PANasta Trial; Cattell Warren versus Blumgart techniques of panreatico-jejunostomy following pancreato-duodenectomy: Study protocol for a randomized controlled trial

PANasta operative manual. (PDF 520 kb

Equity in Global Health Law - Policy Brief

Equity has been sorely lacking in pandemic preparedness and response, and COVID-19 is but the latest example (O’Cuinn and Switzer, 2019; Rourke, 2019). The response to COVID-19 was characterised by nationalism, inequity in access to diagnostics, vaccines, therapeutics and personal protective equipment (PPE) between the Global North and the Global South, as well as discriminatory, and in some instances racist, border closures chiefly impacting low- and middle-income countries. In response to the widespread inequity witnessed during the COVID-19 pandemic, Member States of the World Health Organisation (WHO) are currently negotiating a new international legal instrument - the Pandemic Treaty - intended to prevent pandemics and mitigate associated inequalities such as vaccine access, and improve compliance with international law during pandemic events. From the initial proposal for the Treaty, through the many rounds of discussions that have occurred to date, it is clear that the new instrument is intended to be grounded in equity, with equity positioned as both an objective and as an operational output (Wenham, Eccleston- Turner & Voss, 2022). However, while equity is recognised as a general principle of international law, it does not have a precise and defined meaning. From the start of negotiations, it was unclear what an instrument ‘grounded’ in equity should look like, what the principle of equity actually means in this context, and how this principle can translate into meaningful obligations within international law more generally, as well as pandemic preparedness and global health governance specifically. In an attempt to answer these questions, we convened - with the assistance of funding from the Scottish Council for Global Affairs and the ESRC IAA Policy Impact Fund - a workshop at King’s College, London at which we gathered together experts on equity from different disciplinary backgrounds in an attempt to understand and conceptualize equity as a legal concept, charting its history, development and application within both domestic and international law. In the following short discussion, we distill some of the lessons at this workshop from both national law as well as other international arenas, before offering suggestions on how this somewhat opaque concept might be effectively operationalised within the Pandemic Treaty. The aim of this discussion is therefore not to engage in a lengthy, academic literature review of the different conceptions of equity found in academic texts - of which there is an abundance of relevant literature - but rather to offer practical insights to the operationalisation of equity to the Pandemic Treaty. What we find is that there is no ‘one’ way to do equity or for an international agreement to be equitable. Our discussions found that equity must be more than an abstract buzzword - simply inserting the word equity into a legal text does not achieve equity. However, international law offers a number of lessons for responding to instances of inequity arising in the absence of a perfect, overarching functional definition of equity

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Research on Innovation: A Review and Agenda for

Innovation is one of the most important issues in business research today. It has been studied in many independent research traditions. Our understanding and study of innovation can benefit from an integrative review of these research traditions. In so doing, we identify 16 topics relevant to marketing science, which we classify under five research fields: - Consumer response to innovation, including attempts to measure consumer innovativeness, models of new product growth, and recent ideas on network externalities; Organizations and innovation, which are increasingly important as product development becomes more complex and tools more effective but demanding; - Market entry strategies, which includes recent research on technology revolution, extensive marketing science research on strategies for entry, and issues of portfolio management; - Prescriptive techniques for product development processes, which have been transformed through global pressures, increasingly accurate customer input, Web-based communication for dispersed and global product design, and new tools for dealing with complexity over time and across product lines; - Defending against market entry and capturing the rewards of innovating, which includes extensive marketing science research on strategies of defense, managing through metrics, and rewards to entrants. For each topic, we summarize key concepts and highlight research challenges. For prescriptive research topics, we also review current thinking and applications. For descriptive topics, we review key findings.innovation, new products, consumer innovativeness, diffusion models, network externalities, strategic entry, defensive strategy, ideation, rewards to entrants, metrics

Equity in Global Health Law

Equity has been sorely lacking in pandemic preparedness and response, and COVID-19 is but the latest example (O’Cuinn and Switzer, 2019; Rourke, 2019). The response to COVID-19 was characterised by nationalism, inequity in access to diagnostics, vaccines, therapeutics and personal protective equipment (PPE) between the Global North and the Global South, as well as discriminatory, and in some instances racist, border closures chiefly impacting low- and middle-income countries. In response to the widespread inequity witnessed during the COVID-19 pandemic, Member States of the World Health Organisation (WHO) are currently negotiating a new international legal instrument - the Pandemic Treaty - intended to prevent pandemics and mitigate associated inequalities such as vaccine access, and improve compliance with international law during pandemic events. From the initial proposal for the Treaty, through the many rounds of discussions that have occurred to date, it is clear that the new instrument is intended to be grounded in equity, with equity positioned as both an objective and as an operational output (Wenham, Eccleston- Turner &amp; Voss, 2022). However, while equity is recognised as a general principle of international law, it does not have a precise and defined meaning. From the start of negotiations, it was unclear what an instrument ‘grounded’ in equity should look like, what the principle of equity actually means in this context, and how this principle can translate into meaningful obligations within international law more generally, as well as pandemic preparedness and global health governance specifically. In an attempt to answer these questions, we convened - with the assistance of funding from the Scottish Council for Global Affairs and the ESRC IAA Policy Impact Fund - a workshop at King’s College, London at which we gathered together experts on equity from different disciplinary backgrounds in an attempt to understand and conceptualize equity as a legal concept, charting its history, development and application within both domestic and international law. In the following short discussion, we distill some of the lessons at this workshop from both national law as well as other international arenas, before offering suggestions on how this somewhat opaque concept might be effectively operationalised within the Pandemic Treaty. The aim of this discussion is therefore not to engage in a lengthy, academic literature review of the different conceptions of equity found in academic texts - of which there is an abundance of relevant literature - but rather to offer practical insights to the operationalisation of equity to the Pandemic Treaty. What we find is that there is no ‘one’ way to do equity or for an international agreement to be equitable. Our discussions found that equity must be more than an abstract buzzword - simply inserting the word equity into a legal text does not achieve equity. However, international law offers a number of lessons for responding to instances of inequity arising in the absence of a perfect, overarching functional definition of equity

Immunocompromised patients with acute respiratory distress syndrome: Secondary analysis of the LUNG SAFE database

Background: The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p &lt; 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p &lt; 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013