scholarly journals Impact of Transmission Intensity on the Accuracy of Genotyping To Distinguish Recrudescence from New Infection in Antimalarial Clinical Trials

2007 ◽  
Vol 51 (9) ◽  
pp. 3096-3103 ◽  
Author(s):  
Bryan Greenhouse ◽  
Christian Dokomajilar ◽  
Alan Hubbard ◽  
Philip J. Rosenthal ◽  
Grant Dorsey
Keyword(s):  
Clinical Trials ◽  
Treatment Failure ◽  
Transmission Intensity ◽  
High Transmission ◽  
Risk Of Treatment ◽  
Parasite Strains

ABSTRACT Antimalarial clinical trials use genotyping techniques to distinguish new infection from recrudescence. In areas of high transmission, the accuracy of genotyping may be compromised due to the high number of infecting parasite strains. We compared the accuracies of genotyping methods, using up to six genotyping markers, to assign outcomes for two large antimalarial trials performed in areas of Africa with different transmission intensities. We then estimated the probability of genotyping misclassification and its effect on trial results. At a moderate-transmission site, three genotyping markers were sufficient to generate accurate estimates of treatment failure. At a high-transmission site, even with six markers, estimates of treatment failure were 20% for amodiaquine plus artesunate and 17% for artemether-lumefantrine, regimens expected to be highly efficacious. Of the observed treatment failures for these two regimens, we estimated that at least 45% and 35%, respectively, were new infections misclassified as recrudescences. Increasing the number of genotyping markers improved the ability to distinguish new infection from recrudescence at a moderate-transmission site, but using six markers appeared inadequate at a high-transmission site. Genotyping-adjusted estimates of treatment failure from high-transmission sites may represent substantial overestimates of the true risk of treatment failure.

scholarly journals Histologic Remission Is Associated With Lower Risk of Treatment Failure in Patients With Crohn Disease in Endoscopic Remission

2020 ◽  
Author(s):  
Hyuk Yoon ◽  
Sushrut Jangi ◽  
Parambir S Dulai ◽  
Brigid S Boland ◽  
Vipul Jairath ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Crohn Disease ◽  
Lower Risk ◽  
Hazard Analysis ◽  
Cumulative Risk ◽  
Treatment Optimization ◽  
Cox Proportional Hazard ◽  
Endoscopic Remission ◽  
Risk Of Treatment

Abstract Background Although achieving histologic remission in ulcerative colitis is established, the incremental benefit of achieving histologic remission in patients with Crohn disease (CD) treated to a target of endoscopic remission is unclear. We evaluated the risk of treatment failure in patients with CD in clinical and endoscopic remission by histologic activity status. Methods In a single-center retrospective cohort study, we identified adults with active CD who achieved clinical and endoscopic remission through treatment optimization. We evaluated the risk of treatment failure (composite of clinical flare requiring treatment modification, hospitalization, and/or surgery) in patients who achieved histologic remission vs persistent histologic activity through Cox proportional hazard analysis. Results Of 470 patients with active CD, 260 (55%) achieved clinical and endoscopic remission with treatment optimization; 215 patients with histology were included (median age, 33 years; 46% males). Overall, 132 patients (61%) achieved histologic remission. No baseline demographic, disease, or treatment factor was associated with achieving histologic remission. Over a 2-year follow-up, patients with CD in clinical and endoscopic remission who achieved histologic remission experienced a 43% lower risk of treatment failure (1-year cumulative risk: 12.9% vs 18.2%; adjusted hazard ratio, 0.57 [95% confidence interval, 0.35-0.94]) as compared with persistent histologic activity. Conclusions Approximately 61% of patients with active CD who achieved clinical and endoscopic remission with treatment optimization simultaneously achieved histologic remission, which was associated with a lower risk of treatment failure. Whether histologic remission should be a treatment target in CD requires evaluation in randomized trials.

Factors associated to first line antiretroviral therapy (ART) failure among HIV/AIDS patients at Sanglah Hospital, Bali

2017 ◽  
pp. 4
Author(s):  
Cok Istri Sri Dharma Astiti ◽  
A.A Sagung Sawitri ◽  
Tuti Parwati
Keyword(s):  
Risk Factors ◽  
Treatment Failure ◽  
Clinical Stage ◽  
Hiv And Aids ◽  
First Line ◽  
Aids Patients ◽  
Factors Associated ◽  
Art Initiation ◽  
Risk Of Treatment ◽  
Hiv Aids

Background and purpose: The incidence of first line ART failure is increasing in the South East Asia region. The main referral hospital in Bali has recorded an increased use of second line ART due to the first line ART failure. This study aims to explore risk factors associated to first line ART failure.Methods: A case control study was conducted among people living with HIV and AIDS at Sanglah Hospital Denpasar who started first line ART between 2004 and 2013. Cases were those who diagnosed as having clinical treatment failure and still on treatment in 2015. Controls were those with no treatment failure. Sex and year of ART initiation were matched between case and control. Data were obtained from medical records that include initial regiments, HIV mode of transmission, the WHO HIV clinical stage, CD4 count, opportunistic infections, body mass index, hemoglobin level, and drug substitution at the beginning and during treatment. Risk factors were analysed using logistic regression.Results: Out of 68 HIV/AIDS patients with clinical ART failure, 72.1% were confirmed with immunological and 36.8% were confirmed with virological failure. Median time before treatment failure was 3.5 years. Factors associated to ART failure were HIV clinical stage IV with (AOR=3.43; 95%CI=1.65-7.13) and being widow/widower (AOR=4.85; 95%CI=1.52-15.53). Patients with TB co-infection have a lower risk for treatment failure due to early diagnosis and treatment through TB-HIV program with (AOR=0.32; 95%CI=0.14-0.70).Conclusions: Higher HIV clinical stage at ART initiation increases the risk of treatment failure. HIV-TB co-infection indirectly reduces the risk of treatment failure.

scholarly journals Risk of Treatment Failure: Response to Czobor and Volavka

2018 ◽  
Vol 175 (9) ◽  
pp. 909-909
Author(s):  
Jari Tiihonen ◽  
Antti Tanskanen ◽  
Heidi Taipale
Keyword(s):  
Treatment Failure ◽  
Risk Of Treatment

scholarly journals Antibiotics for uncomplicated skin abscesses: systematic review and network meta-analysis

BMJ Open ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. e020991 ◽  
Author(s):  
Wen Wang ◽  
Wenwen Chen ◽  
Yanmei Liu ◽  
Reed Alexander C Siemieniuk ◽  
Ling Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Treatment Failure ◽  
Meta Analysis ◽  
Late Recurrence ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
High Quality ◽  
Moderate Quality ◽  
The Impact ◽  
Risk Of Treatment

ObjectiveTo assess the impact of adjunctive antibiotic therapy on uncomplicated skin abscesses.DesignSystematic review and network meta-analysis.Data sourcesMedline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov.Study selectionA BMJ Rapid Recommendation panel provided input on design, important outcomes and the interpretation of the results. Eligible randomised controlled trials (RCTs) included a comparison of antibiotics against no antibiotics or a comparison of different antibiotics in patients with uncomplicated skin abscesses, and reported outcomes prespecified by the linked guideline panel.Review methodsReviewers independently screened abstracts and full texts for eligibility, assessed risk of bias and extracted data. We performed random-effects meta-analyses that compared antibiotics with no antibiotics, along with a limited number of prespecified subgroup hypotheses. We also performed network meta-analysis with a Bayesian framework to compare effects of different antibiotics. Quality of evidence was assessed with The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsFourteen RCTs including 4198 patients proved eligible. Compared with no antibiotics, antibiotics probably lower the risk of treatment failure (OR 0.58, 95% CI 0.37 to 0.90; low quality), recurrence within 1 month (OR 0.48, 95% CI 0.30 to 0.77; moderate quality), hospitalisation (OR 0.55, 95% CI 0.32 to 0.94; moderate quality) and late recurrence (OR 0.64, 95% CI 0.48 to 0.85; moderate quality). However, relative to no use, antibiotics probably increase the risk of gastrointestinal side effects (trimethoprim and sulfamethoxazole (TMP-SMX): OR 1.28, 95% CI 1.04 to 1.58; moderate quality; clindamycin: OR 2.29, 95% CI 1.35 to 3.88; high quality) and diarrhoea (clindamycin: OR 2.71, 95% CI 1.50 to 4.89; high quality). Cephalosporins did not reduce the risk of treatment failure compared with placebo (moderate quality).ConclusionsIn patients with uncomplicated skin abscesses, moderate-to-high quality evidence suggests TMP-SMX or clindamycin confer a modest benefit for several important outcomes, but this is offset by a similar risk of adverse effects. Clindamycin has a substantially higher risk of diarrhoea than TMP-SMX. Cephalosporins are probably not effective.

PP126 MEA In Italy: Correlation Between Time To Payment By Result And Time To Off Treatment Curve

2017 ◽  
Vol 33 (S1) ◽  
pp. 131-132
Author(s):  
Gabriele Vittoria ◽  
Antonio Fascì ◽  
Matteo Ferrario ◽  
Giovanni Giuliani
Keyword(s):  
Clinical Trials ◽  
Treatment Failure ◽  
Median Time ◽  
Real Life ◽  
Standard Of Care ◽  
Phase Iii ◽  
Experimental Drug ◽  
The Mean ◽  
Line Of Therapy ◽  
Mean Time

INTRODUCTION:Payment by result agreements have been quite widely used in Italy to provide access for high costs oncologic drugs and minimize uncertainties of real life benefits (1). The aim of this analysis was to overview the Roche experience in terms of Payment by Result (Pbr) in oncology and investigate the relation between timing for the evaluation of treatment failures and observed Time to Off Treatment (TTOT) from Phase III clinical trials (2).METHODS:A retrospective analysis of the Roche payment by results schemes in place in Italy was conducted. For each drug included in the analysis it was collected: (i) the negotiated timing to assess the treatment failure for payment by result, (ii) the median time to off treatment curve observed in clinical trials for the experimental drug, (iii) the median time to off treatment observed in clinical trials for the control arm. The mean ratios between timing to assess the treatment failure for payment by result and the time to off treatment observed for the experimental drug or the median time to off treatment observed in the control arm were calculated to identify potential correlations. High level of correlation was expected if ratio was close to 1 (±.2).RESULTS:Roche products or different indications of the same product were identified as candidates for the analysis from 2008 to 2016. The timing for the evaluation of treatment failures for Pbr varies between 2 and 9 months, depending on the type of tumor and line of therapy. The mean Time to Payment By Result (TTPbr) / Control arm Time To Off Treatment (cTTOT) ratio was 1.16 (±.37) while the mean Time to Payment By Result (TTPbr) / Experimental arm Time To Off Treatment (eTTOT) ratio was .71 (±.13). Data analysis according to different time periods shows that the mean TTPbr/cTTOT and TTPbr/eTTOT for drugs negotiated from 2008 to 2015 were respectively 1.07 and 1.39 whereas for drugs negotiated in 2016 were respectively and .63 and 1.CONCLUSIONS:Good level of correlation between TTPbr and cTTOT was found. This finding is in line with the methodology used by Italian Medicines Agency so far, leveraging the cTTOT as the most appropriate proxy to assess any incremental effect of a new drug compared to the previous Standard of Care. The analysis over time of TTPbr shows that in the first years of payment by result negotiation TTPbr is more correlated to the cTTOT whereas in the last years is moving closer to the experimental one.

PWE-065 Antibodies-to-infliximab post induction can help identify inflammatory bowel disease patients at risk of treatment failure

2018 ◽  
Author(s):  
Gloria Shwe Zin Tun ◽  
Sister Laura Marshall ◽  
Sister Kerry Robinson ◽  
Sister Alison Wright ◽  
Dr Alenka Brookes ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
At Risk ◽  
Treatment Failure ◽  
Bowel Disease ◽  
Post Induction ◽  
Patients At Risk ◽  
Inflammatory Bowel ◽  
Risk Of Treatment

24 HIGHER BODY MASS INDEX IS ASSOCIATED WITH INCREASED RISK OF TREATMENT FAILURE AND SURGERY IN BIOLOGIC-TREATED PATIENTS WITH ULCERATIVE COLITIS

2018 ◽  
Vol 154 (1) ◽  
pp. S102
Author(s):  
Soumya Kurnool ◽  
Nghia H. Nguyen ◽  
James Proudfoot ◽  
Parambir S. Dulai ◽  
Brigid S. Boland ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Body Mass Index ◽  
Treatment Failure ◽  
Body Mass ◽  
Increased Risk ◽  
Risk Of Treatment

scholarly journals Malaria Transmission Pattern in an Area Selected for Clinical Trials in the Sudanian Area of Senegal (West Africa)

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
El Hadji Amadou Niang ◽  
Aissatou Touré ◽  
El Hadji Malick Ngom ◽  
Lassana Konaté ◽  
Ousmane Faye ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Malaria Transmission ◽  
Rainy Season ◽  
Entomological Inoculation Rate ◽  
Field Trials ◽  
Transmission Intensity ◽  
Heterogeneous Distribution ◽  
Transmission Pattern ◽  
Peak Intensity ◽  
Human Landing

Malaria transmission pattern was studied in 3 villages (Toubanding, Daga Ndoup, and Keur Samba Guèye) situated within an area selected for clinical trials. The study was conducted in the rainy season from July to December 2011. The main objective of this work was to gather baseline data on malaria transmission intensity and other entomological parameters before the advent of clinical trials. Mosquitoes were collected by Human-Landing Collections (HLCs) and by pyrethrum spray catches (PSCs). Five anopheline species were collected, namely,An. arabiensis,An. gambiae,An. funestus,An. pharoensis, andAn. rufipes, giving a heterogeneous distribution within the study area. The populations dynamics of the vectors varied temporarily in each village depending on the pattern of the rainy season. Transmission intensity estimated by the entomological inoculation rate (EIR) was measured in each of the three villages with the variations linked to the microecological differences between the villages. Measurements were calculated for August, September, and October and were found to vary between 4 and 30 infected bites per person over the study period with a peak intensity observed in September. These results indicate that epidemiological field trials on malaria could be conducted in this area on the basis of the differences observed with transmission intensity, micro-ecological variations, and the objectives of the trials.

Does less frequent routine monitoring of patients on a stable, fully suppressed cART regimen lead to an increased risk of treatment failure?

AIDS ◽  
2008 ◽  
Vol 22 (17) ◽  
pp. 2381-2390 ◽  
Author(s):  
Joanne Reekie ◽  
Amanda Mocroft ◽  
Helen Sambatakou ◽  
Ladislav Machala ◽  
Antonio Chiesi ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Cart Regimen ◽  
Routine Monitoring ◽  
Increased Risk ◽  
Risk Of Treatment
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