Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Systematic review of use and interpretation of dietary diversity indicators in nutrition- sensitive agriculture literature

International audienceIn the past decade, food group dietary diversity indicators (FGIs) have increasingly been used to assess the impact of agriculture on food security or nutrition. Following a structured search strategy and a two-phase screening process, 46 studies investigating associations between agriculture and food security or nutrition through the use of simple FGIs were assessed for how the indicators were constructed and interpreted. Most studies based on individual level FGIs were consistent with published guidance, while many of the studies measuring households’ dietary diversity were not, particularly in terms of interpretation of the indicators or of food group classification. Efforts are needed to harmonize the way FGIs are used and interpreted in order to enhance comparability across studies and allow meta-analyses of the association between agriculture and food security or nutrition

A Simple 3-Parameter Model for Examining Adaptation in Speech and Voice Production

Sensorimotor adaptation experiments are commonly used to examine motor learning behavior and to uncover information about the underlying control mechanisms of many motor behaviors, including speech production. In the speech and voice domains, aspects of the acoustic signal are shifted/perturbed over time via auditory feedback manipulations. In response, speakers alter their production in the opposite direction of the shift so that their perceived production is closer to what they intended. This process relies on a combination of feedback and feedforward control mechanisms that are difficult to disentangle. The current study describes and tests a simple 3-parameter mathematical model that quantifies the relative contribution of feedback and feedforward control mechanisms to sensorimotor adaptation. The model is a simplified version of the DIVA model, an adaptive neural network model of speech motor control. The three fitting parameters of SimpleDIVA are associated with the three key subsystems involved in speech motor control, namely auditory feedback control, somatosensory feedback control, and feedforward control. The model is tested through computer simulations that identify optimal model fits to six existing sensorimotor adaptation datasets. We show its utility in (1) interpreting the results of adaptation experiments involving the first and second formant frequencies as well as fundamental frequency; (2) assessing the effects of masking noise in adaptation paradigms; (3) fitting more than one perturbation dimension simultaneously; (4) examining sensorimotor adaptation at different timepoints in the production signal; and (5) quantitatively predicting responses in one experiment using parameters derived from another experiment. The model simulations produce excellent fits to real data across different types of perturbations and experimental paradigms (mean correlation between data and model fits across all six studies = 0.95 ± 0.02). The model parameters provide a mechanistic explanation for the behavioral responses to the adaptation paradigm that are not readily available from the behavioral responses alone. Overall, SimpleDIVA offers new insights into speech and voice motor control and has the potential to inform future directions of speech rehabilitation research in disordered populations. Simulation software, including an easy-to-use graphical user interface, is publicly available to facilitate the use of the model in future studies.</p

Persistent environmental contaminants in human milk: Concentrations and time trends in Italy

Breast milk monitoring studies of persistent and toxic environmental contaminants are of primary importance for carrying out an adequate risk assessment at the actual levels of human exposure and represent a major source of information on infant perinatal exposure. Milk specimens from mothers of the general population of the Venice and Rome areas were collected over the 1998-2001 period, pooled, and analyzed for selected persistent organic pollutants such as polychlorodibenzodioxins (PCDDs), polychlorodibenzofurans (PCDFs), polychlorobiphenyls (PCBs), organochlorinated pesticides (p,p'-DDE, p,p'-DDT, hexachlorobenzene), and polybromodiphenyl ethers (PBDEs), and the heavy metals Cd, Co, Cu, Hg, Mn, Pb, Sn, and Zn. The goal was to verify whether mother milk from the Venice area, whose lagoon is partly under direct industrial impact, had a contaminant load greater than that from the Rome area, primarily urban. For mothers from the Venice area, the correlation between fish and fishery product consumption and contaminant concentrations in milk was also explored, with however inconclusive results. The concentrations of PCDDs, PCDFs, dioxin-like PCBs, and organochlorinated pesticides determined in this study were compared with those available from a previous analytical work carried out on 1987 human milk pools of domestic origin: the declining trend of the aforesaid contaminants in milk is confirmed to be in agreement with what was observed in other European countries. The breast milk content of (137)Cs and (40)K radionuclides was also determined and compared with data obtained in other research programmes carried out in Italy: the health risk for breastfed infants was deemed to be not significant

Mortality from cancer and other causes among airline cabin attendants in Europe: a collaborative cohort study in eight countries

There is concern about the health effects of exposure to cosmic radiation during air travel. To study the potential health effects of this and occupational exposures, the authors investigated mortality patterns among more than 44,000 airline cabin crew members in Europe. A cohort study was performed in eight European countries, yielding approximately 655,000 person-years of follow-up. Observed numbers of deaths were compared with expected numbers based on national mortality rates. Among female cabin crew, overall mortality (standardized mortality ratio (SMR) = 0.80, 95% confidence interval (CI): 0.73, 0.88) and all-cancer mortality (SMR = 0.78, 95% CI: 0.66, 0.95) were slightly reduced, while breast cancer mortality was slightly but nonsignificantly increased (SMR = 1.11, 95% CI: 0.82, 1.48). In contrast, overall mortality (SMR = 1.09, 95% CI: 1.00, 1.18) and mortality from skin cancer (for malignant melanoma, SMR = 1.93, 95% CI: 0.70, 4.44) among male cabin crew were somewhat increased. The authors noted excess mortality from aircraft accidents and from acquired immunodeficiency syndrome in males. Among airline cabin crew in Europe, there was no increase in mortality that could be attributed to cosmic radiation or other occupational exposures to any substantial extent. The risk of skin cancer among male crew members requires further attention

Occupational risks for uveal melanoma results from a case-control study in nine European countries.

International audienceOBJECTIVE: Uveal melanoma is a rare disease with poor prognosis and largely unknown etiology. We studied potential occupational risk factors. METHODS: A population based case-control study was undertaken during 1995-1997 in nine European countries using population and colon cancer controls with personal interviews. Occupational exposure to sunlight and artificial UV radiation was assessed with a job exposure matrix. In total, 320 uveal melanoma cases were eligible at pathology review, and 292 cases were interviewed, participation 91%. Out of 3357 population controls, 2062 were interviewed, 61%, and out of 1272 cancer controls 1094 were interviewed, 86%. RESULTS: Using population controls, occupational exposure to sunlight was not associated with an increased risk (RR=1.24, 95% CI=0.88-1.74), while an excess risk found with use of colon cancer controls was attributed to confounding factors. An excess risk in welders was restricted to the French part of the data. Cooks, RR=2.40; cleaners, RR 2.15; and laundry workers, RR=3.14, were at increased risk of uveal melanoma. CONCLUSION: Our study does overall not support an association between occupational sunlight exposure and risk of uveal melanoma. The finding of an excess risk of eye melanoma in cooks in several European countries is intriguing

Development of a dichotomous indicator for population-level assessment of dietary diversity in women of reproductive age

Background: Dietary diversity is a key element of diet quality, but diets of women of reproductive age (WRA; aged 15-49 y) in resource-poor settings are often deficient in a range of micronutrients. Previous work showed associations between simple food-group diversity indicators (FGIs) and micronutrient adequacy among WRA. For operational and advocacy purposes, however, there is strong demand for a dichotomous indicator reflecting an acceptable level of dietary diversity. Objective: The aim of the study was to develop a dichotomous indicator of dietary diversity inWRA. Methods: We performed a secondary analysis of 9 data sets containing quantitative dietary data from WRA in resource-poor settings (total n = 4166). From the raw dietary data, we calculated an individual "mean probability of adequacy" (MPA) across 11 micronutrients. Several candidate FGIs were constructed. Indicator performance in predicting an MPA > 0.60 was assessed within each data set by using receiver-operating characteristic analysis and sensitivity and specificity analysis at various FGI cutoffs. The analysis was performed separately for nonpregnant and nonlactating (NPNL) women and for lactating women. Results: We identified 2 "best candidate" dichotomous indicators on the basis of 9- or 10-point food-group scores (FGI-9 and FGI-10) with a cutoff of ≥ 5 food groups. Both were significantly correlated to MPA in each site (P < 0.001). Areas under the curve were moderate, ranging from 0.62 to 0.82 among NPNL women and from 0.56 to 0.90 among lactating women. Comparisons of results slightly favored FGI-10 for all women. Conclusions: When resource-intensive dietary methods are not feasible, a simple dichotomous indicator based on a cutoff of ≥ 5 of 10 defined food groups reflects "minimum dietary diversity for women of reproductive age." According to the conclusions of a consensus meeting of experts, this indicator is well suited for population-level assessment, advocacy, and possibly also for tracking of change in dietary diversity across time.</p