Publications by authors named "D Lewis"

5,599 Publications

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Errors of commission or omission: The net risk safety analysis conversation we should be having around automated insulin delivery systems.

Authors:
Dana M Lewis

Diabet Med 2021 Sep 12:e14687. Epub 2021 Sep 12.

OpenAPS, Seattle, Washington, USA.

The question of safety often arises when discussing automated insulin delivery systems, but discussion of safety is often anchored on a comparison to the risk to a person without diabetes, overlooking the risks of living with insulin-requiring diabetes. We should use a net risk safety perspective for evaluating diabetes technology that takes into account the ongoing risks of insulin management for people living with diabetes.
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http://dx.doi.org/10.1111/dme.14687DOI Listing
September 2021

Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study.

Lancet 2021 Sep 8. Epub 2021 Sep 8.

Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands.

Background: Patients with relapsed or refractory B-cell non-Hodgkin lymphoma have few treatment options. We aimed to establish the safety and recommended phase 2 dose of epcoritamab, a novel bispecific antibody that targets CD3 and CD20 and induces T-cell-mediated cytotoxic activity against CD20+ malignant B cells.

Methods: For the dose-escalation part of this phase 1/2 study, we enrolled adults (aged ≥18 years) with relapsed or refractory CD20+ B-cell non-Hodgkin lymphoma at ten sites across four countries (Denmark, the Netherlands, the UK, and Spain). Eligible patients received priming and intermediate doses followed by full doses of subcutaneous epcoritamab administered in 28-day cycles; each subsequent cohort involved escalation of the priming, intermediate, or full dose (0·0128-60 mg). The primary objectives were to determine the maximum tolerated dose and the recommended phase 2 dose. Safety, antitumour activity, pharmacokinetics, and immune biomarkers were also assessed. This study is registered with ClinicalTrials.gov, NCT03625037, with the dose-expansion part ongoing.

Findings: Between June 26, 2018, and July 14, 2020, we enrolled 73 patients with relapsed, progressive, or refractory CD20+ mature B-cell non-Hodgkin lymphoma. 68 patients received escalating full doses (0·0128-60 mg) of subcutaneous epcoritamab. No dose-limiting toxic effects were observed, and the maximum tolerated dose was not reached; the full dose of 48 mg was identified as the recommended phase 2 dose. All 68 patients received at least one dose of epcoritamab and were included in safety analyses: common adverse events were pyrexia (47 patients [69%]), primarily associated with cytokine release syndrome (CRS; 40 [59%], all grade 1-2), and injection site reactions (32 [47%]; 31 grade 1). There were no grade 3 or higher CRS events. No discontinuations occurred due to treatment-related adverse events or treatment-related deaths. Overall response rate in patients with relapsed or refractory diffuse large B-cell lymphoma was 68% (95% CI 45-86), with 45% achieving a complete response at full doses of 12-60 mg. At 48 mg, the overall response rate was 88% (47-100), with 38% achieving a complete response. Patients with relapsed or refractory follicular lymphoma had an overall response rate of 90% (55-100), with 50% achieving a complete response at full doses of 0·76-48 mg. Epcoritamab induced robust and sustained B-cell depletion, and CD4+ and CD8+ T-cell activation and expansion, with modest increases in cytokine levels.

Interpretation: Single-agent subcutaneous epcoritamab for treatment of patients with relapsed or refractory B-cell non-Hodgkin lymphoma merits investigation in ongoing phase 2 and phase 3 studies.

Funding: Genmab and AbbVie.
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http://dx.doi.org/10.1016/S0140-6736(21)00889-8DOI Listing
September 2021

Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum.

Front Immunol 2021 23;12:714090. Epub 2021 Aug 23.

Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, United States.

Although most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation. An elastic net model described the relationship between GA and immunome (R=0.85, p=8.75e-14), and unsupervised clustering highlighted previously unrecognized GA-dependent immune dynamics, including decreasing basal MAP-kinase/NFκB signaling in antigen presenting cells; increasing responsiveness of cytotoxic lymphocytes to interferon-α; and decreasing frequency of regulatory and invariant T cells, including NKT-like cells and CD8CD161 T cells. Knowledge gained from the analysis of the neonatal immune landscape across GA provides a mechanistic framework to understand the unique susceptibility of preterm infants to both hyper-inflammatory diseases and infections.
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http://dx.doi.org/10.3389/fimmu.2021.714090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420969PMC
August 2021

Flexible nanoporous activated carbon for adsorption of organics from industrial effluents.

Nanoscale 2021 Sep 7. Epub 2021 Sep 7.

Department of Materials, University of Manchester, Oxford Road, Manchester M13 9PL, UK.

This paper reports a study involving the formation of a self-assembled polymeric monolayer on the surface of a high surface area activated carbon to engineer its affinity towards organic contaminants. A nanoporous activated carbon cloth with a surface area of ∼1220 m g and a pore volume of ∼0.42 cm g was produced by chemical impregnation, carbonisation and high-temperature CO activation of a commercially available viscose rayon cloth. The subsequent modification with a silane polymer resulted in a nanoscale self-assembled monolayer that made it selective towards organic solvents (contact angle <10°) and repellant towards water (contact angle >145°). The adsorbent showed more than 95% efficiency in the separation of various types of oil/water mixtures under neutral, basic and acidic conditions. Benefiting from inherent nanoscale features, a robust hierarchical structure and a thermally stable monolayer (∼300 °C), this nanoporous adsorbent maintained high efficiency for more than 20 cycles and separated surfactant stabilised emulsion with >92% oil removal efficiency. The adsorbent was studied extensively with a series of advanced characterisation techniques to establish the formation mechanism and performance in emulsion separation. Findings from this work provide crucial insights towards large-scale implementation of surface engineered activated carbon-based materials for a wide range of industrial separation applications.
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http://dx.doi.org/10.1039/d1nr03242aDOI Listing
September 2021

Adverse Events in the Digital Age: Finding the Sharpest Tool in the Box.

Ther Innov Regul Sci 2021 Sep 7. Epub 2021 Sep 7.

Chief Medical Office and Patient Safety, Global Drug Development, Novartis Pharma GmbH, Oeflinger Strasse 44, 79664, Wehr, Germany.

Digital health arrived to society and it generates data which is growing exponentially. Pharma and medical device industry recently embarked on this journey. Digital tools became everyday experience both in development as well as post-market settings. These non-traditional data sources may contain relevant safety, efficacy, effectiveness and other knowledge, which are valuable for understanding and further characterizing safety profile of a given medicinal and medical device product. It is however unclear what new responsibilities are associated with the use of such tools and data generated / collected by them. Current regulatory framework does not provide very clear guidance on it. Teams are struggling to interpret expectations originated from regulations, ethics and patients. We present practical approaches for data management and we suggest that a detailed assessment of projects is conducted to identify obligations for screening digitally-sourced data. Compliance with regulations is obligatory, but it is also incumbent on the sponsor to define a data management strategy covering the purpose of the activities, and the value of the data gathered. Decisions thereafter should be aligned with the mission, vision, and objectives defined by the sponsor.
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http://dx.doi.org/10.1007/s43441-021-00337-1DOI Listing
September 2021
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