Use of a Large Language Model to Assess Clinical Acuity of Adults in the Emergency Department.

Importance: The introduction of large language models (LLMs), such as Generative Pre-trained Transformer 4 (GPT-4; OpenAI), has generated significant interest in health care, yet studies evaluating their performance in a clinical setting are lacking. Determination of clinical acuity, a measure of a patient's illness severity and level of required medical attention, is one of the foundational elements of medical reasoning in emergency medicine. Objective: To determine whether an LLM can accurately assess clinical acuity in the emergency department (ED). Design, Setting, and Participants: This cross-sectional study identified all adult ED visits from January 1, 2012, to January 17, 2023, at the University of California, San Francisco, with a documented Emergency Severity Index (ESI) acuity level (immediate, emergent, urgent, less urgent, or nonurgent) and with a corresponding ED physician note. A sample of 10 000 pairs of ED visits with nonequivalent ESI scores, balanced for each of the 10 possible pairs of 5 ESI scores, was selected at random. Exposure: The potential of the LLM to classify acuity levels of patients in the ED based on the ESI across 10 000 patient pairs. Using deidentified clinical text, the LLM was queried to identify the patient with a higher-acuity presentation within each pair based on the patients' clinical history. An earlier LLM was queried to allow comparison with this model. Main Outcomes and Measures: Accuracy score was calculated to evaluate the performance of both LLMs across the 10 000-pair sample. A 500-pair subsample was manually classified by a physician reviewer to compare performance between the LLMs and human classification. Results: From a total of 251 401 adult ED visits, a balanced sample of 10 000 patient pairs was created wherein each pair comprised patients with disparate ESI acuity scores. Across this sample, the LLM correctly inferred the patient with higher acuity for 8940 of 10 000 pairs (accuracy, 0.89 [95% CI, 0.89-0.90]). Performance of the comparator LLM (accuracy, 0.84 [95% CI, 0.83-0.84]) was below that of its successor. Among the 500-pair subsample that was also manually classified, LLM performance (accuracy, 0.88 [95% CI, 0.86-0.91]) was comparable with that of the physician reviewer (accuracy, 0.86 [95% CI, 0.83-0.89]). Conclusions and Relevance: In this cross-sectional study of 10 000 pairs of ED visits, the LLM accurately identified the patient with higher acuity when given pairs of presenting histories extracted from patients' first ED documentation. These findings suggest that the integration of an LLM into ED workflows could enhance triage processes while maintaining triage quality and warrants further investigation.

"Should We Phenobarb-it-All?" A Phenobarbital-Based Protocol for Non-Intensive Care Unit Trauma Patients at High Risk of or Experiencing Alcohol Withdrawal.

BACKGROUND: Alcohol use is frequent in trauma patients and alcohol withdrawal syndrome (AWS) is associated with significant morbidity. Benzodiazepines are commonly used for AWS, but may cause neurologic and respiratory adverse events (AEs). The objective was to evaluate the effectiveness and safety of a phenobarbital-based protocol for the treatment of AWS in non-intensive care unit (ICU) trauma patients. METHODS: Adult non-ICU trauma patients at high risk of or experiencing AWS PRE and POST implementation of a phenobarbital-based protocol were included. Outcomes were AWS-related complications (AWS-RC), benzodiazepine use, adjunctive medication use, hospital length of stay (HLOS), and medication-related AEs. Subgroup analyses were performed on patients with traumatic brain injury (TBI), rib fractures, and at high risk of severe AWS. RESULTS: Overall, 110 patients were included (51 PRE, 59 POST). AWS-RC developed in 17 PRE patients compared to 10 POST patients (33% vs 17%; P = .05). PRE patients were more likely to receive benzodiazepines (88% vs 42%, P < .0001) and higher total dose (11 vs 4 mg lorazepam equivalent; P = .001). No difference noted in HLOS (8 vs 8 days, P = .27), adjunctive medication use (49% vs 54%, P = .60), or AEs (57% vs 39%, P = .06). There was no difference in AWS-RC in the TBI subgroup (P = .19), less AEs in the rib fracture POST subgroup (P = .04), and less AWS-RC in the high risk of severe AWS POST subgroup (P = .03). DISCUSSION: A phenobarbital-based protocol in trauma patients is effective in preventing AWS-RC and decreasing benzodiazepine use without increasing AEs.

P. aeruginosa CtpA protease adopts a novel activation mechanism to initiate the proteolytic process.

During bacterial cell growth, hydrolases cleave peptide cross-links between strands of the peptidoglycan sacculus to allow new strand insertion. The Pseudomonas aeruginosa carboxyl-terminal processing protease (CTP) CtpA regulates some of these hydrolases by degrading them. CtpA assembles as an inactive hexamer composed of a trimer-of-dimers, but its lipoprotein binding partner LbcA activates CtpA by an unknown mechanism. Here, we report the cryo-EM structures of the CtpA-LbcA complex. LbcA has an N-terminal adaptor domain that binds to CtpA, and a C-terminal superhelical tetratricopeptide repeat domain. One LbcA molecule attaches to each of the three vertices of a CtpA hexamer. LbcA triggers relocation of the CtpA PDZ domain, remodeling of the substrate binding pocket, and realignment of the catalytic residues. Surprisingly, only one CtpA molecule in a CtpA dimer is activated upon LbcA binding. Also, a long loop from one CtpA dimer inserts into a neighboring dimer to facilitate the proteolytic activity. This work has revealed an activation mechanism for a bacterial CTP that is strikingly different from other CTPs that have been characterized structurally.

Group B Streptococcus Infection and Obstetric Hemorrhage Risk.

OBJECTIVE: To elucidate the association between GBS infection and maternal risk for obstetric hemorrhage (OBH) and OBH-related morbidities (OBH-M). METHODS: This was a retrospective cohort study of all deliveries with a documented GBS status at a single large academic medical center from 2018 to 2019. GBS status was determined by either urine culture or rectovaginal culture collected during the antepartum period. The primary outcomes were quantitative blood loss (QBL), OBH, and a composite of OBH-M. Secondary outcomes were individual components of the OBH-M composite and frequency of hemorrhage-related interventions utilized intrapartum and postpartum. A stratified analysis was conducted examining only patients who were diagnosed intrapartum with an intrapartum intraamniotic infection (III). RESULTS: Of 4679 pregnant individuals who delivered a live infant between January 1, 2018 and January 1,2019 with a documented GBS status, 1,487 were identified as GBS positive (+) and 3192 were identified as GBS negative (-). The GBS + group did not have significantly higher QBL (p = 0.29) or rate of OBH (p = 0.35). There were no significant differences by GBS status in OBH morbidity (p = 0.79) or its individual components or frequency of individual pharmacologic or non-pharmacologic OBHrelated interventions. There were also no significant differences by GBS status among patients with an III. CONCLUSIONS FOR PRACTICE: GBS infection at the time of delivery was not associated with increased risk for OBH or OBH-M. Further research is needed to further explore the relationship between peripartum infections and OBH risk.

Characterisation of digital therapeutic clinical trials: a systematic review with natural language processing.

Digital therapeutics (DTx) are a somewhat novel class of US Food and Drug Administration-regulated software that help patients prevent, manage, or treat disease. Here, we use natural language processing to characterise registered DTx clinical trials and provide insights into the clinical development landscape for these novel therapeutics. We identified 449 DTx clinical trials, initiated or expected to be initiated between 2010 and 2030, from ClinicalTrials.gov using 27 search terms, and available data were analysed, including trial durations, locations, MeSH categories, enrolment, and sponsor types. Topic modelling of eligibility criteria, done with BERTopic, showed that DTx trials frequently exclude patients on the basis of age, comorbidities, pregnancy, language barriers, and digital determinants of health, including smartphone or data plan access. Our comprehensive overview of the DTx development landscape highlights challenges in designing inclusive DTx clinical trials and presents opportunities for clinicians and researchers to address these challenges. Finally, we provide an interactive dashboard for readers to conduct their own analyses.

Longitudinal brain structure changes in Parkinson's disease: A replication study.

CONTEXT: An existing major challenge in Parkinson's disease (PD) research is the identification of biomarkers of disease progression. While magnetic resonance imaging is a potential source of PD biomarkers, none of the magnetic resonance imaging measures of PD are robust enough to warrant their adoption in clinical research. This study is part of a project that aims to replicate 11 PD studies reviewed in a recent survey (JAMA neurology, 78(10) 2021) to investigate the robustness of PD neuroimaging findings to data and analytical variations. OBJECTIVE: This study attempts to replicate the results in Hanganu et al. (Brain, 137(4) 2014) using data from the Parkinson's Progression Markers Initiative (PPMI). METHODS: Using 25 PD subjects and 18 healthy controls, we analyzed the rate of change of cortical thickness and of the volume of subcortical structures, and we measured the relationship between structural changes and cognitive decline. We compared our findings to the results in the original study. RESULTS: (1) Similarly to the original study, PD patients with mild cognitive impairment (MCI) exhibited increased cortical thinning over time compared to patients without MCI in the right middle temporal gyrus, insula, and precuneus. (2) The rate of cortical thinning in the left inferior temporal and precentral gyri in PD patients correlated with the change in cognitive performance. (3) There were no group differences in the change of subcortical volumes. (4) We did not find a relationship between the change in subcortical volumes and the change in cognitive performance. CONCLUSION: Despite important differences in the dataset used in this replication study, and despite differences in sample size, we were able to partially replicate the original results. We produced a publicly available reproducible notebook allowing researchers to further investigate the reproducibility of the results in Hanganu et al. (2014) when more data is added to PPMI.

Association between duration of intrapartum oxytocin exposure and obstetric hemorrhage.

PURPOSE: Prolonged duration of intrapartum oxytocin exposure is included as a risk factor within widely adopted obstetric hemorrhage risk stratification tools. However, the duration of exposure that confers increased risk is poorly understood. This study aimed to assess the association between duration of intrapartum oxytocin exposure and obstetric blood loss, as measured by quantitative blood loss, and hemorrhage-related maternal morbidity. METHODS: This was a retrospective cohort study of all deliveries from 2018 to 2019 at a single medical center. We included patients who had received any intrapartum oxytocin, and we categorized them into 1 of 5 groups: > 0-2, ≥ 2-4, ≥ 4-6, ≥ 6-12, and ≥ 12 h of intrapartum oxytocin exposure. The primary outcomes were mean quantitative blood loss, proportion with obstetric hemorrhage (defined as quantitative blood loss ≥ 1000 mL), and proportion with obstetric hemorrhage-related morbidity, a composite of hemorrhage-related morbidity outcomes. Secondary outcomes were hemorrhage-related pharmacologic and procedural interventions. A stratified analysis was also conducted to examine primary and secondary outcomes by delivery mode. RESULTS: Of 5332 deliveries between January 1, 2018 and December 31, 2019 at our institution, 2232 (41.9%) utilized oxytocin for induction or augmentation. 326 (14.6%) had exposure of > 0-2 h, 295 (13.2%) ≥ 2-4 h, 298 (13.4%) ≥ 4-6 h, 562 (25.2%) ≥ 6-12 h, and 751 (33.6%) ≥ 12 h. Across all deliveries, there was higher mean quantitative blood loss (p < 0.01) as well as increased odds of obstetric hemorrhage (adjusted odds ratio [aOR] 1.52, 95% confidence interval [CI] 1.21-1.91) for those with ≥ 12 h of oxytocin compared to all groups between > 0-12 h of exposure. In our stratified analysis, ≥ 12 h of oxytocin exposure was associated with higher mean quantitative blood loss (p = 0.04) and odds of obstetric hemorrhage in vaginal deliveries (aOR 1.47, 95% CI: 1.03-2.11), though not in cesarean deliveries (aOR 1.16, 95% CI 0.82-1.62). There were no differences in proportion with obstetric hemorrhage-related morbidity across all deliveries (p = 0.40) or in the stratified analysis. CONCLUSION: Intrapartum oxytocin exposure of ≥ 12 h was associated with increased quantitative blood loss and odds of obstetric hemorrhage in vaginal, but not cesarean, deliveries.

Defining 'obstetric haemorrhage': Blood loss volume and severe morbidity.

AIMS AND OBJECTIVES: Our goal is to describe the association between total quantitative blood loss (QBL) and risk of obstetric haemorrhage-related morbidity (OBH-M) to assess the utility of the current definition of obstetric haemorrhage (OBH). METHODS: This was a retrospective cohort study completed of all patients who had a live delivery at the only urban safety-net hospital over a 2-year period from 2018 to 2019. We categorized deliveries into 10 equally sized deciles based on QBL and compared the proportion with OBH-M in each. Among the two deciles with the highest proportions of OBH-M, we stratified deliveries into seven groups of ascending intervals of 250cc QBL. Finally, we compared the positive predictive value (PPV) of the standard definition of OBH (QBL ≥ 1000cc) to a definition extrapolated from our stratified analysis. The primary outcome was proportion of deliveries within each QBL decile affected by OBH-M. The secondary outcome was PPV. RESULTS: We found a significant increase in OBH-M from decile 9 (895-1201cc QBL) to decile 10 (1205-8325cc QBL) (p < 0.001). In our stratified analysis, we found QBL of 1500cc to be an inflection point for an increased proportion of OBH-M. Our secondary analysis showed an increased PPV for OBH-M using QBL of 1500cc (20.5%) compared with that of QBL 1000cc (9.8%). CONCLUSIONS: Our findings suggest that a higher QBL threshold than the currently accepted definition of OBH is more predictive of OBH-M.

Joint Efforts of Replicative Helicase and SSB Ensure Inherent Replicative Tolerance of G-Quadruplex.

G-quadruplex (G4) is a four-stranded noncanonical DNA structure that has long been recognized as a potential hindrance to DNA replication. However, how replisomes effectively deal with G4s to avoid replication failure is still obscure. Here, using single-molecule and ensemble approaches, the consequence of the collision between bacteriophage T7 replisome and an intramolecular G4 located on either the leading or lagging strand is examined. It is found that the adjacent fork junctions induced by G4 formation incur the binding of T7 DNA polymerase (DNAP). In addition to G4, these inactive DNAPs present insuperable obstacles, impeding the progression of DNA synthesis. Nevertheless, T7 helicase can dismantle them and resolve lagging-strand G4s, paving the way for the advancement of the replication fork. Moreover, with the assistance of the single-stranded DNA binding protein (SSB) gp2.5, T7 helicase is also capable of maintaining a leading-strand G4 structure in an unfolded state, allowing for a fraction of T7 DNAPs to synthesize through without collapse. These findings broaden the functional repertoire of a replicative helicase and underscore the inherent G4 tolerance of a replisome.

An inhibitor/anti-inhibitor system controls the activity of lytic transglycosylase MltF in Pseudomonas aeruginosa.

IMPORTANCE: A peptidoglycan cell wall is an essential component of almost all bacterial cell envelopes, which determines cell shape and prevents osmotic rupture. Antibiotics that interfere with peptidoglycan synthesis have been one of the most important treatments for bacterial infections. Peptidoglycan must also be hydrolyzed to incorporate new material for cell growth and division and to help accommodate important envelope-spanning systems. However, the enzymes that hydrolyze peptidoglycan must be carefully controlled to prevent autolysis. Exactly how this control is achieved is poorly understood in most cases but is a highly active area of current research. Identifying hydrolase control mechanisms has the potential to provide new targets for therapeutic intervention. The work here reports the important discovery of a novel inhibitor/anti-inhibitor system that controls the activity of a cell wall hydrolase in the human pathogen Pseudomonas aeruginosa, which also affects resistance to an antibiotic used in the clinic.

Comparing Oral Versus Intravenous Antibiotics Administration for Cellulitis Infection: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Cellulitis is defined as an infection of the skin that is usually characterized by localized but poorly demarcated areas of erythema, swelling, and pain. Erysipelas is a subtype of cellulitis that is characterized by a more superficial infection, often involving the face. Because gram-positive bacteria are the most common infective agent, beta-lactam antibiotics such as cephalosporins are commonly used. However, guidelines and physician preference vary widely as different antibiotic options and routes of administration exist, in addition to the fact that most cases are treated empirically without microbiological lab guidance. This lack of standardization in evidence, guidelines, and physician practice prompted this systematic review and meta-analysis of both randomized trial data and cohort studies to aggregate the currently available evidence for the optimal routes of antibiotic administration in cellulitis treatment. OBJECTIVE: The primary objective of our review is to compare the efficacy of oral versus intravenous antibiotic administration for cellulitis infections, thereby providing clinicians with evidence-based guidelines for treatment. METHODS: We will search MEDLINE, Embase, and CENTRAL through Ovid as well as Web of Science and CINAHL for all available literature comparing different routes of antibiotic administration in the treatment of cellulitis and erysipelas. We will perform title and abstract as well as full-text screening in duplicate according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines and then extract the relevant data using a prepiloted data sheet. The primary outcome for our review is the duration of infection resolution, and secondary outcomes such as incidence of sepsis, mortality, hospital admission, and Clostridium difficile infection. We will assess the risk of bias in our included studies using the RoB 2.0 (revised tool for Risk of Bias in randomized trials) and ROBINS-I (Risk of bias in non-randomized studies for interventions) tools, with a final quality assessment using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework and a sensitivity analysis to examine heterogeneity. RESULTS: We will publish the final results of our systematic review in a peer-reviewed academic journal. This project received no funding or financial assistance. Data analysis is currently underway, and the results are expected to be submitted for publication in late November 2023. CONCLUSIONS: To our knowledge, this will be the most up-to-date review of the best available evidence comparing different routes of antibiotic administration for cellulitis. Because of the vast selection of antibiotic options available and the empirical nature of the treatment, we anticipate heterogeneity within our data but nonetheless hope to provide aggregated evidence on the efficacy of intravenous versus oral administration of antibiotics in cellulitis treatment. We hope the results from this study will better inform physician practices in the future for cellulitis infections. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48342.

Chromatinization modulates topoisomerase II processivity.

Type IIA topoisomerases are essential DNA processing enzymes that must robustly and reliably relax DNA torsional stress. While cellular processes constantly create varying torsional stress, how this variation impacts type IIA topoisomerase function remains obscure. Using multiple single-molecule approaches, we examined the torsional dependence of eukaryotic topoisomerase II (topo II) activity on naked DNA and chromatin. We observed that topo II is ~50-fold more processive on buckled DNA than previously estimated. We further discovered that topo II relaxes supercoiled DNA prior to plectoneme formation, but with processivity reduced by ~100-fold. This relaxation decreases with diminishing torsion, consistent with topo II capturing transient DNA loops. Topo II retains high processivity on buckled chromatin (~10,000 turns) and becomes highly processive even on chromatin under low torsional stress (~1000 turns), consistent with chromatin's predisposition to readily form DNA crossings. This work establishes that chromatin is a major stimulant of topo II function.

Exploration of the Tunability of BRD4 Degradation by DCAF16 Trans-labelling Covalent Glues.

Small molecules that can induce protein degradation by inducing proximity between a desired target and an E3 ligase have the potential to greatly expand the number of proteins that can be manipulated pharmacologically. Current strategies for targeted protein degradation are mostly limited in their target scope to proteins with preexisting ligands. Alternate modalities such as molecular glues, as exemplified by the glutarimide class of ligands for the CUL4CRBN ligase, have been mostly discovered serendipitously. We recently reported a trans-labelling covalent glue mechanism which we named 'Template-assisted covalent modification', where an electrophile decorated small molecule binder of BRD4 was effectively delivered to a cysteine residue on an E3 ligase DCAF16 as a consequence of a BRD4-DCAF16 protein-protein interaction. Herein, we report our medicinal chemistry efforts to evaluate how various electrophilic modifications to the BRD4 binder, JQ1, affect DCAF16 trans-labeling and subsequent BRD4 degradation efficiency. We discovered a decent correlation between the ability of the electrophilic small molecule to induce ternary complex formation between BRD4 and DCAF16 with its ability to induce BRD4 degradation. Moreover, we show that a more solvent-exposed warhead presentation is optimal for DCAF16 recruitment and subsequent BRD4 degradation. Unlike the sensitivity of CUL4CRBN glue degraders to chemical modifications, the diversity of covalent attachments in this class of BRD4 glue degraders suggests a high tolerance and tunability for the BRD4-DCAF16 interaction. This offers a potential new avenue for a rational design of covalent glue degraders by introducing covalent warheads to known binders.

Chromatinization Modulates Topoisomerase II Processivity.

Type IIA topoisomerases are essential DNA processing enzymes that must robustly and reliably relax DNA torsional stress in vivo. While cellular processes constantly create different degrees of torsional stress, how this stress feeds back to control type IIA topoisomerase function remains obscure. Using a suite of single-molecule approaches, we examined the torsional impact on supercoiling relaxation of both naked DNA and chromatin by eukaryotic topoisomerase II (topo II). We observed that topo II was at least ~ 50-fold more processive on plectonemic DNA than previously estimated, capable of relaxing > 6000 turns. We further discovered that topo II could relax supercoiled DNA prior to plectoneme formation, but with a ~100-fold reduction in processivity; strikingly, the relaxation rate in this regime decreased with diminishing torsion in a manner consistent with the capture of transient DNA loops by topo II. Chromatinization preserved the high processivity of the enzyme under high torsional stress. Interestingly, topo II was still highly processive (~ 1000 turns) even under low torsional stress, consistent with the predisposition of chromatin to readily form DNA crossings. This work establishes that chromatin is a major stimulant of topo II function, capable of enhancing function even under low torsional stress.

An inhibitor/anti-inhibitor system controls the activity of lytic transglycosylase MltF in Pseudomonas aeruginosa.

Most bacterial cell envelopes contain a cell wall layer made of peptidoglycan. The synthesis of new peptidoglycan is critical for cell growth, division and morphogenesis, and is also coordinated with peptidoglycan hydrolysis to accommodate the new material. However, the enzymes that cleave peptidoglycan must be carefully controlled to avoid autolysis. In recent years, some control mechanisms have begun to emerge, although there are many more questions than answers for how most cell wall hydrolases are regulated. Here, we report a novel cell wall hydrolase control mechanism in Pseudomonas aeruginosa , which we discovered during our characterization of a mutant sensitive to the overproduction of a secretin protein. The mutation affected an uncharacterized Sel1-like repeat protein encoded by the PA3978 locus. In addition to the secretin-sensitivity phenotype, PA3978 disruption also increased resistance to a ß-lactam antibiotic used in the clinic. In vivo and in vitro analysis revealed that PA3978 binds to the catalytic domain of the lytic transglycosylase MltF and inhibits its activity. ΔPA3978 mutant phenotypes were suppressed by deleting mltF , consistent with them having been caused by elevated MltF activity. We also discovered another interaction partner of PA3978 encoded by the PA5502 locus. The phenotypes of a ΔPA5502 mutant suggested that PA5502 interferes with the inhibitory function of PA3978 towards MltF, and we confirmed that activity for PA5502 in vitro . Therefore, PA3978 and PA5502 form an inhibitor/anti-inhibitor system that controls MltF activity. We propose to name these proteins Ilt (inhibitor of lytic transglycosylase) and Lii (lytic transglycosylase inhibitor, inhibitor). IMPORTANCE: A peptidoglycan cell wall is an essential component of almost all bacterial cell envelopes, which determines cell shape and prevents osmotic rupture. Antibiotics that interfere with peptidoglycan synthesis have been one of the most important treatments for bacterial infections. Peptidoglycan must also be hydrolyzed to incorporate new material for cell growth and division, and to help accommodate important envelope-spanning systems. However, the enzymes that hydrolyze peptidoglycan must be carefully controlled to prevent autolysis. Exactly how this control is achieved is poorly understood in most cases, but is a highly active area of current research. Identifying hydrolase control mechanisms has the potential to provide new targets for therapeutic intervention. The work here reports the important discovery of a novel inhibitor/anti-nhibitor system that controls the activity of a cell wall hydrolase in the human pathogen Pseudomonas aeruginosa , and which also affects resistance to an antibiotic used in the clinic.

Complementary and alternative medicine mention and recommendations in inflammatory bowel disease guidelines: systematic review and assessment using AGREE II.

BACKGROUND: Many patients with inflammatory bowel disease (IBD) use complementary and alternative medicine (CAM) for disease management. There is, however, a communication gap between patients and healthcare professionals regarding CAM use, where patients are hesitant to disclose CAM use to providers. The purpose of this study was to identify the quantity and assess the quality of CAM recommendations in IBD clinical practice guidelines (CPGs) using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. METHODS: MEDLINE, EMBASE, and CINAHL were systematically searched from 2011 to 2022 to find CPGs for the treatment and/or management of IBD. The Guidelines International Network (GIN) and National Center for Complementary and Integrative Health (NCCIH) websites were also searched. Eligible CPGs were assessed using the AGREE II instrument. RESULTS: Nineteen CPGs made CAM recommendations for IBD and were included in this review. Average scaled domain percentages of CPGs were as follows (overall CPG, CAM section): scope and purpose (91.5%, 91.5%), clarity of presentation (90.3%, 64.0%), editorial independence (57.0%, 57.0%), stakeholder involvement (56.7%, 27.8%), rigour of development (54.7%, 45.9%), and applicability (14.6%, 2.1%). CONCLUSIONS: The majority of CPGs with CAM recommendations were of low quality and their CAM sections scored substantially lower relative to other therapies in the overall CPG. In future updates, CPGs with low scaled-domain percentages could be improved in accordance with AGREE II and other guideline development resources. Further research investigating how CAM therapies can best be incorporated into IBD CPGs is warranted.

Evaluating Survival After Hospitalization Due to Immune-Related Adverse Events From Checkpoint Inhibitors.

BACKGROUND: As immune checkpoint inhibitors (CPI) are increasingly approved for cancer treatment, hospitalizations related to severe immune-related adverse events (irAE) will increase. Here, we identify patients hospitalized due to irAEs and describe survival outcomes across irAE, CPI, and cancer type. METHODS: We identified patients hospitalized at our institution from January 2012 to December 2020 due to irAEs. Survival was analyzed using Kaplan-Meier survival curves with log-rank tests. RESULTS: Of 3137 patients treated with CPIs, 114 (3.6%) were hospitalized for irAEs, resulting in 124 hospitalizations. Gastrointestinal (GI)/hepatic, endocrine, and pulmonary irAEs were the most common causes of irAE-related hospitalization. After CPI initiation, the average time to hospitalization was 141 days. Median survival from hospital admission was 980 days. Patients hospitalized due to GI/hepatic and endocrine irAEs had longer median survival than patients with pulmonary irAEs (795 and 949 days vs. 83 days [P < .001]). Patients with melanoma and renal cell carcinoma had longer median survival than patients with lung cancer (2792 days and not reached vs. 159 days [P < .001]). There was longer median survival in the combination group compared to the PD-(L)1 group (1471 vs. 529 days [P = .04]). CONCLUSIONS: As CPI use increases, irAE-related hospitalizations will as well. These findings suggest that among patients hospitalized for irAEs, survival differs by irAE and cancer type, with worse survival for patients with irAE pneumonitis or lung cancer. This real-world data contributes to research pertaining to hospitalization due to severe irAEs, which may inform patient counseling and treatment decision-making.