calculated at general practice (GP) level by age category (children<=10 years/adults) and season for LAIV pilot and non-pilot areas between 2013/14 and 2015/16. To estimate the LAIV (primary school age children only) intervention effect, a random effects model was fitted. A multivariable random-effects Poisson regression investigated the association of antibiotic prescribing rates in children with LAIV uptake (2-3-year-olds only) at GP practice level. RTI antibiotic prescribing rates for children <=10 years and adults showed clear seasonal trends and were lower in LAIV-pilot and non-pilot areas after the introduction of the LAIV programme in 2013. The reductions for RTI prescriptions (children) were similar (within 3%) in all areas, which coincided with the start the UK AMR strategy. Antibiotic prescribing was significantly (p < 0.0001) related to LAIV uptake in 2-3-year-olds with antibiotic prescribing reduced by 2.7% (95% CI: 2.1% to 3.4%) for every 10% increase in uptake. We found no evidence the LAIV programme for primary school age children resulted in reductions in RTI antibiotic prescribing, however we detected a significant inverse association between increased vaccine uptake in pre-school age children and antibiotic prescribing at GP level. The temporal association of reduced RTI and UTI antibiotic prescribing with the launch of the UK's AMR Strategy in 2013 highlights the importance of a multifaceted approach to tackle AMR.

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.

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.

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.

Quantitative tooth wear analysis of index teeth compared to complete dentition.

OBJECTIVES: Recent software advancements have facilitated quantification of erosive tooth wear progression using intraoral scans. This paper investigated if wear on commonly affected surfaces (central incisors and first molars) was representative of wear on the full arch. METHODS: Bimaxillary digital intraoral scans (True Definition, 3 M, USA) of patients (n = 30) from the monitoring arm of the Radboud Tooth Wear Project, were taken at baseline and at 3 years (+/-10months). The occlusal/incisal surface of each tooth (excluding 3rd molars) was analysed for volume change and volume change per mm of analysed surface area in WearCompare (www.leedsdigitaldentistry.com/Wearcompare) following previously published protocols. Data were normal, descriptives and multi-level linear regression analysis was performed in Stata v15.1 taking patient level and surface type data into account. RESULTS: Data from 556 surfaces in 29 patients were included in analysis. Per patient, mean volume loss (95 % CI) was -0.91mm3(-1.28,-0.53) on all surfaces, -1.85mm3(-2.83,-0.86) on index surfaces, -2.53mm3(-3.91,-1.15) on molar surfaces and -0.83 mm3(-1.34,-0.31) on upper central incisal surfaces. Statistical differences were observed between analysing all surfaces and index teeth(p = 0.002) in addition to molar surfaces(p < 0.0001). Mean volume loss per mm2 of surface analysed was -0.024 mm3 (-0.031,-0.017), -0.028mm3 (-0.041,-0.014), -0.030mm3 (-0.046,-0.013) and -0.025mm3 (-0.041,-0.010) for all surfaces, index surfaces, first molar surfaces and central incisor surfaces respectively with no statistical differences between groups. CONCLUSIONS: Wear on upper central incisors was not statistically different to full arch wear analysis. If the surface area is standardised, wear on both index surfaces are statistically similar to wear on the full arch. CLINICAL SIGNIFICANCE: These results suggest that analysing rates of wear on index teeth can be a resource-saving substitute for analysing rates of wear on the entire dentition, provided the surface area is standardised. If whole surfaces are analysed, the molar surfaces will show greater rates of wear.

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.

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.

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.