Feasibility of diffusion-tensor and correlated diffusion imaging for studying white-matter microstructural abnormalities: Application in COVID-19.

There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion magnetic resonance imaging (MRI) methods for detecting such effects. In this work, the performances of three single-shell-compatible diffusion MRI modeling methods are compared for detecting the effect of COVID-19, including diffusion-tensor imaging, diffusion-tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self-isolated patients at the study initiation and 3-month follow-up, along with age- and sex-matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single-shell methods to demonstrate COVID-19-related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID-19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID-19 related white-matter microstructural pathology manifests as a change in tissue diffusivity. Interestingly, different b-values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3-month follow-up, likely due to the limited size of the follow-up cohort. To summarize, correlated diffusion imaging is shown to be a viable single-shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection.

Topological data analysis in medical imaging: current state of the art.

Machine learning, and especially deep learning, is rapidly gaining acceptance and clinical usage in a wide range of image analysis applications and is regarded as providing high performance in detecting anatomical structures and identification and classification of patterns of disease in medical images. However, there are many roadblocks to the widespread implementation of machine learning in clinical image analysis, including differences in data capture leading to different measurements, high dimensionality of imaging and other medical data, and the black-box nature of machine learning, with a lack of insight into relevant features. Techniques such as radiomics have been used in traditional machine learning approaches to model the mathematical relationships between adjacent pixels in an image and provide an explainable framework for clinicians and researchers. Newer paradigms, such as topological data analysis (TDA), have recently been adopted to design and develop innovative image analysis schemes that go beyond the abilities of pixel-to-pixel comparisons. TDA can automatically construct filtrations of topological shapes of image texture through a technique known as persistent homology (PH); these features can then be fed into machine learning models that provide explainable outputs and can distinguish different image classes in a computationally more efficient way, when compared to other currently used methods. The aim of this review is to introduce PH and its variants and to review TDA's recent successes in medical imaging studies.

Effects of post-acute COVID-19 syndrome on the functional brain networks of non-hospitalized individuals.

Introduction: The long-term impact of COVID-19 on brain function remains poorly understood, despite growing concern surrounding post-acute COVID-19 syndrome (PACS). The goal of this cross-sectional, observational study was to determine whether there are significant alterations in resting brain function among non-hospitalized individuals with PACS, compared to symptomatic individuals with non-COVID infection. Methods: Data were collected for 51 individuals who tested positive for COVID-19 (mean age 41±12 yrs., 34 female) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19 (mean age 41±14 yrs., 9 female), with both groups assessed an average of 4-5 months after COVID testing. None of the participants had prior neurologic, psychiatric, or cardiovascular illness. Resting brain function was assessed via functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded. Results: Individuals with COVID-19 had lower temporal and subcortical functional connectivity relative to controls. A greater number of ongoing post-COVID symptoms was also associated with altered functional connectivity between temporal, parietal, occipital and subcortical regions. Discussion: These results provide preliminary evidence that patterns of functional connectivity distinguish PACS from non-COVID infection and correlate with the severity of clinical outcome, providing novel insights into this highly prevalent disorder.

Sulfonamidoboronic Acids as "Cross-Class" Inhibitors of an Expanded-Spectrum Class C Cephalosporinase, ADC-33, and a Class D Carbapenemase, OXA-24/40: Strategic Compound Design to Combat Resistance in Acinetobacter baumannii.

Acinetobacter baumannii is a Gram-negative organism listed as an urgent threat pathogen by the World Health Organization (WHO). Carbapenem-resistant A. baumannii (CRAB), especially, present therapeutic challenges due to complex mechanisms of resistance to ß-lactams. One of the most important mechanisms is the production of ß-lactamase enzymes capable of hydrolyzing ß-lactam antibiotics. Co-expression of multiple classes of ß-lactamases is present in CRAB; therefore, the design and synthesis of "cross-class" inhibitors is an important strategy to preserve the efficacy of currently available antibiotics. To identify new, nonclassical ß-lactamase inhibitors, we previously identified a sulfonamidomethaneboronic acid CR167 active against Acinetobacter-derived class C ß-lactamases (ADC-7). The compound demonstrated affinity for ADC-7 with a Ki = 160 nM and proved to be able to decrease MIC values of ceftazidime and cefotaxime in different bacterial strains. Herein, we describe the activity of CR167 against other ß-lactamases in A. baumannii: the cefepime-hydrolysing class C extended-spectrum ß-lactamase (ESAC) ADC-33 and the carbapenem-hydrolyzing OXA-24/40 (class D). These investigations demonstrate CR167 as a valuable cross-class (C and D) inhibitor, and the paper describes our attempts to further improve its activity. Five chiral analogues of CR167 were rationally designed and synthesized. The structures of OXA-24/40 and ADC-33 in complex with CR167 and select chiral analogues were obtained. The structure activity relationships (SARs) are highlighted, offering insights into the main determinants for cross-class C/D inhibitors and impetus for novel drug design.

Rapid tissue prototyping with micro-organospheres.

In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be established rapidly from patient tissues or cells. MOSs retain key biological features and responses to chemo-, targeted, and radiation therapies compared with organoids. The small size and large surface-to-volume ratio of MOSs enable various applications including quantitative assessment of nutrient dependence, pathogen-host interaction for anti-viral drug screening, and a rapid potency assay for chimeric antigen receptor (CAR)-T therapy. An automated MOS imaging pipeline combined with machine learning overcomes plating variation, distinguishes tumorspheres from stroma, differentiates cytostatic versus cytotoxic drug effects, and captures resistant clones and heterogeneity in drug response. This pipeline is capable of robust assessments of drug response at individual-tumorsphere resolution and provides a rapid and high-throughput therapeutic profiling platform for precision medicine.

Children, media, and the clarity of crises in 2020

The article briefs about the children safety, media, and the clarity of crises in 2020. 2020 was a YEAR. The main headline was, of course, the COVID-19 pandemic. In the span of days or weeks, hundreds of millions of people around the globe were compelled to rapidly, and radically, alter their daily lives. Wearing masks and maintaining six feet of physical distance from others became routine behaviors. Boundaries between home, work, and school evaporated, as work moved home from the office and children's schoolwork shifted from the classroom to the kitchen table. Caregiving roles of all kinds expanded as social infrastructures shrunk down to the household unit. And social inequalities at all levels were laid bare, from the gendered nature of caring for children, to "essential worker" classifications that disproportionately exposed those workers to risk of COVID-19 infection. The special issue is comprised entirely of commentary-length manuscripts. This format provided their CAM community an opportunity for a peer-reviewed, competitive publication in a format that was more attainable and inclusive during a year of challenges that often felt - and still feels, at the time of this writing - insurmountable on many days. Authors see this special issue as a yearbook for the CAM community of an extraordinary time that will reverberate in their personal and professional lives, and their world, for years to come. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Social and parasocial relationships during COVID-19 social distancing

The COVID-19 pandemic provided an extraordinarily unique opportunity to investigate how sudden, involuntary alterations to social routines influenced not just social relationships, but also parasocial relationships with fictional characters and celebrities. Results from a four-wave panel survey administered during the COVID-19 pandemic (N = 166) revealed that social relationships maintained their stability during social distancing, particularly among participants who increased mediated social engagement with friends and those low in attachment anxiety. Parasocial closeness with media personae increased over time, suggesting that favorite media personae became more meaningful as participants engaged in social distancing. Parasocial closeness increased with greater intensity among participants who increased parasocial engagement, reduced face-to-face social engagement with friends, increased mediated social engagement with friends, and those low in attachment anxiety. Results are discussed in terms of the potential influence of increased mediated social engagement with real-life friends on the parasocial processing of celebrities and fictional characters. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

A Randomized Clinical Trial Testing Hydroxychloroquine for Reduction of SARS-CoV-2 Viral Shedding and Hospitalization in Early Outpatient COVID-19 Infection.

Early in the COVID-19 pandemic, no effective treatment existed to prevent clinical worsening of COVID-19 among recently diagnosed outpatients. At the University of Utah, Salt Lake City, Utah, we conducted a phase 2 prospective parallel group randomized placebo-controlled trial (NCT04342169) to determine whether hydroxychloroquine given early in disease reduces the duration of SARS-CoV-2 shedding. We enrolled nonhospitalized adults (≥18 years of age) with a recent positive diagnostic test for SARS-CoV-2 (within 72 h of enrollment) and adult household contacts. Participants received either 400 mg hydroxychloroquine by mouth twice daily on day 1 followed by 200 mg by mouth twice daily on days 2 to 5 or oral placebo with the same schedule. We performed SARS-CoV-2 nucleic acid amplification testing (NAAT) on oropharyngeal swabs on days 1 to 14 and 28 and monitored clinical symptomatology, rates of hospitalization, and viral acquisition by adult household contacts. We identified no overall differences in the duration of oropharyngeal carriage of SARS-CoV-2 (hazard ratio of viral shedding time comparing hydroxychloroquine to placebo, 1.21; 95% confidence interval [CI], 0.91, 1.62). Overall, 28-day hospitalization incidence was similar between treatments (4.6% hydroxychloroquine versus 2.7% placebo). No differences were seen in symptom duration, severity, or viral acquisition in household contacts between treatment groups. The study did not reach the prespecified enrollment target, which was likely influenced by a steep decline in COVID-19 incidence corresponding to the initial vaccine rollout in the spring of 2021. Oropharyngeal swabs were self-collected, which may introduce variability in these results. Placebo treatments were not identical to hydroxychloroquine treatments (capsules versus tablets) which may have led to inadvertent participant unblinding. In this group of community adults early in the COVID-19 pandemic, hydroxychloroquine did not significantly alter the natural history of early COVID-19 disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT04342169). IMPORTANCE Early in the COVID-19 pandemic, no effective treatment existed to prevent clinical worsening of COVID-19 among recently diagnosed outpatients. Hydroxychloroquine received attention as a possible early treatment; however, quality prospective studies were lacking. We conducted a clinical trial to test the ability of hydroxychloroquine to prevent clinical worsening of COVID-19.

Wastewater concentrations of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus, rhinovirus, and seasonal coronavirus nucleic-acids during the COVID-19 pandemic: a surveillance study.

BACKGROUND: Respiratory disease is a major cause of morbidity and mortality; however, surveillance for circulating respiratory viruses is passive and biased. Wastewater-based epidemiology has been used to understand SARS-CoV-2, influenza A, and respiratory syncytial virus (RSV) infection rates at a community level but has not been used to investigate other respiratory viruses. We aimed to use wastewater-based epidemiology to understand community viral respiratory infection occurrence. METHODS: A retrospective wastewater-based epidemiology surveillance study was carried out at a large wastewater treatment plant located in California, USA. Using droplet digital RT-PCR, we measured RNA concentrations of influenza A and influenza B viruses, RSV A and RSV B, parainfluenza (1-4) viruses, rhinovirus, seasonal coronaviruses, and metapneumovirus in wastewater solids three times per week for 17 months (216 samples) between Feb 1, 2021, and June 21, 2022. Novel probe-based RT-PCR assays for non-influenza viral targets were developed and validated. We compared viral RNA concentrations to positivity rates for viral infections from clinical specimens submitted to California Sentinel Clinical Laboratories (sentinel laboratories) to assess concordance between the two datasets. FINDINGS: We detected RNA from all tested viruses in wastewater solids. Human rhinovirus (median concentration 4300 [0-9500] copies per gram dry weight) and seasonal human coronaviruses (35 000 [17 000-56 000]) were found at the highest concentrations. Concentrations of viral RNA correlated significantly and positively with positivity rates of associated viral diseases from sentinel laboratories (tau 0·32-0·57, p<0·0009); the only exceptions were influenza B and RSV A, which were rarely detected in wastewater solids. Measurements from wastewater indicated coronavirus OC43 dominated the seasonal human coronavirus infections whereas parainfluenza 3 dominated among parainfluenza infections during the study period. Concentrations of all tested viral RNA decreased noticeably after the omicron BA.1 surge suggesting a connection between changes in human behaviour during the surge and transmission of all respiratory viruses. INTERPRETATION: Wastewater-based epidemiology can be used to obtain information on circulation of respiratory viruses at a localised, community level without the need to test many individuals because a single sample of wastewater represents the entire contributing community. Results from wastewater can be available within 24 h of sample collection, generating real time information to inform public health responses, clinical decision making, and individual behaviour modifications. FUNDING: CDC Foundation.

Population-based evaluation of the effectiveness of nirmatrelvir-ritonavir for reducing hospital admissions and mortality from COVID-19.

BACKGROUND: A randomized controlled trial involving a high-risk, unvaccinated population that was conducted before the Omicron variant emerged found that nirmatrelvir-ritonavir was effective in preventing progression to severe COVID-19. Our objective was to evaluate the effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 while Omicron and its subvariants predominate. METHODS: We conducted a population-based cohort study in Ontario that included all residents who were older than 17 years of age and had a positive polymerase chain reaction test for SARS-CoV-2 between Apr. 4 and Aug. 31, 2022. We compared patients treated with nirmatrelvir-ritonavir with patients who were not treated and measured the primary outcome of hospital admission from COVID-19 or all-cause death at 1-30 days, and a secondary outcome of all-cause death. We used weighted logistic regression to calculate weighted odds ratios (ORs) with confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. RESULTS: The final cohort included 177 545 patients, 8876 (5.0%) who were treated with nirmatrelvir-ritonavir and 168 669 (95.0%) who were not treated. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. We found that the occurrence of hospital admission or death was lower in the group given nirmatrelvir-ritonavir than in those who were not (2.1% v. 3.7%; weighted OR 0.56, 95% CI 0.47-0.67). For death alone, the weighted OR was 0.49 (95% CI 0.39-0.62). Our findings were similar across strata of age, drug-drug interactions, vaccination status and comorbidities. The number needed to treat to prevent 1 case of severe COVID-19 was 62 (95% CI 43-80), which varied across strata. INTERPRETATION: Nirmatrelvir-ritonavir was associated with significantly reduced odds of hospital admission and death from COVID-19, which supports use to treat patients with mild COVID-19 who are at risk for severe disease.

Antibiotic resistance associated with the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings. DATA SOURCE: A search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022. STUDY ELIGIBILITY: Studies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted. METHODS: Pooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed. RESULTS: Of 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67-1.47) or proportion (risk ratio 0.91, 95% CI: 0.55-1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92-2.92; risk ratio 1.08, 95% CI: 0.91-1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03-1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40). CONCLUSION: The COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.

Multi-center validation of an artificial intelligence system for detection of COVID-19 on chest radiographs in symptomatic patients.

OBJECTIVES: While chest radiograph (CXR) is the first-line imaging investigation in patients with respiratory symptoms, differentiating COVID-19 from other respiratory infections on CXR remains challenging. We developed and validated an AI system for COVID-19 detection on presenting CXR. METHODS: A deep learning model (RadGenX), trained on 168,850 CXRs, was validated on a large international test set of presenting CXRs of symptomatic patients from 9 study sites (US, Italy, and Hong Kong SAR) and 2 public datasets from the US and Europe. Performance was measured by area under the receiver operator characteristic curve (AUC). Bootstrapped simulations were performed to assess performance across a range of potential COVID-19 disease prevalence values (3.33 to 33.3%). Comparison against international radiologists was performed on an independent test set of 852 cases. RESULTS: RadGenX achieved an AUC of 0.89 on 4-fold cross-validation and an AUC of 0.79 (95%CI 0.78-0.80) on an independent test cohort of 5,894 patients. Delong's test showed statistical differences in model performance across patients from different regions (p < 0.01), disease severity (p < 0.001), gender (p < 0.001), and age (p = 0.03). Prevalence simulations showed the negative predictive value increases from 86.1% at 33.3% prevalence, to greater than 98.5% at any prevalence below 4.5%. Compared with radiologists, McNemar's test showed the model has higher sensitivity (p < 0.001) but lower specificity (p < 0.001). CONCLUSION: An AI model that predicts COVID-19 infection on CXR in symptomatic patients was validated on a large international cohort providing valuable context on testing and performance expectations for AI systems that perform COVID-19 prediction on CXR. KEY POINTS: • An AI model developed using CXRs to detect COVID-19 was validated in a large multi-center cohort of 5,894 patients from 9 prospectively recruited sites and 2 public datasets. • Differences in AI model performance were seen across region, disease severity, gender, and age. • Prevalence simulations on the international test set demonstrate the model's NPV is greater than 98.5% at any prevalence below 4.5%.

The Connection between Gardening and Outdoor Activity during the COVID-19 Pandemic and Perceptions of Hope, Hopelessness, and Levels of Stress, Anxiety, and Depression

During the past few years, Americans have experienced a wide variety of stressors, including political tensions, racial/civil unrest, and the coronavirus disease 2019 (COVID-19) pandemic. All of these have led to uncertainty within society. Chronic feelings of helplessness can lead to depression or feelings of hopelessness in those who perceive their situation as unchanging. The purpose of this study was to evaluate the impacts of gardening and outdoor activities during the COVID-19 pandemic on perceptions of hope, hopelessness, and levels of depression, stress, and anxiety. Participants of this study were recruited through online social media platforms such as Facebook and Instagram;458 participants completed the 21-item Depression Anxiety and Stress Scale inventory as well as the Hope Scale. Our data indicated that individuals who self-reported themselves as gardeners had significantly more positive scores related to levels of stress, anxiety, and depression and a sense of hope. Furthermore, gardeners had lower levels of self-reported depression, anxiety, and stress when compared with those who did not identify themselves as gardeners. The gardeners also had a more positive outlook regarding hope for the future. Additionally, a significant positive correlation was found between the number of hours spent participating in gardening and a sense of hope, and a negative correlation was found between the number of hours gardening and stress levels. Similarly, there was a significant negative correlation between the number of hours spent participating in any outdoor activity and self-reported levels of stress, anxiety, or depression;however, there was a positive correlation between the number of hours spent participating in any outdoor activity and a sense of hope. Our data suggested that more hours spent outside gardening or participating in recreational activities led to less perceived stress, anxiety, and depression and greater levels of hope for the future. © 2023, American Society for Horticultural Science. All rights reserved.

The Cardiac Effects of COVID-19 on Young Competitive Athletes: Results from the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA).

The Outcomes Registry for Cardiac Conditions in Athletes (ORCCA) study is a large-scale prospective investigation evaluating the cardiovascular effects and outcomes of SARS-CoV-2 infection on young competitive athletes. This review provides an overview of the key results from the ORCCA study. Results from the ORCCA study have provided important insights into the clinical impact of SARS-CoV-2 infection on the cardiovascular health of young competitive athletes and informed contemporary screening and return to sport practices. Key results include defining a low prevalence of both cardiac involvement and adverse cardiovascular outcomes after SARS-CoV-2 infection and evaluating the utility of a return-to-play cardiac evaluation. Future aims of the ORCCA study include the longer-term evaluation of cardiovascular outcomes among athletes post-SARS-CoV-2 infection and the transition to investigating outcomes in young athletes with potentially high-risk genetic or structural cardiac diagnoses.

A cross-sectional study of hospital antimicrobial stewardship programmes in the COVID-19 era.

Background: Antimicrobial resistance (AMR) continues to be a global public health issue amid the COVID-19 pandemic; however, unprecedented demands on hospital antimicrobial stewardship programmes (ASPs) potentially altered their core activities. Objective: We sought to understand how ASPs have been involved in and impacted by the pandemic. Methods: The 2021 Ontario ASP Landscape Survey was developed based on previous provincial questionnaires and emerging literature on the impact of COVID-19 on hospital ASPs. After pre-testing and piloting, the online questionnaire was distributed to hospital antimicrobial stewardship practitioners in the fall of 2021. Descriptive statistics and inductive thematic analysis were performed. Results: The response rate was 78% (98/125 organizations); 96% (94/98) of organizations had or were in the process of formalizing an ASP and 53% (50/94) reported designated funding/resources. Despite 82% reporting no change in dedicated full-time equivalents during the pandemic, ASPs were frequently involved in developing treatment guidelines/clinical pathways (51%), anticipating/managing drug shortages (46%) and obtaining investigational use drugs (32%). While many core ASP activities continued, prospective audit and feedback and prescriber education were modified or suspended by 43% and 40% of programmes, respectively. Decreased frequency, adaptation of activities (i.e. virtual or other technology) and challenges with staffing/resources were commonly reported themes. Knowledge translation (KT) activities and 'collaboration and coordination' also emerged as salient themes. Conclusions: Hospital antimicrobial stewardship practitioners in Ontario have made significant contributions to the pandemic response while continuing to deliver adapted ASP services, despite resource constraints. Moving forward, ASPs will need to continue building capacity while leveraging broader networks to advance the antimicrobial stewardship agenda.

Evolving Needs of Critical Care Trainees during the COVID-19 Pandemic: A Qualitative Study.

Background: Critical care trainees were integral in the coronavirus disease (COVID-19) pandemic response. Several perspective pieces have provided insight into the pandemic's impact on critical care training. Surveys of program directors and critical care trainees have focused on curricular impact. There is a lack of data from the trainee perspective on curricular enhancements, career development, and emotional and well-being needs to succeed in a critical care career in the ongoing COVID-19 pandemic. Objective: Our objective was to elicit perspectives from critical care trainees on their personal and professional needs as they continue to serve in the COVID-19 pandemic. Methods: This was a hypothesis-generating qualitative study. Individuals in a U.S. critical care training program during the COVID-19 pandemic participated in either focus groups or semistructured interviews. Interviews were conducted between July 2020 and March 2021 until data saturation was achieved. Audio recordings were professionally transcribed and analyzed using qualitative content analysis. A codebook was generated by two independent coders, with a third investigator reconciling codes when there were discrepancies. Themes and subthemes were identified from these codes. Results: Thirteen participants were interviewed. The major themes identified were as follows: 1) Curricular adaptation is necessary to address evolving changes in trainee needs; 2) COVID-19 impacted career development and highlighted that trainees need individualized help to meet their goals; 3) receiving social support at work from peers and leaders is vital for the sustained well-being of trainees; 4) fostering and maintaining a sense of meaning and humanity in one's work is important; and 5) trainees desire assistance and support to process their emotions and experiences. Conclusion: The needs expressed by critical care trainees are only partially captured in conceptual models of physician well-being. The need for multilevel workplace social networks and identifying meaning in one's work have been magnified in this pandemic. The themes discussing curricular gaps, career development needs, and skills to process work-related trauma are less well captured in preexisting conceptual models and point to areas where further research and intervention development are needed.

Antimicrobial resistance in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Frequent use of antibiotics in patients with COVID-19 threatens to exacerbate antimicrobial resistance. We aimed to establish the prevalence and predictors of bacterial infections and antimicrobial resistance in patients with COVID-19. METHODS: We did a systematic review and meta-analysis of studies of bacterial co-infections (identified within ≤48 h of presentation) and secondary infections (>48 h after presentation) in outpatients or hospitalised patients with COVID-19. We searched the WHO COVID-19 Research Database to identify cohort studies, case series, case-control trials, and randomised controlled trials with populations of at least 50 patients published in any language between Jan 1, 2019, and Dec 1, 2021. Reviews, editorials, letters, pre-prints, and conference proceedings were excluded, as were studies in which bacterial infection was not microbiologically confirmed (or confirmed via nasopharyngeal swab only). We screened titles and abstracts of papers identified by our search, and then assessed the full text of potentially relevant articles. We reported the pooled prevalence of bacterial infections and antimicrobial resistance by doing a random-effects meta-analysis and meta-regression. Our primary outcomes were the prevalence of bacterial co-infection and secondary infection, and the prevalence of antibiotic-resistant pathogens among patients with laboratory-confirmed COVID-19 and bacterial infections. The study protocol was registered with PROSPERO (CRD42021297344). FINDINGS: We included 148 studies of 362 976 patients, which were done between December, 2019, and May, 2021. The prevalence of bacterial co-infection was 5·3% (95% CI 3·8-7·4), whereas the prevalence of secondary bacterial infection was 18·4% (14·0-23·7). 42 (28%) studies included comprehensive data for the prevalence of antimicrobial resistance among bacterial infections. Among people with bacterial infections, the proportion of infections that were resistant to antimicrobials was 60·8% (95% CI 38·6-79·3), and the proportion of isolates that were resistant was 37·5% (26·9-49·5). Heterogeneity in the reported prevalence of antimicrobial resistance in organisms was substantial (I2=95%). INTERPRETATION: Although infrequently assessed, antimicrobial resistance is highly prevalent in patients with COVID-19 and bacterial infections. Future research and surveillance assessing the effect of COVID-19 on antimicrobial resistance at the patient and population level are urgently needed. FUNDING: WHO.

Justice, Authority and the COVID-19 Infodemic: Libraries as Trust Systems in a Post- Trust World

This article examines the intersection of trust, authority, the COVID-19 infodemic, and what this convergence may suggest for the growing emphasis on social justice in American libraries. It considers the library as an honor system-or, more accurately, a trust system-both in its essential character and its operations. It begins with the proposition that libraries are and will remain trusted institutions, and that they have an instrumental and intellectual role to play in combating the ill effects of the pandemic through blunting the impact of the infodemic. However, even if libraries are positioned to help provide clarity and direction, they face distinct challenges in delivering services to a public that is increasingly skeptical of their role as a traditional authority in providing information, stewarding culture, and representing community interests. Incorporating concepts from John Rawls' framework for social justice, this article seeks to explore the notions of interpersonal and institutional trust as requirements for democratic stability and a just society. Specifically, it seeks to analyze some of the ethical dilemmas that this post-trust era presents to librarians, their institutions, and the communities they serve. How might libraries contribute to re-establishing and sustaining interpersonal and institutional trust at the community and societal level?

Effect of SARS-CoV-2 digital droplet RT-PCR assay sensitivity on COVID-19 wastewater based epidemiology

We developed and implemented a framework for examining how molecular assay sensitivity for a viral RNA genome target affects its utility for wastewater-based epidemiology. We applied this framework to digital droplet RT-PCR measurements of SARS-CoV-2 and Pepper Mild Mottle Virus genes in wastewater. Measurements were made using 10 replicate wells which allowed for high assay sensitivity, and therefore enabled detection of SARS-CoV-2 RNA even when COVID-19 incidence rates were relatively low (~10−5). We then used a computational downsampling approach to determine how using fewer replicate wells to measure the wastewater concentration reduced assay sensitivity and how the resultant reduction affected the ability to detect SARS-CoV-2 RNA at various COVID-19 incidence rates. When percent of positive droplets was between 0.024% and 0.5% (as was the case for SARS-CoV-2 genes during the Delta surge), measurements obtained with 3 or more wells were similar to those obtained using 10. When percent of positive droplets was less than 0.024% (as was the case prior to the Delta surge), then 6 or more wells were needed to obtain similar results as those obtained using 10 wells. When COVID-19 incidence rate is low (~ 10−5), as it was before the Delta surge and SARS-CoV-2 gene concentrations are <104 cp/g, using 6 wells will yield a detectable concentration 90% of the time. Overall, results support an adaptive approach where assay sensitivity is increased by running 6 or more wells during periods of low SARS-CoV-2 gene concentrations, and 3 or more wells during periods of high SARS-CoV-2 gene concentrations.