IQR Range Research Articles

Evaluating the World Health Organization's HEARTS Model for Hypertension and Diabetes Management: A Pilot Implementation Study in Guatemala.

The World Health Organization HEARTS Technical Package is a widely implemented global initiative to improve the primary care management of cardiovascular disease risk factors. The study's objective is to report outcomes from a pilot implementation trial of integrated hypertension and diabetes management based on the HEARTS model in Guatemala. We conducted a single-arm pilot implementation trial over 6 months from October 2023 to May 2024 in 11 Guatemalan Ministry of Health primary care facilities in two districts. The pilot evaluated a package of five HEARTS-aligned implementation strategies to improve the pharmacological treatment of hypertension and diabetes. The primary outcomes were feasibility and acceptability, measured through 20 structured interviews with Ministry of Health employees and by examining enrollment and retention. Secondary outcomes included a suite of implementation and clinical outcomes, including treatment rate. The study enrolled 964 patients, of whom 58.8% had hypertension only, 30.4% had diabetes only, and 10.8% had both conditions. Surveys on feasibility and acceptability among Ministry of Health staff had a median score of 5.0 (IQR: 5.0 to 5.0) and 5.0 (IQR range: 4.8 to 5.0), respectively, exceeding the prespecified benchmark of ≥3.5. Both districts achieved the prespecified benchmark of enrolling ≥25 hypertension patients and ≥25 diabetes patients. Only 36% of patients attended a follow-up visit within three months, lower than the prespecified benchmark of ≥75%. M treatment rates during the pilot increased by 22.3 (95% CI: 16.2 to 28.4; P<0.001) and 3.5 (95% CI: -1.6 to 8.7; P=0.17) patients per month for hypertension and diabetes, respectively. Implementation of an integrated hypertension and diabetes model based on HEARTS was generally feasible and acceptable in the Ministry of Health in Guatemala. Findings can refine national scale-up in Guatemala and inform HEARTS implementation projects in other settings.

A Construction of Virtual Reality Technology Teaching Model to Improve Table Tennis Skills for University Students

Background and Aims: To explore and build virtual reality physical education courses, and create a new teaching model of "VR+ teaching" to improve the quality of talent training and teaching effect. This study will build a teaching model of virtual reality technology to improve college students' table tennis skills, trying to enable learners to complete real-time interaction of multiple senses with the help of sensing devices in virtual sports situations, and then combine the goal incentive and feedback mechanism to improve students' self-efficacy and learning interest, which can not only promote the diversified development of sports skill learning but also promote the development of sports skill learning. It also provides a reference for the application of virtual reality technology in physical education. The purpose of this study is to construct of virtual reality technology teaching model to improve table tennis skills for university students. Methodology: The survey included faculty and students at the three universities. Current number of teachers and students: Yunnan University has 1855 students and 66 teachers; Yunnan Normal University has 1980 students and 95 teachers. Yunnan Minzu University has 1531 students and 65 teachers. In this study, the experts were interviewed by telephone interview, face-to-face interview, and summary interview, using the method of interview outline. Questionnaires were distributed to students and teachers on-site and by webmail. The Delphi Method expert questionnaire was issued to 19 experts. Results: Most of the teachers are willing to use virtual reality technology to teach table tennis. They think virtual reality technology will improve their teaching effectiveness. Construct a virtual reality teaching model for improving college students' table tennis skills, and construct a virtual reality teaching model for improving college students' table tennis skills from five dimensions: teaching idea, teaching goal, teaching content, teaching process, and teaching evaluation. Most people agree on all issues (IQR range 0.00-1). Conclusion: Virtual reality technology is applied to table tennis teaching in colleges and universities so that students can quickly enter the role, and effectively improve the dull feeling caused by being bored and unable to hit the ball in the learning process of table tennis. While learning table tennis knowledge and skills, learners actively explore and complete the construction of new knowledge. It provides a new teaching concept for the reform of table tennis teaching and the multiple development of physical education curricula in colleges and universities and also promotes the deep integration of education informatization and physical education teaching in the new era.

VALIDATE—Utilization of the Viz.ai mobile stroke care coordination platform to limit delays in LVO stroke diagnosis and endovascular treatment

BackgroundThousands of hospitals worldwide have adopted mobile artificial intelligence (AI)-based stroke care coordination platforms. Studies exploring the benefit of these platforms have been scrutinized due to small sample size, serial cohort design, and measurement of metrics with multiple determinants. In this large multi-center study, we evaluated the ability of an AI-based stroke care coordination platform to expedite contact with the interventionalist (NIR) for potential thrombectomy.MethodsAcute stroke consultations seen by TeleSpecialists, LLC physicians at 166 facilities (17 states) utilizing Viz.ai software (AI) vs. no AI software (non-AI) were extracted from the TeleCare by TeleSpecialists™ database from December 1, 2021, through March 31, 2022. The primary outcome was time from patient arrival to first contact with the interventionalist to discuss need for potential thrombectomy (Arrival-to-NIR notification).ResultsA total of 14,116 cases were analyzed. Compared to the non-AI cohort, Arrival-to-NIR notification in the AI cohort was: (1) 39.5 min faster (44.13% reduction, p &amp;lt; 0.001) in the overall analysis; (2) 33.0 min faster (34.0% reduction, p &amp;lt; 0.001) in the non-thrombectomy (non-TC) facility subgroup analysis; and (3) 34.0 min faster (43.59% reduction, p &amp;lt; 0.001) in the thrombectomy capable (TC) facility subgroup analysis. IQR range comparison demonstrated a significant improvement in uniformity of stroke workflow across all AI subgroups. Significant, albeit small, confounding biases were revealed in the data. The presence of AI within the non-TC subgroup correlated with a lower acceptance rate for thrombectomy by the NIR (delta = −10.79% absolute and 23.17% relative reduction, p &amp;lt; 0.0001).ConclusionsWhile this study was limited by our inability to capture detailed neuroimaging timelines and patient outcomes, it suggests a potential significant benefit of AI-based stroke care coordination platforms and underscores the critical need to development robust “big data” systems to study the effects of AI, and other emerging technologies, on stroke systems of care.

Abstract PO1-05-01: Cyclin-dependent Kinase 4/6 Inhibitors Combined with Radiotherapy in the Management of Brain Metastases in HR-positive/HER2-negative Breast Cancer Patients

Abstract Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus endocrine therapy demonstrated overall survival benefits in advanced breast cancer patients (ABC), hormone receptor-positive, HER2-negative (HR+/HER2-) and remains the mainstay in the first and second-line treatment. Brain metastases are rare at the beginning of treatment in this group of patients and are found more often during subsequent lines of treatment and other subtypes of breast cancer. However, there is a paucity of data on the safety and efficacy of multimodality CDK4/6i and radiotherapy treatment in the management of brain metastases. Thus, we performed a retrospective analysis of ABC patients (pts) treated at our institution with radiation therapy to the brain and CDK4/6i. Pts who received radiotherapy before CDK4/6i initiation or concurrently with CDK4/6i (group 1) were compared to the patients who progressed in the brain during CDK4/6i treatment and then received radiotherapy (group 2). The primary endpoint was progression-free survival (PFS) in group 1 vs. group 2; the secondary endpoints were local control (LC) within the brain in group 1 vs. group 2 and severe toxicity. Materials/Methods: Among 379 pts who received CDK4/6i, 26 pts (6.9%) received radiotherapy to the brain. 17 pts received radiotherapy before or concurrent with CDK4/6i and were included in group 1. Nine pts received radiotherapy after CDK4/6i discontinuation due to disease progression and comprised group 2. Results: The median age was 51.5 years (IQR range 41-62). Six pts had de novo metastatic disease. The majority of patients were treated in the first-line setting (15 pts, 58%). 17 pts received ribociclib, 7 palbociclib, and 2 abemaciclib. 15 pts received letrozole as an endocrine compound and 11 pts fulvestrant. 19 pts (73%) received previous chemotherapy. Six pts had an ECOG performance status of 0, 15 pts ECOG 1, and 5 pts ECOG 2. The most common local treatment was whole-brain radiotherapy with a total dose of 20 Gy delivered in 5 fractions (fr) (11 pts: 4 pts VMAT, 2 pts IMRT, 3 pts 3D, and 2 pts 2D). Eight pts received stereotactic radiation therapy (6 pts with Linac: 2 pts 24 Gy/2 fr, 2 pts 24 Gy/3 fr, 2 pts 25 Gy/5 fr; 1 pt GammKnife 20 Gy/1 fr, 1 pt Cyberknife 15 Gy/3 fr). Six- and 12-month PFS in group 1 was 88.2% (95% CI74.1-100) and 58.8% (95% CI: 37.7- 91.8), respectively, whereas in group 2, six- and 12-month PFS was 55.6% (95%CI: 31- 99.7) and 44.4% (95% CI: 21- 92.2), respectively. Six- and 12-month LC in group 1 was 92.3% (95%CI: 78.9-100) and 83.9% (65.7-100), respectively. LC in group 2 was poor: 3-month LC was only 66.7 (30-100). At a median follow-up of 8.8 months, no unanticipated toxicity was reported. Conclusion: Multimodality treatment with CDK4/6i and radiotherapy to the brain is safe and effective. Patients who developed metastases during CDK4/6i treatment tend to have a worse prognosis in comparison to those who received prior radiotherapy. CDK4/6i following radiotherapy seems to be an effective and valuable treatment option in this particular metastatic breast cancer population. Citation Format: Marcin Kubeczko, Dorota Gabryś, Anna Polakiewicz-Gilowska, Aleksandra Krzywon, Donata Gräupner, Barbara Łanoszka, Marta Mianowska-Malec, Aleksandra Leśniak, Katarzyna Świderska, Konstanty Chomik, Barbara Grandys, Michał Jarząb. Cyclin-dependent Kinase 4/6 Inhibitors Combined with Radiotherapy in the Management of Brain Metastases in HR-positive/HER2-negative Breast Cancer Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-01.

Insights from a single centre implementation of a digitally-enabled atrial fibrillation virtual ward.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and poses a significant public health burden. Virtual wards are a novel approach utilising digital solutions to provide hospital-level care remotely; their rollout has become a key priority for the UK National Health Service to expand acute care capacity. We devised and implemented a digitally-enabled AF virtual ward to monitor patients being established onto medical therapy following an AF diagnosis or an AF-related hospitalisation. Patients were onboarded either as outpatients to avoid admission or on discharge after an acute AF hospitalisation. Remote monitoring was undertaken using a clinically validated photoplethysmography-based smartphone app. Over a 1-2 week period, patients performed twice daily measurements of heart rate and rhythm and provided corresponding symptoms. A traffic light system guided frequency of telephone assessments by specialist practitioners. Red flag symptoms or abnormal heart rate parameters prompted an urgent care escalation. We report our experience of the first 73 patients onboarded to the AF virtual ward from October 2022 to June 2023 (mean age 65 years, median 68 years, IQR range 27-101 years; 33 females). Thirty-nine (53%) patients had red flag features requiring care escalation, of whom 9 (23%) were advised to attend ED (emergency department) for urgent assessment, 10 (26%) attended for expedited review and 14 (36%) required medication changes. By 3 months post-monitoring, only 3 patients (4%) had re-attended ED with an arrhythmia-related presentation. Virtual ward patients had an average 3-day shorter inpatient stay (mean duration 4 days) compared with AF patients hospitalised prior to virtual ward implementation (mean duration 7 days). Overall, 22 arrhythmia-related readmissions were prevented via the virtual ward model. In this study, we present a novel implementation of a digitally-enabled virtual ward for the acute management of patients with newly diagnosed or poorly controlled AF. Our pilot data indicate that this model is feasible and is potentially cost-effective. Further longitudinal study is needed to definitively evaluate long-term clinical utility and safety.

The Double Burden of Malnutrition among Adolescents from Zimbabwe: A Cross-Sectional Study

(1) Background: The double burden of malnutrition (DBM) is an emerging public health concern among children and adolescents in developing countries. This study investigated the prevalence and factors associated with being underweight and overweight among adolescents. (2) Methods: This cross-sectional study was conducted among 423 adolescents across 10 high schools in Harare. A questionnaire was used to collect data and weight for height-z-scores were used to compute body mass index. Pearson’s Chi-Square and multinomial logistic regression were used to test for associations and explore factors associated with being underweight or overweight at (p &lt; 0.05). (3) Results: The median and IQR range for the participants was 16 (14–19) years. There were more girls 53.2%, than boys 46.8% (p = 0.002), and more 14–16-year-olds 54.1%, than 17–19-year-olds (p = 0.070). More boys 10% than girls 9.1% were underweight, whereas more girls 21.8% than boys 9.3% were overweight and obese (p = 0.002). By age, more 14–16-year -olds were underweight 12.7% than 17–19-year-olds 5.9%, whereas more 17–19-year-olds 16.2% were overweight than 14–16-year-olds (p = 0.070). Significant factors associated with being underweight were inadequate balanced nutrition knowledge [OR = 1.49 (0.139–0.997), p = 0.049], being in the 14–16 years age group [OR = 2.56 (1.137–5.779), p = 0.023], having formally employed [OR = 2.34 (1.008–5.428), p = 0.048] and unemployed [OR = 5.17 (1.263–21.116), p = 0.022] household heads. Significant factors associated with overweight were being a girl [OR = 0.32 (0.168–2.561), p &lt; 0.001, and having formally employed household heads [OR = 2.00 (1.044–1.206), p = 0.037]. The employment status of the household head (being formally employed) was the only factor which associated with both underweight and overweight statuses. (4) Conclusions: Although underweight and overweight statuses co-exist, among adolescents, those who are overweight appear to be more than those who are underweight. Significant factors associated with being underweight were inadequate nutrition knowledge, being 14–16 years old, and having formally employed or unemployed parents. While being a girl and having formally employed parents were significant determinants of the overweight status. This paper calls for more awareness of DBM and context-specific interventions targeting obesity in a country where undernutrition has been traditionally prioritized at policy and program levels.

FDA pooled analysis of overall survival according to depth of response as a continuous variable in frontline advanced immuno-oncology renal cell carcinoma trials.

418 Background: Retrospective analyses of individual studies of immune-oncology-containing combinations (IOC) for advanced renal cell carcinoma (aRCC) suggest that depth of response (DepOR; % reduction from baseline in sum of target lesion diameters) is associated with overall survival (OS). However, these analyses are limited by use of DepOR categories with a small number of patients and guarantee-time bias. We therefore sought to investigate the relationship of week 12 DepOR as a continuous variable with OS, hypothesizing not only complete but also deep partial responses might portend favorable longer-term survival. Methods: We pooled data from patients with treatment (tx)-naïve aRCC enrolled in randomized IO-based frontline aRCC trials submitted to FDA that included a Week 12 imaging assessment. We developed 36-month (mo) overall survival (OS) prediction models based on Week 12 DepOR per Independent Review Committee using Cox proportional hazards with natural spline in the IO-TKI combination (IOC) and sunitinib (SUN) groups. To avoid guarantee-time bias, OS was defined from date of an individual patient’s 12-week imaging, among the subset of patients who were alive and in follow-up at the Week 12 scan. Results: Four trials met inclusion criteria (KEYNOTE-426, JAVELIN Renal 100, CheckMate 9ER, CheckMate 214); in total there were 1364 patients in the IOC group and 1267 patients in the SUN group. Eligibility criteria, baseline patient characteristics, and endpoints were similar both between the trials and between tx groups. Deepest response occurred at median 31 weeks (interquartile range [IQR], 18-55) in the IOC group and 29 weeks (IQR range, 17-48) in the SUN group. At Week 12, 34.7% of patients had DepOR of at least 30%; median DepOR was 27.6% (interquartile range [IQR] 8.7 to 43.4%) in the IOC and 13.7% (IQR 2.5 to 26.3%) in the SUN group. DepOR and 36-month OS were correlated throughout the entire range of DepOR in both tx groups; at each DepOR, the IOC group had slightly higher 36-mo OS over SUN. We saw similar results modeling 24-month OS compared to 36-month OS. Conclusions: This pooled exploratory analysis suggests that deeper response is associated with better 36-month OS in patients treated with IOC or SUN and slightly higher probability of 36-month OS for any given DepOR for IOC vs. SUN. We saw no plateau in OS as DepOR approached complete response. However, caution should be used when interpreting DepOR at the tails due to sparse data. Further work characterizing the relationship between DepOR and OS at the trial level may advance understanding of the utility of DepOR as an early endpoint in signal-seeking trials and to facilitate efficient drug development. Additionally, identifying patients with favorable long-term prognosis based on DepOR provides hypotheses for new trial designs.

Airway management with Hi-flow nasal cannula oxygen in children with severe laryngeal obstruction

BackgroundThe aim of this study was to report our initial experience in airway management in young children with severe laryngeal obstruction. Hi-flow nasal cannula oxygen (HFNO) with spontaneous respiration was used as a new airway management strategy in young children undergoing suspension laryngoscopic surgery. MethodsChildren aged between 1 day and 24 months scheduled for suspension laryngoscopy were retrospectively studied. The data collected included the patients' age, gender, American Society of Anaesthesiologists physical status classification, comorbidities, preoperative physiological status, methods of induction and maintenance of anesthesia, course of the disease and surgical options, lowest oxygen saturation recorded, transcutaneous CO2, duration of operation, and patients' need for rescue methods. ResultsA total of 38 patients successfully underwent suspension laryngoscopy under HFNO with spontaneous respiration. 19 patients were less than 1 year old (7 neonates), while the other half were less than or equal to 2 years old. The median [IQR (range)] lowest oxygen saturation recorded during the operation was 98 [93–99 (91–99)] %. The median [IQR (range)] duration of HFNO with spontaneous respiration was 65 [45–100 (30–200)] minutes. The median [IQR (range)] PCO2/PtcCO2 at the end of the spontaneous ventilation period was 54 [48–63 (39–70)] mmHg, which was the same as the preoperative PCO2 despite a long operation time. ConclusionsHFNO with spontaneous respiration emerged as a new airway management strategy in young children with severe laryngeal obstruction that was beneficial in maintaining oxygenation and was superior to transnasal humidified rapid insufflation ventilatory exchange (THRIVE) in terms of the rising rate of PCO2 in these patients, thereby prolonging the safety time of the operation.

Long-term outcomes and risk factors for reoperation after subaortic stenosis resection in children and adults

Abstract Background Sub-valvular aortic stenosis (SAS) is an extremely heterogeneous form of left ventricular outflow tract (LVOT) obstruction, which can lead to aortic valve damage. Although corrective surgery is considered the most effective treatment, rates of recurrence and reoperation are still high. Previous studies have focused on predictors of reoperation in several subgroups of patients with SAS, but rarely in the whole population of patients with SAS. Purpose We sought to describe long-term outcomes after SAS resection and to determine the predictors of reoperation after successful primary resection. Methods We retrospectively reviewed the records of patients who underwent SAS resection between 1994 and 2021 at our institution with at least 12 months’ follow-up. Patients with a single-ventricle physiology and idiopathic hypertrophic cardiomyopathy were excluded. Demographic, surgical and echocardiographic data were analyzed. Outcomes were reoperation after successful primary resection, death and morbidities, including postoperative complete heart block and aortic regurgitation (AR) grade at latest follow-up. Results Seventy-six patients (paediatric, n = 72 and adult, n = 4) who underwent SAS resection were included in the analysis. Median length of postoperative follow-up was 11.1 years (IQR range: 7.3 – 15.7 years), with two late deaths. Reoperation due to recurrent obstruction or severe AR occurred in 24 patients (31.6%). Median time to reoperation was 7.5 years (IQR range: 3.6 – 11 years). Overall freedom from reoperation at 5 years and 10 years was 84.6% and 69.1% respectively. Gender and association with other cardiac defects did not differ significantly between those with reoperation and those without. In multivariate analysis, independent predictors of reoperation were age at first surgery younger than 5 years (HR 3.54, 95% CI 1.06 – 11.83; P = 0.040) and tunnel-type lesions (HR 4.42, 95% CI 1.70 – 11.51; P = 0.002). Three patients (3.9%) had complete heart block and required placement of an implantable pacemaker. Following SAS resection, progression of AR was common (39/68, 57.3%) but only 5 patients (7.3%) developed sufficient regurgitation to require surgical repair or replacement. Conclusions Reoperation is not infrequent after surgical relief of SAS and reaches a plateau after 10 years. Younger age at first surgery and tunnel-type SAS independently predict reoperation. Progression of AR after corrective surgery of SAS is common, but fortunately only a minority of patients develop hemodynamically significant AR requiring reintervention.

Bendamustine Versus Fludarabine and Cyclophosphamide for Lymphodepletion Prior to CAR-T Therapy

Background As CAR-T treatment volumes and approved indications rapidly expand, identifying optimal lymphodepleting chemotherapy (LDC) regimens is an urgent and unmet need. A combination of fludarabine and cyclophosphamide (flu/cy) is most commonly performed. However, an ongoing international fludarabine shortage1 has led to the use of bendamustine (benda), a potent lymphotoxin, as LDC, with initial reports suggesting similar efficacy with less toxicity2, 3. We performed a multi-center retrospective analysis of patients with non-Hodgkin lymphoma (NHL) who have received benda or flu/Cy LDC prior to infusion of FDA-approved CAR-T products across the Sarah Cannon Transplant and Cellular Therapy Network (SCTCTN). We hypothesized that, compared with flu/cy, benda is noninferior in terms of lymphodepletion, hematologic recovery, CAR-T response and toxicities, as well as resource utilization. Methods We retrospectively analyzed 215 NHL patients receiving benda (46) or flu/cy (169) LDC prior to commercial CAR-T from 2018-2023 in the SCTCTN CAR-T registry. Patients on clinical trials, who received CAR-T for other malignancies than NHL, or were within 30 days of CAR-T infusion were excluded. Absolute lymphocyte count (ALC), neutrophil, and platelet kinetics were measured. Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) were graded according to consensus criteria of the American Society of Transplant and Cellular Therapy (ASTCT), and the occurrence, maximum grade, days to onset/resolution, and tocilizumab dosing were recorded. Overall survival (OS), progression free survival (PFS), and resource utilization (length of stay in hospital and ICU requirement) were recorded. Results Characteristics of patients receiving benda and flu/cy were matched in terms of age, gender, race, ethnicity, NHL subtype, performance status. Flu/cy and benda produced deep absolute lymphocyte count (ALC) nadirs by the date of CAR-T infusion (day 0) with subsequent partial recovery by day 30. Lymphodepletion nadir at day 0 was deeper [P&amp;lt;0.001] with flu/cy (ALC 0.03 K/uL, IQR range 0.01-0.05) than benda (ALC 0.21 K/uL, IQR range 0.1-0.3) but not at other time points. The kinetics of neutrophil and platelet recovery were similar between groups suggesting an equivalent extent of marrow suppression. Parameters of resource utilization such as inpatient hospitalization, length of stay, ICU utilization, and the use of tocilizumab were similar between flu/cy and benda recipients. Conclusion In a large cohort of real-world CAR-T recipients, benda produced efficient lymphodepletion and equivalent outcomes compared to traditional flu/cy. While flu/cy produces a deeper nadir than benda at day 0, this difference did not exert clinical relevance.

Clinical outcomes and genomic landscape of patients (pts) with EGFR-mutant lung cancer (EGFR+ LC) with central nervous system (CNS) metastases (mets).

e21146 Background: CNS mets are a major cause of morbidity and mortality in pts with LC. Up to 50% of pts with EGFR+ LC develop CNS mets over their disease course despite improvements in anti-EGFR therapies. The genomics alterations present in CNS mets in pts with EGFR+ LC and how these may compare to paired systemic samples has not been reported. Furthermore, it is unknown whether there are baseline clinicogenomic features that differ between EGFR+ LC pts with or without (w/wo) CNS mets. Methods: From an institutional database of LC pts with available next-generation sequencing (NGS) completed by MSK-IMPACT, we identified all EGFR+ LCs with molecularly characterized CNS tumor samples (CTS). We subsequently identified all pts with EGFR+ LCs with available paired CTS and systemic tumor samples (STS) profiled with MSK-IMPACT. All pts treated with 1L osimertinib with MSK-IMPACT available on their STS were also identified. We assessed clinicogenomic features of all selected EGFR+ LCs. Comparisons of frequencies of genes altered by somatic alterations were performed using Fisher’s exact test and logistic regression. Results: From 2014 to 2022, 90 EGFR+ LC pts with NGS performed on CTS were identified [brain metastasis (BrM), n = 38; leptomeningeal w/wo BrM (LM), n = 52]. 69 pts (77%) were female, median age 59 (IQR range:53-66 years), and 51 pts (57%) were never smokers. Patterns of EGFR+ were exon 19del (n = 43), L858R (n = 27) and atypical (n = 20). No genomic mutations were differentially altered in pts with LM vs BrM. Paired CTS and STS were available for 28 pts, where numerically higher rates of CDKN2A, CDKN2B loss and RAC1 amplification were seen in the CTS (respectively 43% vs 18%, 43% vs 18%, and 21% vs 0%, q &gt; 0.05 for all). A total of 263 pts on 1L osi had NGS on their STS performed:136 pts (52%) had CNS mets during their disease course to date [94 pts (69%) de novo CNS mets; 42 pts with on-treatment CNS mets with median time to CNS mets of 25 mo (IQR: 13.5-35.3 mo)]. Between pts w/wo a lifetime history of CNS mets, there were no differences in sex, smoking history, EGFR alterations and co-alterations. CARD11 alterations were numerically higher in STS in pts with CNS mets (12% vs 2%, q &gt; 0.05). Conclusions: In patients with EGFR+ LC, there were no genomic alterations that were significantly enriched in CNS mets compared to systemic disease, and no systemic genomic alterations that differentiate pts w/wo CNS mets.

FDA pooled analysis of overall survival according to depth of response as a continuous variable in frontline advanced immuno-oncology renal cell carcinoma trials.

e16532 Background: Retrospective analyses of individual studies of immune-oncology-containing combinations (IOC) for advanced renal cell carcinoma (aRCC) suggest that depth of response (DepOR; % reduction from baseline in sum of target lesion diameters) is associated with overall survival (OS). However, these analyses are limited by use of DepOR categories with a small number of patients and guarantee-time bias. We therefore sought to investigate the relationship of week 12 DepOR as a continuous variable with OS, hypothesizing not only complete but also deep partial responses might portend favorable longer-term survival. Methods: We pooled data from patients with treatment (tx)-naïve aRCC enrolled in randomized IO-based frontline aRCC trials submitted to FDA that included a Week 12 imaging assessment. We developed 36-month (mo) overall survival (OS) prediction models based on Week 12 DepOR per Independent Review Committee using Cox proportional hazards with natural spline in the IO-TKI combination (IOC) and sunitinib (SUN) groups. To avoid guarantee-time bias, OS was defined from date of an individual patient’s 12-week imaging, among the subset of patients who were alive and in follow-up at the Week 12 scan. Results: Four trials met inclusion criteria (KEYNOTE-426, JAVELIN Renal 100, CheckMate 9ER, CheckMate 214); in total, there were 1364 patients in the IOC group and 1267 patients in the SUN group. Eligibility criteria, baseline patient characteristics, and endpoints were similar both between the trials and between tx groups. Deepest response occurred at median 31 weeks (interquartile range [IQR], 18-55) in the IOC group and 29 weeks (IQR range, 17-48) in the SUN group. At Week 12, 34.7% of patients had DepOR of at least 30%; median DepOR was 27.6% (interquartile range [IQR] 8.7 to 43.4%) in the IOC and 13.7% (IQR 2.5 to 26.3%) in the SUN group. DepOR and 36-month OS were correlated throughout the entire range of DepOR in both tx groups; at each DepOR, the IOC group had slightly higher 36-mo OS over SUN. We saw similar results modeling 24-month OS compared to 36-month OS. Conclusions: This pooled exploratory analysis suggests that deeper response is associated with better 36-month OS in patients treated with IOC or SUN and slightly higher probability of 36-month OS for any given DepOR for IOC vs. SUN. We saw no plateau in OS as DepOR approached complete response. However, caution should be used when interpreting DepOR at the tails due to sparse data. Further work characterizing the relationship between DepOR and OS at the trial level may advance understanding of the utility of DepOR as an early endpoint in signal-seeking trials and to facilitate efficient drug development. Additionally, identifying patients with favorable long-term prognosis based on DepOR provides hypotheses for new trial designs.

MP25-05 PROGRAM DIRECTORS' PERSPECTIVES ON THE ASSESSMENT OF RESIDENCY APPLICANTS IN THE POST-USMLE STEP 1 ERA: A STRONG CASE FOR STANDARDIZED LETTERS OF RECOMMENDATION?

You have accessJournal of UrologyCME1 Apr 2023MP25-05 PROGRAM DIRECTORS' PERSPECTIVES ON THE ASSESSMENT OF RESIDENCY APPLICANTS IN THE POST-USMLE STEP 1 ERA: A STRONG CASE FOR STANDARDIZED LETTERS OF RECOMMENDATION? Angeline Johny, Patrick J. Shenot, Charles Green, Leah Chisholm, Steve Riggs, Stephen V. Jackman, Aqsa A. Khan, Peter N. Kolettis, Brian K. McNeil, and Wesley A. Mayer Angeline JohnyAngeline Johny More articles by this author , Patrick J. ShenotPatrick J. Shenot More articles by this author , Charles GreenCharles Green More articles by this author , Leah ChisholmLeah Chisholm More articles by this author , Steve RiggsSteve Riggs More articles by this author , Stephen V. JackmanStephen V. Jackman More articles by this author , Aqsa A. KhanAqsa A. Khan More articles by this author , Peter N. KolettisPeter N. Kolettis More articles by this author , Brian K. McNeilBrian K. McNeil More articles by this author , and Wesley A. MayerWesley A. Mayer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003253.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The USMLE Step 1 exam evolved into a key metric utilized by program directors (PDs) in assessing candidates for residency. The transition to a USMLE Step 1 binary pass/fail scoring system has resulted in a loss of an important objective assessment. With national movements towards pass/fail systems for clerkship grading and trends towards abandonment of class ranking, assessing residency applications is becoming increasingly challenging. METHODS: The Society for Academic Urologists (SAU) convened a task force to, in part, assess the perspectives of urology PDs regarding the importance of various aspects of a residency application for predicting clinical performance. An anonymous survey was disseminated to all urology program directors in the United States. Perspectives on 11 potential application predictors of clinical performance and demographics were recorded. Descriptive statistics characterized PD responses. Friedman’s Test and pairwise Wilcoxon tests were used to evaluate the relative ranks assigned to application elements by PD’s. RESULTS: There was a 60.5% response rate (89/147). Letters of recommendation (LOR) was ranked as the most important predictor, with a mean of 2.39, median of 2 (IQR range 1- 3). Clerkship grades and USMLE Step 1 were comparable and ranked second with mean scores of 4.3, and 4.62 respectively. Medical school reputation ranked the lowest with a mean score of 8.47. There was significant heterogeneity among categories, however this was less so for LORs which predominated as the most important factor among application elements (p<0.001). CONCLUSIONS: To our knowledge, this is the largest sample size assessing program director perspectives on application factors that predict clinical performance. The second (clerkship grades) and third (USLME Step 1) most important factors moving to binary pass/fail systems creates an opportunity for actionable change to improve assessment objectivity. Our data demonstrate LOR to be the most important factor of residency applications. Thus, there may be a strong argument for moving towards a standardized LOR to maximize this tool, mitigate bias, and improve inter-reviewer reliability. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e344 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Angeline Johny More articles by this author Patrick J. Shenot More articles by this author Charles Green More articles by this author Leah Chisholm More articles by this author Steve Riggs More articles by this author Stephen V. Jackman More articles by this author Aqsa A. Khan More articles by this author Peter N. Kolettis More articles by this author Brian K. McNeil More articles by this author Wesley A. Mayer More articles by this author Expand All Advertisement PDF downloadLoading ...

A randomized trial of individualized opioid prescription protocol versus fixed quantity for post-cesarean pain management

To evaluate whether an individualized opioid prescription protocol (IOPP) with a shared decision-making component is non-inferior to a fixed quantity prescription of opioid tablets for outpatient cesarean pain management at 1-week post-discharge. We performed a non-inferiority open-label trial at 31 US sites (NCT04296396). Prior to hospital discharge, participants who had undergone cesarean delivery were randomly assigned to IOPP or fixed quantity (20 tablets of 5mg oxycodone) and followed through 90 days postpartum. In the IOPP group, individuals received education on post-operative pain expectations, opioid side effects, and the number of recommended tablets based on their morphine milligram equivalent (MME) use in the past 24 hours. They then selected a quantity of post-discharge tablets (up to 20) to be prescribed. The primary outcome was moderate to severe pain (≥ 4) at 1-week post-discharge on the Brief Pain Inventory (BPI, 0-10) in the last 24 hrs. Secondary outcomes were pain scores and post-discharge opioid prescriptions within 90 days. A planned sample size of 5500 tested non-inferiority of IOPP compared to fixed quantity assuming 90% power, type I error 0.025 1-sided and inferiority margin of 5%. From Sep 2020 through March 2022, of 9963 eligible individuals, 5520 (55%) were enrolled (n=2748 IOPP, n=2772 fixed). Baseline characteristics were similar between groups. In the IOPP group, participants requested a median of 14 tablets (IQR range 6-20). The primary outcome rate was not inferior between the IOPP and fixed groups (59% vs. 60%, Risk Difference -0.7; 95% CI -3.4, 2.0), and worst pain was similar throughout follow-up (Figure). The proportion filling an opioid prescription after discharge was similar between groups (7.6% vs 6.2%, relative risk 1.22, 95% CI [1.00, 1.48]). Reported opioid-related side effects were similar between groups (13.5% vs. 13.9%, p=0.7). Compared to fixed quantity opioid prescription, IOPP was non-inferior for outpatient post-cesarean pain management at 1-week post discharge.

Long-Term Follow-up of Dutch Patients with Sickle Cell Disease Diagnosed By Newborn Screening - Effect on the Morbidity and Mortality in the Netherlands

Background: Sickle cell disease (SCD) is associated with increased morbidity and mortality compared to the general population. To enable early preventive measures to improve clinical outcome, newborn screening for SCD was introduced in January 2007 in the Netherlands. The objective of this study is to assess the residual risk of death and the incidence of major disease-related complications during the first fifteen years of life in children diagnosed with SCD by newborn screening. Methods: In this prospective, national multicenter cohort study, all children born after 1 January 2007 and diagnosed with SCD by newborn screening were included. Following informed consent, data were collected from medical files on SCD genotype, treatment, mortality and occurrence of major disease-related complications including hospitalization for vaso-occlusive crises (VOC), severe infections (sepsis, meningitis, osteomyelitis) and neurological complications. Overall survival and survival without specific SCD-related complications were analyzed by Kaplan-Meier curves. Results: Preliminary data of 197 (38%) of the 520 eligible subjects from 8 centers in the Netherlands, with a total follow-up of 1,585 patient-years are presented. The median age on July 1st 2022 was 8.0 years (IQR range: 4.0 - 11.0 years). The majority of children (55%) had severe SCD (genotypes HbSS or HbSβ0 thalassemia), the remainder had another genotype including HbSC or HbSβ+ thalassemia. Survival at the age of 15 years was 99.5%. One patient died at the age of 1 year due to pneumococcal sepsis. Eight patients (4%) had a severe infection (meningitis, sepsis, osteomyelitis) caused by Streptococcus Pneumoniae in 3/8 cases with 1 fatal outcome as described above. Two patients experienced a symptomatic cerebral infarction at the age of 11 months and 1.5 years, respectively. Both patients had comorbidities, increasing the risk of a cerebral infarction. The mean survival time without admission for VOC was 7.3 years (95% CI: 6.2-8.5) for HbSS/HbSβ0 thalassemia and 11.5 years (95% CI: 10.1-12.8) for HbSC/HbSβ+ thalassemia, respectively (p < 0.001) (Figure 1). Conclusion: In this Dutch cohort of neonatally screened patients with SCD, infectious complications were the main cause of severe comorbidity and mortality. Further analysis to identify risk factors for infectious complications will be performed in the final analyses to target additional preventive measures that may lower the risk of infection in this specific group of patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

High JAK2V617F allele burden is associated with an increased burden of coronary artery calcification in MPNs

Abstract Background Patients with the haematological cancers Philadelphia-negative Myeloproliferative Neoplasms (MPNs), have an increased risk of coronary artery and aortic valve calcification, and an increased risk of myocardial infarctions. The most common acquired mutation in MPNs, the JAK2V617F mutation, has been linked to increased risk of thrombosis. Aims To exam the association between the JAK2V617F mutation, its allele burden, and coronary artery and aortic valve calcification. Methods One hundred and sixty one patients with MPN disease from one specialized haematological outpatient clinic where included. Information on demographics, smoking, alcohol habits and co-morbidities were registered. Blood samples were drawn for determination of the JAK2V617 mutation and allele burden. Patients were examined by cardiac computer tomography in order to determine their coronary artery calcium score (CACS) and aortic valve calcification (AVC) score. The association between the JAK2V617F mutation, its allele burden and coronary artery and aortic calcification was investigated with univariate and multivariate logistic regression analysis, adjusting for age, sex, ischemic heart disease (IHD), stroke, smoking, obesity, hypertension, hypercholesterolemia, diabetes mellitus, and family history of IHD or stroke in the multivariate analysis. Results Of the 161 patients (52% male, mean age 65.5±10.5 years), 137 (85%) were JAK2V617F positives, and the JAK2V617F allele burden was quantified in 120. The median JAK2V617F allele burden was 12% (IQR range 6–33%). There were 42 (26%) patients with a CACS &amp;gt;400, and 93 (58%) patients AVC. Among the JAK2V617F positive patients, 38 (24%) had a CACS &amp;gt;400 and 81 (59%) had AVC. In the 32 patients with a JAK2V617F allele burden&amp;gt;33%, 19 (59%) had a CACS &amp;gt;400 and 26 (81%) had AVC. In the univariate logistic regression analysis the presence of JAK2V617F mutation was not associated with a CACS &amp;gt;400 (Odds Ratio (OR) 1.92, 95% confidence interval (CI) 0.62–5.98, p=0.26). Similar result was found for the analysis on AVC (OR 1.45, 95% CI 0.61–3.45, p=0.41). In contrast, a JAK2V617F allele burden &amp;gt;33% was significantly associated with a CACS &amp;gt;400 (OR 5.31, 95% CI 2.23–12.66, p=0.0002), and similarly with AVC (OR 4.14, 95% CI 1.55–11.05, p=0.0045). In the multivariate adjusted analysis, a JAK2V617F allele burden &amp;gt;33% was significantly associated with a CACS &amp;gt;400 (OR 2.08, 95% CI 0.43–10.10, p=0.36), but not with AVC (OR 0.90, 95% CI 0.27–3.03, p=0.86). In the adjusted analysis the association between a JAK2V617F allele burden &amp;gt;33% and CACS &amp;gt;400 was significant (OR3.86, 95% CI 1.14–13.09, p=0.031), but the analysis on AVC was not (OR 1.59, 95% CI 0.42–6.04, p=0.50). Conclusion There is a significant association between a JAK2V617F allele burden &amp;gt;33% and the burden of coronary calcification in MPNs, measured as a CACS &amp;gt;400. The association remains significant after adjustment for cardiovascular risk factors. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Region Sjællands Sundhedsvidenskabelige ForskningsfondTømrermester Jørgen Holm og hustru Elisa F. Hansens Mindelegat

Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19

BackgroundCOVID-19 patients carry an increased rate of thrombosis. It is controversial to which extent thrombi in the pulmonary arterial tree really contribute to disease severity with hypoxemia secondary to microvascular/lung parenchymal damage with viral alveolitis considered to play the main role in critical disease. ObjectivesThe primary objective was to compare post-mortem lung disease from fatal COVID-19 pneumonia in patients with macroscopically evident pulmonary arterial tree thrombosis and patients without, by characterizing the immunohistochemical nature of thrombi, and by comparing clinical and laboratory features of these patients with other COVID-19 patients who died but without evidence of pulmonary arterial thrombosis (controls). Patients and methods13 COVID-19 pneumonia cases (mean age ± standard deviation: 74 ± 6.5 years) with macroscopically visible pulmonary arterial thrombosis were compared to 14 controls. Hematoxylin and Eosin stained slides were reviewed choosing those with visible pulmonary thrombi which were further characterized by immunohistochemistry, in particular for the inflammatory infiltrates. Ante mortem serum markers relevant to pulmonary embolism were evaluated in both groups. ResultsTwenty arterial thrombi (5 cases with multiple thrombi) were selected for study and were composed by white blood cells (WBC) [median, IQR range: 10 % (5–12.25)], mainly neutrophils [58 % (35.2–64.5)]. Cases with thrombosis showed significantly higher levels of platelet count [median, IQR range: 195000/mmc (157750–274,500) vs 143,500 (113000–175,250), p = 0.011], LDH [854 U/L (731–1315) vs 539 (391.5–660), p = 0.003] at admission, and D-dimer at ICU transfer [25,072 FEU (6951–50,531) vs 1024 (620–5501), p = 0.003]. ConclusionsImmunothrombotically driven arterial thrombi in COVID-19 patients are associated with D-Dimer and LDH elevations, thus linking inflammation, coagulopathy and organ damage in fatal COVID-19.

Cannula cricothyroidotomy in the impalpable neck: An observational study of simulated 'can't intubate, can't oxygenate' scenarios by teams following a cannula-first algorithm in live anaesthetised pigs.

Live animal models can be used to train anaesthetists to perform emergency front-of-neck-access. Cannula cricothyroidotomy success reported in previous wet lab studies contradicts human clinical data. This prospective, observational study reports success of a cannula-first 'can't intubate, can't oxygenate' algorithm for impalpable anatomy during high fidelity team simulations using live, anaesthetised pigs.Forty-two trained anaesthesia teams were instructed to follow the Royal Perth Hospital can't intubate, can't oxygenate algorithm to re-oxygenate a desaturating pig with impalpable neck anatomy (mean (standard deviation, SD) 16.2 (3.5) kg); mean (SD) tracheal internal diameter 11 (1.4) mm. Teams were informed that failure would prompt veterinary-led euthanasia.All teams performed percutaneous cannula cricothyroidotomy as the initial technique, with a median (interquartile range, IQR (range)) start time of 42 (35-50 (24-93)) s. First-pass percutaneous cannula success was 29% to both insufflate tracheal oxygen and re-oxygenate. Insufflation success improved with repeated percutaneous attempts (up to three), but prolonged hypoxia time increasingly necessitated euthanasia (insufflation 57%; re-oxygenation 48%). First, second and third percutaneous attempts achieved insufflation at median (IQR (range)) 74 (64-91 (46-110)) s, 111 (95-136 (79-150)) s and 141 (127-159 (122-179)) s, respectively. Eighteen teams failed with percutaneous cannulae and performed scalpel techniques, predominantly dissection cannulation (n = 17) which achieved insufflation in all cases (insufflation 100%; re-oxygenation 47%). Scalpel attempts were started at median (IQR (range)) 142 (133-218 (97-293)) s and achieved insufflation at 232 (205-303 (152-344)) s.While percutaneous cannula cricothyroidotomy could rapidly re-oxygenate, the success rate was low and teams repeated attempts beyond the recommended 60 s time frame, delaying transition to the more successful dissection cannula technique. We recommend this 'cannula-first' can't intubate, can't oxygenate algorithm adopts a 'single best effort' strategy for percutaneous cannula, with failure prompting a scalpel technique.

Ustekinumab for the treatment of moderate to severe ulcerative colitis: a multicentre UK cohort study

ObjectiveUstekinumab is an interleukin-12/interleukin-23 receptor antagonist licensed for the treatment of ulcerative colitis (UC). Clinical trial data were promising; however, real-world data are limited. We assessed the safety and effectiveness...

Seroconversion after anti-SARS-CoV-2 mRNA vaccinations among moderate-to-severe psoriatic patients receiving systemic biologicals-Prospective observational cohort study.

It is unclear whether biological antipsoriatic therapies affect seroconversion after messenger ribonucleic acid (mRNA)‐based antisevere acute respiratory syndrome coronavirus 2 (anti‐SARS‐CoV‐2) vaccinations. To assess antibody formation and the incidence of side effects after anti‐SARS‐CoV‐2 mRNA vaccinations in psoriatic patients receiving different biologicals compared to healthy controls. 102 moderate‐to‐severe psoriatic patients (56.2 [±13.5] years) and 55 age‐matched healthy (56.4 ± 13.6 years) volunteers were included in our study. Ten to 21 days after the administration of the second dosage of BNT162b2 or mRNA‐1273 vaccine, antibody levels specific to the SARS‐CoV‐2 spike (S) protein receptor binding domain were monitored. The incidence of postvaccination side effects was recorded and compared to real‐life data in the literature. Of the 102 patients, 57 (55.88%) received tumor necrosis factor (TNF), 28 (27.45%) received interleukin (IL)‐12/23, 16 (15.68%) received IL‐17, and 1 (0.99%) received IL‐23 inhibitors. No significant differences in the median serum level of anti‐SARS‐CoV‐2S antibody were observed between the study population and the control group (median IQR range: 1681.0 U/mL (600.0–4844.0) versus 1984.0 U/mL (1000.0–3136.0; p = 0.82). The most frequent side effects of the mRNA vaccines within 7 days after the administration of both dosages were arm pain on the side of injection (23.53% and 23.53%), fatigue (9.80% and 13.72%), headache (4.9% and 5.88%), and chills or shivering (4.9% and 8.82%). Detectable antibodies against SARS‐CoV‐2S protein appear 10–21 days after the administration of the second dosage of BNT162b2 or mRNA‐1273 vaccines in moderate‐to‐severe psoriatic patients receiving biologicals, similar to those of healthy controls.