Delivery Science Research Articles

Optimal designs using generalized estimating equations in cluster randomized crossover and stepped wedge trials.

Cluster randomized crossover and stepped wedge cluster randomized trials are two types of longitudinal cluster randomized trials that leverage both the within- and between-cluster comparisons to estimate the treatment effect and are increasingly used in healthcare delivery and implementation science research. While the variance expressions of estimated treatment effect have been previously developed from the method of generalized estimating equations for analyzing cluster randomized crossover trials and stepped wedge cluster randomized trials, little guidance has been provided for optimal designs to ensure maximum efficiency. Here, an optimal design refers to the combination of optimal cluster-period size and optimal number of clusters that provide the smallest variance of the treatment effect estimator or maximum efficiency under a fixed total budget. In this work, we develop optimal designs for multiple-period cluster randomized crossover trials and stepped wedge cluster randomized trials with continuous outcomes, including both closed-cohort and repeated cross-sectional sampling schemes. Local optimal design algorithms are proposed when the correlation parameters in the working correlation structure are known. MaxiMin optimal design algorithms are proposed when the exact values are unavailable, but investigators may specify a range of correlation values. The closed-form formulae of local optimal design and MaxiMin optimal design are derived for multiple-period cluster randomized crossover trials, where the cluster-period size and number of clusters are decimal. The decimal estimates from closed-form formulae can then be used to investigate the performances of integer estimates from local optimal design and MaxiMin optimal design algorithms. One unique contribution from this work, compared to the previous optimal design research, is that we adopt constrained optimization techniques to obtain integer estimates under the MaxiMin optimal design. To assist practical implementation, we also develop four SAS macros to find local optimal designs and MaxiMin optimal designs.

Establishing evidence criteria for implementation strategies in the US: a Delphi study for HIV services

BackgroundThere are no criteria specifically for evaluating the quality of implementation research and recommending implementation strategies likely to have impact to practitioners. We describe the development and application of the Best Practices Tool, a set of criteria to evaluate the evidence supporting HIV-specific implementation strategies.MethodsWe developed the Best Practices Tool from 2022–2023 in three phases. (1) We developed a draft tool and criteria based on a literature review and key informant interviews. We purposively selected and recruited by email interview participants representing a mix of expertise in HIV service delivery, quality improvement, and implementation science. (2) The tool was then informed and revised through two e-Delphi rounds using a survey delivered online through Qualtrics. The first and second round Delphi surveys consisted of 71 and 52 open and close-ended questions, respectively, asking participants to evaluate, confirm, and make suggestions on different aspects of the rubric. After each survey round, data were analyzed and synthesized as appropriate; and the tool and criteria were revised. (3) We then applied the tool to a set of research studies assessing implementation strategies designed to promote the adoption and uptake of evidence-based HIV interventions to assess reliable application of the tool and criteria.ResultsOur initial literature review yielded existing tools for evaluating intervention-level evidence. For a strategy-level tool, additions emerged from interviews, for example, a need to consider the context and specification of strategies. Revisions were made after both Delphi rounds resulting in the confirmation of five evaluation domains – research design, implementation outcomes, limitations and rigor, strategy specification, and equity – and four evidence levels – best, promising, more evidence needed, and harmful. For most domains, criteria were specified at each evidence level. After an initial pilot round to develop an application process and provide training, we achieved 98% reliability when applying the criteria to 18 implementation strategies.ConclusionsWe developed a tool to evaluate the evidence supporting implementation strategies for HIV services. Although specific to HIV in the US, this tool is adaptable for evaluating strategies in other health areas.

Nanoparticle Uptake and Bioaccumulation in Pisum sativum L. (Green Pea) Analyzed via Dark-Field Microscopy, Infrared Spectroscopy, and Principal Component Analysis Combined with Machine Learning

The green pea (Pisum sativum L.) is an economically, nutritionally, and culturally important legume. It is a crop that is subject to various investigations due to its popularity with the development of various protocols in different topics, except for nano-biotechnological studies. This work was carried out to evaluate the uptake, distribution, translocation, and bioaccumulation of the single-walled carbon nanotubes (CNTs) and gold nanoparticles (AuNPs) within the economically important plant Pisum sativum morphologically and anatomically with a dark-field microscopy system. Data were analyzed for morphological parameters such as stem, tendril, root length, number, shape, width-length of the stipules, and root-stem-stipule. Our results proved the stimulation for growth and anatomical parameters such as CNTs aggregates and AuNPs particles at paranchyma, cortex, spongia cells, starch formation and accumulation in lenticels, stoma cells, and stomatal pores. In this study, we compared the utilization of the entire available Attenuated Total Reflectance—Fourier Transform Infrared Spectroscopy (ATR-FTIR) spectral range (525–4000 cm−1) for conducting principal component analysis (PCA) without excluding any specific spectral wavenumbers with the spectral range chosen based on larger PCA loadings. The results demonstrate that for both chosen spectral ranges of the PCA score plots, utilizing only the first three principal components (PCs), we effectively visually separated three groups: (1) plants treated with Au NPs, (2) plants treated with CNTs, and (3) control plants without nanoparticle treatment using ATR-FTIR spectral data from combined samples of root, stem, and leaves from the Pisum sativum plant. Our investigation shows that green pea, a species of the Fabaceae family, is low-cost, fast, and non-toxic and requires an environmentally safe process in the area of nanotechnology in bio-application regarding the green synthesis of nanoparticles; it is a step for green mining, phytoremediation, delivering drugs, and biomolecules. Our findings show that green pea and the Fabaceae family have more advantages for the biological synthesis of C-Au nanoparticles and guide soil health, agricultural development, pharmaceuticals, drug delivery science, and other types of medicinal investigations with a new approach, while a lot of economic plants in the Fabaceae family will be available for the green synthesis of more NPs with single and rapid protocols and will be a popular family in nano-biotechnological studies in the next few decades.

2023 Inaugural Healthcare Delivery Science: Innovation and Partnerships for Health Equity Research (DESCIPHER) Symposium.

This article provides an overview of presentations and discussions from the inaugural Healthcare Delivery Science: Innovation and Partnerships for Health Equity Research (DESCIPHER) Symposium. The symposium brought together esteemed experts from various disciplines to explore models for translating evidence-based interventions into practice. The symposium highlighted the importance of disruptive innovation in healthcare, the need for multi-stakeholder engagement, and the significance of family and community involvement in healthcare interventions. The article concluded with a call to action for advancing healthcare delivery science to achieve health equity.

Tailored therapies: Exploring macromolecule based delivery science for personalized medicine

The advent of personalized medicine has revolutionized healthcare, transitioning from a one-size-fits-all model to tailored therapies that address the unique genetic, environmental, and lifestyle factors of individual patients. Central to this shift is the field of macromolecule-based delivery science which involves the use of biologically derived or synthetically engineered macromolecules, like proteins, nucleic acids, and polysaccharides. These macromolecules have shown immense potential in improving the specificity, efficacy and safety of therapeutic interventions, paving the way for more precise and effective treatments. Macromolecule-based delivery systems are designed to overcome the limitations of traditional small-molecule drugs, such as poor solubility, rapid degradation, nonspecific distribution and potential toxicity. Unlike small molecules, macromolecules can be engineered for high specificity toward target cells or tissues, reducing off-target effects and enhancing therapeutic outcomes. The ability to modify and functionalize these macromolecules with various chemical and biological entities allows for the development of multifunctional delivery platforms capable of addressing complex pathophysiological conditions. These systems have been instrumental in targeting specific antigens on cancer cells, leading to highly effective therapies with reduced systemic toxicity. In addition, RNA-based therapies offer innovative solutions for gene silencing and protein replacement, providing hope for patients with previously untreatable genetic disorders.

Patient care in complex Sociotechnological ecosystems and learning health systems.

The learning health system (LHS) model was proposed to provide real-time, bi-directional flow of learning using data captured in health information technology systems to deliver rapid learning in healthcare delivery. As highlighted by the landmark National Academy of Medicine report "Crossing the Quality Chasm," the U.S. healthcare delivery industry represents complex adaptive systems, and there is an urgent need to develop innovative methods to identify efficient team structures by harnessing real-world care delivery data found in the electronic health record (EHR). We offer a discussion surrounding the complexities of team communication and how solutions may be guided by theories such as the Multiteam System (MTS) framework and the Multitheoretical Multilevel Framework of Communication Networks. To advance healthcare delivery science and promote LHSs, our team has been building a new line of research using EHR data to study MTS in the complex real world of cancer care delivery. We are developing new network metrics to study MTSs and will be analyzing the impact of EHR communication network structures on patient outcomes. As this research leads to patient care delivery interventions/tools, healthcare leaders and healthcare professionals can effectively use health IT data to implement the most evidence-based collaboration approaches in order to achieve the optimal LHS and patient outcomes.

Creating pragmatic, rapid‐cycle, evidence‐based innovation: The Kaiser Permanente Northern California Delivery Science and Applied Research (DARE) program

AbstractIntroductionOngoing crises in the quality, affordability, sustainability, value, and equity of U.S. healthcare call for rapid, massive‐scale innovations across multiple specialties. Physician groups and healthcare organizations commit significant monetary and personnel investments for innovation and improvement efforts, but most lack over‐arching systems theory‐supported conceptual frameworks for efficiently coordinating the timely, large‐volume idea generation, refinement, prioritization, evidence development, implementation, and re‐evaluation strategies needed for rapid‐cycle improvements in health care delivery, outcomes, and value.MethodsThis article describes one large‐scale, generalizable model: The Permanente Medical Group's (TPMG) Delivery Science and Applied Research (DARE) program within Kaiser Permanente Northern California. This organization‐level initiative was designed to: (1) elicit clinical innovation and quality concerns across clinical specialties; (2) prioritize these questions for next‐step evaluations; (3) create dedicated analytic, research, and clinical expertise to rapidly study the questions generated; (4) develop communities of clinician‐researchers, embedded within their specialties' clinical operations, who gather ideas for evaluation, generate evidence, and facilitate implementation of research results (a.k.a. evidence‐based innovators); and (5) broadly disseminate findings, to connect results with potential next‐step implementation.ResultsThe DARE program and its components rapidly led to more than 200 recently completed or ongoing projects, informed care changes, influenced national guidelines, developed communities of evidence‐based clinician innovators in 15 specialties, and empowered new paths for career diversity and physician wellness. Key factors in the DARE program's success include explicitly defining high‐impact ideas; engaging researchers with analysts experienced with large clinical data systems; developing several research funding mechanisms scaled to project size; prioritizing rapid and efficient project completion; supporting clinician‐investigators embedded within their specialties; and structured organization‐wide dissemination of findings for informing potential implementation.ConclusionsHigh‐volume, evidence‐based innovation programs can be important, scale‐able, reproducible models for different settings for increasing quality, affordability, sustainability, value, and equity in healthcare and furthering the difficult‐to‐achieve concept of developing sustainable learning healthcare systems.

A recent update on gastro retentive drug delivery systems

Gastro retentive drug delivery systems (GRDDS) have garnered significant attention in recent years due to their potential to enhance therapeutic efficacy and patient compliance by prolonging gastric residence time and optimizing drug release kinetics. This review provides a comprehensive overview of the latest advancements in GRDDS, focusing on formulation strategies, design principles, and evaluation methodologies. Various approaches such as floating systems, mucoadhesive systems, expandable systems, and magnetic systems are discussed in detail, highlighting their mechanisms of action and applications in targeted drug delivery. Furthermore, recent innovations in materials science and formulation technologies have enabled the development of novel GRDDS with improved biocompatibility, stability, and controlled release profiles. The review also addresses challenges associated with GRDDS, including physiological variability, drug stability, and regulatory considerations, and proposes potential strategies to overcome these obstacles. Additionally, the clinical relevance of GRDDS in the treatment of various gastrointestinal disorders and their future prospects in personalized medicine and targeted therapy are explored. Overall, this review aims to provide valuable insights into the current state-of-the-art in GRDDS research and its implications for the advancement of drug delivery science.

Impact of the Hydrocarbon Chain Length of Biodegradable Ester-Bonded Cationic Gemini Surfactants on Self-Assembly, In Vitro Gene Transfection, Cytotoxicity, and Antimicrobial Activity.

Gemini surfactants, due to their unique structural features and enhanced properties compared to conventional surfactants, are becoming more popular in the domain of colloid and interface science, drug delivery, and gene delivery science. This distinct class of surfactants forms a wide range of self-assembled aggregates depending on their chemical structure and environmental conditions. The present work aims to develop Gemini with three distinct chain lengths linked through the ester group and quaternary nitrogen head groups that can bind DNA molecules and ultimately serve as vectors for DNA transfection. Thus, we synthesized three distinct cationic Gemini with 12, 14, and 16 carbons in their tails and studied the effect of the hydrocarbon chain length on their physicochemical properties and biological applications. The self-assembly of these Geminis in aqueous solution was investigated by a number of techniques, including surface tension, electrical conductivity, fluorescence probe, calorimetry, dynamic light scattering, and atomic force microscopy. All three Gemini were extremely surface active and self-assembled above a very low critical micelle concentration. Calorimetric studies suggested the formation of thermodynamically favorable aggregates in an aqueous medium. Chain length dependence was observed in the size as well as the morphology of the aggregates. These Gemini ions were found to bind DNA strongly, as indicated by the high binding constant values. In vitro gene transfection studies using the RAW 264.7 cell line suggested that all three cationic Gemini had transfection efficiencies comparable to that of commercial standard turbofectamine. MTT assay was also performed for concentration selection while using these Gemini as transfection vectors. Overall, it was observed that Gemini had very little cytotoxicity within the investigated concentration range, highlighting the significance of the ester link within the structure. When compared with known antimicrobials such as kanamycin and ampicillin, all three Gemini furnished excellent antimicrobial activity in both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) microorganisms.

A Review on Innovative Drug Delivery Platforms

In recent years, the field of drug delivery has undergone a transformative shift with the introduction of innovative platforms that transcend conventional methods, providing accurate and efficient means for delivering therapeutic agents. This exploration delves into the distinctive features and potential impacts of these pioneering platforms, charting a course for the future of pharmaceutical interventions. In this review article, the advancements regarding the nanotechnology-enabled delivery, lipid-based drug delivery systems, targeted drug delivery, implantable drug delivery systems, 3D printing in drug delivery, stimuli-responsive delivery systems, mRNA and gene delivery platforms and microfluidic - based delivery systems were discussed. These innovative drug delivery platforms represent a dynamic frontier in pharmaceutical research and development. They afford unprecedented control over drug properties, release kinetics and targeting strategies. As research continues to push the boundaries of drug delivery science, these innovations hold the potential to revolutionize the treatment of various diseases, ushering in safer, more effective and patient-centric therapeutic solutions.

Messenger RNA Therapy for Female Reproductive Health.

Female reproductive health has traditionally been an underrepresented area of research in the drug delivery sciences. This disparity is also seen in the emerging field of mRNA therapeutics, a class of medicines that promises to treat and prevent disease by upregulating protein expression in the body. Here, we review advances in mRNA therapies through the lens of improving female reproductive health. Specifically, we begin our review by discussing the fundamental structure and biochemical modifications associated with mRNA-based drugs. Then, we discuss various packaging technologies, including lipid nanoparticles, that can be utilized to protect and transport mRNA drugs to target cells in the body. Last, we conclude our review by discussing the usage of mRNA therapy for addressing pregnancy-related health and vaccination against sexually transmitted diseases in women. Of note, we also highlight relevant clinical trials using mRNA for female reproductive health while also providing their corresponding National Clinical Trial identifiers. In undertaking this review, our aim is to provide a fundamental background understanding of mRNA therapy and its usage to specifically address female health issues with an overarching goal of providing information toward addressing gender disparity in certain aspects of health research.

Phonophoresis in Physiotherapy: Mechanisms, Applications, and Emerging Trends for Enhanced Drug Delivery and Therapeutic Efficacy

Phonophoresis, a widely utilized treatment in physiotherapy, combines topically applied gel or cream-based medications with ultrasonic therapy to enhance percutaneous absorption of pharmacological agents. The procedure employs ultrasound frequencies of 0.7 to 1.1 MHz with intensities ranging from 0.0 to 3.0 Watts per cm². Indications for phonophoresis span various inflammatory, deformative, dermatological, and rheumatic/neurological conditions. Recent studies suggest its clinical efficacy in pain relief and improved function, especially in conditions like lateral epicondylitis and osteoarthritis. The mechanism of action involves both thermal and non-thermal effects, with cavitation playing a key role in enhancing transdermal transport. Phonophoresis offers a non-invasive alternative for drug delivery, bypassing hepatic metabolism and minimizing systemic side effects. Various medicinal gels, particularly diclofenac, are used for transdermal drug delivery through phonophoresis. Low frequency phonophoresis has gained attention for enhancing transdermal transport, especially for macromolecules. Its applications extend beyond physiotherapy to include ocular drug delivery, nail therapy, gene therapy, and sports sciences. Clinical studies demonstrate the effectiveness of phonophoresis in conditions like anterior knee pain, tuberculous lymphadenitis, acute low back pain, and latent myofascial trigger points. Dosage considerations emphasize optimizing thermal effects without causing tissue damage. Studies highlight the potential of phonophoresis in relieving pain and improving function, particularly in knee osteoarthritis. Additionally, phonophoresis with Phyllanthus amarus nanoparticle gel shows promise in reducing pain and enhancing functional capacity in symptomatic knee osteoarthritis. In summary, phonophoresis stands as a valuable modality in physiotherapy, showcasing diverse applications and demonstrating clinical efficacy in various musculoskeletal and inflammatory conditions. Further research is warranted to explore its full potential and optimize treatment protocols.

Preparation and Unique Three-Dimensional Self-Assembly Property of Starfish Ferritin.

The structure and assembly properties of ferritin derived from aquatic products remain to be explored. Constructing diverse three-dimensional (3D) protein architectures with the same building blocks has important implications for nutrient delivery, medicine and materials science. Herein, ferritin from Asterias forbesii (AfFer) was prepared, and its crystal structure was resolved at 1.91 Å for the first time. Notably, different from the crystal structure of other reported ferritin, AfFer exhibited a BCT lattice arrangement in its crystals. Bioinspired by the crystal structure of AfFer, we described an effective approach for manufacturing 3D porous, crystalline nanoarchitectures by redesigning the shared protein interface involved in different 3D protein arrays. Based on this strategy, two 3D superlattices of body-centered tetragonal and simple cubicwere constructed with ferritin molecules as the building blocks. This study provided a potentially generalizable strategy for constructing different 3D protein-based crystalline biomaterials with the same building blocks.

Potential forensic applications of carbon nanodots

Nanotechnology is a flourishing branch of research due to the incredible properties nanomaterials exhibit over their massive counterparts. Carbon nanodots are the members of the carbon nanoparticle family with prominent properties like hydrophilicity, low toxicity, biocompatibility, increased stability and ease of functionalization. They are excellent replacement to metal based quantum dots which are highly toxic. Carbon nanodots are being used in the fields of medicine, environmental science, drug delivery and forensic science. Applications of carbon nanodots can be seen in bio imaging, bio sensing, cancer diagnosis and treatment, biological activities, solar cells and as photo catalysts. Forensic science is the science behind crime investigation and evidence analysis. Development of novel, rapid, on site testing materials for accurate, specific and sensitive detection of forensic evidences is required for delivery of justice to the victims of crime. Carbon nanodots have shown promising applications in the field of forensic science as well. Use of carbon nanodots as invisible ink for anti-counterfeiting application of currency and security documents and use of these nanomaterials in development of latent fingerprints are some forensic applications. Carbon nanodots based detection of food contaminants, heavy metal poisons, pesticides, illicit drugs and explosives are other forensic applications. Carbon nanodots are showing a future direction in development of on field testing kits for forensic evidences.

Nebuliser therapy in critical care: The past, present and future

Nebulisers are devices that reduce a body of liquid into a fine aerosol suitable for inhalation. Utilising the efficiency of pulmonary drug absorption, they offer a safe and powerful modality for local and systemic drug delivery in the treatment of critical illness. In comparison to conventional jet (JN) and ultrasonic nebulisers (USN), the advent of vibrating mesh nebulisers (VMN) has significantly improved the therapeutic potential of modern devices. This review article aims to summarise the history and evolution of nebulisers from first inception through to the modern vibrating mesh technology. It provides an overview on the basic science of nebulisation and pulmonary drug delivery, and the current use of nebulised therapies in critical care.

A Unified Strategy to Improve Lipid Nanoparticle Mediated mRNA Delivery Using Adenosine Triphosphate.

A central goal of chemical and drug delivery sciences is to maximize the therapeutic efficacy of a given drug at the lowest possible dose. Here, we report a generalizable strategy that can be utilized to improve the delivery of mRNA drugs using lipid nanoparticles (LNPs), the clinically approved chemistry platforms utilized in the Moderna and Pfizer/BioNTech COVID-19 vaccines. In brief, our strategy updates the chemistry of LNPs to incorporate adenosine triphosphate (ATP) alongside mRNA, a modification that results in upward of a 79-fold increase in LNP-delivered mRNA-encoded protein expression in vitro and a 24-fold increase in vivo when compared to parent mRNA LNP formulations that do not contain ATP. Notably, we find that our ATP co-delivery strategy increases LNP-delivered mRNA-encoded protein expression across eight different LNP chemistries and three different cell lines, under normoxia and hypoxia, and in a well-tolerated fashion. Notably, our strategy also improves the expression of mRNA encoding for intracellular and secreted proteins both in vitro and in vivo, highlighting the utility of leveraging ATP co-delivery within mRNA LNPs as a means to increase protein expression. In developing this strategy, we hope that we have provided a simple yet powerful approach to improving mRNA LNPs that may one day be useful in developing therapies for human disease.

Natural polymers as potential P-glycoprotein inhibitors: Pre-ADMET profile and computational analysis as a proof of concept to fight multidrug resistance in cancer

P-glycoprotein (P-gp) is known as the "multidrug resistance protein" because it contributes to tumor resistance to several different classes of anticancer drugs. The effectiveness of such polymers in treating cancer and delivering drugs has been shown in a wide range of in vitro and in vivo experiments. The primary objective of the present study was to investigate the inhibitory effects of several naturally occurring polymers on P-gp efflux, as it is known that P-gp inhibition can impede the elimination of medications. The objective of our study is to identify polymers that possess the potential to inhibit P-gp, a protein involved in drug resistance, with the aim of enhancing the effectiveness of anticancer drug formulations. The ADMET profile of all the selected polymers (Agarose, Alginate, Carrageenan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid) has been studied, and binding affinities were investigated through a computational approach using the recently released crystal structure of P-gp with PDB ID: 7O9W. The advanced computational study was also done with the help of molecular dynamics simulation. The aim of the present study is to overcome MDR resulting from the activity of P-gp by using such polymers that can inhibit P-gp when used in formulations. The docking scores of native ligand, Agarose, Alginate, Carrageenan, Chitosan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid were found to be −10.7, −8.5, −6.6, −8.7, −8.6, −24.5, −6.7, −8.3, and −7.9, respectively. It was observed that, Cyclodextrin possess multiple properties in drug delivery science and here also demonstrated excellent binding affinity. We propose that drug efflux-related MDR may be prevented by the use of Agarose, Carregeenan, Chitosan, Cyclodextrin, Hyaluronic acid, and/or Polysialic acid in the administration of anticancer drugs.

Pharmacotherapy and pulmonary fibrosis risk after SARS-CoV-2 infection: a prospective nationwide cohort study in the United States

Pulmonary fibrosis is characterized by lung parenchymal destruction and can increase morbidity and mortality. Pulmonary fibrosis commonly occurs following hospitalization for SARS-CoV-2 infection. As there are medications that modify pulmonary fibrosis risk, we investigated whether distinct pharmacotherapies (amiodarone, cancer chemotherapy, corticosteroids, and rituximab) are associated with differences in post-COVID-19 pulmonary fibrosis incidence. We used the National COVID-19 Cohort Collaboration (N3C) Data Enclave, which aggregates and harmonizes COVID-19 data across the United States, to assess pulmonary fibrosis incidence documented at least 60 days after COVID-19 diagnosis among adults hospitalized between January 1st, 2020 and July 6th, 2022 without pre-existing pulmonary fibrosis. We used propensity scores to match pre-COVID-19 drug-exposed and unexposed cohorts (1:1) based on covariates with known influence on pulmonary fibrosis incidence, and estimated the association of drug exposure with risk for post-COVID-19 pulmonary fibrosis. Sensitivity analyses considered pulmonary fibrosis incidence documented at least 30- or 90-days post-hospitalization and pulmonary fibrosis incidence in the COVID-19-negative N3C population. Among 5,923,394 patients with COVID-19, we analyzed 452,951 hospitalized adults, among whom pulmonary fibrosis incidence was 1.1 per 100-person-years. 277,984 hospitalized adults with COVID-19 were included in our primary analysis, among whom all drug exposed cohorts were well-matched to unexposed cohorts (standardized mean differences <0.1). The post-COVID-19 pulmonary fibrosis incidence rate ratio (IRR) was 2.5 (95% CI 1.2-5.1, P=0.01) for rituximab, 1.6 (95% CI 1.3-2.0, P<0.0001) for chemotherapy, and 1.2 (95% CI 1.0-1.3, P=0.02) for corticosteroids. Amiodarone exposure had no significant association with post-COVID-19 pulmonary fibrosis (IRR=0.8, 95% CI 0.6-1.1, P=0.24). In sensitivity analyses, pre-COVID-19 corticosteroid use was not consistently associated with post-COVID-19 pulmonary fibrosis. In the COVID-19 negative hospitalized population (n=1,240,461), pulmonary fibrosis incidence was lower overall (0.6 per 100-person-years) and for patients exposed to all four drugs. Recent rituximab or cancer chemotherapy before COVID-19 infection in hospitalized patients is associated with increased risk for post-COVID-19 pulmonary fibrosis. The analyses described in this publication were conducted with data or tools accessed through the NCATS N3C Data Enclave https://covid.cd2h.org and N3C Attribution & Publication Policy v1.2-2020-08-25b supported by NIHK23HL146942, NIHK08HL150291, NIHK23HL148387, NIHUL1TR002389, NCATSU24 TR002306, and a SECURED grant from the Walder Foundation/Center for Healthcare Delivery Science and Innovation, University of Chicago. WFP received a grant from the Greenwall Foundation. This research was possible because of the patients whose information is included within the data and the organizations (https://ncats.nih.gov/n3c/resources/data-contribution/data-transfer-agreement-signatories) and scientists who have contributed to the on-going development of this community resource (https://doi.org/10.1093/jamia/ocaa196).

Global Salvation Inc.: Sir Michael Barber’s education for the apocalypse and the church of Deliverology®

ABSTRACT Drawing on insights from philosophy and theology, we explore the relationship between religion, data and global education policy through an analysis of the career of Sir Michael Barber, widely regarded as an authority on the reform of public services and an influential policy entrepreneur. The analysis provides a novel perspective which illuminates how secularised salvation narratives and apocalyptic symbolism have become more prominent in his work as he rose to become a global actor. The story is entwined with the turn towards New Public Management (NPM) in education, the rise of international large-scale assessments (ILSAs), and the transition from speculative faith to salvation through the ‘science of delivery’. We follow Barber's role in formalising the faith as a secular political theology, and promoting it globally through Delivery Units and the management doctrine of Deliverology®. The analysis closes by reflecting on the practical implications of the movement, which is now woven into the institutional ideologies and reform strategies of major international organisations, agencies and corporations as part of a wider shift towards New Global Management (NGM) in global education governance.

Taking Stock of Care Delivery Transformation

This Viewpoint discusses how the same realism and rigor for evaluating biomedical innovations can be applied to the science of care delivery.