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OBJECTIVE: To translate and validate the 'Sinhala' language version of the European Organization for Research and Treatment of Cancer head-and-neck cancer-specific health-related quality-of-life questionnaire module, the QLQ-H&N35, for use in Sri Lanka. METHODS: Psychometric testing assessed the hypothesized scale structure, scale reliability, construct validity and acceptability of the translated version of the QLQ-H&N35 in a consecutive series of 196 newly diagnosed head-and-neck cancer patients, recruited from tertiary-care oncology treatment centres in Sri Lanka. RESULTS: Compliance was high (97.5%), although nearly 40% of patients required assistance with completion of the questionnaire. Twenty-four sexually inactive patients declined to answer one or both items of the sexuality scale. Multi-trait scaling confirmed the overall scale structure, with good item-convergent (100%) and -discriminant (93.8%) validity, and scaling success (86.8%) rates. Cronbach's alpha coefficients exceeded 0.70 for all scales, except problems with sexuality (0.60) and problems with senses (0.61), which also evidenced a lower scaling success rate (50%). Confirmation of construct validity included satisfactory results for inter-scale correlations and known-groups comparisons for most scales; most correlations were statistically significant (p<0.01), with conceptually related scales showing relatively higher correlation. Most scale scores were able to discriminate clearly between pre- and current treatment patients. CONCLUSIONS: Results of the study provide strong support for the psychometric robustness of the 'Sinhala' version of the QLQ-H&N35. It may be advisable to interpret the two items assessing sensory problems separately, and to elicit information on sexuality from only those who are sexually active. [ABSTRACT FROM AUTHOR] more...

DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart. Using the Illumina HumanMethylation450 BeadChip, DNA methylation was measured in blood samples from 5606 Melbourne Collaborative Cohort Study (MCCS) participants. For 1088 of them, these measures were repeated using blood samples collected a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models. Independent data from the London Life Sciences Prospective Population (LOLIPOP) (N = 4042) and Cooperative Health Research in the Augsburg Region (KORA) (N = 1662) cohorts were used to replicate associations discovered in the MCCS. Cross-sectional analyses identified 1414 CpGs associated with alcohol intake at P < 10 -7 , 1243 of which had not been reported previously. Of these novel associations, 1078 were replicated (P < .05) using LOLIPOP and KORA data. Using the MCCS data, we also replicated 403 of 518 previously reported associations. Interaction analyses suggested that associations were stronger for women, non-smokers, and participants genetically predisposed to consume less alcohol. Of the 1414 CpGs, 530 were differentially methylated (P < .05) in former compared with current drinkers. Longitudinal associations between the change in alcohol intake and the change in methylation were observed for 513 of the 1414 cross-sectional associations. Our study indicates that alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with alcohol consumption changes in adulthood., (© 2019 Society for the Study of Addiction.) more...

Background/objectives: Loss of expression of mismatch repair (MMR) proteins is frequently observed in sebaceous skin lesions and can be a herald for Lynch syndrome. The aim of this study was to identify clinico-pathological predictors of MMR deficiency in sebaceous neoplasia that could aid dermatologists and pathologists in determining which sebaceous lesions should undergo MMR immunohistochemistry (IHC)., Methods: An audit of sebaceous skin lesions (excluding hyperplasia) where pathologist-initiated MMR IHC was performed between January 2009 to December 2016 was undertaken from a single pathology practice identifying 928 lesions from 882 individuals. Lesions were further analysed for differences in gender, age at diagnosis, lesion type and anatomic location, stratified by MMR status., Results: The 882 individuals (67.7% male) had a mean (SD) age of diagnosis of 68.4 ± 13.3 years. Nearly two-thirds of the lesions were sebaceous adenomas, with 82.6% of all lesions occurring on the head and neck. MMR deficiency, observed in 282 of the 919 lesions (30.7%), was most common in sebaceous adenomas (210/282; 74.5%). MMR-deficient lesions occurred predominantly on the trunk or limbs (64.7%), compared with 23.2% in head or neck (P < 0.001). Loss of MSH2 and MSH6 protein expression was most frequent pattern of loss (187/281; 66.5%). The highest AUC for discriminating MMR-deficient sebaceous lesions from MMR-proficient lesions was observed for the ROC curve based on subgroups defined by type and anatomic location of the sebaceous lesion (AUC = 0.68)., Conclusion: The best combination of measured clinico-pathological features achieved only modest positive predictive values, sensitivity and specificity for identifying MMR-deficient sebaceous skin lesions., (© 2018 The Australasian College of Dermatologists.) more...

Background and Aims: In Australia, as in many countries, alcohol consumption increased dramatically during the second half of the 20th century, with increased availability of alcohol, relaxation of attitudes towards drinking and shifting roles and opportunities for women as facilitating factors. We sought to investigate drinking trends by gender and birth cohort in Australia during this period., Design: Retrospective cohort study., Setting, Participants and Measurements: Using the usual frequency and quantity of beverage-specific alcohol intake for 10-year periods from age 20, reported retrospectively from 40 789 participants aged 40-69 years (born 1920-49) at recruitment to the Melbourne Collaborative Cohort Study in 1990-94, we compared trends in alcohol consumption by sex in Australia between 1950 and 1990. Participants' average daily consumption for age decades were transformed to estimated intakes for 1950, 1960, 1970, 1980 and 1990., Findings: Alcohol consumption was higher for men than women during each decade. Alcohol consumption increased for both sexes in the 1950s, 1960s and 1970s, and fell after 1980. The rise before 1980 was roughly equal in absolute terms for both sexes, but much greater relative to 1950 for women. Women born during 1930-39 and 1940-49 drank more alcohol during early-middle adulthood (ages 20-40) than women born during 1920-29. In the 1980s, the fall was greater in absolute terms for men, but roughly equal relative to 1950 for both sexes. In both sexes, the decline in drinking in the 1980s for birth-decade cohorts was roughly in parallel., Conclusions: Specific birth cohorts were influential in the rise in alcohol consumption by Australian women born in 1920-49 after World War II. Much of the convergence with men's drinking after 1980 reflects large reductions in drinking among men., (© 2018 Society for the Study of Addiction.) more...

Aims: To assess the relationship between ambulance attendances, emergency department (ED) presentations and hospital admissions for acute alcohol intoxication and the timing of public holidays, sporting and social events., Design: Time-series analysis was used to explore trends in intoxication in the context of major events., Setting: Population of Melbourne, Victoria, Australia between 2000 and 2009., Participants: All patients attended by ambulance, presenting to hospital EDs, or admitted to hospital who were classified as acutely alcohol intoxicated., Measurement: Analysis of daily numbers of presentations for acute alcohol intoxication associated with major events were undertaken, including lead and lag effects. Analyses controlled for day of week and month of year to address temporal and seasonal variations., Findings: Alcohol intoxication presentations were significantly elevated the day before all public holidays, with intoxication cases on the day of public holidays only higher on New Year's Day (ambulance 6.57, 95% confidence intervals (CI): 3.4-9.74; ED 3.34, 95% CI: 1.28-5.4) and ANZAC Day (ambulance 3.71, 95% CI: 0.68-6.75). The Australian Football League (AFL) Grand Final (ED 2.37, 95% CI: 0.55-4.19), Commonwealth Games (ED 2.45, 95% CI: 0.6-4.3) and Melbourne Cup Day (ambulance 6.14, 95% CI: 2.42-9.85) represented the sporting events with significant elevations in acute intoxication requiring medical attention. The last working day before Christmas was the only social event where a significant increase in acute intoxication occurred (ambulance 8.98, 95% CI: 6.8-11.15)., Conclusions: Acute alcohol intoxication cases requiring ambulance, emergency department and hospital in-patient treatment increase substantially on the day preceding public holidays and other major social events., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.) more...