The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses.

The lipid envelope of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an essential component of the virus; however, its molecular composition is undetermined. Addressing this knowledge gap could support the design of antiviral agents as well as further our understanding of viral-host protein interactions, infectivity, pathogenicity, and innate immune system clearance. Lipidomics revealed that the virus envelope comprised mainly phospholipids (PLs), with some cholesterol and sphingolipids, and with cholesterol/phospholipid ratio similar to lysosomes. Unlike cellular membranes, procoagulant amino-PLs were present on the external side of the viral envelope at levels exceeding those on activated platelets. Accordingly, virions directly promoted blood coagulation. To investigate whether these differences could enable selective targeting of the viral envelope in vivo, we tested whether oral rinses containing lipid-disrupting chemicals could reduce infectivity. Products containing PL-disrupting surfactants (such as cetylpyridinium chloride) met European virucidal standards in vitro; however, components that altered the critical micelle concentration reduced efficacy, and products containing essential oils, povidone-iodine, or chlorhexidine were ineffective. This result was recapitulated in vivo, where a 30-s oral rinse with cetylpyridinium chloride mouthwash eliminated live virus in the oral cavity of patients with coronavirus disease 19 for at least 1 h, whereas povidone-iodine and saline mouthwashes were ineffective. We conclude that the SARS-CoV-2 lipid envelope i) is distinct from the host plasma membrane, which may enable design of selective antiviral approaches; ii) contains exposed phosphatidylethanolamine and phosphatidylserine, which may influence thrombosis, pathogenicity, and inflammation; and iii) can be selectively targeted in vivo by specific oral rinses.

Healthy eating and lifestyle in pregnancy (HELP): a cluster randomised trial to evaluate the effectiveness of a weight management intervention for pregnant women with obesity on weight at 12 months postpartum.

OBJECTIVE: To assess whether a weight management intervention for pregnant women with obesity was effective in reducing body mass index (BMI) 12 months after giving birth. METHODS: Pragmatic, cluster randomised controlled trial (RCT) with embedded cost-effectiveness analysis. 598 women with a BMI of ≥30 kg/m2 (between 12 and 20 weeks gestation) were recruited from 20 secondary care maternity units in England and Wales. BMI at 12 months postpartum was the primary outcome. A range of clinical and behavioural secondary outcomes were examined. INTERVENTIONS: Women attending maternity units randomised to intervention were invited to a weekly weight management group, which combined expertise from a commercial weight loss programme with clinical advice from midwives. Both intervention and control participants received usual care and leaflets on diet and physical activity in pregnancy. RESULTS: Mean (SD) BMI at 12 months postpartum was 36.0 kg/m2 (5.2) in the control group, and 37.5 kg/m2 (6.7) in the intervention group. After adjustment for baseline BMI, the intervention effect was -0.02 (95% CI -0.04 to 0.01). The intervention group had an improved healthy eating score (3.08, 95% CI 0.16 to 6.00, p < 0.04), improved fibre score (3.22, 1.07 to 5.37, p < 0.01) and lower levels of risky drinking at 12 months postpartum compared to the control group (OR 0.45, 0.27 to 0.74, p < 0.002). The net incremental monetary benefit was not statistically significantly different between arms, although the probability of the intervention being cost-effective was above 60%, at policy-relevant thresholds. CONCLUSIONS: There was no significant difference between groups on the primary outcome of BMI at 12 months. Analyses of secondary outcomes indicated improved healthy eating and lower levels of risky drinking. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25260464.

Human papillomavirus infection is rare in nonmalignant tonsil tissue in the UK: implications for tonsil cancer precursor lesions.

The incidence of human papillomavirus (HPV)-associated tonsil cancer is increasing but the prevalence of HPV, and of premalignant precursors, in tonsil tissue is unknown. We aimed to assess prevalence of HPV infection in nonmalignant tonsillar crypt epithelia and to histopathologically characterise positive samples. Formalin-fixed paraffin-embedded (FFPE) tonsil tissue specimens were obtained from an age- and sex-stratified random sample of patients aged 0-69 years whose paired tonsils were archived following elective tonsillectomy at hospitals throughout England and Southern Scotland from 2004 to 2008. Homogenised fresh-frozen tonsil tissue was also obtained from archive for two random subsets of males aged 25-34 and over 44. HPV status was assessed in all samples for 20 mucosal HPV types by GP5+/6+ polymerase chain reaction (PCR) enzyme immunoassay and by HPV16 type-specific PCR targeting the E6 gene. In the homogenised material, HPV status was also assessed for 44 HPV types by SPF10-PCR enzyme immunoassay. Of 4,095 randomly sampled FFPE specimens, amplifiable DNA was extracted from 3,377 (82.5%) and from 511 of 524 (97.5%) homogenised tonsils. HPV DNA was identified in 0 of 3,377 (0%, 95% CI 0-0.089%) fixed samples and 0 of 511 (0%, 95% CI 0-0.58%) homogenised samples. This suggests HPV infection may be rare in tonsil reticulated crypt epithelia. Furthermore, we found no evidence of HPV-associated premalignant neoplasia. These data suggest that if HPV-associated premalignant lesions do occur, they are likely to be rare and may have a high risk of progression to carcinoma.

Healthy eating and lifestyle in pregnancy (HELP): a protocol for a cluster randomised trial to evaluate the effectiveness of a weight management intervention in pregnancy.

BACKGROUND: Approximately 1 in 5 pregnant women in the United Kingdom are obese. In addition to being associated generally with poor health, obesity is known to be a contributing factor to pregnancy and birth complications and the retention of gestational weight can lead to long term obesity.This paper describes the protocol for a cluster randomised trial to evaluate whether a weight management intervention for obese pregnant women is effective in reducing women's Body Mass Index at 12 months following birth. METHODS/DESIGN: The study is a cluster randomised controlled trial involving 20 maternity units across England and Wales. The units will be randomised, 10 to the intervention group and 10 to the control group. 570 pregnant women aged 18 years or over, with a Body Mass Index of +/=30 (kg/m2) and between 12 and 20 weeks gestation will be recruited. Women allocated to the control group will receive usual care and two leaflets giving advice on diet and physical activity. In addition to their usual care and the leaflets, women allocated to the intervention group will be offered to attend a weekly 1.5 hour weight management group, which combines expertise from Slimming World with clinical advice and supervision from National Health Service midwives, until 6 weeks postpartum.Participants will be followed up at 36 weeks gestation and at 6 weeks, 6 months and 12 months postpartum. Body Mass Index at 12 months postpartum is the primary outcome. Secondary outcomes include pregnancy weight gain, quality of life, mental health, waist-hip ratio, child weight centile, admission to neonatal unit, diet, physical activity levels, pregnancy and birth complications, social support, self-regulation and self-efficacy. A cost effectiveness analysis and process evaluation will also be conducted. DISCUSSION: This study will evaluate the effectiveness of a theory-based intervention developed for obese pregnant women. If successful the intervention will equip women with the necessary knowledge and skills to enable them to make healthier choices for themselves and their unborn child. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN25260464 Date of registration: 16th April 2010.

Option Grids to facilitate shared decision making for patients with Osteoarthritis of the knee: protocol for a single site, efficacy trial.

BACKGROUND: Despite policy interest, an ethical imperative, and evidence of the benefits of patient decision support tools, the adoption of shared decision making (SDM) in day-to-day clinical practice remains slow and is inhibited by barriers that include culture and attitudes; resources and time pressures. Patient decision support tools often require high levels of health and computer literacy. Option Grids are one-page evidence-based summaries of the available condition-specific treatment options, listing patients' frequently asked questions. They are designed to be sufficiently brief and accessible enough to support a better dialogue between patients and clinicians during routine consultations. This paper describes a study to assess whether an Option Grid for osteoarthritis of the knee (OA of the knee) facilitates SDM, and explores the use of Option Grids by patients disadvantaged by language or poor health literacy. METHODS/DESIGN: This will be a stepped wedge exploratory trial involving 72 patients with OA of the knee referred from primary medical care to a specialist musculoskeletal service in Oldham. Six physiotherapists will sequentially join the trial and consult with six patients using usual care procedures. After a period of brief training in using the Option Grid, the same six physiotherapists will consult with six further patients using an Option Grid in the consultation. The primary outcome will be efficacy of the Option Grid in facilitating SDM as measured by observational scores using the OPTION scale. Comparisons will be made between patients who have received the Option Grid and those who received usual care. A Decision Quality Measure (DQM) will assess quality of decision making. The health literacy of patients will be measured using the REALM-R instrument. Consultations will be observed and audio-recorded. Interviews will be conducted with the physiotherapists, patients and any interpreters present to explore their views of using the Option Grid. DISCUSSION: Option Grids offer a potential solution to the barriers to implementing traditional decision aids into routine clinical practice. The study will assess whether Option Grids can facilitate SDM in day-to-day clinical practice and explore their use with patients disadvantaged by language or poor health literacy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN94871417.

Implementing GRADE: calculating the risk difference from the baseline risk and the relative risk.

A key step in implementing the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system is the estimation of a risk difference based on estimates of the baseline risk and the relative risk estimated from different sources. In this paper we describe a simple and effective method to calculate confidence intervals (CIs) for the risk difference for this situation. Whenever an independent source is available to estimate the baseline risk for the population to which the effect estimates should be applied, this source should be used and CIs for the absolute risk difference should be calculated taking all sources of uncertainty into account.

Confidence intervals for odds ratio and relative risk based on the inverse hyperbolic sine transformation.

The inverse hyperbolic sine transformation can be used to shorten the standard delta logit interval for the odds ratio and the delta log interval for the relative risk. As it stands, this transformation does not provide sufficient coverage. A pseudo-frequency modification is suggested and evaluated. The modification achieves an improvement in coverage for both the odds ratio and the relative risk and a further improvement in interval width for the odds ratio. We also find that another closed form interval, called MOVER-R Wilson, which is based on the method of variance estimates recovery, performs well. When the more complex and software demanding intervals, such as the asymptotic score, are unavailable, the adjusted inverse sinh intervals and MOVER-R Wilson provide two simple approaches to interval estimation of the odds ratio and the relative risk.

Clinical trials evaluating desensitising agents. Some design and analysis issues.

INTRODUCTION: The purpose of this short communication is to draw attention to an efficient design for trials to evaluate desensitising agents, and an appropriate statistical analysis. METHODS: Two recent sensitivity trials conducted by the Bristol Dental School Clinical Trials Group are reviewed. RESULTS: The methodology used was effective to establish efficacy of the products evaluated. CONCLUSIONS: This methodology is recommended for wider use. CLINICAL SIGNIFICANCE: Effective clinical trial methodology enables establishment of efficacy of desensitising products leading to patient benefit.

Total and free testosterone concentrations are strongly influenced by age and central obesity in men with type 1 and type 2 diabetes but correlate weakly with symptoms of androgen deficiency and diabetes-related quality of life.

OBJECTIVE: Testosterone levels are commonly lowered in men with diabetes, but it is unclear how these relate to symptoms of hypogonadism and quality of life. We sought to investigate the relationship between testosterone levels, symptoms of androgen deficiency, erectile function and quality of life in men with type 1 and type 2 diabetes. DESIGN AND SUBJECTS: Cross-sectional study of 115 men with type 2 diabetes, 93 men with type 1 diabetes and 121 healthy controls. MEASUREMENTS: Total, bioavailable and free testosterone levels were measured or calculated by Vermuelen's formula. Quality of life and symptom scores were assessed by the Audit of Diabetes Dependent Quality of Life (ADDQoL), androgen deficiency in the aging male (ADAM) and International Index of Erectile Function (IIEF) questionnaires. RESULTS: Forty-five and sixty-one per cent of men with type 2 diabetes had low total and calculated free testosterone (CFT) levels, respectively. Total testosterone (TT) levels were not lowered in men with type 1 diabetes, but 32% had low CFT. After adjustment for age and waist circumference, only CFT in men with type 2 diabetes (-0·037 nm, 95% CI -0·075 to -0·0003, P = 0.048) remained lowered compared with controls. CFT correlated weakly with ADAM (r = -0·26, 95% CI -0.42 to -0·08, P = 0·006), IIEF (r = 0.19, 95% CI 0.01-0.37, P = 0.042) and ADDQoL (r = 0.21, 95% CI 0·03 to 0·38, P = 0·022) scores in men with type 2, but not type 1 diabetes. Age exerted the predominant effect on erectile function in both groups, in a model incorporating age, testosterone level and complications. CONCLUSIONS: Testosterone levels are strongly affected by age and central obesity in men with type 1 and type 2 diabetes but correlate weakly with symptoms of androgen deficiency and erectile function. Testosterone levels do not appear to be a major determinant of quality of life in patients with diabetes.

The risk of cervical cancer associated with specific types of human papillomavirus: a case-control study in a UK population.

Mounting evidence supports incorporation of HPV testing into cervical screening; however, the optimal test format and target population have yet to be confirmed. Assessment of the potential benefits of type-specific testing requires estimation of the risk associated with infection with individual HPV types. However, the risk posed by individual HPV types may be population specific and influenced by cervical screening practice. The existing data on HPV type-specific risk is derived largely from unscreened populations. Our study addressed the lack of data on HPV type-specific risk in cytologically screened populations using a case-control study of 262 invasive cervical cancers diagnosed in Wales between 2000 and 2006, and 8,428 controls who attended for cytological screening in 2004. The analysis showed that the odds ratios (ORs) for infection with HPV 16 and 18 are considerable; 2770 (95% CI 1050-7320) and 950 (95% CI 330-2740), respectively, and that the OR for other oncogenic types are in general considerably less (ranging, where quantified, from 20.2 to 386 in the same population). The effect of age on OR associated with particular HPV types was also assessed; this indicated that infection with a high-risk HPV in women older than 40 years was associated with an approximately 30-fold increased risk of invasive cervical cancer relative to women younger than 40 years. These results indicate that there is significant prognostic information associated with knowledge of HPV type.

A randomised controlled trial to compare the efficacy of an aluminium lactate/potassium nitrate/hydroxylapatite toothpaste with a control toothpaste for the prevention of dentine hypersensitivity.

OBJECTIVES: To determine the efficacy of a cosmetic aluminium lactate/potassium nitrate/hydroxylapatite toothpaste for the reduction of dentine hypersensitivity (DH) pain as compared to a control toothpaste containing potassium nitrate. METHODS: The study was a randomised, examiner-blind, two treatment arm, parallel controlled trial in healthy adults with at least 2 sensitive teeth (Schiff >2). At baseline, immediately after treatment and at 7 and 14 days of twice-daily brushing of the test or control toothpaste the sensitivity of 2 test teeth was measured following iced-water (Schiff and VAS) and tactile (Yeaple probe) stimuli, and a whole mouth plaque score was obtained. Participants also completed a whole-mouth VAS and DHEQ15 quality of life questionnaire at baseline, 7 and 14 days. RESULTS: Both toothpastes reduced DH in test teeth, but pain reduction in the test group was significantly better at all timepoints and by all measures (p = 0.005, tooth-level VAS immediately after brushing; p < 0.001 all other comparisons). There was a relative risk reduction of Schiff sensitivity of 55 % immediately after brushing which rose to 81 % after 7 and 88.6 % after 14 days (all p < 0.001). There were no differences in plaque, whole mouth VAS or DHEQ15 scores at any time point. CONCLUSION: This study demonstrated the efficacy of an aluminium lactate/potassium nitrate/hydroxylapatite toothpaste compared to a potassium nitrate control toothpaste for the prevention of dentine hypersensitivity both immediately and over a 2 week period. This agent appears to have potential for pain alleviation from the common oral pain condition of DH and further research is warranted. CLINICAL SIGNIFICANCE: DH pain, whilst transient in nature, is arresting in magnitude, affecting quality of life. Daily application of efficacious toothpastes can relieve DH pain however, as yet, there is no gold standard treatment. The results of this study support further investigation of an aluminium lactate/potassium nitrate/hydroxylapatite toothpaste for DH management.

Randomised controlled trial of a microneedle patch with a topical anaesthetic for relieving the pain of dental injections.

OBJECTIVES: To determine whether a microneedle patch combined with 5% topical lidocaine reduces dental injection pain more than a patch without microneedles combined with 5% topical lidocaine. METHODS: This proof of principle randomised, two-treatment, double-blind, crossover split-unit design study in 16 healthy participants investigated levels of perceived pain from 3 increasing pain provoking challenges, when topical 5% lidocaine dental gel was applied to the oral mucosa with a microneedle patch and a patch with no microneedles, prior to infiltration with local anaesthesia on 2 visits. Pain was assessed by visual analogue scale (VAS) and 4-point verbal rating scale (VRS). RESULTS: 15 participants completed the study. Mean pain scores, lower at buccal sites, increased in both groups across challenges 1-3: Test palatal 5.1, 11.9, 26.8; buccal 0.7, 2.8, 18.3; Control palatal 12.3, 18.7, 39.5; buccal 4.0, 6.9, 30.6. The microneedle patch plus lidocaine significantly lowered VAS pain scores at both sites for all challenges, the biggest mean difference seen palatally after challenge 3 (12.7, p < 0.001). VRS pain scores were also significantly reduced for test compared to control for all 3 challenges (p = 0.014). Buccal scores favoured the microneedle patch, significantly for pain challenge 3 (p = 0.025). No adverse events occurred. CONCLUSIONS: Prior oral application of a microneedle patch combined with 5% topical lidocaine gel reduced the pain experienced from dental infiltration. Microneedle patch use in the dental setting offers the prospect of improving degree and depth of anaesthesia from topically applied anaesthetic gel, without itself causing any pain. CLINICAL SIGNIFICANCE: Dental injections are associated with fear and anxiety. Application of a microneedle patch, combined with topical anaesthetic, to the oral mucosa prior to delivery of the injection reduces the pain from this dental procedure. This novel technique may allay patients' apprehension of local anaesthesia and improve quality of life outcomes.

Reduced total testosterone concentrations in young healthy South Asian men are partly explained by increased insulin resistance but not by altered adiposity.

OBJECTIVE: To compare ethnic differences in total, free and bioavailable testosterone amongst young healthy South Asian and Caucasian men. DESIGN AND SUBJECTS: Cross-sectional study of 134 healthy men (age 20-40 years) of South Asian (n = 67) or Caucasian (n = 67) origin, recruited from hospital staff and students working in Newport, UK. Subjects were excluded if they had a fasting plasma glucose >5.9 mmol/l, central obesity [waist circumference ≥ 94 cm (Caucasian) or ≥ 90 cm (South Asian)] or significant other disease. MEASUREMENTS: Fasting plasma glucose, total testosterone (determined by immunoassay and mass spectrometry), albumin, sex hormone-binding globulin (SHBG) and insulin were measured. Free and bioavailable testosterone were calculated using Vermeulen's formula, and insulin resistance was estimated by HOMA-IR. RESULTS: The South Asians were slightly older (P = 0.04), shorter (P < 0.001), lighter (P < 0.001), more insulin resistant (P = 0.006), and had a lower body mass index BMI (P = 0.012), waist circumference (P = 0.043) and SHBG (P = 0.001) than the Caucasians. Total testosterone was significantly lower in South Asians (mass spectrometry: geometric mean 16.3 nmol/l; 95% reference interval 9.3-28.6 nmol/l) compared with Caucasians (mass spectrometry: geometric mean 18.4 nmol/l; 95% reference interval 10.6-31.9 nmol/l; P = 0.015), but calculated free and bioavailable testosterone were not different between groups. Adjusting for HOMA-IR, but not BMI or waist circumference, partly attenuated the differences in total testosterone. CONCLUSIONS: Total, but not free, testosterone concentrations are lower in healthy South Asian men than in Caucasians. These differences are apparent at a young age and may be partly attributable to alterations in insulin sensitivity.

Supporting informed decision making online in 20 minutes: an observational web-log study of a PSA test decision aid.

BACKGROUND: Web-based decision aids are known to have an effect on knowledge, attitude, and behavior; important components of informed decision making. We know what decision aids achieve in randomized controlled trials (RCTs), but we still know very little about how they are used and how this relates to the informed decision making outcome measures. OBJECTIVE: To examine men's use of an online decision aid for prostate cancer screening using website transaction log files (web-logs), and to examine associations between usage and components of informed decision making. METHODS: We conducted an observational web-log analysis of users of an online decision aid, Prosdex. Men between 50 and 75 years of age were recruited for an associated RCT from 26 general practices across South Wales, United Kingdom. Men allocated to one arm of the RCT were included in the current study. Time and usage data were derived from website log files. Components of informed decision making were measured by an online questionnaire. RESULTS: Available for analysis were 82 web-logs. Overall, there was large variation in the use of Prosdex. The mean total time spent on the site was 20 minutes. The mean number of pages accessed was 32 (SD 21) out of a possible 60 pages. Significant associations were found between increased usage and increased knowledge (Spearman rank correlation [rho] = 0.69, P < .01), between increased usage and less favorable attitude towards PSA testing (rho = -0.52, P < .01), and between increased usage and reduced intention to undergo PSA testing (rho = -0.44, P < .01). A bimodal distribution identified two types of user: low access and high access users. CONCLUSIONS: Increased usage of Prosdex leads to more informed decision making, the key aim of the UK Prostate Cancer Risk Management Programme. However, developers realistically have roughly 20 minutes to provide useful information that will support informed decision making when the patient uses a web-based interface. Future decision aids need to be developed with this limitation in mind. We recommend that web-log analysis should be an integral part of online decision aid development and analysis. TRIAL REGISTRATION: ISRCTN48473735; http://www.controlled-trials.com/ISRCTN48473735 (Archived by WebCite at http://www.webcitation.org/5pqeF89tS).

Supporting informed decision making for prostate specific antigen (PSA) testing on the web: an online randomized controlled trial.

BACKGROUND: Men considering the prostate specific antigen (PSA) test for prostate cancer, an increasingly common male cancer, are encouraged to make informed decisions, as the test is limited in its accuracy and the natural history of the condition is poorly understood. The Web-based PSA decision aid, Prosdex, was developed as part of the UK Prostate Cancer Risk Management Programme in order to help men make such informed decisions. OBJECTIVES: The aim of this study was to evaluate the effect of the Web-based PSA decision aid, Prosdex, on informed decision making. METHODS: A Web-based randomized controlled trial was conducted in South Wales, United Kingdom. Men aged 50 to 75 who had not previously had a PSA test were randomly allocated to two intervention and two control groups. Participants in the intervention groups either viewed Prosdex or were given a paper version of the text. The main outcome measures were the three components of informed decision making: (1) knowledge of prostate cancer and PSA, (2) attitude toward PSA testing, (3) behavior using a proxy measure, intention to undergo PSA testing. Decisional conflict and anxiety were also measured as was uptake of the PSA test. Outcomes were measured by means of an online questionnaire for the Prosdex group, the paper version group, and one of two control groups. Six months later, PSA test uptake was ascertained from general practitioners' records, and the online questionnaire was repeated. Results are reported in terms of the Mann-Whitney U-statistic divided by the product of the two sample sizes (U/mm), line of no effect 0.50. RESULTS: Participants were 514 men. Compared with the control group that completed the initial online questionnaire, men in the Prosdex group had increased knowledge about the PSA test and prostate cancer (U/mn 0.70; 95% CI 0.62 - 0.76); less favourable attitudes to PSA testing (U/mn 0.39, 95% CI 0.31 - 0.47); were less likely to undergo PSA testing (U/mn 0.40, 95% CI 0.32 - 0.48); and had less decisional conflict (U/mn 0.32, 95% CI 0.25 - 0.40); while anxiety level did not differ (U/mn 0.50, 95% CI 0.42 - 0.58). For these outcomes there were no significant differences between men in the Prosdex group and the paper version group. However, in the Prosdex group, increased knowledge was associated with a less favourable attitude toward testing (Spearman rank correlation [rho] = -0.49, P < .001) and lower intention to undergo testing (rho = -0.27, P = .02). After six months, PSA test uptake was lower in the Prosdex group than in the paper version and the questionnaire control group (P = .014). Test uptake was also lower in the control group that did not complete a questionnaire than in the control group that did, suggesting a possible Hawthorne effect of the questionnaire in favour of PSA testing. CONCLUSIONS: Exposure to Prosdex was associated with improved knowledge about the PSA test and prostate cancer. Men who had a high level of knowledge had a less favourable attitude toward and were less likely to undergo PSA testing. Prosdex appears to promote informed decision making regarding the PSA test. TRIAL REGISTRATION: ISRCTN48473735; http://www.controlled-trials.com/ISRCTN48473735 (Archived by WebCite at http://www.webcitation.org/5r1TLQ5nK).

A novel cervical tooth wear and recession index, the cervical localisation code, and its application in the prevention and management of dentine hypersensitivity.

OBJECTIVES: To design and validate a new index to assess tooth wear (TW) in the cervical region and its association with gingival recession (GR), for use both in research studies and as resource in General Dental Practice, with focused prevention and management strategiesparticularly related to aetiology of dentine hypersensitivity provided for each Code score. METHODS: Codes to reflect clinical presentations of the cervical region in health and disease recording both TW and GR were defined. Validation of the Code was undertaken by 3 trained examiners who scored buccal and lingual surfaces of eligible teeth in 42 adult healthy volunteers. Each volunteer underwent 4 identical clinical examinations, being assessed twice by the examiner who performed the first and last exam. RESULTS: Cervical Localisation Code definitions were A: no GR, no coronal TW, B: no GR, distinct coronal TW, C: GR but no coronal TW, D: GR with distinct coronal and root TW. For validation 2073 eligible tooth surfaces were scored. There were only 57 within and 201 between examiner disagreements, the most common being between scores C and D. CONCLUSIONS: The Cervical Localisation Code was used reproducibly by three independent examiners. It will provide focussed data on the cervical region in research studies allowing the association of patient reported dietary and lifestyle factors with specific lesion types, and a tool to aid the management of clinical scenarios, specifically those that lead to dentine hypersensitivity in general dental practice. CLINICAL SIGNIFICANCE: Exposure of dentine at the cervical margin by TW and/or GR often results in dentine hypersensitivity, however current TW indices do not record TW location or GR presence. The Cervical Localisation Code captures both parameters and suggests likely aetiology for dentine hypersensitivity and guide clinical management of the cervical region.

A randomised controlled trial investigating efficacy of a novel toothpaste containing calcium silicate and sodium phosphate in dentine hypersensitivity pain reduction compared to a fluoride control toothpaste.

OBJECTIVES: To compare a calcium silicate and sodium phosphate toothpaste (CSSP) with a fluoride negative control toothpaste for dentine hypersensitivity (DH) pain reduction after 14, 28 and 29 days. METHODS: This was a double blind, parallel study in 247 healthy adults with DH (Schiff score >2, tactile 10-20 g) in 2 teeth in different quadrants of the mouth. After acclimatisation, participants were randomised to CSSP or control toothpaste. After measuring baseline sensitivity products were applied twice-daily by toothbrushing, and once daily massaging into the sensitive teeth. Sensitivity was assessed following airblast (Schiff and VAS) and tactile (Yeaple probe) stimuli at baseline, 14 and 28 days, and at 29 days, 12 h after last product application. Participants completed a quality of life questionnaire at each study visit up to day 28. RESULTS: After 14, 28 and 29 days the CSSP group had significantly lower Schiff, lower VAS and higher Yeaple probe scores compared to control (VAS at 14 days, p < 0.04; all other comparisons, p < 0.001). Quality of life scores improved in both groups, but no significant differences between groups were observed. CONCLUSIONS: The CSSP toothpaste was more effective than the fluoride control toothpaste at reducing DH pain with benefit persisting 12 h following application. CLINICAL SIGNIFICANCE: This novel calcium silicate and sodium phosphate toothpaste (CSSP) toothpaste is an effective twice-daily treatment when brushed on the teeth for dentine hypersensitivity sufferers compared to brushing with a conventional fluoride paste. Twice-daily brushing provides a sustained effect for long-lasting pain relief from dentine hypersensitivity.

A randomised controlled trial to determine patient experience of a magnetostrictive stack scaler as compared to a piezoelectric scaler, in supportive periodontal therapy.

OBJECTIVES: To compare the pain/discomfort experienced by patients in supportive periodontal therapy, following treatment with a piezoelectric ultrasonic scaler, designed for use with warmed water irrigation, and a magnetostrictive ultrasonic scaler. METHODS: This was a single-centre, randomised, split mouth study with regard to side, and crossover with regard to treatment order. Patients attending general dental practice for supportive periodontal therapy were randomised to receive treatment from one scaler on the left and the other scaler on the right-hand side of the mouth, the left side of the mouth always being treated first. The piezo scaler (Tigon+®) was used with room temperature irrigation for half of the participants (approx 20 °C) and warmed water irrigation (approx 36 °C) for the other half. The magnetostrictive scaler (Cavitron Select SPS 30K®) was used with room temperature irrigation (approx 20 °C) only. Participants rated their pain/discomfort, noise and vibration by VAS scale. RESULTS: 140 participants completed the study. Mean VAS scores for all measures were significantly better for the piezo scaler used with warm irrigation as compared to the magnetostrictive scaler p < 0.001. When both scalers were used with room temperature irrigant, there were no significant differences in the VAS scores between scalers (pain/discomfort, p = 0.68; noise p = 0.2; vibration p = 0.85). CONCLUSIONS: Participants indicated to statistical significance, less pain/discomfort, noise and vibration when the piezo scaler (Tigon+®) device was used with warmed irrigant, compared to the magnetostrictive scaler (Cavitron Select SPS 30K®). There were no significant differences between the instruments when room temperature irrigant was used. CLINICAL SIGNIFICANCE: Regular scaling in supportive periodontal therapy, is essential for maintenance of susceptible patients, however it can be painful due to dentine hypersensitivity deterring patients from attending. Using a piezo scaler with warm water improves patient quality of life and subsequent oral health. This may have positive effects on patient attendance. ISRCTN REGISTERED: ISRCTN15573995.

Detection of breast cancer metastasis in sentinel lymph nodes using intra-operative real time GeneSearch BLN Assay in the operating room: results of the Cardiff study.

BACKGROUND: Intra-operative assessment is not routinely performed in the UK due to poor sensitivity of available methods and overburdened pathology resources. We conducted a prospective clinical feasibility study of the GeneSearch Breast Lymph Node (BLN) Assay (Veridex, LLC, Warren, NJ) to confirm its potential usefulness within the UK healthcare system. METHODS: In the assay 50% of the lymph node was processed to detect the presence of cytokeratin-19 and mammaglobin mRNA. The assay was calibrated to detect metastases >0.2 mm. Assay results were compared to H&E performed on each face of approximately 2 mm alternating node slabs and 3 additional sections cut at approximately 150 microm interval from each face of the node slab. RESULTS: 124 sentinel lymph nodes were removed from 82 breast cancer patients. The assay correctly identified all 6 patients with sentinel node macrometastases (>2.0 mm), and 2 of 3 patients with sentinel node micrometastases (0.2-2.0 mm). Sentinel lymph nodes in 4 patients were assay positive but histology negative. Two of these four patients had isolated tumor cells seen by histology. The overall concordance with histology was 93.9% (77/82), with sensitivity of 88.9% (8/9, 95% CI 56.5-98%), specificity of 94.6% (69/73, 95% CI 86.7-97.8%), positive predictive value of 66.7% (8/12, 95% CI 39.1-86.2%) and negative predictive value of 98.6% (69/70, 95% CI 92.3-99.7%). The assay was performed in a median time of 32 min (range 26-69 min). CONCLUSION: Intra-operative assessment of sentinel lymph node can be performed rapidly and accurately using the GeneSearch BLN Assay.