Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers.

Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.

Impact of low iodine diets on ablation success in differentiated thyroid cancer: A mixed-methods systematic review and meta-analysis.

BACKGROUND: Debate remains regarding whether to recommend a low iodine diet (LID) before radioactive-iodine treatment and its duration and stringency. This mixed-methods review aimed to determine if iodine status affects treatment success, the most effective diet to reduce iodine status, and how LID impacts wellbeing. METHODS: Five electronic databases were searched until February 2021. An effectiveness synthesis (quantitative studies) and views synthesis (qualitative, survey, and experience-based evidence) were conducted individually and then integrated. Quality assessment was undertaken. RESULTS: Fifty-six quantitative and three qualitative studies were identified. There was greater ablation success for those with an iodine status of <50 mcg/L (or mcg/gCr) compared with ≥250 (odds ratio [OR] = 2.63, 95% confidence interval [CI], 1.18-5.86, n = 283, GRADE certainty of evidence very low). One study compared <50 mcg/L (or mcg/gCr) to 100-199 and showed similar rates of ablation success (OR = 1.59, 95% CI, 0.48-6.15, n = 113; moderate risk of bias). People following a stricter LID before ablation had similar rates of success to a less-strict diet (OR = 0.67, 95% CI, 0.26-1.73, n = 256, GRADE certainty of evidence very low). A stricter LID reduced iodine status more than a less strict (SMD = -0.40, 95% CI, -0.56 to -0.24, n = 816), and reduction was seen after 1 and 2 weeks. The main challenges were a negative impact on psychological health, over restriction, confusion, and difficulty for sub-groups. CONCLUSIONS: Although a LID of 1-2 weeks reduces iodine status, it remains unclear whether iodine status affects treatment success as only a few low-quality studies have examined this. LIDs are challenging for patients. Higher-quality studies are needed to confirm whether a LID is necessary.

Associations between markers of social functioning and depression and quality of life in survivors of head and neck cancer: Findings from the Head and Neck Cancer 5000 study.

OBJECTIVE: To investigate associations between markers of social functioning (trouble with social eating and social contact), depression and health-related quality of life (QOL) among head and neck cancer survivors. METHODS: This cross-sectional analysis included individuals with oral cavity, oropharynx, larynx, salivary gland and thyroid cancers from Head and Neck 5000 alive at 12 months. Trouble with social eating and social contact were measured using items from EORTC QLQ-H&N35 and QOL using EORTC QLQ-C30; responses were converted into a score of 0-100, with a higher score equalling more trouble or better QOL. A HADS subscale score of ≥8 was considered significant depression. Associations between tertiles of trouble with social eating and social contact and depression and QoL were assessed using multivariable logistic and linear regression (with robust errors), respectively. RESULTS: Of 2561 survivors, 23% reported significant depression. The median QOL score was 75.0 (interquartile range 58.3-83.3). For trouble with social eating, after confounder adjustment, those in the intermediate and highest tertiles had higher odds of depression (intermediate: OR = 4.5, 95% CI 3.19-6.45; high: OR = 21.8, 15.17-31.18) and lower QOL (intermediate:ß = -8.7, 95% CI -10.35 to -7.14; high: ß = -24.8, -26.91 to -22.77). Results were similar for trouble with social contact. CONCLUSION: We found strong clinically important associations between markers of social functioning and depression and QOL. More effective interventions addressing social eating and contact are required. These may help survivors regain their independence, reduce levels of isolation and loneliness, and depression, and improve QOL outcomes generally.

A qualitative exploration of attitudes to walking in the retirement life change.

BACKGROUND: Walking is a simple activity that could help to reduce the prevalence of chronic diseases in all populations. Furthermore, an inverse dose-response relationship exists between steps taken and risk of premature death and cardiovascular events in middle-aged and older adults. There is a lack of information on how to effectively engage older adults around retirement age in walking. This qualitative study explored attitudes towards walking in older people with regard to habits, intensity, preferences and strategies for increasing walking behaviour. METHODS: In-depth qualitative interviews were conducted with 26 older adults who were either close to retirement or recently retired. An inductive thematic analysis was conducted. RESULTS: Three themes were identified from the data; 1) Engagement and perceived value of walking; was focused on the meaning of walking for the participant and the attributes they associate with their walking practice. 2) Integration and connectivity of walking; was focused on how participants integrate walking in their daily lives and whether walking can be practiced as a viable means of connectivity. 3) Strategies to increase walking; was focused on what factors motivate participants in their walking practice and what strategies they perceived to be beneficial to increase walking distance and intensity at an individual level. DISCUSSION: The views of walking in people of retirement age were represented within 3 key themes. The factors contained in these themes that may influence future walking practice are discussed with regard to future strategies to promote walking in the retirement life change. CONCLUSION: It may be beneficial to promote qualitative aspects of walking practice and strive for regularity rather than intensity of walking to accrue the social, psychological and intellectual benefits reported by individuals in the retirement life change.

Quality of life following treatment for T1a glottic cancer with surgery or radiotherapy: outcomes from the Head and Neck 5000 cohort.

OBJECTIVES: To investigate the quality of life in patients treated with either RT or surgery alone for T1a glottic carcinoma. DESIGN: This prospective cohort study aims to assess generic- and disease-specific patient-reported QoL in patients treated with either surgery or RT for T1a glottic carcinoma. SETTINGS: Multicentre, secondary care specialist head and neck units in the UK. PARTICIPANTS: Participants were recruited as part of the multicentre, prospective Head and Neck 5000 cohort between 2011 and 2014. MAIN OUTCOME MEASURES: Baseline demographic data were collected. All participants completed the EORTC QLQ C30 and EORTC QLQ H&N35 questionnaires at baseline, 4 months, 12 months and after 36 months. RESULTS: One hundred and twenty three participants received radiotherapy only (n = 68) or surgery only (n = 55). Overall QoL scores were similar between both groups. The median (IQR) EORTC QLQ C30 summary scores at 12 months were 89.3 (79.1, 95.7) and 92.6 (74.4, 97.9) for the radiotherapy and surgery groups respectively. The equivalent summary scores for the EORTC QLQ H&N35 were 91.9 (83.8, 94.9) and 90.4 (85.5, 94.9). There was a modest difference in some QoL subscales between the groups, but no differences existed beyond 4 months. CONCLUSIONS: Patient-reported QoL is similar following either radiotherapy or surgery for T1a glottic carcinoma. These data support current guidance recommended TLM for this disease.

Evaluating shared genetic influences on nonsyndromic cleft lip/palate and oropharyngeal neoplasms.

It has been hypothesised that nonsyndromic cleft lip/palate (nsCL/P) and cancer may share aetiological risk factors. Population studies have found inconsistent evidence for increased incidence of cancer in nsCL/P cases, but several genes (e.g., CDH1, AXIN2) have been implicated in the aetiologies of both phenotypes. We aimed to evaluate shared genetic aetiology between nsCL/P and oral cavity/oropharyngeal cancers (OC/OPC), which affect similar anatomical regions. Using a primary sample of 5,048 OC/OPC cases and 5,450 controls of European ancestry and a replication sample of 750 cases and 336,319 controls from UK Biobank, we estimate genetic overlap using nsCL/P polygenic risk scores (PRS) with Mendelian randomization analyses performed to evaluate potential causal mechanisms. In the primary sample, we found strong evidence for an association between a nsCL/P PRS and increased odds of OC/OPC (per standard deviation increase in score, odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.04, 1.13; p = .000053). Although confidence intervals overlapped with the primary estimate, we did not find confirmatory evidence of an association between the PRS and OC/OPC in UK Biobank (OR 1.02; 95% CI: 0.95, 1.10; p = .55). Mendelian randomization analyses provided evidence that major nsCL/P risk variants are unlikely to influence OC/OPC. Our findings suggest possible shared genetic influences on nsCL/P and OC/OPC.

Survival advantage in patients with human papillomavirus-driven oropharyngeal cancer and variation by demographic characteristics and serologic response: Findings from Head and Neck 5000.

BACKGROUND: Patients with human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) experience better survival than those with HPV-negative OPC. It is unclear whether this benefit varies by demographic characteristics and serologic response. METHODS: Records from 1411 patients with OPC who had HPV serology data were analyzed. HPV status was based on HPV type 16 (HPV16) E6 serology. Participants were followed for a median of 5.9 years, and Cox proportional hazards models were used to estimate hazard ratios (HRs). The association between HPV status and overall survival was analyzed by age group, sex, smoking status, tumor site, HPV antibody levels, and HPV antibody pattern. Models were adjusted for age, sex, smoking status, and comorbidity. RESULTS: For the overall association between HPV status and survival, the fully adjusted HR was 0.43 (95% CI, 0.33-0.56). The HR was 0.19 (95% CI, 0.10-0.35) for participants aged ≤54 years, 0.38 (95% CI, 0.25-0.56) for those aged 55 to 64 years, and 0.73 (95% CI, 0.47-1.13) for those aged ≥65 years (P for interaction = .023). There was no clear evidence for an interaction by sex, smoking status, or tumor site. Survival did not differ according to E6 antibody levels in those who were seropositive. All seropositivity patterns were associated with increased survival compared with a pattern of seronegativity for all antibodies. Patients who are positive for E1, E2, E6, and E7 may experience better survival. CONCLUSIONS: HPV status confers a survival advantage across all groups. This survival advantage is more marked for younger patients. The HPV antibody pattern, but not the antibody level, may also affect survival.

Educational Attainment of Children Born with Unilateral Cleft Lip and Palate in the United Kingdom.

OBJECTIVE: This study evaluated association between functional outcomes in children born with unilateral cleft lip and palate (UCLP) and educational attainment. DESIGN: Cleft Care UK (CCUK) was a United Kingdom (UK) wide cross-sectional study. SETTING: UK Cleft Teams (data collected from all UK sites providing centralized cleft services). PATIENTS, PARTICIPANTS: Five-year olds born with nonsyndromic UCLP (n = 268). MAIN OUTCOME MEASURE(S): National tests for educational attainment Key Stage 1 (KS1) undertaken by children at age 7 were linked to CCUK data to describe differences in educational attainment. Associations between functional outcomes and KS1 results were evaluated using regression analysis. We adjusted for birth month, gender, and an area-based measure of socioeconomic status. RESULTS: Data were available for 205 children with UCLP. These children scored lower than national average (NA) scores across all subject areas, with a 0.62 lower score observed in the Average Point Score (APS; P = .01). There was association between being in a lower category for a cleft related outcomes and poorer KS1 results, with a trend for poorer attainment with higher numbers of poor functional outcomes. Those with 3 or more poor outcomes had a -2.26 (-3.55 to -0.97) lower APS compared to those with 0 to 1 poor outcomes. CONCLUSIONS: Children born with UCLP have poorer educational attainment at age 7 across all subject areas though differences were modest. Children with poor functional outcomes at age 5 had worse educational outcomes age 7. Improvements in functional outcomes could enhance educational outcomes.

Epstein-Barr virus and human papillomavirus serum antibodies define the viral status of nasopharyngeal carcinoma in a low endemic country.

Epstein-Barr virus (EBV) causes nasopharyngeal carcinoma (NPC) in endemic regions, where almost every tumor is EBV-positive. In Western populations, NPC is rare, and human papillomavirus infection (HPV) has been suggested as another viral cause. We validated multiplex serology with molecular tumor markers, to define EBV-positive, HPV-positive and EBV-/HPV-negative NPCs in the United Kingdom, and analyzed survival differences between those groups. Sera from NPC cases (n = 98) and age- and sex-matched controls (n = 142) from the Head and Neck 5000 clinical cohort study were analyzed. IgA and IgG serum antibodies against 13 EBV antigens were measured and compared with EBER in situ hybridization (EBER-ISH) data of 41 NPC tumors (29 EBER-ISH positive, 12 negative). IgG antibodies to EBV LF2 correctly diagnosed EBV-positive NPCs in 28 of 29 cases, while all EBER-ISH negative NPCs were seronegative to LF2 IgG (specificity = 100%, sensitivity = 97%). HPV early antigen serology was compared to HPV molecular markers (p16 expression, HPV DNA and RNA) available for 41 NPCs (13 positive, 28 negative). Serology matched molecular HPV markers in all but one case (specificity = 100%, sensitivity = 92%). EBV and HPV infections were mutually exclusive. Overall, 67% of the analyzed NPCs were defined as EBV-positive, 18% as HPV-positive and 14% as EBV/HPV-negative. There was no statistical evidence of a difference in survival between the three groups. These data provide evidence that both, EBV-positive and HPV-positive NPCs are present in a low incidence country, and that EBV and HPV serum antibodies correlate with the viral status of the tumor.

A systematic review of reviews identifying UK validated dietary assessment tools for inclusion on an interactive guided website for researchers: www.nutritools.org.

Background: Health researchers may struggle to choose suitable validated dietary assessment tools (DATs) for their target population. The aim of this review was to identify and collate information on validated UK DATs and validation studies for inclusion on a website to support researchers to choose appropriate DATs.Design: A systematic review of reviews of DATs was undertaken. DATs validated in UK populations were extracted from the studies identified. A searchable website was designed to display these data. Additionally, mean differences and limits of agreement between test and comparison methods were summarized by a method, weighting by sample size.Results: Over 900 validation results covering 5 life stages, 18 nutrients, 6 dietary assessment methods, and 9 validation method types were extracted from 63 validated DATs which were identified from 68 reviews. These were incorporated into www.nutritools.org. Limits of agreement were determined for about half of validations. Thirty four DATs were FFQs. Only 17 DATs were validated against biomarkers, and only 19 DATs were validated in infant/children/adolescents.Conclusions: The interactive www.nutritools.org website holds extensive validation data identified from this review and can be used to guide researchers to critically compare and choose a suitable DAT for their research question, leading to improvement of nutritional epidemiology research.

Disease trajectories, place and mode of death in people with head and neck cancer: Findings from the 'Head and Neck 5000' population-based prospective clinical cohort study.

BACKGROUND: Few large studies describe initial disease trajectories and subsequent mortality in people with head and neck cancer. This is a necessary first step to identify the need for palliative care and associated services. AIM: To analyse data from the Head and Neck 5000 study to present mortality, place and mode of death within 12 months of diagnosis. DESIGN: Prospective cohort study. PARTICIPANTS: In total, 5402 people with a new diagnosis of head and neck cancer were recruited from 76 cancer centres in the United Kingdom between April 2011 and December 2014. RESULTS: Initially, 161/5402 (3%) and 5241/5402 (97%) of participants were treated with 'non-curative' and 'curative' intent, respectively. Within 12 months, 109/161 (68%) in the 'non-curative' group died compared with 482/5241 (9%) in the 'curative' group. Catastrophic bleed was the terminal event for 10.4% and 9.8% of people in 'non-curative' and 'curative' groups, respectively; terminal airway obstruction was recorded for 7.5% and 6.3% of people in the same corresponding groups. Similar proportions of people in both groups died in a hospice (22.9% 'non-curative'; 23.5% 'curative') and 45.7% of the 'curative' group died in hospital. CONCLUSION: In addition to those with incurable head and neck cancer, there is a small but significant 'curative' subgroup of people who may have palliative needs shortly following diagnosis. Given the high mortality, risk of acute catastrophic event and frequent hospital death, clarifying the level and timing of palliative care services engagement would help provide assurance as to whether palliative care needs are being met.

Range and timing of surgery, and surgical sequences used, in primary repair of complete unilateral cleft lip and palate: The Cleft Care UK study.

OBJECTS: To describe the range of surgery used to repair the lip and palate in the UK with specific interest in the sequence/timing used in complete unilateral cleft lip and palate (cUCLP). SETTING AND SAMPLE POPULATION: The Cleft Care UK study, a cross-sectional study of 268 5-year-olds, born from 2005 to 2007, with complete unilateral cleft lip and palate. MATERIALS & METHODS: Information on surgery was extracted from medical notes by surgeons during research clinics and transcribed onto a standardized questionnaire. RESULTS: Surgical data were available for 251 (94%) children from all cleft centres in the UK (n = 18). Over a two-year period, 32 surgeons used 10 different surgical sequences in primary repair of the cleft lip and palate. The most frequently used sequence was repair of cleft lip and anterior hard palate followed by repair of posterior hard palate and soft palate (70%). Four surgical sequences were used only once. Most surgeons had a preferred sequence, but 38% (11/29) used more than one sequence during the study period. The timing of repair of the lip, the hard palate and the soft palate varied with surgical sequence, and also between surgeons, even adjusting for the different sequences used. CONCLUSION: Despite centralization of cleft services in the UK, there remains considerable variation in both the sequence and timing of surgical repair of cleft lip and palate in infancy. Further work is required to understand whether these factors are associated with differences in outcome.

Closer to the Truth on National Fistula Prevalence After Unilateral Complete Cleft Lip and Palate Repair? The Cleft Care UK Study.

OBJECTIVES: To (1) determine the prevalence of nonperialveolar palatal fistula up to age 5 following repair of unilateral cleft lip and palate (UCLP) in the United Kingdom, (2) examine the association of palatoplasty techniques with fistula occurrence, and (3) describe the frequency of fistula repairs and their success. DESIGN: Cross-sectional study. SETTING: All 11 centralized regional cleft centers in the United Kingdom. PARTICIPANTS: Two hundred sixty-eight children born between 2005 and 2007 recruited by Cleft Care UK, a nationwide cross-sectional study of all 5-year-old children born with nonsyndromic UCLP. MAIN OUTCOME MEASURE: Nonperialveolar palatal fistula prevalence up to age 5. RESULTS: Fistulas were found in 72 children (31.3%, 95% confidence interval: 25.4%-37.7%) and had no significant association with palate repair sequences. Twenty-four fistulas were repaired by age 5, 12 of which had data showing 10 (83.3%) successful repairs. CONCLUSION: The prevalence of nonperialveolar fistulas following primary palatoplasty of UCLP in the United Kingdom was higher than previously reported. This information should be part of the preoperative discussion with families. Prospective collection of the presence of fistulas will be necessary before we can associate the occurrence of fistulas with a surgeon, institution, surgical technique, or protocol of care.

Is There a Correlation Between Nasolabial Appearance and Dentoalveolar Relationships in Patients With Repaired Unilateral Cleft Lip and Palate?

OBJECTIVE: To determine whether a relationship exists between the aesthetic scores given to photographic records of the nasolabial region of patients with repaired unilateral cleft lip and palate (UCLP) and the 5-Year Olds' Index scores of study models for the same participants. DESIGN: Retrospective study. SETTING: University of Bristol Dental Hospital, United Kingdom. PARTICIPANTS: Patients with nonsyndromic UCLP previously enrolled in the Cleft Care UK (CCUK) Study. METHODS: The CCUK participants, who had both study models and photographs (frontal and worm's eye view), were identified and their records retrieved. These were rated by 2 consultants and 2 senior registrars in orthodontics. The 5-Year Olds' Index was used to score the study models, and at a separate sitting, a 5-point Likert scale was used to score the cropped frontal and worm's eye view photographs of the same children. The results were analyzed using intraclass correlation coefficients and Cohen κ. MAIN OUTCOME MEASURES: Correlation between the aesthetic scores of the photographic views and the concordant 5-Year Olds' Index scores of the study models. RESULTS: The intraclass correlation coefficient scores showed very poor agreement between the photographic views and their concordant study models. The level of inter- and intra-rater reliability was strongest when scoring the study models. CONCLUSIONS: There was no agreement between the scores given to various photographic views and their corresponding study models. Scoring the study models using the 5-Year Olds' Index was the most reliable outcome measure for this age-group.

Dietary restriction during the treatment of cancer: results of a systematic scoping review.

BACKGROUND: Diets that restrict energy or macronutrient intake (e.g. fasting/ketogenic diets (KDs)) may selectively protect non-tumour cells during cancer treatment. Previous reviews have focused on a subset of dietary restrictions (DR) or have not performed systematic searches. We conducted a systematic scoping review of DR at the time of cancer treatment. METHODS: MEDLINE, Embase, CINAHL, AMED and Web of Science databases were searched for studies of adults undergoing DR alongside treatment for cancer. Search results were screened against inclusion/exclusion criteria. Data from included studies were extracted by two independent reviewers. Results were summarised narratively. RESULTS: Twenty-three independent studies (34 articles), with small sample sizes, met the inclusion criteria. Four categories were identified: KDs (10 studies), fasting (4 studies), protein restriction (5 studies) and combined interventions (4 studies). Diets were tolerated well, however adherence was variable, particularly for KDs. Biomarker analysis in KDs and fasting resulted in the expected increase in ketones or reduction in insulin-like growth factors, respectively, however they did not reduce glucose. CONCLUSIONS: Future research with adequately powered studies is required to test the effects of each DR intervention on treatment toxicities and outcomes. Further research into improving adherence to DR may improve the feasibility of larger trials.

Outcome Measures in UCLP: The Modified 5-Year-Olds'-Index-Development and Reliability.

OBJECTIVE: Can we reliably discriminate severity within the existing categories of the 5-Year-Olds' Index? DESIGN: Retrospective method comparison and development study. SETTING: School of Oral and Dental Science, University of Bristol. METHODS: Dental study models of 5-year-olds with unilateral cleft lip and palate (UCLP) were collected from the archives of 2 national cleft surveys (n = 351). One hundred randomly selected models were ranked to construct the modified 5-Year-Olds' Index and also scored using a visual analogue scale (VAS). Reliability testing was performed on 51 study models. Visual analogue scale scores were used to aid statistical analysis and investigate the reliability of a VAS for outcome measurement. The modified 5-Year-Olds' Index was then applied to 198 study models of 5-year-olds with UCLP. RESULTS: The modified 5-Year-Olds' Index showed excellent intra and interexaminer agreement (intraclass correlation > 0.94) and good discrimination of severity. When applied to the Cleft Care UK participants (n = 198), the modified 5-Year-Olds' Index showed good discrimination of severity within the better categories (groups 1-3) of the 5-Year-Olds' Index. Visual analogue Scale scores resulted in unacceptable variation between measurements. CONCLUSIONS: The new modified 5-Year-Olds' Index is a reliable method of assessing outcomes at 5 years of age and showed improved discriminatory power between the "better" outcome categories than the original 5-Year-Olds' Index. A VAS was found to be unsuitable for assessing outcome at 5 years of age for children with UCLP.

Squamous cell carcinoma of the nasal cavity: A descriptive analysis of cases from the head and neck 5000 study.

OBJECTIVES: This paper aims to provide contemporary epidemiological data on squamous cell carcinoma (SCC) of the nasal cavity, which represents a rare type of head and neck cancer. DESIGN, SETTING & PARTICIPANTS: A descriptive analysis of people with nasal cavity SCC treated with curative intent from the Head and Neck 5000 study; a multicentre clinical cohort study of people from the UK with head and neck cancer. People with tumours of the nasopharynx, paranasal sinuses and other sub-sites of the head and neck were excluded. MAIN OUTCOME MEASURES: Demographic data and treatment details are presented for all participants. The main outcomes were overall survival and survival according to categories of characteristics (eg, smoker vs non-smoker); these were explored using Kaplan-Meier plots. RESULTS: Thirty people with nasal cavity SCC were included in the study, of which most were male (67%) and current or ex-smokers (70%). The majority (70%) presented with early-stage (T1/2, N0) tumours. Cervical lymph node metastases at presentation were rare, occurring in only one person. Nine people died during the follow-up period (30%). Worse survival outcomes were seen in people with moderate or severe co-morbidities. CONCLUSIONS: This paper provides epidemiological data on nasal cavity SCC in the UK. Patterns of disease and survival outcomes are described, identifying high-risk groups. Further studies should explore whether primary treatment modality alters survival.

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

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

Healthcare professionals' views of the enhanced recovery after surgery programme: a qualitative investigation.

BACKGROUND: The Enhanced Recovery After Surgery (ERAS) programme is an approach to the perioperative care of patients which aims to improve outcomes and speed up recovery after surgery. Although the evidence base appears strong for this programme, the implementation of ERAS has been slow. This study aimed to gain an understanding of the facilitating factors and challenges of implementing the programme with a view to providing additional contextual information to aid implementation. The study had a particular focus on the nutritional elements as these have been highlighted as important. METHODS: The study employed qualitative research methods, guided by the Normalisation Process Theory (NPT) to explore the experiences and opinions of 26 healthcare professionals from a range of disciplines implementing the programme. RESULTS: This study identified facilitating factors to the implementation of ERAS: alignment with evidence based practice, standardising practice, drawing on the evidence base of other specialties, leadership, teamwork, ERAS meetings, patient involvement and education, a pre-operative assessment unit, staff education, resources attached to obtaining The Commissioning for Quality and Innovation (CQUIN) money, the ward layout, data collection and feedback, and adapting the care pathway. A number of implementation challenges were also identified: resistance to change, standardisation affecting personalised patient care, the buy-in of relevant stakeholders, keeping ERAS visible, information provision to patients, resources, palatability of nutritional drinks, aligning different ward cultures, patients going to non-ERAS departments, spreading the programme within the hospital, differences in health issue, and utilising a segmental approach.  CONCLUSIONS: The findings presented here provide useful contextual information from diverse surgical specialties to inform healthcare providers when implementing ERAS in practice. Addressing the challenges and utilising the facilitating factors identified in this study, could speed up the rate at which ERAS is adopted, implemented and embedded.

Are photographs a suitable alternative to dental study casts when assessing primary surgical outcome in children born with unilateral cleft lip and palate?

OBJECTIVE: To compare the use of the 5-year-olds' index on both dental study casts and intraoral photographs when measuring primary surgical outcome for children born with unilateral cleft lip and palate (UCLP). DESIGN: A cross-sectional study. SETTING: Models and photographs collected from cleft units across the UK as part of the CCUK (Cleft Care UK) study were scored by two clinicians at the School of Oral and Dental Sciences, Bristol, UK. PARTICIPANTS: Five-year-old children born with UCLP as part of the CCUK study. One hundred and ninety-eight had dental study casts available and 49 had intraoral photographs available. METHODS: The records of both groups, that is study casts (n = 198) and photographs (n = 49) were scored using the 5-year-olds' index on two occasions by two examiners. RESULTS: Reliability of scoring is reduced for intraoral photographs compared with dental study casts. Using weighted Kappa the inter-rater reliability for dental study casts was 0.72 to 0.77 and the inter-rater reliability for intraoral photographs was 0.52 to 0.59. LIMITATIONS: The photographs and study casts were not matched for each individual and were collected by a number of different clinicians in each unit, both of which will have had an effect on the quality and consistency of the final records. CONCLUSIONS: Dental study casts provide more reliable results and thus still represent the gold standard when assessing primary surgical outcome in cleft care using the 5-year-olds' index.