18 results on '"Velásquez, Gustavo E."'
Search Results
2. Low detection rate of RT-PCR-confirmed COVID-19 using IgM/IgG rapid antibody tests in a large community sample in Lima, Peru
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Law, Stephanie, Tovar, Marco A., Franke, Molly F., Calderon, Roger, Palomino, Santiago, Valderrama, Gissella, Llanos, Fernando, Velásquez, Gustavo E., Mitnick, Carole D., and Lecca, Leonid
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- 2023
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3. Scientific advances and the end of tuberculosis: a report from the Lancet Commission on Tuberculosis
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Reid, Michael, Agbassi, Yvan Jean Patrick, Arinaminpathy, Nimalan, Bercasio, Alyssa, Bhargava, Anurag, Bhargava, Madhavi, Bloom, Amy, Cattamanchi, Adithya, Chaisson, Richard, Chin, Daniel, Churchyard, Gavin, Cox, Helen, Denkinger, Claudia M, Ditiu, Lucica, Dowdy, David, Dybul, Mark, Fauci, Anthony, Fedaku, Endalkachew, Gidado, Mustapha, Harrington, Mark, Hauser, Janika, Heitkamp, Petra, Herbert, Nick, Herna Sari, Ani, Hopewell, Philip, Kendall, Emily, Khan, Aamir, Kim, Andrew, Koek, Irene, Kondratyuk, Sergiy, Krishnan, Nalini, Ku, Chu-Chang, Lessem, Erica, McConnell, Erin V, Nahid, Payam, Oliver, Matt, Pai, Madhukar, Raviglione, Mario, Ryckman, Theresa, Schäferhoff, Marco, Silva, Sachin, Small, Peter, Stallworthy, Guy, Temesgen, Zelalem, van Weezenbeek, Kitty, Vassall, Anna, Velásquez, Gustavo E, Venkatesan, Nandita, Yamey, Gavin, Zimmerman, Armand, Jamison, Dean, Swaminathan, Soumya, and Goosby, Eric
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- 2023
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4. Experience with 4-month rifapentine and moxifloxacin-based tuberculosis treatment in San Francisco
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Louie, Janice K, primary, Agraz-Lara, Rocio, additional, Velásquez, Gustavo E, additional, Phillips, Allison, additional, and Szumowski, John D, additional
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- 2024
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5. Pharmacokinetic-Pharmacodynamic Evidence From a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis.
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Ngo, Huy X, Xu, Ava Y, Velásquez, Gustavo E, Zhang, Nan, Chang, Vincent K, Kurbatova, Ekaterina V, Whitworth, William C, Sizemore, Erin, Bryant, Kia, Carr, Wendy, Weiner, Marc, Dooley, Kelly E, Engle, Melissa, Dorman, Susan E, Nahid, Payam, Swindells, Susan, Chaisson, Richard E, Nsubuga, Pheona, Lourens, Madeleine, and Dawson, Rodney
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DRUG therapy for tuberculosis ,CHAOS theory ,PATIENT safety ,DRUG side effects ,RESEARCH funding ,BODY weight ,LOGISTIC regression analysis ,DOSE-effect relationship in pharmacology ,DRUG efficacy ,SIMULATED patients ,RIFAMPIN ,PROPORTIONAL hazards models ,PHARMACODYNAMICS - Abstract
Background The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes. Methods We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months; TB-related unfavorable outcomes at 9, 12, and 18 months using Cox proportional hazard models; and all trial-defined safety outcomes using logistic regression. Results Our model-derived rifampicin exposure ranged from 4.57 mg · h/L to 140.0 mg · h/L with a median of 41.8 mg · h/L. Pharmacokinetic simulations demonstrated that flat-dosed rifampicin provided exposure coverage similar to the weight-banded dose. Exposure-efficacy analysis (n = 680) showed that participants with rifampicin exposure below the median experienced similar hazards of stable culture conversion and TB-related unfavorable outcomes compared with those with exposure above the median. Exposure-safety analysis (n = 722) showed that increased rifampicin exposure was not associated with increased grade 3 or higher adverse events or serious adverse events. Conclusions Flat-dosing of rifampicin at 600 mg daily may be a reasonable alternative to the incumbent weight-banded dosing strategy for the standard-of-care 6-month regimen. Future research should assess the optimal dosing strategy for rifampicin, at doses higher than the current recommendation. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Experience With Four-Month Rifapentine and Moxifloxacin–Based Tuberculosis Treatment in San Francisco.
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Louie, Janice K, Agraz-Lara, Rocio, Velásquez, Gustavo E, Phillips, Allison, and Szumowski, John D
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TUBERCULOSIS ,RANDOMIZED controlled trials ,TREATMENT effectiveness - Abstract
Background A multicountry randomized controlled trial has demonstrated that pan-susceptible pulmonary tuberculosis (TB) can be successfully treated with a 4-month regimen of daily isoniazid, rifapentine, moxifloxacin, and pyrazinamide (HPMZ). We piloted HPMZ in San Francisco (SF) using a modified version of the US Centers for Disease Control and Prevention HPMZ treatment guidelines. Methods In this retrospective cohort, patients consecutively referred to SF TB clinic were evaluated for HPMZ eligibility based on preestablished inclusion/exclusion criteria. All underwent evaluation and management according to national recommendations. We reviewed the medical records of those initiated on HPMZ. Results From August 2021 to December 2023, 30 (18.8%) of 160 patients diagnosed with active TB met HPMZ inclusion criteria; of these, 22 (13.8%) started HPMZ. The median age (range) was 32.5 (14–86) years, 17 (77.3%) were otherwise healthy, and 19 (86.4%) had pulmonary TB, including 7 (36.8%) with cavitary disease. Eighteen (81.8%) patients had an adverse event, with 11 (50%) prematurely discontinuing HPMZ; the most common adverse events were vomiting, elevated transaminases, and rash. To date, 9 (40.9%) have completed treatment, with most achieving criteria for cure. One patient was diagnosed with possible TB recurrence and restarted standard TB treatment. Conclusions Our experience, with half of patients to date prematurely discontinuing HPMZ, illustrates the challenge of extrapolating findings from TB clinical trials commonly conducted in high-incidence, non-US settings to US clinical practice. Further experience may help identify best practices for implementing HPMZ, including identifying predictors of which patients may be most likely to benefit from and tolerate this regimen. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Recent advances in the treatment of tuberculosis
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Motta, Ilaria, primary, Boeree, Martin, additional, Chesov, Dumitru, additional, Dheda, Keertan, additional, Günther, Gunar, additional, Horsburgh JR, C. Robert, additional, Kherabi, Yousra, additional, Lange, Christoph, additional, Lienhardt, Christian, additional, McIlleron, Helen M., additional, Paton, Nicholas I., additional, Stagg, Helen R., additional, Thwaites, Guy, additional, Udwadia, Zarir, additional, Van Crevel, Reinout, additional, Velásquez, Gustavo E., additional, Wilkinson, Robert J., additional, and Guglielmetti, Lorenzo, additional
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- 2023
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8. Respiratory, Cardiac, and Neuropsychiatric Manifestations of Postacute Sequelae of Coronavirus Disease 2019 in Lima, Peru
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Rahman, Rifat S, primary, Tovar, Marco A, additional, Peinado, Jesús, additional, Palomino, J Santiago, additional, Ramirez, Claudio, additional, Llanos-Zavalaga, Fernando, additional, Peralta, Ernesto, additional, Valderrama, Gissela, additional, Ramos Cordova, Lourdes B, additional, Sanchez Cortez, Lucero I, additional, Rodriguez, German, additional, LaHood, Allison N, additional, Franke, Molly F, additional, Mitnick, Carole D, additional, Lecca, Leonid, additional, and Velásquez, Gustavo E, additional
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- 2023
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9. Promise and Peril of Pretomanid–Rifamycin Regimens for Drug-susceptible Tuberculosis
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Velásquez, Gustavo E., primary and Nahid, Payam, additional
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- 2023
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10. Additional file 1 of Low detection rate of RT-PCR-confirmed COVID-19 using IgM/IgG rapid antibody tests in a large community sample in Lima, Peru
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Law, Stephanie, Tovar, Marco A., Franke, Molly F., Calderon, Roger, Palomino, Santiago, Valderrama, Gissella, Llanos, Fernando, Velásquez, Gustavo E., Mitnick, Carole D., and Lecca, Leonid
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Additional file 1. Table S1. Reported symptoms of all participants with sample collected (and tested) for serologic antibody test on same day as sample that resulted in RT-PCR positive for SARS-CoV-2 (n=492); no symptom duration outliers excluded. Table S2. Reported symptoms of all participants with sample collected (and tested) for serologic antibody test on same day as sample that resulted in RT-PCR positive for SARS-CoV-2 (n=492); mild and extreme symptom duration outliers excluded. Table S3. Sensitivity of the rapid antibody test# by symptom duration and outlier exclusion criteria. Fig. S1. Plots of antibody test sensitivity against the number of weeks since onset of symptoms among those who reported at least one symptom before testing, using the RT-PCR test as the reference, stratified by the types of outliers excluded in the analysis: extreme outliers, which were defined as persons whose time since symptom onset was longer than the third quartile plus 3 times the interquartile range (IQR, defined as the difference between the first and third quartile of the reported times since onset for a given symptom); mild outliers were those beyond the third quartile plus 1.5 times the IQR); or no outliers excluded. The circles show the crude estimated sensitivity and the error bars show the Wilson’s score 95% confidence intervals. The plotted lines are the fitted segmented linear regressions for the rapid antibody tests. Table S4. Segmented regression analyses of antibody test sensitivity by weeks since symptom onset, by symptom duration outlier exclusion criteria. Table S5. Overall antibody test sensitivity* per week since symptom onset for common symptoms. Table S6.Segmented regression analyses of antibody test sensitivity versus weeks since symptom onset, by symptom.
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- 2023
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11. Recent advances in the treatment of tuberculosis
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Motta, Ilaria, Boeree, Martin, Chesov, Dumitru, Dheda, Keertan, Günther, Gunar, Horsburgh, C Robert, Kherabi, Yousra, Lange, Christoph, Lienhardt, Christian, McIlleron, Helen M, Paton, Nicholas I, Stagg, Helen R, Thwaites, Guy, Udwadia, Zarir, Van Crevel, Reinout, Velásquez, Gustavo E, Wilkinson, Robert J, and Guglielmetti, Lorenzo
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610 Medicine & health - Abstract
BACKGROUND Tuberculosis is a global health challenge and one of the leading causes of death worldwide. In the last decade, the tuberculosis treatment landscape has dramatically changed. After long years of stagnation, new compounds entered the market (bedaquiline, delamanid and pretomanid) and phase III clinical trials have shown promising results towards shortening duration of treatment for both drug-susceptible (Study 31/A5349, TRUNCATE-TB, SHINE) and drug-resistant tuberculosis (STREAM, NiX-TB, ZeNix, TB-PRACTECAL). Dose optimization of rifamycins and repurposed drugs have also brought hopes of further development of safe and effective regimens. Consequently, international and World Health Organization clinical guidelines have been updated multiple times in the last years to keep pace with these advances. OBJECTIVES This narrative review aims to summarize the state-of-the-art on treatment of drug-susceptible and drug-resistant tuberculosis, as well as recent trials results and an overview of ongoing clinical trials. SOURCES A non-systematic literature review was conducted in PubMed and MEDLINE, focusing on the treatment of tuberculosis. Ongoing clinical trials were listed according to the authors' knowledge, and completed consulting clinicaltrials.gov and other publicly available websites (www.resisttb.org/clinical-trials-progress-report, www.newtbdrugs.org/pipeline/trials). CONTENT This review summarizes the recent, major changes in the landscape for drug-susceptible and drug-resistant treatment, with a specific focus on their potential impact on patient outcomes and programmatic TB management. Moreover, insights in host-directed therapies, and advances in pharmacokinetic and pharmacogenomics are discussed. A thorough outline of ongoing therapeutic clinical trials is presented, highlighting different approaches and goals in current TB clinical research. IMPLICATIONS Future research should be directed to individualize regimens and protect these recent breakthroughs by preventing and identifying the selection of drug resistance and providing widespread, affordable, patient-centered access to new treatment options for all people affected by tuberculosis.
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- 2023
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12. Clinical Outcomes of Individuals with COVID-19 and Tuberculosis during the Pre-Vaccination Period of the Pandemic: A Systematic Review
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Jhaveri, Tulip A., primary, Fung, Celia, additional, LaHood, Allison N., additional, Lindeborg, Andrew, additional, Zeng, Chengbo, additional, Rahman, Rifat, additional, Bain, Paul A., additional, Velásquez, Gustavo E., additional, and Mitnick, Carole D., additional
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- 2022
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13. Diagnostic Performance Assessment of Saliva RT-PCR and Nasopharyngeal Antigen for the Detection of SARS-CoV-2 in Peru
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Calderón, Roger I., primary, Jhaveri, Tulip A., additional, Tovar, Marco A., additional, Palomino, J. Santiago, additional, Barreda, Nadia N., additional, Sanabria, Oswaldo M., additional, Peinado, Jesús, additional, Ramirez, Claudio, additional, Llanos Zavalaga, L. Fernando, additional, Valderrama, Gissela, additional, Franke, Molly F., additional, Mitnick, Carole D., additional, Lecca, Leonid, additional, and Velásquez, Gustavo E., additional
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- 2022
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14. Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies Among Market and City Bus Depot Workers in Lima, Peru.
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Tovar, Marco, Peinado, Jesús, Palomino, Santiago, Llanos, Fernando, Ramírez, Claudio, Valderrama, Gisella, Calderón, Roger I, Williams, Roger B, Velásquez, Gustavo E, Mitnick, Carole D, Franke, Molly F, and Lecca, Leonid
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COVID-19 ,EMPLOYEES ,DISEASE prevalence ,PUBLIC sector ,VIRAL antibodies ,GROCERY industry ,TRANSPORTATION - Abstract
We report severe acute respiratory syndrome coronavirus 2 antibody positivity among market and city bus depot workers in Lima, Peru. Among 1285 vendors from 8 markets, prevalence ranged from 27% to 73%. Among 488 workers from 3 city bus depots, prevalence ranged from 11% to 47%. Self-reported symptoms were infrequent. [ABSTRACT FROM AUTHOR]
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- 2022
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15. Scientific advances and the end of tuberculosis: a report from the LancetCommission on Tuberculosis
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Reid, Michael, Agbassi, Yvan Jean Patrick, Arinaminpathy, Nimalan, Bercasio, Alyssa, Bhargava, Anurag, Bhargava, Madhavi, Bloom, Amy, Cattamanchi, Adithya, Chaisson, Richard, Chin, Daniel, Churchyard, Gavin, Cox, Helen, Denkinger, Claudia M, Ditiu, Lucica, Dowdy, David, Dybul, Mark, Fauci, Anthony, Fedaku, Endalkachew, Gidado, Mustapha, Harrington, Mark, Hauser, Janika, Heitkamp, Petra, Herbert, Nick, Herna Sari, Ani, Hopewell, Philip, Kendall, Emily, Khan, Aamir, Kim, Andrew, Koek, Irene, Kondratyuk, Sergiy, Krishnan, Nalini, Ku, Chu-Chang, Lessem, Erica, McConnell, Erin V, Nahid, Payam, Oliver, Matt, Pai, Madhukar, Raviglione, Mario, Ryckman, Theresa, Schäferhoff, Marco, Silva, Sachin, Small, Peter, Stallworthy, Guy, Temesgen, Zelalem, van Weezenbeek, Kitty, Vassall, Anna, Velásquez, Gustavo E, Venkatesan, Nandita, Yamey, Gavin, Zimmerman, Armand, Jamison, Dean, Swaminathan, Soumya, and Goosby, Eric
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- 2023
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16. Risk-stratified treatment for drug-susceptible pulmonary tuberculosis.
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Chang VK, Imperial MZ, Phillips PPJ, Velásquez GE, Nahid P, Vernon A, Kurbatova EV, Swindells S, Chaisson RE, Dorman SE, Johnson JL, Weiner M, Sizemore EE, Whitworth W, Carr W, Bryant KE, Burton D, Dooley KE, Engle M, Nsubuga P, Diacon AH, Nhung NV, Dawson R, and Savic RM
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- Humans, Male, Female, Adult, Middle Aged, Moxifloxacin therapeutic use, Risk Factors, Treatment Outcome, Mycobacterium tuberculosis drug effects, Drug Therapy, Combination, Young Adult, Rifampin analogs & derivatives, Rifampin therapeutic use, Rifampin adverse effects, Tuberculosis, Pulmonary drug therapy, Tuberculosis, Pulmonary microbiology, Antitubercular Agents therapeutic use, Antitubercular Agents adverse effects
- Abstract
The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment., (© 2024. The Author(s).)
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- 2024
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17. Percent of lung involved in disease on chest X-ray predicts unfavorable treatment outcome in pulmonary tuberculosis.
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Ghanem M, Srivastava R, Ektefaie Y, Hoppes D, Rosenfeld G, Yaniv Z, Grinev A, Xu AY, Yang E, Velásquez GE, Harrison L, Rosenthal A, Savic RM, Jacobson KR, and Farhat MR
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Radiology may better define tuberculosis (TB) severity and guide duration of treatment. We aimed to systematically study baseline chest X-rays (CXR) and their association with TB treatment outcome using real-world data. We used logistic regression to associate TB treatment outcomes with CXR findings, including percent of lung involved in disease (PLI), cavitation, and Timika score, alone or in combination with other clinical characteristics, stratifying by drug resistance status and HIV (n = 2,809). We fine-tuned convolutional neural nets (CNN) to automate PLI measurement from the CXR DICOM images (n = 5,261). PLI is the only CXR finding associated with unfavorable outcome across drug resistance and HIV subgroups [Rifampicin-susceptible disease without HIV, adjusted odds ratio (aOR) 1·11 (1·01, 1·22), P-value 0·025]. The most informed model of baseline characteristics tested predicts outcome with a validation mean area under the curve (AUC) of 0·769. PLI and Timika (AUC 0·656 and 0·655 respectively) predict unfavorable outcomes better than cavitary information (best AUC 0·591). The addition of PLI improves prediction compared to sex and age alone (AUC 0·680 and 0·627, respectively).PLI>25% provides a better separation of favorable and unfavorable outcomes compared to PLI>50%. The best performing ensemble of CNNs has an AUC 0·850 for PLI>25% and mean absolute error of 11·7% for the PLI value. PLI is better than cavitation for predicting unfavorable treatment outcome in pulmonary TB in non-clinical trial settings and it can be accurately and automatically predicted with CNNs., One Sentence Summary: The percent of lung involved in disease improves prediction of unfavorable outcomes in pulmonary tuberculosis when added to clinical characteristics.
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- 2024
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18. Pyrazinamide Safety, Efficacy, and Dosing for Treating Drug-Susceptible Pulmonary Tuberculosis: A Phase 3, Randomized, Controlled Clinical Trial.
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Xu AY, Velásquez GE, Zhang N, Chang VK, Phillips PP, Nahid P, Dorman SE, Kurbatova EV, Whitworth WC, Sizemore E, Bryant K, Carr W, Brown NE, Engle ML, Nhung NV, Nsubuga P, Diacon A, Dooley KE, Chaisson RE, Swindells S, and Savic RM
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Rationale: Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/ACTG A5349 represents the largest Phase 3 randomized controlled therapeutic trial to date for such investigation., Objectives: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure with efficacy and safety outcomes. We aimed to determine pyrazinamide dosing strategies that optimize risks and benefits., Methods: We analyzed pyrazinamide steady-state pharmacokinetic data using population nonlinear mixed-effects models. We evaluated the contribution of pyrazinamide exposure to long-term efficacy using parametric time-to-event models and safety outcomes using logistic regression. We evaluated optimal dosing with therapeutic windows targeting ≥95% durable cure and safety within the observed proportion of the primary safety outcome., Measurements and Main Results: Among 2255 participants with 6978 plasma samples, pyrazinamide displayed 7-fold exposure variability (151-1053 mg·h/L). Body weight was not a clinically relevant predictor of drug clearance and thus did not justify the need for weight-banded dosing. Both clinical and safety outcomes were associated with pyrazinamide exposure, resulting in a therapeutic window of 231-355 mg·h/L for the control and 226-349 mg·h/L for the rifapentine-moxifloxacin regimen. Flat dosing of pyrazinamide at 1000 mg would have permitted an additional 13.1% (n=96) participants allocated to the control and 9.2% (n=70) to the rifapentine-moxifloxacin regimen dosed within the therapeutic window, compared to the current weight-banded dosing., Conclusions: Flat dosing of pyrazinamide at 1000 mg daily would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis. Clinical trial registration available at www., Clinicaltrials: gov, ID: NCT02410772. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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- 2024
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