Twitter communication of the UK public on dental health and care during a COVID lockdown: "My kingdom for a dentist".

BACKGROUND: The COVID-19 pandemic forced a UK-wide closure of dental services. An understanding of public concerns about dental care was urgently needed to inform careful resumption of paused dental services. AIM: To describe public concerns about dental care during lockdown. BASIC RESEARCH DESIGN: Framework analysis of relevant Twitter posts identified collected using the Awario tool. RESULTS: Of 1863 tweets manually screened for eligibility, 285 were relevant, as they contained views expressed by the public. The number of tweets by country were proportionate to the population size. The key views expressed in tweets focused on: 'oral health impact' ('oral health and self-care', 'types of dental problems', 'managing symptoms at home', 'views on consequences of delaying treatment') and 'dental service or care provision' ('views on managing dental care response', 'experiences with access to dental care'). CONCLUSIONS: The impact of COVID-19 on dental services raised many physical and mental health concerns for the public, highlighting their importance. Online profiles and social media communication platforms can be used to provide convenient, and timely information on public perceptions of dental care.

The Value of Preventative Dental Care: A Discrete-Choice Experiment.

Scale and polish (SP) and oral hygiene advice (OHA) are commonly provided in primary care dental practice to help prevent periodontal disease. These services are widely consumed by service users, incurring substantial cost, without any clear evidence of clinical benefit. This article aims to elicit general population preferences and willingness to pay (WTP) for preventative dental care services and outcomes. An online discrete-choice experiment (DCE) was completed by a nationally representative sample of the UK general population. Respondents each answered 10 choice tasks that varied in terms of service attributes (SP, OHA, and provider of care), outcomes (bleeding gums and aesthetics), and cost. Choice tasks were selected using a pivoted segmented experimental design to improve task realism. An error components panel logit model was used to analyze the data. Marginal WTP (mWTP) for each attribute and level was calculated. In total, 667 respondents completed the DCE. Respondents valued more frequent SP, care provided by a dentist, and personalized OHA. Respondents were willing to pay for dental packages that generated less frequent ("never" or "hardly ever") bleeding on brushing and teeth that look and feel at least "moderately clean." Respondents were willing to pay more (+£145/y) for improvements in an aesthetic outcome from "very unclean" (-£85/y) to "very clean" (+£60/y) than they were for reduced bleeding frequency (+£100/y) from "very often" (-£54/y) to "never" (+£36/y). The general population value routinely provided SP, even in the absence of reductions in bleeding on brushing. Dental care service providers must consider service user preferences, including preferences for both health and nonhealth outcomes, as a key factor in any service redesign. Furthermore, the results provide mWTP estimates that can be used in cost-benefit analysis of these dental care services.

Acute and chronic effects of multivitamin/mineral supplementation on objective and subjective energy measures.

BACKGROUND: Vitamins and minerals play an essential role within many cellular processes including energy production and metabolism. Previously, supplementation with a multivitamin/mineral (MVM) for ≥28 days resulted in improvements to cognition and subjective state. We have also demonstrated shifts in metabolism during cognitively demanding tasks following MVM in females, both acutely and following 8-week supplementation. The current study aimed to assess these effects further in males and females using metabolically challenging exercise and cognitive tasks. METHODS: The current randomised, placebo-controlled, parallel groups study investigated the effects of a MVM complex in 82 healthy young (18-35y) exercisers. Subjective ratings and substrate metabolism were assessed during 30 min each of increasingly effortful incremental exercise and demanding cognitive tasks. Assessments took place on acute study days following a single dose (Day 1) of MVM, containing 3 times recommended daily allowance of water-soluble vitamins plus CoQ10, and following 4-week supplementation (Day 28). RESULTS: Energy expenditure (EE) was increased during cognitive tasks following MVM across Day 1 and Day 28, with greater effects in males. In males, MVM also increased carbohydrate oxidation and energy expenditure during exercise across Day 1 and Day 28. In females, mental tiredness was lower during exercise; increases in physical tiredness following 30 min of exercise were attenuated; and stress ratings following cognitive tasks were reduced following MVM. In males, MVM only lowered mental tiredness following 10 min of exercise. These effects were apparent irrespective of day, but effects on mental tiredness were greater on Day 28. Ferritin levels were also higher on Day 28 in those receiving MVM. CONCLUSION: These findings extend on existing knowledge, demonstrating increased carbohydrate oxidation and increased energy expenditure in males following MVM supplementation for the first time. Importantly, they show modulation of energy expenditure and subjective tiredness following a single dose, providing further evidence for acute effects of MVM. Differential effects in men and women suggest that sex may play an important role in the effects of MVM on energy metabolism and should be considered in future research. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03003442. Registered 22nd November 2016 - retrospectively registered.

Protocol for a Randomised controlled trial to Evaluate the effectiveness and cost benefit of prescribing high dose FLuoride toothpaste in preventing and treating dEntal Caries in high-risk older adulTs (reflect trial).

BACKGROUND: Dental caries in the expanding elderly, predominantly-dentate population is an emerging public health concern. Elderly individuals with heavily restored dentitions represent a clinical challenge and significant financial burden for healthcare systems, especially when their physical and cognitive abilities are in decline. Prescription of higher concentration fluoride toothpaste to prevent caries in older populations is expanding in the UK, significantly increasing costs for the National Health Services (NHS) but the effectiveness and cost benefit of this intervention are uncertain. The Reflect trial will evaluate the effectiveness and cost benefit of General Dental Practitioner (GDP) prescribing of 5000 ppm fluoride toothpaste and usual care compared to usual care alone in individuals 50 years and over with high-risk of caries. METHODS/DESIGN: A pragmatic, open-label, randomised controlled trial involving adults aged 50 years and above attending NHS dental practices identified by their dentist as having high risk of dental caries. Participants will be randomised to prescription of 5000 ppm fluoride toothpaste (frequency, amount and duration decided by GDP) and usual care only. 1200 participants will be recruited from approximately 60 dental practices in England, Scotland and Northern Ireland and followed up for 3 years. The primary outcome will be the proportion of participants receiving any dental treatment due to caries. Secondary outcomes will include coronal and root caries increments measured by independent, blinded examiners, patient reported quality of life measures, and economic outcomes; NHS and patient perspective costs, willingness to pay, net benefit (analysed over the trial follow-up period and modelled lifetime horizon). A parallel qualitative study will investigate GDPs' practises of and beliefs about prescribing the toothpaste and patients' beliefs and experiences of the toothpaste and perceived impacts on their oral health-related behaviours. DISCUSSION: The Reflect trial will provide valuable information to patients, policy makers and clinicians on the costs and benefits of an expensive, but evidence-deficient caries prevention intervention delivered to older adults in general dental practice. TRIAL REGISTRATION: ISRCTN: 2017-002402-13 registered 02/06/2017, first participant recruited 03/05/2018. Ethics Reference No: 17/NE/0329/233335. Funding Body: Health Technology Assessment funding stream of National Institute for Health Research. Funder number: HTA project 16/23/01. Trial Sponsor: Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL. The Trial was prospectively registered.

Prioritizing research areas for antibiotic stewardship programmes in hospitals: a behavioural perspective consensus paper.

SCOPE: Antibiotic stewardship programmes (ASPs) are necessary in hospitals to improve the judicious use of antibiotics. While ASPs require complex change of key behaviours on individual, team organization and policy levels, evidence from the behavioural sciences is underutilized in antibiotic stewardship studies across the world, including high-income countries (HICs). A consensus procedure was performed to propose research priority areas for optimizing effective implementation of ASPs in hospital settings using a behavioural perspective. METHODS: A workgroup for behavioural approaches to ASPs was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). Eighteen clinical and academic specialists in antibiotic stewardship, implementation science and behaviour change from four HICs with publicly funded healthcare systems (e.g. Canada, Germany, Norway and the UK) met face-to-face to agree on broad research priority areas using a structured consensus method. Question addressed and recommendations: The consensus process assessing the ten identified research priority areas resulted in recommendations that need urgent scientific interest and funding to optimize effective implementation of ASPs for hospital inpatients in HICs with publicly funded healthcare systems. We suggest and detail behavioural science evidence-guided research efforts in the following areas: (a) comprehensively identifying barriers and facilitators to implementing ASPs and clinical recommendations intended to optimize antibiotic prescribing; (b) identifying actors ('who') and actions ('what needs to be done') of ASPs and clinical teams; (c) synthesizing available evidence to support future research and planning for ASPs; (d) specifying the activities in current ASPs with the purpose of defining a control group for comparison with new initiatives; (e) defining a balanced set of outcomes and measures to evaluate the effects of interventions focused on reducing unnecessary exposure to antibiotics; (f) conducting robust evaluations of ASPs with built-in process evaluations and fidelity assessments; (g) defining and designing ASPs; (h) establishing the evidence base for impact of ASPs on resistance; (i) investigating the role and impact of government and policy contexts on ASPs; and (j) understanding what matters to patients in ASPs in hospitals. CONCLUSIONS: Assessment, revisions and updates of our priority-setting exercise should be considered at intervals of 2 years. To propose research priority areas in low- and middle-income countries, the methodology reported here could be applied.

Long term outcomes of simple clinical risk stratification in management of differentiated thyroid cancer.

OBJECTIVE: To establish the long term outcomes of risk stratified management of differentiated thyroid cancer (DTC). BACKGROUND: Guidelines for management of DTC lack a strong evidence base and expose patients to overtreatment. This prospective study of patients diagnosed with DTC between 1977 and 2012 describes the long term outcomes of a conservative risk stratified (AMES) management policy. METHODS: Outcomes were analysed around patient and tumour characteristics, primary intervention (surgery ± radioiodine (RAI)), in terms of mortality, recurrence and reintervention. RESULTS: Median follow-up in 348 patients was 14 years: mean age 48 (range 10-91) years, 257 (73.9%) female, 222 (68.3%) papillary cancer, tumour size 3.4 ± 2.0 cm (mean ± SD). 89 (25.6%) AMES high risk, 116 (33.3%) TNM stage III/IV and 16 (4.6%) had distant metastases. Primary surgery comprised lobectomy in 189 (54.3%): 11 (5.8%) patients had subsequent completion total thyroidectomy with cancer present in five. Primary nodal surgery was performed in 142 (40.8%) patients. 35 (13.5%) low and 43 (48.3%) high risk patients received RAI following initial surgery. Overall disease specific survival (DSS) was 92.1% at 10 years and 90.7% at 20 years. DSS at 20 years was 99.2% in low risk cases. AMES risk scoring predicted both survival and recurrence. Patients receiving RAI and AMES high risk were significantly associated with increased risk of death and recurrence. CONCLUSIONS: Routine total thyroidectomy and RAI are not justifiable for low risk DTC. Treatment should be tailored to risk and AMES risk stratification remains a simple reliable clinical tool.

Erratum to: Cognitive and mood improvements following acute supplementation with purple grape juice in healthy young adults.

In the original publication of the article, on page 7, paragraph "Discussion", line 12, 'blackcurrant has been observed to increase digit vigilance reaction time' should read as 'blackcurrant has been observed to decrease digit vigilance reaction time'.

Cognitive and mood improvements following acute supplementation with purple grape juice in healthy young adults.

PURPOSE: Berry-derived phenolic compounds found in grapes have been associated with a number of health benefits, including the augmentation of human brain function and cognition. Previous intervention studies of Concord grape juice have demonstrated improvement to memory and driving ability following 3- to 4-month supplementation in middle-aged and older adults. However, no studies to date have demonstrated acute cognitive benefits of grape juice, and investigation of these effects in young adults is lacking. METHODS: This randomised, placebo-controlled, double-blind, counterbalanced-crossover study, assessed the effects of 230 ml purple grape juice or sugar-matched control in 20 healthy young adults. Computerised measures of episodic memory, working memory, attention and mood were completed at baseline and following a 20-min absorption period. RESULTS: Purple grape juice significantly improved reaction time on a composite attention measure (p = 0.047) and increased calm ratings (p = 0.046) when compared to placebo. Order effects also indicated an enduring positive effect on pre-dose memory reaction time (p = 0.018) and post-dose calm ratings (p = 0.019) when purple grape was consumed first. CONCLUSIONS: These findings in a small sample of healthy young adults suggest that purple grape juice can acutely enhance aspects of cognition and mood. No significant effects of juice were observed on memory measures, suggesting that these may be less susceptible to manipulation following acute supplementation in healthy young adults. Potential mechanisms underlying these effects include modulation of cerebral blood flow, glucoregulation and inhibition of monoamine oxidase activity, all of which require further exploration.

Effectiveness of open and arthroscopic rotator cuff repair (UKUFF): a randomised controlled trial.

AIMS: The appropriate management for patients with a degenerative tear of the rotator cuff remains controversial, but operative treatment, particularly arthroscopic surgery, is increasingly being used. Our aim in this paper was to compare the effectiveness of arthroscopic with open repair of the rotator cuff. PATIENTS AND METHODS: A total of 273 patients were recruited to a randomised comparison trial (136 to arthroscopic surgery and 137 to open surgery) from 19 teaching and general hospitals in the United Kingdom. The surgeons used their usual preferred method of repair. The Oxford Shoulder Score (OSS), two years post-operatively, was the primary outcome measure. Imaging of the shoulder was performed at one year after surgery. The trial is registered with Current Controlled Trials, ISRCTN97804283. RESULTS: The mean OSS improved from 26.3 (standard deviation (sd) 8.2) at baseline, to 41.7 (sd 7.9) two years post-operatively for arthroscopic surgery and from 25.0 (sd 8.0) to 41.5 (sd 7.9) for open surgery. Intention-to-treat (ITT) analysis showed no statistical difference between the groups at two years (difference in OSS score -0.76; 95% confidence interval (CI) -2.75 to 1.22; p = 0.452). The confidence interval excluded the pre-determined clinically important difference in the OSS of three points. The rate of re-tear was not significantly different between the two groups (46.4% for arthroscopic and 38.6% for open surgery; 95% CI -6.9 to 25.8; p = 0.256). Healed repairs had the most improved OSS. These findings were the same when analysed per-protocol. CONCLUSION: There is no evidence of difference in effectiveness between open and arthroscopic repair of rotator cuff tears. The rate of re-tear is high in both groups, for all sizes of tear and ages and this adversely affects the outcome. Cite this article: Bone Joint J 2017;99-B:107-15.

Montmorency Tart cherries (Prunus cerasus L.) modulate vascular function acutely, in the absence of improvement in cognitive performance.

Cerebral blood volume and metabolism of oxygen decline as part of human ageing, and this has been previously shown to be related to cognitive decline. There is some evidence to suggest that polyphenol-rich foods can play an important role in delaying the onset or halting the progression of age-related health disorders such as CVD and Alzheimer's disease and to improve cognitive function. In the present study, an acute, placebo-controlled, double-blinded, cross-over, randomised Latin-square design study with a washout period of at least 14 d was conducted on twenty-seven, middle-aged (defined as 45-60 years) volunteers. Participants received either a 60 ml dose of Montmorency tart cherry concentrate (MC), which contained 68·0 (sd 0·26) mg cyanidin-3-glucoside/l, 160·75 (sd 0·55) mean gallic acid equivalent/l and 0·59 (sd 0·02) mean Trolox equivalent/l, respectively, or a placebo. Cerebrovascular responses, cognitive performance and blood pressure were assessed at baseline and 1, 2, 3 and 5 h following consumption. There were significant differences in concentrations of total Hb and oxygenated Hb during the task period 1 h after MC consumption (P≤0·05). Furthermore, MC consumption significantly lowered systolic blood pressure (P≤0·05) over a period of 3 h, with peak reductions of 6±2 mmHg at 1 h after MC consumption relative to the placebo. Cognitive function and mood were not affected. These results show that a single dose of MC concentrate can modulate certain variables of vascular function; however, this does not translate to improvements in cognition or mood.

Costs, quality of life and cost-effectiveness of arthroscopic and open repair for rotator cuff tears: an economic evaluation alongside the UKUFF trial.

AIMS: A trial-based comparison of the use of resources, costs and quality of life outcomes of arthroscopic and open surgical management for rotator cuff tears in the United Kingdom NHS was performed using data from the United Kingdom Rotator Cuff Study (UKUFF) randomised controlled trial. PATIENTS AND METHODS: Using data from 273 patients, healthcare-related use of resources, costs and quality-adjusted life years (QALYs) were estimated at 12 months and 24 months after surgery on an intention-to-treat basis with adjustment for covariates. Uncertainty about the incremental cost-effectiveness ratio for arthroscopic versus open management at 24 months of follow-up was incorporated using bootstrapping. Multiple imputation methods were used to deal with missing data. RESULTS: There were no significant differences between the arthroscopic and open groups in terms of total mean use and cost of resources or QALYs at any time post-operatively. Open management dominated arthroscopic management in 59.8% of bootstrapped cost and effect differences. The probability that arthroscopic management was cost-effective compared with open management at a willingness-to-pay threshold of £20 000 per QALY gained was 20.9%. CONCLUSION: There was no significant overall difference in the use or cost of resources or quality of life between arthroscopic and open management in the trial. There was uncertainty about which strategy was most cost-effective. Cite this article: Bone Joint J 2016;98-B:1648-55.

Reporting and dealing with missing quality of life data in RCTs: has the picture changed in the last decade?

PURPOSE: Missing data are a major problem in the analysis of data from randomised trials affecting power and potentially producing biased treatment effects. Specifically focussing on quality of life outcomes, we aimed to report the amount of missing data, whether imputation was used and what methods and was the missing mechanism discussed from four leading medical journals and compare the picture to our previous review nearly a decade ago. METHODS: A random selection (50 %) of all RCTS published during 2013-2014 in BMJ, JAMA, Lancet and NEJM was obtained. RCTs reported in research letters, cluster RCTs, non-randomised designs, review articles and meta-analysis were excluded. RESULTS: We included 87 RCTs in the review of which 35 % the amount of missing primary QoL data was unclear, 31 (36 %) used imputation. Only 23 % discussed the missing data mechanism. Nearly half used complete case analysis. Reporting was more unclear for secondary QoL outcomes. Compared to the previous review, multiple imputation was used more prominently but mainly in sensitivity analysis. CONCLUSIONS: Inadequate reporting and handling of missing QoL data in RCTs are still an issue. There is a large gap between statistical methods research relating to missing data and the use of the methods in applications. A sensitivity analysis should be undertaken to explore the sensitivity of the main results to different missing data assumptions. Medical journals can help to improve the situation by requiring higher standards of reporting and analytical methods to deal with missing data, and by issuing guidance to authors on expected standard.

A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood.

RATIONALE: Evidence suggests interactive effects of the tea components caffeine and L-theanine on behaviour, yet no data exists exploring the impact of the two on cerebral blood flow (CBF). OBJECTIVES: The current placebo-controlled, double-blind, counterbalanced, crossover study examined the effects of caffeine and L-theanine on CBF and extended previous cognitive and mood findings by using lower doses than previous studies of a similar methodology, which more closely reflect the ratios present in tea. METHODS: Twelve habitual consumers and 12 non-habitual consumers of caffeine each received 75 mg caffeine, 50 mg L-theanine, 75 mg caffeine plus 50 mg L-theanine, and placebo in a counterbalanced order across four separate visits. CBF was measured via near-infrared spectroscopy with cognition and mood assessed at baseline and 30 min post-dose. Salivary caffeine and peripheral haemodynamics were co-monitored. RESULTS: Caffeine reduced oxygenated haemoglobin (oxy-Hb), increased deoxygenated haemoglobin (deoxy-Hb), improved performance on attention tasks and increased overall mood ratings. Increases in deoxy-Hb following caffeine were more pronounced in non-consumers. Some evidence for increased deoxy-Hb remained when caffeine was combined with L-theanine, but this effect was attenuated and the effects of caffeine on oxy-Hb, cognition and mood were eradicated. CONCLUSIONS: Combining L-theanine with caffeine, at levels and ratios equivalent to one to two cups of tea, eliminated the vasoconstrictive effect and behavioural effects of caffeine. This supports previous findings of an interaction between these substances, despite a lack of effects of L-theanine in isolation. However, at the levels tested here, this did not lead to a positive impact on behaviour.

Cost-effectiveness of ultrasound-guided foam sclerotherapy, endovenous laser ablation or surgery as treatment for primary varicose veins from the randomized CLASS trial.

BACKGROUND: The treatment of patients with varicose veins constitutes a considerable workload and financial burden to the National Health Service. This study aimed to assess the cost-effectiveness of ultrasound-guided foam sclerotherapy (UGFS) and endovenous laser ablation (EVLA) compared with conventional surgery as treatment for primary varicose veins. METHODS: Participant cost and utility data were collected alongside the UK CLASS multicentre randomized clinical trial, which compared EVLA, surgery and UGFS. Regression methods were used to estimate the effects of the alternative treatments on costs to the health service and quality-adjusted life-years (QALYs) at 6 months. A Markov model, incorporating available evidence on clinical recurrence rates, was developed to extrapolate the trial data over a 5-year time horizon. RESULTS: Compared with surgery at 6 months, UGFS and EVLA reduced mean costs to the health service by £655 and £160 respectively. When additional overhead costs associated with theatre use were included, these cost savings increased to £902 and £392 respectively. UGFS produced 0·005 fewer QALYs, whereas EVLA produced 0·011 additional QALYs. Extrapolating to 5 years, EVLA was associated with increased costs and QALYs compared with UGFS (costing £3640 per QALY gained), and generated a cost saving (£206-439) and QALY gain (0·078) compared with surgery. Applying a ceiling willingness-to-pay ratio of £20 000 per QALY gained, EVLA had the highest probability (78·7 per cent) of being cost-effective. CONCLUSION: The results suggest, for patients considered eligible for all three treatment options, that EVLA has the highest probability of being cost-effective at accepted thresholds of willingness to pay per QALY.

Optical coherence tomography for the diagnosis of neovascular age-related macular degeneration: a systematic review.

UNLABELLED: The purpose is to study the diagnostic performance of optical coherence tomography (OCT) and alternative diagnostic tests for neovascular age-related macular degeneration (nAMD). Methods employed are as follows:systematic review and meta-analysis; INDEX TEST: OCT including time-domain (TD-OCT) and the most recently developed spectral domain (SD-OCT); comparator tests: visual acuity, clinical evaluation (slit lamp), Amsler chart, colour fundus photographs, infra-red reflectance, red-free images/blue reflectance, fundus autofluorescence imaging (FAF), indocyanine green angiography (ICGA), preferential hyperacuity perimetry (PHP), and microperimetry; reference standard: fundus fluorescein angiography. Databases searched included MEDLINE, MEDLINE In Process, EMBASE, Biosis, SCI, the Cochrane Library, DARE, MEDION, and HTA database. Last literature searches: March 2013. Risk of bias assessed using QUADAS-2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic (HSROC) curves. Twenty-two studies (2 abstracts and 20 articles) enrolling 2124 participants were identified, reporting TD-OCT (12 studies), SD-OCT (1 study), ICGA (8 studies), PHP (3 studies), Amsler grid, colour fundus photography and FAF (1 study each). Most studies were considered to have a high risk of bias in the patient selection (55%, 11/20), and flow and timing (40%, 8/20) domains. In a meta-analysis of TD-OCT studies, sensitivity and specificity (95% CI) were 88% (46-98%) and 78% (64-88%), respectively. There was insufficient information to undertake meta-analysis for other tests. TD-OCT is a sensitive test for detecting nAMD, although specificity was only moderate. Data on SD-OCT are sparse. Diagnosis of nAMD should not rely solely on OCT.

A cross-specialty survey to assess the application of risk stratified surgery for differentiated thyroid cancer in the UK.

INTRODUCTION: This study describes variability of treatment for differentiated thyroid cancer among thyroid surgeons, in the context of changing patterns of thyroid surgery in the UK. METHODS: Hospital Episodes Statistics on thyroid operations between 1997 and 2012 were obtained for England. A survey comprising six scenarios of varying 'risk' was developed. Patient/tumour information was provided, with five risk stratified or non-risk stratified treatment options. The survey was distributed to UK surgical associations. Respondent demographics were categorised and responses analysed by assigned risk stratified preference. RESULTS: From 1997 to 2012, the Hospital Episode Statistics data indicated there was a 55% increase in the annual number of thyroidectomies with a fivefold increase in otolaryngology procedures and a tripling of cancer operations. Of the surgical association members surveyed, 264 respondents reported a thyroid surgery practice. Management varied across and within the six scenarios, and was not related consistently to the level of risk. Associations were demonstrated between overall risk stratified preference and higher volume practice (>25 thyroidectomies per year) (p=0.011), fewer years of consultant practice (p=0.017) and multidisciplinary team participation (p=0.037). Logistic regression revealed fewer years of consultant practice (odds ratio [OR]: 0.96/year in practice, 95% confidence interval [CI]: 0.922-0.997, p=0.036) and caseload of >25/year (OR 1.92, 95% CI: 1.044-3.522, p=0.036) as independent predictors of risk stratified preference. CONCLUSIONS: There is a substantial contribution to thyroid surgery in the UK by otolaryngology surgeons. Adjusting management according to established case-based risk stratification is not widely applied. Higher caseload was associated with a preference for management tailored to individual risk.

Protocol for the United Kingdom Rotator Cuff Study (UKUFF): a randomised controlled trial of open and arthroscopic rotator cuff repair.

This protocol describes a pragmatic multicentre randomised controlled trial (RCT) to assess the clinical and cost effectiveness of arthroscopic and open surgery in the management of rotator cuff tears. This trial began in 2007 and was modified in 2010, with the removal of a non-operative arm due to high rates of early crossover to surgery. Cite this article: Bone Joint Res 2014;3:155-60.

Reduction in cryptosporidiosis associated with introduction of enhanced filtration of drinking water at Loch Katrine, Scotland.

Previous evidence has suggested an association between cryptosporidiosis and consumption of unfiltered drinking water from Loch Katrine in Scotland. Before September 2007, the water was only micro-strained and chlorinated; however, since that time, coagulation and rapid gravity filtration have been installed. In order to determine risk factors associated with cryptosporidiosis, including drinking water, we analysed data on microbiologically confirmed cases of cryptosporidiosis from 2004 to 2010. We identified an association between the incidence of cryptosporidiosis and unfiltered Loch Katrine drinking water supplied to the home (odds ratio 1.86, 95% confidence interval 1.11-3.11, P = 0.019). However, while filtration appears to be associated with initially reduced rates of cryptosporidiosis, evidence suggests it may paradoxically make those consumers more susceptible to other transmission routes in the long-term. These findings support implementation of similar treatment for other unfiltered drinking-water supplies, as a means of reducing cryptosporidiosis associated with drinking water.

Candidate epitopes for measurement of hCG and related molecules: the second ISOBM TD-7 workshop.

Participants of the Second International Workshop (WS) on human chorionic gonadotropin (hCG) of the International Society of Oncology and Biomarkers Tissue Differentiation 7 (ISOBM TD-7) have characterized in detail a panel of 69 antibodies (Abs) directed against hCG and hCG-related variants that were submitted by eight companies and research groups. Specificities of the Abs were determined using the First WHO International Reference Reagents for six hCG variants, i.e., hCG, hCGn, hCGß, hCGßn, hCGßcf, and hCGα, which are calibrated in SI units, and hLH. Molecular epitope localizations were assigned to the ISOBM-mAbs by comparing ISOBM-Ab specificity, sandwich compatibility, and mutual inhibition profiles, to those of 17 reference monoclonal (m)Abs of known molecular epitope specificities. It appeared that 48 Abs recognized hCGß-, 8 hCGα-, and 13 αß-heterodimer-specific epitopes. Twenty-seven mAbs were of pan hCG specificity, two thereof with no (<0.1%; epitope ß1), 12 with low (<1.0%; epitopes ß2/4), and 13 with high (>>1%; epitopes ß3/5) hLH cross-reactivity. The majority of hCGß epitopes recognized were located in two major antigenic domains, one on the peptide chain of the tips of ß-sheet loops 1 and 3 (epitopes ß2-6; 27 mAbs) and the second around the cystine knot (e.g., epitopes ß1, ß7, and ß10; 9 mAbs). Four mAbs recognized epitopes on hCGßcf-only (e.g., epitopes ß11 and ß13) and six mAbs epitopes on the remote hCGß-carboxyl-terminal peptide (epitopes ß8 and ß9 corresponding to amino acids 135-144 and 111-116, respectively). For routine diagnostic measurements, methods are used that either detect hCG-only, hCGß-only, or hCG together with hCGß or hCG together with hCGß and hCGßcf. Sandwich assays that measure hCG plus hCGß and eventually hCGßcf should recognize the protein backbone of the analytes preferably on an equimolar basis, should not cross-react with hLH and not be susceptible to blunting of signal by nonmeasured variants like hCGßcf. Such assays can be constructed using pairs of mAbs directed against the cystine knot-associated epitope ß1 (Asp10, Asp60, and Gln89) in combination with epitopes ß2 or ß4 located at the top of ß-sheet loops 1 + 3 of hCGß involving aa hCGß20-25 + 68-77. In summary, the results of the First and Second ISOBM TD-7 WSs on hCG provide the basis for harmonization of specificities and epitopes of mAbs to be used in multifunctional and selective diagnostic hCG methods for different clinical purposes.

Clinical and economic evaluation of laparoscopic surgery compared with medical management for gastro-oesophageal reflux disease: 5-year follow-up of multicentre randomised trial (the REFLUX trial).

BACKGROUND: Despite promising evidence that laparoscopic fundoplication provides better short-term relief of gastro-oesophageal reflux disease (GORD) than continued medical management, uncertainty remains about whether benefits are sustained and outweigh risks. OBJECTIVE: To evaluate the long-term clinical effectiveness, cost-effectiveness and safety of laparoscopic surgery among people with GORD requiring long-term medication and suitable for both surgical and medical management. DESIGN: Five-year follow-up of a randomised trial (with parallel non-randomised preference groups) comparing a laparoscopic surgery-based policy with a continued medical management policy. Cost-effectiveness was assessed alongside the trial using a NHS perspective for costs and expressing health outcomes in terms of quality-adjusted life-years (QALYs). SETTING: Follow-up was by annual postal questionnaire and selective hospital case notes review; initial recruitment in 21 UK hospitals. PARTICIPANTS: Questionnaire responders among the 810 original participants. At entry, all had documented evidence of GORD and symptoms for > 12 months. Questionnaire response rates (years 1-5) were from 89.5% to 68.9%. INTERVENTIONS: Three hundred and fifty-seven participants were recruited to the randomised comparison (178 randomised to surgical management and 179 randomised to continued medical management) and 453 to the preference groups (261 surgical management and 192 medical management). The surgeon chose the type of fundoplication. MAIN OUTCOME MEASURES: Primary: disease-specific outcome measure (the REFLUX questionnaire); secondary: Short Form questionnaire-36 items (SF-36), European Quality of Life-5 Dimensions (EQ-5D), NHS resource use, reflux medication, complications. RESULTS: The randomised groups were well balanced. By 5 years, 63% in the randomised surgical group and 13% in the randomised medical management group had received a total or partial wrap fundoplication (85% and 3% in the preference groups), with few perioperative complications and no associated deaths. At 1 year (and 5 years) after surgery, 36% (41%) in the randomised surgical group - 15% (26%) of those who had surgery - were taking proton pump inhibitor medication compared with 87% (82%) in the randomised medical group. At each year, differences in the REFLUX score significantly favoured the randomised surgical group (a third of a SD; p< 0.01 at 5 years). SF-36 and EQ-5D scores also favoured surgery, but differences attenuated over time and were generally not statistically significant at 5 years. The worse the symptoms at trial entry, the larger the benefit observed after surgery. Those randomised to medical management who subsequently had surgery had low baseline scores that markedly improved after surgery. Following fundoplication, 3% had surgical treatment for a complication and 4% had subsequent reflux-related operations - most often revision of the wrap. Dysphagia, flatulence and inability to vomit were similar in the two randomised groups. The economic analysis indicated that surgery was the more cost-effective option for this patient group. The incremental cost-effectiveness ratio for surgery in the base case was £7028 per additional QALY; these findings were robust to changes in approaches and assumptions. The probability of surgery being cost-effective at a threshold of £20,000 per additional QALY was > 0.80 for all analyses. CONCLUSIONS: After 5 years, laparoscopic fundoplication continues to provide better relief of GORD symptoms with associated improved health-related quality of life. Complications of surgery were uncommon. Despite being initially more costly, a surgical policy is highly likely to be cost-effective. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15517081. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 22. See the HTA programme website for further project information.