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1.
Musa A Khalil E Hailu A Olobo J Balasegaram M Omollo R Edwards T Rashid J Mbui J Musa B Abuzaid AA Ahmed O Fadlalla A El-Hassan A Mueller M Mucee G Njoroge S Manduku V Mutuma G Apadet L Lodenyo H Mutea D Kirigi G Yifru S Mengistu G Hurissa Z Hailu W Weldegebreal T Tafes H Mekonnen Y Makonnen E Ndegwa S Sagaki P Kimutai R Kesusu J Owiti R Ellis S Wasunna M 《PLoS neglected tropical diseases》2012,6(6):e1674
Background
Alternative treatments for visceral leishmaniasis (VL) are required in East Africa. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India.Methods
A multi-centre randomized-controlled trial (RCT) to compare efficacy and safety of PM (20 mg/kg/day for 21 days) and PM plus sodium stibogluconate (SSG) combination (PM, 15 mg/kg/day and SSG, 20 mg/kg/day for 17 days) with SSG (20 mg/kg/day for 30 days) for treatment of VL in East Africa. Patients aged 4–60 years with parasitologically confirmed VL were enrolled, excluding patients with contraindications. Primary and secondary efficacy outcomes were parasite clearance at 6-months follow-up and end of treatment, respectively. Safety was assessed mainly using adverse event (AE) data.Findings
The PM versus SSG comparison enrolled 205 patients per arm with primary efficacy data available for 198 and 200 patients respectively. The SSG & PM versus SSG comparison enrolled 381 and 386 patients per arm respectively, with primary efficacy data available for 359 patients per arm. In Intention-to-Treat complete-case analyses, the efficacy of PM was significantly lower than SSG (84.3% versus 94.1%, difference = 9.7%, 95% confidence interval, CI: 3.6 to 15.7%, p = 0.002). The efficacy of SSG & PM was comparable to SSG (91.4% versus 93.9%, difference = 2.5%, 95% CI: −1.3 to 6.3%, p = 0.198). End of treatment efficacy results were very similar. There were no apparent differences in the safety profile of the three treatment regimens.Conclusion
The 17 day SSG & PM combination treatment had a good safety profile and was similar in efficacy to the standard 30 day SSG treatment, suggesting suitability for VL treatment in East Africa.Clinical Trials Registration
www.clinicaltrials.gov NCT00255567相似文献2.
Olliaro PL Vaillant MT Belizario VJ Lwambo NJ Ouldabdallahi M Pieri OS Amarillo ML Kaatano GM Diaw M Domingues AC Favre TC Lapujade O Alves F Chitsulo L 《PLoS neglected tropical diseases》2011,5(6):e1165
Background
Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally.Methodology/Principal Findings
Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n = 428) or 60 mg/kg (n = 428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%–98% at individual sites) with 40 mg/kg and 92.8% (88%–97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR = 0.78, 95%CI = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001). At 24 h post-dosing, 456 patients (54%) had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%).Conclusion
A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S. japonicum. The results of this study support WHO recommendation and should be used to inform policy decisions in the countries.Trial Registration
Controlled-Trials.com ISRCTN29273316 ClinicalTrials.gov NCT00403611相似文献3.
Strayer DR Carter WA Stouch BC Stevens SR Bateman L Cimoch PJ Lapp CW Peterson DL;Chronic Fatigue Syndrome AMP- Study Group Mitchell WM 《PloS one》2012,7(3):e31334
Background
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a severely debilitating disease of unknown pathogenesis consisting of a variety of symptoms including severe fatigue. The objective of the study was to examine the efficacy and safety of a TLR-3 agonist, rintatolimod (Poly I: C12U), in patients with debilitating CFS/ME.Methods and Findings
A Phase III prospective, double-blind, randomized, placebo-controlled trial comparing twice weekly IV rintatolimod versus placebo was conducted in 234 subjects with long-standing, debilitating CFS/ME at 12 sites. The primary endpoint was the intra-patient change from baseline at Week 40 in exercise tolerance (ET). Secondary endpoints included concomitant drug usage, the Karnofsky Performance Score (KPS), Activities of Daily Living (ADL), and Vitality Score (SF 36). Subjects receiving rintatolimod for 40 weeks improved intra-patient placebo-adjusted ET 21.3% (p = 0.047) from baseline in an intention-to-treat analysis. Correction for subjects with reduced dosing compliance increased placebo-adjusted ET improvement to 28% (p = 0.022). The improvement observed represents approximately twice the minimum considered medically significant by regulatory agencies. The rintatolimod cohort vs. placebo also reduced dependence on drugs commonly used by patients in an attempt to alleviate the symptoms of CFS/ME (p = 0.048). Placebo subjects crossed-over to receive rintatolimod demonstrated an intra-patient improvement in ET performance at 24 weeks of 39% (p = 0.04). Rintatolimod at 400 mg twice weekly was generally well-tolerated.Conclusions/Significance
Rintatolimod produced objective improvement in ET and a reduction in CFS/ME related concomitant medication usage as well as other secondary outcomes.Trial Registration
ClinicalTrials.gov NCT00215800相似文献4.
Poravuth Y Socheat D Rueangweerayut R Uthaisin C Pyae Phyo A Valecha N Rao BH Tjitra E Purnama A Borghini-Fuhrer I Duparc S Shin CS Fleckenstein L 《PloS one》2011,6(1):e14501
Background
New antimalarials are needed for P. vivax and P. falciparum malaria. This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria.Methods and Findings
This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3–≤60 years) with microscopically confirmed P. vivax mono-infection were randomized (1∶1) to receive pyronaridine-artesunate (target dose 7.2∶2.4 mg/kg to 13.8∶4.6 mg/kg) or chloroquine (standard dose) once daily for three days. Each treatment group included 228 randomized patients. Outcomes for the primary endpoint, Day-14 cure rate in the per-protocol population, were 99.5%, (217/218; 95%CI 97.5, 100) with pyronaridine-artesunate and 100% (209/209; 95%CI 98.3, 100) with chloroquine. Pyronaridine was non-inferior to chloroquine: treatment difference −0.5% (95%CI −2.6, 1.4), i.e., the lower limit of the 2-sided 95%CI for the treatment difference was greater than −10%. Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21, 28, 35 and 42. Parasite clearance time was shorter with pyronaridine-artesunate (median 23.0 h) versus chloroquine (32.0 h; p<0.0001), as was fever clearance time (median 15.9 h and 23.8 h, respectively; p = 0.0017). Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5% with pyronaridine-artesunate, 6.1% with chloroquine (p = 0.048, log-rank test). Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8% and 12.4%, respectively (p = 0.022, log rank test). There were no deaths. Adverse events occurred in 92/228 (40.4%) patients with pyronaridine-artesunate and 72/228 (31.6%) with chloroquine. Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate.Conclusion
Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine. As pyronaridine-artesunate is also efficacious against P. falciparum malaria, this combination has potential utility as a global antimalarial drug.Trial registration
Clinicaltrials.gov NCT00440999相似文献5.
Bethell D Se Y Lon C Tyner S Saunders D Sriwichai S Darapiseth S Teja-Isavadharm P Khemawoot P Schaecher K Ruttvisutinunt W Lin J Kuntawungin W Gosi P Timmermans A Smith B Socheat D Fukuda MM 《PloS one》2011,6(5):e19283
Background
The emergence of artemisinin resistance has raised concerns that the most potent antimalarial drug may be under threat. The currently recommended daily dose of artesunate (AS) is 4 mg/kg, and is administered for 3 days together with a partner antimalarial drug. This study investigated the impact of different AS doses on clinical and parasitological responses in malaria patients from an area of known artemisinin resistance in western Cambodia.Methods
Adult patients with uncomplicated P. falciparum malaria were randomized into one of three 7-day AS monotherapy regimens: 2, 4 or 6 mg/kg/day (total dose 14, 28 and 42 mg/kg). Clinical, parasitological, pharmacokinetic and in vitro drug sensitivity data was collected over a 7-day inpatient period and during weekly follow-up to 42 days.Results
143 patients were enrolled (n = 75, 40 and 28 to receive AS 2, 4 and 6 mg/kg/day respectively). Cure rates were high in all treatment groups at 42 days despite almost half the patients remaining parasitemic on Day 3. There was no impact of increasing AS dose on median parasite clearance times, median parasite clearance rates or on the proportion of patients remaining parasitemic on Day 3. However at the lowest dose used (2 mg/kg/d) patients with parasitemia >10,000/µL had longer median (IQR) parasite clearance times than those with parasitemia <10,000/µL (63 (48–75) vs. 84 (66–96) hours, p<0.0001). 19% of patients in the high-dose arm developed neutropenia (absolute neutrophil count <1.0×109/L) by Day 14 and resulted in the arm being halted early.Conclusion
There is no pharmacodynamic benefit of increasing the daily dose of AS (4mg/kg) currently recommended for short-course combination treatment of uncomplicated malaria, even in regions with emerging artemisinin resistance, as long as the partner drug retains high efficacy.Trial Registration
ClinicalTrials.gov . NCT00722150相似文献6.
Enders J Zimmermann E Rief M Martus P Klingebiel R Asbach P Klessen C Diederichs G Wagner M Teichgräber U Bengner T Hamm B Dewey M 《PloS one》2011,6(8):e23494
Background
Claustrophobia is a common problem precluding MR imaging. The purpose of the present study was to assess whether a short-bore or an open magnetic resonance (MR) scanner is superior in alleviating claustrophobia.Methods
Institutional review board approval and patient informed consent were obtained to compare short-bore versus open MR. From June 2008 to August 2009, 174 patients (139 women; mean age = 53.1 [SD 12.8]) with an overall mean score of 2.4 (SD 0.7, range 0 to 4) on the Claustrophobia Questionnaire (CLQ) and a clinical indication for imaging, were randomly assigned to receive evaluation by open or by short-bore MR. The primary outcomes were incomplete MR examinations due to a claustrophobic event. Follow-up was conducted 7 months after MR imaging. The primary analysis was performed according to the intention-to-treat strategy.Results
With 33 claustrophobic events in the short-bore group (39% [95% confidence interval [CI] 28% to 50%) versus 23 in the open scanner group (26% [95% CI 18% to 37%]; P = 0.08) the difference was not significant. Patients with an event were in the examination room for 3.8 min (SD 4.4) in the short-bore and for 8.5 min (SD 7) in the open group (P = 0.004). This was due to an earlier occurrence of events in the short-bore group. The CLQ suffocation subscale was significantly associated with the occurrence of claustrophobic events (P = 0.003). New findings that explained symptoms were found in 69% of MR examinations and led to changes in medical treatment in 47% and surgery in 10% of patients. After 7 months, perceived claustrophobia increased in 32% of patients with events versus in only 11% of patients without events (P = 0.004).Conclusions
Even recent MR cannot prevent claustrophobia suggesting that further developments to create a more patient-centered MR scanner environment are needed.Trial Registration
ClinicalTrials.gov NCT00715806相似文献7.
Hailu A Musa A Wasunna M Balasegaram M Yifru S Mengistu G Hurissa Z Hailu W Weldegebreal T Tesfaye S Makonnen E Khalil E Ahmed O Fadlalla A El-Hassan A Raheem M Mueller M Koummuki Y Rashid J Mbui J Mucee G Njoroge S Manduku V Musibi A Mutuma G Kirui F Lodenyo H Mutea D Kirigi G Edwards T Smith P Muthami L Royce C Ellis S Alobo M Omollo R Kesusu J Owiti R Kinuthia J;Leishmaniasis East Africa Platform 《PLoS neglected tropical diseases》2010,4(10):e709
Background
Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India.Methods
This was a 3-arm multicentre, open-label, randomized, controlled clinical trial to compare three treatment regimens for VL in East Africa: paromomycin sulphate (PM) at 15 mg/kg/day for 21 days versus sodium stibogluconate (SSG) at 20 mg/kg/day for 30 days; and the combination of both dose regimens for 17 days. The primary efficacy endpoint was cure based on parasite-free tissue aspirates taken 6 months after treatment.Findings
Overall, 135 patients per arm were enrolled at five centres in Sudan (2 sites), Kenya (1) and Ethiopia (2), when the PM arm had to be discontinued due to poor efficacy. The trial has continued with the higher dose of PM as well as the combination of PM and SSG arms. These results will be reported later. Baseline patient characteristics were similar among treatment arms. The overall cure with PM was significantly inferior to that with SSG (63.8% versus 92.2%; difference 28.5%, 95%CI 18.8% to 38.8%, p<0.001). The efficacy of PM varied among centres and was significantly lower in Sudan (14.3% and 46.7%) than in Kenya (80.0%) and Ethiopia (75.0% and 96.6%). No major safety issues with PM were identified.Conclusion
The efficacy of PM at 15 mg/kg/day for 21 days was inadequate, particularly in Sudan. The efficacy of higher doses and the combination treatment warrant further studies. 相似文献8.
Dabora SL Franz DN Ashwal S Sagalowsky A DiMario FJ Miles D Cutler D Krueger D Uppot RN Rabenou R Camposano S Paolini J Fennessy F Lee N Woodrum C Manola J Garber J Thiele EA 《PloS one》2011,6(9):e23379
Background
Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.Methods
We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas.Results
36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1–2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline).Conclusions
Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC.Trial Registration
Clinicaltrials.gov NCT00126672相似文献9.
van der Kam S Swarthout T Niragira O Froud A Sompwe EM Mills C Roll S Tinnemann P Shanks L 《PloS one》2012,7(4):e35006
Background
Catch-up growth after an infection is essential for children to maintain good nutritional status. To prevent malnutrition, WHO recommends that children are given one additional healthy meal per day during the 2 weeks after onset of illness. We investigated to what extent ready-to-use therapeutic food (RUTF) promotes catch-up growth in children after an acute, uncomplicated episode of Plasmodium falciparum malaria.Methods
We did an open randomised trial of children aged 6–59 months with confirmed malaria who attended a Médecins Sans Frontières-supported outpatient clinic in Katanga Province, Democratic Republic of Congo. All children received a clinical examination and malaria treatment. Patients were then randomly assigned to either an RUTF group, who received daily supplemental RUTF (a high-protein peanut-based paste) for 14 days, or to a control group, who received no supplemental food. Children were weighed at baseline and on days 14 and 28. The primary outcome was mean weight change after 14 days'' RUTF. Analysis was by intention-to-treat.Results
93 children received RUTF and 87 received no food supplementation. At day 14, the RUTF group had a mean weight gain of 353 g compared with 189 g in the control group (difference 164 [95%CI 52–277], p = 0.005). However, at day 28 there was no statistically significant difference between the groups (539 g versus 414 g, respectively [p = 0.053]). Similarly, rate of weight gain per kg bodyweight per day was significantly higher at day 14 in the RUTF group (2.4 g/kg per day versus 1.3 g/kg per day, p = 0.005) but at day 28 was 1.9 g/kg per day in the RUTF group versus 1.5 g/kg per day in the control group (p = 0.076).Conclusions
Children receiving RUTF for 14 days after effective treatment of an uncomplicated malaria episode had a faster weight gain than children not given supplementation, reducing the period that children were at risk of malnutrition.Trial Registration
ClinicalTrials.gov NCT00819858相似文献10.
Background and Rationale
Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT) along with reduced plasma free fatty acids (FFA) and leptin in animal models. It is unclear whether the same acute effects occur in humans.Methodology/Principal Findings
A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8) and female (7) subjects [18–30 years old, BMI 18.5–25]. Subjects received placebo or olanzapine (10 mg/day) for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA). Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC) by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105) during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203) and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170), whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166) and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184), respectively after olanzapine. Other measures were unchanged.Conclusions/Significance
Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics.Trial Registration
ClinicalTrials.gov NCT00741026相似文献11.
Mallory RM Malkin E Ambrose CS Bellamy T Shi L Yi T Jones T Kemble G Dubovsky F 《PloS one》2010,5(10):e13755
Background
The safety, tolerability, and immunogenicity of a monovalent intranasal 2009 A/H1N1 live attenuated influenza vaccine (LAIV) were evaluated in children and adults.Methods/Principal Findings
Two randomized, double-blind, placebo-controlled studies were completed in children (2–17 y) and adults (18–49 y). Subjects were assigned 4∶1 to receive 2 doses of H1N1 LAIV or placebo 28 days apart. The primary safety endpoint was fever ≥38.3°C during days 1–8 after the first dose; the primary immunogenicity endpoint was the proportion of subjects experiencing a postdose seroresponse. Solicited symptoms and adverse events were recorded for 14 days after each dose and safety data were collected for 180 days post-final dose. In total, 326 children (H1N1 LAIV, n = 261; placebo, n = 65) and 300 adults (H1N1 LAIV, n = 240; placebo, n = 60) were enrolled. After dose 1, fever ≥38.3°C occurred in 4 (1.5%) pediatric vaccine recipients and 1 (1.5%) placebo recipient (rate difference, 0%; 95% CI: –6.4%, 3.1%). No adults experienced fever following dose 1. Seroresponse rates in children (H1N1 LAIV vs. placebo) were 11.1% vs. 6.3% after dose 1 (rate difference, 4.8%; 95% CI: –9.6%, 13.8%) and 32.0% vs. 14.5% after dose 2 (rate difference, 17.5%; 95% CI: 5.5%, 27.1%). Seroresponse rates in adults were 6.1% vs. 0% (rate difference, 6.1%; 95% CI: –5.6%, 12.6%) and 14.9% vs. 5.6% (rate difference, 9.3%; 95% CI: –0.8%, 16.3%) after dose 1 and dose 2, respectively. Solicited symptoms after dose 1 (H1N1 LAIV vs. placebo) occurred in 37.5% vs. 32.3% of children and 41.7% vs. 31.7% of adults. Solicited symptoms occurred less frequently after dose 2 in adults and children. No vaccine-related serious adverse events occurred.Conclusions/Significance
In subjects aged 2 to 49 years, two doses of H1N1 LAIV have a safety and immunogenicity profile similar to other previously studied and efficacious formulations of seasonal trivalent LAIV.Trial Registration
ClinicalTrials.gov , NCT00946101 NCT00945893相似文献12.
Lo YL Lin TY Fang YF Wang TY Chen HC Chou CL Chung FT Kuo CH Feng PH Liu CY Kuo HP 《PloS one》2011,6(11):e27769
Objectives
There are safety issues associated with propofol use for flexible bronchoscopy (FB). The bispectral index (BIS) correlates well with the level of consciousness. The aim of this study was to show that BIS-guided propofol infusion is safe and may provide better sedation, benefiting the patients and bronchoscopists.Methods
After administering alfentanil bolus, 500 patients were randomized to either propofol infusion titrated to a BIS level of 65-75 (study group) or incremental midazolam bolus based on clinical judgment to achieve moderate sedation. The primary endpoint was safety, while the secondary endpoints were recovery time, patient tolerance, and cooperation.Results
The proportion of patients with hypoxemia or hypotensive events were not different in the 2 groups (study vs. control groups: 39.9% vs. 35.7%, p = 0.340; 7.4% vs. 4.4%, p = 0.159, respectively). The mean lowest blood pressure was lower in the study group. Logistic regression revealed male gender, higher American Society of Anesthesiologists physical status, and electrocautery were associated with hypoxemia, whereas lower propofol dose for induction was associated with hypotension in the study group. The study group had better global tolerance (p<0.001), less procedural interference by movement or cough (13.6% vs. 36.1%, p<0.001; 30.0% vs. 44.2%, p = 0.001, respectively), and shorter time to orientation and ambulation (11.7±10.2 min vs. 29.7±26.8 min, p<0.001; 30.0±18.2 min vs. 55.7±40.6 min, p<0.001, respectively) compared to the control group.Conclusions
BIS-guided propofol infusion combined with alfentanil for FB sedation provides excellent patient tolerance, with fast recovery and less procedure interference.Trial Registration
ClinicalTrials. gov NCT00789815相似文献13.
Background
Cardiovascular diseases are expanding to a major social-economic burden in the Western World and undermine man''s deep desire for healthy ageing. Epidemiological studies suggest that flavanol-rich foods (e.g. grapes, wine, chocolate) sustain cardiovascular health. For an evidenced-based application, however, sound clinical data on their efficacy are strongly demanded.Methods
In a double-blind, randomized, placebo-controlled intervention study we supplemented 28 male smokers with 200 mg per day of monomeric and oligomeric flavanols (MOF) from grape seeds. At baseline, after 4 and 8 weeks we measured macro- and microvascular function and a cluster of systemic biomarkers for major pathological processes occurring in the vasculature: disturbances in lipid metabolism and cellular redox balance, and activation of inflammatory cells and platelets.Results
In the MOF group serum total cholesterol and LDL decreased significantly (P≤0.05) by 5% (n = 11) and 7% (n = 9), respectively in volunteers with elevated baseline levels. Additionally, after 8 weeks the ratio of glutathione to glutathione disulphide in erythrocytes rose from baseline by 22% (n = 15, P<0.05) in MOF supplemented subjects. We also observed that MOF supplementation exerts anti-inflammatory effects in blood towards ex vivo added bacterial endotoxin and significantly reduces expression of inflammatory genes in leukocytes. Conversely, alterations in macro- and microvascular function, platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, fibrinogen, prostaglandin F2alpha, plasma antioxidant capacity and gene expression levels of antioxidant defense enzymes did not reach statistical significance after 8 weeks MOF supplementation. However, integrating all measured effects into a global, so-called vascular health index revealed a significant improvement of overall vascular health by MOF compared to placebo (P≤0.05).Conclusion
Our integrative multi-biomarker approach unveiled the pleiotropic vascular health benefit of an 8 weeks supplementation with 200 mg/d MOF in humans.Trial Registration
ClinicalTrials.gov NCT00742287相似文献14.
Machado PR Ampuero J Guimarães LH Villasboas L Rocha AT Schriefer A Sousa RS Talhari A Penna G Carvalho EM 《PLoS neglected tropical diseases》2010,4(12):e912
Background
Cutaneous leishmaniasis (CL) is treated with parenteral drugs for decades with decreasing rate cures. Miltefosine is an oral medication with anti-leishmania activity and may increase the cure rates and improve compliance.Methodology/Principal Findings
This study is a randomized, open-label, controlled clinical trial aimed to evaluate the efficacy and safety of miltefosine versus pentavalent antimony (Sbv) in the treatment of patients with CL caused by Leishmania braziliensis in Bahia, Brazil. A total of 90 patients were enrolled in the trial; 60 were assigned to receive miltefosine and 30 to receive Sbv. Six months after treatment, in the intention-to-treat analyses, the definitive cure rate was 53.3% in the Sbv group and 75% in the miltefosine group (difference of 21.7%, 95% CI 0.08% to 42.7%, p = 0.04). Miltefosine was more effective than Sbv in the age group of 13–65 years-old compared to 2–12 years-old group (78.9% versus 45% p = 0.02; 68.2% versus 70% p = 1.0, respectively). The incidence of adverse events was similar in the Sbv and miltefosine groups (76.7% vs. 78.3%). Vomiting (41.7%), nausea (40%), and abdominal pain (23.3%) were significantly more frequent in the miltefosine group while arthralgias (20.7%), mialgias (20.7%) and fever (23.3%) were significantly more frequent in the Sbv group.Conclusions
This study demonstrates that miltefosine therapy is more effective than standard Sbv and safe for the treatment of CL caused by Leishmania braziliensis in Bahia, Brazil.Trial Registration
Clinicaltrials.gov Identifier NCT00600548相似文献15.
Dicko A Barry A Dicko M Diallo AI Tembine I Dicko Y Dara N Sidibe Y Santara G Conaré T Chandramohan D Cousens S Milligan PJ Diallo DA Doumbo OK Greenwood B 《PloS one》2011,6(8):e23390
Background
Intermittent preventive treatment of malaria in children (IPTc) is a promising strategy for malaria control. A study conducted in Mali in 2008 showed that administration of three courses of IPTc with sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) at monthly intervals reduced clinical malaria, severe malaria and malaria infection by >80% in children under 5 years of age. Here we report the results of a follow-on study undertaken to establish whether children who had received IPTc would be at increased risk of malaria during the subsequent malaria transmission season.Methods
Morbidity from malaria and the prevalence of malaria parasitaemia and anaemia were measured in children who had previously received IPTc with SP and AQ using similar surveillance methods to those employed during the previous intervention period.Results
1396 of 1508 children (93%) who had previously received IPTc and 1406 of 1508 children (93%) who had previously received placebos were followed up during the high malaria transmission season of the year following the intervention. Incidence rates of clinical malaria during the post-intervention transmission season (July –November 2009) were 1.87 (95% CI 1.76 –1.99) and 1.73 (95% CI; 1.62–1.85) episodes per child year in the previous intervention and placebo groups respectively; incidence rate ratio (IRR) 1.09 (95% CI 0.99 –1.21) (P = 0.08). The prevalence of malaria infection was similar in the two groups, 7.4% versus 7.5%, prevalence ratio (PR) of 0.99 (95% CI 0.73–1.33) (P = 0.95). At the end of post-intervention malaria transmission season, the prevalence of anaemia, defined as a haemoglobin concentration<11g/dL, was similar in the two groups (56.2% versus 55.6%; PR = 1.01 [95% CI 0.91 – 1.12]) (P = 0.84).Conclusion
IPTc with SP+AQ was not associated with an increase in incidence of malaria episodes, prevalence of malaria infection or anaemia in the subsequent malaria transmission season.Trial Registration
ClinicalTrials.gov NCT00738946相似文献16.
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17.
Aide P Aponte JJ Renom M Nhampossa T Sacarlal J Mandomando I Bassat Q Manaca MN Leach A Lievens M Vekemans J Dubois MC Loucq C Ballou WR Cohen J Alonso PL 《PloS one》2010,5(11):e13838
Background
The RTS,S/AS02D vaccine has been shown to have a promising safety profile, to be immunogenic and to confer protection against malaria in children and infants.Methods and Findings
We did a randomized, controlled, phase I/IIb trial of RTS,S/AS02D given at 10, 14 and 18 weeks of age staggered with routine immunization vaccines in 214 Mozambican infants. The study was double-blind until the young child completed 6 months of follow-up over which period vaccine efficacy against new Plasmodium falciparum infections was estimated at 65.9% (95% CI 42.6–79.8, p<0.0001). We now report safety, immunogenicity and estimated efficacy against clinical malaria up to 14 months after study start. Vaccine efficacy was assessed using Cox regression models. The frequency of serious adverse events was 32.7% in the RTS,S/AS02D and 31.8% in the control group. The geometric mean titers of anti-circumsporozoite antibodies declined from 199.9 to 7.3 EU/mL from one to 12 months post dose three of RTS,S/AS02D, remaining 15-fold higher than in the control group. Vaccine efficacy against clinical malaria was 33% (95% CI: −4.3–56.9, p = 0.076) over 14 months of follow-up. The hazard rate of disease per 2-fold increase in anti-CS titters was reduced by 84% (95% CI 35.1–88.2, p = 0.003).Conclusion
The RTS,S/AS02D malaria vaccine administered to young infants has a good safety profile and remains efficacious over 14 months. A strong association between anti-CS antibodies and risk of clinical malaria has been described for the first time. The results also suggest a decrease of both anti-CS antibodies and vaccine efficacy over time.Trial Registration
ClinicalTrials.gov NCT00197028相似文献18.
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19.
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20.
Kitamura M Nakashima K Kowashi Y Fujii T Shimauchi H Sasano T Furuuchi T Fukuda M Noguchi T Shibutani T Iwayama Y Takashiba S Kurihara H Ninomiya M Kido J Nagata T Hamachi T Maeda K Hara Y Izumi Y Hirofuji T Imai E Omae M Watanuki M Murakami S 《PloS one》2008,3(7):e2611