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: Objective: To determine the test‐retest repeatability of a self‐completed survey with items capturing skin cancer risk factors. Methods: We invited 238 randomly selected participants of the QSkin II cohort to complete the baseline survey a second time. Responses were compared using kappa statistics and intraclass correlation coefficients to quantify agreement for categorical and continuous variables, respectively. We compared the performance of key items with that observed in an earlier repeatability study using the same survey instrument in an independent cohort. Results: Measures of phenotypic characteristics had moderate to almost‐perfect test‐retest repeatability (e.g. eye colour weighted kappa (κ[sub.w]) = 0.87, 95% confidence interval [CI]: 0.81, 0.92). Items measuring sun exposure showed lower agreement (κ[sub.w] range 0.36‐0.54) compared with phenotypic characteristics (κ[sub.w] range 0.59‐0.87). Items relating to treatment of skin cancers demonstrated almost‐perfect test‐retest repeatability (e.g. excisions for skin cancers κ[sub.w] 0.85, 95%CI: 0.80, 0.89). In aggregate, the repeatability of key items was very similar across the two independent repeatability samples. Conclusion: Fair to almost‐perfect repeatability for self‐reported skin cancer risk factors was robust across independent and temporally distant cohorts. Implications for public health: These self‐assessed risk factors for skin cancer are repeatable and suitable for use in clinical practice and research., Skin cancer is Australia's ‘national cancer’; this nation suffers the highest incidence of cutaneous melanoma and keratinocyte cancer in the world.[sup.1-3] Ultraviolet radiation exposure is the principal environmental risk factor; [...]

ObjectivesThe International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE.Study designInterLACE is an individual-level pooled study of 20 observational studies (12 of which are longitudinal) from ten countries. Variables were harmonized across studies to create a new and systematic synthesis of life-course data.Main outcome measuresHarmonized data were derived in three domains: 1) socio-demographic and lifestyle factors, 2) female reproductive characteristics, and 3) chronic disease outcomes (cardiovascular disease (CVD) and diabetes).ResultsInterLACE pooled data from 229,054 mid-aged women. Overall, 76% of the women were Caucasian and 22% Japanese; other ethnicities (of 300 or more participants) included Hispanic/Latin American (0.2%), Chinese (0.2%), Middle Eastern (0.3%), African/black (0.5%), and Other (1.0%). The median age at baseline was 47 years (Inter-quartile range (IQR): 41-53), and that at the last follow-up was 56 years (IQR: 48-64). Regarding reproductive characteristics, half of the women (49.8%) had their first menstruation (menarche) at 12-13 years of age. The distribution of menopausal status and the prevalence of chronic disease varied considerably among studies. At baseline, most women (57%) were pre- or peri-menopausal, 20% reported a natural menopause (range 0.8-55.6%) and the remainder had surgery or were taking hormones. By the end of follow-up, the prevalence rates of CVD and diabetes were 7.2% (range 0.9-24.6%) and 5.1% (range 1.3-13.2%), respectively.ConclusionsThe scale and heterogeneity of InterLACE data provide an opportunity to strengthen evidence concerning the relationships between reproductive health through life and subsequent risks of chronic disease, including cross-cultural comparisons.

Tobacco smoking is a strong risk factor for cancer, but associations with basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) of the skin have been inconsistent. We prospectively investigated the associations between cigarette smoking and 3-year incidence of first primary BCC or SCC in the QSkin cohort (n=43765). Smoking history was self-reported at baseline; newly diagnosed and surgically treated BCCs and SCCs were ascertained through linkage to the national health insurance scheme and verified by histopathology reports. We restricted our analyses to white participants who at baseline reported no past history of skin cancer excisions or cutaneous melanoma (registry-confirmed) and no more than 5 destructively-treated skin lesions (n=18830). Cox proportional hazards regression analysis was used to examine the association between smoking status and risk of BCC and SCC, adjusted for demographic and phenotypic characteristics and sun exposure history. Current smokers had significantly lower risks of BCC (HR 0.6; 95% CI, 0.4-0.9) but significantly increased risks of SCC (HR 1.9; 95% CI, 1.1-3.1) compared with never smokers. Former smoking was not associated. In analyses restricted to people with no past history of destructively-treated lesions (n=13323), we found a non-significant decreased risk of BCC (HR 0.8; 95% CI, 0.5-1.3) and a significant increased risk of SCC (HR 2.3; 95% CI, 1.3-4.4) among current smokers compared to never smokers. Future analyses will investigate associations with age at initiation, duration and intensity of smoking, and time since quitting. These findings suggest current smoking is a risk factor for cutaneous SCC but not BCC.

The costs of diagnosing and treating basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) are the highest of all cancers in Australia. However, information regarding incidence, multiplicity and risk are scarce as keratinocyte cancers (KCs) are not captured by most registries. To address these gaps, we initiated the QSKIN Study in 2010 recruiting 43,794 Queensland residents from a population register (participation 24%). Participants self-completed a baseline survey recording information on residential history, sun exposure, phenotype and medical and family history. We identified keratinocyte cancers through linkage to the national insurance register, confirming histopathology where possible. During the first three years of follow-up, 6936 (17%) participants had at least one KC excised; 1626 (4%) had 3 or more excisions. Of lesions with known histology, there were 9713 BCCs (in 4080 people) and 3505 SCCs (in 1782 people). We developed a tool to predict the risk of developing KC using backwards stepwise logistic regression models. The primary model retained terms for 10 items, including history of >20 prior skin cancers excised (OR 8.6), >50 skin lesions destroyed (OR 3.4), age >70 years (OR 3.5) and fair skin color (OR 1.8). Discrimination was high (Area under ROC 0.80, 95%CI 0.79-0.81) and the model appeared well calibrated. Among those reporting no prior history of skin cancer, a model with 10 factors (including age, sex, ethnicity and phenotypic factors) predicted KC events with reasonable discrimination (AUROC 0.72, 95% CI 0.70-0.75). The tool is undergoing external validation in primary care skin cancer clinics.

Estrogens have photosensitizing properties, but few prospective studies have examined the relationship between hormonal and reproductive factors and incidence of basal cell carcinoma (BCC) in women. Previous findings have been inconsistent, particularly in relation to parity and use of oral contraceptives (OCs) and menopausal hormone therapy (MHT). Given the heterogeneity in the literature, we sought to examine the association between hormonal and reproductive factors and BCC risk in a cohort of women (n=23,879) enrolled in the QSkin Study in 2011. The baseline survey included questions about use of OCs and MHT, age at menarche, menopausal status, age at menopause and parity. We restricted our analysis to white women with no past history of treatments for skin cancer and less than 6 treatments for actinic keratoses (n=11,204) and used Cox proportional hazards models to estimate the hazards ratio associated with each potential hormonal/reproductive factor and first histologically confirmed BCC, while taking account of the potentially confounding influence of sun exposure history, phenotypic characteristics, body mass index and smoking history. During a median follow-up duration of 2.95 years, 352 women developed BCC. In preliminary analyses, amongst post-menopausal women, ever use of MHT at baseline was associated with an increased risk of developing BCC compared to never users (adjusted HR1.4; 95%CI 1.1-1.9), but risk did not differ by duration of use. We found no association between parity, age at menarche, age at menopause or use of OCs and BCC incidence. Future work will examine whether MHT use is associated with an increased risk of a second primary BCC.

Background Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause. Methods and findings A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause ( Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73-2.44) (p < 0.001) and early menopause (1.80; 1.66-1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04-1.23; p = 0.006) and 1.15 (1.05-1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45-49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15-20 years, the risk was markedly higher for premature (15.58; 11.29-19.86; p < 0.001) and early (6.55; 5.04-8.52; p < 0.001) menopause. Also, current smokers with 11-15 pack-years had over 4-fold (4.35; 2.78-5.92; p < 0.001) and 3-fold (3.01; 2.15-4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98-1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias. Conclusions The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause., Author(s): Dongshan Zhu 1, Hsin-Fang Chung 1, Nirmala Pandeya 1,2, Annette J. Dobson 1, Janet E. Cade 3, Darren C. Greenwood 3, Sybil L. Crawford 4, Nancy E. Avis 5, [...]

OBJECTIVE: To assess the effects of a 3-year programme aimed at controlling scabies on five small lagoon islands in the Solomon Islands by monitoring scabies, skin sores, streptococcal skin contamination, serology and haematuria in the island children. METHODS: Control was achieved by treating almost all residents of each island once or twice within 2 weeks with ivermectin (160-250 mg/kg), except for children who weighed less than 15 kg and pregnant women, for whom 5% permethrin cream was used. Reintroduction of scabies was controlled by treating returning residents and visitors, whether or not they had evident scabies. FINDINGS: Prevalence of scabies dropped from 25% to less than 1% (P < 0.001); prevalence of sores from 40% to 21% (P < 0.001); streptococcal contamination of the fingers in those with and without sores decreased significantly (P = 0.02 and 0.047, respectively) and anti-DNase B levels decreased (P = 0.002). Both the proportion of children with haematuria and its mean level fell (P = 0.002 and P < 0.001, respectively). No adverse effects of the treatments were seen. CONCLUSION: The results show that ivermectin is an effective and practical agent in the control of scabies and that control reduces the occurrence of streptococcal skin disease and possible signs of renal damage in children. Integrating community-based control of scabies and streptococcal skin disease with planned programmes for controlling filariasis and intestinal nematodes could be both practical and produce great health benefits.

Objective: Participation rates have been declining in case-control studies, particularly among controls, raising concerns about possible bias. Formal assessments of the effect of low participation on odds ratios (OR) are seldom presented however. We sought to quantify possible bias using multiple imputation techniques. Methods: Using data from two Australian case-control studies, we estimated the relative risks of oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC), and serous ovarian cancer (SOC) associated with smoking and body mass index (BMI). We compared ORs observed using self-reported data from participating controls with ORs derived using imputed exposures for non-participating controls. Results: Participating controls were less likely than non-participants to smoke currently. Smoking remained significantly associated with oesophageal cancer even under the most extreme assumption of smoking prevalence among non-participants (OSCC: observed OR 6.54, 4.62-9.28, imputed OR 3.94, 2.83-5.49; OAC: observed OR 2.69, 1.87-3.85 imputed OR 1.58, 1.13-2.22). For SOC however, risks associated with smoking were attenuated to null under plausible smoking assumptions among non-participants. BMI distributions were similar among participating and non-participating controls, and risk estimates were essentially unchanged. Conclusion and implications: Bias is not an inevitable consequence of low control participation and depends on the association examined. Sensitivity analyses can assist in interpretation of results. Key words: bias, imputation, case-control study, smoking, Body mass index, oesophageal cancer, ovarian cancer. doi: 10.1111/j.1753-6405.2009.00401.x