Leveraging Disruptions to Create an Equitable, Age-Friendly, Learning Health System

In a learning health system, the system’s own data and the experiences of its workforce are integrated with external evidence to provide better care. In an age-friendly health system, core principles of age-friendly care are integrated into every point in the system. Disruptions caused by the COVID-19 pandemic, and the innovations that addressed them, present an opportunity to discuss how these two frameworks may be combined and leveraged to transform care for older adults. We will present examples of pandemic-related disruptions, including rapid changes in how patients and providers move within and between facilities and the significant toll on healthcare workers’ mental health. We will also highlight innovative solutions to these disruptions that could transform healthcare systems. Critical to these points is a discussion of how these disruptions have disproportionately impacted healthcare workers and patients of color and how the innovations must be implemented using an anti-racist, health equity lens.

Marduk’s Basket and the Heavenly Treasury: Comparing Charity in the Dialogue of Pessimism and Sirach

The article treats the value of economic generosity (usātu) in the Babylonian Dialogue of Pessimism and compares it to almsgiving in the biblical book of Sirach. It attempts to resolve a longstanding obscurity: whether usātu is placed in Marduk’s “ring” (kippatu) or “basket” (qappatu). External evidence suggests that, while both readings have support and a similar theological significance, the reading “basket” (qappatu) is preferable and should be related to the temple quppu, “cash box,” used for collecting donations. The article then addresses the relevance of mortality to the Dialogue’s discussion of doing usātu. Appeal to other Akkadian wisdom literature suggests that doing usātu was connected with a reward of extra life. An analysis of the theological structure of usātu in the Dialogue and Akkadian wisdom literature leads to a comparison with the theology of almsgiving and the heavenly treasury in Ben Sira and other Second Temple Jewish literature.

A multi-center, adaptive, randomized, platform trial to evaluate the effect of repurposed medicines in outpatients with early coronavirus disease 2019 (COVID-19) and high-risk for complications: the TOGETHER master trial protocol

Background: There remains a need for an effective and affordable outpatient treatment for early COVID-19. Multiple repurposed drugs have shown promise in treating COVID-19. We describe a master protocol that will assess the efficacy of different repurposed drugs as treatments for early COVID-19 among outpatients at a high risk for severe complications. Methods: The TOGETHER Trial is a multi-center platform adaptive randomized, placebo-controlled, clinical trial. Patients are included if they are at least 18 years of age, have a positive antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and have an indication for high risk of disease severity, including co-morbidities, older age, or high body mass index. Eligible patients are randomized with equal chance to an investigational product (IP) or to placebo.The primary endpoint is hospitalization defined as either retention in a COVID-19 emergency setting for greater than 6 hours or transfer to tertiary hospital due to COVID-19. Secondary outcomes include mortality, adverse events, adherence, and viral clearance. Scheduled interim analyses are conducted and reviewed by the Data and Safety Monitoring Committee (DSMC), who make recommendations on continuing or stopping each IP. The platform adaptive design go-no-go decision rules are extended to dynamically incorporate external evidence on COVID-19 interventions from ongoing independent randomized clinical trials. Discussion: Results from this trial will assist in the identification of therapeutics for the treatment of early diagnosed COVID-19. The novel methodological extension of the platform adaptive design to dynamically incorporate external evidence is one of the first of its kind and may provide highly valuable information for all COVID-19 trials going forward. Clinicaltrials.gov registration: NCT04727424 (27/01/2021)

Use of external evidence for design and Bayesian analysis of clinical trials: a qualitative study of trialists’ views

Background Evidence from previous studies is often used relatively informally in the design of clinical trials: for example, a systematic review to indicate whether a gap in the current evidence base justifies a new trial. External evidence can be used more formally in both trial design and analysis, by explicitly incorporating a synthesis of it in a Bayesian framework. However, it is unclear how common this is in practice or the extent to which it is considered controversial. In this qualitative study, we explored attitudes towards, and experiences of, trialists in incorporating synthesised external evidence through the Bayesian design or analysis of a trial. Methods Semi-structured interviews were conducted with 16 trialists: 13 statisticians and three clinicians. Participants were recruited across several universities and trials units in the United Kingdom using snowball and purposeful sampling. Data were analysed using thematic analysis and techniques of constant comparison. Results Trialists used existing evidence in many ways in trial design, for example, to justify a gap in the evidence base and inform parameters in sample size calculations. However, no one in our sample reported using such evidence in a Bayesian framework. Participants tended to equate Bayesian analysis with the incorporation of prior information on the intervention effect and were less aware of the potential to incorporate data on other parameters. When introduced to the concepts, many trialists felt they could be making more use of existing data to inform the design and analysis of a trial in particular scenarios. For example, some felt existing data could be used more formally to inform background adverse event rates, rather than relying on clinical opinion as to whether there are potential safety concerns. However, several barriers to implementing these methods in practice were identified, including concerns about the relevance of external data, acceptability of Bayesian methods, lack of confidence in Bayesian methods and software, and practical issues, such as difficulties accessing relevant data. Conclusions Despite trialists recognising that more formal use of external evidence could be advantageous over current approaches in some areas and useful as sensitivity analyses, there are still barriers to such use in practice.

Elliott Carter's Analysis of his Piano Sonata (1945-46)

In 1948, Elliott Carter penned an analysis of his Piano Sonata for Edgard Varèse. His analysis of the first movement, in particular, makes one ask why Carter did not subsume its recurrent two-tempo structure under “first group” of its sonata form. Given Carter’s sophistication, was he experiencing a moment of music historical “agnosia,” since two-tempo expositions inform familiar Beethoven works such as Piano Sonata, op.31, no.2 and String Quartet in Bb, op.130. This paper explores Carter’s “agnosia” by way of internal and external evidence. Internally, it revisits the thematic chart he attached to the 1948 analysis and goes on to posit the idea that the work’s quintal neo-tonality so saturates its thematic network themes as to distort the composer’s analysis of the form, historical precedents irrespective. Externally, the paper compares three works by Beethoven to Carter’s Sonata as regards its two-tempo structure, using concepts borrowed from Hepokoski and Darcy’s Elements of Sonata Theory (1999). Finally, the author revisits writings of Carter and his circle that may explain why his analysis downplayed historical precedents to the Piano Sonata.

Haftarot bij Paulus. De liturgische context van citaten als onderdeel van intertekstualiteit

This article argues that the liturgical use of biblical texts should be included in an intertextual analysis. Rabbinic sources demonstrate a certain consensus on the liturgical reading cycles from the Torah and the Prophets in the early synagogue. Although the content of these cycles is not certain, external evidence disclose established connections between readings from the Torah and the Prophets (the haftarah-readings) in the first century CE. Paul’s letters display similar connections and a comparable hermeneutical strategy, as illustrated by a careful exegesis of Romans 15,9-12, Galatians 4,21-31, and 2 Corinthians 3.

A multi-center, adaptive, randomized, platform trial to evaluate the effect of repurposed medicines in outpatients with early coronavirus disease 2019 (COVID-19) and high-risk for complications: the TOGETHER master trial protocol

Background: Although vaccines are currently available for coronavirus disease 2019 (COVID-19), there remains a need for an effective and affordable outpatient treatment for early COVID-19. Multiple repurposed drugs have shown promise in treating COVID-19. We describe a master protocol that will assess the efficacy of different repurposed drugs as treatments for early COVID-19 among outpatients at a high risk for severe complications. Methods: The TOGETHER Trial is an international (currently in Brazil and Africa), multi-center platform adaptive randomized, placebo-controlled, clinical trial. Patients are included if they are at least 18 years of age, have a positive antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and have an indication for high risk of disease severity, including co-morbidities, older age, or high body mass index. Eligible patients are randomized with equal chance to an investigational product (IP) or to placebo. The primary endpoint is hospitalization due to clinical worsening of COVID-19 or emergency room required observation for more than 6 hours up to 28 days after randomization. Key secondary endpoints include viral clearance, clinical improvement, hospitalization for any cause, mortality for any cause, and safety and tolerability of each IP. Scheduled interim analyses are conducted and reviewed by the Data and Safety Monitoring Committee (DSMC), who make recommendations on continuing or stopping each IP. The platform adaptive design go-no-go decision rules are extended to dynamically incorporate external evidence on COVID-19 interventions from ongoing independent randomized clinical trials. Discussion: Results from this trial will assist in the identification of therapeutics for COVID-19 that can easily be scaled in low- and middle-income settings. The novel methodological extension of the platform adaptive design to dynamically incorporate external evidence is one of the first of its kind and may provide highly valuable information for all COVID-19 trials going forward. Clinicaltrials.gov registration: NCT04727424 (27/01/2021)

Defining and Identifying Secondary Layers

This essay examines the criteria for defining and identifying secondary layers of composition in the Pentateuch. It considers both external evidence (e.g. the evidence from different ancient versions of the text and ancient rewritten texts) and internal evidence. The essay concludes with an extended examination of the Genesis texts that contain the promises to the patriarchs.

Introduction

Chapter 1 introduces the topic of investigation by explaining the research problem and the state of the art. It shows how some modern scholars believe that classical Muslim sources include scarce information on conversion and consider them the wrong sources for studying the phenomenon. Drawing straightforward links between historiographical reports and events which may have happened centuries earlier is problematic, especially in the absence of actual documentation. However, it is important to study conversion depictions in early Islamic historiographical accounts. Through analyzing a vast number of Arabic Muslim historical accounts, historiography reveals a great deal about conversion. The chapter explains the theoretical basis of the investigation and the methodology of marrying history and historiography by tracing the interplay between historical phenomena and historiographical depictions; external evidence is investigated, then internal criticism is applied. The chapter lists the conversion themes detected, lays out the major arguments of the investigation, and explains the research plan and the outline of the book.

Understanding evidence-based medicine using a funnel analogy

The framework of evidence-based medicine (EBM) consisting of the best available external evidence, clinical expertise, and patient values/circumstances is often described by educators and clinicians as “three legs to a stool”. Unfortunately, this analogy seems to be easily misunderstood as separate pillars equally weighted and considered independently from each other. This may be causing confusion and imperfect adoption by physical therapists.EBM may be better described as a sequential “funneling down” of information instead of as a three-legged stool. The totality of the evidence goes in at the top to be synthesized by clinical expertise into manageable concepts that can then be presented as options to the patient who is the ultimate decision maker. This may be a better way to process information into a more usable format for the support of patients.