Radiogenic risk of solid cancer incidence in persons exposed to radiation in childhood in the Southern Urals

The aim of this work is to assess the radiogenic risk of solid cancers incidence in the members of the Urals Childhood Exposure Cohort. The cohort includes people exposed under 20 years of age as a result of two radiation accidents at the Mayak Production Association in the Southern Urals (discharges of radioactive waste into the Techa River and the formation of the East Ural radioactive trace). The number of the cohort for solid cancer incidence analysis is 31,578 individuals. All the members were postnatally exposed and some of them – in-utero. Some of their parents were exposed before conception. 2,018 solid cancers were registered on the incidence catchment area during the period 1956-2018, the total amount of person years was 818,083. The analysis was carried out by the Poisson regression method with a simple parametric excess relative risk model. 95% confidence intervals were estimated with maximum likelihood approach. Only a postnatal dose was used in the first solid cancer incidence analysis of this cohort members with due account for preconception exposure of parents. TRDS-2016 mean postnatal dose accumulated over the entire follow-up period in the stomach of cohort members was 0.047 Gy. The analysis showed linear dependence of solid cancer incidence excess relative risk on postnatal dose. Excess relative risk was 0.66/Gy, р=0.006 with a five-year latency period. While estimating excess relative risk in different age groups at the beginning of exposure, a significant risk was present only in the age group under 1 year and amounted to 2.16/Gy; р<0.02 at the onset of exposure. The present results are in agreement with the results of the solid cancer incidence risk analysis both in the Techa River Cohort of exposed In-Utero where a statistically significant excess relative risk from a postnatal dose was revealed, and with the results of risk analysis in the Japanese cohort of people exposed in-utero and in early childhood.

Reduced cardiorespiratory fitness is a mediator of excess all-cause mortality in rheumatoid arthritis: the Trøndelag Health Study

ObjectivesInvestigate if low cardiorespiratory fitness (CRF) was associated with and acted as a mediator of excess all-cause mortality rate in persons suffering from rheumatoid arthritis (RA) compared with the general population.MethodsAll-cause mortality was analysed using Cox regression modelling in patients with RA (n=348) and controls (n=60 938) who took part in the second (1995–1997) and third (2006–2008) waves of the longitudinal population-based Trøndelag Health Study in Norway. A mediation analysis was performed to investigate if excess relative risk of mortality in RA was mediated by low estimated CRF (eCRF).ResultsDuring the follow-up until 31 December 2018 (mean 19.3 years), the mortality rate among patients with RA (n=127, 36.5%) was higher than among controls (n=12 942, 21.2%) (p<0.001). Among controls and patients with RA, 51% and 26%, respectively, had eCRF above the median for their age and sex (p<0.001). The final Cox model included RA status and eCRF, adjusted for hypertension, body mass index, smoking, cholesterol, diabetes and creatinine. eCRF below median for sex and age category was associated with increased mortality (p<0.001). The total excess relative risk of mortality in patients with RA was 28% (95% CI 2% to 55%, p=0.035), in which RA itself contributed 5% and the direct and indirect contributions of low eCRF accounted for 23%.ConclusionsLow eCRF was an important mediator of the increased all-cause mortality rate found in RA. Our data indicate that patients with RA should be given advice to perform physical activity that increases CRF, along with optimised treatment with antirheumatic drugs, from the time of diagnosis.

Estimating of radiation risks of malignant neoplasms among Russian Chernobyl cleanup workers

The paper considers radiation risks of solid cancer incidence and mortality, as well as risk of leu-kemia incidence (other than chronic lymphocytic leukemia) among Russian Chernobyl cleanup workers (liquidators). The study of the cohort of liquidators carried out at the National Radiation Epidemiological Registry (NRER) was based on the follow-up data collected from 1992 over 2019. The size of the Chernobyl cleanup workers cohort exceeded 65 thousand people, their av-erage age at the time of entering the exclusion zone was 34 years, the average external gamma radiation dose received by liquidators during their cleanup work was about 0.133 Gy. Radiation-induced risks of solid cancer incidence and mortality in the study cohort were statistically signifi-cant, the risk magnitude rose with increasing the follow-up length. For the maximum follow-up period, from 1992 over 2019, the excess relative risk coefficient for solid cancer incidence was ERR/Gy=0.62, 95% CI (0.29; 0.98), and excess relative risk coefficient for solid cancer mortality was ERR/Gy=0.74, 95% CI (0.32; 1.22), the estimated coefficients were in good agreement with similar coefficients calcu-lated for the Russian liquidators with the use of ICRP radiation risk models. Non-parametric esti-mates of relative radiation risk within the same dose intervals for solid cancers and for leukemias in the cohort of liquidators were statistically significant for radiation doses above 0.150 Gy. For radiation doses below 0,150 Гр the linear non-threshold model is conservative, i.e. there was ev-idence for statistically significant radiation risk of leukemia incidence among liquidators during the first 11 years after the accident, from 1986 over 1997, ERR/Gy=4.41, 95% CI (0.24; 14.23). In later years, until 2018 there was no evidence of radiation-related risk of leukemia incidence. Out-comes of future studies will impact on optimization of radiological protection, development of reference levels for Russian general public exposure and improvement of the system for delivery of targeted medical care to people exposed to radiation.

Targeting continuity of care and polypharmacy to reduce drug–drug interaction

Drug–drug interaction (DDI) is common among the elderly, and it can have detrimental effects on patients. However, how DDI can be targeted has been under-researched. This study investigates whether DDI can be reduced by targeting continuity of care (COC) through reducing polypharmacy. Population claims data of Taiwan National Health Insurance were used to conduct a 7-year-long longitudinal study on patients aged ≥ 65 years (n = 2,318,766). Mediation analysis with counterfactual method and a 4-way decomposition of the effect of COC on DDI was conducted. Mediation effect through excessive polypharmacy differed from that through lower-level polypharmacy. Compared with the low COC group, the high COC group demonstrated reduced excess relative risk of DDI by 26% (excess relative risk = − 0.263; 95% Confidence Interval (CI) = − 0.263 to − 0.259) to 30% (excess relative risk = − 0.297; 95% CI = − 0.300 to − 0.295) with excessive polypharmacy as the mediator. The risk only reduced by 8% (excess relative risk = − 0.079; 95% CI, − 0.08 to − 0.078) to 10% (excess relative risk = − 0.096; 95% CI, − 0.097 to − 0.095) when the mediator was changed to lower-level polypharmacy. The effect of COC on DDI was mediated by polypharmacy, and the mediation effect was higher with excessive polypharmacy. Therefore, to reduce DDI in the elderly population, different policy interventions should be designed by considering polypharmacy levels to maximize the positive effect of COC on DDI.

Solid cancer incidence risk in in the Ural cohort of the accidentally exposed population: 1956–2017

To date, the study of the effects of chronic exposure of the South Ural population has been carried out in two separate cohorts – in the Techa River Cohort and in the East Urals Radioactive Trace Cohort. In 2019, the Ural cohort of accidentally exposed population was formed. It included the population exposed in two radiation situations in the Southern Urals in the 1950s. The number of the combined cohort for the cancer incidence analysis was about 60 thousand people, the follow-up period was extended to 2017, the number of solid cancers was 4537, and the number of person-years was 1283267, which is 3 times more than when analyzing the effects of exposure in each of the two radiation situations separately. In the incidence analysis of all solid cancer types, we used the dose accumulated in the walls of the stomach, which corresponds to the dose accumulated in most organs and tissues with the exception of bone tissue and red bone marrow. The mean dose to the stomach accumulated over the entire follow-up period for cohort members was 38 mGy, the maximum -1.13 Gy. The paper presents the first results of solid cancer incidence risk analysis in the combined cohort, which show a statistically significant dose dependence of the incidence in case of chronic exposure in the range of low and medium doses. The sex and age-averaged excess relative risk value of 0.075/100 mGy (the 95% confidence interval is 0.039–0.113) is comparable to that obtained in the studies of the Japanese cohort of atomic bomb survivors. The statistically significant excess relative risk value of 0.047/100 mGy, obtained separately for men, is in good agreement with that in professional cohorts where men prevail – in the cohort of the Chernobyl NPP accident clean-up workers and in the cohort of professional workers in the three countries (UK, France, USA). The established cohort with a long follow-up period has a great potential for furthermore detailed studies of the effects of radiation and non-radiation factors on public health.

LEUKEMIA INCIDENCE AND MORTALITY OF RECOVERY OPERATION WORKERS OF THE CHERNOBYL ACCIDENT: ASSESSMENT OF RADIATION RISKS FOR THE FOLLOW-UP PERIOD OF 1986–2014

Leukemia incidence in the cohort of Russian male recovery operation workers (liquidators) was estimated at 78110 people for the follow-up period 1986-2014. The average age of the liquidators at the time of entry into the zone of works for liquidation of the Chernobyl accident was 34 years. Radiation risk of leukemia incidence (with the exception of chronic lymphocytic leukemia) was analyzed for liquidators who had official data on the individual dose of external gamma radiation of the entire body accumulated over the period of work. During the follow-up period, 157 cases of leukemia were detected (with the exception of chronic lymphocytic leukemia). Collection and verification of data of hemoblastoses cases among persons exposed to radiation exposure was carried out according to a specially developed algorithm. The average dose of the liquidators was 108 mGy. During the period 1986–1997 was established a statistically significant (p<0.05) linear dose dependence of the leukemia incidence with an excess relative risk of ERR/Gy=4.17 (90% CI: 0.18, 13.24). From 1998 until the end of the follow-up period, as well as for the entire follow-up period (from 1986 to 2014), no statistically significant estimates of excess relative risk were found. For mortality, no statistically significant estimates of excess relative risk and relative risk were found for any of the observation periods. The obtained estimates of the radiation risk of morbidity indicate that a statistically significant excess leukemia incidence of liquidators, which may be associated with external gamma irradiation, is manifested in the first decade after exposure.