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1.
J Urol ; : 101097JU0000000000003929, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573938

RESUMO

PURPOSE: To determine changes in patient reported hematuria and urinary symptoms after hyperbaric oxygen (HBO2) treatment for radiation cystitis (RC). METHODS: We analyzed prospectively data from the Multicenter Registry for Hyperbaric Oxygen Therapy Consortium collected within a week of beginning and ending HBO2. Measures included the modified Radiation Therapy Oncology Group (RTOG) Hematuria Scale, Urinary Distress Inventory Short Form (UDI-6), and EuroQOL EQ-5D-5L. RTOG hematuria and UDI scores were compared using the sign test. Logistic regression was used to evaluate characteristics associated with hematuria improvement. RESULTS: 470 registry patients had RC. The median age, number of HBO2 sessions, and years after radiation were 73 (IQR 12) years, 39 (IQR 10) sessions, and 5 (IQR 8) years respectively. 84% (393/470) had prostate-cancer-related radiation. EQ-5D-5L scores improved from 0.83 (IQR 0.14) to 0.85 (IQR 0.22), P < .001. 370 had complete RTOG hematuria scores which improved from 2 (IQR 2) to 0 (IQR 2), P < .001. 246 had complete UDI-6 ratings which decreased from 33.3 (IQR 44) to 22.2 (IQR 33) P < .001. Regression analysis of those with visible hematuria pre HBO2, showed lower improvement odds associated with higher HBO2 hematuria scores (OR: 0.44; 95% confidence interval (CI) 0.26-0.73, P < .01), a smoking history (OR: 0.44, 95% CI: 0.21-0.92, P = .03), or a non-prostate cancer history (0.32 (95%CI:0.10-0.99, P = .05). CONCLUSIONS: HBO2 for RC improved reported hematuria, urinary function, and quality of life. Higher baseline hematuria scores, smoking, and non-prostate cancer history were associated with a lower odds of hematuria improvement.

2.
PLoS Pathog ; 20(4): e1012087, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38557815

RESUMO

Prion diseases uniquely manifest in three distinct forms: inherited, sporadic, and infectious. Wild-type prions are responsible for the sporadic and infectious versions, while mutant prions cause inherited variants like fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). Although some drugs can prolong prion incubation times up to four-fold in rodent models of infectious prion diseases, no effective treatments for FFI and fCJD have been found. In this study, we evaluated the efficacy of various anti-prion drugs on newly-developed knock-in mouse models for FFI and fCJD. These models express bank vole prion protein (PrP) with the pathogenic D178N and E200K mutations. We applied various drug regimens known to be highly effective against wild-type prions in vivo as well as a brain-penetrant compound that inhibits mutant PrPSc propagation in vitro. None of the regimens tested (Anle138b, IND24, Anle138b + IND24, cellulose ether, and PSCMA) significantly extended disease-free survival or prevented mutant PrPSc accumulation in either knock-in mouse model, despite their ability to induce strain adaptation of mutant prions. Our results show that anti-prion drugs originally developed to treat infectious prion diseases do not necessarily work for inherited prion diseases, and that the recombinant sPMCA is not a reliable platform for identifying compounds that target mutant prions. This work underscores the need to develop therapies and validate screening assays specifically for mutant prions, as well as anti-prion strategies that are not strain-dependent.


Assuntos
Síndrome de Creutzfeldt-Jakob , Doenças Priônicas , Príons , Animais , Camundongos , Príons/metabolismo , Doenças Priônicas/tratamento farmacológico , Doenças Priônicas/genética , Doenças Priônicas/metabolismo , Síndrome de Creutzfeldt-Jakob/tratamento farmacológico , Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/metabolismo , Proteínas Priônicas/genética , Proteínas Priônicas/metabolismo , Encéfalo/patologia , Arvicolinae/metabolismo
3.
Cancers (Basel) ; 16(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38610975

RESUMO

PURPOSE: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). METHODS: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. RESULTS: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy.

4.
bioRxiv ; 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37808761

RESUMO

Prion diseases uniquely manifest in three distinct forms: inherited, sporadic, and infectious. Wild-type prions are responsible for the sporadic and infectious versions, while mutant prions cause inherited variants like fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). Although some drugs can prolong prion incubation times up to four-fold in rodent models of infectious prion diseases, no effective treatments for FFI and fCJD have been found. In this study, we evaluated the efficacy of various anti-prion drugs on newly-developed knock-in mouse models for FFI and fCJD. These models express bank vole prion protein (PrP) with the pathogenic D178N and E200K mutations. We applied various drug regimens known to be highly effective against wild-type prions in vivo as well as a brain-penetrant compound that inhibits mutant PrP Sc propagation in vitro . None of the regimens tested (Anle138b, IND24, Anle138b + IND24, cellulose ether, and PSCMA) significantly extended disease-free survival or prevented mutant PrP Sc accumulation in either knock-in mouse model, despite their ability to induce strain adaptation of mutant prions. Paradoxically, the combination of Anle138b and IND24 appeared to accelerate disease by 16% and 26% in kiBVI E200K and kiBVI D178N mice, respectively, and accelerated the aggregation of mutant PrP molecules in vitro . Our results show that anti-prion drugs originally developed to treat infectious prion diseases do not necessarily work for inherited prion diseases, and that the recombinant sPMCA is not a reliable platform for identifying compounds that target mutant prions. This work underscores the need to develop therapies and validate screening assays specifically for mutant prions.

5.
Cancer Res Commun ; 3(8): 1678-1687, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37649812

RESUMO

Compared with urban areas, rural areas have higher cancer mortality and have experienced substantially smaller declines in cancer incidence in recent years. In a New Hampshire (NH) and Vermont (VT) survey, we explored the roles of rurality and educational attainment on cancer risk behaviors, beliefs, and other social drivers of health. In February-March 2022, two survey panels in NH and VT were sent an online questionnaire. Responses were analyzed by rurality and educational attainment. Respondents (N = 1,717, 22%) mostly lived in rural areas (55%); 45% of rural and 25% of urban residents had high school education or less and this difference was statistically significant. After adjustment for rurality, lower educational attainment was associated with smoking, difficulty paying for basic necessities, greater financial difficulty during the COVID-19 pandemic, struggling to pay for gas (P < 0.01), fatalistic attitudes toward cancer prevention, and susceptibility to information overload about cancer prevention. Among the 33% of respondents who delayed getting medical care in the past year, this was more often due to lack of transportation in those with lower educational attainment (21% vs. 3%, P = 0.02 adjusted for rurality) and more often due to concerns about catching COVID-19 among urban than rural residents (52% vs. 21%; P < 0.001 adjusted for education). In conclusion, in NH/VT, smoking, financial hardship, and beliefs about cancer prevention are independently associated with lower educational attainment but not rural residence. These findings have implications for the design of interventions to address cancer risk in rural areas. Significance: In NH and VT, the finding that some associations between cancer risk factors and rural residence are more closely tied to educational attainment than rurality suggest that the design of interventions to address cancer risk should take educational attainment into account.


Assuntos
COVID-19 , Neoplasias , Humanos , New Hampshire/epidemiologia , Pandemias , Vermont/epidemiologia , Assunção de Riscos , Neoplasias/epidemiologia , Inquéritos e Questionários
6.
Cancer Res Commun ; 3(8): 1538-1550, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37583435

RESUMO

We tested the hypotheses that adult cancer incidence and mortality in the Northeast region and in Northern New England (NNE) were different than the rest of the United States, and described other related cancer metrics and risk factor prevalence. Using national, publicly available cancer registry data, we compared cancer incidence and mortality in the Northeast region with the United States and NNE with the United States overall and by race/ethnicity, using age-standardized cancer incidence and rate ratios (RR). Compared with the United States, age-adjusted cancer incidence in adults of all races combined was higher in the Northeast (RR, 1.07; 95% confidence interval [CI] 1.07-1.08) and in NNE (RR 1.06; CI 1.05-1.07). However compared with the United States, mortality was lower in the Northeast (RR, 0.98; CI 0.98-0.98) but higher in NNE (RR, 1.05; CI 1.03-1.06). Mortality in NNE was higher than the United States for cancers of the brain (RR, 1.16; CI 1.07-1.26), uterus (RR, 1.32; CI 1.14-1.52), esophagus (RR, 1.36; CI 1.26-1.47), lung (RR, 1.12; CI 1.09-1.15), bladder (RR, 1.23; CI 1.14-1.33), and melanoma (RR, 1.13; CI 1.01-1.27). Significantly higher overall cancer incidence was seen in the Northeast than the United States in all race/ethnicity subgroups except Native American/Alaska Natives (RR, 0.68; CI 0.64-0.72). In conclusion, NNE has higher cancer incidence and mortality than the United States, a pattern that contrasts with the Northeast region, which has lower cancer mortality overall than the United States despite higher incidence. Significance: These findings highlight the need to identify the causes of higher cancer incidence in the Northeast and the excess cancer mortality in NNE.


Assuntos
Neoplasias , Adulto , Humanos , Incidência , New England/epidemiologia , Fatores de Risco , Estados Unidos/epidemiologia , Neoplasias/epidemiologia
7.
Prev Med ; 175: 107649, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37517458

RESUMO

The early COVID-19 pandemic was associated with cessation of screening services, but the prevalence of ongoing delays in cancer screening into the third year of the pandemic are not well-characterized. In February/March 2022, a population-based survey assessed cancer needs in New Hampshire and Vermont. The associations between cancer screening delays (breast, cervical, colorectal or lung cancer) and social determinants of health, health care access, and cancer attitudes and beliefs were tested. Distributions and Rao-Scott chi-square tests were used for hypothesis testing and weighted to represent state populations. Of 1717 participants, 55% resided in rural areas, 96% identified as White race, 50% were women, 36% had high school or less education. Screening delays were reported for breast cancer (28%), cervical cancer (30%), colorectal cancer (24%), and lung cancer (30%). Delays were associated with having higher educational attainment (lung), urban living (colorectal), and having Medicaid insurance (breast, cervical). Low confidence in ability to obtain information about cancer was associated with screening delays across screening types. The most common reason for delay was the perception that the screening test was not urgent (31% breast, 30% cervical, 28% colorectal). Cost was the most common reason for delayed lung cancer screening (36%). COVID-19 was indicated as a delay reason in 15-29% of respondents; 12-20% reported health system capacity during the pandemic as a reason for delay, depending on screening type. Interventions that address sub-populations and reasons for screening delays are needed to mitigate the impact of the COVID-19 pandemic on cancer burden and mortality.


Assuntos
Neoplasias da Mama , COVID-19 , Neoplasias Colorretais , Neoplasias Pulmonares , Neoplasias do Colo do Útero , Humanos , Feminino , Masculino , Detecção Precoce de Câncer , Autorrelato , Pandemias/prevenção & controle , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/epidemiologia , Programas de Rastreamento
8.
PLoS One ; 18(4): e0269324, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37011054

RESUMO

INTRODUCTION: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium. METHODS: Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay). RESULTS: Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001). CONCLUSION: Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia.


Assuntos
Melanoma , MicroRNAs , Ácidos Nucleicos , Humanos , Fixação de Tecidos/métodos , MicroRNAs/análise , Melanoma/genética , DNA/genética , Inclusão em Parafina/métodos , Formaldeído
10.
Undersea Hyperb Med ; 49(3): 275-287, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36001560

RESUMO

Introduction: The International Multicenter Registry for Hyperbaric Oxygen Therapy (International Report Registered Identifier DERR1-10.2196/18857) was established in 2011 to capture outcomes and complications data for both Undersea and Hyperbaric Medical Society (UHMS) approved and selected unapproved hyperbaric oxygen (HBO2) therapy indications. Methods: A Research Electronic Data Capture (REDCap) template was designed and distributed to all participating centers for prospective data collection. Centers contributed de-identified demographic, treatment, complications, and outcome data. This report provides summary data on sites and enrollment, as well as pre- and post-treatment data on quality of life (EQ-5D-5L questionnaire), head and neck radiationoutcomes, non-healing wounds (Strauss score), and idiopathic sudden sensorineural hearing loss. Data were analyzed mainly using the Wilcoxon signed-rank test. Results: Twenty-two centers contributed data for 2,880 patients. The most common UHMS-approved indication was delayed radiation injury, followed by enhancement of wound healing, and carbon monoxide poisoning. One hundred and twenty-five patients were treated for non-UHMS approved indications. Quality of life, head and neck radiation symptoms, Strauss wound scores, and hearing were significantly improved after HBO2. Complication rates were low and comparable to previous reports. The registry also offered the ability to analyze factors that affect outcomes, such as smoking and severity of hearing loss. Discussion: The registry accrues prospective data on defined outcomes from multiple centers and allows for analysis of factors affecting outcomes. This registry does not have a control group, which is a limitation. Nevertheless, the registry provides a unique, comprehensive dataset on HBO2 outcomes from multiple centers internationally.


Assuntos
Intoxicação por Monóxido de Carbono , Perda Auditiva Súbita , Oxigenoterapia Hiperbárica , Intoxicação por Monóxido de Carbono/terapia , Perda Auditiva Súbita/terapia , Humanos , Oxigenoterapia Hiperbárica/métodos , Oxigênio/efeitos adversos , Qualidade de Vida , Sistema de Registros
11.
Pigment Cell Melanoma Res ; 35(6): 605-612, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35876628

RESUMO

It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for mutation, methylation and microRNAs. Preliminary results from mutation profiling and clinical pathologic correlates show the distribution of four driver mutation sub-types: 31% BRAF; 18% NRAS; 21% NF1; 26% Triple Wild Type. BRAF mutant tumors had younger age at diagnosis, more associated nevi, more tumor infiltrating lymphocytes, and fewer thick tumors although at generally more advanced stage. NF1 mutant tumors were frequent on the head/neck in older patients with severe solar elastosis, thicker tumors but in earlier stages. Triple Wild Type tumors were predominantly male, frequently on the leg, with more perineural invasion. Mutations in TERT, TP53, CDKN2A and ARID2 were observed often, with TP53 mutations occurring particularly frequently in the NF1 sub-type. The InterMEL study will provide the most extensive multi-omic profiling of early-stage melanoma to date. Initial results demonstrate a nuanced understanding of the mutational and clinicopathological landscape of these early-stage tumors.


Assuntos
Melanoma , MicroRNAs , Neoplasias Cutâneas , Humanos , Masculino , Idoso , Feminino , Melanoma/patologia , Neoplasias Cutâneas/tratamento farmacológico , Proteínas Proto-Oncogênicas B-raf/genética , Mutação/genética
13.
Cancer Epidemiol Biomarkers Prev ; 31(10): 1896-1906, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-35861625

RESUMO

BACKGROUND: In a 2018 descriptive study, cancer incidence in children (age 0-19) in diagnosis years 2003 to 2014 was reported as being highest in New Hampshire and in the Northeast region. METHODS: Using the Cancer in North America (CiNA) analytic file, we tested the hypotheses that incidence rates in the Northeast were higher than those in other regions of the United States either overall or by race/ethnicity group, and that rates in New Hampshire were higher than the Northeast region as a whole. RESULTS: In 2003 to 2014, pediatric cancer incidence was significantly higher in the Northeast than other regions of the United States overall and among non-Hispanic Whites and Blacks, but not among Hispanics and other racial minorities. However, there was no significant variability in incidence in the states within the Northeast overall or by race/ethnicity subgroup. Overall, statistically significantly higher incidence was seen in the Northeast for lymphomas [RR, 1.15; 99% confidence interval (CI), 1.10-1.19], central nervous system neoplasms (RR, 1.12; 99% CI, 1.07-1.16), and neuroblastoma (RR, 1.13; 99% CI, 1.05-1.21). CONCLUSIONS: Pediatric cancer incidence is statistically significantly higher in the Northeast than in the rest of the United States, but within the Northeast, states have comparable incidence. Differences in cancer subtypes by ethnicity merit further investigation. IMPACT: Our analyses clarify and extend previous reports by statistically confirming the hypothesis that the Northeast has the highest pediatric cancer rates in the country, by providing similar comparisons stratified by race/ethnicity, and by assessing variability within the Northeast.


Assuntos
Etnicidade , Neoplasias , Adolescente , Adulto , Criança , Pré-Escolar , Hispânico ou Latino , Humanos , Incidência , Lactente , Recém-Nascido , Neoplasias/epidemiologia , Grupos Raciais , Estados Unidos/epidemiologia , População Branca , Adulto Jovem
14.
PLoS One ; 17(5): e0268566, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35594279

RESUMO

OBJECTIVES: To characterize the experiences of providers in completing the cause of death section on death certificates, with particular reference to deaths in people who have cancer. METHODS: Focus groups were conducted until thematic saturation was reached, resulting in four groups over three months. Participants were from a variety of specialties and levels and types of training. Focus groups were recorded and transcribed verbatim and analyzed using constant comparison analysis. RESULTS: Three types of challenges to case classification were identified. 1) Infrastructural and procedural challenges encountered when completing death certificates, including the rigid structure of the form, lack of training in its completion, and lack of real-time feedback. 2) Clinical uncertainty and the varied approaches providers take to determine the cause of death based on their perception of the purpose of the death certificate. 3) Choosing cause of death in decedents with a history of cancer. CONCLUSIONS: There are specific and substantial challenges in the death certification process that lead to errors in documenting the cause of death, but many of these challenges could be addressed with structural change to the forms or mechanism of training. Using these data to inform change could improve the death certification process and reliability of this data.


Assuntos
Tomada de Decisão Clínica , Atestado de Óbito , Causas de Morte , Grupos Focais , Humanos , Reprodutibilidade dos Testes , Incerteza
15.
J Clin Lipidol ; 16(3): 345-355, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35461764

RESUMO

BACKGOUND: Circulating oxysterols, cholesterol metabolites with important signaling functions, are increasingly being recognized as candidate biomarkers for several diseases, but associations with demographic and health characteristics remain poorly described. OBJECTIVE: This study aims to characterize associations of major circulating oxysterols with sex, age, race/ethnicity, body mass index (BMI), lifestyle factors, and use of common medications. METHODS: We measured plasma concentrations of 27-hydroxycholesterol (27-OHC), 25-hydroxycholesterol (25-OHC), 24(S)-hydroxycholesterol (24(S)-OHC), 7ɑ-hydroxycholesterol (7ɑ-OHC), and 4ß-hydroxycholesterol (4ß-OHC) from 1,440 participants of a completed clinical trial for the chemoprevention of colorectal adenomas. Adjusted percent difference in means were calculated using linear regression. RESULTS: Women had 18% (95% CI, 14%, 22%) lower 27-OHC and 21% (15%, 27%) higher 4ß-OHC than men. Blacks had 15% (7%, 23%) higher 4ß-OHC than Non-Hispanic Whites, and Asian or Pacific Islanders had 19% (2%, 35%) higher 7ɑ-OHC than Non-Hispanic Whites. Individuals of BMI ≥35 kg/m2 had 33% (25%, 41%) lower 4ß-OHC than those <25 kg/m2. Current smokers had 15% (5%, 24%) higher 7ɑ-OHC than never smokers, and daily alcohol drinkers had 17% (10%, 24%) higher 7ɑ-OHC than never drinkers. Statin use was associated with lower concentrations of all 5 oxysterols. Differences in mean <15% were found for characteristics such as age, total dietary energy intake, physical activity, diabetes, and anti-inflammatory drug use. CONCLUSION: Circulating oxysterols are uniquely associated with multiple demographic and health characteristics.


Assuntos
Diabetes Mellitus , Oxisteróis , Biomarcadores , Colesterol , Demografia , Feminino , Humanos , Masculino
16.
JAMA Dermatol ; 158(4): 414-425, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35262623

RESUMO

Importance: Nonkeratinocyte skin cancers are an important cause of morbidity and mortality for immunosuppressed solid organ transplant recipients (SOTRs), but the spectrum of disease and risk factor characteristics are unknown. Objective: To characterize the spectrum of disease and risk factors for common and rare nonkeratinocyte skin cancers in SOTRs. Design, Setting, and Participants: This population-based cohort study included 444 497 SOTRs who underwent a transplant in the US between January 1, 1987, and December 31, 2017, using linked data from the national transplant registry and 32 cancer registries. Data analysis was conducted from April 1, 2021, to September 30, 2021. Main Outcomes and Measures: Standardized incidence ratios (SIRs) were used to assess risk relative to the general population, and Poisson regression was used to evaluate risk factors. Results: A total of 2380 nonkeratinocyte skin cancers were identified among 444 497 SOTRs (median age at transplant, 50 years; range, 0-96 years; 274 276 [61.7%] male; 272 241 [61.2%] non-Hispanic White). Melanoma was the most common cancer (1471 [61.8%]), followed by Merkel cell carcinoma (334 [14.0%]), Kaposi sarcoma (186 [7.8%]), sebaceous carcinoma (170 [7.1%]), and cutaneous lymphomas (108 [4.5%]). Risks were most strongly elevated for cancers associated with viruses, including Kaposi sarcoma (SIR, 20.5; 95% CI, 17.7-23.7), Merkel cell carcinoma (SIR, 16.2; 95% CI, 14.5-18.1), and extranodal natural killer/T-cell lymphoma (SIR, 44.3; 95% CI, 5.37-160). Risks were also significantly elevated for sebaceous carcinoma (SIR, 15.2; 95% CI, 13.0-17.7), anaplastic large cell lymphoma (SIR, 6.82; 95% CI, 4.53-9.85), and diffuse large B-cell lymphoma (SIR, 5.17; 95% CI, 3.28-7.76). Several characteristics were independently associated with greater risk for multiple skin cancer types, including male sex, older age at transplant, factors associated with UV radiation exposure (non-Hispanic White race and ethnicity, living in an area with higher UV radiation exposure, and posttransplant diagnosis of keratinocyte carcinoma), and increasing time since transplantation. Treatment with mammalian target of rapamycin inhibitors was associated with reduced melanoma incidence (incidence rate ratio, 0.75; 95% CI, 0.57-0.98). A total of 847 skin cancers (39.4%) occurred on the head and neck. Conclusions and Relevance: The findings of this cohort study suggest that viruses, UV radiation exposure, and immunosuppression are associated with the development of skin cancer in SOTRs. Certain high-risk subgroups may benefit from increased skin surveillance, and treatment with mammalian target of rapamycin inhibitors could be effective for melanoma chemoprevention in the transplant population.


Assuntos
Carcinoma de Célula de Merkel , Melanoma , Transplante de Órgãos , Sarcoma de Kaposi , Neoplasias Cutâneas , Carcinoma de Célula de Merkel/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Melanoma/epidemiologia , Transplante de Órgãos/efeitos adversos , Sistema de Registros , Fatores de Risco , Sarcoma de Kaposi/epidemiologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Serina-Treonina Quinases TOR , Transplantados
18.
Artigo em Inglês | MEDLINE | ID: mdl-35055441

RESUMO

Trichloroethylene (TCE) is a well-documented kidney carcinogen based on a substantial body of evidence including mechanistic and animal studies, as well as reports from occupational settings. However, the cancer risks for those in residential exposures such as TCE contamination in groundwater are much less clear. The objective of this study was to perform a detailed spatio-temporal analysis of estimated residential TCE exposure in New Hampshire, US. We identified kidney cancer cases (n = 292) and age-, gender-matched controls (n = 448) from the Dartmouth-Hitchcock Health System and queried a commercial financial database for address histories. We used publically available data on TCE levels in groundwater measured at contaminated sites in New Hampshire and then modeled the spatial dispersion and temporal decay. We overlaid geospatial residential locations of cases and controls with yearly maps of estimated TCE levels to estimate median exposures over the 5, 10, and 15-year epochs before diagnosis. The 50th-75th percentile of estimated residential exposure over a 15-year period was associated with increased kidney cancer risk (adjusted Odds Ratio (OR) 1.78 95% CI 1.05-3.03), compared to <50th percentile. This finding supports the need for groundwater monitoring of TCE contaminated sites to identify potential public health risks.


Assuntos
Água Subterrânea , Neoplasias Renais , Tricloroetileno , Animais , Água Subterrânea/análise , Rim/química , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/epidemiologia , Solventes , Tricloroetileno/análise
19.
J Registry Manag ; 49(3): 88-91, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37260926

RESUMO

Identifying potential duplicate cancer cases across state boundaries has been a topic of interest for many years. Duplicate cases could distort our understanding of the burden of cancer in a state, region, or even nationally, and waste cancer surveillance resources. This paper reports a pilot quality improvement project to use a publicly available tool to encrypt a standard set of patient identifiers and then link cases across state boundaries as a way to identify and reconcile possible duplicate cases among a group of neighboring states. The paper describes the protocol, challenges, and preliminary results, and suggests future efforts.


Assuntos
Neoplasias , Humanos , Neoplasias/epidemiologia , Registros
20.
PNAS Nexus ; 1(2): pgac031, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-36713316

RESUMO

Does information about how other people feel about COVID-19 vaccination affect immunization intentions? We conducted preregistered survey experiments in Great Britain (5,456 respondents across 3 survey waves from September 2020 to February 2021), Canada (1,315 respondents in February 2021), and the state of New Hampshire in the United States (1,315 respondents in January 2021). The experiments examine the effects of providing accurate public opinion information to people about either public support for COVID-19 vaccination (an injunctive norm) or public beliefs that the issue is contentious. Across all 3 countries, exposure to this information had minimal effects on vaccination intentions even among people who previously held inaccurate beliefs about support for COVID-19 vaccination or its perceived contentiousness. These results suggest that providing information on public opinion about COVID vaccination has limited additional effect on people's behavioral intentions when public discussion of vaccine uptake and intentions is highly salient.

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