Interleukin-6 blocking agents for treating COVID-19: a living systematic review.

BACKGROUND: It has been reported that people with COVID-19 and pre-existing autoantibodies against type I interferons are likely to develop an inflammatory cytokine storm responsible for severe respiratory symptoms. Since interleukin 6 (IL-6) is one of the cytokines released during this inflammatory process, IL-6 blocking agents have been used for treating people with severe COVID-19. OBJECTIVES: To update the evidence on the effectiveness and safety of IL-6 blocking agents compared to standard care alone or to a placebo for people with COVID-19. SEARCH METHODS: We searched the World Health Organization (WHO) International Clinical Trials Registry Platform, the Living OVerview of Evidence (L·OVE) platform, and the Cochrane COVID-19 Study Register to identify studies on 7 June 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) evaluating IL-6 blocking agents compared to standard care alone or to placebo for people with COVID-19, regardless of disease severity. DATA COLLECTION AND ANALYSIS: Pairs of researchers independently conducted study selection, extracted data and assessed risk of bias. We assessed the certainty of evidence using the GRADE approach for all critical and important outcomes. In this update we amended our protocol to update the methods used for grading evidence by establishing minimal important differences for the critical outcomes. MAIN RESULTS: This update includes 22 additional trials, for a total of 32 trials including 12,160 randomized participants all hospitalized for COVID-19 disease. We identified a further 17 registered RCTs evaluating IL-6 blocking agents without results available as of 7 June 2022.  The mean age range varied from 56 to 75 years; 66.2% (8051/12,160) of enrolled participants were men. One-third (11/32) of included trials were placebo-controlled. Twenty-two were published in peer-reviewed journals, three were reported as preprints, two trials had results posted only on registries, and results from five trials were retrieved from another meta-analysis. Eight were funded by pharmaceutical companies.  Twenty-six included studies were multicenter trials; four were multinational and 22 took place in single countries. Recruitment of participants occurred between February 2020 and June 2021, with a mean enrollment duration of 21 weeks (range 1 to 54 weeks). Nineteen trials (60%) had a follow-up of 60 days or more. Disease severity ranged from mild to critical disease. The proportion of participants who were intubated at study inclusion also varied from 5% to 95%. Only six trials reported vaccination status; there were no vaccinated participants included in these trials, and 17 trials were conducted before vaccination was rolled out. We assessed a total of six treatments, each compared to placebo or standard care. Twenty trials assessed tocilizumab, nine assessed sarilumab, and two assessed clazakizumab. Only one trial was included for each of the other IL-6 blocking agents (siltuximab, olokizumab, and levilimab). Two trials assessed more than one treatment. Efficacy and safety of tocilizumab and sarilumab compared to standard care or placebo for treating COVID-19 At day (D) 28, tocilizumab and sarilumab probably result in little or no increase in clinical improvement (tocilizumab: risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.11; 15 RCTs, 6116 participants; moderate-certainty evidence; sarilumab: RR 0.99, 95% CI 0.94 to 1.05; 7 RCTs, 2425 participants; moderate-certainty evidence). For clinical improvement at ≥ D60, the certainty of evidence is very low for both tocilizumab (RR 1.10, 95% CI 0.81 to 1.48; 1 RCT, 97 participants; very low-certainty evidence) and sarilumab (RR 1.22, 95% CI 0.91 to 1.63; 2 RCTs, 239 participants; very low-certainty evidence). The effect of tocilizumab on the proportion of participants with a WHO Clinical Progression Score (WHO-CPS) of level 7 or above remains uncertain at D28 (RR 0.90, 95% CI 0.72 to 1.12; 13 RCTs, 2117 participants; low-certainty evidence) and that for sarilumab very uncertain (RR 1.10, 95% CI 0.90 to 1.33; 5 RCTs, 886 participants; very low-certainty evidence). Tocilizumab reduces all cause-mortality at D28 compared to standard care/placebo (RR 0.88, 95% CI 0.81 to 0.94; 18 RCTs, 7428 participants; high-certainty evidence). The evidence about the effect of sarilumab on this outcome is very uncertain (RR 1.06, 95% CI 0.86 to 1.30; 9 RCTs, 3305 participants; very low-certainty evidence). The evidence is uncertain for all cause-mortality at ≥ D60 for tocilizumab (RR 0.91, 95% CI 0.80 to 1.04; 9 RCTs, 2775 participants; low-certainty evidence) and very uncertain for sarilumab (RR 0.95, 95% CI 0.84 to 1.07; 6 RCTs, 3379 participants; very low-certainty evidence). Tocilizumab probably results in little to no difference in the risk of adverse events (RR 1.03, 95% CI 0.95 to 1.12; 9 RCTs, 1811 participants; moderate-certainty evidence). The evidence about adverse events for sarilumab is uncertain (RR 1.12, 95% CI 0.97 to 1.28; 4 RCT, 860 participants; low-certainty evidence).  The evidence about serious adverse events is very uncertain for tocilizumab (RR 0.93, 95% CI 0.81 to 1.07; 16 RCTs; 2974 participants; very low-certainty evidence) and uncertain for sarilumab (RR 1.09, 95% CI 0.97 to 1.21; 6 RCTs; 2936 participants; low-certainty evidence). Efficacy and safety of clazakizumab, olokizumab, siltuximab and levilimab compared to standard care or placebo for treating COVID-19 The evidence about the effects of clazakizumab, olokizumab, siltuximab, and levilimab comes from only one or two studies for each blocking agent, and is uncertain or very uncertain. AUTHORS' CONCLUSIONS: In hospitalized people with COVID-19, results show a beneficial effect of tocilizumab on all-cause mortality in the short term and probably little or no difference in the risk of adverse events compared to standard care alone or placebo. Nevertheless, both tocilizumab and sarilumab probably result in little or no increase in clinical improvement at D28. Evidence for an effect of sarilumab and the other IL-6 blocking agents on critical outcomes is uncertain or very uncertain. Most of the trials included in our review were done before the waves of different variants of concern and before vaccination was rolled out on a large scale. An additional 17 RCTs of IL-6 blocking agents are currently registered with no results yet reported. The number of pending studies and the number of participants planned is low. Consequently, we will not publish further updates of this review.

Interventions to increase cervical screening uptake among immigrant women: A systematic review and meta-analysis.

Numerous intervention studies have attempted to increase cervical screening uptake among immigrant women, nonetheless their screening participation remains low. This systematic review and meta-analysis aimed to summarise the evidence on interventions to improve cervical screening among immigrant women globally and identify their effectiveness. Databases PubMed, EMBASE, Scopus, PsycINFO, ERIC, CINAHL and CENTRAL were systematically searched from inception to October 12, 2021, for intervention studies, including randomised and clinical controlled trials (RCT, CCT) and one and two group pre-post studies. Peer-reviewed studies involving immigrant and refugee women, in community and clinical settings, were eligible. Comparator interventions were usual or minimal care or attention control. Data extraction, quality appraisal and risk of bias were assessed by two authors independently using COVIDENCE software. Narrative synthesis of findings was carried out, with the main outcome measure defined as the cervical screening uptake rate difference pre- and post-intervention followed by random effects meta-analysis of trials and two group pre-post studies, using Comprehensive Meta-Analysis software, to calculate pooled rate ratios and adjustment for publication bias, where found. The protocol followed PRISMA guidelines and was registered prospectively with PROSPERO (CRD42020192341). 1,900 studies were identified, of which 42 (21 RCTS, 4 CCTs, and 16 pre-post studies) with 44,224 participants, were included in the systematic review, and 28 with 35,495 participants in the meta-analysis. Overall, the uptake difference rate for interventions ranged from -6.7 to 96%. Meta-analysis demonstrated a pooled rate ratio of 1.15 (95% CI 1.03-1.29), with high heterogeneity. Culturally sensitive, multicomponent interventions, using different modes of information delivery and self-sampling modality were most promising. Interventions led to at least 15% increase in cervical screening participation among immigrant women. Interventions designed to overcome logistical barriers and use multiple channels to communicate culturally appropriate health promotion messages are most effective at achieving cervical screening uptake among immigrant women.

Invited Commentary: Modern Epidemiology Confronts COVID-19-Reflections From Psychiatric Epidemiology.

Dimitris et al. (Am J Epidemiol. 2022;191(6):980-986) outline how the coronavirus disease 2019 (COVID-19) pandemic has, with mixed results, put epidemiology under the spotlight. While epidemiologic theory and methods have been critical in many successes, the ongoing global death toll from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the sometimes chaotic public messaging underscore that epidemiology as a field has room for improvement. Here, we use examples from psychiatric epidemiologic studies conducted during the COVID-19 era to reflect on errors driven by overlooking specific major methodological advances of modern epidemiology. We focus on: 1) use of nonrepresentative sampling in online surveys, which limits the potential knowledge to be gained from descriptive studies and amplifies collider stratification bias in causal studies; and 2) failure to acknowledge multiple versions of exposures (e.g., lockdown, school closure) and differences in prevalence of effect measure modifiers across contexts, which causes violations of the consistency assumption and lack of effect transportability. We finish by highlighting: 1) the heterogeneity of psychiatric epidemiologic results during the pandemic across place and sociodemographic groups and over time; 2) the importance of following the foundational advancements of modern epidemiology even in emergency settings; and 3) the need to limit the role of political agendas in cherry-picking and reporting epidemiologic evidence.

Robustness of reported postacute health outcomes in children with SARS-CoV-2 infection: a systematic review.

OBJECTIVE: To systematically assess the robustness of reported postacute SARS-CoV-2 infection health outcomes in children. METHODS: A search on PubMed and Web of Science was conducted to identify studies published up to 22 January 2022 that reported on postacute SARS-CoV-2 infection health outcomes in children (<18 years) with follow-up of ≥2 months since detection of infection or ≥1 month since recovery from acute illness. We assessed the consideration of confounding bias and causality, as well as the risk of bias. RESULTS: 21 studies including 81 896 children reported up to 97 symptoms with follow-up periods of 2.0-11.5 months. Fifteen studies had no control group. The reported proportion of children with post-COVID syndrome was between 0% and 66.5% in children with SARS-CoV-2 infection (n=16 986) and between 2.0% and 53.3% in children without SARS-CoV-2 infection (n=64 910). Only two studies made a clear causal interpretation of an association between SARS-CoV-2 infection and the main outcome of 'post-COVID syndrome' and provided recommendations regarding prevention measures. The robustness of all 21 studies was seriously limited due to an overall critical risk of bias. CONCLUSIONS: The robustness of reported postacute SARS-CoV-2 infection health outcomes in children is seriously limited, at least in all the published articles we could identify. None of the studies provided evidence with reasonable certainty on whether SARS-CoV-2 infection has an impact on postacute health outcomes, let alone to what extent. Children and their families urgently need much more reliable and methodologically robust evidence to address their concerns and improve care.

Online Contingent Attention Training (OCAT): transfer effects to cognitive biases, rumination, and anxiety symptoms from two proof-of-principle studies.

The aim of the present research was to develop and test the efficacy of a novel online contingent attention training (i.e., OCAT) to modify attention and interpretation biases, improve emotion regulation, and reduce emotional symptom levels in the face of major stressors. Two proof-of-principle studies were carried out. In study 1, 64 undergraduates who were about to start a major stressful period (i.e., final exams) were randomized to undergo 10 days of active OCAT or a sham-control training. Emotion regulation (habitual use of rumination and reappraisal) and symptom levels (depression and anxiety) were assessed before and after the intervention. In study 2, the same 2 × 2 mixed design was used with 58 individuals from the general population undergoing a major stressful situation (the lockdown period at the beginning of the COVID-19 pandemic in 2020). In both studies, the OCAT group showed significant improvements on attention towards negative information and interpretation biases in comparison to the sham-control group. Additionally, changes in cognitive biases transferred to reductions of participants' use of rumination and anxiety symptom levels. These results show preliminary evidence regarding the efficacy of the OCAT to target attention and interpretation biases as well as to improve emotion regulation processes and to buffer against the effects of major stressors.

Sample size calculations for pathogen variant surveillance in the presence of biological and systematic biases.

Tracking the emergence and spread of pathogen variants is an important component of monitoring infectious disease outbreaks. To that end, accurately estimating the number and prevalence of pathogen variants in a population requires carefully designed surveillance programs. However, current approaches to calculating the number of pathogen samples needed for effective surveillance often do not account for the various processes that can bias which infections are detected and which samples are ultimately characterized as a specific variant. In this article, we introduce a framework that accounts for the logistical and epidemiological processes that may bias variant characterization, and we demonstrate how to use this framework (implemented in a publicly available tool) to calculate the number of sequences needed for surveillance. Our framework is designed to be easy to use while also flexible enough to be adapted to various pathogens and surveillance scenarios.

Diagnostic models predicting paediatric viral acute respiratory infections: a systematic review.

OBJECTIVES: To systematically review and evaluate diagnostic models used to predict viral acute respiratory infections (ARIs) in children. DESIGN: Systematic review. DATA SOURCES: PubMed and Embase were searched from 1 January 1975 to 3 February 2022. ELIGIBILITY CRITERIA: We included diagnostic models predicting viral ARIs in children (<18 years) who sought medical attention from a healthcare setting and were written in English. Prediction model studies specific to SARS-CoV-2, COVID-19 or multisystem inflammatory syndrome in children were excluded. DATA EXTRACTION AND SYNTHESIS: Study screening, data extraction and quality assessment were performed by two independent reviewers. Study characteristics, including population, methods and results, were extracted and evaluated for bias and applicability using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies and PROBAST (Prediction model Risk Of Bias Assessment Tool). RESULTS: Of 7049 unique studies screened, 196 underwent full text review and 18 were included. The most common outcome was viral-specific influenza (n=7; 58%). Internal validation was performed in 8 studies (44%), 10 studies (56%) reported discrimination measures, 4 studies (22%) reported calibration measures and none performed external validation. According to PROBAST, a high risk of bias was identified in the analytic aspects in all studies. However, the existing studies had minimal bias concerns related to the study populations, inclusion and modelling of predictors, and outcome ascertainment. CONCLUSIONS: Diagnostic prediction can aid clinicians in aetiological diagnoses of viral ARIs. External validation should be performed on rigorously internally validated models with populations intended for model application. PROSPERO REGISTRATION NUMBER: CRD42022308917.

Are encapsulated pesticides less harmful to human health than their conventional alternatives? Protocol for a systematic review of in vitro and in vivo animal model studies.

BACKGROUND: The gradual increase in the global population has led to the rising demand for agricultural products worldwide. This required the introduction of environment- and public health-friendly advanced technologies for plant protection to guard yields from pest destruction in a sustainable way. Encapsulation technology is a promising procedure to increase the effectiveness of pesticide active ingredients while reducing human exposure and environmental impact. Despite the presumed favorable properties of encapsulated pesticide formulations on human health, it is necessary to systematically assess whether they are less harmful to human health than conventional pesticide products. OBJECTIVES: We aim to systematically review the literature to answer the question of whether micro- or nano-encapsulated pesticide formulations exert different degrees of toxicity than their conventional (not-encapsulated) counterparts in in vivo animal and in vitro (human, animal, and bacterial cell) non-target models. The answer is important to estimate the possible differences in the toxicological hazards of the two different types of pesticide formulations. Because our extracted data will come from different models, we also aim to perform subgroup analyses to investigate how toxicity varies across different models. A pooled toxicity effect estimate will also be performed by meta-analysis when appropriate. METHODS: The systematic review will follow the guidelines developed by the National Toxicology Program's Office of Health Assessment and Translation (NTP/OHAT). The protocol adheres to the Preferred Reporting Items for Systematic Reviews and meta-analyses Protocol (PRISMA-P) statement. PubMed (NLM), Scopus (Elsevier), Web of Science Core Collection (Clarivate), Embase (Elsevier), and Agricola (EBSCOhost) electronic databases will be comprehensively searched in September 2022 to identify eligible studies using multiple search terms of "pesticide", "encapsulation" and "toxicity" along with their synonyms and other words that are semantically related. The reference lists of all eligible articles and retrieved reviews will be manually screened to identify additional relevant papers. ELIGIBILITY CRITERIA: We will include peer-reviewed experimental (non-target in vivo animal model and in vitro human, animal, and bacterial cell cultures) studies published as full-text articles in English language that simultaneously investigate the effect of any micro- or nano-encapsulated pesticide formulation, applied in all ranges of concentrations, duration, and routes of exposure, and its corresponding active ingredient(s) or its conventional non-encapsulated product formulation(s) used in the same ranges of concentrations, duration, and routes of exposure on the same pathophysiological outcome. We will exclude studies that examine pesticidal activity on target organisms, cultures of cells isolated from target organisms exposed in vivo or in vitro, and those using biological materials isolated from target organisms/cells. STUDY APPRAISAL AND SYNTHESIS: Studies identified by the search will be screened and managed according to the review inclusion and exclusion criteria in the Covidence systematic review tool by two reviewers, who will also blindly extract the data and assess the risk of bias of included studies. The OHAT risk of bias tool will be applied to evaluate the quality and risk of bias in the included studies. Study findings will be synthesized narratively by important features of the study populations, design, exposure, and endpoints. If findings make it possible, a meta-analysis will be performed on identified toxicity outcomes. To rate the certainty in the body of evidence, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

[Mathematical models for COVID-19 infection estimation: essential considerations and projections in Colombia]. / Modelos matemáticos estimadores de la infección por COVID-19: consideraciones esenciales y proyecciones en Colombia.

OBJECTIVE: To estimate the COVID-19 infection behavior in Colombia using mathematical models. METHODS: Two mathematical models were constructed to estimate imported confirmed cases and related confirmed cases of COVID-19 infection in Colombia, respectively. The phenomenology of imported confirmed cases is modeled with sigmoidal function, while related confirmed cases are modeled using a combination of exponential functions and polynomial algebraic functions. The fitting algorithms based on least squares methods and direct search methods are used to determine the parameters of the models. RESULTS: The sigmodial model performs a highly convergent estimation of the reported confirmed cases of COVID-19 infection to May 28, 2020. This model achieved a prediction error of 0.5 % measured using the normalized root mean square error. The model of the confirmed cases reported as related shows a 3.5 % prediction error and a low bias of -0.01 associated with overestimation. CONCLUSIONS: This work shows that the mathematical models allow to predict the behavior of the infection efficiently and effectively by COVID 19 in Colombia when the imported cases and the related cases of infection are independently considered.

OBJETIVO: Estimar el comportamiento de la infección por COVID-19 en Colombia mediante modelos matemáticos. MÉTODOS: Se construyeron dos modelos matemáticos para estimar los casos confirmados importados y los casos confirmados relacionados de la infección por COVID-19 en Colombia, respectivamente. La fenomenología de los casos confirmados importados es modelada con una función sigmoidal, mientras que los casos confirmados relacionados son modelados mediante una combinación de funciones exponenciales y funciones algebraicas polinomiales. Se utilizan algoritmos de ajuste basados en métodos de mínimos cuadrados y métodos de búsqueda directa para la determinación de los parámetros de los modelos. RESULTADOS: El modelo sigmodial realiza una estimación altamente convergente de los datos reportados, al 28 de mayo de 2020, de los casos confirmados importados de infección por COVID-19. El modelo muestra un error de predicción de 0,5%, que se mide usando la raíz del error cuadrático medio normalizado. El modelo para los casos confirmados reportados como relacionados muestra un error en la predicción del 3,5 % y un sesgo bajo del -0,01 asociado a la sobrestimación. CONCLUSIONES: El presente trabajo evidencia que los modelos matemáticos permiten eficaz y efectivamente predecir el comportamiento de la infección por COVID-19 en Colombia cuando los casos importados y los casos relacionados de infección son consideradores de manera independiente.

Towards robust and accurate estimates of the incubation time distribution, with focus on upper tail probabilities and SARS-CoV-2 infection.

Quarantine length for individuals who have been at risk for infection with SARS-CoV-2 has been based on estimates of the incubation time distribution. The time of infection is often not known exactly, yielding data with an interval censored time origin. We give a detailed account of the data structure, likelihood formulation and assumptions usually made in the literature: (i) the risk of infection is assumed constant on the exposure window and (ii) the incubation time follows a specific parametric distribution. The impact of these assumptions remains unclear, especially for the right tail of the distribution which informs quarantine policy. We quantified bias in percentiles by means of simulation studies that mimic reality as close as possible. If assumption (i) is not correct, then median and upper percentiles are affected similarly, whereas misspecification of the parametric approach (ii) mainly affects upper percentiles. The latter may yield considerable bias. We suggest a semiparametric method that provides more robust estimates without the need of a parametric choice. Additionally, we used a simulation study to evaluate a method that has been suggested if all infection times are left censored. It assumes that the width of the interval from infection to latest possible exposure follows a uniform distribution. This assumption gave biased results in the exponential phase of an outbreak. Our application to open source data suggests that focus should be on the level of information in the observations, as expressed by the width of exposure windows, rather than the number of observations.

The emotion bias of health product consumers in the context of COVID-19.

The ongoing COVID-19 has led to an increase in negative emotions and health awareness among consumers. This paper discusses the emotion bias of Chinese consumers during the three periods: the pre-COVID-19 period, the COVID-19 lockdown period, and the COVID-19 normalization period. This study takes health products as the research object and crawls relevant reviews on the JD platform to classify products. The data were classified into emotion, the intensity of emotion was calculated, and the logistic regression model and variance analysis were used to analyze the difference in emotion expression. The study reveals that consumers are willing to express fear and sadness during the COVID-19 lockdown era and are willing to express like emotions before the pandemic compared to the three periods. There are also differences in the emotional intensity of different product reviews. The intensity of emotional expression is more vigorous for consumers who purchase nutritional products, while for those who purchase healthcare equipment, the intensity of emotional expression is lower. This study offers the emotion bias of consumers in response to COVID-19 to provide a theoretical basis and reference solution for implementing marketing strategies for health product companies.

Effects of home healthcare for adults with chronic respiratory diseases and post-COVID-19 syndrome on hospital bed turnover rate: a protocol of systematic review with meta-analysis.

INTRODUCTION: Chronic respiratory diseases (CRDs) have a high prevalence, morbidity and mortality worldwide. After the COVID-19 pandemic, the number of patients readmitted after hospital discharge increased. For some populations, early hospital discharge and home healthcare may reduce health costs in patients treated at home when compared with those hospitalised. This study aims to systematically review the effectiveness of home healthcare for patients with CRDs and post-COVID-19 syndrome. METHODS AND ANALYSIS: We will search on MEDLINE, CENTRAL, Embase and PsycINFO. We will include randomised controlled trials (RCTs) and non-RCT studies reported in full text and abstracts. No language restriction will be applied. We will include studies related to adults with a diagnosis of CRDs or post-COVID-19 syndrome that compared in-patient hospital care with any home healthcare. We will exclude studies with participants with neurological, mental diseases, cancer or pregnant women. Two review authors will screen abstracts and select the eligible studies. To investigate the risk of bias, we will use the Cochrane 'Risk of Bias' tool for RCT, and the Risk of Bias In Non-randomised Studies-of Interventions for non-RCT. We will use the five Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) considerations to assess the quality of the evidence. Patients and the public will be involved in the preparation, execution and implementation phases of the review. ETHICS AND DISSEMINATION: No ethical approval is required because only published data will be analysed. The publication of the results in peer-reviewed journals and at relevant conferences will guide the direction of future research in the field and healthcare practice. The results will also be disseminated in plain language on social media to disseminate the knowledge to society and the public interested in the topic.

Survey mode and nonresponse bias: A meta-analysis based on the data from the international social survey programme waves 1996-2018 and the European social survey rounds 1 to 9.

The constant increase in survey nonresponse and fieldwork costs are the reality of survey research. Together with other unpredictable events occurring in the world today, this increase poses a challenge: the necessity to accelerate a switch from face-to-face data collection to different modes, that have usually been considered to result in lower response rates. However, recent research has established that the simple response rate is a feeble measure of study quality. Therefore, this article aims to analyze the effect of survey characteristics, especially the survey mode, on the nonresponse bias. The bias measure used is the internal criteria first proposed by Sodeur and first applied by Kohler. The analysis is based on the survey documentation and results from the International Social Survey Programme waves 1996-2018 and the European Social Survey rounds 1 to 9. Random-effects three-level meta-regression models, based on data from countries from each inhabited continent, were created in order to estimate the impact of the survey mode or modes, sampling design, fieldwork experience, year of data collection, and response rate on the nonresponse bias indicator. Several ways of nesting observations within clusters were also proposed. The results suggest that using mail and some types of mixed-mode surveys were connected to lower nonresponse bias than using face-to-face mode surveys.

Nonsystematic Reporting Biases of the SARS-CoV-2 Variant Mu Could Impact Our Understanding of the Epidemiological Dynamics of Emerging Variants.

Developing a timely and effective response to emerging SARS-CoV-2 variants of concern (VOCs) is of paramount public health importance. Global health surveillance does not rely on genomic data alone to identify concerning variants when they emerge. Instead, methods that utilize genomic data to estimate the epidemiological dynamics of emerging lineages have the potential to serve as an early warning system. However, these methods assume that genomic data are uniformly reported across circulating lineages. In this study, we analyze differences in reporting delays among SARS-CoV-2 VOCs as a plausible explanation for the timing of the global response to the former VOC Mu. Mu likely emerged in South America in mid-2020, where its circulation was largely confined. In this study, we demonstrate that Mu was designated as a VOC ∼1 year after it emerged and find that the reporting of genomic data for Mu differed significantly than that of other VOCs within countries, states, and individual laboratories. Our findings suggest that nonsystematic biases in the reporting of genomic data may have delayed the global response to Mu. Until they are resolved, the surveillance gaps that affected the global response to Mu could impede the rapid and accurate assessment of future emerging variants.

Quantifying implicit biases in refereeing using NBA referees as a testbed.

Implicit biases occur automatically and unintentionally and are particularly present when we have to make split second decisions. One such situations appears in refereeing, where referees have to make an instantaneous decision on a potential violation. In this work I revisit and extend some of the existing work on implicit biases in refereeing. In particular, I focus on refereeing in the NBA and examine three different types of implicit bias; (i) home-vs-away bias, (ii) bias towards individual players or teams, and, (iii) racial bias. For this study, I use play-by-play data and data from the Last 2 min reports the league office releases for games that were within 5 points in the last 2 min since the 2015 season. The results indicate that the there is a bias towards the home team-particularly pronounced during the playoffs-but it has been reduced since the COVID-19 pandemic. Furthermore, there is robust statistical evidence that specific players benefit from referee decisions more than expected from pure chance. However, I find no evidence of negative bias towards individual players, or towards specific teams. Finally, my analysis on racial bias indicates the absence of any bias.

Addressing Cognitive Biases in Interpreting an Elevated Lactate in a Patient with Type 1 Diabetes and Thiamine Deficiency.

We present the case of a young woman admitted for diabetic ketoacidosis with persistent, asymptomatic lactic acid (LA) elevation during the evolving COVID-19 pandemic. Cognitive biases in interpreting an elevated LA in this patient's care resulted in an extensive infectious workup instead of the low-cost and potentially diagnostic provision of empiric thiamine. We discuss clinical patterns and etiologies of LA elevation and the role of thiamine deficiency. We also address cognitive biases potentially affecting the interpretation of elevated lactate levels and provide guidance for clinicians to determine appropriate patients for empiric thiamine administration.

How COVID-19 News Affect Older Adults' Mental Health-Evidence of a Positivity Bias.

BACKGROUND: Media affects the trajectory of many individuals' mental health-with media news, individuals experience negative bias more than positive bias. However, there is also evidence of an age-related positivity effect, with negativity bias generally fading with age. With the rise of COVID-19 cases, older adults (aged 55 years and older) who consume media frequently are at a high risk for declining mental health. To date, there has been no research on the positivity vs. negativity bias of media news on older adults. Here, we investigated whether positivity or negativity bias plays a larger role in affecting how older adults react to COVID-19 news. METHODS: Sixty-nine older adults (aged 55-95) answered questions about their weekly media consumption and how closely they followed news relating to COVID-19. They also completed a general health questionnaire. They were then randomly assigned to read either positive or negative COVID-19 news (n = 35 and 34, respectively). The adults were asked if the news made them feel happy or fearful, and if they wanted to read more about the news or ignore the news. RESULTS: An analysis revealed that the more often older adults consumed media and the more closely they followed COVID-19 news, the more they felt unhappy and depressed. Importantly, older adults who read positive news reported stronger responses than those who read negative news. Older adults appeared to have a strong positivity bias for COVID-19 news, reporting feeling happy and wanting to read about positive news. In contrast, negative COVID-19 news did not evoke similar levels of response from the older adults. CONCLUSIONS: Media consumption of COVID-19 news does negatively impact the mental well-being of older adults, but older adults appear to have a strong positivity bias and a lack of negativity bias for COVID-19 news. These findings suggest that older adults can remain hopeful and positive during periods of public health crises and intense stress, which is essential to sustaining their mental well-being during difficult times.

Ethnic minority representation in UK COVID-19 trials: systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has highlighted health disparities affecting ethnic minority communities. There is growing concern about the lack of diversity in clinical trials. This study aimed to assess the representation of ethnic groups in UK-based COVID-19 randomised controlled trials (RCTs). METHODS: A systematic review and meta-analysis were undertaken. A search strategy was developed for MEDLINE (Ovid) and Google Scholar (1st January 2020-4th May 2022). Prospective COVID-19 RCTs for vaccines or therapeutics that reported UK data separately with a minimum of 50 participants were eligible. Search results were independently screened, and data extracted into proforma. Percentage of ethnic groups at all trial stages was mapped against Office of National Statistics (ONS) statistics. Post hoc DerSimonian-Laird random-effects meta-analysis of percentages and a meta-regression assessing recruitment over time were conducted. Due to the nature of the review question, risk of bias was not assessed. Data analysis was conducted in Stata v17.0. A protocol was registered (PROSPERO CRD42021244185). RESULTS: In total, 5319 articles were identified; 30 studies were included, with 118,912 participants. Enrolment to trials was the only stage consistently reported (17 trials). Meta-analysis showed significant heterogeneity across studies, in relation to census-expected proportions at study enrolment. All ethnic groups, apart from Other (1.7% [95% CI 1.1-2.8%] vs ONS 1%) were represented to a lesser extent than ONS statistics, most marked in Black (1% [0.6-1.5%] vs 3.3%) and Asian (5.8% [4.4-7.6%] vs 7.5%) groups, but also apparent in White (84.8% [81.6-87.5%] vs 86%) and Mixed 1.6% [1.2-2.1%] vs 2.2%) groups. Meta-regression showed recruitment of Black participants increased over time (p = 0.009). CONCLUSIONS: Asian, Black and Mixed ethnic groups are under-represented or incorrectly classified in UK COVID-19 RCTs. Reporting by ethnicity lacks consistency and transparency. Under-representation in clinical trials occurs at multiple levels and requires complex solutions, which should be considered throughout trial conduct. These findings may not apply outside of the UK setting.