Enrollment Site Research Articles

Single dose intravenous iron versus oral iron for treatment of maternal iron deficiency anemia: A randomized clinical trial.

Maternal iron deficiency anemia is a persistent global health challenge with increased risk of adverse perinatal outcomes. Obstetric guidelines advocate for first line treatment of moderate iron deficiency anemia with twice daily oral iron, however rates of iron deficiency anemia in pregnancy remain above global targets and are rising. Determine whether single dose intravenous (IV) iron for maternal iron deficiency anemia in the second trimester is superior to twice daily oral iron in reducing incidence of low birthweight (LBW) infants and maternal anemia at delivery. This is a parallel, three-arm, semi-blind superiority randomized controlled multicenter trial across four sites in India from March 15, 2021-May 12th 2023. Participants were singleton pregnancies at 14-17 weeks with moderate iron deficiency anemia (Hb 7.0-9.9g/dL) who were randomized 1:1:1 to (1) 60mg oral ferrous sulphate twice daily; or single dose infusion of (2) IV ferric derisomaltose or (3) IV ferric carboxymaltose. Two IV arms were selected as these are the only two IV iron formulations publicly available in India. All participants received folic acid supplementation throughout pregnancy and anti-helminthic therapy, as recommended by national guidelines. The dual primary outcomes were: (1) LBW (<2500 grams [g]) and (2) attainment of a maternal non-anemic state (NAS) (Hb ≥11·0 g/dL at 30-34 weeks or delivery) for each IV iron arm vs oral iron; IV iron arms were not compared to each other. Secondary outcomes included safety measures, and other maternal and infant outcomes. Participants with Hb<7g/dL or <1g/dL improvement on therapy received rescue treatment with IV iron or blood transfusion as determined by their provider. Sensitivity analyses included defining NAS as achieving Hb≥11.0 without need for rescue therapy. Comparison of each IV iron arm to oral iron was conducted with a two-sided alpha set at 0.0005 for achieving non-anemic state and 0.0245 for low birthweight for each IV iron arm using a Cochran-Mantel-Haenszel (CMH) chi-square test stratified by enrollment site. The oral iron, ferric derisomaltose, and ferric carboxymaltose arms included 1450, 456, and 1462 participants respectively. There was a reduced rate of LBW with IV ferric carboxymaltose (25·2%, Relative Risk [RR] 0·87 [97·55% CI 0·75,0·99], p=.017), but not IV ferric derisomaltose (29·1%, RR 0·98 [97·55% CI 0·86,1·12], p=.71) vs oral iron (29.3%). Achievement of NAS was not improved: IV ferric carboxymaltose (RR 1·05 [99·95% CI 0·97-1·15]) and IV ferric derisomaltose (RR 1·06 [99·95% CI 0·98, 1·16]) vs oral (69.7%). In sensitivity analysis, there was increased rate of NAS in both IV ferric derisomaltose (RR 1.25 (1.13-1.396), p<0.0001) and IV ferric carboxymaltose (RR 1.24 (1.12-1.38), p<0.0001) vs oral iron. First-line treatment of moderate maternal iron deficiency anemia with single dose infusion of IV iron results in a reduced incidence of LBW infants (IV ferric carboxymaltose vs oral) and a higher incidence of attaining maternal NAS without use of additional iron or blood transfusion (IV ferric carboxymaltose and ferric derisomaltose vs oral). Clinical guidelines should address the potential benefit of single dose IV iron as the primary treatment of moderate iron deficiency anemia in pregnancy.

Twelve-Month Health Status Response Following Peripheral Vascular Intervention for Femoropopliteal Lesions Using Zilver PTX Databases Focusing on the Role of Preprocedural Health Status, Comorbid Risks, and Global Setting

Tailoring resources of peripheral vascular interventions (PVIs) to those who stand to gain the most would allow for more equitable and value-based care. One way of evaluating the benefit of PVIs in patients with symptomatic peripheral artery disease is evaluating their health status and identifying predictors of health status response 12months after the intervention. Patients who underwent femoropopliteal PVI between March 2005 and August 2008 from the Zilver PTX randomized trial and single-arm study were combined into a single cohort for secondary data analysis. The preprocedural and 12-month health status was assessed by the EuroQol-5D-3L (EQ-5D). First, we evaluated the 12-month EQ-5D Index (per 1-unit increase), adjusted for treatment condition and patient characteristics using a linear regression. Second, using the minimally clinically important difference threshold for the EQ-5D Index, we identified 12-month nonresponders (worsened or no change) vs responders (improved) and conducted an adjusted logistic regression model. A total of 513 patients were included (mean age: 67.8± 9.2years; 25.1% female), with 17.8% U.S. and 82.2% non-U.S. global enrollment sites. The minimally clinically important difference for the EQ-5D was 0.058. For 12-month health status after PVI, a total of 57.9% improved, 31.4% experienced no change, and 10.7% worsened, relative to their preprocedural health status. Patients who were more likely to be nonresponders were more likely to have a history of carotid artery disease or were located at a U.S. enrolling center. The majority of patients reported improved or stable health status after femoral-popliteal PVI. Approximately 4 in 10 patients were nonresponders, with the highest risk for nonresponse including individuals with existing carotid disease or those undergoing PVIs in the U.S. vs non-U.S.

Impact of Clinical Trial Enrollment on Thrombolysis Workflow in a Mobile Stroke Unit: Results from the AcT Trial.

The Edmonton-based mobile stroke unit (MSU), which transports patients to the University of Alberta Hospital (UAH), enrolled patients in the Intravenous Tenecteplase Compared with Alteplase for Acute Ischemic Stroke (AcT) trial. We examined the feasibility of trial enrollment in MSU, its impact on acute stroke workflow metrics and functional outcomes at 90-120 days. In this post hoc analysis, patients were divided into three groups based on enrollment site: MSU (n = 43), UAH (n = 273) and non-UAH (n = 1261). All patients were enrolled with a deferred consent process. The primary outcome for this analysis was the feasibility of enrollment defined as the proportion of patients receiving intravenous thrombolysis (IVT) during the study period who were enrolled in the trial. Multiple linear and binary logistic regression was used to evaluate the adjusted effect of the study groups on acute stroke workflow metrics and functional outcomes at 90-120 days. 100% of eligible IVT-treated patients in the MSU during the study period were enrolled in the AcT trial. Covariate-adjusted linear regression showed shorter door-to-needle (17.2 [9.7-24.6] min) and CT-to-needle (10.7 [4.2-17.1] min) times in the MSU compared to UAH and non-UAH sites. There was no difference in the proportion of patients with an excellent functional outcome (mRS 0-1) at 90-120 days or symptomatic intracerebral hemorrhage (ICH) at 24 hours between groups. Enrollment in the AcT trial from the MSU was feasible. MSU-enrolled patients demonstrated faster door-to-needle and CT-to-needle times, resulting in earlier IVT administration and similar rates of symptomatic ICH.

Communication Bridge-2 randomized controlled trial: Recruitment and baseline features.

Non-pharmacological interventions may offer significant benefits to the quality of life for persons with primary progressive aphasia (PPA) and their care partners but have lacked efficacy trials. To help fill the efficacy gap, we provide the feasibility of recruitment, enrollment, randomization, and baseline data for the Communication Bridge-2 (CB2) randomized controlled trial (RCT). CB2 is the first international, single enrollment site, Phase 2, Stage 2, parallel-group, active control, RCT delivered via video chat to individuals with PPA and their care partners. Participants were recruited, screened, and randomized into one of two speech-language intervention arms. Ninety-five participant dyads (PPA mean baseline age: 67.1; 48% female) from four countries were enrolled and randomized. Global recruitment, enrollment, and randomization of individuals with PPA into a video chat-delivered non-pharmacologic RCT is feasible. This trial provides a potential model for conducting rigorous non-pharmacologic efficacy trials for Alzheimer's disease and related dementias. Primary progressive aphasia (PPA) negatively impacts communication participation. Communication Bridge-2 (CB2) is a telemedicine-delivered randomized controlled trial. CB2 included global recruitment and randomization of 95 PPA participant dyads. CB2, the first international superiority trial for PPA using video chat shows feasibility. The study provides a model for rigorous non-pharmacologic trials for Alzheimer's disease and related dementias.

Using Artificial Intelligence to Identify Three Presenting Phenotypes of Chiari Type-1 Malformation and Syringomyelia.

Chiari type-1 malformation (CM1) and syringomyelia (SM) are common related pediatric neurosurgical conditions with heterogeneous clinical and radiological presentations that offer challenges related to diagnosis and management. Artificial intelligence (AI) techniques have been used in other fields of medicine to identify different phenotypic clusters that guide clinical care. In this study, we use a novel, combined data-driven and clinician input feature selection process and AI clustering to differentiate presenting phenotypes of CM1 + SM. A total of 1340 patients with CM1 + SM in the Park Reeves Syringomyelia Research Consortium registry were split a priori into internal and external cohorts by site of enrollment. The internal cohort was used for feature selection and clustering. Features with high Laplacian scores were identified from preselected groups of clinically relevant variables. An expert clinician survey further identified features for inclusion that were not selected by the data-driven process. The feature selection process identified 33 features (28 from the data-driven process and 5 from the clinician survey) from an initial pool of 582 variables that were incorporated into the final model. A K-modes clustering algorithm was used to identify an optimum of 3 clusters in the internal cohort. An identical process was performed independently in the external cohort with similar results. Cluster 1 was defined by older CM1 diagnosis age, small syringes, lower tonsil position, more headaches, and fewer other comorbidities. Cluster 2 was defined by younger CM1 diagnosis age, more bulbar symptoms and hydrocephalus, small syringes, more congenital medical issues, and more previous neurosurgical procedures. Cluster 3 was defined by largest syringes, highest prevalence of spine deformity, fewer headaches, less tonsillar ectopia, and more motor deficits. This is the first study that uses an AI clustering algorithm combining a data-driven feature selection process with clinical expertise to identify different presenting phenotypes of CM1 + SM.

National Liver Cancer Screening Trial (TRACER) study protocol.

Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice. The National Liver Cancer Screening Trial is an adaptive pragmatic randomized phase IV trial, which began enrollment in January 2024, comparing ultrasound-based versus biomarker-based screening in 5500 patients with chronic hepatitis B infection or cirrhosis from any etiology. Eligible patients are randomly assigned in a 1:1 ratio to semi-annual screening with ultrasound ± alpha-fetoprotein (arm A) or semi-annual screening with GALAD (arm B). Randomization is stratified by enrollment site, liver disease severity (per Child-Pugh class), liver disease etiology (viral, nonviral, and noncirrhotic HBV), and sex. Patients are being recruited from 15 sites (a mix of tertiary care academic referral centers, safety-net health systems, and large community health systems) over a 3-year period, and the primary endpoint, reduction in late-stage HCC, will be assessed at the end of year 5.5. The results of this trial will inform the best strategy for HCC screening and early-stage detection in patients with chronic liver diseases. If GALAD shows superiority, HCC screening would primarily shift from an ultrasound-based strategy to the adoption of the biomarker panel. NCT06084234. The TRACER Study is actively enrolling.

A prediction model for the walking and balance milestone in Parkinson's disease

BackgroundWalking and balance impairments, represented by freezing of gait and falls, are significant contributors to disability in advanced Parkinson's disease (PD) patients. However, the composite measure of the Walking and Balance Milestone (WBMS) has not been thoroughly investigated. MethodsThis study included 606 early-stage PD patients from the Parkinson's Progression Markers Initiative (PPMI) database, with a disease duration of less than 2 years and no WBMS at baseline. Patients were divided into a model development cohort (70 %) and a validation cohort (30 %) according to the enrollment site. Longitudinal follow-up data over a period of 12 years were analyzed. ResultsAmong all 606 patients, the estimated probability of being WBMS-free at the 5th and 10th year was 88 % and 60 %, respectively. Five clinical variables (Age, Symbol Digit Modalities Test (SDMT), postural instability and gait difficulty (PIGD) score, Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part I (MDS-UPDRS-I) score, and REM Sleep Behavior Disorder (RBD) were used to construct the Cox predictive model. The C-index of the model was 0.75 in the development cohort and 0.76 in the validation cohort. By optimizing the PIGD and MDS-UPDRS-I variables, an easy-to-use model was achieved with comparable predictive performance. ConclusionA predictive model based on five baseline clinical measures (Age, SDMT, PIGD score, MDS-UPDRS-I score, RBD) could effectively estimate the risk of the WBMS in early PD patients. This model is valuable for prognostic counseling and clinical intervention trials for gait and balance impairment.

Barriers to hospital-at-home acceptance: a systematic review of reasons for patient refusal.

Hospital-at-home (H@H) models have gained recognition as a safe and potentially cost-effective solution for the current rising global healthcare needs. However, despite these models' potential, their adoption has been limited partly due to patients refusing care at home. This systematic review analyses the reasons behind their refusal. We searched five databases: Embase, Google Scholar, PubMed, Scopus, and Web of Science, limiting our search to papers from 2005 to 2024. Our search focused on papers reporting patient-provided reasons for declining treatment in a H@H setting without language or country restrictions. In addition to reasons for refusal, we extracted patient demographics and predictors for refusal to ensure a broad understanding of the factors influencing patient decisions. The quality of the studies included was evaluated using the Mixed Methods Appraisal Tool (MMAT) version 2018. From the 1,067 articles identified, seven met our inclusion criteria. The papers reported reasons from 418 patients participating in diverse H@H models from the United States, United Kingdom, Spain, and Singapore, primarily focusing on acute home-based care. The most common reasons for declination included concerns about model effectiveness, safety at home, preference for in-hospital care, physician advice, family burden, and visitor concerns. Additionally, common significant demographic factors associated with decliners were the enrollment site, partnership or marital status, risk of adverse outcomes, and previous healthcare utilization. Understanding patients' motivations for declining H@H is crucial for its successful implementation. Targeted communication strategies and collaboration between healthcare providers are paramount to ensure that patients understand the benefits and safety of H@H models. Future research should explore effective communication and engagement techniques to address patient apprehensions and broaden H@H adoption.

Trial Factors Associated With Completion of Clinical Trials Evaluating AI: Retrospective Case-Control Study.

Evaluation of artificial intelligence (AI) tools in clinical trials remains the gold standard for translation into clinical settings. However, design factors associated with successful trial completion and the common reasons for trial failure are unknown. This study aims to compare trial design factors of complete and incomplete clinical trials testing AI tools. We conducted a case-control study of complete (n=485) and incomplete (n=51) clinical trials that evaluated AI as an intervention of ClinicalTrials.gov. Trial design factors, including area of clinical application, intended use population, and intended role of AI, were extracted. Trials that did not evaluate AI as an intervention and active trials were excluded. The assessed trial design factors related to AI interventions included the domain of clinical application related to organ systems; intended use population for patients or health care providers; and the role of AI for different applications in patient-facing clinical workflows, such as diagnosis, screening, and treatment. In addition, we also assessed general trial design factors including study type, allocation, intervention model, masking, age, sex, funder, continent, length of time, sample size, number of enrollment sites, and study start year. The main outcome was the completion of the clinical trial. Odds ratio (OR) and 95% CI values were calculated for all trial design factors using propensity-matched, multivariable logistic regression. We queried ClinicalTrials.gov on December 23, 2023, using AI keywords to identify complete and incomplete trials testing AI technologies as a primary intervention, yielding 485 complete and 51 incomplete trials for inclusion in this study. Our nested propensity-matched, case-control results suggest that trials conducted in Europe were significantly associated with trial completion when compared with North American trials (OR 2.85, 95% CI 1.14-7.10; P=.03), and the trial sample size was positively associated with trial completion (OR 1.00, 95% CI 1.00-1.00; P=.02). Our case-control study is one of the first to identify trial design factors associated with completion of AI trials and catalog study-reported reasons for AI trial failure. We observed that trial design factors positively associated with trial completion include trials conducted in Europe and sample size. Given the promising clinical use of AI tools in health care, our results suggest that future translational research should prioritize addressing the design factors of AI clinical trials associated with trial incompletion and common reasons for study failure.

Cryo-PRO facilitates whole blood cryopreservation for single-cell RNA sequencing of immune cells from clinical samples.

Single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) has enhanced our understanding of host immune mechanisms in small cohorts, particularly in diseases with complex and heterogeneous immune responses such as sepsis. However, PBMC isolation from blood requires technical expertise, training, and approximately two hours of onsite processing using Ficoll density gradient separation ('Ficoll') for scRNA-seq compatibility, precluding large-scale sample collection at most clinical sites. To minimize onsite processing, we developed Cryo-PRO (Cryopreservation with PBMC Recovery Offsite), a method of PBMC isolation from cryopreserved whole blood that allows immediate onsite sample cryopreservation and subsequent PBMC isolation in a central laboratory prior to sequencing. We compared scRNA-seq results from samples processed using Cryo-PRO versus standard onsite Ficoll separation in 23 patients with sepsis. Critical scRNA-seq outputs including cell substate fractions and marker genes were similar for each method across multiple cell types and substates, including an important monocyte substate enriched in patients with sepsis (Pearson correlation 0.78, p<0.001; 70% of top marker genes shared). Cryo-PRO reduced onsite sample processing time from >2 hours to <15 minutes and was reproducible across two enrollment sites, thus demonstrating potential for expanding scRNA-seq in multicenter studies of sepsis and other diseases.

The Association Between Hypothyroidism and Cognitive Function Change in Women across the Menopause Transition: The Study of Women's Health Across the Nation.

Background: Patients treated for hypothyroidism with levothyroxine (LT4) monotherapy may present with persistent hypothyroidism symptoms, including cognitive symptoms, despite having a normal thyroid stimulating hormone (TSH) level. It remains unclear whether LT4 monotherapy is sufficient to normalize cognitive function outcomes over time. Methods: This is a multisite longitudinal study of a diverse group of women during midlife representing 5 ethnic/racial groups from 7 enrollment sites across the United States in the Study of Women's Health Across the Nation. Women were screened for a history of thyroid disease and the use of LT4. The study consisted of two primary groups: women with LT4-treated hypothyroidism and control women without thyroid disease. Each participant completed up to 9 cognitive assessments over the study period testing processing speed, working memory, and episodic memory (immediate and delayed recall). Multivariable generalized linear mixed models of scores for each cognitive assessment were developed to determine the association between LT4-treated hypothyroidism and cognitive function trajectories. Covariates included sociodemographic, clinical characteristics, and menopausal status (pre/early peri, late peri, and surgical/post). Sensitivity analyses were conducted to assess the impact of abnormal TSH levels and practice effects (i.e., improvements in scoring after repeated testing). Results: Of the 2033 women who were included in the study, 227 (11.2%) met criteria for LT4-treated hypothyroidism. At baseline, both processing speed and working memory scores were higher in LT4-treated women (mean processing speed scores: 56.5 vs 54.4; p value = 0.006; mean working memory scores: 6.8 vs 6.4; p value = 0.018). However, when considering the effect of LT4-treated hypothyroidism over time, there were no significant differences in the rate of cognitive decline (in any measure) between the hypothyroidism and control groups with or without covariate adjustment. The results were similar when considering LT4-treated women with abnormal TSH levels or after minimizing practice effects. Conclusions: We observed no difference in cognitive decline between women with LT4-treated hypothyroidism and women without thyroid disease. For similar aged patients with cognitive complaints, if thyroid function testing is normal, clinicians should consider causes other than inadequate thyroid hormone treatment to explain these symptoms.

Towards a Crisis Management Playbook: Hospice and Palliative Team Members’ Views Amid COVID-19

ContextThe critical role of hospice and palliative care in response to the COVID-19 pandemic is well recognized, but there is limited evidence to guide healthcare leadership through future crises. ObjectivesOur goal was to support future organizational resilience by exploring hospice and palliative team members’ perspectives on crisis leadership during the COVID-19 pandemic in New York City (NYC). MethodsThis qualitative descriptive study used individual, semi-structured interviews of purposively sampled interdisciplinary team members. Enrollment sites were two large NYC metro hospice care organizations and one outpatient palliative care practice. We asked participants to complete a demographic form and a 45–60 minute interview. We used descriptive statistics and thematic analysis, respectively, for data analysis. We triangulated the data by presenting preliminary study findings to a group of clinicians (n=21) from one of the referring organizations. ResultsParticipants (n=30) were professionally diverse (e.g., nurses, physicians, social workers, chaplains, administrators), experienced (mean=17 years; 10 years in hospice), and highly educated (83% ≥ master's degree). About half (n=15) self-identified as white, non-Hispanic, and nearly half (n=13) self-identified as being from a racial/ethnic minoritized group. Two (n=2) did not wish to self-identify. We identified four themes that reflected challenges and adaptive responses to providing care during a crisis: Stay Open and Stay Safe; Act Flexibly; Lead Adaptively; and Create a Culture of Solidarity. ConclusionWhile additional work is indicated, findings offer direction for a crisis management playbook to guide leadership in hospice, palliative care, and other healthcare settings in future crises.

Representation and Race in Adolescent Idiopathic Scoliosis Research: Disparities in Curve Magnitude and Follow-Up.

Prospective Cohort Study. The present study aims to determine if the racial representation of patients enrolled in a large prospective scoliosis registry is reflective of the general United States population. Further, we studied whether there was an association between race, pre-operative parameters, outcomes and loss to follow-up. Prospectively collected data for patients who underwent spinal fusion for adolescent idiopathic scoliosis (AIS) was reviewed, including self-reported race/ethnicity. The U.S. pediatric population and U.S. patients enrolled in the prospective registry were compared. The data obtained was analyzed for variations between races, for pre-operative variables and follow-up. Of the 2210 included patients in the registry 66% of patients reported as White, while 52% of the 2018 U.S. pediatric population reported as White. 15% of the registry reported as Hispanic/Latino compared to 22% of the U.S. pediatric population, 13% Black compared to 14% of the U.S. pediatric population, and 4% Asian compared to 5% of the U.S. pediatric population. Asian and White patients had statistically significant higher 2-year follow-up in all but one of six enrollment sites (P < 0.001). Native American, Other, and Hispanic/Latino patients had the highest BMIs. Native American and Black patients had the highest pre-op thoracic Cobb angles. Pre-op ages of Black, Hispanic, and Native American patients were statistically lower (P < 0.01). This study demonstrates the association between race and patient follow-up and pre-operative factors in patients who underwent surgery for AIS. Black, Native American, and Hispanic populations were underrepresented both at pre-op and follow-up when compared to their relative proportion in the U.S. pediatric population.

Association between low maternal serum aflatoxin B1 exposure and adverse pregnancy outcomes in Mombasa, Kenya, 2017-2019: Anested matched case-control study.

We examined the association between serum aflatoxin B1-lysine adduct (AFB1-lys) levels in pregnant women and adverse pregnancy outcomes (low birthweight, miscarriage and stillbirth) through a nested matched case-control study of pregnant women enroled at ≤28 weeks' gestation in Mombasa, Kenya, from 2017 to 2019. Cases comprised women with an adverse birth outcome, defined as either delivery of a singleton infant weighing <2500 g, or a miscarriage, or a stillbirth, while controls were women who delivered a singleton live infant with a birthweight of ≥2500 g. Cases were matched to controls at a ratio of 1:2 based on maternal age at enrolment, gestational age at enrolment and study site. The primary exposure was serum AFB1-lys. The study included 125 cases and 250 controls. The median gestation age when serum samples were collected was 23.0 weeks (interquartile range [IQR]: 18.1-26.0) and 23.5 (IQR: 18.1-26.5) among cases and controls, respectively. Of the 375 tested sera, 145 (38.7%) had detectable serum AFB1-lys: 36.0% in cases and 40.0% in controls. AFB1-lys adduct levels were not associated with adverse birth outcomes on multivariable analysis. Mid-upper arm circumference was associated with a 6% lower odds of adverse birth outcome for every unit increase (p = 0.023). Two-fifths of pregnant women had detectable levels of aflatoxin midway through pregnancy. However, we did not detect an association with adverse pregnancy outcomes, likely because of low serum AFB1-lys levels and low power, restricting meaningful comparison. More research is needed to understand the public health risk of aflatoxin in pregnant women to unborn children.

Interpreter usage and associations with latent tuberculosis infection treatment acceptance and completion in the USA among non-U.S.-born persons, 2012-2017.

Latent tuberculosis infection (LTBI) screening and treatment interventions that are tailored to optimize acceptance among the non-U.S.-born population are essential for U.S. tuberculosis elimination. We investigated the impact of medical interpreter use on LTBI treatment acceptance and completion among non-U.S.-born persons in a multisite study. The Tuberculosis Epidemiologic Studies Consortium was a prospective cohort study that enrolled participants at high risk for LTBI at ten U.S. sites with 18 affiliated clinics from 2012 to 2017. Non-U.S.-born participants with at least one positive tuberculosis infection test result were included in analyses. Characteristics associated with LTBI treatment offer, acceptance, and completion were evaluated using multivariable logistic regression with random intercepts to account for clustering by enrollment site. Our primary outcomes were whether use of an interpreter was associated with LTBI treatment acceptance and completion. We also evaluated whether interpreter usage was associated treatment offer and whether interpreter type was associated with treatment offer, acceptance, or completion. Among 8,761 non-U.S.-born participants, those who used an interpreter during the initial interview had a significantly greater odds of accepting LTBI treatment than those who did not use an interpreter. There was no association between use of an interpreter and a clinician's decision to offer treatment or treatment completion once accepted. Characteristics associated with lower odds of treatment being offered included experiencing homelessness and identifying as Pacific Islander persons. Lower treatment acceptance was observed in Black and Latino persons and lower treatment completion by participants experiencing homelessness. Successful treatment completion was associated with use of shorter rifamycin-based regimens. Interpreter type was not associated with LTBI treatment offer, acceptance, or completion. We found greater LTBI treatment acceptance was associated with interpreter use among non-U.S.-born individuals.

Rethinking Data Collection Methods During the Pandemic: Development and Implementation of CATI for the All of Us Research Program.

The All of Us Research Program is a longitudinal cohort study aiming to build a diverse database to advance precision medicine. The COVID-19 pandemic hindered the ability of participants to receive in-person assistance at enrollment sites to complete digital surveys. Therefore, the program implemented Computer-Assisted Telephone Interviewing (CATI) to facilitate survey completion remotely to combat the disrupted data collection procedures. In January 2021, All of Us implemented a 1-year CATI Pilot supporting 9399 participants and resulting in 16 337 submitted surveys. The pilot showed that CATI was successful in increasing survey completion and retention activities for the All of Us Research Program, given the additional remote support offered to participants. Given the success of the CATI Pilot, multimodal survey administration will continue.

Effect of human milk-based fortification in extremely preterm infants fed exclusively with breast milk: a randomised controlled trial

Mortality and severe morbidity remain high in extremely preterm infants. Human milk-based nutrient fortifiers may prevent serious complications and death. We aimed to investigate whether supplementation with human milk-based fortifier (HMBF), as compared to bovine milk-based fortifier (BMBF), reduced the incidence of the composite outcome of necrotising enterocolitis (NEC), sepsis, and mortality in extremely preterm infants exclusively fed human milk. In this multicentre, randomised controlled trial at 24 neonatal units in Sweden, extremely preterm infants born between gestational week 22+0 and 27+6 fed exclusively human breast milk (mother's own and/or donor milk), were randomly assigned (1:1) to receive targeted fortification with either HMBF or BMBF. Randomisation was conducted before the enteral feeds reached 100mL/kg/day, and was stratified by enrolment site, gestational age, singleton/twin, and sex. The allocation was concealed before inclusion, but after randomisation the study was not blinded for the clinical staff. For the NEC diagnosis, the study group was masked to an independent radiologist, and the final assessment of NEC and culture-proven sepsis was done by a blinded consensus panel review. The primary outcome was the composite of NEC stage II-III, culture-proven sepsis, and mortality from inclusion to discharge, no longer than postmenstrual week 44+0, in the intention-to-treat population (ClinicalTrials.gov, NCT03797157). Between February 21st, 2019, and May 21st, 2021, 229 neonates were randomly assigned (115 HMBF, 114 BMBF). After exclusion of one infant due to parents' withdrawal of consent, 228 infants were included in the intention-to-treat analysis. Of the 115 infants assigned to HMBF, 41 (35.7%) fulfilled the criteria of either NEC, sepsis, or death, compared with 39 (34.5%) of 113 infants assigned to BMBF (OR 1.05, 95% CI 0.61-1.81, p=0.86). Adverse events did not differ significantly between groups. Supplementation with HMBF, as compared with BMBF, did not reduce the incidence of the composite outcome of NEC, sepsis, or death. Our results do not support routine supplementation with HMBF as a nutritional strategy to prevent NEC, sepsis, or death in extremely preterm infants exclusively fed human milk. ALF grant, Prolacta Bioscience, Swedish Research Council, and Research Council for Southeast Sweden.

COVID-19 Convalescent Plasma Therapy: Long-term Implications.

The long-term effect of coronavirus disease 2019 (COVID-19) acute treatments on postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is unknown. The CONTAIN-Extend study explores the long-term impact of COVID-19 convalescent plasma (CCP) therapy on postacute sequelae of SARS-CoV-2 infection (PASC) symptoms and general health 18 months following hospitalization. The CONTAIN-Extend study examined 281 participants from the original CONTAIN COVID-19 trial (CONTAIN-RCT, NCT04364737) at 18 months post-hospitalization for acute COVID-19. Symptom surveys, global health assessments, and biospecimen collection were performed from November 2021 to October 2022. Multivariable logistic and linear regression estimated associations between the randomization arms and self-reported symptoms and Patient-Reported Outcomes Measurement Information System (PROMIS) scores and adjusted for covariables, including age, sex, race/ethnicity, disease severity, and CONTAIN enrollment quarter and sites. There were no differences in symptoms or PROMIS scores between CCP and placebo (adjusted odds ratio [aOR] of general symptoms, 0.95; 95% CI, 0.54-1.67). However, females (aOR, 3.01; 95% CI, 1.73-5.34), those 45-64 years (aOR, 2.55; 95% CI, 1.14-6.23), and April-June 2020 enrollees (aOR, 2.39; 95% CI, 1.10-5.19) were more likely to report general symptoms and have poorer PROMIS physical health scores than their respective reference groups. Hispanic participants (difference, -3.05; 95% CI, -5.82 to -0.27) and Black participants (-4.48; 95% CI, -7.94 to -1.02) had poorer PROMIS physical health than White participants. CCP demonstrated no lasting effect on PASC symptoms or overall health in comparison to the placebo. This study underscores the significance of demographic factors, including sex, age, and timing of acute infection, in influencing symptom reporting 18 months after acute hypoxic COVID-19 hospitalization.

Palliative Care Consultation and Family-Centered Outcomes in Patients With Unplanned Intensive Care Unit Admissions.

Context: Hospitalized patients who experience unplanned intensive care unit (ICU) admissions face significant challenges, and their family members have unique palliative care needs. Objectives: To identify predictors of palliative care consultation among hospitalized patients with unplanned ICU admissions and to examine the association between palliative care consultation and family outcomes. Methods: We conducted a prospective cohort study of patients with unplanned ICU admissions at two medical centers in Seattle, WA. This study was approved by the institutional review board at the University of Washington (STUDY00008182). Using multivariable logistic regression, we examined associations between patient characteristics and palliative care consultation. Family members completed surveys assessing psychological distress within 90 days of patient discharge. Adjusted ordinal probit or binary logistic regression models were used to identify associations between palliative care consultation and family symptoms of psychological distress. Results: In our cohort (n = 413 patients and 272 family members), palliative care was consulted for 24% of patients during hospitalization (n = 100), with the majority (93%) of these consultations occurring after ICU admission. Factors associated with palliative care consultation after ICU transfer included enrollment site (OR, 2.29; 95% CI: 1.17-4.50), Sequential Organ Failure Assessment score at ICU admission (OR, 1.12; 95% CI: 1.05-1.19), and reason for hospital admission (kidney dysfunction [OR, 7.02; 95% CI: 1.08-45.69]). There was no significant difference in family symptoms of depression or posttraumatic stress based on palliative care consultation status. Conclusions: For patients experiencing unplanned ICU admission, palliative care consultation often happened after transfer and was associated with illness severity, comorbid illness, and hospital site. Patient death was associated with family symptoms of psychological distress.

2895. Expanding PrEP by Embedding Navigators in High STI Testing Clinical Sites

Abstract Background Opportunities for PrEP continue to be missed in key populations. We established a PrEP navigation program (“SNAPS”) with the goals to (1) increase PrEP uptake among groups disproportionately impacted by HIV and (2) preserve and improve PrEP adherence in an NYC safety-net hospital setting.Table 1:Demographic Profiles For Pre-SNAPS and Post-SNAPS Individuals.Chi-squared or t-test approximation may be incorrect due to small sample size.Table 2.MPR for Post-SNAPS Individuals After 1 Year of Follow-up. Chi-squared or t-test approximation may be incorrect due to small sample size. Methods SNAPS consisted of 5 components: (1) Surveillance of clinical sites where STI testing is high but PrEP use is rare e.g., ED and Women’s Health Clinic (WHC), (2) Navigation for PrEP-eligible individuals (3) Accelerated follow-up with PrEP experts, (4) Point-of-care counseling and lab testing, and (5) Seamless longitudinal care. SNAPS launched 6/2019 with 2 full-time navigators. One year pre- vs post-SNAPS implementation we compared the sociodemographic profiles of PrEP initiators, their site of enrollment, and their medication possession ratios (MPRs), a proxy for PrEP adherence. Those on PrEP were a mixture of urgent and continuity care adults initiating PrEP at a safety-net hospital system. Bivariable analyses, employing Chi-square and t-test statistics, were conducted to compare sociodemographic profiles and MPR pre- vs post-SNAPS. Results We analyzed data on 274 (n=147 pre-SNAPS and n=127 post-SNAPS) individuals on PrEP. Compared to the pre-SNAPS period, post-SNAPS individuals were more likely to be cisgender women (33.9% vs 13.6%), Black or Latinx (84.3% vs 49.6%), uninsured (35.4% vs 29.3%), and Spanish speaking (58.3% vs 17.0%) (Table 1). Post-SNAPS individuals were more likely to be started on PrEP from the ED (51.2% vs 0%) or WHC clinic (10.2% vs 0%). Mean MPR for post-SNAPS was significantly lower than pre-SNAPS, 0.64 vs 0.89 (p &amp;lt; 0.001). Among post-SNAPS individuals, MSM were more likely to have higher MPRs compared to MSW and WSM individuals (Table 2). Furthermore, no difference in MPR was noted by race, preferred language, or insurance type. Conclusion SNAPS successfully identified and linked key populations historically missed for PrEP opportunities. Efforts to improve SNAPS should target medication adherence. Disclosures All Authors: No reported disclosures