Mutation based approaches to the treatment of anaplastic thyroid cancer.

OBJECTIVE: The treatment of anaplastic thyroid cancer (ATC) has continued to rapidly evolve over time. Increased utilization of novel, personalized therapies based upon the tumour's somatic mutation status has recently been integrated. The aim of this case series is to describe a series of patients that underwent rapid genomic testing upon their diagnosis of ATC, allowing for the early integration of novel therapies. DESIGN: A fast track pathway for genomic tumour analysis of patients with ATC was implemented at a single academic cancer hospital in January of 2020. PATIENTS: All patients were evaluated by head and neck surgery, endocrinology, and medical oncology upon diagnosis of ATC. MEASUREMENTS: Genetic work-up was completed, which prompted a recommendation for dual BRAF/MEK inhibition with dabrafenib and trametinib for tumours with BRAF V600E mutation. For patients whose tumours were BRAF V600E wild-type, pembrolizumab with lenvatinib was offered. RESULTS: A total of four patients were included in this series. Two patients (50%) had tumours that were BRAF V600E positive. Among patients that were BRAF V600E positive, both patients initiated urgent dabrafenib and trametinib dual tyrosine kinase inhibitor (TKI) therapy; with one patient demonstrating near-complete clinical response allowing for posttreatment surgery, while the other demonstrated decreased tumour burden. Among patients who were BRAF V600E wild-type, lenvatinib and pembrolizumab were recommended off-label; one patient demonstrated decreased tumour burden, but developed severe pure red cell aplasia, while the other patient is demonstrating an early clinical response. CONCLUSIONS: The integration of early genomic analysis and personalized neoadjuvant TKI therapy into the treatment of ATC can greatly benefit patient care outcomes and optimize tumour control.

Interventions with pregnant women, new mothers and other primary caregivers for preventing early childhood caries.

BACKGROUND: Dental caries is one of the most common chronic diseases of childhood and is associated with adverse health and economic consequences for infants and their families. Socioeconomically disadvantaged children have a higher risk of early childhood caries (ECC). OBJECTIVES: To assess the effects of interventions with pregnant women, new mothers or other primary caregivers of infants in the first year of life, for preventing ECC (from birth to six years of age). SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 14 January 2019), Cochrane Pregnancy and Childbirth Group's Trials Register (to 22 January 2019), Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Register of Studies, to 14 January 2019), MEDLINE Ovid (1946 to 14 January 2019), Embase Ovid (1980 to 14 January 2019) and CINAHL EBSCO (1937 to 14 January 2019). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on language or publication status. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing one or more interventions with pregnant women, mothers, or other caregivers of infants in the first year of life (intervention types included clinical, oral health education/promotion such as hygiene education, breastfeeding and other dietary advice, and policy or health service), versus standard care or placebo or another intervention. For inclusion, trials had to report at least one caries outcome. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, extracted data, assessed risk of bias, and assessed certainty of evidence using the GRADE approach. MAIN RESULTS: We included 17 RCTs (4 cluster-randomised), involving 23,732 caregivers (mainly mothers) and their children. Eleven RCTs assessed four oral health education/promotion interventions against standard care: child diet advice, child diet and feeding practice advice, breastfeeding promotion and support, and oral hygiene with child diet and feeding practice advice. Six trials assessed clinical interventions in mother's dentition, four trials chlorhexidine (CHX, a commonly prescribed antiseptic agent) or iodine-NaF application and prophylaxis versus placebo, and two trials xylitol against CHX or CHX + xylitol. At most, three trials (maximum of 1148 children and 130 mothers) contributed data to any comparison. For many trials, risk of bias was judged unclear due to lack of methodological details reported, and there was high risk of attrition bias in some trials. None of the included trials indicated receiving funding that is likely to have influenced their results. The trials were performed in high-, middle- and low-income countries. In nine trials, participants were socioeconomically disadvantaged. For child diet and feeding practice advice versus standard care, we observed a probable 15 per cent reduced risk of caries presence in primary teeth with the intervention (RR 0.85, 95% CI 0.75 to 0.97; 3 trials; 782 participants; moderate-certainty evidence), and there may be a lower mean dmfs (decayed, missing, filled primary surfaces) score (MD -0.29, 95% CI -0.58 to 0; 2 trials; 757 participants; low-certainty evidence); however, we are uncertain regarding the difference between the groups in mean dmft (decayed, missing, filled teeth) score (MD -0.90, 95% CI -1.85 to 0.05; 1 trial; 340 participants; very low-certainty evidence). For breastfeeding promotion and support versus standard care, we observed that there may be little or no a difference between groups in the risk of caries presence in primary teeth (RR 0.96, 95% CI 0.89 to 1.03; 2 trials; 1148 participants; low-certainty evidence), or mean dmft score (MD -0.12, 95% CI -0.59 to 0.36; 2 trials; 652 participants; low-certainty evidence). Dmfs was not reported for this comparison. We are uncertain whether child diet advice only compared with standard care reduces risk of caries presence in primary teeth (RR 1.08, 95% CI 0.34 to 3.37; 1 trial; 148 participants; very low-certainty evidence). Dmfs and dmft were not reported for this comparison. For oral hygiene, child diet and feeding practice advice versus standard care, we observed little or no reduced risk of caries presence in primary teeth (RR 0.91, 95% CI 0.75 to 1.10; 2 trials; 365 participants; low-certainty evidence), and are uncertain regarding difference between the groups in mean dmfs score (MD -0.99, 95% CI -2.45 to 0.47; 1 trial; 187 participants; very low-certainty evidence) and dmft score (MD -0.30, 95% CI -0.96 to 0.36; 1 trial; 187 participants; very low-certainty evidence). We observed there may be little or no difference in risk of caries presence in primary teeth between antimicrobial and placebo treatment in mother's dentition (RR 0.97, 95% CI 0.80 to 1.19; 3 trials; 479 participants; very low-certainty evidence). No trials assessing this comparison reported dmfs or dmft. For xylitol compared with CHX antimicrobial treatment, we observed there may be a lower mean dmft score with xylitol (MD -2.39; 95% CI -4.10 to -0.68; 1 trial, 113 participants; low-certainty evidence); however, we are uncertain regarding the difference between groups in caries presence in primary teeth (RR 0.62, 95% CI 0.27 to 1.39; 1 trial, 96 participants; very low-certainty evidence). Neither trial evaluating this comparison reported dmfs. No trials assessed a health policy or service intervention. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that providing advice on diet and feeding to pregnant women, mothers or other caregivers with children up to the age of one year probably leads to a slightly reduced risk of early childhood caries (ECC). The remaining evidence is low to very low certainty and is insufficient for determining which, if any, other interventions types and features may be effective for preventing ECC. Large, high-quality RCTs of oral health education/promotion, clinical, and policy and service access interventions, are warranted to determine effects and relative effects of different interventions and inform practice. We have identified 12 studies currently in progress. Those designing future studies should describe the intervention components, setting and participants, consider if and how effects are modified by intervention features and participant characteristics, and adopt a consistent approach to measuring and reporting ECC.

MOLECULAR PROFILE AND CLINICAL OUTCOMES IN DIFFERENTIATED THYROID CANCER PATIENTS PRESENTING WITH BONE METASTASIS.

Objective: Differentiated thyroid cancer patients uncommonly present with bone metastasis as the initial manifestation. Their molecular profile is largely unknown. The aim of this study was to evaluate the histopathology, molecular profiles, and response to radioactive iodine therapy in these patients. Methods: Eight patients presented with symptomatic bone metastasis from an unknown primary tumor. We identified these patients by performing a retrospective chart review. Pathology slides were reviewed and the molecular analysis of 112 thyroid cancer-related genes was performed on bone metastasis specimens using targeted next-generation sequencing. Results: These patients presented with long bone fractures, spinal cord compression, or intractable bone pain. Histopathologic analysis of the bone and thyroid tumor specimens revealed follicular variant of papillary carcinoma in 7 patients and tall cell variant papillary carcinoma in 1 patient. Primary tumor size ranged from 0.4 to 7.5 cm. All patients received high dose radioiodine therapy following thyroidectomy. Molecular analysis revealed telomerase reverse transcriptase (TERT) mutations in 7 (88%) tumors, 4 (50%) contained co-occurring TERT and RAS GTPase gene (RAS) mutations, 2 had isolated TERT mutations, and 1 had TERT and proto-oncogene B-Raf (BRAF) V600E mutations, respectively. Tumors carrying RAS, TERT, or a combination of these mutations were radioiodine-avid, with predictable tumor response and reduction in serum thyroglobulin levels. One patient with radioiodine-refractory disease harbored BRAF and TERT mutations. Conclusion: These results demonstrate that differentiated thyroid cancers presenting with bone metastasis independent of the primary tumor size have a high prevalence of TERT mutations, frequently coexisting with RAS mutations. This molecular signature may predict a favorable response to radioiodine therapy. Abbreviations: BRAF = proto-oncogene B-Raf; DNA = deoxyribonucleic acid; DTC = differentiated thyroid cancer; FV = follicular variant; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; RAS = Ras GTPase gene; TERT = telomerase reverse transcriptase; TG = thyroglobulin.

Cholangiocarcinoma and high-grade dysplasia in young patients with primary sclerosing cholangitis.

INTRODUCTION: Cholangiocarcinoma (CCA) is very often an adulthood disease with primary sclerosing cholangitis (PSC) as one of the risk factors. It is rarely seen in the pediatric population, and when it is diagnosed before adulthood, it can be associated with PSC as well as HIV infection, biliary atresia, radiation therapy, and choledochal cyst. Although there have been some case reports of pediatric CCA, cases of childhood CCA associated with PSC are still relatively rare. AIM: To describe the clinical and pathologic features of CCA in pediatric patients with previously diagnosed PSC. METHODS: Retrospective study RESULTS: Four patients with PSC (age range 15-18, mean 17 years) were included in this study. All patients underwent ERCP for diagnosis. Tissue samples obtained included routine cytology and FISH. ERCP was used to target sites for tissue acquisition in all patients. 3/4 of patients have inflammatory bowel disease (two Crohn's disease and one ulcerative colitis). Alkaline phosphatase was elevated in 3/4 patients, aspartate aminotransferase/alanine aminotransferase were elevated in 2/4 patients, and total bilirubin/direct bilirubin were elevated in 2/4 patients. 4/4 patients had positive FISH studies, and 3/4 patients had brush cytology concerning for CCA. 2/4 patients received chemotherapy, one patient underwent orthotopic liver transplant, and one patient underwent Whipple procedure. Two patients died soon after being diagnosed. CONCLUSIONS: Young patients with PSC can develop CCA. This finding has implications for both screening and surveillance for cancer in pediatric patients with PSC.

Dropper method for cytology slide staining: An effective and sustainable approach to eliminating cross contamination.

Cytopathology laboratories must ensure effective measures to prevent cross-contamination during slide staining. As such, slides with high potential for cross-contamination are usually stained separately, by dipping slides into a series of Romanowsky-type stains, with periodic (usually weekly) filtering and replacement of stains used. Our 5-year experience and a validation study of an alternative dropper method is presented. In this method, cytology slides are placed in a staining rack, a small amount of stain is applied to each using a dropper. Because of the small amount of stain used, this dropper method requires no filtering or reuse of stain, eliminating the possibility of cross contamination and reducing the total amount of stain used. In our 5-year experience, we report a complete elimination of cross contamination due to staining, excellent staining quality, and a slight reduction in overall stain expenditure.

Protocol for "Seal or Varnish?" (SoV) trial: a randomised controlled trial to measure the relative cost and effectiveness of pit and fissure sealants and fluoride varnish in preventing dental decay.

BACKGROUND: Dental caries remains a significant public health problem, prevalence being linked to social and economic deprivation. Occlusal surfaces of first permanent molars are the most susceptible site in the developing permanent dentition. Cochrane reviews have shown pit and fissure sealants (PFS) and fluoride varnish (FV) to be effective over no intervention in preventing caries. However, the comparative cost and effectiveness of these treatments is uncertain. The primary aim of the trial described in this protocol is to compare the clinical effectiveness of PFS and FV in preventing dental caries in first permanent molars in 6-7 year-olds. Secondary aims include: establishing the costs and the relative cost-effectiveness of PFS and FV delivered in a community/school setting; examining the impact of PFS and FV on children and their parents/carers in terms of quality of life/treatment acceptability measures; and examining the implementation of treatment in a community setting. METHODS/DESIGN: The trial design comprises a randomised, assessor-blinded, two-arm, parallel group trial in 6-7 year old schoolchildren. Clinical procedures and assessments will be performed at 66 primary schools, in deprived areas in South Wales. Treatments will be delivered via a mobile dental clinic. In total, 920 children will be recruited (460 per trial arm). At baseline and annually for 36 months dental caries will be recorded using the International Caries Detection and Assessment System (ICDAS) by trained and calibrated dentists. PFS and FV will be applied by trained dental hygienists. The FV will be applied at baseline, 6, 12, 18, 24 and 30 months. The PFS will be applied at baseline and re-examined at 6, 12, 18, 24, and 30 months, and will be re-applied if the existing sealant has become detached/is insufficient. The economic analysis will estimate the costs of providing the PFS versus FV. The process evaluation will assess implementation and acceptability through acceptability scales, a schools questionnaire and interviews with children, parents, dentists, dental nurses and school staff. The primary outcome measure will be the proportion of children developing new caries on any one of up to four treated first permanent molars. DISCUSSION: The objectives of this study have been identified by the National Institute for Health Research as one of importance to the National Health Service in the UK. The results of this trial will provide guidance on which of these technologies should be adopted for the prevention of dental decay in the most susceptible tooth-surface in the most at risk children. TRIAL REGISTRATIONS: ISRCTN ref: ISRCTN17029222 EudraCT: 2010-023476-23 UKCRN ref: 9273.

Response rates to questionnaire-based studies in the contemporary dental literature: A systematic review.

OBJECTIVES: This systematic review aimed to investigate what is a reasonable response rate for dental questionnaire-based studies in recent literature and to assess the factors that affect the response rates. METHODS: We used MEDLINE/PubMed to search the dental literature of 2021 (January-October). Two reviewers independently assessed studies eligibility and extracted data using standardized electronic extraction form. RESULTS: One hundred and seventy-two studies were eligible, of these a total of 149 response rates were reported from 133 studies, whereas the remaining 39 studies were excluded as they did not report response rates. The median response rate across the included studies was 77% (mean = 70.8%). We found significant negative correlation between the response rate and the actual number of distributed questionnaires (sample size) (r = -0.4127; P < 0.001). We also found an association between the response rate and the area of distribution, e.g., national or international (P = 0.0012). However, a wide variation was observed in the quality of information reported within this review and we did not find clear evidence of association between the response rate and other variables such as questionnaire piloting, number of questions in the questionnaire and the journal impact factor. CONCLUSIONS: The findings of this systematic review confirm the association between the response rate and the sample size, where the response rate increases when the sample size less than 300 participants. In addition, a higher response rate could be achieved when the study conducted within the same institution (e.g., university). SIGNIFICANCE: Questionnaire-based research can provide answers to several questions that could not be answered by other types of research related to the field of dentistry, dental health practitioners and students' attitudes and behaviours and more. Questionnaire-based publications can effectively contribute to dental research; thus, dental journals should consider development of a minimum set of guidelines in the reporting of questionnaire-based manuscripts.

Allele-specific PCR with competitive probe blocking for sensitive and specific detection of BRAF V600E in thyroid fine-needle aspiration specimens.

OBJECTIVE: To detect BRAF V600E mutation in thyroid fine-needle aspiration (FNA) slides and needle rinses (NR). STUDY DESIGN: Tumor-enriched DNA was extracted from FNA smears, formalin-fixed paraffin-embedded (FFPE) sections, or NR specimens from 37 patients with confirmed papillary thyroid carcinoma or benign findings. An allele-specific primer selectively amplified the 1799 T>A BRAF mutation while simultaneously blocking amplification of wild-type (WT) BRAF with an unlabeled probe during PCR. Mutation detection was accomplished by melting analysis of the probe. RESULTS: Allele-specific/blocking probe PCR confirmed the BRAF mutation status for 20 of 24 paired FNA/FFPE samples previously tested by fluorescent probe real-time PCR. For the other 4 cases, the sensitive PCR method detected the BRAF mutation in all paired FNA/FFPE samples. Previously, the mutation had been detected in only the FFPE samples. The BRAF mutation was also detected in some NR specimens. CONCLUSION: Treatment of patients with thyroid nodules is guided by FNA biopsy, which can be scantly cellular, necessitating a sensitive test that can detect low levels of BRAF V600E mutation in a WT background. We report increased detection of BRAF V600E in FNA specimens using allele-specific/blocking probe PCR, which has an analytical sensitivity of 0.01%.

The influence of a short training program on the clinical examination of dental restorations.

PURPOSE: To investigate how a simple restoration evaluation training program affected restoration replacement decision making by a group of 16 dentists. METHOD: The clinical examination of 66 dental restorations in nine female patients was carried out by two groups of dentists: one having previously received training in restoration assessment. The results of these assessments were compared to a gold standard for restoration integrity determined by two experienced clinicians applying US Public Health Service criteria. All evaluations were completed under controlled clinical conditions with standard equipment and lighting. The results of the clinical examinations between the trained (test) group and the untrained (control) group were compared to each other and the gold standard. RESULTS: The trained group scheduled fewer restorations for replacement (6.00±3.01 and 9.71±3.15; p=0.034), in a shorter time (27.86±3.45 mins and 36.71±3.74 mins; p=0.003) and showed greater agreement with the study's gold standard for restoration replacement (0.85±0.27 and 0.79±0.06; p=0.002). CONCLUSION: Within the limits of this study, examiner training can significantly improve the reliability of restoration replacement decision making by dentists.

Factors associated with dental fluorosis among Malaysian children exposed to different fluoride concentrations in the public water supply.

OBJECTIVES: To determine the prevalence of dental fluorosis, and factors associated with its occurrence in two cohorts of children exposed to different fluoride concentrations in the Malaysian water supply. METHODS: A cross-sectional study was conducted among lifelong residents (n = 1,155) aged 9 and 12 years old living in fluoridated and nonfluoridated areas. Malaysian children aged 12 years were born when the level of fluoride in the public water supply was 0.7 ppm while those aged 9 years were born after the level was reduced to 0.5 ppm. Fluorosis was blind scored using standardized photographs of maxillary central incisors using Dean's criteria. Fluoride exposures and other factors were assessed by parental questionnaire. Data were analyzed using descriptive statistics, Chi-squared analyses, and logistic regression. RESULTS: Fluorosis prevalence was lower (31.9 percent) among the younger children born after the reduction of fluoride concentration in the water, compared to a prevalence of 38.4 percent in the older cohort. Early tooth brushing practices and fluoridated toothpaste were not statistically associated with fluorosis status. However, the prevalence of fluorosis was significantly associated with parents' education level, parents' income, fluoridated water, type of infant feeding method, age breast feeding ceased, use of formula milk, duration of formula milk intake, and type of water used to reconstitute formula milk via simple logistic regression. Fluoridated water remained a significant risk factor for fluorosis in multiple logistic regression. CONCLUSIONS: Fluorosis was lower among children born after the adjustment of fluoride concentration in the water. Fluoridated water remained as a strong risk factor for fluorosis after downward adjustment of its fluoride concentration.

Fluoride-containing orthodontic adhesives and decalcification in patients with fixed appliances: a systematic review.

INTRODUCTION: Our objectives were to (1) systematically review the literature on the effectiveness of fluoride-containing adhesives in controlling decalcification in fixed orthodontic patients, (2) determine which fluoride-containing adhesives provide protection against decalcification, and (3) make recommendations on the usage of fluoride-containing adhesives in patients with fixed orthodontic appliances. METHODS: In this systematic review, we searched published and unpublished material in any language using general and specialist databases; key orthodontic journals were searched by hand. Predefined inclusion criteria based on objective outcome measures for decalcification, presence of a comparison group, and the study design were applied to select the studies. Included studies were double extracted onto predesigned data extraction sheets. RESULTS: A qualitative analysis of 5 randomized controlled trials and 5 clinical trials is presented. CONCLUSIONS: It is impossible to make recommendations on the use of fluoride-containing orthodontic adhesives during fixed orthodontic treatment. However, there is evidence to suggest that (1) glass ionomer cement is more effective than composite resin in preventing white spot formation, but the evidence is weak; (2) further research is required to determine the effectiveness of the various fluoride-containing orthodontic adhesives; and (3) common outcome measures and reporting standards would assist future researchers.

The impact of stopping or reducing the level of fluoride in public water supplies on dental fluorosis: a systematic review.

OBJECTIVE: The increased availability of fluoride and concern over the impact of fluorosis, have led to guidance suggesting a decrease or cease in the optimal concentration of fluoride in water fluoridation schemes. To date there have been no systematic reviews looking at both impact of fluoride reduction and total cessation. This review aimed to examine the impact of stopping or reducing the level of fluoride in public water supplies on dental fluorosis. CONTENT: Multiple databases were searched (MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the Web of Science). Two reviewers independently screened sources, extracted data and assessed study quality. Results were synthesised qualitatively and quantitatively. The main outcome measure was the prevalence of dental fluorosis. SUMMARY: Six studies of cross-sectional design were included. Two studies were scored as evidence level B (moderate) and the remaining four publications were evidence level C (poor). Meta-analysis indicated fluorosis prevalence was significantly decreased following either a reduction in the concentration of fluoride or cessation of adding fluoride to the water supply (OR:6.68; 95% CI:2.48 to 18.00). OUTLOOK: The evidence suggests a significant decrease in the prevalence of fluorosis post cessation or reduction in the concentration of fluoride added to the water supply. However, this work demonstrates that when studies are subject to current expectations of methodological and experimental rigour, there is limited evidence with low methodological quality to determine the effect of stopping or reducing the concentration of fluoride in the water supply on dental fluorosis.

The FiCTION trial: Child oral health-related quality of life and dental anxiety across three treatment strategies for managing caries in young children.

OBJECTIVES: The FiCTION trial compared co-primary outcomes (dental pain and/or infection) and secondary outcomes (child oral health-related quality of life [COHRQOL], child dental anxiety, cost-effectiveness, caries development/progression and acceptability) across three treatment strategies (Conventional with Prevention [C + P]; Biological with Prevention [B + P]; Prevention Alone [PA]) for managing caries in children in primary care. COHRQOL and child dental anxiety experiences are reported upon here. METHODS: A multi-centre, 3-arm, parallel-group, unblinded patient-randomized controlled trial of 3- to 7-year-olds treated under NHS contracts was conducted in 72 general dental practices in England, Wales and Scotland. Child participants (with at least one primary molar with dentinal caries) were randomized (1:1:1) to one of three treatment arms with the intention of being managed according to allocated arm for 3 years (minimum 23 months). Randomization was via a centrally administered system using random permuted blocks of variable length. At baseline and final visit, accompanying parents/caregivers completed a parental questionnaire including COHRQOL (16 item P-CPQ-16), and at every visit, child- and parental-questionnaire-based data were collected for child-based dental trait and state anxiety. Statistical analyses were conducted on complete cases from the modified intention-to-treat (mITT) analysis set. RESULTS: A total of 1144 children were randomized (C + P: 386; B + P: 381; PA: 377). The mITT analysis set included the 1058 children who attended at least one study visit (C + P: 352; B + P: 352; PA: 354). Median follow-up was 33.8 months (IQR: 23.8, 36.7). The P-CPQ-16 overall score could be calculated after simple imputation at both baseline and final visit for 560 children (C + P: 189; B + P: 189; PA: 182). There was no evidence of a difference in the estimated adjusted mean P-CPQ-16 at the final visit which was, on average, 0.3 points higher (97.5% CI: -1.1 to 1.6) in B + P than C + P and 0.2 points higher, on average, (97.5% CI: -1.2 to 1.5) in PA than for C + P. Child dental trait anxiety and child dental state anxiety, measured at every treatment visit, showed no evidence of any statistically or clinically significant difference between arms in adjusted mean scores averaged over all follow-up visits. CONCLUSIONS: The differences noted in COHRQOL and child-based dental trait and dental state anxiety measures across three treatment strategies for managing dental caries in primary teeth were small, and not considered to be clinically meaningful. The findings highlight the importance of including all three strategies in a clinician's armamentarium, to manage childhood caries throughout the young child's life and achieve positive experiences of dental care.

Best-practice prevention alone or with conventional or biological caries management for 3- to 7-year-olds: the FiCTION three-arm RCT.

BACKGROUND: Historically, lack of evidence for effective management of decay in primary teeth has caused uncertainty, but there is emerging evidence to support alternative strategies to conventional fillings, which are minimally invasive and prevention orientated. OBJECTIVES: The objectives were (1) to assess the clinical effectiveness and cost-effectiveness of three strategies for managing caries in primary teeth and (2) to assess quality of life, dental anxiety, the acceptability and experiences of children, parents and dental professionals, and caries development and/or progression. DESIGN: This was a multicentre, three-arm parallel-group, participant-randomised controlled trial. Allocation concealment was achieved by use of a centralised web-based randomisation facility hosted by Newcastle Clinical Trials Unit. SETTING: This trial was set in primary dental care in Scotland, England and Wales. PARTICIPANTS: Participants were NHS patients aged 3-7 years who were at a high risk of tooth decay and had at least one primary molar tooth with decay into dentine, but no pain/sepsis. INTERVENTIONS: Three interventions were employed: (1) conventional with best-practice prevention (local anaesthetic, carious tissue removal, filling placement), (2) biological with best-practice prevention (sealing-in decay, selective carious tissue removal and fissure sealants) and (3) best-practice prevention alone (dietary and toothbrushing advice, topical fluoride and fissure sealing of permanent teeth). MAIN OUTCOME MEASURES: The clinical effectiveness outcomes were the proportion of children with at least one episode (incidence) and the number of episodes, for each child, of dental pain or dental sepsis or both over the follow-up period. The cost-effectiveness outcomes were the cost per incidence of, and cost per episode of, dental pain and/or dental sepsis avoided over the follow-up period. RESULTS: A total of 72 dental practices were recruited and 1144 participants were randomised (conventional arm, n = 386; biological arm, n = 381; prevention alone arm, n = 377). Of these, 1058 were included in an intention-to-treat analysis (conventional arm, n = 352; biological arm, n = 352; prevention alone arm, n = 354). The median follow-up time was 33.8 months (interquartile range 23.8-36.7 months). The proportion of children with at least one episode of pain or sepsis or both was 42% (conventional arm), 40% (biological arm) and 45% (prevention alone arm). There was no evidence of a difference in incidence or episodes of pain/sepsis between arms. When comparing the biological arm with the conventional arm, the risk difference was -0.02 (97.5% confidence interval -0.10 to 0.06), which indicates, on average, a 2% reduced risk of dental pain and/or dental sepsis in the biological arm compared with the conventional arm. Comparing the prevention alone arm with the conventional arm, the risk difference was 0.04 (97.5% confidence interval -0.04 to 0.12), which indicates, on average, a 4% increased risk of dental pain and/or dental sepsis in the prevention alone arm compared with the conventional arm. Compared with the conventional arm, there was no evidence of a difference in episodes of pain/sepsis among children in the biological arm (incident rate ratio 0.95, 97.5% confidence interval 0.75 to 1.21, which indicates that there were slightly fewer episodes, on average, in the biological arm than the conventional arm) or in the prevention alone arm (incident rate ratio 1.18, 97.5% confidence interval 0.94 to 1.48, which indicates that there were slightly more episodes in the prevention alone arm than the conventional arm). Over the willingness-to-pay values considered, the probability of the biological treatment approach being considered cost-effective was approximately no higher than 60% to avoid an incidence of dental pain and/or dental sepsis and no higher than 70% to avoid an episode of pain/sepsis. CONCLUSIONS: There was no evidence of an overall difference between the three treatment approaches for experience of, or number of episodes of, dental pain or dental sepsis or both over the follow-up period. FUTURE WORK: Recommendations for future work include exploring barriers to the use of conventional techniques for carious lesion detection and diagnosis (e.g. radiographs) and developing and evaluating suitable techniques and strategies for use in young children in primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77044005. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 1. See the NIHR Journals Library website for further project information.

WHAT WAS THE QUESTION?: Tooth decay is common; it can lead to pain, days off school for children and days off work for parents and is a financial burden to the NHS. There is uncertainty about the best way of managing decay in young children. This trial aimed to find out whether or not there was a difference in the amount of pain and/or infection suffered by children having their decay treated with one of the following: fillings, having decay sealed in or using preventative treatment alone. Which method represented the best value was also explored. WHAT DID WE DO?: For young children with decay, the Filling Children's Teeth: Indicated Or Not? (FiCTION) trial compared the difference between fillings, sealing in the decay and using preventative treatment alone over 3 years in NHS dental practices in Scotland, England and Wales. We recruited 1144 children aged 3­7 years with one or more holes in their baby back teeth (molars), but without pain/infection, and placed them at random into one of three groups: (1) tooth numbing, removing decay and filling(s) with preventative treatment; (2) sealing in decay with fillings or caps and preventative treatment but no numbing; or (3) preventative treatment alone. WHAT DID WE FIND?: Recruitment was challenging but was achieved. There was no evidence of a difference in children's experience of pain or infection, quality of life or dental anxiety between groups. All three ways of treating decay were acceptable to children, parents and dental professionals. Sealing in with preventative treatment was most likely to be considered the best way of managing children's decay if we are willing to pay a minimum of £130 to avoid an episode of pain or infection. WHAT DOES THIS MEAN?: As there was no evidence of a difference between the three treatment groups in pain/infection experienced, treatment choice should continue to be based on shared decision-making between the child, parent and clinician to agree the best option for the individual child.

Health food blogger: friend or foe?

Objectives The Scientific Advisory Committee on Nutrition (SACN) and the World Health Organisation (WHO) have recently updated nutritional guidelines for a reduced sugar intake. With the increased popularity of online health-food bloggers and 'refined-sugar free' recipes, this review looked to analyse recipes from popular online bloggers to validate the veracity of their 'sugar-free' and 'healthy' claims and assess their adherence to recently implemented nutritional guidelines.Method Four bloggers were randomly selected from the Amazon top 10 booklist and their online blogs were consulted for a selection of recipes which were then nutritionally analysed in relation to their sugar and fat content.Results Eighty percent of the recipes analysed contained more fat than a Mars bar and 70% contained more fat than a popular online cake recipe, while 25% of the recipes contained over half of the recommended daily sugar intake as advised by the SACN and the WHO. None of the bloggers analysed used evidence-based approaches for the advice on their blogs.Conclusion Bloggers offer an invaluable platform to disseminate dietary advice to the public; however the recipes in this analysis were not healthy alternatives. The challenge is for government and health organisations to use this platform to promote alternative healthy eating options that align to current national and international guidance.

Characterization of PD-L1 Immunohistochemical Expression in Cell Blocks With Different Specimen Fixation and Processing Methods.

Interpretative criteria for programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) have been largely based on data from formalin-fixed, paraffin-embedded tissues, despite the fact that cytologic specimens, especially cell blocks, are often the only or most readily available tissue for testing. Unlike biopsy specimens, however, cytology sample processing methods can vary markedly. The purpose of this study was to evaluate the effects of several common preanalytic variables on PD-L1 IHC. Two cell lines with strong expression of PD-L1 (H441) and no expression (MCF7) were cultured in vitro. Harvested cells were collected in PreservCyt, CytoLyt, cell culture media (RPMI), saline, and formalin. Cell blocks were prepared by the plasma-thromboplastin method or Cellient automated system and stained with the FDA-approved 28-8 PD-L1 antibody per protocol. PD-L1 expression was scored manually by 3 pathologists for stain intensity and localization and compared across preparation methods. Several IHC staining patterns were observed: complete membranous, partial membranous, globular, and cytoplasmic, with some overlap. Cellient blocks had the best interobserver agreement and cytomorphology, highest proportion of strong complete membranous staining (82%), and least amount of cytoplasmic (11%) and globular staining (8%). RPMI, saline, and formalin samples demonstrated increased amounts of cytoplasmic and globular staining relative to Cellient, while CytoLyt exhibited the poorest performance overall. Interpretation of PD-L1 IHC on cell blocks is feasible for most processing methods examined, but may require recognition of increased cytoplasmic and globular staining in some sample types. Cellient cell blocks demonstrated superior performance compared with other methods.

Lymphoepithelioma-like carcinoma of the uterine cervix: Cytomorphologic features and diagnostic pitfalls by liquid-based cytology.

Lymphoepithelioma-like carcinoma (LELC) is a rare variant of cervical squamous cell carcinoma with unclear HPV and EBV association. Due to the accompanying and often obscuring lymphocytic inflammation, malignant cells may be difficult to recognize on cytologic samples and can mimic several more common benign and atypical cervical lesions. In this case report, we describe the cytomorphologic findings of LELC by liquid-based cytology in a 59-year-old Caucasian woman who was positive for high risk HPV but had no visible cervical lesions. We also discuss the differential diagnosis, diagnostic pitfalls, and practical considerations for diagnosis.

The impact of a reduction in fluoride concentration in the Malaysian water supply on the prevalence of fluorosis and dental caries.

OBJECTIVE: To assess the prevalence and severity of dental fluorosis and caries among Malaysian children following the reduction in fluoride concentration from 0.7 to 0.5 parts per million (ppm) in the public water supply. METHODS: This study involved lifelong residents aged 9- and 12-year-olds in fluoridated and nonfluoridated areas in Malaysia (n = 1155). In the fluoridated area, children aged 12 years and 9 years were exposed to 0.7 and 0.5 ppm, respectively, at the times when maxillary central incisors developed. Standardized photographs of maxillary central incisors were blind scored for fluorosis using Dean's criteria. Dental caries was examined using ICDAS-II criteria. RESULTS: The prevalence of fluorosis (Dean's score ≥ 2) among children in the fluoridated area (35.7%, 95% CI: 31.9%-39.6%) was significantly higher (P < 0.001) than children in the nonfluoridated area (5.5%, 95% CI: 3.6%-7.4%). Of those in the fluoridated area, the prevalence of fluorosis decreased from 38.4% (95% CI: 33.1%-44.3%) for 12-year-olds to 31.9% (95% CI: 27.6%-38.2%) for 9-year-olds, although this difference was not statistically significant (P = 0.139). The mean caries experience in the permanent dentition was significantly lower in the fluoridated area than in the nonfluoridated area for both age groups (P < 0.05). In the multivariate models, the difference in the differences of caries experience between fluoridated and nonfluoridated areas remained statistically significant. This suggests that caries-preventive effect is still maintained at 0.5 ppm. CONCLUSION: Findings indicate that the change in fluoride level from 0.7 to 0.5 ppm has reduced fluorosis and maintains a caries-preventive effect. Although there is a reduction in fluorosis prevalence, the difference was not statistically significant.

Evaluation of the SharkCore® needle for EUS-guided core biopsy of pancreatic neuroendocrine tumors.

BACKGROUND AND OBJECTIVES: EUS guided core biopsy was once rarely performed but is now entering mainstream practice. Neuroendocrine tumors often warrant core biopsy as sufficient tissue must be obtained to allow for special staining to ensure a correct diagnosis. Traditionally these lesions were sampled with FNA needles. We performed a retrospective pilot study to evaluate the clinical value and efficacy of the a new EUS core needle biopsy needle as compared to a standard EUS FNA needle in the evaluation of patients with known or suspected neuroendocrine tumors. METHODS: A retrospective analysis of the first 10 patients (between January 2015 and April 2016) to undergo EUS-FNA with the SharkCore® needle at the University of Utah School of Medicine/Huntsman Cancer Center with neuroendocrine tumors. Each case was retrospectively reviewed by a board certified cytopathologist (BLW) for the following cytologic parameters on the aspirate smears or touch/squash preparations: overall cellularity [1 (low) to 3 (high)], percentage of obtained cells that were lesional/representative (<25%, 26%-50%, and >50%), relative ease of interpretation [1 (difficult) to 3 (easy)]. Pathologic material and reporting records were also reviewed for each case to confirm the number of needle passes to achieve diagnostic adequacy, the presence or absence diagnostic material on H&E slide (from cell block, if prepared), whether a definitive diagnosis was able to be rendered, and the presence or absence of a true core/core fragments (within the cell block, if prepared). RESULTS: A total of 20 patients underwent EUS-FNA for suspected neuroendocrine lesions. Ten patients underwent either transgastric or transduodenal EUS-FNA with the 22 gauge SharkCore® needle. The comparison cohort of 10 patients underwent either transgastric or transduodenal EUS-FNA with the standard 22 gauge Echotip® needle. The SharkCore® needle required a fewer mean number of needle passes to obtain diagnostic adequacy than the Echotip® (P=0.0074). For cases with cell blocks, the SharkCore® needle produced diagnostic material in 100% of cases, whereas Echotip® produced diagnostic material in 60% of cases. There was no significant difference between specimen cellularity, percentage of lesional material, or ease of interpretation between the two needle types. CONCLUSION: Our pilot investigation targeting patients with known or suspected pancreatic NETs indicates that the SharkCore® needle shows promise in obtaining suitable tissue for ancillary testing that can allow for more definitive pathologic interpretations on EUS FNA specimens. Fewer passes were needed with the core needle when compared to a standard needle.