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1.
Kolaczinski K Leslie T Ali I Durrani N Lee S Barends M Beshir K Ord R Hallett R Rowland M 《PloS one》2012,7(1):e28957
Introduction
Antimalarial resistance has led to a global policy of artemisinin-based combination therapy. Despite growing resistance chloroquine (CQ) remained until recently the official first-line treatment for falciparum malaria in Pakistan, with sulfadoxine-pyrimethamine (SP) second-line. Co-treatment with the gametocytocidal primaquine (PQ) is recommended for transmission control in South Asia. The relative effect of artesunate (AS) or primaquine, as partner drugs, on clinical outcomes and gametocyte carriage in this setting were unknown.Methods
A single-blinded, randomized trial among Afghan refugees in Pakistan compared six treatment arms: CQ; CQ+(single-dose)PQ; CQ+(3 d)AS; SP; SP+(single-dose)PQ, and SP+(3 d)AS. The objectives were to compare treatment failure rates and effect on gametocyte carriage, of CQ or SP monotherapy against the respective combinations (PQ or AS). Outcomes included trophozoite and gametocyte clearance (read by light microscopy), and clinical and parasitological failure.Findings
A total of 308 (87%) patients completed the trial. Failure rates by day 28 were: CQ 55/68 (81%); CQ+AS 19/67 (28%), SP 4/41 (9.8%), SP+AS 1/41 (2.4%). The addition of PQ to CQ or SP did not affect failure rates (CQ+PQ 49/67 (73%) failed; SP+PQ 5/33 (16%) failed). AS was superior to PQ at clearing gametocytes; gametocytes were seen on d7 in 85% of CQ, 40% of CQ+PQ, 21% of CQ+AS, 91% of SP, 76% of SP+PQ and 23% of SP+AS treated patients. PQ was more effective at clearing older gametocyte infections whereas AS was more effective at preventing emergence of mature gametocytes, except in cases that recrudesced.Conclusions
CQ is no longer appropriate by itself or in combination. These findings influenced the replacement of CQ with SP+AS for first-line treatment of uncomplicated falciparum malaria in the WHO Eastern Mediterranean Region. The threat of SP resistance remains as SP monotherapy is still common. Three day AS was superior to single-dose PQ for reducing gametocyte carriage.Trial Registration
ClinicalTrials.gov bold> 相似文献2.
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3.
El-Sayed B El-Zaki SE Babiker H Gadalla N Ageep T Mansour F Baraka O Milligan P Babiker A 《PloS one》2007,2(12):e1311
Background
In areas of seasonal malaria transmission, treatment of asymptomatic carriers of malaria parasites, whose parasitaemia persists at low densities throughout the dry season, could be a useful strategy for malaria control. We carried out a randomized trial to compare two drug regimens for clearance of parasitaemia in order to identify the optimum regimen for use in mass drug administration in the dry season.Methodology and Principal Findings
A two-arm open-label randomized controlled trial was conducted during the dry season in an area of distinct seasonal malaria in two villages in Gedarif State in eastern Sudan. Participants were asymptomatic adults and children aged over 6 months, with low-density P. falciparum infection detected by PCR. Participants were randomized to receive artesunate/sulfadoxine-pyrimethamine (AS+SP) combination for three days with or without a dose of primaquine (PQ) on the fourth day. Parasitaemia detected by PCR on days 3, 7 and 14 after the start of treatment and gametocytes detected by RT-PCR on days 7 and 14 were then recorded. 104 individuals who had low density parasitaemia at screening were randomized and treated during the dry season. On day 7, 8.3% were positive by PCR in the AS+SP+PQ group and 6.5% in the AS+SP group (risk difference 1.8%, 95%CI −10.3% to +13.8%). At enrolment, 12% (12/100) were carrying gametocytes. This was reduced to 6.4% and 4.4% by day 14 (Risk difference 1.9% (95%CI −9.3% to +13.2%) in AS+SP+PQ and AS+SP groups, respectively.Conclusion
Addition of primaquine to artemisinin combination treatment did not improve elimination of parasitaemia and prevention of gametocyte carriage in carriers with low-density parasitaemia in the dry season.Trial Registration
ClinicalTrials.gov NCT00330902 相似文献4.
Konaté AT Yaro JB Ouédraogo AZ Diarra A Gansané A Soulama I Kangoyé DT Kaboré Y Ouédraogo E Ouédraogo A Tiono AB Ouédraogo IN Chandramohan D Cousens S Milligan PJ Sirima SB Greenwood BM Diallo DA 《PloS one》2011,6(8):e23391
Background
Interventions that reduce exposure to malaria infection may lead to delayed malaria morbidity and mortality. We investigated whether intermittent preventive treatment of malaria in children (IPTc) was associated with an increase in the incidence of malaria after cessation of the intervention.Methods
An individually randomised, trial of IPTc, comparing three courses of sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) with placebos was implemented in children aged 3–59 months during the 2008 malaria transmission season in Burkina Faso. All children in the trial were given a long lasting insecticide treated net; 1509 children received SP+AQ and 1505 received placebos. Passive surveillance for malaria was maintained until the end of the subsequent malaria transmission season in 2009, and active surveillance for malaria infection, anaemia and malnutrition was conducted.Results
On thousand, four hundred and sixteen children (93.8%) and 1399 children (93.0%) initially enrolled in the intervention and control arms of the trial respectively were followed during the 2009 malaria transmission season. During the period July 2009 to November 2009, incidence rates of clinical malaria were 3.84 (95%CI; 3.67–4.02) and 3.45 (95%CI; 3.29–3.62) episodes per child during the follow up period in children who had previously received IPT or placebos, indicating a small increase in risk for children in the former intervention arm (IRR = 1.12; 95%CI 1.04–1.20) (P = 0.003). Children who had received SP+AQ had a lower prevalence of malaria infection (adjusted PR: 0.88 95%CI: 0.79–0.98) (P = 0.04) but they had a higher parasite density (P = 0.001) if they were infected. There was no evidence that the risks of moderately severe anaemia (Hb<8 g/dL), wasting, stunting, or of being underweight in children differed between treatment arms.Conclusion
IPT with SP+AQ was associated with a small increase in the incidence of clinical malaria in the subsequent malaria transmission season.Trial Registration
ClinicalTrials.gov NCT00738946 相似文献5.
Churchyard GJ Morgan C Adams E Hural J Graham BS Moodie Z Grove D Gray G Bekker LG McElrath MJ Tomaras GD Goepfert P Kalams S Baden LR Lally M Dolin R Blattner W Kalichman A Figueroa JP Pape J Schechter M Defawe O De Rosa SC Montefiori DC Nabel GJ Corey L Keefer MC;NIAID HIV Vaccine Trials Network 《PloS one》2011,6(8):e21225
Background
The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean.Methods
480 participants were evenly randomized to receive either: DNA (4 mg IM by Biojector) at 0, 1 and 2 months, followed by rAd5 (1010 PU IM by needle/syringe) at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost.Results
The vaccine was well tolerated and safe. T-cell responses, detected by interferon-γ (IFN-γ) ELISpot to global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively) and most secreted ≥2 cytokines. The vaccine induced a high frequency (83.7%–94.6%) of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients.Conclusion
The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.Trial Registration:
ClinicalTrials.gov NCT00125970 相似文献6.
Tebas P Tuluc F Barrett JS Wagner W Kim D Zhao H Gonin R Korelitz J Douglas SD 《PloS one》2011,6(9):e24180
Background
Neurokinin-1 receptor (NK1R) antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic.Methods
We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm3 and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml) and randomized within each stratum to receive aprepitant at 125 mg QD(Low), or 250 mg QD(High), or placebo(PL) for 14 days, and followed for 42 days.Results
Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low), 250 (High), and PL groups). 63% were male; 37% white; mean (SD) age 43 (9.3) years. Geometric mean baseline viral load (copies/ml) for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI) change in log10 viral load at day 14 for Low, High, and PL was −0.02(−0.24,+0.20), −0.05(−0.21,+0.10), and +0.04(−0.08,+0.16), respectively. The number of subjects with AEs was 4(44.4%), 5(62.5%), and 1(10%) for Low, High, and PL. No Grade 4 AEs occurred.Conclusions
Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity.Trial Registration
ClinicalTrials.gov NCT00428519 相似文献7.
Koblin BA Casapia M Morgan C Qin L Wang ZM Defawe OD Baden L Goepfert P Tomaras GD Montefiori DC McElrath MJ Saavedra L Lau CY Graham BS;NIAID HIV Vaccine Trials Network 《PloS one》2011,6(9):e24517
Background
In the development of HIV vaccines, improving immunogenicity while maintaining safety is critical. Route of administration can be an important factor.Methodology/Principal Findings
This multicenter, open-label, randomized trial, HVTN 069, compared routes of administration on safety and immunogenicity of a DNA vaccine prime given intramuscularly at 0, 1 and 2 months and a recombinant replication-defective adenovirus type 5 (rAd5) vaccine boost given at 6 months by intramuscular (IM), intradermal (ID), or subcutaneous (SC) route. Randomization was computer-generated by a central data management center; participants and staff were not blinded to group assignment. The outcomes were vaccine reactogenicity and humoral and cellular immunogenicity. Ninety healthy, HIV-1 uninfected adults in the US and Peru, aged 18–50 were enrolled and randomized. Due to the results of the Step Study, injections with rAd5 vaccine were halted; thus 61 received the booster dose of rAd5 vaccine (IM: 20; ID:21; SC:20). After the rAd5 boost, significant differences by study arm were found in severity of headache, pain and erythema/induration. Immune responses (binding and neutralizing antibodies, IFN-γ ELISpot HIV-specific responses and CD4+ and CD8+ T-cell responses by ICS) at four weeks after the rAd5 booster were not significantly different by administration route of the rAd5 vaccine boost (Binding antibody responses: IM: 66.7%; ID: 70.0%; SC: 77.8%; neutralizing antibody responses: IM: 11.1%; ID: 0.0%; SC 16.7%; ELISpot responses: IM: 46.7%; ID: 35.3%; SC: 44.4%; CD4+ T-cell responses: IM: 29.4%; ID: 20.0%; SC: 35.3%; CD8+ T-cell responses: IM: 29.4%; ID: 16.7%; SC: 50.0%.)Conclusions/Significance
This study was limited by the reduced sample size. The higher frequency of local reactions after ID and SC administration and the lack of sufficient evidence to show that there were any differences in immunogenicity by route of administration do not support changing route of administration for the rAd5 boost.Trial Registration
ClinicalTrials.gov NCT00384787 相似文献8.
Nankabirwa J Cundill B Clarke S Kabatereine N Rosenthal PJ Dorsey G Brooker S Staedke SG 《PloS one》2010,5(10):e13438
Background
Intermittent preventive treatment (IPT) is a promising malaria control strategy; however, the optimal regimen remains unclear. We conducted a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single course of sulfadoxine-pyrimethamine (SP), amodiaquine + SP (AQ+SP) or dihydroartemisinin-piperaquine (DP) among schoolchildren to inform IPT.Methods
Asymptomatic girls aged 8 to 12 years and boys aged 8 to 14 years enrolled in two primary schools in Tororo, Uganda were randomized to receive one of the study regimens or placebo, regardless of presence of parasitemia at enrollment, and followed for 42 days. The primary outcome was risk of parasitemia at 42 days. Survival analysis was used to assess differences between regimens.Results
Of 780 enrolled participants, 769 (98.6%) completed follow-up and were assigned a treatment outcome. The risk of parasitemia at 42 days varied significantly between DP (11.7% [95% confidence interval (CI): 7.9, 17.1]), AQ+SP (44.3% [37.6, 51.5]), and SP (79.7% [95% CI: 73.6, 85.2], p<0.001). The risk of parasitemia in SP-treated children was no different than in those receiving placebo (84.6% [95% CI: 79.1, 89.3], p = 0.22). No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003).Conclusions
DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren. Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa.Trial Registration
ClinicalTrials.gov NCT00852371 相似文献9.
Wang P Holst C Andersen MR Astrup A Bouwman FG van Otterdijk S Wodzig WK van Baak MA Larsen TM Jebb SA Kafatos A Pfeiffer AF Martinez JA Handjieva-Darlenska T Kunesova M Saris WH Mariman EC 《PloS one》2011,6(2):e16773
Background
Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI) diet improved weight maintenance.Objective
To identify blood predictors for weight change after weight loss following the dietary intervention within the Diogenes study.Design
Blood samples were collected at baseline and after 8-week low caloric diet-induced weight loss from 48 women who continued to lose weight and 48 women who regained weight during subsequent 6-month dietary intervention period with 4 diets varying in protein and GI levels. Thirty-one proteins and 3 steroid hormones were measured.Results
Angiotensin I converting enzyme (ACE) was the most important predictor. Its greater reduction during the 8-week weight loss was related to continued weight loss during the subsequent 6 months, identified by both Logistic Regression and Random Forests analyses. The prediction power of ACE was influenced by immunoproteins, particularly fibrinogen. Leptin, luteinizing hormone and some immunoproteins showed interactions with dietary protein level, while interleukin 8 showed interaction with GI level on the prediction of weight maintenance. A predictor panel of 15 variables enabled an optimal classification by Random Forests with an error rate of 24±1%. A logistic regression model with independent variables from 9 blood analytes had a prediction accuracy of 92%.Conclusions
A selected panel of blood proteins/steroids can predict the weight change after weight loss. ACE may play an important role in weight maintenance. The interactions of blood factors with dietary components are important for personalized dietary advice after weight loss.Registration
ClinicalTrials.gov NCT00390637 相似文献10.
Bell DJ Nyirongo SK Mukaka M Zijlstra EE Plowe CV Molyneux ME Ward SA Winstanley PA 《PloS one》2008,3(2):e1578
Background
In Malawi, there has been a return of Plasmodium falciparum sensitivity to chloroquine (CQ) since sulfadoxine-pyrimethamine (SP) replaced CQ as first line treatment for uncomplicated malaria. When used for prophylaxis, Amodiaquine (AQ) was associated with agranulocytosis but is considered safe for treatment and is increasingly being used in Africa. Here we compare the efficacy, safety and selection of resistance using SP or CQ+SP or artesunate (ART)+SP or AQ+SP for the treatment of uncomplicated falciparum malaria.Methodology and Findings
455 children aged 1–5 years were recruited into a double-blinded randomised trial comparing SP to the three combination therapies. Using intention to treat analysis with missing outcomes treated as successes, and without adjustment to distinguish recrudescence from new infections, the day 28 adequate clinical and parasitological response (ACPR) rate for SP was 25%, inferior to each of the three combination therapies (p<0.001). AQ+SP had an ACPR rate of 97%, higher than CQ+SP (81%) and ART+SP (70%), p<0.001. Nineteen children developed a neutropenia of ≤0.5×103 cells/µl by day 14, more commonly after AQ+SP (p = 0.03). The mutation pfcrt 76T, associated with CQ resistance, was detected in none of the pre-treatment or post-treatment parasites. The prevalence of the pfmdr1 86Y mutation was higher after treatment with AQ+SP than after SP, p = 0.002.Conclusions
The combination AQ+SP was highly efficacious, despite the low efficacy of SP alone; however, we found evidence that AQ may exert selective pressure for resistance associated mutations many weeks after treatment. This study confirms the return of CQ sensitivity in Malawi and importantly, shows no evidence of the re-emergence of pfcrt 76T after treatment with CQ or AQ. Given the safety record of AQ when used as a prophylaxis, our observations of marked falls in neutrophil counts in the AQ+SP group requires further scrutiny.Trial Registration
Controlled-Trials.com ISRCTN22075368 相似文献11.
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12.
Roukens AH Soonawala D Joosten SA de Visser AW Jiang X Dirksen K de Gruijter M van Dissel JT Bredenbeek PJ Visser LG 《PloS one》2011,6(12):e27753
Background
Yellow fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to yellow fever vaccine develops more slowly in elderly than in younger subjects.Method
We vaccinated young volunteers (18–28 yrs, N = 30) and elderly travelers (60–81 yrs, N = 28) with YF-17D and measured their neutralizing antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5, 10, 14 and 28 days after vaccination.Results
Ten days after vaccination seroprotection was attained by 77% (23/30) of the young participants and by 50% (14/28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean Titer of younger participants was higher than the GMT of the elderly participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8–4.7, p = 0.00004) and at day 14 +1.8 IU/ml (95% CI 1.1–2.9, p = 0.02, using a mixed linear model. Viraemia was more common in the elderly (86%, 24/28) than in the younger participants (60%, 14/30) (p = 0.03) with higher YF-17D RNA copy numbers in the elderly participants.Conclusions
We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD.Trial Registration
Trialregitser.nl NTR1040 相似文献13.
Background
Interest in developing physically active pediculicides has identified new active substances. The objective was to evaluate a new treatment for clinical efficacy.Methods and Findings
We describe the selection of 1,2-octanediol as a potential pediculicide. Clinical studies were community based. The main outcome measure was no live lice, after two treatments, with follow up visits over 14 days.Study 1 was a proof of concept with 18/20 (90%) participants cured.Study 2 was a multicentre, parallel, randomised, observer-blind study (520 participants) that compared 0.5% malathion liquid with 1,2-octanediol lotion (20% alcohol) applied 2–2.5 hours or 8 hours/overnight. 1,2-octanediol lotion was significantly (p<0.0005) more effective with success for 124/175 (70.9%) RR = 1.50 (97.5% CI, 1.22 to 1.85) for 2–2.5 hours, and 153/174 (87.9%) RR = 1.86 (97.5% CI, 1.54 to 2.26) for 8 hours/overnight compared with 81/171 (47.4%) for malathion.Study 3, a two centre, parallel, randomised, observer-blind study (121 participants), compared 1,2-octanediol lotion, 2–2.5 hours with 1,2-octanediol alcohol free mousse applied for 2–2.5 hours or 8 hours/overnight. The mousse applied for 8 hours/overnight cured 31/40 (77.5%), compared with 24/40 (60.0%) for lotion (RR = 1.29, 95% CI, 0.95 to 1.75; NNT = 5.7) but mousse applied for 2–2.5 hours 17/41 (41.5%) was less effective than lotion (RR = 0.69, 95% CI, 0.44 to 1.08).Adverse events were more common using 1,2-octanediol lotion at both 2–2.5 hours (12.0%, p = 0.001) and 8 hours/overnight (14.9%, p<0.0005), compared with 0.5% malathion (2.3%). Similar reactions were more frequent (p<0.045) using lotion compared with mousse.Conclusions
1,2-octanediol was found to eliminate head louse infestation. It is believed to disrupt the insect''s cuticular lipid, resulting in dehydration. The alcohol free mousse is more acceptable exhibiting significantly fewer adverse reactions.Trial registrations
Controlled-Trials.com ISRCTN66611560, ISRCTN91870666, ISRCTN28722846 相似文献14.
Background
The effectiveness of intermittent preventive treatment of malaria in pregnancy (IPTp) may be compromised by the spread of resistance to sulphadoxine/pyrimethamine (SP) across Africa. But little informtion exists on alternative drugs for IPTp or alternative strategies for the prevention of malaria in pregnancy. Therefore, we have investigated whether screening with a rapid diagnostic test and treatment of those who are positive (IST) at routine antenatal clinic attendances is as effective and as safe as SP-IPTp in pregnant women.Methods and Findings
During antenatal clinic sessions in six health facilities in Ghana held between March 2007 and September 2007, 3333 pregnant women who satisfied inclusion criteria were randomised into three intervention arms (1) standard SP-IPTp, (2) IST and treatment with SP or (3) IST and treatment with amodiaquine+artesunate (AQ+AS). All women received a long-lasting insecticide treated net. Study women had a maximum of three scheduled follow-up visits following enrolment. Haemoglobin concentration and peripheral parasitaemia were assessed between 36 and 40 weeks of gestation. Birth weight was measured at delivery or within 72 hours for babies delivered at home. Parasite prevalence at enrolment in primigravidae and in multigravidae was 29.6% and 10.2% respectively. At 36–40 weeks of gestation the prevalence of asymptomatic parasitaemia was 12.1% in study women overall and was very similar in all treatment groups. The risk of third trimester severe anaemia or low birth weight did not differ significantly between the three treatment groups regardless of gravidity. IST with AQ+AS or SP was not inferior to SP-IPTp in reducing the risk of low birth weight (RD = -1.17[95%CI; -4.39-1.02] for IST-SP vs. SP-IPTp and RD = 0.78[95%CI; -2.11-3.68] for IST-AQAS vs. SP-IPTp); third trimester severe anaemia (RD = 0.29[95%CI; -0.69-1.30] for IST-SP vs. SP-IPTp and RD = -0.36[95%CI;-1.12-0.44] for IST-AQAS vs. SP-IPTp).Conclusion
The results of this study suggest that in an area of moderately high malaria transmission, IST with SP or AS+AQ may be a safe and effective strategy for the control of malaria in pregnancy. However, it is important that these encouraging findings are confirmed in other geographical areas and that the impact of IST on placental malaria is investigated.Trial Registration
ClinicalTrials.gov NCT00432367 [NCT00432367] 相似文献15.
Godart N Berthoz S Curt F Perdereau F Rein Z Wallier J Horreard AS Kaganski I Lucet R Atger F Corcos M Fermanian J Falissard B Flament M Eisler I Jeammet P 《PloS one》2012,7(1):e28249
Research on treatments in anorexia nervosa (AN) is scarce. Although most of the therapeutic programs used in ‘real world practice’ in AN treatment resort to multidisciplinary approaches, they have rarely been evaluated.
Objective
To compare two multidimensional post-hospitalization outpatients treatment programs for adolescents with severe AN: Treatment as Usual (TAU) versus this treatment plus family therapy (TAU+FT).Method
Sixty female AN adolescents, aged 13 to 19 years, were included in a randomized parallel controlled trial conducted from 1999 to 2002 for the recruitment, and until 2004 for the 18 months follow-up. Allocation to one of the two treatment groups (30 in each arm) was randomised. The TAU program included sessions for the patient alone as well as sessions with a psychiatrist for the patient and her parents. The TAU+FT program was identical to the usual one but also included family therapy sessions targeting intra-familial dynamics, but not eating disorder symptoms. The main Outcome Measure was the Morgan and Russell outcome category (Good or Intermediate versus Poor outcome). Secondary outcome indicators included AN symptoms or their consequences (eating symptoms, body mass index, amenorrhea, number of hospitalizations in the course of follow-up, social adjustment). The evaluators, but not participants, were blind to randomization.Results
At 18 months follow-up, we found a significant group effect for the Morgan and Russell outcome category in favor of the program with family therapy (Intention-to-treat: TAU+FT :12/30 (40%); TAU : 5/29 (17.2%) p = 0.05; Per Protocol analysis: respectively 12/26 (46.2%); 4/27 (14.8%), p = 0.01). Similar group effects were observed in terms of achievement of a healthy weight (i.e., BMI≥10th percentile) and menstrual status.Conclusions
Adding family therapy sessions, focusing on intra-familial dynamics rather than eating symptomatology, to a multidimensional program improves treatment effectiveness in girls with severe AN.Trial Registration
Controlled-trials.com ISRCTN71142875 相似文献16.
Sokhna C Cissé B Bâ el H Milligan P Hallett R Sutherland C Gaye O Boulanger D Simondon K Simondon F Targett G Lines J Greenwood B Trape JF 《PloS one》2008,3(1):e1471
Summary
In the Sahel, most malaria deaths occur among children 1–4 years old during a short transmission season. A trial of seasonal intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and a single dose of artesunate (AS) showed an 86% reduction in the incidence of malaria in Senegal but this may not be the optimum regimen. We compared this regimen with three alternatives.Methods
2102 children aged 6–59 months received either one dose of SP plus one dose of AS (SP+1AS) (the previous regimen), one dose of SP plus 3 daily doses of AS (SP+3AS), one dose of SP plus three daily doses of amodiaquine (AQ) (SP+3AQ) or 3 daily doses of AQ and AS (3AQ+3AS). Treatments were given once a month on three occasions during the malaria transmission season. The primary end point was incidence of clinical malaria. Secondary end-points were incidence of adverse events, mean haemoglobin concentration and prevalence of parasites carrying markers of resistance to SP.Findings
The incidence of malaria, and the prevalence of parasitaemia at the end of the transmission season, were lowest in the group that received SP+3AQ: 10% of children in the group that received SP+1AS had malaria, compared to 9% in the SP+3AS group (hazard ratio HR 0.90, 95%CI 0.60, 1.36); 11% in the 3AQ+3AS group, HR 1.1 (0.76–1.7); and 5% in the SP+3AQ group, HR 0.50 (0.30–0.81). Mutations associated with resistance to SP were present in almost all parasites detected at the end of the transmission season, but the prevalence of Plasmodium falciparum was very low in the SP+3AQ group.Conclusions
Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria.Trial Registration
Clinicaltrials.gov NCT00132548 相似文献17.
Manion M Rodriguez B Medvik K Hardy G Harding CV Schooley RT Pollard R Asmuth D Murphy R Barker E Brady KE Landay A Funderburg N Sieg SF Lederman MM 《PloS one》2012,7(1):e30306
Background
Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation.Methods
To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNα for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNα treatment.Results
The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (p = 0.006). These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cells = 2.62% at baseline and 2.17% after 12 weeks of interferon therapy). As plasma HIV levels fell with interferon therapy, this was correlated with a “paradoxical” increase in CD8+ T cell activation (p<0.001).Conclusion
Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection. 相似文献18.
Talbot HK Rock MT Johnson C Tussey L Kavita U Shanker A Shaw AR Taylor DN 《PloS one》2010,5(12):e14442
Background
Currently controversy exists about the immunogenicity of seasonal trivalent influenza vaccine in certain populations, especially the elderly. STF2.4×M2e (VAX102) is a recombinant fusion protein that links four copies of the ectodomain of influenza virus matrix protein 2 (M2e) antigen to Salmonella typhimurium flagellin, a TLR5 ligand. The objectives of this study were to assess the feasibility of giving VAX102 and TIV in combination in an effort to achieve greater immunogenicity and to provide cross-protection.Methodology/Principal Findings
Eighty healthy subjects, 18-49 years old, were enrolled in May and June 2009 in a double-blind, randomized, controlled trial at two clinical sites. Subjects were randomized to receive either TIV + VAX102 or TIV + placebo. Both arms tolerated the vaccines. Pain at the injection site was more severe with TIV + VAX102. Two weeks after immunization the HAI responses to the H1 and H3 antigens of TIV were higher in those that received TIV + VAX102 than in TIV + placebo (309 vs 200 and 269 vs 185, respectively), although statistically non-significant. There was no difference in the HAI of the B antigen. In the TIV + VAX102 arm, the geometric mean M2e antibody concentration was 0.5 µg/ml and 73% seroconverted.Conclusions/Significance
The combination of TIV + VAX102 has the potential to increase the immune response to the influenza A components of TIV and to provide M2e immunity which may protect against influenza A strains not contained in seasonal TIV.Trial Registration
ClinicalTrials.gov NCT00921973 相似文献19.
Schmidt SL Hickey MS Koblenz KM Klamer H Botero MF Pfaffenbach KT Pagliassotti MJ Melby CL 《PloS one》2011,6(2):e16987
Background
Young adult Mexican Americans (MA) exhibit lower insulin sensitivity (Si) than nonHispanic whites (NHW), even when controlling for fitness and adiposity. It is unclear if MA are as responsive to the same lifestyle intervention as NHW.Objective
We developed a model to examine cardiometabolic plasticity (i.e., changes in Si and plasma lipids) in MA compared to NHW adults in response to a diet-exercise intervention.Design
Sedentary subjects (20 NHW: 11F, 9M, 23.0 y, 25.5 kg/m2; 17 MA: 13F, 4M, 22.7 y, 25.4 kg/m2) consumed their habitual diets and remained sedentary for 7 days, after which fasting blood samples were obtained, and a 3-h intravenous glucose tolerance test (IVGTT) was performed with the insulin area under the curve (IAUC) used to estimate Si. Subjects then completed a 7-day diet/exercise intervention (diet: low saturated fat, low added sugar, high fiber; exercise: cycling, six total sessions lasting 40–45 min/session at 65% VO2 max). Pre-intervention tests were repeated.Results
Pre intervention IAUC was 28% higher (p<0.05) in MA (IAUC pre = 2298 µU*180 min/mL) than in NHW (IAUC = 1795 µU*180 min/mL). Following the intervention, there was a significant reduction in IAUC in MA (29%) and NHW (32%), however, the IAUC remained higher (p<0.05) for MA (post = 1635 µU*180 min/mL) than for NHW (post = 1211 µU*180 min/mL). Pre test plasma lipids were not different in MA compared to NHW. Plasma cholesterol and TG concentrations significantly improved in both groups, but concentrations of low density lipoprotein-cholesterol and small dense LDL particles significantly improved only in the NHW.Conclusion
With a short-term diet-exercise intervention, the magnitude of improvements in Si and serum cholesterol and TG in Hispanics are similar to those in NHW. However, because at the outset MA were less insulin sensitive compared to NHW, within the short timeframe studied the ethnic gap in insulin sensitivity remained. 相似文献20.
Four Artemisinin-Based Combinations 《PLoS medicine》2011,8(11):e1001119