A Randomized Controlled Trial of the Value of Phenotypic Testing in Addition to Genotypic Testing for HIV Drug Resistance

2005 ◽  
Vol 38 (5) ◽  
pp. 553-559 ◽  
Author(s):  
&NA;
2013 ◽  
Vol 28 (3) ◽  
pp. 233-241 ◽  
Author(s):  
Gustavo F. Westin ◽  
Cesar A. Perez ◽  
Emilie Wang ◽  
Stefan Glück

The goal of therapy for patients with metastatic breast cancer (MBC) is prolonging life and palliation of symptoms. Thus the preferred approach remains to use, at least initially, non-cytotoxic drugs. In hormone receptor-positive breast cancer the sequential use of single anti-estrogen drugs, e.g. tamoxifen, aromatase inhibitors, and many others is standard, but eventually drug resistance will lead to failure of these compounds and a switch to chemotherapy will be necessary. Reversing resistance to anti-estrogen therapy in MBC is one of the strategies to avoid and delay the use of cytotoxic compounds. The mammalian target of rapamycin (mTOR) has been recently associated with in vitro reversal of drug resistance, including tamoxifen resistance. A number of early clinical studies have confirmed the concept and, more recently, everolimus was successfully tested in a randomized controlled trial in postmenopausal patients who progressed on previous anti-estrogen therapy for MBC. This manuscript will review the biology, preclinical and clinical data including the randomized controlled trial that lead to the approval of everolimus by the US FDA.


2019 ◽  
Author(s):  
Ayse Ercumen ◽  
Jade Benjamin-Chung ◽  
Benjamin F. Arnold ◽  
Audrie Lin ◽  
Alan E. Hubbard ◽  
...  

AbstractBackgroundSoil transmitted helminths (STH) infect >1.5 billion people. Mass drug administration (MDA) reduces infection; however, drug resistance is emerging and reinfection occurs rapidly. We conducted a randomized controlled trial in Bangladesh (WASH Benefits,NCT01590095) to assess whether water, sanitation, hygiene and nutrition interventions, alone and combined, reduce STH in a setting with ongoing MDA.Methodology/Principal FindingsWe randomized clusters of pregnant women into water treatment, sanitation, handwashing, combined water+sanitation+handwashing (WSH), nutrition, nutrition+WSH (N+WSH) or control arms. After 2.5 years of intervention, we enumerated STH infections in children aged 2-12 years with Kato-Katz. We estimated intention-to-treat intervention effects on infection prevalence and intensity. Participants and field staff were not blinded; laboratory technicians and data analysts were blinded.In 2012-2013, we randomized 5551 women in 720 clusters. In 2015-2016, we enrolled 7795 children of 4102 available women for STH follow-up and collected stool from 7187. Prevalence among controls was 36.8% forA. lumbricoides, 9.2% for hookworm and 7.5% forT. trichiura. Most infections were low-intensity. Compared to controls, the water intervention reduced hookworm (prevalence ratio [PR]=0.69 (0.50, 0.95), prevalence difference [PD]=−2.83 (−5.16, −0.50)) but did not affect other STH. Sanitation improvements reducedT. trichiura(PR=0.71 (0.52, 0.98), PD=−2.17 (−4.03, −0.38)), had a similar borderline effect on hookworm and no effect onA. lumbricoides. Handwashing and nutrition interventions did not reduce any STH. WSH and N+WSH reduced hookworm prevalence by 29-33% (2-3 percentage points) and marginally reducedA. lumbricoides. Effects on infection intensity were similar.Conclusions/SignificanceIn a low-intensity infection setting with MDA, we found modest but sustained hookworm reduction from water treatment, sanitation and combined WSH interventions. Interventions more effectively reduced STH species with no persistent environmental reservoirs. Our findings highlight waterborne transmission for hookworm and suggest that water treatment and sanitation improvements can augment MDA programs to interrupt STH transmission.Author summarySoil-transmitted helminths (STH) infect >1.5 billion people worldwide. Mass-administration of deworming drugs is the cornerstone of global strategy for STH control but treated individuals often rapidly get reinfected and there is also concern about emerging drug resistance. Interventions to treat drinking water, wash hands at critical times and isolate human feces from the environment through improved sanitation could reduce STH transmission by reducing the spread of ova from the feces of infected individuals into the environment and subsequently to new hosts, while nutrition improvements could reduce host susceptibility to infection. Existing evidence on the effect of these interventions on STH is scarce. In a setting with ongoing mass-drug administration, we assessed the effect of individual and combined water, sanitation, handwashing and nutrition interventions on STH infection in children. Approximately 2.5 years after delivering interventions, we found reductions in STH infection from water treatment and sanitation interventions; there was no reduction from the handwashing and nutrition interventions. While the reductions were modest in magnitude compared to cure rates achieved by deworming drugs, they indicated sustained reduction in environmental transmission. The reductions were more pronounced for STH species that do not have persistent environmental reservoirs. These findings suggest that water treatment and sanitation interventions can augment mass-drug administration programs in striving toward elimination of STH.


2020 ◽  
Vol 29 (1S) ◽  
pp. 412-424
Author(s):  
Elissa L. Conlon ◽  
Emily J. Braun ◽  
Edna M. Babbitt ◽  
Leora R. Cherney

Purpose This study reports on the treatment fidelity procedures implemented during a 5-year randomized controlled trial comparing intensive and distributed comprehensive aphasia therapy. Specifically, the results of 1 treatment, verb network strengthening treatment (VNeST), are examined. Method Eight participants were recruited for each of 7 consecutive cohorts for a total of 56 participants. Participants completed 60 hr of aphasia therapy, including 15 hr of VNeST. Two experienced speech-language pathologists delivered the treatment. To promote treatment fidelity, the study team developed a detailed manual of procedures and fidelity checklists, completed role plays to standardize treatment administration, and video-recorded all treatment sessions for review. To assess protocol adherence during treatment delivery, trained research assistants not involved in the treatment reviewed video recordings of a subset of randomly selected VNeST treatment sessions and completed the fidelity checklists. This process was completed for 32 participants representing 2 early cohorts and 2 later cohorts, which allowed for measurement of protocol adherence over time. Percent accuracy of protocol adherence was calculated across clinicians, cohorts, and study condition (intensive vs. distributed therapy). Results The fidelity procedures were sufficient to promote and verify a high level of adherence to the treatment protocol across clinicians, cohorts, and study condition. Conclusion Treatment fidelity strategies and monitoring are feasible when incorporated into the study design. Treatment fidelity monitoring should be completed at regular intervals during the course of a study to ensure that high levels of protocol adherence are maintained over time and across conditions.


2019 ◽  
Vol 62 (12) ◽  
pp. 4464-4482 ◽  
Author(s):  
Diane L. Kendall ◽  
Megan Oelke Moldestad ◽  
Wesley Allen ◽  
Janaki Torrence ◽  
Stephen E. Nadeau

Purpose The ultimate goal of anomia treatment should be to achieve gains in exemplars trained in the therapy session, as well as generalization to untrained exemplars and contexts. The purpose of this study was to test the efficacy of phonomotor treatment, a treatment focusing on enhancement of phonological sequence knowledge, against semantic feature analysis (SFA), a lexical-semantic therapy that focuses on enhancement of semantic knowledge and is well known and commonly used to treat anomia in aphasia. Method In a between-groups randomized controlled trial, 58 persons with aphasia characterized by anomia and phonological dysfunction were randomized to receive 56–60 hr of intensively delivered treatment over 6 weeks with testing pretreatment, posttreatment, and 3 months posttreatment termination. Results There was no significant between-groups difference on the primary outcome measure (untrained nouns phonologically and semantically unrelated to each treatment) at 3 months posttreatment. Significant within-group immediately posttreatment acquisition effects for confrontation naming and response latency were observed for both groups. Treatment-specific generalization effects for confrontation naming were observed for both groups immediately and 3 months posttreatment; a significant decrease in response latency was observed at both time points for the SFA group only. Finally, significant within-group differences on the Comprehensive Aphasia Test–Disability Questionnaire ( Swinburn, Porter, & Howard, 2004 ) were observed both immediately and 3 months posttreatment for the SFA group, and significant within-group differences on the Functional Outcome Questionnaire ( Glueckauf et al., 2003 ) were found for both treatment groups 3 months posttreatment. Discussion Our results are consistent with those of prior studies that have shown that SFA treatment and phonomotor treatment generalize to untrained words that share features (semantic or phonological sequence, respectively) with the training set. However, they show that there is no significant generalization to untrained words that do not share semantic features or phonological sequence features.


2001 ◽  
Vol 26 (1) ◽  
pp. 67-71 ◽  
Author(s):  
S. A. Ahmadi-Abhari ◽  
S. Akhondzadeh ◽  
S. M. Assadi ◽  
O. L. Shabestari ◽  
Z. M. Farzanehgan ◽  
...  

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