Melody Y. Hou

Crystal structure of the Atx1 metallochaperone protein at 1.02 Å resolution

BACKGROUND Metallochaperone proteins function in the trafficking and delivery of essential, yet potentially toxic, metal ions to distinct locations and particular proteins in eukaryotic cells. The Atx1 protein shuttles copper to the transport ATPase Ccc2 in yeast cells. Molecular mechanisms for copper delivery by Atx1 and similar human chaperones have been proposed, but detailed structural characterization is necessary to elucidate how Atx1 binds metal ions and how it might interact with Ccc2 to facilitate metal ion transfer. RESULTS The 1.02 A resolution X-ray structure of the Hg(II) form of Atx1 (HgAtx1) reveals the overall secondary structure, the location of the metal-binding site, the detailed coordination geometry for Hg(II), and specific amino acid residues that may be important in interactions with Ccc2. Metal ion transfer experiments establish that HgAtx1 is a functional model for the Cu(I) form of Atx1 (CuAtx1). The metal-binding loop is flexible, changing conformation to form a disulfide bond in the oxidized apo form, the structure of which has been solved to 1.20 A resolution. CONCLUSIONS The Atx1 structure represents the first structure of a metallochaperone protein, and is one of the largest unknown structures solved by direct methods. The structural features of the metal-binding site support the proposed Atx1 mechanism in which facile metal ion transfer occurs between metal-binding sites of the diffusible copper-donor and membrane-tethered copper-acceptor proteins. The Atx1 structural motif represents a prototypical metal ion trafficking unit that is likely to be employed in a variety of organisms for different metal ions.

Using Daily Text-Message Reminders to Improve Adherence With Oral Contraceptives: A Randomized Controlled Trial

OBJECTIVE: To estimate whether women receiving daily text-message reminders have increased oral contraceptive pill adherence compared with women not receiving reminders. METHODS: This randomized controlled trial estimated whether there was an effect of daily text-message reminders on oral contraceptive pill adherence of new oral contraceptive pill users. Pill-taking was tracked for 3 months by an electronic monitoring device with wireless data collection. During the study period, participants assigned the intervention received a daily reminder text message. Eighty-two women were assigned randomly to detect a 1.6±2.0 pill difference (90% power, 5% &agr;, 15% dropout). RESULTS: Participants were 79% white, non-Hispanic, 99% high school graduates, and 99% nulliparous with a mean age of 22 years. Most reported condom use with past coital activity, and more than half reported prior emergency contraception use. The mean number of missed pills per cycle did not differ significantly between the groups: 4.9±3.0 for the text-message group and 4.6±3.5 for the control group (P=.60). The number of missed pills per cycle increased over the course of the study, but this pattern did not increase differentially between the groups. Adherence recorded by the electronic monitoring device indicated much poorer adherence than that recorded by patient diaries. Despite poor pill-taking, there were no pregnancies. CONCLUSION: Daily text-message reminders did not improve oral contraceptive pill adherence. Although the lack of benefit may be attributed to the frequent use of alternative reminder systems in the control group, the rate of missed pills when measured objectively was still very high in both groups. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov, NCT00733707. LEVEL OF EVIDENCE: I

Administration of the etonogestrel contraceptive implant on the day of mifepristone for medical abortion: a pilot study.

OBJECTIVE We sought to determine satisfaction and continuation rates of the contraceptive implant when placed on the initial visit for first-trimester medical abortion. STUDY DESIGN In this pilot study, we placed the implant within 15 min of mifepristone administration. We assessed satisfaction with implant placement timing, 1-year implant continuation and abortion completion. RESULTS We enrolled 20 participants. Sixteen (80%) returned for follow-up, and all had complete abortion. At 1 year, of 16 participants contacted, 14 (87.5%) were satisfied with implant insertion timing, and 14 (87.5%) continued the implant. CONCLUSIONS Initiation of the contraceptive implant on the initial visit for medical abortion resulted in high satisfaction and continuation rates. IMPLICATIONS This pilot study provides important groundwork for future larger studies to assess initiation of the contraceptive implant on the day of mifepristone for medical abortion.

Uterine Evacuation for Second-trimester Fetal Death and Maternal Morbidity

OBJECTIVE: To estimate maternal morbidity associated with uterine evacuation for second-trimester fetal demise compared with that associated with induced second-trimester abortion. METHODS: This retrospective cohort study compared the maternal outcomes of two cohorts: 1) women diagnosed with fetal demise between 14 and 24 weeks who subsequently underwent dilation and evacuation or induction of labor; and 2) women undergoing induced abortion between 14 and 24 weeks by either dilation and evacuation or induction of labor. The primary outcome was major maternal morbidity. Assuming morbidity rates of 11% for fetal demise and 1% for induced second-trimester abortion, 94 patients were needed per group to detect significant difference in maternal morbidity (80% power, 5% alpha). RESULTS: We identified 121 women with fetal demise and 121 women who underwent induced abortion for inclusion. There were no maternal deaths. In crude and adjusted analyses, treatment for fetal demise was not associated with increased maternal morbidity (25 of 121) compared with induced abortion (27 of 121) (adjusted odds ratio [OR], 1.15; 95% confidence interval [CI], 0.57–2.32). There were more blood transfusions in the fetal demise group (N=7) compared with the induced-abortion group (N=1) (P=.07). Induction of labor was more morbid than dilation and evacuation after adjusting for confounders (OR 5.36; 95% CI 2.46–11.69), primarily as a result of increased odds of infection requiring intravenous antibiotics. Gestational age of 20 weeks or greater was significantly associated with maternal morbidity (OR 2.59; 95% CI 1.39–4.84). CONCLUSION: In the second trimester, uterine evacuation for fetal demise was not significantly associated with maternal morbidity compared with induced abortion. Induction of labor was more morbid than dilation and evacuation as a result of an increased risk of presumed infection. LEVEL OF EVIDENCE: II

Mifepristone vs. osmotic dilator insertion for cervical preparation prior to surgical abortion at 14–16 weeks: a randomized trial ☆ ☆☆ ★

BACKGROUND Cervical preparation is recommended before second-trimester abortion. We investigated the use of a pharmacologic method of preparation, mifepristone, as compared to osmotic dilators for surgical abortions at 14-16 weeks. STUDY DESIGN This was a randomized, parallel-group study with concealed allocation. Women were allocated to receive osmotic dilators or mifepristone 200 mg orally 24 h prior to abortion. The study population was 50 women seeking surgical abortion at 14-16 menstrual weeks in a hospital-based abortion service. The primary outcome was the length of time to perform the procedure; the study had 80% power to detect a difference of more than 3 min in procedure time. Secondary outcomes included cervical dilation, side effects and acceptability. RESULTS The mean abortion time for the osmotic dilator group was 8.00 min [95% confidence interval (CI) 6.75-11.47], and that for the mifepristone group was 9.87 min (95% CI 8.93-11.36). Side effects of pain were more common in the osmotic dilator group. CONCLUSION Mifepristone did not increase the time for abortion by more than the prespecified margin (3 min). Women preferred mifepristone to osmotic dilators.

Situating stigma in stratified reproduction: Abortion stigma and miscarriage stigma as barriers to reproductive healthcare

OBJECTIVES To examine whether race and reported history of abortion are associated with abortion stigma and miscarriage stigma, both independently and comparatively. STUDY DESIGN Self-administered surveys with 306 new mothers in Boston and Cincinnati, United States. MAIN OUTCOME MEASURES Abortion stigma perception (ASP); miscarriage stigma perception (MSP); and comparative stigma perception (CSP: abortion stigma perception net of miscarriage stigma perception). RESULTS Regardless of whether or not they reported having an abortion, white women perceived abortion (ASP) to be more stigmatizing than Black and Latina women. Perceptions of miscarriage stigma (MSP), on the other hand, were dependent on reporting an abortion. Among those who reported an abortion, Black women perceived more stigma from miscarriage than white women, but these responses were flipped for women who did not report abortion. Reporting abortion also influenced our comparative measure (CSP). Among those who did report an abortion, white women perceived more stigma from abortion than miscarriage, while Black and Latina women perceived more stigma from miscarriage than abortion. CONCLUSIONS By measuring abortion stigma in comparison to miscarriage stigma, we can reach a more nuanced understanding of how perceptions of reproductive stigmas are stratified by race and reported reproductive history. Clinicians should be aware that reproductive stigmas do not similarly affect all groups. Stigma from specific reproductive outcomes is more or less salient dependent upon a womans social position and lived experience.

Do clinical experts rely on the Cochrane library

In part because of limited public access, Cochrane reviews are underused in the United States compared with other developed nations. To assess use of these reviews by opinion leaders, we examined citation of Cochrane reviews in the Clinical Expert Series of Obstetrics & Gynecology from inception through June of 2007. We reviewed all 54 articles for mention of Cochrane reviews, then searched for potentially relevant Cochrane reviews that the authors could have cited. Thirty-six of 54 Clinical Expert Series articles had one or more relevant Cochrane reviews published at least two calendar quarters before the Clinical Expert Series article. Of these 36 articles, 19 (53%) cited one or more Cochrane reviews. We identified 187 instances of relevant Cochrane reviews, of which 40 (21%) were cited in the Clinical Expert Series articles. No temporal trends were evident in citation of Cochrane reviews. Although about one half of Clinical Expert Series articles cited relevant Cochrane reviews, most eligible reviews were not referenced. Wider use of Cochrane reviews could strengthen the scientific basis of this popular series.

Long-Acting Reversible Contraception Initiation With a 2- to 3-Week Compared With a 6-Week Postpartum Visit.

OBJECTIVE To evaluate whether a department policy changing the scheduling of the postpartum visit from 6 weeks to 2-3 weeks after delivery is associated with higher long-acting reversible contraception initiation at the postpartum visit. METHODS We conducted a quasiexperimental before-after study to evaluate long-acting reversible contraception initiation, specifically an intrauterine device or contraceptive implant, at the postpartum visit between women scheduled for follow-up at 6 weeks (before policy change) and 2-3 weeks after delivery (after policy change). Secondary outcomes included postpartum visit completion, overall contraception initiation at the postpartum visit, overall contraceptive use at 6 months after delivery, and repeat pregnancies by 6 months postpartum. We obtained delivery and postpartum information using the electronic medical record and contacted participants 3 and 6 months after delivery to assess contraception use and repeat pregnancies. RESULTS We enrolled 586 participants between December 2014 and November 2015, of whom 512 women (256 in each cohort) continued to meet eligibility criteria after delivery. Long-acting reversible contraception initiation rates at the postpartum visit were lower in the 2- to 3-week (16.5%, 95% CI 12.2-21.8) compared with the 6-week group (31.1%, 95% CI 25.2-37.7, P<.01), primarily as a result of patient and health care provider preferences for delaying intrauterine device insertion to a later visit. More women completed a scheduled 2- to 3-week postpartum visit (90.2%, 95% CI 86.0-93.3) compared with a 6-week visit (81.6%, 95% CI 76.4-85.9, P<.01). Deferral of any contraception initiation was higher in the 2- to 3-week group (27.3%, 95% CI 21.9-33.4) compared with the 6-week group (15.8%, 95% CI 11.5-21.4, P<.01), but there were no differences in overall contraceptive use patterns at 6 months postpartum. No intrauterine device perforations or expulsions were observed in women who underwent insertion at 2-3 weeks postpartum. Five pregnancies were reported in each cohort by 6 months after delivery. CONCLUSION Scheduling a visit at 2-3 weeks after delivery was not associated with increased long-acting reversible contraception initiation at this visit despite higher postpartum visit attendance.

An updated assessment of postpartum sterilization fulfillment after vaginal delivery

OBJECTIVE To describe sterilization completion rates after vaginal delivery and indications for unfulfilled procedures. STUDY DESIGN We used labor and delivery operating room and delivery logs to identify all women over 20years of age with a completed live vaginal birth beyond 24weeks gestation over a 33-month period (March 1, 2012 to November 30, 2014). We reviewed the electronic medical records of all of these patients and identified those who requested a sterilization procedure as indicated in a physicians admission note or antenatal record. RESULTS We identified 3514 live vaginal births beyond 24weeks gestation during the study period of which 219 requested postpartum sterilization. Sterilization occurred in 114 (52%). The most common reason for unfulfilled procedures was lack of valid federally mandated consent (n=46 [44%]). Fifty-nine percent (27 of 46) of these women had little or no prenatal care. Only one (0.5%) woman had documented completion of consent with the required time elapsed prior to delivery and no consent form available. Of the women with valid consent documentation, the most common indication for an unfulfilled procedure was patient refusal (n=30 [51%]). Body mass index was an independent predictor of an unfulfilled procedure (p<.001) among women with adequate consent. CONCLUSIONS Inability to complete federally mandated consent is a principal cause of unfulfilled postpartum sterilization and primarily affects women desiring sterilization who lack sufficient prenatal care. Of women who meet consent criteria, the primary reason women eligible for sterilization did not undergo the procedure was due to withdrawing their request. IMPLICATIONS Because women commonly do not undergo a requested sterilization after vaginal deliveries, antepartum counseling should include alternate contraception choices. Documented consent that fulfills all federally mandated criteria remains the most common barrier to requested sterilization after vaginal delivery; providers and policymakers should work together to help unburden women from this mandate.

Comparing office and telephone follow-up after medical abortion ☆ ☆☆

OBJECTIVES Compare proportion lost to follow-up, successful abortion, and staff effort in women who choose office or telephone-based follow-up evaluation for medical abortion at a teaching institution. STUDY DESIGN We performed a chart review of all medical abortions provided in the first three years of service provision. Women receiving mifepristone and misoprostol could choose office follow-up with an ultrasound evaluation one to two weeks after mifepristone or telephone follow-up with a scheduled telephone interview at one week post abortion and a second telephone call at four weeks to review the results of a home urine pregnancy test. RESULTS Of the 176 medical abortion patients, 105 (59.7%) chose office follow-up and 71 (40.3%) chose telephone follow-up. Office evaluation patients had higher rates of completing all required follow-up compared to telephone follow-up patients (94.3% vs 84.5%, respectively, p=.04), but proportion lost to follow-up was similar in both groups (4.8% vs 5.6%, respectively, p=1.0). Medical abortion efficacy was 94.0% and 92.5% in women who chose office and telephone follow-up, respectively. We detected two (1.2%) ongoing pregnancies, both in the office group. Staff rescheduled 15.0% of appointments in the office group. For the telephone follow-up cohort, staff made more than one phone call to 43.9% and 69.4% of women at one week and four weeks, respectively. CONCLUSIONS Proportion lost to follow-up is low in women who have the option of office or telephone follow-up after medical abortion. Women who choose telephone-based evaluation compared to office follow-up may require more staff effort for rescheduling of contact, but overall outcomes are similar. IMPLICATIONS Although women who choose telephone evaluation may require more rescheduling of contact as compared to office follow-up, having alternative follow-up options may decrease the proportion of women who are lost to follow-up.