41 results on '"Bangdiwala, Ananta"'
Search Results
2. Estimating Survival in Melanoma Patients With Brain Metastases: An Update of the Graded Prognostic Assessment for Melanoma Using Molecular Markers (Melanoma-molGPA).
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Sperduto, Paul W, Jiang, Wen, Brown, Paul D, Braunstein, Steve, Sneed, Penny, Wattson, Daniel A, Shih, Helen A, Bangdiwala, Ananta, Shanley, Ryan, Lockney, Natalie A, Beal, Kathryn, Lou, Emil, Amatruda, Thomas, Sperduto, William A, Kirkpatrick, John P, Yeh, Norman, Gaspar, Laurie E, Molitoris, Jason K, Masucci, Laura, Roberge, David, Yu, James, Chiang, Veronica, and Mehta, Minesh
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Humans ,Melanoma ,Brain Neoplasms ,Proto-Oncogene Proteins B-raf ,Genetic Markers ,Prognosis ,Karnofsky Performance Status ,Regression Analysis ,Age Factors ,Aged ,Aged ,80 and over ,Middle Aged ,Clinical Decision-Making ,Brain Cancer ,Neurosciences ,Clinical Research ,Rare Diseases ,Patient Safety ,Cancer ,Brain Disorders ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Other Physical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeTo update the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for a markedly heterogeneous patient population, patients with melanoma and brain metastases, using a larger, more current cohort, including molecular markers.MethodsThe original Melanoma-GPA is based on data from 483 patients whose conditions were diagnosed between 1985 and 2005. This is a multi-institutional retrospective database analysis of 823 melanoma patients with newly diagnosed brain metastases from January 1, 2006, to December 31, 2015. Multivariable analyses identified significant prognostic factors, which were weighted and included in the updated index (Melanoma-molGPA). Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios to design the updated Melanoma-molGPA in which scores of 4.0 and 0.0 are associated with the best and worst prognoses, as with all of the diagnosis-specific GPA indices. Log-rank tests were used to compare adjacent classes.ResultsThere were 5 significant prognostic factors for survival (age, Karnofsky performance status [KPS], extracranial metastases [ECM], number of brain metastases, and BRAF status), whereas only KPS and the number of brain metastases were significant in the original Melanoma-GPA. Median survival improved from 6.7 to 9.8 months between the 2 treatment eras, and the median survival times for patients with Melanoma-molGPA of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 4.9, 8.3, 15.8, and 34.1 months (P
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- 2017
3. The Prognostic Value of BRAF, C-KIT, and NRAS Mutations in Melanoma Patients With Brain Metastases.
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Sperduto, Paul W, Jiang, Wen, Brown, Paul D, Braunstein, Steve, Sneed, Penny, Wattson, Daniel A, Shih, Helen A, Bangdiwala, Ananta, Shanley, Ryan, Lockney, Natalie A, Beal, Kathryn, Lou, Emil, Amatruda, Thomas, Sperduto, William A, Kirkpatrick, John P, Yeh, Norman, Gaspar, Laurie E, Molitoris, Jason K, Masucci, Laura, Roberge, David, Yu, James, Chiang, Veronica, and Mehta, Minesh
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Humans ,Melanoma ,Brain Neoplasms ,Proto-Oncogene Proteins B-raf ,Antineoplastic Agents ,Prognosis ,Immunotherapy ,Linear Models ,Proportional Hazards Models ,Statistics ,Nonparametric ,Retrospective Studies ,Mutation ,Genes ,ras ,Time Factors ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Proto-Oncogene Proteins c-kit ,Molecular Targeted Therapy ,Brain Cancer ,Cancer ,Brain Disorders ,Clinical Research ,Neurosciences ,Rare Diseases ,Other Physical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeBrain metastases are a common problem in patients with melanoma, but little is known about the effect of gene mutations on survival in these patients.Methods and materialsWe created a retrospective multi-institutional database of 823 patients with melanoma and brain metastases diagnosed between 2006 and 2015. Clinical parameters, gene mutation status (BRAF, C-KIT, NRAS), and treatment were correlated with survival. Treatment patterns and outcomes were compared with a prior era (1985-2005).ResultsBRAF status was known in 584 of 823 patients (71%). BRAF, NRAS, and C-KIT mutations were present in 51%, 22%, and 11% of tested patients, respectively. The median time from primary diagnosis to brain metastasis was 32 months, and overall median survival (MS) from the time of initial treatment of brain metastases was 10 months. MS for BRAF-positive and BRAF-negative patients was 13 months and 9 months, respectively (P=.02). There was no significant difference in MS in patients with or without NRAS or C-KIT mutations. The time from primary diagnosis to brain metastasis did not vary by mutation and was not associated with survival after the diagnosis of brain metastases. MS for the 1985 to 2005 and 2006 to 2015 cohorts was 6.7 months and 10.0 months, respectively (P
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- 2017
4. The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases
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Sperduto, Paul W, Yang, T Jonathan, Beal, Kathryn, Pan, Hubert, Brown, Paul D, Bangdiwala, Ananta, Shanley, Ryan, Yeh, Norman, Gaspar, Laurie E, Braunstein, Steve, Sneed, Penny, Boyle, John, Kirkpatrick, John P, Mak, Kimberley S, Shih, Helen A, Engelman, Alex, Roberge, David, Arvold, Nils D, Alexander, Brian, Awad, Mark M, Contessa, Joseph, Chiang, Veronica, Hardie, John, Ma, Daniel, Lou, Emil, Sperduto, William, and Mehta, Minesh P
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Lung Cancer ,Rare Diseases ,Lung ,Clinical Research ,Adenocarcinoma ,Aged ,Aged ,80 and over ,Anaplastic Lymphoma Kinase ,Antineoplastic Agents ,Brain Neoplasms ,ErbB Receptors ,Female ,Genetic Markers ,Genetic Predisposition to Disease ,Humans ,Incidence ,Lung Neoplasms ,Male ,Middle Aged ,Mutation ,Polymorphism ,Single Nucleotide ,Prevalence ,Protein-Tyrosine Kinases ,Receptor Protein-Tyrosine Kinases ,Retrospective Studies ,Risk Factors ,Survival Rate ,United States ,Other Physical Sciences ,Oncology & Carcinogenesis ,Oncology and carcinogenesis ,Theoretical and computational chemistry ,Medical and biological physics - Abstract
PurposeLung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno).MethodsA multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials.ResultsOf 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR-/+ was 10/15 months (P=.02) and for ALK-/+ was 10/20 months (P
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- 2016
5. 1490. Predictors of Early Mortality in HIV-associated Tuberculous Meningitis
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Kagimu, Enock, primary, Bangdiwala, Ananta, additional, Kasibante, John, additional, Kabahubya, Mable, additional, Gakuru, Jane, additional, Timothy, Mugabi, additional, Namombwe, Suzan, additional, Kimuda, Sarah, additional, Kasozi, Derrick, additional, Rutakingirwa, Morris K, additional, Ssebambulidde, Kenneth, additional, Tugume, Lillian, additional, Nuwagira, Edwin, additional, Okurut, Samuel, additional, Nsangi, Laura, additional, Atukunda, Mucunguzi, additional, Ellis, Jayne P, additional, Williams, Darlisha A, additional, Musubire, Abdu Kisekka, additional, Boulware, David R, additional, Meya, David, additional, Bahr, Nathan C, additional, and Cresswell, Fiona V, additional
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- 2023
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6. Baseline Cytomegalovirus Viremia at Cryptococcal Meningitis Diagnosis Is Associated With Long-term Increased Incident TB Disease and Mortality in a Prospective Cohort of Ugandan Adults With HIV
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Ellis, Jayne, primary, Bangdiwala, Ananta S, additional, Skipper, Caleb P, additional, Tugume, Lillian, additional, Nsangi, Laura, additional, Matovu, John, additional, Pastick, Katelyn A, additional, Ssebambulidde, Kenneth, additional, Morawski, Bozena M, additional, Musubire, Abdu K, additional, Schleiss, Mark R, additional, Moore, David A J, additional, Jarvis, Joseph N, additional, Boulware, David R, additional, Meya, David B, additional, and Castelnuovo, Barbara, additional
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- 2023
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7. LEVEL (Logical Explanations & Visualizations of Estimates in Linear mixed models): recommendations for reporting multilevel data and analyses
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Monsalves, Maria Jose, Bangdiwala, Ananta Shrikant, Thabane, Alex, and Bangdiwala, Shrikant Ishver
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- 2020
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8. Diagnostic and Prognostic Value of Cerebrospinal Fluid Lactate and Glucose in HIV-Associated Tuberculosis Meningitis
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Nuwagira, Edwin, primary, Huppler Hullsiek, Kathy, additional, Jjunju, Samuel, additional, Rutakingirwa, Morris, additional, Kasibante, John, additional, Tadeo, Kiiza Kandole, additional, Kagimu, Enock, additional, Tugume, Lillian, additional, Ssebambulidde, Kenneth, additional, Musubire, Abdu K., additional, Bangdiwala, Ananta, additional, Muzoora, Conrad, additional, Meya, David B., additional, Boulware, David R., additional, Bahr, Nathan C., additional, and Creswell, Fiona V., additional
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- 2022
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9. Evaluation of the effectiveness of a South African laboratory cryptococcal antigen screening programme using a retrospective cohort and a cluster-randomised trial design
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DeSanto, Daniel J, primary, Bangdiwala, Ananta S, additional, Van Schalkwyk, Erika, additional, Skipper, Caleb P, additional, Greene, Greg, additional, Paxton, Juliet, additional, Huppler Hullsiek, Kathy, additional, Mashau, Rudzani, additional, Rajasingham, Radha, additional, Boulware, David R, additional, and Govender, Nelesh P, additional
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- 2022
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10. Neurocognitive outcomes of tuberculous meningitis in a primarily HIV-positive Ugandan cohort
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Quinn, Carson M, primary, Kasibante, John, additional, Namudde, Alice, additional, Bangdiwala, Ananta S, additional, Kabahubya, Mable, additional, Nakasujja, Noeline, additional, Lofgren, Sarah, additional, Elliott, Alison, additional, Boulware, David R, additional, Meya, David B, additional, and Cresswell, Fiona V, additional
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- 2022
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11. Feasibility of SARS-CoV-2 Antibody Testing in Remote Outpatient Trials
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Lofgren, Sarah M, primary, Okafor, Elizabeth C, additional, Colette, Alanna A, additional, Pastick, Katelyn A, additional, Skipper, Caleb P, additional, Pullen, Matthew F, additional, Nicol, Melanie R, additional, Bold, Tyler D, additional, Bangdiwala, Ananta S, additional, Engen, Nicole W, additional, Collins, Lindsey, additional, Williams, Darlisha A, additional, Axelrod, Margaret L, additional, Thielen, Beth K, additional, Hullsiek, Kathy H, additional, Boulware, David R, additional, and Rajasingham, Radha, additional
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- 2021
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12. Neurocognitive outcomes of HIV-associated tuberculous meningitis
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Quinn, Carson M, primary, Kasibante, John, additional, Namudde, Alice, additional, Bangdiwala, Ananta S, additional, Kabahubya, Mable, additional, Nakasujja, Noeline, additional, Lofgren, Sarah, additional, Elliott, Alison, additional, Boulware, David R, additional, Meya, David B, additional, and Cresswell, Fiona V, additional
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- 2021
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13. The effect of sertraline on depression and associations with persistent depression in survivors of HIV-related cryptococcal meningitis
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Lofgren, Sarah M, Velamakanni, Sruti S, Huppler Hullsiek, Katherine, Bangdiwala, Ananta S, Namudde, Alice, Musubire, Abdu K, Mpoza, Edward, Abassi, Mahsa, Pastick, Katelyn A, Nuwagira, Edwin, Evans, Emily E, Rajsasingham, Radha, Williams, Darlisha A, Muzoora, Conrad, Creswell, Fiona V, Rhein, Joshua, Bond, David J, Nakasujja, Noeline, Meya, David B, and Boulware, David R
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Background: Depression is a risk factor for worse outcomes in persons living with HIV/AIDS and has a prevalence more than three times as high as in the general population. Despite this, there are few randomized studies of antidepressants in HIV-infected Africans. Methods: We enrolled 460 HIV-infected Africans with cryptococcal meningitis into a randomized clinical trial of adjunctive sertraline vs placebo (2015-2017). We defined depression using depression using a Center for Epidemiologic Studies Depression Scale (CES-D) score of >15, and severe depression as >26 at one and three months after meningitis diagnosis and initiation of treatment.We evaluated the relationship between sertraline and depression, as well as associations with persistent depression, at three months. Results: At one- and three-months post meningitis diagnosis, 62% (108/174) and 44% (74/169) of all subjects had depression (CES>15), respectively. At three months, sertraline-treated subjects had consistent risk for depression as placebo-treated subjects but were significantly less likely to have severe depression (CES>26) (OR 0.335; 95%CI, 0.130-0.865). Of those with depression at one month, sertraline-treated subjects were less likely than placebo-treated subjects to be depressed at three months (p=0.05). Sertraline was the only factor we found significant in predicting persistent depression at three months among those who had depression at one month. Conclusions: Depression is highly prevalent in HIV-infected persons who have survived cryptococcal meningitis. We found that sertraline is associated with a modest reduction in depression in those with depression at baseline and a significant decrease in severe depression.
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- 2021
14. Fujifilm SILVAMP TB LAM Assay on Cerebrospinal Fluid for the Detection of Tuberculous Meningitis in Adults With Human Immunodeficiency Virus
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Quinn, Carson M, Kagimu, Enock, Okirworth, Michael, Bangdiwala, Ananta S, Mugumya, Gerald, Ramachandran, Prashanth S, Wilson, Michael R, Meya, David B, Cresswell, Fiona V, Bahr, Nathan C, and Boulware, David R
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urologic and male genital diseases - Abstract
BACKGROUND: Tuberculous meningitis (TBM) has a high fatality rate, with inadequate diagnostic tests being a major contributor. The rollout of Xpert MTB/Rif and Xpert MTB/RIF Ultra (Xpert Ultra) have improved time-to-diagnosis with sensitivities similar to culture, yet test availability and sensitivity are inadequate. The TB lipoarabinomannan lateral flow assay (AlereLAM) offers ease of use, but its low sensitivity in cerebrospinal fluid (CSF) limits clinical utility for TBM. The Fujifilm SILVAMP TB LAM (FujiLAM) assay has excellent sensitivity in urine, but performance on cerebrospinal fluid is uncertain. METHODS: We conducted a prospective cohort study at Kiruddu National Referral Hospital in Kampala, Uganda, enrolling patients suspected to have TBM. CSF was tested using AlereLAM, Xpert Ultra, culture, and FujiLAM. Results were compared with 2 reference standards: probable and definite TBM or definite TBM alone by the uniform TBM case definition. RESULTS: Of 101 patients enrolled (95/101 HIV-positive), 34 had definite TBM and 24 had probable TBM. FujiLAM sensitivity on CSF was 52% (30/58) for definite or probable TBM compared with 55% (32/58) for Xpert Ultra. AlereLAM had lower sensitivity than FujiLAM in the subgroup of patients tested with both assays (14% [4/28] vs 50% [14/28]; P < .01). FujiLAM specificity was 98% (42/43) for patients without probable or definite TBM. CONCLUSIONS: FujiLAM showed higher sensitivity than AlereLAM, with sensitivity potentially approaching that of Xpert Ultra. FujiLAM could improve time-to-treatment-initiation, especially in settings where the more technical Xpert Ultra system might not be feasible. Large confirmatory studies are needed.
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- 2021
15. High-Dose Oral and Intravenous Rifampicin for the Treatment of Tuberculous Meningitis in Predominantly Human Immunodeficiency Virus (HIV)-Positive Ugandan Adults : A Phase II Open-Label Randomized Controlled Trial
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Cresswell, Fiona, V, Meya, David B., Kagimu, Enock, Grint, Daniel, Te Brake, Lindsey, Kasibante, John, Martyn, Emily, Rutakingirwa, Morris, Quinn, Carson M., Okirwoth, Micheal, Tugume, Lillian, Ssembambulidde, Kenneth, Musubire, Abdu K., Bangdiwala, Ananta S., Buzibye, Allan, Muzoora, Conrad, Svensson, Elin, Aarnoutse, Rob, Boulware, David R., Elliott, Alison M., Cresswell, Fiona, V, Meya, David B., Kagimu, Enock, Grint, Daniel, Te Brake, Lindsey, Kasibante, John, Martyn, Emily, Rutakingirwa, Morris, Quinn, Carson M., Okirwoth, Micheal, Tugume, Lillian, Ssembambulidde, Kenneth, Musubire, Abdu K., Bangdiwala, Ananta S., Buzibye, Allan, Muzoora, Conrad, Svensson, Elin, Aarnoutse, Rob, Boulware, David R., and Elliott, Alison M.
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Background: High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in human immunodeficiency virus (HIV) coinfection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity. Methods: In this phase II open-label trial, Ugandan adults with suspected TBM were randomized to standard-of-care control (PO-10, rifampicin 10 mg/kg/day), intravenous rifampicin (IV-20, 20 mg/kg/day), or high-dose oral rifampicin (PO-35, 35 mg/kg/day). We performed PK sampling on days 2 and 14. The primary outcomes were total exposure (AUC(0-24)), maximum concentration (C-max), CSF concentration, and grade 3-5 adverse events. Results: We enrolled 61 adults, 92% were living with HIV, median CD4 count was 50 cells/mu L (interquartile range [IQR] 46-56). On day 2, geometric mean plasma AUC(0-24hr) was 42.9.h mg/L with standard-of-care 10 mg/kg dosing, 249.h mg/L for IV-20 and 327.h mg/L for PO-35 (P<.001). In CSF, standard of care achieved undetectable rifampicin concentration in 56% of participants and geometric mean AUC(0-24hr) 0.27 mg/L, compared with 1.74 mg/L (95% confidence interval [CI] 1.2-2.5) for IV-20 and 2.17 mg/L (1.6-2.9) for PO-35 regimens (P<.001). Achieving CSF concentrations above rifampicin minimal inhibitory concentration (MIC) occurred in 11% (2/18) of standard-of-care, 93% (14/15) of IV-20, and 95% (18/19) of PO-35 participants. Higher serum and CSF levels were sustained at day 14. Adverse events did not differ by dose (P=.34). Conclusions: Current international guidelines result in sub-therapeutic CSF rifampicin concentration for 89% of Ugandan TBM patients. High-dose intravenous and oral rifampicin were safe and respectively resulted in exposures similar to 6- and similar to 8-fold higher than standard of care, and CSF levels above the MIC.
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- 2021
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16. Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial
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Rajasingham, Radha, Bangdiwala, Ananta S, Nicol, Melanie R, Skipper, Caleb P, Pastick, Katelyn A, Axelrod, Margaret L, Pullen, Matthew F, Nascene, Alanna A, Williams, Darlisha A, Engen, Nicole W, Okafor, Elizabeth C, Rini, Brian I, Mayer, Ingrid A, McDonald, Emily G, Lee, Todd C, Li, Peter, MacKenzie, Lauren J, Balko, Justin M, Dunlop, Stephen J, Hullsiek, Katherine H, Boulware, David R, Lofgren, Sarah M, Abassi, Mahsa, Balster, Andrew, Collins, Lindsey B, Drobot, Glen, Krakower, Douglas S, Lother, Sylvain A, MacKay, Dylan S, Meyer-Mueller, Cameron, Selinsky, Stephen, Solvason, Dayna, Zarychanski, Ryan, and Zash, Rebecca
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0301 basic medicine ,Microbiology (medical) ,Canada ,medicine.medical_specialty ,Health Personnel ,Placebo ,Loading dose ,law.invention ,03 medical and health sciences ,Pre-exposure prophylaxis ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Intensive care ,medicine ,Clinical endpoint ,Humans ,030212 general & internal medicine ,Online Only Articles ,SARS-CoV-2 ,business.industry ,Hydroxychloroquine ,COVID-19 Drug Treatment ,Clinical trial ,030104 developmental biology ,Infectious Diseases ,Pre-Exposure Prophylaxis ,business ,medicine.drug - Abstract
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing coronavirus disease 2019 (COVID-19) pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure. Methods We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, COVID-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine loading dose then 400 mg once or twice weekly for 12 weeks. The primary endpoint was confirmed or probable COVID-19–compatible illness. We measured hydroxychloroquine whole-blood concentrations. Results We enrolled 1483 healthcare workers, of whom 79% reported performing aerosol-generating procedures. The incidence of COVID-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events/person-year with once-weekly and 0.28 events/person-year with twice-weekly hydroxychloroquine compared with 0.38 events/person-year with placebo. For once-weekly hydroxychloroquine prophylaxis, the hazard ratio was .72 (95% CI, .44–1.16; P = .18) and for twice-weekly was .74 (95% CI, .46–1.19; P = .22) compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82–120) with once-weekly and 200 ng/mL (IQR, 159–258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed COVID-19–compatible illness (154 ng/mL) versus participants without COVID-19 (133 ng/mL; P = .08). Conclusions Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed COVID-19 or COVID-19–compatible illness among healthcare workers. Clinical Trials Registration Clinicaltrials.gov NCT04328467.
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- 2020
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17. Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19
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Skipper, Caleb P., Pastick, Katelyn A., Engen, Nicole W., Bangdiwala, Ananta S., Abassi, Mahsa, Lofgren, Sarah M., Williams, Darlisha A., Okafor, Elizabeth C., Pullen, Matthew F., Nicol, Melanie R., Nascene, Alanna A., Hullsiek, Kathy H., Cheng, Matthew P., Luke, Darlette, Lother, Sylvain A., MacKenzie, Lauren J., Drobot, Glen, Kelly, Lauren E., Schwartz, Ilan S., Zarychanski, Ryan, McDonald, Emily G., Lee, Todd C., Rajasingham, Radha, and Boulware, David R.
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stomatognathic diseases ,Original Research - Abstract
There is no known effective oral therapy for early COVID-19. This randomized, double-blind, placebo-controlled trial evaluated effects of oral hydroxychloroquine on symptoms and disease severity in adult outpatients with early COVID-19., Background: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19). Objective: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients. Design: Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668) Setting: Internet-based trial across the United States and Canada (40 states and 3 provinces). Participants: Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset. Intervention: Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo. Measures: Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days. Results: Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, −0.27 points [95% CI, −0.61 to 0.07 points]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non–COVID-19–related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29). Limitations: Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages. Conclusion: Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19. Primary Funding Source: Private donors., Visual Abstract. Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 There is no known effective oral therapy for early COVID-19. This randomized, double-blind, placebo-controlled trial evaluated effects of oral hydroxychloroquine on symptoms and disease severity in adult outpatients with early COVID-19. Visual Abstract. Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 There is no known effective oral therapy for early COVID-19. This randomized, double-blind, placebo-controlled trial evaluated effects of oral hydroxychloroquine on symptoms and disease severity in adult outpatients with early COVID-19.
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- 2020
18. Xpert MTB/RIF Ultra for the diagnosis of HIV-associated tuberculous meningitis: a prospective validation study
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Cresswell, Fiona V, Tugume, Lillian, Bahr, Nathan C, Kwizera, Richard, Bangdiwala, Ananta S, Musubire, Abdu K, Rutakingirwa, Morris, Kagimu, Enock, Nuwagira, Edwin, Mpoza, Edward, Rhein, Joshua, Williams, Darlisha A, Muzoora, Conrad, Grint, Daniel, Elliott, Alison M, Meya, David B, Boulware, David R, and ASTRO-CM team
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INTRODUCTION: Tuberculous meningitis accounts for 1-5% of tuberculosis cases. Diagnostic delay contributes to poor outcomes. We evaluated the performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis diagnosis. METHODS: In this prospective validation study, we tested the cerebrospinal fluid (CSF) of adults presenting with suspected meningitis (ie, headache or altered mental status with clinical signs of meningism) to the Mulago National Referral Hospital and Mbarara Regional Referral Hospital in Uganda. We centrifuged the CSF, resuspended the cell pellet in 2 mL CSF, and tested 0·5 mL aliquots with Xpert Ultra, Xpert MTB/RIF (Xpert), and mycobacterial growth indicator tube (MGIT) culture. We quantified diagnostic performance against the uniform case definition of probable or definite tuberculous meningitis and a composite microbiological reference standard. FINDINGS: From Nov 25, 2016, to Jan 24, 2019, we screened 466 adults with suspected meningitis and tested 204 for tuberculous meningitis. Uniform clinical case definition classified 51 participants as having probable or definite tuberculous meningitis. Against this uniform case definition, Xpert Ultra had 76·5% sensitivity (95% CI 62·5-87·2; 39 of 51 patients) and a negative predictive value of 92·7% (87·6-96·2; 153 of 165), compared with 55·6% sensitivity (44·0-70·4; 25 of 45; p=0·0010) and a negative predictive value of 85·8% (78·9-91·1; 121 of 141) for Xpert and 61·4% sensitivity (45·5-75·6; 27 of 44; p=0·020) and negative predictive value of 85·2% (77·4-91·1; 98 of 115) for MGIT culture. Against the composite microbiological reference standard, Xpert Ultra had sensitivity of 92·9% (80·5-98·5; 39 of 42), higher than Xpert at 65·8% (48·6-80·4; 25 of 38; p=0·0063) and MGIT culture at 72·2% (55·9-86·2; 27 of 37; p=0·092). Xpert Ultra detected nine tuberculous meningitis cases missed by Xpert and MGIT culture. INTERPRETATION: Xpert Ultra detected tuberculous meningitis with higher sensitivity than Xpert and MGIT culture in this HIV-positive population. However, with a negative predictive value of 93%, Xpert Ultra cannot be used as a rule-out test. Clinical judgment and novel highly sensitive point-of-care tests are still required. FUNDING: Wellcome Trust, National Institute of Health, National Institute of Neurologic Diseases and Stroke, Fogarty International Center, and National Institute of Allergy and Infectious Diseases.
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- 2020
19. Lessons Learned From Conducting Internet-Based Randomized Clinical Trials During a Global Pandemic
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Pullen, Matthew F, primary, Pastick, Katelyn A, additional, Williams, Darlisha A, additional, Nascene, Alanna A, additional, Bangdiwala, Ananta S, additional, Okafor, Elizabeth C, additional, Hullsiek, Katherine Huppler, additional, Skipper, Caleb P, additional, Lofgren, Sarah M, additional, Engen, Nicole, additional, Abassi, Mahsa, additional, McDonald, Emily G, additional, Lee, Todd C, additional, Rajasingham, Radha, additional, and Boulware, David R, additional
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- 2020
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20. Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19
- Author
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Lofgren, Sarah M, primary, Nicol, Melanie R, additional, Bangdiwala, Ananta S, additional, Pastick, Katelyn A, additional, Okafor, Elizabeth C, additional, Skipper, Caleb P, additional, Pullen, Matthew F, additional, Engen, Nicole W, additional, Abassi, Mahsa, additional, Williams, Darlisha A, additional, Nascene, Alanna A, additional, Axelrod, Margaret L, additional, Lother, Sylvain A, additional, MacKenzie, Lauren J, additional, Drobot, Glen, additional, Marten, Nicole, additional, Cheng, Matthew P, additional, Zarychanski, Ryan, additional, Schwartz, Ilan S, additional, Silverman, Michael, additional, Chagla, Zain, additional, Kelly, Lauren E, additional, McDonald, Emily G, additional, Lee, Todd C, additional, Hullsiek, Kathy H, additional, Boulware, David R, additional, and Rajasingham, Radha, additional
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- 2020
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21. Phase I EnACT Trial of the Safety and Tolerability of a Novel Oral Formulation of Amphotericin B
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Skipper, Caleb P., primary, Atukunda, Mucunguzi, additional, Stadelman, Anna, additional, Engen, Nicole W., additional, Bangdiwala, Ananta S., additional, Hullsiek, Katherine H., additional, Abassi, Mahsa, additional, Rhein, Joshua, additional, Nicol, Melanie R., additional, Laker, Eva, additional, Williams, Darlisha A., additional, Mannino, Raphael, additional, Matkovits, Theresa, additional, Meya, David B., additional, and Boulware, David R., additional
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- 2020
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22. High dose oral rifampicin to improve survival from adult tuberculous meningitis: A randomised placebo-controlled double-blinded phase III trial (the HARVEST study)
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Marais, Suzaan, primary, Cresswell, Fiona V, additional, Hamers, Raph L., additional, te Brake, Lindsey H.M., additional, Ganiem, Ahmad R., additional, Imran, Darma, additional, Bangdiwala, Ananta, additional, Martyn, Emily, additional, Kasibante, John, additional, Kagimu, Enock, additional, Musubire, Abdu, additional, Maharani, Kartika, additional, Estiasari, Riwanti, additional, Kusumaningrum, Ardiana, additional, Kusumadjayanti, Nadytia, additional, Yunivita, Vycke, additional, Naidoo, Kogieleum, additional, Lessells, Richard, additional, Moosa, Yunus, additional, Svensson, Elin M., additional, Huppler Hullsiek, Katherine, additional, Aarnoutse, Rob E., additional, Boulware, David R., additional, van Crevel, Reinout, additional, Ruslami, Rovina, additional, and Meya, David B., additional
- Published
- 2020
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23. Symptoms of COVID-19 Outpatients in the United States
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Pullen, Matthew F, primary, Skipper, Caleb P, additional, Hullsiek, Kathy H, additional, Bangdiwala, Ananta S, additional, Pastick, Katelyn A, additional, Okafor, Elizabeth C, additional, Lofgren, Sarah M, additional, Rajasingham, Radha, additional, Engen, Nicole W, additional, Galdys, Alison, additional, Williams, Darlisha A, additional, Abassi, Mahsa, additional, and Boulware, David R, additional
- Published
- 2020
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24. Standardized Urine-Based Tuberculosis (TB) Screening With TB-Lipoarabinomannan and Xpert MTB/RIF Ultra in Ugandan Adults With Advanced Human Immunodeficiency Virus Disease and Suspected Meningitis
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Cresswell, Fiona V, primary, Ellis, Jayne, primary, Kagimu, Enock, primary, Bangdiwala, Ananta S, primary, Okirwoth, Michael, primary, Mugumya, Gerald, primary, Rutakingirwa, Morris, primary, Kasibante, John, primary, Quinn, Carson M, primary, Ssebambulidde, Kenneth, primary, Rhein, Joshua, primary, Nuwagira, Edwin, primary, Tugume, Lillian, primary, Martyn, Emily, primary, Skipper, Caleb P, primary, Muzoora, Conrad, primary, Grint, Daniel, primary, Meya, David B, primary, Bahr, Nathan C, primary, Elliott, Alison M, primary, and Boulware, David R, primary
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- 2020
- Full Text
- View/download PDF
25. High dose oral rifampicin to improve survival from adult tuberculous meningitis: A randomised placebo-controlled double-blinded phase III trial (the HARVEST study)
- Author
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Marais, Suzaan, primary, Cresswell, Fiona V, additional, Hamers, Raph L., additional, te Brake, Lindsey H.M., additional, Ganiem, Ahmad R., additional, Imran, Darma, additional, Bangdiwala, Ananta, additional, Martyn, Emily, additional, Kasibante, John, additional, Kagimu, Enock, additional, Musubire, Abdu, additional, Maharani, Kartika, additional, Estiasari, Riwanti, additional, Kusumaningrum, Ardiana, additional, Kusumadjayanti, Nadytia, additional, Yunivita, Vycke, additional, Naidoo, Kogieleum, additional, Lessells, Richard, additional, Moosa, Yunus, additional, Svensson, Elin M., additional, Huppler Hullsiek, Katherine, additional, Aarnoutse, Rob E., additional, Boulware, David R., additional, van Crevel, Reinout, additional, Ruslami, Rovina, additional, and Meya, David B., additional
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- 2019
- Full Text
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26. Erratum to: The Changing Epidemiology of HIV-Associated Adult Meningitis, Uganda 2015–2017
- Author
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Ellis, Jayne, primary, Bangdiwala, Ananta S, additional, Cresswell, Fiona V, additional, Rhein, Joshua, additional, Nuwagira, Edwin, additional, Ssebambulidde, Kenneth, additional, Tugume, Lillian, additional, Rajasingham, Radha, additional, Bridge, Sarah C, additional, Muzoora, Conrad, additional, Meya, David B, additional, and Boulware, David R, additional
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- 2019
- Full Text
- View/download PDF
27. Seizures in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: Predictors and Outcomes
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Pastick, Katelyn A, primary, Bangdiwala, Ananta S, additional, Abassi, Mahsa, additional, Flynn, Andrew G, additional, Morawski, Bozena M, additional, Musubire, Abdu K, additional, Eneh, Prosperity C, additional, Schutz, Charlotte, additional, Taseera, Kabanda, additional, Rhein, Joshua, additional, Hullsiek, Kathy Huppler, additional, Nicol, Melanie R, additional, Vidal, Jose E, additional, Nakasujja, Noeline, additional, Meintjes, Graeme, additional, Muzoora, Conrad, additional, Meya, David B, additional, and Boulware, David R, additional
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- 2019
- Full Text
- View/download PDF
28. The Changing Epidemiology of HIV-Associated Adult Meningitis, Uganda 2015–2017
- Author
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Ellis, Jayne, Bangdiwala, Ananta S, Cresswell, Fiona V, Rhein, Joshua, Nuwagira, Edwin, Ssebambulidde, Kenneth, Tugume, Lillian, Rajasingham, Radha, Bridge, Sarah C, Muzoora, Conrad, Meya, David B, Boulware, David R, and ASTRO-CM Team
- Abstract
BACKGROUND: Central nervous system (CNS) infections remain a major public health problem in Sub-Saharan Africa, causing 15%-25% of AIDS-related deaths. With widespread availability of antiretroviral therapy (ART) and the introduction of improved diagnostics, the epidemiology of infectious meningitis is evolving. METHODS: We prospectively enrolled adults presenting with HIV-associated meningitis in Kampala and Mbarara, Uganda, from March 2015 to September 2017. Participants had a structured, stepwise diagnostic algorithm performed of blood cryptococcal antigen (CrAg), CSF CrAg, Xpert MTB/RIF for tuberculous (TB) meningitis (TBM), Biofire multiplex polymerase chain reaction, and traditional microscopy and cultures. RESULTS: We screened 842 consecutive adults with HIV presenting with suspected meningitis: 57% men, median age 35 years, median CD4 26 cells/mcL, and 55% presented on ART. Overall, 60.5% (509/842) were diagnosed with first-episode cryptococcal meningitis and 7.4% (62/842) with second episode. Definite/probable TB meningitis was the primary diagnosis in 6.9% (58/842); 5.3% (n = 45) had microbiologically confirmed (definite) TB meningitis. An additional 7.8% (66/842) did not meet the diagnostic threshold for definite/probable TBM but received empiric TBM therapy. Bacterial and viral meningitis were diagnosed in 1.3% (11/842) and 0.7% (6/842), respectively. The adoption of a cost-effective stepwise diagnostic algorithm allowed 79% (661/842) to have a confirmed microbiological diagnosis at an average cost of $44 per person. CONCLUSIONS: Despite widespread ART availability, Cryptococcus remains the leading cause of HIV-associated meningitis. The second most common etiology was TB meningitis, treated in 14.7% overall. The increased proportion of microbiologically confirmed TBM cases reflects the impact of new improved molecular diagnostics.
- Published
- 2019
29. Symptomatic Cryptococcal Antigenemia Presenting as Early Cryptococcal Meningitis With Negative Cerebral Spinal Fluid Analysis
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Ssebambulidde, Kenneth, Bangdiwala, Ananta S, Kwizera, Richard, Kandole, Tadeo Kiiza, Tugume, Lillian, Kiggundu, Reuben, Mpoza, Edward, Nuwagira, Edwin, Williams, Darlisha A, Lofgren, Sarah M, Abassi, Mahsa, Musubire, Abdu K, Cresswell, Fiona V, Rhein, Joshua, Muzoora, Conrad, Hullsiek, Kathy Huppler, Boulware, David R, Meya, David B, and Adjunctive Sertraline for Treatment of HIV-associated Cryptococc
- Abstract
BACKGROUND: Individuals with cryptococcal antigenemia are at high risk of developing cryptococcal meningitis if untreated. The progression and timing from asymptomatic infection to cryptococcal meningitis is unclear. We describe a subpopulation of individuals with neurologic symptomatic cryptococcal antigenemia but negative cerebral spinal fluid (CSF) studies. METHODS: We evaluated 1201 human immunodeficiency virus-seropositive individuals hospitalized with suspected meningitis in Kampala and Mbarara, Uganda. Baseline characteristics and clinical outcomes of participants with neurologic-symptomatic cryptococcal antigenemia and negative CSF cryptococcal antigen (CrAg) were compared to participants with confirmed CSF CrAg+ cryptococcal meningitis. Additional CSF testing included microscopy, fungal culture, bacterial culture, tuberculosis culture, multiplex FilmArray polymerase chain reaction (PCR; Biofire), and Xpert MTB/Rif. RESULTS: We found 56% (671/1201) of participants had confirmed CSF CrAg+ cryptococcal meningitis and 4% (54/1201) had neurologic symptomatic cryptococcal antigenemia with negative CSF CrAg. Of those with negative CSF CrAg, 9% (5/54) had Cryptococcus isolated on CSF culture (n = 3) or PCR (n = 2) and 11% (6/54) had confirmed tuberculous meningitis. CSF CrAg-negative patients had lower proportions with CSF pleocytosis (16% vs 26% with ≥5 white cells/μL) and CSF opening pressure >200 mmH2O (16% vs 71%) compared with CSF CrAg-positive patients. No cases of bacterial or viral meningitis were detected by CSF PCR or culture. In-hospital mortality was similar between symptomatic cryptococcal antigenemia (32%) and cryptococcal meningitis (31%; P = .91). CONCLUSIONS: Cryptococcal antigenemia with meningitis symptoms was the third most common meningitis etiology. We postulate this is early cryptococcal meningoencephalitis. Fluconazole monotherapy was suboptimal despite Cryptococcus-negative CSF. Further studies are warranted to understand the clinical course and optimal management of this distinct entity. CLINICAL TRIALS REGISTRATION: NCT01802385.
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- 2018
30. Performance of Lipoarabinomannan Assay using Cerebrospinal fluid for the diagnosis of Tuberculous meningitis among HIV patients
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Kwizera, Richard, primary, Cresswell, Fiona V., additional, Mugumya, Gerald, additional, Okirwoth, Micheal, additional, Kagimu, Enock, additional, Bangdiwala, Ananta S., additional, Williams, Darlisha A., additional, Rhein, Joshua, additional, Boulware, David R., additional, and Meya, David B., additional
- Published
- 2019
- Full Text
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31. Lessons Learned From Conducting Internet-Based Randomized Clinical Trials During a Global Pandemic.
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Pullen, Matthew F, Pastick, Katelyn A, Williams, Darlisha A, Nascene, Alanna A, Bangdiwala, Ananta S, Okafor, Elizabeth C, Hullsiek, Katherine Huppler, Skipper, Caleb P, Lofgren, Sarah M, Engen, Nicole, Abassi, Mahsa, McDonald, Emily G, Lee, Todd C, Rajasingham, Radha, and Boulware, David R
- Subjects
CLINICAL trials ,COVID-19 pandemic ,PANDEMICS ,EXPERIMENTAL design ,DISEASE prevalence ,HEALTH care reminder systems - Abstract
As the severe acute respiratory syndrome coronavirus 2 pandemic evolved, it was apparent that well designed and rapidly conducted randomized clinical trials were urgently needed. However, traditional clinical trial design presented several challenges. Notably, disease prevalence initially varied by time and region, and the pockets of outbreaks evolved geographically over time. Coupled with an occupational hazard from in-person study visits, timely recruitment would prove difficult in a traditional in-person clinical trial. Thus, our team opted to launch nationwide internet-based clinical trials using patient-reported outcome measures. In total, 2795 participants were recruited using traditional and social media, with screening and enrollment performed via an online data capture system. Follow-up surveys and survey reminders were similarly managed through this online system with manual participant outreach in the event of missing data. In this report, we present a narrative of our experience running internet-based clinical trials and provide recommendations for the design of future clinical trials during a world pandemic. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
32. Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study
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Bahr, Nathan C, Nuwagira, Edwin, Evans, Emily E, Cresswell, Fiona V, Bystrom, Philip V, Byamukama, Adolf, Bridge, Sarah C, Bangdiwala, Ananta S, Meya, David B, Denkinger, Claudia M, Muzoora, Conrad, Boulware, David R, and ASTRO-CM Trial Team
- Abstract
BACKGROUND: WHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50-70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis. METHODS: We prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda. HIV-infected adults with suspected meningitis (eg, headache, nuchal rigidity, altered mental status) were screened consecutively at Mbarara Regional Referral Hospital. We centrifuged CSF, resuspended the pellet in 2 mL of CSF, and tested 0·5 mL with mycobacteria growth indicator tube culture, 1 mL with Xpert, and cryopreserved 0·5 mL, later tested with Xpert Ultra. We assessed diagnostic performance against uniform clinical case definition or a composite reference standard of any positive CSF tuberculous test. FINDINGS: From Feb 27, 2015, to Nov 7, 2016, we prospectively evaluated 129 HIV-infected adults with suspected meningitis for tuberculosis. 23 participants were classified as probable or definite tuberculous meningitis by uniform case definition, excluding Xpert Ultra results. Xpert Ultra sensitivity was 70% (95% CI 47-87; 16 of 23 cases) for probable or definite tuberculous meningitis compared with 43% (23-66; 10/23) for Xpert and 43% (23-66; 10/23) for culture. With composite standard, we detected tuberculous meningitis in 22 (17%) of 129 participants. Xpert Ultra had 95% sensitivity (95% CI 77-99; 21 of 22 cases) for tuberculous meningitis, which was higher than either Xpert (45% [24-68]; 10/22; p=0·0010) or culture (45% [24-68]; 10/22; p=0·0034). Of 21 participants positive by Xpert Ultra, 13 were positive by culture, Xpert, or both, and eight were only positive by Xpert Ultra. Of those eight, three were categorised as probable tuberculous meningitis, three as possible tuberculous meningitis, and two as not tuberculous meningitis. Testing 6 mL or more of CSF was associated with more frequent detection of tuberculosis than with less than 6 mL (26% vs 7%; p=0·014). INTERPRETATION: Xpert Ultra detected significantly more tuberculous meningitis than did either Xpert or culture. WHO now recommends the use of Xpert Ultra as the initial diagnostic test for suspected tuberculous meningitis. FUNDING: National Institute of Neurologic Diseases and Stroke, Fogarty International Center, National Institute of Allergy and Infectious Disease, UK Medical Research Council/DfID/Wellcome Trust Global Health Trials, Doris Duke Charitable Foundation.
- Published
- 2017
33. Tuberculous meningitis diagnosis and outcomes during the Xpert MTB/Rif era: a 6.5-year cohort study in Uganda
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Cresswell, Fiona V., primary, Bangdiwala, Ananta S., additional, Bahr, Nathan C., additional, Trautner, Emily, additional, Nuwagira, Edwin, additional, Ellis, Jayne P., additional, Rajasingham, Radha, additional, Rhein, Joshua, additional, Williams, Darlisha A., additional, Muzoora, Conrad, additional, Elliott, Alison M., additional, Meya, David B., additional, and Boulware, David R., additional
- Published
- 2018
- Full Text
- View/download PDF
34. Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda
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Cresswell, Fiona V., primary, Bangdiwala, Ananta S., additional, Bahr, Nathan C., additional, Trautner, Emily, additional, Nuwagira, Edwin, additional, Ellis, Jayne P., additional, Rajasingham, Radha, additional, Rhein, Joshua, additional, Williams, Darlisha A., additional, Muzoora, Conrad, additional, Elliott, Alison M., additional, Meya, David B., additional, and Boulware, David R., additional
- Published
- 2018
- Full Text
- View/download PDF
35. Absence of cerebrospinal fluid pleocytosis in tuberculous meningitis is a common occurrence in HIV co-infection and a predictor of poor outcomes
- Author
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Cresswell, Fiona V., primary, Bangdiwala, Ananta S., additional, Meya, David B., additional, Bahr, Nathan C., additional, Vidal, Jose E., additional, Török, M. Estée, additional, Thao, Le Thi Phuong, additional, Thwaites, Guy E., additional, and Boulware, David R., additional
- Published
- 2018
- Full Text
- View/download PDF
36. BMET-06. IMPROVED SURVIVAL AND PROGNOSTIC ABILITY IN LUNG CANCER PATIENTS WITH BRAIN METASTASES: AN UPDATE OF THE GRADED PROGNOSTIC ASSESSMENT FOR LUNG CANCER USING MOLECULAR MARKERS (LUNG-molGPA)
- Author
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Sperduto, Paul, primary, Yang, T. Jonathan, additional, Beal, Kathryn, additional, Pan, Hubert, additional, Brown, Paul, additional, Bangdiwala, Ananta, additional, Shanley, Ryan, additional, Yeh, Norman, additional, Gaspar, Laurie E., additional, Braunstein, Steve, additional, Sneed, Penny, additional, Boyle, John M., additional, Kirkpatrick, John, additional, Mak, Kimberley, additional, Shih, Helen, additional, Engelman, Alex, additional, Roberge, David, additional, Arvold, Nils, additional, Alexander, Brian, additional, Awad, Mark, additional, Contessa, Joseph, additional, Chiang, Veronica, additional, Hardie, John, additional, Ma, Daniel, additional, Lou, Emil, additional, Sperduto, William, additional, and Mehta, Minesh, additional
- Published
- 2016
- Full Text
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37. Clinical Significance of Pulmonary Nodules in the Pretransplant Evaluation of Liver Transplant Recipients With Hepatocellular Carcinoma.
- Author
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Serrano, Oscar K., Olgun, Deniz C., Goduguchinta, Varshita, Bangdiwala, Ananta, Odegard, Marjorie N., Kandaswamy, Raja, Matas, Arthur J., Lake, John R., Pruett, Timothy L., and Chinnakotla, Srinath
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- 2018
- Full Text
- View/download PDF
38. Impact of Daptomycin Minimum Inhibitory Concentration (MIC) on Outcomes of Patients with Hematologic Malignancies and Hematopoietic Stem Cell Transplant (HSCT) Recipients with Vancomycin-Resistant Enterococci (VRE) Bloodstream Infection (BSI)
- Author
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Chong, Pearlie P., primary, van Duin, David, additional, Bangdiwala, Ananta, additional, Ivanova, Anastasia, additional, Kerr, Alan, additional, Weber, David J., additional, Gilligan, Peter H., additional, Khan, Tippu, additional, and Shea, Thomas C., additional
- Published
- 2015
- Full Text
- View/download PDF
39. Evaluation of the Impact of Anti-Thymocyte Globulin (ATG) on Post-Hematopoietic Cell Transplant (HCT) Outcomes in Patients Undergoing Allogeneic HCT
- Author
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Kaminski, Katie S., primary, Beechinor, Ryan, additional, Lebovic, Rachel, additional, Roth, Mary, additional, Bangdiwala, Ananta, additional, Ballarini, Nicolas, additional, Ivanova, Anastasia, additional, Chong, Pearlie P., additional, Jamieson, Katarzyna, additional, Shea, Thomas C., additional, and Rao, Kamakshi V., additional
- Published
- 2015
- Full Text
- View/download PDF
40. Detrimental Outcomes of Unmasking Cryptococcal Meningitis With Recent ART Initiation.
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Rhein, Joshua, Hullsiek, Kathy H, Evans, Emily E, Tugume, Lillian, Nuwagira, Edwin, Ssebambulidde, Kenneth, Kiggundu, Reuben, Mpoza, Edward, Musubire, Abdu K, and Bangdiwala, Ananta S
- Abstract
Background Increased antiretroviral therapy (ART) availability has been associated with more patients developing cryptococcosis after ART initiation. Despite this changing epidemiology, data regarding cryptococcal meningitis in those already receiving ART are limited. We compared clinical presentations and outcomes among ART-naïve and ART-experienced Ugandans. Methods We prospectively enrolled 605 HIV-infected persons with first-episode cryptococcal meningitis from August 2013 to May 2017 who received amphotericin-based combination therapy. We classified participants by ART status and ART duration and compared groups for 2-week survival. Results Overall, 46% (281/605) of participants were receiving ART at presentation. Compared with those not receiving ART, those receiving ART had higher CD4 counts (P <.001) and lower cerebrospinal fluid fungal burdens (P <.001). Of those receiving ART, 56% (156/281) initiated ART within 6 months, and 18% (51/281) initiated ART within 14 days. Two-week mortality did not differ by ART status (27% in both ART-naïve and ART-experienced%; P >.99). However, 47% (24/51) of those receiving ART for ≤14 days died within 2 weeks, compared with 19% (20/105) of those receiving ART for 15–182 days and 26% (32/125) of those receiving ART for >6 months (P <.001). Among persons receiving ART for >6 months, 87% had HIV viral loads >1000 copies/mL. Conclusions Cryptococcosis after ART initiation is common in Africa. Patients initiating ART who unmask cryptococcal meningitis are at a high risk of death. Immune recovery in the setting of central nervous system infection is detrimental, and management of this population requires further study. Implementing pre-ART cryptococcal antigen screening is urgently needed to prevent cryptococcal meningitis after ART initiation. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
41. The Changing Epidemiology of HIV-Associated Adult Meningitis, Uganda 2015-2017.
- Author
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Ellis J, Bangdiwala AS, Cresswell FV, Rhein J, Nuwagira E, Ssebambulidde K, Tugume L, Rajasingham R, Bridge SC, Muzoora C, Meya DB, and Boulware DR
- Abstract
Background: Central nervous system (CNS) infections remain a major public health problem in Sub-Saharan Africa, causing 15%-25% of AIDS-related deaths. With widespread availability of antiretroviral therapy (ART) and the introduction of improved diagnostics, the epidemiology of infectious meningitis is evolving., Methods: We prospectively enrolled adults presenting with HIV-associated meningitis in Kampala and Mbarara, Uganda, from March 2015 to September 2017. Participants had a structured, stepwise diagnostic algorithm performed of blood cryptococcal antigen (CrAg), CSF CrAg, Xpert MTB/RIF for tuberculous (TB) meningitis (TBM), Biofire multiplex polymerase chain reaction, and traditional microscopy and cultures., Results: We screened 842 consecutive adults with HIV presenting with suspected meningitis: 57% men, median age 35 years, median CD4 26 cells/mcL, and 55% presented on ART. Overall, 60.5% (509/842) were diagnosed with first-episode cryptococcal meningitis and 7.4% (62/842) with second episode. Definite/probable TB meningitis was the primary diagnosis in 6.9% (58/842); 5.3% (n = 45) had microbiologically confirmed (definite) TB meningitis. An additional 7.8% (66/842) did not meet the diagnostic threshold for definite/probable TBM but received empiric TBM therapy. Bacterial and viral meningitis were diagnosed in 1.3% (11/842) and 0.7% (6/842), respectively. The adoption of a cost-effective stepwise diagnostic algorithm allowed 79% (661/842) to have a confirmed microbiological diagnosis at an average cost of $44 per person., Conclusions: Despite widespread ART availability, Cryptococcus remains the leading cause of HIV-associated meningitis. The second most common etiology was TB meningitis, treated in 14.7% overall. The increased proportion of microbiologically confirmed TBM cases reflects the impact of new improved molecular diagnostics., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2019
- Full Text
- View/download PDF
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