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1.
Liu Huang Tao Zhang Conghua Xie Xin Liao Qianqian Yu Jueping Feng Hong Ma Jing Dai Min Li Jigui Chen Aihua Zang Qian Wang Shuwang Ge Kai Qin Juan Cai Xianglin Yuan 《PloS one》2013,8(10)
Background
Rapid response to chemotherapy in metastatic colorectal cancer (mCRC) patients (response within 12 weeks of chemotherapy) may increase the chance of complete resection and improved survival. Few molecular markers predict irinotecan-induced rapid response and survival. Single-nucleotide polymorphisms (SNPs) in solute carrier genes are reported to correlate with the variable pharmacokinetics of irinotecan and folate in cancer patients. This study aims to evaluate the predictive role of 3 SNPs in mCRC patients treated with irinotecan and fluoropyrimidine-containing regimens.Materials and Methods
Three SNPs were selected and genotyped in 137 mCRC patients from a Chinese prospective multicenter trial (NCT01282658). The chi-squared test, univariate and multivariable logistic regression model, and receiver operating characteristic analysis were used to evaluate correlations between the genotypes and rapid response. Kaplan-Meier survival analysis and Cox proportional hazard models were used to evaluate the associations between genotypes and survival outcomes. Benjamini and Hochberg False Discovery Rate correction was used in multiple testingResults
Genotype GA/AA of SNP rs2306283 of the gene SLCO1B1 and genotype GG of SNP rs1051266 of the gene SLC19A1 were associated with a higher rapid response rate (odds ratio [OR] =3.583 and 3.521, 95%CI =1.301-9.871 and 1.271-9.804, p=0.011 and p=0.013, respectively). The response rate was 70% in patients with both genotypes, compared with only 19.7% in the remaining patients (OR = 9.489, 95%CI = 2.191-41.093, Fisher''s exact test p=0.002). Their significances were all maintained even after multiple testing (all p c < 0.05). The rs2306283 GA/AA genotype was also an independent prognostic factor of longer progression-free survival (PFS) (hazard ratio = 0.402, 95%CI = 0.171-0.945, p=0.037). None of the SNPs predicted overall survival.Conclusions
Polymorphisms of solute carriers’ may be useful to predict rapid response to irinotecan plus fluoropyrimidine and PFS in mCRC patients.Trial Registry
ClinicalTrials.gov NCT01282658 http://www.clinicaltrials.gov/ct2/show/NCT01282658 相似文献2.
Deepika S. Darbari Zhengyuan Wang Minjung Kwak Mariana Hildesheim James Nichols Darlene Allen Catherine Seamon Marlene Peters-Lawrence Anna Conrey Mary K. Hall Gregory J. Kato James G. Taylor VI 《PloS one》2013,8(11)
Background
Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.Methods
Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations for painful VOC treatment during the 12 months prior to evaluation.Results
Higher baseline hematocrit (p = 0.0008), ferritin (p = 0.005), and HDL cholesterol (p = 0.01) were independently associated with 1 or more painful VOCs requiring an ED visit or hospitalization for acute pain. During a median follow-up of 5 years, mortality was higher in the ED visit/hospitalization group (relative risk [RR] 2.68, 95% CI 1.1-6.5, p = 0.03). Higher tricuspid regurgitatant jet velocity (TRV) (RR 2.41, 95% CI 1.5-3.9, p < 0.0001), elevated ferritin (RR 4.00, 95% CI 1.8-9.0, p = 0.001) and lower glomerular filtration rate (RR=2.73, 95% CI 1.6-4.6, p < 0.0001) were also independent risk factors for mortality.Conclusions
Severe painful VOCs remain a marker for SCA disease severity and premature mortality in a modern cohort along with other known risk factors for death including high TRV, high ferritin and lower renal function. The number of patient reported pain crises requiring healthcare utilization is an easily obtained outcome that could help to identify high risk patients for disease modifying therapies.Trial Registration
ClinicalTrials.gov NCT00011648 http://clinicaltrials.gov/ 相似文献3.
Objectives
To compare the impact of scheduling caesarean section prior to versus after 39 completed weeks of gestation on the occurrence of unscheduled caesarean section and rescheduling of the procedure.Methods
Secondary analysis from a multicentre randomised open-label trial including singleton pregnant women with a healthy foetus and a reliable due date. Women were allocated by computerized telephone randomisation to planned caesarean section at 38 weeks and three days or 39 weeks and three days. The outcomes were unscheduled deliveries with provided reasons, such as spontaneous labour onset or supervening complications, and any changes in the scheduled delivery date. Statistical analyses were according to intention-to-treat using Fisher’s exact test.Results
From March 2009 to June 2011 1,274 women were included. Median difference in gestational age at delivery was six days. Compared to the 38 weeks group, the women in the 39 weeks group were more likely to have an unscheduled caesarean section (15.2% vs. 9.3%; RR 1.64, 95% CI 1.21; 2.22), to deliver between 6 pm and 8 am (10 % vs. 6%; RR 1.68, 95% CI 1.14; 2.47), or to have the procedure rescheduled (36.7% vs. 23%; RR 1.6, 95% CI 1.34;1.90).Conclusions
Scheduling caesarean section after 39 weeks leads to a 60% increase in unscheduled caesarean sections and a 70% increase in delivery outside regular work hours as compared to scheduling of the procedure prior to 39 weeks.Trial Registration
www.clinicaltrials.gov NCT00835003 http://www.clinicaltrials.gov/ct2/show/NCT00835003?term=NCT00835003&rank=1 相似文献4.
Context
Circulating levels of metabolically protective and adverse cytokines are altered in obese humans and rodent models. However, it is not clear whether these cytokines are altered rapidly in response to over-nutrition, or as a later consequence of the obese state.Methods
Forty sedentary healthy individuals were examined prior to and at 3 and 28 days of high fat overfeeding (+1250 kCal/day, 45% fat). Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), adiposity, serum levels of adiponectin and fibroblast growth factor-21 (FGF21), fatty acid binding protein-4 (FABP4), lipocalin-2 and plasminogen activator factor-1 (PAI1) were assessed. Statistics were performed by repeated measures ANOVA.Results
Overfeeding increased weight, body fat and liver fat, fasting glucose, insulin and reduced insulin sensitivity by clamp (all P <0.05). Metabolically protective cytokines, adiponectin and FGF21 were increased at day 3 of overfeeding (P ≤0.001) and adiponectin was also elevated at day 28 (P=0.001). FABP4, lipocalin-2 and PAI-1 were not changed by overfeeding at either time point.Conclusion
Metabolically protective cytokines, adiponectin and FGF-21, were increased by over nutrition and weight gain in healthy humans, despite increases in insulin resistance. We speculate that this was in attempt to maintain glucose homeostasis in a state of nutritional excess. PAI-I, FABP4 and lipocalin 2 were not altered by overfeeding suggesting that changes in these cytokines may be a later consequence of the obese state. Clinical trial registration: www.clinicaltrials.gov (NCT00562393) 相似文献5.
Daniel H. Johnson Deborah Sutherland Edward P. Acosta Husamettin Erdem Danielle Richardson David W. Haas 《PloS one》2013,8(12)
Background
Antiretroviral drugs vary in their central nervous system penetration, with better penetration possibly conferring neurocognitive benefit during human immunodeficiency virus (HIV) therapy. The efflux transporter gene ABCB1 is expressed in the blood-brain barrier, and an ABCB1 variant (3435C→T) has been reported to affect ABCB1 expression. The integrase inhibitor raltegravir is a substrate for ABCB1. We examined whether ABCB1 3435C→T affects raltegravir disposition into cerebrospinal fluid (CSF), and explored associations with polymorphisms in other membrane transporter genes expressed in the blood-brain barrier.Methods
Forty healthy, HIV-negative adults of European descent (20 homozygous for ABCB1 3435 C/C, 20 homozygous for 3435 T/T, each group divided equally between males and females) were given raltegravir 400 mg twice daily for 7 days. With the final dose, plasma was collected for pharmacokinetic analysis at 9 timepoints over 12 hours, and CSF collected 4 hours post dose.Results
The 4-hour CSF concentration correlated more strongly with 2-hour (r2=0.76, P=1.12x10-11) than 4-hour (r2=0.47, P=6.89x10-6) single timepoint plasma concentration, and correlated strongly with partial plasma area-under-the-curve values (AUC0-4h r2=0.86, P=5.15x10-16). There was no significant association between ABCB1 3435C→T and ratios of CSF-to-plasma AUC or concentration (p>0.05 for each comparison). In exploratory analyses, CSF-to-plasma ratios were not associated with 276 polymorphisms across 16 membrane transporter genes.Conclusions
Among HIV-negative adults, CSF raltegravir concentrations do not differ by ABCB1 3435C→T genotype but strongly correlate with plasma exposure.Trial Registration
ClinicalTrials.gov NCT00729924 http://clinicaltrials.gov/show/NCT00729924 相似文献6.
Objective
To investigate the effectiveness of educational poster on improving secondary school students'' knowledge of emergency management of dental trauma.Methods
A cluster randomised controlled trial was conducted. 16 schools with total 671 secondary students who can read Chinese or English were randomised into intervention (poster, 8 schools, 364 students) and control groups (8 schools, 305 students) at the school level. Baseline knowledge of dental trauma was obtained by a questionnaire. Poster containing information of dental trauma management was displayed in a classroom for 2 weeks in each school in the intervention group whereas in the control group there was no display of such posters. Students of both groups completed the same questionnarie after 2 weeks.Results
Two-week display of posters improved the knowledge score by 1.25 (p-value = 0.0407) on average.Conclusion
Educational poster on dental trauma management significantly improved the level of knowledge of secondary school students in Hong Kong.Trial Registration
HKClinicalTrial.com HKCTR-1343 ClinicalTrials.gov NCT01809457 相似文献7.
8.
Background
Transpulmonary thermodilution allows the measurement of cardiac index for high risk surgical patients. Oncologic patients often have a central venous access (port-a-catheter) for chronic treatment. The validity of the measurement by a port-a-catheter of the absolute cardiac index and the detection of changes in cardiac index induced by fluid challenge are unknown.Methods
We conducted a monocentric prospective study. 27 patients were enrolled. 250 ml colloid volume expansions for fluid challenge were performed during ovarian cytoreductive surgery. The volume expansion-induced changes in cardiac index measured by transpulmonary thermodilution by a central venous access (CIcvc) and by a port-a-catheter (CIport) were recorded.Results
23 patients were analyzed with 123 pairs of measurements. Using a Bland and Altman for repeated measurements, the bias (lower and upper limits of agreement) between CIport and CIcvc was 0.14 (−0.59 to 0.88) L/min/m2. The percentage error was 22%. The concordance between the changes in CIport and CIcvc observed during volume expansion was 92% with an r = 0.7 (with exclusion zone). No complications (included sepsis) were observed during the follow up period.Conclusions
The transpulmonary thermodilution by a port-a-catheter is reliable for absolute values estimation of cardiac index and for measurement of the variation after fluid challenge.Trial Registration
clinicaltrials.gov NCT02063009 相似文献9.
Objective
To assess the clinical effect of medication monitoring using the West Wales Adverse Drug Reaction (ADR) Profile for Respiratory Medicine.Design
Single-site parallel-arm pragmatic trial using stratified randomisation.Setting
Nurse-led respiratory outpatient clinic in general hospital in South Wales.Participants
54 patients with chronic respiratory disease receiving bronchodilators, corticosteroids or leukotriene receptor antagonists.Intervention
Following initial observation of usual nursing care, we allocated participants at random to receive at follow up: either the West Wales ADR Profile for Respiratory Medicine in addition to usual care (‘intervention arm’ with 26 participants); or usual care alone (‘control arm’ with 28 participants).Main Outcome Measures
Problems reported and actions taken.Results
We followed up all randomised participants, and analysed data in accordance with treatment allocated. The increase in numbers of problems per participant identified at follow up was significantly higher in the intervention arm, where the median increase was 20.5 [inter-quartile range (IQR) 13–26], while that in the control arm was −1 [−3 to +2] [Mann-Whitney U test: z = 6.28, p<0.001]. The increase in numbers of actions per participant taken at follow up was also significantly higher in the intervention arm, where the median increase was 2.5 [1]–[4] while that in the control arm was 0 [−1.75 to +1] [Mann-Whitney U test: z = 4.40, p<0.001].Conclusion
When added to usual nursing care, the West Wales ADR Profile identified more problems and prompted more nursing actions. Our ADR Profile warrants further investigation as a strategy to optimise medication management.Trial Registration
Controlled-trials.com ISRCTN10386209 相似文献10.
Alphonse Ouédraogo Alfred B. Tiono Désiré Kargougou Jean Baptiste Yaro Esperance Ouédraogo Youssouf Kaboré David Kangoye Edith C. Bougouma Adama Gansane Noelie Henri Amidou Diarra Souleymane Sanon Issiaka Soulama Amadou T. Konate Nora L. Watson Valerie Brown Jenny Hendriks Maria Grazia Pau Isabella Versteege Edison Wiesken Jerald Sadoff Issa Nebie Sodiomon B. Sirima 《PloS one》2013,8(11)
Background
Ad35.CS.01 is a pre-erythrocytic malaria candidate vaccine. It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite (CS) surface antigen inserted in a replication deficient Adenovirus 35 backbone. A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe. The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa.Methods
A double blind, randomized, controlled, dose escalation, phase Ib trial was conducted in a rural area of Balonghin, the Saponé health district (Burkina Faso). Forty-eight healthy adults aged 18-45 years were randomized into 4 cohorts of 12 to receive three vaccine doses (day 0, 28 and 84) of 109, 1010, 5X1010, 1011 vp of Ad35.CS.01 or normal saline by intra muscular injection. Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events. Severe and serious adverse events were collected throughout the participant study duration (12 months from the first vaccination). Humoral and cellular immune responses were measured on study days 0, 28, 56, 84, 112 and 140.Results
Of the forty-eight subjects enrolled, forty-four (91.7%) received all three scheduled vaccine doses. Local reactions, all of mild severity, occurred in thirteen (27.1%) subjects. Severe (grade 3) laboratory abnormalities occurred in five (10.4%) subjects. One serious adverse event was reported and attributed to infection judged unrelated to vaccine. The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35.Conclusion
Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population. These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies.Trial Registration
ClinicalTrials.gov NCT01018459 http://clinicaltrials.gov/ct2/show/NCT01018459 相似文献11.
Clare L. Atzema Peter C. Austin Libo Wu Michael Brzozowski Michael J. Feldman Michael McDonnell Laurie Mazurik 《PloS one》2013,8(11)
Background
Emergency department discharge instructions are variably understood by patients, and in the setting of emergency department crowding, innovations are needed to counteract shortened interaction times with the physician. We evaluated the effect of viewing an online video of diagnosis-specific discharge instructions on patient comprehension and recall of instructions.Methods
In this prospective, single-center, randomized controlled trial conducted between November 2011 and January 2012, we randomized emergency department patients who were discharged with one of 38 diagnoses to either view (after they left the emergency department) a vetted online video of diagnosis-specific discharge instructions, or to usual care. Patients were subsequently contacted by telephone and asked three standardized questions about their discharge instructions; one point was awarded for each correct answer. Using an intention-to-treat analysis, differences between groups were assessed using univariate testing, and with logistic regression that accounted for clustering on managing physician. A secondary outcome measure was patient satisfaction with the videos, on a 10-point scale.Results
Among 133 patients enrolled, mean age was 46.1 (s.d.D. 21.5) and 55% were female. Patients in the video group had 19% higher mean scores (2.5, s.d. 0.7) than patients in the control group (2.1, s.d. 0.8) (p=0.002). After adjustment for patient age, sex, first language, triage acuity score, and clustering, the odds of achieving a fully correct score (3 out of 3) were 3.5 (95% CI, 1.7 to 7.2) times higher in the video group, compared to the control group. Among those who viewed the videos, median rating of the videos was 10 (IQR 8 to 10).Conclusions
In this single-center trial, patients who viewed an online video of their discharge instructions scored higher on their understanding of key concepts around their diagnosis and subsequent care. Those who viewed the videos found them to be a helpful addition to standard care.Trial Registration
ClinicalTrials.gov NCT01361932 http://clinicaltrials.gov/ct2/show/NCT01361932?term=nct01361932&rank=1 相似文献12.
Denise C. Hsu Stephen J. Kerr Thatri Iampornsin Sarah L. Pett Anchalee Avihingsanon Parawee Thongpaeng John J. Zaunders Sasiwimol Ubolyam Jintanat Ananworanich Anthony D. Kelleher David A. Cooper 《PloS one》2013,8(10)
Objectives
Restoration of Cytomegalovirus-specific-CD4 T cell (CMV-Sp-CD4) responses partly accounts for the reduction of CMV-disease with antiretroviral-therapy (ART), but CMV-Sp-CD4 may also drive immune activation and immunosenescence. This study characterized the dynamics of CMV-Sp-CD4 after ART initiation and explored associations with CD4 T cell recovery as well as frequency of naïve CD4 T cells at week 96.Methods
Fifty HIV-infected, ART-naïve Thai adults with CD4 T cell count ≤350cells/µL and starting ART were evaluated over 96 weeks (ClinicalTrials.gov identifier NCT01296373). CMV-Sp-CD4 was detected by co-expression of CD25/CD134 by flow cytometry after CMV-antigen stimulation.Results
All subjects were CMV sero-positive, 4 had quantifiable CMV-DNA (range 2.3-3.9 log10 copies/mL) at baseline but none had clinically apparent CMV-disease. Baseline CMV-Sp-CD4 response was positive in 40 subjects. Those with CD4 T cell count <100cells/µL were less likely to have positive baseline CMV-Sp-CD4 response (P=0.003). Positive baseline CMV-Sp-CD4 response was associated with reduced odds of quantifiable CMV-DNA (P=0.022). Mean CD4 T cell increase at week 96 was 213 cells/µL. This was associated positively with baseline HIV-VL (P=0.001) and negatively with age (P=0.003). The frequency of CMV-Sp-CD4 increased at week 4 (P=0.008), then declined. Those with lower baseline CMV-Sp-CD4 (P=0.009) or CDC category C (P<0.001) had greater increases in CMV-Sp-CD4 at week 4. At week 96, CD4 T cell count was positively (P<0.001) and the frequency of CMV-Sp-CD4 was negatively (P=0.001) associated with the percentage of naïve CD4 T cells.Conclusions
Increases in CMV-Sp-CD4 with ART occurred early and were greater in those with more advanced immunodeficiency. The frequency of CMV-Sp-CD4 was associated with reduced naïve CD4 T cells, a marker associated with immunosenescence. 相似文献13.
Juan Macías Luis F. López-Cortés Francisco Téllez Eva Recio Guillermo Ojeda-Burgos MaJosé Ríos Antonio Rivero-Juárez Marcial Delgado Rivas- Jeremías Juan A. Pineda 《PloS one》2015,10(12)
Background
Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients.Patients and Methods
This was an open-label, single arm, multicenter phase II pilot clinical trial () enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 μg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure). A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control. NCT01529073Results
Two (9.5%) of 21 patients included in the trial compared with 5 (21.7%) of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416). Virological failure was due to lack of response in 13 (62%) individuals recruited in the trial. Two (9.5%) patients included in the trial and two (9.5%) individuals from the historical cohort discontinued permanently due to adverse events.Conclusions
No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy.Trial Registration
ClinicalTrials.gov NCT01529073相似文献14.
Patricia L. Hibberd Lauren Kleimola Anne-Maria Fiorino Christine Botelho Miriam Haverkamp Irina Andreyeva Debra Poutsiaka Claire Fraser Gloria Solano-Aguilar David R. Snydman 《PloS one》2014,9(12)
Background
Although Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed by 2 to 5 million people daily since the mid 1990s, there are few clinical trials describing potential harms of LGG, particularly in the elderly.Objectives
The primary objective of this open label clinical trial is to assess the safety and tolerability of 1×1010 colony forming units (CFU) of LGG administered orally twice daily to elderly volunteers for 28 days. The secondary objectives were to evaluate the effects of LGG on the gastrointestinal microbiome, host immune response and plasma cytokines.Methods
Fifteen elderly volunteers, aged 66–80 years received LGG capsules containing 1×1010 CFU, twice daily for 28 days and were followed through day 56. Volunteers completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits in the Clinical Research Center at baseline, day 28 and day 56 to determine whether adverse events had occurred. Assessments included prompted and open-ended questions.Results
There were no serious adverse events. The 15 volunteers had a total of 47 events (range 1–7 per volunteer), 39 (83%) of which were rated as mild and 40% of which were considered related to consuming LGG. Thirty-one (70%) of the events were expected, prompted symptoms while 16 were unexpected events. The most common adverse events were gastrointestinal (bloating, gas, and nausea), 27 rated as mild and 3 rated as moderate. In the exploratory analysis, the pro-inflammatory cytokine interleukin 8 decreased during LGG consumption, returning towards baseline one month after discontinuing LGG (p = 0.038) while there was no difference in other pro- or anti-inflammatory plasma cytokines.Conclusions
Lactobacillus rhamnosus GG ATCC 53103 is safe and well tolerated in healthy adults aged 65 years and older.Trial Registration
ClinicalTrials.gov NCT 01274598 相似文献15.
Inez Wens Ulrik Dalgas Frank Vandenabeele Maartje Krekels Lotte Grevendonk Bert O. Eijnde 《PloS one》2014,9(9)
Background
The impact of multiple sclerosis (MS) on skeletal muscle characteristics, such as muscle fiber cross sectional area (CSA), fiber type proportion, muscle strength and whole muscle mass, remains conflicting.Methods
In this cross sectional study, body composition and muscle strength of the quadriceps were assessed in 34 MS (EDSS: 2.5±0.19) patients and 18 matched healthy controls (HC). Hereafter a muscle biopsy (m.vastus lateralis) was taken.Results
Compared to HC, mean muscle fiber CSA of all fibers, as well as CSA of type I, II and IIa fibers were smaller and muscle strength of the quadriceps was lower in MS patients. Whole body composition was comparable between groups. However, compared to HC, the biopsied leg tended to have a higher fat percentage (p = 0.1) and a lower lean mass (p = 0.06) in MS patients.Conclusion
MS seems to negatively influence skeletal muscle fiber CSA, muscle strength and muscle mass of the lower limbs of mildly affected MS patients. This emphasises the need for rehabilitation programs focusing on muscle preservation of the lower limb.Trial Registration
ClinicalTrials.gov NCT01845896 相似文献16.
Ingeborg A. Brouwer Johanna M. Geleijnse Veronique M. Klaasen Liesbeth A. Smit Erik J. Giltay Janette de Goede Annemieke C. Heijboer Daan Kromhout Martijn B. Katan 《PloS one》2013,8(12)
Background
Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer.Methods
The Alpha Omega Trial (ClinicalTrials.gov Identifier: ) was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 2×2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60–80 years with an initial PSA concentration <4 ng/mL. They received either 2 g per day of ALA or placebo in margarine spreads for 40 months. T-tests and logistic regression were used to assess the effects of ALA supplementation on changes in serum PSA (both continuously and as a dichotomous outcome, cut-off point: >4 ng/mL). NCT00127452Findings
Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: −0.02 to 0.22) ng/mL (P = 0·12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84–1.58).Interpretation
An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from −0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer.Trial registration information
ClinicalTrials.gov; Identifier: . URL: http://www.clinicaltrials.gov/ct2/show/ NCT00127452. NCT00127452相似文献17.
18.
Christian Wolf Jagdev Sidhu Christian Otoul Dexter L. Morris Jennifer Cnops Jorg Taubel Barbara Bennett 《PloS one》2013,8(3)
Background
Lymphocyte inhibition by antagonism of α4 integrins is a validated therapeutic approach for relapsing multiple sclerosis (RMS).Objective
Investigate the effect of CDP323, an oral α4-integrin inhibitor, on lymphocyte biomarkers in RMS.Methods
Seventy-one RMS subjects aged 18–65 years with Expanded Disability Status Scale scores ≤6.5 were randomized to 28-day treatment with CDP323 100 mg twice daily (bid), 500 mg bid, 1000 mg once daily (qd), 1000 mg bid, or placebo.Results
Relative to placebo, all dosages of CDP323 significantly decreased the capacity of lymphocytes to bind vascular adhesion molecule-1 (VCAM-1) and the expression of α4-integrin on VCAM-1–binding cells. All but the 100-mg bid dosage significantly increased total lymphocytes and naive B cells, memory B cells, and T cells in peripheral blood compared with placebo, and the dose-response relationship was shown to be linear. Marked increases were also observed in natural killer cells and hematopoietic progenitor cells, but only with the 500-mg bid and 1000-mg bid dosages. There were no significant changes in monocytes. The number of samples for regulator and inflammatory T cells was too small to draw any definitive conclusions.Conclusions
CDP323 at daily doses of 1000 or 2000 mg induced significant increases in total lymphocyte count and suppressed VCAM-1 binding by reducing unbound very late antigen-4 expression on lymphocytes.Trial Registration
ClinicalTrials.gov NCT00726648. 相似文献19.
Maria Egede Johansen Jens-Ulrik Jensen Morten Heiberg Bestle Lars Hein Anne ?berg Lauritsen Hamid Tousi Kim Michael Larsen Jesper L?ken Thomas Mohr Katrin Thormar P?r I. Johansson Alessandro Cozzi-Lepri Jens D. Lundgren 《PloS one》2013,8(11)
Background
Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients. Several antimicrobials have been implicated, although experimental evidence to demonstrate causality is limited. We report, using a randomized trial, the potential of antimicrobials to induce thrombocytopenia.Methods
Randomized trial allocated patients to antimicrobial treatment according to standard- of-care (SOC group) or drug-escalation in case of procalcitonin increases (high-exposure group). Patients were followed until death or day 28. Thrombocytopenia defined as absolute (platelet count ≤100x109/L) or relative (≥20% decrease in platelet count). Analyses were performed in the two randomized groups and as a merged cohort.Results
Of the 1147 patients with platelet data available, 18% had absolute thrombocytopenia within the first 24 hours after admission to intensive care unit and additional 17% developed this complication during follow-up; 57% developed relative thrombocytopenia during follow-up. Absolute and relative thrombocytopenia day 1-4 was associated with increased mortality (HR: 1.67 [95% CI: 1.30 to 2.14]; 1.71 [95% CI: 1.30 to 2.30], P<0.0001, respectively). Patients in the high-exposure group received more antimicrobials including piperacillin/tazobactam, meropenem and ciprofloxacin compared with the SOC group, whereas cefuroxime was used more frequently in the SOC group (p<0.05). Risk of absolute and relative thrombocytopenia (RR: 0.9 [0.7-1.3], p=0.7439; 1.2 [1.0-1.4], p=0.06; respectively), as well as absolute platelet count (daily difference, high-exposure vs. SOC -1.7 [-3.8-0.5], p=0.14) was comparable between groups. In observational analyses, use of ciprofloxacin and piperacillin/tazobactam predicted risk of relative thrombocytopenia (vs. cefuroxime, RR: 2.08 [1.48-2.92]; 1.44 [1.10-1.89], respectively), however only ciprofloxacin were associated with a reduction in absolute platelet count (p=0.0005).Conclusion
High exposure to broad-spectrum antimicrobials does not result in a reduction in thrombocytopenia in critically ill patients. However, single use of ciprofloxacin, and less so piperacillin/tazobactam, may contribute to a lower platelet count.Trial Registration
ClinicalTrials.gov NCT00271752 http://clinicaltrials.gov/ct2/show/NCT00271752 相似文献20.
Janne C. de Ruyter Martijn B. Katan Lothar D. J. Kuijper Djin G. Liem Margreet R. Olthof 《PloS one》2013,8(10)