Regulation of Laboratory-Developed Tests in Preventive Oncology: Emerging Needs and Opportunities.

Cancer predictive or diagnostic assays, offered as Laboratory-Developed Tests (LDTs), have been subject to regulatory authority and enforcement discretion by the US Food and Drug Administration. Many LDTs enter the market without US Food and Drug Administration or any regulatory review. The Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Amendments focuses on analytic performance, but has limited oversight of the quality or utility of LDTs, including whether patients have been harmed as a result of their use. Increasingly, LDTs for cancer risk or early detection have been marketed directly to consumers, with many LDT developers depicting these tests, requested by patients but ordered by personal or company-associated physicians, as procedures falling under the practice of medicine. This patchwork of regulation and enforcement uncertainty regarding LDTs and public concerns about accuracy of tests given emergency authorization during the COVID-19 pandemic led to the Verifying Accurate Leading-edge IVCT (in vitro clinical test) Development Act of 2021. This pending federal legislation represents an opportunity to harmonize regulatory policies and address growing concerns over quality, utility, and safety of LDTs for cancer genomics, including tests marketed directly to consumers. We review here questions regarding the potential benefits and harms of some cancer-related LDTs for cancer risk and presymptomatic molecular diagnosis, increasingly marketed to oncologists or directly to the worried well. We offer specific proposals to strengthen oversight of the accuracy and clinical utility of cancer genetic testing to ensure public safety.

Evaluating the elevation of authoritative health content online during the COVID-19 pandemic

Purpose - To respond to the COVID-19 "infodemic" and combat fraud and misinformation about the virus, social media platforms coordinated with government healthcare agencies around the world to elevate authoritative content about the novel coronavirus. These public health authorities included national and global public health organisations, such as the Centers for Disease Control and Prevention (CDC) and the World Health Organisation (WHO). In this article, the authors evaluate the effectiveness of this strategy by asking two key questions: (1) Did people engage with authoritative health content on social media? (2) Was this content trusted? Design/methodology/approach - The authors explore these issues by drawing on data from a global online questionnaire on "Public Trust in Experts" (n = 429) conducted during the initial phase of the pandemic in May 2020, a crucial period when reliable information was urgently required to influence behaviour and minimise harm. Findings - The authors found that while the majority of those surveyed noticed authoritative health content online, there remained significant issues in terms of Internet users trusting the information shared by government healthcare agencies and public health authorities online. Originality/value - In what follows, the authors examine the role of trust in implementing this novel public health strategy and assess the capacity for such policies to reduce individual and social harm. Peer review - The peer review history for this article is available at: https://publons.com/publon/10.1108/OIR-12-2021-0655

Forest loss shapes the landscape suitability of Kyasanur Forest disease in the Western Ghats, India

Background Anthropogenic pressure in biodiversity hotspots is increasingly recognised as a major driver of the spillover and expansion of zoonotic disease. In the Western Ghats region of India, a devastating tick-borne zoonosis, Kyasanur Forest disease (KFD), has been expanding rapidly beyond its endemic range in recent decades. While it has been suggested that anthropogenic pressure in the form of land use changes that lead to the loss of native forest may be directly contributing to the expanding range of KFD, clear evidence has not yet established the association between forest loss and KFD risk. Methods The current study sought to investigate the relationship between KFD landscape suitability and both forest loss and mammalian species richness to inform its epidemiology and infection ecology. Forty-seven outbreaks of KFD between 1 January, 2012 and 30 June, 2019 were modelled as an inhomogeneous Poisson process. Results Both forest loss (relative risk (RR) = 1.83;95% C.I. 1.33 – 2.51) and mammalian species richness (RR = 1.29;95% C.I. 1.16 – 1.42) were strongly associated with increased risk of KFD. Conclusions These results provide the first evidence of a clear association between increasing forest loss and risk for KFD. Moreover, the findings also highlight the importance of forest loss in areas of high biodiversity. This evidence supports integrative approaches to public health that incorporate conservation strategies simultaneously protective of humans, animals, and the environment. Key messages The association between deforestation and KFD risk suggest potential benefit in leveraging conservation efforts in the service of public health. [ABSTRACT FROM AUTHOR] Copyright of International Journal of Epidemiology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Incidence and Outcomes of Acute Kidney Injury in Patients Admitted to Hospital With COVID-19: A Retrospective Cohort Study.

BACKGROUND: The incidence of acute kidney injury (AKI) in patients with COVID-19 and its association with mortality and disease severity is understudied in the Canadian population. OBJECTIVE: To determine the incidence of AKI in a cohort of patients with COVID-19 admitted to medicine and intensive care unit (ICU) wards, its association with in-hospital mortality, and disease severity. Our aim was to stratify these outcomes by out-of-hospital AKI and in-hospital AKI. DESIGN: Retrospective cohort study from a registry of patients with COVID-19. SETTING: Three community and 3 academic hospitals. PATIENTS: A total of 815 patients admitted to hospital with COVID-19 between March 4, 2020, and April 23, 2021. MEASUREMENTS: Stage of AKI, ICU admission, mechanical ventilation, and in-hospital mortality. METHODS: We classified AKI by comparing highest to lowest recorded serum creatinine in hospital and staged AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) system. We calculated the unadjusted and adjusted odds ratio for the stage of AKI and the outcomes of ICU admission, mechanical ventilation, and in-hospital mortality. RESULTS: Of the 815 patients registered, 439 (53.9%) developed AKI, 253 (57.6%) presented with AKI, and 186 (42.4%) developed AKI in-hospital. The odds of ICU admission, mechanical ventilation, and death increased as the AKI stage worsened. Stage 3 AKI that occurred during hospitalization increased the odds of death (odds ratio [OR] = 7.87 [4.35, 14.23]). Stage 3 AKI that occurred prior to hospitalization carried an increased odds of death (OR = 5.28 [2.60, 10.73]). LIMITATIONS: Observational study with small sample size limits precision of estimates. Lack of nonhospitalized patients with COVID-19 and hospitalized patients without COVID-19 as controls limits causal inferences. CONCLUSIONS: Acute kidney injury, whether it occurs prior to or after hospitalization, is associated with a high risk of poor outcomes in patients with COVID-19. Routine assessment of kidney function in patients with COVID-19 may improve risk stratification. TRIAL REGISTRATION: The study was not registered on a publicly accessible registry because it did not involve any health care intervention on human participants.

Optimal governance and implementation of vaccination programmes to contain the COVID-19 pandemic.

Since the recent introduction of several viable vaccines for SARS-CoV-2, vaccination uptake has become the key factor that will determine our success in containing the COVID-19 pandemic. We argue that game theory and social network models should be used to guide decisions pertaining to vaccination programmes for the best possible results. In the months following the introduction of vaccines, their availability and the human resources needed to run the vaccination programmes have been scarce in many countries. Vaccine hesitancy is also being encountered from some sections of the general public. We emphasize that decision-making under uncertainty and imperfect information, and with only conditionally optimal outcomes, is a unique forte of established game-theoretic modelling. Therefore, we can use this approach to obtain the best framework for modelling and simulating vaccination prioritization and uptake that will be readily available to inform important policy decisions for the optimal control of the COVID-19 pandemic.

The Royal College of surgeons multidisciplinary guidelines on elective tracheostomy insertion in COVID-19 ventilated patients.

BACKGROUND: The current COVID-19 pandemic has placed enormous strain on healthcare systems worldwide. Understanding of COVID-19 is rapidly evolving. Pneumonia associated with COVID-19 may lead to respiratory failure requiring mechanical ventilation. The rise in patients requiring mechanical ventilation may lead to an increase in tracheostomies being performed in patients with COVID-19. Performing tracheostomy in patients with active SARS-CoV-2 infection poses a number of challenges. METHODS: These guidelines were written following multidisciplinary agreement between Otolaryngology, Head and Neck Surgery, Respiratory Medicine and the Department of Anaesthetics and Critical Care Medicine in the Royal College of Surgeons in Ireland. A literature review was performed and a guideline for elective tracheostomy insertion in patients with COVID-19 proposed. CONCLUSION: The decision to perform tracheostomy in patients with COVID-19 should be undertaken by senior members of the multidisciplinary team. Steps should be taken to minimise risks to healthcare workers.

Whence the next pandemic? The intersecting global geography of the animal-human interface, poor health systems and air transit centrality reveals conduits for high-impact spillover.

The health and economic impacts of infectious disease pandemics are catastrophic as most recently manifested by coronavirus disease 2019 (COVID-19). The emerging infections that lead to substantive epidemics or pandemics are typically zoonoses that cross species boundaries at vulnerable points of animal-human interface. The sharing of space between wildlife and humans, and their domesticated animals, has dramatically increased in recent decades and is a key driver of pathogen spillover. Increasing animal-human interface has also occurred in concert with both increasing globalisation and failing health systems, resulting in a trifecta with dire implications for human and animal health. Nevertheless, to date we lack a geographical description of this trifecta that can be applied strategically to pandemic prevention. This investigation provides the first geographical quantification of the intersection of animal-human interfaces, poor human health system performance and global connectivity via the network of air travel. In so doing, this work provides a systematic, data-driven approach to classifying spillover hazard based on the distribution of animal-human interfaces while simultaneously identifying globally connected cities that are adjacent to these interfaces and which may facilitate global pathogen dissemination. We present this geography of high-impact spillover as a tool for developing targeted surveillance systems and improved health infrastructure in vulnerable areas that may present conduits for future pandemics.

The challenges of responding to misinformation during a pandemic: content moderation and the limitations of the concept of harm

Social media have been central in informing people about the COVID-19 pandemic. They influence the ways in which information is perceived, communicated and shared online, especially with physical distancing measures in place. While these technologies have given people the opportunity to contribute to public discussions about COVID-19, the narratives disseminated on social media have also been characterised by uncertainty, disagreement, false and misleading advice. Global technology companies have responded to these concerns by introducing new content moderation policies based on the concept of harm to tackle the spread of misinformation and disinformation online. In this essay, we examine some of the key challenges in implementing these policies in real time and at scale, calling for more transparent and nuanced content moderation strategies to increase public trust and the quality of information about the pandemic consumed online.