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Childhood cancer survivors are at increased risk for second primary leukemia (SPL), but there is little consensus on the magnitude of some risk factors because of the small size of previous studies. We performed a pooled analysis of all published studies with detailed treatment data, including estimated active bone marrow (ABM) dose received during radiation therapy and doses of specific chemotherapeutic agents for childhood cancer diagnosed from 1930 through 2000, in order to more thoroughly investigate treatment‐related risks of SPL. A total of 147 SPL cases (of which 69% were acute myeloid leukemia [AML]) were individually matched to 522 controls, all from four case‐control studies including patients from six countries (France, United Kingdom, United States, Canada, Italy and Netherlands). Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were calculated using conditional logistic regression, and the excess OR per Gray (EOR/Gy) was also calculated. After accounting for the other therapies received, topoisomerase II inhibitor was associated with an increased SPL risk (highest tertile vs none: OR = 10.0, 95% CI: 3.7‐27.3). Radiation dose to the ABM was also associated with increased SPL risk among those not receiving chemotherapy (EOR/Gy = 1.6, 95% CI: 0.1‐14.3), but not among those who received chemotherapy (CT). SPL were most likely to occur in the first decade following cancer treatment. Results were similar when analyses were restricted to AML. The evidence of interaction between radiation and CT has implications for leukemogenic mechanism. The results for topoisomerase II inhibitors are particularly important given their increasing use to treat childhood cancer. What's new? Childhood cancer survivors are at increased risk for second primary leukemia (SPL), but which treatments confer the greatest risk? In this study, the authors found that topoisomerase II inhibitors increased the risk of SPL by as much as 10‐fold, which was far higher than for other chemotherapies. Radiation therapy also increased the subsequent risk of SPL, but only in patients who didn't also receive chemotherapy. Given the poor prognosis of SPL, these results should help inform surveillance guidelines for childhood cancer survivors, and guide assessment of leukemia risks for specific treatment protocols. [ABSTRACT FROM AUTHOR]

Recent analyses have suggested decreases over time in colorectal cancer incidence at older ages (≥55 years) but increases at younger ages (20–54 years). Understanding the geographic heterogeneity of incidence facilitates resource allocation for potential interventions and advances our knowledge of differential etiologies for these cancers. We performed age‐period‐cohort analysis using 2000–2014 county‐level incidence from the Surveillance, Epidemiology, and End Results (SEER) database, estimating relative risk (RR) and age‐adjusted annual percent change (Net Drifts) simultaneously for 612 counties via a hierarchical model, separately for colon and rectum cancer, stratified by age group (20–54 vs. 55–84). We also studied correlates of RR and Net Drift with various county‐level characteristics. In all SEER counties, colon and rectum cancer incidence rates increased at ages 20–54, whereas rates decreased at ages 55–84. There was marked heterogeneity in both RR and Net Drift among states and counties for both cancer types. Maps of county RR and Net Drift revealed localized clusters in several states. For both cancer types, counties with high RR and unfavorable Net Drift tended to have higher prevalence of obesity and diabetes and to be of a lower socioeconomic status. Counties with higher overall screening rates tended to have lower Net Drifts for both cancer types. Increasing colorectal cancer incidence in the younger age group is geographically widespread, although there is significant heterogeneity in temporal trends and risk both within and between states. These geographic patterns correlate with different county‐level characteristics depending on cancer type and age group. What's new? In the United States, colorectal cancer incidence is on the rise in young, unscreened populations. In order to facilitate resource allocation for potential interventions for these populations, a better understanding of geographic differences in colorectal cancer incidence is needed. Here, we quantify the spatial heterogeneity of colorectal cancer incidence among U.S. states and counties in the Surveillance, Epidemiology, and End Results database to show that from 2000‐2014 incidence rates increased among persons ages 20‐54, while rates decreased in older populations. Increasing incidence in younger, unscreened populations is geographically widespread with clusters that correlate to well‐established county‐level risk factors, including obesity and diabetes. [ABSTRACT FROM AUTHOR]

Solar ultraviolet radiation is the primary risk factor for skin cancers and sun‐related eye disorders. Estimates of individual ambient ultraviolet irradiance derived from ground‐based solar measurements and from satellite measurements have rarely been compared. Using self‐reported residential history from 67 189 persons in a nationwide occupational US radiologic technologists' cohort, we estimated ambient solar irradiance using data from ground‐based meters and noontime satellite measurements. The mean distance moved from city of longest residence in childhood increased from 137.6 km at ages 13–19 to 870.3 km at ages ≥65, with corresponding increases in absolute latitude difference moved. At ages 20/40/60/80, the Pearson/Spearman correlation coefficients of ground‐based and satellite‐derived potential solar ultraviolet exposure, using irradiance and cumulative radiant exposure metrics, were high (=0.87–0.92). There was also moderate correlation (Pearson/Spearman correlation coefficients = 0.51–0.60) between irradiance at birth and at last‐known address, for ground‐based and satellite data. Satellite‐based lifetime estimates of ultraviolet radiation were generally 14–15% lower than ground‐based estimates, albeit with substantial uncertainties, possibly because ground‐based estimates incorporate fluctuations in cloud and ozone, which are incompletely incorporated in the single noontime satellite‐overpass ultraviolet value. If confirmed elsewhere, the findings suggest that ground‐based estimates may improve exposure assessment accuracy and potentially provide new insights into ultraviolet radiation–disease relationships in epidemiologic studies. The results of this study showed that in this large (~70 000) US occupational cohort of medical radiation workers, measures of potential irradiance and potential cumulative radiant exposure associated with solar ultraviolet radiation derived from ground‐based measures are highly correlated with measures derived from NASA satellite data. Satellite‐based lifetime estimates of ultraviolet radiation were generally 14–15% lower than ground‐based estimates, albeit with substantial uncertainties. There is also moderate correlation with irradiance at last known address and at birth, a reflection of the modest distance moved from city of residence in childhood over the course of life for persons in this cohort. [ABSTRACT FROM AUTHOR]

Although childhood exposure to ionizing radiation is a well‐established risk factor for thyroid cancer, the risk associated with adulthood exposure remains unclear. We prospectively examined the association between cumulative, low‐to‐moderate dose occupational radiation exposure to the thyroid and thyroid cancer incidence in the U.S. Radiologic Technologists cohort. The study included 89,897 members who completed at least two of four mailed questionnaires and were cancer‐free at the time of the first questionnaire. Cumulative occupational thyroid radiation dose (mean = 57 mGy, range = 0–1,600 mGy) was estimated based on self‐reported work histories, historical data and, during the years 1960–1997, 783,000 individual film badge measurements. During follow‐up, we identified 476 thyroid cancer cases. We used Poisson regression to estimate excess relative risk of thyroid cancer per 100 milliGray (ERR/100 mGy) absorbed dose to the thyroid gland. After adjusting for attained age, sex, birth year, body mass index and pack‐years smoked, we found no association between thyroid dose and thyroid cancer risk (ERR/100 mGy = −0.05, 95% CI <–0.10, 0.34). In this large cohort study of radiologic technologists, protracted, low‐to‐moderate dose ionizing radiation exposure to the thyroid gland in adulthood was not associated with an increased risk of thyroid cancer. What's new? Exposure to ionizing radiation is a known risk factor for thyroid cancer. Little is known, however, about the impact of low‐to‐moderate cumulative occupational radiation exposure on thyroid cancer risk. In the present evaluation, radiation doses to the thyroid were reconstructed based on badge dose readings and work history for U.S. radiologic technologists and on literature review. The results show no association between cumulative occupational radiation thyroid dose and thyroid cancer incidence after adjusting for multiple risk factors, including age, sex and body mass index. The findings help clarify the role of adulthood radiation exposure in thyroid cancer development. [ABSTRACT FROM AUTHOR]

Background: Flight attendants may have an increased risk of some cancers from occupational exposure to cosmic radiation and circadian disruption. Methods: The incidence of thyroid, ovarian, and uterine cancer among ∼6000 female flight attendants compared to the US population was evaluated via life table analyses. Associations of these cancers, melanoma, and cervical cancer with cumulative cosmic radiation dose and metrics of circadian disruption were evaluated using Cox regression. Results: Incidence of thyroid, ovarian, and uterine cancer was not elevated. No significant, positive exposure‐response relations were observed. Weak, non‐significant, positive relations were observed for thyroid cancer with cosmic radiation and time zones crossed and for melanoma with another metric of circadian disruption. Conclusions: We found little evidence of increased risk of these cancers from occupational cosmic radiation or circadian disruption in female flight attendants. Limitations include few observed cases of some cancers, limited data on risk factors, and misclassification of exposures. [ABSTRACT FROM AUTHOR]

Age-period-cohort (APC) models are widely used to analyze population-level rates, particularly cancer incidence and mortality. These models are used for descriptive epidemiology, comparative risk analysis, and extrapolating future disease burden. Traditional APC models have 2 major limitations: (1) they lack parsimony because they require estimation of deviations from linear trends for each level of age, period, and cohort; and (2) rates observed at similar ages, periods, and cohorts are treated as independent, ignoring any correlations between them that may lead to biased parameter estimates and inefficient standard errors. We propose a novel approach to estimation of APC models using a spatially correlated Poisson model that accounts for over-dispersion and correlations in age, period, and cohort, simultaneously. We treat the outcome of interest as event rates occurring over a grid defined by values of age, period, and cohort. Rates defined in this manner lend themselves to well-established approaches from spatial statistics in which correlation among proximate observations may be modeled using a spatial random effect. Through simulations, we show that in the presence of spatial dependence and over-dispersion: (1) the correlated Poisson model attains lower AIC; (2) the traditional APC model produces biased trend parameter estimates; and (3) the correlated Poisson model corrects most of this bias. We illustrate our approach using brain and breast cancer incidence rates from the Surveillance Epidemiology and End Results Program of the United States. Our approach can be easily extended to accommodate comparative risk analyses and interpolation of cells in the Lexis with sparse data. [ABSTRACT FROM AUTHOR]

To evaluate risk of thyroid neoplasia nearly 30 years following exposure to radioactive iodine (I-131) from the 1986 Chernobyl nuclear accident, we conducted a fifth cycle of thyroid screening of the Ukrainian-American cohort during 2012-2015, following four previous screening cycles started in 1998. We identified 47 thyroid cancers (TC) and 33 follicular adenomas (FA) among 10,073 individuals who were <18 years at the time of the accident and had a mean I-131 dose of 0.62 Gy. We found a significant I-131 dose response for both TC and FA, with an excess odd ratio per Gy of 1.36 (95% CI: 0.39-4.15) and 2.03 (95% CI: 0.55-6.69), respectively. The excess risk of malignant and benign thyroid neoplasia persists nearly three decades after exposure and underscores the importance of continued follow-up of this cohort to characterize long-term pattern of I-131 risk. [ABSTRACT FROM AUTHOR]

Keywords: Snake bites; Envenomation; Emergency treatment EN Snake bites Envenomation Emergency treatment 191 192 2 08/17/22 20220815 NES 220815 B Despite its potential value, a number of questions require answers before its role in clinical practice becomes clear b For many clinicians working in rural Australia, people bitten by snakes can present significant diagnostic and logistical challenges. Is D-dimer the new test for venom-induced consumption coagulopathy after snakebite? Isbister and colleagues found that 95% of people who had not been envenomed had D-dimer values below 2.5 mg/L. Could we use clinical findings or other simple investigations (such as the 20-minute whole blood clotting test, 20WBCT2) to increase the proportion ruled out?. [Extracted from the article]

The recently demonstrated radiation-induction of chronic lymphocytic leukemia (CLL) raises the question as to whether the amount of radiation exposure influences any of the clinical characteristics of the disease. We evaluated the relationship between bone marrow radiation doses and clinical characteristics and survival of 79 CLL cases diagnosed during 1986-2006 in a cohort of 110 645 male workers who participated in the cleanup work of the Chornobyl nuclear accident in Ukraine in 1986. All diagnoses were confirmed by an independent International Hematology Panel. Patients were followed up to the date of death or end of follow-up on 31 October 2010. The median age at diagnosis was 57 years. Median bone marrow dose was 22.6 milligray (mGy) and was not associated with time between exposure and clinical diagnosis of CLL (latent period), age, peripheral blood lymphocyte count or clinical stage of disease in univariate and multivariate analyses. Latent period was significantly shorter among those older at first exposure, smokers and those with higher frequency of visits to the doctor prior to diagnosis. A significant increase in the risk of death with increasing radiation dose was observed (p = 0.03, hazard ratio = 2.38, 95% confidence interval: 1.11,5.08 comparing those with doses ≥22 mGy to doses <22 mGy). After adjustment for radiation dose, survival of CLL cases was significantly shorter among those with younger age at first exposure, higher peripheral blood lymphocyte count, more advanced clinical stage of disease and older age at diagnosis (all p < 0.05). This is the first study to examine association between bone marrow radiation doses from the Chornobyl accident and clinical manifestations of the CLL in Chornobyl cleanup workers. The current study provides new evidence on the association of radiation dose and younger age at first radiation exposure at Chornobyl with shorter survival after diagnosis. Future studies are necessary with more cases in order to improve the statistical power of these analyses and to determine their significance. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Flight attendants may have elevated breast cancer incidence (BCI). We evaluated BCI's association with cosmic radiation dose and circadian rhythm disruption among 6,093 female former U.S. flight attendants. Methods We collected questionnaire data on BCI and risk factors for breast cancer from 2002-2005. We conducted analyses to evaluate (i) BCI in the cohort compared to the U.S. population; and (ii) exposure-response relations. We applied an indirect adjustment to estimate whether parity and age at first birth (AFB) differences between the cohort and U.S. population could explain BCI that differed from expectation. Results BCI was elevated but may be explained by lower parity and older AFB in the cohort than among U.S. women. BCI was not associated with exposure metrics in the cohort overall. Significant positive associations with both were observed only among women with parity of three or more. Conclusions Future cohort analyses may be informative on the role of these occupational exposures and non-occupational risk factors. Am. J. Ind. Med. 58:252-266, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND Recent studies of children and adolescents who were exposed to radioactive iodine-131 (I-131) after the 1986 Chernobyl nuclear accident in Ukraine exhibited a significant dose-related increase in the risk of thyroid cancer, but the association of radiation doses with tumor histologic and morphologic features is not clear. METHODS A cohort of 11,664 individuals in Belarus who were aged ≤18 years at the time of the accident underwent 3 cycles of thyroid screening during 1997 to 2008. I-131 thyroid doses were estimated from individual thyroid activity measurements taken within 2 months after the accident and from dosimetric questionnaire data. Demographic, clinical, and tumor pathologic characteristics of the patients with thyroid cancer were analyzed using 1-way analysis of variance, chi-square tests or Fisher exact tests, and logistic regression. RESULTS In total, 158 thyroid cancers were identified as a result of screening. The majority of patients had T1a and T1b tumors (93.7%), with many positive regional lymph nodes (N1; 60.6%) but few distant metastases (M1; <1%). Higher I-131 doses were associated with higher frequency of solid and diffuse sclerosing variants of thyroid cancer ( P < .01) and histologic features of cancer aggressiveness, such as lymphatic vessel invasion, intrathyroidal infiltration, and multifocality (all P < .03). Latency was not correlated with radiation dose. Fifty-two patients with self-reported thyroid cancers which were diagnosed before 1997 were younger at the time of the accident and had a higher percentage of solid variant cancers compared with patients who had screening-detected thyroid cancers (all P < .0001). CONCLUSIONS I-131 thyroid radiation doses were associated with a significantly greater frequency of solid and diffuse sclerosing variants of thyroid cancer and various features of tumor aggressiveness. Cancer 2015;121:457-466. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND In their previous analysis of papillary thyroid carcinomas (PTCs) from an Ukrainian-American cohort that was exposed to iodine-131 (131I) from the Chernobyl accident, the authors identified RET/PTC rearrangements and other driver mutations in 60% of tumors. METHODS In this study, the remaining mutation-negative tumors from that cohort were analyzed using RNA sequencing (RNA-Seq) and reverse transcriptase-polymerase chain reaction to identify novel chromosomal rearrangements and to characterize their relation with radiation dose. RESULTS The ETS variant gene 6 ( ETV6)-neurotrophin receptor 3 ( NTRK3) rearrangement ( ETV6- NTRK3) was identified by RNA-Seq in a tumor from a patient who received a high 131I dose. Overall, the rearrangement was detected in 9 of 62 (14.5%) post-Chernobyl PTCs and in 3 of 151 (2%) sporadic PTCs ( P = .019). The most common fusion type was between exon 4 of ETV6 and exon 14 of NTRK3. The prevalence of ETV6-NTRK3 rearrangement in post-Chernobyl PTCs was associated with increasing 131I dose, albeit at borderline significance ( P = .126). The group of rearrangement-positive PTCs ( ETV6-NTRK3, RET/PTC, PAX8-PPARγ) was associated with significantly higher dose response compared with the group of PTCs with point mutations ( BRAF, RAS; P < .001). In vitro exposure of human thyroid cells to 1 gray of 131I and γ-radiation resulted in the formation of ETV6-NTRK3 rearrangement at a rate of 7.9 × 10−6 cells and 3.0 × 10−6 cells, respectively. CONCLUSIONS The authors report the occurrence of ETV6- NTRK3 rearrangements in thyroid cancer and demonstrate that this rearrangement is significantly more common in tumors associated with exposure to 131I and has a borderline significant dose response. Moreover, ETV6-NTRK3 rearrangement can be directly induced in thyroid cells by ionizing radiation in vitro and, thus, may represent a novel mechanism of radiation-induced carcinogenesis. Cancer 2014;120:799-807. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Childhood exposure to iodine-131 from the 1986 nuclear accident in Chernobyl, Ukraine, led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited.Methods: Mutational analysis was performed on 62 PTCs diagnosed in a Ukrainian cohort of patients who were < 18 years old in 1986 and received 0.008 to 8.6 Gy of (131) I to the thyroid. Associations between mutation types and (131) I dose and other characteristics were explored.Results: RET/PTC (ret proto-oncogene/papillary thyroid carcinoma) rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ (paired box 8/peroxisome proliferator-activated receptor gamma) rearrangement were identified. A significant negative association with (131) I dose for BRAF and RAS point mutations and a significant concave association with (131) I dose, with an inflection point at 1.6 Gy and odds ratio of 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements were found. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared with point mutations, rearrangements were associated with residence in the relatively iodine-deficient Zhytomyr region, younger age at exposure or surgery, and male sex.Conclusions: These results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with (131) I dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and (131) I exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. [ABSTRACT FROM AUTHOR]

Retinoblastoma (RB) is an important ocular malignancy of childhood. It has been commonly accepted for some time that knockout of the two alleles of the RB1 gene is the principal molecular target associated with the occurrence of RB. In this article, we examine the validity of the two-hit theory for RB by comparing the fit of a stochastic model with two or more mutational stages. Unlike many such models, our model assumes a fully stochastic stem cell compartment, which is crucial to its behavior. Models are fitted to a population-based dataset comprising 1,553 cases of RB for the period 1962-2000 in Great Britain (England, Scotland and Wales). The population incidence of RB is best described by a fully stochastic model with two stages, although models with a deterministic stem cell compartment yield equivalent fit; models with three or more stages fit much less well. The results strongly suggest that knockout of the two alleles of the RB1 gene is necessary and may be largely sufficient for the development of RB, in support of Knudson's two-hit hypothesis. [ABSTRACT FROM AUTHOR]

Purpose: To determine more accurate regression formulas for estimating peak skin dose (PSD) from reference air kerma (RAK) or kerma-area product (KAP). Methods: After grouping of the data from 21 procedures into 13 clinically similar groups, assessments were made of optimal clustering using the Bayesian information criterion to obtain the optimal linear regressions of (log-transformed) PSD vs RAK, PSD vs KAP, and PSD vs RAK and KAP. Results: Three clusters of clinical groups were optimal in regression of PSD vs RAK, seven clusters of clinical groups were optimal in regression of PSD vs KAP, and six clusters of clinical groups were optimal in regression of PSD vs RAK and KAP. Prediction of PSD using both RAK and KAP is significantly better than prediction of PSD with either RAK or KAP alone. The regression of PSD vs RAK provided better predictions of PSD than the regression of PSD vs KAP. The partial-pooling (clustered) method yields smaller mean squared errors compared with the complete-pooling method. Conclusion: PSD distributions for interventional radiology procedures are log-normal. Estimates of PSD derived from RAK and KAP jointly are most accurate, followed closely by estimates derived from RAK alone. Estimates of PSD derived from KAP alone are the least accurate. Using a stochastic search approach, it is possible to cluster together certain dissimilar types of procedures to minimize the total error sum of squares. [ABSTRACT FROM AUTHOR]

The article describes the case of a 49 year old man who was brought to a hospital emergency department an hour after purposely taking in multiple medications such as verapamil, morphine sulfate and diazepan. The patient was given a high-dose of insulin euglycaemic therapy (HIET) after remaining hypotensive. The patient remained haemodynamically stable after HIET was resumed and was discharged a day later after psychiatric clearance. HIET was found to be as an accepted therapy for calcium channel blocker (CCB) toxicity.

The article reflects on the study by Isbister and colleagues who recommended new approach for snakebite management based on the Australian Snakebite Project (ASP). He mentions that the recommendations by Isbister and colleagues are based on the recorded serum venom levels of patients who participated in the ASP study. He states that the recommendations from Isbister and colleagues reflect a major change on how snakebites should be managed.

A letter to the editor is presented in response to the article by N. Lintzeris, S. Lee and L. Scopelliti regarding their study on the naltrexone implants.