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1.
J Radiol Prot ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33752181

RESUMO

Radiation doses of parents exposed from the Chornobyl accident as cleanup workers or evacuees were estimated in the NCI-NRCRM trio (i.e. father, mother, offspring) study aimed at investigating the radiation effects on germline de novo mutations in children as well as other outcomes. Paternal (testes) and maternal (ovaries) gonadal doses were calculated along with associated uncertainty distributions for the following exposure pathways: (i) external irradiation during the cleanup mission, (ii) external irradiation during residence in Pripyat, and (iii) external irradiation and (iv) ingestion of radiocesium isotopes, such as 134Cs and 137Cs, during residence in settlements other than Pripyat. Gonadal doses were reconstructed for 298 trios for the periods from the time of the accident on 26 April 1986 to two time points before the child's date of birth (DOB): 51 (DOB-51) and 38 (DOB-38) weeks. The two doses, DOB-51 and DOB-38 were equal (within 1 mGy) on most occasions, except for 35 fathers where the conception of the child occurred within three-months of exposure or during exposure. The arithmetic mean of gonadal DOB-38 doses was 227 mGy (median: 11 mGy, range 0-4,080 mGy) and 8.5 mGy (median: 1.0 mGy, range 0-550 mGy) for fathers and for mothers, respectively. Gonadal doses varied considerably depending on the exposure pathway, the highest gonadal DOB-38 doses being received during the cleanup mission (mean doses of 376 mGy and 34 mGy, median of 144 mGy and 7.4 mGy for fathers and mothers, respectively), followed by exposure during residence in Pripyat (7.7 mGy and 13 mGy for mean, 7.2 mGy and 6.2 mGy for median doses), and during residence in other settlements (2.0 mGy and 2.1 mGy for mean, 0.91 mGy and 0.81 mGy for median doses). Monte-Carlo simulations were used to estimate the parental gonadal doses and associated uncertainties. The geometric standard deviations (GSDs) in the individual parental stochastic doses due to external irradiation during cleanup mission varied from 1.2 to 4.7 (mean of 1.8), during residence in Pripyat varied from 1.4 to 2.8 (mean of 1.8) while the mean GSD in doses received during residence in settlements other than Pripyat were 1.3 and 1.4 for external irradiation and ingestion of radiocesium isotopes, respectively.

3.
Ann Intern Med ; 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33316174

RESUMO

BACKGROUND: Excess death estimates quantify the full impact of the coronavirus disease 2019 (COVID-19) pandemic. Widely reported U.S. excess death estimates have not accounted for recent population changes, especially increases in the population older than 65 years. OBJECTIVE: To estimate excess deaths in the United States in 2020, after accounting for population changes. DESIGN: Surveillance study. SETTING: United States, March to August 2020. PARTICIPANTS: All decedents. MEASUREMENTS: Age-specific excess deaths in the United States from 1 March to 31 August 2020 compared with 2015 to 2019 were estimated, after changes in population size and age were taken into account, by using Centers for Disease Control and Prevention provisional death data and U.S. Census Bureau population estimates. Cause-specific excess deaths were estimated by month and age. RESULTS: From March through August 2020, 1 671 400 deaths were registered in the United States, including 173 300 COVID-19 deaths. An average of 1 370 000 deaths were reported over the same months during 2015 to 2019, for a crude excess of 301 400 deaths (128 100 non-COVID-19 deaths). However, the 2020 U.S. population includes 5.04 million more persons aged 65 years and older than the average population in 2015 to 2019 (a 10% increase). After population changes were taken into account, an estimated 217 900 excess deaths occurred from March through August 2020 (173 300 COVID-19 and 44 600 non-COVID-19 deaths). Most excess non-COVID-19 deaths occurred in April, July, and August, and 34 900 (78%) were in persons aged 25 to 64 years. Diabetes, Alzheimer disease, and heart disease caused the most non-COVID-19 excess deaths. LIMITATION: Provisional death data are underestimated because of reporting delays. CONCLUSION: The COVID-19 pandemic resulted in an estimated 218 000 excess deaths in the United States between March and August 2020, and 80% of those deaths had COVID-19 as the underlying cause. Accounting for population changes substantially reduced the excess non-COVID-19 death estimates, providing important information for guiding future clinical and public health interventions. PRIMARY FUNDING SOURCE: National Cancer Institute.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33200204

RESUMO

Children undergoing computed tomography (CT) scans have an increased risk of cancer in subsequent years, but it is unclear how much of the excess risk is due to reverse causation bias or confounding, rather than to causal effects of ionising radiation. An examination of the relationship between excess cancer risk and organ dose can help to resolve these uncertainties. Accordingly, we have estimated doses to 33 different organs arising from over 900 000 CT scans between 1985 and 2005 in our previously described cohort of almost 12 million Australians aged 0-19 years. We used a multi-tiered approach, starting with Medicare billing details for government-funded scans. We reconstructed technical parameters from national surveys, clinical protocols, regulator databases and peer-reviewed literature to estimate almost 28 000 000 individual organ doses. Doses were age-dependent and tended to decrease over time due to technological improvements and optimisation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32923912

RESUMO

PURPOSE: Radiotherapy for childhood cancer is associated with elevated subsequent neoplasm (SN) risk, but the contribution of rare variants in DNA damage response and radiation sensitivity genes to SN risk is unknown. PATIENTS AND METHODS: We conducted whole-exome sequencing in a cohort of childhood cancer survivors originally diagnosed during 1970 to 1986 (mean follow-up, 32.7 years), with reconstruction of doses to body regions from radiotherapy records. We identified patients who developed SN types previously reported to be related to radiotherapy (RT-SNs; eg, basal cell carcinoma [BCC], breast cancer, meningioma, thyroid cancer, sarcoma) and matched controls (sex, childhood cancer type/diagnosis, age, SN location, radiation dose, survival). Conditional logistic regression assessed SN risk associated with potentially protein-damaging rare variants (SnpEff, ClinVar) in 476 DNA damage response or radiation sensitivity genes with exact permutation-based P values using a Bonferroni-corrected significance threshold of P < 8.06 × 10-5. RESULTS: Among 5,105 childhood cancer survivors of European descent, 1,108 (21.7%) developed at least 1 RT-SN. Out-of-field RT-SN risk, excluding BCC, was associated with homologous recombination repair (HRR) gene variants (patient cases, 23.2%; controls, 10.8%; odds ratio [OR], 2.6; 95% CI, 1.7 to 3.9; P = 4.79 × 10-5), most notably but nonsignificantly for FANCM (patient cases, 4.0%; matched controls, 0.6%; P = 9.64 × 10-5). HRR variants were not associated with likely in/near-field RT-SNs, excluding BCC (patient cases, 12.7%; matched controls, 12.9%; P = .92). Irrespective of radiation dose, risk for RT-SNs was also associated with EXO1 variants (patient cases, 1.8%; controls, 0.4%; P = 3.31 × 10-5), another gene implicated in DNA double-strand break repair. CONCLUSION: In this large-scale discovery study, we identified novel associations between RT-SN risk after childhood cancer and potentially protein-damaging rare variants in genes involved in DNA double-strand break repair, particularly HRR. With replication, these results could affect screening recommendations for childhood cancer survivors and risk-benefit assessments of treatment approaches.

6.
JAMA Netw Open ; 3(9): e2016217, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32915234

RESUMO

Importance: Life expectancy has decreased in the US, driven largely by increases in drug poisoning, suicide, and alcohol-induced deaths. Assessing whether patterns of these causes differ is required to inform public health interventions. Objective: To compare patterns and trends in drug poisoning, suicide, and alcohol-induced death rates by geography and demographic characteristics. Design, Setting, and Participants: This serial cross-sectional study used national vital statistics data from the entire US population from January 1, 2000, to December 31, 2017, among US residents aged 20 to 64 years. Data were analyzed from January through August 2019. Exposures: Age, sex, race/ethnicity, county-level percentage of unemployment, rurality, and geography. Main Outcomes and Measures: Deaths were categorized as due to drug poisoning, suicide, or alcohol-induced causes based on underlying cause of death. Age-standardized incidence rates and annual percentage changes (APCs) in rates were estimated. Clusters of high-rate counties were identified with hot spot analysis. Excess deaths during 2001 to 2017 were estimated for each cause as the difference between the number of deaths observed and expected if rates had remained stable starting in 2000. Results: During 2000 to 2017, 1 446 177 drug poisoning, suicide, and alcohol-induced premature deaths occurred in the US, including 563 765 drug poisoning deaths (age-standardized rate: 17.6 per 100 000 person-years [PYs]), 517 679 suicides (age-standardized rate: 15.8 per 100 000 PYs), and 364 733 alcohol-induced deaths (age-standardized rate: 10.5 per 100 000 PYs), totaling 451 596 more deaths than expected based on 2000 rates. High drug poisoning death rates were clustered in the Northeast through Appalachia, yet rates of suicide and alcohol-induced deaths were highest in the West. Only suicide death rates were highest in rural areas. Drug poisoning death rates were highest among people aged 35 to 49 years (age-standardized rate: 23.7 per 100 000 PYs), whereas suicide and alcohol-induced death rates peaked among people aged 50 to 64 years (suicide age-standardized rate: 19.6 per 100 000 PYs; alcohol-induced age-standardized death rate: 26.8 per 100 000 PYs). Increases occurred over time across racial/ethnic groups, although trajectories and inflection years varied. Drug poisoning (2013-2017 APC, 15.0% [95% CI, 11-8%-18.3%] per year) and alcohol-induced death rates (2012-2017 APC, 4.1% [95% CI, 3.3%-4.9%] per year) have accelerated recently, while increases in suicide death rates have largely increased at a constant trajectory (2000-2017 APC, 1.8% [95% CI, 1.7%-1.9%] per year). Conclusions and Relevance: This cross-sectional study found that demographic characteristics and geographic patterns varied by cause of death, suggesting that increasing death rates from these causes were not concentrated in 1 group or region. Specialized interventions tailored for the underlying drivers of each cause of death are urgently needed.

7.
Cancer Causes Control ; 31(11): 1011-1019, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32839916

RESUMO

PURPOSE: Previous studies have shown an overall decreased risk of second cancers among prostate cancer survivors, but this has not been comprehensively examined by race/ethnicity. We conducted a retrospective cohort study of 716,319 one-year survivors of prostate cancer diagnosed at ages 35-84 during 2000-2015 as reported to 17 US Surveillance, Epidemiology and End Results (SEER) registries. METHODS: We estimated standardized incidence ratios (SIRs) for second primary non-prostate malignancies by race/ethnicity (non-Latino white, Black, Asian/Pacific Islander [API] and Latino), by Gleason, and by time since prostate cancer diagnosis. Poisson regression models were used to test heterogeneity between groups with the expected number as the offset. RESULTS: 60,707 second primary malignancies were observed. SIRs for all second cancers combined varied significantly by race/ethnicity: SIRwhite: 0.88 (95% confidence interval: 0.87-0.89), SIRLatino: 0.92 (0.89-0.95), SIRBlack: 0.97 (0.95-0.99), and SIRAPI: 1.05 (1.01-1.09) (p-heterogeneity < 0.001). SIRs for all cancers combined were higher among survivors of higher vs. lower Gleason prostate cancers irrespective of race/ethnicity. We observed significant heterogeneity by race/ethnicity in SIRs for 9 of 14 second cancer types investigated including lung, bladder, kidney, and liver. CONCLUSIONS: Our results confirm that most prostate cancer survivors have lower risks of second cancers than expected, but the magnitude varied by race/ethnicity. Exceptionally, API men had small but significantly increased risk. Further research to understand drivers of the observed race/ethnicity heterogeneity is warranted.


Assuntos
Sobreviventes de Câncer , Segunda Neoplasia Primária/epidemiologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupos Étnicos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Risco , Programa de SEER , Estados Unidos
8.
J Natl Cancer Inst Monogr ; 2020(56): 188-200, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32657347

RESUMO

BACKGROUND: Ionizing radiation is an established carcinogen, but risks from low-dose exposures are controversial. Since the Biological Effects of Ionizing Radiation VII review of the epidemiological data in 2006, many subsequent publications have reported excess cancer risks from low-dose exposures. Our aim was to systematically review these studies to assess the magnitude of the risk and whether the positive findings could be explained by biases. METHODS: Eligible studies had mean cumulative doses of less than 100 mGy, individualized dose estimates, risk estimates, and confidence intervals (CI) for the dose-response and were published in 2006-2017. We summarized the evidence for bias (dose error, confounding, outcome ascertainment) and its likely direction for each study. We tested whether the median excess relative risk (ERR) per unit dose equals zero and assessed the impact of excluding positive studies with potential bias away from the null. We performed a meta-analysis to quantify the ERR and assess consistency across studies for all solid cancers and leukemia. RESULTS: Of the 26 eligible studies, 8 concerned environmental, 4 medical, and 14 occupational exposure. For solid cancers, 16 of 22 studies reported positive ERRs per unit dose, and we rejected the hypothesis that the median ERR equals zero (P = .03). After exclusion of 4 positive studies with potential positive bias, 12 of 18 studies reported positive ERRs per unit dose (P = .12). For leukemia, 17 of 20 studies were positive, and we rejected the hypothesis that the median ERR per unit dose equals zero (P = .001), also after exclusion of 5 positive studies with potential positive bias (P = .02). For adulthood exposure, the meta-ERR at 100 mGy was 0.029 (95% CI = 0.011 to 0.047) for solid cancers and 0.16 (95% CI = 0.07 to 0.25) for leukemia. For childhood exposure, the meta-ERR at 100 mGy for leukemia was 2.84 (95% CI = 0.37 to 5.32); there were only two eligible studies of all solid cancers. CONCLUSIONS: Our systematic assessments in this monograph showed that these new epidemiological studies are characterized by several limitations, but only a few positive studies were potentially biased away from the null. After exclusion of these studies, the majority of studies still reported positive risk estimates. We therefore conclude that these new epidemiological studies directly support excess cancer risks from low-dose ionizing radiation. Furthermore, the magnitude of the cancer risks from these low-dose radiation exposures was statistically compatible with the radiation dose-related cancer risks of the atomic bomb survivors.

9.
J Natl Cancer Inst Monogr ; 2020(56): 154-175, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32657350

RESUMO

BACKGROUND: Outcome assessment problems and errors that could lead to biased risk estimates in low-dose radiation epidemiological studies of cancer risks have not been systematically evaluated. METHODS: Incidence or mortality risks for all cancers or all solid cancers combined and for leukemia were examined in 26 studies published in 2006-2017 involving low-dose (mean dose ≤100 mGy) radiation from environmental, medical, or occupational sources. We evaluated the impact of loss to follow-up, under- or overascertainment, outcome misclassification, and changing classifications occurring similarly or differentially across radiation dose levels. RESULTS: Loss to follow-up was not reported in 62% of studies, but when reported it was generally small. Only one study critically evaluated the completeness of the sources of vital status. Underascertainment of cancers ("false negatives") was a potential shortcoming for cohorts that could not be linked with high-quality population-based registries, particularly during early years of exposure in five studies, in two lacking complete residential history, and in one with substantial emigration. False positives may have occurred as a result of cancer ascertainment from self- or next-of-kin report in three studies or from enhanced medical surveillance of exposed patients that could lead to detection bias (eg, reporting precancer lesions as physician-diagnosed cancer) in one study. Most pediatric but few adult leukemia studies used expert hematopathology review or current classifications. Only a few studies recoded solid cancers to the latest International Classification of Diseases or International Classification of Diseases for Oncology codes. These outcome assessment shortcomings were generally nondifferential in relation to radiation exposure level except possibly in four studies. CONCLUSION: The majority of studies lacked information to enable comprehensive evaluation of all major sources of outcome assessment errors, although reported data suggested that the outcome assessment limitations generally had little effect on risk or biased estimates towards the null except possibly in four studies.

10.
J Natl Cancer Inst Monogr ; 2020(56): 97-113, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32657348

RESUMO

Whether low-dose ionizing radiation can cause cancer is a critical and long-debated question in radiation protection. Since the Biological Effects of Ionizing Radiation report by the National Academies in 2006, new publications from large, well-powered epidemiological studies of low doses have reported positive dose-response relationships. It has been suggested, however, that biases could explain these findings. We conducted a systematic review of epidemiological studies with mean doses less than 100 mGy published 2006-2017. We required individualized doses and dose-response estimates with confidence intervals. We identified 26 eligible studies (eight environmental, four medical, and 14 occupational), including 91 000 solid cancers and 13 000 leukemias. Mean doses ranged from 0.1 to 82 mGy. The excess relative risk at 100 mGy was positive for 16 of 22 solid cancer studies and 17 of 20 leukemia studies. The aim of this monograph was to systematically review the potential biases in these studies (including dose uncertainty, confounding, and outcome misclassification) and to assess whether the subset of minimally biased studies provides evidence for cancer risks from low-dose radiation. Here, we describe the framework for the systematic bias review and provide an overview of the eligible studies.

11.
J Natl Cancer Inst Monogr ; 2020(56): 133-153, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32657349

RESUMO

BACKGROUND: Low-dose, penetrating photon radiation exposure is ubiquitous, yet our understanding of cancer risk at low doses and dose rates derives mainly from high-dose studies. Although a large number of low-dose cancer studies have been recently published, concern exists about the potential for confounding to distort findings. The aim of this study was to describe and assess the likely impact of confounding and selection bias within the context of a systematic review. METHODS: We summarized confounding control methods for 26 studies published from 2006 to 2017 by exposure setting (environmental, medical, or occupational) and identified confounders of potential concern. We used information from these and related studies to assess evidence for confounding and selection bias. For factors in which direct or indirect evidence of confounding was lacking for certain studies, we used a theoretical adjustment to determine whether uncontrolled confounding was likely to have affected the results. RESULTS: For medical studies of childhood cancers, confounding by indication (CBI) was the main concern. Lifestyle-related factors were of primary concern for environmental and medical studies of adult cancers and for occupational studies. For occupational studies, other workplace exposures and healthy worker survivor bias were additionally of interest. For most of these factors, however, review of the direct and indirect evidence suggested that confounding was minimal. One study showed evidence of selection bias, and three occupational studies did not adjust for lifestyle or healthy worker survivor bias correlates. Theoretical adjustment for three factors (smoking and asbestos in occupational studies and CBI in childhood cancer studies) demonstrated that these were unlikely to explain positive study findings due to the rarity of exposure (eg, CBI) or the relatively weak association with the outcome (eg, smoking or asbestos and all cancers). CONCLUSION: Confounding and selection bias are unlikely to explain the findings from most low-dose radiation epidemiology studies.

12.
Radiother Oncol ; 151: 33-39, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32679305

RESUMO

PURPOSE: To investigate the relationship between oesophagus dose-volume distribution and long-term risk of oesophageal cancer after radiation therapy for breast cancer. MATERIALS AND METHODS: In a case-control study nested within a cohort of 289,748 ≥5-year survivors of female breast cancer treated in 1943-2003 in five countries, doses to the second primary cancer (DSPC) and individual dose-volume histograms (DVH) to the entire oesophagus were reconstructed for 252 oesophageal cancer cases and 488 matched controls (median follow-up time: 13, range: 5-37 years). Using conditional logistic regression, we estimated excess odds ratios (EOR) of oesophageal cancer associated with DVH metrics. We also investigated whether DVH metrics confounded or modified DSPC-related -risk estimates. RESULTS: Among the DVH metrics evaluated, median dose (Dmedian) to the entire oesophagus had the best statistical performance for estimating risk of all histological types combined (EOR/Gy = 0.071, 95% confidence interval [CI]: 0.018 to 0.206). For squamous cell carcinoma, the most common subtype, the EOR/Gy for Dmedian increased by 31% (95% CI: 3% to 205%) for each increment of 10% of V30 (p = 0.02). Adjusting for DVH metrics did not materially change the EOR/Gy for DSPC, but there was a borderline significant positive interaction between DSPC and V30 (p = 0.07). CONCLUSION: This first study investigating the relationship between oesophagus dose-volume distribution and oesophageal cancer risk showed an increased risk per Gy for Dmedian with larger volumes irradiated at high doses. While current techniques allows better oesophagus sparing, constraints applied to Dmedian and V30 could potentially further reduce the risk of oesophageal cancer.

13.
JAMA Netw Open ; 3(7): e209660, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32701159

RESUMO

Importance: The long-term health effects of radioactive iodine (RAI) and antithyroid drug (ATD) treatments compared with surgery for hyperthyroidism remain uncertain. Objective: To compare solid cancer mortality rates associated with RAI and ATD treatments vs surgical management for hyperthyroidism. Design, Setting, and Participants: This multicenter cohort study assessed patients treated for hyperthyroidism from January 1, 1946, to December 31, 1964, with follow-up through December 31, 2014. Data analysis was performed from August 1, 2019, to April 23, 2020. Exposures: Management with RAI, ATDs, surgical intervention, or combinations of these treatments. Main Outcomes and Measures: Comparisons of solid cancer mortality rates in each treatment group with expected rates from the general population were assessed using standardized mortality ratios (SMRs), and internal comparisons were assessed using hazard ratios (HRs) adjusted for age, sex, and underlying diagnosis (Graves disease or toxic nodular goiter). Results: Of 31 363 patients (24 894 [79.4%] female; mean [SD] age, 46.9 [14.8] years) included in the study, 28 523 (90.9%) had Graves disease. The median follow-up time was 26.0 years (interquartile range, 12.3-41.9 years). Important differences in patient characteristics existed across treatment groups at study entry. Notably, the drug-only group (3.6% of the cohort) included a higher proportion of patients with prior cancers (7.3% vs 1.9%-4.0%), contributing to an elevated SMR for solid cancer mortality. After excluding prior cancers, solid cancer SMRs were not elevated in any of the treatment groups (SMR for surgery only, 0.82 [95% CI, 0.66-1.00]; SMR for drugs only, 0.90 [95% CI, 0.74-1.09]; SMR for drugs and surgery, 0.88 [95% CI, 0.84-0.94]; SMR for RAI only, 0.90 [95% CI, 0.84-0.96]; SMR for surgery and RAI, 0.66 [95% CI, 0.52-0.85]; SMR for drugs and RAI, 0.94 [95% CI, 0.89-1.00]; and SMR for drugs, surgery, and RAI, 0.85 [95% CI, 0.75-0.96]), and no significant HRs for solid cancer death were observed across treatment groups. Among RAI-treated patients, HRs for solid cancer mortality increased significantly across levels of total administered activity (1.08 per 370 MBq; 95% CI, 1.03-1.13 per 370 MBq); this association was stronger among patients treated with only RAI (HR, 1.19 per 370 MBq; 95% CI, 1.09-1.30 per 370 MBq). Conclusions and Relevance: After controlling for known sources of confounding, the study found no significant differences in the risk of solid cancer mortality by treatment group. However, among RAI-treated patients, a modest positive association was observed between total administered activity and solid cancer mortality, providing further evidence in support of a dose-dependent association between RAI and solid cancer mortality.

14.
JAMA Netw Open ; 3(2): e1921451, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32083687

RESUMO

Importance: Notable increases in mortality from alcohol-induced causes over the past 2 decades in the United States have been reported. However, comprehensive assessments of trends in alcohol-induced mortality by sex, age, race/ethnicity, and social and geographic factors are lacking. Objective: To examine trends in alcohol-induced mortality rates from 2000 to 2016, comparing results by demographic characteristics including sex, race/ethnicity, age, county-level socioeconomic status, and geographic location. Design, Setting, and Participants: This serial cross-sectional study used US national vital statistics data for years 2000 to 2016 for all US residents older than 15 years. Data analysis was conducted from January to September 2019. Exposures: Trends in alcohol-induced mortality by sex, race/ethnicity, age, county-level socioeconomic status (ie, median income, percentage of unemployed residents, percentage of residents with a bachelor's degree), rurality level, and US state. Main Outcomes and Measures: Alcohol-induced mortality, ie, deaths for which alcohol holds a population-attributable fraction of 1. Deaths were expressed per 100 000 residents as absolute and age-standardized rates. Mortality trends were measured as average annual percentage changes (AAPCs) for the entire period (ie, 2000-2016) and annual percentage changes (APCs) for individual periods of change within the study period. Results: A total of 425 045 alcohol-induced deaths were identified from 2000 to 2016 (2000: 19 627 deaths; 14 979 [76.3%] men; 2016: 34 857 deaths; 25 213 [73.3%] men). The rate of alcohol-induced deaths increased substantially among men (AAPC, 1.4%; 95% CI, 1.0% to 1.8%) and women (AAPC, 3.1%; 95% CI, 2.6% to 3.6%) and accelerated recently (men, 2012-2016: APC, 4.2%; 95% CI, 3.1% to 5.3%; women, 2013-2016: APC, 7.1%; 95% CI, 5.1% to 9.1%). The largest increases by race/ethnicity were observed among American Indian and Alaska Native men (AAPC, 3.3%; 95% CI, 2.6% to 4.0%), American Indian and Alaska Native women (AAPC, 4.2%; 95% CI, 3.8% to 4.6%), and white women (AAPC, 4.1%; 95% CI, 3.6% to 4.7%). Despite initial declines among black women, black men, and Latino men (eg, Latino men, 2000-2003: APC, -5.1%; 95% CI, -9.8% to -0.1%; 2003-2013: APC, -0.6%; 95% CI, -1.4% to 0.2%), increases occurred later in the study period (eg, Latino men, 2013-2016: APC, 4.1%; 95% CI, 0.3% to 8.1%). The rates of increase varied by age group and in turn by racial/ethnic group. Among white individuals, large absolute increases occurred in midlife (eg, men aged 55-59 years, 2000-2003: 25.5 deaths per 100 000 residents; 2013-2016: 43.3 deaths per 100 000 residents; women aged 50-54 years, 2000-2003: 7.4 deaths per 100 000 residents; 2013-2016: 16.5 deaths per 100 000 residents), although APCs were also large for ages 25 to 34 years, ranging from 4.6% to 6.9% per year among men and from 7.3% to 12.0% among women. Among American Indian and Alaska Native individuals, increases throughout the age range were observed, with the largest absolute increase occurring for ages 45 to 49 years among men (2000-2013: 113.6 deaths per 100 000 residents; 2013-2016: 193.1 deaths per 100 000 residents) and for ages 50 to 54 among women (2000-2013: from 56.1 deaths per 100 000 residents; 2013-2016: 105.1 deaths per 100 000 residents). Conclusions and Relevance: This study found large increases in alcohol-induced death rates across age and racial/ethnic subgroups of the US population, which have accelerated over recent years. Large increases in alcohol-induced deaths among younger age groups may be associated with future increases in alcohol-related disease.


Assuntos
Consumo de Bebidas Alcoólicas/mortalidade , Transtornos Relacionados ao Uso de Álcool/mortalidade , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
15.
JAMA Netw Open ; 3(2): e1921085, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32049297

RESUMO

Importance: Premature death rates vary in the United States by race/ethnicity. Despite their socioeconomic disadvantages, US Latino populations have lower premature mortality rates than do US white populations, a phenomenon termed the "Latino or Hispanic paradox." Objective: To investigate whether there is a broader Latin American paradox by comparing premature mortality rates in the United States according to race/ethnicity with rates in Latin America and Puerto Rico from 2001 to 2015. Design, Setting, and Participants: This descriptive cross-sectional study used mortality data from the World Health Organization Mortality Database. All deaths occurring in individuals aged 20 to 64 years among US Latino, African American, white, and Puerto Rican and 12 other Latin American populations from January 2001 to December 2015 were selected. The data analysis began in October 2018. Exposures: Age, sex, race/ethnicity, and country. Main Outcomes and Measures: All-cause mortality, cause-specific mortality, age-standardized mortality rates (AMSRs), and average annual percentage change in mortality rates during 2001 to 2015. Results: During 2001 to 2015, 22 million deaths (8 million women and 14 million men) occurred among individuals aged 20 to 64 years in the selected populations. Among women, US Latina individuals had the lowest premature mortality rates (ASMR for 2015, 144 deaths per 100 000 population) and US African American women had the highest premature mortality rate (ASMR for 2015, 340 deaths per 100 000 population) of the 16 populations studied. Rates among US white women shifted from the sixth lowest in 2001 (ASMR, 231 deaths per 100 000 population) to the 12th lowest in 2015 (ASMR, 235 deaths per 100 000 population). Among men, Peru had the lowest premature mortality rates (ASMR for 2015, 219 deaths per 100 000 population), and Belize had the highest premature mortality rates (ASMR for 2015, 702 deaths per 100 000 population). White men in the United States shifted from the fifth lowest rates in 2001 (ASMR, 396 deaths per 100 000 population) to the eighth lowest rates in 2015 (ASMR, 394 deaths per 100 000 population). Rates for both women and men decreased in all the populations studied from 2001 to 2015 (average annual percentage change range, 0.4% to 3.8% per year) except among US white populations, for which the rate plateaued (average annual percentage change, 0.02% per year [95% CI, -0.3% to 0.2% per year] for women; -0.2% per year [95% CI, -0.4% to 0.0% per year] for men) and among Nicaraguan men, for whom the rates increased (0.6% per year [95% CI, 0.2% to 1.0% per year]). The populations with the lowest mortality rates in 2015 had lower rates from all major causes, but rates were particularly lower for heart disease (21 deaths per 100 000 population) and cancer (50 deaths per 100 000 population). Conclusions and Relevance: Premature mortality rates are lower for US Latino populations and several Latin American countries than for US white populations, suggesting that there may be a broader Latin American paradox. This analysis also highlights the high premature mortality rates among US African American populations, especially women, compared with many Latin American populations.


Assuntos
Mortalidade Prematura/tendências , Adulto , Estudos Transversais , Feminino , Humanos , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
16.
Radiat Res ; 193(2): 95-106, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31794291

RESUMO

Quantification of radiation dose to normal tissue during radiotherapy is critical for assessing risk for radiotherapy-related late effects, including subsequent neoplasms (SNs). Case-control studies of SNs typically reconstruct absorbed radiation dose to the specific SN location using individual treatment parameters. A simplified method estimates the maximum prescribed target dose to the body region in which the SN arises. We compared doses and risk estimates from these methods using data from case-control studies of subsequent brain tumors (64 cases, 244 controls) and breast cancer (94 cases, 358 controls) nested within the Childhood Cancer Survivor Study (≥5-year survivors of childhood cancer diagnosed 1970-1986). The weighted kappa statistic [95% confidence interval (CI)] evaluating agreement between categorical (>0-9.9/10-19.9/20-29.9/≥30 Gy) body-region and tumor location-specific doses was 0.95 (0.91-0.98) for brain and 0.76 (0.69-0.82) for breast. The body-region and location-specific doses were assigned to the same dose category for a smaller proportion of patients treated with fields delivering a heterogeneous dose across the tissue of interest (e.g., partial brain field = 57.1%; mantle field = 61.3%) than patients treated with fields delivering a more homogeneous dose (e.g., whole brain field = 100%). Excess odds ratios per Gy (95% CI) from conditional logistic regression were 1.25 (0.33-6.33) and 1.20 (0.31-6.14) for brain tumors and 0.21 (0.05-0.77) and 0.10 (0.02-0.44) for breast cancer, using location-specific and body-region doses, respectively. We observed that body-region doses can approximate location-specific doses when the tissue of interest is clearly in the radiation field or outside the treated body region. Agreement is lower when there is greater ambiguity of SN location relative to the treatment field.


Assuntos
Neoplasias Induzidas por Radiação/epidemiologia , Doses de Radiação , Radioterapia/efeitos adversos , Relatório de Pesquisa , Sobreviventes/estatística & dados numéricos , Adolescente , Criança , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Modelos Estatísticos , Dosagem Radioterapêutica , Medição de Risco , Fatores de Tempo
17.
Cancer Epidemiol ; 64: 101664, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31884334

RESUMO

BACKGROUND: While radiotherapy is a major risk factor for thyroid cancer after childhood cancer, factors contributing to increased thyroid cancer risk after adulthood cancer remain unclear. METHODS: We evaluated second primary papillary thyroid cancer (PTC) risk among 3,175,216 ≥ 1-year adult survivors of non-thyroid malignancies from US population-based cancer registries (2000-2015), using standardized incidence ratios (SIRs). Because heightened surveillance may increase detection of indolent thyroid tumors and earlier detection of advanced tumors, we examined SIRs by PTC stage and time since first cancer (latency). RESULTS: SIRs for second primary PTC (N = 4333) were statistically-significantly 1.2-3.5-fold elevated overall and after 23/27 first cancer types evaluated, with generally similar risks for localized and regional/distant PTC. SIRs for regional/distant PTC (N = 1501) were highest after pancreatic (SIR = 3.7; 95% confidence interval [CI] = 1.9-6.5) and soft tissue (SIR = 4.2; 95%CI = 2.8-6.2) cancers, followed by melanoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma, and larynx, kidney, and brain/central nervous system (SIRs = 2.0-2.9) cancers. SIRs typically decreased with increasing latency but remained statistically-significantly elevated for regional/distant-PTC ≥5 years after diagnosis of cancers of the rectum, pancreas, lung/bronchus, soft tissue, female breast, uterine corpus, prostate, and kidney, and after melanoma, Hodgkin lymphoma, CLL/SLL, and follicular lymphoma. Neither total nor regional/distant PTC were clearly associated with initial course of radiotherapy or chemotherapy. CONCLUSIONS: PTC risk was elevated after a range of first primary adult cancers but was not clearly related to treatment. Although surveillance may contribute to elevated short-term risks of PTC, longer-term elevations in regional/distant PTC may be attributable to shared risk factors.


Assuntos
Segunda Neoplasia Primária/etiologia , Câncer Papilífero da Tireoide/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Sobreviventes de Câncer/estatística & dados numéricos , Coleta de Dados , Feminino , História do Século XXI , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Programa de SEER , Câncer Papilífero da Tireoide/patologia , Estados Unidos , Adulto Jovem
18.
J Clin Oncol ; 38(7): 686-697, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31877085

RESUMO

PURPOSE: To determine whether recommended amounts of leisure-time physical activity (ie, 7.5-15 metabolic equivalent task [MET] hours/week) are associated with lower cancer risk, describe the shape of the dose-response relationship, and explore associations with moderate- and vigorous-intensity physical activity. METHODS: Data from 9 prospective cohorts with self-reported leisure-time physical activity and follow-up for cancer incidence were pooled. Multivariable Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% CIs of the relationships between physical activity with incidence of 15 types of cancer. Dose-response relationships were modeled with restricted cubic spline functions that compared 7.5, 15.0, 22.5, and 30.0 MET hours/week to no leisure-time physical activity, and statistically significant associations were determined using tests for trend (P < .05) and 95% CIs (< 1.0). RESULTS: A total of 755,459 participants (median age, 62 years [range, 32-91 years]; 53% female) were followed for 10.1 years, and 50,620 incident cancers accrued. Engagement in recommended amounts of activity (7.5-15 MET hours/week) was associated with a statistically significant lower risk of 7 of the 15 cancer types studied, including colon (8%-14% lower risk in men), breast (6%-10% lower risk), endometrial (10%-18% lower risk), kidney (11%-17% lower risk), myeloma (14%-19% lower risk), liver (18%-27% lower risk), and non-Hodgkin lymphoma (11%-18% lower risk in women). The dose response was linear in shape for half of the associations and nonlinear for the others. Results for moderate- and vigorous-intensity leisure-time physical activity were mixed. Adjustment for body mass index eliminated the association with endometrial cancer but had limited effect on other cancer types. CONCLUSION: Health care providers, fitness professionals, and public health practitioners should encourage adults to adopt and maintain physical activity at recommended levels to lower risks of multiple cancers.

19.
Br J Radiol ; 93(1107): 20190673, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31600082

RESUMO

OBJECTIVE: The Pediatric Proton/Photon Consortium Registry (PPCR) is a comprehensive data registry composed of pediatric patients treated with radiation. It was established to expedite outcomes-based research. The attributes which allow the PPCR to be a successful collaboration are reviewed. METHODS AND MATERIALS: Current eligibility criteria are radiotherapy patients < 22 years treated at one of the 15 US participating institutions. Detailed health and treatment data are collected about the disease presentation and treatment exposures, and annually thereafter, in REDCap (Research Electronic Data Capture). DICOM (Digital Imaging and Communications in Medicine) imaging and radiation plans are collected through MIM/MIMcloud. An optional patient-reported quality-of-life (PedsQL) study is administered at 10 sites. RESULTS: Accrual started October 2012 with 2,775 participants enrolled as of 25 July 2019. Most patients, 62.0%, were treated for central nervous system (CNS) tumors, the most common of which are medulloblastoma (n = 349), ependymoma (n = 309), and glial/astrocytoma tumors (n = 279). The most common non-CNS diagnoses are rhabdomyosarcoma (n = 284), Ewing's sarcoma (n = 153), and neuroblastoma (n = 130). While the majority of participants are US residents, 18.7% come from 36 other countries. Over 685 patients participate in the PedsQL study. CONCLUSIONS: The PPCR is a valuable research platform capable of answering countless research questions that will ultimately improve patient care. Centers outside of the USA are invited to participate directly or may engage with the PPCR to align data collection strategies to facilitate large-scale international research. ADVANCES IN KNOWLEDGE: For investigators looking to carry out research in a large pediatric oncology cohort or interested in registry work, this paper provides an updated overview of the PPCR.


Assuntos
Coleta de Dados/normas , Neoplasias/radioterapia , Fótons/uso terapêutico , Terapia com Prótons/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Adolescente , Astrocitoma/radioterapia , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias Cerebelares/radioterapia , Criança , Pré-Escolar , Computação em Nuvem , Ependimoma/radioterapia , Feminino , Glioma/radioterapia , Humanos , Lactente , Cooperação Internacional , Masculino , Meduloblastoma/radioterapia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Autorrelato , Adulto Jovem
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