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1.
Orthopedics ; 47(1): 52-56, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37216564

RESUMO

Cannabidiol (CBD)-containing supplements are used by children with cerebral palsy (CP), but the prevalence and efficacy of their use have not been studied. We sought to describe CBD use patterns and perceived efficacy in the pediatric population with CP, evaluating any association between CBD use and health-related quality of life. Patients with CP were prospectively enrolled, and caregivers were offered the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) Questionnaire and a survey assessing CBD use. Of 119 participants, 20 (16.8%) endorsed CBD use (CBD+) and 99 (83.2%) denied it (CBD-). Participants in the CBD+ group had worse functional status (85% Gross Motor Function Classification System level IV-V for CBD+ vs 37.4% for CBD-, P<.001) and lower health-related quality of life (mean CPCHILD score of 49.3 for CBD+ vs 62.2 for CBD-, P=.001). Spasticity was the rationale most cited for CBD use (29%), followed by pain and anxiety (both 22.6%). CBD was perceived to be most effective for improving emotional health, spasticity, and pain. Fifty percent of the patients in the CBD+ group underwent surgery in the previous 2 years and most endorsed a general benefit in the postoperative setting. The most common side effects noted were fatigue and increased appetite (both 12%). Most participants endorsed no side effects (60%). CBD may serve as a useful adjunct for some children with CP, especially those with worse disease severity. Caregivers perceive CBD as offering some benefits, particularly in the domains of emotional health, spasticity, and pain. We found no evidence of severe adverse events in our small cohort. [Orthopedics. 2024;47(1):52-56.].


Assuntos
Canabidiol , Paralisia Cerebral , Humanos , Criança , Qualidade de Vida , Canabidiol/uso terapêutico , Paralisia Cerebral/tratamento farmacológico , Paralisia Cerebral/complicações , Índice de Gravidade de Doença , Dor
2.
Cureus ; 15(11): e48575, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38073935

RESUMO

Background While there has been a growing emphasis on evaluating the patient's perspective of health outcomes, caregiver expectations of post-orthopedic procedure disability and pain in a pediatric population are yet to be investigated. This study evaluates whether caregivers' preoperative expectations of pain and function differ from their child's early outcomes after surgical orthopedic intervention. Methodology Patients eight to 18 years old undergoing elective orthopedic surgery were enrolled. The caregivers of consented patients completed a survey at the child's preoperative appointment to predict their postoperative pain and disability. The child was given the same survey during their postoperative visit four to six weeks after surgery to assess actual levels of functioning following the procedure. Scores were analyzed to study correlations between patient and caregiver responses (n = 48). Results Caregivers underestimated their child's postoperative psychosocial functioning, as evidenced by the Psychosocial Health Summary Score, and overestimated pain, as demonstrated by the Numeric Pain Rating Scale. The Pediatric Quality of Life Inventory scores showed caregivers had differing expectations of the impact surgery had across various aspects of the physical, emotional, social, and school functioning domains. Higher parental pain catastrophizing was associated with underestimated predictions of their child's psychosocial functioning after surgery. No significant difference was found in the patient's physical functioning, as shown by the Physical Health Summary Score. Conclusions Surgical intervention is a major event that can provoke anxiety for parents and caregivers. Understanding differences in caregiver perspectives and early postoperative patient outcomes provides physicians valuable insights. Explaining to caregivers that patient psychosocial factors and functional outcomes after surgery are commonly better than expected can alleviate anxiety and prevent catastrophizing. This knowledge can help guide caregiver expectations and plans for their child's postoperative pain control and functional recovery.

3.
Cancer Res ; 83(15): 2513-2526, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37311042

RESUMO

Immunotherapy resistance in non-small cell lung cancer (NSCLC) may be mediated by an immunosuppressive microenvironment, which can be shaped by the mutational landscape of the tumor. Here, we observed genetic alterations in the PTEN/PI3K/AKT/mTOR pathway and/or loss of PTEN expression in >25% of patients with NSCLC, with higher frequency in lung squamous carcinomas (LUSC). Patients with PTEN-low tumors had higher levels of PD-L1 and PD-L2 and showed worse progression-free survival when treated with immunotherapy. Development of a Pten-null LUSC mouse model revealed that tumors with PTEN loss were refractory to antiprogrammed cell death protein 1 (anti-PD-1), highly metastatic and fibrotic, and secreted TGFß/CXCL10 to promote conversion of CD4+ lymphocytes into regulatory T cells (Treg). Human and mouse PTEN-low tumors were enriched in Tregs and expressed higher levels of immunosuppressive genes. Importantly, treatment of mice bearing Pten-null tumors with TLR agonists and anti-TGFß antibody aimed to alter this immunosuppressive microenvironment and led to tumor rejection and immunologic memory in 100% of mice. These results demonstrate that lack of PTEN causes immunotherapy resistance in LUSCs by establishing an immunosuppressive tumor microenvironment that can be reversed therapeutically. SIGNIFICANCE: PTEN loss leads to the development of an immunosuppressive microenvironment in lung cancer that confers resistance to anti-PD-1 therapy, which can be overcome by targeting PTEN loss-mediated immunosuppression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , PTEN Fosfo-Hidrolase , Linfócitos T Reguladores , Animais , Humanos , Camundongos , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Microambiente Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico
4.
Artigo em Inglês | MEDLINE | ID: mdl-36338797

RESUMO

The purpose of this study was to evaluate the impact of an 8-week remote summer program in supporting underrepresented students interested in orthopaedic surgery. Methods: We received 115 applications, and a total of 17 students participated in the program (14.8%). Nine faculty mentors were matched with 1 or 2 students each. The program delivered a curriculum from June-August 2021 consisting of (1) weekly instructional courses on research-related topics led by a content expert; (2) weekly faculty lectures discussing topics including orthopaedic topics, diversity in medicine, leadership, and work-life balance; and (3) a research experience paired with a faculty mentor and peer mentor. We surveyed students to measure skill progression, satisfaction, and overall program evaluation. Preprogram/postprogram evaluation, midprogram check-in, and student feedback surveys were collected. Results: Program participants represented a range of race and ethnic backgrounds, research experience levels, and various geographic locations across the United States. The cohort included a high rate of female (42%) and Black (35%) participants. On average, postprogram survey scores indicated that participants believed that the summer program improved their research skills (9.6 of 10), improved their orthopaedic interest (8.9 of 10), and improved mentorship and networking (9.1 of 10). For feedback surveys, 14 respondents of 15 total responses (93%) felt they were adequately matched to their faculty mentor. Twelve (80%) felt they had realistic deliverables for research projects within the 8-week program. Thirteen (87%) indicated they contributed to an abstract or manuscript as a coauthor. Conclusion: Our findings indicate that students improved their research skills, interest, and confidence to pursue orthopaedic residency and mentorship/networks in the field. The long-term goal is to improve the accessibility and quality of mentorship for underrepresented students in order to foster an equitable pathway into the field of orthopaedic surgery.

5.
Int J Mol Sci ; 23(3)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35162988

RESUMO

Melanoma is an aggressive skin cancer that has become increasingly prevalent in western populations. Current treatments such as surgery, chemotherapy, and high-dose radiation have had limited success, often failing to treat late stage, metastatic melanoma. Alternative strategies such as immunotherapies have been successful in treating a small percentage of patients with metastatic disease, although these treatments to date have not been proven to enhance overall survival. Several melanoma antigens (Ags) proposed as targets for immunotherapeutics include tyrosinase, NY-ESO-1, gp-100, and Mart-1, all of which contain both human leukocyte antigen (HLA) class I and class II-restricted epitopes necessary for immune recognition. We have previously shown that an enzyme, gamma-IFN-inducible lysosomal thiol-reductase (GILT), is abundantly expressed in professional Ag presenting cells (APCs), but absent or expressed at greatly reduced levels in many human melanomas. In the current study, we report that increased GILT expression generates a greater pool of antigenic peptides in melanoma cells for enhanced CD4+ T cell recognition. Our results suggest that the induction of GILT in human melanoma cells could aid in the development of a novel whole-cell vaccine for the enhancement of immune recognition of metastatic melanoma.


Assuntos
Melanoma , Compostos de Sulfidrila , Apresentação de Antígeno , Antígenos de Neoplasias , Antígenos HLA , Humanos , Lisossomos/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Peptídeos
6.
Cancer Discov ; 11(7): 1736-1753, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33707235

RESUMO

In lung adenocarcinoma, oncogenic EGFR mutations co-occur with many tumor suppressor gene alterations; however, the extent to which these contribute to tumor growth and response to therapy in vivo remains largely unknown. By quantifying the effects of inactivating 10 putative tumor suppressor genes in a mouse model of EGFR-driven Trp53-deficient lung adenocarcinoma, we found that Apc, Rb1, or Rbm10 inactivation strongly promoted tumor growth. Unexpectedly, inactivation of Lkb1 or Setd2-the strongest drivers of growth in a KRAS-driven model-reduced EGFR-driven tumor growth. These results are consistent with mutational frequencies in human EGFR- and KRAS-driven lung adenocarcinomas. Furthermore, KEAP1 inactivation reduced the sensitivity of EGFR-driven tumors to the EGFR inhibitor osimertinib, and mutations in genes in the KEAP1 pathway were associated with decreased time on tyrosine kinase inhibitor treatment in patients. Our study highlights how the impact of genetic alterations differs across oncogenic contexts and that the fitness landscape shifts upon treatment. SIGNIFICANCE: By modeling complex genotypes in vivo, this study reveals key tumor suppressors that constrain the growth of EGFR-mutant tumors. Furthermore, we uncovered that KEAP1 inactivation reduces the sensitivity of these tumors to tyrosine kinase inhibitors. Thus, our approach identifies genotypes of biological and therapeutic importance in this disease.This article is highlighted in the In This Issue feature, p. 1601.


Assuntos
Acrilamidas/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Acrilamidas/farmacologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Compostos de Anilina/farmacologia , Animais , Antineoplásicos/farmacologia , Modelos Animais de Doenças , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos
7.
Orthop J Sports Med ; 8(10): 2325967120959725, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33195716

RESUMO

BACKGROUND: Investigations of the female athlete triad (Triad) in high school athletes have found that 36% had low energy availability, 54% had menstrual abnormalities, and 16% had low bone mineral density (BMD). Limited data are available showing the prevalence of these risk factors in high school distance runners or regarding best practice on screening for the Triad in the adolescent population. PURPOSE: To (1) evaluate the prevalence of Triad risk factors and iron supplementation in high school distance runners and (2) pilot a screening tool for Triad risk score. STUDY DESIGN: Descriptive epidemiology study. METHODS: The study population included female high school athletes who participated in cross-country/track. Participants completed a survey including questions regarding dietary habits, menstrual history, and bone stress injury (BSI) history. They then underwent evaluation of 25-hydroxyvitamin D, free triiodothyronine (T3), and dual-energy x-ray absorptiometry scan to measure body fat and BMD through use of age-, sex-, and ethnicity-matched Z scores. Triad scores were calculated. Relationships were analyzed using Spearman correlation coefficient. RESULTS: There were 38 study participants (mean age, 16.9 years). Average body mass index was 19.8 kg/m2. Disordered eating or eating disorders were reported in 76.3% of runners; in addition, 23.7% reported delayed menarche, 45.9% had a history of amenorrhea or oligomenorrhea, 42.1% had low BMD (Z score < -1.0), and 15.8% reported prior BSI. Low free T3 was significantly associated with higher Triad risk scores (r S = -0.36; P = .028). More than 42% of athletes were supplementing iron. CONCLUSION: The prevalence of Triad risk factors in high school distance runners was high. Free T3 was inversely associated with Triad score, which may serve as an indicator of low energy availability. Nearly half of the athletes were using iron supplementation.

8.
Int J Qual Health Care ; 32(10): 658-662, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32986101

RESUMO

OBJECTIVE: Identifying when and how often decisions are made based on high-quality evidence can inform the development of evidence-based treatment plans and care pathways, which have been shown to improve quality of care and patient safety. Evidence to guide decision-making, national guidelines and clinical pathways for many conditions in pediatric orthopedic surgery are limited. This study investigated decision-making rationale and quantified the evidence supporting decisions made by pediatric orthopedic surgeons in an outpatient clinic. DESIGN/SETTING/PARTICIPANTS/INTERVENTION(S)/MAIN OUTCOME MEASURE(S): We recorded decisions made by eight pediatric orthopedic surgeons in an outpatient clinic and the surgeon's reported rationale behind the decisions. Surgeons categorized the rationale for each decision as one or a combination of 12 possibilities (e.g. 'Experience/anecdote,' 'First principles,' 'Trained to do it,' 'Arbitrary/instinct,' 'General study,' 'Specific study'). RESULTS: Out of 1150 total decisions, the most frequent decisions were follow-up scheduling, followed by bracing prescription/removal. The most common decision rationales were 'First principles' (n = 310, 27.0%) and 'Experience/anecdote' (n = 253, 22.0%). Only 17.8% of decisions were attributed to scientific studies, with 7.3% based on studies specific to the decision. As high as 34.6% of surgical intervention decisions were based on scientific studies, while only 10.4% of follow-up scheduling decisions were made with studies in mind. Decision category was significantly associated with a basis in scientific studies: surgical intervention and medication prescription decisions were more likely to be based on scientific studies than all other decisions. CONCLUSIONS: With increasing emphasis on high value, evidence-based care, understanding the rationale behind physician decision-making can educate physicians, identify common decisions without supporting evidence and help create clinical care pathways in pediatric orthopedic surgery. Decisions based on evidence or consensus between surgeons can inform pathways and national guidelines that minimize unwarranted variation in care and waste. Decision support tools and aids could also be implemented to guide these decisions.


Assuntos
Procedimentos Ortopédicos , Ortopedia , Cirurgiões , Criança , Tomada de Decisão Clínica , Humanos
10.
Cancer Epidemiol Biomarkers Prev ; 28(8): 1353-1363, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31147314

RESUMO

BACKGROUND: Hispanics are the largest minority population in the United States (18%). They represent a heterogeneous and growing population. Cancer is the leading cause of death among Hispanics, yet few studies have described cancer mortality burden by specific Hispanic group nationwide. METHODS: Cancer-related deaths from U.S. death certificates for the years 2003-2012 were analyzed for decedents identifying as Mexican, Puerto Rican, Cuban, and Central or South American. We calculated descriptive statistics, including potential years of lives lost (PYLL), age-adjusted rates, standardized mortality ratios, and fitted JoinPoint regression models, to evaluate annual trends by Hispanic group, using non-Hispanic Whites (NHW) as the reference population. RESULTS: We identified 287,218 cancer-related deaths among Hispanics and 4,570,559 among NHWs. Mortality trends were heterogeneous across Hispanic groups. Female NHWs and male Puerto Ricans had the greatest rates of adjusted PYLL per 1,000 (NHWs, 19.6; Puerto Ricans, 16.5). Liver cancer was ranked among the top 5 cancer-related deaths for every Hispanic group, but not for NHWs. Stomach cancer mortality was twice as high for most Hispanic groups when compared with NHWs and especially high for Mexicans [male standardized mortality ratio (SMR), 2.07; 95% confidence interval (CI), 2.01-2.13; female SMR, 2.62; 95% CI, 2.53-2.71]. CONCLUSIONS: We observed marked heterogeneity in cancer mortality across Hispanic groups. Several cancers affect Hispanics disproportionately compared with NHWs. Screening programs in Hispanics should be considered for stomach and liver cancer. IMPACT: Disaggregated analysis of Hispanics is needed to fully understand cancer burden among the diverse Hispanic population and is critical for cancer prevention and control efforts.


Assuntos
Hispânico ou Latino/estatística & dados numéricos , Americanos Mexicanos/estatística & dados numéricos , Neoplasias/etnologia , Neoplasias/mortalidade , Fatores Etários , Cuba/etnologia , Feminino , Humanos , Incidência , Masculino , Mortalidade/tendências , Neoplasias/epidemiologia , Porto Rico/etnologia , Fatores de Risco , Fatores Sexuais , América do Sul/etnologia , Taxa de Sobrevida , Estados Unidos/epidemiologia
11.
Ethn Dis ; 29(2): 287-296, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057314

RESUMO

Objective: To determine the association between language and ideal cardiovascular health among Asian Americans and Latinos. Design/Study Participants: Cross-sectional study using 2011-2016 National Health and Nutrition Examination Survey of Asian Americans (n=2,009) and Latinos (n=3,906). Interventions: Participants were classified according to language spoken at home (only/mostly English spoken, both English and native language spoken equally, or mostly/only native language spoken). Outcomes: Ideal, intermediate and poor cardiovascular health status for smoking, blood pressure, glucose level, and total cholesterol. Results: The majority of Asian Americans and Latinos had ideal smoking status, but those who only/mostly spoke English were more likely to smoke compared with those who spoke only/mostly spoke their native language. Approximately one third of Asian Americans and Latinos had intermediate (ie, borderline or treated to goal) levels of cardiovascular health for blood pressure, glucose level and total cholesterol. In adjusted models, those who spoke only/mostly their native language were significantly less likely to have poor smoking or hypertension status than those who spoke only/mostly English. Among Latinos, only/mostly Spanish speakers were more likely to have poor/ intermediate glucose levels (PR=1.35, 95% CI =1.21, 1.49) than those who spoke only/ mostly English, becoming statistically non-significant after adjusting for education and income. Conclusion: We found significant variation in ideal cardiovascular health attainment by language spoken at home in two of the largest immigrant groups in the United States. Findings suggest the need for language and culturally tailored public health and clinical initiatives to reduce cardiovascular risk in diverse populations.


Assuntos
Aculturação , Asiático/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Hipertensão/etiologia , Fumar/etnologia , Adulto , Pressão Sanguínea , Sistema Cardiovascular , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estados Unidos
12.
Clin Cancer Res ; 25(15): 4592-4602, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30824587

RESUMO

Immune-checkpoint inhibitors (ICI), particularly inhibitors of the PD-1 axis, have altered the management of non-small cell lung cancer (NSCLC) over the last 10 years. First demonstrated to improve outcomes in second-line or later therapy of advanced disease, ICIs were shown to improve overall survival compared with chemotherapy in first-line therapy for patients whose tumors express PD-L1 on at least 50% of cells. More recently, combining ICIs with chemotherapy has been shown to improve survival in patients with both squamous and nonsquamous NSCLC, regardless of PD-L1 expression. However, PD-L1 and, more recently, tumor mutational burden have not proven to be straightforward indicative biomarkers. We describe the advances to date in utilizing these biomarkers, as well as novel markers of tumor inflammation, to ascertain which patients are most likely to benefit from ICIs. Ongoing translational work promises to improve the proportion of patients who benefit from these agents.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Ensaios Clínicos como Assunto , Humanos , Fatores Imunológicos/uso terapêutico
13.
Diabetes Res Clin Pract ; 148: 169-178, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30641162

RESUMO

AIMS: Deaths attributable to diabetes may be underestimated using an underlying cause of death (COD) approach in U.S. death records. This study sought to characterize the burden of diabetes deaths using a multiple-cause of death approach (underlying and contributing COD) and to identify temporal changes in co-reported causes of death among those with diabetes listed anywhere on their death records. METHODS: COD were identified using data from the National Center for Health Statistics from 2003 to 2016. We calculated age-adjusted mortality rates for diabetes as the underlying or contributing COD by race/ethnicity. We used ICD-10 codes to identify leading causes of death among those with and without diabetes on their death records. We compared temporal changes in deaths due to cardiovascular disease, cerebrovascular disease, cancer, and other causes. RESULTS: The study population included 34,313,964 decedents aged ≥25 from 2003 to 2016. Diabetes was listed as an underlying COD in approximately 3.0% (n = 1,031,000) and 6.7% (n = 2,295,510) of the death records, respectively. Decedents with diabetes listed as an underlying COD experienced a 16% decline in mortality, and the race/ethnicity-specific average annual percentage changes (AAPC) showed significant declining trends for most groups (AAPC ranged from 0.18 to -2.83%). Cardiovascular disease remained the leading underlying COD among diabetes-attributable deaths, although its proportion of deaths fell from 31 to 27% over time. Co-reported COD diversified, and were more likely to include hypertension and hypertensive renal disease among those with diabetes on their death records. CONCLUSIONS: Our findings underscore the importance of using a multiple-cause-of-death approach for more completely characterizing diabetes' contribution to mortality.


Assuntos
Causas de Morte , Diabetes Mellitus/mortalidade , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/mortalidade , Causalidade , Causas de Morte/tendências , Atestado de Óbito , Diabetes Mellitus/etnologia , Etnicidade , Feminino , Disparidades nos Níveis de Saúde , Humanos , Hipertensão/etnologia , Hipertensão/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade , Grupos Raciais , Estados Unidos/epidemiologia
14.
Ann Intern Med ; 169(12): 836-844, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30422275

RESUMO

Background: Recent data suggest that the United States is in the midst of an epidemiologic transition in the leading cause of death. Objective: To examine county-level sociodemographic differences in the transition from heart disease to cancer as the leading cause of death in the United States. Design: Observational study. Setting: U.S. death records, 2003 to 2015. Participants: Decedents aged 25 years or older, classified by racial/ethnic group. Measurements: All-cause, heart disease, and cancer mortality stratified by quintiles of county median household income. Age- and sex-adjusted mortality rates and average annual percentage of change were calculated. Results: Heart disease was the leading cause of death in 79% of counties in 2003 and 59% in 2015. Cancer was the leading cause of death in 21% of counties in 2003 and 41% in 2015. The shift to cancer as the leading cause of death was greatest in the highest-income counties. Overall, heart disease mortality rates decreased by 28% (30% in high-income counties vs. 22% in low-income counties) from 2003 to 2015, and cancer mortality rates decreased by 16% (18% in high-income counties vs. 11% in low-income counties). In the lowest-income counties, heart disease remained the leading cause of death among all racial/ethnic groups, and improvements were smaller for both heart disease and cancer. Limitation: Use of county median household income as a proxy for socioeconomic status. Conclusion: Data show that heart disease is more likely to be the leading cause of death in low-income counties. Low-income counties have not experienced the same decrease in mortality rates as high-income counties, which suggests a later transition to cancer as the leading cause of death in low-income counties. Primary Funding Source: National Institute on Minority Health and Health Disparities.


Assuntos
Status Econômico , Cardiopatias/mortalidade , Renda , Neoplasias/mortalidade , Distribuição por Idade , Causas de Morte , Etnicidade , Cardiopatias/economia , Cardiopatias/etnologia , Humanos , Neoplasias/economia , Neoplasias/etnologia , Fatores Raciais/economia , Distribuição por Sexo , Estados Unidos/epidemiologia
15.
Cancer Discov ; 7(12): 1420-1435, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29025772

RESUMO

Mechanisms of acquired resistance to immune checkpoint inhibitors (ICI) are poorly understood. We leveraged a collection of 14 ICI-resistant lung cancer samples to investigate whether alterations in genes encoding HLA Class I antigen processing and presentation machinery (APM) components or interferon signaling play a role in acquired resistance to PD-1 or PD-L1 antagonistic antibodies. Recurrent mutations or copy-number changes were not detected in our cohort. In one case, we found acquired homozygous loss of B2M that caused lack of cell-surface HLA Class I expression in the tumor and a matched patient-derived xenograft (PDX). Downregulation of B2M was also found in two additional PDXs established from ICI-resistant tumors. CRISPR-mediated knockout of B2m in an immunocompetent lung cancer mouse model conferred resistance to PD-1 blockade in vivo, proving its role in resistance to ICIs. These results indicate that HLA Class I APM disruption can mediate escape from ICIs in lung cancer.Significance: As programmed death 1 axis inhibitors are becoming more established in standard treatment algorithms for diverse malignancies, acquired resistance to these therapies is increasingly being encountered. Here, we found that defective antigen processing and presentation can serve as a mechanism of such resistance in lung cancer. Cancer Discov; 7(12); 1420-35. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1355.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe I/metabolismo , Neoplasias Pulmonares/genética , Humanos , Neoplasias Pulmonares/metabolismo , Transdução de Sinais
16.
Cancer ; 123(24): 4860-4867, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28881423

RESUMO

BACKGROUND: Well-differentiated thyroid carcinoma has a favorable prognosis, but patients with multiple recurrences have drastically lower survival. Filipinos in the United States are known to have high rates of thyroid cancer incidence and disease recurrence. To the authors' knowledge, it is unknown whether Filipinos also have higher thyroid cancer mortality rates. METHODS: The authors studied thyroid cancer mortality in Filipino, non-Filipino Asian (NFA), and non-Hispanic white (NHW) adults using US death records (2003-2012) and US Census data. Age-adjusted mortality rates and proportional mortality ratios (PMRs) were calculated. Sex, nativity status, age at death, and educational attainment also were examined. RESULTS: The authors examined 19,940,952 deaths. The age-adjusted mortality rates due to thyroid cancer were highest in Filipinos (1.72 deaths per 100,000 population; 95% confidence interval [95% CI], 1.51-1.95) compared with NFAs (1.03 per 100,000 population; 95% CI, 0.95-1.12) and NHWs (1.17 per 100,000 population; 95% CI, 1.16-1.18). Compared with NHWs, higher proportionate mortality was observed in Filipino women (3-5 times higher) across all age groups, and among Filipino men, the PMR was 2 to 3 times higher in the subgroup aged >55 years. Filipinos who completed a higher educational level had a notably higher PMR (5.0) compared with their counterparts who had not (3.5). CONCLUSIONS: Negative prognostic factors for thyroid cancer traditionally include age >45 years and male sex. The results of the current study demonstrate that Filipinos die of thyroid cancer at higher rates than NFA and NHW individuals of similar ages. Highly educated Filipinos and Filipino women may be especially at risk of poor thyroid cancer outcomes. Filipino ethnicity should be factored into clinical decision making in the management of patients with thyroid cancer. Cancer 2017;123:4860-7. © 2017 American Cancer Society.


Assuntos
Asiático/estatística & dados numéricos , Causas de Morte , Neoplasias da Glândula Tireoide/etnologia , Neoplasias da Glândula Tireoide/mortalidade , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Bases de Dados Factuais , Atestado de Óbito , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Filipinas/etnologia , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Análise de Sobrevida , Neoplasias da Glândula Tireoide/patologia , Estados Unidos , População Branca/estatística & dados numéricos
17.
Prev Med ; 99: 222-227, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28219784

RESUMO

Little evidence exists examining cardiovascular risk factors among Asian Americans and how social determinants such as nativity status and education pattern risk in the United States (U.S.) context. We used the National Health and Nutrition Examination Survey, which purposely oversampled Asian Americans from 2011 to 2014, and examined prevalence of Type II diabetes, smoking and obesity for Asian Americans (n=1363) and non-Latino Whites (n=4121). We classified Asian Americans as U.S. or foreign-born and by years in the U.S. Obesity status was based on standard body mass index (BMI) cut points of ≥30kg/m2 and Asian-specific cut points (BMI≥25kg/m2) that may be more clinically relevant for this population. We fit separate logistic regression models for each outcome using complex survey design methods and tested for the joint effect of race, nativity and education on each outcome. Diabetes and obesity prevalence (applying Asian-specific BMI cut points) were higher among Asian Americans when compared to non-Latino Whites but smoking prevalence was lower. These patterns remained in fully adjusted models and showed small increases with longer duration in the U.S. Joint effects models showed higher odds of prevalent Type II diabetes and obesity (Asian-specific) for foreign-born Asians, regardless of years in the U.S. and slightly higher risk for low education, when compared to non-Latino Whites with high education. Smoking models showed significant interaction effects between race and education for non-Latino Whites only. Our study supports the premise that social as well as clinical factors should be considered when developing health initiatives for Asian Americans.


Assuntos
Asiático/estatística & dados numéricos , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia/etnologia , Asiático/psicologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/epidemiologia , Obesidade/etnologia , Fatores de Risco , Fumar/epidemiologia , Fumar/etnologia , Estados Unidos
18.
BMJ Open ; 6(10): e012201, 2016 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-27793837

RESUMO

BACKGROUND: With immigration and minority populations rapidly growing in the USA, it is critical to assess how these populations fare after immigration, and in subsequent generations. Our aim is to compare death rates and cause of death across foreign-born, US-born and country of origin Chinese and Japanese populations. METHODS: We analysed all-cause and cause-specific age-standardised mortality rates and trends using 2003-2011 US death record data for Chinese and Japanese decedents aged 25 or older by nativity status and sex, and used the WHO Mortality Database for Hong Kong and Japan decedents in the same years. Characteristics such as age at death, absolute number of deaths by cause and educational attainment were also reported. RESULTS: We examined a total of 10 458 849 deaths. All-cause mortality was highest in Hong Kong and Japan, intermediate for foreign-born, and lowest for US-born decedents. Improved mortality outcomes and higher educational attainment among foreign-born were observed compared with developed Asia counterparts. Lower rates in US-born decedents were due to decreased cancer and communicable disease mortality rates in the US heart disease mortality was either similar or slightly higher among Chinese-Americans and Japanese-Americans compared with those in developed Asia counterparts. CONCLUSIONS: Mortality advantages in the USA were largely due to improvements in cancer and communicable disease mortality outcomes. Mortality advantages and higher educational attainments for foreign-born populations compared with developed Asia counterparts may suggest selective migration. Findings add to our limited understanding of the racial and environmental contributions to immigrant health disparities.


Assuntos
Povo Asiático , Causas de Morte , Emigrantes e Imigrantes , Emigração e Imigração , Adulto , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Feminino , Disparidades nos Níveis de Saúde , Hong Kong , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Características de Residência , Estados Unidos/epidemiologia
19.
Cancer Epidemiol Biomarkers Prev ; 25(10): 1371-1382, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27694108

RESUMO

BACKGROUND: Asian Americans (AA) are the fastest growing U.S. population, and when properly distinguished by their ethnic origins, exhibit substantial heterogeneity in socioeconomic status, health behaviors, and health outcomes. Cancer is the second leading cause of death in the United States, yet trends and current patterns in the mortality burden of cancer among AA ethnic groups have not been documented. METHODS: We report age-adjusted rates, standardized mortality ratios, and modeled trends in cancer-related mortality in the following AA ethnicities: Asian Indians, Chinese, Filipinos, Japanese, Koreans, and Vietnamese, from 2003 to 2011, with non-Hispanic whites (NHW) as the reference population. RESULTS: For most cancer sites, AAs had lower cancer mortality than NHWs; however, mortality patterns were heterogeneous across AA ethnicities. Stomach and liver cancer mortality was very high, particularly among Chinese, Koreans, and Vietnamese, for whom these two cancer types combined accounted for 15% to 25% of cancer deaths, but less than 5% of cancer deaths in NHWs. In AA women, lung cancer was a leading cause of death, but (unlike males and NHW females) rates did not decline over the study period. CONCLUSIONS: Ethnicity-specific analyses are critical to understanding the national burden of cancer among the heterogeneous AA population. IMPACT: Our findings highlight the need for disaggregated reporting of cancer statistics in AAs and warrant consideration of tailored screening programs for liver and gastric cancers. Cancer Epidemiol Biomarkers Prev; 25(10); 1371-82. ©2016 AACR.


Assuntos
Asiático/estatística & dados numéricos , Neoplasias/epidemiologia , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Distribuição por Sexo , Estados Unidos
20.
PLoS One ; 10(4): e0124341, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25915940

RESUMO

BACKGROUND: Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups. METHODS AND FINDINGS: We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs. CONCLUSIONS: Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.


Assuntos
Asiático/etnologia , Causas de Morte/tendências , Transtornos Cerebrovasculares/mortalidade , Diabetes Mellitus/mortalidade , Feminino , Cardiopatias/mortalidade , Humanos , Masculino , Neoplasias/mortalidade , Fatores Sexuais , Suicídio/estatística & dados numéricos
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