Results from "Live Well", a randomized controlled community-based participatory intervention to prevent obesity in new immigrant mother-child dyads.

BACKGROUND: Upon arrival, the prevalence of overweight and obesity is lower in new immigrants than their native counterparts in the U.S. With longer residency in the U.S., these differences converge over time, followed by higher prevalence among immigrants than native U.S. residents. Results from the Live Well project in the Greater Boston area demonstrate the viability of utilizing a culturally adapted, community-based participatory research (CBPR) approach to reduce weight gain among newly immigrated mother-child dyads. METHODS: Haitian, Latina, and Brazilian mother-child dyads (n = 390), new to the U.S. (fewer than 10 years) were enrolled in a one- to two-year long CBPR lifestyle intervention that targeted dietary and physical activity behaviors. Attendance was recorded to establish dose. Demographics, anthropometrics, and relevant covariates were collected from participants at baseline, 6, 12, 18, and 24 months. Body Mass Index (BMI) was calculated using objectively measured height and weight. Linear mixed regression models were used to assess change in BMI and BMI z-score of mothers and children respectively. RESULTS: At baseline, nearly 75% of mothers and 50% of children were either overweight or obese (BMI ≥ 25.0 and BMI z-score ≥ 85th percentile, respectively). Only 20% of mothers attended all 12 intervention sessions in year 1. Using intent-to-treat analyses, no significant time, intervention, or time × intervention effects were observed for weight change of mothers or children at follow-up. Mothers in the highest quantile (those who attended all 12 intervention sessions) had significant reductions in BMI at 18 months (1.76 units lower, 95%CI: -3.14, -0.37) and 24 months (2.61 units, 95%CI -3.92, -1.29) compared to mothers in the lower quantiles, including those with no exposure. Such dose effects on BMI z-scores were not noted for children. CONCLUSIONS: Findings from Live Well demonstrate the viability of utilizing a CBPR approach to address overweight and obesity among immigrant mothers. Given the higher-than-expected prevalence of overweight and obesity among mother-child dyads by ~ 6 years of U.S. residency, and lower maternal participation rates in the intervention, additional research is necessary to identify the optimal intervention length, retention strategies, and approach to jointly support healthy maternal and child weight.

An elevated OmpA expression during the production of a recombinant protein in Escherichia coli.

Escherichia coli cells rapidly respond to changes in the environment. Such response must be anticipated upon development of fermentation strategy for commercial purposes. The response may signal changes in cell physiology, which is critical for the cell growth and the level of the target protein production. One of the responses is the elevated expression of membrane proteins to tightly control the trafficking of molecules into and out from the cells. Normally, the expression level of the membrane protein is basal as the fermentation is carried out in physiological conditions. Here, we reported an elevated expression of the outer membrane protein A (OmpA) during a series of fermentation conduct, starting from the shake flask, 1-L to finally 10-L fermentor. The incidence led to a lower expression of the target protein and thereby resulting in lower process efficiency. OmpA expression was concomitant to the bacterial growth and already observed in the early exponential phase. Despite the drawback, this phenomenon actually inspires the observation of OmpA expression as one of the indicators for the E. coli cells response to the fermentation conditions. This auxiliary check would prevent the higher OmpA expression that led to the low expression of the target protein.

Perceptions of Practitioner Support for Patient Autonomy are Associated with Delayed Health Care Seeking among Haitian Immigrant Women in South Florida.

Few empirical studies have evaluated how perceptions of the patient-provider relationship affect health care seeking among Haitian immigrants. In this cross-sectional study, we examined whether perceptions of practitioner support for patient autonomy facilitate or hinder health care seeking among Haitian women enrolled in a cervical self-sampling trial. Perceived autonomy support was measured using an adapted health care climate questionnaire. Associations between perceived autonomy support and health care seeking were modeled using logistic regression and classification and regression trees. Covariates included socioeconomic and structural access indicators. Dependent variables included receipt of any medical care in the past year and delayed health care seeking. Having a usual source of care was strongly associated with both dependent variables. Lower perceived autonomy support was associated with delayed health care seeking in regression models and classification and regression trees. Addressing the capacity of health workers to deliver autonomy-supportive care is essential for improving health services utilization in vulnerable populations.

Health-Related Quality of Life, Depressive Symptoms, and Kidney Transplant Access in Advanced CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Among individuals with chronic kidney disease (CKD), poor self-reported health is associated with adverse outcomes including hospitalization and death. We sought to examine the association between health-related quality-of-life (HRQoL) and depressive symptoms in advanced CKD and subsequent access to the kidney transplant waiting list. STUDY DESIGN: Prospective cohort study. SETTING & POPULATION: 1,676 Chronic Renal Insufficiency Cohort (CRIC) study participants with estimated glomerular filtration rates ≤ 30 mL/min/1.73 m2 at study entry or during follow-up. EXPOSURES: HRQoL ascertained by 5 scales of the Kidney Disease Quality of Life-36 Survey (Physical Component Summary [PCS], Mental Component Summary, Symptoms, Burdens, and Effects), with higher scores indicating better HRQoL, and depressive symptoms ascertained using the Beck Depression Inventory. OUTCOMES: Time to kidney transplant wait-listing and time to pre-emptive wait-listing. ANALYTIC APPROACH: Time-to-event analysis using Cox proportional hazards regression. RESULTS: During a median follow-up of 5.1 years, 652 (39%) participants were wait-listed, of whom 304 were preemptively wait-listed. Adjusted for demographics, comorbid conditions, estimated glomerular filtration rate slope, and cognitive function, participants with the highest scores on the Burden and Effects scales, respectively, had lower rates of wait-listing than those with the lowest scores on the Burden (wait-listing adjusted hazard ratio [aHR], 0.70; 95% CI, 0.57-0.85; P < 0.001) and Effects scales (wait-listing aHR, 0.74; 95% CI, 0.59-0.92; P = 0.007). Participants with fewer depressive symptoms (ie, Beck Depression Inventory score < 14) had lower wait-listing rates than those with more depressive symptoms (aHR, 0.81; 95% CI, 0.66-0.99; P = 0.04). Participants with lower Burden and Effects scale scores and those with higher Symptoms and PCS scores had higher pre-emptive wait-listing rates (aHR in highest tertile of PCS relative to lowest tertile, 1.58; 95% CI, 1.12-2.23; P = 0.01). LIMITATIONS: Unmeasured confounders. CONCLUSIONS: Self-reported health in late-stage CKD may influence the timing of kidney transplantation.

Declaración de posición del Grupo de la Comisión Lancet de Hipertensión con respecto a la mejora mundial de las normas de exactitud para los dispositivos de medición de la presión arterial

[RESUMEN]. La Comisión Lancet de Hipertensión determinó que una medida clave para responder a la carga mundial que representa la hipertensión arterial era mejorar la calidad de las mediciones de la presión arterial, mediante la utilización de dispositivos cuya exactitud haya sido validada. En la actualidad existen 3000 dispositivos comercializados, pero muchos no tienen datos publicados sobre pruebas de exactitud conformes a las normas científicas establecidas. La falta de regulación o su ineficiencia, que permiten la autorización de dispositivos para uso comercial sin una validación oficial, posibilitan este problema. Además, han surgido tecnologías nuevas de medición de la presión arterial (por ejemplo, los sensores sin brazalete) sobre las cuales no existe unanimidad en la comunidad científica con respecto a las normas de exactitud de la medición. En conjunto, estos aspectos contribuyen a la disponibilidad generalizada de tensiómetros de consultorio o domiciliarios que ofrecen una exactitud limitada o incierta, que llevan a diagnósticos, manejo y farmacoterapia inapropiados de la hipertensión a escala mundial. Los problemas más importantes relacionados con la exactitud de los dispositivos de medición de la presión arterial se pueden resolver mediante el requisito regulatorio de una validación independiente obligatoria de los dispositivos, en consonancia con la norma ISO universalmente aceptada. Esta es una recomendación básica y constituye una necesidad internacional acuciante. Otras recomendaciones clave son la elaboración de normas de validación específicas para las tecnologías nuevas de medición de la presión arterial y la publicación en línea de listas de los dispositivos nuevos exactos que están a la disposición de los usuarios y los profesionales de salud. Las recomendaciones están en consonancia con las políticas de la Organización Mundial de la Salud sobre los dispositivos médicos y la atención universal de la salud. El cumplimiento de las recomendaciones aumentará la disponibilidad mundial de dispositivos de medición de la presión arterial que sean exactos y tendrá como efecto un mejor diagnóstico y tratamiento, reduciendo así la carga mundial de la hipertensión.

[ABSTRACT]. The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.

[RESUMO]. A Comissão Lancet sobre Hipertensão Arterial identificou que uma iniciativa central para enfrentar a carga mundial da hipertensão arterial seria a melhoria na qualidade da mensuração da pressão arterial pelo uso aparelhos de pressão arterial validados quanto à acurácia. Atualmente, existem mais de 3 000 aparelhos de pressão arterial disponíveis comercialmente; entretanto, muitos não têm dados publicados sobre testes de acurácia realizados de acordo com padrões científicos estabelecidos. Este problema resulta de regulamentação fraca ou inexistente, o que permite a aprovação para uso comercial de dispositivos sem validação formal. Além disso, surgiram novas tecnologias de mensuração da pressão arterial (por exemplo, sensores sem algemas) sem consenso científico quanto aos padrões de acurácia. No conjunto, essas questões contribuem para a oferta generalizada de dispositivos de pressão arterial clínica e domiciliar com acurácia limitada ou incerta, levando a diagnóstico, gerenciamento e tratamento inadequados da hipertensão em escala global. Os problemas mais significativos relacionados com a acurácia dos dispositivos de pressão arterial podem ser resolvidos por regulamentação que imponha a obrigatoriedade de validação independente dos aparelhos de pressão arterial, de acordo com a norma universalmente aceita pela Organização Internacional de Normalização. Esta é uma recomendação fundamental para a qual existe uma necessidade internacional urgente. Outras recomendações essenciais incluem o desenvolvimento de padrões de validação especificamente para novas tecnologias de mensuração da pressão arterial e listas on-line de aparelhos com acurácia adequada que sejam acessíveis aos consumidores e profissionais de saúde. As recomendações estão alinhadas com as políticas da Organização Mundial da Saúde (OMS) sobre dispositivos médicos e atenção universal à saúde. A adesão às recomendações aumentaria a oferta global de dispositivos de pressão arterial com acurácia adequada e resultaria em melhor diagnóstico e tratamento da hipertensão arterial, diminuindo assim a carga mundial dessa doença.

Declaración de posición del Grupo de la Comisión Lancet de Hipertensión con respecto a la mejora mundial de las normas de exactitud para los dispositivos de medición de la presión arterial / Lancet Commission on Hypertension Group position statement on the global improvement of accuracy standards for devices that measure blood pressure / Posicionamento do Grupo da Lancet Commission on Hypertension sobre a melhoria global dos padrões de acurácia para aparelhos que medem a pressão arterial

Objetivos. El boletín de notas de México correspondiente al 2018 evalúa las oportunidades a disposición de la población infantil y joven mexicana para que puedan desarrollar niveles adecuados de actividad física y sueño, y disminuyan el sedentarismo.Métodos. El boletín es un sistema de vigilancia que recopila los datos obtenidos en las encuestas nacionales, censos, documentos gubernamentales, sitios web, literatura gris y estudios publicados con respecto al análisis de 16 indicadores en 4 categorías: comportamientos diarios, estado físico, entornos y fuentes influyentes, y estrategias e inversión. Los datos fueron cotejados con los puntos de referencia establecidos. A cada indicador se le asignó una calificación entre 1 y 10 (< 6 significa reprobado) o fue marcado como "incompleto" si los datos eran nulos o insuficientes. Resultados. Las calificaciones obtenidas para los comportamientos diarios fueron: actividad física en general: 4; participación en actividades deportivas organizadas: 5; juego activo: 3; modalidades de transporte activas: 5; sueño: 7; y sedentarismo: 3. El estado físico obtuvo un 7. Las calificaciones para los entornos y fuentes influyentes fueron: familiares y pares: "incompleto"; escuela: 3; comunidad y entorno: 4. Para las estrategias e inversión: estrategias gubernamentales: 6; entidades no gubernamentales: 2.Conclusiones. Las bajas calificaciones obtenidas en 11 de los 16 indicadores demuestran que las escuelas, las familias, las comunidades y el gobierno tienen que aunar esfuerzos para mejorar las oportunidades que tiene la población infantil y joven en México para desarrollar niveles de actividad física satisfactorios.(AU)

ABSTRACT The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.(AU)

RESUMO A Comissão Lancet sobre Hipertensão Arterial identificou que uma iniciativa central para enfrentar a carga mundial da hipertensão arterial seria a melhoria na qualidade da mensuração da pressão arterial pelo uso aparelhos de pressão arterial validados quanto à acurácia. Atualmente, existem mais de 3 000 aparelhos de pressão arterial disponíveis comercialmente; entretanto, muitos não têm dados publicados sobre testes de acurácia realizados de acordo com padrões científicos estabelecidos. Este problema resulta de regulamentação fraca ou inexistente, o que permite a aprovação para uso comercial de dispositivos sem validação formal. Além disso, surgiram novas tecnologias de mensuração da pressão arterial (por exemplo, sensores sem algemas) sem consenso científico quanto aos padrões de acurácia. No conjunto, essas questões contribuem para a oferta generalizada de dispositivos de pressão arterial clínica e domiciliar com acurácia limitada ou incerta, levando a diagnóstico, gerenciamento e tratamento inadequados da hipertensão em escala global. Os problemas mais significativos relacionados com a acurácia dos dispositivos de pressão arterial podem ser resolvidos por regulamentação que imponha a obrigatoriedade de validação independente dos aparelhos de pressão arterial, de acordo com a norma universalmente aceita pela Organização Internacional de Normalização. Esta é uma recomendação fundamental para a qual existe uma necessidade internacional urgente. Outras recomendações essenciais incluem o desenvolvimento de padrões de validação especificamente para novas tecnologias de mensuração da pressão arterial e listas on-line de aparelhos com acurácia adequada que sejam acessíveis aos consumidores e profissionais de saúde. As recomendações estão alinhadas com as políticas da Organização Mundial da Saúde (OMS) sobre dispositivos médicos e atenção universal à saúde. A adesão às recomendações aumentaria a oferta global de dispositivos de pressão arterial com acurácia adequada e resultaria em melhor diagnóstico e tratamento da hipertensão arterial, diminuindo assim a carga mundial dessa doença.(AU)

Feasibility of Assessing Sodium-Associated Body Fluid Composition in End-Stage Renal Disease.

BACKGROUND: Cardiovascular disease accounts for more than half of all deaths in the hemodialysis (HD) population. Although much of this mortality is associated with fluid overload (FO), FO is difficult to measure, and many HD patients have significant pulmonary congestion despite the absence of clinical presentation. Cohort studies have observed that FO, as measured by bioimpedance spectroscopy (BIS), correlates with mortality. Other studies have observed that lower sodium intake is associated with less fluid-related weight gain, improved hypertension, and survival. Whether sodium intake influences FO in HD patients as measured by BIS is not known. OBJECTIVE: The aims of the study were to determine the feasibility of assessing the impact of sodium restriction on body fluid composition as measured by BIS among patients with three levels of sodium intake and to determine if there are statistical and/or clinical differences in BIS measures across sodium intake groups. METHODS: We used a double-blinded randomized controlled trial design with three levels of sodium restriction, 2,400 mg per day, 1,500 mg per day, and unrestricted (control group), to test our aims. Forty-two HD patients from a tertiary acute care academic institution associated with three urban DaVita dialysis centers were enrolled. Participants remained in the inpatient center for 5 days and 4 nights and were randomly assigned to sodium intake groups. Body fluid composition was measured with BIS. RESULTS: Recruitment, enrollment, and retention statistics supported the feasibility of the study design. Regression analyses showed that there were no statistically significant differences among sodium intake groups on any of the outcomes. DISCUSSION: Our data suggest the need for additional research into the effects of sodium restriction on body fluid composition.

Hemodynamic Patterns Identified by Impedance Cardiography Predict Mortality in the General Population: The PREVENCION Study.

Background Blood pressure is determined by the interactions between the heart and arterial properties, and subjects with identical blood pressure may have substantially different hemodynamic determinants. Whether arterial hemodynamic indices quantified by impedance cardiography ( ICG ), a simple operator-independent office procedure, independently predict all-cause mortality in adults from the general population, and specifically among those who do not meet criteria for American College of Cardiology/American Heart Association stage 2 hypertension, is currently unknown. Methods and Results We studied 1639 adults aged 18 to 80 years from the general population. We used ICG to measure hemodynamic parameters and metrics of cardiac function. We assessed the relationship between hemodynamic parameters measured at baseline and all-cause mortality over a mean follow-up of 10.9 years. Several ICG parameters predicted death. The strongest predictors were total arterial compliance index (standardized hazard ratio=0.38; 95% confidence interval=0.31-0.46; P<0.0001) and indices of cardiac contractility: velocity index (standardized hazard ratio=0.45; 95% confidence interval=0.37-0.55; P<0.0001) and acceleration index (standardized hazard ratio=0.44; 95% confidence interval=0.35-0.55; P<0.0001). These remained independently predictive of death after adjustment for multiple confounders, as well as systolic and diastolic blood pressure. Among subjects without stage 2 hypertension (n=1563), indices of cardiac contractility were independently predictive of death and identified a subpopulation (25% of non-stage-2 hypertensives) that demonstrated a high 10-year mortality risk, equivalent to that of stage 2 hypertensives. Conclusions Hemodynamic patterns identified by ICG independently predict mortality in the general population. The predictive value of ICG applies even in the absence of American College of Cardiology/American Heart Association stage 2 hypertension and identifies higher-risk individuals who are in earlier stages of the hypertension continuum.

Variation in type II endometrial cancer risk by Hispanic subpopulation: An exploratory analysis.

BACKGROUND: Minorities have demonstrated an increased risk for type II endometrial cancers, but no data exists about risk among minority subpopulations. Our objective was to evaluate heterogeneity in risk of type II endometrial cancer (EC) histologies across race and Hispanic sub-groups using data from Florida's statewide cancer registry (FCDS). METHODS: FCDS contains data on N=26,416 women diagnosed with EC from 2004 to 2013. Our analysis included women ≥18years of age who were classified as non-Hispanic White (NHW), non-Hispanic Black (NHB) or belonged to one of five Hispanic sub-groups, and had a histology code consistent with type I or type II EC. Binary logistic regression analyses were performed to model risk of type II versus type I ECs across racial and ethnic groups relative to NHW. RESULTS: Relative to NHW, overall odds of being diagnosed with a type II EC were significantly higher in NHB (OR=2.64, 95%CI: 2.38-2.92), Cubans (OR=1.35, 95%CI: 1.08-1.68) and South and Central Americans (SCA) (OR=1.84, 95%CI: 1.40-2.43). Compared to NHW, odds of serous EC were significantly higher in Cubans (OR=2.15, 95% CI: 1.51-3.05) and NHB (OR=2.51, 95% CI: 2.11-2.97); odds of carcinosarcoma (CS) were significantly higher in NHB (OR=2.97, 95% CI: 2.47-3.57) and Puerto Ricans (OR=2.35, 95%CI: 1.32-4.17); and odds of grade III adenocarcinoma (AG3) were significantly higher in NHB (OR=1.60, 95% CI: 1.42-1.81) and SCA (OR=1.76, 95%CI: 1.29-2.40). CONCLUSION: Risk of type II EC varies considerably across Hispanic sub-groups, with Cubans, Puerto Ricans and SCA characterized by elevated odds for specific type II histologies.

Carotid Artery Wall Thickness in Obese and Nonobese Adults With Obstructive Sleep Apnea Before and Following Positive Airway Pressure Treatment.

Study objectives: Debate persists as to whether obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. The purpose of this study was to compare carotid intima-media thickness (IMT), an early sign of atherosclerosis, in obese and nonobese adults with OSA before and following positive airway pressure (PAP) treatment. Methods: A total of 206 adults newly diagnosed with OSA with an apnea-hypopnea index (AHI) of 15-75 events/hour and 53 controls with AHI <10 were studied. Waist circumference was used to classify participants as obese and nonobese. Bilateral common carotid artery B-mode ultrasound was performed at baseline to assess IMT, arterial diameter, arterial-wall mass, and circumferential wall stress. Measurements were repeated in 118 participants with OSA who completed a 4-month PAP treatment and had an average daily use over that period of ≥4 hours/day. Results: No significant differences in carotid IMT, diameter, or arterial-wall mass were present at baseline between participants with OSA and controls stratified by waist circumference, after adjusting for other cardiovascular risk factors. In participants with OSA, who had adequate PAP adherence over the 4-month treatment, carotid artery diameter significantly increased (mean change [95% confidence interval] = 0.13 [0.06, 0.20] mm; p = .0004), but no significant changes in carotid IMT, arterial-wall mass, and circumferential stress were observed in obese and nonobese participants. Conclusions: Regardless of obesity status, carotid IMT is not increased in adults with moderate to severe OSA versus controls and does not change following 4 months of PAP treatment.

Patient Perspectives on Barriers to Surgical Care and the Impact of Mobile Surgery in Ecuador.

BACKGROUND: An estimated 5 billion people worldwide lack access to timely safe surgical care (Gawande in Lancet 386(9993):523-525, 2015). A mere 6% of all surgical procedures occur in the poorest countries where over a third of the world's population lives (Meara et al. in Surgery 158(1):3-6, 2015). Mobile surgical units like the Cinterandes Foundation endeavor to bring surgical care directly to these communities who otherwise would lack access to safe surgery. This study examines the barriers patients encounter in seeking surgical care in rural communities of Ecuador and their impressions on how mobile surgery addresses such barriers. METHODS: Open interviews were conducted with Cinterandes' patients who had undergone an operation in the mobile surgical unit between 06/25/2013 and 06/25/2014 (n = 101). Interviews were structured to explore two main domains: (1) examining barriers patients have in accessing surgery, (2) assessing patients' opinion of how mobile surgery helped in overcoming such barriers. RESULTS: Patient inconvenience (70%), cost (21%), and lack of trust in local hospitals (24%) were the main cited barriers to surgical access. Increased patient convenience (53%), cheaper surgical care (34%), and trust in Cinterandes (47%) were the main cited benefits to mobile surgery. CONCLUSION: Mobile surgery provided by Cinterandes effectively overcomes many barriers patients encounter when seeking surgical care in rural Ecuador: decreased patient wait times, limited number of referrals to multiple locations, and decreased cost. Partnering with local clinics within the communities and bringing care much closer to patients' homes may provide a better patient friendly health care delivery system for rural Ecuador.

Isosorbide Dinitrate, With or Without Hydralazine, Does Not Reduce Wave Reflections, Left Ventricular Hypertrophy, or Myocardial Fibrosis in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Wave reflections, which are increased in patients with heart failure with preserved ejection fraction, impair diastolic function and promote pathologic myocardial remodeling. Organic nitrates reduce wave reflections acutely, but whether this is sustained chronically or affected by hydralazine coadministration is unknown. METHODS AND RESULTS: We randomized 44 patients with heart failure with preserved ejection fraction in a double-blinded fashion to isosorbide dinitrate (ISDN; n=13), ISDN+hydralazine (ISDN+hydral; n=15), or placebo (n=16) for 6 months. The primary end point was the change in reflection magnitude (RM; assessed with arterial tonometry and Doppler echocardiography). Secondary end points included change in left ventricular mass and fibrosis, measured with cardiac magnetic resonance imaging, and the 6-minute walk distance. ISDN reduced aortic characteristic impedance (mean baseline=0.15 [95% CI, 0.14-0.17], 3 months=0.11 [95% CI, 0.10-0.13], 6 months=0.10 [95% CI, 0.08-0.12] mm Hg/mL per second; P=0.003) and forward wave amplitude (Pf, mean baseline=54.8 [95% CI, 47.6-62.0], 3 months=42.2 [95% CI, 33.2-51.3]; 6 months=37.0 [95% CI, 27.2-46.8] mm Hg, P=0.04), but had no effect on RM (P=0.64), left ventricular mass (P=0.33), or fibrosis (P=0.63). ISDN+hydral increased RM (mean baseline=0.39 [95% CI, 0.35-0.43]; 3 months=0.31 [95% CI, 0.25-0.36]; 6 months=0.44 [95% CI, 0.37-0.51], P=0.03), reduced 6-minute walk distance (mean baseline=343.3 [95% CI, 319.2-367.4]; 6 months=277.0 [95% CI, 242.7-311.4] meters, P=0.022), and increased native myocardial T1 (mean baseline=1016.2 [95% CI, 1002.7-1029.7]; 6 months=1054.5 [95% CI, 1036.5-1072.3], P=0.021). A high proportion of patients experienced adverse events with active therapy (ISDN=61.5%, ISDN+hydral=60.0%; placebo=12.5%; P=0.007). CONCLUSIONS: ISDN, with or without hydralazine, does not exert beneficial effects on RM, left ventricular remodeling, or submaximal exercise and is poorly tolerated. ISDN+hydral appears to have deleterious effects on RM, myocardial remodeling, and submaximal exercise. Our findings do not support the routine use of these vasodilators in patients with heart failure with preserved ejection fraction. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT01516346.

Pharmacokinetics and Pharmacodynamics of Inorganic Nitrate in Heart Failure With Preserved Ejection Fraction.

RATIONALE: Nitrate-rich beetroot juice has been shown to improve exercise capacity in heart failure with preserved ejection fraction, but studies using pharmacological preparations of inorganic nitrate are lacking. OBJECTIVES: To determine (1) the dose-response effect of potassium nitrate (KNO3) on exercise capacity; (2) the population-specific pharmacokinetic and safety profile of KNO3 in heart failure with preserved ejection fraction. METHODS AND RESULTS: We randomized 12 subjects with heart failure with preserved ejection fraction to oral KNO3 (n=9) or potassium chloride (n=3). Subjects received 6 mmol twice daily during week 1, followed by 6 mmol thrice daily during week 2. Supine cycle ergometry was performed at baseline (visit 1) and after each week (visits 2 and 3). Quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire. The primary efficacy outcome, peak O2-uptake, did not significantly improve (P=0.13). Exploratory outcomes included exercise duration and quality of life. Exercise duration increased significantly with KNO3 (visit 1: 9.87, 95% confidence interval [CI] 9.31-10.43 minutes; visit 2: 10.73, 95% CI 10.13-11.33 minute; visit 3: 11.61, 95% CI 11.05-12.17 minutes; P=0.002). Improvements in the Kansas City Cardiomyopathy Questionnaire total symptom (visit 1: 58.0, 95% CI 52.5-63.5; visit 2: 66.8, 95% CI 61.3-72.3; visit 3: 70.8, 95% CI 65.3-76.3; P=0.016) and functional status scores (visit 1: 62.2, 95% CI 58.5-66.0; visit 2: 68.6, 95% CI 64.9-72.3; visit 3: 71.1, 95% CI 67.3-74.8; P=0.01) were seen after KNO3. Pronounced elevations in trough levels of nitric oxide metabolites occurred with KNO3 (visit 2: 199.5, 95% CI 98.7-300.2 µmol/L; visit 3: 471.8, 95% CI 377.8-565.8 µmol/L) versus baseline (visit 1: 38.0, 95% CI 0.00-132.0 µmol/L; P<0.001). KNO3 did not lead to clinically significant hypotension or methemoglobinemia. After 6 mmol of KNO3, systolic blood pressure was reduced by a maximum of 17.9 (95% CI -28.3 to -7.6) mm Hg 3.75 hours later. Peak nitric oxide metabolites concentrations were 259.3 (95% CI 176.2-342.4) µmol/L 3.5 hours after ingestion, and the median half-life was 73.0 (interquartile range 33.4-232.0) minutes. CONCLUSIONS: KNO3 is potentially well tolerated and improves exercise duration and quality of life in heart failure with preserved ejection fraction. This study reinforces the efficacy of KNO3 and suggests that larger randomized trials are warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02256345.

Heart Failure, Left Ventricular Remodeling, and Circulating Nitric Oxide Metabolites.

BACKGROUND: Stable plasma nitric oxide (NO) metabolites (NOM), composed predominantly of nitrate and nitrite, are attractive biomarkers of NO bioavailability. NOM levels integrate the influence of NO-synthase-derived NO production/metabolism, dietary intake of inorganic nitrate/nitrite, and clearance of NOM. Furthermore, nitrate and nitrite, the most abundant NOM, can be reduced to NO via the nitrate-nitrite-NO pathway. METHODS AND RESULTS: We compared serum NOM among subjects without heart failure (n=126), subjects with heart failure and preserved ejection fraction (HFpEF; n=43), and subjects with heart failure and reduced ejection fraction (HFrEF; n=32). LV mass and extracellular volume fraction were measured with cardiac MRI. Plasma NOM levels were measured after reduction to NO via reaction with vanadium (III)/hydrochloric acid. Subjects with HFpEF demonstrated significantly lower unadjusted levels of NOM (8.0 µmol/L; 95% CI 6.2-10.4 µmol/L; ANOVA P=0.013) than subjects without HF (12.0 µmol/L; 95% CI 10.4-13.9 µmol/L) or those with HFrEF (13.5 µmol/L; 95% CI 9.7-18.9 µmol/L). There were no significant differences in NOM between subjects with HFrEF and subjects without HF. In a multivariable model that adjusted for age, sex, race, diabetes mellitus, body mass index, current smoking, systolic blood pressure, and glomerular filtration rate, HFpEF remained a predictor of lower NOM (ß=-0.43; P=0.013). NOM did not correlate with LV mass, or LV diffuse fibrosis. CONCLUSIONS: HFpEF, but not HFrEF, is associated with reduced plasma NOM, suggesting greater endothelial dysfunction, enhanced clearance, or deficient dietary ingestion of inorganic nitrate. Our findings may underlie the salutary effects of inorganic nitrate supplementation demonstrated in recent clinical trials in HFpEF.

Blood Pressure Effects of Yoga, Alone or in Combination With Lifestyle Measures: Results of the Lifestyle Modification and Blood Pressure Study (LIMBS).

The authors conducted a study to assess the effects of yoga on blood pressure (BP). Patients were randomized to yoga (Blood Pressure Education Program [BPEP]), or a combined program (COMBO). Ambulatory BP was measured at baseline and at 12 and 24 weeks. Data are presented for all enrolled patients (n=137) and for completers only (n=90). Systolic BP (SBP) and diastolic BP (DBP) were significantly decreased within all groups at 12 and 24 weeks (P<.001) for enrolled patients and completers. SBP was significantly reduced in the yoga and COMBO groups as compared with the BPEP group at 12 weeks in all enrolled and completers. SBP differences were no longer significant at 24 weeks between groups in all enrolled patients; however, there was a greater reduction in SBP at 24 weeks in completers favoring BPEP over yoga. No differences in DBP between groups or in BP between the yoga and COMBO groups were present. The authors did not observe an additive benefit from combining yoga with BPEP measures. Reasons for this are unclear at this time. BP lowering with yoga, however, was similar to that achieved with lifestyle measures.