Effectiveness of Chlamydia trachomatis expedited partner therapy in pregnancy.

BACKGROUND: Expedited partner therapy for Chlamydia trachomatis has had mixed efficacy in different populations, but limited data exist on the efficacy of the therapy in a pregnant population. OBJECTIVE: This study aimed to evaluate the real-world effectiveness of establishing a prenatal expedited partner therapy program in eradicating chlamydia before delivery and to examine the maternal and neonatal outcomes between women who received expedited partner therapy for chlamydia and women who received standard partner referral testing and treatment during pregnancy. STUDY DESIGN: An expedited partner therapy program was implemented on August 21, 2019, at a public hospital in a county with high chlamydia prevalence. Pregnant women were provided with single-dose packets of azithromycin to treat partners following a diagnosis of chlamydia infection. We prospectively observed pregnant women treated in the expedited partner therapy program who delivered at our institution in the same year and compared the outcomes with a historic cohort from the previous year that had traditional partner referral testing and treatment. We excluded women with concurrent gonorrhea, HIV, syphilis, or current intimate partner violence. The primary outcome was chlamydia reinfection or no-cure rates at repeat testing in 4 to 6 weeks following treatment or at the 36-week prenatal care screening. Secondary outcomes included obstetrical, maternal, and neonatal outcomes, including premature rupture of membranes, chorioamnionitis, endometritis, neonatal intensive care unit admission, neonatal sepsis, pneumonia, and conjunctivitis. RESULTS: The rate of chlamydia infection was 3.6% over a 2-year period in our delivered population. In the year following the implementation of the expedited partner therapy, compared with 419 women (mean±standard deviation, 23.4±5.5 years) who were diagnosed with chlamydia infection in the previous year, 471 women (mean±standard deviation age, 23.8±5.3 years) who delivered at our institution were diagnosed with chlamydia infection. There was no difference in race, parity, prenatal care attendance, or concomitant sexually transmitted infections. Compared with the pre-expedited partner therapy group, the rate of reinfection in the post-expedited partner therapy group was not statistically different (60/471 [13%] vs 61/419 [15%]; odds ratio, 0.86 [95% confidence interval 0.58-1.26]). In a per-protocol analysis, 72 women (17%) in the pre-expedited partner therapy group and 389 women (83%) in post-expedited partner therapy group received expedited partner therapy; reinfection was not statistically different between groups (P=.47). There was no difference in secondary outcomes, although a trend toward improved rates of endometritis was noted in the post-expedited partner therapy group (odds ratio, 0.13; 95% confidence interval, 0.02-1.02). CONCLUSION: The implementation of a prenatal expedited partner therapy program did not affect the rate of chlamydia reinfection before delivery. Treatment of chlamydia in an inner-city population has multiple factors that lead to successful treatment. Future efforts to reduce sexually transmitted infection and chlamydia reinfection rates in an at-risk population should include exploring patient education and safe sex practices beyond expedited partner therapy alone during pregnancy.

Does simulation improve clinical performance in management of postpartum hemorrhage?

BACKGROUND: Although simulation is now widely used to improve teamwork and communication, data demonstrating improvement in clinical outcomes are limited. OBJECTIVE: This study aimed to examine the clinical performance and outcomes associated with postpartum hemorrhage because of uterine atony following the implementation of a multidisciplinary simulation program. STUDY DESIGN: This was a prospective observational study of response to postpartum hemorrhage because of uterine atony in an academic medical center before (epoch 1: July 2017-June 2018) and after (epoch 2: July 2019-June 2020) implementing a multidisciplinary simulation program. A total of 22 postpartum hemorrhage simulations were performed from July 2018 to June 2019 involving more than 300 nursing, obstetrical, and anesthesia providers. The simulation program focused on managing postpartum hemorrhage events and improving teamwork and communication of the multidisciplinary teams. To evaluate the clinical effectiveness of the simulation program, the primary outcome was response to postpartum hemorrhage defined as the time from the administration of uterotonic medications to transfusion of the first unit of blood in the first 12 hours following delivery, comparing epoch 2 to epoch 1 following the implementation of a simulation program. Statistical analysis included the use of the Pearson chi-square test, Wilcoxon rank-sum test, Hodges-Lehmann statistic for differences, and bootstrap methods with a P value of <.05 considered significant. RESULTS: Between July 1, 2017, and June 30, 2018, there were 12,305 patients who delivered, of which 495 patients (4%) required transfusion. Between July 1, 2019, and June 30, 2020, there were 12,414 patients who delivered, of which 480 patients (4%) required transfusion. When isolating cases of postpartum hemorrhage because of uterine atony in both transfused groups, there were 157 women in the presimulation group (epoch 1) and 165 women in the postsimulation group (epoch 2), respectively. There was no difference in age, race, parity, or perinatal outcomes between the 2 epochs. Women in epoch 2 began receiving blood products significantly earlier in the first 12 hours following delivery compared with women in epoch 1 (51 [range, 28-125] minutes vs 102 [range, 32-320] minutes; P=.005). In addition, there was a significantly decreased variation in the time from the administration of uterotonic medications to transfusion of blood in epoch 2 (P=.035). Furthermore, women in epoch 2 had significantly lower estimated blood loss than women in epoch 1 (1250 [range, 1000-1750] mL vs 1500 [range, 1000-2000] mL; P=.032). CONCLUSION: The implementation of a multidisciplinary simulation program at a large academic center focusing on the management of postpartum hemorrhage was associated with an improved clinical response. Specifically, there were significantly faster times from the administration of uterotonic medications to transfusion of blood, decreased variance in the time from the administration of uterotonic medications to transfusion of blood, and lower estimated blood loss following the implementation of a simulation program. Because delay in treatment is a major cause of preventable maternal death in obstetrical hemorrhage, the results in our study provided clinical evidence that a simulation program may improve patient outcomes in such emergencies.

MICU1 imparts the mitochondrial uniporter with the ability to discriminate between Ca2+ and Mn2+.

The mitochondrial uniporter is a Ca2+-activated Ca2+ channel complex that displays exceptionally high conductance and selectivity. Here, we report cellular metal toxicity screens highlighting the uniporter's role in Mn2+ toxicity. Cells lacking the pore-forming uniporter subunit, MCU, are more resistant to Mn2+ toxicity, while cells lacking the Ca2+-sensing inhibitory subunit, MICU1, are more sensitive than the wild type. Consistent with these findings, Caenorhabditis elegans lacking the uniporter's pore have increased resistance to Mn2+ toxicity. The chemical-genetic interaction between uniporter machinery and Mn2+ toxicity prompted us to hypothesize that Mn2+ can indeed be transported by the uniporter's pore, but this transport is prevented by MICU1. To this end, we demonstrate that, in the absence of MICU1, both Mn2+ and Ca2+ can pass through the uniporter, as evidenced by mitochondrial Mn2+ uptake assays, mitochondrial membrane potential measurements, and mitoplast electrophysiology. We show that Mn2+ does not elicit the conformational change in MICU1 that is physiologically elicited by Ca2+, preventing Mn2+ from inducing the pore opening. Our work showcases a mechanism by which a channel's auxiliary subunit can contribute to its apparent selectivity and, furthermore, may have implications for understanding how manganese contributes to neurodegenerative disease.

Challenges in Using Progestin to Prevent Singleton Preterm Births: Current Knowledge and Clinical Advice.

Preterm birth is the leading cause of infant morbidity and mortality in children younger than 5 years old and accounts for approximately 35% of newborn deaths worldwide. The use of progestogen therapy for prevention of preterm birth has been one of the most controversial topics in modern obstetrics. Progestogens can be classified as natural or synthetic. Progesterone is a natural progestogen while progestins such as 17-alpha-hydroxyprogesterone caproate (17OHP-C) are synthetic steroid hormones. Evidence supporting the use of progestogens varies by formulation and populations studied. After more than a decade, the US Food and Drug Administration has withdrawn accelerated approval of 17OHP-C for the prevention of recurrent preterm birth in pregnant individuals with a singleton gestation. With this decision, there is no current FDA-approved treatment for prevention of spontaneous preterm birth. In this review, we provide a historical context behind the rise and fall of 17OHP-C clinical application, highlight the challenges behind the data supporting progestogen use, and offer suggestions on how to make an impact on preterm birth moving forward.

Evaluating strength of recommendations for commonly administered medications in lactating women.

OBJECTIVE: To characterize the data on medications for lactating people in the LactMed database and evaluate the strength of the data for the most commonly administered medications in lactating women. METHODS: A retrospective analysis of all medications in the LactMed database in 12/2020 was performed. Each medication was classified into one of three categories: absent data, minimal-moderate data, strong data pertaining to safety in lactation. No data was defined as no available research studies associated with the medication. Minimal-moderate data was defined as absent research studies in one or more of the four LactMed categories: maternal drug levels, infant drug levels, effects on infants, effects on lactation, or if data was limited to a case report or observational study. Strong data was classified as availability of research studies in all four LactMed categories with data derived from pharmacokinetic/pharmacodynamic, cohort, case control, or randomized control studies. Additionally, the most commonly used medications in lactating women as defined by prior literature were analyzed for strength of data. RESULTS: 1408 medications were evaluated: 714 (51%) had no associated data, 664 (47%) had minimal-moderate data, and 30 (2%) had strong data. Maternal drug level category had the highest proportion of rigorous supportive data while the effect on lactation category had the least supportive data. Of the most common mediations used in lactating women, sex hormones (contraception) and the nervous system medication classes had the most robust supportive data while respiratory, blood forming organs, and galactogogues had the weakest supportive data. CONCLUSION: There is significant variability and dearth in the quality of data guiding recommendations for use of medications in lactation providing numerous opportunities for research.

A prospective study of antepartum anxiety screening in patients with and without a history of spontaneous preterm birth.

BACKGROUND: Maternal stress has been identified as one of the most common clinical phenotypes associated with preterm birth. The American College of Obstetricians and Gynecologists recommends anxiety screening at least once in the perinatal period. The prevalence of perinatal anxiety is challenged by the absence of formalized screening protocols and underreporting in high-risk populations, such as those with a history of adverse pregnancy outcomes. OBJECTIVE: This study administered a validated anxiety screening tool in a cohort of patients with and without a previous spontaneous preterm birth and compared differences in score and rate of a positive screen between groups. Moreover, this study evaluated perinatal outcomes associated with a positive screen and described a referral protocol involving evaluation by a perinatal mental health counselor and clinical diagnoses. A hypothesis was made that patients with a previous history of spontaneous preterm birth would have higher self-reported anxiety symptoms than controls and that those with recurrent preterm delivery at <35 weeks of gestation would have the highest anxiety screening scores. STUDY DESIGN: This was a prospective observational cohort study administering the Generalized Anxiety Disorder 7-item screen to patients enrolled in 2 prenatal care clinics at our institution. The preterm birth cohort consisted of patients with a history of spontaneous preterm labor, premature rupture of membranes, or cervical insufficiency compared with the control cohort without this history. Screening was initiated at entry to prenatal care or referral to our high-risk obstetrical clinic. The inclusion criteria included English- or Spanish-speaking patients and singleton pregnancy, and the exclusion criteria included pregnancies complicated by a major congenital anomaly, enrollment after 34 weeks of gestation, delivery at <20 weeks of gestation, and incomplete delivery data. Referral to a mental health counselor was offered to those with a Generalized Anxiety Disorder 7-item screen score of ≥10. Perinatal outcomes as a comparison between the Generalized Anxiety Disorder 7-item screen-positive group and Generalized Anxiety Disorder 7-item screen-negative group were performed with statistical methods, including the Student t test, chi-square test, and Wilcoxon rank-sum test, with a P value of <.05 to determine significance. RESULTS: Between September 2020 and December 2021, 1349 participants were analyzed, with 143 patients (11%) in the previous preterm birth cohort and 1206 (89%) patients in the control cohort. Patients with a history of preterm birth and subsequent delivery at ≤35 weeks of gestation in the study pregnancy had significantly higher Generalized Anxiety Disorder 7-item screen scores than controls with delivery after 35 weeks of gestation (median score: 4 [interquartile range, 1-9] vs 2 [interquartile range, 0-6], respectively; P=.006). Overall, 187 participants (14%) screened positive with significantly higher rates in the previous preterm birth group than in the control group (20% vs 13%; P=.036). Of note, 117 patients (63%) accepted a referral, and 32 patients (17%) with a positive screen were diagnosed with a perinatal mood disorder. CONCLUSION: Patients with recurrent preterm birth have higher self-reported anxiety using the Generalized Anxiety Disorder 7-item screen than controls. Of those with a positive screen, 17% were diagnosed with a perinatal mood disorder.

Clostridium and Bacteroides bacteremia as initial presentation of uterine carcinosarcoma.

•Anaerobic bacteremia with gynecologic pathology can lead to rapid deterioration.•Frequent physical examination and bedside assessment are critical in management.•Surgical intervention is often necessary for Clostridium and Bacteroides infection.

Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.

Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS). Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology.