Citations

Abstract Objectives Surface the urgent dilemma that healthcare delivery organizations (HDOs) face navigating the US Food and Drug Administration (FDA) final guidance on the use of clinical decision support (CDS) software. Materials and Methods We use sepsis as a case study to highlight the patient safety and regulatory compliance tradeoffs that 6129 hospitals in the United States must navigate. Results Sepsis CDS remains in broad, routine use. There is no commercially available sepsis CDS system that is FDA cleared as a medical device. There is no public disclosure of an HDO turning off sepsis CDS due to regulatory compliance concerns. And there is no public disclosure of FDA enforcement action against an HDO for using sepsis CDS that is not cleared as a medical device. Discussion and Conclusion We present multiple policy interventions that would relieve the current tension to enable HDOs to utilize artificial intelligence to improve patient care while also addressing FDA concerns about product safety, efficacy, and equity.

Background: Bystander cardiopulmonary resuscitation (BCPR) significantly improves survival from out-of-hospital cardiac arrest (OHCA). Telecommunicator CPR (TCPR) has been shown to increase BCPR rates, yet TCPR performance varies widely. We assess whether a bundled TCPR protocol, training, and continuous quality improvement (CQI) intervention improves TCPR performance. Methods: The intervention was implemented at a regional 9-1-1 dispatch center and had three main components: (1) the installation of the AHA-recommended 2-question TCPR protocol, (2) training to enhance telecommunicator OHCA recognition and (3) CQI with system and case-level feedback. Training included a two-hour lecture, 30 minutes of video training, and one hour of simulation training. Audio recordings of suspected OHCAs from pre (P1, 10/5/10 - 11/6/11) and post-intervention (P2, 11/7/11 - 11/4/13) periods were collected by searching center archives for calls originally processed as cardiac arrests. Recordings were analyzed according to six key TCPR metrics. Times to telecommunicator recognition of cardiac arrest, start of TCPR instructions, and initiation of chest compressions were measured using a standardized timestamp format. Results: Rates of OHCA recognition (80% to 95%, p<0.0001), TCPR instructions started (32% to 72%, p<0.0001), and bystander chest compressions initiated (18% to 70%, p<0.001) all increased significantly. Reductions in the time from call receipt to the start of TCPR instructions (176s to 133s, p<0.0001) and to the start of compressions (265s to 162s, p<0.0001) were also observed. Conclusion: This bundled protocol, training and CQI intervention was associated with a significant increase in TCPR rates and a reduction in the time to first chest compression.

Background: Bystander CPR (BCPR) and telephone CPR (TCPR) are associated with improved OHCA outcomes. It has been shown that BCPR increases the proportion of patients with an initial shockable cardiac rhythm (VF/VT) when encountered by EMS. It is unknown whether TCPR does the same. Objective: To assess whether TCPR is independently associated with an increase in initial shockable cardiac rhythms during OHCA. Methods: Data from 9-1-1 audio recordings, first care EMS reports and hospital records were linked for OHCAs of presumed cardiac origin (1/2011-12/2014). Three cohorts were analyzed: TCPR, BCPR or no CPR. Using no CPR as the reference group, we assessed whether TCPR and BCPR were independently associated with initial shockable rhythms in a logistic regression model controlling for gender, event location, witness status and EMS response interval. Results: After exclusions, 2715 adult OHCA events with linked outcome data were analyzed (median age: 63; male: 66.8%; 33.3% witnessed arrest). Median response interval was 5 min. The BCPR rate (lay rescuer CPR without telephone instructions) was 24.8% and survival in this group was 15.4%. The TCPR rate (lay rescuer CPR with telephone instructions) was 40.2% and survival in this group was 11.7%. For the no-CPR group, 20.5% had an initial shockable rhythm. For the BCPR group, 34.6 % had an initial shockable rhythm. For the TCPR group, 23.2% had an initial shockable rhythm. Provision of BCPR and of TCPR were each independently associated with shockable rhythms [aOR (BCPR) = 1.7, 95% CI: 1.33-2.17, p=0.0001; aOR (TCPR) = 1.3, 95% CI: 1.04-1.63, p=0.0001]. Conclusion: The provision of both BCPR and TCPR were independently associated with an increased rate of initial shockable cardiac rhythms and an increase in survival to hospital discharge compared to no CPR.

Abstract Background: Multi-cancer early detection (MCED) tests are being established as a novel approach to screen for multiple cancer types with one test. A blood-based MCED test using cell-free DNA targeted methylation patterns to detect a shared cancer signal and predict a cancer signal origin (CSO) has demonstrated feasibility. An initial return of results study (PATHFINDER; NCT04241796) reported performance of a refined version of the MCED test, including a 43.1% positive predictive value (PPV), 98.5% negative predictive value (NPV), 99.5% specificity, and 88.0% CSO accuracy. To build on this work, the PATHFINDER 2 study (NCT05155605) will evaluate safety and performance of the MCED test in larger, more diverse populations. Methods: PATHFINDER 2 is a prospective, multicenter, interventional study. Participants ≥50 years of age will be enrolled, with specific targets to improve diversity (age, sex, race/ethnicity) and few exclusions due to comorbid conditions. Exclusion criteria include current clinical suspicion of cancer or recent cancer/treatment (within 3 years). Participants will undergo blood draw for MCED testing, followed by return of results (cancer signal detection and CSO) to the investigator and diagnostic evaluations if a cancer signal is detected. A confirmatory PET-CT scan will be performed when CSO-directed workups do not result in a cancer diagnosis. Participants will be followed for approximately 3 years. Primary endpoints include 1) MCED test safety in terms of diagnostic testing triggered by a positive result (number/type of procedures and adverse events) and 2) test performance (PPV, NPV, specificity, sensitivity, CSO accuracy, cancer detection rate and number needed to screen). Secondary endpoints include participant reported outcomes (eg, anxiety), utilization of guideline-recommended cancer screening, and cancer detection rate of confirmatory PET-CT, amongst others. The study plans to enroll approximately 35,000 participants across North America. Sites were selected based on geographic location, catchment area demographics, and practice setting (academic vs non-academic). Enrollment targets for age, sex and race/ethnicity (White [non-Hispanic] 72%; Hispanic or Latino 11%; African American or Black 11%; Asian, Native Hawaiian or Other Pacific Islander 6%; American Indian/Alaska Native 1%) were derived from US Census data. Strategies to promote diverse recruitment include translation of participant-facing documents across multiple languages, participant and healthcare provider educational material, and site-led community outreach campaigns. MCED testing is an emerging, potentially paradigm-changing strategy in cancer screening, and PATHFINDER 2 is designed to characterize the safety, performance, and clinical implementation of the MCED test as a screening tool in a broad and representative population. Citation Format: Karthik V. Giridhar, Michael J. Demeure, Raymond H. Kim, Justin A. Chen, Shirish Gadgeel, Dax Kurbegov, Margarita Lopatin, Roland Matthews, Marc Matrana, Charles McDonnell, Donald Richards, Benjamin Rybicki, Gretchen Stipec, Nima Nabavizadeh. PATHFINDER 2: A prospective study to evaluate safety and performance of a multi-cancer early detection test in a population setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4784.

320 Background: sRT is used in men with prostate cancer (PC) recurrence following radical prostatectomy (RP) signaled by a persistent or delayed elevation in PSA. It was previously reported that the use of AAT with RT improved cancer control and overall survival (OS). Long-term follow-up (FU) results are presented here. Methods: From 1998to 2003, 760 eligible post-RP patients with Stage pT3N0 or with pT2N0 and positive margins and PSA from 0.2 to 4.0 ng/mL were randomly assigned on a double-blinded, placebo-controlled trial of RT + placebo vs. RT + anti-androgen therapy (AAT) (24 months of bicalutamide, 150mg daily) during and after RT (64.8 Gy in 36 fractions prostate bed). The primary endpoint was OS estimated using Kaplan-Meier method. Time to PC death and metastatic PC (competing risk of death without an event) was estimated using cumulative incidence. The hazard ratio (HR) was obtained using Cox models (OS) and subdistribution HRs (sHRs) used the Fine-Gray model (time to PC death and metastatic PC). All tests are one-sided based on study design. Results: Median FU for surviving patients was 19 years. OS at 18 years was 53% [95% confidence interval (CI): 47-58%] for RT + AAT and 43% [95% CI: 38-48%] for RT + placebo (adjusted HR 0.82 [95% CI: 0.67-1.00], p = 0.025). The 18-year incidence of centrally reviewed PC deaths were 18% [95% CI: 14-22%] RT + AAT and 28% [95% CI: 23-32%] RT + placebo (adjusted sHR = 0.57 [95% CI: 0.42-0.78], p<0.001). The 18-year incidence of metastatic PC was 22% [95% CI: 18-26%] and 31% [95% CI: 26-35%] for AAT and placebo arms respectively with adjusted sHR = 0.59 [95% CI: 0.44-0.80, p<0.001]. Subgroup analyses is shown in the Table. Conclusions: Long term results of 24-month duration AAT during and after sRT are consistent with the primary report with significantly improved long-term OS, reduced incidence of metastatic PC and PC death for RT+AAT. Statistically significant metastatic PC was noted for Gleason score 8-10, study entry PSA>1.5 and margin positive patients and borderline significance was observed in patients with study entry PSA 0.7-1.5. Clinical trial information: NCT00002874 . [Table: see text]

Study Design Cadaveric study. Objectives The purpose of this study was to compare a novel, integrated 3D navigational system (NAV) and conventional fluoroscopy in the accuracy, efficiency, and radiation exposure of thoracolumbar percutaneous pedicle screw (PPS) placement. Methods Twelve skeletally mature cadaveric specimens were obtained for twelve individual surgeons. Each participant placed bilateral PS at 11 segments, from T8 to S1. Prior to insertion, surgeons were randomized to the sequence of techniques and the side (left or right). Following placement, a CT scan of the spine was obtained for each cadaver, and an independent reviewer assessed the accuracy of screw placement using the Gertzbein grading system. Outcome metrics of interest included a comparison of breach incidence/severity, screw placement time, total procedure time, and radiation exposure between the techniques. Bivariate statistics were employed to compare outcomes at each level. Results A total of 262 screws (131 using each technique) were placed. The incidence of cortical breaches was significantly lower with NAV compared to FG (9% vs 18%; P = .048). Of breaches with NAV, 25% were graded as moderate or severe compared to 39% in the FG subgroup ( P = .034). Median time for screw placement was significantly lower with NAV (2.7 vs 4.1 min/screw; P = .012), exclusive of registration time. Cumulative radiation exposure to the surgeon was significantly lower for NAV-guided placement (9.4 vs 134 μGy, P = .02). Conclusions The use of NAV significantly decreased the incidence of cortical breaches, the severity of screw breeches, screw placement time, and radiation exposure to the surgeon when compared to traditional FG.

AbstractPurpose has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging–Dynamic Contrast‐Enhanced (OSIPI‐DCE) challenge was designed to benchmark methods to better help the efforts to standardize measurement.MethodsA framework was created to evaluate values produced by DCE‐MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' values, the applied software, and a standard operating procedure. These were evaluated using the proposed score defined with accuracy, repeatability, and reproducibility components.ResultsAcross the 10 received submissions, the score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0–1 = lowest–highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility.ConclusionsThis study reports results from the OSIPI‐DCE challenge and highlights the high inter‐software variability within estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real‐world clinical setting, many of these tools may perform differently with different benchmarking methodology.

Abstract Background The impact of ongoing efforts to decrease opioid use on patients with cancer remains undefined. Our objective was to determine trends in new and additional opioid use in patients with and without cancer. Methods This retrospective cohort study used data from Surveillance, Epidemiology, and End Results program–Medicare for opioid-naive patients with solid tumor malignancies diagnosed from 2012 through 2017 and a random sample of patients without cancer. We identified 238 470 eligible patients with cancer and further focused on 4 clinical strata: patients without cancer, patients with metastatic cancer, patients with nonmetastatic cancer treated with surgery alone (“surgery alone”), and patients with nonmetastatic cancer treated with surgery plus chemotherapy or radiation therapy (“surgery+”). We identified new, early additional, and long-term additional opioid use and calculated the change in predicted probability of these outcomes from 2012 to 2017. Results New opioid use was higher in patients with cancer (46.4%) than in those without (6.9%) (P &lt; .001). From 2012 to 2017, the predicted probability of new opioid use was more stable in the cancer strata (relative declines: 0.1% surgery alone; 2.4% surgery+; 8.8% metastatic cancer), than in the noncancer stratum (20.0%) (P &lt; .001 for each cancer to noncancer comparison). Early additional use declined among surgery patients (‒14.9% and ‒17.5% for surgery alone and surgery+, respectively) but was stable among patients with metastatic disease (‒2.8%, P = .50). Conclusions Opioid prescribing declined over time at a slower rate in patients with cancer than in patients without cancer. Our study suggests important but tempered effects of the changing opioid climate on patients with cancer.

Diabetes Technology Society organized an expert consensus panel to develop metrics for research in the use of continuous glucose monitors (CGMs) in a hospital setting. The experts met virtually in small groups both before and after an April 13, 2023 virtual meeting of the entire panel. The goal of the panel was to develop consensus definitions in anticipation of greater use of CGMs in hospital settings in the future. Establishment of consensus definitions of inpatient analytical metrics will be easier to compare outcomes between studies. Panelists defined terms related to 10 dimensions of measurements related to the use of CGMs including (1) hospital hypoglycemia, (2) hospital hyperglycemia, (3) hospital time in range, (4) hospital glycemic variability, (5) hospital glycemia risk index, (6) accuracy of CGM devices and reference methods for CGMs in the hospital, (7) meaningful time blocks for hospital glycemic goals, (8) hospital CGM data sufficiency, (9) using CGM data for insulin dosing, and (10) miscellaneous factors. The panelists voted on 51 proposed recommendations. Based on the panel vote, 51 recommendations were classified as either strong (43) or mild (8). Additional research is needed on CGM performance in the hospital. This consensus report is intended to support that type of research intended to improve outcomes for hospitalized people with diabetes.