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Mobile health supported real-time guidance and debriefing for newborn resuscitation: A pilot study of LIVEBORN feedback
Full text linkBasic resuscitation practices, particularly bag-mask ventilation, reduce newborn deaths from respiratory depression. There is strong scientific premise for improving bag-mask ventilation with feedback strategies, but there are significant barriers to bedside feedback in low-resource settings. To address these barriers, we developed LIVEBORN, a mobile health application to support feedback for newborn resuscitations. LIVEBORN uses data on provider actions and the newborn’s condition entered in real-time by an observer to provide real-time guidance during resuscitation and support debriefing after resuscitation. In a pilot study, we designed and then evaluated strategies to incorporate LIVEBORN Feedback into clinical practice at two health facilities in the Democratic Republic of the Congo, with one facility allocated to real-time guidance and one to debriefing. Providers at each facility used a participatory research methodology called Trials of Improved Practices to design and refine their strategy prior to pilot testing. The primary outcome of the pilot study was the feasibility of observing resuscitation care with LIVEBORN, defined as the percentage of births observed using LIVEBORN with a threshold of at least 50% of births observed to achieve feasibility. We also evaluated usability with the System Usability Scale and explored midwives’ perceptions of LIVEBORN Feedback in focus group discussions. During the pilot test, we found both strategies to be feasible with 74% of births observed with LIVEBORN at the real-time guidance facility and 67% at the debriefing facility. The strategy was also sufficiently usable with a System Usability Scale median score of 68 (Q1 65, Q3 78). Midwives perceived LIVEBORN Feedback to be helpful and believed it could save lives, but sometimes disagreed with LIVEBORN Feedback’s guidance to ventilate. In conclusion, we identified context-specific, feasible strategies for incorporating LIVEBORN Feedback into clinical care. We are now evaluating the effectiveness of LIVEBORN Feedback in a randomized control trial
Implementation Challenges of a Multi-Center Financial Navigation Intervention: A Qualitative Analysis of Operational Process Data
Full text linkIntroduction The Lessening the Impact of Financial Toxicity (LIFT) intervention—a financial navigation intervention—demonstrated preliminary effectiveness. Scaling LIFT to an eight-site single-arm trial, however, posed implementation challenges that were not present in the single-site pilot study. Here, we analyze factors influencing LIFT implementation. Methods We used a deductive-inductive hybrid qualitative approach to analyze transcribed meeting recordings from 55 technical assistance (TA) and 23 peer support (PS) calls with financial navigators (FN). First, we deductively coded all implementation-relevant content into the five domains of the Consolidated Framework for Implementation Research (CFIR). We then inductively generated themes and sub-themes within each of the CFIR domains. Coder reliability was assessed at multiple points during coding via coder consensus. Results The qualitative analysis of nearly 78 h of TA and PS calls with FNs resulted in 18 themes and 91 sub-themes across the six CFIR domains. Outer setting themes (7 themes, 37 sub-themes) included institutional workforce problems, limited organizational resources for specific needs, and the unpredictability of external resource application success. Determinants in the inner setting (3 themes, 18 sub-themes) included existing clinical infrastructure and navigators’ competing responsibilities in the clinic. Determinants in the individual domain (2 themes, 11 sub-themes) were the navigator workload and the patient motivation to engage in LIFT. Determinants in the innovation domain (2 themes, 5 sub-themes) were the intervention structure (ie, sequence and timing of LIFT activities). The most common implementation strategies (ie, process; 4 themes, 23 sub-themes) were pacing intervention content to meet patient needs, reframing the study to appeal to patients, and changing intervention delivery (eg, allowing phone visits). Conclusions This analysis highlights the challenges of implementing FN across multiple oncology sites, with workforce and administrative barriers being key challenges. Operational process data such as TA and PS calls can provide valuable information to guide implementation.Plain Language Summary Cancer-related financial hardship is common, and financial navigation (FN) interventions such as the Lessening the Impact of Financial Toxicity (LIFT) program aim to mitigate financial hardship. While LIFT demonstrated preliminary effectiveness in a single-site pilot, scaling to eight oncology sites introduced new implementation challenges. This study examined factors influencing LIFT implementation across sites using qualitative analysis of 78 hours of transcribed recordings from 55 technical assistance and 23 peer support calls with financial navigators. Guided by the Consolidated Framework for Implementation Research (CFIR), we identified determinants across five domains: Outer setting, inner setting, individuals, process, and innovation. Eighteen themes and 91 sub-themes emerged. Outer setting factors included workforce shortages, limited institutional resources for patient needs (eg, housing), and the unpredictability of external financial aid. Inner setting factors involved existing clinical infrastructure and navigators’ competing clinical responsibilities. Individual-level factors included navigator workload and patient motivation to engage. Innovation-related factors centered on the structure and timing of LIFT activities, while process-related determinants included pacing intervention delivery, reframing LIFT to align with patient needs, and adapting delivery methods (eg, phone visits during COVID-19). Overall, findings highlight the breadth of implementation challenges when implementing financial navigation across multiple sites. Routine analysis of operational data can inform ongoing program tailoring and enhance financial navigation implementation in oncology care
BCMA-directed mRNA CAR-T cell therapy for myasthenia gravis: exploratory biomarker analysis of a placebo-controlled phase 2b trial
Full text linkChimeric antigen receptor (CAR)-T cell therapies have the potential to transform treatment of autoimmune disease by resetting the immune system. However, adoption of cell therapies in the autoimmune space is limited by hurdles such as inpatient administration, lymphodepletion and safety concerns around cytokine release syndrome and non-specific immunosuppression. RNA-based cell therapy has potential to address these limitations. Here we report prespecified exploratory analyses from a successful placebo-controlled, double-blind, randomized phase 2b trial in patients with generalized myasthenia gravis who received Descartes-08, an autologous, RNA-encoded anti-B cell maturation antigen (BCMA) CAR-T cell therapy. In 66.7% of patients (n = 10/15), transient targeting of BCMA with Descartes-08 administered in an outpatient setting without lymphodepletion resulted in durable clinical efficacy. Comparison of Descartes-08-treated (n ≤ 19) and placebo (n ≤ 15) cohorts by flow cytometry, serum profiling, multiplexing cytokine analysis and bulk/single-cell transcriptional analysis reveals a precision retuning of self-reactivity demonstrated by increased pro-immune function, decreased activity of BCMA+ plasma cells and plasmacytoid dendritic cells and reductions in disease-associated cytokines, such as IL-6. Furthermore, antibody and T cell receptor analysis revealed altered circulating repertoires of self-reactive antibodies and T cell clones among Descartes-08 participants. These effects occurred without immune suppression, indicated by the lack of decline in vaccine-specific antibodies or hypogammaglobulinemia. Our findings unveil a new type of immune reset and support the development of BCMA-targeted RNA cell therapies as a more accessible therapy for autoimmune diseases. ClinicalTrials.gov identifier: NCT04146051
Association of Intended Mode of Delivery With Neonatal and Maternal Outcomes at 22–25 Weeks of Gestation
Full text linkOBJECTIVE:
To compare the risk of neonatal and maternal morbidity and mortality among individuals who delivered between 22 and 25 weeks of gestation by intended mode of delivery.
METHODS:
This was a secondary analysis of an observational cohort including participants with a singleton pregnancy delivered by planned cesarean delivery or after a trial of labor from 22 0/7 to 25 6/7 weeks of gestation. This analysis was limited to those who received both antenatal steroids and neonatal resuscitation. The primary outcome was a composite of neonatal death or severe neonatal morbidity. Secondary outcomes included neonatal mortality and measures of neonatal and maternal morbidity. Multivariable logistic regression analyses were used to adjust for prespecified covariates.
RESULTS:
Among 277 eligible individuals, 149 (53.8%) had a planned cesarean delivery, and 128 (46.2%) had a trial of labor, of whom 12 (9.4%) delivered by cesarean. The two groups were similar except for more frequent hypertensive disorders (47.7% vs 26.6%, P<.001) and lower median birth weight (620 g versus 660 g, P=.02) among those with planned cesarean delivery. There was no difference in the primary neonatal composite outcome (73.8% vs 79.7%, adjusted odds ratio [AOR] 0.68, 95% CI, 0.35–1.33) between groups or secondary neonatal outcomes. Planned cesarean delivery was associated with a higher frequency of maternal sepsis (6.0% vs 1.6%, AOR 8.28, 95% CI, 1.32–51.8) and postpartum readmission (8.1% vs 0.8%, AOR 12.0, 95% CI, 1.48–97.5) compared with trial of labor. Other adverse maternal outcomes were more frequent among planned cesarean deliveries but were not statistically significant.
CONCLUSION:
In this multisite registry, there was no difference in composite neonatal mortality or severe morbidity based on the intended mode of delivery, as well as no difference in secondary neonatal outcomes. Planned cesarean delivery was associated with increased maternal morbidity
Hypoaminoacidemia and Pyroglutamic Aciduria: Potential Biomarkers in Malnutrition‐Related Hyperammonemia
Full text linkHyperammonemia is a medical emergency, and the cause must be identified quickly in order to treat appropriately. Malnutrition is a known risk factor for hyperammonemia; however, there are limited reliable lab indicators used to identify malnutrition. Early identification of the etiology of hyperammonemia is crucial to optimizing care, specifically reintroduction of appropriate amounts of protein into the diet. Herein, we discuss three patients with complex medical histories and clinical signs of malnutrition who presented with hyperammonemia. In all three patients, both hypoaminoacidemia and pyroglutamic aciduria were observed. Specifically, all patients had low tyrosine, tryptophan, methionine, and branched‐chain amino acids. Recognizing this biochemical pattern could result in more rapid initiation of supplementing protein, a primary tenet of treatment in malnutrition‐related hyperammonemia. We highlight the unique features of malnutrition‐related hyperammonemia, propose mechanisms to explain the pattern, and suggest a framework for managing these cases.SynopsisWe present three patients who underwent a metabolic work‐up for hyperammonemia, later found to have malnutrition‐related hyperammonemia and a biochemical pattern of hypoaminoacidemia and pyroglutamic aciduria suggesting that this pattern could be used to indicate the diagnosis earlier and therefore allow for more rapid initiation of protein supplementation
The Financialization of Modern Dentistry: A Meta-Analysis of Equity Arbitrage, Valuation Hierarchies, and the Consolidation Lifecycle
Full text linkThe United States dental industry is currently navigating a profound structural metamorphosis, transitioning from a fragmented landscape of independent owner-operators to a consolidated sector dominated by Dental Support Organizations (DSOs) and private equity sponsors. This meta-analysis synthesizes extensive data from 2024 through early 2026 to deconstruct the financial mechanisms driving this consolidation, with a specific focus on the phenomenon of equity arbitrage. The research posits that the primary driver of consolidation is not merely operational efficiency but a financial arbitrage opportunity created by the disparity in valuation multiples between singular clinical assets (trading at 4–6× EBITDA) and aggregated platforms (trading at 10–14× EBITDA). This report provides an exhaustive review of valuation functions, establishing a deterministic model for estimating practice value without the need for comprehensive audits. Furthermore, it analyzes the liquidity constraints facing solo practitioners, contrasting their extended "time-to-close" horizons against the capital velocity of DSOs. The findings indicate that while headline valuation multiples have stabilized following the inflationary pressures of 2023–2024, a significant bifurcation has emerged: premium, infrastructure-ready platforms command historical highs, while solo practices face increasing liquidity discounts and structural barriers to exit
A patient-centric paradigm and tool for clinical research: the DOOR is open.
Full text linkRandomized clinical trials are the gold standard for evaluating the benefits and harms of interventions and yet may not provide the evidence needed to inform medical decision-making, an ultimate goal for clinical research. Commonly used design and analysis approaches are often not suited to answer the most important questions to inform clinical practice, specifically how do resulting patient experiences, when comprehensively considering benefits and harms, compare between therapeutic alternatives? The standard approach of siloed analysis of one outcome at a time: (i) does not incorporate associations between multiple outcomes; (ii) does not recognize the cumulative nature of multiple outcomes in individual patients or recognize important gradations of global patient response; (iii) suffers from competing risk complexities during interpretation of individual outcomes; (iv) provides for ambiguous generalizability with respect to benefit:risk since efficacy and safety analyses are often conducted on different populations. Evaluation of treatment effect heterogeneity to identify subgroups for treatment or avoidance of treatment is typically evaluated based on a single efficacy or safety endpoint and rarely evaluated based on the overall benefit:risk. Methods that quantify and compare the patient experience are needed. The desirability of outcome ranking (DOOR) is a paradigm for the design, monitoring, analysis, interpretation, and reporting of clinical trials and other research studies based on patient-centric benefit:risk evaluation, developed to address these issues and advance clinical trial science. Aligning the clinical research strategy with the relevant question for clinical practice will enhance research applicability. Careful design and comprehensive analyses are critical for DOOR paradigm application. We provide a recommended statistical analysis plan for research studies implementing DOOR, describe its elements, and illustrate analysis application using examples. A freely available online tool for the recommended analyses and the design of studies implementing the DOOR paradigm is provided.ClinicalTrials.gov ID: NCT05641298
Streamlined Self-Collection Screening for Sexually Transmitted Infections and Human Papillomavirus
Full text linkKey Points Question What is the prevalence of human papillomavirus (HPV) and other sexually transmitted infections (STIs) with simultaneous testing of mailed self-collection kits in a population of low-income women? Findings In this secondary analysis of a randomized clinical trial including 327 intervention participants, nearly 1 in 6 participants tested positive for other STIs, the same rate as those positive for HPV. Meaning These findings suggest that streamlining testing for both HPV and other STIs may address multiple preventive care needs among underscreened women. This secondary analysis of a randomized clinical trial evaluates whether self-testing for chlamydia, gonorrhea, and trichomoniasis at the same time as human papillomavirus improves uptake of testing among underscreened women. Importance Human papillomavirus (HPV) self-collection increases cervical cancer screening uptake among women underscreened for cervical cancer, particularly those from marginalized low-income and racial and ethnic backgrounds. Underscreened women are also at high risk for other sexually transmitted infections (STIs) that can be similarly screened via self-collection. Objective To evaluate an intervention streamlining testing for other STIs alongside HPV self-collected samples among low-income women. Design, Setting, and Participants This is a secondary analysis of the My Body, My Test–3 study, a randomized clinical trial testing a mailed self-collection intervention to improve cervical cancer screening. The My Body, My Test–3 study was conducted from April 2016 to December 2019 in 22 counties in North Carolina among low-income women overdue for cervical cancer screening. This analysis included participants randomized to the trial intervention group with valid STI and HPV results. Data analysis occurred from October 2024 to February 2025. Intervention The intervention included a mailed self-collection kit and instructions to self-collect a cervicovaginal sample. Samples were tested for other STIs and HPV using the Aptima assay. Main Outcomes and Measures The primary outcome was a positive test result for other STIs (including chlamydia, gonorrhea, and trichomoniasis). A risk factor analysis was conducted to identify factors associated with testing positive for other STIs. Secondary outcomes included rate of follow-up care and perceptions of self-collection among participants with positive STI results. Results Among 327 participants (median [IQR] age, 42 [25-63] years; 38 [8.6%] Hispanic, 146 [44.7%] non-Hispanic Black, and 133 [40.7%] non-Hispanic White), 51 (15.6%) tested positive for other STIs and 51 (15.6%) tested positive for HPV; 7 (2.1%) tested positive for both. Risk factors for other STIs included non-Hispanic Black race and ethnicity compared with non-Hispanic White race and ethnicity (adjusted odds ratio [aOR], 4.1; 95% CI, 1.5-11.6), having 2 or more sexual partners in the last year compared with having none (aOR, 5.7; 95% CI, 1.0-31.4), single marital status compared with married or partnered status (aOR, 5.6; 95% CI, 1.1-27.9), and current smoking compared with none (aOR, 4.1; 95% CI, 1.7-10.4). Among participants who tested positive for other STIs, 34 (66.7%) received follow-up care. Most participants (130 [84.4%]) preferred testing for both HPV and other STIs in the future. Conclusions and Relevance In this secondary analysis of a randomized clinical trial of 327 participants, nearly 1 in 6 tested positive for other STIs via streamlined testing in a mailed HPV self-collection intervention. Self-collection may improve both cervical cancer and STI screening for women from marginalized backgrounds. Trial Registration ClinicalTrials.gov Identifier: NCT0265188
Prognostic Impact of RTK–RAS Alterations in FOLFOX-Treated Early-Onset Colorectal Cancer Revealed by Artificial Intelligence-Driven Precision Oncology
Full text linkBackground/Objectives: Early-onset colorectal cancer (EOCRC; diagnosed before age 50) is rising at an accelerated rate, with a disproportionate impact on underserved populations. While alterations in the receptor tyrosine kinase–RAS (RTK–RAS) signaling pathway play a fundamental role in colorectal cancer (CRC) biology, their prognostic significance in the setting of FOLFOX chemotherapy—particularly across different age groups and ancestral backgrounds—remains insufficiently characterized. We sought to characterize age-, ancestry-, and treatment-specific associations between RTK–RAS alterations and clinical outcomes using an AI-enabled precision oncology framework. Methods: We analyzed 2515 CRC cases, including 266 Hispanic/Latino (H/L) and 2249 non-Hispanic White (NHW) patients, stratified by age at onset, ancestry, and FOLFOX treatment status. Mutation frequencies were assessed using Fisher’s exact and chi-square tests, while overall survival was analyzed with Kaplan–Meier methods. The AI-HOPE and AI-HOPE–RTK–RAS conversational artificial intelligence platforms were used to integrate clinical, genomic, and treatment data via multi-parameter, natural language–based queries. Results: In early-onset Hispanic/Latino patients, ERBB2 and NF1 mutations occurred at significantly lower frequencies in FOLFOX-treated cases compared with untreated cases (p = 0.01 for both). In late-onset H/L patients, NTRK2 mutations were depleted in FOLFOX-treated tumors (p = 0.04). In untreated early-onset H/L patients, MAPK3 and NF1 mutations were enriched relative to NHW counterparts. Among early-onset NHW patients, IGF1R and ERRFI1 mutations were less frequent with FOLFOX exposure, while multiple RTK–RAS genes were reduced in FOLFOX-treated late-onset NHW patients. Survival analyses revealed worse overall survival in FOLFOX-untreated early-onset NHW patients with RTK–RAS alterations (p = 0.029), but improved survival in FOLFOX-treated late-onset NHW patients (p = 0.048). Conclusions: RTK–RAS pathway alterations demonstrate strong age-, ancestry-, and treatment-specific prognostic effects and may serve as precision biomarkers of differential chemotherapy response. AI-enabled analytics substantially accelerated integrative biomarker discovery, supporting their utility for advancing precision oncology in EOCRC
General approach to achieving electrochemical aptamer-based sensor sensitivity of buffer in blood plasma
Full text linkElectrochemical aptamer-based (E-AB) sensors enable the accurate measurement of target concentrations in complex matrices such as plasma or serum. However, to function effectively in these environments, the aptamers must resist nonspecific binding to proteins and other interferants. Many research literature and commercially available (“off-the-shelf”) aptamers, originally selected without consideration for biofluid compatibility, are prone to such nonspecific interactions, which diminish sensor output and compromise sensitivity. To address this challenge and expand the utility of existing aptamer sequences, we present a tunable, generalizable method to restore the EC50 of E-AB sensors in plasma to levels comparable to those in buffer. We validate this approach using three therapeutically relevant small molecules: the antiretroviral emtricitabine (FTC), the antibiotic tobramycin, and the antimalarial hydroxyquinoline. Applying our method, we recovered EC50 values of 11 ± 3 µM for FTC (buffer: 10.4 ± 0.6 µM), 281 ± 91 µM for tobramycin (buffer: 190 ± 16 µM), and 1.1 ± 0.6 µM for hydroxyquinoline (buffer: 900 ± 95 µM). This strategy should enable the broader application of published small-molecule-binding aptamers for biofluid measurements, regardless of their original selection conditions