Understanding Barriers to Contraception Screening and Referral in Female Adolescents and Young Adults with Cancer.

Background: Contraception screening and referral occur infrequently in cancer care for young women of reproductive age. Barriers to contraception screening and referral in this setting have not been thoroughly identified. Objectives: We sought to understand oncology clinicians' current practices and perceptions of barriers to screening and referring young women for adequate contraception during cancer treatment. Methods: We conducted individual semi-structured interviews with 19 oncology clinicians whom we recruited from an urban, northeast medical center. Participants included physicians, advanced practice clinicians, and nurses in surgical and medical oncology. The interview guide addressed core components of the Promoting Action on Research Implementation in Health Services framework, and subsequent directed content analysis identified themes indicative of barriers to contraception screening and referral. Findings: Participants varied significantly in their current contraception screening practices; many conflated early pregnancy diagnosis or pregnancy avoidance counseling with contraception, whereas others described inaccurate contraceptive recommendations for specific clinical scenarios. Participants also lacked clarity of roles and responsibilities within the oncologic care team for contraception and assumed that another team member had addressed contraception. Participants perceived themselves to lack adequate education about contraception, which precluded contraception discussions. Conclusion: We recommend cancer centers consider these possible barriers to contraception screening and referral by promoting development of institutional guidelines to standardize contraception screening and referral, clarifying roles and responsibilities for contraception discussions within the care team, and expanding oncology clinician education on contraception. National professional organizations should work to expand guidelines to inform and support this process in clinical practice.

Emerging therapy for endometriosis.

INTRODUCTION: Endometriosis is a chronic disease manifested by pain and infertility due to ectopic implantation of endometrial glands and stroma causing inflammation. Treatment of endometriosis utilizes a significant amount of health-care resources and requires chronic therapy. Management involves a combination of surgical and medical interventions and requires long-term treatment to avoid repeated surgeries. AREAS COVERED: Whereas medical therapies exist for management of endometriosis-related pain, each class has its limitations including side effects, cost, and known duration of relief of symptoms. Development of effective, well-tolerated medical therapies that are appropriate for long-term use is crucial to provide adequate treatment for this chronic disease. This review discusses the various medical therapies available, their limitations, and emerging therapies being developed to address many of these concerns. EXPERT OPINION: The authors recommend chronic suppressive therapy for management of endometriosis symptoms, particularly in the postoperative setting. Empiric treatment is appropriate for those patients without evidence of severe disease. Currently available option may not be effective for nor tolerated by all patients. Newer compounds, including gonadotropin-releasing antagonists and aromatase inhibitors combined with hormonal contraceptives, offer possible alternatives to currently available therapies.

Calcineurin activates interleukin-6 transcription in mouse skeletal muscle in vivo and in C2C12 myotubes in vitro.

Expression of the cytokine interleukin-6 (IL-6) by skeletal muscle is hugely increased in response to a single bout of endurance exercise, and this appears to be mediated by increases in intracellular calcium. We examined the effects of endurance exercise on IL-6 mRNA levels and promoter activity in skeletal muscle in vivo, and the role of the calcium-activated calcineurin signaling pathway on muscle IL-6 expression in vivo and in vitro. IL-6 mRNA levels in the mouse tibialis anterior (TA) were increased 2-10-fold by a single bout of treadmill exercise or by 3 days of voluntary wheel running. Moreover, an IL-6 promoter-driven luciferase transgene was activated in TA by both treadmill and wheel-running exercise and by injection with a calcineurin plasmid. Exercise also increased muscle mRNA expression of the calcineurin regulatory gene MCIP1, as did treatment of C(2)C(12) myotubes with the calcium ionophore A23187. Cotransfection of C(2)C(12) myotubes with a constitutively active calcineurin construct significantly increased while cotransfection with the calcineurin inhibitor CAIN inhibited activity of a mouse IL-6 promoter-reporter construct. Cotransfection with a myocyte enhancer-factor-2 (MEF-2) expression construct increased basal IL-6 promoter activity and augmented the effects of calcineurin cotransfection, while cotransfection with the MEF-2 antagonist MITR repressed calcineurin-activated IL-6 promoter activity in vitro. Surprisingly, cotransfection with a dominant-negative form of another calcineurin-activated transcription factor, nuclear factor activator of T cells (NFAT), greatly potentiated both basal and calcineurin-stimulated IL-6 promoter activity in C(2)C(12) myotubes. Mutation of the MEF-2 DNA binding sites attenuated, while mutation of the NFAT DNA binding sites potentiated basal and calcineurin-activated IL-6 promoter activity. Finally, CREB and C/EBP were necessary for basal IL-6 promoter activity and sufficient to increase IL-6 promoter activity but had minimal roles in calcineurin-activated IL-6 promoter activity. Together, these results suggest that IL-6 transcription in skeletal muscle cells can be activated by a calcineurin-MEF-2 axis which is antagonized by NFAT.