Background Regression to the mean (RTM) is a statistical phenomenon that can make natural variation in repeated data look like real change. It happens when unusually large or small measurements tend to be followed by measurements that are closer to the mean. Methods We give some examples of the phenomenon, and discuss methods to overcome it at the design and analysis stages of a study. Results The effect of RTM in a sample becomes more noticeable with increasing measurement error and when follow-up measurements are only examined on a sub-sample selected using a baseline value. Conclusions RTM is a ubiquitous phenomenon in repeated data and should always be considered as a possible cause of an observed change. Its effect can be alleviated through better study design and use of suitable statistical methods.

Half of all cancers in the United States are skin cancers. We have previously shown in a 4.5-year randomized controlled trial in an Australian community that squamous cell carcinomas (SCC) but not basal cell carcinomas (BCC) can be prevented by regular sunscreen application to the head, neck, hands, and forearms. Since cessation of the trial, we have followed participants for a further 8 years to evaluate possible latency of preventive effect on BCCs and SCCs. After prolonged follow-up, BCC tumor rates tended to decrease but not significantly in people formerly randomized to daily sunscreen use compared with those not applying sunscreen daily. By contrast, corresponding SCC tumor rates were significantly decreased by almost 40% during the entire follow-up period (rate ratio, 0.62; 95% confidence interval, 0.38-0.99). Regular application of sunscreen has prolonged preventive effects on SCC but with no clear benefit in reducing BCC. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2546–8)

Background Global concern about vitamin D deficiency has fuelled debates on photoprotection and the importance of solar exposure to meet vitamin D requirements. Objectives To review the published evidence to reach a consensus on the influence of photoprotection by sunscreens on vitamin D status, considering other relevant factors. Methods An international panel of 13 experts in endocrinology, dermatology, photobiology, epidemiology and biological anthropology reviewed the literature prior to a 1‐day meeting in June 2017, during which the evidence was discussed. Methods of assessment and determining factors of vitamin D status, and public health perspectives were examined and consequences of sun exposure and the effects of photoprotection were assessed. Results A serum level of ≥ 50 nmol L⁻¹ 25(OH)D is a target for all individuals. Broad‐spectrum sunscreens that prevent erythema are unlikely to compromise vitamin D status in healthy populations. Vitamin D screening should be restricted to those at risk of hypovitaminosis, such as patients with photosensitivity disorders, who require rigorous photoprotection. Screening and supplementation are advised for this group. Conclusions Sunscreen use for daily and recreational photoprotection does not compromise vitamin D synthesis, even when applied under optimal conditions. What's already known about this topic? Knowledge of the relationship between solar exposure behaviour, sunscreen use and vitamin D is important for public health but there is confusion about optimal vitamin D status and the safest way to achieve this. Practical recommendations on the potential impact of daily and/or recreational sunscreens on vitamin D status are lacking for healthy people. What does this study add? Judicious use of daily broad‐spectrum sunscreens with high ultraviolet (UV) A protection will not compromise vitamin D status in healthy people. However, photoprotection strategies for patients with photosensitivity disorders that include high sun‐protection factor sunscreens with high UVA protection, along with protective clothing and shade‐seeking behaviour are likely to compromise vitamin D status. Screening for vitamin D status and supplementation are recommended in patients with photosensitivity disorders.

We investigated the validity of food intake estimates obtained by a self-administered FFQ relative to weighed food records (WFR) and the extent to which demographic, anthropometric, and social characteristics explain differences between these methods. A community-based sample of 96 Australian adults completed a FFQ and 12 d of WFR over 12 mo. The FFQ was adapted to the Australian setting from the questionnaire used in the US Nurses' Health Study. Spearman rank correlation coefficients ranged from 0.08 for “other vegetables” to 0.88 for tea. Exact agreement by quartiles of intake ranged from 27% (eggs) to 63% (tea). Differences between FFQ and WFR regressed on personal characteristics were significantly associated with at least 1 characteristic for 20 of the 37 foods. Sex was significantly associated with differences for 17 food groups, including 5 specific vegetable groups and 2 “total” fruit and vegetable groups. Use of dietary supplements and the presence of a medical condition were associated with differences for 5 foods; age, school leaving age, and occupation were associated with differences for 1–3 foods. BMI was not associated with differences for any foods. Regression models explained from 3% (whole-meal bread) to 37% (for all cereals and products) of variation in differences between methods. We conclude that the relative validity of intake estimates obtained by FFQ is different for men and women for a large number of foods. These results highlight the need for appropriate adjustment of diet-disease relations for factors affecting the validity of food intake estimates.

Importance With emerging new systemic treatments for metastatic melanoma, early detection of disease recurrence is increasingly important. Objective To investigate the risk of melanoma recurrence in patients with a localized melanoma at a high risk of metastasis. Design, Setting, and Participants A total of 1254 patients with newly diagnosed, histologically confirmed tumor category T1b to T4b melanoma in Queensland, Australia, were recruited prospectively between October 1, 2010, and October 1, 2014, for participation in a cohort study. Data analysis was conducted from February 8, 2018, to February 20, 2019. We used Cox proportional hazards regression analysis to examine associations between patient and tumor factors and melanoma recurrence. Exposures Disease-free survival (DFS) by melanoma tumor category defined by the 7th vs 8th editions of theAJCC Cancer Staging Manual(AJCC 7vsAJCC 8). Main Outcomes and Measures Melanoma recurrences were self-reported through follow-up questionnaires administered every 6 months and confirmed by histologic or imaging findings. Results Of 1254 patients recruited, 825 individuals (65.8%) agreed to participate. Thirty-six were found to be ineligible after providing consent and a further 89 patients were excluded after reclassifying tumors usingAJCC 8, leaving 700 participants with high-risk primary melanoma (mean [SD] age, 62.2 [13.5] years; 410 [58.6%] men). Independent predictors of recurrence were head or neck site of primary tumor, ulceration, thickness, and mitotic rate greater than 3/mm²(hazard ratio, 2.36; 95% CI, 1.19-4.71). Ninety-four patients (13.4%) developed a recurrence within 2 years of diagnosis: 66 tumors (70.2%) were locoregional, and 28 tumors (29.8%) developed at distant sites. After surgery for locoregional disease, 37 of 64 patients (57.8%) remained disease free at 2 years, 7 patients (10.9%) developed new locoregional recurrence, and 20 patients (31.3%), developed distant disease. Two-year DFS was similar when comparingAJCC 7andAJCC 8, for T1b (AJCC 7, 253 [93.3% DFS]; AJCC 8, 242 [93.0% DFS]) and T4b (AJCC 7 and AJCC 8, 50 [68.0% DFS] category tumors in both editions. Patients with T2a to T4a tumors who did not have a sentinel lymph node biopsy (SLNB) at diagnosis had lower DFS than patients with the same tumor category and a negative SLNB (T2a: 136 [91.1%; 95% CI, 86.4-95.9] vs 96 [96.9%; 95 % CI, 93.4-100.0]; T4a: 33 [78.8%; 95% CI, 64.8-92.7] vs 6 [83.3; 95% CI, 53.5-100.0]). Conclusions and Relevance These findings suggest that 13.4% of patients with a high-risk primary melanoma will experience disease recurrence within 2 years. Head or neck location of initial tumor, SLNB positivity, and signs of rapid tumor growth may be associated with primary melanoma recurrence.

Objectives: To provide a reference range for plasma total homocysteine (tHcy), an independent risk factor for vascular disease, and to explore relationships with nutritional indices for people aged 65 y and over, in the UK National Diet and Nutrition Survey (NDNS). Design: The survey procedures described in the National Diet and Nutrition Survey Report (1997) included a health-and-lifestyle interview, a four-day weighed diet record, anthropometric and blood pressure measurements and a fasting blood sample for biochemical indices, including tHcy. Setting: Eighty randomly selected postcode sectors from mainland Britain during 1995–1996. Subjects: Of 2060 people interviewed, 1527 were visited by the nurse, 1276 gave a blood sample and 972 had tHcy measured. About 80% were in their own homes and the remainder were in nursing homes or similar institutions. Results: Significant cross-sectional relationships, both univariate and multivariate were found between tHcy and index concentrations of folate and vitamin B₁₂ (P<0.0001), and between tHcy and plasma creatinine, urea, calcium, zinc, α₁-antichymotrypsin, lutein and cysteine (P=0.013 to <0.0001). Dietary nutrient analyses showed an association with folate intake. tHcy was also correlated with age and with domicile (free-living or institution), with history of vascular disease and with use of four classes of drugs, two of which are prescribed for vascular diseases. There was a north-south gradient in tHcy (P=0.005), and also in food choices, blood micronutrient indices and vascular disease prevalence. Conclusions: The concentrations of tHcy found in this study provide a reference range for people aged 65 y and over, in mainland Britain. tHcy is a valuable functional index of micronutrient status and intakes for British people aged 65 y and over, which can assist the development of health-promotion strategies. Sponsorship: This study was part of the National Diet and Nutrition Survey of people aged 65 y and over, which was funded jointly by the Ministry of Agriculture, Fisheries and Food and the Department of Health, and conducted by Social Community Planning and Research in conjunction with the MRC Dunn Nutrition Unit. The authors acknowledge financial support for the study from the Department of Health, the European Commission and British Heart Foundation.