Faculty Bibliography

Importance:Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective:To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants:An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions:Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures:The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results:Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance:Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration:ClinicalTrials.gov Identifier: NCT04505774.

OBJECTIVES/OBJECTIVE:We evaluated the effectiveness of Moms2B, a community-based group pregnancy and parenting program, in an effort to assess whether the program improved pregnancy and infant outcomes. METHODS:We conducted a retrospective matched exposure cohort study comparing women exposed to the Moms2B program during pregnancy (two or more prenatal visits) who delivered a singleton live birth or stillbirth (≥ 20 weeks gestation) from 2011-2017 to a closely matched group of women not exposed to the program. Primary outcomes were preterm birth and low birth weight. Propensity score methods were used to provide strong control for confounders. RESULTS:The final analytic file comprised 675 exposed pregnancies and a propensity score-matched group of 1336 unexposed pregnancies. Most of the women were non-Hispanic Black. We found evidence of better outcomes among pregnancies exposed to Moms2B versus unexposed pregnancies, particularly for the primary outcome of low birth weight [9.45% versus 12.00%, respectively, risk difference (RD) = -2.55, 95% confidence interval (CI) = (-5.44, 0.34)]. Point estimates for all adverse pregnancy outcomes uniformly favored exposure to Moms2B. CONCLUSIONS FOR PRACTICE/UNASSIGNED:Our findings suggest that participation in the Moms2B program improves pregnancy and infant outcomes. The program offers an innovative group model of pregnancy and parenting support for women, especially in non-Hispanic Black women with high-risk pregnancies.

OBJECTIVE: We aimed to assess the relationship between obstetric history and incidence of short cervical length (CL) at <24 weeks gestational age (GA) in women with a prior spontaneous preterm birth (PTB). STUDY DESIGN/METHODS: Women with a singleton gestation and a history of spontaneous PTB on progesterone who received prenatal care at a single center from 2011 to 2016 were included. Those who did not undergo screening or had a history-indicated cerclage were excluded. The associations between short CL (<25 mm) before 24 weeks and obstetrical factors including: number of prior PTBs, history of term birth, and GA of earliest spontaneous PTB were estimated through modified Poisson regression, adjusting for confounding factors. Multiple pregnancies for the same woman were accounted for through robust sandwich standard error estimation. RESULTS: = 0.70). CONCLUSION/CONCLUSIONS: GA of earliest spontaneous PTB, but not the number of prior PTBs, is associated with short CL. Nevertheless, women with a history of later PTBs remain at sufficiently high risk of having a short CL at <24 weeks gestation that we cannot recommend modifications to existing CL screening guidelines in this group of women. KEY POINTS/CONCLUSIONS:· Prior 16 to 236/7 weeks birth is a key risk factor for CL <25 mm.. · One in five women with prior late PTB had a short CL.. · Number of PTBs is a less important risk factor..

OBJECTIVE:To evaluate the prehospital obstetric population that utilizes emergency medical services (EMS) and their association with hypertensive disorders of pregnancy. METHODS:We conducted a retrospective evaluation of one year of all medical calls from a large, municipal, midwestern fire department. Inclusion criteria included all pregnant patients transported to a hospital by EMS. Descriptive statistics were calculated to evaluate prehospital event information (e.g., zip code, time, and duration of call), patient characteristics, and clinical management data regarding blood pressure. Census data were used to compare neighborhood information with poverty rates. RESULTS:Of the 1,575 identified patients, 64.4% (1015/1575) presented with obstetric complaints, 57.4% (700/1220) were in their third trimester and 72.7% (686/944) were multiparous. The median call duration was 17 (interquartile range 12-22) minutes. In the areas where EMS usage was highest, one quarter of individuals lived below the poverty level. Of the studied population, 32.0% (504/1575) were found to be hypertensive; 14.9% (75/504) of hypertensive patients were found to have severe hypertension. Only one patient (1/1575, 0.06%) presented with a chief complaint of hypertension; the rest were discovered by EMS. The highest rates of hypertension were noted in wealthier areas of the city. Patients with severe hypertension were more likely to present with seizures, consistent with eclampsia. CONCLUSION/CONCLUSIONS:Hypertension is common in the obstetric population using EMS. Prehospital management of hypertensive disorders of pregnancy may focus on identification and treatment of severe pre-eclampsia or eclampsia. Areas with longer call times may consider treatment of severe hypertension. Prehospital treatment of hypertensive disorders of pregnancy could be optimized.

BACKGROUND:Tobacco smoking is associated with a reduced risk of developing sarcoidosis, and we previously reported that nicotine normalizes immune responses to environmental antigens in patients with active pulmonary sarcoidosis. The effects of nicotine on the progression of pulmonary sarcoidosis are unknown. RESEARCH QUESTION/OBJECTIVE:Is nicotine treatment well tolerated, and will it improve lung function in patients with active pulmonary sarcoidosis? STUDY DESIGN AND METHODS/METHODS:, quantitative lung texture score based on CT texture analysis, Fatigue Assessment Score (FAS), St. George's Respiratory Questionnaire (SGRQ), and the Sarcoidosis Assessment Tool. RESULTS:and FAS improved marginally in the nicotine-treated group, compared with those on placebo. No improvement was observed in lung texture score, FAS, St. George's Respiratory Questionnaire score, or the Sarcoidosis Assessment Tool. There were no reported serious adverse events or evidence of nicotine addiction. INTERPRETATION/CONCLUSIONS:Nicotine treatment was well tolerated in patients with active pulmonary sarcoidosis, and the preliminary findings of this pilot study suggest that it may reduce disease progression, based on FVC. CLINICAL TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov; No.: NCT02265874; URL: www.clinicaltrials.gov.

BACKGROUND:Key informants of the Appalachian community questioned whether their unique environmental stressors would alter their immune response to HPV infections. The primary aim of this study is to determine predictors of HPV seroprevalence to at least one of the four vaccine related HPV types prior to vaccination using a psychoneuroimmunologic model in Appalachian women. METHOD/METHODS:Women ages 18-26 years old (n=185) who had not received HPV vaccination provided cervical HPV DNA and blood samples. HPV DNA was identified through Hybrid Capture 2 assay and then genotyped for HPV 6, 11, 16 and 18 by Roche Linear Array. Competitive Luminex Immunoassay (cLIA) measured the type specific antibodies to HPV 6, 11, 16, and 18 in mMerck/ml. Nine psychoneuroimmunology scales measuring attributes of stress were self-completed. RESULTS:HPV DNA was detected in 50% (92/183) of participants, with only 14% (26/183) positive for HPV 6/11/16/18 DNA. Seropositivity for at least one anti-HPV 6/11/16 or 18, on the other hand, was present in 35% (64/183) of women, with only 10 % (19/183) concomitantly infected and seropositive for the vaccine related types. Perceived stress scale was not a strong predictor of HPV seropositivity. CONCLUSION/CONCLUSIONS:Both HPV infection and vaccine related HPV type seropositivity is common among Appalachian women aged 18-26 years. The anticipated effect of environmental stressors on HPV seropositivity was not seen when multiple predictors were considered.

OBJECTIVES/OBJECTIVE:We examined whether provision of contraception at discharge following delivery was associated with lower rates of postpartum visit (PPV) attendance. METHODS:We conducted a retrospective cohort study of women who received pregnancy care at a Midwestern medical center in 2013. Attendance at the postpartum visit was compared for women with sterilization, contraception initiated prior to discharge (depot medroxyprogesterone acetate or etonogestrel implant), hormonal contraception prescription, or no contraception provided at postpartum discharge. Poisson regression models with robust standard errors were used to estimate the relative risk of postpartum visit attendance controlling for age, race, and parity, insurance status, and histories of both depression and drug abuse. RESULTS:Of the 1015 women who met inclusion criteria, 55% had been prescribed contraception, had initiated contraception prior to discharge, or were sterilized at the time of discharge following delivery. After adjustment for confounders, there was no association between receiving contraception and PPV attendance (relative risk for prescribed contraception = 1.09 [95% CI 0.85, 1.39], for contraception initiated prior to discharge = 0.83 [95% CI 0.67, 1.03], for sterilization = 0.86 [95% CI 0.63, 1.17] compared to no contraception). CONCLUSIONS:We found no evidence that prescribing or administering contraception post-delivery was associated with lower rates of return for postpartum follow up. IMPLICATIONS/CONCLUSIONS:This single site study suggests that providing effective contraception at discharge following delivery does not appear to impact PPV attendance.

OBJECTIVE:To evaluate the effect of providing quasi-contextualized speech therapy, defined as metacognitive, compensatory, or strategy training applied to cognitive and language impairments to facilitate the performance of future real-life activities, on functional outcomes up to 1 year following traumatic brain injury (TBI). SETTING/METHODS:Acute inpatient rehabilitation. PARTICIPANTS/METHODS:Patients enrolled during the TBI-Practice-Based Evidence (TBI-PBE) study (n = 1760), aged 14 years or older, who sustained a severe, moderate, or complicated mild TBI, received speech therapy in acute inpatient rehabilitation at one of 9 US sites, and consented to follow-up 3 and 9 months postdischarge from inpatient rehabilitation. DESIGN/METHODS:Propensity score methods applied to a database consisting of multisite, prospective, longitudinal observational data. MAIN MEASURES/METHODS:Participation Assessment with Recombined Tools-Objective-17, FIM Motor and Cognitive scores, Satisfaction With Life Scale, and Patient Health Questionnaire-9. RESULTS:When at least 5% of therapy time employed quasi-contextualized treatment, participants reported better community participation during the year following discharge. Quasi-contextualized treatment was also associated with better motor and cognitive function at discharge and during the year after discharge. The benefit, however, may be dependent upon a balance of rehabilitation time that relied on contextualized treatment. CONCLUSIONS:The use of quasi-contextualized treatment may improve outcomes. Care should be taken, however, to not provide quasi-contextualized treatment at the expense of contextualized treatment.

PURPOSE/OBJECTIVE:Given clinical activity of AR-42, an oral histone deacetylase inhibitor, in hematologic malignancies and preclinical activity in solid tumors, this phase 1 trial investigated the safety and tolerability of AR-42 in patients with advanced solid tumors, including neurofibromatosis type 2-associated meningiomas and schwannomas (NF2). The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). Secondary objectives included determining pharmacokinetics and clinical activity. METHODS:This phase I trial was an open-label, single-center, dose-escalation study of single-agent AR-42 in primary central nervous system and advanced solid tumors. The study followed a 3 + 3 design with an expansion cohort at the MTD. RESULTS:Seventeen patients were enrolled with NF2 (n = 5), urothelial carcinoma (n = 3), breast cancer (n = 2), non-NF2-related meningioma (n = 2), carcinoma of unknown primary (n = 2), small cell lung cancer (n = 1), Sertoli cell carcinoma (n = 1), and uveal melanoma (n = 1). The recommended phase II dose is 60 mg three times weekly, for 3 weeks of a 28-day cycle. DLTs included grade 3 thrombocytopenia and grade 4 psychosis. The most common treatment-related adverse events were cytopenias, fatigue, and nausea. The best response was stable disease in 53% of patients (95% CI 26.6-78.7). Median progression-free survival (PFS) was 3.6 months (95% CI 1.2-9.1). Among evaluable patients with NF2 or meningioma (n = 5), median PFS was 9.1 months (95% CI 1.9-not reached). CONCLUSION/CONCLUSIONS:Single-agent AR-42 is safe and well tolerated. Further studies may consider AR-42 in a larger cohort of patients with NF2 or in combination with other agents in advanced solid tumors. TRIAL REGISTRATION/BACKGROUND:NCT01129193, registered 5/24/2010.