Low radon exposures and lung cancer risk: joint analysis of the Czech, French, and Beaverlodge cohorts of uranium miners.

It is well established that high radon exposures increase the risk of lung cancer mortality. The effects of low occupational exposures and the factors that confound and modify this risk are not clear and are needed to inform current radiation protection of miners. The risk of lung cancer mortality at low radon exposures (< 100 working-level months) was assessed in the joint cohort analysis of Czech, French, and Canadian uranium miners, employed in 1953 or later. Statistical analysis was based on linear Poisson regression modeling with grouped cohort survival data. Two sensitivity analyses were used to assess potential confounding from tobacco smoking. A statistically significant linear relationship between radon exposure and lung cancer mortality was found. The excess relative risk per working-level month was 0.022 (95% confidence intervals: 0.013-0.034), based on 408 lung cancer deaths and 394,236 person-years of risk. Time since exposure was a statistically significant modifier; risk decreased with increasing time since exposure. A tendency for a decrease in risk with increasing attained age was observed, but this was not statistically significant. Exposure rate was not found to be a modifier of the excess relative risk. The potential confounding effect of tobacco smoking was estimated to be small and did not substantially change the radon-lung cancer mortality risk estimates. This joint cohort analysis provides strong evidence for an increased risk of lung cancer mortality from low occupational radon exposures. The results suggest that radiation protection measures continue to be important among current uranium miners

The preventative role of exogenous melatonin administration to patients with advanced cancer who are at risk of delirium: study protocol for a randomized controlled trial

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Delirium is a very common and distressing neuropsychiatric syndrome in palliative care. Increasing age, the presence of dementia and advanced cancer are well-known predisposing risk factors for delirium development. Sleep-wake cycle disturbance is frequently seen during delirium and melatonin has a pivotal role in the regulation of circadian rhythms. Current evidence across various settings suggests a potential preventative role for melatonin in patients at risk of delirium, but no studies are currently reported in patients with advanced cancer. The aim of this article is to describe the design of a feasibility study that is being conducted to inform a larger randomized, placebo-controlled, double-blind trial (RCT) to evaluate the role of exogenously administered melatonin in preventing delirium in patients with advanced cancer. Methods/Design Adult patients with a cancer diagnosis who are admitted to the palliative care unit will be randomized into a treatment or placebo group. The pharmacological intervention consists of a single daily dose of immediate-release melatonin (3 mg) at 21:00 ± 1 h, from day 1 to day 28 of admission. The primary objective of this initial study is to assess the feasibility of conducting the proposed RCT by testing recruitment and retention rates, appropriateness of study outcome measures, acceptability of study procedures and effectiveness of the blinding process. The primary outcome measure of the proposed larger RCT is time to first inpatient incident episode of delirium. We also plan to collect data on incident rates of delirium and patient-days of delirium, adjusting for length of admission. Discussion The outcomes of this feasibility study will provide information on recruitment and retention rates, protocol violation frequency, effectiveness of the blinding process, acceptability of the study procedures, and safety of the proposed intervention. This will inform the design of a fully powered randomized controlled trial to evaluate the preventative role of melatonin administration in patients with advanced cancer. Trial registration Registered with ClinicalTrials.gov: NCT02200172 Registered on 21 July 2014. Health Canada protocol number: BRI-MELAT-2013 (Final approved protocol version (Version 3): 18 June 2014) (Notice of Amended Authorization (NOA) received 14 November 2014). Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1525-8) contains supplementary material, which is available to authorized users

Potentially inappropriate prescribing in long-term care residents and its association with probable delirium.

Objective: Medications can increase the risk of delirium due to drug toxicities, polypharmacy, and drug interactions. This study examined potentially inappropriate prescribing (PIP) of medication and its association with probable delirium among long-term care residents. Approach: We conducted a cross-sectional study of long-term care residents in Ontario, Canada between January 1, 2016 and December 31, 2019. Routinely collected long-term care resident assessment data from the Resident Assessment Instrument – Minimum Dataset (RAI-MDS) was linked to prescription claims data to ascertain probable delirium and medication use in the two weeks preceding the index assessment. PIP was measured via the STOPP/START criteria and Beers criteria, with residents classified as having 0, 1, 2, or 3+ PIPs. Associations between PIP and probable delirium was assessed via bivariate and multivariable logistic regression models. Results The study population included 171,190 long-term care residents. The mean age was 84.5 years, 66.8% were female, and 62.9% had dementia. Probable delirium was documented on 3.7% of resident assessments. Over half (51.8%) of residents had 1+ PIP and 21% had 3+ PIPs according to the STOPP/START criteria. The odds of probable delirium increased as the number of PIPs increased. Probable delirium was 1.86 times more likely (95% confidence interval 1.74-1.98) in residents with 3+ PIPs compared to those with no PIPs after confounder adjustment. Similar findings were observed when PIP was evaluated using the Beers criteria. Conclusion This population-based study highlighted that potentially inappropriate medication prescribing was highly prevalent and was significantly associated with the increased likelihood of probable delirium among long-term care residents

Validation of mobile phone use recall in the multinational MOBI‐kids study

Potential differential and non‐differential recall error in mobile phone use(MPU) in the multinational MOBI‐Kids case–control study were evaluated.We compared self‐reported MPU with network operator billing record data up to 3 months, 1 year, and 2 years before the interview date from 702subjects aged between 10 and 24 years in eight countries. Spearman rankcorrelations, Kappa coefficients and geometric mean ratios (GMRs) wereused. No material differences in MPU recall estimates between cases andcontrols were observed. The Spearman rank correlation coefficientsbetween self‐reported and recorded MPU in the most recent 3 monthswere 0.57 and 0.59 for call number and for call duration, respectively. Thenumber of calls was on average underestimated by the participants(GMR = 0.69), while the duration of calls was overestimated (GMR = 1.59).Country, years since start of using a mobile phone, age at time of interview,and sex did not appear to influence recall accuracy for either call number orcall duration. A trend in recall error was seen with level of self‐reportedMPU, with underestimation of use at lower levels and overestimation of useat higher levels for both number and duration of calls. Although bothsystematic and random errors in self‐reported MPU among participantswere observed, there was no evidence of differential recall error betweencases and controls. Nonetheless, these sources of exposure measurementerror warrant consideration in interpretation of the MOBI‐Kids case–controlstudy results on the association between children's use of mobile phonesand potential brain cancer risk

Hierarchical Regression for Multiple Comparisons in a Case-Control Study of Occupational Risks for Lung Cancer

BACKGROUND Occupational studies often involve multiple comparisons and therefore suffer from false positive findings. Semi-Bayes adjustment methods have sometimes been used to address this issue. Hierarchical regression is a more general approach, including Semi-Bayes adjustment as a special case, that aims at improving the validity of standard maximum-likelihood estimates in the presence of multiple comparisons by incorporating similarities between the exposures of interest in a second-stage model. METHODOLOGY/PRINCIPAL FINDINGS We re-analysed data from an occupational case-control study of lung cancer, applying hierarchical regression. In the second-stage model, we included the exposure to three known lung carcinogens (asbestos, chromium and silica) for each occupation, under the assumption that occupations entailing similar carcinogenic exposures are associated with similar risks of lung cancer. Hierarchical regression estimates had smaller confidence intervals than maximum-likelihood estimates. The shrinkage toward the null was stronger for extreme, less stable estimates (e.g., "specialised farmers": maximum-likelihood OR: 3.44, 95%CI 0.90-13.17; hierarchical regression OR: 1.53, 95%CI 0.63-3.68). Unlike Semi-Bayes adjustment toward the global mean, hierarchical regression did not shrink all the ORs towards the null (e.g., "Metal smelting, converting and refining furnacemen": maximum-likelihood OR: 1.07, Semi-Bayes OR: 1.06, hierarchical regression OR: 1.26). CONCLUSIONS/SIGNIFICANCE Hierarchical regression could be a valuable tool in occupational studies in which disease risk is estimated for a large amount of occupations when we have information available on the key carcinogenic exposures involved in each occupation. With the constant progress in exposure assessment methods in occupational settings and the availability of Job Exposure Matrices, it should become easier to apply this approach

The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk

The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people