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1.
Daniel R. Feikin Godfrey Bigogo Allan Audi Sherri L. Pals George Aol Charles Mbakaya John Williamson Robert F. Breiman Charles P. Larson 《PloS one》2014,9(5)
Background
Zinc treatment shortens diarrhea episodes and can prevent future episodes. In rural Africa, most children with diarrhea are not brought to health facilities. In a village-randomized trial in rural Kenya, we assessed if zinc treatment might have a community-level preventive effect on diarrhea incidence if available at home versus only at health facilities.Methods
We randomized 16 Kenyan villages (1,903 eligible children) to receive a 10-day course of zinc and two oral rehydration solution (ORS) sachets every two months at home and 17 villages (2,241 eligible children) to receive ORS at home, but zinc at the health–facility only. Children’s caretakers were educated in zinc/ORS use by village workers, both unblinded to intervention arm. We evaluated whether incidence of diarrhea and acute lower respiratory illness (ALRI) reported at biweekly home visits and presenting to clinic were lower in zinc villages, using poisson regression adjusting for baseline disease rates, distance to clinic, and children’s age.Results
There were no differences between village groups in diarrhea incidence either reported at the home or presenting to clinic. In zinc villages (1,440 children analyzed), 61.2% of diarrheal episodes were treated with zinc, compared to 5.4% in comparison villages (1,584 children analyzed, p<0.0001). There were no differences in ORS use between zinc (59.6%) and comparison villages (58.8%). Among children with fever or cough without diarrhea, zinc use was low (<0.5%). There was a lower incidence of reported ALRI in zinc villages (adjusted RR 0.68, 95% CI 0.46–0.99), but not presenting at clinic.Conclusions
In this study, home zinc use to treat diarrhea did not decrease disease rates in the community. However, with proper training, availability of zinc at home could lead to more episodes of pediatric diarrhea being treated with zinc in parts of rural Africa where healthcare utilization is low.Trial Registration
ClinicalTrials.gov NCT00530829相似文献2.
Ahmed S. Rahman Mohammad Rafiqul Islam Tracey P. Koehlmoos Mohammad Jyoti Raihan Mohammad Mehedi Hasan Tahmeed Ahmed Charles P. Larson 《PloS one》2014,9(11)
Purpose/Objective
The evolving Non-Governmental Organization (NGO) sector in Bangladesh provides health services directly, however some NGOs indirectly provide services by working with unlicensed providers. The primary objective of this study was to examine the impact of NGO training of unlicensed providers on diarrhoea management and the scale up of zinc treatment in rural populations.Methods
An uncontrolled, single-arm trial for a training and support intervention on diarrhoea outcomes was employed in a rural sub-district of Bangladesh during 2008. Two local NGOs and their catchment populations were chosen for the study. The intervention included training of unlicensed health care providers in the management of acute childhood diarrhoea, particularly emphasizing zinc treatment. In addition, community-based promotion of zinc treatment was carried out. Baseline and endline ecologic surveys were carried out in intervention and control villages to document changes in treatments received for diarrhoea in under-five children.Results
Among surveyed household with an active or recent acute childhood diarrhoea episode, 69% sought help from a health provider. Among these, 62.8% visited an unlicensed private provider. At baseline, 23.9% vs. 22% of control and intervention group children with diarrhoea had received zinc of any type. At endline (6 months later) this had changed to 15.3% vs. 30.2%, respectively. The change in zinc coverage was significantly higher in the intervention villages (p<0.01). Adherence with giving zinc for 10 days or more was significantly higher in the intervention households (9.2% vs. 2.5%; p<0.01). Child''s age, duration of diarrhoea, type of diarrhoea, parental year of schooling as well as oral rehydration solution (ORS) and antibiotic usage were significant predictors of zinc usage.Conclusion
Training of unlicensed healthcare providers through NGOs increased zinc coverage in the diarrhoea management of under-five children in rural Bangladesh households.Trial Registration
ClinicalTrials.gov NCT02143921相似文献3.
Rachel Peletz Martin Simunyama Kelvin Sarenje Kathy Baisley Suzanne Filteau Paul Kelly Thomas Clasen 《PloS one》2012,7(10)
Background
Unsafe drinking water presents a particular threat to people living with HIV/AIDS (PLHIV) due to the increased risk of opportunistic infections, diarrhea-associated malabsorption of essential nutrients, and increased exposure to untreated water for children of HIV-positive mothers who use replacement feeding to reduce the risk of HIV transmission. This population may particularly benefit from an intervention to improve water quality in the home.Methods and Findings
We conducted a 12-month randomized, controlled field trial in Zambia among 120 households with children <2 years (100 with HIV-positive mothers and 20 with HIV-negative mothers to reduce stigma of participation) to assess a high-performance water filter and jerry cans for safe storage. Households were followed up monthly to assess use, drinking water quality (thermotolerant coliforms (TTC), an indicator of fecal contamination) and reported diarrhea (7-day recall) among children <2 years and all members of the household. Because previous attempts to blind the filter have been unsuccessful, we also assessed weight-for-age Z-scores (WAZ) as an objective measure of diarrhea impact. Filter use was high, with 96% (596/620) of household visits meeting the criteria for users. The quality of water stored in intervention households was significantly better than in control households (3 vs. 181 TTC/100 mL, respectively, p<0.001). The intervention was associated with reductions in the longitudinal prevalence of reported diarrhea of 53% among children <2 years (LPR = 0.47, 95% CI: 0.30–0.73, p = 0.001) and 54% among all household members (LPR = 0.46, 95% CI: 0.30–0.70, p<0.001). While reduced WAZ was associated with reported diarrhea (−0.26; 95% CI: −0.37 to −0.14, p<0.001), there was no difference in WAZ between intervention and control groups.Conclusion
In this population living with HIV/AIDS, a water filter combined with safe storage was used correctly and consistently, was highly effective in improving drinking water quality, and was protective against diarrhea.Trial Registration
Clinicaltrials.gov NCT01116908相似文献4.
Jaime Altcheh Guillermo Moscatelli Guido Mastrantonio Samanta Moroni Norberto Giglio Maria Elena Marson Griselda Ballering Margarita Bisio Gideon Koren Facundo García-Bournissen 《PLoS neglected tropical diseases》2014,8(5)
Introduction
Chagas disease, caused by the parasite Trypanosoma cruzi, can lead to long term cardiac morbidity. Treatment of children with benznidazole is effective, but no pediatric pharmacokinetics data are available and clinical pharmacology information on the drug is scarce.Patients and Methods
Prospective population pharmacokinetic (PK) cohort study in children 2–12 years old with Chagas disease treated with oral benznidazole 5–8 mg/kg/day BID for 60 days. (clinicaltrials.gov #). NCT00699387Results
Forty children were enrolled in the study. Mean age was 7.3 years. A total of 117 samples were obtained from 38 patients for PK analysis. A one compartment model best fit the data. Weight-corrected clearance rate (CL/F) showed a good correlation with age, with younger patients having a significantly higher CL/F than older children and adults. Simulated median steady-state benznidazole concentrations, based on model parameters, were lower for children in our study than for adults and lowest for children under 7 years of age. Treatment was efficacious in the 37 patients who completed the treatment course, and well tolerated, with few, and mild, adverse drug reactions (ADRs).Discussion
Observed benznidazole plasma concentrations in children were markedly lower than those previously reported in adults (treated with comparable mg/kg doses), possibly due to a higher CL/F in smaller children. These lower blood concentrations were nevertheless associated to a high therapeutic response in our cohort. Unlike adults, children have few adverse reactions to the drug, suggesting that there may be a direct correlation between drug concentrations and incidence of ADRs. Our results suggest that studies with lower doses in adults may be warranted.Trial Registration
ClinicalTrails.gov NCT00699387相似文献5.
Rajkumar Venkatramani Marcio Malogolowkin Tom B. Davidson William May Richard Sposto Leo Mascarenhas 《PloS one》2013,8(7)
Background
To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of irinotecan administered in combination with vincristine, temozolomide and bevacizumab in children with refractory solid tumors.Methods
The study design included two dose levels (DL) of irinotecan given intravenously once daily for 5 consecutive days (DL1: 30 mg/m2, and DL2: 50 mg/m2), combined with vincristine 1.5 mg/m2 on days 1 and 8, temozolomide 100 mg/m2 on days 1-5, and bevacizumab 15mg/kg on day 1, administered every 21 days for a maximum of 12 cycles.Results
Thirteen patients were enrolled and 12 were evaluable for toxicity Dose limiting toxicity observed included grade 3 hyperbilirubinemia in 1 of 6 patients on DL1, and grade 3 colitis in 1 of 6 patients on DL2. DL 2 was the determined MTD. A total of 87 cycles were administered. Myelosuppression was mild. Grade 1-2 diarrhea occurred in the majority of cycles with grade 3 diarrhea occurring in only one cycle. Grade 2 hypertension developed in two patients. Severe hemorrhage, intestinal perforation, posterior leukoencephalopathy or growth plate abnormalities were not observed. Objective responses were noted in three Wilms tumor patients and one each of medulloblastoma and hepatocellular carcinoma. Five patients completed all 12 cycles of protocol therapy.Conclusions
Irinotecan 50 mg/m2/day for 5 days was the MTD when combined with vincristine, temozolomide and bevacizumab administered on a 21 day schedule. Encouraging anti-tumor activity was noted.Trial Registration
ClinicalTrials.gov; ; http://clinicaltrials.gov/show/ NCT00993044 NCT00993044相似文献6.
Bertrand Lell Selidji Agnandji Isabelle von Glasenapp Sonja Haertle Sunny Oyakhiromen Saadou Issifou Johan Vekemans Amanda Leach Marc Lievens Marie-Claude Dubois Marie-Ange Demoitie Terrell Carter Tonya Villafana W. Ripley Ballou Joe Cohen Peter G. Kremsner 《PloS one》2009,4(10)
Background
The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion – based formulation (AS02) and a formulation based on liposomes (AS01).Methods & Principal Findings
In this Phase II, double-blind study (), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01E or RTS,S/AS02D, on a 0–1–2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02D/AS01E) of 0.88 (95% CI: 0.68–1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated. NCT00307021Conclusions
RTS,S/AS01E proved similarly as well tolerated and immunogenic as RTS,S/AS02D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan.Trial Registration
ClinicalTrials.gov. NCT00307021相似文献7.
《PloS one》2013,8(3)
Background
Heterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified vaccinia Virus Ankara (MVA) vectored vaccines is a strategy recently shown to be capable of inducing strong cell mediated responses against several antigens from the malaria parasite. ChAd63-MVA expressing the Plasmodium falciparum pre-erythrocytic antigen ME-TRAP (multiple epitope string with thrombospondin-related adhesion protein) is a leading malaria vaccine candidate, capable of inducing sterile protection in malaria naïve adults following controlled human malaria infection (CHMI).Methodology
We conducted two Phase Ib dose escalation clinical trials assessing the safety and immunogenicity of ChAd63-MVA ME-TRAP in 46 healthy malaria exposed adults in two African countries with similar malaria transmission patterns.Results
ChAd63-MVA ME-TRAP was shown to be safe and immunogenic, inducing high-level T cell responses (median >1300 SFU/million PBMC).Conclusions
ChAd63-MVA ME-TRAP is a safe and highly immunogenic vaccine regimen in adults with prior exposure to malaria. Further clinical trials to assess safety and immunogenicity in children and infants and protective efficacy in the field are now warranted.Trial Registration
Pactr.org PACTR2010020001771828 http://www.pactr.org/ Pactr.org PACTR201008000221638 http://www.pactr.org/ ClinicalTrials.gov NCT01373879 ClinicalTrials.gov NCT01373879 NCT01379430 NCT01379430相似文献8.
Chen Wang Zhenguo Zhai Yuanhua Yang Yadong Yuan Zhaozhong Cheng Lirong Liang Huaping Dai Kewu Huang Weixuan Lu Zhonghe Zhang Xiansheng Cheng Ying H Shen China Venous Thromboembolism Study Group 《Respiratory research》2009,10(1):128
Backgrounds
Urokinase (UK) 2 200 U/kg·h for 12 hours infusion(UK-12 h)is an ACCP recommended regimen in treating acute pulmonary embolism (PE). It is unclear whether this dose and time can be reduced further. We compared the efficacy and safety of 20, 000 U/kg for 2 hours (UK-2 h) with the UK-12 h regime in selected PE patients.Methods
A randomized trial involving 129 patients was conducted. Patients with acute PE were randomly assigned to receive either UK-12 h (n = 70), or UK-2 h (n = 59). The efficacy was determined by the improvement of right heart dysfunction and perfusion defect at 24 h and 14 d post UK treatment. The bleeding incidence, death rate and PE recurrence were also evaluated.Results
Similarly significant improvements in right heart dysfunction and lung perfusion defects were observed in both groups. Overall bleeding incidents were low in both groups. Major bleeding directly associated with UK infusion occurred in one patient in the UK-2 h group and one in the UK-12 h group. Mortality rates were low, with one reported fatal recurrent in the UK-12 h group and none in the UK-2 h group. When the rate of bleeding, death and PE recurrence were compared separately in the hemodynamic instability and the massive anatomic obstruction subgroups, no significant difference was found.Conclusions
The UK-2 h regimen exhibits similar efficacy and safety as the UK-12 h regimen for acute PE.Trial Registration
Clinical trial registered with http://clinicaltrials.gov/ct2/show/ (Identifier: NCT00799968) NCT 00799968相似文献9.
Daniel M?usezahl Andri Christen Gonzalo Duran Pacheco Fidel Alvarez Tellez Mercedes Iriarte Maria E. Zapata Myriam Cevallos Jan Hattendorf Monica Daigl Cattaneo Benjamin Arnold Thomas A. Smith John M. Colford Jr 《PLoS medicine》2009,6(8)
Background
Solar drinking water disinfection (SODIS) is a low-cost, point-of-use water purification method that has been disseminated globally. Laboratory studies suggest that SODIS is highly efficacious in inactivating waterborne pathogens. Previous field studies provided limited evidence for its effectiveness in reducing diarrhoea.Methods and Findings
We conducted a cluster-randomized controlled trial in 22 rural communities in Bolivia to evaluate the effect of SODIS in reducing diarrhoea among children under the age of 5 y. A local nongovernmental organisation conducted a standardised interactive SODIS-promotion campaign in 11 communities targeting households, communities, and primary schools. Mothers completed a daily child health diary for 1 y. Within the intervention arm 225 households (376 children) were trained to expose water-filled polyethyleneteraphtalate bottles to sunlight. Eleven communities (200 households, 349 children) served as a control. We recorded 166,971 person-days of observation during the trial representing 79.9% and 78.9% of the total possible person-days of child observation in intervention and control arms, respectively. Mean compliance with SODIS was 32.1%. The reported incidence rate of gastrointestinal illness in children in the intervention arm was 3.6 compared to 4.3 episodes/year at risk in the control arm. The relative rate of diarrhoea adjusted for intracluster correlation was 0.81 (95% confidence interval 0.59–1.12). The median length of diarrhoea was 3 d in both groups.Conclusions
Despite an extensive SODIS promotion campaign we found only moderate compliance with the intervention and no strong evidence for a substantive reduction in diarrhoea among children. These results suggest that there is a need for better evidence of how the well-established laboratory efficacy of this home-based water treatment method translates into field effectiveness under various cultural settings and intervention intensities. Further global promotion of SODIS for general use should be undertaken with care until such evidence is available.Trial Registration
www.ClinicalTrials.gov Please see later in the article for Editors'' Summary NCT00731497相似文献10.
Laura W. Goff Nilay Thakkar Liping Du Emily Chan Benjamin R. Tan Dana B. Cardin Howard L. McLeod Jordan D. Berlin Barbara Zehnbauer Chloe Fournier Joel Picus Andrea Wang-Gillam Wooin Lee A. Craig Lockhart 《PloS one》2014,9(9)
Background
Retrospective studies indicate associations between TSER (thymidylate synthase enhancer region) genotypes and clinical outcomes in patients receiving 5-FU based chemotherapy, but well-controlled prospective validation has been lacking.Methods
In this phase II study ( registered through ClinicalTrials.gov, http://clinicaltrials.gov/show/ NCT00515216), patients with “good risk” TSER genotypes (at least one TSER*2 allele) were treated with FOLFOX chemotherapy to determine whether prospective patient selection can improve overall response rates (ORR) in patients with gastric and gastroesophageal junction (GEJ) cancers, compared with historical outcomes in unselected patients (estimated 43%). NCT00515216Results
The ORR in genotype-selected patients was 39.1% (9 partial responses out of 23 evaluable patients, 95% CI, 22.2 to 59.2), not achieving the primary objective of improving ORR. An encouraging disease control rate (DCR, consisting of partial responses and stable diseases) of 95.7% was noted and patients with homozygous TSER*2 genotype showed better tumor response.Conclusions
In this first prospective, multi-institutional study in patients with gastric or GEJ cancers, selecting patients with at least one TSER*2 allele did not improve the ORR but led to an encouraging DCR. Further studies are needed to investigate the utility of selecting patients homozygous for the TSER*2 allele and additional genomic markers in improving clinical outcomes for patients with gastric and GEJ cancers.Trial Registration
ClinicalTrials.gov NCT00515216相似文献11.
Roberto Esposito Franco Cilli Valentina Pieramico Antonio Ferretti Antonella Macchia Marco Tommasi Aristide Saggino Domenico Ciavardelli Antonietta Manna Riccardo Navarra Filippo Cieri Liborio Stuppia Armando Tartaro Stefano L. Sensi 《PloS one》2013,8(7)
Background
There is growing debate on the use of drugs that promote cognitive enhancement. Amphetamine-like drugs have been employed as cognitive enhancers, but they show important side effects and induce addiction. In this study, we investigated the use of modafinil which appears to have less side effects compared to other amphetamine-like drugs. We analyzed effects on cognitive performances and brain resting state network activity of 26 healthy young subjects.Methodology
A single dose (100 mg) of modafinil was administered in a double-blind and placebo-controlled study. Both groups were tested for neuropsychological performances with the Raven’s Advanced Progressive Matrices II set (APM) before and three hours after administration of drug or placebo. Resting state functional magnetic resonance (rs-FMRI) was also used, before and after three hours, to investigate changes in the activity of resting state brain networks. Diffusion Tensor Imaging (DTI) was employed to evaluate differences in structural connectivity between the two groups. Protocol ID: Modrest_2011; ; http://clinicaltrials.gov/ct2/show/ NCT01684306. NCT01684306Principal Findings
Results indicate that a single dose of modafinil improves cognitive performance as assessed by APM. Rs-fMRI showed that the drug produces a statistically significant increased activation of Frontal Parietal Control (FPC; p<0.04) and Dorsal Attention (DAN; p<0.04) networks. No modifications in structural connectivity were observed.Conclusions and Significance
Overall, our findings support the notion that modafinil has cognitive enhancing properties and provide functional connectivity data to support these effects.Trial Registration
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/ NCT01684306. NCT01684306相似文献12.
13.
Ishani Ganguli Jamie E. Collins William M. Reichmann Elena Losina Jeffrey N. Katz Christian Arbelaez Laurel A. Donnell-Fink Rochelle P. Walensky 《PloS one》2013,8(1)
Background
HIV infection remains a major US public health concern. While HIV-infected individuals now benefit from earlier diagnosis and improved treatment options, progress is tempered by large numbers of newly diagnosed patients who are lost to follow-up prior to disease confirmation and linkage to care.Methodology
In the randomized, controlled USHER trial, we offered rapid HIV tests to patients presenting to a Boston, MA emergency department. Separate written informed consent was required for confirmatory testing. In a secondary analysis, we compared participants with reactive results who did and did not complete confirmatory testing to identify factors associated with refusal to complete the confirmation protocol.Principal Findings
Thirteen of 62 (21.0%, 95% CI (11.7%, 33.2%)) participants with reactive rapid HIV tests refused confirmation; women, younger participants, African Americans, and those with fewer HIV risks, with lower income, and without primary care doctors were more likely to refuse. We projected that up to four true HIV cases were lost at the confirmation stage.Conclusions
These findings underscore the need to better understand the factors associated with refusal to confirm reactive HIV testing and to identify interventions that will facilitate confirmatory testing and linkage to care among these populations.Trial Registration
ClinicalTrials.gov ; NCT00502944. NCT01258582相似文献14.
Uzma N. Sarwar Laura Novik Mary E. Enama Sarah A. Plummer Richard A. Koup Martha C. Nason Robert T. Bailer Adrian B. McDermott Mario Roederer John R. Mascola Julie E. Ledgerwood Barney S. Graham the VRC study team 《PloS one》2014,9(9)
Background
Needle-free delivery improves the immunogenicity of DNA vaccines but is also associated with more local reactogenicity. Here we report the first comparison of Biojector and needle administration of a candidate rAd5 HIV vaccine.Methods
Thirty-one adults, 18–55 years, 20 naive and 11 prior rAd5 vaccine recipients were randomized to receive single rAd5 vaccine via needle or Biojector IM injection at 1010 PU in a Phase I open label clinical trial. Solicited reactogenicity was collected for 5 days; clinical safety and immunogenicity follow-up was continued for 24 weeks.Results
Overall, injections by either method were well tolerated. There were no serious adverse events. Frequency of any local reactogenicity was 16/16 (100%) for Biojector compared to 11/15 (73%) for needle injections. There was no difference in HIV Env-specific antibody response between Biojector and needle delivery. Env-specific antibody responses were more than 10-fold higher in subjects receiving a booster dose of rAd5 vaccine than after a single dose delivered by either method regardless of interval between prime and boost.Conclusions
Biojector delivery did not improve antibody responses to the rAd5 vaccine compared to needle administration. Homologous boosting with rAd5 gene-based vectors can boost insert-specific antibody responses despite pre-existing vector-specific immunity.Trial Registration
Clinicaltrials.gov NCT00709605 NCT00709605相似文献15.
Kazuki Ide Hiroshi Yamada Kumi Matsushita Miki Ito Kei Nojiri Kiichiro Toyoizumi Keiji Matsumoto Yoichi Sameshima 《PloS one》2014,9(5)
Background
The anti-influenza virus activity of green tea catechins has been demonstrated in experimental studies, but clinical evidence has been inconclusive. School-aged children play an important role in the infection and spread of influenza in the form of school-based outbreaks. Preventing influenza infection among students is essential for reducing the frequency of epidemics and pandemics. As a non-pharmaceutical intervention against infection, gargling is also commonly performed in Asian countries but has not yet been extensively studied.Methods and Findings
A randomized, open label, 2-group parallel study of 757 high school students (15 to 17 years of age) was conducted for 90 days during the influenza epidemic season from December 1st, 2011 to February 28th, 2012, in 6 high schools in Shizuoka Prefecture, Japan. The green tea gargling group gargled 3 times a day with bottled green tea, and the water gargling group did the same with tap water. The water group was restricted from gargling with green tea. The primary outcome measure was the incidence of laboratory-confirmed influenza using immunochromatographic assay for antigen detection. 757 participants were enrolled and 747 participants completed the study (384 in the green tea group and 363 in the water group). Multivariate logistic regression indicated no significant difference in the incidence of laboratory-confirmed influenza between the green tea group (19 participants; 4.9%) and the water group (25 participants; 6.9%) (adjusted OR, 0.69; 95%CI, 0.37 to 1.28; P = 0.24). The main limitation of the study is the adherence rate among high school students was lower than expected.Conclusions
Among high school students, gargling with green tea three times a day was not significantly more efficacious than gargling with water for the prevention of influenza infection. In order to adequately assess the effectiveness of such gargling, additional large-scale randomized studies are needed.Trial Registration
ClinicalTrials.gov NCT01225770相似文献16.
Oliver Laeyendecker Estelle Piwowar-Manning Agnes Fiamma Michal Kulich Deborah Donnell Deb Bassuk Caroline E. Mullis Craig Chin Priscilla Swanson John Hackett Jr William Clarke Mark Marzinke Greg Szekeres Glenda Gray Linda Richter Michel W. Alexandre Suwat Chariyalertsak Alfred Chingono David D. Celentano Stephen F. Morin Michael Sweat Thomas Coates Susan H. Eshleman 《PloS one》2013,8(7)
Background
National Institute of Mental Health Project Accept (HIV Prevention Trials Network [HPTN] 043) is a large, Phase III, community-randomized, HIV prevention trial conducted in 48 matched communities in Africa and Thailand. The study intervention included enhanced community-based voluntary counseling and testing. The primary endpoint was HIV incidence, assessed in a single, cross-sectional, post-intervention survey of >50,000 participants.Methods
HIV rapid tests were performed in-country. HIV status was confirmed at a central laboratory in the United States. HIV incidence was estimated using a multi-assay algorithm (MAA) that included the BED capture immunoassay, an avidity assay, CD4 cell count, and HIV viral load.Results
Data from Thailand was not used in the endpoint analysis because HIV prevalence was low. Overall, 7,361 HIV infections were identified (4 acute, 3 early, and 7,354 established infections). Samples from established infections were analyzed using the MAA; 467 MAA positive samples were identified; 29 of those samples were excluded because they contained antiretroviral drugs. HIV prevalence was 16.5% (range at study sites: 5.93% to 30.8%). HIV incidence was 1.60% (range at study sites: 0.78% to 3.90%).Conclusions
In this community-randomized trial, a MAA was used to estimate HIV incidence in a single, cross-sectional post-intervention survey. Results from this analysis were subsequently used to compare HIV incidence in the control and intervention communities.Trial Registration
ClinicalTrials.gov NCT00203749相似文献17.
Ulrika J. Gunnerud Cornelia Heinzle Jens J. Holst Elin M. ?stman Inger M. E. Bj?rck 《PloS one》2012,7(9)
Background
Whey proteins have insulinogenic properties and the effect appears to originate from a specific postprandial plasma amino acid pattern. The insulinogenic effect can be mimicked by a specific mixture of the five amino acids iso, leu, lys, thr and val.Objective
The objective was to evaluate the efficacy of pre-meal boluses of whey or soy protein with or without added amino acids on glycaemia, insulinemia as well as on plasma responses of incretins and amino acids at a subsequent composite meal. Additionally, plasma ghrelin and subjective appetite responses were studied.Design
In randomized order, fourteen healthy volunteers were served a standardized composite ham sandwich meal with either water provided (250 ml) during the time course of the meal, or different pre-meal protein drinks (PMPD) (100 ml provided as a bolus) with additional water (150 ml) served to the meal. The PMPDs contained 9 g protein and were based on either whey or soy protein isolates, with or without addition of the five amino acids (iso, leu, lys, thr and val) or the five amino acids + arg.Results
All PMPD meals significantly reduced incremental area for plasma glucose response (iAUC) during the first 60 min. All whey based PMPD meals displayed lower glycemic indices compared to the reference meal. There were no significant differences for the insulinemic indices. The early insulin response (iAUC 0–15 min) correlated positively to plasma amino acids, GIP and GLP-1 as well as to the glycemic profile. Additionally, inverse correlations were found between insulin iAUC 0–15 min and the glucose peak.Conclusion
The data suggests that a pre-meal drink containing specific proteins/amino acids significantly reduces postprandial glycemia following a composite meal, in absence of elevated insulinemic excursions. An early phase insulinemic response induced by plasma amino acids and incretins appears to mediate the effect.Trial Registration
ClinicalTrials.gov < NCT01586780> NCT01586780相似文献18.
Clara Menéndez Azucena Bardají Betuel Sigauque Sergi Sanz John J. Aponte Samuel Mabunda Pedro L. Alonso 《PloS one》2010,5(2)
Background
In the global context of a reduction of under-five mortality, neonatal mortality is an increasingly relevant component of this mortality. Malaria in pregnancy may affect neonatal survival, though no strong evidence exists to support this association.Methods
In the context of a randomised, placebo-controlled trial of intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine (SP) in 1030 Mozambican pregnant women, 997 newborns were followed up until 12 months of age. There were 500 live borns to women who received placebo and 497 to those who received SP.Findings
There were 58 infant deaths; 60.4% occurred in children born to women who received placebo and 39.6% to women who received IPTp (p = 0.136). There were 25 neonatal deaths; 72% occurred in the placebo group and 28% in the IPTp group (p = 0.041). Of the 20 deaths that occurred in the first week of life, 75% were babies born to women in the placebo group and 25% to those in the IPTp group (p = 0.039). IPTp reduced neonatal mortality by 61.3% (95% CI 7.4%, 83.8%); p = 0.024].Conclusions
Malaria prevention with SP in pregnancy can reduce neonatal mortality. Mechanisms associated with increased malaria infection at the end of pregnancy may explain the excess mortality in the malaria less protected group. Alternatively, SP may have reduced the risk of neonatal infections. These findings are of relevance to promote the implementation of IPTp with SP, and provide insights into the understanding of the pathophysiological mechanisms through which maternal malaria affects fetal and neonatal health.Trial Registration
ClinicalTrials.gov NCT00209781相似文献19.
Lennart Greiff Anders Cervin Cecilia Ahlstr?m-Emanuelsson Gun Almqvist Morgan Andersson Jan Dolata Leif Eriksson Edward H?gest?tt Anders K?llén Per Norlén Inga-Lisa Sj?lin Henrik Widegren 《Respiratory research》2012,13(1):53
Background
Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile.Objective
To evaluate the efficacy and safety of intranasal AZD8848.Methods
In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg) was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (). In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg) was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days ( NCT00688779). Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. NCT00770003Results
AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848.Conclusions
Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis.Trial registration
and NCT00688779 as indicated above. NCT00770003相似文献20.
Ayse Ercumen Abu Mohd. Naser Leanne Unicomb Benjamin F. Arnold John M. Colford Jr. Stephen P. Luby 《PloS one》2015,10(3)