Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical Trial.

Importance: Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. Objective: To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. Design, Setting, and Participants: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF ( Interventions: Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. Main Outcomes and Measures: The primary end point was a change in peak oxygen uptake (V̇o2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). Results: Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak V̇o2 was 1196 mL/min (interquartile range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak V̇o2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6 m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, -2.4 to 4.4), all P \u3e .05. Conclusions and Relevance: Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. Trial Registration: clinicaltrials.gov Identifier: NCT02188784

Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. METHODS: In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (-381 accelerometer units; 95% confidence interval [CI], -780 to 17; P=0.06) and a significant decrease in hours of activity per day (-0.30 hours; 95% CI, -0.55 to -0.05; P=0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (-439 accelerometer units; 95% CI, -792 to -86; P=0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels. CONCLUSIONS: Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02053493.)

Ефективністіь спучуючого покриття для вогнезахисту дерев’яних споруд

Studies of the effect of wood flame retardant on ignition have established the parameters of flame propagation and combustion suppression, which makes it possible to influence this process. It is proved that they consist in creating a layer on the surface of the material, which prevents heating to a critical temperature, when intensive decomposition begins with the release of the required amount of flammable gases and their ignition. This makes it possible to determine the effect of fire protection and the properties of protective compositions on the process of inhibiting the rate of wood burning. During the tests of wood samples it was found that the untreated sample took 52 s, the flame spread throughout the sample for 100 s instead, the sample fire-retardant "FIREWALL-ATTIK" did not catch fire, impregnating solution ВС-13 and "FIREWALL-SV-1", Namely a mixture of 271.1 g/m2, took 570 and 560 s, the spread of flame on the surface occurred only in the first areas, the maximum flue gas temperature was 86 and 89 °C for more than 5 times, and the flammability index decreased to 4. For the sample protected by "FIREWALL-LAC" ignition occurred at the last second, the flame was recorded at level 0. For the sample fire-protected by "FIREWALL-WOOD" coating no ignition occurred, combustibility index 0. Due to this, it became possible to determine the conditions for changing the parameters of combustion and braking in fire protection of wood by forming a barrier to thermal conductivity. The results of comparing the experimental data of wood burning rate with the obtained analytical equations showed the correspondence between them. Thus, there is reason to argue about the possibility of targeted regulation of fire protection processes of wood by using fire-retardant coatings capable of forming a protective layer on the surface of the material, which inhibits the rate of wood burning.Проведеними дослідженнями встановлено вплив вогнезахисту деревини на займання й визначено параметри поширення полум’я та пригнічення горіння, що дає можливість впливати на цей процес. Доведено, що вони полягають у створенні на поверхні матеріалу шару, який запобігає прогріванню до критичної температури, коли починається інтенсивний розклад з виділенням необхідної кількості горючих газів та їх займання. Завдяки цьому стає можливим визначення впливу вогнезахисту та властивостей захисних композицій на процес гальмування швидкості вигорання деревини. Під час випробувань зразків деревини було встановлено, що необроблений зразок зайнявся на 52 с, полум’я поширилося по всьому зразку протягом 100 с натомість, зразок, вогнезахищений «ФАЄРВОЛ-АТТІК», не загорівся, просочувальним розчином БС-13 та «ФАЄРВОЛ-СВ-1», а саме сумішшю у кількості 271,1 г/м2, зайнявся на 570 та 560 с, поширення полум’я поверхнею відбулося тільки на перші ділянки, максимальна температура димових газів становила 86 та 89 °C за час, більший понад 5 разів, а індекс горючості знизився до 4. Для зразка, захищеного засобом «ФАЄРВОЛ-ЛАК», займання відбулося на останній секунді, полум’я зафіксовано на рівні 0. Для зразка, вогнезахищеного покриттям «ФАЄРВОЛ-ВУД» загорання не відбулося, оскільки на поверхні утворився захисний шар пінококсу, індекс горючості 0. Завдяки цьому стало можливим визначення умов зміни параметрів горіння та гальмування при вогнезахисті деревини шляхом утворення бар'єру для теплопровідності. Результати співставлення експериментальних даних швидкості вигорання деревини з отриманим аналітичним рівняннями показали відповідність між ними. Таким чином, є підстави стверджувати про можливість спрямованого регулювання процесів вогнезахисту деревини шляхом застосування вогнезахисних покриттів, здатних утворювати на поверхні матеріалу захисний шар, який гальмує швидкість вигорання деревини

Human Cardiac-Specific cDNA Array for Idiopathic Dilated Cardiomyopathy: Sex-Related Differences

Idiopathic dilated cardiomyopathy (IDCM) constitutes a large portion of patients with heart failure of unknown etiology. Up to 50% of all transplant recipients carry this clinical diagnosis. Female-specific gene expression in IDCM has not been explored. We report sex-related differences in the gene expression profile of ventricular myocardium from patients undergoing cardiac transplantation. We produced and sequenced subtractive cDNA libraries, using human left ventricular myocardium obtained from male transplant recipients with IDCM and nonfailing human heart donors. With the resulting sequence data, we generated a custom human heart failure microarray for IDCM containing 1,145 cardiac-specific oligonucleotide probes. This array was used to characterize RNA samples from female IDCM transplant recipients. We identified a female gene expression pattern that consists of 37 upregulated genes and 18 downregulated genes associated with IDCM. Upon functional analysis of the gene expression pattern, deregulated genes unique to female IDCM were those that are involved in energy metabolism and regulation of transcription and translation. For male patients we found deregulation of genes related to muscular contraction. These data suggest that 1) the gene expression pattern we have detected for IDCM may be specific for this disease and 2) there is a sex-specific profile to IDCM. Our observations further suggest for the first time ever novel targets for treatment of IDCM in women and men

Combining multivariate statistics and the think-aloud protocol to assess Human-Computer Interaction barriers in symptom checkers

[EN] Symptom checkers are software tools that allow users to submit a set of symptoms and receive advice related to them in the form of a diagnosis list, health information or triage. The heterogeneity of their potential users and the number of different components in their user interfaces can make testing with end-users unaffordable. We designed and executed a two-phase method to test the respiratory diseases module of the symptom checker Erdusyk. Phase I consisted of an online test with a large sample of users (n = 53). In Phase I, users evaluated the system remotely and completed a questionnaire based on the Technology Acceptance Model. Principal Component Analysis was used to correlate each section of the interface with the questionnaire responses, thus identifying which areas of the user interface presented significant contributions to the technology acceptance. In the second phase, the think-aloud procedure was executed with a small number of samples (n = 15), focusing on the areas with significant contributions to analyze the reasons for such contributions. Our method was used effectively to optimize the testing of symptom checker user interfaces. The method allowed kept the cost of testing at reasonable levels by restricting the use of the think-aloud procedure while still assuring a high amount of coverage. The main barriers detected in Erdusyk were related to problems understanding time repetition patterns, the selection of levels in scales to record intensities, navigation, the quantification of some symptom attributes, and the characteristics of the symptoms. (C) 2017 Elsevier Inc. All rights reserved.This work was supported by Helse Nord [grant HST1121-13], the Faculty of Health Sciences from UIT The Arctic University of Norway [researcher code 1108], and The Research Council of Norway [grant 248150/O70]. We thank Professor Emeritus Rafael Romero-Villafranca for reviewing the statistical analysis of this paper.Marco-Ruiz, L.; Bones, E.; De La Asuncion, E.; Gabarron, E.; Aviles-Solis, JC.; Lee, E.; Traver Salcedo, V.... (2017). Combining multivariate statistics and the think-aloud protocol to assess Human-Computer Interaction barriers in symptom checkers. Journal of Biomedical Informatics. 74:104-122. https://doi.org/10.1016/j.jbi.2017.09.002S1041227

Does home oxygen therapy (HOT) in addition to standard care reduce disease severity and improve symptoms in people with chronic heart failure? A randomised trial of home oxygen therapy for patients with chronic heart failure

Background: Home oxygen therapy (HOT) is commonly used for patients with severe chronic heart failure(CHF) who have intractable breathlessness. There is no trial evidence to support its use.Objectives: To detect whether or not there was a quality-of-life benefit from HOT given as long-termoxygen therapy (LTOT) for at least 15 hours per day in the home, including overnight hours, comparedwith best medical therapy (BMT) in patients with severely symptomatic CHF.Design: A pragmatic, two-arm, randomised controlled trial recruiting patients with severe CHF. It includeda linked qualitative substudy to assess the views of patients using home oxygen, and a free-standingsubstudy to assess the haemodynamic effects of acute oxygen administration.Setting: Heart failure outpatient clinics in hospital or the community, in a range of urban andrural settings.Participants: Patients had to have heart failure from any aetiology, New York Heart Association (NYHA)class III/IV symptoms, at least moderate left ventricular systolic dysfunction, and be receiving maximallytolerated medical management. Patients were excluded if they had had a cardiac resynchronisation therapydevice implanted within the past 3 months, chronic obstructive pulmonary disease fulfilling the criteria forLTOT or malignant disease that would impair survival or were using a device or medication that wouldimpede their ability to use LTOT.Interventions: Patients received BMT and were randomised (unblinded) to open-label LTOT, prescribed for15 hours per day including overnight hours, or no oxygen therapy.Main outcome measures: The primary end point was quality of life as measured by the Minnesota Livingwith Heart Failure (MLwHF) questionnaire score at 6 months. Secondary outcomes included assessing theeffect of LTOT on patient symptoms and disease severity, and assessing its acceptability to patientsand carers.Results: Between April 2012 and February 2014, 114 patients were randomised to receive either LTOT orBMT. The mean age was 72.3 years [standard deviation (SD) 11.3 years] and 70% were male. Ischaemicheart disease was the cause of heart failure in 84%; 95% were in NYHA class III; the mean left ventricularejection fraction was 27.8%; and the median N-terminal pro-B-type natriuretic hormone was 2203 ng/l.The primary analysis used a covariance pattern mixed model which included patients only if they provided datafor all baseline covariates adjusted for in the model and outcome data for at least one post-randomisationtime point (n = 102: intervention, n = 51; control, n = 51). There was no difference in the MLwHF questionnairescore at 6 months between the two arms [at baseline the mean score was 54.0 (SD 18.4) for LTOT and54.0 (SD 17.9) for BMT; at 6 months the mean score was 48.1 (SD 18.5) for LTOT and 49.0 (SD 20.2) forBMT; adjusted mean difference –0.10, 95% confidence interval (CI) –6.88 to 6.69; p = 0.98]. At 3 months,the adjusted mean MLwHF questionnaire score was lower in the LTOT group (–5.47, 95% CI –10.54 to–0.41; p = 0.03) and breathlessness scores improved, although the effect did not persist to 6 months.There was no effect of LTOT on any secondary measure. There was a greater number of deaths in the BMTarm (n = 12 vs. n = 6). Adherence was poor, with only 11% of patients reporting using the oxygenas prescribed.Conclusions: Although the study was significantly underpowered, HOT prescribed for 15 hours per dayand subsequently used for a mean of 5.4 hours per day has no impact on quality of life as measured bythe MLwHF questionnaire score at 6 months. Suggestions for future research include (1) a trial of patientswith severe heart failure randomised to have emergency oxygen supply in the house, supplied by cylindersrather than an oxygen concentrator, powered to detect a reduction in admissions to hospital, and (2) astudy of bed-bound patients with heart failure who are in the last few weeks of life, powered to detectchanges in symptom severity.Trial registration: Current Controlled Trials ISRCTN60260702.Funding: This project was funded by the NIHR Health Technology Assessment programme and will bepublished in full in Health Technology Assessment; Vol. 19, No. 75. See the NIHR Journals Library websitefor further project information