PURPOSE OF REVIEW:High-quality research is essential to enhance the delivery and outcomes of supportive care for patients with cancer. In this review, we discuss key challenges and potential solutions for conducting supportive care clinical trials in oncology. RECENT FINDINGS:Structural barriers to supportive care research include limited infrastructure and investigators, insufficient funding, a paucity of foundational research, and a lack of standardized terminologies. Process barriers involve challenges in patient recruitment and retention, intervention design, control selection, and outcome assessments. Recognition of these barriers enables the development of targeted strategies to overcome them. Encouragingly, there is growing awareness of the importance of supportive care among investigators, clinicians, patients, and healthcare administrators, leading to an increase in research activity, funding, and publications. Research centers and professional organizations dedicated to supportive care are actively building capacity and fostering collaboration. Additionally, innovative study designs, personalized outcome measures, and multicenter research networks offer promising strategies to enhance both the quantity and quality of clinical trials. SUMMARY:Through interdisciplinary collaborations, we can continue to strengthen the infrastructure and refine the processes in supportive care trials. These efforts will help build a robust evidence base and ultimately improve outcomes for patients with cancer.

Accurate illness understanding is a necessary component of goal-concordant care. Few prior studies have investigated systematic screening for illness understanding. The objectives of this study were to determine the extent of agreement between patient-reported and oncologist-documented cancer treatment intent using systematic screening and to explore the association between such agreement and patient characteristics. We implemented illness understanding screening for patients who presented to our supportive care center (SCC). We compared patient responses regarding chance of cure and primary treatment goal on a survey administered at their initial consultation visit with the oncologist-documented treatment intent in the electronic health record. The analysis included 300 patients (mean age, 59 years); most were women (56

The coronavirus disease 2019 (COVID-19) pandemic highlights the importance of identifying high risk pathogens, defining the immunity gaps and developing preemptive vaccination strategies. Here, we establish a high-resolution surrogate virus neutralization test detecting neutralizing antibodies against multiple virus families simultaneously, demonstrating good concordance with traditional assays. Extensive serosurveillance of pre-pandemic sera from different continents reveals low prevalence human exposures to different beta-coronaviruses, and identifies individuals with prior exposure to ACE2-binding MERS-like viruses. Furthermore, COVID-19 vaccination induces significant cross-neutralizing antibodies against clade 1b, 1c, and 3 but not clade 1a sarbecoviruses. Similarly, MERS and Nipah convalescent sera neutralize cognate viruses but have limited cross-neutralization against other related merbecoviruses and henipaviruses that utilize DPP4 and ephrin B2 receptors. Finally, a cross-clade prime-and-boost vaccination strategy using antigenically distinct antigens could induce broadly neutralizing antibodies against related viruses beyond vaccine antigens, supporting broad-spectrum beta coronavirus vaccine development.

Home oxygen therapy is a well-accepted treatment for advanced respiratory disease; however, there are substantial evidence gaps and implementation challenges. The patient experience varies widely; oxygen therapy devices are often poorly matched to patient needs; and adherence is suboptimal. Recent clinical trials have failed to demonstrate positive outcomes of home oxygen therapy across a range of indications and patient groups, raising new questions regarding which patients will benefit. We convened a home oxygen therapy summit, bringing together experts in the fields of hypoxia biology, biomarkers, home oxygen therapy, behavioural science, and clinical trials, to identify the critical steps necessary to advance the science and practice of home oxygen therapy. Prescription of oxygen therapy depends on identification of hypoxaemia, with or without evidence of end-organ dysfunction. However, this does not acknowledge that hypoxaemia does not always yield hypoxia, and ignores adaptation to hypoxia. There is a pressing need for a hypoxia biomarker that is sensitive and specific, reflects the mechanisms of adaptation and maladaptation to chronic hypoxia, and is responsive to change with supplemental oxygen. Advances in research and clinical care will require more “usable” devices that meet the needs of patients and provide value for payers. Optimising oxygen devices will require new technologies with greater portability and greater capacity for oxygen delivery. Registry-based clinical trials may allow measurement of long-term outcomes and identification of patients most likely to benefit from oxygen therapy. Collaborations between patients, clinicians, researchers, payers and industry will be critical to drive this field forward.

Placebo effect is commonly observed in symptom management randomized clinical trials. However, there are currently no established predictive biomarkers of placebo response. We examined the patterns of association between placebo response and baseline plasma cytokine levels for 10 symptoms in patients with cancer. This is an exploratory analysis of the double-blind, randomized ABCD trial, which compared high-dose dexamethasone to placebo for dyspnea treatment in patients with cancer (clinicaltrials.gov; NCT03367156). The primary outcome was change in dyspnea intensity. Four plasma cytokines (TNF, IL-6, IL-8, and IL-10) and 10 Edmonton Symptom Assessment System symptoms were measured at baseline, day 7, and day 14. Generalized additive models and exploratory analyses were used to examine the patterns of association between baseline cytokine levels and symptom responses on day 7 and day 14 in placebo and dexamethasone groups. This analysis included data from 45 patients. In the placebo group, we observed a significant negative association (p < 0.05) between ≥ 1 of the measured cytokines’ baseline levels across multiple symptoms on day 7 (5/10 symptoms) and day 14 (3/10 symptoms), including appetite, drowsiness, nausea, and pain. Exploratory analysis revealed a negative association in the placebo group in 33/40 cytokine-symptom response combinations for day 7 (p < 0.001) and 29/40 combinations for day 14 (p = 0.006). Our preliminary findings suggest patients with high baseline cytokine levels may be less likely to report placebo response for multiple symptoms. Upon further confirmation, these findings may have implications for future clinical trial design. In this exploratory analysis, we observed that patients with cancer were less likely to report placebo response for multiple symptoms if they had higher levels of baseline cytokines. These preliminary findings have important potential implications for placebo-controlled clinical trials, including patient selection, design of interventional controls, and trial interpretation. Additionally, they invite further research on possible mechanistic links between inflammation and placebo effect.

PURPOSE:We previously found that baseline cytokine levels predicted dyspnea response to dexamethasone and placebo in patients with cancer. However, cytokine immunoassays are impractical for clinical applications, highlighting the need for alternative inflammatory biomarkers. We sought to examine the predictive value of albumin, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for dyspnea response to dexamethasone or placebo in patients with cancer. METHODS:This is a secondary analysis of the Alleviating Breathlessness in Cancer Patients with Dexamethasone randomized clinical trial in which patients with cancer and moderate-to-high dyspnea received either dexamethasone or matching placebo for 14 days. We used generalized additive models to examine associations between baseline albumin, NLR, and PLR and dyspnea numeric rating scale (NRS) response to dexamethasone or placebo. RESULTS:Clinical bloodwork was available for 63 patients. Both the dexamethasone and placebo groups had a significant decrease in dyspnea by day 14 (mean change -1.8 and -1.9, respectively), with no significant between-group differences (-0.1 [95% CI, -1.1 to 1.3]). In the dexamethasone group, lower baseline albumin was significantly associated with a greater reduction in dyspnea NRS (day 14 slope: +1.2, P = .05); in contrast, higher baseline albumin was significantly associated with a greater reduction of dyspnea NRS in the placebo group (day 14 slope: -3.0, P = .004). No associations were found between baseline NLR or PLR levels and dyspnea response to either dexamethasone or placebo. CONCLUSION:Hypoalbuminemia may be a potential differential biomarker of dyspnea response to dexamethasone and placebo. On further validation, these findings may facilitate future personalized clinical trial design and tailoring of dyspnea interventions.

BACKGROUND:People living with idiopathic pulmonary fibrosis (IPF) often experience rapid disease progression and high burden of distressing symptoms. Timely referral to specialist palliative care for people with IPF is uncommon. OBJECTIVES:This study aims to establish consensus on criteria that would prompt a referral to specialist palliative care for people living with IPF. METHODS:An international Delphi study was conducted over 3 online rounds between April and July 2025 to identify consensus among expert clinicians and researchers on the referral criteria for specialist palliative care for people living with IPF. Consensus was defined a priori as agreement of at least 70%. A focus group of people with lived experience of IPF or specialist palliative care was conducted to provide feedback on the relevance and acceptability of the putative referral criteria. RESULTS:Up to 46 expert panelists participated in the Delphi study. Panelists included physicians (78%-83%) and nurses (15%-20%) with specialist qualifications in respiratory (80%-84%) or palliative medicine (31%-35%). Consensus was reached on 17 major criteria and 40 minor criteria relating to "hospital utilization," "respiratory therapies," "symptom distress," "comorbidities," "exacerbation of IPF," "time-based factors," and "psychosocial factors." Focus group participants (n = 6) broadly concurred with the agreement rates from the panelists, albeit often leaning toward earlier indicators than those which reached final consensus as major criteria. CONCLUSIONS:Consensus referral criteria for specialist palliative care referral in IPF are presented, which emphasize comprehensive needs assessment and open communication between clinicians and patients. Future work is needed to examine the implementation of these criteria in clinical respiratory care.

PURPOSE:Despite evidence supporting the benefits of early referral to palliative care (PC), many patients with advanced cancer continue to experience delayed referral or no referral at all. This study evaluated trends in outpatient PC consultation over 7 years at a comprehensive cancer center and identified predictors of timely referral to PC. METHODS:We randomly selected 700 patients seen at our outpatient supportive care center (100 per year, 2017-2023). Demographics, cancer diagnosis, symptom burden, date of outpatient PC consultation, and survival status were retrieved from their electronic medical records. The primary outcome was overall survival (OS), defined as time from outpatient PC consultation to death or last follow-up. Timely referral to PC was defined as occurring ≥6 months before death or last follow-up from outpatient PC consultation. Univariable and multivariable logistic regression models identified predictors associated with timely referral. RESULTS:Among 700 patients (median age 62 years, 54% female, 92% with advanced cancer), the median OS increased from 9.3 months in 2017 to 31.7 months in 2021 (P = .0001). The median follow-up for living individuals at the data cutoff was 19.1 months. The median number of PC visits increased from 3 to 7 between 2017 and 2023. Four hundred forty-nine (72%) patients received timely referral. In multivariable analysis, timely referral was independently associated with male sex (odds ratio [OR], 1.85; P = .014), head and neck cancer (OR, 4.64; P < .001), hematologic malignancies (OR, 3.31; P = .013), lower pain (OR, 0.9; P = .008), lower anorexia (OR, 0.88; P = .001), year of consultation (OR, 1.12; P = .038), and better performance status (OR, 0.70; P = .006). CONCLUSION:This study reveals a gradual and consistent shift toward earlier PC referral at a comprehensive cancer center, demonstrating that timely referral to PC with a follow-up of 30+ months is possible.

OBJECTIVES:No studies examining clinical outcomes for patients transferred to an acute palliative care unit (APCU) from an intensive care unit (ICU) versus a non-ICU exist. The objectives were to determine the proportions and outcomes of patients being discharged alive from an APCU after being transferred from an ICU versus a non-ICU. METHODS:All patients transferred to our APCU from an ICU from 1 September 2021 to 31 August 2023 and an equally sized random sample of patients transferred from a non-ICU during the same period were identified. Demographics, clinical characteristics and outcomes were compared between the two groups. RESULTS:400 patients (214 ICU and 186 non-ICU) were included (mean age, 62 years (SD, 14.3); 51.3% women; 63.8% in a relationship; 67.8% white). Non-ICU patients were more likely to be discharged alive than were ICU patients (32.8% (95% CI 26.5 to 39.8%) vs 22.4% (95% CI 17.4 to 28.5%); p=0.02). Of the 109 patients discharged from our APCU, most went either to hospice care at home (54.1%, n=59) or to inpatient hospice care (40.4%, n=44), and there was no difference in discharge location between the ICU and the non-ICU groups (p=0.93). On multivariable analysis, APCU mortality was more likely in the group overall among patients who were receiving oxygen via a high-flow nasal cannula (HFNC) (OR, 2.47 (1.25 to 4.90); p=0.01). CONCLUSIONS:Despite the APCU mortality in this cohort being high, 22.4% of patients transferring from the ICU were successfully discharged to the community. HFNC use at the time of APCU transfer was independently associated with increased odds of APCU mortality.

OBJECTIVES:Immunocompromised status has been shown to be a risk factor for SARS-CoV-2 viral rebound. However, no studies have assessed the long-term clinical consequences of viral rebound in the immunocompromised population. This study aimed to examine the association of early viral rebound with postacute conditions among immunocompromised patients. METHODS:We conducted a retrospective cohort study using territory-wide electronic health records from the Hospital Authority and the Department of Health in Hong Kong. The study cohort consisted of immunocompromised adults aged 18 years or older who tested positive for SARS-CoV-2 between 26 February 2022 and 9 November 2023, and who were hospitalized with COVID-19. Patients were classified as having early viral rebound or not having early viral rebound based on the cycle threshold values within 21 days of the positive RT-PCR test result. The primary outcome was postacute all-cause inpatient death, evaluated starting from 21 days after the positive RT-PCR test. RESULTS:A total of 1296 immunocompromised adults were included in this study (46.4% [601 of 1296] were female; median [interquartile range] age, 68 [59-76] years). In all, 22.3% (289 of 1296) patients were categorized as having early viral rebound. Haematological malignancy was significantly associated with early viral rebound (hazard ratio 1.52, 95% CI 1.09-2.12, p 0.014). Early viral rebound was significantly associated with a higher risk of postacute inpatient death (hazard ratio 1.53, CI 1.16-2.02, p 0.002). CONCLUSIONS:This study demonstrated an association between early viral rebound and post-COVID mortality among immunocompromised individuals.

1505 Background: Patients with advanced cancer undergoing Phase I therapies often experience high symptom burden and complications, which may result in acute care encounters (i.e., emergency department [ED] visits and hospitalizations). Few studies have characterized these acute care encounters in Phase I patients. Furthermore, it is unclear if these encounters were avoidable and whether remote symptom monitoring (RSM) could reduce acute care utilization. We performed a secondary analysis of a randomized clinical trial to assess the impact of RSM on ED visits and hospitalizations in Phase I patients. Methods: This is a secondary analysis of a randomized clinical trial comparing specialist palliative care (SPC) alone and SPC+RSM in patients with advanced cancer enrolled in Phase I trials at MD Anderson Cancer Center. The key outcomes were the frequency of ED visits and hospitalizations over 6 months following enrollment. We documented the main presenting symptoms and reasons for acute care encounters. Additionally, two independent reviewers assessed whether these encounters were potentially avoidable, defined as whether timely outpatient involvement (e.g., nursing telephone call, clinic visit) could have prevented the encounter. We compared the outcomes between the two study groups using Fisher’s exact test. Results: Among 100 enrolled patients (mean age 64, 63% female, 33% gastrointestinal cancers, median survival 221 [95% CI 171, 271] days), 43 were in the SPC group and 57 were in the SPC+RSM group. 22/43 (51%) SPC patients and 30/57 (53%) SPC+RSM patients had at least one ED visit over 6 m (P=0.61, Table). 15/43 (35%) SPC patients and 21/57 (37%) had at least one hospitalization over 6 m (P=0.63, Table). Only 4/84 (5%) ED visits and 0/100 (0%) of the admissions were deemed avoidable. The most common presenting symptoms were pain (ED 27%, hospitalizations 30%) and respiratory distress (ED 23%, hospitalization 23%). The main reasons for acute care encounters were disease progression (ED 49%, hospitalizations 58%), acute complications (ED 26%, hospitalizations 28%) and treatment-related complications (ED 13%, admissions 11%). Conclusions: Phase I patients had high rates of ED visits and hospitalizations even when they were followed by SPC. The addition of RSM did not reduce the rates of these encounters. A vast majority of these visits were deemed unavoidable, attributed to disease progression and acute complications. These findings underscore the need for novel interventions to support Phase I patients as they navigate the acute care system near the end of life. Clinical trial information: NCT04989556 . Frequency of acute care utilization over 6 months in phase I patients. ED Visits ED Visits Hospitalizations Hospitalizations # of visits SPC n=43 (%) SPC+RSM n=57 (%) SPC n=43 (%) SPC+RSM n=57 (%) 0 21 (49) 27 (47) 25 (58) 36 (63) 1 16 (37) 16 (28) 14 (33) 12 (21) 2 4 (9) 8 (14) 3 (7) 7 (12) 3 1 (2) 5 (9) 1 (2) 1 (2) 4 0 0 0 0 5 1 (2) 1 (2) 0 1 (2)

INTRODUCTION:Exertional dyspnoea is highly debilitating. Previous single-dose studies found that prophylactic administration of fentanyl buccal tablet (FBT) improved exertional dyspnoea. In this randomised trial, we compared daily use of prophylactic FBT, oral morphine and placebo on exertional dyspnoea over 14 days. METHODS:This parallel, double-blind, randomised clinical trial enrolled opioid-tolerant patients with cancer and exertional dyspnoea. After a 5-day observation period, patients were randomised (1:1:1) to receive FBT, morphine or placebo 30 min before daily structured activity for 14 days. Shuttle walk tests (SWTs) were conducted on days 1/5/8/12/15/19. The primary outcome was change in modified Borg Scale dyspnoea intensity during SWTs from day 5 to day 19, analysed using a mixed effects model with treatment, time and treatment×time interaction. SWT distance was a key secondary outcome. RESULTS:67 patients were enrolled and 56 (84%) were randomised. Over the 14-day blinded phase, we observed a significant decrease in the magnitude of dyspnoea intensity change during the SWTs in all three groups, with no significant difference by treatment group (slope change from day 5 to day 19: FBT -2.2 (95% CI -2.9 to -1.6); morphine -1.9 (95% CI -2.7 to -1.2); placebo -2.2 (95% CI -3 to -1.4); time effect p<0.001, treatment×time effect p=0.79). SWT distance increased significantly over time (FBT +93 m; morphine +84 m; placebo +76 m) but did not differ by treatment (p=0.71). Few adverse events were reported. CONCLUSION:All three groups reported less dyspnoea while walking farther; however, no difference was detected between opioids and placebo. These findings should be considered preliminary given the underpowered sample. TRIAL REGISTRATION NUMBER:NCT04188418.

12102 Background: Serious illness conversations (SICs) are essential in aligning medical care with the values and goals of patients with advanced cancer. It is unclear if hematologic and solid tumors specialists (i.e., physicians [MDs] and advanced practice providers [APPs]) differ in their comfort level with SICs, which may drive end-of-life care outcomes. We compared the comfort level with SICs between hematologic and solid tumor specialists and examined contributing factors. Methods: We surveyed 186 hematology and 186 solid tumor specialists at MD Anderson Cancer Center. The 64-question survey examined their comfort with SICs under 5 domains (Transitions of Care [TOC, primary outcome], Dying Process [EOL], Prognosis, Goals, Advance Care Planning [ACP]). Responses were rated from 0 (extremely uncomfortable) to 10 (extremely comfortable). The TOC domain included 4 questions (i.e., stopping cancer therapy / transfusions / artificial nutrition and recommending hospice). We compared groups using simple linear and multivariable models accounting for specialist demographics. Results: 245 specialists completed this survey, with a response rate of 66%. Hematologic and solid tumor specialists both reported high comfort with TOC (7.0 [2.4] vs 7.1 [2.2]), with no significant difference between groups (mean difference [95% CI]: 0.1 [-0.5, 0.7]; P=0.78). In univariate analysis, APPs were significantly less comfortable with TOC than MDs among both hematologic (2 [1.2, 2.8]; P<0.0001) and solid tumor specialists (1.4 [0.7, 2.2]; P=0.001). In multivariate analysis, APPs remained the only significant variable associated with less comfort with TOC in hematologic (1.5 [0.4, 2.7]) and solid tumor groups (1.2 [0.2, 2.1]). Similarly, we found no significant difference between hematologic and solid tumor specialists in comfort level with the other 4 SIC domains and observed significant differences between APPs and MDs (Table). Conclusions: Both hematologic and solid tumor specialists reported high levels of comfort with SIC; however, APPs were significantly less comfortable. Given that APPs are increasingly involved in SIC, our study underscores the need to provide more training and support for APPs. Self-reported comfort levels for 5 SIC domains. Mean [SD] MD vs. APP Mean differences [95% CI]; p-value Domains Solid MD Solid APP Heme MD Heme APP Heme Solid TOC 7.8 [1.7] 6.4 [2.5] 8.1 [1.9] 6.1 [2.4] 2 [1.2,2.8]; <.0001 1.4 [0.7,2.2]; 0.001 Prognosis 8.5 [1.4] 7.1 [2.1] 8.6 [1.8] 6.8 [1.8] 1.9 [1.2,2.5]; <.0001 1.4 [0.8,2]; <.0001 Goals 8.5 [1.2] 7.8 [1.7] 8.9 [1.4] 7.5 [1.9] 1.4 [0.8,2]; <.0001 0.7 [0.1,1.2]; 0.09 EOL 7.9 [1.9] 6.3 [2.6] 8 [2.3] 6.2 [2.8] 1.8 [0.9,2.7]; 0.0005 1.6 [0.8,2.4]; 0.0009 ACP 8.6 [1.2] 7.2 [2.5] 9.1 [1.1] 7.3 [2.4] 1.7 [1,2.5]; <.0001 1.4 [0.7,2.1]; 0.0006

BACKGROUND:Accumulating evidence indicates that SARS-CoV-2 infection is associated with a broad spectrum of post-acute COVID sequelae, including diabetes. While nirmatrelvir/ritonavir and molnupiravir have demonstrated efficacy in reducing acute COVID-19 severity, their protective effects against post-COVID diabetes remain uncertain. In this study, we aimed to evaluate the effectiveness of these antiviral agents in reducing post-COVID diabetes risks, including new-onset diabetes in non-diabetic individuals and exacerbated diabetes in those with pre-existing diabetes. METHODS:We emulate target randomized controlled trials of COVID-19 antivirals in hospitalized patients who tested positive for SARS-CoV-2 between March 11, 2022, and October 10, 2023, in Hong Kong. Two analytic patient cohorts for assessing incident diabetes and exacerbation of diabetes for rehospitalization, including those with or without diabetes confirmed before the index date, were identified. Cloning, censoring, and weighting were used to emulate the target trials of nirmatrelvir/ritonavir and molnupiravir, involving treatment arm and control arm within each trial. Cause-specific Cox proportional hazard model and an extended form of Cox model for modeling recurrent hospitalizations were used to estimate the hazard ratio (HR) between arms in each trial, adjusting for baseline covariates. RESULTS:Among 88,643 hospitalized patients first time infected by SARS-CoV-2 identified, 35,997 and 18,865 eligible patients were included in the two analytic cohorts for the analysis on newly onset diabetes and exacerbated diabetes for rehospitalization, respectively. The median follow-up period ranged from 344 to 365 days across treatment and control arms of target trials. Compared with the no treatment arm, non-diabetic patients who received nirmatrelvir/ritonavir showed a significantly lower risk of post-COVID incident diabetes (HR: 0.75, 95% CI: 0.61 to 0.92). A reduced risk of diabetes rehospitalizations (HR: 0.70, 95% CI: 0.60 to 0.81) was observed among the diabetic patients. No significant associations were found for the use of molnupiravir and post-COVID diabetes outcomes. CONCLUSIONS:Our study demonstrates the effectiveness of nirmatrelvir/ritonavir in reducing the risks of post-acute COVID sequelae of diabetes in the hospitalized population, regardless of their diabetic status, whereas molnupiravir showed no significant benefit. Our findings offer valuable clinical insights for managing diabetes during the post-acute phase of SARS-CoV-2 infection.

Background:Dyspnea is one of the most distressing symptoms in patients with advanced cancer. Although systemic opioids are recommended as first-line pharmacologic treatment, 30-50% of patients do not achieve adequate relief. Midazolam is often used for persistent dyspnea despite opioid administration; however, robust evidence supporting its efficacy as a second-line treatment remains limited. Objectives:To evaluate the feasibility of a randomized controlled trial assessing the efficacy and safety of continuous subcutaneous midazolam infusion as second-line treatment for persistent dyspnea despite morphine administration in hospitalized patients with advanced cancer. Methods:A protocol for a multicenter, randomized, double-blind, placebo-controlled feasibility trial (J-SUPPORT2201/JORTC-PAL22) is described. The trial is being conducted at nine sites in Japan. Population:Participants are hospitalized adult patients with advanced cancer who are not receiving active anticancer treatment and who experience dyspnea at rest (Integrated Palliative Care Outcome Scale dyspnea score ≥2) despite continuous morphine infusion. Intervention/Control:Protocol treatment includes standardized morphine escalation plus continuous subcutaneous infusion of midazolam (9 or 6 mg/day for vulnerable patients) or placebo for 24 hours. Measurements:The primary endpoint is feasibility, defined as completion of protocol treatment at 24 hours. Secondary endpoints include dyspnea intensity, anxiety, rescue morphine use, communication, adverse events, and 30-day survival. Conclusions:This feasibility trial will provide methodological insights and preliminary clinical data regarding midazolam as a second-line option for persistent dyspnea despite morphine infusion in patients with advanced cancer and help design future confirmatory trials.

CONTEXT:Chatbots are increasingly used by the public, but their performance in answering questions about complex health topics, such as cannabis, is unknown. OBJECTIVES:To evaluate responses of three popular chatbots regarding cannabis and its use for cancer-related symptoms. METHODS:We asked ChatGPT, Google Gemini, and Microsoft Co-Pilot to answer questions about cannabis derived from the Centers for Disease Control website and American Society of Clinical Oncology guidelines regarding cannabis. Responses were collected on February 6, 2025. Six physicians with expertise in this field scored responses for accuracy and comprehensiveness (0-10 scale). Reliability of references was scored separately (0-10 scale). Readability was assessed using Flesch-Kincaid Grade Level, Flesch Reading Ease scores. RESULTS:Mean accuracy scores (SD) for ChatGPT, Gemini, and Co-Pilot were 9.0 (1.8), 8.8 (2.3), and 8.3 (2.3), respectively. Co-Pilot significantly underperformed in accuracy compared to ChatGPT (mean difference -0.62, 95% CI: -1.11, 0.14; P = 0.008). Mean comprehensiveness scores (SD) for ChatGPT, Gemini, and Co-Pilot were 8.1 (2.2), 8.5 (2.2), and 7.2 (2.4), respectively. ChatGPT and Gemini performed better than Co-Pilot in comprehensiveness (mean difference Co-Pilot vs. ChatGPT: -0.88 [95% CI: 1.34, -0.42; P < 0.001]; mean difference Co-Pilot vs. Gemini: -1.28 [95% CI: -1.74, -0.82; P < 0.001]). Inaccurate or misleading statements regarding cannabis formulations and symptom benefits were identified, with missing information on adverse effects and drug interactions. Gemini had the lowest reliability (4.1). Readability among all chatbots was poor. CONCLUSION:Despite overall high accuracy and comprehensiveness scores, chatbots made some misleading, inaccurate statements or missed information. For now, their answers should be interpreted with caution.

The next pandemic will likely be caused by a respiratory virus, due to the presence of many such viruses at the human-animal interface, their high rate of mutation (most being RNA viruses), and their high transmissibility. Despite the experience of the last pandemic, some problems will always be present when large populations encounter a novel respiratory virus for the first time.

INTRODUCTION:End-of-life delirium causes substantial distress for patients and families. Personalized sedation goals (PSGs) offer a patient-centered approach to delirium management by defining treatment targets based on caregiver preferences. We compared haloperidol, lorazepam, haloperidol plus lorazepam, and placebo in achieving caregiver-defined PSGs for agitated end-of-life delirium. METHODS:This preplanned secondary analysis used data from a multicenter, double-blind, double-dummy, parallel-group randomized clinical trial conducted from July 16, 2019, to June 8, 2023, with 30-day follow-up. Patients with advanced cancer and persistent agitation despite nonpharmacologic measures and standard-dose haloperidol were enrolled from three acute palliative care units in the United States and Taiwan. Participants received haloperidol dose escalation, lorazepam rotation, combination therapy, or placebo. Caregivers defined PSGs at enrollment. A personalized response was defined as a Richmond Agitation-Sedation Scale score within ±1 category of the PSG. RESULTS:Of 245 eligible patients, 111 were enrolled and 72 included in the primary analysis. Caregiver-defined PSGs were available for 67 patients included in this secondary analysis. At 24 hours, PSG achievement differed significantly across groups (p = 0.02): lorazepam 10/13 (76.9%), combination therapy 8/13 (61.5%), placebo 7/13 (53.8%), and haloperidol 3/14 (21.4%). Compared with haloperidol, lorazepam (odds ratio = 12.2; 95% CI = 2.0-75.1; p = 0.01) and combination therapy (odds ratio = 5.9; 95% CI = 1.1-32.0; p = 0.04) were more likely to achieve caregiver-defined PSGs. CONCLUSIONS:Lorazepam-based regimens were more likely than haloperidol alone to achieve caregiver-defined sedation goals, supporting their role in goal-concordant care for agitated end-of-life delirium.