An Epidemiological Study of Lung Cancer and Selected Other Cancers among Namibian Uranium Workers.

The Rössing Uranium Limited (RUL) open-cast uranium mine in Namibia has operated since 1976. Studies of underground uranium miners from Europe and North America have shown increased cancer risks (principally lung cancer). We explored the association between radiation doses and selected cancers in RUL mineworkers. Employees with at least one-year of continuous employment between 1976 and 2010 were included. Incident cancer cases [lung, extra-thoracic airways (ETA), leukemia, brain and kidney] occurring before the end of 2015 were identified from the Namibian and South African National Cancer Registries, and RUL's occupational health provider. Using a case-cohort design, data on exposure and confounding factors were collected for all cancer cases among the study cohort and a stratified random sample (sub-cohort) of the cohort, including cases. Radiation doses were estimated based on annual dose records held by RUL. In total, 76 cancer cases (32 lung, 18 ETA, 8 leukemia, 9 brain, 9 kidney) and a sub-cohort of 1,121 sampled from 7,901 RUL employees were included. A weighted Cox model, adjusted for available known confounders, produced a rate ratio (95% CI) for lung cancer of 1.42 (0.42, 4.77) and 1.22 (0.26, 5.68), respectively, for medium and higher cumulative lung dose categories compared to the lower category, and 1.04 (0.95, 1.13) for a dose increase of 10 mSv. This study faced considerable challenges with respect to case ascertainment, exposure estimates, and ensuring accuracy of key variables. Persuasive consistent evidence for elevated cancer risk was not found for radiation or other exposures studied at the Rössing uranium mine.

Factors associated with carer psychological and physical health during end-of-life caregiving: an observational analysis of a population-based post-bereavement survey of carers of people with cancer.

OBJECTIVE: Family caregivers play an essential role in end-of-life care but suffer considerable impact on their own health. A better understanding of main factors related to carers' health is important to inform interventions. The purpose of the study was to test for the first time the potential impact of a comprehensive set of observable variables on carer health during end-of-life caregiving within a population-based carer sample. DESIGN: National retrospective, cross-sectional, 4-month post-bereavement postal census survey of family carers of people who died from cancer. SETTING AND PARTICIPANTS: Relatives who registered a death from cancer during a 2-week period in England were identified from death certificates by the Office of National Statistics; response rate was 1504/5271 (28.5%). OUTCOME MEASURES: Carers' mental health was measured through General Health Questionnaire (GHQ)-12; general health was measured through EuroQoL EQ-Visual Analogue Scale (EQ-5D VAS). METHODS: Survey questions to measure potential variables associated with carer health were based on past research and covered patients' symptoms and functioning; caregiving activities and hours; informal and formal help received; work hours, other caregiving, volunteering; changes to work, income and expenditure; sleep and relaxation; and demographic variables. Bivariate analyses and ordinary least square regression were performed to investigate these variables' relationship with outcomes. RESULTS: Patients' psychological symptoms and functioning, caregiving hours, female gender and self-sought formal help related to worse mental health. General practitioner and social care input and relaxation related to better mental health. Patients' psychological symptoms, caregiving hours and female gender were associated with worse general health, and older age, employment and relaxation were associated with better general health. CONCLUSIONS: Improvements in carers' health overall may be made by focusing on potential impacts of patients' psychological symptoms on carers, facilitating respite and relaxation, and paying particular attention to factors affecting female carers.

Organising Support for Carers of Stroke Survivors (OSCARSS): a cluster randomised controlled trial with economic evaluation.

OBJECTIVE: Investigated clinical effectiveness and cost-effectiveness of a person-centred intervention for informal carers/caregivers of stroke survivors. DESIGN: Pragmatic cluster randomised controlled trial (cRCT) with economic and process evaluation. SETTING: Clusters were services, from a UK voluntary sector specialist provider, delivering support primarily in the homes of stroke survivors and informal carers. PARTICIPANTS: Adult carers in participating clusters were referred to the study by cluster staff following initial support contact. INTERVENTIONS: Intervention 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 MEASURES: Participants 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 MASKING: Clusters 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. RESULTS: Between 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. CONCLUSIONS: The 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 NUMBER: ISRCTN58414120.

Organising Support for Carers of Stroke Survivors (OSCARSS): study protocol for a cluster randomised controlled trial, including health economic analysis.

BACKGROUND: Stroke often results in chronic disability, with partners and family members taking on the role of informal caregiver. There is considerable uncertainty regarding how best to identify and address carers' needs. The Carer Support Needs Assessment Tool (CSNAT) is a carer-led approach to individualised assessment and support for caregiving that may be beneficial in palliative care contexts. CSNAT includes an implementation toolkit. Through collaboration, including with service users, we adapted CSNAT for stroke and for use in a UK stroke specialist organisation providing long-term support. The main aims of OSCARSS are to investigate the clinical and cost-effectiveness of CSNAT-Stroke relative to current practice. This paper focuses on the trial protocol, with the embedded process evaluation reported separately. METHODS: Longitudinal, multi-site, pragmatic, cluster randomised controlled trial with a health economic analysis. Clusters are UK services randomised to CSNAT-Stroke intervention or usual care, stratified by size of service. Eligible carer participants are: adults aged > 18 years; able to communicate in English; referred to participating clusters; and seen face-to-face at least once by the provider, for support. The 'date seen' for initial support denotes the start of intervention (or control) and carers are referred to the research team after this for study recruitment. Primary outcome is caregiver strain (FACQ - Strain) at three months after 'date seen'. Secondary outcomes include: caregiver distress; positive caregiving appraisals (both FACQ subscales); Pound Carer Satisfaction with Services; mood (HADs); and health (EQ-5D5L) at three months. All outcomes are followed up at six months. Health economic analyses will use additional data on caregiver health service utilisation and informal care provision. DISCUSSION: OSCARSS is open to recruitment at the time of article submission. Study findings will allow us to evaluate the clinical and cost-effectiveness of the CSNAT-Stroke intervention, directed at improving outcomes for informal carers of stroke survivors. Trial findings will be interpreted in the context of our embedded process evaluation including qualitative interviews with those who received and provided services as well as data on treatment fidelity. OSCARSS will contribute to knowledge of the unmet needs of informal stroke caregivers and inform future stroke service development. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN58414120 . Registered on 26 July 2016.

Personal exposure to static and time-varying magnetic fields during MRI procedures in clinical practice in the UK.

BACKGROUND: MRI has developed into one of the most important medical diagnostic imaging modalities, but it exposes staff to static magnetic fields (SMF) when present in the vicinity of the MR system, and to radiofrequency and switched gradient electromagnetic fields if they are present during image acquisition. We measured exposure to SMF and motion-induced time-varying magnetic fields (TVMF) in MRI staff in clinical practice in the UK to enable extensive assessment of personal exposure levels and variability, which enables comparison to other countries. METHODS: 8 MRI facilities across National Health Service sites in England, Wales and Scotland were included, and staff randomly selected during the days when measurements were performed were invited to wear a personal MRI-compatible dosimeter and keep a diary to record all procedures and tasks performed during the measured shift. RESULTS: 98 participants, primarily radiographers (71%) but also other healthcare staff, anaesthetists and other medical staff were included, resulting in 149 measurements. Average geometric mean peak SMF and TVMF exposures were 448 mT (range 20-2891) and 1083 mT/s (9-12 355 mT/s), and were highest for radiographers (GM=559 mT and GM=734 mT/s). Time-weighted exposures to SMF and TVMF (GM=16 mT (range 5-64) and GM=14 mT/s (range 9-105)) and exposed-time-weighted exposures to SMF and TVMF (GM=27 mT (range 11-89) and GM=17 mT/s (range 9-124)) were overall relative low-primarily because staff were not in the MRI suite for most of their shifts-and did not differ significantly between occupations. CONCLUSIONS: These results are comparable to the few data available from the UK but they differ from recent data collected in the Netherlands, indicating that UK staff are exposed for shorter periods but to higher levels. These data indicate that exposure to SMF and TVMF from MRI scanners cannot be extrapolated across countries.

Design and analysis of trials with a partially nested design and a binary outcome measure.

Where treatments are administered to groups of patients or delivered by therapists, outcomes for patients in the same group or treated by the same therapist may be more similar, leading to clustering. Trials of such treatments should take account of this effect. Where such a treatment is compared with an un-clustered treatment, the trial has a partially nested design. This paper compares statistical methods for this design where the outcome is binary. Investigation of consistency reveals that a random coefficient model with a random effect for group or therapist is not consistent with other methods for a null treatment effect, and so this model is not recommended for this design. Small sample performance of a cluster-adjusted test of proportions, a summary measures test and logistic generalised estimating equations and random intercept models are investigated through simulation. The expected treatment effect is biased for the logistic models. Empirical test size of two-sided tests is raised only slightly, but there are substantial biases for one-sided tests. Three formulae are proposed for calculating sample size and power based on (i) the difference of proportions, (ii) the log-odds ratio or (iii) the arc-sine transformation of proportions. Calculated power from these formulae is compared with empirical power from a simulations study. Logistic models appeared to perform better than those based on proportions with the likelihood ratio test performing best in the range of scenarios considered. For these analyses, the log-odds ratio method of calculation of power gave an approximate lower limit for empirical power.

Transient health symptoms of MRI staff working with 1.5 and 3.0 Tesla scanners in the UK.

OBJECTIVES: Recent studies have consistently shown that amongst staff working with MRI, transient symptoms directly attributable to the MRI system including dizziness, nausea, tinnitus, and concentration problems are reported. This study assessed symptom prevalence and incidence in radiographers and other staff working with MRI in healthcare in the UK. METHODS: One hundred and four volunteer staff from eight sites completed a questionnaire and kept a diary to obtain information on subjective symptoms and work practices, and wore a magnetic field dosimeter during one to three randomly selected working days. Incidence of MRI-related symptoms was obtained for all shifts and prevalence of MRI-related and reference symptoms was associated to explanatory factors using ordinal regression. RESULTS: Incident symptoms related to working with MRI were reported in 4% of shifts. Prevalence of MRI-related, but not reference symptoms were associated with number of hours per week working with MRI, shift length, and stress, but not with magnetic field strength (1.5 and 3 T) or measured magnetic field exposure. CONCLUSIONS: Reporting of prevalent symptoms was associated with longer duration of working in MRI departments, but not with measured field strength of exposure. Other factors related to organisation and stress seem to contribute to increased reporting of MRI-related symptoms. KEY POINTS: • Routine work with MRI is associated with increased reporting of transient symptoms • No link to the strength of the magnetic field was demonstrated. • Organisational factors and stress additionally contribute to reporting of MRI-related symptoms.

Performance of bias-correction methods for exposure measurement error using repeated measurements with and without missing data.

It is known that measurement error leads to bias in assessing exposure effects, which can however, be corrected if independent replicates are available. For expensive replicates, two-stage (2S) studies that produce data 'missing by design', may be preferred over a single-stage (1S) study, because in the second stage, measurement of replicates is restricted to a sample of first-stage subjects. Motivated by an occupational study on the acute effect of carbon black exposure on respiratory morbidity, we compare the performance of several bias-correction methods for both designs in a simulation study: an instrumental variable method (EVROS IV) based on grouping strategies, which had been recommended especially when measurement error is large, the regression calibration and the simulation extrapolation methods. For the 2S design, either the problem of 'missing' data was ignored or the 'missing' data were imputed using multiple imputations. Both in 1S and 2S designs, in the case of small or moderate measurement error, regression calibration was shown to be the preferred approach in terms of root mean square error. For 2S designs, regression calibration as implemented by Stata software is not recommended in contrast to our implementation of this method; the 'problematic' implementation of regression calibration although substantially improved with use of multiple imputations. The EVROS IV method, under a good/fairly good grouping, outperforms the regression calibration approach in both design scenarios when exposure mismeasurement is severe. Both in 1S and 2S designs with moderate or large measurement error, simulation extrapolation severely failed to correct for bias.

Instrumental variables vs. grouping approach for reducing bias due to measurement error.

Attenuation of the exposure-response relationship due to exposure measurement error is often encountered in epidemiology. Given that error cannot be totally eliminated, bias correction methods of analysis are needed. Many methods require more than one exposure measurement per person to be made, but the `group mean OLS method,' in which subjects are grouped into several a priori defined groups followed by ordinary least squares (OLS) regression on the group means, can be applied with one measurement. An alternative approach is to use an instrumental variable (IV) method in which both the single error-prone measure and an IV are used in IV analysis. In this paper we show that the `group mean OLS' estimator is equal to an IV estimator with the group mean used as IV, but that the variance estimators for the two methods are different. We derive a simple expression for the bias in the common estimator which is a simple function of group size, reliability and contrast of exposure between groups, and show that the bias can be very small when group size is large. We compare this method with a new proposal (group mean ranking method), also applicable with a single exposure measurement, in which the IV is the rank of the group means. When there are two independent exposure measurements per subject, we propose a new IV method (EVROS IV) and compare it with Carroll and Stefanski's (CS IV) proposal in which the second measure is used as an IV; the new IV estimator combines aspects of the `group mean' and `CS' strategies. All methods are evaluated in terms of bias, precision and root mean square error via simulations and a dataset from occupational epidemiology. The `group mean ranking method' does not offer much improvement over the `group mean method.' Compared with the `CS' method, the `EVROS' method is less affected by low reliability of exposure. We conclude that the group IV methods we propose may provide a useful way to handle mismeasured exposures in epidemiology with or without replicate measurements. Our finding may also have implications for the use of aggregate variables in epidemiology to control for unmeasured confounding.