Real-world Management Research Articles

1178 Management of SFA Disease Delineated by Disease Type – a Multicentre European Analysis

Abstract Aim The study aimed to assess how SFA disease is treated in patients with critical limb ischaemia and patients with claudication. Method Data was collected from the RandomSTOP European registry database. Patients were categorised into those with critical limb ischaemic (CLTI) and those with claudication (nCLTI). Patient demographics were stratified by sex, Rutherford classification, lesion length, smoking status, history of diabetes, history of chronic kidney disease, history of hypertension and pre-admission medications. Procedural variables were stratified by type of treatment. Post-operative complications including perforation, dissection, embolization and in hospital reintervention were compared. Chi-squared analyses were used to compare the two groups. Results Data on 1,567 patients who underwent surgery for SFA disease was analysed. 64% (n = 1,009) of patients had CLTI, and 36% (n = 558) had nCLTI. Those with CLTI were statistically significantly more likely to be older (p<0.0001****) and female (p<0.0001****). Those with CLTI were more likely to have CKD (p<0.0001****) and diabetes (p = 0.002**) Those with nCLTI were statistically significantly more likely to be on a statin and antiplatelet (p<0.0001****). Most patients underwent percutaneous transluminal angioplasty (PTA), (75% of CLTI and 84% of nCLTI) with some form of vessel preparation (the most common being Drug Coated Balooning; 36% CLTI and 64% nCLTI). Those with CLTI had greater incidence of post-operative complications including perforation (p = 0.002**), embolization (p = 0.0004***) and secondary intervention (p = 0.016). Conclusions This is one of the largest contemporary series on the real-world management of SFA disease. Vessel preparation and PTA appear to be the mainstay of managing complex SFA disease.

Clinical and economic implications of epilepsy management across treatment lines in Spain: a real-life database analysis

BackgroundEpilepsy is a chronic brain disease characterized by recurrent seizures. We investigated real-world management of epilepsy across treatment lines in Spain, including healthcare resource use (HRU) and associated costs.MethodsThis was a retrospective study of real-life data from epilepsy patients prescribed antiseizure medication (ASM) between January 2016 and December 2021. Patients were grouped according to their line of treatment (1st, 2nd, 3rd and 4th +) during the recruitment period. Demographic and clinical characteristics, comorbidities and concomitant medications were analyzed during the baseline period (6 months before starting treatment line); antiepileptic treatments, concomitant medications, HRU and associated costs were analyzed during follow-up.ResultsThe study included 5006 patients. Treatment duration decreased as treatment lines progressed (mean ± SD progression time: 523.2 ± 279.1 days from 1st to 2nd line, 351.6 ± 194.4 days from 2nd to 3rd line; 272.7 ± 139.3 days from 3rd to 4th + line). Significant HRU differences were found with subsequent treatment lines, including an increase in hospital admissions and patients on sick leave. Mean (95% CI) adjusted total costs per patient were €2974/year (2773–3175) in the 1st line and €5735/year (5043–6428) in the 4th + line. There was an increase in adjusted direct and total costs with subsequent treatment lines; the mean difference in total costs between cohorts was €2761 (p < 0.001). The highest direct costs were associated with epilepsy medication, days at the hospital and specialist visits.ConclusionOur data revealed a progressive increase in the use of resources and associated costs across subsequent epilepsy treatment lines.

Real-World Clinical Characteristics, Management, and Outcomes of 44 Paediatric Patients with Hypopigmented Mycosis Fungoides.

Hypopigmented mycosis fungoides is a rare form of mycosis fungoides that is characterized by achromic lesions, early onset of disease, a predilection for darker skinned populations, and a predominance of CD8+ T cells. Due to the rarity and heterogeneous presentation of hypopigmented mycosis fungoides, there are no criteria that clearly define the clinical characteristics and treatment regimens for this condition. This retrospective study of 44 paediatric patients with hypopigmented mycosis fungoides aimed to summarize their epidemiological and clinical characteristics and assess the effectiveness and safety of different treatment regimens. Clinical manifestations were further classified into 3 morphological groups: hypopigmented lesions, papules overlying hypopigmented lesions, and erythematous plaques overlying hypopigmented lesions. In addition, the results of this study suggest that interferon alpha might be an effective and well-tolerated therapy that could shorten the treatment time to complete response compared with other treatments. Maintenance therapy and long-term follow-up reduced the recurrence rate.

Pemphigus Disease and Area Index: Unmet needs in the real-world management of pemphigus.

Over the past few decades, a number of scoring instruments have been developed to assess the severity and activity of autoimmune bullous diseases (AIBDs) (Daneshpazhooh et al., 2019; Nili et al., 2020; Nili et al., 2021; Nili et al., 2022). The Pemphigus Disease Area Index (PDAI), developed by the International Pemphigus Definitions Group, is an easy-to-use, quick, and reliable method for determining pemphigus severity. As a reliable and effective tool in clinical trials, PDAI may also have some limitations and might require some revisions to be used on a daily basis. Here, we propose some recommendations to improve the use of PDAI in the clinical setting.

Treatment pattern and health care resource utilization for Taiwanese patients with migraine: a population-based study.

Given the substantial disease burden, appropriate and effective management of migraine is a public health priority. To gain insights into real-world migraine management practices in Taiwan, current treatment patterns, costs, and health care resource use were assessed. This was a retrospective, longitudinal study using the Taiwan National Health Insurance Research Database. Included patients had an initial diagnosis of migraine (defined using International Classification of Diseases codes) between 1 January 2013 and 31 December 2017. Data analyzed included demographics; the use, number, and type of acute and preventive medications; and drug and medical services costs. Data were stratified according to migraine type (chronic [CM] or episodic [EM] migraine). A total of 312,718 patients were included in the analyses: 53,992 (17.3%) had CM and 258,726 (82.7%) had EM. Most patients (81.7%) had used acute and/or preventive medications; acute medications used more frequently than preventive medications (78.0% vs. 20.2%). Acute medications were used by 81.6 and 77.3% of patients with CM and EM, respectively. Commonly used acute medications were acetaminophen (68.8%), ergots (49.4%), and non-steroidal anti-inflammatory drugs (38.4%); the use of triptans (6.0%), tramadol (3.1%), and other opioids (0.2%) was less common. A total of 28.6 and 18.5% of patients with CM and EM, respectively, used preventive medications. Flunarizine (68.9%), propranolol (40.7%), and topiramate (16.0%) were the most commonly used preventive medications. Most patients had used 1-2 acute or preventive medications, with the use of ≥3 acute or preventive medications more common in patients with CM than EM. Average total medical cost per annum was 4,169 New Taiwan Dollars (NTDs) per CM patient and 2,928 NTDs per EM patient, with CM patients having higher costs associated with medical service utilization and acute medication use. These real-world data suggest unmet needs for Taiwanese patients with migraine, including under-utilization of preventive medications and greater costs and health care resource use for patients with CM versus EM. These findings provide important information on treatment patterns, cost, and health care resource use for patients with migraine in Taiwan.

Developing a predictive model for an emerging epidemic on cassava in sub-Saharan Africa

The agricultural productivity of smallholder farmers in sub-Saharan Africa (SSA) is severely constrained by pests and pathogens, impacting economic stability and food security. An epidemic of cassava brown streak disease, causing significant yield loss, is spreading rapidly from Uganda into surrounding countries. Based on sparse surveillance data, the epidemic front is reported to be as far west as central DRC, the world’s highest per capita consumer, and as far south as Zambia. Future spread threatens production in West Africa including Nigeria, the world’s largest producer of cassava. Using innovative methods we develop, parameterise and validate a landscape-scale, stochastic epidemic model capturing the spread of the disease throughout Uganda. The model incorporates real-world management interventions and can be readily extended to make predictions for all 32 major cassava producing countries of SSA, with relevant data, and lays the foundations for a tool capable of informing policy decisions at a national and regional scale.

Management of Neovascular Age-Related Macular Degeneration Treatment in France from 2008-2018: The Nationwide LANDSCAPE Study.

The aim of this study was to describe the management of neovascular age-related macular degeneration (nAMD) in French patients between 2008 and 2018. This was a retrospective longitudinal cohort study using exhaustive nationwide health records from the French National Health Information database. Enrollment criteria were adults aged ≥ 50 years, nAMD diagnosis, or reimbursement for nAMD treatments (anti-vascular epithelial growth factor [VEGF] injection or dynamic phototherapy with verteporfin). Exclusion criteria were high myopia, diagnosis of other retinal diseases, and treatments for other macular diseases (dexamethasone implant, laser). Main outcome measures were consumption of medical care and nAMD treatments per calendar year and number of years of follow-up. Between 2008 and 2018, we identified 342,961 patients who have been treated for nAMD. Median duration of ophthalmological follow-up exceeded 7years (90months). The median annual number of ophthalmology consultations decreased from nine visits in year 1 after treatment initiation to four visits from year 7 onwards. The median duration of nAMD treatment was 10.1months for all patients, with 48.5% of patients undergoing treatment for < 1year. Only 24.4% of patients had maintained treatment at year 11. Patients remaining under treatment had a median of four anti-VEGF treatments per year throughout the 10-year study period. Ranibizumab was the more common first-line treatment (67.5% of patients) compared to aflibercept (32.4%). About 20% of patients who initiated treatment switched treatment at least once. LANDSCAPE provides exhaustive nationwide data on the real-world management of nAMD in France over a 10-year period. Further investigation into short treatment duration is required, especially in terms of understanding its relation to visual outcomes.

Treatment Persistence and Medication Switch Associated With Subsequent Fractures After Osteoporotic Fractures.

Despite prevalent anti-osteoporosis medication (AOM) switching in real-world osteoporosis management, few studies have evaluated the impact of persistent AOM treatment, allowing for AOM switching, on the risk of subsequent fracture. We examined the association between persistence in AOM and subsequent fractures, allowing for medication switching among patients with osteoporotic fractures. This retrospective cohort study used Taiwan National Health Insurance claims data to select patients who initiated AOM between 2013 and 2016. Treatment persistence was defined as use of any AOM on a given day of interest with a 45-day grace period. Medication switch was allowed for persistence if remaining on treatment. AOMs with long-lasting inhibition of bone resorption (zoledronate and denosumab) were categorized as high-potency; others as low-potency. Multivariate Cox models were used to evaluate risk of subsequent fractures ≥3 months after initiating AOM. A total of 119 473 patients were included (mean [SD] follow-up 46.4 [15.6] months), and 26.8% switched from the index AOM. Within 1 year, 52% remained persistent with AOM. Compared to patients with persistent AOM, those not persistent had higher risk of subsequent hip (adjusted hazard ratio [aHR] = 1.31; 95% CI, 1.21-1.42), vertebral (aHR = 1.17; 95% CI, 1.13-1.22), and radius fractures (aHR = 1.16; 95% CI, 1.08-1.25). Patients with persistent AOM who switched from high- to low-potency AOM had higher risk of subsequent vertebral fractures than those with persistent AOM and no potency switch (aHR = 1.28; 95% CI, 1.02-1.60). Patients with non-persistent AOM had higher risk of subsequent fractures than persistent users when allowing AOM switch. Switching AOM potency may influence the risk of subsequent vertebral fractures and warrants further investigation.

Low Cost Evolutionary Neural Architecture Search (LENAS) Applied to Traffic Forecasting

Traffic forecasting is an important task for transportation engineering as it helps authorities to plan and control traffic flow, detect congestion, and reduce environmental impact. Deep learning techniques have gained traction in handling such complex datasets, but require expertise in neural architecture engineering, often beyond the scope of traffic management decision-makers. Our study aims to address this challenge by using neural architecture search (NAS) methods. These methods, which simplify neural architecture engineering by discovering task-specific neural architectures, are only recently applied to traffic prediction. We specifically focus on the performance estimation of neural architectures, a computationally demanding sub-problem of NAS, that often hinders the real-world application of these methods. Extending prior work on evolutionary NAS (ENAS), our work evaluates the utility of zero-cost (ZC) proxies, recently emerged cost-effective evaluators of network architectures. These proxies operate without necessitating training, thereby circumventing the computational bottleneck, albeit at a slight cost to accuracy. Our findings indicate that, when integrated into the ENAS framework, ZC proxies can accelerate the search process by two orders of magnitude at a small cost of accuracy. These results establish the viability of ZC proxies as a practical solution to accelerate NAS methods while maintaining model accuracy. Our research contributes to the domain by showcasing how ZC proxies can enhance the accessibility and usability of NAS methods for traffic forecasting, despite potential limitations in neural architecture engineering expertise. This novel approach significantly aids in the efficient application of deep learning techniques in real-world traffic management scenarios.

Real-world adherence to toxicity management guidelines for immune checkpoint inhibitor-induced diabetes mellitus.

Immune checkpoint inhibitors(ICIs) have improved survival and are increasingly used for cancer. However, ICIs use may be limited by immune-related adverse events (irAEs), such as ICI-induced diabetes mellitus(ICI-DM). The objective of the present study was to characterize ICI-DM patients and real-world adherence to guidelines. The present study was a retrospective review of electronic records of ICI-DM patients at the First Affiliated Hospital of Nanjing Medical University between July 2018 and October 2022. 34.8% (8/23)patients monitored blood glucose in every treatment cycle. The proportion of patients with severe diabetic ketoacidosis(DKA) was lower in the tight glycemic monitoring group than the non-tight glycemic monitoring group (16.7% vs. 55.6%, p = 0.049). 78.3%(18/23) patients with hyperglycemia visited a non-endocrinologist first, but 95.7% of patients were then referred to an endocrinologist. Twenty patients were tested for distinguishing the etiology of hyperglycemia and 20% patients with positive glutamic acid decarboxylase antibody(GADA), 55% with C-peptide <3.33pmol/L. High screening rates for other ICI-induced endocrinopathies were observed and half of the patients with ICI-DM developed other endocrine gland irAEs, with the most common being thyroiditis. Moreover, five patients developed non-endocrine serious adverse events(SAEs). Twelve (52.2%) patients were withdrawn from ICI due to ICI-DM. The time to progression of tumor in ICI-DM patients in the continue and interruption group was longer than in the withdrawal group (333.5 ± 82.5 days vs. 183.1 ± 62.4 days, p = 0.161). Only 17.4% of ICI-DM patients were completely managed according to guidelines. Thus, the present study proposed a screening, diagnosis, and management algorithm for ICI-DM in real-world practice. The present study reported the largest number of ICI-DM cases described in a single institute, providing insight into real-world ICI-DM management guideline adherence and highlighting the clinical challenges in ICI-DM management.

The clinical management of children with achondroplasia in Italy: results of clinician and parent/caregiver surveys.

This study aimed to assess the real-world management of achondroplasia in Italy. Two online surveys addressed to (1) parents/caregivers of individuals with achondroplasia and (2) Italian clinicians managing individuals with achondroplasia were conducted to assess real-world perspectives on achondroplasia management. Both surveys collected data on either patient or clinician demographics, details on diagnoses and referrals, disease complications, and views/experiences with limb lengthening surgery. In total, 42 parents/caregivers and 19 clinicians (from 18 hospitals) completed the surveys. According to parents/caregivers, achondroplasia diagnosis was most commonly made in the third trimester of gestation (55% of respondents), with a genetic test performed to confirm the diagnosis in all but one case. In contrast, the clinicians indicated that, while achondroplasia was typically suspected during the prenatal period (78%), diagnosis was more frequently confirmed postnatally (72%). Parents/caregivers reported that the greatest impact of achondroplasia-related complications occurred in their children between the ages of 2-5years. The most significant complications were otitis, sleep apnoea, stenosis of the foramen magnum or pressure on the spinal cord, and hearing difficulties. Lengthening surgery had been presented as a treatment option to 92% of responding parents/caregivers, with 76% of clinicians viewing surgery favourably. Typically, clinicians' reasons for suggesting limb lengthening surgery were to improve patient quality of life, increase patient autonomy and self-acceptance, improve trunk-limb disproportion, short stature and walking, and ensure that all possible treatment options had been presented to the parents/caregivers. This survey provides insight into the real-world management of individuals with achondroplasia in Italy.

Burden of disease and real-world treatment patterns of patients with systemic lupus erythematosus in the Australian OPAL dataset

ObjectiveTo describe the demographics, disease burden and real-world management of patients with systemic lupus erythematosus (SLE) in Australian community practice.MethodsPatients with a physician diagnosis of SLE and at least 1 visit between 1 January 2009 and 31 March 2021 were identified in the OPAL dataset, an aggregated collection of data extracted from the electronic medical records of patients managed by 112 Australian rheumatologists. Demographics, basic clinical features and prescribed medications were described, with medication combinations used as a surrogate of disease severity.ResultsOf 5133 patients with a diagnosis of lupus, 4260 (83%) had SLE. Of these SLE patients, almost 90% of patients were female, with a median age of 49 years [IQR 37–61] at first-recorded visit. Of the 2285 SLE patients whose most recent visit was between 1 January 2019 and 31 March 2021, 52.5% had mild disease, 29.9% had moderate-severe disease and 7.4% had very severe disease. Visit frequency increased with disease severity. Most patients (85.8%) were treated with hydroxychloroquine, typically prescribed as first line-of-therapy.ConclusionIn this large real-world Australian cohort of patients with SLE, a substantial burden of disease was identified, with a significant proportion (almost one-third of patients) considered to have moderate to severe disease based on medication use. This study provides a greater understanding of the path from symptom onset to treatment and the heterogeneous presentation of patients with SLE who are treated in community practice in Australia.Key messages• Most published studies describing patients with SLE are derived from specialist lupus centres, typically in the hospital setting, therefore little is known about the characteristics of patients with SLE who are receiving routine care in community clinics.• The OPAL dataset is a large collection of clinical data from the electronic medical records of rheumatologists predominantly practising in private community clinics, which is where the majority (73–80%) of adult rheumatology services are conducted in Australia [1–3] . Since data from community care has not been widely available for SLE research, this study contributes important insight into this large and under-reported patient population.• To improve access to care and effective treatments, and reduce the burden of SLE in Australia, a greater understanding of the characteristics and unmet needs of patients with SLE managed in the community setting is required.

Real-world Management of CML: Outcomes and Treatment Patterns.

Chronic myeloid leukemia (CML) is a disease that previously signified a poor prognosis, but treatment options and outcomes have improved over the last several decades. Despite this, challenges remain in optimal management in clinical practice, as the characteristics in trial populations differ from patients who are treated in a real-world setting. This review describes recent updates in real-world treatment patterns and outcomes in patients with CML. Several analyses describing real-world practice patterns show that tyrosine kinase inhibitors (TKIs) are the most commonly prescribed agents in multiple lines of therapy. First-generation (1G) and second-generation (2G) TKIs are the most commonly prescribed, even in the third line and beyond. Third-generation (3G) TKIs are typically utilized in patients with resistant disease who are younger with fewer comorbidities. Hematopoietic stem cell transplant (HSCT) is utilized significantly less, given other treatment options available. The goals of treatment with CML have shifted to quality of life, cost savings, and treatment-free response (TFR). Despite clear guidelines for attempting TFR, discontinuation practice patterns remain inconsistent. TKIs are the mainstay of CML treatment, including those in later lines of therapy. In real-world practice, several challenges still remain with regard to optimal management. Specifically, ideal sequencing of treatments, side effect profiles of tyrosine kinase inhibitors (TKIs), current role and timing of transplant, and adherence to recommendations for attempting to achieve a treatment-free response (TFR). A national registry could characterize these practice patterns in order to find ways to optimize care for CML patients.

Periinterventional Management of Edoxaban in Major Procedures: Results from the DRESDEN NOAC REGISTRY.

Background Edoxaban is a non-vitamin K dependent oral anticoagulant (NOAC) licensed for venous thromboembolism (VTE) treatment or stroke prevention in atrial fibrillation. Major surgical procedures are not uncommon in anticoagulated patients but data on perioperative edoxaban management are scarce. Patients and Methods Using data from the prospective DRESDEN NOAC REGISTRY, we extracted data on major surgical procedures in edoxaban patients. Periinterventional edoxaban management patterns and rates of outcome events were evaluated until day 30 after procedure. Results Between 2011 and 2021, 3,448 procedures were identified in edoxaban patients, including 287 (8.3%) major procedures. A scheduled interruption of edoxaban was observed in 284/287 major procedures (99%) with a total median edoxaban interruption time of 11.0 days (25-75th percentile: 5.0-18.0 days). Heparin bridging was documented in 183 procedures (46 prophylactic dosages, 111 intermediate and 26 therapeutic dosages). Overall, 7 (2.4%; 95% CI: 1.2-4.9%) major cardiovascular events (5 VTE, 2 arterial thromboembolic events) and 38 major bleedings (13.2%; 95% CI: 9.8-17.7%) were observed and 6 patients died (2.1%; 95% CI: 1.0-4.5%). Rates of major cardiovascular events with or without heparin bridging were comparable (4/137; 2.9%; 95% CI: 1.1-7.3% vs. 3/82; 3.7%; 95% CI: 1.3-10.2%). Major bleedings occurred numerically more frequent in patients receiving heparin bridging (23/137; 16.8%; 95% CI: 11.5-23.9%) versus procedures without heparin bridging (9/82; 11.0%; 95% CI: 5.9-19.6%). Conclusion Within the limitations of our study design, real-world periprocedural edoxaban management seems effective and safe. Use of heparin bridging seems to have limited effects on reducing vascular events but may increase bleeding risk.

422 Healthcare disparities in atopic dermatitis: insights from TARGET-DERM registry

Abstract Atopic dermatitis disproportionately affects diverse patient populations. Furthermore, complex factors may influence the burden of disease and access to treatment amongst different racial and ethnic groups. The aim of this study is to evaluate health disparities and real-world management patterns in distinct populations treated for AD in routine clinical practice. The study included patients with AD (≥age 6) enrolled in TARGET-DERM, an observational, longitudinal study of over 2500 participants across 43 US academic/community centers. Participants were classified in four race/ethnicity categories as reported in enrollment forms and/or patient self-reported: non-Hispanic (NH) White, Black, Asian/Pacific Islander (API) and Hispanic. Patient characteristics analysed included demographics, clinical characteristics, investigator-assessed and patient-reported outcomes, and treatment history. A total of 1928 patients (mean age 34 years; 58% female; 60% enrolled at community-based centers) were included, encompassing 251 NH-Black (13%), 271 NH-API (14%), 288 Hispanic (15%) and 1118 NH-White (58%) participants. Most (71%) had a medical comorbid condition with 30% having ≥3 conditions. Private insurance was highest among NH-APIs (82%) and NH-Whites (70%), Medicaid was highest among Hispanics (46%) and NH-Blacks (27%), and uninsured was highest among NH-Blacks (18%) and NH-Whites (12%). At enrollment, clinical disease severity assessments [vIGA-AD, TBSA and vIGA-ADxTBSA (VxT)] varied by race/ethnicity, also suggesting healthcare disparities. Lowest severity was among NH-Whites (25.9% vIGA-AD clear/almost clear, 26.7% VxT clear/almost clear and median TBSA 5%), followed by Hispanics (21.7%, 18.2% and 7%), NH-Blacks (15.7%, 15.3% and 10%), and NH-APIs (10.7%, 13.8% and 8%). No differences were identified in the distribution of traditional systemic therapies across groups. However, in multivariable analysis (adjusted for age, sex, insurance status, comorbidities, vIGA and treatment status), NH-Blacks and Hispanics were less likely to be treated with advanced systemic therapies than NH-Whites [odds ratio (OR) of 0.67 and 0.70, respectively; P &amp;lt; 0.01]. Similarly, NH-APIs were more likely to have higher vIGA-AD scores than NH-Whites (OR = 1.57; P &amp;lt; 0.01). Non-Hispanic Blacks also had higher vIGA-AD scores than NH-Whites (OR = 1.42; P &amp;lt; 0.05) when controlling for all covariates other than treatment type (P &amp;lt; 0.05), adjustment for which renders the estimated black–white disparity nonsignificant. (OR = 1.32, P = 0.11). Descriptively comparing patient-reported outcome distributions identified no significant differences (P &amp;gt; 0.12). Despite presenting with more severe disease, Blacks and Hispanics have significantly lower odds of using advanced systemic therapy relative to NH-Whites, suggestive of an access disparity leading to disparities in disease control. These disadvantages persist after adjusting for an array of demographic, socioeconomic and medical history characteristics. The results highlight real-world evidence of racial and ethnic disparities among patients with AD.

Predicting near-term, out-of-sample fish passage, guidance, and movement across diverse river environments by cognitively relating momentary behavioral decisions to multiscale memories of past hydrodynamic experiences

Predicting the behavior of individuals acting under their own motivation is a challenge shared across multiple scientific fields, from economic to ecological systems. In rivers, fish frequently change their orientation even when stimuli are unchanged, which makes understanding and predicting their movement in time-varying environments near built infrastructure particularly challenging. Cognition is central to fish movement, and our lack of understanding is costly in terms of time and resources needed to design and manage water operations infrastructure that is able to meet the multiple needs of human society while preserving valuable living resources. An open question is how best to cognitively account for the multi-modal, -attribute, -alternative, and context-dependent decision-making of fish near infrastructure. Here, we leverage agent- and individual-based modeling techniques to encode a cognitive approach to mechanistic fish movement behavior that operates at the scale in which water operations river infrastructure is engineered and managed. Our cognitive approach to mechanistic behavior modeling uses a Eulerian-Lagrangian-agent method (ELAM) to interpret and quantitatively predict fish movement and passage/entrainment near infrastructure across different and time-varying river conditions. A goal of our methodology is to leverage theory and equations that can provide an interpretable version of animal movement behavior in complex environments that requires a minimal number of parameters in order to facilitate the application to new data in real-world engineering and management design projects. We first describe concepts, theory, and mathematics applicable to animals across aquatic, terrestrial, avian, and subterranean domains. Then, we detail our application to juvenile Pacific salmonids in the Bay-Delta of California. We reproduce observations of salmon movement and passage/entrainment with one field season of measurements, year 2009, using five simulated behavior responses to 3-D hydrodynamics. Then, using the ELAM model calibrated from year 2009 data, we predict the movement and passage/entrainment of salmon for a later field season, year 2014, which included a novel engineered fish guidance boom not present in 2009. Central to the fish behavior model’s performance is the notion that individuals are attuned to more than one hydrodynamic signal and more than one timescale. We find that multi-timescale perception can disentangle multiplex hydrodynamic signals and inform the context-based behavioral choice of a fish. Simulated fish make movement decisions within a rapidly changing environment without global information, knowledge of which direction is downriver/upriver, or path integration. The key hydrodynamic stimuli are water speed, the spatial gradient in water speed, water acceleration, and fish swim bladder pressure. We find that selective tidal stream transport in the Bay-Delta is a superset of the fish-hydrodynamic behavior repertoire that reproduces salmon movement and passage in dam reservoir environments. From a cognitive movement ecology perspective, we describe how a behavior can emerge from a repertoire of multiple fish-hydrodynamic responses that are each tailored to suit the animal’s recent past experience (localized environmental context). From a movement behavior perspective, we describe how different fish swim paths can emerge from the same local hydrodynamic stimuli. Our findings demonstrate that a cognitive approach to mechanistic fish movement behavior modeling does not always require the maximum possible spatiotemporal resolution for representing the river environmental stimuli although there are concomitant tradeoffs in resolving features at different scales. From a water operations perspective, we show that a decision-support tool can successfully operate outside the calibration conditions, which is a necessary attribute for tools informing future engineering design and management actions in a world that will invariably look different than the past.

Real-World Frequency and Management of Ocular Adverse Events in Eyes with Neovascular Age-Related Macular Degeneration Treated with Brolucizumab.

Intraocular inflammation (IOI)-related adverse events (AEs) that may result in severe vision loss have been associated with the anti-vascular endothelial growth factor brolucizumab. In this study, we investigate the timing, management and resolution of IOI-related AEs in a large cohort of patients treated with at least one injection of brolucizumab in routine clinical practice. Retrospective review of medical records from patients with neovascular age-related macular degeneration treated with ≥ 1 brolucizumab injection between October 2019 and November 2021 at the Retina Associates of Cleveland, Inc. clinics. Of the 482 eyes included in the study, IOI-related AEs occurred in 22 (4.6%) eyes. Four (0.8%) eyes developed retinal vasculitis (RV) and of these, 2 (0.4%) had concomitant retinal vascular occlusion (RO). Most eyes [14/22 (64%)] developed the AE within 3months and 4/22 (18%) within 3-6months of the first brolucizumab injection. The median [interquartile range (IQR)] time from the last brolucizumab injection to development of the IOI-related AE was 13 (4-34) days. At the time of event, 3 (0.6%) eyes with IOI (no RV/RO) developed severe vision loss of ≥ 30 ETDRS letters, and a further 5 (1.0%) eyes (1 with IOI + RV, 1 with IOI + RV + RO) developed moderate vision loss of ≥ 15 letters compared with their last visual acuity (VA) prior to the AE. The median (IQR) vision loss was -6.8 (-19.9, -0.0) letters. Taking the best VA at either 3 or 6months after AE resolution (or stability for occlusive events), VA decreased by ≥ 5 letters compared with prior to the AE in 3 (14%) of the 22 affected eyes, and was preserved (< 5-letter loss) in 18 (82%) eyes. In this real-world study, most IOI-related AEs occurred early after brolucizumab treatment initiation. With appropriate monitoring and management of IOI-related AEs, vision loss associated with brolucizumab may be limited.

Duration and effectiveness of glucose-lowering regimens in the real world management of diabetes: Data from the Australian EXTEND45 Linked Cohort Study

BackgroundDiabetes is a common condition that often requires increasing intensity of glucose lowering regimens. We describe the population trends in the intensity of regimens, and associations of achieved HbA1c and treatment persistence. MethodsWe performed an episode-based analysis of the EXTEND-45 dataset, assessing trends in glucose lowering therapy and the associated outcomes of HbA1c and treatment persistence. Trends from 2009 to 2014 were assessed for each intensity level of a glucose lowering therapy regimen, according to the year prescribed. Episodes were defined as the length of time that an individual adhered to a regimen through ongoing prescription, and this was used as to define persistence. Mean HbA1c were calculated for each episode. Persistence and HbA1c were compared across the different regimens of treatment intensity. ResultsThe intensity of glucose lowering therapy remained stable over time with around one third of episodes utilising a single glucose lowering agent. Mean HbA1c was higher for insulin-based treatment (mean 7.9 % SD = 1.3 %), and lowest for episodes of no glucose lowering treatment (mean 6.3 % (SD = 0.8 %). Around half of participants achieved glycemic targets of 7 %. While there was considerable variation in persistence, the median persistence was around 3 months (94 days, IQR 51–201 days). ConclusionsTherapeutic intensity for diabetes has remained stable over 9 years. Whilst there was considerable variability in persistence with glucose lowering regimens, the mean duration of all regimens was less than a year. Requirement for higher intensity treatment with insulin was related to poorer glycemic control.

Antibiotic practice and stewardship in the management of neutropenic fever: A survey of US institutions

Background: Neutropenic fever management decisions are complex and result in prolonged duration of broad-spectrum antibiotics. Strategies for antibiotic stewardship in this context have been studied, including de-escalation of antibiotics prior to resolution of neutropenia, with unclear implementation. Here, we present the first survey study to describe real-world neutropenic fever management practices in US healthcare institutions, with particular emphasis on de-escalation strategies after initiation of broad-spectrum antibiotics. Methods: Using REDCap, we conducted a survey of US healthcare institutions through the SHEA Research Network (SRN). Questions pertained to antimicrobial prophylaxis and supportive care in the management of oncology patients and neutropenic fever management (including specific antimicrobial choices and clinical scenarios). Hematologic malignancy hospitalization (2020) and bone-marrow transplantation (2016–2020) volumes were obtained from CMS and Health Resources &amp; Services Administration databases, respectively. Results: Overall, 23 complete responses were recorded (response rate, 35.4%). Collectively, these entities account for ~11.0% of hematologic malignancy hospitalizations and 13.3% bone marrow transplantations nationwide. Of 23 facilities, 19 had institutional guidelines for neutropenic fever management and 18 had institutional guidelines for prophylaxis, with similar definitions for neutropenic fever. Firstline treatment universally utilized antipseudomonal broad-spectrum IV antibiotics (20 of 23 use cephalosporin, 3 of 23 use penicillin agent, and no respondents use carbapenem). Fluoroquinolone prophylaxis was common for leukemia induction patients (18 of 23) but was mixed for bone-marrow transplantation (10 of 23). We observed significant heterogeneity in treatment decisions. For stable neutropenic fever patients with no clinical source of infection identified, 13 of 23 respondents continued IV antibiotics until ANC (absolute neutrophil count) recovery. The remainder had criteria for de-escalation back to prophylaxis prior to this (eg, a fever-free period). Respondents were more willing to de-escalate prior to ANC recovery in patients with identified clinical sources (14 of 23 de-escalations in patients with pneumonia) or microbiological sources (15 of 23 de-escalations in patients with bacteremia) after dedicated treatment courses. In free-text responses, several respondents described opportunities for more systemic de-escalation for antimicrobial stewardship in these scenarios. Conclusions: Our results illustrate the real-world management of neutropenic fever in US hospitals, including initiation of therapy, prophylaxis, and treatment duration. We found significant heterogeneity in de-escalation of empiric antibiotics relative to ANC recovery, highlighting a need for more robust evidence for and adoption of this practice.Disclosures: None

RWD62 Real-World Characterization and Management of Alopecia Areata Patients in the U.S.

Alopecia areata (AA) is a chronic autoimmune condition estimated to affect approximately 2% of people worldwide. The disease can have a substantial impact on quality of life and mental health, particularly for women. As novel systemic treatments become available, a better understanding of patients and their management is needed.