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1.
Patumrat Sripan Sophie Le Coeur Billy Amzal Lily Ingsrisawang Patrinee Traisathit Nicole Ngo-Giang-Huong Kenneth McIntosh Tim R. Cressey Suraphan Sangsawang Boonsong Rawangban Prateep Kanjanavikai Jean-Marc Tréluyer Gonzague Jourdain Marc Lallemant Sa?k Urien 《PloS one》2015,10(5)
BackgroundAntiretroviral treatments decrease HIV mother-to-child transmission through pre/post exposure prophylaxis and reduction of maternal viral load. We modeled in-utero and intra-partum HIV transmissions to investigate the preventive role of various antiretroviral treatments interventions.MethodsWe analysed data from 3,759 women-infant pairs enrolled in 3 randomized clinical trials evaluating (1) zidovudine monotherapy, (2) zidovudine plus perinatal single-dose nevirapine or (3) zidovudine plus lopinavir/ritonavir for the prevention of mother-to-child transmission of HIV in Thailand. All infants were formula-fed. Non-linear mixed effect modeling was used to express the viral load evolution under antiretroviral treatments and the probability of transmission.ResultsMedian viral load was 4 log10 copies/mL (Interquartile range: 3.36–4.56) before antiretroviral treatments initiation. An Emax model described the viral load time-course during pregnancy. Half of the maximum effect of zidovudine (28% decrease) and lopinavir/ritonavir (72% decrease) were achieved after 98 and 12 days, respectively. Adjusted on viral load at baseline (Odds ratio = 1.50 [95% confidence interval: 1.34, 1.68] per log10 copies/mL increment), antiretroviral treatments duration (OR = 0.80 [0.75, 0.84] per week increment) but not the nature of antiretroviral treatments were associated with in-utero transmission. Adjusted on gestational age at delivery (<37 weeks, OR = 2.37 [1.37, 4.10]), baseline CD4 (Odds ratio = 0.79 [0.72, 0.88] per 100 cells/mm3 increment) and predicted viral load at delivery (OR = 1.47 [1.25, 1.64] per log10 copies/mL increment), single-dose nevirapine considerably reduced intra-partum transmission (OR = 0.32 [0.2, 0.51]).ConclusionThese models determined the respective contributions of various antiretroviral strategies on prevention of mother-to-child transmission. This can help predict the efficacy of new antiretroviral treatments and/or prevention of mother-to-child transmission strategies particularly for women with no or late antenatal care who are at high risk of transmitting HIV to their offspring.
Trial Registration
This analysis is based on secondary data obtained from three clinical trials. ClinicalTrials.gov. , NCT00386230, NCT00398684. NCT00409591相似文献2.
Miguel W. Tregnaghi Xavier Sáez-Llorens Pio López Hector Abate Enrique Smith Adriana Pósleman Arlene Calvo Digna Wong Carlos Cortes-Barbosa Ana Ceballos Marcelo Tregnaghi Alexandra Sierra Mirna Rodriguez Marisol Troiti?o Carlos Carabajal Andrea Falaschi Ana Leandro Maria Mercedes Castrejón Alejandro Lepetic Patricia Lommel William P. Hausdorff Dorota Borys Javier Ruiz Gui?azú Eduardo Ortega-Barría Juan P. Yarzábal Lode Schuerman 《PLoS medicine》2014,11(6)
BackgroundThe relationship between pneumococcal conjugate vaccine–induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed.ConclusionsEfficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice.
Trial registration
www.ClinicalTrials.gov Please see later in the article for the Editors'' Summary NCT00466947相似文献3.
Kenneth K. Mugwanya Craig W. Hendrix Nelly R. Mugo Mark Marzinke Elly T. Katabira Kenneth Ngure Nulu B. Semiyaga Grace John-Stewart Timothy R. Muwonge Gabriel Muthuri Andy Stergachis Connie L. Celum Jared M. Baeten 《PLoS medicine》2016,13(9)
BackgroundAs pre-exposure prophylaxis (PrEP) becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women.ConclusionIn this short-term study of daily directly observed oral PrEP in HIV-uninfected breastfeeding women, the estimated infant doses from breast milk and resultant infant plasma concentrations for tenofovir and emtricitabine were 12,500 and >200-fold lower than the respective proposed infant therapeutic doses, and tenofovir was not detected in 94% of infant plasma samples. These data suggest that PrEP can be safely used during breastfeeding with minimal infant drug exposure.
Trial Registration
ClinicalTrials.gov, Identifier: NCT02776748相似文献4.
Julie E. Ledgerwood Abbie R. Bellamy Robert Belshe David I. Bernstein Srilatha Edupuganti Shital M. Patel Phyllis Renehan Thad Zajdowicz Richard Schwartz Richard Koup Robert T. Bailer Galina V. Yamshchikov Mary E. Enama Uzma Sarwar Brenda Larkin Barney S. Graham VRC study team 《PloS one》2015,10(5)
BackgroundThe efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost.MethodsFour sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3) 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI) was the secondary objective.ResultsThe DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study.ConclusionWhile DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative.
Trial Registration
ClinicalTrials.gov NCT01498718相似文献5.
Britt Christensen Maja Ludvigsen Birgitte Nellemann John J. Kopchick Bent Honoré Jens Otto L. J?rgensen 《PloS one》2015,10(2)
IntroductionDespite implementation of the biological passport to detect erythropoietin abuse, a need for additional biomarkers remains. We used a proteomic approach to identify novel serum biomarkers of prolonged erythropoiesis-stimulating agent (ESA) exposure (Darbepoietin-α) and/or aerobic training.MethodsSerum proteins were separated according to charge and molecular mass (2D-gel electrophoresis). The identity of proteins from spots exhibiting altered intensity was determined by mass spectrometry.ResultsSix protein spots changed in response to Darbepoietin-α treatment. Comparing all 4 experimental groups, two protein spots (serotransferrin and haptoglobin/haptoglobin related protein) showed a significant response to Darbepoietin-α treatment. The haptoglobin/haptoglobin related protein spot showed a significantly lower intensity in all subjects in the training-ESA group during the treatment period and increased during the washout period.ConclusionAn isoform of haptoglobin/haptoglobin related protein could be a new anti-doping marker and merits further research.
Trial Registration
ClinicalTrials.gov NCT01320449相似文献6.
Verena Veulemans Tobias Zeus Laura Kleinebrecht Jan Balzer Katharina Hellhammer Amin Polzin Patrick Horn Alexander Blehm Jan-Philipp Minol Patric Kr?pil Ralf Westenfeld Tienush Rassaf Artur Lichtenberg Malte Kelm 《PloS one》2016,11(4)
BackgroundPreprocedural manual multi-slice-CT-segmentation tools (MSCT-ST) define the gold standard for planning transcatheter aortic valve replacement (TAVR). They are able to predict the perpendicular line of the aortic annulus (PPL) and to indicate the corresponding C-arm angulation (CAA). Fully automated planning-tools and their clinical relevance have not been systematically evaluated in a real world setting so far.ConclusionsA-MSCT-analysis provides precise preprocedural information on CAA for optimal visualization of the aortic annulus compared to the M-MSCT gold standard. Intraprocedural application of this information during TAVR significantly reduces the levels of contrast and radiation exposure.
Trial Registration
ClinicalTrials.gov NCT01805739相似文献7.
Frank Baiden Jane Bruce Jayne Webster Mathilda Tivura Rupert Delmini Seeba Amengo-Etego Seth Owusu-Agyei Daniel Chandramohan 《PloS one》2016,11(4)
BackgroundMalaria-endemic countries in sub-Saharan Africa are shifting from the presumptive approach that is based on clinical judgement (CJ) to the test-based approach that is based on confirmation through test with rapid diagnostic tests (RDT). It has been suggested that the loss of the prophylactic effect of presumptive-administered ACT in children who do not have malaria will result in increase in their risk of malaria and anaemia.ConclusionThe test-based approach to the management of malaria did not increase the incidence of malaria or anaemia among under-five children in this setting.
Trial Registration
ClinicalTrials.gov NCT00832754相似文献8.
Pascal Tétreault Ali Mansour Etienne Vachon-Presseau Thomas J. Schnitzer A. Vania Apkarian Marwan N. Baliki 《PLoS biology》2016,14(10)
Placebo response in the clinical trial setting is poorly understood and alleged to be driven by statistical confounds, and its biological underpinnings are questioned. Here we identified and validated that clinical placebo response is predictable from resting-state functional magnetic-resonance-imaging (fMRI) brain connectivity. This also led to discovering a brain region predicting active drug response and demonstrating the adverse effect of active drug interfering with placebo analgesia. Chronic knee osteoarthritis (OA) pain patients (n = 56) underwent pretreatment brain scans in two clinical trials. Study 1 (n = 17) was a 2-wk single-blinded placebo pill trial. Study 2 (n = 39) was a 3-mo double-blinded randomized trial comparing placebo pill to duloxetine. Study 3, which was conducted in additional knee OA pain patients (n = 42), was observational. fMRI-derived brain connectivity maps in study 1 were contrasted between placebo responders and nonresponders and compared to healthy controls (n = 20). Study 2 validated the primary biomarker and identified a brain region predicting drug response. In both studies, approximately half of the participants exhibited analgesia with placebo treatment. In study 1, right midfrontal gyrus connectivity best identified placebo responders. In study 2, the same measure identified placebo responders (95% correct) and predicted the magnitude of placebo’s effectiveness. By subtracting away linearly modeled placebo analgesia from duloxetine response, we uncovered in 6/19 participants a tendency of duloxetine enhancing predicted placebo response, while in another 6/19, we uncovered a tendency for duloxetine to diminish it. Moreover, the approach led to discovering that right parahippocampus gyrus connectivity predicts drug analgesia after correcting for modeled placebo-related analgesia. Our evidence is consistent with clinical placebo response having biological underpinnings and shows that the method can also reveal that active treatment in some patients diminishes modeled placebo-related analgesia.Trial Registration ClinicalTrials.gov ClinicalTrials.gov NCT02903238 NCT01558700相似文献
9.
William Stohl Joan T. Merrill R. John Looney Jill Buyon Daniel J. Wallace Michael H. Weisman Ellen M. Ginzler Blaire Cooke Donna Holloway Arunan Kaliyaperumal Kameswara Rao Kuchimanchi Tsui Chern Cheah Erik Rasmussen John Ferbas Shelley S. Belouski Wayne Tsuji Debra J. Zack 《Arthritis research & therapy》2015,17(1)
IntroductionBlisibimod is a potent B cell-activating factor (BAFF) antagonist that binds to both cell membrane-expressed and soluble BAFF. The goal of these first-in-human studies was to characterize the safety, tolerability, and pharmacokinetic and pharmacodynamic profiles of blisibimod in subjects with systemic lupus erythematosus (SLE).MethodsSLE subjects with mild disease that was stable/inactive at baseline received either a single dose of blisibimod (0.1, 0.3, 1, or 3 mg/kg subcutaneous [SC] or 1, 3, or 6 mg/kg intravenous [IV]) or placebo (phase 1a; N = 54), or four weekly doses of blisibimod (0.3, 1, or 3 mg/kg SC or 6 mg/kg IV) or placebo (phase 1b; N = 63). Safety and tolerability measures were collected, and B cell subset measurements and pharmacokinetic analyses were performed.ResultsAll subjects (93 % female; mean age 43.7 years) carried the diagnosis of SLE for ≥ 1 year. Single- and multiple-dose treatment with blisibimod produced a decrease in the number of naïve B cells (24–76 %) and a transient relative increase in the memory B cell compartment, with the greatest effect on IgD-CD27+; there were no notable changes in T cells or natural killer cells. With time, memory B cells reverted to baseline, leading to a calculated 30 % reduction in total B cells by approximately 160 days after the first dose. In both the single- and multiple-dosing SC cohorts, the pharmacokinetic profile indicated slow absorption, dose-proportional exposure from 0.3 through 3.0 mg/kg SC and 1 through 6 mg/kg IV, linear pharmacokinetics across the dose range of 1.0–6.0 mg/kg, and accumulation ratios ranging from 2.21 to 2.76. The relative increase in memory B cells was not associated with safety signals, and the incidence of adverse events, anti-blisibimod antibodies, and clinical laboratory abnormalities were comparable between blisibimod- and placebo-treated subjects.ConclusionsBlisibimod changed the constituency of the B cell pool and single and multiple doses of blisibimod exhibited approximate dose-proportional pharmacokinetics across the dose range 1.0–6.0 mg/kg. The safety and tolerability profile of blisibimod in SLE was comparable with that of placebo. These findings support further studies of blisibimod in SLE and other B cell-mediated diseases.
Trial registration
Clinicaltrials.gov . Registered 11 May 2015. NCT02443506 Registered 7 April 2015. NCT02411136相似文献10.
Adam R. Aluisio Zabihullah Maroof Daniel Chandramohan Jane Bruce Mohammad I. Masher Semira Manaseki-Holland Jeroen H. J. Ensink 《PloS one》2015,10(2)
IntroductionChildhood diarrheal illnesses are a major public health problem. In low-income settings data on disease burden and factors associated with diarrheal illnesses are poorly defined, precluding effective prevention programs. This study explores factors associated with recurrent diarrheal illnesses among children in Kabul, Afghanistan.MethodsA cohort of 1–11 month old infants was followed for 18 months from 2007–2009. Data on diarrheal episodes were gathered through active and passive surveillance. Information on child health, socioeconomics, water and sanitation, and hygiene behaviors was collected. Factors associated with recurrent diarrheal illnesses were analyzed using random effects recurrent events regression models.Results3,045 children were enrolled and 2,511 (82%) completed 18-month follow-up. There were 14,998 episodes of diarrheal disease over 4,200 child-years (3.51 episodes/child-year, 95%CI 3.40–3.62). Risk of diarrheal illness during the winter season was 63% lower than the summer season (HR = 0.37, 95%CI 0.35–0.39, P<0.001). Soap for hand washing was available in 72% of households and 11.9% had toilets with septic/canalization. Half of all mothers reported using soap for hand washing. In multivariate analysis diarrheal illness was lower among children born to mothers with post-primary education (aHR = 0.79, 95%CI 0.69–0.91, p = 0.001), from households where maternal hand washing with soap was reported (aHR = 0.83, 95%CI 0.74–0.92, p<0.001) and with improved sanitation facilities (aHR = 0.76, 95%CI 0.63–0.93, p = 0.006). Malnourished children from impoverished households had significantly increased risks for recurrent disease [(aHR = 1.15, 95%CI 1.03–1.29, p = 0.016) and (aHR = 1.20, 95%CI 1.05–1.37, p = 0.006) respectively].ConclusionsMaternal hand washing and improved sanitation facilities were protective, and represent important prevention points among public health endeavors. The discrepancy between soap availability and utilization suggests barriers to access and knowledge, and programs simultaneously addressing these aspects would likely be beneficial. Enhanced maternal education and economic status were protective in this population and these findings support multi-sector interventions to combat illness.
Trial Registration
www.ClinicalTrials.gov NCT00548379https://www.clinicaltrials.gov/ct2/show/ NCT00548379相似文献11.
Teun Bousema Gillian Stresman Amrish Y. Baidjoe John Bradley Philip Knight William Stone Victor Osoti Euniah Makori Chrispin Owaga Wycliffe Odongo Pauline China Shehu Shagari Ogobara K. Doumbo Robert W. Sauerwein Simon Kariuki Chris Drakeley Jennifer Stevenson Jonathan Cox 《PLoS medicine》2016,13(4)
BackgroundMalaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities.ConclusionsDespite high coverage, the impact of interventions targeting malaria vectors and human infections on nPCR parasite prevalence was modest, transient, and restricted to the targeted hotspot areas. Our findings suggest that transmission may not primarily occur from hotspots to the surrounding areas and that areas with highly heterogeneous but widespread malaria transmission may currently benefit most from an untargeted community-wide approach. Hotspot-targeted approaches may have more validity in settings where human settlement is more nuclear.
Trial registration
ClinicalTrials.gov NCT01575613相似文献12.
Stephanie Fischinger Deniz Cizmeci Davy Deng Shannon P. Grant Nicole Frahm Julie McElrath Jonathan Fuchs Pierre-Alexandre Bart Giuseppe Pantaleo Michael Keefer William O. Hahn Nadine Rouphael Gavin Churchyard Zoe Moodie Yeycy Donastorg Hendrik Streeck Galit Alter 《PLoS pathogens》2021,17(11)
Despite the advent of long-acting anti-retroviral therapy able to control and prevent infection, a preventative vaccine remains a global priority for the elimination of HIV. The moderately protective RV144 vaccine trial suggested functional IgG1 and IgG3 antibodies were a potential correlate of protection, but the RV144-inspired HVTN702 validation trial failed to demonstrate efficacy despite inducing targeted levels of IgG1/IgG3. Alterations in inserts, and antigens, adjuvant, and regimen also resulted in vaccine induced target quantitative levels of the immune correlates, but drove qualitative changes to the humoral immune response, pointing to the urgent need to define the influence of vaccine strategies on shaping antibody quality, not just quantity. Thus, defining how distinct prime/boost approaches tune long-lived functional antibodies represents an important goal in vaccine development. Here, we compared vaccine responses in Phase I and II studies in humans utilizing various combinations of DNA/vector, vector/vector and DNA/protein HIV vaccines. We found that adenoviral vector immunization, compared to pox-viral vectors, resulted in the most potent IgG1 and IgG3 responses, linked to highly functional antibody activity, including assisting NK cell related functions. Minimal differences were observed in the durability of the functional humoral immune response across vaccine regimens, except for antibody dependent phagocytic function, which persisted for longer periods in the DNA/rAd5 and rAd35/rAd5 regimen, likely driven by higher IgG1 levels. Collectively, these findings suggest adenoviral vectors drive superior antibody quality and durability that could inform future clinical vaccine studies.Trial registration: ClinicalTrials.gov , NCT00801697, NCT00961883, NCT02207920, NCT00125970). NCT02852005相似文献
13.
Rudolf W. Ammann Katrin D. M. Stumpe Felix Grimm Peter Deplazes Sabine Huber Kaja Bertogg Dorothee R. Fischer Beat Müllhaupt 《PLoS neglected tropical diseases》2015,9(9)
Background/AimsBenzimidazoles are efficacious for treating non-resectable alveolar echinococcosis (AE), but their long-term parasitocidal (curative) effect is disputed. In this study, we prospectively analyzed the potential parasitocidal effect of benzimidazoles and whether normalization of FDG-PET/CT scans and anti-Emll/3-10-antibody levels could act as reliable "in vivo" parameters of AE-inactivation permitting to abrogate chemotherapy with a low risk for AE-recurrence.MethodThis prospective study included 34 patients with non-resectable AE subdivided into group A (n = 11), followed-up after diagnosis and begin of chemotherapy at months 6, 12 and 24, and group B (n = 23) with a medium duration of chemotherapy of 10 (range 2–25) years. All patients were assessed by FDG-PET/CT examinations and anti-EmII/3-10 serology. Chemotherapy was abrogated in patients with normalization of FDG-PET/CT and serum anti-EmII/3-10 levels. These patients were closely followed-up for AE recurrence. Endpoint (parasitocidal efficacy) was defined by the absence of AE-recurrence >24 months after stopping treatment.ResultsNormalization of FDG-PET/CT scan and anti-EmII/3-10 levels occurred in 11 of 34 patients (32%). After abrogation of chemotherapy in these 11 patients, there was no evidence of AE-recurrence within a median of 70.5 (range 16–82) months. However, the patients’ immunocompetence appears pivotal for the described long-term parasitocidal effect of benzimidazoles.ConclusionsThe combination of negative FDG-PET/CT-scans and anti-EmII/3-10 antibody levels seem to be reliable parameters for assessing in vivo AE-larval inactivity after long-term benzimidazole chemotherapy.
Trial Registration
clinicaltrials.gov: NCT00658294相似文献14.
Ilse C. Schrieks Dina Ripken Annette Stafleu Renger F. Witkamp Henk F. J. Hendriks 《PloS one》2015,10(5)
BackgroundThe endocannabinoid system is suggested to play a regulatory role in mood. However, the response of circulating endocannabinoids (ECs) to mood changes has never been tested in humans. In the present study, we examined the effects of mood changes induced by ambiance and moderate alcohol consumption on plasma ECs 2-arachidonoylglycerol (2-AG), anandamide (AEA), and some N-acylethanolamine (NAE) congeners in humans.MethodsHealthy women (n = 28) participated in a randomized cross-over study. They consumed sparkling white wine (340 mL; 30 g alcohol) or alcohol-free sparkling white wine (340 mL; <2 g alcohol) as part of a standard evening meal in a room with either a pleasant or an unpleasant ambiance.ResultsPlasma concentrations of palmitoylethanolamide (PEA) and stearoylethanolamide (SEA) increased after 30 min in the unpleasant ambiance, while they decreased in the pleasant ambiance. Changes in ECs and their NAE congeners correlated with mood states, such as happiness and fatigue, but in the pleasant ambiance without alcohol only. ECs and their NAE congeners were correlated with serum free fatty acids and cortisol.ConclusionThis is the first human study to demonstrate that plasma NAEs are responsive to an unpleasant meal ambiance. Furthermore, associations between mood states and ECs and their NAE congeners were observed.
Trial Registration
Clinicaltrials.gov NCT01426022相似文献15.
16.
Matthew R. Golden Roxanne P. Kerani Mark Stenger James P. Hughes Mark Aubin Cheryl Malinski King K. Holmes 《PLoS medicine》2015,12(1)
BackgroundExpedited partner therapy (EPT), the practice of treating the sex partners of persons with sexually transmitted infections without their medical evaluation, increases partner treatment and decreases gonorrhea and chlamydia reinfection rates. We conducted a stepped-wedge, community-level randomized trial to determine whether a public health intervention promoting EPT could increase its use and decrease chlamydia test positivity and gonorrhea incidence in women.ConclusionsA public health intervention promoting the use of free PDPT substantially increased its use and may have resulted in decreased chlamydial and gonococcal infections at the population level.
Trial Registration
ClinicalTrials.gov NCT01665690相似文献17.
ImportanceThe rapid uptake of mobile phones in low and middle-income countries over the past decade has provided public health programs unprecedented access to patients. While programs have used text messages to improve medication adherence, there have been no high-powered trials evaluating their impact on tuberculosis treatment outcomes.ObjectiveTo measure the impact of Zindagi SMS, a two-way SMS reminder system, on treatment success of people with drug-sensitive tuberculosis.DesignWe conducted a two-arm, parallel design, effectiveness randomized controlled trial in Karachi, Pakistan. Individual participants were randomized to either Zindagi SMS or the control group. Zindagi SMS sent daily SMS reminders to participants and asked them to respond through SMS or missed (unbilled) calls after taking their medication. Non-respondents were sent up to three reminders a day.SettingPublic and private sector tuberculosis clinics in Karachi, Pakistan.ParticipantsNewly-diagnosed patients with smear or bacteriologically positive pulmonary tuberculosis who were on treatment for less than two weeks; 15 years of age or older; reported having access to a mobile phone; and intended to live in Karachi throughout treatment were eligible to participate. We enrolled 2,207 participants, with 1,110 randomized to Zindagi SMS and 1,097 to the control group.ResultsWe found no significant difference between the Zindagi SMS or control groups for treatment success (719 or 83% vs. 903 or 83%, respectively, p = 0·782). There was no significant program effect on self-reported medication adherence reported during unannounced visits during treatment.ConclusionIn this large-scale randomized controlled effectiveness trial of SMS medication reminders for tuberculosis treatment, we found no significant impact.
Trial Registration
The trial was registered with ClinicalTrials.gov, . NCT01690754相似文献18.
Matthijs Kox Lucas T. van Eijk Tim Verhaak Tim Frenzel Harmke D. Kiers Jelle Gerretsen Johannes G. van der Hoeven Lilian Kornet Avram Scheiner Peter Pickkers 《Arthritis research & therapy》2015,17(1)
IntroductionVagus nerve stimulation (VNS) exerts beneficial anti-inflammatory effects in various animal models of inflammation, including collagen-induced arthritis, and is implicated in representing a novel therapy for rheumatoid arthritis. However, evidence of anti-inflammatory effects of VNS in humans is very scarce. Transvenous VNS (tVNS) is a newly developed and less invasive method to stimulate the vagus nerve. In the present study, we determined whether tVNS is a feasible and safe procedure and investigated its putative anti-inflammatory effects during experimental human endotoxemia.MethodsWe performed a randomized double-blind sham-controlled study in healthy male volunteers. A stimulation catheter was inserted in the left internal jugular vein at spinal level C5–C7, adjacent to the vagus nerve. In the tVNS group (n = 10), stimulation was continuously performed for 30 minutes (0–10 V, 1 ms, 20 Hz), starting 10 minutes before intravenous administration of 2 ng kg−1Escherichia coli lipopolysaccharide (LPS). Sham-instrumented subjects (n = 10) received no electrical stimulation.ResultsNo serious adverse events occurred throughout the study. In the tVNS group, stimulation of the vagus nerve was achieved as indicated by laryngeal vibration. Endotoxemia resulted in fever, flu-like symptoms, and hemodynamic changes that were unaffected by tVNS. Furthermore, plasma levels of inflammatory cytokines increased sharply during endotoxemia, but responses were similar between groups. Finally, cytokine production by leukocytes stimulated with LPS ex vivo, as well as neutrophil phagocytosis capacity, were not influenced by tVNS.ConclusionstVNS is feasible and safe, but does not modulate the innate immune response in humans in vivo during experimental human endotoxemia.
Trial registration
Clinicaltrials.gov . Registered 12 September 2013. NCT01944228相似文献19.
Vivian F. Go Constantine Frangakis Nguyen Le Minh Carl Latkin Tran Viet Ha Tran Thi Mo Teerada Sripaipan Wendy W. Davis Carla Zelaya Pham The Vu David D. Celentano Vu Minh Quan 《PloS one》2015,10(5)
IntroductionInjecting drug use is a primary driver of HIV epidemics in many countries. People who inject drugs (PWID) and are HIV infected are often doubly stigmatized and many encounter difficulties reducing risk behaviors. Prevention interventions for HIV-infected PWID that provide enhanced support at the individual, family, and community level to facilitate risk-reduction are needed.Methods455 HIV-infected PWID and 355 of their HIV negative injecting network members living in 32 sub-districts in Thai Nguyen Province were enrolled. We conducted a two-stage randomization: First, sub-districts were randomized to either a community video screening and house-to-house visits or standard of care educational pamphlets. Second, within each sub-district, participants were randomized to receive either enhanced individual level post-test counseling and group support sessions or standard of care HIV testing and counseling. This resulted in four arms: 1) standard of care; 2) community level intervention; 3) individual level intervention; and 4) community plus individual intervention. Follow-up was conducted at 6, 12, 18, and 24 months. Primary outcomes were self-reported HIV injecting and sexual risk behaviors. Secondary outcomes included HIV incidence among HIV negative network members.ResultsFewer participants reported sharing injecting equipment and unprotected sex from baseline to 24 months in all arms (77% to 4% and 24% to 5% respectively). There were no significant differences at the 24-month visit among the 4 arms (Wald = 3.40 (3 df); p = 0.33; Wald = 6.73 (3 df); p = 0.08). There were a total of 4 HIV seroconversions over 24 months with no significant difference between intervention and control arms.DiscussionUnderstanding the mechanisms through which all arms, particularly the control arm, demonstrated both low risk behaviors and low HIV incidence has important implications for policy and prevention programming.
Trial Registration
ClinicalTrials.gov NCT01689545相似文献20.
Benedikt Ley Mohammad Shafiul Alam Kamala Thriemer Mohammad Sharif Hossain Mohammad Golam Kibria Sarah Auburn Eugenie Poirot Ric N. Price Wasif Ali Khan 《PloS one》2016,11(4)
BackgroundThe Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy.MethodsPatients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0–2) plus single dose primaquine (0.75mg/kg on day2) for P. falciparum infections, or with chloroquine (days 0–2) plus 14 days primaquine (3.5mg/kg total over 14 days) for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website ().ResultsBetween September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections). Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2–27.3) hours for P. falciparum, 20.0 (IQR: 9.5–22.7) hours for P. vivax and 16.6 (IQR: 10.0–46.0) hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174) had severe G6PD deficiency (<10% activity), five participants (5/174) had mild G6PD deficiency (10–60% activity). The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0%) and -7.4% (95%CI: -4.5 to -10.4%) respectively.ConclusionThe current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal individuals was attributable to acute malaria rather than primaquine administration. NCT02389374