Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing-remitting MS.

BACKGROUND: Alemtuzumab efficacy and safety was demonstrated in CARE-MS I and extension studies (CAMMS03409; TOPAZ). OBJECTIVE: Evaluate serum neurofilament light chain (sNfL) in CARE-MS I patients and highly active disease (HAD) subgroup, over 7 and 2 years for alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a), respectively. METHODS: Patients received SC IFNB-1a 44 µg 3×/week or alemtuzumab 12 mg/day at baseline and month 12, with further as-needed 3-day courses. sNfL was measured using single-molecule array (Simoa™). HAD definition was ⩾2 relapses in year before randomization and ⩾1 baseline gadolinium-enhancing lesion. RESULTS: Baseline median sNfL levels were similar in alemtuzumab (n = 354) and SC IFNB-1a-treated (n = 159) patients (31.7 vs 31.4 pg/mL), but decreased with alemtuzumab versus SC IFNB-1a until year 2 (Y2; 13.2 vs 18.7 pg/mL; p < 0.0001); 12.7 pg/mL for alemtuzumab at Y7. Alemtuzumab-treated patients had sNfL at/below healthy control median at Y2 (72% vs 47%; p < 0.0001); 73% for alemtuzumab at Y7. HAD patients (n = 102) had higher baseline sNfL (49.4 pg/mL) versus overall population; alemtuzumab HAD patients attained similar levels (Y2, 12.8 pg/mL; Y7, 12.7 pg/mL; 75% were at/below control median at Y7). CONCLUSION: Alemtuzumab was superior to SC IFNB-1a in reducing sNfL, with levels in alemtuzumab patients remaining stable through Y7. CLINICALTRIALS.GOV IDENTIFIER: NCT00530348, NCT00930553, NCT02255656.

Evaluation of peer teaching and deliberate practice to teach veterinary surgery.

OBJECTIVE: To assess the impact of peer teaching and deliberate practice on surgical skills acquisition and retention in first- and second-year veterinary students. STUDY DESIGN: Randomized, prospective, comparative study. SAMPLE POPULATION: Eighteen first-year and 25 second-year students from 1 college of veterinary medicine who had previously demonstrated proficiency in basic surgical skills. METHODS: Forty-three participants were divided into 3 groups: the test group (group A, n = 15), who participated in a structured peer-assisted learning program using deliberate practice; the time-practice control group (group B, n = 15), who participated in an unstructured peer-supported environment; and the assessment-only control group (group C, n = 13), who participated in the assessments. Participants performed a subcutaneous mass removal on a cadaver model and were assessed via a global rating system. Three assessment points were evaluated: pretraining, immediate posttraining, and retention. RESULTS: The number of participants who achieved acceptable or excellent grand total scores in group A increased after training. Among all participants, 22% in group A, 35% in group B, and 38% in group C did not achieve an acceptable total score at the retention assessment. CONCLUSION: The study population improved in skill level and retention through the use of standardized video and peer instruction with attention to effective learning strategies, particularly deliberate practice. CLINICAL SIGNIFICANCE: Use and enhancement of the format introduced in this study could augment veterinary surgical education.

Tiludronate and clodronate do not affect bone structure or remodeling kinetics over a 60 day randomized trial.

BACKGROUND: Tiludronate and clodronate are FDA-approved bisphosphonate drug therapies for navicular disease in horses. Although clinical studies have determined their ability to reduce lameness associated with skeletal disorders in horses, data regarding the effect on bone structure and remodeling is lacking. Additionally, due to off-label use of these drugs in young performance horses, effects on bone in young horses need to be investigated. Therefore, the purpose of this randomized, experimental pilot study was to determine the effect of tiludronate and clodronate on normal bone cells, structure and remodeling after 60 days in clinically normal, young horses. Additionally, the effect of clodronate on bone healing 60 days after an induced defect was investigated. RESULTS: All horses tolerated surgery well, with no post-surgery lameness and all acquired biopsies being adequate for analyses. Overall, tiludronate and clodronate did not significantly alter any bone structure or remodeling parameters, as evaluated by microCT and dynamic histomorphometry. Tiludronate did not extensively impact bone formation or resorption parameters as evaluated by static histomorphometry. Similarly, clodronate did not affect bone formation or resorption after 60 days. Sixty days post-defect, healing was minimally affected by clodronate. CONCLUSIONS: Tiludronate and clodronate do not appear to significantly impact bone tissue on a structural or cellular level using standard dose and administration schedules.

Assessment of tuber coxae bone biopsy in the standing horse.

OBJECTIVE: To describe a biopsy technique in standing horses with minimal morbidity that consistently provides a substantial bone biopsy with intact, undamaged architecture. STUDY DESIGN: Experimental, prospective study. ANIMALS: Ten Thoroughbred horses. METHODS: Biopsies were obtained from the tuber coxae of 10 sedated, standing horses using an oscillating saw. Bilateral biopsies, separated by 60 days, were evaluated with micro-computed tomography (microCT). The first biopsy was prepared for decalcified histology; the second for undecalcified histology. Both biopsies were evaluated qualitatively for histologic quality. RESULTS: The biopsy technique did not result in any significant complications, was well tolerated and all biopsies were of good histologic quality. CONCLUSION: Cortical and trabecular bone biopsies can be successfully collected from the tuber coxa using a simple technique that creates minimal morbidity and allows sequential samples to be collected. The biopsies were larger than those described previously, provided adequate bone for multiple histologic sections, and had intact, undamaged architecture on examination with microCT and light microscopy.

Exploring the potential duty of care in clinical genomics under UK law.

Genome-wide sequencing technologies are beginning to be used in projects that have both clinical diagnostic and research components. The clinical application of this technology, which generates a huge amount of information of varying diagnostic certainty, involves addressing a number of challenges to establish appropriate standards. In this article, we explore the way that UK law may respond to three of these key challenges and could establish new legal duties in relation to feedback of findings that are unrelated to the presenting condition (secondary, additional or incidental findings); duties towards genetic relatives as well as the patient and duties on the part of researchers and professionals who do not have direct contact with patients. When considering these issues, the courts will take account of European and international comparisons, developing guidance and relevant ethical, social and policy factors. The UK courts will also be strongly influenced by precedent set in case law.

Micromanipulation of InP lasers with optoelectronic tweezers for integration on a photonic platform.

The integration of light sources on a photonic platform is a key aspect of the fabrication of self-contained photonic circuits with a small footprint that does not have a definitive solution yet. Several approaches are being actively researched for this purpose. In this work we propose optoelectronic tweezers for the manipulation and integration of light sources on a photonic platform and report the positional and angular accuracy of the micromanipulation of standard Fabry-Pérot InP semiconductor laser die. These lasers are over three orders of magnitude bigger in volume than any previously assembled with optofluidic techniques and the fact that they are industry standard lasers makes them significantly more useful than previously assembled microdisk lasers. We measure the accuracy to be 2.5 ± 1.4 µm and 1.4 ± 0.4° and conclude that optoelectronic tweezers are a promising technique for the micromanipulation and integration of optoelectronic components in general and semiconductor lasers in particular.

Has the biobank bubble burst? Withstanding the challenges for sustainable biobanking in the digital era.

Biobanks have been heralded as essential tools for translating biomedical research into practice, driving precision medicine to improve pathways for global healthcare treatment and services. Many nations have established specific governance systems to facilitate research and to address the complex ethical, legal and social challenges that they present, but this has not lead to uniformity across the world. Despite significant progress in responding to the ethical, legal and social implications of biobanking, operational, sustainability and funding challenges continue to emerge. No coherent strategy has yet been identified for addressing them. This has brought into question the overall viability and usefulness of biobanks in light of the significant resources required to keep them running. This review sets out the challenges that the biobanking community has had to overcome since their inception in the early 2000s. The first section provides a brief outline of the diversity in biobank and regulatory architecture in seven countries: Australia, Germany, Japan, Singapore, Taiwan, the UK, and the USA. The article then discusses four waves of responses to biobanking challenges. This article had its genesis in a discussion on biobanks during the Centre for Health, Law and Emerging Technologies (HeLEX) conference in Oxford UK, co-sponsored by the Centre for Law and Genetics (University of Tasmania). This article aims to provide a review of the issues associated with biobank practices and governance, with a view to informing the future course of both large-scale and smaller scale biobanks.

Comparison of hydroxyethyl starch colloids with crystalloids for surgical patients: A systematic review and meta-analysis.

BACKGROUND: Fluid therapy is one of the most ubiquitous medical therapeutic interventions. There is a debate over whether colloids or crystalloids are better for fluid resuscitation. Recent large trials and meta-analyses suggest no mortality benefit and possible harm with hydroxyethyl starch (HES) use. However, these trials were conducted in critically ill and septic patients and their applicability to perioperative patients has been challenged. OBJECTIVE: We aimed to evaluate the impact of HES use in scheduled and elective surgical patients. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). ELIGIBILITY CRITERIA: Only RCTs comparing the use of the synthetic colloid HES with any crystalloid in adults undergoing noncardiac surgery (up to 24 h postop) were considered eligible. For each eligible trial, we extracted the outcomes of all-cause mortality within 90 days, length of hospital stay, major infectious complications, acute kidney injury (AKI) and renal replacement therapy (RRT). RESULTS: We identified 1555 citations, selected 90 for full-text evaluation, and identified 13 eligible RCTs. Trials were small (n = 20 to 202) with low event rates. There was a trend to increased mortality with HES within 90 days [13/373 vs. 3/368; risk ratio 2.97; 95% confidence interval (95% CI) 0.96 to 9.19; I = 0%], no difference in AKI and RRT (risk ratio 1.11; 95% CI 0.26 to 4.69; I = 34%), and no difference in major infectious complications (risk ratio 1.19; 95% CI 0.59 to 2.39; I = 0%). Patients resuscitated with HES had a shorter length of hospital stay (mean difference -1.52 days; 95% CI -2.87 to -0.18), although heterogeneity was high (I = 90%). CONCLUSION: This meta-analysis, based on small studies with low event rates, suggests that there are currently insufficient data to identify a difference in outcomes associated with crystalloids and HES in scheduled or elective noncardiac surgery.

Two-photon absorption and all-optical modulation in germanium-on-silicon waveguides for the mid-infrared.

The nonlinear absorption properties of a germanium-on-silicon waveguide have been characterized across the two-photon absorption (TPA) transmission window. The results show that the TPA parameters in germanium waveguides are much stronger than the peak values in silicon, in good agreement with selected measurements conducted in bulk materials. Exploiting the large nonlinear absorption near the bandedge, efficient all-optical modulation is achieved with a modulation depth of ∼8 dB and a response time <5 ps.

Mid-infrared all-optical modulation in low-loss germanium-on-silicon waveguides.

All-optical modulation has been demonstrated in a germanium-on-silicon rib waveguide over the mid-infrared wavelength range of 2-3 µm using a free-carrier absorption scheme. Transmission measurements have shown the waveguides to have low propagation losses that are relatively independent of wavelength out to 3.8 µm, indicating that the modulation could be extended further into the mid-infrared region for applications in sensing and spectroscopy. By monitoring the material recovery, the free-carrier lifetime of the micron-sized waveguides has been estimated to be ∼18 ns, allowing for modulation speeds within the megahertz regime.

An in vitro biomechanical comparison of hydroxyapatite coated and uncoated ao cortical bone screws for a limited contact: dynamic compression plate fixation of osteotomized equine 3rd metacarpal bones.

OBJECTIVES: To compare the monotonic biomechanical properties of a broad 4.5 mm limited contact-dynamic compression plate (LC-DCP) fixation secured with hydroxyapatite (HA) coated cortical bone screws (HA-LC-DCP) versus uncoated cortical bone screws (AO-LC-DCP) to repair osteotomized equine 3rd metacarpal (MC3) bones. STUDY DESIGN: Experimental. SAMPLE POPULATION: Adult equine cadaveric MC3 bones (n = 12 pair). METHODS: Twelve pairs of equine MC3 were divided into 3 test groups (4 pairs each) for: (1) 4 point bending single cycle to failure testing; (2) 4 point bending cyclic fatigue testing; and (3) torsional single cycle to failure testing. For the HA-LC-DCP-MC3 construct, an 8-hole broad LC-DCP (Synthes Ltd, Paoli, PA) was secured on the dorsal surface of each randomly selected MC3 bone with a combination of four 5.5 mm and four 4.5 mm HA-coated cortical screws. For the AO-LC-DCP-MC3 construct, an 8-hole 4.5 mm broad LC-DCP was secured on the dorsal surface of the contralateral MC3 bone with a combination of four 5.5 mm and four 4.5 mm uncoated cortical screws. All MC3 bones had mid-diaphyseal osteotomies. Mean test variable values for each method were compared using a paired t-test within each group. Significance was set at P < .05. RESULTS: Mean yield load, yield bending moment, composite rigidity, failure load, and failure bending moment, under 4 point bending, single cycle to failure, of the HA-LC-DCP fixation were significantly greater than those of the AO-LC-DCP fixation. Mean ± SD values for the HA-LC-DCP and the AO-LC-DCP fixation techniques, respectively, in single cycle to failure under 4 point bending were: yield load, 26.7 ± 2.15 and 16.3 ± 1.38 kN; yield bending moment, 527.4 ± 42.4 and 322.9 ± 27.2 N-m; composite rigidity, 5306 ± 399 and 3003 ± 300 N-m/rad; failure load, 40.6 ± 3.94 and 26.5 ± 2.52 kN; and failure bending moment, 801.9 ± 77.9 and 522.9 ± 52.2 N-m. Mean cycles to failure in 4 point bending of the HA-LC-DCP fixation (116,274 ± 13,211) was significantly greater than that of the AO-LC-DCP fixation 47,619 ± 6580. Mean yield load, mean composite rigidity, and mean failure load under torsional testing, single cycle to failure was significantly greater for the broad HA-LC-DCP fixation compared with the AO-LC-DCP fixation. In single cycle to failure under torsion, mean ± SD values for the HA-LC-DCP and the AO-LC-DCP fixation techniques, respectively, were: yield load, 101.3 ± 14.68 and 70.54 ± 10.20 N-m; composite rigidity, 437.9 ± 32.9 and 220.7 ± 17.6 N-m/rad; and failure load: 105.7 ± 15.5 and 75.28 ± 10.1 N-m. CONCLUSION: HA-LC-DCP was superior to AO-LC-DCP in resisting the static overload forces (palmarodorsal 4 point bending and torsional) and in resisting cyclic fatigue under palmarodorsal 4 point bending.

Functional properties of human ferroportin, a cellular iron exporter reactive also with cobalt and zinc.

Iron homeostasis is achieved by regulating the intestinal absorption of the metal and its recycling by macrophages. Iron export from enterocytes or macrophages to blood plasma is thought to be mediated by ferroportin under the control of hepcidin. Although ferroportin was identified over a decade ago, little is understood about how it works. We expressed in Xenopus oocytes a human ferroportin-enhanced green fluorescent protein fusion protein and observed using confocal microscopy its exclusive plasma-membrane localization. As a first step in its characterization, we established an assay to detect functional expression of ferroportin by microinjecting oocytes with (55)Fe and measuring efflux. Ferroportin expression increased the first-order rate constants describing (55)Fe efflux up to 300-fold over control. Ferroportin-mediated (55)Fe efflux was saturable, temperature-dependent (activation energy, Ea ≈ 17 kcal/mol), maximal at extracellular pH ≈ 7.5, and inactivated at extracellular pH < 6.0. We estimated that ferroportin reacts with iron at its intracellular aspect with apparent affinity constant < 10(-7) M. Ferroportin expression also stimulated efflux of (65)Zn and (57)Co but not of (64)Cu, (109)Cd, or (54)Mn. Hepcidin treatment of oocytes inhibited efflux of (55)Fe, (65)Zn, and (57)Co. Whereas hepcidin administration in mice resulted in a marked hypoferremia within 4 h, we observed no effect on serum zinc levels in those same animals. We conclude that ferroportin is an iron-preferring cellular metal-efflux transporter with a narrow substrate profile that includes cobalt and zinc. Whereas hepcidin strongly regulated serum iron levels in the mouse, we found no evidence that ferroportin plays an important role in zinc homeostasis.

Feltman: evaluating the acceptability of a diabetes education tool for Aboriginal health workers.

There is an urgent need to address the lack of Aboriginal-specific diabetes prevention and management resources. Following consultation with Victorian Aboriginal health workers, the Victorian Aboriginal Community Controlled Health Organisation and Diabetes Australia - Victoria developed 'Feltman', a life-sized felt body showing the main organs involved in the digestion and metabolism of food, and the main parts of the body affected by diabetes. Feltman was distributed to all Victorian Aboriginal Community Controlled Health Organisations and an additional 32 Victorian organisations. In total, 276 people from 57 organisations were trained to use Feltman. An online evaluation survey was developed and sent to all people who were trained to use Feltman in Victoria. Sixty-six people completed the survey. All respondents agreed Feltman was an appropriate tool for the Aboriginal community, 89% of health workers felt more confident in their ability to discuss diabetes with their community but would like further training to maintain skills and confidence and 70% of workers had used Feltman with the community. Qualitative feedback noted its strength as a highly visual resource that was popular with the Aboriginal community. Workers reported that Feltman was a highly acceptable diabetes education resource, which they believed had increased knowledge and improved the management of diabetes among clients.

A multicentre cross-sectional observational study to determine the effect of living with frailty on digital exclusion from video consultations: (Access-VIGIL).

OBJECTIVES: Many older people regularly access digital services, but many others are totally excluded. Age alone may not explain these discrepancies. As health care services offer more video consultations, we aimed to determine if living with frailty is a significant risk factor for digital exclusion in accessing video consultations, and if this changes if a person has a support network to help with access. DESIGN: We undertook a muticenter cross-sectional survey across South West England. SETTING AND PARTICIPANTS: Patients in primary care, hospital at home, and secondary care services were enrolled between February 21 and April 12, 2022. METHODS: The primary outcome was complete digital exclusion defined as no individual access or network support access to video consultations. Secondary analysis looked at the person's digital exclusion when ignoring any network support. The association between frailty and outcomes was analyzed with logistic regression. In addition, older people's digital skills, motivation, and confidence were examined. RESULTS: 255 patients were included in the analysis. The median age was 63 years (interquartile range 43-77) with 148 (57%) women. Complete digital exclusion was rare (5.1%). Only 1 of 155 who were not frail (Clinical Frailty Scale 1-3) experienced complete digital exclusion compared with 12 of 99 (10.7%) who were living with frailty (Clinical Frailty Scale 4-8). There was no association between frailty and complete digital exclusion. Frailty was associated with individual digital exclusion when no network support was available to assist. CONCLUSIONS AND IMPLICATIONS: When taking into account a person's support network, complete digital exclusion from video consultation was rare. When no support network was available, frailty was associated with individual digital exclusion. Health care services should ask about a person's support network to help people living with frailty access video consultations.

Clinically relevant doses of tiludronate do not affect bone remodelling in pasture-exercised horses.

BACKGROUND: Bisphosphonates are widely used in equine athletes to reduce lameness associated with skeletal disorders. Widespread off-label use has led to concern regarding potential negative effects on bone healing, but little evidence exists to support or refute this. OBJECTIVES: To investigate the influence of clinically relevant doses of tiludronate on bone remodelling and bone healing. STUDY DESIGN: Randomised, controlled in vivo experiments. METHODS: Each horse had a single tuber coxae biopsied (Day 0), then were divided into a treatment (IV tiludronate) or control (IV saline) group. Treatments were administered 30 and 90 days following initial biopsy. Biopsy of the tuber coxae was repeated on Day 60 to evaluate bone healing following a single treatment. Oxytetracycline was administered on Days 137 and 147 to label bone formation. The contralateral tuber coxae was biopsied on Day 150 to evaluate effects of repeated treatment. Bone biopsies were evaluated with micro-computed tomography and/or dynamic histomorphometry using standard techniques. RESULTS: Nineteen horses completed the study, with no complications following the biopsies and treatments. No significant differences in the trabecular bone parameters or bone formation rate were observed between treatment groups. MAIN LIMITATIONS: The use of a first-generation bisphosphonate may mean some effects of these drugs are underrepresented using this model. The results pertain to the tuber coxae and may not reflect injury or the healing response that occurs in long bones in training or racing. CONCLUSIONS: In this model, tiludronate did not affect normal bone remodelling in the horse, despite repeat dosages.

Workplace-based assessments in Foundation Programme training: do trainees in difficulty use them differently?

CONTEXT: Trainee-led workplace-based assessment (WPBA) is increasingly used in postgraduate medical training. Trainees in difficulty are known to behave differently from their peers; these differences may be reflected in their use of WPBAs and may give new insights into the behaviour and assessment of struggling trainees. METHODS: Data were extracted for 76 115 assessments, completed by 1900 UK Foundation Programme (FP) trainees. Of these 1900 trainees, 95 (5%) were FP trainees in difficulty (FTiDs). We analysed aspects of the use of WPBAs, using multiple logistic regressions, to compare the behaviours of FTiDs with those of their peers. RESULTS: Of 48 possible comparisons, only two (i.e. the rate expected to occur by chance) showed statistically significant differences: relative to their peers, FTiDs were more likely to choose nurse assessors in direct observations of procedural skills (odds ratio [OR] 7.05, 95% confidence interval [CI] 1.23-40.43) and more likely to choose non-clinical assessors for assessments using the mini-peer assessment tool (OR 30.44, 95% CI 1.34-689.29). CONCLUSIONS: Key features of assessor choice for FTiDs are familiarity and likelihood of receiving a positive assessment. This analysis has not demonstrated that FTiDs use WPBAs any differently from their peers who are not in difficulty, although it does suggest associations and trends that require further exploration. These null results are interesting and raise hypotheses for prospective confirmation or disproof, and for further qualitative work investigating how struggling trainees use WPBAs in order to guide the future implementation of WPBAs in postgraduate training.

Ethical and legal considerations influencing human involvement in the implementation of artificial intelligence in a clinical pathway: A multi-stakeholder perspective.

Introduction: Ethical and legal factors will have an important bearing on when and whether automation is appropriate in healthcare. There is a developing literature on the ethics of artificial intelligence (AI) in health, including specific legal or regulatory questions such as whether there is a right to an explanation of AI decision-making. However, there has been limited consideration of the specific ethical and legal factors that influence when, and in what form, human involvement may be required in the implementation of AI in a clinical pathway, and the views of the wide range of stakeholders involved. To address this question, we chose the exemplar of the pathway for the early detection of Barrett's Oesophagus (BE) and oesophageal adenocarcinoma, where Gehrung and colleagues have developed a "semi-automated", deep-learning system to analyse samples from the CytospongeTM TFF3 test (a minimally invasive alternative to endoscopy), where AI promises to mitigate increasing demands for pathologists' time and input. Methods: We gathered a multidisciplinary group of stakeholders, including developers, patients, healthcare professionals and regulators, to obtain their perspectives on the ethical and legal issues that may arise using this exemplar. Results: The findings are grouped under six general themes: risk and potential harms; impacts on human experts; equity and bias; transparency and oversight; patient information and choice; accountability, moral responsibility and liability for error. Within these themes, a range of subtle and context-specific elements emerged, highlighting the importance of pre-implementation, interdisciplinary discussions and appreciation of pathway specific considerations. Discussion: To evaluate these findings, we draw on the well-established principles of biomedical ethics identified by Beauchamp and Childress as a lens through which to view these results and their implications for personalised medicine. Our findings are not only relevant to this context but have implications for AI in digital pathology and healthcare more broadly.

Ethical and legal implications of implementing risk algorithms for early detection and screening for oesophageal cancer, now and in the future.

BACKGROUND: Oesophageal cancer has significant morbidity and mortality but late diagnosis is common since early signs of disease are frequently misinterpreted. Project DELTA aims to enable earlier detection and treatment through targeted screening using a novel risk prediction algorithm for oesophageal cancer (incorporating risk factors of Barrett's oesophagus including prescriptions for acid-reducing medications (CanPredict)), together with a non-invasive, low-cost sampling device (CytospongeTM). However, there are many barriers to implementation, and this paper identifies key ethical and legal challenges to implementing these personalised prevention strategies for Barrett's oesophagus/oesophageal cancer. METHODS: To identify ethical and legal issues relevant to the deployment of a risk prediction tool for oesophageal cancer into primary care, we adopted an interdisciplinary approach, incorporating targeted informal literature reviews, interviews with expert collaborators, a multidisciplinary workshop and ethical and legal analysis. RESULTS: Successful implementation raises many issues including ensuring transparency and effective risk communication; addressing bias and inequity; managing resources appropriately and avoiding exceptionalism. Clinicians will need support and training to use cancer risk prediction algorithms, ensuring that they understand how risk algorithms supplement rather than replace medical decision-making. Workshop participants had concerns about liability for harms arising from risk algorithms, including from potential bias and inequitable implementation. Determining strategies for risk communication enabling transparency but avoiding exceptionalist approaches are a significant challenge. Future challenges include using artificial intelligence to bolster risk assessment, incorporating genomics into risk tools, and deployment by non-health professional users. However, these strategies could improve detection and outcomes. CONCLUSIONS: Novel pathways incorporating risk prediction algorithms hold considerable promise, especially when combined with low-cost sampling. However immediate priorities should be to develop risk communication strategies that take account of using validated risk algorithms, and to ensure equitable implementation. Resolving questions about liability for harms arising should be a longer-term objective.

Dupilumab Efficacy in Steroid-Dependent Severe Asthma by Baseline Oral Corticosteroid Dose.

BACKGROUND: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/-13, key and central drivers of type 2 inflammation in multiple diseases. In the phase 3 LIBERTY ASTHMA VENTURE (VENTURE) study (NCT02528214), dupilumab versus placebo reduced oral corticosteroid (OCS) dose and improved clinical outcomes in patients with OCS-dependent severe asthma. Dupilumab efficacy in patients with varying disease burden (defined by baseline OCS dose) has not been assessed. OBJECTIVE: This post hoc analysis of VENTURE evaluated dupilumab efficacy across subgroups defined by baseline OCS dose. METHODS: The OCS dose, proportion no longer needing OCS at week 24, annualized severe exacerbation rate, and least squares mean change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 second at week 24 were evaluated in VENTURE patients with OCS-dependent severe asthma receiving dupilumab 300 mg every 2 weeks versus placebo, categorized by a baseline OCS dose of less than 10 mg/d or 10 or more mg/d. RESULTS: Dupilumab reduced daily OCS dose from baseline at week 24 in both dose groups. In dupilumab-/placebo-treated patients with a baseline OCS dose of less than 10 mg/d and 10 or more mg/d, 72%/42% and 37%/23% stopped OCS by week 24 (P < .01/P < .05), respectively. Dupilumab significantly reduced the annualized severe exacerbation rate by 71% and 48% (P < .01/P < .05). At week 24, dupilumab improved pre- and post-bronchodilator forced expiratory volume in 1 second in patients in both dose groups. CONCLUSIONS: In patients with OCS-dependent severe asthma receiving lower or higher baseline OCS doses, dupilumab significantly reduced the OCS dose and improved the likelihood of no longer requiring OCS while also reducing exacerbations and improving lung function.