Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Lessons learned from academic medical centers’ response to the COVID-19 pandemic in partnership with the Navajo Nation

IntroductionStructural forces that drive health inequalities are magnified in crises. This was especially true during the COVID-19 pandemic, and minority communities were particularly affected. The University of California San Francisco and Health, Equity, Action, Leadership Initiative jointly sent volunteer teams of nurses and doctors to work in the Navajo Nation during the COVID-19 pandemic. This presented an opportunity to explore how academic medical centers (AMCs) could effectively partner with vulnerable communities to provide support during healthcare crises. Therefore, the aims of this study were to describe volunteers' perspectives of academic-community partnerships by exploring their personal, professional and societal insights and lessons learned based on their time in the Navajo Nation during COVID-19.MethodsWe recruited key informants using purposeful sampling of physicians and nurses who volunteered to go to the Navajo Nation during the spring 2020 COVID-19 surge, as well as hospital administrators and leaders involved in organizing the COVID-19 efforts. We used in-depth qualitative interviews to explore key informants' experiences pre-departure, during their stay, and after their return, as well as perspectives of the partnership between an AMC and the Navajo Nation. We used thematic analysis to systematically identify, analyze and report patterns (themes) within the data.ResultsIn total, 37 clinicians and hospital administrators were interviewed including 14 physicians, 16 nurses, and 7 health system leaders. Overall, we found 4 main themes each with several subthemes that defined the partnership between the AMC and the Navajo Nation. Mission and values incorporated civic duty, community engagement, leadership commitment and employee dedication. Solidarity, trust and humility encompassed pre-existing trust, workforce sustainability, humility and erasure of 'savior narratives.' Coordination included logistical coordination, flexibility, selectivity of who and what traveled to the response and coordination around media response. Workforce preparation and support encompassed understanding of historical context and providing healthcare in limited settings, dangers of inadequate preparation and the need for emotional support.ConclusionThis study provides guidelines which AMCs might use to develop and improve partnerships they have or would like to develop with vulnerable communities. These guidelines may even be broadly applied to partnerships outside of a pandemic response. Importantly, such partnerships need to be built with trust and with an eye towards sustainability and long-term relationships as opposed to 'medical missions'

Lessons learned from academic medical centers' response to the COVID-19 pandemic in partnership with the Navajo Nation.

IntroductionStructural forces that drive health inequalities are magnified in crises. This was especially true during the COVID-19 pandemic, and minority communities were particularly affected. The University of California San Francisco and Health, Equity, Action, Leadership Initiative jointly sent volunteer teams of nurses and doctors to work in the Navajo Nation during the COVID-19 pandemic. This presented an opportunity to explore how academic medical centers (AMCs) could effectively partner with vulnerable communities to provide support during healthcare crises. Therefore, the aims of this study were to describe volunteers' perspectives of academic-community partnerships by exploring their personal, professional and societal insights and lessons learned based on their time in the Navajo Nation during COVID-19.MethodsWe recruited key informants using purposeful sampling of physicians and nurses who volunteered to go to the Navajo Nation during the spring 2020 COVID-19 surge, as well as hospital administrators and leaders involved in organizing the COVID-19 efforts. We used in-depth qualitative interviews to explore key informants' experiences pre-departure, during their stay, and after their return, as well as perspectives of the partnership between an AMC and the Navajo Nation. We used thematic analysis to systematically identify, analyze and report patterns (themes) within the data.ResultsIn total, 37 clinicians and hospital administrators were interviewed including 14 physicians, 16 nurses, and 7 health system leaders. Overall, we found 4 main themes each with several subthemes that defined the partnership between the AMC and the Navajo Nation. Mission and values incorporated civic duty, community engagement, leadership commitment and employee dedication. Solidarity, trust and humility encompassed pre-existing trust, workforce sustainability, humility and erasure of 'savior narratives.' Coordination included logistical coordination, flexibility, selectivity of who and what traveled to the response and coordination around media response. Workforce preparation and support encompassed understanding of historical context and providing healthcare in limited settings, dangers of inadequate preparation and the need for emotional support.ConclusionThis study provides guidelines which AMCs might use to develop and improve partnerships they have or would like to develop with vulnerable communities. These guidelines may even be broadly applied to partnerships outside of a pandemic response. Importantly, such partnerships need to be built with trust and with an eye towards sustainability and long-term relationships as opposed to 'medical missions'

The multifaceted role of PIP2 in leukocyte biology

Phosphatidylinositol 4,5-bisphosphate (PIP2) represents about 1 % of plasma membrane phospholipids and behaves as a pleiotropic regulator of a striking number of fundamental cellular processes. In recent years, an increasing body of literature has highlighted an essential role of PIP2 in multiple aspects of leukocyte biology. In this emerging picture, PIP2 is envisaged as a signalling intermediate itself and as a membrane-bound regulator and a scaffold of proteins with specific PIP2 binding domains. Indeed PIP2 plays a key role in several functions. These include directional migration in neutrophils, integrin-dependent adhesion in T lymphocytes, phagocytosis in macrophages, lysosomes secretion and trafficking at immune synapse in cytolytic effectors and secretory cells, calcium signals and gene transcription in B lymphocytes, natural killer cells and mast cells. The coordination of these different aspects relies on the spatio-temporal organisation of distinct PIP2 pools, generated by the main PIP2 generating enzyme, phosphatidylinositol 4-phosphate 5-kinase (PIP5K). Three different isoforms of PIP5K, named α, β and γ, and different splice variants have been described in leukocyte populations. The isoform-specific coupling of specific isoforms of PIP5K to different families of activating receptors, including integrins, Fc receptors, toll-like receptors and chemokine receptors, is starting to be reported. Furthermore, PIP2 is turned over by multiple metabolising enzymes including phospholipase C (PLC) γ and phosphatidylinositol 3-kinase (PI3K) which, along with Rho family small G proteins, is widely involved in strategic functions within the immune system. The interplay between PIP2, lipid-modifying enzymes and small G protein-regulated signals is also discussed

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health