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INTRODUCTION: Geographic variation in diagnosed cases of Alzheimer's disease and related dementias (ADRD) could be due to underlying population risk or differences in intensity of new case identification. Areas with low ADRD diagnostic intensity could be targeted for additional surveillance efforts. METHODS: Medicare claims were used for a cohort of older adults across hospital referral regions (HRRs). ADRD-specific regional diagnosis intensity was measured as the ratio of expected new ADRD cases (estimated using population demographics, risk factors, and practice intensity) compared to observed ADRD-diagnosed cases. RESULTS: Crude new ADRD diagnosis rate ranged from 1.7 to 5.4 per 100 across HRRs. ADRD-specific diagnosis intensity ranged from 0.69 to 1.47 and varied most for Black, Hispanic, and the youngest (66-74) subgroups. Across all subgroups, ADRD diagnosis intensity was associated with 2-fold difference in receiving an ADRD diagnosis. DISCUSSION: Where one resides influences the likelihood of receiving an ADRD diagnosis, particularly among those 66-74 years of age and minoritized groups. HIGHLIGHTS: Rate of new Alzheimer's disease and related dementias (ADRD) case identification varies geographically across the United States. Variation in case identification is greatest in Black, Hispanic, and young-old groups. Intensity of diagnosis (ie, case identification) unrelated to population risk differs across place. Likelihood of receiving an ADRD diagnosis varies 2-fold based on place of residence.
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Demencia , Medicare , Humanos , Anciano , Estados Unidos/epidemiología , Masculino , Femenino , Demencia/epidemiología , Demencia/diagnóstico , Medicare/estadística & datos numéricos , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Factores de Riesgo , Estudios de Cohortes , Hispánicos o Latinos/estadística & datos numéricosRESUMEN
The purpose was to examine the degree to which perceived risk for diabetes differed by race and ethnicity among U.S. adults with undiagnosed prediabetes. The study was a cross-sectional analysis of data from 4005 participants (aged ≥20 years) in the National Health and Nutrition Examination Survey (NHANES) program between 2011 and 2018. Individuals with prediabetes were identified using glycohemoglobin (HbA1c) data. Logistic regression was used to estimate the association between race and ethnicity and perceived risk of diabetes while adjusting for age and sex, educational level, family history of diabetes, BMI, and healthcare factors (health insurance coverage and routine place to go for healthcare). Nearly three-quarters (71.8%) of adults with undiagnosed prediabetes reported no perceived risk for diabetes. Rates of perceived risk for diabetes did not change significantly in any racial and ethnic groups from 2011 to 12 to 2017-18. In models adjusted for individual characteristics, identifying as Non-Hispanic Black was associated with a 34% higher likelihood of reporting no perceived risk compared to identifying as Non-Hispanic White (OR 1.34, 95% CI:1.03-1.74). Identifying as Hispanic was associated with a 29% higher likelihood of reporting no perceived risk compared to identifying as Non-Hispanic White (OR 1.29, 95% CI: 1.01, 1.66). Healthcare factors may have less influence on diabetes risk perception. Future public health efforts should improve diabetes risk communication efforts across racial and ethnic groups, emphasizing Non-Hispanic Black and Hispanic populations.
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Diabetes Mellitus , Estado Prediabético , Adulto , Estudios Transversales , Diabetes Mellitus/diagnóstico , Humanos , Encuestas Nutricionales , Estado Prediabético/diagnóstico , Prevalencia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Grip strength is commonly used to assess hand function among older adults. While shown to be associated with disability, the degree to which grip strength specifically predicts hand limitations is unknown. AIMS: The primary aim of this study was to evaluate grip strength as a predictor of hand limitations. METHODS: Using the 2011-14 National Health and Nutrition Examination Survey (NHANES), we classified older adults reporting one or more hand limitations versus those with no limitations. Odds ratios were used to assess the association between grip strength (separated into quartiles) and the likelihood of a hand limitation while controlling for sex, race/ethnicity, education level, income, and pain. Receiver operator characteristic (ROC) curves were used to evaluate the degree to which grip strength discriminates between older adults with and without a hand limitation. RESULTS: We identified 2064 older adults (age ≥ 65), 31% of whom reported a hand-related limitation. Older adults with very low grip strength (weakest quartile) were more likely to report at least one limitation (OR: 6.1, 95% CI: 3.2, 11.8) than those with high grip strength (strongest quartile). However, grip strength had poor to moderate discrimination of hand limitations (ROC area under curves: 0.65-0.81). DISCUSSION: While self-reported hand limitations were associated with lower grip strength; overall, it is a relatively poor predictor of hand impairments among older adults. CONCLUSION: Better assessments are needed to adequately evaluate upper extremity impairments to help older adults maintain functional independence.
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Personas con Discapacidad , Fuerza de la Mano , Humanos , Anciano , Encuestas Nutricionales , Extremidad Superior , AutoinformeRESUMEN
BACKGROUND: Oncology settings increasingly use patient experience data to evaluate clinical performance. Given that older patients with hematologic malignancies are a high-risk population, this study examined factors associated with patient-reported health care experiences during the first year of their cancer diagnosis. METHODS: Cross-sectional study using the 2000-2015 SEER-CAHPS® data to examine patient experiences of Medicare enrollees with a primary diagnosis of leukemia or lymphoma. The primary outcomes were three CAHPS assessments: overall care, personal doctor, and health plan overall. We estimated case-mix adjusted and fully adjusted associations between factors (i.e., clinical and sociodemographic) and the CAHPS outcomes using bivariate statistical tests and multiple linear regression. RESULTS: The final sample included 1,151 patients, with 431 diagnosed with leukemia and 720 diagnosed with lymphoma (median time from diagnosis to survey 6 months). Patients who completed the survey further apart from the diagnosis date reported significantly higher adjusted ratings of care overall (ß .39, p = .008) than those closer to diagnosis. American Indian/Alaska Native, Asian, and Pacific Islander patients had lower adjusted ratings of care overall (ß - .73, p = .003) than Non-Hispanic white patients. Multimorbidity was significantly associated with higher adjusted personal doctor ratings (ß .26, p = .003). CONCLUSIONS: Unfavorable patient experiences among older adults diagnosed with hematologic malignancies warrant targeted efforts to measure and improve care quality. Future measurement of experiences of cancer care soon after diagnosis, coupled with careful sampling of high-priority populations, will inform oncology leaders and clinicians on strategies to improve care for high-risk, high-cost populations.
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Neoplasias Hematológicas/terapia , Anciano , Anciano de 80 o más Años , Comorbilidad , Estudios Transversales , Femenino , Encuestas de Atención de la Salud , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/etnología , Humanos , Masculino , Medicare , Nativos de Hawái y Otras Islas del Pacífico , Evaluación del Resultado de la Atención al Paciente , Satisfacción del Paciente/estadística & datos numéricos , Calidad de la Atención de Salud/estadística & datos numéricos , Programa de VERF , Estados Unidos , Población BlancaRESUMEN
BACKGROUND: Spine conditions are costly and a major cause of disability. A growing body of evidence suggests that healthcare utilization and spending are driven by provider availability, which varies geographically and is a topic of healthcare policy debate. OBJECTIVE: To estimate the effect of provider availability on spine spending. DESIGN: Retrospective cohort study using relocation as a natural experiment. PARTICIPANTS: Fee-for-service Medicare beneficiaries over age 65 who relocated to a new hospital referral region between 2010 and 2014. MAIN MEASURES: We used generalized linear models to evaluate how changes in per-beneficiary availability of three types of healthcare providers (primary care physicians, spine surgeons, and chiropractors) affected annual per-beneficiary spine spending. We evaluated increases and decreases in provider availability separately. To account for the relative sizes of the provider workforces, we also calculated estimates of the effects of changes in national workforce size on changes in national spine spending. KEY RESULTS: The association between provider availability and spending was generally stronger among beneficiaries who experienced a decrease (versus an increase) in availability. Of the three provider groups, spine surgeon availability was most strongly associated with spending. Among beneficiaries who experienced a decrease in availability, a decrease in one spine surgeon per 10,000 beneficiaries was associated with a decrease of $36.97 (95% CI: $12.51, $61.42) in annual spending per beneficiary, versus a decrease of $1.41 (95% CI: $0.73, $2.09) for a decrease in primary care physician availability. However, changes in the national workforce size of primary care physicians were associated with the largest changes in national spine spending. CONCLUSIONS: Provider availability affects individual spine spending, with substantial changes observed at the national level. The effect depends on provider type and whether availability increases or decreases. Policymakers should consider how changes in the size of the physician workforce affect healthcare spending.
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Gastos en Salud , Medicare , Anciano , Planes de Aranceles por Servicios , Accesibilidad a los Servicios de Salud , Humanos , Estudios Retrospectivos , Estados UnidosRESUMEN
BACKGROUND: Gabapentinoid use for long-term cancer pain control may be problematic, given unclear mechanisms of action and increased concerns for physical dependence. The purpose of this report is to examine trends of gabapentinoid use among US adults with cancer from 2005 to 2015. METHODS: We conducted a serial, cross-sectional study using data from the Medical Expenditure Panel Survey (MEPS). We performed multiple logistic regression to examine the annual percentages of gabapentinoid users, which were adjusted for age, sex, and US region of residence. The amount of gabapentinoid prescriptions filled in 2015 was also estimated. RESULTS: The adjusted percentage of gabapentinoid users in 2015 was 5.60% (3.79%, 7.41%), 2.39 times greater than the percentage in 2005 (p < .001). By 2015, the number of gabapentinoid prescriptions had grown to approximately 3.52 million (2.40 million, 4.65 million). CONCLUSION: We observed greater than a twofold increase in the trend of gabapentinoid medication use among US adults with cancer. Investigations on the long-term efficacy of gabapentinoids for complex pain syndromes, and mitigation of risks, is essential to guide informed clinical management and keep patients safe.
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Analgésicos/uso terapéutico , Dolor en Cáncer/tratamiento farmacológico , Gabapentina/uso terapéutico , Neoplasias/tratamiento farmacológico , Manejo del Dolor/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Dolor en Cáncer/epidemiología , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/epidemiología , Estudios Transversales , Femenino , Gabapentina/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Cuidados Paliativos/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/etiología , Encuestas y Cuestionarios , Estados Unidos/epidemiología , Adulto JovenRESUMEN
OBJECTIVES: To examine national trends in the use of various pharmacological pain medication classes by race/ethnicity among the US pain population. METHODS: We used data from the Medical Expenditure Panel Survey to conduct a nationally representative, serial cross-sectional study of the noninstitutionalized US adult population from 2000 to 2015. We identified adults with moderate or severe self-reported pain and excluded individuals with cancer. We used complex survey design to provide national estimates of the percentage of adults with noncancer pain who received prescription pain medications among 4 groups: non-Hispanic White, non-Hispanic Black, Hispanic or Latino, and other. RESULTS: The age- and gender-adjusted percentage of prescription opioid use increased across all groups, with the greatest increase among non-Hispanic White individuals. By 2015, the percentage of non-Hispanic Black adults using opioids approximated that of non-Hispanic White adults-in 2015, approximately 23% of adults in these 2 groups used opioids. CONCLUSIONS: To our knowledge, this is the first evidence of a narrowing divide in opioid prescribing by race. However, in the context of the national epidemic of opioid-related addiction and mortality, opioid-related risks do not appear commensurate with the purported benefits.
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Negro o Afroamericano/estadística & datos numéricos , Prescripciones de Medicamentos/estadística & datos numéricos , Hispánicos o Latinos/estadística & datos numéricos , Dolor/tratamiento farmacológico , Población Blanca/estadística & datos numéricos , Estudios Transversales , Humanos , Trastornos Relacionados con Opioides/epidemiología , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: In the current payment paradigm, reimbursement is partially based on patient satisfaction scores. We sought to understand the relationship between prescription opioid use and satisfaction with care among adults who have musculoskeletal conditions. METHODS: We performed a cross-sectional study using nationally representative data from the 2008-2014 Medical Expenditure Panel Survey. We assessed whether prescription opioid use is associated with satisfaction with care among US adults who had musculoskeletal conditions. Specifically, using 5 key domains of satisfaction with care, we examined the association between opioid use (overall and according to the number of prescriptions received) and high satisfaction, defined as being in the top quartile of overall satisfaction ratings. RESULTS: Among 19,566 adults with musculoskeletal conditions, we identified 2,564 (13.1%) who were opioid users, defined as receiving 1 or more prescriptions in 2 six-month time periods. In analyses adjusted for sociodemographic characteristics and health status, compared with nonusers, opioid users were more likely to report high satisfaction with care (odds ratio = 1.32; 95% CI, 1.18-1.49). According to the level of use, a stronger association was noted with moderate opioid use (odds ratio = 1.55) and heavy opioid use (odds ratio = 1.43) (P <.001 for trend). CONCLUSIONS: Among patients with musculoskeletal conditions, those using prescription opioids are more likely to be highly satisfied with their care. Considering that emerging reimbursement models include patient satisfaction, future work is warranted to better understand this relationship.
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Analgésicos Opioides/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Enfermedades Musculoesqueléticas/tratamiento farmacológico , Satisfacción Personal , Estudios Transversales , Femenino , Estado de Salud , Humanos , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , New Hampshire , Manejo del Dolor/métodos , Puntaje de Propensión , AutoinformeRESUMEN
Hepatitis C virus (HCV) is an enveloped RNA virus responsible for 170 million cases of viral hepatitis worldwide. Over 50% of chronically infected HCV patients develop hepatic steatosis, and steatosis can be induced by expression of HCV core protein (core) alone. Additionally, core must associate with cytoplasmic lipid droplets (LDs) for steatosis development and viral particle assembly. Due to the importance of the LD as a key component of hepatic lipid storage and as a platform for HCV particle assembly, it seems this dynamic subcellular organelle is a gatekeeper in the pathogenesis of viral hepatitis. Here, we hypothesized that core requires the host LD scaffold protein, perilipin (PLIN)3, to induce hepatic steatosis. To test our hypothesis in vivo, we have studied core-induced hepatic steatosis in the absence or presence of antisense oligonucleotide-mediated knockdown of PLIN3. PLIN3 knockdown blunted HCV core-induced steatosis in transgenic mice fed either chow or a moderate fat diet. Collectively, our studies demonstrate that the LD scaffold protein, PLIN3, is essential for HCV core-induced hepatic steatosis and provide new insights into the pathogenesis of HCV.
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Hígado Graso/genética , Hepatitis C/metabolismo , Hígado/metabolismo , Perilipina-3/genética , Animales , Hígado Graso/metabolismo , Hígado Graso/patología , Técnicas de Silenciamiento del Gen , Genotipo , Hepacivirus , Hepatitis C/genética , Hepatitis C/patología , Hepatitis C/virología , Humanos , Gotas Lipídicas/metabolismo , Gotas Lipídicas/patología , Gotas Lipídicas/virología , Metabolismo de los Lípidos/genética , Hígado/patología , Hígado/virología , Ratones , Oligonucleótidos Antisentido/administración & dosificación , Oligonucleótidos Antisentido/genética , Perilipina-3/antagonistas & inhibidoresRESUMEN
PURPOSE: The purpose of this population-based study was to examine health-related quality of life (HRQOL) and functional status among breast cancer survivors with heart failure. METHODS: We examined Medicare Health Outcomes Survey data from women aged 65 and older diagnosed with breast cancer in the past 5 years. Surveys were linked to Surveillance, Epidemiology, and End Results cancer registries. Each woman identified with self-reported heart failure (n = 239) was matched to controls without heart failure (n = 685) using propensity scores. The Short Form-36/Veterans Rand-12 measured eight domains of HRQOL. Functional status impairment was measured by limitations in six activities of daily living (ADLs). Linear models estimated associations between heart failure status and HRQOL. Logistic regression models estimated odds ratios for associations between heart failure and ADL impairment. We examined associations for the total study population and subgroups stratified by cancer stage. RESULTS: Among all study participants, heart failure was associated with significant deficits in every HRQOL domain and impairment in all ADLs (p < 0.01, ORs ranged from 1.74 to 2.47). After stratification by cancer stage, heart failure was associated with physical HRQOL deficits across all cancer stages (physical function, vitality, general health) and mental HRQOL deficits only in women with stage I/II cancer (role-emotional, social function). Women with early stage cancer experienced the greatest HRQOL deficits associated with heart failure. CONCLUSIONS: Heart failure in breast cancer survivors is associated with substantial HRQOL deficits and functional status impairment, particularly in early stage cancer. Tailored interventions are needed to improve physical function and mental wellbeing in this high-risk population.
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Neoplasias de la Mama/psicología , Insuficiencia Cardíaca/psicología , Calidad de Vida/psicología , Sobrevivientes/psicología , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Insuficiencia Cardíaca/patología , Humanos , Medicare , Autoinforme , Encuestas y Cuestionarios , Estados UnidosRESUMEN
BACKGROUND: The Affordable Care Act (ACA), often called "Obamacare," is a controversial law that has been implemented gradually since its enactment in 2010. Polls have consistently shown that public opinion of the ACA is quite negative. OBJECTIVE: The aim of our study was to examine the extent to which Twitter data can be used to measure public opinion of the ACA over time. METHODS: We prospectively collected a 10% random sample of daily tweets (approximately 52 million since July 2011) using Twitter's streaming application programming interface (API) from July 10, 2011 to July 31, 2015. Using a list of key terms and ACA-specific hashtags, we identified tweets about the ACA and examined the overall volume of tweets about the ACA in relation to key ACA events. We applied standard text sentiment analysis to assign each ACA tweet a measure of positivity or negativity and compared overall sentiment from Twitter with results from the Kaiser Family Foundation health tracking poll. RESULTS: Public opinion on Twitter (measured via sentiment analysis) was slightly more favorable than public opinion measured by the Kaiser poll (approximately 50% vs 40%, respectively) but trends over time in both favorable and unfavorable views were similar in both sources. The Twitter-based measures of opinion as well as the Kaiser poll changed very little over time: correlation coefficients for favorable and unfavorable public opinion were .43 and .37, respectively. However, we found substantial spikes in the volume of ACA-related tweets in response to key events in the law's implementation, such as the first open enrollment period in October 2013 and the Supreme Court decision in June 2012. CONCLUSIONS: Twitter may be useful for tracking public opinion of health care reform as it appears to be comparable with conventional polling results. Moreover, in contrast with conventional polling, the overall amount of tweets also provides a potential indication of public interest of a particular issue at any point in time.
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Reforma de la Atención de Salud/métodos , Patient Protection and Affordable Care Act/estadística & datos numéricos , Opinión Pública , Medios de Comunicación Sociales/estadística & datos numéricos , HumanosRESUMEN
BACKGROUND: Advanced practice clinicians (APCs) including nurse practitioners and physician assistants are increasingly used to deliver care, yet little is known about these providers as a usual source of primary care. PURPOSE: This study examined the extent to which APCs serve as a usual source of care and the impact of such use on health care expenditures and quality. METHODS: We performed a cross-sectional study by identifying 90,279 adults from the 2002 to 2013 Medical Expenditure Panel Survey who self-reported their usual source of care as either an APC or a primary care physician (PCP). Using complex survey design methods to make national estimates, we compared annual health care expenditures and quality measures among adults whose usual source of care is an APC to that of adults whose usual source of care is a PCP. DISCUSSION: Nationally, 32 million adults visit an APC each year, yet only 1.4 million adults report their usual source of care to be an APC. In adjusted analyses, mean annual health care expenditures were $7,323 among APC patients vs. $7,959 among PCP patients, a difference of -$635 (95% confidence interval [-$1,408 to $138]). Across specific health services, APC patients trended toward having lower expenditures except for marginally higher expenditures on emergency room visits ($256 vs. $227 p < .001). APC patients were similar to that of PCP patients across health care quality measures. CONCLUSIONS: Few U.S. adults report their usual source of care to be an APC. Health care spending and quality measures are similar between APC patients and PCP patients. Expanding use of APCs as a usual source of care will likely not lead to increased health care spending.
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Enfermería de Práctica Avanzada/organización & administración , Atención a la Salud/organización & administración , Atención a la Salud/estadística & datos numéricos , Enfermeras Practicantes/organización & administración , Asistentes Médicos/organización & administración , Atención Primaria de Salud/organización & administración , Atención Primaria de Salud/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Encuestas de Atención de la Salud , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos , Adulto JovenRESUMEN
RATIONALE: Cholesterol esters (CE), especially cholesterol oleate, generated by hepatic and intestinal sterol O-acyltransferase 2 (SOAT2) play a critical role in cholesterol homeostasis. However, it is unknown whether the contribution of intestine-derived CE from SOAT2 would have similar effects in promoting atherosclerosis progression as for liver-derived CE. OBJECTIVE: To test whether, in low-density lipoprotein receptor null (LDLr(-/-)) mice, the conditional knockout of intestinal SOAT2 (SOAT2(SI-/SI-)) or hepatic SOAT2 (SOAT2(L-/L-)) would equally limit atherosclerosis development compared with the global deletion of SOAT2 (SOAT2(-/-)). METHODS AND RESULTS: SOAT2 conditional knockout mice were bred with LDLr(-/-) mice creating LDLr(-/-) mice with each of the specific SOAT2 gene deletions. All mice then were fed an atherogenic diet for 16 weeks. SOAT2(SI-/SI-)LDLr(-/-) and SOAT2(-/-)LDLr(-/-) mice had significantly lower levels of intestinal cholesterol absorption, more fecal sterol excretion, and lower biliary cholesterol levels. Analysis of plasma LDL showed that all mice with SOAT2 gene deletions had LDL CE with reduced percentages of cholesterol palmitate and cholesterol oleate. Each of the LDLr(-/-) mice with SOAT2 gene deletions had lower accumulations of total cholesterol and CE in the liver compared with control mice. Finally, aortic atherosclerosis development was significantly lower in all mice with global or tissue-restricted SOAT2 gene deletions. Nevertheless, SOAT2(-/-)LDLr(-/-) and SOAT2(L-/L-)LDLr(-/-) mice had less aortic CE accumulation and smaller aortic lesions than SOAT2(SI-/SI-)LDLr(-/-) mice. CONCLUSIONS: SOAT2-derived CE from both the intestine and liver significantly contribute to the development of atherosclerosis, although the CE from the hepatic enzyme appeared to promote more atherosclerosis development.
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Aorta/metabolismo , Aterosclerosis/metabolismo , Ésteres del Colesterol/metabolismo , Absorción Intestinal/fisiología , Hígado/metabolismo , Esterol O-Aciltransferasa/deficiencia , Animales , Aorta/patología , Aterosclerosis/sangre , Aterosclerosis/patología , Ésteres del Colesterol/sangre , Femenino , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Esterol O-Aciltransferasa 2RESUMEN
Sterol O-acyltransferase 2 (SOAT2; also known as ACAT2) is considered as a new therapeutic target for the treatment or prevention of hypercholesterolemia and atherosclerosis. Fungal pyripyropene A (PPPA: 1,7,11-triacyl type), the first SOAT2-selective inhibitor, proved orally active in vivo using atherogenic mouse models. The purpose of the present study was to demonstrate that the PPPA derivatives (PRDs) prove more effective in the mouse models than PPPA. Among 196 semisynthetic PPPA derivatives, potent, SOAT2-selective, and stable PRDs were selected. In vivo antiatherosclerotic activity of selected PRDs was tested in apolipoprotein E knockout (Apoe(-/-)) mice or low-density lipoprotein receptor knockout (Ldlr(-/-)) mice fed a cholesterol-enriched diet (0.2% cholesterol and 21% fat) for 12 weeks. During the PRD treatments, no detrimental side effects were observed. Among three PRDs, Apoe(-/-) mice treated with PRD125 (1-,11-O-benzylidene type) at 1 mg/kg/day had significantly lower total plasma cholesterol concentration by 57.9 ± 9.3%; further, the ratio of cholesteryl oleate to cholesteryl linoleate in low-density lipoprotein was lower by 55.6 ± 7.5%, respectively. The hepatic cholesteryl ester levels and SOAT2 activity in the small intestines and livers of the PRD-treated mice were selectively lowered. The atherosclerotic lesion areas in the aortae of PRD125-treated mice were significantly lower at 62.2 ± 13.1%, respectively. Furthermore, both PRDs were also orally active in atherogenic Ldlr(-/-) mice. Among the PRDs tested, PRD125 was the most potent in both mouse models. These results suggest that SOAT2-selective inhibitors such as PRD125 have a high potential as poststatin agents for treatment and/or prevention in patients with atherosclerosis and hypercholesterolemia.
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Anticolesterolemiantes/química , Aterosclerosis/tratamiento farmacológico , Hipercolesterolemia/tratamiento farmacológico , Piridinas/química , Sesquiterpenos/química , Esterol O-Aciltransferasa/antagonistas & inhibidores , Animales , Anticolesterolemiantes/síntesis química , Anticolesterolemiantes/farmacología , Aorta/patología , Apolipoproteínas E/genética , Aterosclerosis/metabolismo , Aterosclerosis/patología , Células CHO , Colesterol/sangre , Ésteres del Colesterol/sangre , Cricetulus , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patología , Gotas Lipídicas/metabolismo , Lipoproteínas/sangre , Hígado/metabolismo , Masculino , Ratones Noqueados , Piridinas/síntesis química , Piridinas/farmacología , Receptores de LDL/genética , Sesquiterpenos/síntesis química , Sesquiterpenos/farmacología , Esterol O-Aciltransferasa/metabolismo , Relación Estructura-Actividad , Esterol O-Aciltransferasa 2Asunto(s)
Desastres , Neoplasias , Trastornos por Estrés Postraumático , Humanos , Neoplasias/epidemiologíaRESUMEN
BACKGROUND: Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. METHODS: Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. RESULTS: In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value < 0.05). Although, associations were attenuated in adjusted analyses - among female fetuses a 1 µg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: -0.151, 0.007) decrease in biparietal head diameter Z-score. CONCLUSIONS: Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation.
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Arsénico/toxicidad , Peso al Nacer/efectos de los fármacos , Exposición a Riesgos Ambientales , Desarrollo Fetal/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/epidemiología , Adolescente , Adulto , Cefalometría , Estudios de Cohortes , Estudios Transversales , Registros Electrónicos de Salud , Femenino , Humanos , Persona de Mediana Edad , New Hampshire/epidemiología , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ultrasonografía Prenatal , Adulto JovenRESUMEN
OBJECTIVE: We used a randomized controlled design to investigate whether using stability balls during the school day was associated with higher levels of on-task behavior and academic achievement and fewer discipline referrals. METHOD: Over 9 mo, students in 2 second-grade classrooms in a southeastern rural elementary school used stability balls as chairs while students in 2 control classrooms used chairs as usual. We collected measures of on-task behavior, standardized measures of literacy and mathematics achievement, and discipline referrals. RESULTS: We found similar levels of on-task behavior and achievement in treatment and control classrooms and a downward trend in disruptive behaviors in treatment classrooms. CONCLUSION: This study did not find use of stability balls for entire general education classrooms to be a practical use of resources for schools. More research with rigorous controlled designs is needed to support the use of stability balls for the general education population.
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Logro , Conducta Infantil , Postura , Equipo Deportivo , Estudiantes , Análisis y Desempeño de Tareas , Niño , Femenino , Humanos , Masculino , Derivación y Consulta , Población Rural , Instituciones AcadémicasRESUMEN
BACKGROUND: Social networking sites such as Facebook have become immensely popular in recent years and present a unique opportunity for researchers to eavesdrop on the collective conversation of current societal issues. OBJECTIVE: We sought to explore doctor-related humor by examining doctor jokes posted on Facebook. METHODS: We performed a cross-sectional study of 33,326 monitored Facebook users, 263 (0.79%) of whom posted a joke that referenced doctors on their Facebook wall during a 6-month observation period (December 15, 2010 to June 16, 2011). We compared characteristics of so-called jokers to nonjokers and identified the characteristics of jokes that predicted joke success measured by having elicited at least one electronic laugh (eg, an LOL or "laughing out loud") as well as the total number of Facebook "likes" the joke received. RESULTS: Jokers told 156 unique doctor jokes and were the same age as nonjokers but had larger social networks (median Facebook friends 227 vs 132, P<.001) and were more likely to be divorced, separated, or widowed (P<.01). In 39.7% (62/156) of unique jokes, the joke was at the expense of doctors. Jokes at the expense of doctors compared to jokes not at the expense of doctors tended to be more successful in eliciting an electronic laugh (46.5% vs 37.3%), although the association was statistically insignificant. In our adjusted models, jokes that were based on current events received considerably more Facebook likes (rate ratio [RR] 2.36, 95% CI 0.97-5.74). CONCLUSIONS: This study provides insight into the use of social networking sites for research pertaining to health and medicine, including the world of doctor-related humor.
Asunto(s)
Médicos , Medios de Comunicación Sociales , Ingenio y Humor como Asunto , Adulto , Comunicación , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The development of disability related to activities of daily living (ADL) is of great concern in the aging population, particularly for Hispanic and Non-Hispanic (NH) Black older adults, where disability prevalence is greater compared to NH Whites. ADL-disability is typically measured across many functional tasks without differentiating upper- versus lower-limb limitations, hindering our understanding of disability burden. Despite the importance of the upper limbs for completing ADL and known age-related declines in function, racial/ethnic differences in upper limb function remain largely unknown. METHODS: We identified 4 292 NH White, NH Black, and Mexican American older adults (≥65) from the 2011-2018 waves of the National Health and Nutrition Examination Survey (NHANES). We classified participants as having a limitation based on their ability to complete 5 upper-limb tasks (preparing meals, eating, dressing, reaching overhead, and grasping small objects) and compared limitation rates across racial/ethnic groups. RESULTS: Compared to NH Whites, NH Black older adults had significantly greater odds of reporting difficulties preparing meals (odds ratio [OR]: 1.36, 95% confidence interval [95% CI]: 1.01, 1.86) and dressing (OR: 1.55, 95% CI: 1.19, 2.02), while Mexican Americans had greater difficulty preparing meals (OR: 1.70, 95% CI: 1.12, 2.58), dressing (OR: 1.63, 95% CI: 1.12, 2.36), and grasping small objects (OR: 1.48, 95% CI: 1.06, 2.07). CONCLUSIONS: Our results demonstrate differences in self-reported upper limb ADL-disability across racial/ethnic groups, particularly for Mexican American older adults. Such findings underscore the need for routine monitoring of upper limb function throughout adulthood to identify limitations and target therapeutic interventions before independence is compromised.