Prescription retinoid and contraception use in women in Australia: A population-based study.

BACKGROUND/OBECTIVES: Oral retinoids are teratogenic, and pregnancy avoidance is an important part of retinoid prescribing. Australia does not have a standardised pregnancy prevention programme for women using oral retinoids, and the contraception strategies for women who use oral retinoids are not well understood. The objectives were to determine trends in the use of prescription retinoids among Australian reproductive-aged women and whether women dispensed oral retinoids used contraception concomitantly. METHODS: This was a population-based study using Australian Pharmaceutical Benefits (PBS) dispensing claims for a random 10% sample of 15-44-year-old Australian women, 2013 - 2021. We described rates and annual trends in dispensing claims for PBS-listed retinoids and contraceptives. We also estimated concomitant oral retinoid and contraceptive use on the day of each retinoid dispensing and determined if there was a period of contraceptive treatment that overlapped. Estimates were then extrapolated to the national level. RESULTS: There were 1,545,800 retinoid dispensings to reproductive-aged women; 57.1% were oral retinoids. The rate of retinoid dispensing to reproductive-aged women increased annually, from 28 dispensings per 1000 population in 2013 to 41 per 1000 in 2021. The rate of oral retinoid dispensing doubled over the study period, from 14 dispensings per 1000 population in 2013 to 28 per 1000 in 2021, while topical retinoid dispensing did not change. Only 25% of oral retinoid dispensings had evidence of concomitant contraceptive use in 2021. CONCLUSIONS: Rates of oral retinoid dispensing have doubled among reproductive-aged women over the past decade. A large percentage of oral retinoid use does not appear to have concomitant contraception use, posing a risk of teratogenic effects in pregnancies.

Impact of Biologic Therapy on Key Cardiovascular Risk Parameters in a Psoriatic Cohort-a Retrospective Review.

BACKGROUND: Psoriasis is a risk factor for cardiovascular disease. Biologic agents have revolutionised psoriatic skin control. This study aims to assess the change in cardiovascular risk factors in a cohort of patients treated with 1 year of continuous biologic treatment. METHODS: A retrospective medical record review was conducted of consecutive patients receiving biologic therapy for chronic plaque psoriasis in a single dermatology centre at a major tertiary hospital in Australia. The effect of biologic therapy on psoriasis was assessed using a psoriasis area severity index (PASI). Cardiovascular risk factors included systolic blood pressure (SBP), diastolic BP (DBP), heart rate (HR) and body mass index (BMI). Measurements at baseline and 1-year follow-up were compared using paired t-tests. RESULTS: A total of 106 patients were reviewed with a median age of 44 years, and 63% of the patients were male. At baseline, mean BMI was 30 (SD 7), mean SBP was 129 (SD 17), mean DBP was 81 (SD 9) and mean HR was 82 (SD 14). Over 12 months, the PASI was reduced from 17.4 (SD 8.5) to 1.4 (SD 1.7, p < 0.001) indicating skin improvement. There was no significant difference from baseline in SBP (difference 2.3 mmHg, 95% CI - 1.4-5.9), DBP (0.6 mmHg, 95% CI - 1.2-2.5), BMI (difference - 0.1 kg/m2, 95% CI - 0.9-0.7) or HR (difference 1.3, 95% CI - 3.9-6.4). CONCLUSION: In patients with psoriasis, markers of cardiovascular disease risk did not improve after 1 year of biologic therapy despite significant improvements in psoriasis skin severity.

Drug survival of biologics in psoriasis: An Australian multicentre retrospective study.

BACKGROUND: Drug survival, which refers to the time from treatment initiation to discontinuation, provides a surrogate measure of the effectiveness of a biologic in a real-world setting (J Invest Dermatol, 2015, 135, 1). The aim of this study was to determine the drug survival of biologics that are currently available in Australia. We also analysed the treatment efficacy of these biologics and reasons for discontinuation. METHODS: Retrospective data from outpatient Dermatology biologic clinics in Westmead Hospital and Royal Prince Alfred Hospital (Sydney, Australia) from April 2006 to December 2020 were collected. Kaplan-Meier analysis was used to calculate drug survival. RESULTS: A total of 306 patients who underwent 566 treatment courses were analysed. Guselkumab was observed to have the longest drug survival, with cumulative drug survival rates of 94.2% ± 4.0 at 1- and 5-years. This was followed by ixekizumab which had a 1-year survival rate of 87.2% ± 4.5 and 5-year survival rate of 59.4% ± 9.5. Ixekizumab and guselkumab were also noted to have superior treatment efficacy compared with other biologics, with PASI-75 rates of 94.9% and 93.8%, respectively. The most common reasons for treatment discontinuation were a lack of initial efficacy to treatment and a loss of efficacy over time despite an initial response, respectively. CONCLUSION: To our knowledge, this is the first Australian study to report on outcomes of multiple new biologics that are currently in use for the treatment of chronic plaque psoriasis. Overall, this study provides insight into patterns of care from a local experience that may help guide the management of moderate-to-severe psoriasis.

Full-body skin examination in screening for cutaneous malignancy: a focus on concealed sites and the practices of Australian dermatologists.

BACKGROUND: Full-body skin examination (FSE) is a vital practice in the diagnosis of cutaneous malignancy. Precisely how FSE should be conducted with respect to concealed site inclusion remains poorly elucidated. OBJECTIVE: To establish the approach of Australian dermatologists to concealed site examination (CSE). METHODS: A cross-sectional study was performed consisting of an online self-administered 11-question survey delivered to fellows of the Australasian College of Dermatologists. RESULTS: There were 237 respondents. Anogenitalia was the least often examined concealed site (4.6%), and 59.9, 32.9, and 14.3% reported always examining the scalp, breasts, and oral mucosa, respectively. Patient concern was the most frequently cited factor prompting examination, while many cited low incidence of pathology and limited chaperone availability as the main barriers to routine examination of these sites. CONCLUSION: Most Australian dermatologists do not routinely examine breasts, oral mucosal, or anogenital sites as part of an FSE. Emphasis should be made on identifying individual patient risk factors and education regarding self-examination of sensitive sites. A consensus approach to the conduct of the FSE, including concealed sites, is needed to better delineate clinician responsibilities and address medicolegal implications.

Serial Cross-Sectional Observations of Sun-Protective Behaviors at an Annual Outdoor Motorsport Event in Tropical Queensland, Australia.

Skin cancer, the most prevalent cancer in Caucasians residing at low latitudes, can primarily be prevented by avoiding overexposure to sunlight. Serial cross-sectional observations were conducted at an outdoor motorsport event held in Townsville, Queensland each July (Southern winter) to determine whether sun-protection habits changed over time. Most (71.1%) of the 1337 attendees observed (97.6% lightly pigmented skin, 64.0% male) wore a hat (any style shading the face), while few (18.5%) wore three-quarter or full-length sleeves. While hat-wearing rates (any style) were similar in 2009 (326, 72.6%) and 2013 (625, 70.4%), the use of sun-protective styles (wide-brimmed/bucket/legionnaires) decreased from 29.2% to 18.6% over the same period, primarily because the use of sun-protective hats halved (from 28.7% to 14.0%) among females, while decreasing from 29.4% to 21.1% in males. Although relatively few individuals wore sun-protective (three-quarter-length or full-length) sleeves regardless of year (OR = 0.117, P < 0.0001), encouragingly, the use of sun-protective sleeves more than doubled between 2009 (10.5%) and 2013 (22.5%). Interestingly females, albeit the minority, at this sporting event were less likely to wear a hat (OR = 0.473, P < 0.0001) than males. These findings highlight the need for continued momentum toward skin cancer primary prevention through sun protection with a dedicated focus on outdoor sporting settings.

The Intersection of Law and Medicine in Full Skin Examination in Screening for Cutaneous Malignancy.

Full skin examination (FSE) is a vital practice in the diagnosis of cutaneous malignancy. Precisely what the FSE entails, however, with respect to concealed site examination (CSE), in particular sensitive sites including the anogenital region, breasts, scalp and oral mucosa, remains poorly elucidated. While the incidence of skin cancer at these sites is low, it carries a poor prognosis. A standardised approach is proposed to FSE with respect to inclusion of CSE to provide: an optimised and uniform approach to patient care, guidance to clinicians performing FSE routinely, and in doing so to protect them medico legally. This article analyses the medico-legal issues pertinent to this issue.

Intermittent fasting two days versus one day per week, matched for total energy intake and expenditure, increases weight loss in overweight/obese men and women.

BACKGROUND: Intermittent fasting (IF), consisting of either a one-day (IF1) or two consecutive days (IF2) per week, is commonly used for optimal body weight loss. Our laboratory has previously shown an IF1 diet combined with 6d/week of protein pacing (P; 4-5 meals/day evenly spaced, ~ 30% protein/day) significantly enhances weight loss, body composition, and cardiometabolic health in obese men and women. Whether an IF1-P or IF2-P, matched for weekly energy intake (EI) and expenditure (EE), is superior for weight loss, body composition, and cardiometabolic health is unknown. METHODS: This randomized control study directly compared an IF1-P (n = 10) versus an IF2-P (n = 10) diet on weight loss and body composition, cardiovascular (blood pressure and lipids), hormone, and hunger responses in 20 overweight men and women during a 4-week weight loss period. Participants received weekly dietary counseling and monitoring of compliance from a registered dietitian. All outcome variables were assessed pre (week 0) and post (week 5). RESULTS: Both groups significantly reduced body weight, waist circumference, percent body fat, fat mass, hunger, blood pressure, lipids, glucose, and increased percent fat-free mass (p < 0.05). However, IF2-P resulted in significantly greater reductions in body weight (-29%) and waist circumference (-38%) compared to IF1-P (p < 0.05), and showed a strong tendency for greater reductions in fat mass, glucose, and hunger levels (p < 0.10) despite similar weekly total EI (IF1-P, 9058 ± 692 vs. IF2-P, 8389 ± 438 kcals/week; p = 0.90), EE (~ 300 kcals/day; p = 0.79), and hormone responses (p > 0.10). CONCLUSIONS: These findings support short-term IF1-P and IF2-P to optimize weight loss and improve body composition, cardiometabolic health, and hunger management, with IF2-P providing enhanced benefits in overweight women and men. TRIAL REGISTRATION: This trial was registered March 03, 2020 at www. CLINICALTRIALS: gov as NCT04327141 .

Effect of the SunSafe Student Ambassador Program on the attitudes, knowledge and behaviour of Australian high-school students towards sun safety: a prospective study.

BACKGROUND: The SunSafe Student Ambassador Program (SSSAP) in Australia uses the peer-to-peer learning environment to educate high-school students about sun-safety. AIMS: To assess whether the SSSAP would improve knowledge, attitudes and behaviours towards sun safety in high-school students and whether this would be sustained at 3 months. METHODS: An assessment survey was delivered before, immediately after and 3 months after participation in the SSSAP in 2019. RESULTS: In total, 503 participants completed the pre-presentation survey, 274 completed the post-presentation survey, and 218 completed both. Immediately following presentation, the total composite score for all 18 knowledge questions increased from a mean ± SD of 11.8 ± 3.5 to 13.8 ± 4.7 (P < 0.001). There was strong evidence for an improvement in one attitude-based question 'Is it healthy to have a tan?' (P < 0.01) and one behaviour question about wearing sunscreen daily (P = 0.02). After 3 months, 235 students were matched to their pre-presentation survey. The composite score of all knowledge questions had improved from 11.2 ± 3.5 to 12.1 ± 4.5 (out of a total of 18) (P < 0.01). There was also an improvement in two attitude questions 'Do you feel better when you have a tan?' (P = 0.03) and 'Is it healthy to have a tan?' (very strong evidence: P < 0.001), and evidence for a reduction in time spent outdoors on a weekday (P = 0.04). CONCLUSION: The SSSAP was associated with improvements in knowledge, attitude and behaviour towards sun safety immediately and at 3 months post-presentation. Further research is required to determine whether these positive effects are sustained and whether they ultimately reduce skin cancers.

Multiple eruptive squamoproliferative lesions during anti-PD1 immunotherapy for metastatic melanoma: Pathogenesis, immunohistochemical analysis and treatment.

Treatment with anti-PD1 inhibitors may enhance the risk for developing low grade squamoproliferative skin tumors. Immunohistochemical (IHC) analysis of the immune tumor microenvironment (TME) allows exploration of the pathogenesis and relationship with the PD1/PDL1 axis. Patients with eruptive keratoacanthoma (KA)-like lesions were recruited from the Melanoma Institute Australia, a tertiary referral specialist melanoma treatment center from January 2015 to August 2017. Clinicopathologic evaluation and IHC features of tumor cells (PDL1 expression) and peritumoral microenvironment (PD1, FOXP3, PDL1, CD4:CD8 expressing cells) in 12 eruptive KA-like lesions, were compared with solitary KAs in age and sex matched non-anti-PD1 treated controls. Four patients with repeated episodes of eruptive KA-like and lichenoid lesions developing 2-7 months after commencing pembrolizumab for AJCC stage IV melanoma, were recruited. Eruptive KA-like squamoproliferative lesions occurred in sun exposed sites and in areas of resolving, concomitant or delayed lichenoid reactions. Histologically, the lesions were well-differentiated squamoproliferative lesions resembling infundibulocystic squamous cell carcinoma or KA. IHC of cases and controls revealed low PDL1 expression of both squamous tumor cells and the TME immune cells. The numbers of immunosuppressive FOXP3 positive Tregs and PD1-expressing T-cells were higher in the cases than the controls but the CD4:CD8 ratio (2:1) was similar. The patients best responded to acitretin and were managed surgically if they demonstrated neoplastic features. Accelerated squamoproliferative growth in actinically damaged keratinocytes associated with lichenoid eruptions may be unmasked in patients treated with anti-PD1 immunotherapy potentially contributed to by a local cutaneous immunosuppressed TME.

Investigating cell autonomy in microorganisms.

Cell-cell signaling in microorganisms is still poorly characterized. In this Methods paper, we describe a genetic procedure for detecting cell-nonautonomous genetic effects, and in particular cell-cell signaling, termed the chimeric colony assay (CCA). The CCA measures the effect of a gene on a biological response in a neighboring cell. This assay can measure cell autonomy for range of biological activities including transcript or protein accumulation, subcellular localization, and cell differentiation. To date, the CCA has been used exclusively to investigate colony patterning in the budding yeast Saccharomyces cerevisiae. To demonstrate the wider potential of the assay, we applied this assay to two other systems: the effect of Grr1 on glucose repression of GAL1 transcription in yeast and the effect of rpsL on stop-codon translational readthrough in Escherichia coli. We also describe variations of the standard CCA that address specific aspects of cell-cell signaling, and we delineate essential controls for this assay. Finally, we discuss complementary approaches to the CCA. Taken together, this Methods paper demonstrates how genetic assays can reveal and explore the roles of cell-cell signaling in microbial processes.