Physician Chart Research Articles

Clinical performance of existing diagnostic criteria for pneumonia in older emergency patients: A prospective cohort study.

Pneumonia accounts for over half a million older adult emergency department (ED) visits annually, but ED pneumonia diagnosis is inaccurate. Geriatric-specific pneumonia diagnostic criteria exist for other settings; no prospective data exist to determine if application in the older adult ED population is feasible. The objective was to prospectively evaluate the utility of four current diagnostic criteria (Loeb; Modified McGeer; Infectious Disease Society of America/American Thoracic Society; American College of Emergency Physicians) in older adult ED patients. This was a prospective, observational cohort study of older adult ED patients ≥65 years of age in two U.S. EDs with suspected pneumonia defined as having chest radiography ordered and treating physician suspicion. The standard we used for defining the presence, absence, or inability to determine a diagnosis of pneumonia diagnosis was expert physician chart adjudication. We report the summary statistics for demographic characteristics and symptoms/exam findings and sensitivity, specificity, and likelihood ratios with 95% confidence intervals of the existing diagnostic criteria. Pre-specified cutoff values of a positive LR >10 and a negative LR <0.3 were considered clinically significant. Of 135 patients enrolled, 27 had pneumonia by adjudicator review. Typical patient-reported pneumonia symptoms, such as fever (18.5%) and new/worse cough (51.9%), were not consistently present in pneumonia. The IDSA/ATS and ACEP criteria had positive LR >10 and negative LR <0.3; however, all confidence intervals included pre-specified cutoffs. Older adults presented to the ED with low frequency of typical pneumonia symptoms. Although existing diagnostic definitions had promising test characteristics, they may not perform well enough for clinical application without refinement.

Concordance of provider chart notation and guideline-based classification of asthma severity

Objective To evaluate concordance of asthma severity classification via physician chart notation compared with guideline-based criteria in adolescents with diagnosed asthma. Methods Of 284 urban primary care and subspecialty clinic patients aged 13–18 years approached through convenience sampling, 203 surveys were completed (RR = 71.5%). We assessed concordance with sensitivity, specificity, and positive predictive values; overall agreement was evaluated with weighted kappa coefficients and McNemar’s test. Results When considering prescribed treatment according to NAEPP guidelines as a gold standard, the sensitivity for chart notation was very good for intermittent (95%) and less for non-intermittent severity ratings (51%, 58%, and 67% for moderate, severe, and mild persistent asthma, respectively). Overall agreement between chart notation and guideline-based asthma criteria ranged from fair-to-good for mild- (k = 0.36), moderate- (k = 0.44), and severe-persistent severity (k = 0.66). Although the agreement for intermittent severity was highest (k = 0.88), it did not significantly differ by between the two classifications (p ≥ 0.05). Conclusions Concordance for all non-intermittent asthma severity classifications varied between physician and medication-driven 2007 NAEPP guideline classifications in an ethnically diverse urban adolescent patient sample. Physicians should remain aware of the potential for this discordance and refer to the guidelines to classify and treat adolescents with asthma.

Abstract 16254: Short and Long-Term Outcomes of Patients With Cardiac Amyloidosis Presenting in Cardiogenic Shock

Background: The characteristics and outcomes of patients with cardiac amyloidosis who present in cardiogenic shock (CS) remains poorly defined. Methods: All patients admitted to Cleveland Clinic Cardiac Intensive Care Unit (CICU) between Jan 1 st , 2010, to Dec 31 st , 2021, with a diagnosis of cardiogenic shock (CS) were retrospectively identified through electronic medical records and confirmed via physician chart review. Patients were further categorized into those with CS with cardiac amyloidosis (C-Amyloid) and CS without cardiac amyloidosis. 30-day and 1-year all-cause mortality was compared between the two groups with Kaplan-Meier (KM) estimates. Results: During the study period, a total of 2775 were patients were admitted to our CICU with CS of which, 29 patients (1%) had confirmed cardiac amyloidosis (C-amyloid). Amongst patients with CS and c-amyloid, 18 patients (62%) had TTR amyloid, 8 (28%) had AL amyloid and 3 were undefined. Compared to patients with other forms of CS, patients with C-amyloid were significantly older (median age of 70 vs 65, p=0.024), had lower prevalence of prior myocardial infarction (21% vs 42%, p=0.037) or coronary artery bypass grafting, and a higher prevalence of chronic kidney disease (69% vs 39%, p=0.002). There were no significant differences in the utilization of right heart catheterization, mechanical circulatory support or mechanical ventilation between the two groups. Comparison of survival probabilities revealed that CS patients with amyloid had similar 30-day (17% vs 21%, p=0.56) and 1-year all-cause mortality (38% vs 31%, p=0.6). Conclusion: Amyloid cardiomyopathy is a rare but unique etiology of CS in the CICU. Observed mortality rates are similar to patients with other forms of CS. Given breakthroughs in therapeutics for this condition, the proportion of patients with this clinical entity is expected to rise.

Emergency department patient and physician survey accuracy compared to chart abstraction in patients with acute respiratory illness.

High-quality research studies in older adults are needed. Unfortunately, the accuracy of chart review data in older adult patients has been called into question by previous studies. Little is known on this topic in patients with suspected pneumonia, a disease with 500,000 annual older adult U.S. emergency department (ED) visits that presents a diagnostic challenge to ED physicians. The study objective was to compare direct interview and chart abstraction as data sources. We present a preplanned secondary analysis of a prospective, observational cohort of ED patients ≥65 years of age with suspected pneumonia in two Midwest EDs. We describe the agreement between chart review and a criterion standard of prospective direct patient survey (symptoms) or direct physician survey (examination findings). Data were collected by chart review and from the patient and treating physician by survey. The larger study enrolled 135 older adults; 134 with complete symptom data and 129 with complete examination data were included in this analysis. Pneumonia symptoms (confusion, malaise, rapid breathing, any cough, new/worse cough, any sputum production, change to sputum) had agreement between patient/legally authorized representative survey and chart review ranging from 47.8% (malaise) to 80.6% (confusion). All examination findings (rales, rhonchi, wheeze) had percent agreement between physician survey and chart review of ≥80%. However, all kappas except wheezing were less than 0.60, indicating weak agreement. Both patient symptoms and examination findings demonstrated discrepancies between chart review and direct survey with larger discrepancies in symptoms reported. Researchers should consider these potential discrepancies during study design and data interpretation.

A Prospective, Multi-Institutional Study of Problematic Plan Detection during Physician Chart Rounds.

We performed a multi-institutional prospective study to determine the detection rate of problematic treatment plans (PP) at physician chart rounds (CR), and to identify factors associated with PP detection. Curative intent PPs with simulated errors (representative of the most common targets of peer review) were generated. Two breast specialists selected twenty appropriate plans for inclusion and assigned them American Association of Physicists in Medicine (AAPM) Task Group 100 severity and detectability scores. The PPs were blinded and embedded at weekly virtual CR at 2 institutions over 12 months. At site A, both breast and lung cases were reviewed by a mix of breast and lung specialists during CR, and at site B, only breast cases were presented and reviewed by breast specialists. At both sites, breast plans were reviewed via slice-by-slice review in the treatment planning system (TPS), and both used a color-coded tool from the TPS to assess adherence to planning directives. Both sites had systematic approaches to case presentation (without a checklist). Site A was usually prospective CR, while site B was exclusively prospective. The following CR elements were recorded: PP detection, time of detection, length of CR, total number of cases presented, plan elements displayed, number and roles of attendees, and detector's role. Analysis was performed using simple statistics with chi-square testing. By PP error type classification, 55.0% pertained to "target volume delineation," 25% to "non-target volume delineation or normal tissue sparing," and 20.0% to "dose prescription or written directives." Detectability was rated ≤5 (<5% likelihood of going undetected) for 60% of PPs, and severity was rated ≥7 ("at least potentially serious toxicity or tumor underdose") for only 30% of PPs. CR lasted a median of 64 minutes at site A (IQR 55-82.5) and 70 minutes at site B (IQR 52.5-81.5). PPs were presented at a median of 34 minutes (IQR 22.5-43, site A) and 41.5 minutes (IQR 23.5-56, site B) after CR start. A median of 16 cases (IQR 13-19) at site A and 32 cases (IQR 25-34.5) at site B were presented per CR session, with a median of 1 PP (site A and B) presented per session (range 1-2). The median time spent per case was 4.0 minutes (Site A) and 2.2 minutes (Site B). The median number of attendings at CR was 4 for site A (range 2-6) and 6.5 for Site B (range 5-10). PP detection rate at site A was 20% (n = 4) and at site B was 70% (n = 14) (p = 0.001). Detections were made by an attending physician in 100% (site A, n = 4) and 92.9% (Site B, n = 13) of PP detections. There were no differences in detection rate by PP error type (p = 0.78), detectability (p = 0.60) or severity score (p = 0.68), or by time PP presented after CR start (p = 0.39). The effectiveness of PP detection at chart rounds can vary greatly between institutions. The study suggests possible areas for improvement but further study is needed to determine best practices.

High burden of clinically significant adverse events associated with contemporary therapy for pediatric T-cell acute lymphoblastic leukemia/lymphoma.

Despite improvements in survival for children with T-cell acute lymphoblastic leukemia and lymphoma (T-ALL/LLy), morbidity remains high. However, data are lacking regarding comprehensive descriptions of clinically relevant adverse events (AEs) experienced during early intensive chemotherapy. This single-institution retrospective study evaluated children aged 1-21 years with T-ALL/T-LLy diagnosed from 2010 to 2020. Physician chart abstraction identified and graded 20 clinically relevant AEs. AE rates were analyzed by T-ALL or LLy, minimal residual disease status, induction steroid, and use of antimicrobial prophylaxis. Statistical comparisons used the Kruskal-Wallis test (continuous variables) and Chi-square or Fisher's exact test (categorical variables). The cohort included 120 patients (T-ALL: 88; T-LLy: 32). Most patients experienced AEs during induction (85 out of 120; 70.8%) and consolidation (89 out of 111; 80.2%). Nonsepsis infection was common in induction (26 out of 120; 21.7%) and consolidation (35 out of 111; 31.5%). Patients treated with dexamethasone during induction had significantly higher rates of nonsepsis infection and/or sepsis during consolidation than those who received prednisone (p<.01). Clinically significant AEs are extremely common during induction and consolidation therapy for patients with T-ALL/LLy. Infectious AEs are particularly prevalent. These results can inform conversations with patients and families and aid in the development of toxicity-related aims in the next generation of, prospective clinical trials in T-ALL/LLy.

Exploring the relationship between the reduction of floor microbial burden and the impact on healthcare-associated infections

Background: Healthcare floors are a vehicle and/or source for potential pathogens that cause healthcare associated infections, and hospital floors are often heavily contaminated with pathogens such as Clostridioides difficile and methicillin-resistant Staphylococcus aureus. However, definitive research linking reductions in floor burden to reductions in HAIs has not yet been established. We sought to evaluate emerging technology for continuous disinfection and its potential impact on HAIs. This study was designed to explore the potential relationship between the reduction of microbial burden of floors and healthcare associated infections. Methods: A prospective study was conducted in a 22-bed medical-surgical intensive care unit in a 180-bed suburban hospital near New Orleans, Louisiana, from November 2021 to June 2022. Using sterile, premoistened sponges, samples were collected from the floors of 10 areas throughout the unit including 2 nurses’ stations, the physician charting area, and 7 patient rooms. The advanced photocatalytic oxidation (aPCO) equipment was then installed in the HVAC ductwork throughout the ICU and activated. Environmental surface sampling of the same floor surfaces was then repeated every 4 weeks for the first 5 months of the study. HAIs were also tracked throughout the entire study period. The facility’s normal cleaning floor protocols using a neutralizing floor cleaner were unchanged and followed during the study. Changes in surface burden were calculated using a repeated-methods ANOVA with post hoc analyses as appropriate. Rates of healthcare associated infections were compared using χ2 analyses. Results: Overall, there was a 99.6% statistically significant decrease in floor environmental surface burden from the baseline to the final postactivation test (Fig. 1). The average colony forming unit count (CFU) decreased from 318,850 CFU per 100 cm2 to just 2,988 CFU per 100 cm2. The unit also saw a statistically significant decrease in publicly reported healthcare associated infections (HO-MRSA, CLABSI, HO-CDI) during the study period compared to the same period a year prior and in the 6 months immediately prior to the beginning of the study (Fig. 2). Conclusions: Advanced photocatalytic oxidation technology resulted in a reduction of microbial burden on the floors of a high-traffic intensive care unit. Statistically significant decreases in healthcare-associated infections was also seen. This study highlights a novel aPCO technology and its efficacy at reducing microbial burden and healthcare-associated infections despite no change in practice.Disclosures: None

De-correlating immune checkpoint inhibitor toxicity and response in melanoma via the microbiome.

9569 Background: Immune-checkpoint inhibitor (ICI) immunotherapy increases survival in patients with melanoma. Yet only half of the patients respond, and 10-40% of patients experience immune-related adverse events (irAEs). Previous studies have found a correlation between the development of an irAE and treatment response. Modifying the gut microbiome could positively affect response to ICIs and reduce toxicities. We sought to determine if the microbiome at the onset of treatment, during an irAE, and at 12 weeks, can predict the response or toxicity during ICI treatment for metastatic melanoma. Methods: Melanoma patients (pts) &gt; 18 yo treated with ICI enrolled in a prospective observational cohort study at The Ohio State University Comprehensive Cancer Center Skin Cancer Clinic. Excluded were patients on corticosteroids at the start of ICI cycle 1, except for adrenal physiologic replacement. Stools were collected at baseline, within 2 days of an adverse event assessed by physician chart review using CTCAE (Common Terminology Criteria for Adverse Events) v5.0, and at 12 weeks. Response (ORR) to ICIs was assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) q12 weeks and progression-free survival recorded. Metagenomic whole-genome shotgun sequencing was performed on an Illumina NovaSeq 6000 and classified using HUMAnN3. The effect of microbe relative abundances on irAEs was modeled by logistic regression with the R package glmm. Results: Of the 88 patients enrolled, 48 had metastatic disease with 32 assessable for response. ORR at 12 weeks was 28% (1 CR, 8 PR, 17 SD, and 6 PD) and 24 patients showed PFS at 12 months. Grade &gt; 2 irAEs were observed in 11/48 pts. Abundance of Bacteroides dorei (False Discovery Rate Corrected p-value = 9.5E-07) and Blautia species CAG:257 (padj = 0.001) were enriched in responders, Prevotella Stercorea (padj = 1.1E-07) and a phage with a predicted target of Salmonella (padj = 8.3E-09) in non-responders. Responders with an irAE had enrichment of Bacteroides plebeius (padj = 4.2E-13) and Bacteroides coprophilus (padj = 0.0002) whereas responders without irAE had enrichment of Eubacterium siraeum (padj = 7.2E-05). Conclusions: Longitudinal and event-driven biospecimen collection in patients treated with ICIs showed several bacteria and viruses but no fungi associated with response, with and without the development of an irAE. The abundance of the two high-taxonomic rank microbe groups is significantly associated with irAEs. The association with the Bacteroides Genus is consistent with previous studies and is associated with response to ICIs. A microbiome abundant in Bacteroides and lacking Prevotella is associated with response to ICI. An abundance of Bacteroides could be a biomarker for irAEs, and an abundance of Eubacterium, a biomarker for response without irAEs. Future analyses are necessary to assign causal roles for microbe biomarkers with specific irAEs. Clinical trial information: NCT05102773 .

Does Prehabilitation Before Surgery Affect Return to Sport in Baseball Pitchers With Partial Ulnar Collateral Ligament Tears?

Purposeful rehabilitation before surgery (prehabilitation) has been researched and implemented in the treatment of anterior cruciate ligament tears. However, it is unclear whether prehabilitation would affect outcomes for baseball pitchers with partial ulnar collateral ligament (UCL) tears. The purpose of this study was to determine whether baseball pitchers with partial UCL tears who completed ≥4 weeks of prehabilitation (prehab group) have different return to play (RTP) outcomes than pitchers with 0 to 3 weeks of preoperative physical therapy (no prehab group). We hypothesized that pitchers in the prehab group would have similar RTP rates compared with pitchers in the no prehab group. Cohort study; Level of evidence, 3. Baseball pitchers of all competitive levels who underwent primary UCL reconstruction (UCLR) or UCL repair between 2010 and 2019 were included. Physician chart notes, magnetic resonance images, and operative notes were screened to confirm primary UCLR or UCL repair of a partial UCL tear and to identify whether the nonoperative treatment had been attempted. Patients were contacted via RedCap for postoperative complications, reoperations, RTP, and patient-reported outcomes (Kerlan-Jobe Orthopaedic Clinic score, Andrews-Timmerman score, Conway-Jobe score, and satisfaction). Overall, 105 baseball pitchers (n = 55 prehab group; n = 50 no prehab group) were included and evaluated at 3.4 ± 2.5 years postoperatively. Six pitchers underwent UCL repair, and 99 pitchers underwent UCLR. All demographic characteristics were similar between groups except the prehab group received a gracilis graft more frequently (76.5% vs 51.2%; P = .038). The RTP rate (prehab [88.1%] vs no prehab [93.8%]; P = .465) was similar between groups. All other postoperative outcomes were also similar between groups, including revision rates and patient-reported outcomes. Postoperative and patient-reported outcomes did not differ significantly between pitchers with partial UCL tears who performed rehabilitation before UCL surgery and pitchers who did not attempt a significant period of rehabilitation before UCL surgery. Clinicians should feel comfortable recommending rehabilitation for patients with partial UCL tears who wish to attempt a period of nonoperative treatment, as postoperative outcomes are not affected if UCL surgery is later needed.

Real-world treatment and quality of life (QOL) in locally advanced or metastatic urothelial carcinoma (la/mUC) in Saudi Arabia, Singapore, South Korea, Taiwan, and Turkey.

462 Background: Little is known about treatment and QOL of la/mUC in Saudi Arabia, South Korea, Turkey, and Taiwan. Therefore, this study assessed patient (pt), tumor, and disease characteristics; treatment sequencing; and QOL in pts with la/mUC treated in these countries. Methods: Data were drawn from the Adelphi mUC Disease-Specific Programme, a real-world, multinational, point-in-time study using validated methodology (Anderson et al. Curr Med Res Opin. 2008;24:3063-72) and included physician surveys, chart reviews, and pt questionnaires (Saudi Arabia, Turkey, and Taiwan only). Data were collected (12/2021–3/2022) from oncologists and urologists and adult pts with confirmed la/mUC. EQ-5D visual analogue scale (VAS; scores: 0 [worst health] to 100 [best health]) and the global health status (QL2) from the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (scores: 0 [low functioning] to 100 [high functioning]) questionnaires were used to assess QOL. Results: Data were provided by 175 physicians for 988 pts (Turkey, n=300; Saudi Arabia, n=240; South Korea, n=298; Taiwan, n=150) with la/mUC. Mean pt age was 66.3 y; 77% were men. Most (77%) pts had no family history of urothelial carcinoma (UC); 30% recorded no risk factors (eg, genetic risk, smoking, occupational exposure). At initial UC diagnosis, the bladder was the initial tumor location in 82% of pts, of whom 67% had la/mUC, and 83% of pts had an Eastern Cooperative Oncology Group performance status 0–2. At data collection, the most common metastatic sites were the lymph nodes (53%), lungs (29%), liver (27%), and bone (21%). Biomarker/tumor testing was not done in 45% of pts. In pts initially diagnosed with nonmetastatic UC (n=346), 28% received neoadjuvant and 31% received adjuvant therapy. Of pts receiving ≥1 line of therapy (LOT) for la/mUC (n=988), 74% received gemcitabine, 60% received cisplatin, 18% received carboplatin, 17% received a programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor, and 4% received best supportive care (BSC) in the first-line (1L) setting; mean duration of therapy (DOT) in 1L was 5.7 mo. Of pts receiving ≥2 LOTs for la/mUC (n=290), 63% received a PD-1/L1 inhibitor and 35% received chemotherapy in the second-line (2L) setting; mean DOT in 2L was 4.9 mo. Of pts receiving ≥3 LOTs for la/mUC (n=87), 59% received chemotherapy (most often cisplatin [46%] or gemcitabine [38%]), 34% received a PD-1/L1 inhibitor, and 10% received BSC only in the third-line (3L) setting; mean DOT in 3L was 4.3 mo. Questionnaires were available for 319 pts. Mean (SD) EQ-5D VAS score was 51.8 (15.6); EORTC QL2 score was 44.6 (19.9). Conclusions: Pts with la/mUC in this multinational study generally received 1L platinum-based and 2L PD-1/L1 inhibitor therapies. These results highlight the need for therapies that improve clinical and QOL outcomes.

1201. Reduction of Methicillin-Resistant Staphylococcus aureus Surface Microbial Burden and related Healthcare Associated Infections with the implementation of an Advanced Photocatalytic Oxidation Technology in a Medical-Surgical Intensive Care Unit

Abstract Background Methicillin Resistant Staphylococcus aureus (MRSA) bacteria have been long established as a major cause of infections. MRSA infections occurring in blood or other sterile sites are associated with poorer health outcomes and an increased risk of mortality, especially when acquired in a healthcare setting. The ongoing COVID-19 pandemic has not only stymied reduction efforts but has precipitated increases in invasive HO-MRSA infections, with increases seen of 12-34% in national MRSA standardized infection ratios in 2020 compared to 2019. The facility had seen similar increases of HO-MRSA infections, defined as a positive culture on or after the 3rd hospital day, despite no change in clinical practice. Methods A prospective study was conducted in a 22 bed Medical-Surgical Intensive Care Unit from November 2021 to March 2022. 50 surface samples were collected from surfaces throughout the unit including two nurses’ stations, physician charting area, and 5 areas in 7 patient rooms. The advanced photocatalytic oxidation (aPCO) equipment was then installed in the HVAC ductwork throughout the ICU and activated. Sampling was then repeated every four weeks during the study period. The facility’s normal disinfection protocols were unchanged. HO-MRSA infections attributed to the unit were also tracked during the study period. Changes in MRSA surface burden were calculated using a repeated methods ANOVA with post hoc analyses as appropriate. Rates of HO-MRSA infections per 1,000 patient days were compared using the chi-square test. Results There was a 98% statistically significant decrease in MRSA surface burden from the baseline to final post-activation test. The average colony forming unit count (CFU) went from 427 to 3 CFU/100cm2 during the same time. HO-MRSA infections also had a statistically significant decrease when compared to the same time frame a year prior and the immediate 6 months prior to the study. Figure 1Average MRSA Surface Reduction Conclusion The aPCO technology resulted in a reduction of MRSA on frequently touched surfaces in a high-traffic ICU. Corresponding decreases in HO-MRSA cases were also seen. This study highlights a novel aPCO technology and its efficacy at reducing microbial burden and healthcare-onset MRSA infections despite no change in practice and through the continued COVID-19 pandemic. Disclosures Caitlin Stowe, MPH, CPH, CIC, CPHQ, VA-BC, ActivePure Medical: Employee|PDI Healthcare: Employee.

Real-World Treatment Patterns and Clinical Outcomes with Brentuximab Vedotin or Other Standard Therapies in Patients with Previously Treated Cutaneous T-Cell Lymphoma (CTCL): A Retrospective Chart Review Study in the United States

INTRODUCTION: CTCLs such as primary cutaneous anaplastic large-cell lymphomas (pcALCLs) uniformly express CD30, whereas mycosis fungoides (MF) heterogeneously express CD30. In ALCANZA (Horwitz 2021), patients with CD30-positive pcALCL or MF randomized to brentuximab vedotin (BV) vs physician's choice of methotrexate or bexarotene had a significantly higher objective response rate (ORR) lasting ≥4 months (ORR4; 54.7% vs 12.5%; P<0.001) and longer median progression-free survival (PFS; 16.7 vs 3.5 months; P<0.001) and time to next treatment (TTNT; 14.2 vs 5.6 months; P<0.001) at a median follow-up of 45.9 months. This study describes real-world patient characteristics, treatment patterns, clinical outcomes, and healthcare resource use (HRU) in CTCL patients treated with BV or other standard therapies (OST) after ≥1 systemic therapy. METHODS: A retrospective, longitudinal physician chart review was conducted from Oct 2021-Jan 2022 (approved by WCG IRB). Physicians were oncologists/hematologists with access to complete medical records for ≥1 eligible patient. Eligible adult patients had pcALCL or MF, previously received ≥1 systemic therapy, and were treated with BV or OST from Nov 2017-Mar 2021. The index date was the initiation of second-line (2L) CTCL systemic therapy. The observation period was from index to the earliest of death, loss to follow-up, or chart abstraction. Treatment patterns were assessed from CTCL diagnosis to end of observation period; clinical outcomes for 2L systemic therapy and HRU were assessed during the observation period. Treatment response was recorded via the Global Response Score (Olsen 2011). TTNT was from index to the earlier of initiation of a new line of therapy or death. Real-world PFS (rwPFS) was from index to earliest of progression, treatment discontinuation due to progression, or death. Overall survival (OS) was from index to death. Median times-to-event were computed using Kaplan-Meier (KM) analysis. Since median times-to-event were not reached in both cohorts for multiple outcomes, restricted mean survival time (RMST), a measure of the average event-free survival time during a specific period estimated by the area under the KM curve, at 1 and 2 years was also estimated. RESULTS: Physicians (n=125; 68.0% community, 75.2% practiced >10 years) abstracted medical charts for 303 patients (BV/OST: n=139/164; male, 66.9%/67.7%; MF, 56.8%/65.9%; ECOG PS 0-1, 86.3%/67.1%). The median observation period for BV and OST was 8.1 (interquartile range: 7.1-10.8) and 8.8 (4.8-11.5) months. Most patients in the BV cohort (96.4%) received BV as 2L systemic therapy. In the OST cohort, the most common 2L therapies were methotrexate (11.6%), mogamulizumab (9.1%), and bendamustine (9.1%) monotherapies. The median (95% CI) duration of 2L therapy for BV and OST was 8.4 (7.1-15.4) and 5.2 (3.9-7.3) months. The rwORR for BV and OST was 82.1% and 66.5%; rwORR4 was 42.5% and 25.0% (Table 1). Median (95% CI) TTNT was not reached (NR; 17.5-NR) for BV and was 13.2 (9.2-NR) months for OST; RMST for TTNT was higher for BV vs OST (1-year: 11.2 [10.8-11.7] vs 8.1 [7.4-8.9] months, P<0.01; 2-years: 20.5 [18.6-22.4] vs 13.7 [11.9-15.5] months, P<0.01). RMST (95% CI) for rwPFS for BV and OST at 1 year was 11.1 (10.5-11.6) vs 8.9 (8.1-9.6) months (P<0.01) and at 2 years was 21.0 (19.1-22.9) vs 15.7 (13.6-17.8) months (P<0.01) (Table 2). Median OS was NR in both cohorts; for BV and OST, 9% and 36% of patients died. RMST (95% CI) for OS for BV and OST at 1 year was 11.3 (10.9-11.7) vs 9.0 (8.3-9.7) months (P<0.01) and at 2 years was 21.3 (19.7-22.8) vs 15.8 (14.1-17.5) months (P<0.01). During the observation period, 30.2% and 39.0% of the BV and OST cohorts had an emergency department visit, and 29.5% and 36.6% had a hospitalization; median (95%CI) hospital length of stay for those with ≥1 hospitalization was 13.7 (CI: 12.6-14.9) and 21.1 (19.9-22.4) days. CONCLUSION: Real-world outcomes with BV in patients with CTCL who received ≥1 prior systemic therapy were consistent with results from ALCANZA, demonstrating favorable clinical outcomes with BV. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Expanded Autoreactive Transitional B Cells in Monogenic Common Variable Immunodeficiency

Introduction Autoimmune cytopenias (AIC) are prevalent in patients with primary immune deficiencies, including common variable immunodeficiency (CVID). They are often refractory and difficult to treat, and patients with autoimmune complications of CVID have a higher risk of mortality than those with an infectious phenotype (Farmer et al. Front Immnol 2017; Resnick et al. Blood 2021). The pathogenesis of AIC in CVID is not well understood, making diagnosis and prognostication challenging. We previously observed a block in development from transitional to follicular B cells in patients with activated PI3K delta syndrome (APDS), a monogenic form of CVID (Farmer et al. Sci Signal 2019). We have now investigated a larger cohort with various causes of monogenic CVID (45% with AIC). We sought to determine if a block in B cell development extended beyond APDS to other patients with monogenic CVID and autoimmunity. We aimed to identify a link between the transitional B cell block and a break in tolerance, as transitional B cells are immature cells with self-reactive properties prior to differentiating into mature follicular B cells (Allman et al. Curr Opin Immunol 2008). Thus, we performed flow cytometry using the 9G4 monoclonal antibody to identify B cells containing the 9G4 idiotope of the immunoglobulin heavy chain VH4-34 gene. This idiotope is associated with autoimmunity (Cappione et al. J Clin Invest 2005; Pugh-Bernard et al. J Clin Invest 2001). Utilizing single-cell Cellular Indexing of Transcriptomes and Epitopes by Sequencing (scCITE-Seq) and B cell receptor (BCR) repertoire, we analyzed patients with APDS to further define heterogeneous B cell populations. We leveraged our access to biospecimens and clinical data from patients with monogenic CVID to study pathologic B cells. Methods Patients were recruited in accordance with the Partners Institutional Review Board. The cohort was queried for cytopenias, including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN), identified by positive history on physician chart review or otherwise captured by review of all clinical details in the Electronic Medical Record. We performed flow cytometry on peripheral blood mononuclear cells with a detailed B cell panel including the 9G4 antibody. We included 20 patients with monogenic CVID (PI3K (n=4), NFKB1 (n=5), and CTLA4 mutations (n=11)) and 12 healthy controls. Nine patients had AIC (ITP (n=3), ITP + AIHA (n=4), ITP + AIN (n=1), ITP + AIHA + AIN (n=1)). We sequenced total CD19+ B cells from 4 patients with APDS and 4 controls using scCITE-Seq. With the Immcantation software suite, we identified clonal clusters based on BCR sequences and constructed maximum parsimony lineage trees for clusters with >5 unique sequences. Results Patients with monogenic CVID and AIC had marked expansion of 9G4+ B cells compared to healthy controls. There was a statistically significant (p<0.05) increase in the percent of 9G4+ B cells in patients with AIC compared to controls in the transitional T1/2, T3a, and T3b B cell subsets, as well as double negative, follicular, activated naïve, marginal zone precursor, and marginal zone subsets. This expansion was particularly pronounced in the transitional B cell population (p<0.001). ScCITE-Seq identified 19 B cell clusters. Clonal B cell populations separated into three predominant IgM isotype clusters in healthy controls (5, 9, and 15), while in patients with APDS there were additional clusters identified, including IgM isotype clusters 0, 2, 3, 10, 13, 17 and IgG isotype clusters 4, 6, 10, 12, and 16 (Figure 1). This suggests that there are novel, isotype-switched B cell states present in patients with APDS that are not present in healthy controls. Conclusions In this study, we investigated B cell populations in patients with monogenic CVID and autoimmunity. We found expansion of transitional B cells characterized by 9G4 positivity. These transitional cells may fail to be eliminated because they are aberrantly activated and differentiate into self-reactive activated B cells and plasmablasts that secrete pathogenic autoantibodies. ScCITE-Seq revealed novel B cell subsets in patients with APDS and could represent an altered state of B cell biology that leads to pathologic autoantibody production and clinical autoimmunity. These results improve identification of heterogeneous B cell subsets and connectivity between subsets. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evaluating disease control following belimumab treatment in patients with SLE enrolled in the US OBSErve study

ObjectiveTo characterise disease control and remission in patients with SLE receiving belimumab for up to 12 months in the real world.MethodsThis post hoc analysis (GSK Study 213502) used data from...

No Longer Beholden – Moving On from Elaborate Chart Notes

Despite recent changes in Medicare billing documentation guidelines, physician chart notes remain far lengthier and more detailed than is required. This is worrisome, as documentation burden is a major contributor to physician burnout. Elements of medical culture which have contributed to the elaborate chart note standard may be used to transform notes, reduce charting burden and improve physician well-being.

Automated Ascertainment of Typhlitis From the Electronic Health Record.

Adverse events (AEs) on Children's Oncology Group (COG) trials are manually ascertained using Common Terminology Criteria for Adverse Events. Despite significant effort, we previously demonstrated that COG typhlitis reporting sensitivity was only 37% when compared with gold standard physician chart abstraction. This study tested an automated typhlitis identification algorithm using electronic health record data. Electronic health record data from children with leukemia age 0-22 years treated at a single institution from 2006 to 2019 were included. Patients were divided into derivation and validation cohorts. Rigorous chart abstraction of validation cohort patients established a gold standard AE data set. We created an automated algorithm to identify typhlitis matching Common Terminology Criteria for Adverse Events v5 that included antibiotics, neutropenia, and non-negated mention of typhlitis in a note. We iteratively refined the algorithm using the derivation cohort and then applied the algorithm to the validation cohort; performance was compared with the gold standard. For patients on trial AAML1031, COG AE report performance was compared with the gold standard. The derivation cohort included 337 patients. The validation cohort included 270 patients (961 courses). Chart abstraction identified 16 courses with typhlitis. The algorithm identified 37 courses with typhlitis; 13 were true positives (sensitivity 81.3%, positive predictive value 35.1%). For patients on AAML1031, chart abstraction identified nine courses with typhlitis, and COG reporting correctly identified 4 (sensitivity 44.4%, positive predictive value 100.0%). The automated algorithm identified true cases of typhlitis with higher sensitivity than COG reporting. The algorithm identified false positives but reduced the number of courses needing manual review by 96% (961 to 37) by detecting potential typhlitis. This algorithm could provide a useful screening tool to reduce manual effort required for typhlitis AE reporting.

Incongruence between Physician, Patient, and Medical Chart Report of Skin Cancer Prevention Counseling.

Skin cancer incidence in the United States has risen rapidly in recent decades, underscoring the need for accessible and effective prevention practices. Skin cancer prevention counseling can lead to increased sun protective behavior and early detection; however, little is understood regarding the frequency and content of counseling among primary care providers (PCPs). We performed multi-center cross-sectional surveys among 53 providers and 3343 of their patients and chart review asking whether skin cancer prevention counseling occurred and details of that counseling. Only 10–25% of patients reported that counseling occurred. Among the providers who reported counseling, there were higher odds that their patients recollected they were advised to use sunscreen or protective clothing, on how to use sunscreen, on signs of skin cancer, to perform a self-skin exam (all p < 0.001), and were provided with written materials (p < 0.01). Eight percent of prevention counseling was chart documented despite being highly associated with patient and physician recollection of counseling (p < 0.001). These results highlight the need for consistent and clear delivery of skin cancer primary prevention.

Adverse events following third dose of mRNA COVID-19 vaccination among nursing home residents who received the primary series.

BackgroundWe sought to compare rates of adverse events among nursing home residents who received an mRNA COVID‐19 vaccine booster dose with those who had not yet received their booster.MethodsWe assessed a prospective cohort of 11,200 nursing home residents who received a primary COVID‐19 mRNA vaccine series at least 6 months prior to September 22, 2021 and received a third “booster dose” between September 22, 2021 and February 2, 2022. Residents lived in 239 nursing homes operated by Genesis HealthCare, spanning 21 U.S. states. We screened electronic health records for 20 serious vaccine‐related adverse events that are monitored following receipt of COVID‐19 vaccination by the CDC's Vaccine Safety Datalink. We matched boosted and yet‐to‐be boosted residents during the same time period, comparing rates of events occurring 14 days after booster administration with those occurring 14 days prior to booster administration. To supplement previously reported background rates of adverse events, we report background rates of medical conditions among nursing home residents during 2020, before COVID‐19 vaccines were administered in nursing homes. Events occurring in 2021–2022 were confirmed by physician chart review. We report unadjusted rates of adverse events and used a false discovery rate procedure to adjust for multiplicity of events tested.ResultsNo adverse events were reported during the 14 days post‐booster. A few adverse events occurred prior to booster (ischemic stroke: 49.4 per 100,000 residents, 95% CI: 21.2, 115.7; venous thromboembolism: 9.9 per 100,000 residents, 95% CI: 1.7, 56.0), though differences in event rates pre‐ versus post‐booster were not statistically significant (p < 0.05) after adjusting for multiple comparisons. No significant differences were detected between post‐booster vaccination rates and prior year 14‐day background rates of medical conditions.ConclusionsNo safety signals were detected following a COVID‐19 mRNA vaccine booster dose in this large multi‐state sample of nursing home residents.

Real-world effectiveness of fremanezumab in migraine patients initiating treatment in the United States: results from a retrospective chart study

BackgroundThe efficacy and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP) and is approved for the preventive treatment of migraine in adults, have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world data can further support those clinical trial data and demonstrate the full clinical benefits of fremanezumab. This chart review assessed the effectiveness of fremanezumab for improving clinical outcomes in adult patients with migraine treated according to real-world clinical practice.MethodsThis retrospective, panel-based, online physician chart review study used electronic case report forms with US physicians. Patient inclusion criteria were a physician diagnosis of migraine, fremanezumab treatment initiation at ≥ 18 years of age after US Food and Drug Administration approval, ≥ 1 dose of fremanezumab treatment, and ≥ 2 assessments of monthly migraine days (MMD; 1 within 30 days before treatment initiation and ≥ 1 after initiation). Changes from baseline in MMD, monthly headache days (MHD), and Migraine Disability Assessment (MIDAS) and 6-item Headache Impact Test (HIT-6) scores were assessed over 6 months. These endpoints were evaluated in the overall population and subgroups divided by dosing schedule and number of prior migraine preventive treatment failures.ResultsThis study included data from 421 clinicians and 1003 patients. Mean age at fremanezumab initiation was 39.7 years, and most patients were female (75.8%). In the overall population, mean baseline MMD and MHD were 12.7 and 14.0, respectively. Mean (percent) reductions from baseline in MMD and MHD, respectively, were − 4.6 (36.2%) and − 4.7 (33.6%) at Month 1, − 6.7 (52.8%) and − 6.8 (48.6%) at Month 3, and − 9.2 (72.4%) and − 9.8 (70.0%) at Month 6. Mean (percent) reductions from baseline in MIDAS and HIT-6 scores also increased over the 6-month study period, from − 6.2 (21.6%) and − 8.4 (14.0%) at Month 1 to − 18.1 (63.1%) and − 16.2 (27.0%) at Month 6, respectively. Improvements in these outcomes over 6 months were observed across all evaluated subgroups.ConclusionsThis real-world study demonstrated effectiveness of fremanezumab treatment for up to 6 months, irrespective of dosing regimen or number of prior migraine preventive treatment failures, reflecting ongoing, clinically meaningful improvements in patient outcomes.

Combining chest X-rays and electronic health record (EHR) data using machine learning to diagnose acute respiratory failure.

When patients develop acute respiratory failure (ARF), accurately identifying the underlying etiology is essential for determining the best treatment. However, differentiating between common medical diagnoses can be challenging in clinical practice. Machine learning models could improve medical diagnosis by aiding in the diagnostic evaluation of these patients. Machine learning models were trained to predict the common causes of ARF (pneumonia, heart failure, and/or chronic obstructive pulmonary disease [COPD]). Models were trained using chest radiographs and clinical data from the electronic health record (EHR) and applied to an internal and external cohort. The internal cohort of 1618 patients included 508 (31%) with pneumonia, 363 (22%) with heart failure, and 137 (8%) with COPD based on physician chart review. A model combining chest radiographs and EHR data outperformed models based on each modality alone. Models had similar or better performance compared to a randomly selected physician reviewer. For pneumonia, the combined model area under the receiver operating characteristic curve (AUROC) was 0.79 (0.77-0.79), image model AUROC was 0.74 (0.72-0.75), and EHR model AUROC was 0.74 (0.70-0.76). For heart failure, combined: 0.83 (0.77-0.84), image: 0.80 (0.71-0.81), and EHR: 0.79 (0.75-0.82). For COPD, combined: AUROC = 0.88 (0.83-0.91), image: 0.83 (0.77-0.89), and EHR: 0.80 (0.76-0.84). In the external cohort, performance was consistent for heart failure and increased for COPD, but declined slightly for pneumonia. Machine learning models combining chest radiographs and EHR data can accurately differentiate between common causes of ARF. Further work is needed to determine how these models could act as a diagnostic aid to clinicians in clinical settings.