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1.
Stephanie Zobrist Marcelo Brito Eduardo Garbin Wuelton M. Monteiro Suellen Clementino Freitas Marcela Macedo Aline Soares Moura Nicole Advani Maria Kahn Sampa Pal Emily Gerth-Guyette Pooja Bansil Gonzalo J. Domingo Dhelio Pereira Marcus VG Lacerda 《PLoS neglected tropical diseases》2021,15(8)
BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency, prevalent in many malaria-endemic countries. G6PD-deficient individuals are susceptible to hemolysis during oxidative stress, which can occur from exposure to certain medications, including 8-aminoquinolines used to treat Plasmodium vivax malaria. Accordingly, access to point-of-care (POC) G6PD testing in Brazil is critical for safe treatment of P. vivax malaria.Methodology/Principal findingsThis study evaluated the performance of the semi-quantitative, POC STANDARD G6PD Test (SD Biosensor, Republic of Korea). Participants were recruited at clinics and through an enriched sample in Manaus and Porto Velho, Brazil. G6PD and hemoglobin measurements were obtained from capillary samples at the POC using the STANDARD and HemoCue 201+ (HemoCue AB, Sweden) tests. A thick blood slide was prepared for malaria microscopy. At the laboratories, the STANDARD and HemoCue tests were repeated on venous samples and a quantitative spectrophotometric G6PD reference assay was performed (Pointe Scientific, Canton, MI). G6PD was also assessed by fluorescent spot test. In Manaus, a complete blood count was performed.Samples were analyzed from 1,736 participants. In comparison to spectrophotometry, the STANDARD G6PD Test performed equivalently in determining G6PD status in venous and capillary specimens under varied operating temperatures. Using the manufacturer-recommended reference value thresholds, the test’s sensitivity at the <30% threshold on both specimen types was 100% (95% confidence interval [CI] venous 93.6%–100.0%; capillary 93.8%–100.0%). Specificity was 98.6% on venous specimens (95% CI 97.9%–99.1%) and 97.8% on capillary (95% CI 97.0%–98.5%). At the 70% threshold, the test’s sensitivity was 96.9% on venous specimens (95% CI 83.8%–99.9%) and 94.3% on capillary (95% CI 80.8%–99.3%). Specificity was 96.5% (95% CI 95.0%–97.6%) and 92.3% (95% CI 90.3%–94.0%) on venous and capillary specimens, respectively.Conclusion/SignificanceThe STANDARD G6PD Test is a promising tool to aid in POC detection of G6PD deficiency in Brazil.Trial registrationThis study was registered with ClinicalTrials.gov (identifier: NCT04033640). 相似文献
2.
Christoph Schindler Kristina Guenther Cosima Hermann Carlos M. Ferrario Christoph Schroeder Sven Haufe Jens Jordan Wilhelm Kirch 《PloS one》2014,9(9)
Experimental studies suggested that statins attenuate vascular AT1 receptor responsiveness. Moreover, the augmented excessive pressor response to systemic angiotensin II infusions in hypercholesterolemic patients was normalized with statin treatment. In 12 hypercholesterolemic patients, we tested the hypothesis that statin treatment attenuates angiotensin II-mediated vasoconstriction in hand veins assessed by a linear variable differential transducer. Subjects ingested daily doses of either atorvastatin (40 mg) or positive control irbesartan (150 mg) for 30 days in a randomized and cross-over fashion. Ang II–induced venoconstriction at minute 4 averaged 59%±10% before and 28%±9% after irbesartan (mean ± SEM; P<0.05) compared to 65%±11% before and 73%±11% after 30 days of atorvastatin treatment. Plasma angiotensin levels increased significantly after irbesartan treatment (Ang II: 17±22 before vs 52±40 pg/mL after [p = 0.048]; Ang-(1–7): 18±10 before vs 37±14 pg/mL after [p = 0.002]) compared to atorvastatin treatment (Ang II: 9±4 vs 11±10 pg/mL [p = 0.40]; Ang-(1–7): 24±9 vs 32±8 pg/mL [p = 0.023]). Our study suggests that statin treatment does not elicit major changes in angiotensin II-mediated venoconstriction or in circulating angiotensin II levels whereas angiotensin-(1–7) levels increased modestly. The discrepancy between local vascular and systemic angiotensin II responses might suggest that statin treatment interferes with blood pressure buffering reflexes.
Trial Registration
ClinicalTrials.gov NCT00154024 相似文献3.
Background
School-based mass treatment with praziquantel is the cornerstone for schistosomiasis control in school-aged children. However, uptake of treatment among school-age children in Uganda is low in some areas. The objective of the study was to examine the effectiveness of a pre-treatment snack on uptake of mass treatment.Methods and Findings
In a cluster randomized trial carried out in Jinja district, Uganda, 12 primary schools were randomized into two groups; one received education messages for schistosomiasis prevention for two months prior to mass treatment, while the other, in addition to the education messages, received a pre-treatment snack shortly before mass treatment. Four weeks after mass treatment, uptake of praziquantel was assessed among a random sample of 595 children in the snack schools and 689 children in the non-snack schools as the primary outcome. The occurrence of side effects and the prevalence and mean intensity of Schistosoma mansoni infection were determined as the secondary outcomes. Uptake of praziquantel was higher in the snack schools, 93.9% (95% CI 91.7%–95.7%), compared to that in the non-snack schools, 78.7% (95% CI 75.4%–81.7%) (p = 0.002). The occurrence of side effects was lower in the snack schools, 34.4% (95% CI 31.5%–39.8%), compared to that in the non-snack schools, 46.9% (95% CI 42.2%–50.7%) (p = 0.041). Prevalence and mean intensity of S. mansoni infection was lower in the snack schools, 1.3% (95% CI 0.6%–2.6%) and 38.3 eggs per gram of stool (epg) (95% CI 21.8–67.2), compared to that in the non-snack schools, 14.1% (95% CI 11.6%–16.9%) (p = 0.001) and 78.4 epg (95% CI 60.6–101.5) (p = 0.001), respectively.Conclusions
Our results suggest that provision of a pre-treatment snack combined with education messages achieves a higher uptake compared to the education messages alone. The use a pre-treatment snack was associated with reduced side effects as well as decreased prevalence and intensity of S. mansoni infection.Trial registration
www.ClinicalTrials.gov NCT01869465 Please see later in the article for the Editors'' Summary 相似文献4.
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 (NCT00515216 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%).Results
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5.
Benjamin Hibbert Bradley Hayley Robert S. Beanlands Michel Le May Richard Davies Derek So Jean-Fran?ois Marquis Marino Labinaz Michael Froeschl Edward R. O’Brien Ian G. Burwash George A. Wells Ali Pourdjabbar Trevor Simard Harold Atkins Christopher Glover 《CMAJ》2014,186(11):E427-E434
Background:
Small studies have yielded divergent results for administration of granulocyte colony-stimulating factor (G-CSF) after acute myocardial infarction. Adequately powered studies involving patients with at least moderate left ventricular dysfunction are lacking.Methods:
Patients with left ventricular ejection fraction less than 45% after anterior-wall myocardial infarction were treated with G-CSF (10 μg/kg daily for 4 days) or placebo. After initial randomization of 86 patients, 41 in the placebo group and 39 in the G-CSF group completed 6-month follow-up and underwent measurement of left ventricular ejection fraction by radionuclide angiography.Results:
Baseline and 6-week mean ejection fraction was similar for the G-CSF and placebo groups: 34.8% (95% confidence interval [CI] 32.6%–37.0%) v. 36.4% (95% CI 33.5%–39.2%) at baseline and 39.8% (95% CI 36.2%–43.4%) v. 43.1% (95% CI 39.2%–47.0%) at 6 weeks. However, G-CSF therapy was associated with a lower ejection fraction at 6 months relative to placebo (40.8% [95% CI 37.4%–44.2%] v. 46.0% [95% CI 42.7%–44.3%]). Both groups had improved left ventricular function, but change in left ventricular ejection fraction was lower in patients treated with G-CSF than in those who received placebo (5.7 [95% CI 3.4–8.1] percentage points v. 9.2 [95% CI 6.3–12.1] percentage points). One or more of a composite of several major adverse cardiac events occurred in 8 patients (19%) within each group, with similar rates of target-vessel revascularization.Interpretation:
In patients with moderate left ventricular dysfunction following anterior-wall infarction, G-CSF therapy was associated with a lower 6-month left ventricular ejection fraction but no increased risk of major adverse cardiac events. Future studies of G-CSF in patients with left ventricular dysfunction should be monitored closely for safety. Trial registration: ClinicalTrials.gov, no. NCT00394498Rapid reperfusion therapy has become the standard treatment for ST-segment elevation myocardial infarction (STEMI), with congestive heart failure and left ventricular dysfunction continuing as the strongest predictors of higher long-term risk.1 To date, no definitive therapies exist to regenerate myocardium following myocardial necrosis, and myocardial preservation is therefore the goal of STEMI care. Contemporary studies have suggested the possibility of myocardial regeneration by endogenous stem and progenitor cell populations, and preliminary clinical studies have hinted at potential benefit.2,3 Studies investigating whether postinfarction myocardial function can be improved by enhancing stem cell–mediated repair are in progress (NCT00936819 and NCT00984178).Granulocyte colony-stimulating factor (G-CSF), an endogenously produced glycoprotein growth factor, when given in pharmacologic doses, stimulates mobilization of hematopoietic stem cells into the peripheral blood. Therapeutically, recombinant synthetic forms have been used to enhance recovery from neutropenia following chemotherapy and for mobilization of stem cells before hematopoietic stem cell transplant.4 Numerous small clinical studies have investigated the potential of G-CSF–induced mobilization of stem cells in the peri-infarction period to enhance left ventricular recovery, but they have yielded discordant results. However, meta-analyses have suggested benefit for left ventricular ejection fraction in subgroups who received G-CSF early after infarction or in patients whose left ventricular dysfunction was mild to moderate.5,6 Larger trials are necessary because, in addition to mobilizing stem cells, G-CSF modulates intracellular signalling cascades within cardiomyocytes and can activate neutrophils, and several trials have been stopped early as a result of excessive in-stent restenosis and acute coronary syndromes in patients with coronary artery disease.7–11 Animal data have similarly yielded discordant results, depending on the dose and timing of G-CSF.12To clarify the role of G-CSF in promoting left ventricular recovery after acute myocardial infarction, we performed an adequately powered randomized clinical trial in patients with moderate left ventricular dysfunction following anterior-wall STEMI. 相似文献6.
Josef S. Smolen Ronald van Vollenhoven Arthur Kavanaugh Vibeke Strand Jiri Vencovsky Michael Schiff Robert Landewé Boulos Haraoui Catherine Arendt Irina Mountian David Carter Désirée van der Heijde 《Arthritis research & therapy》2015,17(1)
IntroductionAs patients with rheumatoid arthritis (RA) receive treatment with anti-tumour necrosis factors over several years, it is important to evaluate their long-term safety and efficacy. The objective of this study was to examine the safety and benefits of certolizumab pegol (CZP)+methotrexate (MTX) treatment for almost 5 years in patients with RA.MethodsPatients who completed the 24-week Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 2 randomized controlled trial (RCT; NCT00160602), or who were American College of Rheumatology (ACR) 20 non-responders at Week 16, entered the open-label extension (OLE; NCT00160641). After ≥6 months treatment with CZP 400 mg every two weeks (Q2W), dose was reduced to 200 mg Q2W, the approved maintenance dose. Safety data are presented from all patients who received ≥1 dose CZP (Safety population, n=612). Efficacy data are presented to Week 232 for the intent-to-treat (ITT, n=492) and Week 24 CZP RCT Completer (n=342) populations, and through 192 weeks of dose-reduction for the Dose-reduction population (patients whose CZP dose was reduced to 200 mg, n=369). Radiographic progression (modified total Sharp score change from RCT baseline >0.5) to Week 128 is reported for the Week 24 CZP Completers.ResultsIn the RCT, 619 patients were randomized to CZP+MTX (n=492) or placebo+MTX (n=127). Overall, 567 patients (91.6%) entered the OLE: 447 CZP and 120 placebo patients. Of all randomized patients, 358 (57.8%) were ongoing at Week 232. Annual drop-out rates during the first four years ranged from 8.4–15.0%. Event rates per 100 patient-years were 163.0 for adverse events (AEs) and 15.7 for serious AEs. Nineteen patients (3.1%) had fatal AEs (incidence rate=0.8). Clinical improvements in the RCT were maintained to Week 232 in the CZP Completers: mean Disease Activity Score 28 (Erythrocyte Sedimentation Rate) change from baseline was −3.4 and ACR20/50/70 responses 68.4%/47.1%/25.1% (non-responder imputation). Similar improvements observed in the ITT were maintained following dose-reduction. 73.2% of CZP Completers had no radiographic progression at Week 128.ConclusionsIn patients with active RA despite MTX therapy, CZP was well tolerated, with no new safety signals identified. CZP provided sustained improvements in clinical outcomes for almost 5 years.
Trial registration
ClinicalTrials.gov, NCT00160602 and NCT00160641. Registered 8 September 2005.Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0767-2) contains supplementary material, which is available to authorized users. 相似文献7.
8.
Manish A. Shah Zev A. Wainberg Daniel V. T. Catenacci Howard S. Hochster James Ford Pamela Kunz Fa-Chyi Lee Howard Kallender Fabiola Cecchi Daniel C. Rabe Harold Keer Anne-Marie Martin Yuan Liu Robert Gagnon Peter Bonate Li Liu Tona Gilmer Donald P. Bottaro 《PloS one》2013,8(3)
Purpose
The receptors for hepatocyte and vascular endothelial cell growth factors (MET and VEGFR2, respectively) are critical oncogenic mediators in gastric adenocarcinoma. The purpose is to examine the safety and efficacy of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, and VEGFR2 receptors, for the treatment of metastatic gastric adenocarcinoma.Patients and Methods
Foretinib safety and tolerability, and objective response rate (ORR) were evaluated in patients using intermittent (240 mg/day, for 5 days every 2 weeks) or daily (80 mg/day) dosing schedules. Thirty evaluable patients were required to achieve alpha = 0.10 and beta = 0.2 to test the alternative hypothesis that single-agent foretinib would result in an ORR of ≥25%. Up to 10 additional patients could be enrolled to ensure at least eight with MET amplification. Correlative studies included tumor MET amplification, MET signaling, pharmacokinetics and plasma biomarkers of foretinib activity.Results
From March 2007 until October 2009, 74 patients were enrolled; 74% male; median age, 61 years (range, 25–88); 93% had received prior therapy. Best response was stable disease (SD) in 10 (23%) patients receiving intermittent dosing and five (20%) receiving daily dosing; SD duration was 1.9–7.2 months (median 3.2 months). Of 67 patients with tumor samples, 3 had MET amplification, one of whom had SD. Treatment-related adverse events occurred in 91% of patients. Rates of hypertension (35% vs. 15%) and elevated aspartate aminotransferase (23% vs. 8%) were higher with intermittent dosing. In both patients with high baseline tumor phospho-MET (pMET), the pMET:total MET protein ratio decreased with foretinib treatment.Conclusion
These results indicate that few gastric carcinomas are driven solely by MET and VEGFR2, and underscore the diverse molecular oncogenesis of this disease. Despite evidence of MET inhibition by foretinib, single-agent foretinib lacked efficacy in unselected patients with metastatic gastric cancer.Trial Registration
ClinicalTrials.gov NCT00725712 相似文献9.
Lynn T. Matthews Sengeziwe Sibeko Leila E. Mansoor Nonhlanhla Yende-Zuma David R. Bangsberg Quarraisha Abdool Karim 《PloS one》2013,8(3)
Background
Antiretroviral prophylaxis may be a critical strategy to reduce periconception HIV transmission. Maximizing the benefit of periconception pharmacologic HIV risk-reduction requires an understanding of the links between pregnancy and adherence to this prevention strategy.Methods
We assessed study gel adherence among women with pregnancies compared to women without pregnancies enrolled in the CAPRISA 004 phase IIB trial of 1% vaginal tenofovir gel. Pregnancy was assessed with monthly urine tests. Adherence was measured monthly and defined as proportion of sex acts covered by two returned, used applicators based on pre- and post-coital dosing. High adherence was defined as a median adherence score of >80%, that is, more than 80% of sex acts were covered by two applications of study gel. A multivariate generalized estimating equations (GEE) model with a binomial distribution was used to assess covariates associated with high adherence (>80%) over time. Median adherence before and after pregnancy was compared using Wilcoxon signed rank test.Results
Among 868 women, 53 had at least 1 pregnancy (4.06 per 100 woman years, 95% CI: 3.04, 5.31). Women with pregnancies had lower median adherence compared to women without pregnancies (50% [IQR: 45–83] vs. 60% [IQR: 50–100], p = 0.02). Women with pregnancies also had a 48% lower odds of high adherence compared to women without pregnancies when adjusting for confounders (aOR 0.52, 95%CI: 0.41–0.66, p<0.0001). Among women with pregnancies, adherence before and after pregnancy was not different (50% [IQR: 46–83] vs. 55% [IQR: 20–100], p = 0.68).Conclusions
Women with pregnancies were less likely to have high adherence to study gel compared to women without pregnancies. Understanding these differences may inform findings from HIV prevention trials and future implementation of antiretroviral prophylaxis for at-risk women who choose to conceive. The protocol for the parent trial is registered on ClinicalTrials.gov, NCT00441298, http://www.clinicaltrials.gov/ct2/show/NCT00441298. 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 NCT00548379 https://www.clinicaltrials.gov/ct2/show/NCT00548379 相似文献11.
Alain Hendlisz Amelie Deleporte Thierry Delaunoit Rapha?l Maréchal Marc Peeters Stéphane Holbrechts Marc Van den Eynde Ghislain Houbiers Bertrand Filleul Jean-Luc Van Laethem Sarah Ceyssens Anna-Maria Barbuto Renaud Lhommel Gauthier Demolin Camilo Garcia Hazem El Mansy Lieveke Ameye Michel Moreau Thomas Guiot Marianne Paesmans Martine Piccart Patrick Flamen 《PloS one》2015,10(9)
Background
Tumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR) heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC).Methods
Standardized FDG-PET/CT was performed at baseline and after the first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day) and capecitabine (1700 mg/m²/day administered D1-14 every 21 days). MR assessment was categorized according to the proportion of metabolically non-responding (non-mR) lesions (stable FDG uptake with SUVmax decrease <15%) among all measurable lesions.Results
Ninety-two patients were included. The median overall survival (OS) and progression-free survival (PFS) were 8.2 months (95% CI: 6.8–10.5) and 4.2 months (95% CI: 3.4–4.8) respectively. In the 79 assessable patients, early PET-CT showed no metabolically refractory lesion in 47%, a heterogeneous mR with at least one non-mR lesion in 32%, and a consistent non-mR or early disease progression in 21%. On exploratory analysis, patients without any non-mR lesion showed a significantly longer PFS (HR 0.34; 95% CI: 0.21–0.56, P-value <0.001) and OS (HR 0.58; 95% CI: 0.36–0.92, P-value 0.02) compared to the other patients. The proportion of non-mR lesions within the tumor load did not impact PFS/OS.Conclusion
The presence of at least one metabolically refractory lesion is associated with a poorer outcome in advanced mCRC patients treated with combined sorafenib-capecitabine. Early detection of treatment-induced mR heterogeneity may represent an important predictive efficacy biomarker in mCRC.Trial Registration
ClinicalTrials.gov NCT01290926 相似文献12.
Patrizia Maria Carrieri Laurent Michel Caroline Lions Julien Cohen Muriel Vray Marion Mora Fabienne Marcellin Bruno Spire Alain Morel Perrine Roux the Methaville Study Group 《PloS one》2014,9(11)
Objective
Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC). This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC) and SC.Methods
In this study, registered at ClinicalTrials.Gov (NCT00657397), opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12) (with an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period), retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT). Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC) on the course of abstinence and retention, respectively.Results
In the ITT analysis (n = 155 in PC, 66 in SC), which compared the proportions of street-opioid abstinent participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively).Conclusions
Under appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence.Trial registration
Number Eudract 2008-001338-28; ClinicalTrials.gov: NCT00657397; International Standard Randomized Controlled Trial Number Register ISRCTN31125511 相似文献13.
Elizabeth L. Turner Siham Sikander Omer Bangash Ahmed Zaidi Lisa Bates John Gallis Nima Ganga Karen O’Donnell Atif Rahman Joanna Maselko 《Trials》2016,17(1)
BackgroundThe negative effects of perinatal depression on the mother and child start early and persist throughout the lifecourse (Lancet 369(9556):145–57, 2007; Am J Psychiatry 159(1):43-7, 2002; Arch Dis Child 77(2):99–101, 1997; J Pak Med Assoc 60(4):329; J Psychosoma Res 49(3):207–16, 2000; Clin Child Fam Psychol Rev 14(1):1–27, 2011). Given that 10–35 % of children worldwide are exposed to perinatal depression in their first year of life (Int Rev Psychiatry 8(1):37–54, 1996), mitigating this intergenerational risk is a global public health priority (Perspect Public Health 129(5):221–7, 2009; Trop Med Int Health 13(4):579–83, 2008; Br Med Bull 101(1):57–79, 2012). However, it is not clear whether intervention with depressed women can have long-term benefits for the mother and/or her child. We describe a study of the effectiveness of a peer-delivered depression intervention delivered through 36 postnatal months, the Thinking Healthy Program Peer-delivered PLUS (THPP+) for women and their children in rural Pakistan.Methods/designThe THPP+ study aims are: (1) to evaluate the effects of an extended 36-month perinatal depression intervention on maternal and index child outcomes using a cluster randomized controlled trial (c-RCT) and (2) to determine whether outcomes among index children of perinatally depressed women in the intervention arm converge with those of index children born to perinatally nondepressed women. The trial is designed to recruit 560 pregnant women who screened positive for perinatal depression (PHQ-9 score ≥10) from 40 village clusters, of which 20 receive the THPP+ intervention. An additional reference group consists of 560 perinatally nondepressed women from the same 40 clusters as the THPP+ trial. The women in the nondepressed group are not targeted to receive the THPP+ intervention; but, by recruiting pregnant women from both intervention and control clusters, we are able to evaluate any carryover effects of the THPP+ intervention on the women and their children. Perinatally depressed women in the THPP+ intervention arm receive bimonthly group-based sessions. Primary outcomes are 3-year maternal depression and 3-year child development indicators. Analyses are intention-to-treat and account for the clustered design.DiscussionThis trial, together with the reference group, has the potential to further our understanding of the early developmental lifecourse of children of both perinatally depressed and perinatally nondepressed women in rural Pakistan and to determine whether intervening with women’s depression in the perinatal period can mitigate the negative effects of maternal depression on 36-month child development.
Trial registration
THPP-P ClinicalTrials.gov Identifier: NCT02111915 (registered on 9 April 2014).THPP+ ClinicalTrials.gov Identifier: NCT02658994 (registered on 21 January 2016).Sponsor: Human Development Research Foundation (HDRF).Electronic supplementary material
The online version of this article (doi:10.1186/s13063-016-1530-y) contains supplementary material, which is available to authorized users. 相似文献14.
Ingeborg A. Brouwer Johanna M. Geleijnse Veronique M. Klaasen Liesbeth A. Smit Erik J. Giltay Janette de Goede Annemieke C. Heijboer Daan Kromhout Martijn B. Katan 《PloS one》2013,8(12)
Background
Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer.Methods
The Alpha Omega Trial (ClinicalTrials.gov Identifier: NCT00127452) was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 2×2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60–80 years with an initial PSA concentration <4 ng/mL. They received either 2 g per day of ALA or placebo in margarine spreads for 40 months. T-tests and logistic regression were used to assess the effects of ALA supplementation on changes in serum PSA (both continuously and as a dichotomous outcome, cut-off point: >4 ng/mL).Findings
Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: −0.02 to 0.22) ng/mL (P = 0·12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84–1.58).Interpretation
An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from −0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer.Trial registration information
ClinicalTrials.gov; Identifier: NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/NCT00127452. 相似文献15.
Bonnie C. Shaddinger Yanmei Xu James H. Roger Colin H. Macphee Malcolm Handel Charlotte A. Baidoo Mindy Magee John J. Lepore Dennis L. Sprecher 《PloS one》2014,9(1)
Background
We explored the theorized upregulation of platelet-activating factor (PAF)– mediated biologic responses following lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibition using human platelet aggregation studies in an in vitro experiment and in 2 clinical trials.Methods and Results
Full platelet aggregation concentration response curves were generated in vitro to several platelet agonists in human plasma samples pretreated with rilapladib (selective Lp-PLA2 inhibitor) or vehicle. This was followed by a randomized, double-blind crossover study in healthy adult men (n = 26) employing a single-agonist dose assay of platelet aggregation, after treatment of subjects with 250 mg oral rilapladib or placebo once daily for 14 days. This study was followed by a second randomized, double-blind parallel-group trial in healthy adult men (n = 58) also treated with 250 mg oral rilapladib or placebo once daily for 14 days using a full range of 10 collagen concentrations (0–10 µg/ml) for characterizing EC50 values for platelet aggregation for each subject. Both clinical studies were conducted at the GlaxoSmithKline Medicines Research Unit in the Prince of Wales Hospital, Sydney, Australia. EC50 values derived from multiple agonist concentrations were compared and no pro-aggregant signals were observed during exposure to rilapladib in any of these platelet studies, despite Lp-PLA2 inhibition exceeding 90%. An increase in collagen-mediated aggregation was observed 3 weeks post drug termination in the crossover study (15.4% vs baseline; 95% confidence interval [CI], 3.9–27.0), which was not observed during the treatment phase and was not observed in the parallel-group study employing a more robust EC50 examination.Conclusions
Lp-PLA2 inhibition does not enhance platelet aggregation.Trial Registration
1) Study 1: ClinicalTrials.gov NCT01745458 2) Study 2: ClinicalTrials.gov NCT00387257 相似文献16.
Shai Efrati Haim Golan Yair Bechor Yifat Faran Shir Daphna-Tekoah Gal Sekler Gregori Fishlev Jacob N. Ablin Jacob Bergan Olga Volkov Mony Friedman Eshel Ben-Jacob Dan Buskila 《PloS one》2015,10(5)
BackgroundFibromyalgia Syndrome (FMS) is a persistent and debilitating disorder estimated to impair the quality of life of 2–4% of the population, with 9:1 female-to-male incidence ratio. FMS is an important representative example of central nervous system sensitization and is associated with abnormal brain activity. Key symptoms include chronic widespread pain, allodynia and diffuse tenderness, along with fatigue and sleep disturbance. The syndrome is still elusive and refractory. The goal of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on symptoms and brain activity in FMS.ConclusionsThe study provides evidence that HBOT can improve the symptoms and life quality of FMS patients. Moreover, it shows that HBOT can induce neuroplasticity and significantly rectify abnormal brain activity in pain related areas of FMS patients.
Trial Registration
ClinicalTrials.gov NCT01827683 相似文献17.
Matthew B. Laurens Peter Billingsley Adam Richman Abraham G. Eappen Matthew Adams Tao Li Sumana Chakravarty Anusha Gunasekera Christopher G. Jacob B. Kim Lee Sim Robert Edelman Christopher V. Plowe Stephen L. Hoffman Kirsten E. Lyke 《PloS one》2013,8(7)
Controlled human malaria infection (CHMI) is a powerful method for assessing the efficacy of anti-malaria vaccines and drugs targeting pre-erythrocytic and erythrocytic stages of the parasite. CHMI has heretofore required the bites of 5 Plasmodium falciparum (Pf) sporozoite (SPZ)-infected mosquitoes to reliably induce Pf malaria. We reported that CHMI using the bites of 3 PfSPZ-infected mosquitoes reared aseptically in compliance with current good manufacturing practices (cGMP) was successful in 6 participants. Here, we report results from a subsequent CHMI study using 3 PfSPZ-infected mosquitoes reared aseptically to validate the initial clinical trial. We also compare results of safety, tolerability, and transmission dynamics in participants undergoing CHMI using 3 PfSPZ-infected mosquitoes reared aseptically to published studies of CHMI using 5 mosquitoes. Nineteen adults aged 18–40 years were bitten by 3 Anopheles stephensi mosquitoes infected with the chloroquine-sensitive NF54 strain of Pf. All 19 participants developed malaria (100%); 12 of 19 (63%) on Day 11. The mean pre-patent period was 258.3 hours (range 210.5–333.8). The geometric mean parasitemia at first diagnosis by microscopy was 9.5 parasites/µL (range 2–44). Quantitative polymerase chain reaction (qPCR) detected parasites an average of 79.8 hours (range 43.8–116.7) before microscopy. The mosquitoes had a geometric mean of 37,894 PfSPZ/mosquito (range 3,500–152,200). Exposure to the bites of 3 aseptically-raised, PfSPZ-infected mosquitoes is a safe, effective procedure for CHMI in malaria-naïve adults. The aseptic model should be considered as a new standard for CHMI trials in non-endemic areas. Microscopy is the gold standard used for the diagnosis of Pf malaria after CHMI, but qPCR identifies parasites earlier. If qPCR continues to be shown to be highly specific, and can be made to be practical, rapid, and standardized, it should be considered as an alternative for diagnosis.
Trial Registration
ClinicalTrials.gov NCT00744133 NCT00744133 相似文献18.
Luis F. López-Cortés Pompeyo Viciana José A. Girón-González Alberto Romero-Palacios Manuel Márquez-Solero Maria A. Martinez-Perez Miguel A. López-Ruz Javier de la Torre-Lima Francisco Téllez-Pérez Marcial Delgado-Fernández Milagros Garcia-Lázaro Fernando Lozano Mohamed O. Mohamed-Balghata 《PloS one》2014,9(5)
19.
Nancy Birungi Lars T. Fadnes Isaac Okullo Arabat Kasangaki Victoria Nankabirwa Grace Ndeezi James K. Tumwine Thorkild Tyllesk?r Stein Atle Lie Anne Nordrehaug ?str?m 《PloS one》2015,10(5)
BackgroundAlthough several studies have shown short term health benefits of exclusive breastfeeding (EBF), its long term consequences have not been studied extensively in low-income contexts. This study assessed the impact of an EBF promotion initiative for 6 months on early childhood caries (ECC) and breastfeeding duration in children aged 5 years in Mbale, Eastern Uganda.MethodsParticipants were recruited from the Ugandan site of the PROMISE- EBF cluster randomised trial (ClinicalTrials.gov no: NCT00397150). A total of 765 pregnant women from 24 clusters were included in the ratio 1:1 to receive peer counselled promotion of EBF as the intervention or standard of care. At the 5 year follow-up, ECC was recorded under field conditions using the World Health Organization’s decayed missing filled tooth (dmft) index. Adjusted negative binomial and linear regression were used in the analysis.ResultsMean breastfeeding duration in the intervention and control groups (n=417) were 21.8 (CI 20.7–22.9) and 21.3(CI 20.7–21.9) months, respectively. The mean dmft was 1.5 (standard deviation [SD] 2.9) and 1.7 (SD 2.9) in the intervention and control groups, respectively. Corresponding prevalence estimates of ECC were 38% and 41%. Negative binomial regression analysis adjusted for cluster effects and loss-to-follow-up by inverse probability weights (IPW) showed an incidence-rate ratio (IRR) of 0.91 (95% CI 0.65–1.2). Comparing the effect of the trial arm on breastfeeding duration showed a difference in months of 0.48 (-0.72 to 1.7).ConclusionPROMISE EBF trial did not impact on early childhood caries or breastfeeding duration at 5 years of age. This study contributes to the body of evidence that promotion of exclusive breastfeeding does not raise oral health concerns. However, the high burden of caries calls for efforts to improve the oral health condition in this setting.
Trial Registration
ClinicalTrials.gov NCT00397150 相似文献20.
Pablo Perel Tim Clayton Doug G. Altman Peter Croft Ian Douglas Harry Hemingway Aroon Hingorani Katherine I. Morley Richard Riley Adam Timmis Danielle Van der Windt Ian Roberts for the PROGRESS Partnership 《PLoS medicine》2014,11(6)