US Academic Medical Centers Research Articles

Medical Decision-Making and Bereavement Experiences After Cardiac Arrest: Qualitative Insights From Surrogates.

Surrogates of incapacitated patients in the intensive care unit (ICU) face decisions related to life-sustaining treatments. Decisional conflict is understudied. To compare experiences of ICU surrogates by reported level of decisional conflict related to treatment decisions after a patient's cardiac arrest preceding death. Convergent mixed methods were used. Bereaved surrogates recruited from a single northeastern US academic medical center completed surveys including the low-literacy Decisional Conflict Scale (moderate-to-high cut point >25) and individual interviews about 1 month after the patient's death. Interview data were analyzed by directed and conventional content analysis. Surrogates were stratified by median total survey score, and interview findings were compared by decisional conflict level. Of 16 surrogates, 7 reported some decisional conflict (median survey score, 0; range, 0-25). About two-thirds decided to withdraw treatments. Three themes emerged from interviews: 2 reflecting decision-making experiences ("the ultimate act"; "the legacy of clinician communication") and 1 reflecting bereavement experiences ("I wish there was a handbook"). Surrogates reporting decisional conflict included those who first pursued but later withdrew treatments after a patient's in-hospital cardiac arrest. Surrogates with decisional conflict described suboptimal support, poor medical understanding, and lack of clarity about patients' treatment preferences. These findings provide insight into bereaved ICU surrogates' experiences. The low overall survey scores may reflect retrospective measurement. Surrogates who pursued treatment were underrepresented. Novel approaches to support bereaved surrogates are warranted.

Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma

AbstractCiltacabtagene autoleucel (cilta-cel) chimeric antigen receptor (CAR) T-cell therapy was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes with cilta-cel in the standard-of-care setting. Patients with RRMM who underwent leukapheresis for cilta-cel manufacturing between 1 March 2022 and 31 December 2022 at 16 US academic medical centers were included. In terms of results, 255 patients underwent leukapheresis and 236 (92.5%) received cilta-cel. Of patients who underwent leukapheresis, 56% would not have met the CARTITUDE-1 trial eligibility criteria. Manufacturing failure rates at first attempt and overall were 6% and 1%, respectively. The median of prior lines of therapy was 6. In treated patients (n = 236), cytokine release syndrome was seen in 75% (grade ≥3, 5%), immune effector cell–associated neurotoxicity syndrome in 14% (grade ≥3, 4%), and delayed neurotoxicity in 10%. Best overall and complete response or better rates were as follows: for patients who received infusion (n = 236), 89% and 70%; patients receiving conforming CAR T-cell product (n = 191), 94% and 74%; and conforming CAR T-cell product with fludarabine/cyclophosphamide lymphodepletion (n = 152), 95% and 76%, respectively. Nonrelapse mortality was 10%, most commonly from infection. After a median follow-up of 13 months from CAR T-cell therapy, the median progression-free survival (PFS) was not reached, with the 12-month estimate being 68% (95% confidence interval, 62-74). High ferritin levels, high-risk cytogenetics, and extramedullary disease were independently associated with inferior PFS, with a signal for prior B-cell maturation antigen–targeted therapy (P = .08). Second primary malignancies excluding nonmelanoma skin cancers were seen in 5.5% and myeloid malignancies/acute leukemia in 1.7%. We observed a favorable efficacy profile of standard-of-care cilta-cel in RRMM, despite more than half the patients not meeting the CARTITUDE-1 eligibility criteria.

Characterizing long-acting injectable antiretroviral therapy eligibility and initiation at a safety net academic medical center in the southeastern United States.

Background: Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) extends dosing intervals from daily to every 8weeks. Equitable implementation requires anticipating and addressing barriers to use. We described LAI-CAB/RPV eligibility and initiation among persons with HIV (PWH) receiving care at a Southeastern US academic medical center. Methods: We included PWH ≥18years, in care 01/01/2020-12/31/2021, and participating in the UNC CFAR HIV Clinical Cohort. We characterized LAI-CAB/RPV eligibility, compared those with and without recent detectable viral load (VL), and described clinical outcomes on LAI-CAB/RPV. Results: Among 1672 PWH, 425 (25.4%) had LAI-CAB/RPV drug-resistance. Among 1238 LAI-eligible PWH, 8.9% had detectable VL. Median age was 53 (interquartile range 40, 61), 54.6% were non-Hispanic Black, and 73.6% male. Over one-third lived >50 miles from clinic, one-fifth were uninsured, and 7.4% reported hazardous alcohol use. Gaps in care (prior 12-month) were more common among PWH with detectable VL versus suppressed (23.1% vs 13.9%, p = 0.03). 6/47 initiated LAI-CAB/RPV had detectable VL prior to injection; >95% sustained suppression and those with detectable VL had a rapid decline in viremia. Conclusions: Three-quarters of PWH were eligible for LAI-CAB/RPV, but equitable implementation may require addressing challenges such as distance to care, inconsistent care engagement, and other comorbid conditions, particularly for PWH with viremia.

Safety and Efficacy of Staged, Bilateral Focused Ultrasound Thalamotomy in Essential Tremor

Unilateral magnetic resonance-guided focused ultrasound ablation of ventralis intermedius nucleus of the thalamus for essential tremor reduces tremor on 1 side, but untreated contralateral or midline symptoms remain limiting for some patients. Historically, bilateral lesioning produced unacceptable risks and was supplanted by deep brain stimulation; increasing acceptance of unilateral focused ultrasound lesioning has led to interest in a bilateral option. To evaluate the safety and efficacy of staged, bilateral focused ultrasound thalamotomy. This prospective, open-label, multicenter trial treated patients with essential tremor from July 2020 to October 2021, with a 12-month follow-up, at 7 US academic medical centers. Of 62 enrolled patients who had undergone unilateral focused ultrasound thalamotomy at least 9 months prior to enrollment, 11 were excluded and 51 were treated. Eligibility criteria included patient age (22 years and older), medication refractory, tremor severity (Clinical Rating Scale for Tremor [CRST] part A score ≥2 for postural or kinetic tremor), and functional disability (CRST part C score ≥2 in any category). A focused ultrasound system interfaced with magnetic resonance imaging allowed real-time alignment of thermography maps with anatomy. Subthreshold sonications allowed target interrogation for efficacy and off-target effects before creating an ablation. Tremor/motor score (CRST parts A and B) at 3 months for the treated side after treatment was the primary outcome measure, and secondary assessments for efficacy and safety continued to 12 months. The mean (SD) population age was 73 (13.9) years, and 44 participants (86.3%) were male. The mean (SD) tremor/motor score improved from 17.4 (5.4; 95% CI, 15.9-18.9) to 6.4 (5.3; 95% CI, 4.9 to 7.9) at 3 months (66% improvement in CRST parts A and B scores; 95% CI, 59.8-72.2; P < .001). There was significant improvement in mean (SD) postural tremor (from 2.5 [0.8]; 95% CI, 2.3 to 2.7 to 0.6 [0.9]; 95% CI, 0.3 to 0.8; P < .001) and mean (SD) disability score (from 10.3 [4.7]; 95% CI, 9.0-11.6 to 2.2 [2.8]; 95% CI, 1.4-2.9; P < .001). Twelve participants developed mild (study-defined) ataxia, which persisted in 6 participants at 12 months. Adverse events (159 of 188 [85%] mild, 25 of 188 [13%] moderate, and 1 severe urinary tract infection) reported most commonly included numbness/tingling (n = 17 total; n = 8 at 12 months), dysarthria (n = 15 total; n = 7 at 12 months), ataxia (n = 12 total; n = 6 at 12 months), unsteadiness/imbalance (n = 10 total; n = 0 at 12 months), and taste disturbance (n = 7 total; n = 3 at 12 months). Speech difficulty, including phonation, articulation, and dysphagia, were generally mild (rated as not clinically significant, no participants with worsening in all 3 measures) and transient. Staged, bilateral focused ultrasound thalamotomy significantly reduced tremor severity and functional disability scores. Adverse events for speech, swallowing, and ataxia were mostly mild and transient. ClinicalTrials.gov Identifier NCT04112381.

Impact of changes in anaesthesia staff assignments on billing compliance, financial margins, and costs of anaesthesia services: development and application of a margin-cost estimation tool

BackgroundThe US Centers for Medicare and Medicaid Services provide guidelines for the coverage of anaesthesia residents and certified registered nurse anaesthetists (CRNAs) by anaesthesiologists. We tested the hypothesis that changes in the anaesthesia staffing model increase billing compliance. MethodsWe analysed 13 926 anaesthesia cases performed between September 2019 and November 2019 (baseline), and between September 2020 and November 2020 (after change in staff model) at a US academic medical centre using an estimation tool. The intervention was assignment of additional 12-h weekday CRNAs plus an additional anaesthesiologist who covered weekdays after 17:00, weekends, and holidays. The proportion of cases with billing compliant coverage (covered either by solo anaesthesiologist or anaesthesiologist covering two or fewer residents or four or fewer CRNAs) was analysed using logistic and segmented regression analyses. ResultsThe change in staff model was associated with a decrease in non-optimal anaesthesia staff assignments from 4.2% to 1.2% of anaesthesia cases (adjusted odds ratio 0.25; 95% confidence interval [CI] 0.20–0.32; P<0.001) and an increase in billable anaesthesia units of 0.6 per anaesthesia case (95% CI 0.4–0.8; P<0.001). An increased revenue margin associated with optimal staffing levels would only be achieved with salary levels at the 25th percentile of relevant benchmark compensation levels. Total staff overtime for all anaesthesia providers decreased (adjusted absolute difference −4.1 total overtime hours per day; 95% CI −7.0 to −1.3; P=0.004). ConclusionsImplementation of a change in anaesthesia staffing model was associated with improved billing compliance, higher billable anaesthesia units, and reduced overtime. The effects of the anaesthesia staff model on revenue and financial margin can be determined using our web-based margin-cost estimation tool.

Pancreatic Cancer Surveillance and Survival of High-Risk Individuals

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with increasing incidence. The majority of PDACs are incurable at presentation, but population-based screening is not recommended. Surveillance of high-risk individuals for PDAC may lead to early detection, but the survival benefit is unproven. To compare the survival of patients with surveillance-detected PDAC with US national data. This comparative cohort study was conducted in multiple US academic medical centers participating in the Cancer of the Pancreas Screening program, which screens high-risk individuals with a familial or genetic predisposition for PDAC. The comparison cohort comprised patients with PDAC matched for age, sex, and year of diagnosis from the Surveillance, Epidemiology, and End Results (SEER) program. The Cancer of the Pancreas Screening program originated in 1998, and data collection was done through 2021. The data analysis was performed from April 29, 2022, through April 10, 2023. Endoscopic ultrasonography or magnetic resonance imaging performed annually and standard-of-care surgical and/or oncologic treatment. Stage of PDAC at diagnosis, overall survival (OS), and PDAC mortality were compared using descriptive statistics and conditional logistic regression, Cox proportional hazards regression, and competing risk regression models. Sensitivity analyses and adjustment for lead-time bias were also conducted. A total of 26 high-risk individuals (mean [SD] age at diagnosis, 65.8 [9.5] years; 15 female [57.7%]) with PDAC were compared with 1504 SEER control patients with PDAC (mean [SD] age at diagnosis, 66.8 [7.9] years; 771 female [51.3%]). The median primary tumor diameter of the 26 high-risk individuals was smaller than in the control patients (2.5 [range, 0.6-5.0] vs 3.6 [range, 0.2-8.0] cm, respectively; P < .001). The high-risk individuals were more likely to be diagnosed with a lower stage (stage I, 10 [38.5%]; stage II, 8 [30.8%]) than matched control patients (stage I, 155 [10.3%]; stage II, 377 [25.1%]; P < .001). The PDAC mortality rate at 5 years was lower for high-risk individuals than control patients (43% vs 86%; hazard ratio, 3.58; 95% CI, 2.01-6.39; P < .001), and high-risk individuals lived longer than matched control patients (median OS, 61.7 [range, 1.9-147.3] vs 8.0 [range, 1.0-131.0] months; 5-year OS rate, 50% [95% CI, 32%-80%] vs 9% [95% CI, 7%-11%]). These findings suggest that surveillance of high-risk individuals may lead to detection of smaller, lower-stage PDACs and improved survival.

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression

The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD. To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT. This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians. Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks. Association between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses. Among the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment. In this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.

BCMA-directed CART therapy in patients with multiple myeloma and CNS involvement.

7519 Background: CART therapy represents a breakthrough in therapy for patients (ptns) with relapsed or refractory (R/R) multiple myeloma (MM). Pts with MM who have CNS involvement are commonly excluded from clinical trials and have limited therapeutic options. We evaluated the safety and efficacy of BCMA-directed CART therapies in ptns with MM and CNS involvement. Methods: 5 US academic medical centers contributed data to this retrospective analysis. 11 ptns with MM with CNS involvement received BCMA-directed CART (7 and 4 pts received ide-cel and cilta-cel, respectively). Results: Eight (72%) ptns were male, 3 (27%) had high-risk (HR) cytogenetics, and 10 (91%) had extramedullary disease (dz). Four (36%) ptns had brain/cranial nerve dz, 1 (9%) had spine dz, and 6 (55%) had both. CNS dz was evident on MRI in 100% of ptns and on CSF in 4 ptns (36%). Five ptns (45%) had ≤60 days between CNS diagnosis and CART therapy, 3 (27%) had &gt;300 days from CNS dz with 2 requiring CNS-directed therapy (CNS-Tx) close to CART during bridging, and 3 (27%) were diagnosed soon after CART infusion. Six (55%) ptns received CNS-Tx as part of bridging; radiotherapy (RT, 2 ptns), RT + intrathecal (IT) chemotherapy (chemo) (2 ptns), IT chemo (1 ptn), and surgery + RT (1 ptn). Five (45%) ptns didn’t receive CNS-Tx as part of bridging for the following reasons; 3 were diagnosed soon post CART and received RT post-infusion, 1 had recent chemo, and 1 was treated for CNS dz 587 days prior to CART and didn’t require CNS-Tx during bridging. Seven ptns (64%) had treated CNS dz at the time of lymphodepleting chemo. Nine (82%) ptns had grade (G) 1/2 CRS and none had G ≥3CRS. Two ptns (18%) had G1 ICANS, 1 (9%) had G3 ICANS, and none had G4 ICANS. Two ptns experienced delayed neurotoxicity post ide-cel, 1 with delayed lethargy that was treated with steroids, and the other with progressive multifocal leukoencephalopathy that was treated with steroids plus pembrolizumab. None had delayed parkinsonian side effects. With a median follow-up of 104 days post-infusion, the best responses achieved were 45% CR/sCR, 18% VGPR, 9% PR, with an overall response (ORR) of 73%. Seven ptns were evaluable for CNS responses by day 90 with a 100% CNS response rate defined by improved imaging findings or clearance of CSF involvement. CNS recurrence occurred in 1 ptn (9%) by day 172 while 5 (45%) had continued systemic response at last assessment. Conclusions: This study suggests that BCMA directed CART therapy in ptns with MM and CNS involvement is safe and feasible. Of the evaluable ptns for CNS response, 100% showed CNS response by day 90. Larger studies with longer follow up are needed to confirm these findings. [Table: see text]

Implementing nasal povidone-iodine decolonization to reduce infections in hemodialysis units: a qualitative assessment.

A substantial proportion of patients undergoing hemodialysis carry Staphylococcus aureus in their noses, and carriers are at increased risk of S. aureus bloodstream infections. Our pragmatic clinical trial implemented nasal povidone-iodine (PVI) decolonization for the prevention of bloodstream infections in the novel setting of hemodialysis units. We aimed to identify pragmatic strategies for implementing PVI decolonization among patients in outpatient hemodialysis units. Qualitative descriptive study. Outpatient hemodialysis units affiliated with five US academic medical centers. Units varied in size, patient demographics, and geographic location. Sixty-six interviewees including nurses, hemodialysis technicians, research coordinators, and other personnel. We conducted interviews with personnel affiliated with all five academic medical centers and conducted thematic analysis of transcripts. Hemodialysis units had varied success with patient recruitment, but interviewees reported that patients and healthcare personnel (HCP) found PVI decolonization acceptable and feasible. Leadership support, HCP engagement, and tailored patient-focused tools or strategies facilitated patient engagement and PVI implementation. Interviewees reported both patients and HCP sometimes underestimated patients' infection risks and experienced infection-prevention fatigue. Other HCP barriers included limited staffing and poor staff engagement. Patient barriers included high health burdens, language barriers, memory issues, and lack of social support. Our qualitative study suggests that PVI decolonization would be acceptable to patients and clinical personnel, and implementation is feasible for outpatient hemodialysis units. Hemodialysis units could facilitate implementation by engaging unit leaders, patients and personnel, and developing education for patients about their infection risk.

An Adaptive Behavioral Intervention for Weight Loss Management

Lifestyle interventions for weight loss are difficult to implement in clinical practice. Self-managed mobile health implementations without or with added support after unsuccessful weight loss attempts could offer effective population-level obesity management. To test whether a wireless feedback system (WFS) yields noninferior weight loss vs WFS plus telephone coaching and whether participants who do not respond to initial treatment achieve greater weight loss with more vs less vigorous step-up interventions. In this noninferiority randomized trial, 400 adults aged 18 to 60 years with a body mass index of 27 to 45 were randomized in a 1:1 ratio to undergo 3 months of treatment initially with WFS or WFS plus coaching at a US academic medical center between June 2017 and March 2021. Participants attaining suboptimal weight loss were rerandomized to undergo modest or vigorous step-up intervention. The WFS included a Wi-Fi activity tracker and scale transmitting data to a smartphone app to provide daily feedback on progress in lifestyle change and weight loss, and WFS plus coaching added 12 weekly 10- to 15-minute supportive coaching calls delivered by bachelor's degree-level health promotionists viewing participants' self-monitoring data on a dashboard; step-up interventions included supportive messaging via mobile device screen notifications (app-based screen alerts) without or with coaching or powdered meal replacement. Participants and staff were unblinded and outcome assessors were blinded to treatment randomization. The primary outcome was the between-group difference in 6-month weight change, with the noninferiority margin defined as a difference in weight change of -2.5 kg; secondary outcomes included between-group differences for all participants in weight change at 3 and 12 months and between-group 6-month weight change difference among nonresponders exposed to modest vs vigorous step-up interventions. Among 400 participants (mean [SD] age, 40.5 [11.2] years; 305 [76.3%] women; 81 participants were Black and 266 were White; mean [SD] body mass index, 34.4 [4.3]) randomized to undergo WFS (n = 199) vs WFS plus coaching (n = 201), outcome data were available for 342 participants (85.5%) at 6 months. Six-month weight loss was -2.8 kg (95% CI, -3.5 to -2.0) for the WFS group and -4.8 kg (95% CI, -5.5 to -4.1) for participants in the WFS plus coaching group (difference in weight change, -2.0 kg [90% CI, -2.9 to -1.1]; P < .001); the 90% CI included the noninferiority margin of -2.5 kg. Weight change differences were comparable at 3 and 12 months and, among nonresponders, at 6 months, with no difference by step-up therapy. A wireless feedback system (Wi-Fi activity tracker and scale with smartphone app to provide daily feedback) was not noninferior to the same system with added coaching. Continued efforts are needed to identify strategies for weight loss management and to accurately select interventions for different individuals to achieve weight loss goals. ClinicalTrials.gov Identifier: NCT02997943.

Neighborhood-Level Disadvantage and Delayed Adjuvant Therapy in Head and Neck Cancer

For patients with head and neck squamous cell carcinoma (HNSCC), initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is recommended by the National Comprehensive Cancer Network Guidelines and the Commission on Cancer. Although individual-level measures of socioeconomic status are associated with receipt of timely, guideline-adherent PORT, the role of neighborhood-level disadvantage has not been examined. To characterize the association of neighborhood-level disadvantage with delays in receiving PORT. This retrospective cohort study included 681 adult patients with HNSCC undergoing curative-intent surgery and PORT from 2018 to 2020 at 4 US academic medical centers. The data were analyzed between June 21, 2023, and March 5, 2024. The primary outcome was delay in initiating guideline-adherent PORT (ie, >6 weeks after surgery). Time-to-PORT (TTP) was a secondary outcome. Census block-level Area Deprivation Index (ADI) scores were calculated and reported as national percentiles (0-100); higher scores indicate greater deprivation. The association of ADI scores with PORT delay was assessed using multivariable logistic regression adjusted for demographic, clinical, and institutional characteristics. PORT initiation across ADI score population quartiles was evaluated with cumulative incidence plots and Cox models. Among 681 patients with HNSCC undergoing surgery and PORT (mean [SD] age, 61.5 [11.2] years; 487 [71.5%] men, 194 [29.5%] women) the PORT delay rate was 60.8% (414/681) and median (IQR) TTP was 46 (40-56) days. The median (IQR) ADI score was 62.0 (44.0-83.0). Each 25-point increase in ADI score was associated with a corresponding 32% increase in the adjusted odds ratio (aOR) of PORT delay (aOR, 1.32; 95% CI, 1.07-1.63) on multivariable regression adjusted for institution, age, race and ethnicity, insurance, comorbidity, cancer subsite, stage, postoperative complications, care fragmentation, travel distance, and rurality. Increasing ADI score population quartiles were associated with increasing TTP (hazard ratio of PORT initiation, 0.71; 95% CI, 0.53-0.96; 0.59; 95% CI, 0.44-0.77; and 0.54; 95% CI, 0.41-0.72; for ADI quartiles 2, 3, and 4 vs ADI quartile 1, respectively). Increasing neighborhood-level disadvantage was independently associated with a greater likelihood of PORT delay and longer TTP in a dose-dependent manner. These findings indicate a critical need for the development of multilevel strategies to improve the equitable delivery of timely, guideline-adherent PORT.

A Granular Approach to Optimal and Fair Patient Placement in Hospital Emergency Departments

Prolonged emergency department (ED) length of stay (LOS) is associated with detrimental effects on patient care quality and outcomes. There is evidence that certain groups of patients experience longer LOS based on their gender or race, especially with regard to the part of LOS that is attributable to waiting to be seen by a clinician. This work tackles the patient prioritization and placement aspects of ED operations with the goal of improving throughput and wait time in a fair, equitable way. We present a novel Mixed Integer Linear Programming (MILP) predictive-prescriptive formulation that incorporates a breakdown of predicted patient ED LOS into actionable pieces. We incorporate considerations for fairness and reformulate the MILP formulation into a compact and computationally tractable formulation that can be solved efficiently in real time. To deal with uncertainty, we propose a sampling-based solution, and provide provable guarantees regarding its convergence, stability and sample complexity. The proposed solution increases the throughput of the ED by [Formula: see text] and decreases the average wait time by [Formula: see text] compared to current hospital practice. In addition, the method is near-optimal in terms of throughput, and produces high-quality solutions in terms of average wait time compared to a clairvoyant oracle. Our proposed approach demonstrates desirable properties when it comes to fairness in patient prioritization, illustrating a path for addressing hidden biases in patient ED wait times and hospital operations as a whole. This work was conducted in collaboration with a large US academic medical center. Data from more than 40,000 patient visits were used to shape and evaluate the predictive-prescriptive models. An important practical contribution is translating a complex algorithm’s output into recommendations that can be operationalized in the context of existing processes in the ED. Specifically, we develop an interpretable metamodel that is trained to mimic the predictive-prescriptive algorithm’s decisions and provides a transparent set of rules for patient placement. The method will be used by the hospital to improve patient flow and quality of care as well as to support more fair and consistent bed allocation decisions.

Case Series of People With HIV on the Long-Acting Combination of Lenacapavir and Cabotegravir: Call for a Trial.

Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents. We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/- RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28-75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL <75 copies/mL) after starting LEN at a median (range) of 8 (4-16) weeks, with 16/34 (47%) suppressed at baseline. In this case series of 34 patients on LEN/CAB, high rates of virologic suppression (94%) were observed. Reasons for using LEN/CAB included adherence challenges and underlying resistance, mostly to NNRTIs. These data support a clinical trial of LEN/CAB among persons with NNRTI resistance.

Association Between Psychosocial Acuity and Glycemic Control in a Pediatric Type 1 Diabetes Clinic.

The purpose of this study was to describe the frequency of psychosocial risk and its associations with glycemic levels in youth with type 1 diabetes (T1D) seen by social work staff during regular clinical care. A retrospective longitudinal analysis of observational clinical data was conducted. Individuals (1-26 years) with known T1D who were seen at a pediatric diabetes clinic in a US academic medical center between 2014 and 2021 were included. Variables included psychosocial acuity, A1C, and demographic characteristics. Chi-square tests, Wilcoxon rank sum tests, and mixed linear regressions were used to examine associations between demographic variables, psychosocial acuity, and A1C. Of 966 patients, 513 (53.1%) were male, 76 (7.9%) were non-Hispanic Black, and 804 (83.2%) were non-Hispanic White. There was a mean of 6.9 annual social work encounters per patient, with 3 psychosocial domains measured at each visit. Results showed that as psychosocial acuity level increased, glycemic control decreased. There were significant differences in A1C according to race/ethnicity, insurance, age, and psychosocial acuity. In a real-world clinical population, psychosocial acuity was associated with glycemic control. Presenting for psychosocial issues in their diabetes clinic was associated with reduced glycemic control among youth with T1D. There is an opportunity to connect pediatric patients with appropriate mental health services and psychosocial supports.

Ethical and Professional Issues Encountered by Fourth-Year Medical Students during a Critical Care Clerkship before and during the COVID-19 Pandemic.

The objective of this study was to describe ethical and professional issues encountered and the ethical and professional values cited by medical students during their critical care clerkship, with a comparison of issues encountered before and during the coronavirus disease 2019 (COVID-19) pandemic. In this single-center, retrospective mixed-methods study, two investigators at a midwestern US academic medical center performed qualitative content analysis on reflections written by fourth-year medical students about ethical and professional issues encountered during their critical care rotations between March 2016 and September 2021. We also analyzed the ethical/professional values mentioned in their reflections. Descriptive and inferential (χ2) statistics were performed to examine differences in issues and values cited before and during the pandemic. Respondents highlighted several key themes identified in prior studies, including decision making (64.1%), communication between clinicians and families (52.2%), and justice-related issues (32.1%), as well as interdisciplinary communication (25.7%) and issues related to the role of students in the intensive care unit (6.1%). Six novel subthemes were identified in this group, predominantly related to resource availability and end-of-life care. Of 343 reflections, 69% were written before the pandemic. Analysis of ethical and professional issues before and during COVID were notable for several significant differences, including increased discussion of inadequate tools/supplies/equipment (1.3% before vs 17.6% during, P = 0.005) and/or access to care (3.9% before vs 17.6% during, P = 0.03) and increased concerns about the tension between law and ethics (21.2% before vs 41.2% during, P = 0.028). Primacy of patient welfare (49.8% before vs 47.2% during, P = 0.659) and patient autonomy (51.1% before vs 38.9% during, P = 0.036) were the most commonly cited ethical principles in both time frames, often discussed concurrently and in tension. Although the COVID-19 pandemic was associated with increased reflection by medical students about resources in the intensive care unit, their perception of ethical issues arising in critical illness remained largely focused on enduring challenges in shared decision-making. These findings should be considered when developing ethics curricula for critical care rotations.

Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network

BackgroundLeveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis.MethodsPatients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day.ResultsResponse rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (ORadj = 3.71 [95%CI = 1.34–10.24]; p = 0.012), > 25% decrease in UPCR from baseline to week 12 (ORadj = 2.61 [95%CI = 1.07–6.41]; p = 0.036), lower chronicity index (ORadj = 1.33 per unit decrease [95%CI = 1.10–1.62]; p = 0.003), and positive anti-dsDNA antibody (ORadj = 2.61 [95%CI = 0.93–7.33]; p = 0.069).ConclusionsCR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula

Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. ClinicalTrials.gov Identifier: NCT01534481.

The Resilient Youth Program: a promising skills-based online program for resiliency and stress management.

Prevention programs that target resilience may help youth address mental health difficulties and promote well-being during public health crises. To examine the preliminary efficacy of the Resilient Youth Program (RYP). The RYP was delivered remotely from a US academic medical centre to youth in the community via a naturalistic pilot study. Data from 66 youth (ages 6-18, Mage = 11.65, SD = 3.02) and their parents were collected via quality assurance procedures (May 2020 to March 2021). Pre/post-intervention child/parent-reported psychological and stress symptoms as well as well-being measures were compared via Wilcoxon signed rank tests. Child/parent-reported skills use data were collected. Among child-reported outcomes, there were significant decreases in physical stress (p = .03), anxiety (p = .004), depressive symptoms (p < .001) and anger (p = .002), as well as increased life satisfaction (p = .02). There were no significant differences in child-reported psychological stress (p = .06) or positive affect (p = .09). Among parent-reported child outcomes, there were significant decreases in psychological (p < .001) and physical stress (p = .03), anxiety (p < .001), depressive symptoms (p < .001), and anger (p < .002) as well as increased positive affect (p < .001) and life satisfaction (p < .001). Effect sizes ranged from small to medium; 77% of youth (73% of parents) reported using RYP skills. Age and gender were not associated with outcome change. The RYP may help reduce psychological/stress symptoms and increase well-being among youth; further research is needed.

The Impact of Chronic Comorbidities on Outcomes in Acute Exacerbations of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a chronic progressive lung disease of unknown cause with a high associated mortality. We aimed to compare the impact of chronic medical conditions on hospital outcomes of patients with acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). This was a retrospective cohort study using the NIS database from 2016 to 2018. We included patients aged 60 and older hospitalized in academic medical centers with the diagnoses of IPF and acute respiratory failure. We examined factors associated with hospital mortality and length of stay (LOS) using survey-weighted multivariate logistic and negative binomial regression. Out of 4975 patients with AE-IPF, 665 (13.4%) did not survive hospitalization. There was no difference in the mean age between survivors and non-survivors. Patients were more likely to be male, predominantly white, and have Medicare coverage. Most non-survivors were from households with higher median income. Hospital LOS was longer among non-survivors than survivors (9.4 days vs. 9.8 days; p < 0.001). After multivariate-logistic regression, diabetes was found to be protective (aOR 0.62, 95% CI 0.50-0.77; p < 0.0001) while chronic kidney disease (CKD) conferred a significantly higher risk of death after AE-IPF (aOR 6.85, 95% CI 1.90-24.7; p = 0.00). Our multivariate adjusted negative binomial regression model for LOS identified obesity (IRR 0.85, 95% CI 0.76-0.94; p ≤ 0.00) and hypothyroidism (IRR 0.90, 95% CI 0.83-0.98; p = 0.02) to be associated with shorter hospital LOS. Our results suggest that CKD is a significant contributor to hospital mortality in AE-IPF, and diabetes mellitus may be protective. Obesity and hypothyroidism are linked with shorter hospital LOS among patients hospitalized with AE-IPF in US academic medical centers.

Shift Volume Directly Impacts Neuroradiology Error Rate at a Large Academic Medical Center: The Case for Volume Limits.

Unlike in Europe and Japan, guidelines or recommendations from specialized radiological societies on workflow management and adaptive intervention to reduce error rates are currently lacking in the United States. This study of neuroradiologic reads at a large US academic medical center, which may hopefully contribute to this discussion, found a direct relationship between error rate and shift volume. CT and MR imaging reports from our institution's Neuroradiology Quality Assurance database (years 2014-2020) were searched for attending physician errors. Data were collected on shift volume specific error rates per 1000 interpreted studies and RADPEER scores. Optimal cutoff points for 2, 3 and 4 groups of shift volumes were computed along with subgroups' error rates. A total of 643 errors were found, 91.7% of which were clinically significant (RADPEER 2b, 3b). The overall error rate (errors/1000 examinations) was 2.36. The best single shift volume cutoff point generated 2 groups: ≤ 26 studies (error rate 1.59) and > 26 studies (2.58; OR: 1.63, P < .001). The best 2 shift volume cutoff points generated 3 shift volume groups: ≤ 19 (1.34), 20-28 (1.88; OR: 1.4, P = .1) and ≥ 29 (2.6; OR: 1.94, P < .001). The best 3 shift volume cutoff points generated 4 groups: ≤ 24 (1.59), 25-66 (2.44; OR: 1.54, P < .001), 67-90 (3.03; OR: 1.91, P < .001), and ≥ 91 (2.07; OR: 1.30, P = .25). The group with shift volume ≥ 91 had a limited sample size. Lower shift volumes yielded significantly lower error rates. The lowest error rates were observed with shift volumes that were limited to 19-26 studies. Error rates at shift volumes between 67-90 studies were 226% higher, compared with the error rate at shift volumes of ≤ 19 studies.