Initial Time Research Articles

503 - Visualizing 3-year treatment outcome trajectories of dupilumab in adults with moderate-to-severe atopic dermatitis in real world practice

Abstract Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with high global prevalence and profound negative impact on the quality of life of children and adults. RELIEVE-AD, a prospective, longitudinal cohort study, included adults with moderate-to-severe AD who initiated dupilumab in real-world clinical practice. Results from RELIEVE-AD showed significant improvements in patient-reported disease control, quality of life, and treatment satisfaction in the overall study population that were sustained through 3 years of dupilumab treatment. Objective To report on response to dupilumab treatment over time at the individual patient-level in adults with moderate-to-­severe AD, using 3-year data from RELIEVE-AD. Methods RELIEVE-AD is a single-arm, prospective, observational study of adults with moderate-to-severe AD prescribed dupilumab and enrolled in the US dupilumab patient support program, who agreed to participate in online surveys at baseline and Months 1, 2, 3, 6, 9, 12, and 30–36. Post hoc analysis of the RELIEVE-AD 3yr data, describing changes from baseline through all post-dupilumab initiation time points at individual patient level, using Sankey plots to assess variability of individual patient response over time for the following patient-reported outcomes: Atopic Dermatitis Control Tool (ADCT) total score-based disease control status, AD-related health status, and AD treatment satisfaction. Results Of 698 patients who completed the baseline survey, 425 completed the Months 30–36 survey. Disease control (as measured by the ADCT) increased rapidly from 5.9% at baseline to 61.0% at Month 1, further increasing to 80.7% at Months 30–36. Patients reported improved AD-related health status at Month 30–36, with 70.9% reporting “Excellent” or “Very Good”, compared to 2.8% at baseline. At Months 30–36, 86.8% of patients reported being “Extremely Satisfied/Very Satisfied/Somewhat Satisfied” with their AD treatment, compared to 17.7% at baseline. All endpoints were significant vs baseline (P < 0.001). Sankey plots of the three outcomes indicated that the majority of patients maintained response over time after achieving the initial response. Conclusion The majority of patients who completed the survey reported benefits of dupilumab, such as AD control, treatment satisfaction, and health status, which remained stable or significantly improved during long-term treatment up to 36 months.

In-house three-dimensional printing for surgical planning: learning curve from a case series of temporomandibular joint and related disorders.

Three-dimensional (3D) printed models can improve the understanding of the structural anatomic changes in cases of temporomandibular joint ankylosis and pseudoankylosis leading to closed jaw locking. Their use in pre-surgical planning and intraoperative guidance has been reported, contributing to the predictability and success of these surgery procedures, which can be quite complex, especially in small animal patients. The use and production of 3D tools and models remain challenging and are so far limited to institutions with high (economical and human) resources. This study aims to propose simplified workflows using open-source software to facilitate an in-house 3D printing process. To illustrate this, three cases of temporomandibular joint ankylosis and one of pseudoankylosis were reviewed, where in-house 3D printed models were used for client communication and surgical management. The 3D models were segmented from computed tomography and printed via stereolithography. They were used to support discussion with clients (n = 4), to allow surgeons to pre-surgical plan and practice (n = 4) and for intraoperative guidance during surgery (n = 2). Surgical cutting guides were produced in one case to improve precision and define more accurately osteotomy lines. It is essential to consider the initial time and financial investment required for establishing an in-house 3D printing production, particularly when there is a need to produce biocompatible tools, such as surgical cutting guides. However, efficient and streamlined workflows encourage the integration of this technology, by accelerating the printing process and reducing the steep learning curves, while open-source software enhances accessibility to these resources.

Real-world management of chronic and postprandial hyperkalemia in CKD patients treated with patiromer: a single-center retrospective study.

Hyperkalemia, one of the most important electrolyte abnormalities of chronic kidney disease (CKD), often limits the use of renin-angiotensin-aldosterone system inhibitors and can increase in the postprandial period. In this study we report a real-world experience with the new non-adsorbed potassium binder patiromer in stage 3b-4 CKD patients. Moreover, we performed a cross-sectional analysis to evaluate, for the first time, the efficacy of patiromer in the control of postprandial potassium concentrations. We retrospectively collected data of 40 patients at the time of patiromer initiation (T0), and after 2 (T2), 6 (T6) and 12 (T12) months of treatment. For cross sectional analysis, a blood sample was collected 2h after the main meal for the evaluation of postprandial potassium concentrations. Eighty-two point five percent of patients (33/40) reached normal potassium concentrations at T2. Serum potassium significantly decreased at T2 compared to T0 (5.13 ± 0.48 vs 5.77 ± 0.41mmol/L, respectively; p < 0.001) and the reduction remained significant during the follow-up (5.06 ± 0.36 at T6 and 5.77 ± 0.41 at T12; p < 0.001 vs T0). Renin-angiotensin-aldosterone system inhibitors were continued by 93% of patients (27/29). Adverse events were reported in 27.5% of patients and were all mild-to-moderate. Postprandial potassium concentrations did not significantly change compared to fasting state potassium measured at T12 (4.53 ± 0.33 vs 5.06 ± 0.36mmol/L; p = 0.15). In a real-world setting of advanced CKD patients, patiromer is a useful treatment for hyperkalemia, since it significantly reduces serum potassium levels over the long term and is able to maintain potassium concentrations in the normal range even in the post-prandial period.

Study on the Gelation Process and Mechanical Properties of Organic Polymer Grouting Materials Applied to Fissure Sealing in Underground Mines.

In this study, organic polymer polyurethane grouting materials were prepared using isocyanate and polyether polyol as the main agents and various additives, the slurry coagulation process was investigated, and the mechanical properties of the polymer samples were tested to explore the influence of the density and soaking time of the polymer on the strength of the samples. The microstructure of the polymer was observed via electron microscopy, and relying on image analysis software, the structural parameters of the polymer cell were analyzed and calculated; the model equation between density and yield strength was established based on the strength model of porous materials developed by Gibson and Ashby. The results show that the initial viscosity and gel time of the polyurethane slurry decrease with the increase of the initial temperature, and the viscosity changes abruptly when the slurry reaches the gel point. The mechanical properties of the polymer increased with increasing density and decreased with increasing soaking time. The interior of the polymer is a porous structure and the pores are approximately spherical; the higher the density of the polymer material, the more uniform the stress distribution of the material, and the higher the percentage of the matrix, which in turn leads to better mechanical properties of the material. The diameter of the polymer cell is negatively correlated with the density, and the model established based on the microscopic parameters of the cell can better predict the yield strength of the polymer. This study helps to deepen the understanding of the microstructure and mechanical properties of polyurethane and provides a certain reference for the application of polyurethane in underground mine reinforcement engineering.

Uncertainties originating from GCM downscaling and bias correction with application to the MIS-11c Greenland Ice Sheet

Abstract. The Marine Isotope Stage 11c (MIS-11c) interglacial is an enigmatic period characterized by a long duration of relatively weak insolation forcing, but it is thought to have been coincident with a large global sea-level rise of 6–13 m. The configuration of the Greenland Ice Sheet during the MIS-11c interglacial highstand is therefore of great interest. Given the constraints of limited data, model-based analysis may be of use but only if model uncertainties are adequately accounted for. A particularly under-addressed issue in coupled climate and ice-sheet modeling is the coupling of surface air temperatures to the ice model. Many studies apply a uniform “lapse rate” accounting for the temperature differences at different altitudes over the ice surface, but this uniformity neglects both regional and seasonal differences in near-surface temperature dependencies on altitude. Herein we provide the first such analysis for MIS-11c Greenland that addresses these uncertainties by comparing one-way coupled Community Earth System Model (CESM) and ice-sheet model results from several different downscaling methodologies. In our study, a spatially and temporally varying temperature downscaling method produced the greatest success rate in matching the constraints of limited paleodata, and it suggests a peak ice volume loss from Greenland during MIS-11c of approximately 50 % compared to present day (∼ 3.9 m contribution to sea-level rise). This result is on the lower bound of existing data- and model-based studies, partly as a consequence of the applied one-way coupling methodology that neglects some feedbacks. Additional uncertainties are examined by comparing two different present-day regional climate analyses for bias correction of temperatures and precipitation, a spread of initialization states and times, and different spatial configurations of precipitation bias corrections. No other factor exhibited greater influence over the simulated Greenland ice sheet than the choice of temperature downscaling scheme.

The effect of the COVID-19 lockdown on women presenting with pelvic organ prolapse.

To determine whether there is a difference in pelvic organ prolapse (POP) stage at time of presentation after lifting coronavirus disease (COVID-19) lockdown restrictions, as compared to before the lockdown. Enhancing our understanding of how healthcare utilization for pelvic floor disorders may be affected by limited accessibility, such as the COVID-19 pandemic, could prove invaluable for similar future circumstances. This is a retrospective study of women with POP at their initial visit. Patients were grouped into two cohorts based on their initial presentation time: pre-COVID-19 lockdown (before March 2020) and post-COVID-19 lockdown (after December 2020). The cohorts were compared using demographic, clinical, and surgical variables. A logistic regression controlling for confounders was used to evaluate the influence of the COVID-19 lockdown on prolapse stage. There were 656 (50.3%) patients in the pre-COVID-19 lockdown cohort and 648 (49.7%) in the post-COVID-19 lockdown cohort. All baseline characteristics were similar between both cohorts except for race (p = 0.015). Treatment choices differed with the post-COVID-19 lockdown cohort having a lower proportion (26.5%) opting for surgery and a higher proportion (50.5%) of patients opting for nonsurgical interventions compared to the pre-COVID-19 lockdown cohort (p = 0.0005). A higher proportion of women presented with stages I and II prolapse in the post-COVID-19 lockdown (70.4%) cohort as compared to the pre-COVID-19 lockdown (62.5%) cohort (p = 0.002). Women in the post-COVID-19 lockdown cohort presented with early stage prolapse with preference for more conservative treatment options.

Optimal timing of GnRH antagonist initiation in IVF-ET: a retrospective cohort study on advanced maternal age women.

Several studies have compared the effects of fixed and flexible gonadotropin releasing hormone antagonist (GnRH-ant) protocols during in vitro fertilization and embryo transfer (IVF-ET). However, which GnRH-ant initiation strategy is better remains controversial. Moreover, no studies have assessed the optimal timing of GnRH-ant initiation in women of advanced maternal age (AMA). In this retrospective cohort study, a total of 472 infertile women aged ≥ 35 years old undergoing their first IVF cycle from August 2015 to September 2021 at a tertiary academic medical center were recruited, of whom 136 followed fixed GnRH-ant protocol and 336 followed flexible GnRH-ant protocol. The primary outcomes measured were the cumulative live birth rate (CLBR) per IVF cycle and the time to live birth (TTLB) from the date of oocyte retrieval. Cox proportional models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of CLBR regarding GnRH-ant timing. No significant difference in CLBR was found between the fixed and flexible GnRH-ant groups (27.9% vs 20.5%, p=0.105). The TTLB was also comparable between groups (10.56 vs 10.30 months, p=0.782). The Kaplan-Meier analysis for CLBR also showed comparable results between groups (P=0.351, HR=0.83; 95%CI: 0.56-1.23). After establishing a multiple Cox proportional hazard model, the fixed GnRH-ant group still had comparable CLBR with the flexible GnRH-ant group (HR=0.85; 95%CI: 0.53-1.38; P=0.518). Subgroup and sensitivity analyses also demonstrated similar results. GnRH-ant protocols can be tailored to the needs of AMA women, and timing of GnRH-ant initiation can be adjusted flexibly.

Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.

Sepsis and septic shock are associated with high mortality, with diagnosis and treatment remaining a challenge for clinicians. Their management classically encompasses hemodynamic resuscitation, antibiotic treatment, life support, and focus control; however, there are aspects that have changed. This narrative review highlights current and avant-garde methods of handling patients experiencing septic shock based on the experience of its authors and the best available evidence in a context of uncertainty. Following the first recommendation of the Surviving Sepsis Campaign guidelines, it is recommended that specific sepsis care performance improvement programs are implemented in hospitals, i.e., "Sepsis Code" programs, designed ad hoc, to achieve this goal. Regarding hemodynamics, the importance of perfusion and hemodynamic coherence stand out, which allow for the recognition of different phenotypes, determination of the ideal time for commencing vasopressor treatment, and the appropriate fluid therapy dosage. At present, this is not only important for the initial timing, but also for de-resuscitation, which involves the early weaning of support therapies, directed elimination of fluids, and fluid tolerance concept. Finally, regarding blood purification therapies, those aimed at eliminating endotoxins and cytokines are attractive in the early management of patients in septic shock.

Fabrication of cellulose nanocrystals/carboxymethyl cellulose/zeolite membranes for methylene blue dye removal: understanding factors, adsorption kinetics, and thermodynamic isotherms.

This study introduces environmentally-friendly nanocellulose-based membranes for AZO dye (methylene blue, MB) removal from wastewater. These membranes, made of cellulose nanocrystals (CNCs), carboxymethyl cellulose (CMC), zeolite, and citric acid, aim to offer eco-friendly water treatment solutions. CNCs, obtained from sugarcane bagasse, act as the foundational material for the membranes. The study aims to investigate both the composition of the membranes (CMC/CNC/zeolite/citric acid) and the critical adsorption factors (initial MB concentration, contact time, temperature, and pH) that impact the removal of the dye. After systematic experimentation, the optimal membrane composition is identified as 60% CNC, 15% CMC, 20% zeolites, and 5% citric acid. This composition achieved a 79.9% dye removal efficiency and a 38.3mg/g adsorption capacity at pH 7. The optimized membrane exhibited enhanced MB dye removal under specific conditions, including a 50mg adsorbent mass, 50ppm dye concentration, 50mL solution volume, 120-min contact time, and a temperature of 25°C. Increasing pH from neutral to alkaline enhances MB dye removal efficiency from 79.9% to 94.5%, with the adsorption capacity rising from 38.3mg/g to 76.5mg/g. The study extended to study the MB adsorption mechanisms, revealing the chemisorption of MB dye with pseudo-second-order kinetics. Chemical thermodynamic experiments determine the Freundlich isotherm as the apt model for MB dye adsorption on the membrane surface. In conclusion, this study successfully develops nanocellulose-based membranes for efficient AZO dye removal, contributing to sustainable water treatment technologies and environmental preservation efforts.

Safety and timing of early therapeutic anticoagulation therapy after craniotomy.

To date, there are few guidelines and studies to guide the timing of initiation of therapeutic anticoagulation (AC) after craniotomy. The goal of this study was to assess the timing, safety, and outcomes of patients following the administration of therapeutic AC after craniotomy. A retrospective case-control study was performed evaluating all craniotomy patients from August 2017 to July 2021. Cases were selected if they received therapeutic AC within ten days of craniotomy. Nineteen out of 1013 craniotomy patients met the inclusion criteria. Indications for therapeutic AC were diverse, including deep venous thrombosis, pulmonary embolism, dural venous sinus thrombosis, mechanical heart valve, and left ventricular thrombus. The mean and median time to therapeutic AC were 5.35 and 5 days, respectively. Three patients developed intracerebral hemorrhage (ICH) that was stable on repeat imaging and did not require any surgical intervention or result in new neurologic deficits. There was no significant association between therapeutic AC and postoperative ICH (P = 0.067). This study demonstrated that the initiation of therapeutic AC in postoperative craniotomy patients from postoperative days 2 to 10 did not result in any major complications. A prospective study is warranted to clarify the indications and safety of therapeutic AC after craniotomy.

Prenatal Care Initiation and Exposure to Teratogenic Medications

With new legal abortion restrictions, timing of prenatal care initiation is critical to allow for discussion of reproductive options among pregnancies exposed to teratogenic medications. To investigate the prevalence of prenatal exposure to teratogenic medications and prenatal care initiation across gestational weeks. This descriptive, population-based cross-sectional study used health encounter data from a national sample of individuals with employer-sponsored health insurance. A validated algorithm identified pregnancies among persons identifying as female that ended with a live or nonlive outcome between January 2017 and December 2019. Data were analyzed from December 2022 to December 2023. Prenatal exposure to any of 137 teratogenic medications, measured via pharmacy and medical claims. Measurement of prenatal care initiation was adapted from the Children's Health Care Quality Measures. Prevalence of prenatal exposure to teratogens and prenatal care initiation by gestational week. Timing of prenatal teratogenic exposure was compared with timing of prenatal care initiation and legal abortion cutoffs. Among 639 994 pregnancies, 472 472 (73.8%; 95% CI, 73.7%-73.9%) had a live delivery (mean [SD] age, 30.9 [5.4] years) and 167 522 (26.2%; 95% CI, 26.1%-26.3%) had a nonlive outcome (mean [SD] age, 31.6 [6.4] years). Of pregnancies with live deliveries, 5.8% (95% CI, 5.7%-5.8%) were exposed to teratogenic medications compared with 3.1% (95% CI, 3.0%-3.2%) with nonlive outcomes. Median time to prenatal care was 56 days (IQR, 44-70 days). By 6 weeks' gestation, 8186 pregnancies had been exposed to teratogenic medications (25.2% [95% CI, 24.7%-25.7%] of pregnancies exposed at any time during gestation; 1.3% [95% CI, 1.3%-1.3%] of all pregnancies); in 6877 (84.0%; 95% CI, 83.2%-84.8%), prenatal care was initiated after 6 weeks or not at all. By 15 weeks, teratogenic exposures had occurred for 48.9% (95% CI, 48.4%-49.5%) of all teratogen-exposed pregnancies (2.5% [2.4-2.5] of all pregnancies); prenatal care initiation occurred after 15 weeks for 1810 (16.8%; 95% CI, 16.1%-17.5%) with live deliveries and 2975 (58.3%; 95% CI, 56.9%-59.6%) with nonlive outcomes. Teratogenic medications most used within the first 15 gestational weeks among live deliveries included antiinfectives (eg, fluconazole), anticonvulsants (eg, valproate), antihypertensives (eg, lisinopril), and immunomodulators (eg, mycophenolate). For nonlive deliveries, most antihypertensives were replaced by vitamin A derivatives. In this cross-sectional study, most exposures to teratogenic medications occurred in early pregnancy and before prenatal care initiation, precluding prenatal risk-benefit assessments. Prenatal care commonly occurred after strict legal abortion cutoffs, prohibiting consideration of pregnancy termination if concerns about teratogenic effects arose.

Current Practices and Safety of Medication Use During Pediatric Rapid Sequence Intubation

OBJECTIVES This study aimed to characterize medication-related practices during and immediately ­following rapid sequence intubation (RSI) in pediatric care units across the United States and to evaluate adverse drug events. METHODS This was a multicenter, observational study of medication practices surrounding intubation in pediatric and neonatal intensive care unit (NICU) and emergency department patients across the United States. RESULTS A total of 172 patients from 13 geographically diverse institutions were included. Overall, 24%, 69%, and 50% received preinduction, induction, and neuromuscular blockade, respectively. Induction and neuromuscular blocking agent (NMBA) use was low in NICU patients (52% and 23%, respectively), whereas nearly all patients intubated outside of the NICU received both (98% and 95%, respectively). NICU patients who received RSI medications were older and weighed more. Despite infrequent use of atropine (21%), only 3 patients developed bradycardia after RSI. Of the 119 patients who received an induction agent, fentanyl (67%) and midazolam (34%) were administered most frequently. Hypotension and hypertension occurred in 23% and 24% of patients, respectively, but were not associated with a single induction agent. Etomidate use was low and not associated with development of adrenal insufficiency. Rocuronium was the most used NMBA (78%). Succinylcholine use was low (11%) and administered despite hyperkalemia in 2 patients. Postintubation sedation and analgesia were not used or inadequate based on timing of initiation in many patients who received a non-depolarizing NMBA. CONCLUSIONS Medication practices surrounding pediatric RSI vary across the United States and may be influenced by patient location, age, and weight.

Abstract WP45: A Collaborative Approach to Improving Inpatient Stroke Code Time Target Metrics

Much effort and education has been placed on pre-hospital and emergency departments to recognize signs and symptoms of acute stroke and time metrics such as door-to-CT, door-to-needle, and door-to-device. For admitted patients with acute onset of stroke symptoms, our data analysis identified a gap in the timeliness of stroke code activation upon symptoms discovery and subsequent delays in CT initiation and treatment. We evaluated our current process and implemented action plans to enhance the current inpatient stroke code process through focused education and training of staff to improve their recognition of acute stroke, timely activation of stroke code and improved CT initiation and treatment times. In 2021, several cardiology pilot units were selected and neuroscience nurse specialists conducted staff education which focused on recognition of stroke signs and symptoms, code activation criteria and response time targets. A resource binder and checklist were created to guide staff in putting together pertinent elements for communication and documentation. Data was collected on stroke code response times and individual feedback was provided. The group meets quarterly to evaluate progress, discuss opportunities for improvement and highlight best practices and outcomes. The checklist was a useful tool in reminding staff of pertinent information to communicate to the stroke team although form completion is not consistent. In 2021-2022, 54% of stroke codes were called within 10 minutes of symptoms discovery. CTH initiation time within 25 minutes of symptoms discovery was achieved in 16.2% of patients. Data analysis showed an opportunity to improve documentation of symptoms discovery time which were missing in 13.8% of cases. This collaborative approach with the pilot units has increased awareness and focus to the inpatient stroke code process. Opportunities exist to improve time target achievements in CTH initiation, treatment, and documentation of symptoms discovery time. Communication between the stroke team and the patient’s primary team has been identified as an essential factor for continued improvement along with on-going staff education.

Effect of Platelet-Rich Plasma at Different Initiation Times on Healing of the Bone-Tendon Interface of the Rotator Cuff in a Mouse Model.

Platelet-rich plasma (PRP) has demonstrated beneficial effects on healing of the bone-tendon interface (BTI). To determine the optimal initiation time for PRP application after rotator cuff repair in an animal model. Controlled laboratory study. A total of 136 C57BL/6 mice were included; 40 mice were used to prepare PRP, while 96 mice underwent acute supraspinatus tendon (SST) repair. The animals were randomly divided into 4 groups: a control group and 3 groups in which PRP was injected into the injury interface immediately after surgery, on the 7th postoperative day (PRP-7d), and on the 14th postoperative day. At 4 and 8 weeks postoperatively, the animals were sacrificed, blood was collected by eyeball removal, and samples of the SST-humerus complex were collected. Histological, imaging, immunological, and biomechanical data were compared among the groups using 1-way analysis of variance with the Bonferroni post hoc test. Histological analysis revealed that the fibrocartilage layer at the BTI was larger in the PRP-7d group compared to the other groups at both 4 and 8 weeks postoperatively. Moreover, the PRP-7d group exhibited improved proteoglycan content and distribution compared to the other groups. Enzyme-linked immunosorbent assay results demonstrated that at 4 weeks postoperatively, higher concentrations of transforming growth factor-β1 and platelet-derived growth factor-BB (PDGF-BB) were seen in the PRP-7d group versus the PRP-14d and control gruops (P < .05), and at 8 weeks postoperatively, the concentration of PDGF-BB was higher in the PRP-7d group versus the control group (P < .05). Biomechanical testing at 4 weeks postoperatively revealed that the failure load and ultimate strength of the SST-humerus complex were superior in the PRP-7d group compared to the other groups (P < .05), at 8 weeks, PRP-7d group was superior to the control group (P < .05). Additionally, at 8 weeks postoperatively, the PRP-7d group exhibited a greater trabecular number and trabecular thickness at the BTI compared to the PRP-14d and control gruops (P < .05). PRP promoted healing of the BTI after a rotator cuff injury at an early stage. A PRP injection on the 7th postoperative day demonstrated superior therapeutic effects compared with injections at other time points.

Nutrition of Newborns with Hypoxic-Ischaemic Encephalopathy during Therapeutic Hypothermia - A Survey of Practice in Polish Neonatal Care Units.

The nutritional practice for newborns with hypoxic-ischaemic encephalopathy during therapeutic hypothermia differs among Polish neonatal care units, as no guidelines are provided. We assessed the prevailing procedures. Data was collected through an anonymous, web-based questionnaire. We surveyed aspects of the current nutritional practices and the reasoning behind the choice of the feeding strategy. Thirty-one responses were obtained (31/33, 94%). Based on participants' estimations, 342 newborns are diagnosed with hypoxic-ischaemic encephalopathy and qualified for therapeutic hypothermia annually. Among them, almost ⅓ is fed exclusively parenterally, while 71% both ways-parenterally and enterally. In the vast majority of units, the introduction of enteral nutrition takes place during the first 48 hours of therapeutic hypothermia, and breast milk is primarily provided, although with substantial first feeding volume differentiation (an average of 2,9 ml/kg (0,3 - 10ml/kg)). Adverse events, such as necrotising enterocolitis, sepsis, and glycemia level disturbances that derive from the initiation of enteral nutrition, are difficult to estimate as no official statistics are provided. The majority of newborns after hypoxic-ischaemic encephalopathy treated with therapeutic hypothermia are fed both parenterally and enterally during the procedure, predominantly with expressed or donor breast milk. However, due to the lack of nutritional guidelines, significant variability of nutritional strategies concerning initiation time, type and volume of enteral feeds given is noted. Therefore, further studies are required to clarify feeding recommendations.

Real-world utilization patterns of radium-223 in metastatic prostate cancer in the United States: An administrative claims database study.

79 Background: Radium (Ra)-223 is approved for use in men with symptomatic castration resistant prostate cancer (CRPC) with bone metastases, demonstrating benefits in terms of overall survival and quality of life with a reliable safety profile. In the rapidly evolving treatment landscape for prostate cancer, real-world (RW) data on Ra-223 utilization are limited. We aimed to examine the RW utilization patterns of Ra-223 in patients with metastatic prostate cancer using a large administrative claims database in the US. Methods: A retrospective cohort of men treated with Ra-223 was identified using the closed claims private payor database of the Komodo Research Dataset covering the period from 01/01/2017 to 06/30/2022. The earliest administration of Ra-223 in men with bone metastatic prostate cancer was considered as index date. Individuals were required to have continuous insurance coverage at least 12-month pre-index (baseline) and least 6-month post index or until death if patients survived &lt; 6 months (follow-up). Logistic regression was used to identify baseline demographic, clinical, medications, or healthcare resource use-related factors associated with receiving 5+ cycles of Ra-223. Results: The study cohort comprised of 1,376 men with a median age of 68 years at the time of Ra-223 initiation. Most men were treated by oncologists (52.2%), having bone only metastases (51.5%), having Charlson comorbidity index (CCI) ≥ 1 (76.2%). Diabetes (34.1%), peripheral vascular disease (29.9%), pulmonary disease (25.9%) and mild liver disease (25.1%) were the most common pre-existing comorbidities. Therapies received prior to Ra-223 were androgen receptor pathway inhibitors (75.4%), chemotherapy (32.1%), sipuleucel-T (13.7%) and bone health agents (73.7%). Ra-223 was utilized as a combination therapy by 26.0% of the overall population, predominately with enzalutamide. Nearly 15%, 38%, and 31% received Ra-223 (mono or combination therapy) as 1st, 2nd, and 3rd line therapy, respectively. Approximately 46% of the overall cohort and 54% of those who survived ≥ 6 months had received 5+ cycles, respectively. In regression analysis, men with short survival (&lt;6 month) [Odds ratio, OR: 0.05, 95% confidence interval (CI): 0.03, 0.10], low CCI (0 vs. 4+) (OR: 0.38, 95% CI:0.19, 0.76), and pulmonary disease (OR: 0.71, 95% CI: 0.52, 0.97) had lower likelihood of completion of 5+ cycles. Conclusions: Nearly half of men completed 5+ cycles of Ra-223 therapy in a large US cohort of relatively young mCRPC men with private health insurance. Advanced disease state with short survival and low comorbidity were key factors associated with lower completion of 5+ cycles. The findings highlight the importance of utilizing Ra-223 early after mCRPC diagnosis, when the probability of &gt;6-month survival is higher, to enhance treatment completion that has been shown to result in better outcomes.

Trends over time in the proportion of sequential treatment and overall survival in patients with metastatic urothelial carcinoma in real-world practice.

606 Background: New approaches involving immune checkpoint inhibitors (ICIs) and antibody-drug conjugates prolong overall survival (OS) in patients with metastatic urothelial carcinoma (mUC). However, the access to such systemic therapy in clinical practice is suboptimal, and whether these agents improve OS in patients with mUC over time remains unclear. In the present study, we investigated the OS trend from the initiation of first-line therapy with these agents to identify changes due to the medication and time of treatment initiation. Methods: We retrospectively evaluated 195 patients who received platinum-based chemotherapy as a first line treatment. The patients were treated with chemotherapy, pembrolizumab, avelumab, or enfortumab vedotin (EV) sequentially and were divided into the following three groups: chemotherapy period (April 2009–June 2017; P1), pembrolizumab period (July 2017–December 2020; P2), and avelumab and EV period (January 2021–August 2022; P3) based on the regulatory approval. Data cutoff was set at July 31, 2023. Results: OS was prolonged over time by the new therapeutic agents, and median OS was 11, 25, not reached, and 35.5 months for patients who were treated with chemotherapy, pembrolizumab, avelumab, or EV, respectively. However, median OS was 14, 18 months, and not reached in P1, P2 and P3, respectively. Analysis by periods showed that OS was significantly longer in P2 than in P1 (HR = 0.62, 95% CI: 0.43–0.89, P = 0.009) and in P3 than in P1 (HR = 0.47, 95% CI: 0.28–0.78, P = 0.015). No difference was observed in OS between P2 and P3 (HR = 0.66, 95% CI: 0.36–1.20, P = 0.21). Overall, the proportion of patients who received ICIs increased over time, as indicated by the fact that 77 and 95 patients received ICIs (pembrolizumab or avelumab) in P2 and P3, respectively. However, the prevalence of the treatment with EV was only 24%, and 43% of patients who received pembrolizumab received best supportive care. Conclusions: This study showed an improvement in OS over time in patients with mUC in real-world practice and may indicate the importance of not missing the appropriate opportunity to receive sequential treatments.

Abstract WP12: Early or Later Anticoagulation in Post-Stroke Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Uncertainty regarding the timing of anticoagulant initiation after an ischemic stroke in patients with atrial fibrillation arises from the lack of extensive data on this matter. We conducted the first meta-analysis, including only randomized controlled trials, to clarify this question. Methods: We systematically searched Embase, PubMed, and Cochrane Library in June 2023 for studies comparing early versus late initiation of anticoagulation post-stroke in patients with atrial fibrillation. Statistical analyses were performed using R software version 5.4.1. Results: We included three studies comprising 2,989 patients. Of these, 1,497 (50%) received early anticoagulation with a direct oral anticoagulant (DOAC), and 1,492 (50%) received later anticoagulation with a DOAC or warfarin. 51.66% of participants were women. The use of early anticoagulation was associated with a lower incidence of recurrent ischemic stroke; nonetheless, this result lacked statistical significance (RR 0.68; 95% CI 0.44-1.04; p=0.07; I 2 =0%). The number of symptomatic intracerebral hemorrhage events was 2 in the early anticoagulation group and 3 events in the later anticoagulation group, with no statistical significance between the groups. Conclusion: Our findings suggest no statistically significant difference in recurrent ischemic stroke and intracerebral bleeding between the initiation of early or later anticoagulation in post-stroke patients with atrial fibrillation.

Longitudinal Analysis of Mpox Virus DNA Detectability From Multiple Specimen Types During Acute Illness: A Cohort Study.

Longitudinal data on the detectability of monkeypox virus (MPXV) genetic material in different specimen types are scarce. We describe MPXV-specific polymerase chain reaction (PCR) results from adults with confirmed mpox infection from Toronto, Canada, including a cohort undergoing weekly collection of specimens from multiple anatomic sites until 1 week after skin lesions had fully healed. We quantified the time from symptom onset to resolution of detectable viral DNA (computed tomography [Ct] ≥ 35) by modeling exponential decay in Ct value as a function of illness day for each site, censoring at the time of tecovirimat initiation. Among 64 men who have sex with men, the median (interquartile range [IQR]) age was 39 (32.75-45.25) years, and 49% had HIV. Twenty received tecovirimat. Viral DNA was detectable (Ct < 35) at baseline in 74% of genital/buttock/perianal skin swabs, 56% of other skin swabs, 44% of rectal swabs, 37% of throat swabs, 27% of urine, 26% of nasopharyngeal swabs, and 8% of semen samples. The median time to resolution of detectable DNA (IQR) was longest for genital/buttock/perianal skin and other skin swabs at 30.0 (23.0-47.9) and 22.4 (16.6-29.4) days, respectively, and shortest for nasopharyngeal swabs and semen at 0 (0-12.1) and 0 (0-0) days, respectively. We did not observe an effect of tecovirimat on the rate of decay in viral DNA detectability in any specimen type (all P > .05). MPXV DNA detectability varies by specimen type and persists for over 3-4 weeks in skin specimens. The rate of decay did not differ by tecovirimat use in this nonrandomized study.

Impact of corticosteroid (CS) exposure on acquired resistance to immune checkpoint inhibitor (ICI) therapy in patients (pts) with metastatic renal cell carcinoma (mRCC): A single centre experience.

404 Background: ICI therapy with Ipilimumab and Nivolumab (I/N) is a first line standard of care option in pts with intermediate – poor risk mRCC, with the longest durable response in this setting. Nonetheless, a high percentage of pts eventually progress on ICI treatment. Currently contributing factors for acquired ICI resistance remain unclear. The impact of CS use on acquired ICI resistance remains controversial and data in mRCC pts is particularly lacking. Methods: We conducted a retrospective analysis of consecutive mRCC pts with primary non-progression to first line I/N. We analysed the use of concurrent CS for all indications including immune related adverse events (IRAE) and compared baseline characteristics of pts who received CS (Cohort A) vs those who did not (Cohort B). Association between CS use, progression and mortality was analysed using multivariable Cox regression model. Adjustment for casemix included IMDC risk score, best response, presence of sarcomatoid/rhabdoid features and brain/liver metastases. Progression free (PFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Results: 64 pts treated with 1L I/N at the Royal Marsden Hospital with primary non-progression between 2016 - 2022 were included. The commonest histological subtype was clear cell (87.5%) with 30% having sarcomatoid/rhabdoid features. All pts had intermediate - poor IMDC risk, with 34% having poor IMDC risk. 47 pts received CS for any indication (Cohort A) and of these 44 pts for IRAE. 17 pts received no CS (Cohort B). Baseline characteristics including IMDC risk, grade and presence of liver/brain metastases were not statistically different between cohorts. 57 pts were eligible for survival analysis with 33 progression events. Median follow up was 22.5 months overall. At multivariable analysis no factors were significantly associated with PFS or OS. Median PFS was 16 months (95% CI 10, 33) in cohort A vs 25 months (95% CI 8, not reached [NR]) in cohort B. PFS was 39% (95% CI 23%, 55%) in Cohort A vs 50% (95% CI 19%, 75%) in Cohort B at 2 years, and 30% (95% CI 15%, 47%) vs 38% (95% CI 10%, 66%), at 3 years respectively. Median OS was 55 months (95% CI 21, NR) in cohort A and NR in cohort B. OS was 60% (95% CI 41%, 74%) in cohort A vs 65% (95% CI 23%, 88%) in cohort B at 2 years and 55% (95% CI 36%, 71%) vs 65% (95% CI 23%, 88%) at 3 years. Cumulative doses and time of CS initiation will be included in the final analysis to determine their impact on above outcomes. Conclusions: Although no statistically significant association was seen between CS use and PFS or OS, our results suggest a trend towards shorter time to progression and survival with CS use in pts on 1L I/N for mRCC. While further analyses regarding the dosage and timing of CS are underway, given this is a single centre retrospective analysis, these results would need to be confirmed in larger studies.