Most studies have some missing data. Jonathan Sterne and colleagues describe the appropriate use and reporting of the multiple imputation approach to dealing with them
Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German 'Federal Institute for Risk Assessment' hosted an 'International Workshop on ...Contact Dermatitis'. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15-20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed.PUBLICATION ABSTRACT
Treatment switching often has a crucial impact on estimates of effectiveness and cost-effectiveness of new oncology treatments. Rank preserving structural failure time models (RPSFTM) and two-stage ...estimation (TSE) methods estimate ‘counterfactual’ (i.e. had there been no switching) survival times and incorporate re-censoring to guard against informative censoring in the counterfactual dataset. However, re-censoring causes a loss of longer term survival information which is problematic when estimates of long-term survival effects are required, as is often the case for health technology assessment decision making. We present a simulation study designed to investigate applications of the RPSFTM and TSE with and without re-censoring, to determine whether re-censoring should always be recommended within adjustment analyses. We investigate a context where switching is from the control group onto the experimental treatment in scenarios with varying switch proportions, treatment effect sizes, treatment effect changes over time, survival function shapes, disease severity and switcher prognosis. Methods were assessed according to their estimation of control group restricted mean survival that would be observed in the absence of switching, up to the end of trial follow-up. We found that analyses which re-censored usually produced negative bias (i.e. underestimating control group restricted mean survival and overestimating the treatment effect), whereas analyses that did not re-censor consistently produced positive bias which was often smaller in magnitude than the bias associated with re-censored analyses, particularly when the treatment effect was high and the switching proportion was low. The RPSFTM with re-censoring generally resulted in increased bias compared to the other methods. We believe that analyses should be conducted with and without re-censoring, as this may provide decision-makers with useful information on where the true treatment effect is likely to lie. Incorporating re-censoring should not always represent the default approach when the objective is to estimate long-term survival times and treatment effects.
Loss to follow-up is often hard to avoid in randomised trials. This article suggests a framework for intention to treat analysis that depends on making plausible assumptions about the missing data ...and including all participants in sensitivity analyses
In oncology trials, control group patients often switch onto the experimental treatment during follow-up, usually after disease progression. In this case, an intention-to-treat analysis will not ...address the policy question of interest – that of whether the new treatment represents an effective and cost-effective use of health care resources, compared to the standard treatment. Rank preserving structural failure time models (RPSFTM), inverse probability of censoring weights (IPCW) and two-stage estimation (TSE) have often been used to adjust for switching to inform treatment reimbursement policy decisions. TSE has been applied using a simple approach (TSEsimp), assuming no time-dependent confounding between the time of disease progression and the time of switch. This is problematic if there is a delay between progression and switch. In this paper we introduce TSEgest, which uses structural nested models and g-estimation to account for time-dependent confounding, and compare it to TSEsimp, RPSFTM and IPCW. We simulated scenarios where control group patients could switch onto the experimental treatment with and without time-dependent confounding being present. We varied switching proportions, treatment effects and censoring proportions. We assessed adjustment methods according to their estimation of control group restricted mean survival times that would have been observed in the absence of switching. All methods performed well in scenarios with no time-dependent confounding. TSEgest and RPSFTM continued to perform well in scenarios with time-dependent confounding, but TSEsimp resulted in substantial bias. IPCW also performed well in scenarios with time-dependent confounding, except when inverse probability weights were high in relation to the size of the group being subjected to weighting, which occurred when there was a combination of modest sample size and high switching proportions. TSEgest represents a useful addition to the collection of methods that may be used to adjust for treatment switching in trials in order to address policy-relevant questions.
This Series shows how racism, xenophobia, discrimination, and the structures that support them are detrimental to health. In this first Series paper, we describe the conceptual model used throughout ...the Series and the underlying principles and definitions. We explore concepts of epistemic injustice, biological experimentation, and misconceptions about race using a historical lens. We focus on the core structural factors of separation and hierarchical power that permeate society and result in the negative health consequences we see. We are at a crucial moment in history, as populist leaders pushing the politics of hate have become more powerful in several countries. These leaders exploit racism, xenophobia, and other forms of discrimination to divide and control populations, with immediate and long-term consequences for both individual and population health. The COVID-19 pandemic and transnational racial justice movements have brought renewed attention to persisting structural racial injustice.
Summary
Background
Fragrance contact allergy is common and is currently screened for using the following European baseline series fragrance markers: fragrance mix (FM)I, FMII, Myroxylon pereirae and ...hydroxyisohexyl 3‐cyclohexene carboxaldehyde.
Objectives
To investigate the validity of patch testing using these fragrance markers in detecting fragrance allergy to 26 individual fragrance substances for which cosmetic ingredient labelling is mandatory within the European Union.
Methods
We conducted a retrospective review of the patch test records of all patients with eczema who underwent testing using the European baseline series, extended with the individual fragrance substances during the period from 2015 to 2016.
Results
Overall, 359 patients (17·2%) reacted to one or more allergens from the labelled fragrance substance series and/or a fragrance marker from the European baseline series. The allergens that were positive with the greatest frequencies were oxidized linalool n = 154; 7·4%, 95% confidence interval (CI) 6·3–8·6, oxidized limonene (n = 89; 4·3%, 95% CI 3·4–5·2) and Evernia furfuracea (n = 44; 2·1%, 95% CI 1·5–2·8). Of the 319 patients who reacted to any of the labelled fragrance substances, only 130 (40·8%) also reacted to a baseline series fragrance marker. The sensitivity of our history‐taking for detecting fragrance allergy was 25·7%.
Conclusions
Given the evolving trends in fragrance allergy, patch testing with FMI, FMII, M. pereirae and hydroxyisohexyl 3‐cyclohexene carboxaldehyde is no longer sufficient for screening for fragrance allergy.
What's already known about this topic?
In Europe, 26 fragrance substances are required to be labelled if present at a concentration of ≥ 0·01 mg g−1 in leave‐on cosmetic products and if present at a concentration of ≥ 0·1 mg g−1 in rinse‐off cosmetic products.
The markers for fragrance allergy in the European baseline series fragrance mix (FM)I, FMII, Myroxylon pereirae and hydroxyisohexyl 3‐cyclohexene carboxaldehyde contain only half of the 26 fragrance substances.
What does this study add?
Currently, the most common fragrance sensitivities in our cohort are sensitivity to oxidized linalool, oxidized limonene (n = 89, 4·3%) and Evernia furfuracea, none of which are represented by the baseline series fragrance markers.
The majority of contact allergy to fragrances is not identified through history‐taking.
Linked Comment: Uter. Br J Dermatol 2018; 178:592–593.
Plain language summary available online
Intelligence is highly heritable
and a major determinant of human health and well-being
. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence
, but ...much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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