Viral coinfection analysis using a MinHash toolkit

Abstract: Background: Human papillomavirus (HPV) is a common sexually transmitted infection associated with cervical cancer that frequently occurs as a coinfection of types and subtypes. Highly similar sublineages that show over 100-fold differences in cancer risk are not distinguishable in coinfections with current typing methods. Results: We describe an efficient set of computational tools, rkmh, for analyzing complex mixed infections of related viruses based on sequence data. rkmh makes extensive use of MinHash similarity measures, and includes utilities for removing host DNA and classifying reads by type, lineage, and sublineage. We show that rkmh is capable of assigning reads to their HPV type as well as HPV16 lineage and sublineages. Conclusions: Accurate read classification enables estimates of percent composition when there are multiple infecting lineages or sublineages. While we demonstrate rkmh for HPV with multiple sequencing technologies, it is also applicable to other mixtures of related sequences

Effects of relationship context on contraceptive use among young women

OBJECTIVES: To understand how relationship status influences contraceptive use among young people. STUDY DESIGN: Data were collected as part of a longitudinal study on hormonal contraception among unmarried adolescent and young women who wanted to avoid pregnancy for at least one year, recruited at family planning clinics in the San Francisco Bay area. Follow-up surveys were completed at 3, 6, and 12 months. Longitudinal analysis was used to examine whether relationship characteristics, including type and length of sexual relationship are associated with current use of effective contraception. RESULTS: Among women with a partner at baseline, 78%, 70%, and 61% had the same partner at 3, 6, and 12 months follow up, respectively. Women in casual relationships were less likely to use effective contraceptive methods, compared to women in consistent relationships (AOR=0.67, p<0.01). Women in new relationships (0–3 months) were less likely to use effective contraceptive methods (AOR=0.60, p<0.001) compared to women in relationships more than one year in length. Younger women (AOR=0.76, p<0.05), black women (AOR=0.67, p<0.05) and Latina women (AOR=0.73, p<0.05) were also significantly less likely to use effective contraception. These effects remained even after controlling for condom use. CONCLUSIONS: Relationship type and length are independently significantly associated with current effective contraceptive use among adolescent and young women. Women in casual relationships and new relationships were significantly less likely to use effective contraceptive methods. IMPLICATIONS: Family planning providers should discuss women’s relationship context and association with contraceptive use in order to help women think of contraception as a long term personal strategy. Since relationship status affects contraceptive use, providers and programs that aim to reduce unintended pregnancy can consider strategies to create a paradigm shift around contraceptive use that focuses on the woman’s reproductive goals, current life stage, and life goals

The Relationship Between Prescription Copayments and Contraceptive Adherence in a New-user Cohort

BackgroundContraceptive nonadherence is an important contributor to unintended pregnancy in the United States. While the elimination of patient cost sharing has been cited as means to improve contraceptive access, little is known about the relationship between cost sharing and ongoing adherence and continuation of chosen methods. The purpose of this study was to examine the relationship between copayment amount and adherence to pharmacy-dispensed contraception in young women.MethodsWe conducted a retrospective cohort study of 39,142 women ages 19-29 with a new prescription for the contraceptive pill, patch, or ring at Kaiser Permanente Northern California during 2011-2014. We examined 12-month nonadherence as measured by timely prescription refills and used multivariable Cox proportional hazards models to assess the association between copayment amount and the risk of nonadherence.ResultsNinety-four percent of women used the pill, and 6% used the patch or ring. Forty percent of patients had no copayment and 25% had a copayment of ≥$30. Nearly 75% of women were nonadherent during the study period. In 2013 and 2014, women with a copayment had a 9% increased risk of nonadherence (adjusted hazard ratio, 1.09; 95% confidence interval, 1.04, 1.14) compared with women with no copayment.ConclusionsPrescription copayments may serve as a barrier to adherence of pharmacy-dispensed contraception. Given recent changes to Affordable Care Act contraceptive coverage requirement, these findings can be used to support state-level and health system-level policies for no-cost contraception, and to determine the potential public health impact of this policy change

Recent intrauterine device use and the risk of precancerous cervical lesions and cervical cancer.

Understanding the effect of contraceptives on the development of precancerous lesions of the cervix and cervical cancer may provide information that is valuable to women in contraceptive decision-making. The purpose of this study was to evaluate the association between recent intrauterine device (IUD) use (by type) and cervical intraepithelial neoplasia 2, 3, adenocarcinoma in situ or cancer (CIN2+ or CIN3+). Case-control study of 17,559 women age 18-49 with incident CIN2+ cases and 5:1 age-matched, incidence-density selected controls (N=87,378) who were members of Kaiser Permanente Northern California Healthcare System from 1996 to 2014. Recent IUD use, within 18 months prior to index, was the exposure of interest. We identified 1,657 IUD users among the cases and 7,925 IUD users among controls. After adjusting for sexually transmitted infection testing, smoking, HPV vaccination, hormonal contraceptive use, parity, race and number of outpatient healthcare system visits, IUD use was associated with an increased rate of CIN2+ [rate ratio (RR) 1.12, 95% confidence interval (1.05-1.18), p&lt;0.001] but not CIN3+ [RR 1.02 (0.93-1.11), p=0.71]. Levonorgestrel-IUD use was associated with an increased rate of CIN2+ [RR 1.18 (1.08-1.30), p&lt;0.001] but not CIN3+ [RR 1.05 (0.91-1.21), p=0.48]. Copper-IUD use was not associated with CIN2+ [RR 0.88 (0.75-1.04), p=0.13] or CIN3+ [RR 0.81 (0.64-1.02), p=0.07]. Recent IUD use had variable weak associations with CIN2+ but was not associated with increased risk of CIN3+. Recent levonorgestrel-IUD use may be associated with CIN2, a lesion with a high rate of regression, but not CIN3, which is considered a true pre-cancerous lesion. The observed association between levonorgestrel-IUDs and CIN2+ was modest but warrants further investigation. It may have clinical importance for contraceptive counseling if this finding is shown to be consistent across other studies and other populations

Labor Induction Outcomes with Outpatient Misoprostol for Cervical Ripening among Low-Risk Women

OBJECTIVE: In 2012, two Kaiser Permanente Northern California (KPNC) hospitals began offering outpatient cervical ripening with oral misoprostol under a study protocol. We evaluated inpatient time from admission to delivery and adverse maternal and neonatal outcomes associated with outpatient use of misoprostol for cervical ripening among low-risk women with term pregnancies. STUDY DESIGN: We conducted a retrospective cohort study comparing three groups: women who received misoprostol (1) outpatient, under a study protocol; (2) inpatient, at the study sites; and (3) inpatient, at all KPNC hospitals. Data were obtained from between 2012 and 2017. The primary outcome was time from inpatient admission to delivery. Secondarily, we evaluated maternal and neonatal outcomes, including the duration and maximum rate of oxytocin administered, rate of cesarean delivery, incidence of chorioamnionitis and blood transfusion, Apgar scores, and neonatal intensive care unit admissions. Demographic and clinical characteristics and outcomes of the outpatient group were compared with both inpatient misoprostol groups using the appropriate statistical test. Variables included in the regression analysis were either statistically significant in the bivariate analyses or have been reported in the literature to be potential confounders: maternal age at admission, race/ethnicity, body mass index, cervical dilation at initial misoprostol, and parity. RESULTS: We analyzed data from 10,253 patients: (1) 345 outpatients, under a study protocol; (2) 1,374 inpatients, at the study sites; and (3) 9,908 inpatients, at all the Kaiser hospitals. Women in the outpatient group were more likely to be white than both inpatient groups (63.3 vs. 56.3% at study sites and 47.1% in all hospitals,  0.002 and \u3c0.001, respectively); other demographics were clinically comparable. Most women undergoing labor induction were nulliparous; however, a greater proportion in the outpatient group were nulliparous compared with inpatient groups (70.8 vs. 61.8% and 64.3%,  = 0.002 and 0.01). On inpatient admission for delivery, women who received outpatient misoprostol were more likely to have a cervical dilation of ≥3 cm (39.8 vs. 12.5% at study sites and 9.7% at all KPNC hospitals,  \u3c 0.001 for both). The outpatient group had a shorter mean time between admission and delivery (23.6 vs. 29.4 at study sites and 29.8 hours at all KPNC,  \u3c 0.001 for both). The adjusted estimated mean difference between the outpatient and inpatient group at all the Kaiser hospitals in time from admission to delivery was -6.48 hours ( \u3c 0.001), and the adjusted estimated mean difference in cervical dilation on admission was +1.02 cm ( \u3c 0.001). There was no difference in cesarean delivery rates between groups. The rate of chorioamnionitis in the outpatient group was higher compared with inpatients at all hospitals (17.7 vs. 10.6%,  0001), but similar when compared with the inpatients at the study sites (17.7 vs. 15.4%,  = 0.29). CONCLUSION: Outpatient use of misoprostol for cervical ripening under the study protocol was associated with reduced inpatient time from admission to delivery compared with inpatient misoprostol. Although there was a higher rate of chorioamnionitis among outpatients under the study protocol compared with inpatients at all hospitals, there was no difference when compared with inpatients at the study sites. There was no difference in rates of cesarean delivery or maternal or neonatal complications with outpatient misoprostol. KEY POINTS: · Outpatient misoprostol patients had 6.46 fewer hours from admission to delivery compared with inpatients at all hospitals.. · There was no difference in the rate of cesareans between the outpatient versus inpatient misoprostol groups.. · Other maternal and neonatal complications were low and comparable among outpatients and inpatients who received misoprostol; this study was not large enough to assess rare safety outcomes.

The association between depression and contraceptive behaviors in a diverse sample of new prescription contraception users.

ObjectiveAmong women initiating new prescription contraception, we investigated the relationship between recent depression and a range of contraceptive behaviors.Study designWe used medical and pharmacy records of 52,325 women ages 19 to 29 who initiated prescription contraception (pills, patches or rings, injectables, and long-acting reversible contraceptives) in 2014-2016 at a large integrated healthcare system in Northern California. Women had continuous enrollment for a year before and after initiating, and no records of prescription contraceptive use in the year before initiating. Depression in the year prior to initiation was dichotomized into (1) no depression indicator (reference group) or (2) depression diagnosis or redeemed antidepressant. Multinomial logistic regression models examined the associations between depression and method type initiated, and contraceptive patterns, timing of discontinuation, inconsistent use, and switching methods over a year after initiating, adjusting for sociodemographics and testing for interactions between depression and having a recent birth or abortion.ResultsWomen with recent depression were more likely to initiate methods other than the pill, and the association was stronger for patches or rings vs pills among those with a recent birth compared to those without. Among women initiating all methods and the pill, those with depression were more likely to discontinue their method, use it inconsistently, and switch from it than use it continuously for a year.ConclusionWomen with recent depression were less likely to initiate the pill; and when the pill was initiated, those with depression were more likely to discontinue use, use it inconsistently, and switch from it.ImplicationsWomen with recent depression indicators should be followed closely to ensure they have the support they need to meet their reproductive goals. Those who wish to avoid pregnancy may benefit from methods that do not require daily use

Viral coinfection analysis using a MinHash toolkit

Abstract: Background: Human papillomavirus (HPV) is a common sexually transmitted infection associated with cervical cancer that frequently occurs as a coinfection of types and subtypes. Highly similar sublineages that show over 100-fold differences in cancer risk are not distinguishable in coinfections with current typing methods. Results: We describe an efficient set of computational tools, rkmh, for analyzing complex mixed infections of related viruses based on sequence data. rkmh makes extensive use of MinHash similarity measures, and includes utilities for removing host DNA and classifying reads by type, lineage, and sublineage. We show that rkmh is capable of assigning reads to their HPV type as well as HPV16 lineage and sublineages. Conclusions: Accurate read classification enables estimates of percent composition when there are multiple infecting lineages or sublineages. While we demonstrate rkmh for HPV with multiple sequencing technologies, it is also applicable to other mixtures of related sequences

Pharmacists' knowledge, perspectives, and experiences with mifepristone dispensing for medication abortion.

BackgroundThe U.S. Food and Drug Administration (FDA) restricts dispensing of mifepristone for medication abortion to certified health care providers at clinical facilities, thus prohibiting pharmacist dispensing. Allowing mifepristone dispensing by pharmacists could improve access to medication abortion.ObjectiveTo assess the feasibility of pharmacists dispensing mifepristone to patients who have undergone evaluation for eligibility and counseling for medication abortion by a clinician.MethodsBefore providing a study training on medication abortion, we administered baseline surveys to pharmacists who participated in a multisite mifepristone-dispensing intervention. The survey assessed medication abortion knowledge-using a 15-item score-and perceptions about the benefits and challenges of the model. We administered follow-up surveys in the study's final month that also assessed the pharmacists' satisfaction and experiences with mifepristone dispensing. To investigate the association of the study intervention with the pharmacists' knowledge, perceptions, and experiences dispensing mifepristone, we conducted multivariable linear regression analyses using generalized estimating equation models, accounting for clustering by individual.ResultsAmong the 72 pharmacists invited from 6 pharmacies, 47 (65%) completed the baseline surveys, and 56 (78%) received training. At the study's end (mean 18 months later), 43 of the 56 pharmacists who received training (77%) completed the follow-up surveys. At follow-up, 36 (83%) respondents were very or somewhat satisfied with mifepristone dispensing, and 24 (56%) reported experiencing no challenges dispensing mifepristone. Four (6%) of the 72 pharmacists invited objected to participating in mifepristone dispensing. In regression analyses, average knowledge scores, perceived ease of implementation, and level of support for the pharmacist-dispensing model were higher at follow-up (P &lt; 0.001).ConclusionMost pharmacists were willing to be trained, dispensed mifepristone with few challenges when given the opportunity, were satisfied with the model, and had higher knowledge levels at follow-up. Our findings support removal of FDA's restriction on pharmacist dispensing of mifepristone