Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial.

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.

Process Evaluation of a Double-Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra-Low-Dose Treatment for Hypertension Within a Federally Qualified Health Center Network (QUARTET USA).

BACKGROUND: This convergent parallel-design mixed-methods process evaluation of the QUARTET USA (Quadruple Ultra-Low-Dose Treatment for Hypertension USA) clinical trial (NCT03640312) explores patient and health care professional perceptions about the use of low-dose quadruple therapy (LDQT) as a novel strategy for hypertension management. METHODS AND RESULTS: A survey of all 62 patients enrolled in the QUARTET USA trial was conducted. A subsample of 13 patients and 11 health care professionals, recruited via purposive sampling, took part in semistructured interviews. At enrollment, 68% of participants (mean [SD] age, 51.7 [11.5] years; 56% self-identified as Hispanic: Mexican ethnicity, 16% as Hispanic: other ethnicity, 16% as Black race, 8% as White race, and 1.6% as South Asian race) reported that their current health depended on blood pressure medications, and 48% were concerned about blood pressure medications. At trial completion, 80% were satisfied with LDQT, 96% were certain the benefits of taking LDQT outweighed the disadvantages, and 96% reported that LDQT was convenient to take. Both patients and health care professionals found LDQT acceptable because it reduced patients' perceived pill burden and facilitated medication adherence. Health care professionals stated that a perceived limitation of LDQT was the inability to titrate doses. Steps to facilitate LDQT implementation include introducing stepped-care combinations and treatment protocols, inclusion in clinical practice guidelines, and eliminating patient cost barriers. CONCLUSIONS: LDQT was an acceptable strategy for hypertension treatment among patients and health care professionals involved in the QUARTET USA clinical trial. Although LDQT was generally perceived as beneficial for maintaining patients' blood pressure control and facilitating adherence, some clinicians perceived limitations in titration inflexibility, adverse effects, and costs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03640312.

Rationale and design for Healthy Hearts for Michigan (HH4M): A pragmatic single-arm hybrid effectiveness-implementation study.

Background: The burden of cardiovascular disease (CVD) is particularly high in several US states, which include the state of Michigan. Hypertension and smoking are two major risk factors for mortality due to CVD. Rural Michigan is disproportionally affected by CVD and by primary care shortages. The Healthy Hearts for Michigan (HH4M) study aims to promote hypertension management and smoking cessation through practice facilitation and quality improvement efforts and is part of the multi-state EvidenceNOW: Building State Capacity initiative to provide external support to primary care practices to improve care delivery. Methods: Primary care practices in rural and underserved areas of Michigan were recruited to join HH4M, a pragmatic, single-arm hybrid Type 2 effectiveness-implementation study during which practice facilitation was delivered at the practice level for 12 months, followed by a 3-month maintenance period. Results: Fifty-four practices were enrolled over a 12-month recruitment period. At baseline, the mean proportion (standard deviation) of patients at the practice level meeting the clinical quality measures were: blood pressure, 0.72 (0.12); tobacco screening, 0.80 (0.30); tobacco cessation intervention, 0.57 (0.28); tobacco screening and cessation intervention: 0.78 (0.26). Conclusion: This three-year research program will evaluate the ability of rural and medically underserved primary care practices to implement the quality improvement model by identifying drivers of and barriers to sustainable implementation, and test whether the model improves (a) blood pressure control and (b) tobacco use screening and cessation.

The evolving role of data & safety monitoring boards for real-world clinical trials.

Introduction: Clinical trials provide the "gold standard" evidence for advancing the practice of medicine, even as they evolve to integrate real-world data sources. Modern clinical trials are increasingly incorporating real-world data sources - data not intended for research and often collected in free-living contexts. We refer to trials that incorporate real-world data sources as real-world trials. Such trials may have the potential to enhance the generalizability of findings, facilitate pragmatic study designs, and evaluate real-world effectiveness. However, key differences in the design, conduct, and implementation of real-world vs traditional trials have ramifications in data management that can threaten their desired rigor. Methods: Three examples of real-world trials that leverage different types of data sources - wearables, medical devices, and electronic health records are described. Key insights applicable to all three trials in their relationship to Data and Safety Monitoring Boards (DSMBs) are derived. Results: Insight and recommendations are given on four topic areas: A. Charge of the DSMB; B. Composition of the DSMB; C. Pre-launch Activities; and D. Post-launch Activities. We recommend stronger and additional focus on data integrity. Conclusions: Clinical trials can benefit from incorporating real-world data sources, potentially increasing the generalizability of findings and overall trial scale and efficiency. The data, however, present a level of informatic complexity that relies heavily on a robust data science infrastructure. The nature of monitoring the data and safety must evolve to adapt to new trial scenarios to protect the rigor of clinical trials.

Guidance on interim analysis methods in clinical trials.

Interim analyses in clinical trials can take on a multitude of forms. They are often used to guide Data and Safety Monitoring Board (DSMB) recommendations to study teams regarding recruitment targets for large, later-phase clinical trials. As collaborative biostatisticians working and teaching in multiple fields of research and across a broad array of trial phases, we note the large heterogeneity and confusion surrounding interim analyses in clinical trials. Thus, in this paper, we aim to provide a general overview and guidance on interim analyses for a nonstatistical audience. We explain each of the following types of interim analyses: efficacy, futility, safety, and sample size re-estimation, and we provide the reader with reasoning, examples, and implications for each. We emphasize that while the types of interim analyses employed may differ depending on the nature of the study, we would always recommend prespecification of the interim analytic plan to the extent possible with risk mitigation and trial integrity remaining a priority. Finally, we posit that interim analyses should be used as tools to help the DSMB make informed decisions in the context of the overarching study. They should generally not be deemed binding, and they should not be reviewed in isolation.

Synaptopodin is necessary for Shigella flexneri intercellular spread.

For many intracellular pathogens, their virulence depends on an ability to spread between cells of an epithelial layer. For intercellular spread to occur, these pathogens deform the plasma membrane into a protrusion structure that is engulfed by the neighboring cell. Although the polymerization of actin is essential for spread, how these pathogens manipulate the actin cytoskeleton in a manner that enables protrusion formation is still incompletely understood. Here, we identify the mammalian actin binding protein synaptopodin as required for efficient intercellular spread. Using a model cytosolic pathogen, Shigella flexneri , we show that synaptopodin contributes to organization of actin around bacteria and increases the length of the actin tail at the posterior pole of the bacteria. We show that synaptopodin presence enables protrusions to form and to resolve at a greater rate, indicating that greater stability of the actin tail enables the bacteria to push against the membrane with greater force. We demonstrate that synaptopodin recruitment around bacteria requires the bacterial protein IcsA, and we show that this recruitment is further enhanced in a type 3 secretion system dependent manner. These data establish synaptopodin as required for intracellular bacteria to reprogram the actin cytoskeleton in a manner that enables efficient protrusion formation and enhance our understanding of the cellular function of synaptopodin. Authors Summary: Intercellular spread is essential for many cytosolic dwelling pathogens during their infectious life cycle. Despite knowing the steps required for intercellular spread, relatively little is known about the host-pathogen interactions that enable these steps to occur. Here, we identify a requirement for the actin binding protein synaptopodin during intercellular spread by cytosolic bacteria. We show synaptopodin is necessary for the stability and recruitment of polymerized actin around bacteria. We also demonstrate synaptopodin is necessary to form plasma membrane structures known as protrusions that are necessary for the movement of these bacteria between cells. Thus, these findings implicate synaptopodin as an important actin-binding protein for the virulence of intracellular pathogens that require the actin cytoskeleton for their spread between cells.

An Approach to Evaluating Multisector Partnerships to Support Evidence-Based Quality Improvement in Primary Care.

BACKGROUND: Quality improvement (QI) interventions in primary care are increasingly designed and implemented by multisector partnerships, yet little guidance exists on how to best monitor or evaluate these partnerships. The goal of this project was to describe an approach for evaluating the development and effectiveness of a multisector partnership using data from the first year of the Healthy Hearts for Michigan (HH4M) Cooperative, a multisector partnership of nine organizations tasked with designing and implementing evidence-based QI strategies for hypertension management and tobacco cessation in 50 rural primary care practices. METHODS: The researchers developed a 49-item online survey focused on factors that facilitate or hinder multisector partnerships, drawing on implementation science and partnership, engagement, and collaboration research. The team surveyed all 44 members of the HH4M Cooperative (79.5% response rate) and conducted interviews with 14 members. The interviews focused on implementation phase-specific goals, accomplishments, and challenges. Descriptive analysis was used for the survey results, and thematic analysis for the interview data. RESULTS: Respondents reported strong overall performance by the Cooperative during its first year, which facilitated the successful completion of several intervention design tasks. Strengths included having a clear purpose and trust and respect among members. Areas for improvement included a need for common terminology, clarification of roles and functions, and improvement in communication across workgroups. Lack of engagement from physician practices due to capacity constraints, exacerbated by the COVID-19 pandemic, was the Cooperative's biggest challenge. CONCLUSION: This multimethod approach to evaluating the development and effectiveness of a multisector partnership yielded practical, actionable feedback to program leaders.

Development and Clinical Evaluation of a Rapid Point of Care Test for Ebola Virus Infection in Humans.

The genus Ebolavirus contains multiple species of viruses that are highly contagious and lethal, often causing severe hemorrhagic fever. To minimize the global threat from Ebola virus disease (EVD), sustainable, field-appropriate tools are needed to quickly screen and triage symptomatic patients and conduct rapid screening of cadavers to ensure proper handling of human remains. The OraQuick® Ebola Rapid Antigen Test is an in vitro diagnostic single-use immunoassay for the qualitative detection of Ebola virus antigens that detects all known species within the genus Ebolavirus. Here, we report the performance of the OraQuick® Ebola Rapid Antigen Test and provide a comparison of its performance with other rapid diagnostic tests (RDTs) for EVD. OraQuick® Ebola demonstrated clinical sensitivity of 84.0% in archived EVD patient venous whole-blood (WB) samples, 90.9% in Ebola virus-infected monkey fingerstick samples, and 97.1% in EVD patient cadaver buccal swabs, as well as clinical specificity of 98.0-100% in venous WB samples and 99.1-100% in contrived saliva samples. It is the only 510(k)-cleared Ebola rapid test, has analytical sensitivity as good as or better than all RDT comparators for EVD, and can detect the Sudan virus. Our data demonstrate that the OraQuick® Ebola Rapid Antigen Test is a sensitive and specific assay that can be used for rapid detection of EBOV in humans and could support efforts for EVD-specific interventions and control over outbreaks.

Comparative effectiveness of a mindfulness-based intervention (M-Body) on depressive symptoms: study protocol of a randomized controlled trial in a Federally Qualified Health Center (FQHC).

BACKGROUND: Mindfulness-based interventions have been shown to improve psychological outcomes including stress, anxiety, and depression in general population studies. However, effectiveness has not been sufficiently examined in racially and ethnically diverse community-based settings. We will evaluate the effectiveness and implementation of a mindfulness-based intervention on depressive symptoms among predominantly Black women at a Federally Qualified Health Center in a metropolitan city. METHODS: In this 2-armed, stratified, individually randomized group-treated controlled trial, 274 English-speaking participants with depressive symptoms ages 18-65 years old will be randomly assigned to (1) eight weekly, 90-min group sessions of a mindfulness-based intervention (M-Body), or (2) enhanced usual care. Exclusion criteria include suicidal ideation in 30 days prior to enrollment and regular (>4x/week) meditation practice. Study metrics will be assessed at baseline and 2, 4, and 6 months after baseline, through clinical interviews, self-report surveys, and stress biomarker data including blood pressure, heart rate, and stress related biomarkers. The primary study outcome is depressive symptom score after 6 months. DISCUSSION: If M-Body is found to be an effective intervention for adults with depressive symptoms, this accessible, scalable treatment will widely increase access to mental health treatment in underserved, racial/ethnic minority communities. TRIAL REGISTRATION: ClinicalTrials.gov NCT03620721. Registered on 8 August 2018.

Development and Clinical Performance of InteliSwab® COVID-19 Rapid Test: Evaluation of Antigen Test for the Diagnosis of SARS-CoV-2 and Analytical Sensitivity to Detect Variants of Concern Including Omicron and Subvariants.

BACKGROUND AND OBJECTIVES: Timely detection of SARS-CoV-2 infection with subsequent contact tracing and rapid isolation are considered critical to containing the pandemic, which continues with the emergence of new variants. Hence, there is an ongoing need for reliable point-of-care antigen rapid diagnostic tests (Ag-RDT). This report describes the development, evaluation, and analytical sensitivity of the diagnostic performance of the InteliSwab® COVID-19 Rapid Test. Methods: Samples from 165 symptomatic subjects were tested with InteliSwab® and the results were compared to RT-PCR to determine the antigen test performance. The analytical sensitivity of InteliSwab® for the detection of different variants was assessed by limit of detection (LOD) determination using recombinant nucleocapsid proteins (NPs) and testing with virus isolates. Western immunoblot independently confirmed that each monoclonal Ab is capable of binding to all variants tested thus far. RESULTS: The overall positivity rate by RT-PCR was 37% for the 165 symptomatic subjects. Based on RT-PCR results as the reference standard, InteliSwab® showed clinical sensitivity and specificity of 85.2% (95% CI, 74.3-92.0%) and 98.1% (95% CI, 93.3-99.7%), respectively. The overall agreement was 93.3% (Kappa index value 0.85; 95% CI, 0.77-0.74) between RT-PCR and InteliSwab® test results. Furthermore, the evaluation of analytical sensitivity for different SARS-CoV-2 variants by InteliSwab® was comparable in the detection of all the variants tested, including Omicron subvariants, BA.4, BA.5, and BQ.1. CONCLUSIONS: Due to the surge of infections caused by different variants from time to time, there is a critical need to evaluate the sensitivity of rapid antigen-detecting tests for new variants. The study findings showed the robust diagnostic performance of InteliSwab® and analytical sensitivity in detecting different SARS-CoV-2 variants, including the Omicron subvariants. With the integrated swab and excellent sensitivity and variant detection, this test has high potential as a point-of-care Ag-RDT in various settings when molecular assays are in limited supply and rapid diagnosis of SARS-CoV-2 is necessary.

Prophylaxis against spontaneous bacterial peritonitis: Too much or too little?

Prophylaxis against spontaneous bacterial peritonitis (SBP) is recommended for select patients with cirrhosis, but long-term antibiotic therapy has risks. We evaluated concordance with guideline recommendations in 179 veterans with cirrhosis; 55% received guideline-concordant management of SBP prophylaxis. Despite stable guideline recommendations since 2012, guideline adherence remains low.

Trajectories of Depressive and Anxiety Symptoms Across Pregnancy and Postpartum in Selective Serotonin Reuptake Inhibitor-Treated Women.

Objective: Tracking perinatal mood and anxiety disorders is championed by the American Psychiatric Association and the International Marcé Society for Perinatal Mental Health. We conducted this study to examine trajectories of monthly depressive and anxiety symptoms through pregnancy and postpartum. Methods: This is a prospective longitudinal observational cohort study of pregnant women interviewed at baseline (≤18th gestational week), every four weeks through delivery and at 6 and 14 weeks postpartum at three urban academic medical centers (N = 85) and a single rural health center (N = 3) from 2016 to 2020. Pregnant women had at least one prior episode of major depressive disorder, were not in a current episode, and were treated with sertraline, fluoxetine, citalopram, or escitalopram. Of 192 women screened, 88 (46%) women enrolled, and 77 (88%) women completed the postpartum follow-up. Symptom trajectories were generated with scores from the Edinburgh Postnatal Depression Scale, the Quick Inventory of Depressive Symptoms, the Generalized Anxiety Disorder Scale, 7-item, and the Patient-Reported Outcomes Measurement Information System Global Health measure. A semi-parametric, group-based mixture model (trajectory analysis) was applied. Results: Three relatively stable depression trajectories emerged, described as Minimal, Mild, and Subthreshold, in each group across pregnancy. Two of the four anxiety trajectories were stable, including Asymptomatic and Minimal, while the third, termed Breakthrough, was ascending with increasing symptoms and the fourth trajectory, described as Mild, had descending symptoms. Conclusions: Screening for anxiety with depression for pregnant women will yield a comprehensive view of psychiatric symptoms and treatment targets in perinatal women.

Efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA): Rationale and design for a randomized controlled trial.

BACKGROUND: Over half of patients with elevated blood pressure require multi-drug treatment to achieve blood pressure control. However, multi-drug treatment may lead to lower adherence and more adverse drug effects compared with monotherapy. OBJECTIVE: The Quadruple Ultra-low-dose Treatment for Hypertension (QUARTET) USA trial was designed to evaluate whether initiating treatment with ultra-low-dose quadruple-combination therapy will lower office blood pressure more effectively, and with fewer side effects, compared with initiating standard dose monotherapy in treatment naive patients with SBP < 180 and DBP < 110 mm Hg and patients on monotherapy with SBP < 160 and DBP < 100 mm Hg. METHODS/DESIGN: QUARTET USA was a prospective, randomized, double-blind trial (ClinicalTrials.gov NCT03640312) conducted in federally qualified health centers in a large city in the US. Patients were randomly assigned (1:1) to either ultra-low-dose quadruple combination therapy or standard dose monotherapy. The primary outcome was mean change from baseline in office systolic blood pressure at 12-weeks, adjusted for baseline values. Secondary outcomes included measures of blood pressure change and variability, medication adherence, and health related quality of life. Safety outcomes included occurrence of serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. A process evaluation aimed to understand provider experiences of implementation and participant experiences around side effects, adherence, and trust with clinical care. DISCUSSION: QUARTET USA was designed to evaluate whether a novel approach to blood pressure control would lower office blood pressure more effectively, and with fewer side effects, compared with standard dose monotherapy. QUARTET USA was conducted within a network of federally qualified healthcare centers with the aim of generating information on the safety and efficacy of ultra-low-dose quadruple-combination therapy in diverse groups that experience a high burden of hypertension.

Changes in Sertraline Plasma Concentrations Across Pregnancy and Postpartum.

Major depressive disorder (MDD) is a common disorder in pregnancy. Although sertraline is the most frequently prescribed antidepressant for pregnant people in the United States, limited information about its pharmacokinetics in pregnancy is available. Our objectives were to characterize plasma sertraline concentration to dose (C/D) ratios across pregnancy and postpartum and investigate the effect of pharmacogenetic variability on sertraline elimination. We performed a prospective observational cohort study in people with a singleton pregnancy ≤ 18 weeks gestation and a lifetime diagnosis of MDD at the 3 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)-funded Obstetrical-Fetal Pharmacology Research Center sites. Subjects (N = 47) were receiving maintenance sertraline therapy and chose to continue it during pregnancy. Blood samples were obtained 24-hours postdose every 4 weeks across pregnancy and twice postpartum for measurement of plasma concentrations of sertraline and desmethylsertraline. Overall mean sertraline C/D ratios were decreased at study onset and remained consistently low until after delivery. During the last 4 weeks of pregnancy the mean sertraline C/D ratio (95% confidence interval (CI)), 0.25 (95% CI, 0.19, 0.3) ng/mL/dose (mg/day), was smaller than the mean ratio at ≥ 8 weeks after delivery, 0.32 (95% CI, 0.27, 0.37) ng/mL/dose (mg/day), a 22% difference. Mean sertraline/desmethylsertraline ratios were highest after birth, which confirmed increased sertraline elimination during pregnancy. Sertraline C/D ratios in participants with functional CYP2C19 activity did not change significantly during pregnancy, whereas ratios in participants with poor or intermediate CYP2C19 activity decreased by 51%. Exploratory pharmacogenomic analysis indicated that pregnant people with poor or intermediate CYP2C19 activity are at risk for subtherapeutic sertraline concentrations during pregnancy.

Examining Participant Dosage and Skill Utilization Associated with Receipt of a Perinatal Depression Preventive Intervention.

This study assessed participant, facilitator, and program-level characteristics associated with intervention dosage among women receiving an evidence-based perinatal depression preventive intervention, Mothers and Babies (MB). We also explored how intervention dosage affected the use and maintenance of core skills taught in the six-session group-based intervention. We conducted a secondary analysis of data from a cluster-randomized controlled trial in which 679 women enrolled in home visiting (HV) programs received MB prenatally. High dose of intervention was defined as attendance at > 50% of MB sessions, while MB skill utilization was measured by asking participants to indicate at 12 and 24 weeks postpartum the extent to which they used 12 core MB skills taught during the intervention. Age and racial concordance between participant and facilitator were significantly associated with intervention dosage. Those receiving higher intervention dosage tended to be older (27.25 ± 5.96 vs. 24.99 ± 5.60, p < 0.01, OR = 1.068 [1.038-1.098]), and received MB from a facilitator with a self-identified race similar to their own (58% vs. 48%, p = 0.04, OR = 1.485 [1.014-2.176]). Primary language of participants was marginally associated with dosage. Participants receiving a higher dose of intervention tended to exhibit greater MB skill utilization, on average at 24 weeks postpartum. These results can be used to identify strategies to promote intervention engagement. They further suggest that greater intervention dosage leads to increased use of core intervention skills that can promote improvements in participants' behaviors and thoughts.

Associations Between Implementation of the Collaborative Care Model and Disparities in Perinatal Depression Care.

OBJECTIVE: To evaluate whether perinatal collaborative care model implementation was associated with a reduction in racial disparities in depression care. METHODS: This retrospective cohort study included pregnant and postpartum people who self-identified as either Black or White, and received prenatal care at academic faculty offices affiliated with an urban quaternary medical center. Individuals were divided into two cohorts to reflect the epochs of implementation. The primary outcome was the frequency of depression screening. The secondary outcome was the frequency of provision of a treatment recommendation for those with a positive depression screen. Antenatal and postpartum care were analyzed separately. A propensity score was used in multivariable models to control for confounders chosen a priori across implementation epoch. Interaction terms were created between race and implementation epoch to identify whether effect modification was present. Subgroup analyses were performed for outcomes with significant race-by-epoch interaction terms. RESULTS: Of the 4,710 individuals included in these analyses, 4,135 (87.8%) self-identified as White and 575 (12.2%) self-identified as Black. Before implementation, Black individuals were more likely to receive screening (adjusted odds ratio [aOR] 2.44) but less likely to have a treatment recommended when a positive screen was identified (aOR 0.05). In multivariable models, race-by-epoch interaction terms were significant for both antenatal screening (P<.001) and antenatal treatment recommendation (P=.045), demonstrating that implementation of the perinatal collaborative care model was associated with reductions in extant racial disparities. After implementation, there were no significant differences by race (referent=White) in screening for antenatal depression (aOR 1.22, 95% CI 0.89-1.68) or treatment recommendations for those who screened positive (aOR 0.64, 95% CI 0.27-1.53). Race-by-epoch interaction terms were not significant in multivariable models for either postpartum screening or treatment recommendation. CONCLUSION: Implementation of the perinatal collaborative care model is associated with a mitigation of racial disparities in antenatal depression care and may be an equity-promoting intervention for maternal health.

Protocol for an attention-matched randomized controlled trial of 2GETHER: a relationship education and HIV prevention program for young male couples.

BACKGROUND: Young men who have sex with men (YMSM) are disproportionately impacted by the HIV epidemic in the USA, and a large number of new infections among YMSM occur in the context of main or primary partnerships. At the same time, healthy romantic relationships promote health and wellbeing by improving social support and encouraging healthy behaviors. Thus, we created 2GETHER: a relationship education and HIV prevention program for young male couples. 2GETHER is delivered face-to-face in a university setting and is composed of two group sessions and two individualized skills coaching sessions. We observed strong support of the feasibility, acceptability, and preliminary efficacy of 2GETHER in a pilot trial. METHODS: We are conducting an attention-matched randomized controlled trial (RCT) to test the efficacy of 2GETHER relative to a control condition based on a well-validated positive affect enhancement program. Enrollment occurred between August 2017 and March 2021 in Chicago and surrounding areas, and we enrolled and randomized 128 dyads (N = 256 individuals). Follow-up is ongoing and we will examine primary and secondary behavioral outcomes at 12 months post-intervention, with interim follow-up at 3, 6, and 9 months post-intervention. The primary biomedical outcome is sexually transmitted infection incidence at a 12-month follow-up. DISCUSSION: 2GETHER is innovative in that it places an equal emphasis on relationship skill building and HIV prevention. Thus, the program has the potential to impact numerous health-related outcomes. Despite challenges related to the recruitment of couples and the COVID-19 pandemic, we were able to enroll a robust sample of young male couples with sufficient power to detect effects on study outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03186534 .

Embedded emergency department physical therapy versus usual care for acute low back pain: a protocol for the NEED-PT randomised trial.

INTRODUCTION: Low back pain is a common problem and a substantial source of morbidity and disability worldwide. Patients frequently visit the emergency department (ED) for low back pain, but many experience persistent symptoms at 3 months despite frequent receipt of opioids. Although physical therapy interventions have been demonstrated to improve patient functioning in the outpatient setting, no randomised trial has yet to evaluate physical therapy in the ED setting. METHODS AND ANALYSIS: This is a single-centre cluster-randomised trial of an embedded ED physical therapy intervention for acute low back pain. We used a covariate-constrained approach to randomise individual physicians (clusters) at an urban academic ED in Chicago, Illinois, USA, to receive, or not receive, an embedded physical therapist on their primary treatment team to evaluate all patients with low back pain. We will then enrol individual ED patients with acute low back pain and allocate them to the embedded physical therapy or usual care study arms, depending on the randomisation assignment of their treating physician. We will follow patients to a primary endpoint of 3 months and compare a primary outcome of change in PROMIS-Pain Interference score and secondary outcomes of change in modified Oswestry Disability Index score and patient-reported opioid use. Our primary approach will be a modified intention-to-treat analysis, whereby all participants who complete at least one follow-up data time point will be included in analyses, regardless of their or their physicians' adherence to their assigned study arm. ETHICS AND DISSEMINATION: This trial is funded by the US Agency for Healthcare Research and Quality (R01HS027426) and was approved by the Northwestern University Institutional Review Board. All physician and patient participants will give written informed consent to study participation. Trial results will be submitted for presentation at scientific meetings and for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04921449).

OraSure InteliSwab™ Rapid Antigen Test Performance with the SARS-CoV-2 Variants of Concern-Alpha, Beta, Gamma, Delta, and Omicron.

The emergence of SARS-CoV-2 in the human population and the resulting COVID-19 pandemic have led to the development of various diagnostic tests. The OraSure InteliSwab™ COVID-19 Rapid Test is a recently developed and FDA emergency use-authorized rapid antigen-detecting test that functions as a lateral flow device targeting the nucleocapsid protein. Due to SARS-CoV-2 evolution, there is a need to evaluate the sensitivity of rapid antigen-detecting tests for new variants, especially variants of concern such as Omicron. In this study, the sensitivity of the OraSure InteliSwab™ Test was investigated using cultured strains of the known variants of concern (VOCs, Alpha, Beta, Gamma, Delta, and Omicron) and the ancestral lineage (lineage A). Based on dilution series in cell culture medium, an approximate limit of detection for each variant was determined. The OraSure InteliSwab™ Test showed an overall comparable performance using recombinant nucleocapsid protein and different cultured variants, with recorded limits of detection ranging between 3.77 × 105 and 9.13 × 105 RNA copies/mL. Finally, the sensitivity was evaluated using oropharyngeal swabs from Syrian golden hamsters inoculated with the six VOCs. Ultimately, the OraSure InteliSwab™ COVID-19 Rapid Test showed no decrease in sensitivity between the ancestral SARS-CoV-2 strain and any VOCs including Omicron.

C-Reactive protein concentrations in reproductive-aged women with major mood disorders.

To examine associations between high sensitivity C-reactive protein (CRP) concentrations and depressive symptoms in reproductive-aged women with mood disorders. Women (N = 86) with major depressive or bipolar disorder in a specialized mood disorders program provided plasma samples which were analyzed for CRP concentrations and categorized by tertiles (T1, low; T2, middle; T3 high). Depressive symptoms were assessed with the Inventory of Depressive Symptoms. We hypothesized that CRP concentrations would be significantly associated with the following: (1) depressive symptoms; (2) pregnancy, (3) body mass index, and (4) counts of white blood cells and absolute neutrophils and percentage of segmented neutrophils. The distribution of CRP concentrations was highly skewed with a median of 2.45 mg/L and an interquartile range 0.90 - 8.17 mg/L. Elevated plasma levels of CRP were not associated with depressive symptoms, which did not differ by tertile group either before or after adjusting for BMI, pregnancy status, and their interactions. Women in T3 had 5 times greater odds of pregnancy compared to women in T1 (p = .021). However, women in T2 had 11% greater BMI on average (p = 0.023), and women in T3 had 47% greater BMI compared to those in T1 (p < 0.001). Women in T3 had higher mean white blood cell counts than those in T1 and T2, the percentage of neutrophils was higher in T2 and T3 compared to T1, and women in T3 had higher absolute neutrophil counts compared to T1. CRP concentrations varied widely and were significantly elevated in reproductive-aged women with high BMI and current pregnancy, but not with depressive symptoms in this sample of depressed women.