Estimating the likelihood of epilepsy from clinically noncontributory electroencephalograms using computational analysis: A retrospective, multisite case-control study.

OBJECTIVE: This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite case-control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder). METHODS: The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (N = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [n = 2], network-based [n = 4], and model-based [n = 2]) were calculated within each recording. Ensemble-based classifiers were developed using a two-tier cross-validation approach. We used standard regression methods to assess whether potential confounding variables (e.g., age, gender, treatment status, comorbidity) impacted model performance. RESULTS: We found levels of balanced accuracy of 68% across the cohort with clinically noncontributory normal EEGs (sensitivity =61%, specificity =75%, positive predictive value =55%, negative predictive value =79%, diagnostic odds ratio =4.64, area under receiver operated characteristics curve =.72). Group level analysis found no evidence suggesting any of the potential confounding variables significantly impacted the overall performance. SIGNIFICANCE: These results provide evidence that the set of biomarkers could provide additional value to clinical decision-making, providing the foundation for a decision support tool that could reduce diagnostic delay and misdiagnosis rates. Future work should therefore assess the change in diagnostic yield and time to diagnosis when utilizing these biomarkers in carefully designed prospective studies.

Well-spread samples with dynamic sample sizes.

A spatial sampling design determines where sample locations are placed in a study area so that population parameters can be estimated with relatively high precision. If the response variable has spatial trends, spatially balanced or well-spread designs give precise results for commonly used estimators. This article proposes a new method that draws well-spread samples over arbitrary auxiliary spaces and can be used for master sampling applications. All we require is a measure of the distance between population units. Numerical results show that the method generates well-spread samples and compares favorably with existing designs. We provide an example application using several auxiliary variables to estimate total aboveground biomass over a large study area in Eastern Amazonia, Brazil. Multipurpose surveys are also considered, where the totals of aboveground biomass, primary production, and clay content (3 responses) are estimated from a single well-spread sample over the auxiliary space.

Characteristics of patients who had a stroke not initially identified during emergency prehospital assessment: a systematic review.

BACKGROUND: Around 25% of patients who had a stroke do not present with typical 'face, arm, speech' symptoms at onset, and are challenging for emergency medical services (EMS) to identify. The aim of this systematic review was to identify the characteristics of acute stroke presentations associated with inaccurate EMS identification (false negatives). METHOD: We performed a systematic search of MEDLINE, EMBASE, CINAHL and PubMed from 1995 to August 2020 using key terms: stroke, EMS, paramedics, identification and assessment. Studies included: patients who had a stroke or patient records; ≥18 years; any stroke type; prehospital assessment undertaken by health professionals including paramedics or technicians; data reported on prehospital diagnostic accuracy and/or presenting symptoms. Data were extracted and study quality assessed by two researchers using the Quality Assessment of Diagnostic Accuracy Studies V.2 tool. RESULTS: Of 845 studies initially identified, 21 observational studies met the inclusion criteria. Of the 6934 stroke and Transient Ischaemic Attack patients included, there were 1774 (26%) false negative patients (range from 4 (2%) to 247 (52%)). Commonly documented symptoms in false negative cases were speech problems (n=107; 13%-28%), nausea/vomiting (n=94; 8%-38%), dizziness (n=86; 23%-27%), changes in mental status (n=51; 8%-25%) and visual disturbance/impairment (n=43; 13%-28%). CONCLUSION: Speech problems and posterior circulation symptoms were the most commonly documented symptoms among stroke presentations that were not correctly identified by EMS (false negatives). However, the addition of further symptoms to stroke screening tools requires valuation of subsequent sensitivity and specificity, training needs and possible overuse of high priority resources.

International severe asthma registry (ISAR): protocol for a global registry.

BACKGROUND: Severe asthma exerts a disproportionately heavy burden on patients and health care. Due to the heterogeneity of the severe asthma population, many patients need to be evaluated to understand the clinical features and outcomes of severe asthma in order to facilitate personalised and targeted care. The International Severe Asthma Registry (ISAR) is a multi-country registry project initiated to aid in this endeavour. METHODS: ISAR is a multi-disciplinary initiative benefitting from the combined experience of the ISAR Steering Committee (ISC; comprising 47 clinicians and researchers across 29 countries, who have a special interest and/or experience in severe asthma management or establishment and maintenance of severe asthma registries) in collaboration with scientists and experts in database management and communication. Patients (≥18 years old) receiving treatment according to the 2018 definitions of the Global Initiative for Asthma (GINA) Step 5 or uncontrolled on GINA Step 4 treatment will be included. Data will be collected on a core set of 95 variables identified using the Delphi method. Participating registries will agree to provide access to and share standardised anonymous patient-level data with ISAR. ISAR is a registered data source on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. ISAR's collaborators include Optimum Patient Care, the Respiratory Effectiveness Group (REG) and AstraZeneca. ISAR is overseen by the ISC, REG, the Anonymised Data Ethics & Protocol Transparency Committee and the ISAR operational committee, ensuring the conduct of ethical, clinically relevant research that brings value to all key stakeholders. CONCLUSIONS: ISAR aims to offer a rich source of real-life data for scientific research to understand and improve disease burden, treatment patterns and patient outcomes in severe asthma. Furthermore, the registry will provide an international platform for research collaboration in respiratory medicine, with the overarching aim of improving primary and secondary care of adults with severe asthma globally.

Improving acute stroke care in regional hospitals: clinical evaluation of the Victorian Stroke Telemedicine program.

OBJECTIVES: To evaluate the impact of the Victorian Stroke Telemedicine (VST) program during its first 12 months on the quality of care provided to patients presenting with suspected stroke to hospitals in regional Victoria. DESIGN: Historical controlled cohort study comparing outcomes during a 12-month control period with those for the initial 12 months of full implementation of the VST program at each hospital. SETTING: 16 hospitals in regional Victoria that participated in the VST program between 1 January 2010 and 30 January 2016. PARTICIPANTS: Adult patients with suspected stroke presenting to the emergency departments of the participating hospitals. MAIN OUTCOME MEASURES: Indicators for key processes of care, including symptom onset-to-arrival, door-to-first medical review, and door-to-CT times; provision and timeliness of provision of thrombolysis to patients with ischaemic stroke. RESULTS: 2887 patients with suspected stroke presented to participating emergency departments during the control period, 3178 during the intervention period; the patient characteristics were similar for both periods. A slightly larger proportion of patients with ischaemic stroke who arrived within 4.5 hours of symptom onset received thrombolysis during the intervention than during the control period (37% v 30%). Door-to-CT scan time (median, 25 min [IQR, 13-49 min] v 34 min [IQR, 18-76 min]) and door-to-needle time for stroke thrombolysis (73 min [IQR, 56-96 min] v 102 min [IQR, 77-128 min]) were shorter during the intervention. The proportions of patients who received thrombolysis and had a symptomatic intracerebral haemorrhage (4% v 16%) or died in hospital (6% v 20%) were smaller during the intervention period. CONCLUSIONS: Telemedicine has provided Victorian regional hospitals access to expert care for emergency department patients with suspected acute stroke. Eligible patients with ischaemic stroke are now receiving stroke thrombolysis more quickly and safely.

Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage: Data From the RIGHT-2 Trial.

Background and Purpose- Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods- We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results- Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45-110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98-3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01-0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions- Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN26986053.

Anti-inflammatory approaches to ischaemic stroke prevention.

Stroke is a major cause of neurological morbidity and mortality. Atherosclerosis is a major contributor to first and recurrent stroke. A growing evidence base indicates that inflammation is a key process in the pathogenesis of atherosclerosis, leading to thromboembolic events. In this review, we summarise the evidence linking inflammation to stroke risk and discuss clinical trials addressing the 'inflammation hypothesis' in coronary disease and stroke. Trial registration number CONVINCE trial ClinicalTrials.gov number; NCT 02898610; Pre-results.

'It was like he was in the room with us': patients' and carers' perspectives of telemedicine in acute stroke.

BACKGROUND: Telemedicine can facilitate delivery of thrombolysis in acute stroke. The aim of this qualitative study was to explore patients' and carers' views of their experiences of using a stroke telemedicine system in order to contribute to the development of reliable and acceptable telemedicine systems and training for health-care staff. METHOD: We recruited patients who had, and carers who were present at, recent telemedicine consultations for acute stroke in three hospitals in NW England. Semi-structured interviews were conducted using an interview guide based on normalization process theory (NPT). Thematic analysis was undertaken. RESULTS: We conducted 24 interviews with 29 participants (16 patients; 13 carers). Eleven interviews pertained to 'live' telemedicine assessments (at the time of admission); nine had mock-up telemedicine assessments (within 48 h of admission); four had both assessments. Using the NPT domains as a framework for analysis, factors relating to coherence (sense making) included people's knowledge and understanding of telemedicine. Cognitive participation (relational work) included interaction between staff and with patients and carers. Issues relating to collective action (operational work) included information exchange and support, and technical matters. Findings relating to reflexive monitoring (appraisal) included positive and negative impressions of the telemedicine process, and emotional reactions. CONCLUSION: Although telemedicine was well accepted by many participants, its use added an additional layer of complexity to the acute stroke consultation. The 'remote' nature of the consultation posed challenges for some patients. These issues may be ameliorated by clear information for patients and carers, staff interpersonal skills, and teamworking.

Object tracking based on incremental Bi-2DPCA learning with sparse structure.

In this paper, we propose a novel object tracking method that can work well in challenging scenarios such as appearance changes, motion blurs, and especially partial occlusions and noise. Our method applies bilateral two-dimensional principal component analysis (Bi-2DPCA) for efficient object modeling and real-time computation requirement. An incremental Bi-2DPCA learning algorithm is proposed for characterizing the appearance changes of newly tracked objects. Also, to account for noise and occlusions, a sparse structure is introduced into our Bi-2DPCA object representation model. With this sparse structure, the appearance of an object can be represented by a linear combination of basis images and an additional noise image. The noise image, which indicates the location of noise and occlusions, can be used to effectively eliminate the influence caused by noise and occlusions and lead to a robust tracker. Instead of the reconstruction error commonly used in eigen-based tracking methods, a more accurate method is adopted for the computation of observation likelihood. The method is based on the energy distribution of coefficient matrix projected by Bi-2DPCA. Experimental results on challenging image sequences demonstrate the effectiveness of the proposed tracking method.

Exploring the various interpretations of "test bias".

Test bias is a hotly debated topic in society, especially as it relates to diverse groups of examinees who often score low on standardized tests. However, the phrase "test bias" has a multitude of interpretations that many people are not aware of. In this article, we explain five different meanings of "test bias" and summarize the empirical and theoretical evidence related to each interpretation. The five meanings are as follows: (a) mean group differences, (b) differential predictive validity, (c) differential item functioning, (d) differing factor structures of tests, and (e) unequal consequences of test use for various groups. We explain in this article why meanings (a) and (e) are not actual forms of test bias and that there are serious concerns about (b). In our conclusion, we discuss the benefits of standardized testing for diverse examinees and urge readers to be careful and precise in their use of the phrase "test bias."

Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial.

BACKGROUND: We compared standard adjuvant anthracycline chemotherapy with anthracycline-taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety. METHODS: BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18-70 years with node-positive, early breast cancer and a Karnofsky score of 80% or more were randomly assigned to adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for six cycles. Randomisation was stratified according to institution and number of involved axillary lymph nodes per patient (one to three vs four or more). Disease-free survival was the primary endpoint and was defined as the interval between randomisation and breast cancer relapse, second primary cancer, or death, whichever occurred first. Efficacy analyses were based on the intention-to-treat principle. BCIRG 001 is registered with ClinicalTrials.gov, number NCT00688740. FINDINGS: Enrolement took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90-126), disease-free survival was 62% (95% CI 58-65) for patients in the TAC group and 55% (51-59) for patients in the FAC group (hazard ratio [HR] 0·80, 95% CI 0·68-0·93; log-rank p=0·0043). 10-year overall survival was 76% (95% CI 72-79) for patients in the TAC group and 69% (65-72) for patients in the FAC group (HR 0·74, 0·61-0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3-4 heart failure occurred in 26 (3%) patients in the TAC group and 17 (2%) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20% or more) was seen in 58 (17%) patients who received TAC and 41 (15%) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC. INTERPRETATION: Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation. FUNDING: Sanofi.

Stroke survivor views on ambulance redirection as a strategy to increase access to thrombectomy in England.

Introduction: Intravenous thrombolysis and mechanical thrombectomy are effective time-sensitive treatments for selected cases of acute ischaemic stroke. While thrombolysis is widely available, thrombectomy can only be provided at facilities with the necessary equipment and interventionists. Suitable patients admitted to other hospitals require secondary transfer, causing delays to treatment. Pre-hospital ambulance redirection to thrombectomy facilities may improve access but treatment eligibility cannot be confirmed pre-hospital. Some redirected patients would travel further and be displaced without receiving thrombectomy. This study aimed to elicit stroke survivor and carer/relative views about the possible consequences of introducing a conceptual, idealised ambulance redirection pathway. Methods: Focus groups were undertaken using a topic guide describing four hypothetical ambulance redirection scenarios and their possible consequences: earlier treatment with thrombectomy; delayed diagnosis of non-stroke 'mimic' conditions; delayed thrombolysis treatment; and delayed diagnosis of haemorrhagic stroke. Meetings were audio recorded, transcribed verbatim and data analysed thematically using emergent coding. Results: Fifteen stroke survivors and carers/relatives participated in three focus groups. There was wide acceptance of possible low-risk consequences of ambulance redirection, including extended travel time, being further from home and experiencing longer hospital stays. Participants were more uncertain about higher-risk consequences, including delays in diagnosis/treatment for patients unsuitable for thrombectomy, but remained positive about ambulance redirection overall. Participants rationalised acceptance of higher-risk consequences by recognising that redirected patients would still access appropriate treatment, even if delayed. In addition, acceptance of ambulance redirection would be increased if there were robust clinical evidence showing net benefit over secondary transfer pathways. Conclusions: Participant views were generally supportive of ambulance redirection to facilitate access to thrombectomy. Further research is needed to demonstrate overall benefit in an NHS context.

Properties of Packed Bed Structures Formed during Filtration: A Two and Three-Dimensional Model.

Agglomeration is an issue that causes many problems during secondary processing for pharmaceutical companies, causing material to need further processing and costing additional time and resources to ensure a satisfactory outcome. A potential source of agglomeration arises from the particle contacts established during filtration that lead to robust agglomerates forming during drying, so that a necessary first step toward understanding agglomeration is to study the packing properties of filtration beds. Here, we present two and three-dimensional models simulating the formation of packed bed structures during filtration. The models use circular and spherical particles of different sizes, mimicking the bimodal particle size distributions sometimes encountered in industrial practice. The statistics of packing and void formation, along with the distribution of interparticle contacts and percolation structures, are presented and discussed in the context of filtration, drying, and agglomeration. The model paves the way for predictive capabilities that can lead to the rational design of processes to minimize the impact of agglomeration.

What factors contribute towards ambulance on-scene times for suspected stroke patients? An observational study.

INTRODUCTION: Pre-hospital stroke care focusses on rapid access to specialist stroke units, but UK ambulance data shows increasing pre-hospital times. This study aimed to describe factors contributing towards ambulance on-scene times (OST) for suspected stroke patients and identify targets for a future intervention. PATIENTS AND METHODS: Ambulance clinicians in North East Ambulance Service were asked to complete a survey after transporting any suspected stroke patients to describe the patient encounter, interventions and timings. Completed surveys were linked with electronic patient care records. Potentially modifiable factors were identified by the study team. Poisson regression analysis quantified the association of selected potentially modifiable factors with OST. RESULTS: About 2037 suspected stroke patients were conveyed between July and December 2021, resulting in 581 fully completed surveys by 359 different clinicians. The median age of patients was 75 years (interquartile range (IQR) 66-83) and 52% of patients were male. Median OST was 33 min (IQR 26-41). Three potentially modifiable factors were identified as contributors to extended OST. Performing additional advanced neurological assessments added 10% to OST (34 vs 31 min, p = 0.008); intravenous cannulation added 13% (35 vs 31 min, p = <0.001) and ECGs added 22% (35 vs 28 min, p = <0.001). CONCLUSIONS: This study identified three potentially modifiable factors that increased pre-hospital OST with suspected stroke patients. This type of data can be used to target interventions at behaviours that extend pre-hospital OST but which have questionable patient benefit. This approach will be evaluated in a follow up study in the North East of England.

Developing an education framework for stroke.

The National Stroke Strategy identified that staff caring for people with stroke needed knowledge and skills, and nationally recognised learning programmes were required. This article describes the development of an education framework for stroke.

Documentation of atrial fibrillation among non-conveyed ambulance patients: a new primary prevention opportunity?

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is a significant risk factor for stroke. Prescription of oral anticoagulant (OAC) medication reduces the risk of AF-related stroke by 64% - yet over 400,000 people in England have undiagnosed (and therefore untreated) AF.Emergency medical services (EMS) encounter a wide range of patients, some of whom may not engage with other healthcare services. AF may be detected by EMS in connection with the cause of the call, or as an incidental finding. While EMS are not traditionally utilised for public health screening, they may offer an opportunity to identify patients with undiagnosed or untreated AF and refer onward.This study aimed to explore what proportion of patients seen by EMS who were not transported to hospital had AF and to estimate how many would potentially benefit from OAC. Methods: A retrospective service evaluation was conducted using routinely collected data from a large UK regional ambulance service. The sample included adults attended by EMS on the 15th of each month in 2019, who were not transported to hospital and where an electrocardiogram was recorded. Of those with AF, we calculated the proportion in whom this was possibly new and report whether OAC was prescribed. Results: There were 859 patients who met the inclusion criteria, of whom 91 (11%) had AF documented. Of the 91 patients with AF, 23 (25%) had no documented history of AF or OAC prescription, so were potentially new diagnoses of AF, who would benefit from consideration of OAC therapy. Conclusion: The EMS assessment offers an opportunity for AF to be identified in patients who were not transported to hospital. EMS may have a role in primary prevention of harm, including stroke, by identifying and referring patients with AF for consideration of OAC.

Employing Constant Rate Filtration To Assess Active Pharmaceutical Ingredient Washing Efficiency.

Washing is a key step in pharmaceutical isolation to remove unwanted crystallization solvents and dissolved impurities (mother liquor) from the active pharmaceutical ingredient (API) filter cake to ensure the purity of the product whilst maximizing yield. It is therefore essential to avoid both product dissolution and impurity precipitation during washing, especially precipitation of impurities caused by the wash solvent acting as an antisolvent, affecting purity and causing agglomerate formation. This work investigates the wash solvent flow through a saturated filter cake to optimize washing by displacement, taking account of diffusional mechanisms and manipulating the wash contact time. Constant rate filtration/washing is employed in this study using readily available laboratory equipment. One advantage of using constant rate filtration in this work is that it allows for the collection of separate aliquots during all stages of filtration, washing, and deliquoring of the API cake. This enables a wash profile to be obtained, as well as providing an overall picture on the mass of API lost during isolation and so can assist in optimizing the washing strategy. Particle size analysis of damp cake obtained straight after washing is also performed using laser diffraction. This allowed for agglomerate formation caused during washing to be distinguished from agglomeration that would be caused by subsequent drying of the wet filter cake. This work aims at improving pharmaceutical product quality, increasing sustainability, and reducing manufacturing cost.

Digital Design of Filtration and Washing of Active Pharmaceutical Ingredients via Mechanistic Modeling.

To facilitate integrated end-to-end pharmaceutical manufacturing using digital design, a model capable of transferring material property information between operations to predict product attributes in integrated purification processes has been developed. The focus of the work reported here combines filtration and washing operations used in active pharmaceutical ingredient (API) purification and isolation to predict isolation performance without the need of extensive experimental work. A fixed Carman-Kozeny filtration model is integrated with several washing mechanisms (displacement, dilution, and axial dispersion). Two limiting cases are considered: case 1 where there is no change in the solid phase during isolation (no particle dissolution and/or growth), and case 2 where the liquid and solid phases are equilibrated over the course of isolation. In reality, all actual manufacturing conditions would be bracketed by these two limiting cases, so consideration of these two scenarios provides rigorous theoretical bounds for assessing isolation performance. This modeling approach aims to facilitate the selection of most appropriate models suitable for different isolation scenarios, without the requirement to use overly complex models for straightforward isolation processes. Mefenamic acid and paracetamol were selected as representative model compounds to assess a range of isolation scenarios. In each case, the objective of the models was to identify the purity of the product reached with a fixed wash ratio and minimize the changes to the crystalline particle attributes that occur during the isolation process. This was undertaken with the aim of identifying suitable criteria for the selection of appropriate filtration and washing models corresponding to relevant processing conditions, and ultimately developing guidelines for the digital design of filtration and washing processes.

Real World Biologic Use and Switch Patterns in Severe Asthma: Data from the International Severe Asthma Registry and the US CHRONICLE Study.

INTRODUCTION: International registries provide opportunities to describe use of biologics for treating severe asthma in current clinical practice. Our aims were to describe real-life global patterns of biologic use (continuation, switches, and discontinuations) for severe asthma, elucidate reasons underlying these patterns, and examine associated patient-level factors. METHODS: This was a historical cohort study including adults with severe asthma enrolled into the International Severe Asthma Registry (ISAR; http://isaregistries.org, 2015-2020) or the CHRONICLE Study (2018-2020) and treated with a biologic. Eleven countries were included (Bulgaria, Canada, Denmark, Greece, Italy, Japan, Kuwait, South Korea, Spain, UK, and USA). Biologic utilization patterns were defined: 1) continuing initial biologic; 2) stopping biologic treatment; or 3) switching to another biologic. Reasons for discontinuation/switching were recorded and comparisons drawn between groups. RESULTS: A total of 3531 patients were included. Omalizumab was the most common initial biologic in 2015 (88.2%) and benralizumab in 2019 (29.6%). Most patients (79%; 2791/3531) continued their first biologic; 10.2% (356/3531) stopped; 10.8% (384/3531) switched. The most frequent first switch was from omalizumab to an anti-IL-5/5R (49.6%; 187/377). The most common subsequent switch was from one anti-IL-5/5R to another (44.4%; 20/45). Insufficient efficacy and/or adverse effects were the most frequent reasons for stopping/switching. Patients who stopped/switched were more likely to have a higher baseline blood eosinophil count and exacerbation rate, lower lung function, and greater health care resource utilization. CONCLUSION: The description of real-life patterns of continuing, stopping, or switching biologics enhances our understanding of global biologic use. Prospective studies involving structured switching criteria could ascertain optimal strategies to identify patients who may benefit from switching.