ObjectivesTo estimate occupational differences in COVID-19 mortality and test whether these are confounded by factors such as regional differences, ethnicity and education or due to non-workplace factors, such as deprivation or prepandemic health.MethodsUsing a cohort study of over 14 million people aged 40–64 years living in England, we analysed occupational differences in death involving COVID-19, assessed between 24 January 2020 and 28 December 2020.We estimated age-standardised mortality rates (ASMRs) per 100 000 person-years at risk stratified by sex and occupation. We estimated the effect of occupation on COVID-19 mortality using Cox proportional hazard models adjusted for confounding factors. We further adjusted for non-workplace factors and interpreted the residual effects of occupation as being due to workplace exposures to SARS-CoV-2.ResultsIn men, the ASMRs were highest among those working as taxi and cab drivers or chauffeurs at 119.7 deaths per 100 000 (95% CI 98.0 to 141.4), followed by other elementary occupations at 106.5 (84.5 to 132.4) and care workers and home carers at 99.2 (74.5 to 129.4). Adjusting for confounding factors strongly attenuated the HRs for many occupations, but many remained at elevated risk. Adjusting for living conditions reduced further the HRs, and many occupations were no longer at excess risk. For most occupations, confounding factors and mediators other than workplace exposure to SARS-CoV-2 explained 70%–80% of the excess age-adjusted occupational differences.ConclusionsWorking conditions play a role in COVID-19 mortality, particularly in occupations involving contact with patients or the public. However, there is also a substantial contribution from non-workplace factors.

ObjectiveInvestigated clinical effectiveness and cost-effectiveness of a person-centred intervention for informal carers/caregivers of stroke survivors.DesignPragmatic cluster randomised controlled trial (cRCT) with economic and process evaluation.SettingClusters were services, from a UK voluntary sector specialist provider, delivering support primarily in the homes of stroke survivors and informal carers.ParticipantsAdult carers in participating clusters were referred to the study by cluster staff following initial support contact.InterventionsIntervention was the Carer Support Needs Assessment Tool for Stroke: a staff-facilitated, carer-led approach to help identify, prioritise and address the specific support needs of carers. It required at least one face-to-face support contact dedicated to carers, with reviews as required. Control was usual care, which included carer support (unstructured and variable).Outcome measuresParticipants provided study entry and self-reported outcome data by postal questionnaires, 3 and 6 months after first contact by cluster staff. Primary outcome: 3-month caregiver strain (Family Appraisal of Caregiving Questionnaire, FACQ). Secondary outcomes: FACQ subscales of caregiver distress and positive appraisals of caregiving, mood (Hospital Anxiety and Depression Scale) and satisfaction with stroke services (Pound). The economic evaluation included self-reported healthcare utilisation, intervention costs and EQ-5D-5L.Randomisation and maskingClusters were recruited before randomisation to intervention or control, with stratification for size of service. Cluster staff could not be masked as training was required for participation. Carer research participants provided self-reported outcome data unaware of allocation; they consented to follow-up data collection only.ResultsBetween 1 February 2017 and 31 July 2018, 35 randomised clusters (18 intervention; 17 control) recruited 414 cRCT carers (208 intervention; 206 control). Study entry characteristics were well balanced. Primary outcome measure: intention-to-treat analysis for 84% retained participants (175 intervention; 174 control) found mean (SD) FACQ carer strain at 3 months to be 3.11 (0.87) in the control group compared with 3.03 (0.90) in the intervention group, adjusted mean difference of −0.04 (95% CI −0.20 to 0.13). Secondary outcomes had similarly small differences and tight CIs. Sensitivity analyses suggested robust findings. Intervention fidelity was not achieved. Intervention-related group costs were marginally higher with no additional health benefit observed on EQ-5D-5L. No adverse events were related to the intervention.ConclusionsThe intervention was not fully implemented in this pragmatic trial. As delivered, it conferred no clinical benefits and is unlikely to be cost-effective compared with usual care from a stroke specialist provider organisation. It remains unclear how best to support carers of stroke survivors. To overcome the implementation challenges of person-centred care in carers’ research and service development, staff training and organisational support would need to be enhanced.Trial registration numberISRCTN58414120.

Mammalian Ether-a-go-go related gene (Erg) family voltage-gated K + channels possess an unusual gating phenotype that specializes them for a role in delayed repolarization. Mammalian Erg currents rectify during depolarization due to rapid, voltage-dependent inactivation, but rebound during repolarization due to a combination of rapid recovery from inactivation and slow deactivation. This is exemplified by the mammalian Erg1 channel, which is responsible for I Kr , a current that repolarizes cardiac action potential plateaus. The Drosophila Erg channel does not inactivate and closes rapidly upon repolarization. The dramatically different properties observed in mammalian and Drosophila Erg homologs bring into question the evolutionary origins of distinct Erg K + channel functions. Erg channels are highly conserved in eumetazoans and first evolved in a common ancestor of the placozoans, cnidarians, and bilaterians. To address the ancestral function of Erg channels, we identified and characterized Erg channel paralogs in the sea anemone Nematostella vectensis. N. vectensis Erg1 (NvErg1) is highly conserved with respect to bilaterian homologs and shares the I Kr -like gating phenotype with mammalian Erg channels. Thus, the I Kr phenotype predates the divergence of cnidarians and bilaterians. NvErg4 and Caenorhabditis elegans Erg (unc-103) share the divergent Drosophila Erg gating phenotype. Phylogenetic and sequence analysis surprisingly indicates that this alternate gating phenotype arose independently in protosomes and cnidarians. Conversion from an ancestral I Kr -like gating phenotype to a Drosophila Erg-like phenotype correlates with loss of the cytoplasmic Ether-a-go-go domain. This domain is required for slow deactivation in mammalian Erg1 channels, and thus its loss may partially explain the change in gating phenotype.sei | CNBHD | Anopheles | PAS