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1.
Paolo Palma Maria Luisa Romiti Carla Montesano Veronica Santilli Nadia Mora Angela Aquilani Stefania Dispinseri Hyppolite K. Tchidjou Marco Montano Lars E. Eriksson Stefania Baldassari Stefania Bernardi Gabriella Scarlatti Britta Wahren Paolo Rossi 《PloS one》2013,8(11)
Subjects
Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm3.Intervention
Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96.Results
Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A.Conclusions
The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population.Trial registration
clinicaltrialsregister.eu _2007-002359-18 IT 相似文献2.
Dany Morisset Petra Kralj Novak Darko Zupani? Kristina Gruden Nada Lavra? Jana ?el 《BMC bioinformatics》2014,15(1)
Background
With the increasing pace of new Genetically Modified Organisms (GMOs) authorized or in pipeline for commercialization worldwide, the task of the laboratories in charge to test the compliance of food, feed or seed samples with their relevant regulations became difficult and costly. Many of them have already adopted the so called "matrix approach" to rationalize the resources and efforts used to increase their efficiency within a limited budget. Most of the time, the "matrix approach" is implemented using limited information and some proprietary (if any) computational tool to efficiently use the available data.Results
The developed GMOseek software is designed to support decision making in all the phases of routine GMO laboratory testing, including the interpretation of wet-lab results. The tool makes use of a tabulated matrix of GM events and their genetic elements, of the laboratory analysis history and the available information about the sample at hand. The tool uses an optimization approach to suggest the most suited screening assays for the given sample. The practical GMOseek user interface allows the user to customize the search for a cost-efficient combination of screening assays to be employed on a given sample. It further guides the user to select appropriate analyses to determine the presence of individual GM events in the analyzed sample, and it helps taking a final decision regarding the GMO composition in the sample. GMOseek can also be used to evaluate new, previously unused GMO screening targets and to estimate the profitability of developing new GMO screening methods.Conclusion
The presented freely available software tool offers the GMO testing laboratories the possibility to select combinations of assays (e.g. quantitative real-time PCR tests) needed for their task, by allowing the expert to express his/her preferences in terms of multiplexing and cost. The utility of GMOseek is exemplified by analyzing selected food, feed and seed samples from a national reference laboratory for GMO testing and by comparing its performance to existing tools which use the matrix approach. GMOseek proves superior when tested on real samples in terms of GMO coverage and cost efficiency of its screening strategies, including its capacity of simple interpretation of the testing results.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-258) contains supplementary material, which is available to authorized users. 相似文献3.
Jorge Aparicio Carmen García-Mora Marta Martín Ma Lourdes Petriz Jaime Feliu Ma Elena Sánchez-Santos Juan Ramón Ayuso David Fuster Carlos Conill Joan Maurel 《PloS one》2014,9(1)
Purpose
Sorafenib, an oral inhibitor of B-raf, VEGFR2, and PDGFR2-beta, acts against pancreatic cancer in preclinical models. Due to the radio-sensitization activity of both sorafenib and gemcitabine, we designed a multicenter, phase I trial to evaluate the safety profile and the recommended dose of this combination used with concomitant radiation therapy.Methods
Patients with biopsy-proven, unresectable pancreatic adenocarcinoma (based on vascular invasion detected by computed tomography) were treated with gemcitabine (300 mg/m2 i.v. weekly ×5 weeks) concurrently with radiation therapy (45 Gy in 25 fractions) and sorafenib (escalated doses in a 3+3 design, from 200 to 800 mg/day). Radiation portals included the primary tumor but not the regional lymph nodes. Patients with planning target volumes (PTV) over 500 cc were excluded. Cases not progressing during chemoradiation were allowed to continue with sorafenib until disease progression.Results
Twelve patients were included. Three patients received 200 mg/day, 6 received 400 mg/day, and 3 received 800 mg/day; PTVs ranged from 105 to 500 cc. No dose-limiting toxicities occurred. The most common grade 2 toxicities were fatigue, neutropenia, nausea, and raised serum transaminases. Treatment was discontinued in one patient because of a reversible posterior leukoencephalopathy. There were no treatment-related deaths.Conclusion
The addition of sorafenib to concurrent gemcitabine and radiation therapy showed a favorable safety profile in unresectable pancreatic adenocarcinoma. A dose of 800 mg/day is recommended for phase II evaluation.Trial Registration
EudraCT 2007-003211-31 ClinicalTrials.gov 00789763 相似文献4.
Background
In order to understand how biological systems function it is necessary to determine the interactions and associations between proteins. Gene fusion prediction is one approach to detection of such functional relationships. Its use is however known to be problematic in higher eukaryotic genomes due to the presence of large homologous domain families. Here we introduce CODA (Co-Occurrence of Domains Analysis), a method to predict functional associations based on the gene fusion idiom.Methodology/Principal Findings
We apply a novel scoring scheme which takes account of the genome-specific size of homologous domain families involved in fusion to improve accuracy in predicting functional associations. We show that CODA is able to accurately predict functional similarities in human with comparison to state-of-the-art methods and show that different methods can be complementary. CODA is used to produce evidence that a currently uncharacterised human protein may be involved in pathways related to depression and that another is involved in DNA replication.Conclusions/Significance
The relative performance of different gene fusion methodologies has not previously been explored. We find that they are largely complementary, with different methods being more or less appropriate in different genomes. Our method is the only one currently available for download and can be run on an arbitrary dataset by the user. The CODA software and datasets are freely available from ftp://ftp.biochem.ucl.ac.uk/pub/gene3d_data/v6.1.0/CODA/. Predictions are also available via web services from http://funcnet.eu/. 相似文献5.
Marek Lommatzsch Ulrike Kraeft Laura Troebs Katharina Garbe Andrea Bier Paul Stoll Sebastian Klammt Michael Kuepper Kai Bratke Johann Christian Virchow 《Respiratory research》2013,14(1):114
Background
Myeloid Dendritic cells are key drivers of inflammation in smoke-related lung diseases, whereas plasmacytoid DCs play a crucial role in the defense against infections. Effects of inhaled corticosteroids (ICS) on airway DCs in smokers are unknown.Methods
In this randomized, double-blind, placebo-controlled clinical trial, 45 active cigarette smokers inhaled placebo, fluticasone or fluticasone plus salmeterol twice daily for 4 weeks. Bronchoalveolar lavage fluid DCs were analyzed using four-color flow cytometry before and after the inhalation period. In addition, fluticasone effects were tested on T-cell proliferation in co-cultures with blood myeloid DCs from smokers.Results
Inhalation of fluticasone plus salmeterol, but not fluticasone alone or placebo, reduced endobronchial concentrations of myeloid DCs (median decrease: 24%), macrophages (median decrease: 26%) and neutrophils (median decrease: 76%). In contrast, fluticasone reduced plasmacytoid DC concentrations independently of salmeterol. There were no changes in the expression of function-associated surface molecules on myeloid DC (such as CD1a, Langerin, BDCA-1, CD83 or CCR5) in all groups after treatment. Fluticasone (either alone or in combination with salmeterol) suppressed T-cell proliferation in co-cultures with blood myeloid DCs from smokers.Conclusions
Resistance to ICS monotherapy in smokers might in part be due to lacking effects on airway myeloid DCs, whereas the increased risk for infections during ICS therapy could be attributable to a reduction in plasmacytoid DCs. Combination therapy of fluticasone with salmeterol is associated with a reduction in airway myeloid DCs, but also airway macrophages and neutrophils.Trial registration
Registered at ClinicalTrials.gov (identifier: ) and the European Clinical Trial Database, EudraCT (identifier: NCT009083622009-009459-40). 相似文献6.
Background
Muscle spindles endings are extremely sensitive to externally applied vibrations, and under such circumstances they convey proprioceptive inflows to the central nervous system that modulate the spinal reflexes excitability or the muscle responses elicited by postural perturbations. The aim of this pilot study is to test the feasibility and effectiveness of a balance training program in association with a wearable proprioceptive stabilizer (Equistasi) that emits focal mechanical vibrations in patients with PD.Methods
Forty patients with PD were randomly divided in two groups wearing an active or inactive device. All the patients received a 2-month intensive program of balance training. Assessments were performed at baseline, after the rehabilitation period (T1), and two more months after (T2). Posturographic measures were used as primary endpoint; secondary measures of outcome included the number of falls and several clinical scales for balance and quality of life.Results
Both groups improved at the end of the rehabilitation period and we did not find significant between-group differences in any of the principal posturographic measures with the exception of higher sway area and limit of stability on the instrumental functional reach test during visual deprivation at T1 in the Equistasi group. As for the secondary outcome, we found an overall better outcome in patients enrolled in the Equistasi group: 1) significant improvement at T1 on Berg Balance Scale (+45.0%, p = .026), Activities-specific Balance Confidence (+83.7, p = .004), Falls Efficacy Scale (−33.3%, p = .026) and PDQ-39 (−48.8%, p = .004); 2) sustained improvement at T2 in terms of UPDRS-III, Berg Balance Scales, Time Up and Go and PDQ-39; 3) significant and sustained reduction of the falls rate.Conclusions
This pilot trial shows that a physiotherapy program for training balance in association with focal mechanical vibration exerted by a wearable proprioceptive stabilizer might be superior than rehabilitation alone in improving patients’ balance.Trial Registration
EudraCT 2013-003020-36 and ClinicalTrials.gov (number not assigned) 相似文献7.
Thorsten Fuereder Volker Wacheck Sabine Strommer Peter Horak Marion Gerschpacher Wolfgang Lamm Danijel Kivaranovic Michael Krainer 《PloS one》2014,9(4)
Background
Endothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC) patients.Patients and methods
Chemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d), in combination with docetaxel (75 mg/m2) or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy.Results
A total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable) counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001). However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30%) patients responded to therapy with a 50% PSA decline, while 9 (64%) patients showed a PSA decline in the combination group (n.s.). The median PFS in the docetaxel monotherapy group was 3.1 months (2.6–3.6 months, 95% CI) and 6.2 months (4.9–7.4 months, 95% CI; p = 0.062) in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable.Conclusion
In summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However, docetaxel/sunitinib therapy resulted in a better response in terms of PSA decline and a trend towards improved PFS.Trial Registery
clinicaltrialsregister.eu EudraCT 2007-003705-27 相似文献8.
9.
GMDD: a database of GMO detection methods 总被引:1,自引:0,他引:1
Wei Dong Litao Yang Kailin Shen Banghyun Kim Gijs A Kleter Hans JP Marvin Rong Guo Wanqi Liang Dabing Zhang 《BMC bioinformatics》2008,9(1):260
Background
Since more than one hundred events of genetically modified organisms (GMOs) have been developed and approved for commercialization in global area, the GMO analysis methods are essential for the enforcement of GMO labelling regulations. Protein and nucleic acid-based detection techniques have been developed and utilized for GMOs identification and quantification. However, the information for harmonization and standardization of GMO analysis methods at global level is needed. 相似文献10.
G?khan Yava? Mehmet Koyutürk Meetha P Gould Sarah McMahon Thomas LaFramboise 《BMC genomics》2014,15(1)
Background
With the advent of paired-end high throughput sequencing, it is now possible to identify various types of structural variation on a genome-wide scale. Although many methods have been proposed for structural variation detection, most do not provide precise boundaries for identified variants. In this paper, we propose a new method, Distribution Based detection of Duplication Boundaries (DB2), for accurate detection of tandem duplication breakpoints, an important class of structural variation, with high precision and recall.Results
Our computational experiments on simulated data show that DB2 outperforms state-of-the-art methods in terms of finding breakpoints of tandem duplications, with a higher positive predictive value (precision) in calling the duplications’ presence. In particular, DB2’s prediction of tandem duplications is correct 99% of the time even for very noisy data, while narrowing down the space of possible breakpoints within a margin of 15 to 20 bps on the average. Most of the existing methods provide boundaries in ranges that extend to hundreds of bases with lower precision values. Our method is also highly robust to varying properties of the sequencing library and to the sizes of the tandem duplications, as shown by its stable precision, recall and mean boundary mismatch performance. We demonstrate our method’s efficacy using both simulated paired-end reads, and those generated from a melanoma sample and two ovarian cancer samples. Newly discovered tandem duplications are validated using PCR and Sanger sequencing.Conclusions
Our method, DB2, uses discordantly aligned reads, taking into account the distribution of fragment length to predict tandem duplications along with their breakpoints on a donor genome. The proposed method fine tunes the breakpoint calls by applying a novel probabilistic framework that incorporates the empirical fragment length distribution to score each feasible breakpoint. DB2 is implemented in Java programming language and is freely available at http://mendel.gene.cwru.edu/laframboiselab/software.php.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-175) contains supplementary material, which is available to authorized users. 相似文献11.
Hanneke de Waal Cornelis J. Stam Marieke M. Lansbergen Rico L. Wieggers Patrick J. G. H. Kamphuis Philip Scheltens Fernando Maestú Elisabeth C. W. van Straaten 《PloS one》2014,9(1)
Background
Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials.Objective
To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD.Design
A 24-week randomised, controlled, double-blind, parallel-group, multi-country study.Participants
179 drug-naïve mild AD patients who participated in the Souvenir II study.Intervention
Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks.Outcome
In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance.Results
The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance.Conclusions
The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions.Trial registration
Dutch Trial Register NTR1975. 相似文献12.
13.
Background
Computational biology contributes to a variety of areas related to life sciences and, due to the growing impact of translational medicine - the scientific approach to medicine in tight relation with basic science -, it is becoming an important player in clinical-related areas. In this study, we use computation methods in order to improve our understanding of the complex interactions that occur between molecules related to Rheumatoid Arthritis (RA).Methodology
Due to the complexity of the disease and the numerous molecular players involved, we devised a method to construct a systemic network of interactions of the processes ongoing in patients affected by RA. The network is based on high-throughput data, refined semi-automatically with carefully curated literature-based information. This global network has then been topologically analysed, as a whole and tissue-specifically, in order to translate the experimental molecular connections into topological motifs meaningful in the identification of tissue-specific markers and targets in the diagnosis, and possibly in the therapy, of RA.Significance
We find that some nodes in the network that prove to be topologically important, in particular AKT2, IL6, MAPK1 and TP53, are also known to be associated with drugs used for the treatment of RA. Importantly, based on topological consideration, we are also able to suggest CRKL as a novel potentially relevant molecule for the diagnosis or treatment of RA. This type of finding proves the potential of in silico analyses able to produce highly refined hypotheses, based on vast experimental data, to be tested further and more efficiently. As research on RA is ongoing, the present map is in fieri, despite being -at the moment- a reflection of the state of the art. For this reason we make the network freely available in the standardised and easily exportable .xml CellDesigner format at ‘www.picb.ac.cn/ClinicalGenomicNTW/temp.html’ and ‘www.celldesigner.org’. 相似文献14.
Martin Floer Erwin Biecker Rüdiger Fitzlaff Hermann R?ming Detlev Ameis Achim Heinecke Steffen Kunsch Volker Ellenrieder Philipp Str?bel Michael Schepke Tobias Meister 《PloS one》2014,9(12)
Objectives
The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC).Methods
This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. Participants: 500 patients (235 males, median age 64[IQR 54–73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR).Results
The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29–41%] vs. 20.7%[95%CI 15–26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01–1.05), male sex (OR 1.74; 95%CI 1.10–2.73), withdrawal time (OR 1.16; 95%CI 1.05–1.30), procedure time (OR 1.07; 95%CI 1.04–1.10), colon cleanliness (OR 0.60; 95%CI 0.39–0.94) and use of Endocuff (OR 2.09; 95%CI 1.34–3.27) were independent predictors of adenoma detection rates.Conclusions
EC increases the adenoma detection rate by 14.7%(95%CI 6.9–22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas.Trial Registration
ClinicalTrials.gov . NCT02034929相似文献15.
Uzma N. Sarwar Laura Novik Mary E. Enama Sarah A. Plummer Richard A. Koup Martha C. Nason Robert T. Bailer Adrian B. McDermott Mario Roederer John R. Mascola Julie E. Ledgerwood Barney S. Graham the VRC study team 《PloS one》2014,9(9)
Background
Needle-free delivery improves the immunogenicity of DNA vaccines but is also associated with more local reactogenicity. Here we report the first comparison of Biojector and needle administration of a candidate rAd5 HIV vaccine.Methods
Thirty-one adults, 18–55 years, 20 naive and 11 prior rAd5 vaccine recipients were randomized to receive single rAd5 vaccine via needle or Biojector IM injection at 1010 PU in a Phase I open label clinical trial. Solicited reactogenicity was collected for 5 days; clinical safety and immunogenicity follow-up was continued for 24 weeks.Results
Overall, injections by either method were well tolerated. There were no serious adverse events. Frequency of any local reactogenicity was 16/16 (100%) for Biojector compared to 11/15 (73%) for needle injections. There was no difference in HIV Env-specific antibody response between Biojector and needle delivery. Env-specific antibody responses were more than 10-fold higher in subjects receiving a booster dose of rAd5 vaccine than after a single dose delivered by either method regardless of interval between prime and boost.Conclusions
Biojector delivery did not improve antibody responses to the rAd5 vaccine compared to needle administration. Homologous boosting with rAd5 gene-based vectors can boost insert-specific antibody responses despite pre-existing vector-specific immunity.Trial Registration
Clinicaltrials.gov NCT00709605 NCT00709605相似文献16.
17.
Study Objectives
To investigate the effect of an eight-week, home-based, personalized, computerized cognitive training program on sleep quality and cognitive performance among older adults with insomnia.Design
Participants (n = 51) were randomly allocated to a cognitive training group (n = 34) or to an active control group (n = 17). The participants in the cognitive training group completed an eight-week, home-based, personalized, computerized cognitive training program, while the participants in the active control group completed an eight-week, home-based program involving computerized tasks that do not engage high-level cognitive functioning. Before and after training, all participants'' sleep was monitored for one week by an actigraph and their cognitive performance was evaluated.Setting
Community setting: residential sleep/performance testing facility.Participants
Fifty-one older adults with insomnia (aged 65–85).Interventions
Eight weeks of computerized cognitive training for older adults with insomnia.Results
Mixed models for repeated measures analysis showed between-group improvements for the cognitive training group on both sleep quality (sleep onset latency and sleep efficiency) and cognitive performance (avoiding distractions, working memory, visual memory, general memory and naming). Hierarchical linear regressions analysis in the cognitive training group indicated that improved visual scanning is associated with earlier advent of sleep, while improved naming is associated with the reduction in wake after sleep onset and with the reduction in number of awakenings. Likewise the results indicate that improved “avoiding distractions” is associated with an increase in the duration of sleep. Moreover, the results indicate that in the active control group cognitive decline observed in working memory is associated with an increase in the time required to fall asleep.Conclusions
New learning is instrumental in promoting initiation and maintenance of sleep in older adults with insomnia. Lasting and personalized cognitive training is particularly indicated to generate the type of learning necessary for combined cognitive and sleep enhancements in this population.Trial Registration
ClinicalTrials.gov NCT00901641http://clinicaltrials.gov/ct2/show/NCT00901641 相似文献18.
Ted Wun Lori Styles Laura DeCastro Marilyn J. Telen Frans Kuypers Anthony Cheung William Kramer Henry Flanner Seungshin Rhee John L. Magnani Helen Thackray 《PloS one》2014,9(7)
Background
Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease.Methods
We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions.Results
The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied.Conclusions
GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM), leukocyte activation (MAC-1, LFA-1, PM aggregates) and the coagulation cascade (tissue factor, thrombin-antithrombin complexes). Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing.Trial Registration
ClinicalTrials.gov NCT00911495相似文献19.
Christine Soong Bochra Kurabi David Wells Lesley Caines Matthew W. Morgan Rebecca Ramsden Chaim M. Bell 《PloS one》2014,9(11)
Importance
The transition from hospital to home can expose patients to adverse events during the post discharge period. Post discharge care including phone calls may provide support for patients returning home but the impact on care transitions is unknown.Objective
To examine the effect of a 72-hour post discharge phone call on the patient''s transition of care experience.Design
Cluster-randomized control trial.Setting
Urban, academic medical center.Participants
General medical patients age 18 and older discharged home after hospitalization.Main Outcomes and Measures
Primary outcome measure was the Care Transition Measure (CTM-3) score, a validated measure of the quality of care transitions. Secondary measures included self-reported adherence to medication and follow up plans, and 30-day composite of emergency department (ED) visits and hospital readmission.Results
328 patients were included in the study over an 6-month period. 114 (69%) received a post discharge phone call, and 214 of all patients in the study completed the follow outcome survey (65% response rate). A small difference in CTM-3 scores was observed between the intervention and control groups (1.87 points, 95% CI 0.47–3.27, p = 0.01). Self-reported adherence to treatment plans, ED visits, and emergency readmission rates were similar between the two groups (odds ratio 0.57, 95% CI 0.13–2.45, 1.20, 95% CI 0.61–2.37, and 1.18, 95% CI 0.53–2.61, respectively).Conclusions and Relevance
A single post discharge phone call had a small impact on the quality of care transitions and no effect on hospital utilization. Higher intensity post discharge support may be required to improve the patient experience upon returning home.Trial Registration
ClinicalTrials.gov NCT01580774相似文献20.