Perceived infertility and contraceptive use in the female, reproductive-age cancer survivor.

OBJECTIVE: To estimate the association between perceived fertility potential and contraception use and to characterize factors important in contraceptive decision making in reproductive-age, female cancer survivors. DESIGN: Cross-sectional study. SETTING: Participants were from two state cancer registries, physician referrals, and cancer survivor advocacy groups in the United States. PATIENT(S): A total of 483 female survivors aged 18-40 years. INTERVENTION(S): Online questionnaire. MAIN OUTCOME MEASURE(S): Contraception use. RESULT(S): Eighty-four percent of participants used contraception; 49.7% used highly effective, World Health Organization tiers I and II methods (surgical sterilization, intrauterine devices, contraceptive implant, combined hormonal contraceptives, medroxyprogesterone acetate, progestin-only pills, contraceptive diaphragm). Contraception non-use was more common among survivors who perceived themselves to be infertile, compared with survivors who perceived themselves to be as or more fertile than similarly aged peers (prevalence ratio 4.0, 95% confidence interval 2.5-7.4). In mediation analysis that adjusted for clinical infertility, 59% of the association between prior chemotherapy and contraception non-use was explained by perceived infertility. Contraception efficacy (n = 62, 25.8%) and ease of use (n = 50, 20.8%) were the most cited reasons for using tier I/II methods; compared with lack of hormones (n = 81, 49.7%) as the predominant reason for using less-effective, tier III/IV methods. CONCLUSION(S): Although female, reproductive-age cancer survivors had high uptake of contraception, those who perceived themselves to be infertile were less likely to use contraception. Throughout survivorship, clinicians should counsel survivors on fertility potential in the context of their prior cancer treatments and on factors, including contraceptive efficacy and hormone-free contraception, that inform reproductive decision making in this population.

Use of emergency contraception among female young adult cancer survivors.

OBJECTIVE: To test whether emergency contraception use in reproductive-aged cancer survivors is higher than in the general U.S. population and evaluate factors associated with use among survivors. DESIGN: A retrospective cohort study compared emergency contraception use between cancer survivors in the Reproductive Window Study on ovarian function after cancer and in the general population in the 2006-2010 National Survey for Family Growth. In a cross-sectional analysis of survivors, multivariable models were used to test associations between participant characteristics and emergency contraception use. SETTING: Not applicable. PATIENT(S): A total of 616 female cancer survivors aged 18-40. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Self-reported emergency contraception use. RESULT(S): The mean age of survivors was 33.4 ± 4.7, at a mean 7.5 years since diagnosis. Breast cancer (22%), Hodgkin lymphoma (18%), and leukemia (8%) were the most common cancers. Since diagnosis, 156 (25.3%) used emergency contraception, 60% because of not otherwise using contraception. Age-adjusted prevalence of use was higher in survivors than in the general population (28.3% [95% confidence interval (CI) 24.7-31.9] vs. 12.0% [95% CI 11.1-12.9]). In multivariable analysis among survivors, nonwhite race (prevalence ratio [PR] 1.3, 95% CI 1.0-1.8), breast cancer (PR 0.6, 95% CI 0.4-1.0), partnered relationship (PR 0.6, 95% CI 0.5-0.9), and older age (age 36-40 vs. 31-35; PR 0.7, 95% CI 0.5-1.0) were associated with emergency contraception. CONCLUSION(S): Female young adult cancer survivors were significantly more likely to use emergency contraception compared with the general population. Populations including nonwhite survivors have a higher risk, suggesting differences in family planning care. Strategies to improve contraception and decrease the need for emergency contraception are needed.

Use of a Hospital-Wide Screening Program for Early Detection of Sepsis in General Surgery Patients.

Sepsis remains a significant source of mortality among hospitalized patients. This study examines the usage of a vital sign-based screening protocol in identifying postoperative patients at risk for sepsis at an academic-affiliated medical center. We identified all general surgery inpatients undergoing abdominopelvic surgery from January to June 2014, and compared those with positive screening tests to a sample of screen-negative controls. Multivariate logistic regression was used to identify predictors of positive screening tests and progression to severe sepsis. In total, 478 patients underwent abdominopelvic operations, 59 had positive screening tests, 33 qualified for sepsis, and six progressed to severe sepsis. Predictors of a positive screening test were presence of cancer [odds ratio (OR) 30.7, 95% confidence interval (CI) 2.2-420], emergency operation (OR 6.5, 95% CI 1.7-24), longer operative time (OR 2.2/h, 95% CI 1.2-4.1), and presence of postoperative infection (OR 6.4, 95% CI 1.5-27). The screening protocol had sensitivity 100 per cent and specificity 88 per cent for severe sepsis. We identified no predictors of severe sepsis. In conclusion, vital sign-based screening provides value by drawing early attention to patients with potential to develop sepsis, but escalation of care for these patients should be based on clinical judgment.

Outcomes of spontaneous and assisted pregnancies in Turner syndrome: the U.S. National Institutes of Health experience.

OBJECTIVE: To assess fetal and maternal outcomes of pregnancies in women with Turner syndrome (TS). DESIGN: Retrospective case series. SETTING: Clinical research center. PATIENT(S): 276 adults with cytogenetically proven TS participating in an intramural natural history protocol. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Menstrual and obstetric histories, 50-cell karyotypes, and cardiovascular evaluation including aortic diameter measurements. RESULT(S): Our cohort included five women with spontaneous pregnancies and five with pregnancies using assisted reproduction (ART). All five women with spontaneous pregnancies had spontaneous puberty, despite 45,X in ≥90% of their 50-cell karyotype. Participants had a total of 13 pregnancies and 14 live births. One child had cerebral palsy; the others were chromosomally and developmentally normal. Delivery was by cesarean section in four out of seven spontaneous and six out of six ART-related pregnancies. One mother experienced preeclampsia in an ART-related twin pregnancy that required a preterm delivery; she has marked but stable aortic dilation years later. CONCLUSION(S): Approximately 2% of our study cohort experienced spontaneous pregnancies despite high-grade X monosomy, and a similar number achieved pregnancy via oocyte donation and ART. The potential for life-threatening cardiovascular complications warrants comprehensive screening before conception or single-embryo transfer, and caution regarding unintentional pregnancies for TS women.

Tnni3k modifies disease progression in murine models of cardiomyopathy.

The Calsequestrin (Csq) transgenic mouse model of cardiomyopathy exhibits wide variation in phenotypic progression dependent on genetic background. Seven heart failure modifier (Hrtfm) loci modify disease progression and outcome. Here we report Tnni3k (cardiac Troponin I-interacting kinase) as the gene underlying Hrtfm2. Strains with the more susceptible phenotype exhibit high transcript levels while less susceptible strains show dramatically reduced transcript levels. This decrease is caused by an intronic SNP in low-transcript strains that activates a cryptic splice site leading to a frameshifted transcript, followed by nonsense-mediated decay of message and an absence of detectable protein. A transgenic animal overexpressing human TNNI3K alone exhibits no cardiac phenotype. However, TNNI3K/Csq double transgenics display severely impaired systolic function and reduced survival, indicating that TNNI3K expression modifies disease progression. TNNI3K expression also accelerates disease progression in a pressure-overload model of heart failure. These combined data demonstrate that Tnni3k plays a critical role in the modulation of different forms of heart disease, and this protein may provide a novel target for therapeutic intervention.

Common deletion polymorphisms in the human genome.

The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies.