Relevance and feasibility of principles for health and environmental risk decision-making.

Globally, national regulatory authorities are both responsible and accountable for health and environmental decisions related to diverse products and risk decision contexts. These authorities provided regulatory oversight and expedited market authorizations of vaccines and other therapeutic products during the COVID-19 pandemic. Regulatory decisions regarding such products and situations depend upon well-established risk assessment and management steps. The underlying processes supporting such decisions were outlined in frameworks describing the complex interactions between factors including risk assessment and management steps as well as principles which help guide risk decision-making. In 2022, experts in risk science proposed a set of 10 guiding principles, further examining the intersection and utility of these principles using 10 diverse risk contexts, and inviting a broader discourse on the application of these principles in risk decision-making. To add to this information, Canadian regulatory practitioners responsible for evaluating health and environmental risks and establishing policies convened at a Health Canada workshop on Principles for Risk Decision-Making. This review reports the results derived from this interactive engagement and provides a first pragmatic analysis of the relevance, importance, and feasibility of such principles for health and environmental risk decision-making within the Canadian regulatory context.

Diagnosis of manganism and manganese neurotoxicity: A workshop report.

With declining exposures to manganese (Mn) in occupational settings, there is a need for more sensitive exposure assessments and clinical diagnostic criteria for manganism and Mn neurotoxicity. To address this issue, a workshop was held on November 12-13, 2020, with international experts on Mn toxicity. The workshop discussions focused on the history of the diagnostic criteria for manganism, including those developed by the Institut de Recherche Robert-Sauvé en Santé et en Sécurité du Travail (IRSST) in Quebec in 2005 and criteria developed by the Chinese government in 2002 and updated in 2006; the utility of biomarkers of exposure; recent developments in magnetic resonance imaging (MRI) for assessing Mn accumulation in the brain and diagnosing manganism; and potential future applications of metabolomics. The suggestions of the participants for updating manganism diagnostic criteria included the consideration of: i) A history of previous occupational and environmental exposure to Mn; ii) relevant clinical symptoms such as dystonia; iii) MRI imaging to document Mn accumulation in the neural tissues, including the basal ganglia; and iv) criteria for the differential diagnosis of manganism and other neurological conditions. Important research gaps include the characterization of Mn exposure and other co-exposures, exploration of the roles of different brain regions with MRI, understanding the complexity of metal ion transporters involved in Mn homeostasis, and a need for information on other neurotransmitter systems and brain regions underlying the pathophysiology of manganism.

Systematic review of epidemiological and toxicological evidence on health effects of fluoride in drinking water.

INTRODUCTION: Fluoride is a naturally occurring substance that is also added to drinking water, dental hygiene products, and food supplements for preventing dental caries. Concerns have been raised about several other potential health risks of fluoride. OBJECTIVE: To conduct a robust synthesis of evidence regarding human health risks due to exposure to fluoride in drinking water, and to develop a point of departure (POD) for setting a health-based value (HBV) for fluoride in drinking water. METHODS: A systematic review of evidence published since recent reviews of human, animal, and in vitro data was carried out. Bradford Hill considerations were used to weigh the evidence for causality. Several key studies were considered for deriving PODs. RESULTS: The current review identified 89 human studies, 199 animal studies, and 10 major in vitro reviews. The weight of evidence on 39 health endpoints was presented. In addition to dental fluorosis, evidence was considered strong for reduction in IQ scores in children, moderate for thyroid dysfunction, weak for kidney dysfunction, and limited for sex hormone disruptions. CONCLUSION: The current review identified moderate dental fluorosis and reduction in IQ scores in children as the most relevant endpoints for establishing an HBV for fluoride in drinking water. PODs were derived for these two endpoints, although there is still some uncertainty in the causal weight of evidence for causality for reducing IQ scores in children and considerable uncertainty in the derivation of its POD. Given our evaluation of the overall weight of evidence, moderate dental fluorosis is suggested as the key endpoint until more evidence is accumulated on possible reduction of IQ scores effects. A POD of 1.56 mg fluoride/L for moderate dental fluorosis may be preferred as a starting point for setting an HBV for fluoride in drinking water to protect against moderate and severe dental fluorosis. Although outside the scope of the current review, precautionary concerns for potential neurodevelopmental cognitive effects may warrant special consideration in the derivation of the HBV for fluoride in drinking water.

Should we screen aging physicians for cognitive decline?

OBJECTIVES: To synthesize evidence relevant for informed decisions concerning cognitive testing of older physicians. METHODS: Relevant literature was systematically searched in Medline, EMBASE, PsycInfo, and ERIC, with key findings abstracted and synthesized. RESULTS: Cognitive abilities of physicians may decline in an age range where they are still practicing. Physician competence and clinical performance may also decline with age. Cognitive scores are lower in physicians referred for assessment because of competency or performance concerns. Many physicians do not accurately self-assess and continue to practice despite declining quality of care; however, perceived cognitive decline, although not an accurate indicator of ability, may accelerate physicians' decision to retire. Physicians are reluctant to report colleagues' cognitive problems. Several issues should be considered in implementing cognitive screening. Most cognitive assessment tools lack normative data for physicians. Scientific evidence linking cognitive test results with physician performance is limited. There is no known level of cognitive decline at which a doctor is no longer fit to practice. Finally, relevant domains of cognitive ability vary across medical specialties. CONCLUSION: Physician cognitive decline may impact clinical performance. If cognitive assessment of older physicians is to be implemented, it should consider challenges of cognitive test result interpretation.

Adjusting for Berkson error in exposure in ordinary and conditional logistic regression and in Poisson regression.

BACKGROUND: INTEROCC is a seven-country cohort study of occupational exposures and brain cancer risk, including occupational exposure to electromagnetic fields (EMF). In the absence of data on individual exposures, a Job Exposure Matrix (JEM) may be used to construct likely exposure scenarios in occupational settings. This tool was constructed using statistical summaries of exposure to EMF for various occupational categories for a comparable group of workers. METHODS: In this study, we use the Canadian data from INTEROCC to determine the best EMF exposure surrogate/estimate from three appropriately chosen surrogates from the JEM, along with a fourth surrogate based on Berkson error adjustments obtained via numerical approximation of the likelihood function. In this article, we examine the case in which exposures are gamma-distributed for each occupation in the JEM, as an alternative to the log-normal exposure distribution considered in a previous study conducted by our research team. We also study using those surrogates and the Berkson error adjustment in Poisson regression and conditional logistic regression. RESULTS: Simulations show that the introduced methods of Berkson error adjustment for non-stratified analyses provide accurate estimates of the risk of developing tumors in case of gamma exposure model. Alternatively, and under some technical assumptions, the arithmetic mean is the best surrogate when a gamma-distribution is used as an exposure model. Simulations also show that none of the present methods could provide an accurate estimate of the risk in case of stratified analyses. CONCLUSION: While our previous study found the geometric mean to be the best exposure surrogate, the present study suggests that the best surrogate is dependent on the exposure model; the arithmetic means in case of gamma-exposure model and the geometric means in case of log-normal exposure model. However, we could present a better method of Berkson error adjustment for each of the two exposure models. Our results provide useful guidance on the application of JEMs for occupational exposure assessments, with adjustment for Berkson error.

Myocarditis and Pericarditis Post-mRNA COVID-19 Vaccination: Insights from a Pharmacovigilance Perspective.

Concerns remain regarding the rare cardiovascular adverse events, myocarditis and pericarditis (myo/pericarditis), particularly in younger individuals following mRNA COVID-19 vaccination. Our study aimed to comprehensively assess potential safety signals related to these cardiac events following the primary and booster doses, with a specific focus on younger populations, including children as young as 6 months of age. Using the Vaccine Adverse Events Reporting System (VAERS), the United States national passive surveillance system, we conducted a retrospective pharmacovigilance study analyzing spontaneous reports of myo/pericarditis. We employed both frequentist and Bayesian methods and conducted subgroup analyses by age, sex, and vaccine dose. We observed a higher reporting rate of myo/pericarditis following the primary vaccine series, particularly in males and mainly after the second dose. However, booster doses demonstrated a lower number of reported cases, with no significant signals detected after the fourth or fifth doses. In children and young adults, we observed notable age and sex differences in the reporting of myo/pericarditis cases. Males in the 12-17 and 18-24-year-old age groups had the highest number of cases, with significant signals for both males and females after the second dose. We also identified an increased reporting for a spectrum of cardiovascular symptoms such as chest pain and dyspnea, which increased with age, and were reported more frequently than myo/pericarditis. The present study identified signals of myo/pericarditis and related cardiovascular symptoms after mRNA COVID-19 vaccination, especially among children and adolescents. These findings underline the importance for continued vaccine surveillance and the need for further studies to confirm these results and to determine their clinical implications in public health decision-making, especially for younger populations.

Effects of vaginal microbiota transfer on the neurodevelopment and microbiome of cesarean-born infants: A blinded randomized controlled trial.

The microbiomes of cesarean-born infants differ from vaginally delivered infants and are associated with increased disease risks. Vaginal microbiota transfer (VMT) to newborns may reverse C-section-related microbiome disturbances. Here, we evaluated the effect of VMT by exposing newborns to maternal vaginal fluids and assessing neurodevelopment, as well as the fecal microbiota and metabolome. Sixty-eight cesarean-delivered infants were randomly assigned a VMT or saline gauze intervention immediately after delivery in a triple-blind manner (ChiCTR2000031326). Adverse events were not significantly different between the two groups. Infant neurodevelopment, as measured by the Ages and Stages Questionnaire (ASQ-3) score at 6 months, was significantly higher with VMT than saline. VMT significantly accelerated gut microbiota maturation and regulated levels of certain fecal metabolites and metabolic functions, including carbohydrate, energy, and amino acid metabolisms, within 42 days after birth. Overall, VMT is likely safe and may partially normalize neurodevelopment and the fecal microbiome in cesarean-delivered infants.

Interventions for COVID-19 Vaccine Hesitancy: A Systematic Review and Narrative Synthesis.

Vaccines effectively protect against COVID-19, but vaccine hesitancy and refusal hinder vaccination rates. This systematic review aimed to (1) review and describe current interventions for addressing COVID-19 vaccine hesitancy/refusal and (2) assess whether these interventions are effective for increasing vaccine uptake. The protocol was registered prospectively on PROSPERO and comprehensive search included Medline, Embase, CINAHL, PsycInfo, and Web of Science databases. Only studies that evaluated the effectiveness of non-financial interventions to address COVID-19 vaccine hesitancy were included, while those focusing intentions or financial incentive were excluded. Risk of bias for all included studies was evaluated using Cochrane risk of bias tools. In total, six articles were included in the review (total participants n = 200,720). A narrative synthesis was performed due to the absence of common quantitative metrics. Except for one randomized controlled trial, all studies reported that interventions were effective, increasing COVID-19 vaccination rates. However, non-randomized studies were subject to confounding biases. Evidence on the effectiveness of COVID-19 vaccine hesitancy interventions remains limited and further evidence is needed for the development of clear guidance on effective interventions to increase vaccine uptake.

Risk of myocarditis and pericarditis in mRNA COVID-19-vaccinated and unvaccinated populations: a systematic review and meta-analysis.

OBJECTIVE: To summarise the available evidence on the risk of myocarditis and/or pericarditis following mRNA COVID-19 vaccination, compared with the risk among unvaccinated individuals in the absence of COVID-19 infection. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic databases (Medline, Embase, Web of Science and WHO Global Literature on Coronavirus Disease), preprint repositories (medRxiv and bioRxiv), reference lists and grey literature were searched from 1 December 2020 until 31 October 2022. STUDY SELECTION: Epidemiological studies of individuals of any age who received at least one dose of an mRNA COVID-19 vaccine, reported a risk of myo/pericarditis and compared the risk of myo/pericarditis to individuals who did not receive any dose of an mRNA COVID-19 vaccine. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently conducted screening and data extraction. The rate of myo/pericarditis among vaccinated and unvaccinated groups was recorded, and the rate ratios were calculated. Additionally, the total number of individuals, case ascertainment criteria, percentage of males and history of SARS-CoV-2 infection were extracted for each study. Meta-analysis was done using a random-effects model. RESULTS: Seven studies met the inclusion criteria, of which six were included in the quantitative synthesis. Our meta-analysis indicates that within 30-day follow-up period, vaccinated individuals were twice as likely to develop myo/pericarditis in the absence of SARS-CoV-2 infection compared to unvaccinated individuals, with a rate ratio of 2.05 (95% CI 1.49-2.82). CONCLUSION: Although the absolute number of observed myo/pericarditis cases remains quite low, a higher risk was detected in those who received mRNA COVID-19 vaccinations compared with unvaccinated individuals in the absence of SARS-CoV-2 infection. Given the effectiveness of mRNA COVID-19 vaccines in preventing severe illnesses, hospitalisations and deaths, future research should focus on accurately determining the rates of myo/pericarditis linked to mRNA COVID-19 vaccines, understanding the biological mechanisms behind these rare cardiac events and identifying those most at risk.

Concomitant use of statins and sodium-glucose co-transporter 2 inhibitors and the risk of myotoxicity reporting: A disproportionality analysis.

AIMS: Recent case reports have suggested that sodium-glucose co-transporter 2 (SGLT2) inhibitors may interact with statins to increase their risk of myotoxicity. We assessed the risk of myotoxicity reporting associated with concomitant use of SGLT2 inhibitors and statins. METHODS: We queried the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 2013 to 2021 for reports including SGLT2 inhibitors, statins or both. We estimated several measures of disproportionate reporting of myopathy and rhabdomyolysis associated with concomitant use of SGLT2 inhibitors and statins: reporting odds ratio (ROR) with 95% confidence interval (CI), Ω shrinkage measure (safety signal if >0) and an extension of the proportional reporting ratio (PRR) (two-criteria set, safety signal if both criteria are met), using the full FAERS dataset as the reference set. In sensitivity analyses, we focussed on specific SGLT2 inhibitor-statin pairs with higher interaction potential (canagliflozin-rosuvastatin, empagliflozin-rosuvastatin) and accounted for stimulated reporting. RESULTS: There were 456 myopathy and 77 rhabdomyolysis reports involving both an SGLT2 inhibitor and a statin. Concomitant use of SGLT2 inhibitors and statins was not associated with an increased risk of myopathy (ROR 0.79, 95% CI 0.70 to 0.89) or rhabdomyolysis (ROR 0.58, 95% CI 0.41 to 0.83) reporting. For both outcomes, the Ω shrinkage measure was negative and only one criterion of the PRR extension was met. SGLT2 inhibitor-statin pairs with higher interaction potential yielded potential signals for rhabdomyolysis; these signals disappeared after accounting for stimulated reporting. CONCLUSION: There was no increased risk of myotoxicity reporting associated with concomitant use of SGLT2 inhibitors and statins or for specific drug pairs.

The incidence of post-traumatic stress disorder following traumatic childbirth: A systematic review and meta-analysis.

BACKGROUND: Although birth trauma may be a risk factor for postpartum post-traumatic stress disorder (PTSD), no systematic review regarding the incidence of postpartum PTSD in women with traumatic childbirth has been reported. OBJECTIVE: To estimate the incidence of PTSD in women following traumatic childbirth by systematically reviewing and synthesizing all available evidence. SEARCH STRATEGY: Six databases were searched using a combination of related terms for birth trauma and PTSD. SELECTION CRITERIA: Cohort and cross-sectional studies that were related to traumatic childbirth and PTSD were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened potentially relevant studies and extracted key data elements. A series of meta-analyses were conducted using STATA 17.0 software, with pooled incidence rates estimated using random effects models. MAIN RESULTS: A total of nine studies were included in this study. The pooled incidence of PTSD after traumatic childbirth was 19.4% (95% confidence interval 11.9%-26.5%). The incidence of PTSD varied with the scales used to assess traumatic birth and PTSD, evaluation times of PTSD after childbirth, and types of study participants. CONCLUSIONS: The incidence of PTSD in women with traumatic childbirth is about 19%, higher than the general obstetric population, suggesting that trauma-related care for them should be enhanced.

A value of information framework for assessing the trade-offs associated with uncertainty, duration, and cost of chemical toxicity testing.

A number of investigators have explored the use of value of information (VOI) analysis to evaluate alternative information collection procedures in diverse decision-making contexts. This paper presents an analytic framework for determining the value of toxicity information used in risk-based decision making. The framework is specifically designed to explore the trade-offs between cost, timeliness, and uncertainty reduction associated with different toxicity-testing methodologies. The use of the proposed framework is demonstrated by two illustrative applications which, although based on simplified assumptions, show the insights that can be obtained through the use of VOI analysis. Specifically, these results suggest that timeliness of information collection has a significant impact on estimates of the VOI of chemical toxicity tests, even in the presence of smaller reductions in uncertainty. The framework introduces the concept of the expected value of delayed sample information, as an extension to the usual expected value of sample information, to accommodate the reductions in value resulting from delayed decision making. Our analysis also suggests that lower cost and higher throughput testing also may be beneficial in terms of public health benefits by increasing the number of substances that can be evaluated within a given budget. When the relative value is expressed in terms of return-on-investment per testing strategy, the differences can be substantial.

Disproportionality analysis of adverse neurological and psychiatric reactions with the ChAdOx1 (Oxford-AstraZeneca) and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines in the United Kingdom.

BACKGROUND: Information on neurological and psychiatric adverse events following immunization (AEFIs) with COVID-19 vaccines is limited. RESEARCH DESIGN & METHODS: We examined and compared neurological and psychiatric AEFIS reports related to BNT162b2 (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines and recorded in the United Kingdom Medicines and Healthcare products Regulatory Agency between 9 December 2020 and 30 June 2021. RESULTS: As of 30 June 2021, 46.1 million doses of ChAdOx1 and 30.3 million doses of BNT162b2 had been administered. The most frequently reported AEFI was headache with 1,686 and 575 cases per million doses of ChAdOx1 and BNT162b2, respectively. AEFIs more frequently reported after CHAdOx1 compared with BNT162b2 vaccination were Guillain-Barré syndrome (OR, 95% CI = 2.53, 1.82-3.51), freezing (6.66, 3.12-14.22), cluster headache (1.53, 1.28-1.84), migraine (1.23,1.17-1.30), postural dizziness (1.24,1.13-1.37), tremor (2.86, 2.68-3.05), headache (1.40, 1.38-1.43), paresthesia (1.11, 1.06-1.16), delirium (1.85, 1.45-2.36), hallucination (2.20, 1.82-2.66), poor quality sleep (1.53, 1.26-1.85), and nervousness (1.54, 1.26-1.89) Reactions less frequently reported with ChAdOx1 than with BNT162b2 were Bell's palsy (0.47, 0.41-0.55), anosmia (0.58, 0.47-0.71), facial paralysis (0.35, 0.29-0.41), dysgeusia (0.68, 0.62-0.73), presyncope (0.48, 0.42-0.55), syncope (0.63, 0.58-0.67), and anxiety (0.75 (0.67-0.85). CONCLUSION: Neurological and psychiatric AEFIs were relatively infrequent, but each vaccine was associated with a distinctive toxic profile.

We examined reports on adverse neurological and psychiatric effects following immunization with BNT162b2 (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) for COVID-19 to the United Kingdom Medicines and Healthcare products Regulatory Agency between 9 December 2020 and 30 June 2021. Adverse effects following immunization (AEFIs) were relatively infrequent. Compared to BNT162b2, Guillain-Barré syndrome, freezing phenomenon, cluster headache, migraine, postural dizziness, tremor, headache, paresthesia, delirium, hallucination, poor quality sleep, and nervousness were more frequently reported for ChAdOx1. Reactions less frequently reported for ChAdOx1 than for BNT162b2 were Bell's palsy, anosmia, facial paralysis, dysgeusia, presyncope, syncope, and anxiety.

Association between exclusive breastfeeding and postpartum post-traumatic stress disorder.

BACKGROUND: Research on the association between breastfeeding and postpartum post-traumatic stress disorder (PTSD) is sparse. This study aimed to examine the association between exclusive breastfeeding up to 42 days after childbirth and postpartum PTSD. METHODS: An epidemiologic study was conducted in a tertiary hospital in China between October 2019 and October 2020. Eligible mothers were recruited at 3 days after childbirth and assessed using the Post-Traumatic Stress Disorder Checklist - Civilian version (PCL-C) for PTSD at 42 days postpartum. The independent association between exclusive breastfeeding up to 42 days after childbirth and postpartum PTSD was estimated using log-binomial regression models, after adjusting for potential confounders. RESULTS: Ninety-two of 759 (12.1%) mothers developed postpartum PTSD within 42 days after childbirth. Compared with partially breastfeeding mothers, exclusively breastfeeding mothers had lower risks of postpartum PTSD (relative risk [RR] 0.28; 95% confidence interval [CI] 0.13, 0.59), re-experience (RR 0.48; 95% CI 0.30, 0.76), avoidance (RR 0.55; 95% CI 0.32, 0.97), and hyperarousal (RR 0.52; 95% CI 0.34, 0.78). After adjustment for family support, parity, mode of delivery, perceived birth trauma, early contact / suckling, and rooming-in, associations between exclusive breastfeeding and postpartum PTSD remained significant: the overall PTSD adjusted relative risk [aRR] was 0.31; (95% CI 0.15, 0.66), with a re-experience aRR of 0.48; (95% CI 0.30, 0.77) and hyperarousal aRR of 0.56; (95% CI 0.37, 0.85). CONCLUSION: Exclusive breastfeeding up to 42 days after childbirth was associated with reduced risk of postpartum PTSD. While the potential for reverse causation cannot be ruled out, strategies to improve rates of exclusive breastfeeding through teaching, counselling, and support may benefit mothers and their infants by reducing the risk of postpartum PTSD.

Development of an Evidence-Based Risk Assessment Framework.

Assessment of potential human health risks associated with environmental and other agents requires careful evaluation of all available and relevant evidence for the agent of interest, including both data-rich and data-poor agents. With the advent of new approach methodologies in toxicological risk assessment, guidance on integrating evidence from mul-tiple evidence streams is needed to ensure that all available data is given due consideration in both qualitative and quantitative risk assessment. The present report summarizes the discussions among academic, government, and private sector participants from North America and Europe in an international workshop convened to explore the development of an evidence-based risk assessment framework, taking into account all available evidence in an appropriate manner in order to arrive at the best possible characterization of potential human health risks and associated uncertainty. Although consensus among workshop participants was not a specific goal, there was general agreement on the key consider-ations involved in evidence-based risk assessment incorporating 21st century science into human health risk assessment. These considerations have been embodied into an overarching prototype framework for evidence integration that will be explored in more depth in a follow-up meeting.

Principles of risk decision-making.

Risk management decisions in public health require consideration of a number of complex, often conflicting factors. The aim of this review was to propose a set of 10 fundamental principles to guide risk decision-making. Although each of these principles is sound in its own right, the guidance provided by different principles might lead the decision-maker in different directions. For example, where the precautionary principle advocates for preemptive risk management action under situations of scientific uncertainty and potentially catastrophic consequences, the principle of risk-based decision-making encourages decision-makers to focus on established and modifiable risks, where a return on the investment in risk management is all but guaranteed in the near term. To evaluate the applicability of the 10 principles in practice, one needs to consider 10 diverse risk issues of broad concern and explore which of these principles are most appropriate in different contexts. The 10 principles presented here afford substantive insight into the process of risk management decision-making, although decision-makers will ultimately need to exercise judgment in reaching appropriate risk decisions, accounting for all of the scientific and extra-scientific factors relevant to the risk decision at hand.

Biomarkers of environmental manganese exposure.

We conducted a critical review on biomarkers of environmental manganese (Mn) exposure to answer the following questions: 1) are there reliable biomarkers of internal Mn exposure (Mn in biological matrices) associated with external metrics of Mn exposure (Mn in environmental media)? and 2) are there accurate reference values (RVs) for Mn in biological matrices? Three bibliographic databases were searched for relevant references and identified references were screened by two independent reviewers. Of the 6342 unique references identified, 86 articles were retained for data abstraction. Our analysis of currently available evidence suggests that Mn levels in blood and urine are not useful biomarkers of Mn exposure in non-occupational settings. The strength of the association between Mn in environmental media and saliva was variable. Findings regarding the utility of hair Mn as a biomarker of environmental Mn exposure are inconsistent. Measurements of Mn in teeth are technically challenging and findings on Mn in tooth components are scarce. In non-occupationally exposed individuals, bone Mn measurements using in vivo neutron activation analysis (IVNAA) are associated with large uncertainties. Findings suggest that Mn in nails may reflect Mn in environmental media and discriminate between groups of individuals exposed to different environmental Mn levels, although more research is needed. Currently, there is no strong evidence for any biological matrix as a valid biomarker of Mn exposure in non-occupational settings. Because of methodological limitations in studies aimed at derivation of RVs for Mn in biological materials, accurate RVs are scarce.

Risk of Myocarditis and Pericarditis among Young Adults following mRNA COVID-19 Vaccinations.

There have been reports of cases of myocarditis and pericarditis as rare complications following mRNA COVID-19 vaccinations among young adults. While most reported cases are mild, this potential vaccine safety signal should be closely monitored. Using data from the CDC and the Vaccine Adverse Event Reporting System (VAERS), we calculated the combined reporting rate of myocarditis and pericarditis stratified by age group, sex, vaccine dose, and manufacturer, and compared these rates to the crude background incidence rates. Compared to the general population prior to the administration of the first COVID-19 vaccines in December 2020, we identified a higher-than-expected reporting rate of myocarditis and pericarditis following mRNA vaccination; the risk was higher after a second vaccine dose, higher in males than in females, and decreased with age. The highest risk was seen in males 12-17 years of age with approximately 6 cases per 100,000 second doses. Our findings suggest an increased risk of myocarditis and pericarditis in young males following a second dose of an mRNA COVID-19 vaccine. Since these findings are based on safety signals derived from passive surveillance data, confirmatory epidemiological studies should be undertaken.

Systemic quinolones and risk of retinal detachment III: a nested case-control study using a US electronic health records database.

BACKGROUND: Quinolones are popular antibiotics that are known for their potency, broad coverage, and reasonable safety. Concerns have been raised about a possible association between quinolones and retinal detachment (RD). METHODS: We conducted a nested case-control study using electronic health records (EHR) from the Health Facts® Database. The initial cohort included all patients who were admitted between 2000 and 2016, with no history of eye disease, and had a minimum medical history of one year. Eligible cases comprised inpatients who were first admitted with a primary diagnosis of RD between 2010 and 2015. Each eligible case was matched without replacement to five unique controls by sex, race, age, and period-at-risk. We used conditional logistic regression to calculate RD risk, adjusting for exposure to other medications, and major risk factors. RESULTS: We identified 772 cases and 3860 controls. Whereas our primary analysis of all subjects revealed no quinolone-associated RD risk, elevated but non-significant risks were noted in African Americans (ciprofloxacin and levofloxacin), those aged 56-70 years old (moxifloxacin), and women (ciprofloxacin). CONCLUSION: Our study did not identify an elevated RD risk within 30 days following systemic administration of quinolone antibiotics. Suggestions of increased risk observed in some population subgroups warrant further investigation.

Prevalence of eczema between cesarean-born and vaginal-born infants within 1 year of age: a systematic review and meta-analysis.

This study aims to quantify the difference in prevalence of eczema between cesarean-born and vaginal-born infants within 1 year of age through a systematic review and meta-analysis. Six electronic databases were searched from inception to August 31, 2021. Studies were included if they reported the prevalence of eczema in infants within 1 year of age with specified mode of delivery. The quality of included studies was assessed using the Joanna Briggs Instrument Critical Appraisal Checklist. Pooled prevalence and odds ratio (OR) were estimated by meta-analyses of included studies. Meta-regression was conducted to explore factors affecting heterogeneity of the prevalence of eczema. Nine studies were included with 3,758 cesarean-born infants and 9,631 vaginal-born infants. The prevalence of eczema in cesarean-born infants [27.8%; 95% confidence interval (CI): 17.7-39.2] was higher than in vaginal-born infants (20.1%; 95% CI: 13.9-28.1), with a pooled OR of 1.31 (95% CI: 1.04-1.65). Subgroup analyses showed that the prevalence of eczema in cesarean-born infants varied according to country, study design, and method of ascertainment. Additionally, the pooled prevalence of eczema in vaginal-born infants differed by age at which eczema was identified. Meta-regression analysis showed that study design and eczema ascertainment method were significant sources of heterogeneity. CONCLUSION: About 28% of cesarean-born infants within 1 year of age developed eczema, significantly higher than the 20% rate or occurrence seen in vaginal-born infants. PROTOCOL REGISTRATION: CRD 42,020,152,437. WHAT IS KNOWN: • Eczema, a complex inflammatory cutaneous disorder characterized by immune mediated inflammation and epidermal barrier dysfunction, is one of the most common allergic disorders in infants. • Eczema may increase the risk of immune-mediated inflammatory disease such as food allergy, asthma, and allergic rhinitis, leading to psychological and social burdens on affected individuals and their families. • Mode of delivery may be associated with the risk of developing eczema, although further studies are needed to clarify such differences. WHAT IS NEW: • This is the first systematic review designed to estimate the prevalence of eczema in cesarean- and vaginal-born infants within 1 year of age. • Cesarean delivery may increase the risk of developing eczema in infants within the first year of life.