Virological outcomes with dolutegravir plus either lamivudine or two NRTIs as switch strategies: a multi-cohort study.

OBJECTIVES: To compare the efficacy of dolutegravir plus lamivudine dual therapy (DT) with that of dolutegravir plus two NRTIs triple therapy (TT) as switch strategies. METHODS: A multicentre cohort of HIV-positive, HBsAg-negative patients with viral suppression (HIV-RNA ≤50 copies/mL) switching to DT or TT was retrospectively selected from the ARCA database. The effect of DT versus TT on virological failure (VF; defined as two consecutive HIV-RNA values >50 copies/mL or one HIV-RNA value ≥200 copies/mL) was evaluated by multivariable Cox regression models, overall and after stratifying for the presence of NRTI resistance-associated mutations (RAMs). RESULTS: From December 2014 to June 2020, 628 patients were eligible: 118 (18.8%) started tenofovir/emtricitabine/dolutegravir, 306 (48.7%) abacavir/lamivudine/dolutegravir and 204 (32.5%) lamivudine/dolutegravir. The DT group had significantly higher nadir and baseline CD4 counts, a higher duration of viral suppression and a lower prevalence of RAMs at historical genotype. Overall, 41 VF occurred after a median of 1.7 years of follow-up, with a lower, but not statistically significant, rate for DT [versus TT, adjusted HR (aHR) = 0.58, 95% CI = 0.25-1.34]. However, DT was associated with less VF in the absence of RAMs when compared with tenofovir-based TT (aHR = 0.20, 95% CI = 0.06-0.67), but not with abacavir-based TT (aHR = 0.43, 95% CI = 0.17-1.11). Conversely, in the setting of pre-existing M184V/I, DT showed a trend to increased risk of VF (versus tenofovir-based TT, aHR = 137.50, 95% CI = 4.24-4464.06; versus abacavir-based TT, aHR = 33.88, 95% CI = 1.75-656.47). CONCLUSIONS: Lamivudine/dolutegravir maintenance DT showed similar efficacy to dolutegravir-based TT; however, past M184V/I may favour VF.

The novel HBx mutation F30V correlates with hepatocellular carcinoma in vivo, reduces hepatitis B virus replicative efficiency and enhances anti-apoptotic activity of HBx N terminus in vitro.

OBJECTIVE: We aimed to investigate HBx genetic elements correlated with hepatitis B virus (HBV) -related hepatocellular carcinoma (HCC) and their impact on (a) HBV replicative efficiency, (b) HBx binding to circular covalently closed DNA (cccDNA), (c) apoptosis and cell-cycle progression, and (d) HBx structural stability. METHODS: This study included 123 individuals chronically infected with HBV: 27 with HCC (77.9% (21/27) genotype D; 22.1% (6/27) genotype A) and 96 without HCC (75% (72/96) genotype D; 25.0% (24/96) genotype A). HepG2 cells were transfected by wild-type or mutated linear HBV genome to assess pre-genomic RNA (pgRNA) and core-associated HBV-DNA levels, HBx-binding onto cccDNA by chromatin immunoprecipitation-based quantitative assay, and rate of apoptosis and cell-cycle progression by cytofluorimetry. RESULTS: F30V was the only HBx mutation correlated with HCC (18.5% (5/27) in HCC patients versus 1.0% (1/96) in non-HCC patients, p 0.002); a result confirmed by multivariate analysis. In vitro, F30V determined a 40% and 60% reduction in pgRNA and core-associated HBV-DNA compared with wild-type (p <0.05), in parallel with a significant decrease of HBx binding to cccDNA and decreased HBx stability. F30V also decreased the percentage of apoptotic cells compared with wild-type (14.8 ± 6.8% versus 19.1 ± 10.1%, p <0.01, without affecting cell-cycle progression) and increased the probability of HBx-Ser-31 being phosphorylated by PI3K-Akt kinase (known to promote anti-apoptotic activity). CONCLUSIONS: F30V was closely correlated with HBV-induced HCC in vivo, reduced HBV replicative efficiency by affecting HBx-binding to cccDNA and increased anti-apoptotic HBx activity in vitro. This suggests that F30V (although hampering HBV's replicative capacity) may promote hepatocyte survival, so potentially allowing persistent production of viral progeny and initiating HBV-driven hepatocarcinogenesis. Investigation of viral genetic markers associated with HCC is crucial to identify those patients at higher risk of HCC, who hence deserve intensive liver monitoring and/or early anti-HBV therapy.

Dentists' attitudes and practices toward provision of orthodontic treatment for children with visual and hearing impairments.

The objective of this study was to determine differences in behavior and attitudes of dentists in Riyadh, Saudi Arabia, in providing orthodontic care for children who are sensory impaired. A self-administered questionnaire was sent to all dentists working in Riyadh to assess the following domains: personal characteristics of the dentists and their practices, provision of dental care for children who are visually-impaired (Vl) and/or hearing-impaired (HI), and their attitude toward providing orthodontic care for these children. Attitudes were measured on two scales and the overall score of these two scales represented each respondent's attitude. Thirty percent of the dentists provided dental care for children with VI and 45.3 percent did for children with HI. The provision of orthodontic care was significantly affected by the country in which the dentists had received their dental training, both for children with VI and HI (p < 0.01), and by number of years they had been in practice for children with VI (p < 0.05). Regression analysis showed that only the country of dental training significantly affected the dentist's attitude score. There were also significant variations in attitudes toward the provision of orthodontic treatment for children with sensory impairment (SI), influenced by dental training and experience. In practical terms, this means that improvement in attitudes needs to be initiated at the dental undergraduate level. Establishing global guidelines for the provision of orthodontic treatment for patients with sensory impairment is likely to assist both professionals and patients.

Awareness of mouth cancer in Great Britain.

OBJECTIVE: There are more than 2,000 new cases of mouth cancer each year in Britain. Early detection is important yet little is known about population awareness of this disease and ability to recognise early signs, particularly among high risk groups. This study aimed to address this issue. METHODS: Data were collected by means of household survey. A total of 3,384 adults were questioned using a national probability sample. Respondents provided information on demographic characteristics, smoking status, and frequency of alcohol use. They were asked whether they had heard of mouth cancer. Their knowledge of early signs and risk factors was assessed. RESULTS: Whereas 95.6% of respondents said they had heard of mouth cancer, their awareness of early signs was low; for example, only 33.8% recognised that white patches in the mouth were a sign. The large majority understood that smoking and chewing tobacco were risk factors (84.7% and 80.1% respectively) but only 19.4% recognised alcohol use as a risk factor. In multiple logistic regression analyses controlling for relevant demographic factors, smokers and those with more frequent alcohol consumption were less likely to recognise early signs. CONCLUSIONS: Awareness of early signs of mouth cancer is low and lower in people who as a result of their behaviour are at higher risk. There is a need to raise awareness in those at most risk.

Levels of toxins in oral tobacco products in the UK.

OBJECTIVE: This study examined the constituents of smokeless tobacco products available in the UK and compared them with products available in India, Sweden, and the USA. METHODS: Seven UK brands of smokeless tobacco, including a tooth cleaning powder, and four international brands of smokeless tobacco were tested for a range of toxins and known carcinogens, such as tobacco specific N-nitrosamines (TSNA), as well as nicotine availability. RESULTS: Ten of the 11 brands tested had detectable levels of tobacco specific nitrosamines, which are proven carcinogens, and levels varied 130-fold. All had detectable levels of benzo(a)pyrene, another proven carcinogen (with around 175-fold variation) and several toxic metals (with nearly 150-fold variation). Nicotine availability varied in the UK products from 0.1 mg/g to 63.2 mg/g. All the tobacco products tested are likely to be hazardous to users' health, but the data indicate that it should be possible to reduce key toxins to non-detectable levels. CONCLUSIONS: Smokeless tobacco products should be regulated and standards set for maximum levels of toxins and carcinogens.

Prevalence of self-assessed tooth discolouration in the United Kingdom.

AIMS: To determine the prevalence of perceived tooth discolouration in the United Kingdom and to investigate socio-demographic variations and satisfaction with own tooth colour. METHODS: A national cross-sectional questionnaire study was carried out using a multistage random probability sample. Assessment of people's perceptions of their own tooth colour was conducted by asking study participants to match colour to the closest of a set of photocards demonstrating different levels of tooth discolouration. A separate question asked how satisfied they were with their tooth colour. Information on socio-demographic characteristics of the population were gathered at the same time. ANALYSIS: Data was coded and entered into SPSS software. Descriptive statistics were used to determine the prevalence of perceived discolouration and satisfaction with own tooth colour. Bivariate and regression analyses were performed to explore the effect of socio-demographic variations. RESULTS: The self-assessment exercise was completed for 3215 subjects. Half of the study population perceived their tooth colour to be normal and 6% perceived that they had severe discolouration, the remainder reported themselves to have levels of tooth discolouration between these two extremes. Satisfaction with tooth colour decreased with increased discolouration. Sex, age, income and smoking, had statistically significant effects on the prevalence of perceived discolouration (P< 0.01). CONCLUSIONS: Half of the people in this study perceived themselves to have tooth discolouration. Results suggest that the general public is concerned about dental appearance in terms of tooth colour, indicated by public dissatisfaction with relatively mildly discoloured teeth. Findings may suggest that a further increase in the demand of tooth whitening services and cosmetic dentistry in general is likely. The changing emphasis and level of perceived dissatisfaction need to be taken into account in planning dental services. Evidence based approaches are needed for the appropriate management of patients who demand treatment of mild discolouration.

Aesthetically objectionable fluorosis in the United Kingdom.

OBJECTIVES: A cross-sectional national survey to explore perceptions of dental fluorosis and to determine the proportion of people regarding fluorosis as aesthetically objectionable at differing levels of defect. METHODS: A survey using a multistage stratified random probability sample of 6,000 UK adult households. Face-to-face interviews were carried out using a structured questionnaire and photographs of different levels of dental fluorosis. Respondents were interviewed about the parameters of satisfaction, attractiveness and need for treatment for dental fluorosis. RESULTS: The proportion of respondents perceiving teeth as unattractive, unsatisfactory and requiring treatment increased with increasing severity of dental fluorosis. Using agreement between the three negative perceptions as a measure, 14% of the sample perceived mild dental fluorosis as aesthetically objectionable, 45% at moderate level and 91% at severe levels. CONCLUSION: Negative perceptions of dental fluorosis were lower than reported previously. Three parameters were included in the approach to estimate aesthetically objectionable fluorosis which may provide a more realistic measure than those used previously. The nature of the index and the sample included suggest that findings of this survey provide a reasonable indicator of the likely impact of water fluoridation. Findings may have important implications for fluoridation policies in the United Kingdom and elsewhere.

Translation and validation of an Arabic version of the UK oral health related quality of life measure (OHQoL-UK) in Syria, Egypt and Saudi Arabia.

OBJECTIVE: The aim of this study was to translate and evaluate the performance of an oral health related quality of life measure--an Arabic version of OHQoL-UK in three middle eastern countries: Syria, Egypt and Saudi Arabia. BASIC RESEARCH DESIGN: Following forward and backwards translation of OHQoL-UK into Arabic and pilot testing the Arabic version among focus groups, a questionnaire containing the instrument was administered to 1,000 adults from the three Arab countries. In addition, the study participants were interviewed about their oral health status, experience of oral health problems in the past year, self-rating of oral health and also some socio-demographic information was collected. RESULTS: Among the three study populations, variations in OHQoL-UK scores were apparent in relation to socio-demographic factors (p<0.01), self-reported number of teeth possessed (p<0.001) and experience of oral health problems in the past year (p<0.01) which supports the construct validity of the instrument. Furthermore, variations in OHQoL-UK scores were apparent in relation to self-rating of oral health status (p<0.01) which supports the criterion validity of the measure. The internal reliability of the instrument was high in the three groups with Cronbach alpha values of above 0.90, indicating good internal consistency. CONCLUSION: The Arabic version of OHQoL-UK, an index of oral health related quality of life demonstrated satisfactory construct validity, criterion validity and internal reliability in Syria, Egypt and Saudi Arabia. This provides further evidence of the instrument's psychometric properties and its cross cultural use.

Disparities in self reported oral health problems among a young Syrian adult population.

OBJECTIVE: To describe the prevalence of dental pain and other oral health problems among a young Syrian adult population and to identify socio-demographic factors associated with these experiences. SUBJECTS: An industrial sample of 400 men and women aged 18-34 years from Damascus, Syria. METHODS: Study participants were interviewed about their experience of oral health problems in the previous year (1998). Socio-demographic information was collected. RESULTS: 93% (369) of the interviews were completed. The prevalence of oral health problems was high, with 96% (353) of respondents claiming that they experienced one or more problems in the previous year. Two thirds of participants (65%, 239) claimed they had dental pain in the previous year. Analysis revealed that dental pain experience was significantly associated with age and gender. Analysis considering all factors revealed that the odds of experiencing dental pain were higher amongst the younger age group (18-24 compared to 25-34 year-olds). CONCLUSION: The prevalence of oral health problems was high among the population studied. Socio-demographic variations in experience of dental pain were apparent, with young men of lower education having the greatest odds of dental pain experience in the previous year.

Construction of an interim obturator using a microwave-polymerized denture base resin.

This article describes a technique for fabricating an interim obturator for maxillectomy patients using a microwave-polymerized denture base resin. The use of microwave irradiation to polymerize this type of resin reduces the time required to fabricate interim obturators and results in prostheses comparable in physical properties and superior in dimensional accuracy to prostheses made with conventional heat-polymerized acrylic denture base resin. The technique is simple and time efficient, and it does not require any special or elaborate laboratory equipment.

Comparison of microwave-polymerized denture base resins.

Three denture base resins, two designed for microwave polymerization and one for host-water-bath-processing, were compared. Results indicated that all four tested thicknesses (3, 6, 11.6, and 17.7 mm) of the water-bath-polymerized samples and one of the microwave-polymerized resins were porosity-free. When the water-bath-polymerized material was microwave processed, porosity was found when resin thickness exceeded 3 mm. When one resin designed for microwave polymerization was irradiated using the high-wattage (513 W), shorter cycle (4 minutes 52 seconds), porosity also occurred when the thickness exceeded 3 mm. Porosity did not occur until there was 9 mm of thickness when the lower-wattage (75.9 W), longer cycle (15 minutes 26 seconds) was used. No significant differences in transverse strength or hardness were noted between the materials.