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.

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.

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.

"Promoting Early Presentation" intervention sustains increased breast cancer awareness in older women for three years: A randomized controlled trial.

Objective In a randomized controlled trial, the Promoting Early Presentation intervention increased older women's breast cancer awareness after two years. We investigated whether this increase was sustained at three years, and the effect on breast screening self-referral. Methods We randomly allocated 867 women attending their final invited breast screening appointment to the Promoting Early Presentation intervention or usual care. We examined breast cancer awareness after three years and breast screening self-referrals after four years. Results Women in the Promoting Early Presentation intervention arm had higher breast cancer awareness at three years than the usual care arm (odds ratio: 10.4; 95% confidence interval: 3.1 to 34.8). There were no differences in proportions self-referring for breast screening between arms, but statistical power was limited. Conclusion The Promoting Early Presentation intervention has a sustained effect on breast cancer awareness in older women. The effect on self-referral for breast screening is unclear.

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.

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.

Role of general practice in the diagnosis of oral cancer.

The incidence of oral cancer is increasing in the United Kingdom. There is evidence that early diagnosis and effective treatment improve survival, but the poor 5-year survival rate (50%), which has not improved for several decades, has been attributed to advanced stage at presentation. To investigate the symptoms associated with cancer of the oral cavity and to explore the role of general practitioners (GP) in the identification and referral of patients, we sent 200 patients questionnaires on the route to diagnosis, symptoms, delay in presentation, and outcomes of consultations with their GP. Of 161 respondents, over half (56%) had been referred to secondary care by their GP and a third (32%) by their dentist. The most commonly reported symptoms were a mouth ulcer (32%), a lump in the face or neck (28%), and pain or soreness in the mouth or throat (27%). Fifteen per cent delayed presentation for more than 3 months. After consultation with a GP (n=109), 53% were referred to a specialist, 22% were referred for tests, 12% were told that their symptom was not serious, and 12% were treated for another condition. GPs have an important role in the identification and referral of people with oral cancer, and the clearly recognised symptoms identified in this study can be used to aid assessment and decision-making. Interventions to promote the prompt identification of oral cancer in general practice such as the opportunistic screening of high-risk patients may help to improve the poor survival rates.

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.

Risk factors and time to symptomatic presentation in leukaemia, lymphoma and myeloma.

BACKGROUND: UK policy aims to improve cancer outcomes by promoting early diagnosis, which for many haematological malignancies is particularly challenging as the pathways leading to diagnosis can be difficult and prolonged. METHODS: A survey about symptoms was sent to patients in England with acute leukaemia, chronic lymphocytic leukaemia (CLL), chronic myeloid leukaemia (CML), myeloma and non-Hodgkin lymphoma (NHL). Symptoms and barriers to first help seeking were examined for each subtype, along with the relative risk of waiting >3 months' time from symptom onset to first presentation to a doctor, controlling for age, sex and deprivation. RESULTS: Of the 785 respondents, 654 (83.3%) reported symptoms; most commonly for NHL (95%) and least commonly for CLL (67.9%). Some symptoms were frequent across diseases while others were more disease-specific. Overall, 16% of patients (n=114) waited >3 months before presentation; most often in CML (24%) and least in acute leukaemia (9%). Significant risk factors for >3 months to presentation were: night sweats (particularly CLL and NHL), thirst, abdominal pain/discomfort, looking pale (particularly acute leukaemias), and extreme fatigue/tiredness (particularly CML and NHL); and not realising symptom(s) were serious. CONCLUSIONS: These findings demonstrate important differences by subtype, which should be considered in strategies promoting early presentation. Not realising the seriousness of some symptoms indicates a worrying lack of public awareness.

Promoting early presentation of breast cancer: a preliminary evaluation of a written intervention.

OBJECTIVES: Older women are more likely to delay presentation with breast cancer, which contributes to poorer survival. We evaluated a written intervention that was designed to provide women with the knowledge, motivation, confidence and skills to present promptly with breast cancer symptoms. METHODS: We assessed acceptability and understanding of the intervention by interviewing 43 women. We used their responses to refine the intervention. We tested the effect of the intervention on breast cancer awareness, confidence and intentions to check breasts and perceived barriers to help-seeking using a self-report questionnaire administered to 61 women prior to and one month after receiving the intervention. Quantitative data were analysed using the McNemar test. RESULTS: Women were not made anxious by the intervention and understood its messages. At one month, a greater proportion of women knew that breast cancer risk increases with age, identified ≥5 non-lump symptoms and reported breast checking at least monthly in comparison to before the intervention was implemented. DISCUSSION: The intervention does not induce anxiety, is understandable, and appears to increase breast cancer awareness. The results provide justification for a more rigorous trial to test efficacy.

An international measure of awareness and beliefs about cancer: development and testing of the ABC.

OBJECTIVES: To develop an internationally validated measure of cancer awareness and beliefs; the awareness and beliefs about cancer (ABC) measure. DESIGN AND SETTING: Items modified from existing measures were assessed by a working group in six countries (Australia, Canada, Denmark, Norway, Sweden and the UK). Validation studies were completed in the UK, and cross-sectional surveys of the general population were carried out in the six participating countries. PARTICIPANTS: Testing in UK English included cognitive interviewing for face validity (N=10), calculation of content validity indexes (six assessors), and assessment of test-retest reliability (N=97). Conceptual and cultural equivalence of modified (Canadian and Australian) and translated (Danish, Norwegian, Swedish and Canadian French) ABC versions were tested quantitatively for equivalence of meaning (≥4 assessors per country) and in bilingual cognitive interviews (three interviews per translation). Response patterns were assessed in surveys of adults aged 50+ years (N≥2000) in each country. MAIN OUTCOMES: Psychometric properties were evaluated through tests of validity and reliability, conceptual and cultural equivalence and systematic item analysis. Test-retest reliability used weighted-κ and intraclass correlations. Construction and validation of aggregate scores was by factor analysis for (1) beliefs about cancer outcomes, (2) beliefs about barriers to symptomatic presentation, and item summation for (3) awareness of cancer symptoms and (4) awareness of cancer risk factors. RESULTS: The English ABC had acceptable test-retest reliability and content validity. International assessments of equivalence identified a small number of items where wording needed adjustment. Survey response patterns showed that items performed well in terms of difficulty and discrimination across countries except for awareness of cancer outcomes in Australia. Aggregate scores had consistent factor structures across countries. CONCLUSIONS: The ABC is a reliable and valid international measure of cancer awareness and beliefs. The methods used to validate and harmonise the ABC may serve as a methodological guide in international survey research.

Rate of latent tuberculosis infection detected by occupational health screening of nurses new to a london teaching hospital.

The prevalence of latent tuberculosis infection in a cohort of nurses new to a London hospital was 7.6% (13 of 171), using an interferon-gamma (IFN-gamma) release assay, and 16.2% (24 of 148), using the tuberculin skin test. On multivariate analysis, birth in a country with tuberculosis prevalence of more than 40 cases per 100,000 population was associated with positive results of both the IFN-gamma release assay and the tuberculin skin test.

Treating high grade gliomas in the elderly: the end of ageism?

Introduction Treating high grade gliomas in the elderly is a challenge for multidisciplinary teams. Most studies on this topic exclude patients aged >65 and a Karnofsky Performance Status (KPS) score of <70, a group most likely to have a poor outcome. We undertook this study to analyze the outcomes in a cohort of patients which included such patients. Methods Ours was a retrospective cohort study. About 71 consecutive patients with high grade gliomas, who were seen in the neurooncology clinic in 2004, were included. The case records of these patients were scrutinized for the demographic, clinical data, follow-up and survival. The cohort was divided into two groups; Age > or =65 and age <65 for analysis. The factors influencing survival were analyzed using the Cox's proportional hazards model in each group. Results In the age group > or =65 years, patients treated with a radical resection +/- adjuvant therapy had a lower risk of death (hazard ratio 0.14, 95%CI 0.04-0.51, P = 0.003) when compared to patients undergoing a biopsy +/- adjuvant therapy and palliative treatment. In the group <65 years, the greater the age, greater was the risk of death (hazard ratio 2.05, 95%CI 1.13-3.73, P = 0.01). The median survival was 12 months in the group <65 years and 5 months in age > or =65 years (P = 0.001). In the group > or =65 years, those patients who had radical resection +/- adjuvant treatment had a median survival of 7 months as compared to 3 months in the patients who had biopsy +/- adjuvant treatment (P = 0.003). KPS, presence of co-morbidities, duration of symptoms, location of the lesion and sex were not found to be significant independent predictors of survival in our study. Conclusions Age is an important predictor of survival in younger patients, however in the elderly treatment matters most. Elderly patients undergoing radical surgery +/- adjuvant treatment had a longer median survival as compared to the elderly patients undergoing a biopsy +/- adjuvant treatment. KPS was not found to be a significant independent predictor of survival probably because of underrepresentation of patients with poor KPS. Radical treatment should not be denied to elderly patients who are deemed fit as the outcome is significantly better.

Evaluation of the potential risk of occupational asthma in dentists exposed to contaminated dental unit waterlines.

INTRODUCTION: Most of the organisms isolated from dental unit waterlines (DUWL) are Gram-negative bacteria, which contain cell wall endotoxin. A consequence of endotoxin exposure is the exacerbation of asthma. OBJECTIVES: This study examined the prevalence and onset of asthma among dentists and determined whether or not these were associated with the microbiological quality of DUWL in their practices. METHODS: 266 randomly selected dentists (100 from rural Northern Ireland, 166 from London) completed a health questionnaire, which included questions on prevalence and time of onset of asthma. Water samples taken from the dental handpieces and surgery washbasin cold taps in all the practices were analysed using standard techniques. The questionnaire data were evaluated using both single and multivariable logistic regression. The variables considered were: smoking; surgery location; time treating patients per week; DUWL counts of Pseudomonas aeruginosa, total Pseudomonas spp., fungi, Mycobacterium spp., total aerobic colony counts (ACC) at 22 degrees C and 37 degrees C. RESULTS: There was no significant association between any of the variables tested in dentists and a history of asthma. A subgroup analysis was performed on dentists (n=33) who reported developing asthma since they started dental training. The final multivariable model indicated that passive smoking (OR 0.08, 95% CI 0.01-0.87, P=0.038) and total aerobic counts of >200 cfu/ml at 37 degrees C (OR 6.72, 95% CI 1.15-39.24, P=0.034) were significant variables for developing asthma since starting training as a dentist. ACC were significantly higher in London (P<0.0001) and London dentists were more likely to have developed asthma since they started training than their Northern Ireland counterparts (OR 4.4, 95% CI 1.09-17.72, P=0.033). CONCLUSIONS: This study suggests that the temporal onset of asthma may be associated with occupational exposure to contaminated DUWL among dentists in London and Northern Ireland.