Hemostasis during low molecular weight heparin anticoagulation for continuous venovenous hemofiltration: a randomized cross-over trial comparing two hemofiltration rates

INTRODUCTION: Renal insufficiency increases the half-life of low molecular weight heparins (LMWHs). Whether continuous venovenous hemofiltration (CVVH) removes LMWHs is unsettled. We studied hemostasis during nadroparin anticoagulation for CVVH, and explored the implication of the endogenous thrombin potential (ETP). METHODS: This cross-over study, performed in a 20-bed teaching hospital ICU, randomized non-surgical patients with acute kidney injury requiring nadroparin for CVVH to compare hemostasis between two doses of CVVH: filtrate flow was initiated at 4 L/h and converted to 2 L/h after 60 min in group 1, and vice versa in group 2. Patients received nadroparin 2850 IU i.v., followed by 380 IU/h continuously in the extracorporeal circuit. After baseline sampling, ultrafiltrate, arterial (art) and postfilter (PF) blood was taken for hemostatic markers after 1 h, and 15 min, 6 h, 12 h and 24 h after converting filtrate flow. We compared randomized groups, and 'early circuit clotting' to 'normal circuit life' groups. RESULTS: Fourteen patients were randomized, seven to each group. Despite randomization, group 1 had higher SOFA scores (median 14 (IQR 11-15) versus 9 (IQR 5-9), p = 0.004). Anti-Xa art activity peaked upon nadroparin bolus and declined thereafter (p = 0.05). Anti-Xa PF did not change in time. Anti-Xa activity was not detected in ultrafiltrate. Medians of all anti-Xa samples were lower in group 1 (anti-Xa art 0.19 (0.12-0.37) vs. 0.31 (0.23-0.52), p = 0.02; anti-Xa PF 0.34 (0.25-0.44) vs. 0.51 (0.41-0.76), p = 0.005). After a steep decline, arterial ETPAUC tended to increase (p = 0.06), opposite to anti-Xa, while postfilter ETPAUC increased (p = 0.001). Median circuit life was 24.5 h (IQR 12-37 h). Patients with 'short circuit life' had longer baseline prothrombin time (PTT), activated thromboplastin time (aPTT), lower ETP, higher thrombin-antithrombin complexes (TAT) and higher SOFA scores; during CVVH, anti-Xa, and platelets were lower; PTT, aPTT, TAT and D-dimers were longer/higher and ETP was slower and depressed. CONCLUSIONS: We found no accumulation and no removal of LMWH activity during CVVH. However, we found that early circuit clotting was associated with more severe organ failure, prior systemic thrombin generation with consumptive coagulopathy, heparin resistance and elevated extracorporeal thrombin generation. ETP integrates these complex effects on the capacity to form thrombin. TRIAL REGISTRATION : Clinicaltrials.gov ID NCT00965328

Tetrastigma loheri Gagnep. Vitaceae

Tetrastigma philippinense Merr. (POWO 2020

Knowledge, attitudes and practice survey about antimicrobial resistance and prescribing among physicians in a hospital setting in Lima, Peru

BACKGROUND: Misuse of antimicrobials (AMs) and antimicrobial resistance (AMR) are global concerns. The present study evaluated knowledge, attitudes and practices about AMR and AM prescribing among medical doctors in two large public hospitals in Lima, Peru, a middle-income country. METHODS: Cross-sectional study using a self-administered questionnaire RESULTS: A total of 256 participants completed the questionnaire (response rate 82%). Theoretical knowledge was good (mean score of 6 +/- 1.3 on 7 questions) in contrast to poor awareness (< 33%) of local AMR rates of key-pathogens. Participants strongly agreed that AMR is a problem worldwide (70%) and in Peru (65%), but less in their own practice (22%). AM overuse was perceived both for the community (96%) and the hospital settings (90%). Patients' pressure to prescribing AMs was considered as contributing to AM overuse in the community (72%) more than in the hospital setting (50%). Confidence among AM prescribing was higher among attending physicians (82%) compared to residents (30%, p < 0.001%). Sources of information considered as very useful/useful included pocket-based AM prescribing guidelines (69%) and internet sources (62%). Fifty seven percent of participants regarded AMs in their hospitals to be of poor quality. Participants requested more AM prescribing educational programs (96%) and local AM guidelines (92%). CONCLUSIONS: This survey revealed topics to address during future AM prescribing interventions such as dissemination of information about local AMR rates, promoting confidence in the quality of locally available AMs, redaction and dissemination of local AM guidelines and addressing the general public, and exploring the possibilities of internet-based training

Differentially Evolved Genes of Salmonella Pathogenicity Islands: Insights into the Mechanism of Host Specificity in Salmonella

BACKGROUND: The species Salmonella enterica (S. enterica) includes many serovars that cause disease in avian and mammalian hosts. These serovars differ greatly in their host range and their degree of host adaptation. The host specificity of S. enterica serovars appears to be a complex phenomenon governed by multiple factors acting at different stages of the infection process, which makes identification of the cause/s of host specificity solely by experimental methods difficult. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have employed a molecular evolution and phylogenetics based approach to identify genes that might play important roles in conferring host specificity to different serovars of S. enterica. These genes are 'differentially evolved' in different S. enterica serovars. This list of 'differentially evolved' genes includes genes that encode translocon proteins (SipD, SseC and SseD) of both Salmonella pathogenicity islands 1 and 2 encoded type three secretion systems, sptP, which encodes an effector protein that inhibits the mitogen-activated protein kinase pathway of the host cell, and genes which encode effector proteins (SseF and SifA) that are important in placing the Salmonella-containing vacuole in a juxtanuclear position. CONCLUSIONS/SIGNIFICANCE: Analysis of known functions of these 'differentially evolved genes' indicates that the products of these genes directly interact with the host cell and manipulate its functions and thereby confer host specificity, at least in part, to different serovars of S. enterica that are considered in this study

A needs assessment study for optimising prescribing practice in secondary care junior doctors: the Antibiotic Prescribing Education among Doctors (APED).

BACKGROUND: Appropriate antimicrobial prescribing is essential for patient care, yet up to half of antimicrobial prescriptions written in the UK are sub-optimal. Improving prescriber education has recently been promoted as a mechanism to optimise antimicrobial use, but identification of key learning objectives to facilitate this is so far lacking. Using qualitative methods we investigated junior doctor knowledge, attitudes, and behaviours around antimicrobial prescribing to identify key areas to address in future educational programmes. METHODS: A cross-sectional survey of qualified doctors in training in West London was undertaken exploring antimicrobial prescribing practices and educational needs. RESULTS: Among 140 junior doctors from 5 London hospitals, a third (34 %) reported prescribing primarily unsupervised, and two thirds (67 %) reported difficulties obtaining prescribing support outside of hours. 20 % stated not feeling confident in writing an antimicrobial prescription, but confidence was increased through having confirmatory diagnostic results (24) and obtaining advice from a senior doctor (26 %); whether this senior was from their own specialty, or an infection-specialist, varied significantly (p < 0.01) by experience. Only a small percentage (5-13 %; depending on number of years post-qualification) of participants stated their previous antimicrobial education was effective. 60 % of those in their first year post qualification reported wanting further education in antimicrobial prescribing, rising to 74 % among more experienced junior doctors. Specific areas of educational need identified were (i) principles of antimicrobial prescribing, (ii) diagnosis of infections, (iii) clinical review of patients with infections, (iv) prescribing in the context of antimicrobial resistance, and (v) laboratory testing and test results. CONCLUSIONS: A significant proportion of junior doctors report lone prescribing of antimicrobials in the context of low self-perceived confidence and knowledge in this field, and frequent difficulty in accessing help when necessary. Innovative training, targeting five specific areas identified through this needs assessment, is urgently needed by junior doctors practising in secondary care

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania

Background Virological response to antiretroviral treatment (ART) in rural Africa is poorly described. We examined virological efficacy and emergence of drug resistance in adults receiving first-line ART for up to 4 years in rural Tanzania. Methods Haydom Lutheran Hospital has provided ART to HIV-infected patients since October 2003. A combination of stavudine or zidovudine with lamivudine and either nevirapine or efavirenz is the standard first-line regimen. Nested in a longitudinal cohort study of patients consecutively starting ART, we carried out a cross-sectional virological efficacy survey between November 2007 and June 2008. HIV viral load was measured in all adults who had completed at least 6 months first-line ART, and genotypic resistance was determined in patients with viral load >1000 copies/mL. Results Virological response was measured in 212 patients, of whom 158 (74.5%) were women, and median age was 35 years (interquartile range [IQR] 29–43). Median follow-up time was 22.3 months (IQR 14.0–29.9). Virological suppression, defined as <400 copies/mL, was observed in 187 patients (88.2%). Overall, prevalence of ≥1 clinically significant resistance mutation was 3.9, 8.4, 16.7 and 12.5% in patients receiving ART for 1, 2, 3 and 4 years, respectively. Among those successfully genotyped, the most frequent mutations were M184I/V (64%), conferring resistance to lamivudine, and K103N (27%), Y181C (27%) and G190A (27%), conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), whereas 23% had thymidine analogue mutations (TAMs), associated with cross-resistance to all nucleoside reverse transcriptase inhibitors (NRTIs). Dual-class resistance, i.e. resistance to both NRTIs and NNRTIs, was found in 64%. Conclusion Virological suppression rates were good up to 4 years after initiating ART in a rural Tanzanian hospital. However, drug resistance increased with time, and dual-class resistance was common, raising concerns about exhaustion of future antiretroviral drug options. This study might provide a useful forecast of drug resistance and demand for second-line antiretroviral drugs in rural Africa in the coming years

[(18)F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for high-grade glioma

BACKGROUND: To compare morphological gross tumor volumes (GTVs), defined as pre- and postoperative gadolinium enhancement on T1-weighted magnetic resonance imaging to biological tumor volumes (BTVs), defined by the uptake of (18)F fluoroethyltyrosine (FET) for the radiotherapy planning of high-grade glioma, using a dedicated positron emission tomography (PET)-CT scanner equipped with three triangulation lasers for patient positioning. METHODS: Nineteen patients with malignant glioma were included into a prospective protocol using FET PET-CT for radiotherapy planning. To be eligible, patients had to present with residual disease after surgery. Planning was performed using the clinical target volume (CTV = GTV union or logical sum BTV) and planning target volume (PTV = CTV + 20 mm). First, the interrater reliability for BTV delineation was assessed among three observers. Second, the BTV and GTV were quantified and compared. Finally, the geometrical relationships between GTV and BTV were assessed. RESULTS: Interrater agreement for BTV delineation was excellent (intraclass correlation coefficient 0.9). Although, BTVs and GTVs were not significantly different (p = 0.9), CTVs (mean 57.8 +/- 30.4 cm(3)) were significantly larger than BTVs (mean 42.1 +/- 24.4 cm(3); p &lt; 0.01) or GTVs (mean 38.7 +/- 25.7 cm(3); p &lt; 0.01). In 13 (68%) and 6 (32%) of 19 patients, FET uptake extended &gt;or= 10 and 20 mm from the margin of the gadolinium enhancement. CONCLUSION: Using FET, the interrater reliability had excellent agreement for BTV delineation. With FET PET-CT planning, the size and geometrical location of GTVs and BTVs differed in a majority of patients

Spared unconscious influences of spatial memory in diencephalic amnesia

Spatial memory is crucial to our daily lives and in part strongly depends on automatic, implicit memory processes. This study investigates the neurocognitive basis of conscious and unconscious influences of object–location memory in amnesic patients with Korsakoff’s syndrome (N = 23) and healthy controls (N = 18) using a process-dissociation procedure in a computerized spatial memory task. As expected, the patients performed substantially worse on the conscious memory measures but showed even slightly stronger effects of unconscious influences than the controls. Moreover, a delayed test administered after 1 week revealed a strong decline in conscious influences in the patients, while unconscious influences were not affected. The presented results suggest that conscious and unconscious influences of spatial memory can be clearly dissociated in Korsakoff’s syndrome