Longitudinal validation of the Fear of COVID-19 Scale in a nationwide United States sample: An item response theory model across three inflection points of the pandemic.

The COVID-19 pandemic's global emergence/spread caused widespread fear. Measurement/tracking of COVID-19 fear could facilitate remediation. Despite the Fear of COVID-19 Scale (FCV-19S)'s validation in multiple languages/countries, nationwide United States (U.S.) studies are scarce. Cross-sectional classical test theory-based validation studies predominate. Our longitudinal study sampled respondents to a 3-wave, nationwide, online survey. We calibrated the FCV-19S using a unidimensional graded response model. Item/scale monotonicity, discrimination, informativeness, goodness-of-fit, criterion validity, internal consistency, and test-retest reliability were assessed. Items 7, 6, and 3 consistently displayed very high discrimination. Other items had moderate-to-high discrimination. Items 3, 6, and 7 were most (items 1 and 5 the least) informative. [Correction added on 18 May 2023, after first online publication: In the preceding sentence, the term 'items one-fifth least' has been changed to 'items 1 and 5 the least'.] Item scalability was 0.62-0.69; full-scale scalability 0.65-0.67. Ordinal reliability coefficient was 0.94; test-retest intraclass correlation coefficient 0.84. Positive correlations with posttraumatic stress/anxiety/depression, and negative correlations with emotional stability/resilience supported convergent/divergent validity. The FCV-19S validly/reliably captures temporal variation in COVID-19 fear across the U.S.

Computer-assisted approaches for measuring, segmenting, and analyzing functional upper extremity movement: a narrative review of the current state, limitations, and future directions.

The analysis of functional upper extremity (UE) movement kinematics has implications across domains such as rehabilitation and evaluating job-related skills. Using movement kinematics to quantify movement quality and skill is a promising area of research but is currently not being used widely due to issues associated with cost and the need for further methodological validation. Recent developments by computationally-oriented research communities have resulted in potentially useful methods for evaluating UE function that may make kinematic analyses easier to perform, generally more accessible, and provide more objective information about movement quality, the importance of which has been highlighted during the COVID-19 pandemic. This narrative review provides an interdisciplinary perspective on the current state of computer-assisted methods for analyzing UE kinematics with a specific focus on how to make kinematic analyses more accessible to domain experts. We find that a variety of methods exist to more easily measure and segment functional UE movement, with a subset of those methods being validated for specific applications. Future directions include developing more robust methods for measurement and segmentation, validating these methods in conjunction with proposed kinematic outcome measures, and studying how to integrate kinematic analyses into domain expert workflows in a way that improves outcomes.

Addressing concerns and adapting psychological techniques for videoconsultations: A practical guide

Objective: The 2020 coronavirus pandemic required many psychologists to rapidly transition to telehealth services to reduce virus exposure. Telepsychology services expanded quickly in Australia. This article seeks to provide simple and practical recommendations for clinicians who are changing their practice. Method: A narrative literature review focusing on psychologists' concerns regarding telehealth-facilitated psychology or telepsychology was undertaken. Results: Research literature and guidelines from peak professional bodies such as The Australian Psychological Society and the American Psychological Association, inform two sections of the article: Common Concerns about Videoconsultations and;Practical Considerations for Effective Videoconsultations. Telepsychology, has numerous benefits, especially during emergency situations. However, concerns regarding efficacy, therapeutic alliance, and the digital divide have contributed to psychologists' unwillingness to use telepsychology. Evidence suggests that efficacy and therapeutic alliance is comparable between telepsychology and in-person services. Simple evidence-based adjustments to therapeutic practice can optimise videoconsultations and increase the effectiveness of telepsychology. Despite the rapid change to videoconsultations, evidence suggests that Australian psychologists need not be concerned about clinical efficacy or therapeutic alliance related to telepsychology. However, it is acknowledged that transitioning to telehealth models of care is disruptive. Conclusion: This paper can assist clinicians in selecting appropriate clients for telepsychology, increase effectiveness and mitigate risks. Key Points: What is already known about this topic: (1) Research supports the clinical efficacy and establishment of therapeutic alliance related to telepsychology services and highlights that concerns regarding the digital divide need to be evidence-based, not based on assumptions. (2) As outlined in this paper, it is important to consider client suitability and ethical considerations prior to delivering telepsychology services. (3) The adaptations to psychological techniques, as highlighted in this paper, can increase the effectiveness of videoconsultations. What this topic adds: (1) An examination of common concerns related to videoconsultations including: efficacy, therapeutic alliance and the digital divide. (2) A practical evidence-based checklist for pre-therapy videoconsultation considerations. (3) An evidence-based checklist of practice adaptations that can increase effectiveness in videoconsultation. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Heterogeneous Treatment Effects of Therapeutic-Dose Heparin in Patients Hospitalized for COVID-19.

Importance: Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making. Objective: To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE. Design, Setting, and Participants: Exploratory analysis of a multiplatform adaptive RCT of therapeutic-dose heparin vs usual care pharmacologic thromboprophylaxis in 3320 patients hospitalized for COVID-19 enrolled in North America, South America, Europe, Asia, and Australia between April 2020 and January 2021. Heterogeneity of treatment effect was assessed 3 ways: using (1) conventional subgroup analyses of baseline characteristics, (2) a multivariable outcome prediction model (risk-based approach), and (3) a multivariable causal forest model (effect-based approach). Analyses primarily used bayesian statistics, consistent with the original trial. Exposures: Participants were randomized to therapeutic-dose heparin or usual care pharmacologic thromboprophylaxis. Main Outcomes and Measures: Organ support-free days, assigning a value of -1 to those who died in the hospital and the number of days free of cardiovascular or respiratory organ support up to day 21 for those who survived to hospital discharge; and hospital survival. Results: Baseline demographic characteristics were similar between patients randomized to therapeutic-dose heparin or usual care (median age, 60 years; 38% female; 32% known non-White race; 45% Hispanic). In the overall multiplatform RCT population, therapeutic-dose heparin was not associated with an increase in organ support-free days (median value for the posterior distribution of the OR, 1.05; 95% credible interval, 0.91-1.22). In conventional subgroup analyses, the effect of therapeutic-dose heparin on organ support-free days differed between patients requiring organ support at baseline or not (median OR, 0.85 vs 1.30; posterior probability of difference in OR, 99.8%), between females and males (median OR, 0.87 vs 1.16; posterior probability of difference in OR, 96.4%), and between patients with lower body mass index (BMI <30) vs higher BMI groups (BMI ≥30; posterior probability of difference in ORs >90% for all comparisons). In risk-based analysis, patients at lowest risk of poor outcome had the highest propensity for benefit from heparin (lowest risk decile: posterior probability of OR >1, 92%) while those at highest risk were most likely to be harmed (highest risk decile: posterior probability of OR <1, 87%). In effect-based analysis, a subset of patients identified at high risk of harm (P = .05 for difference in treatment effect) tended to have high BMI and were more likely to require organ support at baseline. Conclusions and Relevance: Among patients hospitalized for COVID-19, the effect of therapeutic-dose heparin was heterogeneous. In all 3 approaches to assessing HTE, heparin was more likely to be beneficial in those who were less severely ill at presentation or had lower BMI and more likely to be harmful in sicker patients and those with higher BMI. The findings illustrate the importance of considering HTE in the design and analysis of RCTs. Trial Registration: ClinicalTrials.gov Identifiers: NCT02735707, NCT04505774, NCT04359277, NCT04372589.

The Impact of the Covid-19 Pandemic on Smoking Among Vulnerable Populations.

AIM: While accumulating evidence suggests that people modified their smoking during the ongoing COVID-19 pandemic, it remains unclear whether those most at risk for tobacco-related health disparities did so. The current study examined changes in smoking among several vulnerable smoker populations during the COVID-19 pandemic. METHODS: A web-based survey was distributed in 2020 to 709 adults with socioeconomic disadvantage, affective disorders, or opioid use disorder who participated in a previous study investigating the effects of very low nicotine content (VLNC) cigarettes on smoking. Current smoking status and rate, and adoption of protective health behaviors in response to the pandemic (e.g., social distancing, mask wearing) were examined. RESULTS: Among 332 survey respondents (46.8% response rate), 84.6% were current smokers. Repeated measures ANOVA showed that current cigarettes/day (CPD) was higher during COVID than pre-COVID (12.9±1.0 vs 11.6±1.0; p<.001). Most respondents had adopted protective health behaviors to prevent infection (>79% for all behaviors). More than half indicated that they were still leaving their homes specifically to buy cigarettes (64.6%) and were buying more packs per visit to the store (54.5%) than pre-COVID. Individuals unemployed at the time of the survey experienced greater increases in CPD (from 11.4±1.4 to 13.3±1.4, p=.024) as did those with higher levels of anxiety (from 11.5±1.1 to 13.6±1.1, p<.001). CONCLUSIONS: Smoking increased during the COVID-19 pandemic in this sample of adults from vulnerable populations, even while most adopted protective health measures to prevent infection. Unemployment and anxiety might identify those at greatest risk for increases in tobacco use. IMPLICATIONS: Individuals from populations especially vulnerable to smoking might be at risk for greater harm from cigarette smoking during times of pandemic-related stress. Public health interventions are warranted to ameliorate increases in smoking among these populations. Special attention should be paid to those experiencing unemployment and high anxiety.

Subcutaneous delivery of an antibody against SARS-CoV-2 from a supramolecular hydrogel depot.

Prolonged maintenance of therapeutically-relevant levels of broadly neutralizing antibodies (bnAbs) is necessary to enable passive immunization against infectious disease. Unfortunately, protection only lasts for as long as these bnAbs remain present at a sufficiently high concentration in the body. Poor pharmacokinetics and burdensome administration are two challenges that need to be addressed in order to make pre- and post-exposure prophylaxis with bnAbs feasible and effective. In this work, we develop a supramolecular hydrogel as an injectable, subcutaneous depot to encapsulate and deliver antibody drug cargo. This polymer-nanoparticle (PNP) hydrogel exhibits shear-thinning and self-healing properties that are required for an injectable drug delivery vehicle. In vitro drug release assays and diffusion measurements indicate that the PNP hydrogels prevent burst release and slow the release of encapsulated antibodies. Delivery of bnAbs against SARS-CoV-2 from PNP hydrogels is compared to standard routes of administration in a preclinical mouse model. We develop a multi-compartment model to understand the ability of these subcutaneous depot materials to modulate the pharmacokinetics of released antibodies; the model is extrapolated to explore the requirements needed for novel materials to successfully deliver relevant antibody therapeutics with different pharmacokinetic characteristics.

Understanding 'hybrid immunity': comparison and predictors of humoral immune responses to SARS-CoV-2 infection and COVID-19 vaccines.

BACKGROUND: Comparing humoral responses in SARS-CoV-2 vaccinees, those with SARS-CoV-2 infection, or combinations of vaccine/infection ('hybrid immunity'), may clarify predictors of vaccine immunogenicity. METHODS: We studied 2660 U.S. Military Health System beneficiaries with a history of SARS-CoV-2 infection-alone (n = 705), vaccination-alone (n = 932), vaccine-after-infection (n = 869), and vaccine-breakthrough-infection (n = 154). Peak anti-spike-IgG responses through 183 days were compared, with adjustment for vaccine product, demography, and comorbidities. We excluded those with evidence of clinical or sub-clinical SARS-CoV-2 reinfection from all groups. RESULTS: Multivariable regression results indicated vaccine-after-infection anti-spike-IgG responses were higher than infection-alone (p < 0.01), regardless of prior infection severity. An increased time between infection and vaccination was associated with a greater post-vaccination IgG response (p < 0.01). Vaccination-alone elicited a greater IgG response, but more rapid waning of IgG (p < 0.01), compared to infection-alone (p < 0.01). BNT162b2 and mRNA-1273 vaccine-receipt was associated with greater IgG responses compared to JNJ-78436735 (p < 0.01), regardless of infection history. Those with vaccine-after-infection or vaccine-breakthrough-infection had a more durable anti-spike-IgG response compared to infection-alone (p < 0.01). CONCLUSIONS: Vaccine-receipt elicited higher anti-spike-IgG responses than infection-alone, although IgG levels waned faster in those vaccinated (compared to infection-alone). Vaccine-after-infection elicits a greater humoral response compared to vaccine or infection alone; and the timing, but not disease severity, of prior infection predicted these post-vaccination IgG responses. While differences between groups were small in magnitude, these results offer insights into vaccine immunogenicity variations that may help inform vaccination timing strategies.

Persistent COVID-19 Symptoms at 6 Months After Onset and the Role of Vaccination Before or After SARS-CoV-2 Infection.

Importance: Understanding the factors associated with post-COVID conditions is important for prevention. Objective: To identify characteristics associated with persistent post-COVID-19 symptoms and to describe post-COVID-19 medical encounters. Design, Setting, and Participants: This cohort study used data from the Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases With Pandemic Potential (EPICC) study implemented in the US military health system (MHS); MHS beneficiaries aged 18 years or older who tested positive for SARS-CoV-2 from February 28, 2020, through December 31, 2021, were analyzed, with 1-year follow-up. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The outcomes analyzed included survey-reported symptoms through 6 months after SARS-CoV-2 infection and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis categories reported in medical records 6 months following SARS-CoV-2 infection vs 3 months before infection. Results: More than half of the 1832 participants in these analyses were aged 18 to 44 years (1226 [66.9%]; mean [SD] age, 40.5 [13.7] years), were male (1118 [61.0%]), were unvaccinated at the time of their infection (1413 [77.1%]), and had no comorbidities (1290 [70.4%]). A total of 728 participants (39.7%) had illness that lasted 28 days or longer (28-89 days: 364 [19.9%]; ≥90 days: 364 [19.9%]). Participants who were unvaccinated prior to infection (risk ratio [RR], 1.39; 95% CI, 1.04-1.85), reported moderate (RR, 1.80; 95% CI, 1.47-2.22) or severe (RR, 2.25; 95% CI, 1.80-2.81) initial illnesses, had more hospitalized days (RR per each day of hospitalization, 1.02; 95% CI, 1.00-1.03), and had a Charlson Comorbidity Index score of 5 or greater (RR, 1.55; 95% CI, 1.01-2.37) were more likely to report 28 or more days of symptoms. Among unvaccinated participants, postinfection vaccination was associated with a 41% lower risk of reporting symptoms at 6 months (RR, 0.59; 95% CI, 0.40-0.89). Participants had higher risk of pulmonary (RR, 2.00; 95% CI, 1.40-2.84), diabetes (RR, 1.46; 95% CI, 1.00-2.13), neurological (RR, 1.29; 95% CI, 1.02-1.64), and mental health-related medical encounters (RR, 1.28; 95% CI, 1.01-1.62) at 6 months after symptom onset than at baseline (before SARS-CoV-2 infection). Conclusions and Relevance: In this cohort study, more severe acute illness, a higher Charlson Comorbidity Index score, and being unvaccinated were associated with a higher risk of reporting COVID-19 symptoms lasting 28 days or more. Participants with COVID-19 were more likely to seek medical care for diabetes, pulmonary, neurological, and mental health-related illness for at least 6 months after onset compared with their pre-COVID baseline health care use patterns. These findings may inform the risk-benefit ratio of COVID-19 vaccination policy.

Estimated Indirect Cost Savings of Using Telehealth Among Nonelderly Patients With Cancer.

Importance: Patients with cancer typically have greater financial hardships and time costs than individuals without cancer. The COVID-19 pandemic has exacerbated this, while posing substantial challenges to delivering cancer care and resulting in important changes in care-delivery models, including the rapid adoption of telehealth. Objective: To estimate patient travel, time, and cost savings associated with telehealth for cancer care delivery. Design, Setting, and Participants: An economic evaluation of cost savings from completed telehealth visits from April 1, 2020, to June 30, 2021, in a single-institution National Cancer Institute-Designated Comprehensive Cancer Center. All patients aged 18 to 65 years who completed telehealth visits within the designated time frame and had a Florida mailing address documented in their electronic medical record were included in the study cohort. Data were analyzed from April 2020 to June 2021. Main Outcomes and Measures: The main outcome was estimated patient cost savings from telehealth, which included 2 components: costs of travel (defined as roundtrip distance saved from car travel) and potential loss of productivity due to the medical visit (defined as loss of income from roundtrip travel plus loss of income from in-person clinic visits). Two different models with a combination of 2 different mileage rates ($0.56 and $0.82 per mile) and census tract-level median hourly wages were used. Results: The study included 25 496 telehealth visits with 11 688 patients. There were 4525 (3795 patients) new or established visits and 20 971 (10 049 patients) follow-up visits. Median (IQR) age was 55.0 (46.0-61.0) years among the telehealth visits, with 15 663 visits (61.4%) by women and 18 360 visits (72.0%) by Hispanic non-White patients. According to cost models, the estimated mean (SD) total cost savings ranged from $147.4 ($120.1) at $0.56/mile to $186.1 ($156.9) at $0.82/mile. For new or established visits, the mean (SD) total cost savings per visit ranged from $176.6 ($136.3) at $0.56/mile to $222.8 ($177.4) at $0.82/mile, and for follow-up visits, the mean (SD) total cost savings per visit was $141.1 ($115.3) at $0.56/mile to $178.1 ($150.9) at $0.82/mile. Conclusions and Relevance: In this economic evaluation, telehealth was associated with savings in patients time and travel costs, which may reduce the financial toxicity of cancer care. Expansion of telehealth oncology services may be an effective strategy to reduce the financial burden among patients with cancer.

Telehealth adoption in cancer clinical trials: An Australian perspective.

INTRODUCTION: Cancer clinical trials have traditionally occurred in-person. However, the COVID-19 pandemic has forced adaptions of all aspects of cancer care (including clinical trials) so they can be delivered remotely. We aimed to quantify and qualify current use of telehealth and how it can be further improved and routinely integrated into cancer clinical trials in Australia. METHODS: We used a mixed-method study design, involving surveys of 14 multi-site Collaborative Cancer Clinical Trial Groups members across Australia (n = 98) and qualitative interviews with trial administrators and clinicians (n = 21). RESULTS: The results of our study indicated a strong willingness to use telehealth for certain transactions of clinical trials because it was perceived as a way of increasing efficiency and reach of services. Hybrid models (including telehealth and in-person methods), which considered transaction, cancer type, and patient preferences were most favorable. Additionally, telehealth allowed for greater equity to access and reduced trial burden but interestingly had little effect on increased diversity and recruitment. Factors influencing telehealth service implementation and uptake included communication among trial stakeholders, training, and learning from the experience of others in the clinical trials community. CONCLUSION: Many but not all aspects of clinical trial care are appropriate to be delivered via telehealth. A hybrid approach provides flexibility to trial delivery and may support greater equity of access to trials in the future. Our findings and actionable recommendations support the need for greater planning, training, and guidelines to enable telehealth to be better integrated into clinical trials. Opportunities exist to expand the use of remote patient monitoring to enable more objective data collection from trial participants in the future.

Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history.

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

Cancer care and management during COVID-19: A comparison of in-person, video and telephone consultations.

In Australia, the COVID-19 pandemic has resulted in the exponential growth in the delivery of telehealth services. Medicare data indicates that the majority of telehealth consultations have used the telephone, despite the known benefits of using video. The aim of this study was to understand the perceived quality and effectiveness of in-person, telephone and videoconsultations for cancer care. Data was collected via online surveys with consumers (n = 1162) and health professionals (n = 59), followed by semi-structured interviews with telehealth experienced health professionals (n = 22) and consumers (n = 18). Data were analysed using descriptive statistics and significance was tested using the chi-square test. A framework analysis and thematic analysis were used for qualitative data. Results indicate telehealth is suitable for use across the cancer care pathway. However, consumers and health professionals perceived videoconsultations facilitated visual communication and improved patients' quality of care. The telephone was appropriate for short transactional consultations such as repeat prescriptions. Consumers were rarely given the choice of consultation modality. The choice of modality depended on a range of factors such as the type of consultation and stage of cancer care. Hybrid models of care utilising in-person, video and telephone should be developed and requires further guidance to promote the adoption of telehealth in cancer care.

Costs to the Medicare Benefits Schedule for general practitioner consultations: A time-series analysis.

The COVID-19 pandemic was a catalyst for the introduction of additional telehealth funding (telehealth item numbers) for general practitioner (GP) consultations through the Medicare Benefits Schedule (MBS) in Australia. This study evaluated the impact of telehealth funding on costs to the MBS for GP consultations from January 2017 to December 2021. An interrupted time series analysis assessed MBS costs (initial and monthly growth) for GP consultations (in-person, videoconference, telephone) before and after additional telehealth item numbers were introduced. From January 2017 to February 2020, total MBS costs for GP consultations were, on average, $545 million per month compared to $592 million per month from March 2020 to December 2021. There was an initial cost increase of approximately $39 million in the first month after additional telehealth funding was introduced (p = 0.0001). Afterwards, there was no significant change in monthly costs (p = 0.539). The introduction of additional MBS telehealth funding increased overall MBS costs for GP consultations. This increased cost for GP telehealth services could save costs to society if it translates into improved continuity of care, decreased hospitalisations, reduced productivity losses and improved patient outcomes. Future policy reform should incorporate a cost-benefit analysis to determine if increased MBS costs for GP consultations are a good investment.

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression.

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.

Neurogenesis is disrupted in human hippocampal progenitor cells upon exposure to serum samples from hospitalized COVID-19 patients with neurological symptoms.

Coronavirus disease 2019 (COVID-19), represents an enormous new threat to our healthcare system and particularly to the health of older adults. Although the respiratory symptoms of COVID-19 are well recognized, the neurological manifestations, and their underlying cellular and molecular mechanisms, have not been extensively studied yet. Our study is the first one to test the direct effect of serum from hospitalised COVID-19 patients on human hippocampal neurogenesis using a unique in vitro experimental assay with human hippocampal progenitor cells (HPC0A07/03 C). We identify the different molecular pathways activated by serum from COVID-19 patients with and without neurological symptoms (i.e., delirium), and their effects on neuronal proliferation, neurogenesis, and apoptosis. We collected serum sample twice, at time of hospital admission and approximately 5 days after hospitalization. We found that treatment with serum samples from COVID-19 patients with delirium (n = 18) decreased cell proliferation and neurogenesis, and increases apoptosis, when compared with serum samples of sex- and age-matched COVID-19 patients without delirium (n = 18). This effect was due to a higher concentration of interleukin 6 (IL6) in serum samples of patients with delirium (mean ± SD: 229.9 ± 79.1 pg/ml, vs. 32.5 ± 9.5 pg/ml in patients without delirium). Indeed, treatment of cells with an antibody against IL6 prevented the decreased cell proliferation and neurogenesis and the increased apoptosis. Moreover, increased concentration of IL6 in serum samples from delirium patients stimulated the hippocampal cells to produce IL12 and IL13, and treatment with an antibody against IL12 or IL13 also prevented the decreased cell proliferation and neurogenesis, and the increased apoptosis. Interestingly, treatment with the compounds commonly administered to acute COVID-19 patients (the Janus kinase inhibitors, baricitinib, ruxolitinib and tofacitinib) were able to restore normal cell viability, proliferation and neurogenesis by targeting the effects of IL12 and IL13. Overall, our results show that serum from COVID-19 patients with delirium can negatively affect hippocampal-dependent neurogenic processes, and that this effect is mediated by IL6-induced production of the downstream inflammatory cytokines IL12 and IL13, which are ultimately responsible for the detrimental cellular outcomes.

Illegal waste fly-tipping in the Covid-19 pandemic: enhanced compliance, temporal displacement, and urban-rural variation.

Objective: Illegal dumping of household and business waste, known as fly-tipping in the UK, is a significant environmental crime. News agencies reported major increases early in the COVID-19 pandemic when waste disposal services were closed or disrupted. This study examines the effect of lockdowns on illegal dumping in the UK. Method: A freedom of information request was sent to all local authorities in the UK asking for records of reported incidents of fly-tipping for before and after the first national lockdown. ARIMA modelling and year-on-year comparison was used to compare observed and expected levels of fly-tipping. Urban and rural local authorities were compared. Results: A statistically significant decline in fly-tipping during the first lockdown was followed by a similar increase when lockdown ended. The effects largely cancelled each other out. There was pronounced variation in urban-rural experience: urban areas, with higher rates generally, experienced most of the initial drop in fly-tipping while some rural authorities experienced an increase. Conclusion: Waste services promote compliance with laws against illegal dumping. When those services were disrupted during lockdown it was expected that fly-tipping would increase but, counter-intuitively, it declined. This enhanced compliance effect was likely due to increased perceived risk in densely populated urban areas. However, as lockdown restrictions were eased, fly-tipping increased to clear the backlog, indicating temporal displacement. Supplementary Information: The online version contains supplementary material available at 10.1186/s40163-022-00170-3.

Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis.

BACKGROUND: A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence. METHODS: Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence. FINDINGS: One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71-0·95, p = 0·008]] and sarilumab [0·80 [0·61-1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81-1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28. CONCLUSIONS: Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.

Protocol for an integrative review: patient and families' perspectives on telehealth in palliative care.

INTRODUCTION: Increases in the use of telehealth in palliative care (telepalliative care) prior to, and during, the COVID-19 pandemic have resulted in a proliferation of studies on the topic. While knowledge is building on how providers and recipients adapt to telepalliative care, no reviews have, as of yet, examined telepalliative care from a patient and family perspective. Therefore, the aim of this integrative review is to explore patients and families' perspectives on telepalliative. METHODS AND ANALYSIS: An integrative review will be performed inspired by the methodology of Remmington and Toronto from March 2022 to December 2022. Medline, Embase, PsycINFO and CINAHL will be searched for primary peer-reviewed studies that describe telepalliative care from patient and families' perspectives. Limiters will be used for age; 18 years+, time; 10 years, and language; English and Danish. Hand searches of authors of included articles and reference lists of included articles will be performed. Two reviewers will independently screen and appraise selected articles using the Mixed Method Appraisal Tool. Conflicts will be resolved through discussions with a third reviewer. Data will be extracted independently by two reviewers into a data matrix with predefined headings and analysed using thematic analysis. Findings will be reported thematically, summarised into a thematic synthesis and discussed in relation to relevant literature. ETHICS AND DISSEMINATION: Ethical approval is not required for this review. Results will be published in an international peer-reviewed journal and presented at a relevant international conference. Reporting of this protocol was guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocol checklist and prospectively reported to PROSPERO (CRD42022301206).

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.