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1.
Background
Reduction of proteinuria and blood pressure (BP) with blockers of the renin-angiotensin system (RAS) impairs the progression of chronic kidney disease (CKD). The aldosterone antagonist spironolactone has an antiproteinuric effect, but its use is limited by side effects. The present study evaluated the short-term antiproteinuric effect and safety of the selective aldosterone antagonist eplerenone in non-diabetic CKD.Study Design
Open randomized cross-over trial.Setting and Participants
Forty patients with non-diabetic CKD and urinary albumin excretion greater than 300 mg/24 hours.Intervention
Eight weeks of once-daily administration of add-on 25–50 mg eplerenone to stable standard antihypertensive treatment including RAS-blockade.Outcomes & Measurements
24 hour urinary albumin excretion, BP, p-potassium, and creatinine clearance.Results
The mean urinary albumin excretion was 22% [CI: 14,28], P<0.001, lower during treatment with eplerenone. Mean systolic BP was 4 mmHg [CI: 2,6], P = 0.002, diastolic BP was 2 mmHg [CI: 0,4], P = 0.02, creatinine clearance was 5% [CI: 2,8], P = 0.005, lower during eplerenone treatment. After correction for BP and creatinine clearance differences between the study periods, the mean urinary albumin excretion was 14% [CI: 4,24], P = 0.008 lower during treatment. Mean p-potassium was 0.1 mEq/L [CI: 0.1,0.2] higher during eplerenone treatment, P<0.001. Eplerenone was thus well tolerated and no patients were withdrawn due to hyperkalaemia.Limitations
Open label, no wash-out period and a moderate sample size.Conclusions
In non-diabetic CKD patients, the addition of eplerenone to standard antihypertensive treatment including RAS-blockade caused a moderate BP independent fall in albuminuria, a minor fall in creatinine clearance and a 0.1 mEq/L increase in p-potassium.Trial Registration
Clinicaltrials.gov NCT00430924相似文献2.
Török ME Nguyen DB Tran TH Nguyen TB Thwaites GE Hoang TQ Nguyen HD Tran TH Nguyen TC Hoang HT Wolbers M Farrar JJ 《PloS one》2011,6(12):e27821
Background
Dexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown.Methods
Vietnamese adults and adolescents with tuberculous meningitis recruited to a randomised, double-blind, placebo-controlled trial of adjunctive dexamethasone were followed-up at five years, to determine the effect of dexamethasone on long-term survival and neurological disability.Results
545 patients were randomised to receive either dexamethasone (274 patients) or placebo (271 patients). 50 patients (9.2%) were lost to follow-up at five years. In all patients two-year survival, probabilities tended to be higher in the dexamethasone arm (0.63 versus 0.55; p = 0.07) but five-year survival rates were similar (0.54 versus 0.51, p = 0.51) in both groups. In patients with grade 1 TBM, but not with grade 2 or grade 3 TBM, the benefit of dexamethasone treatment tended to persist over time (five-year survival probabilities 0.69 versus 0.55, p = 0.07) but there was no conclusive evidence of treatment effect heterogeneity by TBM grade (p = 0.36). The dexamethasone group had a similar proportion of severely disabled patients among survivors at five years as the placebo group (17/128, 13.2% vs. 17/116, 14.7%) and there was no significant association between dexamethasone treatment and disability status at five years (p = 0.32).Conclusions
Adjunctive dexamethasone appears to improve the probability of survival in patients with TBM, until at least two years of follow-up. We could not demonstrate a five-year survival benefit of dexamethasone treatment which may be confined to patients with grade 1 TBM.Trial Registration
ClinicalTrials.gov NCT01317654?term = tuberculous+meningitis&rank = 3 NCT01317654相似文献3.
Katzmarzyk PT Champagne CM Tudor-Locke C Broyles ST Harsha D Kennedy BM Johnson WD 《PloS one》2011,6(10):e26667
Background
The purpose of this study was to determine if a short-term pedometer-based intervention results in immediate increases in time spent in moderate-to-vigorous physical activity (MVPA) compared to a minimal educational intervention.Methods
A sample of 43 overweight adults 35 to 64 years of age participated in a one week pedometer-based feasibility trial monitored by accelerometry. Participants were randomized into a one-week education-only group or a group that also wore a pedometer. Accelerometer-measured MVPA was measured over 7 days at baseline and again for 7 days immediately post-intervention.Results
Minutes of MVPA increased significantly in the overall sample (p = 0.02); however, the effect of adding the pedometer to the education program was not significant (p = 0.89). Mean (±SE) MVPA increased from 12.7±2.4 min/day to 16.2±3.6 min/day in the education-only group and from 13.2±3.3 min/day to 16.3±3.9 min/day in the education+pedometer group. The correlation between change in steps/day and change in MVPA was 0.69 (p<0.0001).Conclusions
The results of this study suggest that the addition of a pedometer to a short-term education program does not produce added benefits with respect to increasing physical activity in the Lower Mississippi Delta.Trial Registration
ClinicalTrials.gov NCT01264757相似文献4.
Background
Cannabis dependence is a significant public health problem. Because there are no approved medications for this condition, treatment must rely on behavioral approaches empirically complemented by such lifestyle change as exercise.Aims
To examine the effects of moderate aerobic exercise on cannabis craving and use in cannabis dependent adults under normal living conditions.Design
Participants attended 10 supervised 30-min treadmill exercise sessions standardized using heart rate (HR) monitoring (60–70% HR reserve) over 2 weeks. Exercise sessions were conducted by exercise physiologists under medical oversight.Participants
Sedentary or minimally active non-treatment seeking cannabis-dependent adults (n = 12, age 25±3 years, 8 females) met criteria for primary cannabis dependence using the Substance Abuse module of the Structured Clinical Interview for DSM-IV (SCID).Measurements
Self-reported drug use was assessed for 1-week before, during, and 2-weeks after the study. Participants viewed visual cannabis cues before and after exercise in conjunction with assessment of subjective cannabis craving using the Marijuana Craving Questionnaire (MCQ-SF).Findings
Daily cannabis use within the run-in period was 5.9 joints per day (SD = 3.1, range 1.8–10.9). Average cannabis use levels within the exercise (2.8 joints, SD = 1.6, range 0.9–5.4) and follow-up (4.1 joints, SD = 2.5, range 1.1–9.5) periods were lower than during the run-in period (both P<.005). Average MCQ factor scores for the pre- and post-exercise craving assessments were reduced for compulsivity (P = .006), emotionality (P = .002), expectancy (P = .002), and purposefulness (P = .002).Conclusions
The findings of this pilot study warrant larger, adequately powered controlled trials to test the efficacy of prescribed moderate aerobic exercise as a component of cannabis dependence treatment. The neurobiological mechanisms that account for these beneficial effects on cannabis use may lead to understanding of the physical and emotional underpinnings of cannabis dependence and recovery from this disorder.Trial Registration
ClinicalTrials.gov ] NCT00838448相似文献5.
Introduction
Iodine is essential for normal fetal and neonatal development. We studied the prevalence and impact on fetal thyroid development of iodine deficiency in pregnant women in the northern part of the Paris conurbation.Materials and Methods
110 patients underwent several determinations of urinary iodine excretion (UIE) and of serum FT4, FT3, and TSH. Fetal thyroid gland size was assessed using ultrasonography.Results
We found evidence of widespread iodine deficiency (mean UIE, 49.8 µg/L [standard deviation, 2.11]). Iodine deficiency did not correlate significantly with maternal thyroid parameters but showed a significant negative correlation with fetal thyroid gland size (rho = 0.25, P = 0.02).Conclusion
Iodine deficiency during pregnancy is still a problem in our geographical area and affects the fetal thyroid gland.Clinical Trials.gov NCT00162539相似文献6.
Furukawa TA Horikoshi M Kawakami N Kadota M Sasaki M Sekiya Y Hosogoshi H Kashimura M Asano K Terashima H Iwasa K Nagasaku M Grothaus LC;GENKI Project 《PloS one》2012,7(4):e35330
Background
Subthreshold depression is highly prevalent in the general population and causes great loss to society especially in the form of reduced productivity while at work (presenteeism). We developed a highly-structured manualized eight-session cognitive-behavioral program with a focus on subthreshold depression in the workplace and to be administered via telephone by trained psychotherapists (tCBT).Methods
We conducted a parallel-group, non-blinded randomized controlled trial of tCBT in addition to the pre-existing Employee Assistance Program (EAP) versus EAP alone among workers with subthreshold depression at a large manufacturing company in Japan. The primary outcomes were depression severity as measured with Beck Depression Inventory-II (BDI-II) and presenteeism as measured with World Health Organization Health and Work Productivity Questionnaire (HPQ). In the course of the trial the follow-up period was shortened in order to increase acceptability of the study.Results
The planned sample size was 108 per arm but the trial was stopped early due to low accrual. Altogether 118 subjects were randomized to tCBT+EAP (n = 58) and to EAP alone (n = 60). The BDI-II scores fell from the mean of 17.3 at baseline to 11.0 in the intervention group and to 15.7 in the control group after 4 months (p<0.001, Effect size = 0.69, 95%CI: 0.32 to 1.05). However, there was no statistically significant decrease in absolute and relative presenteeism (p = 0.44, ES = 0.15, −0.21 to 0.52, and p = 0.50, ES = 0.02, −0.34 to 0.39, respectively).Conclusion
Remote CBT, including tCBT, may provide easy access to quality-assured effective psychotherapy for people in the work force who present with subthreshold depression. Further studies are needed to evaluate the effectiveness of this approach in longer terms. The study was funded by Sekisui Chemicals Co. Ltd.Trial Registration
ClinicalTrials.gov NCT00885014相似文献7.
Magbanua MJ Roy R Sosa EV Weinberg V Federman S Mattie MD Hughes-Fulford M Simko J Shinohara K Haqq CM Carroll PR Chan JM 《PloS one》2011,6(9):e24004
Background
Studies suggest that micronutrients may modify the risk or delay progression of prostate cancer; however, the molecular mechanisms involved are poorly understood. We examined the effects of lycopene and fish oil on prostate gene expression in a double-blind placebo-controlled randomized clinical trial.Methods
Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-month intervention of lycopene (n = 29) or fish oil (n = 27) supplementation or placebo (n = 28). Gene expression in morphologically normal prostate tissue was studied at baseline and at 3 months via cDNA microarray analysis. Differential gene expression and pathway analyses were performed to identify genes and pathways modulated by these micronutrients.Results
Global gene expression analysis revealed no significant individual genes that were associated with high intake of fish or tomato at baseline or after 3 months of supplementation with lycopene or fish oil. However, exploratory pathway analyses of rank-ordered genes (based on p-values not corrected for multiple comparisons) revealed the modulation of androgen and estrogen metabolism in men who routinely consumed more fish (p = 0.029) and tomato (p = 0.008) compared to men who ate less. In addition, modulation of arachidonic acid metabolism (p = 0.01) was observed after 3 months of fish oil supplementation compared with the placebo group; and modulation of nuclear factor (erythroid derived-2) factor 2 or Nrf2-mediated oxidative stress response for either supplement versus placebo (fish oil: p = 0.01, lycopene: p = 0.001).Conclusions
We did not detect significant individual genes associated with dietary intake and supplementation of lycopene and fish oil. However, exploratory analyses revealed candidate in vivo pathways that may be modulated by these micronutrients.Trial Registration
ClinicalTrials.gov NCT00402285相似文献8.
Challenges in Developing a Validated Biomarker for Angiogenesis Inhibitors: The Motesanib Experience
Michael B. Bass Bin Yao Yong-Jiang Hei Yining Ye Gerard J. Davis Michael T. Davis Barbara A. Kaesdorf Sabrina S. Chan Scott D. Patterson 《PloS one》2014,9(10)
Purpose
We sought to develop placental growth factor as a predictive pharmacodynamic biomarker for motesanib efficacy as first-line therapy in patients with advanced nonsquamous non–small-cell lung cancer.Experimental Design
Placental growth factor was evaluated at baseline and study week 4 (after 3 weeks treatment) in an exploratory analysis of data from a randomized phase 2 study of motesanib 125 mg once daily plus carboplatin/paclitaxel and in a prespecified analysis of data from a randomized, double-blind phase 3 study of motesanib 125 mg once daily plus carboplatin/paclitaxel vs placebo plus carboplatin/paclitaxel (MONET1). Associations between fold-change from baseline in placental growth factor and overall survival were evaluated using Cox proportional hazards models.Results
In the phase 2 study, serum placental growth factor increased from baseline a mean 2.8-fold at study week 4. Patients with ≥2.2-fold change from baseline in placental growth factor (n = 18) had significantly longer overall survival than those with <2.2-fold change (n = 19; 22.9 vs 7.9 months; hazard ratio, 0.30; 95% CI, 0.12–0.74; P = 0.009). Consequently, placental growth factor was investigated as a pharmacodynamic biomarker in the phase 3 MONET1 study. There was no association between log-transformed placental growth factor fold-change from baseline to week 4 (continuous variable) and overall survival (hazard ratio, 0.98; 95% CI, 0.79–1.22; P = 0.868). MONET1 did not meet its primary endpoint of overall survival. Likewise, median overall survival was similar among patients with ≥2.0-fold change in placental growth factor (n = 229) compared with <2.0-fold change (n = 127; 14.8 vs 13.8 months; hazard ratio, 0.88; 95% CI, 0.67–1.15, P = 0.340).Conclusions
Our results illustrate the challenges of successfully translating phase 2 biomarker results into phase 3 studies.Trial Registration
ClinicalTrials.gov , NCT00460317 NCT00369070相似文献9.
Solà R Valls RM Godàs G Perez-Busquets G Ribalta J Girona J Heras M Cabré A Castro A Domenech G Torres F Masana L Anglés N Reguant J Ramírez B Barriach JM 《PloS one》2012,7(2):e31103
Background
Cocoa, mixed with other food ingredients, intake can have beneficial effects on cardiovascular disease (CVD) biomarkers. We compared the effects of 4 cocoa cream products on some of these biomarkers.Methods and Findings
In this multi-centered, randomized, controlled, double-blind, parallel trial, volunteers (n = 113; age range: 43–65 years) who were pre-hypertensive, stage-1 hypertensive and hypercholesterolemic received one of 4 cocoa cream products (13 g/unit; 1 g cocoa/unit, 6 units/d; 465 Kcal/d) added to a low saturated fat diet for 4 weeks. The groups were: A) (n = 28), cocoa cream considered as control; B) (n = 28), cocoa+hazelnut cream (30 g/d hazelnuts); C) (n = 30), cocoa+hazelnuts+phytosterols (2 g/d); and D) (n = 27), cocoa+hazelnuts+phytosterols+soluble fiber (20 g/d) the patented “LMN product”. Primary outcome measures were BP, LDL-c, apolipoprotein B-100 (Apo B), ApoB/ApoA ratio, oxidized LDL (oxLDL) and high-sensitive C-reactive protein (hsCRP) determined at baseline and post-cocoa cream product intake. Statistical analysis used was ANCOVA or mixed models (in case of repeated measurements), with baseline observation included as a covariate. After 4 weeks, compared to product A, product C reduced LDL-c by 11.2%, Apo B by 8.1% and ApoB/ApoA ratio by 7.8% (P = 0.01). LMN decreased LDL-c by 9.2%, Apo B-100 by 8.5%, ApoB/ApoA ratio by 10.5%, hsCRP by 33.4% and oxLDL by 5.9% (P = 0.01). Surprisingly, even “control” product A reduced systolic BP (−7.89 mmHg; 95%CI: −11.45 to −4.3) and diastolic BP (−5.54 mmHg; 95%CI: −7.79 to −3.29). The BP reductions were similar with the other 3 products. Limitations of the study are that the trial period was relatively short and that a better “BP control” product would have been preferable.Conclusion
The creams (particularly the LMN) have anti-inflammatory and antioxidant effects in addition to lowering LDL-c, Apo B and ApoB/ApoA ratio. Thus, the soluble fiber effects amplified with sterols (as contained in the cocoa creams) provide new dietary therapeutic perspectives.Trial Registration
Clinicaltrials.gov NCT00511420相似文献10.
C Nagel F Prange S Guth J Herb N Ehlken C Fischer F Reichenberger S Rosenkranz HJ Seyfarth E Mayer M Halank E Grünig 《PloS one》2012,7(7):e41603
Background
Aim of this prospective study was to evaluate the effects of exercise training in patients with inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH).Methods
Thirty-five consecutive patients with invasively confirmed inoperable or residual CTEPH (16 women;19 men; mean age 61±15 years, mean pulmonary artery pressure, 63±20 mmHg; primary inoperable n = 33, persisting pulmonary hypertension after pulmonary endarterectomy n = 2) on stable disease-targeted medication received exercise training in-hospital for 3 weeks and continued at home for 15 weeks. Medication remained unchanged during the study period. Efficacy parameters have been evaluated at baseline, after 3 and 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of median 36.4 months (interquartile range 26.6–46.6 months).Results
All patients tolerated exercise training without severe adverse events. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 61±54 meters after 3 weeks (p<0.001) and by 71±70 meters after 15 weeks (p = 0.001), as well as scores of quality-of-life questionnaire, peak oxygen consumption and maximal workload. NT-proBNP improved significantly after 3 weeks of exercise training (p = 0.046). The 1-year survival rate was 97%, 2-year survival rate was 94% and the 3-year-survival 86% respectively.Conclusion
Training as add-on to medical therapy may be effective in patients with CTEPH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further multicentric randomized controlled studies are needed to confirm these promising results.Trial Registration
ClinicalTrials.gov NCT01398345相似文献11.
A Alkhalaf N Kleefstra KH Groenier HJ Bilo RO Gans P Heeringa JL Scheijen CG Schalkwijk GJ Navis SJ Bakker 《PloS one》2012,7(7):e40427
Background
Formation of advanced glycation endproducts (AGEs), endothelial dysfunction, and low-grade inflammation are intermediate pathways of hyperglycemia-induced vascular complications. We investigated the effect of benfotiamine on markers of these pathways in patients with type 2 diabetes and nephropathy.Methods
Patients with type 2 diabetes and urinary albumin excretion in the high-normal and microalbuminuric range (15–300 mg/24h) were randomized to receive benfotiamine (n = 39) or placebo (n = 43). Plasma and urinary AGEs (N ε-(carboxymethyl) lysine [CML], N ε-(Carboxyethyl) lysine [CEL], and 5-hydro-5-methylimidazolone [MG-H1]) and plasma markers of endothelial dysfunction (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1], soluble E-selectin) and low-grade inflammation (high-sensitivity C-reactive protein [hs-CRP], serum amyloid-A [SAA], myeloperoxidase [MPO]) were measured at baseline and after 6 and 12 weeks.Results
Compared to placebo, benfotiamine did not result in significant reductions in plasma or urinary AGEs or plasma markers of endothelial dysfunction and low-grade inflammation.Conclusions
Benfotiamine for 12 weeks did not significantly affect intermediate pathways of hyperglycemia-induced vascular complications.Trial Regristration
ClinicalTrials.gov NCT00565318相似文献12.
Emmanuelle Kesse-Guyot Hélène Charreire Valentina A. Andreeva Mathilde Touvier Serge Hercberg Pilar Galan Jean-Michel Oppert 《PloS one》2012,7(10)
Background
The deleterious health effects of sedentary behaviors, independent of physical activity, are increasingly being recognized. However, associations with cognitive performance are not known.Purpose
To estimate the associations between different sedentary behaviors and cognitive performance in healthy older adults.Methods
Computer use, time spent watching television (TV), time spent reading and habitual physical activity levels were self-reported twice (in 2001 and 2007) by participants in the SUpplémentation en Vitamines et MinérauX (SU.VI.MAX and SU.VI.MAX2) study. Cognitive performance was assessed at follow-up (in 2007–2009) via a battery of 6 neuropsychological tests used to derive verbal memory and executive functioning scores. Analyses (ANCOVA) were performed among 1425 men and 1154 women aged 65.6±4.5 at the time of the neuropsychological evaluation. We estimated mean differences with 95% confidence intervals (95%CI) in cognitive performance across categories of each type of sedentary behavior.Results
In multivariable cross-sectional models, compared to non-users, participants using the computer for >1 h/day displayed better verbal memory (mean difference = 1.86; 95%CI: 0.95, 2.77) and executive functioning (mean difference = 2.15; 95%CI: 1.22, 3.08). A negative association was also observed between TV viewing and executive functioning. Additionally, participants who increased their computer use by more than 30 min between 2001 and 2007 showed better performance on both verbal memory (mean difference = 1.41; 95%CI: 0.55, 2.27) and executive functioning (mean difference = 1.41; 95%CI: 0.53, 2.28) compared to those who decreased their computer use during that period.Conclusion
Specific sedentary behaviors are differentially associated with cognitive performance. In contrast to TV viewing, regular computer use may help maintain cognitive function during the aging process.Clinical Trial Registration
clinicaltrial.gov (number ). NCT00272428相似文献13.
Patkar A Gilmer W Pae CU Vöhringer PA Ziffra M Pirok E Mulligan M Filkowski MM Whitham EA Holtzman NS Thommi SB Logvinenko T Loebel A Masand P Ghaemi SN 《PloS one》2012,7(4):e34757
Objective
To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD).Methods
73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d) or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE), while also meeting 2 or 3 (but not more nor less) DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery- Åsberg Depression Rating Scale (MADRS) scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo.Results
The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038). Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036). Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms.Conclusions
There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state.Trial Registration
Clinicaltrials.gov NCT00490542相似文献14.
Cizza G Ronsaville DS Kleitz H Eskandari F Mistry S Torvik S Sonbolian N Reynolds JC Blackman MR Gold PW Martinez PE;P.O.W.E.R. 《PloS one》2012,7(1):e28912
Background
Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes.Methods
Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin.Results
Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup.Conclusions
Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences.Trial Registration
ClinicalTrials.gov NCT00006180相似文献15.
N Mangalat Y Liu NY Fatheree MJ Ferris MR Van Arsdall Z Chen MH Rahbar WA Gleason J Norori DQ Tran JM Rhoads 《PloS one》2012,7(9):e43910
Background
There are few carefully-designed studies investigating the safety of individual probiotics approved under Investigational New Drug policies.Objectives
The primary aim of this prospective, double-blind placebo-controlled trial was to investigate if daily treatment of adults with Lactobacillus reuteri DSM 17938 (LR) for 2 months is safe and well-tolerated. Our secondary aim was to determine if LR treatment has immune effects as determined by regulatory T cell percentages, expression of toll-like receptors (TLR)-2 and −4 on circulating peripheral blood mononuclear cells (PMBCs), cytokine expression by stimulated PBMC, and intestinal inflammation as measured by fecal calprotectin.Methods
Forty healthy adults were randomized to a daily dose of 5×108 CFUs of LR (n = 30) or placebo (n = 10) for 2 months. Participants completed a daily diary card and had 7 clinic visits during treatment and observation.Results
There were no severe adverse events (SAEs) and no significant differences in adverse events (AEs). There were no differences in PBMC subclasses, TLRs, or cytokine expression after treatment. The probiotic-treated group had a significantly higher fecal calprotectin level than the placebo group after 2 months of treatment: 50 µg/g (IQR 24–127 µg/g) vs. 17 µg/g (IQR 11–26 µg/g), p = 0.03, although values remained in the normal clinical range (0–162.9 µg/g). LR vials retained >108 CFUs viable organisms/ml.Conclusions
LR is safe and well tolerated in adults, without significant changes in immunologic markers. There was a small but significant increase in fecal calprotectin, perhaps indicating some element of immune recognition at the intestinal level.Trial Registration
Clinical Trials.gov NCT00922727相似文献16.
Ramjee G van der Straten A Chipato T de Bruyn G Blanchard K Shiboski S Cheng H Montgomery E Padian N;MIRA team 《PloS one》2008,3(10):e3488
Background
We evaluated the effectiveness of the Ortho All-Flex Diaphragm, lubricant gel (Replens®) and condoms compared to condoms alone on the incidence of chlamydial and gonococcal infections in an open-label randomized controlled trial among women at risk of HIV/STI infections.Methods
We randomized 5045 sexually-active women at three sites in Southern Africa. Participants who tested positive for curable STIs were treated prior to enrollment as per local guidelines. Women were followed quarterly and tested for Chlamydia trachomatis (CT) or Neisseria gonorrhoeae (GC) infection by nucleic-acid amplification testing (Roche Amplicor®) using first-catch urine specimens. STIs detected at follow-up visits were treated. We compared the incidence of first infection after randomization between study arms in both intent-to-treat (ITT) and per-protocol populations.Findings
Baseline demographic, behavioral and clinical characteristics were balanced across study arms. Nearly 80% of participants were under 35 years of age. Median follow-up time was 21 months and the retention rate was over 93%. There were 471 first chlamydia infections, 247 in the intervention arm and 224 in the control arm with an overall incidence of 6.2/100 woman-years (wy) (relative hazard (RH) 1.11, 95% Confidence Interval (CI): 0.93–1.33; p = 0.25) and 192 first gonococcal infections, 95 in the intervention arm and 97 in the control arm with an overall incidence of 2.4/100wy (RH 0.98, 95%CI: 0.74–1.30; p = 0.90). Per protocol results indicated that when diaphragm adherence was defined as “always use” since the last visit, there was a significant reduction in the incidence of GC infection among women randomized to the intervention arm (RH 0.61, 95%CI: 0.41–0.91, P = 0.02).Interpretation
There was no difference by study arm in the rate of acquisition of CT or GC. However, our per-protocol results suggest that consistent use of the diaphragm may reduce acquisition of GC.Trial Registration
ClinicalTrials.gov [ NCT00121459] NCT00121459相似文献17.
Maciej S. Buchowski Nobuko Hongu Sari Acra Li Wang Joshua Warolin L. Jackson Roberts II 《PloS one》2012,7(10)
Objectives
It is not established to what extent caloric intake must be reduced to lower oxidative stress in humans. The aim of this study was to determine the effect of short-term, moderate caloric restriction on markers of oxidative stress and inflammation in overweight and obese premenopausal women.Materials/Methods
Randomized trial comparison of 25% caloric restriction (CR) or control diet in 40 overweight or obese women (body mass index 32±5.8 kg/m2) observed for 28 days and followed for the next 90 days. Weight, anthropometry, validated markers of oxidative stress (F2-isoprostane) and inflammation (C-reactive protein), adipokines, hormones, lipids, interleukins, and blood pressure were assessed at baseline, during the intervention, and at follow-up.Results
Baseline median F2-isoprostane concentration (57.0, IQR = 40.5–79.5) in the CR group was 1.75-fold above average range for normal weight women (32.5 pg/ml). After starting of the caloric restriction diet, F2-isoprostane levels fell rapidly in the CR group, reaching statistical difference from the control group by day 5 (median 33.5, IQR = 26.0–48.0, P<0.001) and remained suppressed while continuing on the caloric restriction diet. Three months after resuming a habitual diet, concentrations of F2-isoprostane returned to baseline elevated levels in ∼80% of the women.Conclusions
Oxidative stress can be rapidly reduced and sustained through a modest reduction in caloric intake suggesting potential health benefits in overweight and obese women.Trial Registration
Clinicaltrials.gov NCT00808275相似文献18.
PA Naesgaard RA León De La Fuente ST Nilsen L Woie T Aarsland C Brede H Staines DW Nilsen 《PloS one》2012,7(9):e43228
Background
Several studies have shown an association between vitamin D deficiency and cardiovascular risk. Vitamin D status is assessed by determination of 25-hydroxyvitamin D [25(OH)D] in serum.Methods
We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D, applying univariate and multivariate analysis.Results
There were statistically significant changes in seasonal 25(OH)D levels. At follow-up, 119 patients had died. The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors, both in the total population and in patients with a troponin T (TnT) release (n = 388). When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality, the hazard ratio (HR) for cardiac death and sudden cardiac death in the total population was 0.37 (95% CI, 0.19–0.73), p = 0.004, 0.23 (95% CI, 0.08–0.67), p = 0.007, and 0.32 (95% CI, 0.11–0.94), p = 0.038, respectively. In patients with TnT release, the respective HR was 0.24 (95% CI, 0.10–0.54), p = 0.001, 0.18 (95% CI, 0.05–0.60), p = 0.006 and 0.25 (95% CI, 0.07–0.89), p = 0.033. 25(OH)D had no prognostic value in patients with no TnT release.Conclusion
Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS.Trial registration
ClinicalTrials.gov NCT01377402相似文献19.
Dorsey ER;Huntington Study Group COHORT Investigators 《PloS one》2012,7(2):e29522
Background
Careful characterization of the phenotype and genotype of Huntington disease (HD) can foster better understanding of the condition.Methods
We conducted a cohort study in the United States, Canada, and Australia of members of families affected by HD. We collected demographic and clinical data, conducted the Unified Huntington''s Disease Rating Scale and Mini-Mental State Examination, and determined Huntingtin trinucleotide CAG repeat length. We report primarily on cross-sectional baseline data from this recently completed prospective, longitudinal, observational study.Results
As of December 31, 2009, 2,318 individuals enrolled; of these, 1,985 (85.6%) were classified into six analysis groups. Three groups had expanded CAG alleles (36 repeats or more): individuals with clinically diagnosed HD [n = 930], and clinically unaffected first-degree relatives who had previously pursued [n = 248] or not pursued [n = 112] predictive DNA testing. Three groups lacked expanded alleles: first-degree relatives who had previously pursued [n = 41] or not pursued [n = 224] genetic testing, and spouses and caregivers [n = 430]. Baseline mean performance differed across groups in all motor, behavioral, cognitive, and functional measures (p<0.001). Clinically unaffected individuals with expanded alleles weighed less (76.0 vs. 79.6 kg; p = 0.01) and had lower cognitive scores (28.5 vs. 29.1 on the Mini Mental State Examination; p = 0.008) than individuals without expanded alleles. The frequency of “high normal” repeat lengths (27 to 35) was 2.5% and repeat lengths associated with reduced penetrance (36 to 39) was 2.7%.Conclusion
Baseline analysis of COHORT study participants revealed differences that emerge prior to clinical diagnosis. Longitudinal investigation of this cohort will further characterize the natural history of HD and genetic and biological modifiers.Trial Registration
Clinicaltrials.gov NCT00313495相似文献20.
Knorr U Vinberg M Hansen A Klose M Feldt-Rasmussen U Hilsted L Hasselstrøm J Gether U Winkel P Gluud C Wetterslev J Kessing LV 《PloS one》2011,6(6):e21224