Sunscreens in the United States: Current Status and Future Outlook.

Incidence rates of nonmelanoma skin cancer and melanoma have been on the rise in the USA for the past 25 years. UV radiation (UVR) exposure remains the most preventable environmental risk factor for these cancers. Aside from sun avoidance, sunscreens continue to provide the best alternative protection. UVR directly damages DNA and causes indirect cellular damage through the creation of reactive oxygen species, the sum of which leads to cutaneous immunosuppression and a tumorigenic milieu. The current generation of sunscreens protect from UVR through two main mechanisms: absorption and deflection. In the USA, the Food and Drug Association (FDA) regulates sunscreen products which are considered over-the-counter drugs. With the release of new FDA testing and labeling requirements in 2011 and the enactment of the Sunscreen Innovation Act in 2014, sunscreen manufacturers are now required to evaluate their products not only on the sun protection factor (SPF) but also on broad-spectrum UVA protection. The American Academy of Dermatology Association and the American Academy of Pediatrics have provided specific recommendations for proper sun protection and sunscreen usage with the continual goal of increasing public awareness and compliance with appropriate sun protective measures. Antioxidants, photolyases, and plant polyphenols remain an interesting avenue of research as additives to sunscreens or stand-alone topical or oral products that appear to modulate the immunosuppressive effects of UVR on the skin. Additionally, although UVR induces endogenous cutaneous production of vitamin D, its damaging effects overshadow this positive benefit, especially in light of the ease of achieving recommended amounts of vitamin D through diet and supplementation.

Use of Systemic Therapies to Manage Focal Hyperhidrosis.

Primary hyperhidrosis (excessive sweating) commonly affects the axillae, palms, soles, scalp, face, and the groin. Patients may have multiple areas involved making localized therapy challenging. Systemic therapy may be necessary and can be used as monotherapy or combined with other hyperhidrosis treatments for optimal outcomes. Systemic therapy can also be used to treat secondary hyperhidrosis and compensatory hyperhidrosis. Patient selection and counseling are key, and monitoring for side effects is required throughout therapy.

Fetal and maternal morbidity in pregnant patients with Lupus: a 10-year US nationwide analysis.

OBJECTIVE: To evaluate and quantify the indicators of fetal and maternal morbidity in deliveries for patients with systemic lupus erythematosus (SLE) compared with deliveries in patients without SLE. METHODS: We used retrospective data from the National Inpatient Sample (NIS) to identify all delivery related hospital admissions of patients with and without SLE from 2008 to 2017 using ICD-9/10 codes. Fetal morbidity indicators included pre-term delivery and intrauterine growth restriction (IUGR). 21 indicators of severe maternal morbidity were identified using standard Centers for Disease Control and Prevention (CDC) definitions. Descriptive statistics, including 95% confidence intervals, were calculated using sample weights from the NIS dataset. RESULTS: Among the 40 million delivery-related admissions, 51 161 patients were reported to have SLE. Patients with SLE had a higher risk of fetal morbidity, including IUGR (8.0% vs 2.7%) and pre-term delivery (14.5% vs 7.3%), than patients without SLE. During delivery, mothers with SLE were nearly four times as likely to require a blood transfusion or develop a cerebrovascular disorder, and 15 times as likely to develop acute renal failure than those without SLE. CONCLUSION: Our study demonstrates that fetal morbidity and severe maternal morbidity occur at a higher rate in patients with SLE compared with those without. This quantitative work can help inform and counsel patients with SLE during pregnancy and planning.

Missing mifepristone at tribal health facilities serving native Americans.

The Risk Evaluation and Mitigation Strategy (REMS) associated with mifepristone limits the number of providers of mifepristone. Mifepristone increases the efficacy of medical management of early pregnancy loss, but difficulties in acquiring the drug causes delays for Indian Health Service and Tribal faciliites attempting to utilize the medication.

Awareness of the option of IUC self-removal among US adolescents.

OBJECTIVE: To assess adolescent awareness of the safety of self-removal of intrauterine contraception (IUC) and explore associations with sociodemographic characteristics, IUC knowledge, and personal experience using an IUC. STUDY DESIGN: We recruited women aged 15 to 20 years from 21 U.S. states and Washington, D.C. Participants completed an online survey assessing their communication with peers about contraception and knowledge and use of IUCs. RESULTS: Few (11%, 95% CI 9%-13%) adolescents knew that IUC self-removal is safe, whether or not they had personally used an IUC (14% vs 8%, p = 0.01). Knowledge that IUCs do not protect users from sexually transmitted infections (99% vs 91%, p < 0.001) and that IUCs can be removed early (99% vs 88%, p < 0.001) was higher among adolescents who had used an IUC than those who had not. Knowledge that IUC use does not adversely affect fertility after IUC removal (86% vs 63%, p < 0.001) and that IUCs are more effective than birth control pills (82% vs 50%, p < 0.001) also differed by personal experience with an IUC. Awareness of the safety of IUC self-removal was not associated with overall knowledge of IUCs. However, adolescents who knew that IUCs are more effective than birth control pills were more likely to be aware of the safety of IUC self-removal (OR = 1.85, 95% CI 1.12-3.05). CONCLUSIONS: Adolescent women in the U.S. possess incomplete knowledge of many important aspects of IUC use, and awareness of the safety of IUC self-removal is particularly low, even among those who have used an IUC. IMPLICATIONS: Efforts to increase adolescent knowledge of IUC should include information about the safety of IUC self-removal in order to safeguard adolescents' reproductive autonomy.

Biomarkers and endosalpingiosis in the ovarian and tubal microenvironment of women at high-risk for pelvic serous carcinoma.

INTRODUCTION: BRCA mutations increase the risk for development of high-grade pelvic serous carcinomas. Tissue biomarkers distinguishing women at high-risk (HR) for ovarian cancer from those at low-risk (LR) may provide insights into tumor initiation pathways. METHODS: A prospective study of 47 HR women (40% BRCA carriers) undergoing risk-reducing salpingo-oophorectomy and 48 LR controls undergoing salpingo-oophorectomy was performed. Ovarian/tubal tissues were harvested. Immunohistochemical analysis of candidate proteins CSF-1, CSF-1R, ErbB4 is presented, with scores separately analyzed in epithelium and stroma, in ampulla, fimbria, ovary, and ovarian endosalpingiosis (ES). Comparison was performed between HR and LR groups. RESULTS: Elevated levels of CSF-1 (p=0.005) or ErbB4 (p=0.005) in the ovarian epithelium, or ErbB4 (p=0.005) in the ovarian stroma, were significantly associated with both the HR status and carrying a BRCA mutation, as was nuclear ErbB4 staining. Ovarian ES, an entity which likely derives from the tubal mucosal epithelium, was also associated with HR (p=0.038) and BRCA mutation status (p=0.011). Among the BRCA carriers only, markers also found association when present in the tube as well as in ovarian ES (p < 0.05). ROCs were generated including in the regression model both CSF-1 and ErbB4 expression levels. A model including CSF-1 in ovarian epithelium, ErbB4 in ovarian stroma, and younger age achieves AUC=0.87 (73% sensitivity, 93% specificity) of detection of the HR status. In BRCA carriers, CSF-1 in ovarian epithelium alone achieves AUC=0.85. CONCLUSIONS: Our data suggest that elevated levels of CSF-1/ErbB4 in the adnexae correlate with HR/BRCA carrier status. CSF-1/CSF-1R signaling is active in ovarian cancer progression; our data suggests a role in its initiation. ErbB4, in particular nuclear ErbB4, may have a role in tumor initiation as well. Ovarian ES, an entity which may represent a latent precursor to low-grade pelvic serous carcinomas, was surprisingly associated with both HR status and the BRCA carrier cohort. In line with these findings, both ErbB4 and CSF-1R expression in ovarian ES correlated with carrying a BRCA mutation. This analysis, which needs to be validated, indirectly suggests a potential link between ovarian ES and the development of pelvic serous carcinoma in women who are BRCA mutation carriers.

Flutamide and biomarkers in women at high risk for ovarian cancer: preclinical and clinical evidence.

We hypothesized that (i) preclinical biologic evidence exists for the role of androgens in ovarian cancer development and (ii) flutamide treatment of women at high risk for ovarian cancer may identify meaningful tissue biomarkers of androgen action and of ovarian cancer initiation. We showed that androgen ablation of male mice led to a 24-fold decrease in tumor burden from serous ovarian cells. In a phase II study, we studied the effect of preoperative flutamide treatment (125 mg/day × 6 weeks) in 12 women versus 47 controls, 47% with BRCA mutation. We analyzed immunohistochemical scores of candidate proteins CSF-1, CSF-1R, and ErbB4 in the epithelium and stroma of fallopian tube, ovary, and ovarian endosalpingiosis. Flutamide decreased the levels, notably, of CSF-1 and ErbB4 in ovarian stroma (P ≤ 0.0006) and ovarian endosalpingiosis (P ≤ 0.01), ErbB4 in ovarian epithelium (P = 0.006), and CSF-1R in ovarian endosalpingiosis (P = 0.009). Our logistic regression model clearly distinguished the flutamide patients from controls (P ≤ 0.0001). Our analysis of the precision of this model of CSF-1 and ErbB4 expression in ovarian stroma achieved 100% sensitivity and 97% specificity (AUC = 0.99). Thus, our data suggest that a short 6-week exposure of flutamide reversed elevated levels of CSF-1 and ErbB4 (both of which we had previously found correlated with high risk status). CSF-1 and ErbB4 in ovarian stroma led to a model with high predictive value for flutamide sensitivity. The effect of flutamide on marker expression in ovarian endosalpingiosis, previously associated with BRCA carrier status, suggests that ovarian endosalpingiosis may be a latent precursor to pelvic serous cancers.

Pap testing and sexual activity among young women in the United States.

OBJECTIVE: To understand whether and how recency of sexual activity is associated with Pap testing rates among young women. METHODS: We analyzed data on self-reported receipt of Pap testing and initiation of sexual activity among young women and girls aged 15 to 24 years using the 2002 National Survey of Family Growth, an in-person, population-based survey of reproductive-aged men and women in the United States. The primary outcome was receiving a Pap test and its relationship to initiation of sexual activity. A multivariable model was used to predict the probability of having had a Pap test in the previous 12 months. RESULTS: Thirty-three percent of the 2,513 women had never had sex. Of these, 13.9% had had a Pap test in the previous year. Sixty-seven percent of sexually-active women aged 15-24 reported receiving a Pap test (corresponding to 13.1 million tests). Approximately 59% women aged 15-20 years old who reported having initiated sexual activity in the previous 3 years also reported a Pap test in the previous year. CONCLUSION: The current guidelines recommend screening 3 years after initiation of vaginal intercourse or at age 21, whichever is earlier. Contrary to the current guidelines, many young women who have not had sex or who initiated sex within the previous 3 years reported having had a Pap test. Assuming that the patterns observed in this study persist, there is an urgent need for education regarding the need to adhere to guidelines to reduce the burden of potentially unnecessary Pap tests in young women. LEVEL OF EVIDENCE: III.