Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial. A randomized trial of IV iron in critical illness

PURPOSE: Both anaemia and allogenic red blood cell transfusion are common and potentially harmful in patients admitted to the intensive care unit. Whilst intravenous iron may decrease anaemia and RBC transfusion requirement, the safety and efficacy of administering iron intravenously to critically ill patients is uncertain. METHODS: The multicentre, randomized, placebo-controlled, blinded Intravenous Iron or Placebo for Anaemia in Intensive Care (IRONMAN) study was designed to test the hypothesis that, in anaemic critically ill patients admitted to the intensive care unit, early administration of intravenous iron, compared with placebo, reduces allogeneic red blood cell transfusion during hospital stay and increases the haemoglobin level at the time of hospital discharge. RESULTS: Of 140 patients enrolled, 70 were assigned to intravenous iron and 70 to placebo. The iron group received 97 red blood cell units versus 136 red blood cell units in the placebo group, yielding an incidence rate ratio of 0.71 [95 % confidence interval (0.43-1.18), P = 0.19]. Overall, median haemoglobin at hospital discharge was significantly higher in the intravenous iron group than in the placebo group [107 (interquartile ratio IQR 97-115) vs. 100 g/L (IQR 89-111), P = 0.02]. There was no significant difference between the groups in any safety outcome. CONCLUSIONS: In patients admitted to the intensive care unit who were anaemic, intravenous iron, compared with placebo, did not result in a significant lowering of red blood cell transfusion requirement during hospital stay. Patients who received intravenous iron had a significantly higher haemoglobin concentration at hospital discharge. The trial was registered at http://www.anzctr.org.au as # ACTRN12612001249842

Improvement of primary care for patients with chronic heart failure: A study protocol for a cluster randomised trial comparing two strategies

<p>Abstract</p> <p>Background</p> <p>Many patients with chronic heart failure (CHF), a common condition with high morbidity and mortality rates, receive treatment in primary care. To improve the management of CHF in primary care, we developed an implementation programme comprised of educational and organisational components, with support by a practice visitor and focus both on drug treatment and lifestyle advice, and on organisation of care within the practice and collaboration with other healthcare providers. Tailoring has been shown to improve the success of implementation programmes, but little is known about what would be best methods for tailoring, specifically with respect to CHF in primary care.</p> <p>Methods/design</p> <p>We describe the study protocol of a cluster randomised controlled trial to examine the effectiveness of tailoring a CHF implementation programme to general practices compared to a standardised way of delivering a programme. The study population will consist of 60 general practitioners (GPs) and the CHF patients they include. GPs are randomised in blocks of four, stratified according to practice size. With a tailored implementation programme GPs prioritise the issues that will form the bases of the support for the practice visits. These may comprise several issues, both educational and organizational.</p> <p>The primary outcome measures are patient's experience of receiving structured primary care for CHF (PACIC, a questionnaire related to the Chronic Care Model), patients' health-related utilities (EQ-5D), and drugs prescriptions using the guideline adherence index. Patients being clustered in practices, multilevel regression analyses will be used to explore the effect of practice size and type of intervention programme. In addition we will examine both changes within groups and differences at follow-up between groups with respect to drug dosages and advice on lifestyle issues. Furthermore, in interviews the feasibility of the programme and goal attainment, organisational changes in CHF care, and formalised cooperation with other disciplines will be assessed.</p> <p>Discussion</p> <p>In the tailoring of the programme we will present the GPs a list with barriers; GPs will assess relevance and possibility to solve these barriers. The list is rigorously developed and tested in various projects. The factors for ordering the barriers are related to the innovation, the healthcare professional, the patient, and the context.</p> <p>CHF patients do not form a homogeneous group. Subgroup analyses will be performed based on the distinction between systolic CHF and CHF with preserved left ventricular function (diastolic CHF).</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN18812755">ISRCTN18812755</a></p

Spatio-Temporal Characteristics of Global Warming in the Tibetan Plateau during the Last 50 Years Based on a Generalised Temperature Zone - Elevation Model

Temperature is one of the primary factors influencing the climate and ecosystem, and examining its change and fluctuation could elucidate the formation of novel climate patterns and trends. In this study, we constructed a generalised temperature zone elevation model (GTEM) to assess the trends of climate change and temporal-spatial differences in the Tibetan Plateau (TP) using the annual and monthly mean temperatures from 1961-2010 at 144 meteorological stations in and near the TP. The results showed the following: (1) The TP has undergone robust warming over the study period, and the warming rate was 0.318°C/decade. The warming has accelerated during recent decades, especially in the last 20 years, and the warming has been most significant in the winter months, followed by the spring, autumn and summer seasons. (2) Spatially, the zones that became significantly smaller were the temperature zones of -6°C and -4°C, and these have decreased 499.44 and 454.26 thousand sq km from 1961 to 2010 at average rates of 25.1% and 11.7%, respectively, over every 5-year interval. These quickly shrinking zones were located in the northwestern and central TP. (3) The elevation dependency of climate warming existed in the TP during 1961-2010, but this tendency has gradually been weakening due to more rapid warming at lower elevations than in the middle and upper elevations of the TP during 1991-2010. The higher regions and some low altitude valleys of the TP were the most significantly warming regions under the same categorizing criteria. Experimental evidence shows that the GTEM is an effective method to analyse climate changes in high altitude mountainous regions

Role of the monocarboxylate transporter MCT1 in the uptake of lactate during active recovery

Purpose We assessed the role of monocarboxylate transporter 1 (MCT1) on lactate clearance during an active recovery after high-intensity exercise, by comparing genetic groups based on the T1470A (rs1049434) MCT1 polymorphism, whose influence on lactate transport has been proven. Methods Sixteen young male elite field hockey players participated in this study. All of them completed two 400 m maximal run tests performed on different days, followed by 40 min of active or passive recovery. Lactate samples were measured immediately after the tests, and at min 10, 20, 30 and 40 of the recoveries. Blood lactate decreases were calculated for each 10-min period. Participants were distributed into three groups according to the T1470A polymorphism (TT, TA and AA). Results TT group had a lower blood lactate decrease than AA group during the 10?20 min period of the active recovery (p = 0.018). This period had the highest blood lactate for the whole sample, significantly differing from the other periods (p ? 0.003). During the passive recovery, lactate declines were constant except for the 0?10-min period (p ? 0.003), suggesting that liver uptake is similar in all the genetic groups, and that the difference seen during the active recovery is mainly due to muscle lactate uptake. Conclusions These differences according to the polymorphic variant T1470A suggest that MCT1 affects the plasma lactate decrease during a crucial period of active recovery, where the maximal lactate amount is cleared (i.e. 10?20 min period)

Effect of ethnomedicinal plants used in folklore medicine in Jordan as antibiotic resistant inhibitors on Escherichia coli

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>occurs naturally in the human gut; however, certain strains that can cause infections, are becoming resistant to antibiotics. Multidrug-resistant <it>E. coli </it>that produce extended-spectrum β lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of urinary tract infections (UTIs) and bloodstream infections may be associated with these community-onsets. This is the first report testing the antibiotic resistance-modifying activity of nineteen Jordanian plants against multidrug-resistant <it>E. coli</it>.</p> <p>Methods</p> <p>The susceptibility of bacterial isolates to antibiotics was tested by determining their minimum inhibitory concentrations (MICs) using a broth microdilution method. Nineteen Jordanian plant extracts (<it>Capparis spinosa </it>L., <it>Artemisia herba-alba Asso, Echinops polyceras </it>Boiss., <it>Gundelia tournefortii </it>L, <it>Varthemia iphionoides </it>Boiss. & Blanche, <it>Eruca sativa Mill</it>., <it>Euphorbia macroclada </it>L., <it>Hypericum trequetrifolium </it>Turra, <it>Achillea santolina </it>L., <it>Mentha longifolia </it>Host, <it>Origanum syriacum </it>L., <it>Phlomis brachydo</it>(Boiss.) Zohary, <it>Teucrium polium </it>L., <it>Anagyris foetida </it>L., <it>Trigonella foenum-graecum </it>L., <it>Thea sinensis </it>L., <it>Hibiscus sabdariffa </it>L., <it>Lepidium sativum </it>L., <it>Pimpinella anisum </it>L.) were combined with antibiotics, from different classes, and the inhibitory effect of the combinations was estimated.</p> <p>Results</p> <p>Methanolic extracts of the plant materials enhanced the inhibitory effects of chloramphenicol, neomycin, doxycycline, cephalexin and nalidixic acid against both the standard strain and to a lesser extent the resistant strain of <it>E. coli</it>. Two edible plant extracts (<it>Gundelia tournefortii L</it>. and <it>Pimpinella anisum L</it>.) generally enhanced activity against resistant strain. Some of the plant extracts like <it>Origanum syriacum </it>L.(Labiateae), <it>Trigonella foenum- graecum </it>L.(Leguminosae), <it>Euphorbia macroclada </it>(Euphorbiaceae) and <it>Hibiscus sabdariffa </it>(Malvaceae) did not enhance the activity of amoxicillin against both standard and resistant <it>E. coli</it>. On the other hand combinations of amoxicillin with other plant extracts used showed variable effect between standard and resistant strains. Plant extracts like <it>Anagyris foetida </it>(Leguminosae) and <it>Lepidium sativum </it>(Umbelliferae) reduced the activity of amoxicillin against the standard strain but enhanced the activity against resistant strains. Three edible plants; Gundelia <it>tournefortii </it>L. (Compositae) <it>Eruca sativa </it>Mill. (Cruciferae), and <it>Origanum syriacum </it>L. (Labiateae), enhanced activity of clarithromycin against the resistant <it>E. coli </it>strain.</p> <p>Conclusion</p> <p>This study probably suggests possibility of concurrent use of these antibiotics and plant extracts in treating infections caused by <it>E. coli </it>or at least the concomitant administration may not impair the antimicrobial activity of these antibiotics.</p

Comparative 3D QSAR study on β1-, β2-, and β3-adrenoceptor agonists

A quantitative structure–activity relationship study of tryptamine-based derivatives of β1-, β2-, and β3-adrenoceptor agonists was conducted using comparative molecular field analysis (CoMFA). Correlation coefficients (cross-validated r2) of 0.578, 0.595, and 0.558 were obtained for the three subtypes, respectively, in three different CoMFA models. All three CoMFA models have different steric and electrostatic contributions, implying different requirements inside the binding cavity. The CoMFA coefficient contour plots of the three models and comparisons among these plots provide clues regarding the main chemical features responsible for the biological activity variations and also result in predictions which correlate very well with the observed biological activity. Based on the analysis, a summary regeospecific description of the requirements for improving β-adrenoceptor subtype selectivity is given

Individual differences in the use of the response scale determine valuations of hypothetical health states: an empirical study

Background. The effects of socio-demographic characteristics of the respondent, including age, on valuation scores of hypothetical health states remain inconclusive. Therefore, we analyzed data from a study designed to discriminate between the effects of respondents' age and time preference on valuations of health states to gain insight in the contribution of individual response patterns to the variance in valuation scores. Methods. A total of 212 respondents from three age g

Physician and Patient Predictors of Evidence-Based Prescribing in Heart Failure: A Multilevel Study

BACKGROUND: The management of patients with heart failure (HF) needs to account for changeable and complex individual clinical characteristics. The use of renin angiotensin system inhibitors (RAAS-I) to target doses is recommended by guidelines. But physicians seemingly do not sufficiently follow this recommendation, while little is known about the physician and patient predictors of adherence. METHODS: To examine the coherence of primary care (PC) physicians' knowledge and self-perceived competencies regarding RAAS-I with their respective prescribing behavior being related to patient-associated barriers. Cross-sectional follow-up study after a randomized medical educational intervention trial with a seven month observation period. PC physicians (n = 37) and patients with systolic HF (n = 168) from practices in Baden-Wuerttemberg. Measurements were knowledge (blueprint-based multiple choice test), self-perceived competencies (questionnaire on global confidence in the therapy and on frequency of use of RAAS-I), and patient variables (age, gender, NYHA functional status, blood pressure, potassium level, renal function). Prescribing was collected from the trials' documentation. The target variable consisted of ≥50% of recommended RAAS-I dosage being investigated by two-level logistic regression models. RESULTS: Patients (69% male, mean age 68.8 years) showed symptomatic and objectified left ventricular (NYHA II vs. III/IV: 51% vs. 49% and mean LVEF 33.3%) and renal (GFR<50%: 22%) impairment. Mean percentage of RAAS-I target dose was 47%, 59% of patients receiving ≥50%. Determinants of improved prescribing of RAAS-I were patient age (OR 0.95, CI 0.92-0.99, p = 0.01), physician's global self-confidence at follow-up (OR 1.09, CI 1.02-1.05, p = 0.01) and NYHA class (II vs. III/IV) (OR 0.63, CI 0.38-1.05, p = 0.08). CONCLUSIONS: A change in physician's confidence as a predictor of RAAS-I dose increase is a new finding that might reflect an intervention effect of improved physicians' intention and that might foster novel strategies to improve safe evidence-based prescribing. These should include targeting knowledge, attitudes and skills