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1.
Morten Würtz Peter H. Nissen Erik Lerkevang Grove Steen Dalby Kristensen Anne-Mette Hvas 《PloS one》2014,9(10)
Background
Platelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms determine platelet aggregation in aspirin-treated individuals.Aim
To identify platelet-related single nucleotide polymorphisms (SNPs) influencing platelet aggregation during aspirin treatment. Furthermore, we explored to what extent changes in cyclooxygenase-1 activity and platelet activation may explain such influence.Methods
We included 985 Danish patients with stable coronary artery disease treated with aspirin 75 mg/day mono antiplatelet therapy. Patients were genotyped for 16 common SNPs in platelet-related genes using standard PCR-based methods (TaqMan). Platelet aggregation was evaluated by whole blood platelet aggregometry employing Multiplate Analyzer (agonists: arachidonic acid and collagen) and VerifyNow Aspirin. Serum thromboxane B2 was measured to confirm aspirin adherence and was used as a marker of cyclooxygenase-1 activity. Soluble P-selectin was used as marker of platelet activation. Platelet aggregation, cyclooxygenase-1 activity, and platelet activation were compared across genotypes in adjusted analyses.Results
The A-allele of the rs12041331 SNP in the platelet endothelial aggregation receptor-1 (PEAR1) gene was associated with reduced platelet aggregation and increased platelet activation, but not with cyclooxygenase-1 activity. Platelet aggregation was unaffected by the other SNPs analyzed.Conclusion
A common genetic variant in PEAR1 (rs12041331) reproducibly influenced platelet aggregation in aspirin-treated patients with coronary artery disease. The exact biological mechanism remains elusive, but the effect of this polymorphism may be related to changes in platelet activation. Furthermore, 14 SNPs previously suggested to influence aspirin efficacy were not associated with on-aspirin platelet aggregation.Clinical Trial Registration
ClinicalTrials.gov NCT01383304相似文献2.
Suzanne C. Gerretsen M. Eline Kooi Alfons G. Kessels Simon Schalla Marcus Katoh Rob J. van der Geest Warren J. Manning Johannes Waltenberger Jos M. A. van Engelshoven Rene M. Botnar Tim Leiner 《PloS one》2010,5(9)
Background
Magnetic resonance imaging (MRI) is sensitive to early atherosclerotic changes such as positive remodeling in patients with coronary artery disease (CAD). We assessed prevalence, quality, and extent of coronary atherosclerosis in a group of healthy subjects compared to patients with confirmed CAD.Methodology
Twenty-two patients with confirmed CAD (15M, 7F, mean age 60.4±10.4 years) and 26 healthy subjects without history of CAD (11M, 15F, mean age 56.1±4.4 years) underwent MRI of the right coronary artery (RCA) and vessel wall (MR-CVW) on a clinical 1.5T MR-scanner. Wall thickness measurements of both groups were compared.Principal Findings
Stenoses of the RCA (both < and ≥50% on CAG) were present in all patients. In 21/22 patients, stenoses detected at MRI corresponded to stenoses detected with conventional angiography. In 19/26 asymptomatic subjects, there was visible luminal narrowing in the MR luminography images. Fourteen of these subjects demonstrated corresponding increase in vessel wall thickness. In 4/26 asymptomatic subjects, vessel wall thickening without luminal narrowing was present. Maximum and mean wall thicknesses in patients were significantly higher (2.16 vs 1.92 mm, and 1.38 vs 1.22 mm, both p<0.05).Conclusions
In this cohort of middle-aged individuals, both patients with stable angina and angiographically proven coronary artery disease, as well as age-matched asymptomatic subjects. exhibited coronary vessel wall thickening detectable with MR coronary vessel wall imaging. Maximum and mean wall thicknesses were significantly higher in patients. The vast majority of asymptomatic subjects had either positive remodeling without luminal narrowing, or non-significant stenosis.Trial registration
ClinicalTrials.gov NCT00456950相似文献3.
Lennart Greiff Anders Cervin Cecilia Ahlstr?m-Emanuelsson Gun Almqvist Morgan Andersson Jan Dolata Leif Eriksson Edward H?gest?tt Anders K?llén Per Norlén Inga-Lisa Sj?lin Henrik Widegren 《Respiratory research》2012,13(1):53
Background
Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile.Objective
To evaluate the efficacy and safety of intranasal AZD8848.Methods
In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg) was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (). In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg) was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days ( NCT00688779). Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. NCT00770003Results
AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848.Conclusions
Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis.Trial registration
and NCT00688779 as indicated above. NCT00770003相似文献4.
Paul W Jones James F Donohue Jerry Nedelman Steve Pascoe Gregory Pinault Cheryl Lassen 《Respiratory research》2011,12(1):161
Background
Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively. We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.Methods
Pooled data from three indacaterol studies (n = 3313) were analysed. Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St. George''s Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1. Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.Results
With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001). Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95. At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease). Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.Conclusions
These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.Trial Registration
ClinicalTrials.gov , NCT00393458, and NCT00463567 NCT00624286相似文献5.
Background
N-acetylcysteine (NAC) or sodium bicarbonate (NaHCO3), singly or combined, inconsistently prevent patients exposed to radiographic contrast media from developing contrast-induced acute kidney injury (CI-AKI).Objective
We asked whether intravenous isotonic saline and either NaHCO3 in 5% dextrose or else a high dose of NAC in 5% dextrose prevent CI-AKI in outpatients exposed to high-osmolal iodinated contrast medium more than does saline alone.Methods
This completed prospective, parallel, superiority, open-label, controlled, computer-randomized, single-center, Brazilian trial () hydrated 500 adult outpatients (214 at high risk of developing CI-AKI) exposed to ioxitalamate during elective coronary angiography and ventriculography. From 1 hour before through 6 hours after exposure, 126 patients (group 1) received a high dose of NAC and saline, 125 (group 2) received NaHCO3 and saline, 124 (group 3) received both treatments, and 125 (group 4) received only saline. NCT01612013Results
Groups were similar with respect to age, gender, weight, pre-existing renal dysfunction, hypertension, medication, and baseline serum creatinine and serum cystatin C, but diabetes mellitus was significantly less prevalent in group 1. CI-AKI incidence 72 hours after exposure to contrast medium was 51.4% (257/500), measured as serum creatinine > (baseline+0.3 mg/dL) and/or serum cystatin C > (1.1· baseline), and 7.6% (38/500), measured as both serum creatinine and serum cystatin C > (baseline+0.3 mg/dL) or > (1.25 · baseline). CI-AKI incidence measured less sensitively was similar among groups. Measured more sensitively, incidence in group 1 was significantly (p<0.05) lower than in groups 2 and 3 but not group 4; adjustment for confounding by infused volume equalized incidence in groups 1 and 3.Conclusion:
We found no evidence that intravenous isotonic saline and either NaHCO3 or else a high dose of NAC prevent CI-AKI in outpatients exposed to high osmolal iodinated contrast medium more than does saline alone.Trial Registration
ClinicalTrials.gov . NCT01612013相似文献6.
Laura W. Goff Nilay Thakkar Liping Du Emily Chan Benjamin R. Tan Dana B. Cardin Howard L. McLeod Jordan D. Berlin Barbara Zehnbauer Chloe Fournier Joel Picus Andrea Wang-Gillam Wooin Lee A. Craig Lockhart 《PloS one》2014,9(9)
Background
Retrospective studies indicate associations between TSER (thymidylate synthase enhancer region) genotypes and clinical outcomes in patients receiving 5-FU based chemotherapy, but well-controlled prospective validation has been lacking.Methods
In this phase II study ( registered through ClinicalTrials.gov, http://clinicaltrials.gov/show/ NCT00515216), patients with “good risk” TSER genotypes (at least one TSER*2 allele) were treated with FOLFOX chemotherapy to determine whether prospective patient selection can improve overall response rates (ORR) in patients with gastric and gastroesophageal junction (GEJ) cancers, compared with historical outcomes in unselected patients (estimated 43%). NCT00515216Results
The ORR in genotype-selected patients was 39.1% (9 partial responses out of 23 evaluable patients, 95% CI, 22.2 to 59.2), not achieving the primary objective of improving ORR. An encouraging disease control rate (DCR, consisting of partial responses and stable diseases) of 95.7% was noted and patients with homozygous TSER*2 genotype showed better tumor response.Conclusions
In this first prospective, multi-institutional study in patients with gastric or GEJ cancers, selecting patients with at least one TSER*2 allele did not improve the ORR but led to an encouraging DCR. Further studies are needed to investigate the utility of selecting patients homozygous for the TSER*2 allele and additional genomic markers in improving clinical outcomes for patients with gastric and GEJ cancers.Trial Registration
ClinicalTrials.gov NCT00515216相似文献7.
Paul W Jones Stephen I Rennard Alvar Agusti Pascal Chanez Helgo Magnussen Leonardo Fabbri James F Donohue Eric D Bateman Nicholas J Gross Rosa Lamarca Cynthia Caracta Esther Garcia Gil 《Respiratory research》2011,12(1):55
Background
The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).Methods
In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843) and II (n = 804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1 <80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George''s Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation.Results
At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p < 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p < 0.001). More patients had a SGRQ improvement ≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p = 0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p = 0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p = 0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p = 0.9). Adverse events were minor in both studies.Conclusion
Aclidinium is effective and well tolerated in patients with moderate to severe COPD.Trial registration
ClinicalTrials.gov: (ACCLAIM/COPD I) and NCT00363896 (ACCLAIM/COPD II). NCT00358436相似文献8.
Carlos K. H. Wong William C. W. Wong Cindy L. K. Lam Y. F. Wan Winnie H. T. Wong K. L. Chung Daisy Dai Eva L. H. Tsui Daniel Y. T. Fong 《PloS one》2014,9(5)
Background
To evaluate the effects of a large population-based patient empowerment programme (PEP) on clinical outcomes and health service utilization rates in type 2 diabetes mellitus (T2DM) patients in the primary care setting.Research Design and Subjects
A stratified random sample of 1,141 patients with T2DM enrolled to PEP between March and September 2010 were selected from general outpatient clinics (GOPC) across Hong Kong and compared with an equal number of T2DM patients who had not participated in the PEP (non-PEP group) matched by age, sex and HbA1C level group.Measures
Clinical outcomes of HbA1c, SBP, DBP and LDL-C levels, and health service utilization rates including numbers of visits to GOPC, specialist outpatient clinics (SOPC), emergency department (ED) and inpatient admissions, were measured at baseline and at 12-month post-recruitment. The effects of PEP on clinical outcomes and health service utilization rates were assessed by the difference-in-difference estimation, using the generalized estimating equation models.Results
Compared with non-PEP group, PEP group achieved additional improvements in clinical outcomes over the 12-month period. A significantly greater percentage of patients in the PEP group attained HbA1C≤7% or LDL-C≤2.6 mmol/L at 12-month follow-up compared with the non-PEP group. PEP group had a mean 0.813 fewer GOPC visits in comparison with the non-PEP group.Conclusions
PEP was effective in improving the clinical outcomes and reduced the general outpatient clinic utilization rate over a 12-month period. Empowering T2DM patients on self-management of their disease can enhance the quality of diabetes care in primary care.Trial Registration
ClinicalTrials.gov NCT01935349相似文献9.
Background
Low rates of adherence to artemisinin-based combination therapy (ACT) regimens increase the risk of treatment failure and may lead to drug resistance, threatening the sustainability of current anti-malarial efforts. We assessed the impact of text message reminders on adherence to ACT regimens.Methods
Health workers at hospitals, clinics, pharmacies, and other stationary ACT distributors in Tamale, Ghana provided flyers advertising free mobile health information to individuals receiving malaria treatment. The messaging system automatically randomized self-enrolled individuals to the control group or the treatment group with equal probability; those in the treatment group were further randomly assigned to receive a simple text message reminder or the simple reminder plus an additional statement about adherence in 12-hour intervals. The main outcome was self-reported adherence based on follow-up interviews occurring three days after treatment initiation. We estimated the impact of the messages on treatment completion using logistic regression.Results
1140 individuals enrolled in both the study and the text reminder system. Among individuals in the control group, 61.5% took the full course of treatment. The simple text message reminders increased the odds of adherence (adjusted OR 1.45, 95% CI [1.03 to 2.04], p-value 0.028). Receiving an additional message did not result in a significant change in adherence (adjusted OR 0.77, 95% CI [0.50 to 1.20], p-value 0.252).Conclusion
The results of this study suggest that a simple text message reminder can increase adherence to antimalarial treatment and that additional information included in messages does not have a significant impact on completion of ACT treatment. Further research is needed to develop the most effective text message content and frequency.Trial Registration
ClinicalTrials.gov NCT01722734相似文献10.
Bertrand Lell Selidji Agnandji Isabelle von Glasenapp Sonja Haertle Sunny Oyakhiromen Saadou Issifou Johan Vekemans Amanda Leach Marc Lievens Marie-Claude Dubois Marie-Ange Demoitie Terrell Carter Tonya Villafana W. Ripley Ballou Joe Cohen Peter G. Kremsner 《PloS one》2009,4(10)
Background
The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion – based formulation (AS02) and a formulation based on liposomes (AS01).Methods & Principal Findings
In this Phase II, double-blind study (), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01E or RTS,S/AS02D, on a 0–1–2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02D/AS01E) of 0.88 (95% CI: 0.68–1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated. NCT00307021Conclusions
RTS,S/AS01E proved similarly as well tolerated and immunogenic as RTS,S/AS02D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan.Trial Registration
ClinicalTrials.gov. NCT00307021相似文献11.
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12.
Henri Blehaut Clotilde Mircher Aimé Ravel Martine Conte Veronique de Portzamparc Gwendael Poret Fran?oise Huon de Kermadec Marie-Odile Rethore Franck G. Sturtz 《PloS one》2010,5(1)
Background
Seven genes involved in folate metabolism are located on chromosome 21. Previous studies have shown that folate deficiency may contribute to mental retardation in Down''s syndrome (DS).Methodology
We investigated the effect of oral folate supplementation (daily dose of 1.0±0.3 mg/kg) on cognitive functions in DS children, aged from 3 to 30 months. They received 1 mg/kg leucovorin or placebo daily, for 12 months, in a single-centre, randomised, double-blind study. Folinic acid (leucovorin, LV) was preferred to folic acid as its bioavailability is higher. The developmental age (DA) of the patients was assessed on the Brunet-Lezine scale, from baseline to the end of treatment.Results
The intent-to-treat analysis (113 patients) did not show a positive effect of leucovorin treatment. However, it identified important factors influencing treatment effect, such as age, sex, and concomitant treatments, including thyroid treatment in particular. A per protocol analysis was carried out on patients evaluated by the same examiner at the beginning and end of the treatment period. This analysis of 87 patients (43 LV-treated vs. 44 patients on placebo) revealed a positive effect of leucovorin on developmental age (DA). DA was 53.1% the normal value with leucovorin and only 44.1% with placebo (p<0.05). This positive effect of leucovorin was particularly strong in patients receiving concomitant thyroxin treatment (59.5% vs. 41.8%, p<0.05). No adverse event related to leucovorin was observed.Conclusion
These results suggest that leucovorin improves the psychomotor development of children with Down''s syndrome, at least in some subgroups of the DS population, particularly those on thyroxin treatment.Trial Registration
ClinicalTrials.gov, NCT00294593相似文献13.
Paul W Jones Julie A Anderson Peter MA Calverley Bartolome R Celli Gary T Ferguson Christine Jenkins Julie C Yates J?rgen Vestbo Michael D Spencer 《Respiratory research》2011,12(1):71
Background
Little is known about factors that determine health status decline in clinical trials of COPD.Objectives
To examine health status changes over 3 years in the TORCH study of salmeterol+fluticasone propionate (SFC) vs. salmeterol alone, fluticasone propionate alone or placebo.Methods
St George''s Respiratory Questionnaire (SGRQ) was administered at baseline then every 6 months.Measurements and Main Results
Data from 4951 patients in 28 countries were available. SFC produced significant improvements over placebo in all three SGRQ domains during the study: (Symptoms -3.6 [95% CI -4.8, -2.4], Activity -2.8 [95% CI -3.9, -1.6], Impacts -3.2 [95% CI -4.3, -2.1]) but the pattern of change over time differed between domains. SGRQ deteriorated faster in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III & IV relative to GOLD stage II (p < 0.001). There was no difference in the relationship between deterioration in SGRQ Total score and forced expiratory volume in one second (FEV1) decline (as % predicted) in men and women. Significantly faster deterioration in Total score relative to FEV1 % predicted was seen in older patients (≥ 65 years) and there was an age-related change in Total score that was independent of change in FEV1. The relationship between deterioration in FEV1 and SGRQ did not differ in different world regions, but patients in Asia-Pacific showed a large improvement in score that was unrelated to FEV1 change.Conclusions
In addition to treatment effects, health status changes in clinical trials may be influenced by demographic and disease-related factors. Deterioration in health status appears to be fastest in older persons and those with severe airflow limitation.Trial Registration
ClinicalTrials.gov: NCT00268216相似文献14.
Birgitte Nygaard Niels Erik Frandsen Lisbet Brandi Knud Rasmussen Ove Vyff Oestergaard Lars Oedum Hans Christian Hoeck Ditte Hansen 《PloS one》2014,9(8)
Background
Vitamin D repletion with high doses of vitamin D is often recommended to patients and healthy subjects. The safety, especially concerning changes in urinary calcium excretion is of great importance.Methods
In a double-blinded, placebo-controlled study in 40 healthy volunteers, we examined the changes in mineral metabolism during supplementation with 3000 IU of oral cholecalciferol daily during 4 months.Results
Both 25(OH)vitamin D and 1,25(OH)2vitamin D increased significantly in the active treated group as compared to the placebo group (186% versus 14% (P<0.001) and 28% versus – 8% (P<0.001)). No change was observed in urinary calcium excretion in the active group compared to the placebo group (P = 0.891). Fibroblast growth factor 23 increased significantly by 10% (P<0.018) in the active group. However, there was no difference in changes in FGF23 between treatment groups (P = 0.457).Conclusion
High dose cholecalciferol significantly increases 25(OH)vitamin D and 1,25(OH)2vitamin D levels compared to placebo. No changes in urinary calcium excretion or other measured components of the mineral metabolism were found between groups.Trial Registration
ClinicalTrials.gov . NCT00952562相似文献15.
Ishani Ganguli Jamie E. Collins William M. Reichmann Elena Losina Jeffrey N. Katz Christian Arbelaez Laurel A. Donnell-Fink Rochelle P. Walensky 《PloS one》2013,8(1)
Background
HIV infection remains a major US public health concern. While HIV-infected individuals now benefit from earlier diagnosis and improved treatment options, progress is tempered by large numbers of newly diagnosed patients who are lost to follow-up prior to disease confirmation and linkage to care.Methodology
In the randomized, controlled USHER trial, we offered rapid HIV tests to patients presenting to a Boston, MA emergency department. Separate written informed consent was required for confirmatory testing. In a secondary analysis, we compared participants with reactive results who did and did not complete confirmatory testing to identify factors associated with refusal to complete the confirmation protocol.Principal Findings
Thirteen of 62 (21.0%, 95% CI (11.7%, 33.2%)) participants with reactive rapid HIV tests refused confirmation; women, younger participants, African Americans, and those with fewer HIV risks, with lower income, and without primary care doctors were more likely to refuse. We projected that up to four true HIV cases were lost at the confirmation stage.Conclusions
These findings underscore the need to better understand the factors associated with refusal to confirm reactive HIV testing and to identify interventions that will facilitate confirmatory testing and linkage to care among these populations.Trial Registration
ClinicalTrials.gov ; NCT00502944. NCT01258582相似文献16.
Louise Balfour Johanna N. Spaans Dean Fergusson Harold Huff Edward J. Mills Charles J. la Porte Sharon Walmsley Neera Singhal Ron Rosenes Nancy Tremblay M. John Gill Hugues Loemba Brian Conway Anita Rachlis Edward Ralph Mona Loutfy Ranjeeta Mallick Rika Moorhouse D. William Cameron 《PloS one》2014,9(1)
Introduction
The MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA) vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection.Objective
We planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates, as well as tolerance and adherence to study interventions.Methods
Participants receive eight capsules twice daily of 1) high-dose or 2) RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression, safety and tolerability. Regression analysis was used to identify correlates of micronutrient levels at baseline. Adherence was measured by residual pill count, self-report using the General Treatment Scale (GTS) and short-term recall HIV Adherence Treatment Scale (HATS).Results
Prior micronutrient supplementation (within 30 days) was 27% at screening and 10% of study population, and was not correlated with baseline micronutrient levels. Low levels were frequent for carotene (24%<1 nmol/L), vitamin D (24%<40 nmol/L) and serum folate (20%<15 nmol/L). The proportion with B12 deficiency (<133 pmol/L) was 2.4%. Lower baseline levels of B12 correlated lower baseline CD4 count (r = 0.21, p = 0.02) with a 21 pmol/L reduction in B12 per 100 cells/µL CD4. Vitamin D levels were higher in men (p<0.001). After a median follow-up of 1.63 years, there were 19 (15%) early withdrawals from the study treatment. Mean treatment adherence using pill count was 88%. Subjective adherence by the GTS was 81% and was moderately but significantly correlated with pill count (r = 0.29, p<0.001). Adherence based on short-term recall (HATS) was >80% in 75% of participants.Conclusion
Micronutrient levels in asymptomatic HIV+ persons are in keeping with population norms, but micronutrient deficiencies are frequent. Adherence levels are high, and will permit a valid evaluation of treatment effects.Trial Registration
ClinicalTrials.gov NCT00798772相似文献17.
Andrea Egger Roland Kreis Sabin Allemann Christoph Stettler Peter Diem Tania Buehler Chris Boesch Emanuel R. Christ 《PloS one》2013,8(8)
Background
Intrahepatocellular (IHCL) and intramyocellular (IMCL) lipids are ectopic lipid stores. Aerobic exercise results in IMCL utilization in subjects over a broad range of exercise capacity. IMCL and IHCL have been related to impaired insulin action at the skeletal muscle and hepatic level, respectively. The acute effect of aerobic exercise on IHCL is unknown. Possible regulatory factors include exercise capacity, insulin sensitivity and fat availability subcutaneous and visceral fat mass).Aim
To concomitantly investigate the effect of aerobic exercise on IHCL and IMCL in healthy subjects, using Magnetic Resonance spectroscopy.Methods
Normal weight, healthy subjects were included. Visit 1 consisted of a determination of VO2max on a treadmill. Visit 2 comprised the assessment of hepatic and peripheral insulin sensitivity by a two-step hyperinsulinaemic euglycaemic clamp. At Visit 3, subcutaneous and visceral fat mass were assessed by whole body MRI, IHCL and IMCL before and after a 2-hours aerobic exercise (50% of VO2max) using 1H-MR-spectroscopy.Results
Eighteen volunteers (12M, 6F) were enrolled in the study (age, 37.6±3.2 years, mean±SEM; VO2max, 53.4±2.9 mL/kg/min). Two hours aerobic exercise resulted in a significant decrease in IMCL (−22.6±3.3, % from baseline) and increase in IHCL (+34.9±7.6, % from baseline). There was no significant correlation between the exercise-induced changes in IMCL and IHCL and exercise capacity, subcutaneous and visceral fat mass and hepatic or peripheral insulin sensitivity.Conclusions
IMCL and IHCL are flexible ectopic lipid stores that are acutely influenced by physical exercise, albeit in different directions.Trial Registration
ClinicalTrial.gov NCT00491582相似文献18.
Chen Wang Zhenguo Zhai Yuanhua Yang Yadong Yuan Zhaozhong Cheng Lirong Liang Huaping Dai Kewu Huang Weixuan Lu Zhonghe Zhang Xiansheng Cheng Ying H Shen China Venous Thromboembolism Study Group 《Respiratory research》2009,10(1):128
Backgrounds
Urokinase (UK) 2 200 U/kg·h for 12 hours infusion(UK-12 h)is an ACCP recommended regimen in treating acute pulmonary embolism (PE). It is unclear whether this dose and time can be reduced further. We compared the efficacy and safety of 20, 000 U/kg for 2 hours (UK-2 h) with the UK-12 h regime in selected PE patients.Methods
A randomized trial involving 129 patients was conducted. Patients with acute PE were randomly assigned to receive either UK-12 h (n = 70), or UK-2 h (n = 59). The efficacy was determined by the improvement of right heart dysfunction and perfusion defect at 24 h and 14 d post UK treatment. The bleeding incidence, death rate and PE recurrence were also evaluated.Results
Similarly significant improvements in right heart dysfunction and lung perfusion defects were observed in both groups. Overall bleeding incidents were low in both groups. Major bleeding directly associated with UK infusion occurred in one patient in the UK-2 h group and one in the UK-12 h group. Mortality rates were low, with one reported fatal recurrent in the UK-12 h group and none in the UK-2 h group. When the rate of bleeding, death and PE recurrence were compared separately in the hemodynamic instability and the massive anatomic obstruction subgroups, no significant difference was found.Conclusions
The UK-2 h regimen exhibits similar efficacy and safety as the UK-12 h regimen for acute PE.Trial Registration
Clinical trial registered with http://clinicaltrials.gov/ct2/show/ (Identifier: NCT00799968) NCT 00799968相似文献19.
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