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INTRODUCTION: Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor approved to treat type 2 diabetes mellitus (T2DM), among other conditions. When dapagliflozin was approved in Europe for treating T2DM (2012), potential safety concerns regarding its effect on kidney function resulted in this post-authorization safety study to assess hospitalization for acute kidney injury (hAKI) among dapagliflozin initiators in a real-world setting. OBJECTIVE: The aim of this study was to evaluate the incidence of hAKI in adults with T2DM initiating dapagliflozin compared with other glucose-lowering drugs (GLDs). METHODS: This noninterventional cohort study identified new users of dapagliflozin and comparator GLDs from November 2012 to February 2019 from three longitudinal, population-based data sources: Clinical Practice Research Datalink (CPRD; United Kingdom), the HealthCore Integrated Research Database (HIRD; United States [US]), and Medicare (US). Electronic algorithms identified occurrences of hAKI, from which a sample underwent validation. Incidence rates for hAKI were calculated, and incidence rate ratios (IRRs) compared hAKI in dapagliflozin with comparator GLDs. Propensity score trimming and stratification were conducted for confounding adjustment. RESULTS: In all data sources, dapagliflozin initiators had a lower hAKI incidence rate than comparator GLD initiators (adjusted IRRs: CPRD, 0.44 [95% confidence interval (CI), 0.22-0.86]; HIRD, 0.76 [95% CI, 0.62-0.93]; Medicare, 0.69 [95% CI, 0.59-0.79]). The adjusted IRR pooled across the data sources was 0.70 (95% CI, 0.62-0.78). Results from sensitivity and stratified analyses were consistent with the primary analysis. CONCLUSIONS: This study, with > 34,000 person-years of real-world dapagliflozin exposure, suggests a decreased risk of hAKI in patients with T2DM exposed to dapagliflozin, aligning with results from dapagliflozin clinical trials. STUDY REGISTRATION: European Union Post-Authorisation Studies Register, EUPAS 11684; ClinicalTrials.gov, NCT02695082.
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Injúria Renal Aguda , Diabetes Mellitus Tipo 2 , Idoso , Adulto , Humanos , Estados Unidos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Estudos de Coortes , Medicare , Compostos Benzidrílicos/efeitos adversos , Glucose/uso terapêutico , Hospitalização , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Hipoglicemiantes/efeitos adversosRESUMO
INTRODUCTION: Pimavanserin is approved in the USA to treat hallucinations and delusions associated with Parkinson's disease psychosis (PDP). OBJECTIVES: We evaluated mortality in patients with PDP after initiation of pimavanserin or comparator atypical antipsychotics, overall, over time, and across subgroups. METHODS: A cohort of patients aged ≥65 years in the USA with PDP newly initiating pimavanserin or a comparator atypical antipsychotic (clozapine, quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole) was identified in 2016-2019 Medicare claims data. All-cause mortality in the propensity score-matched treatment groups was compared with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated with Cox-proportional hazards models. Cumulative incidence curves and time period-specific models evaluated risk over time. Subgroup and sensitivity analyses were performed, including a sub-cohort of long-term care (LTC) or skilled nursing facility (SNF) residents. RESULTS: We identified 2892 pimavanserin initiators and 19,083 comparator initiators (overall 47% female, mean age = 80.9 years, LTC/SNF residents = 30%). Before matching, pimavanserin users had fewer severe comorbidities and more anti-Parkinson medication use than comparators. Matching resulted in 2891 patients in both groups, and all covariates were well balanced. In the matched cohort, the HR for mortality for pimavanserin versus comparator was 0.78 (95% CI 0.67-0.91), with the lowest time period-specific HRs in the first 180 days. Hazard ratios were similar across sensitivity analyses and subgroups. In LTC/SNF residents, the HR was 0.78 (95% CI 0.60-1.01). CONCLUSION: The observed mortality rates were lower among patients treated with pimavanserin compared with those treated with other atypical antipsychotics. STUDY REGISTRATION: European Union Post-authorization Study (EU PAS) register number 46331.
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Antipsicóticos , Doença de Parkinson , Transtornos Psicóticos , Humanos , Idoso , Feminino , Estados Unidos/epidemiologia , Idoso de 80 Anos ou mais , Masculino , Antipsicóticos/efeitos adversos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Estudos de Coortes , Medicare , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/complicaçõesRESUMO
INTRODUCTION: At the time of dapagliflozin's approval in Europe (2012) to treat patients with type 2 diabetes mellitus, concerns regarding acute liver injury and severe complications of urinary tract infection (sUTI) led to two post-authorization safety (PAS) studies of these outcomes to monitor the safety of dapagliflozin in real-world use. OBJECTIVE: To investigate the incidence of hospitalization for acute liver injury (hALI) or sUTI (pyelonephritis or urosepsis) among patients initiating dapagliflozin compared with other glucose-lowering drugs (GLDs). METHODS: These two noninterventional cohort studies identified initiators of dapagliflozin and comparator GLDs in November 2012-February 2019 using data from three longitudinal, population-based data sources: Clinical Practice Research Datalink (UK), the HealthCore Integrated Research Database (USA), and the Medicare database (USA). Outcomes (hALI and sUTI) were identified with electronic algorithms. Incidence rates were estimated by exposure group. Incidence rate ratios (IRRs) were calculated comparing dapagliflozin to comparator GLDs, using propensity score trimming and stratification to address confounding. The sUTI analyses were conducted separately by sex. RESULTS: In all data sources, hALI and sUTI incidence rates were generally lower in dapagliflozin initiators than comparator GLD initiators. The adjusted IRR (95% confidence interval) pooled across data sources for hALI was 0.85 (0.59-1.24) and for sUTI was 0.76 (0.60-0.96) in females and 0.74 (0.56-1.00) in males. Findings from sensitivity analyses were largely consistent with the primary analyses. CONCLUSIONS: These real-world studies do not suggest increased risks of hALI or sUTI, and they suggest a potential decreased risk of sUTI with dapagliflozin exposure compared with other GLDs.
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Diabetes Mellitus Tipo 2 , Infecções Urinárias , Masculino , Feminino , Humanos , Idoso , Estados Unidos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Medicare , Compostos Benzidrílicos/efeitos adversos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Fígado , Hipoglicemiantes/efeitos adversosRESUMO
BACKGROUND: Little is known about the incidence of clinical events and treatment patterns among older adults with dementia-related psychosis. Given that dementia-related psychosis comprises various dementia types, this study describes the incidence of clinical events and treatment patterns by dementia type after patients with dementia are diagnosed with psychosis. METHODS: Adults aged ≥ 65 years with dementia and newly diagnosed with psychosis were identified in US Medicare claims during 2013-2018. Baseline characteristics were evaluated at the time of the psychosis diagnosis. After the initial psychosis diagnosis, incidence rates (IRs) of clinical events (e.g., falls/fractures, infections, healthcare utilization), mortality, and patterns of antipsychotic treatment were described for each dementia type (Alzheimer's disease [AD], Parkinson's disease dementia [PDD], dementia with Lewy bodies [DLB], frontotemporal dementia [FTD], vascular dementia [VD], and unspecified dementia). Daily mean cumulative counts were estimated to describe the incidence of recurrent events over time. Mortality was described using Kaplan-Meier survival curves. RESULTS: We identified 484,520 patients with dementia-related psychosis: mean age, 84 years (standard deviation, 7.8); female, 66%. At the time of psychosis diagnosis, the most prevalent type of dementia was unspecified dementia (56%), followed by AD (31%), VD (12%), PDD (10%), DLB (3%), and FTD (< 1%), and most patients had scores indicating severe illness on the Charlson Comorbidity Index (71%) and frailty index (62%). Across all dementia types, IRs (per 100 person-years) were high for emergency department visits, oral anti-infective use, and urinary tract infections after the initial psychosis diagnosis. Patients with DLB had the highest incidence of most clinical outcomes. After 1 year of follow-up, the cumulative probability of death was about 30% for all dementia types, and after 5 years, was about 80% among patients with DLB, VD, AD, or PDD and about 60%-65% among patients with FTD or unspecified dementia. CONCLUSIONS: Patients with dementia-related psychosis had a high burden of comorbidities, frailty, emergency department visits, infections, and death. Specifically, after DRP diagnosis, patients with DLB and VD had the highest burden of clinical events of interest.
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Doença de Alzheimer , Antipsicóticos , Fragilidade , Demência Frontotemporal , Doença por Corpos de Lewy , Doença de Parkinson , Transtornos Psicóticos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Antipsicóticos/uso terapêutico , Feminino , Humanos , Doença por Corpos de Lewy/diagnóstico , Masculino , Medicare , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/terapia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Parkinson's disease-related psychosis increases patients' risk of falls. Pimavanserin is an atypical antipsychotic approved in the USA in 2016 for the treatment of hallucinations and delusions associated with Parkinson's disease-related psychosis. OBJECTIVE: We aimed to compare the risk of falls/fractures among patients with Parkinson's disease-related psychosis treated with pimavanserin vs other atypical antipsychotics. PATIENTS AND METHODS: We identified a cohort of patients with Parkinson's disease-related psychosis aged ≥ 40 years initiating either pimavanserin or a comparator antipsychotic (clozapine, quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole) in US commercial insurance and supplementary Medicare claims (2015-2019). Comparators were propensity score matched 2:1 with pimavanserin initiators; incidence rates of falls/fractures were compared using incidence rate ratios (IRRs) and 95% confidence intervals (CIs). RESULTS: We identified 112 eligible pimavanserin initiators and 982 comparators. Pimavanserin initiators were younger and had fewer severe comorbidities, indicators of impairment, and healthcare encounters, though they had higher Parkinson's disease medication use. The crude incidence rates [cases/100 person-years] (95% CI) for composite falls/fractures were 17.8 (7.7-35.0) for pimavanserin and 40.8 (35.0-47.4) for comparators. Matching retained 108 pimavanserin initiators and 216 comparators-all characteristics were well balanced after matching-with a matched IRR (pimavanserin vs comparator) of 0.71 (95% CI 0.27-1.67). Sensitivity analysis IRR estimates were consistently below 1.00, with a sensitivity analysis not requiring a diagnosis of psychosis resulting in an IRR estimate of 0.55 (95% CI 0.34-0.86). CONCLUSIONS: The results of this study do not suggest an increase in the risk of falls or fractures associated with pimavanserin compared with other antipsychotics in patients with Parkinson's disease-related psychosis. Sensitivity analyses suggest a decreased risk.
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BACKGROUND: Patients with breast cancer who overexpress the human epidermal growth factor receptor 2 (HER2) and subsequently develop brain metastasis (BM) typically experience poor quality of life and low survival. We conducted a comprehensive literature review to identify prognostic factors for BM and predictors of survival after developing BM, and the effects of therapies with different mechanisms of action among patients with HER2+ breast cancer (BC). METHODS: A prespecified search strategy was used to identify research studies investigating BM in patients with HER2+ BC published in English during January 1, 2009-to June 25, 2021. Articles were screened using a two-phase process, and data from selected articles were extracted. RESULTS: We identified 25 published articles including 4097 patients with HER2+ BC and BM. Prognostic factors associated with shorter time to BM diagnosis after initial BC diagnosis included younger age, hormone receptor negative status, larger tumor size or higher tumor grade, and lack of treatment with anti-HER2 therapy. Factors predictive of longer survival after BM included having fewer brain lesions (< 3 or a single lesion) and receipt of any treatment after BM, including radiosurgery, neurosurgery and/or systemic therapy. Patients receiving combination trastuzumab and lapatinib therapy or trastuzumab and pertuzumab therapy had the longest median survival compared with other therapies assessed in this review. CONCLUSIONS: More research is needed to better understand risk factors for BM and survival after BM in the context of HER2+ BC, as well as the assessment of new anti-HER2 therapy regimens that may provide additional therapeutic options for BM in these patients.
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Neoplasias Encefálicas/mortalidade , Neoplasias da Mama/mortalidade , Receptor ErbB-2/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico , Taxa de SobrevidaRESUMO
PURPOSE: Anti-human epidermal growth factor receptor 2 (HER2) therapies are associated with interstitial lung disease (ILD), also referred to as pneumonitis. In this literature review, we describe the incidence of ILD among patients with HER2-positive metastatic breast cancer (MBC) receiving anti-HER2 therapies, and we describe existing recommendations for monitoring and managing drug-induced ILD among these patients. METHODS: We searched PubMed and Embase to identify clinical trials and postmarket observational studies that investigated anti-HER2 therapies for HER2-positive MBC, reported on ILD, and were published during January 1, 2009 to July 15, 2019. Articles were screened by two researchers; data were extracted from the full-text articles. RESULTS: The 18 articles selected for this review assessed 9,886 patients who received trastuzumab (8 articles), lapatinib (4 articles), trastuzumab emtansine (3 articles), trastuzumab deruxtecan (2 articles), or trastuzumab duocarmazine (1 article). The overall incidence of all-grade ILD was 2.4% (n = 234), with 66.7% (n = 156) occurring as grade 1-2 events, 0.5% grade 3-4 (n = 54; incidence), and 0.2% grade 5 (n = 16; incidence). The highest ILD incidence (21.4%) was among patients receiving trastuzumab combined with everolimus and paclitaxel. Ten studies indicated that ILD events were managed via dose interruption, dose reduction, or treatment discontinuation; two studies included detailed guidelines on managing drug-induced ILD. CONCLUSIONS: ILD is a well-described adverse drug reaction associated with several anti-HER2 drugs. Published ILD management guidelines are available for few anti-HER2 treatment regimens; however, guidance for monitoring for anti-HER2 drug-induced ILD is lacking.
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Ado-Trastuzumab Emtansina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Camptotecina/análogos & derivados , Imunoconjugados/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Pneumonia/induzido quimicamente , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/efeitos adversos , Ado-Trastuzumab Emtansina/administração & dosagem , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Gerenciamento Clínico , Monitoramento de Medicamentos , Everolimo/administração & dosagem , Feminino , Humanos , Imunoconjugados/administração & dosagem , Incidência , Lapatinib/efeitos adversos , Doenças Pulmonares Intersticiais/epidemiologia , Metástase Neoplásica , Paclitaxel/administração & dosagem , Pneumonia/epidemiologia , Receptor ErbB-2/análise , Trastuzumab/administração & dosagemRESUMO
IMPORTANCE: Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. OBJECTIVES: To identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. DESIGN, SETTING, AND PARTICIPANTS: This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10â¯181â¯074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. EXPOSURES: Birth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. MAIN OUTCOMES AND MEASURES: Cancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. RESULTS: Compared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjusted P < .05) after accounting for multiple comparisons. Cancers most frequently associated with nonchromosomal defects were hepatoblastoma and neuroblastoma. CONCLUSIONS AND RELEVANCE: Several significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes.
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Acute leukemia is the most common pediatric malignancy. Some studies suggest early-life exposures to air pollution increase risk of childhood leukemia. Therefore, we explored the association between maternal residential proximity to major roadways and risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Information on cases with acute leukemia (n = 2030) was obtained for the period 1995-2011 from the Texas Cancer Registry. Birth certificate controls were frequency matched (10:1) on birth year (n = 20,300). Three residential proximity measures were assessed: (1) distance to nearest major roadway, (2) residence within 500 meters of a major roadway, and (3) roadway density. Multivariate logistic regression was used to generate adjusted odds ratios (aOR) and 95% confidence intervals (CI). Mothers who lived ≤500 meters to a major roadway were not more likely to have a child who developed ALL (OR = 1.03; 95% CI: 0.91-1.16) or AML (OR = 0.84; 95% CI: 0.64-1.11). Mothers who lived in areas characterized by high roadway density were not more likely to have children who developed ALL (OR = 1.06, 95% CI: 0.93-1.20) or AML (OR = 0.83, 95% CI: 0.61-1.13). Our results do not support the hypothesis that maternal proximity to major roadways is strongly associated with childhood acute leukemia. Future assessments evaluating the role of early-life exposure to environmental factors on acute leukemia risk should explore novel methods for directly measuring exposures during relevant periods of development.
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Poluentes Atmosféricos/análise , Leucemia Mieloide Aguda/epidemiologia , Exposição Materna , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Características de Residência , Emissões de Veículos/análise , Doença Aguda , Adulto , Poluição do Ar , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Razão de Chances , Texas/epidemiologiaRESUMO
BACKGROUND: Epidemiological knowledge and predictors of melanoma among children and adolescents in multiethnic populations are limited. PROCEDURE: Using data from the Texas Cancer Registry (TCR) and the Surveillance, Epidemiology, and End Results (SEER) 13 database, we identified incident melanoma cases diagnosed at 0-20 years old during 1995-2013 in Texas and the United States, respectively. Using negative binomial regression, associations between demographic factors and melanoma incidence rates (IR) were evaluated by calculating incidence rate ratios (IRR) and 95% confidence intervals (CI). Annual percent change in IRs was assessed with joinpoint regression. RESULTS: Overall, the melanoma IR was 4.16 (TCR, n = 634) and 4.84 (SEER, n = 1260) per million. Females, adolescents, non-Hispanic (NH) whites, and Hispanics had higher IRs compared with other groups (P < 0.05). In adjusted analyses, Hispanics had a higher incidence of melanoma than NH non-whites (Texas IRR = 2.17; 95% CI, 1.30-3.61; SEER IRR = 2.88; 95% CI, 1.97-4.21). In Texas, NH whites with melanoma were more likely to live in low poverty areas, whereas the opposite trend was observed in Hispanics. Melanoma IRs increased throughout 1995-2004 followed by an average annual decrease of 7.6% (95% CI, -12.6%, -2.2%) in Texas and 6.0% (95% CI, -8.5%, -3.4%) in SEER during 2005-2013 (P < 0.05). However, these decreasing trends were not observed among Hispanics or those <10 years old. CONCLUSION: Although the overall melanoma IR in children and adolescents appears to be decreasing, this trend is not evident among Hispanics and young children, implicating the need for further research investigating the etiologies and risk factors in these groups.
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Etnicidade/estatística & dados numéricos , Melanoma/epidemiologia , Sistema de Registros/estatística & dados numéricos , Neoplasias Cutâneas/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Prognóstico , Fatores de Risco , Programa de SEER , Texas/epidemiologia , Adulto JovemRESUMO
The ETS family of transcription factors is involved in several normal remodeling events and pathological processes including tumor progression. ETS transcription factors are divided into subfamilies based on the sequence and location of the ETS domain. ETV5 (Ets variant gene 5; also known as ERM) is a member of the PEA3 subfamily. Our meta-analysis of normal, benign, and malignant thyroid samples demonstrated that ETV5 expression is upregulated in papillary thyroid cancer and was predominantly associated with BRAF V600E or RAS mutations. However, the precise role of ETV5 in these lesions is unknown. In this study, we used the KTC1 cell line as a model for human advanced papillary thyroid cancer (PTC) because the cells harbor the heterozygous BRAF (V600E) mutation together with the C250T TERT promoter mutation. The role of ETV5 in PTC proliferation was tested using RNAi followed by high-throughput screening. Signaling pathways driving ETV5 expression were identified using specific pharmacological inhibitors. To determine if ETV5 influences the expression of epithelial-to-mesenchymal (EMT) markers in these cells, an EMT PCR array was used, and data were confirmed by qPCR and ChIP-qPCR. We found that ETV5 is critical for PTC cell growth, is expressed downstream of the MAPK pathway, and directly upregulates the transcription factor TWIST1, a known marker of intravasation and metastasis. Increased ETV5 expression could therefore be considered as a marker for advanced PTCs and a possible future therapeutic target.
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Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Mutação , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Fatores de Transcrição/metabolismo , Proteína 1 Relacionada a Twist/genética , Biomarcadores , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Transição Epitelial-Mesenquimal , Humanos , Imuno-Histoquímica , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais , Câncer Papilífero da Tireoide/patologiaRESUMO
Anophthalmia and microphthalmia are a set of rare, yet severe, birth defects considered to be part of a spectrum of developmental ocular malformations ranging from smaller than average to completely absent eyes. Despite their clinical significance, little is known about the etiologies of these conditions. The goal of this study was to expand our understanding of the epidemiology of anophthalmia and microphthalmia. Data for this population-based assessment were obtained from the Texas Birth Defects Registry (TBDR) and Center for Health Statistics for the period 1999-2009. Descriptive analyses and estimates of birth prevalence and prevalence ratios (PR) were determined for this defect. There were 1,262 definite anophthalmia and microphthalmia patients identified in the TBDR, with an overall combined prevalence of 3.0 per 10,000 live births. More than half (55.7%) of the patients had at least one chromosome abnormality or syndrome. In addition, 92.4% of nonsyndromic patients (i.e., have no recorded chromosome abnormalities or syndromes) had at least one additional birth defect. After adjustment for multiple factors, the prevalence of nonsyndromic anophthalmia and microphthalmia was higher among mothers who had ≥2 previous fetal deaths (PR = 1.43, 95% confidence interval [CI]: 1.03-1.97) and among mothers with any reported diabetes (PR = 2.08, 95% CI: 1.49-2.90). Our results confirm that children with anophthalmia and microphthalmia frequently have genetic syndromes or are born with other major birth defects. Our findings add to the limited body of literature on anophthalmia and microphthalmia as well as help define subgroups of women who are more likely to have children with this malformation.
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Anoftalmia/epidemiologia , Microftalmia/epidemiologia , Adolescente , Adulto , Anoftalmia/diagnóstico , Anoftalmia/genética , Anoftalmia/história , Feminino , Variação Genética , História do Século XXI , Humanos , Masculino , Microftalmia/diagnóstico , Microftalmia/genética , Microftalmia/história , Pessoa de Meia-Idade , Fenótipo , Vigilância da População , Prevalência , Sistema de Registros , Síndrome , Texas/epidemiologia , Adulto JovemRESUMO
The environmental determinants of pediatric embryonal tumors remain unclear. Because of the growing concern over the impact of exposures to traffic-related air pollution on pediatric cancer, we conducted a population-based study evaluating the impact of maternal residential proximity to major roadways on the risk of pediatric embryonal tumors in offspring. We identified children diagnosed with neuroblastoma, Wilms tumor, retinoblastoma, or hepatoblastoma at <5 years of age from the Texas Cancer Registry and selected unaffected controls from birth certificates. Two residential proximity measures were used: (1) distance to the nearest major roadway, and (2) within 500 m of a major roadway. Logistic regression was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for each proximity measure on pediatric embryonal tumors. The odds of an embryonal tumor were increased in children born to mothers living within 500 m of a major roadway (aOR = 1.24, 95% CI: 1.00, 1.54). This was consistent for most tumor subtypes, with the strongest associations observed for unilateral retinoblastoma (aOR = 2.57, 95% CI: 1.28, 5.15, for every kilometer closer the mother lived to the nearest major roadway). These findings contribute to the growing evidence that traffic-related air pollution may increase risk for certain pediatric tumors.
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Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Sistema de Registros , Emissões de Veículos/toxicidade , Adulto , Poluentes Atmosféricos , Estudos de Casos e Controles , Criança , Feminino , Habitação , Humanos , Lactente , Modelos Logísticos , Masculino , Neoplasias Embrionárias de Células Germinativas/etiologia , Razão de Chances , Texas/epidemiologiaRESUMO
OBJECTIVE: Cholangiocarcinoma (CCA) is a biliary malignancy found primarily in adults. The incidence of CCA in children is unknown. The aim of this study was to describe characteristics of CCA in children and adolescents. METHODS: Using the Surveillance, Epidemiology, and End Results Program (SEER 18) database, we identified incident cases of CCA diagnosed at <20 years of age during the period of 1973 to 2013. Additionally, we reviewed published case reports describing pediatric patients with CCA. We calculated descriptive statistics for CCA cases identified in SEER and in case reports. Kaplan-Meier analysis was performed to determine median and 3-year overall survival (OS) rates. RESULTS: We identified 15 children and adolescents diagnosed as having CCA from SEER 18 with an incidence rate of 0.0036 per 100,000. Two-thirds of cases were male, and the majority were white (nâ=â10). The median age at diagnosis was 17 years (range: 11-19 years). Nine tumors were intrahepatic, 3 extrahepatic, and 3 unspecified. One-third had distal metastases at diagnosis. Eight patients underwent surgical resection including liver transplant in two. Six patients were alive at the time of follow-up. Patients without surgical treatment did not survive. Three-year OS was 50%. Twenty-two children with CCA were found in the literature with a median age at diagnosis of 15 years (range: 3-18 years). Half were male, and 90% had an underlying gastrointestinal comorbidity. Three-year OS was 35.3%. CONCLUSIONS: CCA in children and adolescents is rare with poor survival. A high proportion of cases had a history of biliary disease. Surgical resection is necessary for cure.
Assuntos
Neoplasias dos Ductos Biliares/epidemiologia , Ductos Biliares Extra-Hepáticos , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/epidemiologia , Adolescente , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/cirurgia , Criança , Pré-Escolar , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Transplante de Fígado , Masculino , Programa de SEER , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The presence of a congenital anomaly is associated with increased childhood cancer risk, likely due to large effects of Down syndrome and chromosomal anomalies for leukemia. Less is known about associations with presence of non-chromosomal anomalies. METHODS: Records of children diagnosed with cancer at <20 years of age during 1984-2013 in Washington State cancer registries were linked to their birth certificates (N = 4,105). A comparison group of children born in the same years was identified. Congenital anomalies were assessed from birth records and diagnosis codes in linked hospital discharge data. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for cancer, and for specific cancer types in relation to the presence of any anomaly and specific anomalies. RESULTS: Having any congenital anomaly was associated with an increased risk of childhood cancer (OR: 1.46, 95% CI 1.28-1.65). Non-chromosomal anomalies were also associated with increased childhood cancer risk overall (OR: 1.35; 95% CI: 1.18-1.54), and with increased risk of several cancer types, including neuroblastoma, renal, hepatoblastoma, soft-tissue sarcoma, and germ cell tumors. Increasing number of non-chromosomal anomalies was associated with a stronger risk of childhood cancer (OR for 3+ anomalies: 3.11, 95% CI: 1.54-6.11). Although central nervous system (CNS) anomalies were associated with CNS tumors (OR: 6.05, 95% CI 2.75-13.27), there was no strong evidence of other non-chromosomal anomalies being specifically associated with cancer occurring in the same organ system or anatomic location. CONCLUSIONS: Non-chromosomal anomalies increased risk of several cancer types. Additionally, we found that increasing number of non-chromosomal anomalies was associated with a stronger risk of cancer. Pooling similar data from many regions would increase power to identify specific associations in order to inform molecular studies examining possible common developmental pathways in the etiologies of birth defects and cancer.
Assuntos
Aberrações Cromossômicas , Neoplasias/genética , Adolescente , Adulto , Criança , Pré-Escolar , Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/genética , Feminino , Humanos , Masculino , Neoplasias/epidemiologia , Fatores de Risco , Washington/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Lymphoma is one of the most common pediatric malignancies; however, there are few well-established risk factors. Therefore, we investigated if maternal and perinatal characteristics influenced the risk of childhood lymphoma. PROCEDURE: Information on cases (n = 374) diagnosed with lymphoma and born in Texas for the period 1995-2011 was obtained from the Texas Cancer Registry. Birth certificate controls were randomly selected at a ratio of 10 controls per 1 case for the same period of 1995-2011. Unconditional logistic regression was used to generate unadjusted (OR) and adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the following histologic subtypes: Hodgkin (HL), Burkitt (BL), and non-BL non-HLs (non-BL NHLs). RESULTS: Overall, our findings indicate specific maternal and perinatal characteristics influence childhood lymphoma risk. Mexico-born mothers were more likely to have offspring who developed BL compared to mothers born in the United States (U.S.; aOR: 2.15; 95% CI: 1.06-4.36). Further, mothers who resided at time of delivery in a county on the U.S.-Mexico border were more likely to give birth to offspring who developed non-BL NHL (aOR: 1.72; 95% CI: 1.11-2.67) compared to mothers not living on the U.S.-Mexico border at time of infant birth. Last, infants born large-for-gestational-age experienced a twofold increase in BL risk (aOR: 2.00; 95% CI: 1.10-3.65). CONCLUSIONS: In this population-based assessment, we confirmed previously reported risk predictors of childhood lymphoma, including sex of infant, while highlighting novel risk factors that warrant assessment in future studies.
Assuntos
Doença de Hodgkin/epidemiologia , Linfoma não Hodgkin/epidemiologia , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , México/epidemiologia , Fatores de Risco , Texas/epidemiologia , Estados Unidos/epidemiologiaRESUMO
In epidemiologic studies of childhood cancer, environmental exposures are often assigned based on either residence at birth or diagnosis without considering the impact of residential mobility. Therefore, we evaluated residential mobility and exposure assignment differences to hazardous air pollutants between birth and diagnosis in children with a central nervous system (CNS) tumor. Children diagnosed with CNS tumors during 1995-2009 (N=1,196) were identified from the Texas Cancer Registry. Census tract-level estimates of 1,3-butadiene and benzene were used to assign quartiles of exposure based on the maternal residence at birth and the child's residence at diagnosis. Overall, 64% of younger (0-4 years) children and 79% of older (5-14 years) children moved between birth and diagnosis. Using mixed-effects ordinal logistic regression, residence at diagnosis compared to birth did not result in a significant change in exposure assignment for younger children; however, older children were more likely to be placed in a lower 1,3-butadiene or benzene exposure quartile based on residence at diagnosis compared to birth (odds ratio (OR)=0.58, 95% confidence interval (CI)=0.45-0.76; OR=0.57, 95% CI=0.44-0.75, respectively). In conclusion, while the majority of children moved between birth and CNS tumor diagnosis, mobility did not significantly impact 1,3-butadiene and benzene exposure assessment in younger children.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Benzeno/efeitos adversos , Butadienos/efeitos adversos , Neoplasias do Sistema Nervoso Central/induzido quimicamente , Neoplasias do Sistema Nervoso Central/epidemiologia , Dinâmica Populacional , Adolescente , Poluentes Atmosféricos/análise , Butadienos/análise , Censos , Criança , Pré-Escolar , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Sistemas de Informação Geográfica , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Exposição Materna/efeitos adversos , Dinâmica Populacional/estatística & dados numéricos , Sistema de Registros , Texas/epidemiologiaRESUMO
BACKGROUND: Rhabdomyosarcoma (RMS) is a rare, highly malignant tumor arising from primitive mesenchymal cells that differentiate into skeletal muscle. Relatively little is known about RMS susceptibility. Based on growing evidence regarding the role of early immunologic challenges on RMS development, we evaluated the role of infections and immunizations on this clinically significant pediatric malignancy. PROCEDURE: RMS cases (n = 322) were enrolled from the third trial coordinated by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 322) were pair matched to cases on race, sex, and age. The following immunizations were assessed: diphtheria, pertussis, and tetanus (DPT); measles, mumps, and rubella; and oral polio vaccine. We also evaluated if immunizations were complete versus incomplete. We examined selected infections including chickenpox, mumps, pneumonia, scarlet fever, rubella, rubeola, pertussis, mononucleosis, and lung infections. Conditional logistic regression models were used to calculate an odds ratio (OR) and 95% confidence interval (CI) for each exposure, adjusted for maternal education and total annual income. RESULTS: Incomplete immunization schedules (OR = 5.30, 95% CI: 2.47-11.33) and incomplete DPT immunization (OR = 1.56, 95% CI: 1.06-2.29) were positively associated with childhood RMS. However, infections did not appear to be associated with childhood RMS. CONCLUSIONS: This is the largest study of RMS to date demonstrating a possible protective effect of immunizations against the development of childhood RMS. Further studies are needed to validate our findings. Our findings add to the growing body of literature, suggesting a protective role of routine vaccinations in childhood cancer and specifically in childhood RMS.
Assuntos
Infecções/complicações , Rabdomiossarcoma/prevenção & controle , Vacinação , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Rabdomiossarcoma/etiologiaRESUMO
Children with human immunodeficiency virus (HIV) have an increased risk of developing Kaposi Sarcoma (KS) and non-Hodgkin lymphoma (NHL) compared to HIV-negative children. We compiled currently published epidemiologic data on KS and NHL among children in sub-Saharan Africa (SSA). Among countries with available data, the median incidence of KS was 2.05/100,000 in the general pediatric population and 67.35/100,000 among HIV-infected children. The median incidence of NHL was 1.98/100,000 among the general pediatric population, while data on NHL incidence among HIV-infected children were lacking. Larger regional studies are needed to better address the dearth of epidemiologic information on pediatric KS and NHL in SSA.
Assuntos
Infecções por HIV/epidemiologia , Linfoma não Hodgkin/epidemiologia , Sarcoma de Kaposi/epidemiologia , África Subsaariana/epidemiologia , Criança , Herpesvirus Humano 4 , Herpesvirus Humano 8 , HumanosRESUMO
AIM: To evaluate patients' expectations regarding the perceived utility of whole-genome sequencing (WGS). MATERIALS & METHODS: We used latent class analysis to characterize individuals enrolled in the MedSeq Project based on their perceived utility of WGS. Multinomial logistic regression was used to evaluate associations between participant characteristics and latent classes. RESULTS: Findings characterized participants into one of three perceived utility groups: enthusiasts, who had a high probability of agreement with all utility items (23%); health conscious, who perceived utility in medically related areas (60%) or skeptics, who had a low probability of agreement with utility items (17%). Trust significantly predicted latent class. CONCLUSION: Understanding differences in perceived utility of WGS may inform strategies for uptake of this technology.