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To investigate factors associated with positive postpartum depression (PPD) screen in pregnancies complicated by fetal congenital cardiac anomaly. We reviewed all records of pregnancies complicated by fetal congenital cardiac anomaly receiving prenatal, intrapartum and postpartum care at our single center, October 2016-October 2019. Maternal, obstetric, and neonatal data were compared between women with and without a positive PPD screen at the 6-week postpartum visit. Out of 415 women referred for fetal congenital cardiac anomaly, 86 women had complete inclusion criteria. Twenty-four women (28%) had a positive PPD screen. The frequencies of planned future infant surgery (73.9 vs. 26.2%, p = 0.01) and neonatal death prior to postpartum visit (12.5 vs. 0%, p = 0.02) were significantly higher among women with a positive PPD screen. In pregnancies complicated by fetal congenital cardiac anomaly, mothers of infants with planned future surgery or neonatal death are at significant risk for postpartum depression.

Obstetrical clinical trials are the foundation of evidence-based medicine during pregnancy. As more obstetrical trials are conducted, understanding the publication characteristics of these trials is of utmost importance to advance obstetrical health.This study aimed to characterize the frequency of publication and trial characteristics associated with publication among obstetrical clinical trials in the United States. We additionally sought to examine time from trial completion to publication.This was a cross-sectional analysis of completed obstetrical trials with an intervention design and at least 1 site in the United States registered to ClinicalTrials.gov from 2007 to 2019. Trial characteristics were cross-referenced with PubMed to determine publication status up to 2021 using the National Clinical Trial identification number. Bivariable analyses were conducted to determine trial characteristics associated with publication. Multivariable logistic regression models controlling for prespecified covariates were generated to estimate the relationship between funding, primary purpose, and therapeutic foci with publication. Additional exploratory analyses of other trial characteristics were conducted. Time to publication was analyzed using Kaplan-Meier curves and Cox regression models.Of the 1879 obstetrical trials with registered completion, a total of 575 (30.6%) had at least 1 site in the United States, were completed before October 1, 2019, and were included in this analysis. Between October 2007 and October 2019, fewer than two-thirds (N=348, 60.5%) of trials reached publication. Annual rates of publication ranged from 46.4% in 2018 to 70.0% in 2007. No difference was observed in publication by funding, primary purpose, or therapeutic foci (all P.05). Trials with characteristics indicating high trial quality-including randomized allocation scheme, ≥50 participants enrolled, ≥2 sites, and presence of a data safety monitoring committee-had increased odds of publication compared with those without such characteristics (all P.05). For example, studies with randomized allocation of intervention had 2-fold greater odds of publication than nonrandomized studies (adjusted odds ratio, 2.09; 95% confidence interval, 1.30-3.37). Studies with ≥150 participants had nearly 8-fold odds of publication (adjusted odds ratio, 7.90; 95% confidence interval, 3.78-17.49) relative to studies with50 participants. Temporal analysis demonstrated variability in time to publication among obstetrical trials, with a median time of 20.1 months after trial completion, and with most trials that reached publication having been published by 40 months. No difference was observed in time to publication by funding, primary purpose, or therapeutic foci (all P.05).Publication of obstetrical trials remains suboptimal, with significant differences observed between trials with indicators of high quality and those without. Most trials that reach publication are published within 2 years of registered completion on ClinicalTrials.gov.

ImportanceClinical trials guide evidence-based obstetrics and gynecology (OB-GYN) but often enroll nonrepresentative participants.ObjectiveTo characterize race and ethnicity reporting and representation in US OB-GYN clinical trials and their subsequent publications and to analyze the association of subspecialty and funding with diverse representation.Design and SettingCross-sectional analysis of all OB-GYN studies registered on ClinicalTrials.gov (2007-2020) and publications from PubMed and Google Scholar (2007-2021). Analyses included logistic regression controlling for year, subspecialty, phase, funding, and site number. Data from 332 417 studies were downloaded. Studies with a noninterventional design, with a registration date before October 1, 2007, without relevance to OB-GYN, with no reported results, and with no US-based study site were excluded.ExposuresOB-GYN subspecialty and funder.Main Outcomes and MeasuresReporting of race and ethnicity data and racial and ethnic representation (the proportion of enrollees of American Indian or Alaskan Native, Asian, Black, Latinx, or White identity and odds of representation above US Census estimates by race and ethnicity).ResultsAmong trials with ClinicalTrials.gov results (1287 trials with 591 196 participants) and publications (1147 trials with 821 111 participants), 662 (50.9%) and 856 (74.6%) reported race and ethnicity data, respectively. Among publications, gynecology studies were significantly less likely to report race and ethnicity than obstetrics (adjusted odds ratio [aOR], 0.54; 95% CI, 0.38-0.75). Reproductive endocrinology and infertility trials had the lowest odds of reporting race and ethnicity (aOR, 0.14; 95% CI, 0.07-0.27; reference category, obstetrics). Obstetrics and family planning demonstrated the most diverse clinical trial cohorts. Compared with obstetric trials, gynecologic oncology had the lowest odds of Black representation (ClinicalTrials.gov: aOR, 0.04; 95% CI, 0.02-0.09; publications: aOR, 0.06; 95% CI, 0.03-0.11) and Latinx representation (ClinicalTrials.gov: aOR, 0.05; 95% CI, 0.02-0.14; publications: aOR, 0.23; 95% CI, 0.10-0.48), followed by urogynecology and reproductive endocrinology and infertility. Urogynecology (ClinicalTrials.gov: aOR, 0.15; 95% CI, 0.05-0.39; publications: aOR, 0.24; 95% CI, 0.09-0.58) had the lowest odds of Asian representation.Conclusions and RelevanceRace and ethnicity reporting and representation in OB-GYN trials are suboptimal. Obstetrics and family planning trials demonstrate improved representation is achievable. Nonetheless, all subspecialties should strive for more equitably representative research.

To characterize gynecology clinical trials over time, compare gynecology subspecialties, and analyze factors associated with early discontinuation, results reporting, and publication.We conducted a cross-sectional analysis of all gynecology trials registered on ClinicalTrials.gov between 2007 and 2020 and their resulting publications. Trials were analyzed with descriptive, multivariable logistic, and Cox regression analyses. Primary exposure variables were trial funding and subspecialty. The three primary outcomes included early discontinuation, results reporting to ClinicalTrials.gov, and publication in a peer-reviewed journal indexed on PubMed.Of 223,690 trials registered on ClinicalTrials.gov between October 2007 and March 2020, only 3.7% focused on gynecology (n=8,174, approximately 3,759,086 participants). Subspecialties included reproductive endocrinology and infertility (n=1,428, 17.5%), gynecologic oncology (n=2,063, 25.2%), urogynecology (n=1,118, 13.7%), family planning (n=648, 7.9%), and other benign gynecology (n=2,917, 35.7%). Only 42.0% of completed trials disseminated results through results reporting and publication. Of all funding types, industry-funded trials were the most likely to be discontinued early (P.001). Academic-funded trials were the least likely to report results (adjusted odds ratio [aOR] 0.38, 95% CI 0.30-0.50) but the most likely to publish (aOR 1.62, 95% CI 1.24-2.12). The number of reproductive endocrinology and infertility trials increased the most of any subspecialty between 2007 and 2020 (6.4% growth rate). Reproductive endocrinology and infertility and family planning trials were the most likely to be stopped early (reproductive endocrinology and infertility: adjusted hazard ratio [aHR] 2.08, 95% CI 1.59-2.71; family planning: aHR 1.55 95% CI 1.06-2.25). When completed, reproductive endocrinology and infertility trials were the least likely to report results (aOR 0.58, 95% CI 0.38-0.88). No significant differences were seen between subspecialties with respect to publication.Gynecology trials comprise only 3.7% of all clinical trials. The paucity of gynecology clinical trials aligns with decades of female underrepresentation in research. When completed, gynecology trials have poor dissemination. Our findings raise concern about bias in the performance, reporting, and publication of gynecology clinical trials.

Fetal lung masses complicate approximately 1 in 2000 live births. Our aim was to determine whether obstetric and neonatal outcomes differ by final fetal lung mass histology.A review of all pregnancies complicated by a prenatally diagnosed fetal lung mass between 2009 and 2017 at a single academic center was conducted. All cases included in the final analysis underwent surgical resection and histology diagnosis was determined by a trained pathologist. Clinical data were obtained from review of stored electronic medical records which contained linked maternal and neonatal records. Imaging records included both prenatal ultrasound and magnetic resonance imaging. Fisher's exact test was used for categorical variables and the Kruskal-Wallis test was used for continuous variables. The level of significance wasOf 61 pregnancies complicated by fetal lung mass during the study period, 45 cases underwent both prenatal care and postnatal resection. Final histology revealed 10 cases of congenital pulmonary airway malformation (CPAM) type 1, nine cases of CPAM type 2, and 16 cases of bronchopulmonary sequestration. There was no difference in initial, maximal, or final CPAM volume ratio between groups, with median final CPAM volume ratio of 0.6 for CPAM type 1, 0.7 for CPAM type 2, and 0.3 for bronchopulmonary sequestration (In our cohort, there was no significant association between histologic lung mass subtypes and any obstetric or neonatal morbidity including respiratory distress.

To investigate factors associated with positive postpartum depression (PPD) screen in pregnancies complicated by fetal congenital cardiac anomaly.We reviewed all records of pregnancies complicated by fetal congenital cardiac anomaly receiving prenatal, intrapartum and postpartum care at our single center, October 2016-October 2019. Maternal, obstetric, and neonatal data were compared between women with and without a positive PPD screen at the 6-week postpartum visit.Out of 415 women referred for fetal congenital cardiac anomaly, 86 women had complete inclusion criteria. Twenty-four women (28%) had a positive PPD screen. The frequencies of planned future infant surgery (73.9 vs. 26.2%, p = 0.01) and neonatal death prior to postpartum visit (12.5 vs. 0%, p = 0.02) were significantly higher among women with a positive PPD screen.In pregnancies complicated by fetal congenital cardiac anomaly, mothers of infants with planned future surgery or neonatal death are at significant risk for postpartum depression.

Background Standard testing fails to identify a pathogen in most patients with febrile neutropenia (FN). We evaluated the ability of the Karius microbial cell-free DNA sequencing test (KT) to identify infectious etiologies of FN and its impact on antimicrobial management. Methods This prospective study (ClinicalTrials.gov; NCT02912117) enrolled and analyzed 55 patients with FN. Up to 5 blood samples were collected per subject within 24 hours of fever onset (T1) and every 2 to 3 days. KT results were compared with blood culture (BC) and standard microbiological testing (SMT) results. Results Positive agreement was defined as KT identification of ≥1 isolate also detected by BC. At T1, positive and negative agreement were 90% (9/10) and 31% (14/45), respectively; 61% of KT detections were polymicrobial. Clinical adjudication by 3 independent infectious diseases specialists categorized Karius results as: unlikely to cause FN (N = 0); definite (N = 12): KT identified ≥1 organism also found by SMT within 7 days; probable (N = 19): KT result was compatible with a clinical diagnosis; possible (N = 10): KT result was consistent with infection but not considered a common cause of FN. Definite, probable, and possible cases were deemed true positives. Following adjudication, KT sensitivity and specificity were 85% (41/48) and 100% (14/14), respectively. Calculated time to diagnosis was generally shorter with KT (87%). Adjudicators determined real-time KT results could have allowed early optimization of antimicrobials in 47% of patients, by addition of antibacterials (20%) (mostly against anaerobes [12.7%]), antivirals (14.5%), and/or antifungals (3.6%); and antimicrobial narrowing in 27.3% of cases. Clinical Trials Registration NCT02912117 Conclusion KT shows promise in the diagnosis and treatment optimization of FN.

In the face of an unprecedented epidemic of Ebola Virus Disease, in September 2014, the US military began sending thousands of personnel to Liberia and supporting areas in Senegal in its largest deployment to the African continent in over two decades. In this review, media reports, published photographs and official statements are evaluated and summarized to identify and describe key time points in the US military response. Specific events include the initial establishment of the Monrovia Medical Unit and the buildup of forces for the expanded mission, which involved enhancement of laboratory testing capacity, construction of Ebola Treatment Units, and training of health care workers. The review concludes with a discussion and critical evaluation of the timeliness of this US military response in the context of the original expectations of the humanitarian community and government officials.

Background Obstetric complications impact over a third of women globally, but are underrepresented in clinical research. Little is known about the comprehensive obstetric clinical trial landscape, how it compares to other fields, or factors associated with the successful completion of obstetric trials. Objectives To characterize obstetric clinical trials registered on ClinicalTrials.gov with the primary objective of identifying features associated with early discontinuation and results reporting. Study Design This is a cross-sectional study with descriptive, logistic regression and cox regression analyses of clinical trials registered on ClinicalTrials.gov. Our primary exposure variables were trial focus (obstetric or non-obstetric) and trial funding (industry, United States government or academic). We conducted additional exploratory analyses of other trial features including design, enrollment, and therapeutic focus. We examined the associations of exposure variables and other trial features with two primary outcomes: early discontinuation and results reporting. Results We downloaded data for all studies (n=332,417) registered on ClinicalTrials.gov from October 1, 2007 to March 9, 2020 from the Aggregate Analysis of the ClinicalTrials.gov database. We excluded studies with a non-interventional design (n=63,697) and those registered before October 1, 2007 (n=45,209). 4,276 (1.9%) obstetric trials (i.e. interventional studies), and 219,235 (98.1%) non-obstetric trials were compared. Among all trials, 2.8% of academic-funded trials, 1.9% of United States government-funded trials, and 0.4% of industry-funded trials focused on obstetrics. The quantity of obstetric trials increased over time (10.8% annual growth rate). Compared to non-obstetric trials, obstetric trials had a greater risk of early discontinuation (adjusted hazard ratio 1.40, 95% confidence interval: 1.21 to 1.62, p

Although some signs of inflammation have been reported previously in patients with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), the data are limited and contradictory. High-throughput methods now allow us to interrogate the human immune system for multiple markers of inflammation at a scale that was not previously possible. To determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration, cytokines of 192 ME/CFS patients and 392 healthy controls were measured using a 51-multiplex array on a Luminex system. Each cytokine’s preprocessed data were regressed on ME/CFS severity plus covariates for age, sex, race, and an assay property of newly discovered importance: nonspecific binding. On average, TGF-β was elevated (P = 0.0052) and resistin was lower (P = 0.0052) in patients compared with controls. Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity: CCL11 (Eotaxin-1), CXCL1 (GROα), CXCL10 (IP-10), IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α. Of the 17 cytokines that correlated with severity, 13 are proinflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease. Only CXCL9 (MIG) inversely correlated with fatigue duration.

Background People living with HIV (PLWH) have a higher prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization and likelihood of recurrent infection than the general population. Simultaneously treating MRSA-colonized household members may improve success with MRSA decolonization strategies. This article describes a pilot trial testing household-level MRSA decolonization and documents methodologic and pragmatic challenges of this approach. Methods We conducted a randomized controlled trial of individual versus individual-plus-household MRSA decolonization to reduce recurrent MRSA. PLWH with a history of MRSA who are patients of an urban HIV clinic received a standard MRSA decolonization regimen. MRSA colonization at 6 months was the primary outcome. Results One hundred sixty-six patients were referred for MRSA screening; 77 (46%) enrolled. Of those, 28 (36%) were colonized with MRSA and identified risk factors consistent with the published literature. Eighteen were randomized and 13 households completed the study. Conclusions This is the first study to report on a household-level MRSA decolonization among PLWH. Challenges included provider referral, HIV stigma, confidentiality concerns over enrolling households, and dynamic living situations. Although simultaneous household MRSA decolonization may reduce recolonization, recruitment and retention challenges specific to PLWH limit the ability to conduct household-level research. Efforts to minimize these barriers are needed to inform evidence-based practice.

In recent years, the United States military has become increasingly involved in providing medical aid during peacetime public health emergencies in the form of foreign disaster relief (FDR). Althou...

Background Standard microbiological testing (MT) fails to identify a pathogen in most chemotherapy recipients with febrile neutropenia (FN), who therefore receive prolonged empiric courses of broad-spectrum antimicrobials (AM). We evaluated the ability of the Karius next-generation sequencing plasma test (KT) to identify infectious etiologies of NF and its impact on AM management. Methods This prospective, observational study enrolled 57 patients with ≤500 neutrophils/mm3. Samples were collected within 24 hours of fever onset (T0) and every 2–3 days. Cell-free plasma DNA was prepared and sequenced in a CLIA/CAP laboratory, human reads excluded, and remaining sequences aligned to a curated pathogen database that includes bacteria, viruses, fungi and parasites. Positive agreement (PA) was defined as KT identification of ≥1 isolate also seen by blood culture (BC). Discordant results were adjudicated by 3 infectious disease specialists as: Definite: KT identified ≥1 organism also seen by MT± 7 days of enrollment; Probable: KT result was a likely cause of NF compatible with clinical diagnosis; Possible: KT result was consistent with an infection but not a common cause of NF. Results 56 results (55 subjects) with valid KT and BC results were analyzed. Compared with BC, KT had a PA of 90% (9/10) and negative agreement of 31% (14/45). KT identified >1 organism in 61% (25/41) of the cases. Definite (13), Probable (24) and Possible (4) cases were classified as True Positives. Using clinical adjudication, KT had a sensitivity of 98% (41/42) and specificity of 100% (14/14). The committee would have changed AM therapy 68% (27/40) of the time, had the KT results been available in real-time (~T52–100h). In 8/19 cases (42%) vancomycin would have been discontinued; in 6/27 cases (22%) and in 5/27 cases (19%), anaerobic coverage or antivirals would have been added earlier. Serial analysis of a Pneumocystis jirovecii infection indicated that earlier diagnosis and treatment may have prevented morbidity and eventual ICU transfer. Conclusion The absence of infectious etiology in NF often leads to broad AM therapy or delay of targeted treatment. Given its sensitivity and ability to detect a breadth of pathogens, the KT can provide useful data for diagnosis and management of NF and may allow for optimization of AM therapy. Disclosures H. Seng, Karius, Inc.: Employee, Salary. R. Aquino, Karius, Inc.: Employee, Salary. D. Hollemon, Karius: Employee, Salary. D. Hong, Karius, Inc.: Employee, Salary. T. Blauwkamp, Karius, Inc.: Board Member, Employee and Shareholder, Salary. M. Kertesz, Karius Inc.: Board Member, Employee and Shareholder, Salary. L. Blair, Karius: Employee, Salary. S. Zompi, Karius, Inc.: Employee, Salary.

Background Blood cultures (BC) fail to detect a pathogen in most patients with neutropenic fever (NF). We examined the performance of the Karius next generation sequencing plasma test (plasma NGS) compared with that of BC in chemotherapy-induced NF. Methods Patients 18 years or older with absolute neutrophil count 7 days were enrolled at the time of BC collection (T0) due to fever. Plasma samples were collected at T0 and twice weekly until neutrophil recovery or discharge. Samples were shipped to the Karius CLIA/CAP laboratory (Redwood City, CA) where cell-free plasma was prepared, DNA extracted, and NGS performed. After removing human reads, remaining sequences were aligned to a curated pathogen database. Organisms present at a significance- level above a predefined threshold were reported. T0 BC and plasma NGS results were compared, excluding organisms (eg, viruses) not recoverable by BC. Positive agreement was defined as plasma NGS identification of at least one isolate seen on BC. Plasma NGS+/BC- results underwent adjudication by 3 infectious diseases specialists. Diagnosis was Definite if microbiology confirmed NGS result within 7 days of enrollment; Probable if clinical, radiologic, and laboratory data were compatible with plasma NGS test result; and otherwise Indeterminate. Results The first 18 patients were evaluated. At the time of enrollment, 6 patients were on antibiotics and 3 were on antifungals. There were 4 positive BC (each monomicrobial) at T0 and all were concordant with plasma NGS. The plasma NGS test identified additional organisms in 2 of the BC+ patients with surgical abdomen. Compared with BC, plasma NGS positive agreement was 100% (4/4) with lack of agreement in 43% (6/14). All 8 NGS+/BC- cases were deemed Probable by adjudication. These included patients with single or mixed organisms in patients with enterocolitis or severe mucositis. In one sample, Aspergillus fumigatus was detected in a patient with new lung nodules. Conclusion The etiologic diagnosis of NF is frequently unknown, leading to broad antibiotics and sometimes delay of targeted treatment. Plasma NGS may provide useful data for managing NF given its ability to detect a breadth of pathogens even when patients are pretreated with antibiotics. Disclosures H. Seng, Karius, Inc: Employee, Salary; D. Hollemon, Karius, Inc: Employee, Salary; D. Hong, Karius, Inc.: Collaborator, Research support and Salary T. A. Blawkamp, Karius Inc.: Board Member and Employee, Salary; M. Kertesz, Karius Inc.: Board Member and Employee, Salary