Management of chemotherapy hypersensitivity reactions and desensitization: An SGO clinical practice statement.

OBJECTIVE: The goal of this practice statement is to help members and their multidisciplinary teams recognize infusion reactions and hypersensitivity reactions in the clinical setting. It will provide recommendations to help guide response to reactions and desensitization when appropriate, to promote safe use of chemotherapeutic agents among all providers in the delivery process. METHODS: A multi-disciplinary team of healthcare professionals from the Society of Gynecologic Oncology Education Committee collaborated to review peer reviewed literature and guidelines to develop a practice statement on the management of chemotherapy hypersensitivity reactions and desensitization regimens. RESULTS: There is always potential for a patient to have a reaction to any medication, with both infusion reactions and hypersensitivity reactions potentially occurring in the treatment of gynecologic cancers. Premedication to prevent reactions should be given at least prior to infusion for regimens that include the most common agents associated with reactions. At the time when reaction is occurring it might be difficult to distinguish between an infusion reaction versus true hypersensitivity given the similarities in signs and symptoms, therefore it is important that orders to manage reactions be included in every chemotherapy order set so the infusion nurse can provide immediate interventions while waiting for the provider to arrive to assess the patient. Desensitization is a potential option to allow the patient to continue to receive the offending agent. While a variety of desensitization regimens have been presented in the literature, the goal is to minimize steps and variability to decrease opportunity for errors during chemotherapy preparation or administration. CONCLUSION: Incorporating a review of the literature and clinical experience from the SGO Education Committee, this paper provides an overview of current approaches for prevention and management of reactions to commonly used chemotherapy agents for gynecologic cancers.

Evaluation of the reach and impact of a UK campaign highlighting obesity as a cause of cancer among the general public and Members of Parliament.

OBJECTIVES: 'Overweight and obesity' is the second biggest preventable cause of cancer after smoking. In 2018, Cancer Research UK launched an awareness raising campaign about the link between overweight and obesity and cancer risk. This study aimed to evaluate the reach and impact of the campaign. STUDY DESIGN: This study was a repeated cross-sectional online survey. METHODS: The campaign consisted of six elements including the main message that 'Obesity is a cause of cancer'. UK adults and Members of Parliament (MPs) were surveyed before the campaign (W1; n = 2124 and n = 151), 1 month (W2; n = 2050 and n = 151) and 3 months after the campaign (W3; n = 2059 and MPs not surveyed). Outcome measures were campaign reach, awareness of overweight and obesity as risk factors for cancer, attitudes towards individuals who are overweight or obese, support for policies to reduce obesity and reactions to the campaign. RESULTS: Overall, 76.2% of MPs and just under half of the public (47.5% in W2 and 36.8% in W3) reported having seen the campaign. Unprompted awareness of obesity as a risk factor increased among the public from 17.1% at W1 to 43.3% in W2 (odds ratio 3.71, 95% confidence interval 3.18-4.33) and 30.3% in W3 (odds ratio 2.11, 95% confidence interval 1.80-2.47). A similar pattern was seen for prompted awareness and among MPs. There were no consistent changes in attitudes towards overweight individuals or support for policies to reduce obesity. CONCLUSIONS: This evaluation suggests that the campaign achieved the primary objective of increasing awareness of the link between obesity and cancer without increasing negative attitudes towards individuals who are overweight or obese.

Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects.

BACKGROUND: Smoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers. METHOD: A smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989-1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA). RESULTS: Altogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results. CONCLUSION: This study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk.

Isolated pituitary fossa metastasis from a primary tonsillar squamous cell carcinoma: case report.

OBJECTIVE: This paper presents a case of an isolated pituitary fossa metastasis on a background of a previously treated tonsillar squamous cell carcinoma. CASE REPORT: A 64-year-old male, diagnosed with a primary p16-negative squamous cell carcinoma in the right tonsil, was treated with a course of chemoradiotherapy with curative intent. Positron emission tomography/computed tomography, performed at six months post-treatment, revealed a good local response and no distant metastases. The patient was placed on routine follow up at two-monthly intervals. Two months into follow up, he presented with a right-sided oculomotor nerve palsy and partial Horner's syndrome. Imaging and biopsy revealed a pituitary fossa metastasis (p16-negative squamous cell carcinoma), and a further positron emission tomography/computed tomography visualised this lesion. He was deemed unsuitable for further intervention and underwent palliative radiotherapy for symptom control. CONCLUSION: This case represents the first reported isolated pituitary fossa metastasis from a tonsillar squamous cell carcinoma. A high degree of clinical suspicion is recommended, along with a low threshold for biopsy and a cautioned use of positron emission tomography/computed tomography, when investigating such patients.

Correction: External validation of risk prediction models for incident colorectal cancer using UK Biobank.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Women's views on screening for Type 2 diabetes after gestational diabetes: a systematic review, qualitative synthesis and recommendations for increasing uptake.

AIM: Many women do not attend recommended glucose testing following a pregnancy affected by gestational diabetes (GDM). We aimed to synthesize the literature regarding the views and experiences of women with a history of GDM on postpartum glucose testing, focusing on barriers and facilitators to attendance. METHODS: We systematically identified qualitative studies that examine women's experiences following GDM relating to glucose testing (diabetes screening) or experience of interventions to promote uptake of testing. We conducted a thematic synthesis to develop descriptive and then analytical themes, then developed recommendations to increase uptake based on the findings. We evaluated the quality of each study and the confidence that we had in the recommendations using published checklists. RESULTS: We included 16 articles after screening 23 160 citations and 129 full texts. We identified four themes of influences relating to the healthcare system and personal factors that affected both ability and motivation to attend: relationship with health care, logistics of appointments and tests, family-related practicalities and concern about diabetes. We developed 10 recommendations addressing diabetes risk information and education, and changes to healthcare systems to promote increased attendance at screening in this population, most with high or moderate confidence. CONCLUSIONS: We have identified a need to improve women's understanding about Type 2 diabetes and GDM, and to adjust healthcare provision during and after pregnancy to decrease barriers and increase motivation for testing. Encouraging higher uptake by incorporating these recommendations into practice will enable earlier management of diabetes and improve long-term outcomes.

Polyornithine-based polyplexes to boost effective gene silencing in CNS disorders.

Gene silencing therapies have successfully suppressed the translation of target proteins, a strategy that holds great promise for the treatment of central nervous system (CNS) disorders. Advances in the current knowledge on multimolecular delivery vehicles are concentrated on overcoming the difficulties in delivery of small interfering (si)RNA to target tissues, which include anatomical accessibility, slow diffusion, safety concerns, and the requirement for specific cell uptake within the unique environment of the CNS. The present work addressed these challenges through the implementation of polyornithine derivatives in the construction of polyplexes used as non-viral siRNA delivery vectors. Physicochemical and biological characterization revealed biodegradability and biocompatibility of our polyornithine-based system and the ability to silence gene expression in primary oligodendrocyte progenitor cells (OPCs) effectively. In summary, the well-defined properties and neurological compatibility of this polypeptide-based platform highlight its potential utility in the treatment of CNS disorders.

Protocol of a two arm randomised, multi-centre, 12-month controlled trial: evaluating the impact of a Cognitive Behavioural Therapy (CBT)-based intervention Supporting UPtake and Adherence to antiretrovirals (SUPA) in adults with HIV.

BACKGROUND: Delay to start antiretroviral therapy (ART) and nonadherence compromise the health and wellbeing of people living with HIV (PLWH), raise the cost of care and increase risk of transmission to sexual partners. To date, interventions to improve adherence to ART have had limited success, perhaps because they have failed to systematically elicit and address both perceptual and practical barriers to adherence. The primary aim of this study is to determine the efficacy of the Supporting UPtake and Adherence (SUPA) intervention. METHODS: This study comprises 2 phases. Phase 1 is an observational cohort study, in which PLWH who are ART naïve and recommended to take ART by their clinician complete a questionnaire assessing their beliefs about ART over 12 months. Phase 2 is a randomised controlled trial (RCT) nested within the observational cohort study to investigate the effectiveness of the SUPA intervention on adherence to ART. PLWH at risk of nonadherence (based on their beliefs about ART) will be recruited and randomised 1:1 to the intervention (SUPA intervention + usual care) and control (usual care) arms. The SUPA intervention involves 4 tailored treatment support sessions delivered by a Research Nurse utilising a collaborative Cognitive Behavioural Therapy (CBT) and Motivational Interviewing (MI) approach. Sessions are tailored to individual needs and preferences based on the individual patient's perceptions and practical barriers to ART. An animation series and intervention manual have been developed to communicate a rationale for the personal necessity for ART and illustrate concerns and potential solutions. The primary outcome is adherence to ART measured using Medication Event Monitoring System (MEMS). Three hundred seventy-two patients will be sufficient to detect a 15% difference in adherence with 80% power and an alpha of 0.05. Costs will be compared between intervention and control groups. Costs will be combined with the primary outcome in cost-effectiveness analyses. Quality adjusted life-years (QALYs) will also be estimated over the follow-up period and used in the analyses. DISCUSSION: The findings will enable patients, healthcare providers and policy makers to make informed decisions about the value of the SUPA intervention. TRIAL REGISTRATION: The trial was retrospectively registered 21/02/2014, ISRCTN35514212 .

The associations between the response efficacy and objective and subjective change in physical activity and diet in the Information and Risk Modification trial.

OBJECTIVES: Many health promotion campaigns and interventions focussing on improving health-related behaviours have been based on targeting response efficacy. This is based on the assumption that response efficacy is an important modifiable determinant of behaviour change. This study aimed to quantify the association between response efficacy and objective and subjective measures of physical activity and diet. STUDY DESIGN: Prospective cohort analysis of data from a randomised controlled trial. METHODS: A total of 953 participants were assessed for response efficacy at baseline and 12 weeks following randomisation to interventions to increase physical activity and improve diet. Subjective measures were collected via a self-report questionnaire that included two questions used to derive the Cambridge Index of physical activity and questions about daily or weekly fruit and vegetable, whole grain, meat and fish intake, based on the dietary guidelines to lower cardiovascular risk. Objective measures were quantified using accelerometers and plasma carotenoids. RESULTS: The mean change in response efficacy for physical activity was +0.5 (standard deviation [SD] 2.0) and for diet was +0.5 (SD 2.1).There were no clinically or statistically significant associations between baseline or change in response efficacy and objective and subjective measures of physical activity or objective measures of diet. There was a small statistically significant association between baseline response efficacy and change in self-reported wholegrain consumption, but this is unlikely to be clinically significant. CONCLUSIONS: Response efficacy is not a fundamental determinant of diet and physical activity and should not be the main focus of interventions targeting these behaviours.

External validation of risk prediction models for incident colorectal cancer using UK Biobank.

BACKGROUND: This study aimed to compare and externally validate risk scores developed to predict incident colorectal cancer (CRC) that include variables routinely available or easily obtainable via self-completed questionnaire. METHODS: External validation of fourteen risk models from a previous systematic review in 373 112 men and women within the UK Biobank cohort with 5-year follow-up, no prior history of CRC and data for incidence of CRC through linkage to national cancer registries. RESULTS: There were 1719 (0.46%) cases of incident CRC. The performance of the risk models varied substantially. In men, the QCancer10 model and models by Tao, Driver and Ma all had an area under the receiver operating characteristic curve (AUC) between 0.67 and 0.70. Discrimination was lower in women: the QCancer10, Wells, Tao, Guesmi and Ma models were the best performing with AUCs between 0.63 and 0.66. Assessment of calibration was possible for six models in men and women. All would require country-specific recalibration if estimates of absolute risks were to be given to individuals. CONCLUSIONS: Several risk models based on easily obtainable data have relatively good discrimination in a UK population. Modelling studies are now required to estimate the potential health benefits and cost-effectiveness of implementing stratified risk-based CRC screening.

Renal haemodynamics and oxygenation during and after cardiac surgery and cardiopulmonary bypass.

Acute kidney injury (AKI) is a common complication following cardiac surgery performed on cardiopulmonary bypass (CPB) and has important implications for prognosis. The aetiology of cardiac surgery-associated AKI is complex, but renal hypoxia, particularly in the medulla, is thought to play at least some role. There is strong evidence from studies in experimental animals, clinical observations and computational models that medullary ischaemia and hypoxia occur during CPB. There are no validated methods to monitor or improve renal oxygenation during CPB, and thus possibly decrease the risk of AKI. Attempts to reduce the incidence of AKI by early transfusion to ameliorate intra-operative anaemia, refinement of protocols for cooling and rewarming on bypass, optimization of pump flow and arterial pressure, or the use of pulsatile flow, have not been successful to date. This may in part reflect the complexity of renal oxygenation, which may limit the effectiveness of individual interventions. We propose a multi-disciplinary pathway for translation comprising three components. Firstly, large-animal models of CPB to continuously monitor both whole kidney and regional kidney perfusion and oxygenation. Secondly, computational models to obtain information that can be used to interpret the data and develop rational interventions. Thirdly, clinically feasible non-invasive methods to continuously monitor renal oxygenation in the operating theatre and to identify patients at risk of AKI. In this review, we outline the recent progress on each of these fronts.

Age and other perioperative risk factors for postoperative systemic inflammatory response syndrome after cardiac surgery.

BACKGROUND: The inflammatory response to surgery varies considerably between individual patients. Age might be a substantial factor in this variability. Our objective was to examine the association of patient age and other potential risk factors with the occurrence of a postoperative systemic inflammatory response syndrome, during the first 24 h after cardiac surgery. METHODS: This was a retrospective cohort study, using linked data from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) Database and the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database. Data from patients who underwent coronary artery bypass grafting and/or valve surgery were used. The association between age and postoperative SIRS was analysed using Poisson regression, and corrected for other risk factors. Restricted cubic splines were used to determine relevant age categories. Results are expressed as risk ratios (RR) with 95% confidence intervals (CI). RESULTS: Data from 28 513 patients were used. In both univariable and multivariable models, increased patient age was strongly associated with reduced postoperative SIRS prevalence. Using 73-83 yr as the reference category, the RRs (95% CI) for the age categories were 1.38 (1.28-1.49) for ≤43 yr, 1.15 (1.09-1.20) for 44-63 yr, 1.05 (1.00-1.09) for 64-72 yr, and 1.03 (0.94-1.12) for >83 yr, respectively. The predictive value for postoperative SIRS of the final model, however, was moderate (c-statistic: 0.61). CONCLUSIONS: We have demonstrated that advanced patient age is associated with a decreased risk of postoperative SIRS among cardiac surgery patients, where patients aged over 72 yr had the lowest risk.

The association between peri-operative acute risk change (ARC) and long-term survival after cardiac surgery.

Acute risk change has been described as the difference in calculated mortality risk between the pre-operative and postoperative periods of cardiac surgery. We aimed to assess whether this was associated with long-term survival after cardiac surgery. We retrospectively analysed 22,570 cardiac surgical patients, with minimum and maximum follow-up of 1.0 and 6.7 years. Acute risk change was calculated as the arithmetic difference between pre- and postoperative mortality risk. 'Rising risk' represented an increase in risk from pre- to postoperative phase. The primary outcome was one-year mortality. Secondary outcomes included mortality at 3 and 5 years and time to death. Univariable and multivariable analyses were undertaken to examine the relationship between acute risk change and outcomes. Rising risk was associated with higher mortality (5.6% vs. 3.5%, p < 0.001). After adjusting for baseline risk, rising risk was independently associated with increased 1-year mortality (OR 2.6, 95%CI 2.2-3.0, p < 0.001). The association of rising risk with long-term survival was greatest in patients with highest baseline risk. Cox regression confirmed rising risk was associated with shorter time to death (HR 1.86, 1.68-2.05, p < 0.001). Acute risk change may represent peri-operative clinical events in combination with unmeasured patient risk and noise. Measuring risk change could potentially identify patterns of events that may be amenable to investigation and intervention. Further work with case review, and risk scoring with shared variables, may identify mechanisms, including the interaction between miscalibration of risk and true differences in peri-operative care.

Multidimensional daily diary of fatigue-fibromyalgia-17 items (MDF-fibro-17). part 1: development and content validity.

BACKGROUND: Fibromyalgia (FM), a disorder characterized by chronic widespread pain and tenderness, affects greater than five million individuals in the United States alone. Patients experience multiple symptoms in addition to pain, and among them, fatigue is one of the most bothersome and disabling. There is a growing body of literature suggesting that fatigue is a multidimensional concept. Currently, to our knowledge, no multidimensional Patient Reported Outcome (PRO) measure of FM-related fatigue meets Food and Drug Administration (FDA) requirements to support a product label claim. Therefore, the objective of this research was to evaluate qualitative and quantitative data previously gathered to inform the development of a comprehensive, multidimensional, PRO measure to assess FM-related fatigue in FM clinical trials. METHODS: Existing qualitative and quantitative data from three previously conducted studies in patients with FM were reviewed to inform the initial development of a multidimensional PRO measure of FM-related fatigue: 1) a concept elicitation study involving in-depth, open-ended interviews with patients with FM in the United States (US) (N = 20), Germany (N = 10), and France (N = 10); 2) a cognitive debriefing and pilot study of a preliminary pool of 23 items (N = 20 US patients with FM); and 3) a methodology study that explored initial psychometrics of the item pool (N = 145 US patients with FM). RESULTS: Five domains were identified that intend to capture the broad experience of FM-related fatigue reported in the qualitative research: the Global Fatigue Experience, Cognitive Fatigue, Physical Fatigue, Motivation, and Impact on Function. Seventeen of the original pool of 23 items were selected to best capture these five dimensions. These 17 items formed the basis of a newly developed multidimensional PRO measure to assess FM-related fatigue in clinical trials: the Multidimensional Daily Diary of Fatigue-Fibromyalgia-17 (MDF-Fibro-17). CONCLUSION: Qualitative analysis, and preliminary quantitative item level data, confirmed that FM-related fatigue is multidimensional and provided strong support for the content validity of the MDF-Fibro-17. The next stage was to quantitatively evaluate the measure to confirm the factor structure, psychometric properties, sensitivity to change, and meaningful change. This has been conducted and is being reported separately.

Multidimensional daily diary of fatigue-fibromyalgia-17 items (MDF-fibro-17): part 2 psychometric evaluation in fibromyalgia patients.

BACKGROUND: The Multidimensional Daily Diary of Fatigue-Fibromyalgia-17 instrument (MDF-Fibro-17) has been developed for use in fibromyalgia (FM) clinical studies and includes 5 domains: Global Fatigue Experience, Cognitive Fatigue, Physical Fatigue, Motivation, and Impact on Function. Psychometric properties of the MDF-Fibro-17 needed to demonstrate the appropriateness of using this instrument in clinical studies are presented. METHODS: Psychometric analyses were conducted to evaluate the factor structure, reliability, validity, and responsiveness of the MDF-Fibro-17 using data from a Phase 2 clinical study of FM patients (N = 381). Confirmatory factor analyses (CFA) were performed to ensure understanding of the multidimensional domain structure, and a secondary factor analysis of the domains examined the appropriateness of calculating a total score in addition to domain scores. Longitudinal psychometric analyses (test-retest reliability and responder analysis) were also conducted on the data from Baseline to Week 6. RESULTS: The CFA supported the 17-item, 5 domain structure of this instrument as the best fit of the data: comparative fit index (CFI) and non-normed fit index (NNFI) were 0.997 and 0.992 respectively, standardized root mean square residual (SRMR) was 0.010 and the root mean square error of approximation (RMSEA) was 0.06. In addition, total score (CFI and NNFI both 0.95) met required standards. For the total and 5 domain scores, reliability and validity data were acceptable: test-retest and internal consistency were above 0.9; correlations were as expected with the Global Fatigue Index (GFI) (0.62-0.75), Fibromyalgia Impact Questionnaire (FIQ) Total (0.59-0.71), and 36-Item Short Form Health Survey (SF-36) vitality (VT) (0.43-0.53); and discrimination was shown using quintile scores for the GFI, FIQ Total, and Pain Numeric Rating Scale (NRS) quartiles. In addition, sensitivity to change was demonstrated with an overall mean responder score of -2.59 using anchor-based methods. CONCLUSION: The MDF-Fibro-17 reliably measures 5 domains of FM-related fatigue and psychometric evaluation confirms that this measure meets or exceeds each of the predefined acceptable thresholds for evidence of reliability, validity, and responsiveness to changes in clinical status. This suggests that the MDF-Fibro-17 is an appropriate and responsive measure of FM-related fatigue in clinical studies.

Evolution of nickel hyperaccumulation and serpentine adaptation in the Alyssum serpyllifolium species complex.

Metal hyperaccumulation is an uncommon but highly distinctive adaptation found in certain plants that can grow on metalliferous soils. Here we review what is known about evolution of metal hyperaccumulation in plants and describe a population-genetic analysis of the Alyssum serpyllifolium (Brassicaceae) species complex that includes populations of nickel-hyperaccumulating as well as non-accumulating plants growing on serpentine (S) and non-serpentine (NS) soils, respectively. To test whether the S and NS populations belong to the same or separate closely related species, we analysed genetic variation within and between four S and four NS populations from across the Iberian peninsula. Based on microsatellites, genetic variation was similar in S and NS populations (average Ho=0.48). The populations were significantly differentiated from each other (overall FST=0.23), and the degree of differentiation between S and NS populations was similar to that within these two groups. However, high S versus NS differentiation was observed in DNA polymorphism of two genes putatively involved in adaptation to serpentine environments, IREG1 and NRAMP4, whereas no such differentiation was found in a gene (ASIL1) not expected to play a specific role in ecological adaptation in A. serpyllifolium. These results indicate that S and NS populations belong to the same species and that nickel hyperaccumulation in A. serpyllifolium appears to represent a case of adaptation to growth on serpentine soils. Further functional and evolutionary genetic work in this system has the potential to significantly advance our understanding of the evolution of metal hyperaccumulation in plants.

Do demographics and tumour-related factors affect nodal yield at neck dissection? A retrospective cohort study.

BACKGROUND: Nodal metastasis is an important prognostic factor in head and neck squamous cell carcinoma. This study aimed to determine the average nodal basin yield per level of neck dissection, and to investigate if age, gender, body mass index, tumour size, depth of tumour invasion and p16 status influence nodal yield. METHOD: A retrospective review of 185 patients with head and neck squamous cell carcinoma generated 240 neck dissection specimens. RESULTS: The respective mean nodal yields for levels I, II, III, IV and V were 5.27, 9.43, 8.49, 7.43 and 9.02 in non-cutaneous squamous cell carcinoma patients, and 4.2, 7.57, 9.65, 4.33 and 12.29 in cutaneous squamous cell carcinoma patients. Multiple regression analysis revealed that p16-positive patients with mucosal squamous cell carcinoma yielded, on average, 2.4 more nodes than their p16-negative peers (p = 0.04, 95 per cent confidence interval = 0.116 to 4.693). This figure was 3.84 (p = 0.008, 95 per cent confidence interval = 1.070 to 6.605) for p16-positive patients with oral cavity squamous cell carcinoma. CONCLUSION: In mucosal squamous cell carcinoma, p16-positive status significantly influenced nodal yield, with the impact being more pronounced in oral cavity squamous cell carcinoma patients.

Identifying people at higher risk of melanoma across the U.K.: a primary-care-based electronic survey.

BACKGROUND: Melanoma incidence is rising rapidly worldwide among white populations. Defining higher-risk populations using risk prediction models may help targeted screening and early detection approaches. OBJECTIVES: To assess the feasibility of identifying people at higher risk of melanoma using the Williams self-assessed clinical risk estimation model in U.K. primary care. METHODS: We recruited participants from the waiting rooms of 22 general practices covering a total population of > 240 000 in three U.K. regions: Eastern England, North East Scotland and North Wales. Participants completed an electronic questionnaire using tablet computers. The main outcome was the mean melanoma risk score using the Williams melanoma risk model. RESULTS: Of 9004 people approached, 7742 (86%) completed the electronic questionnaire. The mean melanoma risk score for the 7566 eligible participants was 17·15 ± 8·51, with small regional differences [lower in England compared with Scotland (P = 0·001) and Wales (P < 0·001), mainly due to greater freckling and childhood sunburn among Scottish and Welsh participants]. After weighting to the age and sex distribution, different potential cut-offs would allow between 4% and 20% of the population to be identified as higher risk, and those groups would contain 30% and 60%, respectively of those likely to develop melanoma. CONCLUSIONS: Collecting data on the melanoma risk profile of the general population in U.K. primary care is both feasible and acceptable for patients in a general practice setting, and provides opportunities for new methods of real-time risk assessment and risk stratified cancer interventions.

Re-operative thyroid surgery: a 20-year prospective cohort study at a tertiary referral centre.

Re-operative thyroid surgery is a relatively uncommon procedure complicated by distorted anatomy and post-operative tissue changes. Surgery may follow initial benign or malignant pathology. Published outcomes vary widely in the literature. This study aims to report our outcomes from re-operative thyroid surgery. Patient demographics and complication rates for consecutive thyroidectomies performed by a single surgeon at a tertiary centre were collected between 1993 and 2013. Outcomes in re-operative surgery are analysed and compared with local and national data. Cases of re-operative surgery following benign disease are further analysed for histology, re-presenting symptoms and time between procedures. Our cohort comprised 1,657 cases including 164 re-operative procedures (101 malignant, 63 benign). Within our cohort re-operative cases were on average 4 years older (mean 49.9 vs 45.9 years, p = 0.001) and had a higher incidence of haematoma formation (4.3 vs 1.7 %, p = 0.033) and transient recurrent laryngeal nerve palsy (5.5 vs 2.5 %, p = 0.044) compared to primary surgery. Rates of permanent hypocalcaemia (2.4 vs 1.8 %, p = 0.540) and permanent RLN palsy (1.8 vs 0.4 %, p = 0.051) were higher in the re-operative group but did not reach significance. Comparison of complications following re-operation for benign and malignant disease revealed no significant differences. Mean interval to re-operation for benign cases was 17.4 years with 74.6 % found to have multinodular goitre at repeat procedure. Re-operative procedures comprised around 10 % of thyroid surgery at our centre. Re-operative cases experienced more complications than primary surgery but permanent rates were low. Re-operative surgery may therefore be safely considered in experienced hands.