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BACKGROUND: This study aimed to determine the recurrence rate in infantile Blount disease (IBD) in a cohort of patients treated with a tibial osteotomy; and also to identify which factors were associated with recurrence. METHODS: We reviewed the records of 20 patients, under the age of 7 years, with IBD (35 involved extremities) treated by proximal tibial realignment osteotomy to physiological valgus at a single institution over 4 years. We then analyzed the data to determine the rate of recurrence and identify the risk factors for recurrence. RESULTS: The mean age of the included patients was 4.2 years (range, 2 to 6 y). We observed a recurrence rate of 40% (n=14) at a mean follow-up of 42 months (range, 21 to 72 mo). Knee instability [odds ratios OR, 6.6; 95% confidence interval (CI), 2.0-22.2], Langenskiöld stage (OR, 6.3; 95% CI, 2.0-19.4), and severity of the deformity, as measured by medial physeal slope (MPS) (OR, 1.2; 95% CI, 1.1-1.4), were associated with recurrence. On multiple logistic regression analysis, MPS remained the most relevant predictor of recurrence. Receiver operating curve analysis showed that an MPS ≥60 degrees predicted recurrence with a sensitivity of 79% and specificity of 95% (area under the curve=0.925). Postoperatively, increased varus alignment on weight-bearing as measured by the tibio-femoral angle was indicative of knee instability and associated with increased odds of recurrence (OR, 1.5; 95% CI, 1.1-1.9; P=0.004). CONCLUSIONS: We observed a recurrence rate of 40% in children with IBD under 7 years treated with acute correction to a tibio-femoral angle of 5 to 10 degrees valgus through a dome proximal tibial osteotomy. Knee instability, Langenskiöld stage, and MPS were associated with recurrence. Cases with an MPS ≥60 degrees seem to be particularly at risk for recurrence. Further research is needed to validate these findings. LEVEL OF EVIDENCE: Level IV.
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Enfermedades del Desarrollo Óseo/cirugía , Articulación de la Rodilla/cirugía , Osteocondrosis/congénito , Osteotomía/estadística & datos numéricos , Tibia/cirugía , Enfermedades del Desarrollo Óseo/diagnóstico por imagen , Niño , Preescolar , Femenino , Placa de Crecimiento , Humanos , Inestabilidad de la Articulación , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Osteocondrosis/diagnóstico por imagen , Osteocondrosis/cirugía , Periodo Posoperatorio , Radiografía , Recurrencia , Factores de Riesgo , Tibia/diagnóstico por imagen , Soporte de PesoRESUMEN
OBJECTIVE: To determine whether circulating levels of two matrix metalloproteinases, MMP-2 and MMP-9, are associated with loss of alveolar bone density (ABD) or height (ABH), or with progression of periodontitis (relative clinical attachment level [RCAL]), among postmenopausal women with local and systemic bone loss. BACKGROUND: This study was planned as part of a 2-year randomized, double-blind, placebo-controlled, clinical trial examining efficacy/safety of subantimicrobial dose doxycycline (20 mg bid) in postmenopausal osteopenic women. This study examines whether serum levels of gelatinases are associated with local changes in the periodontium. METHODS: A sample of 113 women received periodontal maintenance for moderate to advanced chronic periodontitis and consented to analysis of stored serum biomarkers. Posterior vertical bitewings were taken, and serum collected, at baseline, one, and 2 years. ABD was determined by computer-assisted densitometric image analysis (CADIA), ABH by the Hausmann et al (1992, J Periodontol 63, 657) method, and RCAL by Florida Probe (every 6 months). MMPs were measured densitometrically on gelatin zymograms using denatured type I collagen as substrate and purified MMP-2 (72 kDa) and MMP-9 (92 kDa) as standards. Evidence of worsening in the periodontium at a tooth site was defined as a change from baseline of, for ABD, at least 14 densitometric units (for subcrestal locations) or 17 units (for crestal locations); of at least 0.4 mm for ABH; and of at least 1.5 mm for RCAL. Logistic regression models, while accounting for clustering, compared the odds of worsening in ABD, ABH, or RCAL, after 2 years of observation, between groups defined by baseline and concurrent levels of serum gelatinases. RESULTS: Changes in ABH and RCAL were not associated with circulating levels of MMP-2 or MMP-9. However, elevated odds of ABD loss over 24 months were associated, among smokers, with both baseline and concurrent levels of MMP-9 in the middle and highest tertile, and with concurrent levels of MMP-2 in the middle (but not the highest) tertile. Elevated odds of ABD loss were also associated, among women within 5 years of menopause, with baseline levels of MMP-2 in the highest tertile. CONCLUSION: Among postmenopausal osteopenic women, loss of ABD was associated, in smokers, with elevated circulating levels of MMP-9 and MMP-2. In those within 5 years of menopause, ABD loss was associated with elevated circulating levels of MMP-2.
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Pérdida de Hueso Alveolar , Densidad Ósea , Enfermedades Óseas Metabólicas , Gelatinasas , Posmenopausia , Método Doble Ciego , Femenino , Gelatinasas/sangre , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To assess relationships between mothers' feeding practices (food as a reward, food for emotion regulation, modelling of healthy eating) and mothers' willingness to purchase child-marketed foods and fruits/vegetables (F&V) requested by their children during grocery co-shopping. DESIGN: Cross-sectional. Mothers completed an online survey that included questions about feeding practices and willingness (i.e. intentions) to purchase child-requested foods during grocery co-shopping. Feeding practices scores were dichotomized at the median. Foods were grouped as nutrient-poor or nutrient-dense (F&V) based on national nutrition guidelines. Regression models compared mothers with above-the-median v. at-or-below-the-median feeding practices scores on their willingness to purchase child-requested food groupings, adjusting for demographic covariates. SETTING: Participants completed an online survey generated at a public university in the USA. SUBJECTS: Mothers (n 318) of 2- to 7-year-old children. RESULTS: Mothers who scored above-the-median on using food as a reward were more willing to purchase nutrient-poor foods (ß=0·60, P<0·0001), mothers who scored above-the-median on use of food for emotion regulation were more willing to purchase nutrient-poor foods (ß=0·29, P<0·0031) and mothers who scored above-the-median on modelling of healthy eating were more willing to purchase nutrient-dense foods (ß=0·22, P<0·001) than were mothers with at-or-below-the-median scores, adjusting for demographic covariates. CONCLUSIONS: Mothers who reported using food to control children's behaviour were more willing to purchase child-requested, nutrient-poor foods. Parental feeding practices may facilitate or limit children's foods requested in grocery stores. Parent-child food consumer behaviours should be investigated as a route that may contribute to children's eating patterns.
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Dieta/psicología , Frutas , Relaciones Madre-Hijo/psicología , Madres/psicología , Verduras , Niño , Conducta Infantil , Preescolar , Comportamiento del Consumidor , Estudios Transversales , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Política Nutricional , Responsabilidad Parental/psicología , Autoinforme , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
We aimed to identify miRNAs whose expression levels in fetal tissues are altered by exposure to a diabetic milieu and elucidate the impact on target protein expression. Gestational diabetes mellitus (GDM) affects both immediate and future disease risk in the offspring. We hypothesized that GDM alters miRNA expression in human umbilical vein endothelial cells (HUVECs) that may influence metabolic processes. A cross-sectional design compared differences in miRNA expression in HUVECs and target protein abundance in placentae between infants of women with GDM (IGDM) and infants born to normoglycaemic controls. miRNAs were identified using microarray profiling and literature review and validated by quantitative PCR (qPCR). In vitro transfection studies explored the impact of the miRNA on target protein expression. Expression of seven miRNA species, miR-30c-5p, miR-452-5p, miR-126-3p, miR-130b-3p, miR-148a-3p, miR-let-7a-5p and miR-let-7g-5p, was higher in the HUVECs of IGDM. Abundance of the catalytic subunit of AMP-activated protein kinase α1 (AMPKα1) was decreased in the HUVECs and BeWo cells (transformed trophoblast cell line) transfected with miR-130b and miR-148a mimics. AMPKα1 expression was also decreased in placental tissues of IGDM. The expression of several miRNAs were altered by in utero exposure to DM in infants of women whose dysglycaemia was very well controlled by current standards. Decreased expression of AMPKα1 as a result of increased levels of miR-130b and miR-148a may potentially explain the decrease in fat oxidation we reported in infants at 1 month of age and, if persistent, may predispose offspring to future metabolic disease.
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Diabetes Gestacional/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , MicroARNs/metabolismo , Adulto , Estudios Transversales , Diabetes Gestacional/genética , Femenino , Perfilación de la Expresión Génica , Humanos , MicroARNs/genética , Placenta/metabolismo , Embarazo , Trofoblastos/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: The primary objective of this study was to investigate whether growth impairment in children with cleft lip is caused by reconstructing the nostril floor using lateral nasal and premaxillary mucoperiosteal flaps. The effects on growth and symmetry of tip rhinoplasty at the time of initial repair, as well as cleft sidedness are similarly investigated. METHODS: An Institutional Review Board approved, retrospective, single-center study at an academic children's hospital from July 2005 to 2010 was designed. Seventy-four patients with unilateral cleft lip ± palate were followed postsurgical repair of the cleft lip deformity. Serial digital photographs from clinical encounters were analyzed. Anthropometric measurements of 10 soft tissue landmarks were extracted from anteroposterior and submental vertex views at serial visits; growth velocities, defined as c = Δd/Δt, were generated using linear mixed models on selected measurements to study time-related changes on growth. The effects on growth and symmetry of primary tip rhinoplasty on perinasal landmarks and nostril floor reconstruction with medial and lateral nasal mucoperiosteal flaps on perioral and perinasal landmarks were analyzed. Proxies for midfacial height (en-al) and maxillary height (al-ch) were used to evaluate the effect of mucoperiosteal dissection, whereas nostril width, height, and angle were used as proxies to evaluate the effects of tip rhinoplasty. RESULTS: Seventy-four patients met the inclusion criteria. Midface height (En-Al) growth velocity was 0.014 mm/month and maxillary height (Al-Ch) was relatively stable at -0.0059 mm/month with no difference between the subgroups. Nostril height growth was -0.0046 mm/month, nostril width was 0.03 mm/mo, and nostril angle -0.09â°/mo showed no difference between patient with or without primary tip rhinoplasty. Patients with complete cleft showed more asymmetry than those with incomplete clefts in lip and maxillary landmarks at T0 (P < 0.001). CONCLUSIONS: Mucoperiosteal reconstruction of the nostril floor at the time of lip repair does not affect anthropometric growth velocities over a 5-year follow-up. Within the limitations of the selected landmarks, primary tip rhinoplasty did not significantly improve symmetry at 5 years, but also did not affect the growth of the nose. Patients with complete clefts display more postoperative asymmetry than those with incomplete clefts.
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Cefalometría/métodos , Labio Leporino/cirugía , Mucosa Nasal/trasplante , Nariz/anatomía & histología , Periostio/trasplante , Rinoplastia/métodos , Colgajos Quirúrgicos/trasplante , Puntos Anatómicos de Referencia/anatomía & histología , Preescolar , Fisura del Paladar/cirugía , Estudios de Cohortes , Asimetría Facial/patología , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Lactante , Labio/anatomía & histología , Masculino , Maxilar/anatomía & histología , Cartílagos Nasales/anatomía & histología , Cartílagos Nasales/cirugía , Nariz/crecimiento & desarrollo , Fotogrametría/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Dimensión VerticalRESUMEN
BACKGROUND: Pigment epithelium-derived factor (PEDF) is a member of the serpin family secreted by adipocytes. Plasma PEDF is increased in obese children and adults. Adults with type 2 diabetes mellitus (T2DM) have higher circulating PEDF but there are no reports in children with T2DM. OBJECTIVE: To compare PEDF concentration in children with T2DM to normal weight and obese children without T2DM and determine associations with anthropometric or serum factors. METHODS: Participants were 34 obese children with T2DM diagnosed by American Diabetes Association (ADA) criteria, 61 normal weight [body mass index (BMI) 25-75 percentile] and 63 obese (BMI ≥ 95 percentile) children of age 8-18 yr. Plasma PEDF was measured in fasting plasma samples. Anthropometric, serum, and body composition (dual-energy x-ray absorptiometry, DXA) data were obtained for each subject to identify potential predictor variables. RESULTS: PEDF was 55% higher (p = 0.001) in the T2DM group compared with normal weight children, but did not differ from obese children. In the T2DM group, fat mass and lean mass both individually predicted PEDF (r² = 0.22 and 0.17, p = 0.02 and p < 0.01, respectively). PEDF was positively correlated with homeostatic model assessment - insulin resistance (HOMA-IR) when all groups were combined (r² = 0.15, p<0.001). CONCLUSIONS: Plasma PEDF was similar in the T2DM and obese groups, therefore, obesity, rather than diabetes, may account for the higher PEDF in children with T2DM compared with normal weight children. PEDF was positively associated with both lean mass and fat mass both of which may contribute to the circulating level of the protein, and potentially to PEDF's association with insulin resistance in obese children with and without diabetes.
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Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Proteínas del Ojo/sangre , Factores de Crecimiento Nervioso/sangre , Obesidad/sangre , Obesidad/complicaciones , Serpinas/sangre , Adolescente , Composición Corporal , Proteína C-Reactiva/metabolismo , Niño , Estudios de Cohortes , Femenino , Humanos , Resistencia a la Insulina , Lípidos/sangre , MasculinoRESUMEN
Diabetes among American Indian (AI) people is a health disparities condition that creates excessive morbidity and mortality. This research delineated culturally constructed models of type 2 diabetes among 97 pregnant women in two large AI nations in Oklahoma. The data analysis of explanatory models of type 2 diabetes revealed the participants' intense anxiety, fear, and dread related to the condition. The sample was further stratified by combinations of diabetes status: 1) absence of type 2 diabetes (n = 66), 2) type 2 diabetes prior to pregnancy (n = 4), and 3) gestational diabetes (n = 27). Patients were interviewed regarding perceptions of the etiology, course, and treatment of diabetes. The research incorporated an integrated phenomenologic and ethnographic approach using structured and semi-structured interviews to yield both quantitative and qualitative data. General findings comprised three main categories of patients' concerns regarding type 2 diabetes as an illness: 1) mechanical acts (i.e., injections), 2) medical complications, and 3) the conceptual sense of diabetes as a "severe" condition. Specific findings included significant fear and anxiety surrounding 1) the health and well-being of the unborn child, 2) the use of insulin injections, 3) blindness, 4) amputation, and 5) death. Paradoxically, although there was only a slight sense of disease severity overall, responses were punctuated with dread of specific outcomes. The latter finding is considered consistent with the presence of chronic diseases that can usually be managed but present risk of severe complications if not well controlled.
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Because adolescents make relatively few visits to clinics for preventive care, their vaccination rates suffer. We examined rates among Minnesota youths to see how they compared with those among teens throughout the United States. We used National Immunization Survey-Teen (NIS-Teen) data to estimate vaccination rates for 13- to 17-year-olds in Minnesota from 2008 through 2013 and compared them to national rates for MCV4, Tdap and HPV vaccines. We also examined rates of provider recommendation for each of the three vaccines and rates of parental intention to vaccinate against HPV. We found rates for all three vaccinations increased between 2008 and 2013, but they continue to be low for both MCV4 (69%) and HPV (38% of females and 9% of males completed the three-dose series in 2013). Fortunately, the percentage of Minnesota clinicians recommending those vaccines is increasing (the percentage recommending HPV vaccination for females increased from 55% in 2008 to 74% in 2013; however, only 44% recommended it for males in 2013). The percentage of parents in Minnesota reporting intent to vaccinate their female children against HPV rose from 52% in 2008 to 58% in 2013; the percentage intending to vaccinate their male children rose from 16% in 2010 to 47% in 2013. Clinicians and public health officials must address how we can improve HPV vaccination rates among adolescents.
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Vacunación/estadística & datos numéricos , Adolescente , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Femenino , Encuestas Epidemiológicas , Humanos , Esquemas de Inmunización , Masculino , Vacunas Meningococicas/administración & dosificación , Minnesota , Vacunas contra Papillomavirus/administración & dosificación , Estados Unidos , Revisión de Utilización de Recursos/estadística & datos numéricosRESUMEN
OBJECTIVE: In January 2008, the Food and Drug Administration (FDA) communicated concerns and, in May 2009, issued a warning about an increased risk of suicidality for all antiepileptic drugs (AEDs). This research evaluated the association between the FDA suicidality communications and the AED prescription claims among members with epilepsy and/or psychiatric disorder. METHODS: A longitudinal interrupted time-series design was utilized to evaluate Oklahoma Medicaid claims data from January 2006 through December 2009. The study included 9289 continuously eligible members with prevalent diagnoses of epilepsy and/or psychiatric disorder and at least one AED prescription claim. Trends, expressed as monthly changes in the log odds of AED prescription claims, were compared across three time periods: before (January 2006 to January 2008), during (February 2008 to May 2009), and after (June 2009 to December 2009) the FDA warning. RESULTS: Before the FDA warning period, a significant upward trend of AED prescription claims of 0.01% per month (99% CI: 0.008% to 0.013%, p<0.0001) was estimated. In comparison to the prewarning period, no significant change in trend was detected during (-20.0%, 99% CI: -70.0% to 30.0%, p=0.34) or after (80.0%, 99% CI: -20.0% to 200.0%, p=0.03) the FDA warning period. After stratification, no diagnostic group (i.e., epilepsy alone, epilepsy and comorbid psychiatric disorder, and psychiatric disorder alone) experienced a significant change in trend during the entire study period (p>0.01). CONCLUSIONS: During the time period considered, the FDA AED-related suicidality warning does not appear to have significantly affected prescription claims of AED medications for the study population.
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Anticonvulsivantes/efectos adversos , Prescripciones de Medicamentos , Epilepsia/tratamiento farmacológico , Suicidio/psicología , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Niño , Preescolar , Epilepsia/psicología , Humanos , Lactante , Análisis de Series de Tiempo Interrumpido , Medicaid , Persona de Mediana Edad , Estados Unidos , United States Food and Drug Administration , Adulto JovenRESUMEN
The purpose of this study was to explore the impact of Medicaid on changes in coverage among women with newly diagnosed breast cancers, in the first years of program implementation. Women and their providers used the program, with nearly double the number of women covered by Medicaid in the three years after implementation. The treatment program, as implemented in Oklahoma, reached the target population and provided coverage to women who previously had none. The study found a promising, though nonsignificant, reduction in the time between diagnosis and treatment among women diagnosed with breast cancer when Medicaid was their primary payer.
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Neoplasias de la Mama/diagnóstico , Detección Precoz del Cáncer , Accesibilidad a los Servicios de Salud/legislación & jurisprudencia , Medicaid/legislación & jurisprudencia , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Factores de Edad , Neoplasias de la Mama/etnología , Femenino , Política de Salud , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Oklahoma , Sistema de Registros , Características de la Residencia , Factores Socioeconómicos , Estados Unidos/epidemiología , Neoplasias del Cuello Uterino/etnologíaRESUMEN
BACKGROUND: Nationally, uptake of adolescent vaccines is variable. OBJECTIVE: To compare adolescent immunization rates and clinician recommendation for adolescent vaccines over time in Oklahoma with the U.S. METHODS: We analyzed the 2010-2012 National Immunization Survey of Teens (NIS-Teen). RESULTS: MCV4 and Tdap are consistently lower in Oklahoma compared to the U.S. HPV rates have been comparable. Parents report that health care providers in Oklahoma are less likely to recommend adolescent vaccines compared to the national average. Intention to not receive HPV in the next 12 months is distressingly high both in Oklahoma and across the nation with both improving. CONCLUSION: Over the three years, Oklahoma's immunization rates consistently underperform national estimates for MCV4 and Tdap but not for HPV. We recommend Oklahoma health care providers improve their vaccination rates through making clear their vaccine recommendations to the parent and patient in the clinical encounter.
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Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra la Influenza/administración & dosificación , Vacunas Meningococicas/administración & dosificación , Vacunas contra Papillomavirus/administración & dosificación , Vacunación/estadística & datos numéricos , Adolescente , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Oklahoma , Guías de Práctica Clínica como Asunto , Estados Unidos , Vacunación/métodos , Vacunación/tendenciasRESUMEN
Diabetes among American Indian (AI) people is a. condition that creates excessive morbidity and mortality and is a significant health disparity. This research delineated culturally constructed models of diabetes mellitus (DM) among 97 pregnant women in 2 large AI Nations to Oklahoma. Analysis of data revealed intense anxiety, fear, and dread related to DM during pregnancy. The sample was stratified by DM status: (a) absence of DM (n = 66), (b) DM prior to pregnancy (n = 4), and (c) gestational (n = 27). Structured and semistructured interviews elicited patient culturally based explanatory models (EMs) of etiology, course, and treatment. The research incorporated an integrated phenomenologic and ethnographic approach and yielded both quantitative and qualitative data. General findings comprised the following main categories of patients' concerns regarding DM as an illness: (a) care-seeking behaviors, (b) medical management, (c) adherence and self-management, (d) complications, and (e) the conceptual sense of DM as a "severe" and feared condition. Many findings varied according to acculturation status, but all included significant fear and anxiety surrounding (a) the health and well-being of the unborn child, (b) the use of insulin injections, (c) blindness, (d) amputation, and (e) death, but with (f) a paradoxically lowered anxiety level about diabetes severity overall, while at the same time expressing extreme dread of specific outcomes. The latter finding is considered consistent with the presence of chronic conditions that can usually be managed, yet still having risk if severe.
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Diabetes Mellitus/etnología , Diabetes Mellitus/psicología , Indígenas Norteamericanos , Mujeres Embarazadas/psicología , Aculturación , Adulto , Ansiedad , Complicaciones de la Diabetes , Diabetes Mellitus/prevención & control , Miedo , Femenino , Humanos , Entrevistas como Asunto , Oklahoma , Aceptación de la Atención de Salud , Cooperación del Paciente , Embarazo , AutocuidadoRESUMEN
Diabetes mellitus (DM) has emerged as an important focus of national public health efforts because of the rapid increase in the burden of this disease. In particular, DM disproportionately affects Native Americans. Adequate management of DM requires that patients participate as active partners in their own care and much of patient activation and empowerment can be attributed to their experience with DM and self-care. That is, the degree to which the patient feels the disease intrudes on his or her daily life would impact the motivation for self-care. We conducted a study in collaboration with 2 tribal nations in Oklahoma, collecting data on survey questions regarding intrusiveness of illness and self-management behaviors from a sample of 159 members of the Chickasaw and Choctaw Nations. Previously validated variables measuring intrusiveness of illness and self-care were included in the survey. Descriptive statistics and bivariate analyses illustrated the distribution of these variables and identified possible tribal and gender differences. Our findings showed that our sample adjusted well to DM and in general exhibited high compliance to self-care. However, our findings also revealed striking gender differences where female respondents were better adjusted to their disease, whereas male respondents reported higher adherence to self-management. Findings from our study, particularly those that describe tribal differences and gender disparities, can inform strategies for case management and patient interactions with providers and the health care system.
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Diabetes Mellitus/etnología , Diabetes Mellitus/prevención & control , Indígenas Norteamericanos , Autocuidado , Manejo de la Enfermedad , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Motivación , Oklahoma , Encuestas y CuestionariosRESUMEN
BACKGROUND: Macroencapsulated pancreatic endoderm cells (PECs) can reverse diabetes in rodents and preclinical studies revealed that thyroid hormones in vitro and in vivo bias PECs to differentiate into insulin-producing cells. In an ongoing clinical trial, PECs implanted in macroencapsulation devices into patients with type 1 diabetes were safe but yielded heterogeneous outcomes. Though most patients developed meal responsive C-peptide, levels were heterogeneous and explanted grafts had variable numbers of surviving cells with variable distribution of endocrine cells. METHODS: We measured circulating triiodothyronine and thyroxine levels in all patients treated at 1 of the 7 sites of the ongoing clinical trial and determined if thyroid hormone levels were associated with the C-peptide or glucagon levels and cell fate of implanted PECs. RESULTS: Both triiodothyronine and thyroxine levels were significantly associated with the proportion of cells that adopted an insulin-producing fate with a mature phenotype. Thyroid hormone levels were inversely correlated to circulating glucagon levels after implantation, suggesting that thyroid hormones lead PECs to favor an insulin-producing fate over a glucagon-producing fate. In mice, hyperthyroidism led to more rapid maturation of PECs into insulin-producing cells similar in phenotype to PECs in euthyroid mice. CONCLUSION: These data highlight the relevance of thyroid hormones in the context of PEC therapy in patients with type 1 diabetes and suggest that a thyroid hormone adjuvant therapy may optimize cell outcomes in some PEC recipients.
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Diabetes Mellitus Tipo 1 , Humanos , Ratones , Animales , Diabetes Mellitus Tipo 1/metabolismo , Péptido C/metabolismo , Tiroxina/metabolismo , Triyodotironina/metabolismo , Endodermo/metabolismo , Endodermo/trasplante , Glucagón/metabolismoRESUMEN
OBJECTIVE: Subantimicrobial-dose doxycycline (SDD) treatment has been reported to reduce the severity of chronic inflammation and to increase serum high-density lipoprotein cholesterol. In a double-blind, placebo-controlled clinical trial, we determined whether SDD affects the ability of serum to facilitate cholesterol removal from macrophages. METHODS: Forty-five postmenopausal osteopenic women with periodontitis were randomly assigned to take placebo (n = 26) or doxycycline hyclate (20 mg, n = 19) tablets twice daily for 2 years. Serum samples were collected at baseline, 1-, and 2-year appointments. The cholesterol efflux capacity of serum from cultured human macrophages (THP-1) was measured. RESULTS: SDD subjects demonstrated a significant increase in serum-mediated cholesterol efflux from macrophages at both time points compared to baseline (p < 0.04 for each). Mean cholesterol efflux levels over the first year of follow-up were 3.0 percentage points (unit change) higher among SDD subjects compared to placebo subjects (p = 0.010), while there was no significant difference in 2-year changes. There were no significant differences in the changes of apolipoprotein A-I, apolipoprotein A-II, or serum amyloid A levels between the groups. CONCLUSIONS: Our results suggest that SDD treatment may reduce the risk of cardiovascular disease in this patient group by increasing the cholesterol efflux capacity of serum.
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Antibacterianos/administración & dosificación , Colesterol/sangre , Doxiciclina/administración & dosificación , Macrófagos/efectos de los fármacos , Anciano , Apolipoproteína A-I/sangre , Apolipoproteína A-II/sangre , Células Cultivadas , Método Doble Ciego , Femenino , Humanos , Macrófagos/metabolismo , Persona de Mediana Edad , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Posmenopausia , Proteína Amiloide A Sérica/análisisRESUMEN
BACKGROUND: We reported that obesity was associated with increased arterial compliance in children, possibly due to accelerated vascular maturation. Here, we explored the additional burden of type 2 diabetes (T2DM) on vascular function in children. METHODS: Fifty normal weight [body mass index (BMI) 25-75%], 58 obese (BMI ≥ 95%), and 34 children with T2DM diagnosed by American Diabetes Association (ADA) criteria ages 10-18 yr were studied. Large and small artery elasticity (LAEI and SAEI, respectively) were measured by diastolic pulse-wave contour analysis. RESULTS: SAEI was 27% higher in children with T2DM compared to normal weight children (p = 0.005). Mean LAEI for those with T2DM not different from either group. In the group with T2DM, both SAEI and LAEI increased with age up to 16 yr, but declined thereafter. The strongest multivariable model predicting SAEI in children with T2DM combined lean mass, systolic blood pressure (SBP), and glucose (r2 = 0.59); for predicting LAEI, the strongest model included height, SBP, and low-density lipid-cholesterol (r2 = 0.61). CONCLUSION: The lower arterial compliance in older adolescents with T2DM compared to that of their peers without diabetes may indicate a premature maturation of the vascular system; however, follow-up will clarify whether these vascular changes portend an early increase in diabetes-associated cardiovascular disease risk.
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Arterias/fisiología , Diabetes Mellitus Tipo 2/fisiopatología , Obesidad/fisiopatología , Resistencia Vascular/fisiología , Adolescente , Glucemia/metabolismo , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Niño , Adaptabilidad , Elasticidad , Femenino , Humanos , Hiperemia/sangre , Insulina/sangre , Masculino , RiesgoRESUMEN
The purpose of this study was to determine if light physical activity (LPA) minimizes the impairment of cardiometabolic risk factors following a typical meal in adolescents. Eighteen adolescents (50% male, 14.8 ± 2.3 yrs) consumed a meal (32% fat, 14% protein, 53% carbohydrate), then completed a walking (1.5 mph for 45 min of each hour) or sitting treatment for 3 hr in randomized order on separate days. Following the meal, HDL cholesterol declined 4.8% but remained higher during walking at 3 hr (42.1 mg/dl ± 9.3) than sitting (8.4% decline; 40.5 mg/dL ± 9.9; treatment x time interaction, p < .03). The 3-hr insulin was lower after walking (24.8 µIU/ml ± 33.4) than sitting (37.8 µIU/ml ± 34.7; treatment x time interaction, p < .0001). Triglycerides increased by ~40% above baseline at 1 and 2 hr, with higher values for walking (treatment x time interaction, p < .02). However by 3 hr, triglycerides were not different from baseline. Area under the curve (AUC) analyses were not significantly different between treatments for any outcomes. Although minor, LPA appears to mitigate the undesirable postprandial changes in HDL cholesterol and insulin but not triglycerides, following a typical meal in adolescents.
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HDL-Colesterol/sangre , Ingestión de Alimentos/fisiología , Periodo Posprandial , Descanso/fisiología , Caminata/fisiología , Adolescente , Análisis de Varianza , Antropometría , Área Bajo la Curva , Análisis Químico de la Sangre , Glucemia/metabolismo , Índice de Masa Corporal , Enfermedades Cardiovasculares/prevención & control , Niño , Estudios de Cohortes , Ingestión de Energía , Prueba de Esfuerzo , Femenino , Humanos , Insulina/metabolismo , Masculino , Actividad Motora , Estudios Prospectivos , Medición de Riesgo , Triglicéridos/metabolismoRESUMEN
OBJECTIVE: The purpose of this study was to assess the practices related to obtaining postoperative pelvic CT scans following acetabular ORIF and revision surgery rates. DESIGN: A 20-question survey published on the Orthopaedic Trauma Association (OTA) website assessed each surgeon's preference and rationale for or against the routine use of postoperative CT scans for acetabular fractures. PARTICIPANTS: Fellowship-trained orthopaedic traumatologists. MAIN OUTCOME MEASUREMENTS: We examined the percentage of surgeons ordering routine postoperative CT scans, surgeon demographics, and revision surgery rates based on these routine CT scan results. RESULTS: Responses were received from 57 surgeons. Practices varied regarding postoperative CT scans, with 16 surgeons (28%, Group A) routinely ordering them and 41 surgeons (72%, Group B) not ordering them on all patients. No significant difference in surgeon demographics were found between the groups. Majority of Group A report a revision surgery rate of <1% based on the results of the postoperative CT. Group A report routine postoperative scans were obtained to assess reduction, hardware placement, identify intra-articular fragments, and for educational purposes. Group B did not obtain routine postoperative CTs due to the following: unlikely to change postoperative treatment, adequate reduction and instrumentation placement assessed intraoperatively and by postoperative radiographs, and increased radiation exposure and cost to patients. Group B did report obtaining postop CT scans on select patients, with inadequate intraoperative imaging and postoperative neurological changes being the most common indications. CONCLUSION: The routine use of postoperative CTs following open reduction internal fixation of acetabular fractures is a controversial topic. While we recognize the role for postoperative CT scans in select patients, our study questions the clinical utility of these scans in all patients and in conclusion do not recommend this protocol.
RESUMEN
Clinical studies on the treatment of type 1 diabetes with device-encapsulated pancreatic precursor cells derived from human embryonic stem cells found that insulin output was insufficient for clinical benefit. We are conducting a phase 1/2, open-label, multicenter trial aimed at optimizing cell engraftment (ClinicalTrials.gov identifier: NCT03163511 ). Here we report interim, 1-year outcomes in one study group that received 2-3-fold higher cell doses in devices with an optimized membrane perforation pattern. ß cell function was measured by meal-stimulated plasma C-peptide levels at 3-month intervals, and the effect on glucose control was assessed by continuous glucose monitoring (CGM) and insulin dosing. Of 10 patients with undetectable baseline C-peptide, three achieved levels ≥0.1 nmol l-1 from month 6 onwards that correlated with improved CGM measures and reduced insulin dosing, indicating a glucose-controlling effect. The patient with the highest C-peptide (0.23 nmol l-1) increased CGM time-in-range from 55% to 85% at month 12; ß cell mass in sentinel devices in this patient at month 6 was 4% of the initial cell mass, indicating directions for improving efficacy.