While undisputedly important, and part of any systematic review (SR) by definition, evaluation of the risk of bias within the included studies is one of the most time-consuming parts of performing an SR. In this paper, we describe a case study comprising an extensive analysis of risk of bias (RoB) and reporting quality (RQ) assessment from a previously published review (CRD42021236047). It included both animal and human studies, and the included studies compared baseline diseased subjects with controls, assessed the effects of investigational treatments, or both. We compared RoB and RQ between the different types of included primary studies. We also assessed the \"informative value\" of each of the separate elements for meta-researchers, based on the notion that variation in reporting may be more interesting for the meta-researcher than consistently high/low or reported/non-reported scores. In general, reporting of experimental details was low. This resulted in frequent unclear risk-of-bias scores. We observed this both for animal and for human studies and both for disease-control comparisons and investigations of experimental treatments. Plots and explorative chi-square tests showed that reporting was slightly better for human studies of investigational treatments than for the other study types. With the evidence reported as is, risk-of-bias assessments for systematic reviews have low informative value other than repeatedly showing that reporting of experimental details needs to improve in all kinds of in vivo research. Particularly for reviews that do not directly inform treatment decisions, it could be efficient to perform a thorough but partial assessment of the quality of the included studies, either of a random subset of the included publications or of a subset of relatively informative elements, comprising, e.g. ethics evaluation, conflicts of interest statements, study limitations, baseline characteristics, and the unit of analysis. This publication suggests several potential procedures.

The collective intelligence of crowds could potentially be harnessed to address global challenges, such as biodiversity loss and species\' extinction. For wisdom to emerge from the crowd, certain conditions are required. Importantly, the crowd should be diverse and people\'s contributions should be independent of one another. Here we investigate a global citizen-science platform-iNaturalist-on which citizens report on wildlife observations, collectively producing maps of species\' spatiotemporal distribution. The organization of global platforms such as iNaturalist around local projects compromises the assumption of diversity and independence, and thus raises concerns regarding the quality of such collectively-generated data. We spent four years closely immersing ourselves in a local community of citizen scientists who reported their wildlife sightings on iNaturalist. Our ethnographic study involved the use of questionnaires, interviews, and analysis of archival materials. Our analysis revealed observers\' nuanced considerations as they chose where, when, and what type of species to monitor, and which observations to report. Following a thematic analysis of the data, we organized observers\' preferences and constraints into four main categories: recordability, community value, personal preferences, and convenience. We show that while some individual partialities can \"cancel each other out\", others are commonly shared among members of the community, potentially biasing the aggregate database of observations. Our discussion draws attention to the way in which widely-shared individual preferences might manifest as spatial, temporal, and crucially, taxonomic biases in the collectively-created database. We offer avenues for continued research that will help better understand-and tackle-individual preferences, with the goal of attenuating collective bias in data, and facilitating the generation of reliable state-of-nature reports. Finally, we offer insights into the broader literature on biases in collective intelligence systems.

The self-controlled case-series (SCCS) research design is increasingly used in pharmacoepidemiologic studies of drug-drug interactions (DDIs), with the target of inference being the incidence rate ratio (IRR) associated with concomitant exposure to the object plus precipitant drug versus the object drug alone. While day-level drug exposure can be inferred from dispensing claims, these inferences may be inaccurate, leading to biased IRRs. Grace periods (periods assuming continued treatment impact after days\' supply exhaustion) are frequently used by researchers, but the impact of grace period decisions on bias from exposure misclassification remains unclear. Motivated by an SCCS study examining the potential DDI between clopidogrel (object) and warfarin (precipitant), we investigated bias due to precipitant or object exposure misclassification using simulations. We show that misclassified precipitant treatment always biases the estimated IRR toward the null, whereas misclassified object treatment may lead to bias in either direction or no bias, depending on the scenario. Further, including a grace period for each object dispensing may unintentionally increase the risk of misclassification bias. To minimize such bias, we recommend 1) avoiding the use of grace periods when specifying object drug exposure episodes; and 2) including a washout period following each precipitant exposed period.

OBJECTIVE: To estimate the size of COVID-19 waves using four indicators across three pandemic periods and assess potential surveillance bias.
METHODS: Case study using data from one region of Switzerland.
METHODS: We compared cases, hospitalizations, deaths, and seroprevalence during three periods including the first three pandemic waves (period 1: Feb-Oct 2020; period 2: Oct 2020-Feb 2021; period 3: Feb-Aug 2021). Data were retrieved from the Federal Office of Public Health or estimated from population-based studies. To assess potential surveillance bias, indicators were compared to a reference indicator, i.e. seroprevalence during periods 1 and 2 and hospitalizations during the period 3. Timeliness of indicators (the duration from data generation to the availability of the information to decision-makers) was also evaluated.
RESULTS: Using seroprevalence (our reference indicator for period 1 and 2), the 2nd wave size was slightly larger (by a ratio of 1.4) than the 1st wave. Compared to seroprevalence, cases largely overestimated the 2nd wave size (2nd vs 1st wave ratio: 6.5), while hospitalizations (ratio: 2.2) and deaths (ratio: 2.9) were more suitable to compare the size of these waves. Using hospitalizations as a reference, the 3rd wave size was slightly smaller (by a ratio of 0.7) than the 2nd wave. Cases or deaths slightly underestimated the 3rd wave size (3rd vs 2nd wave ratio for cases: 0.5; for deaths: 0.4). The seroprevalence was not useful to compare the size of these waves due to high vaccination rates. Across all waves, timeliness for cases and hospitalizations was better than for deaths or seroprevalence.
CONCLUSIONS: The usefulness of indicators for assessing the size of pandemic waves depends on the type of indicator and the period of the pandemic.

The chemical composition of foods is complex, variable, and dependent on many factors. This has a major impact on nutrition research as it foundationally affects our ability to adequately assess the actual intake of nutrients and other compounds. In spite of this, accurate data on nutrient intake are key for investigating the associations and causal relationships between intake, health, and disease risk at the service of developing evidence-based dietary guidance that enables improvements in population health. Here, we exemplify the importance of this challenge by investigating the impact of food content variability on nutrition research using three bioactives as model: flavan-3-ols, (-)-epicatechin, and nitrate. Our results show that common approaches aimed at addressing the high compositional variability of even the same foods impede the accurate assessment of nutrient intake generally. This suggests that the results of many nutrition studies using food composition data are potentially unreliable and carry greater limitations than commonly appreciated, consequently resulting in dietary recommendations with significant limitations and unreliable impact on public health. Thus, current challenges related to nutrient intake assessments need to be addressed and mitigated by the development of improved dietary assessment methods involving the use of nutritional biomarkers.
Studies about the health benefits of foods or nutrients are often inconsistent. One study may find a health benefit of a particular food and may recommend that people increase their consumption of this food to reduce their disease risk. Yet another study may find the opposite. Inconsistent study results fuel confusion and frustration, and reduce trust in research. Limitations in the studies’ designs are likely to be blamed for the inconsistent findings. For example, many studies rely on participants to self-report their food intake and on databases of the nutritional content of food. But people may not accurately report their food intake. Foods vary in their nutritional content, even between two items of the same food such as two apples. And how individuals metabolize foods can further affect the nutrients they receive. Nutritional biomarkers are a potential alternative to measuring dietary intake of specific nutrients. Biomarkers are compounds the body produces when it metabolizes a specific nutrient. Measuring biomarkers therefore give scientists a more accurate and unbiased assessment of nutrient intake. Ottaviani et al. conducted a study to test the differences when estimating nutrient intake using nutritional biomarkers compared with more conventional tools. They analyzed data from a nutrition study that involved over 18,000 participants. The experiments used computer modelling to assess study results using self-reported food intake in combination with food composition database information, or measures of three biomarkers estimating the intake of flavan-3-ols, epicatechin, and nitrates. The models showed that self-reported intake and food database information often led to inaccurate results that did not align well with biomarker measurements. Measuring nutritional biomarkers provides a more accurate and unbiased assessment of nutritional intake. Using these measurements instead of traditional methods for measuring nutrient intake may help increase the reliability of nutrition research. Scientists must work to identify and confirm biomarkers of nutrients to facilitate this work. Using these more precise nutrient measurements in studies may result in more consistent results. It may also lead to more trustworthy recommendations for consumers.

UNASSIGNED: Recent studies showed that Black patients more often have falsely normal oxygen saturation on pulse oximetry compared to White patients. However, whether the racial differences in occult hypoxemia are mediated by other clinical differences is unknown.
UNASSIGNED: We conducted a retrospective case-control study utilizing two large ICU databases (eICU and MIMIC-IV). We defined occult hypoxemia as oxygen saturation on pulse oximetry within 92-98% despite oxygen saturation on arterial blood gas below 90%. We assessed associations of commonly measured clinical factors with occult hypoxemia using multivariable logistic regression and conducted mediation analysis of the racial effect.
UNASSIGNED: Among 24,641 patients, there were 1,855 occult hypoxemia cases and 23,786 controls. In both datasets, Black patients were more likely to have occult hypoxemia (unadjusted odds ratio 1.66 [95%-CI: 1.41-1.95] in eICU and 2.00 [95%-CI: 1.22-3.14] in MIMIC-IV). In multivariable models, higher respiratory rate, PaCO2 and creatinine as well as lower hemoglobin were associated with increased odds of occult hypoxemia. Differences in the commonly measured clinical markers accounted for 9.2% and 44.4% of the racial effect on occult hypoxemia in eICU and MIMIC-IV, respectively.
UNASSIGNED: Clinical differences, in addition to skin tone, might mediate some of the racial differences in occult hypoxemia.

Observational studies of foods and health are susceptible to bias, particularly from confounding between diet and other lifestyle factors. Common methods for deriving dose-response meta-analysis (DRMA) may contribute to biased or overly certain risk estimates. We used DRMA models to evaluate the empirical evidence for colorectal cancer (CRC) association with unprocessed red meat (RM) and processed meats (PM), and the consistency of this association for low and high consumers under different modeling assumptions. Using the Global Burden of Disease project\'s systematic reviews as a start, we compiled a data set of studies of PM with 29 cohorts contributing 23,522,676 person-years and of 23 cohorts for RM totaling 17,259,839 person-years. We fitted DRMA models to lower consumers only [consumption < United States median of PM (21 g/d) or RM (56 g/d)] and compared them with DRMA models using all consumers. To investigate impacts of model selection, we compared classical DRMA models against an empirical model for both lower consumers only and for all consumers. Finally, we assessed if the type of reference consumer (nonconsumer or mixed consumer/nonconsumer) influenced a meta-analysis of the lowest consumption arm. We found no significant association with consumption of 50 g/d RM using an empirical fit with lower consumption (relative risk [RR] 0.93 (0.8-1.02) or all consumption levels (1.04 (0.99-1.10)), while classical models showed RRs as high as 1.09 (1.00-1.18) at 50g/day. PM consumption of 20 g/d was not associated with CRC (1.01 (0.87-1.18)) when using lower consumer data, regardless of model choice. Using all consumption data resulted in association with CRC at 20g/day of PM for the empirical models (1.07 (1.02-1.12)) and with as little as 1g/day for classical models. The empirical DRMA showed nonlinear, nonmonotonic relationships for PM and RM. Nonconsumer reference groups did not affect RM (P = 0.056) or PM (P = 0.937) association with CRC in lowest consumption arms. In conclusion, classical DRMA model assumptions and inclusion of higher consumption levels influence the association between CRC and low RM and PM consumption. Furthermore, a no-risk limit of 0 g/d consumption of RM and PM is inconsistent with the evidence.

Researchers interested in causal questions must deal with two sources of error: random error (random deviation from the true mean value of a distribution), and bias (systematic deviance from the true mean value due to extraneous factors). For some causal questions, randomization is not feasible, and observational studies are necessary. Bias poses a substantial threat to the validity of observational research and can have important consequences for health policy developed from the findings. The current piece describes bias and its sources, outlines proposed methods to estimate its impacts in an observational study, and demonstrates how these methods may be used to inform debate on the causal relationship between medically assisted reproduction (MAR) and health outcomes, using cancer as an example. In doing so, we aim to enlighten researchers who work with observational data, especially regarding the health effects of MAR and infertility, on the pitfalls of bias, and how to address them. We hope that, in combination with the provided example, we can convince readers that estimating the impact of bias in causal epidemiologic research is not only important but necessary to inform the development of robust health policy and clinical practice recommendations.

The slow descent in TB burden, the COVID-19 pandemic, along with the rise of multidrug-resistant strains of Mycobacterium tuberculosis, seriously threaten TB control and the goals of the End TB strategy. To fight back, several vaccine candidates are under development, with some of them undergoing the phases 2B and 3 of the development pipeline. The impact of these vaccines on the general population needs to be addressed using disease-transmission models, and, in a country like China, which last year ranked third in number of cases worldwide, and where the population is aging at a fast pace, the impact of TB vaccination campaigns may depend heavily upon the age of targeted populations, the mechanistic descriptions of the TB vaccines and the coupling between TB dynamics and demographic evolution.
In this work, we studied the potential impact of a new TB vaccine in China targeting adolescents (15-19 y.o.) or older adults (60-64 y.o.), according to varying vaccine descriptions that represent reasonable mechanisms of action leading to prevention of disease, or prevention of recurrence, each of them targetting specific routes to TB disease. To measure the influence of the description of the coupling between transmission dynamics and aging in TB transmission models, we explored two different approaches to compute the evolution of the contact matrices, which relate to the spreading among different age strata.
Our findings highlight the dependence of model-based impact estimates on vaccine profiles and the chosen modeling approach for describing the evolution of contact matrices. Our results also show, in line with previous modeling works, that older adult vaccination is a suitable option in China to reduce the incidence of TB as long as the vaccine is able to protect already exposed individuals.
This study underscores the importance of considering vaccine characteristics and demographic dynamics in shaping TB control strategies. In this sense, older adult vaccination emerges as a promising avenue for mitigating TB transmission in China but also remarks the need for tailored intervention strategies aligned with demographic trends.

The self-controlled case series (SCCS) is a commonly adopted study design in the assessment of vaccine and drug safety. Recurrent event data collected from SCCS studies are typically analyzed using the conditional Poisson model which assumes event times are independent within-cases. This assumption is violated in the presence of event dependence, where the occurrence of an event influences the probability and timing of subsequent events. When event dependence is suspected in an SCCS study, the standard recommendation is to include only the first event from each case in the analysis. However, first event analysis can still yield biased estimates of the exposure relative incidence if the outcome event is not rare. We first demonstrate that the bias in first event analysis can be even higher than previously assumed when subpopulations with different baseline incidence rates are present and describe an improved method for estimating this bias. Subsequently, we propose a novel partitioned analysis method and demonstrate how it can reduce this bias. We provide a recommendation to guide the number of partitions to use with the partitioned analysis, illustrate this recommendation with an example SCCS study of the association between beta-blockers and acute myocardial infarction, and compare the partitioned analysis against other SCCS analysis methods by simulation.