Introduction

Emergency contraception (EC) is a way to significantly reduce the chance of becoming pregnant after an episode of unprotected intercourse. Considerable data support the safety of all available and emerging options for EC. Areas covered: This review presents a comprehensive summary of the literature regarding the safety of EC as well as directions for further study. PubMed was searched for all relevant studies published prior to June 2017. Expertopinion: All available methods of EC (i.e., ulipristal acetate pills, levonorgestrel pills, and the copper-IUD), carry only mild side effects and serious adverse events are essentially unknown. The copper IUD has the highest efficacy of EC methods. Given the excellent safety profiles of mifepristone and the levonorgestrel IUD, research is ongoing related to use of these products for EC.

Importance

Isotretinoin, an effective anti-acne therapy, is a known teratogen that is strictly regulated through the iPLEDGE program. However, since this program has not significantly reduced rates of pregnancies exposed to isotretinoin, new strategies for reducing rates of isotretinoin-exposed pregnancies are needed.

Objective

To explore women's experiences with counseling about isotretinoin risk reduction.

Design, setting, and participants

Structured interviews were conducted between January and September 2012. Two independent coders performed content analysis using a grounded theory approach. The study participants were 16 women who had used isotretinoin to treat severe skin disease and who were recruited from a single urban community via flyers displayed on college campuses, at dermatology clinics, and at student health facilities.

Main outcomes and measures

Perceptions of isotretinoin-associated risks and understanding of ways teratogenic risks can be avoided.

Results

Participants clearly understood that isotretinoin is teratogenic but had less understanding of contraceptive methods that effectively prevent pregnancy. Most described the counseling they received as anxiety provoking. Few were counseled about highly effective reversible contraceptives such as the subdermal implant or intrauterine contraception; most counseling focused on oral contraceptives. Women cited multiple influences on their contraceptive choices, including friends, family, physicians, the internet, and other media; however, some expressed concerns about the accuracy of these sources of information. For many, iPLEDGE was their first introduction to contraception. When presented with evidence-based information on the relative effectiveness of available contraceptives, participants expressed surprise that this was not part of the iPLEDGE materials.

Conclusions and relevance

Since few clinicians provide women information on highly effective (ie, intrauterine or subdermal) contraceptives, the iPLEDGE program increases anxiety about isotretinoin more than it helps women feel protected from the teratogenic risks of isotretinoin.

Background

When used within 5 days of unprotected sex, emergency contraception (EC) can reduce the risk of pregnancy. Our objective was to explore how often women seeking clinic-based pregnancy testing who do not desire pregnancy might benefit from EC and examine variables associated with patients asking for EC when use is indicated.

Study design

Women seeking pregnancy testing or EC from an inner-city Title-X-funded family planning clinic between January 2011 and June 2012 were invited to complete surveys.

Results

Twenty-seven percent (n=79) of respondents were seeking EC, and 73% (n=215) were seeking pregnancy testing. Of those seeking pregnancy testing, 39% might have benefited from same-day use of EC pills. Women who had never used EC and who had more than one episode of unprotected sex within the past month were less likely to request EC when use was indicated, while single women were more likely to request EC.

Conclusions

Counseling regarding EC options is particularly important for women seeking same-day pregnancy testing who do not desire pregnancy.

Purpose

Alpelisib is a PI3K alpha (PI3Kα)-selective inhibitor approved for the treatment of hormone receptor-positive/HER2-negative (HR+/HER2-) PIK3CA-mutated advanced breast cancer (ABC) based on the SOLAR-1 trial, which defined 11 substitutions in exons 7, 9, and 20 in PIK3CA (SOLAR1m). We report alpelisib effectiveness for ABC harboring SOLAR1m, as well as other pathogenic PIK3CA mutations (OTHERm) using comprehensive genomic profiling (CGP).

Experimental design

A total of 33,977 tissue and 1,587 liquid biopsies were analyzed using hybrid capture-based CGP covering the entire coding sequence of PIK3CA. Clinical characteristics and treatment history were available for 10,750 patients with ABC in the deidentified Flatiron Health-Foundation Medicine clinico-genomic database (FH-FMI CGDB).

Results

PIK3CAm were detected in 11,767/33,977 (35%) of tissue biopsies, including 2,300 (7%) samples with OTHERm and no SOLAR1m. Liquid biopsy had 77% sensitivity detecting PIK3CAm, increasing to 95% with circulating tumor DNA fraction ≥2%. In patients with HR+/HER2- ABC and PIK3CAm receiving alpelisib/fulvestrant (ALP+FUL; n = 182) or fulvestrant alone (FUL; n = 119), median real-world progression-free survival (rwPFS) was 5.9 months on ALP+FUL [95% confidence interval (CI): 5.1-7.4] versus 3.1 months on FUL (95% CI: 2.7-3.7; P < 0.0001). In patients with OTHERm, median rwPFS was 4.0 months on ALP+FUL (95% CI: 2.8-10.1) versus 2.5 months on FUL (95% CI: 2.2-3.7; P = 0.0054).

Conclusions

CGP detects diverse PIK3CAm in a greater number of patients with ABC than PCR hotspot testing; 20% of patients with PIK3CAm do not have SOLAR1m. These patients may derive benefit from alpelisib. See related commentary by Tau and Miller, p. 989.

Huntington disease is a neurodegenerative disorder caused by a gene (HTT) with a unique feature of trinucleotide repeats ranging from 10 to 35 in healthy people; when expanded beyond 39 repeats, Huntington disease develops. Animal models demonstrate that HTT is vital to brain development; however, this has not been studied in humans. Moreover, evidence suggests that triplet repeat genes may have been vital in evolution of the human brain. Here we evaluate brain structure using magnetic resonance imaging and brain function using cognitive tests in a sample of school-aged children ages 6 to 18 years old. DNA samples were processed to quantify the number of CAG repeats within HTT. We find that the number of repeats in HTT, below disease threshold, confers advantageous changes in brain structure and general intelligence (IQ): the higher the number of repeats, the greater the change in brain structure, and the higher the IQ. The pattern of structural brain changes associated with HTT is strikingly different between males and females. HTT may confer an advantage or a disadvantage depending on the repeat length, playing a key role in either the evolution of a superior human brain or development of a uniquely human brain disease. © 2016 Wiley Periodicals, Inc.