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1.
Gynecol Oncol ; 181: 118-124, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38150836

RESUMO

OBJECTIVE: To evaluate patterns and trends of uterine cancer among Hispanic subgroups. METHODS: The United States Cancer Statistics (USCS), National Cancer Database (NCDB), and World Population Review were used to obtain data on incidence, demographic characteristics, and cancer histology. Joinpoint regression program was used for statistical analysis. RESULTS: Based on 2001-2017 USCS data, the overall incidence of uterine cancer was 27.46 vs. 23.29/100,000 in Hispanics vs. non-Hispanic Whites. There was an over 2-fold higher annual increase in the incidence in Hispanics (1.94%; p < 0.001) vs. Whites (0.85%; p < 0.001), particularly in local stage disease. There was an increase in grade 1 endometrioid carcinoma (1.48%; p < 0.001 vs. -0.52%; p = 0.1) and aggressive histologic subtypes (4.04% p = 0.000 vs. 2.53% p = 0.000) in Hispanics vs. Whites. Using the NCDB (2004-2015), we analyzed 17,351 Hispanics by subgroup (Mexican, South/Central American, Puerto Rican, Cuban, and Dominican). Over the 12 years, there was an increase in the proportion of uterine cancer diagnoses in all Hispanics (5.2% to 11.0%; p < 0.0001). Dominican patients experienced the largest increase in diagnosis (2.6% to 14.9%; p < 0.0001), the highest proportion of advanced disease at 28.0% (p < 0.0001), and the highest incidence of non-endometrioid histologies at 37.1% (p < 0.0001). World Population Review 2023 revealed the highest female obesity rates in Puerto Rico (51.4%), the Dominican Republic (34.1%), and Mexico (32.8%). CONCLUSION: Uterine cancer incidence is increased in Hispanics, with the largest increase in Dominican women with more advanced stages and high-risk histologic subtypes. The impact of obesity on cancer risk, especially in Puerto Ricans, Dominicans, and Mexicans, warrants further investigation.


Assuntos
População do Caribe , Hispânico ou Latino , População Norte-Americana , Neoplasias Uterinas , Estados Unidos/epidemiologia , Humanos , Feminino , Porto Rico/epidemiologia , Neoplasias Uterinas/epidemiologia , Obesidade
2.
Gynecol Oncol ; 182: 24-31, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38246043

RESUMO

OBJECTIVE: To evaluate the patterns and trends of uterine cancer among Asian subgroups living in the U.S. METHODS: Data were obtained from United States Cancer Statistics (2001-2017), National Cancer Database (2004-2015), and World Population Review (2023). SEER*Stat version 8.3.9.2, Joinpoint regression program 4.9.0.0, and SAS v 9.4 were employed for statistical analysis. RESULTS: Based on data from 778,891 women in the United States Cancer Statistics database, Asians had a 3.4-fold higher rate of incident uterine cancer compared to White populations (2.14% vs. 0.63%; p < 0.001). Using the National Cancer Database, 7,641 Asian women from six subgroups were analyzed: Filipino, Korean, Indian/Pakistani, Vietnamese, Chinese, and Japanese. Indian and Pakistani women had the greatest increase in the proportion of cancer diagnoses (5.0% to 14.4%; p = 0.0003). Additionally, Indian and Pakistani patients had higher comorbidity scores while Koreans had the lowest (22.7% vs. 10.7%, p < 0.0001). Regarding stage of disease, 25.3% of Filipinos presented with advanced stage disease compared to 19.2% of Indians and Pakistanis (p = 0.0001). Furthermore, Filipinos had the highest proportion of non-endometrioid cancers at 18.4% compared to other subgroups (p = 0.0003). Using the World Population Review, female obesity was highest in Pakistan (8.6%) and the Philippines (7.5%) and lowest in Vietnam (2.6%). CONCLUSION: Uterine cancer incidence increased at higher rates among Asians compared to White populations. Specifically, Indian and Pakistani uterine cancer patients were more likely to have higher comorbidity rates and Filipino patients had more advanced stage cancer with non-endometrioid histologies than other Asian subgroups. Further research is warranted to better understand these trends.


Assuntos
Asiático , População do Sul da Ásia , Neoplasias Uterinas , Feminino , Humanos , Povo Asiático , Incidência , Estados Unidos/epidemiologia , Neoplasias Uterinas/epidemiologia , Brancos , Etnicidade
3.
Biophys J ; 122(7): 1211-1218, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36793216

RESUMO

Fluorescently labeled oligonucleotides are powerful tools for characterizing DNA processes; however, their use is limited by the cost and sequence requirements of current labeling technologies. Here, we develop an easy, inexpensive, and sequence-independent method for site-specifically labeling DNA oligonucleotides. We utilize commercially synthesized oligonucleotides containing phosphorothioate diester(s) in which a nonbridging oxygen is replaced with a sulfur (PS-DNA). The increased nucleophilicity of the thiophosphoryl sulfur relative to the phosphoryl oxygen permits selective reactivity with iodoacetamide compounds. As such, we leverage a long-existing bifunctional linker, N,N'-bis(α-iodoacetyl)-2-2'-dithiobis(ethylamine) (BIDBE), that reacts with PS-DNAs to leave a free thiol, allowing conjugation of the wide variety of commercial maleimide-functionalized compounds. We optimized BIDBE synthesis and its attachment to PS-DNA and then fluorescently labeled the BIDBE-PS-DNA using standard protocols for labeling cysteines. We purified the individual epimers, and using single-molecule Förster resonance energy transfer (FRET), we show that the FRET efficiency is independent of the epimeric attachment. Subsequently, we demonstrate that an epimeric mixture of double-labeled Holliday junctions (HJs) can be used to characterize their conformational properties in the absence and presence of the structure-specific endonuclease Drosophila melanogaster Gen. Finally, we use a biochemical activity assay to show that this double-labeled HJ is functional for cleavage by Gen and that the double-labeled HJ allows multiple DNA species to be identified in a single experiment. In conclusion, our results indicate that dye-labeled BIDBE-PS-DNAs are comparable to commercially labeled DNAs at a significantly reduced cost. Notably, this technology could be applied to other maleimide-functionalized compounds, such as spin labels, biotin, and proteins. The sequence independence of labeling, coupled with its ease and low cost, enables unrestricted exploration of dye placement and choice, providing the potential for creation of differentially labeled DNA libraries and opening previously inaccessible experimental avenues.


Assuntos
DNA , Drosophila melanogaster , Animais , Drosophila melanogaster/metabolismo , DNA/metabolismo , Oligonucleotídeos , Enxofre/química , Corantes Fluorescentes/química , Maleimidas/química
4.
J Infect Dis ; 226(7): 1127-1139, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-35417025

RESUMO

BACKGROUND: We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings. METHODS: After screening 16 822 citations, we identified 9 articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria. RESULTS: Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], -212.4 to -31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, -95.3 to -12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, -62.6 to -3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, -51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection. CONCLUSIONS: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.


Assuntos
Vírus do Sarampo , Sarampo , Anticorpos Antivirais , Humanos , Sarampo/prevenção & controle , Vacina contra Sarampo , Vacinação
5.
J Biol Chem ; 296: 100312, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33482195

RESUMO

Elevated plasma triglycerides are a risk factor for coronary artery disease, which is the leading cause of death worldwide. Lipoprotein lipase (LPL) reduces triglycerides in the blood by hydrolyzing them from triglyceride-rich lipoproteins to release free fatty acids. LPL activity is regulated in a nutritionally responsive manner by macromolecular inhibitors including angiopoietin-like proteins 3 and 4 (ANGPTL3 and ANGPTL4). However, the mechanism by which ANGPTL3 inhibits LPL is unclear, in part due to challenges in obtaining pure protein for study. We used a new purification protocol for the N-terminal domain of ANGPTL3, removing a DNA contaminant, and found DNA-free ANGPTL3 showed enhanced inhibition of LPL. Structural analysis showed that ANGPTL3 formed elongated, flexible trimers and hexamers that did not interconvert. ANGPTL4 formed only elongated flexible trimers. We compared the inhibition of ANGPTL3 and ANGPTL4 using human very-low-density lipoproteins as a substrate and found both were noncompetitive inhibitors. The inhibition constants for the trimeric ANGPTL3 (7.5 ± 0.7 nM) and ANGPTL4 (3.6 ± 1.0 nM) were only 2-fold different. Heparin has previously been reported to interfere with ANGPTL3 binding to LPL, so we questioned if the negatively charged heparin was acting in a similar fashion to the DNA contaminant. We found that ANGPTL3 inhibition is abolished by binding to low-molecular-weight heparin, whereas ANGPTL4 inhibition is not. Our data show new similarities and differences in how ANGPTL3 and ANGPTL4 regulate LPL and opens new avenues of investigating the effect of heparin on LPL inhibition by ANGPTL3.


Assuntos
Proteína 4 Semelhante a Angiopoietina/química , Proteínas Semelhantes a Angiopoietina/química , Doença da Artéria Coronariana/genética , Lipase Lipoproteica/química , Conformação Proteica , Proteína 3 Semelhante a Angiopoietina , Proteína 4 Semelhante a Angiopoietina/genética , Proteína 4 Semelhante a Angiopoietina/ultraestrutura , Proteínas Semelhantes a Angiopoietina/genética , Proteínas Semelhantes a Angiopoietina/ultraestrutura , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Heparina/farmacologia , Humanos , Lipase Lipoproteica/genética , Lipase Lipoproteica/ultraestrutura , Lipoproteínas VLDL/química , Lipoproteínas VLDL/genética , Ligação Proteica/efeitos dos fármacos , Especificidade por Substrato , Triglicerídeos/sangue
6.
Clin Infect Dis ; 73(1): 83-90, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32384142

RESUMO

BACKGROUND: Vaccine effectiveness (VE) studies provide essential evidence on waning vaccine-derived immunity, a major threat to pertussis control. We evaluated how study design affects estimates by comparing 2 case-control studies conducted in Ontario, Canada. METHODS: We compared results from a test-negative design (TND) with a frequency-matched design (FMD) case-control study using pertussis cases from 2005-2015. In the first study, we identified test-negative controls from the public health laboratory that diagnosed cases and, in the second, randomly selected controls from patients attending the same physicians that reported cases, frequency matched on age and year. We compared characteristics of cases and controls using standardized differences. RESULTS: In both designs, VE estimates for the early years postimmunization were consistent with clinical trials (TND, 84%; FMD, 89% at 1-3 years postvaccination) but diverged as time since last vaccination increased (TND, 41%; FMD, 74% by 8 years postvaccination). Overall, we observed lower VE and faster waning in the TND than the FMD. In the TND but not FMD, controls differed from cases in important confounders, being younger, having more comorbidities, and higher healthcare use. Differences between the controls of each design were greater than differences between cases. TND controls were more likely to be unvaccinated or incompletely vaccinated than FMD controls (P < .001). CONCLUSIONS: The FMD adjusted better for healthcare-seeking behavior than the TND. Duration of protection from pertussis vaccines is unclear because estimates vary by study design. Caution should be exercised by experts, researchers, and decision makers when evaluating evidence on optimal timing of boosters.


Assuntos
Vacina contra Coqueluche , Coqueluche , Estudos de Casos e Controles , Humanos , Ontário/epidemiologia , Vacinação , Coqueluche/epidemiologia , Coqueluche/prevenção & controle
7.
Clin Chem ; 68(1): 192-203, 2021 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-34969116

RESUMO

BACKGROUND: The urinary tract is not sterile and is populated by microbial communities that influence urinary health. Men who have sex with men (MSM) are understudied yet have increased risk factors for genitourinary infections. Our objective was to interrogate the composition of MSM urinary microbiota. METHODS: Midstream urine specimens (n = 129) were collected from MSM (n = 63) and men seen for routine care (clinical cohort, n = 30). Demographics and sexual/medical history were documented. Specimens underwent culture using standard-of-care and enhanced methods designed to isolate fastidious and anaerobic microorganisms. Isolates were identified by MALDI-TOF mass spectrometry or 16S rRNA gene sequencing. RESULTS: The MSM cohort was younger (mean (SD), 35.4 (11.26) years) compared to the clinical cohort (62.7 (15.95) years). Organism recovery was significantly increased using enhanced vs standard culture for the MSM (mean of 9.1 vs 0.6 species/sample [P < 0.001]) and clinical (7.8 vs 0.9 species/sample [P < 0.001]) cohorts. The microbial composition of MSM urine specimens was dominated by Gram-positive and anaerobic microbes and clustered distinctly from that of clinical urine specimens. Composition of microbial species recovered within the same subject was dynamic between urine specimens but more similar relative to inter-individual comparisons. Principal coordinate analysis showed no correlation between urinary microbiota composition and age, recent antibiotic use, sexually transmitted infection/HIV status, or sexual practices. CONCLUSIONS: Enhanced culture recovered a large diversity of microbial species from MSM urine specimens, especially taxa typically associated with mucosal surfaces. These findings may increase understanding of urologic disease in MSM and improve diagnostic methods for detection of genitourinary infections.


Assuntos
Microbiota , Minorias Sexuais e de Gênero , Infecções Urinárias , Homossexualidade Masculina , Humanos , Masculino , RNA Ribossômico 16S/genética , Infecções Urinárias/diagnóstico
8.
Biochemistry ; 59(38): 3626-3638, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32857494

RESUMO

Elongating ketosynthases (KSs) catalyze carbon-carbon bond-forming reactions during the committed step for each round of chain extension in both fatty acid synthases (FASs) and polyketide synthases (PKSs). A small α-helical acyl carrier protein (ACP) shuttles fatty acyl intermediates between enzyme active sites. To accomplish this task, the ACP relies on a series of dynamic interactions with multiple partner enzymes of FAS and associated FAS-dependent pathways. Recent structures of the Escherichia coli FAS ACP, AcpP, in covalent complexes with its two cognate elongating KSs, FabF and FabB, provide high-resolution details of these interfaces, but a systematic analysis of specific interfacial interactions responsible for stabilizing these complexes has not yet been undertaken. Here, we use site-directed mutagenesis with both in vitro and in vivo activity analyses to quantitatively evaluate these contacting surfaces between AcpP and FabF. We delineate the FabF interface into three interacting regions and demonstrate the effects of point mutants, double mutants, and region deletion variants. Results from these analyses reveal a robust and modular FabF interface capable of tolerating seemingly critical interface mutations with only the deletion of an entire region significantly compromising activity. Structure and sequence analyses of FabF orthologs from related type II FAS pathways indicate significant conservation of type II FAS KS interface residues and, overall, support its delineation into interaction regions. These findings strengthen our mechanistic understanding of molecular recognition events between ACPs and FAS enzymes and provide a blueprint for engineering ACP-dependent biosynthetic pathways.


Assuntos
Acetiltransferases/metabolismo , Proteína de Transporte de Acila/metabolismo , Proteínas de Escherichia coli/metabolismo , Ácido Graxo Sintase Tipo II/metabolismo , Ácidos Graxos/biossíntese , Acetiltransferases/genética , Proteína de Transporte de Acila/genética , Escherichia coli/enzimologia , Proteínas de Escherichia coli/genética , Ácido Graxo Sintase Tipo II/genética , Mutagênese Sítio-Dirigida , Mutação Puntual
9.
J Public Health (Oxf) ; 42(3): e272-e277, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-31608381

RESUMO

BACKGROUND: Adolescents make decisions about their own vaccinations and will be the childhood vaccine decision makers of tomorrow. It is therefore essential to educate adolescents about the risks of vaccine-preventable diseases and immunization safety. This study evaluated the impact of an interactive education initiative among adolescents at a high school in North Bay Ontario. METHODS: An anonymized questionnaire to assess students' knowledge, attitudes and beliefs about immunization and vaccine-preventable diseases was administered before and after delivering an interactive session. Chi-squared and Kruskal-Wallis tests were performed to test for differences between pre and post responses. RESULTS: The intervention increased the students' awareness that measles is a disease that affects their generation (P < 0.05). Improvements were also noted in the perceived risk of pertussis (P < 0.05) and tetanus (0.05). After the session, respondents were also more willing to participate with their parents in decisions affecting their healthcare (P < 0.05). Students' perception of vaccine safety also improved (P < 0.001). CONCLUSIONS: Post survey results suggest that the interactive educational intervention had a positive effect on the adolescents' perceptions and attitudes towards immunization. Further research is required to determine the impact of this type of intervention on adolescents' future decision-making with respect to immunization.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Vacinação/psicologia , Vacinas , Adolescente , Criança , Humanos , Pais , Vacinas/efeitos adversos
10.
Circ Res ; 121(11): 1251-1262, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29021296

RESUMO

RATIONALE: The phenotypes of vascular smooth muscle cells (vSMCs) comprise a continuum bounded by predominantly contractile and synthetic cells. Some evidence suggests that contractile vSMCs can assume a more synthetic phenotype in response to ischemic injury, but the mechanisms that activate this phenotypic switch are poorly understood. OBJECTIVE: To determine whether lactate, which increases in response to regional ischemia, may promote the synthetic phenotype in vSMCs. METHODS AND RESULTS: Experiments were performed with vSMCs that had been differentiated from human induced pluripotent stem cells and then cultured in glucose-free, lactate-enriched (L+) medium or in standard (L-) medium. Compared with the L- medium, the L+ medium was associated with significant increases in synthetic vSMC marker expression, proliferation, and migration and with significant declines in contractile and apoptotic activity. Furthermore, these changes were accompanied by increases in the expression of monocarboxylic acid transporters and were generally attenuated both by the blockade of monocarboxylic acid transporter activity and by transfection with iRNA for NDRG (N-myc downstream regulated gene). Proteomics, biomarker, and pathway analyses suggested that the L+ medium tended to upregulate the expression of synthetic vSMC markers, the production of extracellular proteins that participate in tissue construction or repair, and the activity of pathways that regulate cell proliferation and migration. Observations in hypoxia-cultured vSMCs were similar to those in L+-cultured vSMCs, and assessments in a swine myocardial infarction model suggested that measurements of lactate levels, lactate-dehydrogenase levels, vSMC proliferation, and monocarboxylic acid transporter and NDRG expression were greater in the ischemic zone than in nonischemic tissues. CONCLUSIONS: These results demonstrate for the first time that vSMCs assume a more synthetic phenotype in a microenvironment that is rich in lactate. Thus, mechanisms that link glucose metabolism to vSMC phenotypic switching could play a role in the pathogenesis and treatment of cardiovascular disease.


Assuntos
Células-Tronco Pluripotentes Induzidas/metabolismo , Ácido Láctico/metabolismo , Músculo Liso Vascular/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Miócitos de Músculo Liso/metabolismo , Animais , Apoptose , Biomarcadores/metabolismo , Hipóxia Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Microambiente Celular , Modelos Animais de Doenças , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Peptídeos e Proteínas de Sinalização Intracelular , L-Lactato Desidrogenase/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Músculo Liso Vascular/patologia , Infarto do Miocárdio/patologia , Miocárdio/patologia , Miócitos de Músculo Liso/patologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fenótipo , Interferência de RNA , Sus scrofa , Fatores de Tempo , Transfecção , Vasoconstrição
11.
Environ Sci Technol ; 53(23): 13906-13918, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31746186

RESUMO

Persistent organic pollutants (POPs), such as dichlorodiphenyltrichloroethane (DDT) and other organochlorine compounds, are abundant in the environment and in foodstuffs from the Indian subcontinent. These environmental contaminants have been associated with a higher risk of diabetes in numerous studies. Asian Indians are well known to have a high risk of diabetes compared with other populations, and this risk is also found in migrant populations of Asian Indians in the United States, Europe, and elsewhere. We hypothesized that high plasma concentrations of POPs in Asian Indian migrants are linked to a variety of diabetes-related pathologies and explored the mechanism for the induction of these effects. We measured 30 environmental pollutants in plasma samples obtained from 147 participants in the Metabolic syndrome and Atherosclerosis in South Asians Living in America pilot study using a gas chromatography-tandem mass spectrometry analytical method that uses less than 0.5 mL of plasma. We found that plasma levels of o,p'-DDT and p,p'-DDT were independently associated with both body mass index (BMI) and waist circumference. Doubling the levels of the sums of these DDTs was associated with insulin insensitivity (-0.38 Matsuda index, p = 0.001), increased adiposity (1.26 kg/m2 BMI and 3.58 cm waist circumference increase, p < 0.0001), circulating insulin (12.9 mIU/L, p = 0.002), hepatic fat (-0.051 HU, p = 0.001), as well as increased odds of obesity (OR = 2.17, p < 0.001, BMI-based; OR = 2.37, p = 0.001, waist-based), prediabetes (OR = 1.55, p = 0.02), diabetes (OR = 1.72, p = 0.01), and fatty liver (OR = 1.66, p = 0.01) in multivariable models accounting for confounding by age, sex, years in the US, education, and fish protein. Furthermore, levels of DDTs were associated with increased hepatic fat and circulating insulin, independent of obesity and confounders. These findings suggest that exposure to DDTs may contribute to the risk of metabolic disease among Asian Indians by affecting hepatic fat levels independent of obesity.


Assuntos
Emigrantes e Imigrantes , Poluentes Ambientais , Animais , Europa (Continente) , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Projetos Piloto , Estados Unidos
12.
BMC Health Serv Res ; 17(1): 479, 2017 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-28701222

RESUMO

BACKGROUND: Rates of Bordetella pertussis have been increasing in Alberta, Canada despite vaccination programs. Waning immunity from existing acellular component vaccines may be contributing to this. Vaccine effectiveness can be estimated using a variety of data sources including diagnostic codes from physician billing claims, public health records, reportable disease and laboratory databases. We sought to determine if diagnostic codes from billing claims (administrative data) are adequately sensitive and specific to identify pertussis cases among patients who had undergone disease-specific laboratory testing. METHODS: Data were extracted for 2004-2014 from a public health communicable disease database that contained data on patients under investigation for B. pertussis (both those who had laboratory tests and those who were epidemiologically linked to laboratory-confirmed cases) in Alberta, Canada. These were deterministically linked using a unique lifetime person identifier to the provincial billing claims database, which contains International Classification of Disease version 9 (ICD-9) diagnostic codes for physician visits. We examined visits within 90 days of laboratory testing. ICD-9 codes 033 (whooping cough), 033.0 (Bordetella pertussis), 033.1 (B. parapertussis), 033.8 (whooping cough, other specified organism), and 033.9 (whooping cough, other unspecified organism) in any of the three diagnostic fields for a claim were classified as being pertussis-specific codes. We calculated sensitivity, specificity, positive (PPV) and negative (NPV) predictive values. RESULTS: We identified 22,883 unique patients under investigation for B. pertussis. Of these, 22,095 underwent laboratory testing. Among those who had a laboratory test, 2360 tested positive for pertussis. The sensitivity of a pertussis-specific ICD-9 code for identifying a laboratory-confirmed case was 38.6%, specificity was 76.9%, PPV was 16.0%, and NPV was 91.6%. CONCLUSION: ICD-9 codes from physician billing claims data have low sensitivity and moderate specificity to identify laboratory-confirmed pertussis among persons tested for pertussis.


Assuntos
Formulário de Reclamação de Seguro , Classificação Internacional de Doenças , Médicos , Coqueluche/diagnóstico , Alberta/epidemiologia , Pesquisa Biomédica , Bases de Dados Factuais , Feminino , Humanos , Lactente , Masculino , Coqueluche/epidemiologia
14.
Mol Ther Methods Clin Dev ; 32(1): 101193, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38352270

RESUMO

Friedreich's ataxia (FRDA) is an autosomal-recessive disorder primarily attributed to biallelic GAA repeat expansions that reduce expression of the mitochondrial protein frataxin (FXN). FRDA is characterized by progressive neurodegeneration, with many patients developing cardiomyopathy that progresses to heart failure and death. The potential to reverse or prevent progression of the cardiac phenotype of FRDA was investigated in a mouse model of FRDA, using an adeno-associated viral vector (AAV8) containing the coding sequence of the FXN gene. The Fxnflox/null::MCK-Cre conditional knockout mouse (FXN-MCK) has an FXN gene ablation that prevents FXN expression in cardiac and skeletal muscle, leading to cardiac insufficiency, weight loss, and morbidity. FXN-MCK mice received a single intravenous injection of an AAV8 vector containing human (hFXN) or mouse (mFXN) FXN genes under the control of a phosphoglycerate kinase promoter. Compared to vehicle-treated FXN-MCK control mice, AAV-treated FXN-MCK mice displayed increases in body weight, reversal of cardiac deficits, and increases in survival without apparent toxicity in the heart or liver for up to 12 weeks postdose. FXN protein expression in heart tissue was detected in a dose-dependent manner, exhibiting wide distribution throughout the heart similar to wild type, but more speckled. These results support an AAV8-based approach to treat FRDA-associated cardiomyopathy.

15.
J Card Fail ; 19(8): 542-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23910583

RESUMO

BACKGROUND: Earlier work has demonstrated significant sex and age disparities in ischemic heart disease. However, it remains unclear if an age or sex gap exists for heart failure (HF) patients. METHODS AND RESULTS: Using data from the 2007-2008 Healthcare Cost and Utilization Project, we constructed hierarchic regression models to examine sex differences and age-sex interactions in HF hospitalizations and in-hospital mortality. Among 430,665 HF discharges, 51% were women and 0.3%, 27%, and 73% were aged <25, 25-64, and >64 years respectively. There were significant sex differences among HF risk factors, with a higher prevalence of coronary disease among men. Men had higher hospitalization rates for HF and in-hospital mortality across virtually all ages. The relationship between age and HF mortality appeared U-shaped; mortality rates for ages <25, 25-64, and >64 years were 2.9%, 1.4%, and 3.8%, respectively. No age-sex interaction was found for in-hospital mortality for adults >25 years old. CONCLUSIONS: Using a large nationally representative administrative dataset we found age and sex disparities in HF outcomes. In general, men fared worse than women regardless of age. Furthermore, we found a U-shaped relationship between age and in-hospital mortality during an HF hospitalization, such that young adults have similar mortality rates to older adults. Additional studies are warranted to elucidate the patient-specific and treatment characteristics that result in these patterns.


Assuntos
Bases de Dados Factuais/tendências , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Mortalidade Hospitalar/tendências , Hospitalização/tendências , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Estados Unidos/epidemiologia , Adulto Jovem
16.
J Community Health ; 38(3): 451-7, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23197135

RESUMO

Prior work has shown significant geographic variation in cardiovascular (CV) risk factors including metabolic syndrome, obesity, and hypercholesterolemia. However, little is known about how variations in CV risk impact cardiovascular disease (CVD)-related hospitalizations. Community-level CV risk factors (hypertension, dyslipidemia, hyperglycemia, and elevated waist circumference) were assessed from community-wide health screenings sponsored by Sister to Sister (STS) from 2008 to 2009 in 17 major US cities. Using data from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS), CVD hospitalizations were identified based on ICD-9 codes for acute myocardial infarction (AMI), congestive heart failure (CHF), and stroke. We linked STS data with HCUP-NIS hospitalizations based on common cities and restricted the analysis to women discharged from hospitals inside the STS cities. Using hierarchical models with city as the random intercept, we assessed the impact of city-specific CV risk factors on between-city variance of AMI, CHF, and stroke. Analyses were also adjusted for patient age and clinical comorbidities. Our analysis yielded a total of 742,445 all-cause discharges across 70 hospitals inside of 13 linked cities. The overall city-specific range proportion of AMI, CHF, and stroke hospitalizations were 1.13 % (0.75-1.59 %), 2.57 % (1.44-3.92 %), and 1.24 % (0.66-1.84 %), respectively. After adjusting for city-specific CV risk factors, between-city variation was no longer statistically significant for all CVD conditions explored. In conclusion, we found that geographic variations in AMI, CHF, and stroke hospitalizations for women may be partially explained by community-level CV risk factors. This finding suggests that interventions to reduce CVD should be tailored to the unique risk profile and needs of high-risk communities.


Assuntos
Doenças Cardiovasculares/epidemiologia , Hospitalização/estatística & dados numéricos , Fatores Etários , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Comorbidade , Dislipidemias/epidemiologia , Feminino , Geografia Médica , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Humanos , Hiperglicemia/epidemiologia , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Características de Residência/estatística & dados numéricos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/terapia , Estados Unidos/epidemiologia , Circunferência da Cintura
17.
J Community Health ; 38(3): 458-62, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23314921

RESUMO

Community-based interventions (CBI) have been targeted as a potential means of tackling cardiovascular disease in women. However, there have been mixed results in terms of their impact on health, with at least some of this being attributed to high attrition rates. This study explores factors that may be contributing to the low retention of women in cardiovascular CBIs. In 2009, Sister to Sister, a national organization that sponsors community health fairs, provided free cardiovascular health screenings for a total of 9,443 women nationwide. All participants were invited to enroll in a 1 year, survey-based observational study to assess the effectiveness of these community health screenings. Of these 9,443 women, 5.9 % actively participated in the follow-up study. Participants were more likely to have health insurance (75.5 vs. 65.3 %, p < 0.001), have an annual income above 75,000 dollars (26.7 vs. 19.7 %, p < 0.001), and identify themselves as white (50.0 vs. 31.5 %, p < 0.001). They were also more likely to have hypertension (32.1 vs. 27.4 %, p = 0.018) and metabolic syndrome (35.7 vs. 20.4 %, p < 0.001). Our results suggest that white, affluent women with health insurance and cardiovascular risk factors are more likely to engage in CBIs that require longitudinal assessment. This study gives insight into the demographics, socioeconomic status, and cardiovascular comorbidities of women who participate in cardiovascular CBIs. The results may prove to be useful in understanding the biopsychosocial barriers to participation in CBIs in order to develop more effective interventions in the future.


Assuntos
Doenças Cardiovasculares/epidemiologia , Serviços de Saúde Comunitária/estatística & dados numéricos , Perda de Seguimento , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/terapia , Feminino , Humanos , Renda/estatística & dados numéricos , Cobertura do Seguro/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Grupos Raciais/estatística & dados numéricos , Fatores de Risco
18.
Obstet Gynecol ; 142(4): 978-986, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37678887

RESUMO

OBJECTIVE: To analyze mortality trends in uterine cancer in the United States over 50 years with an emphasis on age and race and ethnicity. METHODS: Data on uterine cancer deaths from 1969 to 2018 were obtained from the National Center for Health Statistics. Trends were examined by age and race and ethnicity after adjustment for the hysterectomy rate and pregnancy. RESULTS: Uterine cancer mortality decreased between 1969 and 1997 (from 6.03 to 4.00/100,000) but increased between 1997 and 2018 (from 4.00 to 5.02/100,000). From 2001 to 2018, mortality rates increased by 1.25-fold across all age groups. In 2018, the mortality rate from uterine cancer for patients aged 70 years or older and 60-69 years was sixfold and threefold higher, respectively, than in younger patients (aged 50-59 years) (54.87/100,000 vs 27.80/100,000 vs 8.70/100,000). The mortality rate for non-Hispanic Black women was 2.2-fold higher than for non-Hispanic White, Hispanic, and non-Hispanic Asian or Pacific Islander women (17.6/100,000 vs 7.82/100,000, 6.54/100,000, and 4.24/100,000, respectively). On an intersection analysis of age and race, non-Hispanic Black women aged older than 60 years had a threefold higher mortality rate than non-Hispanic White women (72/100,000 vs 24/100,000). A notable finding was that young non-Hispanic Black and Hispanic women (30-39 years) had the highest annual increases in mortality at 3.3% and 3.8% per year compared with 2.2% in non-Hispanic White women. CONCLUSION: Since 2001, the uterine cancer mortality rate has increased across all four racial and ethnic groups examined, with the highest increase seen among non-Hispanic Black women. The largest increase in mortality was observed among younger non-Hispanic Black and Hispanic women.


Assuntos
Neoplasias Uterinas , Feminino , Humanos , Gravidez , Etnicidade , Hispânico ou Latino , Histerectomia , Estados Unidos/epidemiologia , Neoplasias Uterinas/mortalidade , Negro ou Afro-Americano
19.
JAMA Pediatr ; 177(4): 410-418, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36848096

RESUMO

Importance: The risk of myocarditis or pericarditis after COVID-19 messenger RNA vaccines varies by age and sex, and there is some evidence to suggest increasing risk with shorter intervals between dose 1 and 2 (ie, interdose interval). Objective: To estimate the incidence of reported myocarditis or pericarditis after BNT162b2 vaccine among adolescents and to describe the clinical information associated with these events. Design, Setting, and Participants: This was a population-based cohort study using passive vaccine safety surveillance data linked to the provincial COVID-19 vaccine registry. Included in the study were all adolescents aged 12 to 17 years in Ontario, Canada, who received 1 or more doses of BNT162b2 vaccine between December 14, 2020, and November 21, 2021, and reported an episode of myocarditis or pericarditis. Data were analyzed from December 15, 2021, to April 22, 2022. Exposure: Receipt of BNT162b2 (Comirnaty [Pfizer-BioNTech]) vaccine. Main Outcomes and Measure: Reported incidence of myocarditis or pericarditis meeting level 1 to 3 of the Brighton Collaboration case definition per 100 000 doses of BNT162b2 administered by age group (12-15 years vs 16-17 years), sex, dose number, and interdose interval. All clinical information associated with symptoms, health care usage, diagnostic test results, and treatment at the time of the acute event were summarized. Results: There were approximately 1.65 million doses of BNT162b2 administered and 77 reports of myocarditis or pericarditis among those aged 12 to 17 years, which met the inclusion criteria during the study period. Of the 77 adolescents (mean [SD] age, 15.0 [1.7] years; 63 male individuals [81.8%]), 51 (66.2%) developed myocarditis or pericarditis after dose 2 of BNT162b2. Overall, 74 individuals (96.1%) with an event were assessed in the emergency department, and 34 (44.2%) were hospitalized (median [IQR] length of stay, 1 [1-2] day). The majority of adolescents (57 [74.0%]) were treated with nonsteroidal anti-inflammatory drugs only, and 11 (14.3%) required no treatment. The highest reported incidence was observed among male adolescents aged 16 to 17 years after dose 2 (15.7 per 100 000; 95% CI, 9.7-23.9). Among those aged 16 to 17 years, the reporting rate was highest in those with a short (ie, ≤30 days) interdose interval (21.3 per 100 000; 95% CI, 11.0-37.2). Conclusions and Relevance: Results of this cohort study suggest that there was variation in the reported incidence of myocarditis or pericarditis after BNT162b2 vaccine among adolescent age groups. However, the risk of these events after vaccination remains very rare and should be considered in relation to the benefits of COVID-19 vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Miocardite , Pericardite , Adolescente , Humanos , Masculino , Vacina BNT162 , Estudos de Coortes , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Miocardite/epidemiologia , Miocardite/etiologia , Ontário/epidemiologia , Pericardite/epidemiologia , Pericardite/etiologia , Vacinação/efeitos adversos
20.
BMC Public Health ; 12: 310, 2012 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-22537320

RESUMO

BACKGROUND: Increases in the number of salmonellosis cases due to Salmonella Enteritidis (SE) in 2010 and 2011 prompted a public health investigation in Ontario, Canada. In this report, we describe the current epidemiology of travel-related (TR) SE, compare demographics, symptoms and phage types (PTs) of TR and domestically-acquired (DA) cases, and estimate the odds of acquiring SE by region of the world visited. METHODS: All incident cases of culture confirmed SE in Ontario obtained from isolates and specimens submitted to public health laboratories were included in this study. Demographic and illness characteristics of TR and DA cases were compared. A national travel survey was used to provide estimates for the number of travellers to various destinations to approximate rates of SE in travellers. Multivariate logistic regression was used to estimate the odds of acquiring SE when travelling to various world regions. RESULTS: Overall, 51.9% of SE cases were TR during the study period. This ranged from 35.7% TR cases in the summer travel period to 65.1% TR cases in the winter travel period. Compared to DA cases, TR cases were older and were less likely to seek hospital care. For Ontario travellers, the adjusted odds of acquiring SE was the highest for the Caribbean (OR 37.29, 95% CI 17.87-77.82) when compared to Europe. Certain PTs were more commonly associated with travel (e.g., 1, 4, 5b, 7a, Atypical) than with domestic infection. Of the TR cases, 88.9% were associated with travel to the Caribbean and Mexico region, of whom 90.1% reported staying on a resort. Within this region, there were distinct associations between PTs and countries. CONCLUSIONS: There is a large burden of TR illness from SE in Ontario. Accurate classification of cases by travel history is important to better understand the source of infections. The findings emphasize the need to make travellers, especially to the Caribbean, and health professionals who provide advice to travellers, aware of this risk. The findings may be generalized to other jurisdictions with travel behaviours in their residents similar to Ontario residents.


Assuntos
Infecções por Salmonella/epidemiologia , Salmonella enteritidis , Viagem , Adolescente , Adulto , Antígua e Barbuda , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Cuba , Transmissão de Doença Infecciosa , República Dominicana , Feminino , Humanos , Lactente , Recém-Nascido , Jamaica , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde , Infecções por Salmonella/fisiopatologia
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