Browsing by Author "Stout, Jason E"
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Item Open Access A Cluster of Nontuberculous Mycobacterial Tenosynovitis Following Hurricane Relief Efforts.(Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-06) Turner, Nicholas A; Sweeney, Mollie I; Xet-Mull, Ana M; Storm, Jeremy; Mithani, Suhail K; Jones, David B; Miles, Jeremy J; Tobin, David M; Stout, Jason EBackground
Nontuberculous mycobacteria (NTM) are a rare cause of infectious tenosynovitis of the upper extremity. Using molecular methods, clinical microbiology laboratories are increasingly reporting identification down to the species level. Improved methods for speciation are revealing new insights into the clinical and epidemiologic features of rare NTM infections.Methods
We encountered 3 cases of epidemiologically linked upper extremity NTM tenosynovitis associated with exposure to hurricane-damaged wood. We conducted whole-genome sequencing to assess isolate relatedness followed by a literature review of NTM infections that involved the upper extremity.Results
Despite shared epidemiologic risk, the cases were caused by 3 distinct organisms. Two cases were rare infections caused by closely related but distinct species within the Mycobacterium terrae complex that could not be differentiated by traditional methods. The third case was caused by Mycobacterium intracellulare. An updated literature review that focused on research that used modern molecular speciation methods found that several species within the M. terrae complex are increasingly reported as a cause of upper extremity tenosynovitis, often in association with environmental exposures.Conclusions
These cases illustrate the importance of molecular methods for speciating phenotypically similar NTM, as well as the limitations of laboratory-based surveillance in detecting point-source outbreaks when the source is environmental and may involve multiple organisms.Item Open Access A long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis.(Nature communications, 2022-08) Kim, Manse; Johnson, Claire E; Schmalstig, Alan A; Annis, Ayano; Wessel, Sarah E; Van Horn, Brian; Schauer, Amanda; Exner, Agata A; Stout, Jason E; Wahl, Angela; Braunstein, Miriam; Victor Garcia, J; Kovarova, MartinaTuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis (Mtb) and is a major cause of morbidity and mortality. Successful treatment requires strict adherence to drug regimens for prolonged periods of time. Long-acting (LA) delivery systems have the potential to improve adherence. Here, we show the development of LA injectable drug formulations of the anti-TB drug rifabutin made of biodegradable polymers and biocompatible solvents that solidifies after subcutaneous injection. Addition of amphiphilic compounds increases drug solubility, allowing to significantly increase formulation drug load. Solidified implants have organized microstructures that change with formulation composition. Higher drug load results in smaller pore size that alters implant erosion and allows sustained drug release. The translational relevance of these observations in BALB/c mice is demonstrated by (1) delivering high plasma drug concentrations for 16 weeks, (2) preventing acquisition of Mtb infection, and (3) clearing acute Mtb infection from the lung and other tissues.Item Open Access A new trial design to accelerate tuberculosis drug development: the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP).(BMC Med, 2016-03-23) Phillips, Patrick PJ; Dooley, Kelly E; Gillespie, Stephen H; Heinrich, Norbert; Stout, Jason E; Nahid, Payam; Diacon, Andreas H; Aarnoutse, Rob E; Kibiki, Gibson S; Boeree, Martin J; Hoelscher, MichaelBACKGROUND: The standard 6-month four-drug regimen for the treatment of drug-sensitive tuberculosis has remained unchanged for decades and is inadequate to control the epidemic. Shorter, simpler regimens are urgently needed to defeat what is now the world's greatest infectious disease killer. METHODS: We describe the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP) as a novel hybrid phase II/III trial design to accelerate regimen development. In the Phase IIC STEP trial, the experimental regimen is given for the duration for which it will be studied in phase III (presently 3 or 4 months) and patients are followed for clinical outcomes of treatment failure and relapse for a total of 12 months from randomisation. Operating characteristics of the trial design are explored assuming a classical frequentist framework as well as a Bayesian framework with flat and sceptical priors. A simulation study is conducted using data from the RIFAQUIN phase III trial to illustrate how such a design could be used in practice. RESULTS: With 80 patients per arm, and two (2.5 %) unfavourable outcomes in the STEP trial, there is a probability of 0.99 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.91 that the proportion of unfavourable outcomes would be less than 8 %. With six (7.5 %) unfavourable outcomes, there is a probability of 0.82 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.41 that it would be less than 8 %. Simulations using data from the RIFAQUIN trial show that a STEP trial with 80 patients per arm would have correctly shown that the Inferior Regimen should not proceed to phase III and would have had a high chance (0.88) of either showing that the Successful Regimen could proceed to phase III or that it might require further optimisation. CONCLUSIONS: Collection of definitive clinical outcome data in a relatively small number of participants over only 12 months provides valuable information about the likelihood of success in a future phase III trial. We strongly believe that the STEP trial design described herein is an important tool that would allow for more informed decision-making and accelerate regimen development.Item Open Access A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania.(BMC Infect Dis, 2014-02-20) Reddy, Elizabeth A; Njau, Boniface N; Morpeth, Susan C; Lancaster, Kathryn E; Tribble, Alison C; Maro, Venance P; Msuya, Levina J; Morrissey, Anne B; Kibiki, Gibson S; Thielman, Nathan M; Cunningham, Coleen K; Schimana, Werner; Shao, John F; Chow, Shein-Chung; Stout, Jason E; Crump, John A; Bartlett, John A; Hamilton, Carol DBACKGROUND: Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] on management of persons with suspected tuberculosis. METHODS: Adults and children with suspected tuberculosis were randomized to standard (direct AFB smear only) or intensified (concentrated AFB smear and tuberculosis culture) diagnostics and followed for 8 weeks. The primary endpoint was appropriate treatment (i.e. antituberculosis therapy for those with tuberculosis, no antituberculous therapy for those without tuberculosis). RESULTS: Seventy participants were randomized to standard (n = 37, 53%) or intensive (n = 33, 47%) diagnostics. At 8 weeks, 100% (n = 22) of participants in follow up randomized to intensive diagnostics were receiving appropriate care, vs. 22 (88%) of 25 participants randomized to standard diagnostics (p = 0.14). Overall, 18 (26%) participants died; antituberculosis therapy was associated with lower mortality (9% who received antiuberculosis treatment died vs. 26% who did not, p = 0.04). CONCLUSIONS: Under field conditions in a high burden setting, the impact of intensified diagnostics was blunted by high early mortality. Enhanced availability of rapid diagnostics must be linked to earlier access to care for outcomes to improve.Item Open Access Annotated Genome Sequences of 16 Lineage 4 Mycobacterium tuberculosis Strains from Guatemala.(Genome announcements, 2018-02) Saelens, Joseph W; Lau-Bonilla, Dalia; Moller, Anneliese; Xet-Mull, Ana M; Medina, Narda; Guzmán, Brenda; Calderón, Maylena; Herrera, Raúl; Stout, Jason E; Arathoon, Eduardo; Samayoa, Blanca; Tobin, David MWhole-genome sequencing has resulted in new insights into the phylogeography of Mycobacterium tuberculosis However, only limited genomic data are available from M. tuberculosis strains in Guatemala. Here we report 16 complete genomes of clinical strains belonging to the Euro-American lineage 4, the most common lineage found in Guatemala and Central America.Item Open Access Application of diagnostic criteria for non-tuberculous mycobacterial disease to a case series of mycobacterial-positive isolates.(Journal of clinical tuberculosis and other mycobacterial diseases, 2019-12) Ghio, Andrew J; Smith, Genee S; DeFlorio-Barker, Stephanie; Messier, Kyle P; Hudgens, Edward; Murphy, Mark S; Maillard, Jean-Marie; Stout, Jason E; Hilborn, Elizabeth DThe American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) have provided guidelines to assist in the accurate diagnosis of lung disease caused by nontuberculous mycobacteria (NTM). These microbiologic, radiographic, and clinical criteria are considered equally important and all must be met to make the diagnosis of NTM lung disease. To assess the significance of the three criteria, each was evaluated for its contribution to the diagnosis of NTM lung disease in a case series. Laboratory reports of any specimen positive for NTM isolation were collected between January 1, 2006 and December 31, 2010 at a university medical center. Medical records were reviewed in detail using a standardized form. The total number of patients with a culture from any site positive for NTM was 297 while the number from respiratory specimens during the same period was 232 (78%). Samples from two of these patients also yielded M. tuberculosis complex and were excluded. While 128 of the remaining 230 patients (55.7%) in the cohort met the microbiologic criterion for diagnosis of NTM lung disease, 151 (65.6%) and 189 (78.3%) met the radiologic and clinical criteria respectively. Only 78 patients (33.9%) met all three criteria provided by the ATS/IDSA for diagnosis of NTM lung disease. This evaluation reaffirms that defining NTM lung disease using either one or two of the criteria provided by the 2007 ATS/IDSA guidelines may significantly overestimate the number of cases of NTM lung disease. Based on the experience of defining NTM lung disease in this case series, recommendations for modification of the ATS/IDSA guidelines are provided which include expansion of both radiologic patterns and the list of symptoms associated with NTM lung disease.Item Open Access Author Correction: Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.(Nature communications, 2021-05-14) Axfors, Cathrine; Schmitt, Andreas M; Janiaud, Perrine; Van't Hooft, Janneke; Abd-Elsalam, Sherief; Abdo, Ehab F; Abella, Benjamin S; Akram, Javed; Amaravadi, Ravi K; Angus, Derek C; Arabi, Yaseen M; Azhar, Shehnoor; Baden, Lindsey R; Baker, Arthur W; Belkhir, Leila; Benfield, Thomas; Berrevoets, Marvin AH; Chen, Cheng-Pin; Chen, Tsung-Chia; Cheng, Shu-Hsing; Cheng, Chien-Yu; Chung, Wei-Sheng; Cohen, Yehuda Z; Cowan, Lisa N; Dalgard, Olav; de Almeida E Val, Fernando F; de Lacerda, Marcus VG; de Melo, Gisely C; Derde, Lennie; Dubee, Vincent; Elfakir, Anissa; Gordon, Anthony C; Hernandez-Cardenas, Carmen M; Hills, Thomas; Hoepelman, Andy IM; Huang, Yi-Wen; Igau, Bruno; Jin, Ronghua; Jurado-Camacho, Felipe; Khan, Khalid S; Kremsner, Peter G; Kreuels, Benno; Kuo, Cheng-Yu; Le, Thuy; Lin, Yi-Chun; Lin, Wu-Pu; Lin, Tse-Hung; Lyngbakken, Magnus Nakrem; McArthur, Colin; McVerry, Bryan J; Meza-Meneses, Patricia; Monteiro, Wuelton M; Morpeth, Susan C; Mourad, Ahmad; Mulligan, Mark J; Murthy, Srinivas; Naggie, Susanna; Narayanasamy, Shanti; Nichol, Alistair; Novack, Lewis A; O'Brien, Sean M; Okeke, Nwora Lance; Perez, Léna; Perez-Padilla, Rogelio; Perrin, Laurent; Remigio-Luna, Arantxa; Rivera-Martinez, Norma E; Rockhold, Frank W; Rodriguez-Llamazares, Sebastian; Rolfe, Robert; Rosa, Rossana; Røsjø, Helge; Sampaio, Vanderson S; Seto, Todd B; Shahzad, Muhammad; Soliman, Shaimaa; Stout, Jason E; Thirion-Romero, Ireri; Troxel, Andrea B; Tseng, Ting-Yu; Turner, Nicholas A; Ulrich, Robert J; Walsh, Stephen R; Webb, Steve A; Weehuizen, Jesper M; Velinova, Maria; Wong, Hon-Lai; Wrenn, Rebekah; Zampieri, Fernando G; Zhong, Wu; Moher, David; Goodman, Steven N; Ioannidis, John PA; Hemkens, Lars GThe original version of this Article contained an error in the spelling of the author Muhammad Shahzad, which was incorrectly given as Muhammad Shehzad. This has now been corrected in both the PDF and HTML versions of the Article.Item Open Access Author Correction: Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.(Nature communications, 2024-02) Axfors, Cathrine; Schmitt, Andreas M; Janiaud, Perrine; Van't Hooft, Janneke; Abd-Elsalam, Sherief; Abdo, Ehab F; Abella, Benjamin S; Akram, Javed; Amaravadi, Ravi K; Angus, Derek C; Arabi, Yaseen M; Azhar, Shehnoor; Baden, Lindsey R; Baker, Arthur W; Belkhir, Leila; Benfield, Thomas; Berrevoets, Marvin AH; Chen, Cheng-Pin; Chen, Tsung-Chia; Cheng, Shu-Hsing; Cheng, Chien-Yu; Chung, Wei-Sheng; Cohen, Yehuda Z; Cowan, Lisa N; Dalgard, Olav; de Almeida E Val, Fernando F; de Lacerda, Marcus VG; de Melo, Gisely C; Derde, Lennie; Dubee, Vincent; Elfakir, Anissa; Gordon, Anthony C; Hernandez-Cardenas, Carmen M; Hills, Thomas; Hoepelman, Andy IM; Huang, Yi-Wen; Igau, Bruno; Jin, Ronghua; Jurado-Camacho, Felipe; Khan, Khalid S; Kremsner, Peter G; Kreuels, Benno; Kuo, Cheng-Yu; Le, Thuy; Lin, Yi-Chun; Lin, Wu-Pu; Lin, Tse-Hung; Lyngbakken, Magnus Nakrem; McArthur, Colin; McVerry, Bryan J; Meza-Meneses, Patricia; Monteiro, Wuelton M; Morpeth, Susan C; Mourad, Ahmad; Mulligan, Mark J; Murthy, Srinivas; Naggie, Susanna; Narayanasamy, Shanti; Nichol, Alistair; Novack, Lewis A; O'Brien, Sean M; Okeke, Nwora Lance; Perez, Léna; Perez-Padilla, Rogelio; Perrin, Laurent; Remigio-Luna, Arantxa; Rivera-Martinez, Norma E; Rockhold, Frank W; Rodriguez-Llamazares, Sebastian; Rolfe, Robert; Rosa, Rossana; Røsjø, Helge; Sampaio, Vanderson S; Seto, Todd B; Shahzad, Muhammad; Soliman, Shaimaa; Stout, Jason E; Thirion-Romero, Ireri; Troxel, Andrea B; Tseng, Ting-Yu; Turner, Nicholas A; Ulrich, Robert J; Walsh, Stephen R; Webb, Steve A; Weehuizen, Jesper M; Velinova, Maria; Wong, Hon-Lai; Wrenn, Rebekah; Zampieri, Fernando G; Zhong, Wu; Moher, David; Goodman, Steven N; Ioannidis, John PA; Hemkens, Lars GCorrection to: Nature Communicationshttps://doi.org/10.1038/s41467-021-22446-z, published online 15 April 2021 The original version of this article contained an error in Table 1, which misidentified the trial included in the meta-analysis registered as NCT04323527 as CloroCOVID19II instead of CloroCOVID19III. The NCT04323527 registration includes the trials CloroCOVID19I and CloroCOVID19III. CloroCOVID19I was not included in the meta-analysis. In addition, the original version of the Methods section inadvertently omitted details of which formulations of hydroxychloroquine or chloroquine the reported dosages refer to. The following information has been included in the legend for Table 1 and in the corrected methods section: “In all trials that used hydroxychloroquine, dosages refer to hydroxychloroquine sulfate. In trials that used chloroquine, the dosages for ARCHAIC, ChiCTR2000030054 and ChiCTR2000031204 refer to chloroquine phosphate, while those for CloroCOVID19II and CloroCOVID19III refer to chloroquine base. The American Journal of Tropical Medicine and Hygiene has issued a retraction note (1) for one of the trials (2) that had been included in the calculations of our meta-analysis. Exclusion of the data from this trial changes neither the results nor inferences of the meta-analysis. For hydroxychloroquine, the original odds ratio for mortality was 1.11 (95% CI: 1.02–1.20; I2 = 0%; 26 trials; 10,012 patients) and excluding the retracted trial the odds ratio for mortality would remain 1.11 (95% CI: 1.02–1.20, I2 = 0%; 25 trials; 9818 patients). Retraction Notice. The American Journal of Tropical Medicine and Hygiene 107, 728-728, https://doi.org/10.4269/ajtmh.1073ret (2022). Abd-Elsalam, S. et al. RETRACTED: Hydroxychloroquine in the Treatment of COVID-19: A Multicenter Randomized Controlled Study. Am J Trop Med Hyg 103, 1635-1639, https://doi.org/10.4269/ajtmh.20-0873 (2020). The errors in Table 1 and in the Methods section have been corrected in both the PDF and HTML versions of the Article.Item Open Access Clinical Features and Treatment Outcomes of Pulmonary Mycobacterium avium-intracellulare Complex With and Without Coinfections.(Open forum infectious diseases, 2022-08) Wang, Grace; Stapleton, Jack T; Baker, Arthur W; Rouphael, Nadine; Creech, C Buddy; El Sahly, Hana M; Stout, Jason E; Jackson, Lisa; Charbek, Edward; Leyva, Francisco J; Tomashek, Kay M; Tibbals, Melinda; Miller, Aaron; Frey, Sharon; Niemotka, Samson; Wiemken, Timothy L; Beydoun, Nour; Alaaeddine, Ghina; Turner, Nicholas; Walter, Emmanuel B; Chamberland, Robin; Abate, GetahunCoinfections are more common in patients with cystic fibrosis and bronchiectasis. Infiltrates on imaging studies are seen more commonly in patients with coinfections, but coinfections did not affect treatment outcomes of pulmonary Mycobacterium avium complex.Item Open Access Clinical utility of indium 111-labeled white blood cell scintigraphy for evaluation of suspected infection.(Open Forum Infect Dis, 2014-09) Lewis, Sarah S; Cox, Gary M; Stout, Jason EBACKGROUND: We sought to characterize the clinical utility of indium 111 ((111)In)-labeled white blood cell (WBC) scans by indication, to identify patient populations who might benefit most from this imaging modality. METHODS: Medical records for all patients who underwent (111)In-labeled WBC scans at our tertiary referral center from 2005 to 2011 were reviewed. Scan indication, results, and final diagnosis were assessed independently by 2 infectious disease physicians. Reviewers also categorized the clinical utility of each scan as helpful vs not helpful with diagnosis and/or management according to prespecified criteria. Cases for which clinical utility could not be determined were excluded from the utility assessment. RESULTS: One hundred thirty-seven scans were included in this analysis; clinical utility could be determined in 132 (96%) cases. The annual number of scans decreased throughout the study period, from 26 in 2005 to 13 in 2011. Forty-one (30%) scans were positive, and 85 (62%) patients were ultimately determined to have an infection. Of the evaluable scans, 63 (48%) scans were deemed clinically useful. Clinical utility varied by scan indication: (111)In-labeled WBC scans were more helpful for indications of osteomyelitis (35/50, 70% useful) or vascular access infection (10/15, 67% useful), and less helpful for evaluation of fever of unknown origin (12/35, 34% useful). CONCLUSIONS: (111)In-labeled WBC scans were useful for patient care less than half of the time at our center. Targeted ordering of these scans for indications in which they have greater utility, such as suspected osteomyelitis and vascular access infections, may optimize test utilization.Item Open Access Community-based HCV screening: knowledge and attitudes in a high risk urban population.(BMC Infect Dis, 2014-02-10) Norton, Brianna L; Voils, Corrine I; Timberlake, Sarah H; Hecker, Emily J; Goswami, Neela D; Huffman, Kim M; Landgraf, Anneka; Naggie, Susanna; Stout, Jason EBACKGROUND: In an attempt to curtail the rising morbidity and mortality from undiagnosed HCV (hepatitis C virus) in the United States, screening guidelines have been expanded to high-risk individuals and persons born 1945-1965. Community-based screening may be one strategy in which to reach such persons; however, the acceptance of HCV testing, when many high-risk individuals may not have access to HCV specific medications, remains unknown. METHODS: We set out to assess attitudes about HCV screening and knowledge about HCV disease at several community-based testing sites that serve high-risk populations. This assessment was paired with a brief HCV educational intervention, followed by post-education evaluation. RESULTS: Participants (n = 140) were surveyed at five sites; two homeless shelters, two drug rehabilitation centers, and a women's "drop-in" center. Personal acceptance of HCV testing was almost unanimous, and 90% of participants reported that they would still want to be tested even if they were unable to receive HCV treatment. Baseline hepatitis C knowledge was poor; however, the brief educational intervention significantly improved knowledge and increased acceptability of testing when medical access issues were explicitly stated. CONCLUSIONS: Despite inconsistencies in access to care and treatment, high-risk communities want to know their HCV status. Though baseline HCV knowledge was poor in this population, a brief on-site educational intervention improved both knowledge and acceptability of HCV testing and care. These data support the establishment of programs that utilize community-based screening, and also provide initial evidence for acceptance of the implementation of the recently expanded screening guidelines among marginalized communities.Item Open Access COVID-19 Trials: Who Participates and Who Benefits?(Southern medical journal, 2022-04) Narayanasamy, Shanti; Mourad, Ahmad; Turner, Nicholas A; Le, Thuy; Rolfe, Robert J; Okeke, Nwora Lance; O'Brien, Sean M; Baker, Arthur W; Wrenn, Rebekah; Rosa, Rossana; Rockhold, Frank W; Naggie, Susanna; Stout, Jason EObjectives
The coronavirus disease 2019 (COVID-19) pandemic has disproportionately afflicted vulnerable populations. Older adults, particularly residents of nursing facilities, represent a small percentage of the population but account for 40% of mortality from COVID-19 in the United States. Racial and ethnic minority individuals, particularly Black, Hispanic, and Indigenous Americans have experienced higher rates of infection and death than the White population. Although there has been an unprecedented explosion of clinical trials to examine potential therapies, participation by members of these vulnerable communities is crucial to obtaining data generalizable to those communities.Methods
We undertook an open-label, factorial randomized clinical trial examining hydroxychloroquine and/or azithromycin for hospitalized patients.Results
Of 53 screened patients, 11 (21%) were enrolled. Ten percent (3/31) of Black patients were enrolled, 33% (7/21) of White patients, and 50% (6/12) of Hispanic patients. Forty-seven percent (25/53) of patients declined participation despite eligibility; 58%(18/31) of Black patients declined participation. Forty percent (21/53) of screened patients were from a nursing facility and 10% (2/21) were enrolled. Enrolled patients had fewer comorbidities than nonenrolled patients: median modified Charlson comorbidity score 2.0 (interquartile range 0-2.5), versus 4.0 (interquartile range 2-6) for nonenrolled patients (P = 0.006). The limitations of the study were the low participation rate and the multiple treatment trials concurrently recruiting at our institution.Conclusions
The high rate of nonparticipation in our trial of nursing facility residents and Black people emphasizes the concern that clinical trials for therapeutics may not target key populations with high mortality rates.Item Open Access Extrapulmonary tuberculosis, human immunodeficiency virus, and foreign birth in North Carolina, 1993 - 2006.(BMC Public Health, 2008-04-04) Kipp, Aaron M; Stout, Jason E; Hamilton, Carol Dukes; Van Rie, AnneliesBACKGROUND: The proportion of extrapulmonary tuberculosis (EPTB) reported in the United States has been gradually increasing. HIV infection and foreign birth are increasingly associated with tuberculosis and understanding their effect on the clinical presentation of tuberculosis is important. METHODS: Case-control study of 6,124 persons with tuberculosis reported to the North Carolina Division of Public health from January 1, 1993 to December 31, 2006. Multivariate logistic regression was used to obtain adjusted odds ratios measuring the associations of foreign birth region and US born race/ethnicity, by HIV status, with EPTB. RESULTS: Among all patients with tuberculosis, 1,366 (22.3%) had EPTB, 563 (9.2%) were HIV co-infected, and 1,299 (21.2%) were foreign born. Among HIV negative patients, EPTB was associated with being foreign born (adjusted ORs 1.36 to 5.09, depending on region of birth) and with being US born, Black/African American (OR 1.84; 95% CI 1.42, 2.39). Among HIV infected patients, EPTB was associated with being US born, Black/African American (OR 2.60; 95% CI 1.83, 3.71) and with foreign birth in the Americas (OR 5.12; 95% CI 2.84, 9.23). CONCLUSION: Foreign born tuberculosis cases were more likely to have EPTB than US born tuberculosis cases, even in the absence of HIV infection. Increasing proportions of foreign born and HIV-attributable tuberculosis cases in the United States will likely result in a sustained burden of EPTB. Further research is needed to explore why the occurrence and type of EPTB differs by region of birth and whether host genetic and/or bacterial variation can explain these differences in EPTB.Item Open Access Feasibility and willingness-to-pay for integrated community-based tuberculosis testing.(BMC Infect Dis, 2011-11-02) Goswami, Neela D; Hecker, Emily; Holland, David P; Naggie, Susanna; Cox, Gary M; Mosher, Ann; Turner, Debbie; Torres, Yvonne; Vickery, Carter; Ahearn, Marshall A; Blain, Michela LM; Rasmussen, Petra; Stout, Jason EBACKGROUND: Community-based screening for TB, combined with HIV and syphilis testing, faces a number of barriers. One significant barrier is the value that target communities place on such screening. METHODS: Integrated testing for TB, HIV, and syphilis was performed in neighborhoods identified using geographic information systems-based disease mapping. TB testing included skin testing and interferon gamma release assays. Subjects completed a survey describing disease risk factors, healthcare access, healthcare utilization, and willingness to pay for integrated testing. RESULTS: Behavioral and social risk factors among the 113 subjects were prevalent (71% prior incarceration, 27% prior or current crack cocaine use, 35% homelessness), and only 38% had a regular healthcare provider. The initial 24 subjects reported that they would be willing to pay a median $20 (IQR: 0-100) for HIV testing and $10 (IQR: 0-100) for TB testing when the question was asked in an open-ended fashion, but when the question was changed to a multiple-choice format, the next 89 subjects reported that they would pay a median $5 for testing, and 23% reported that they would either not pay anything to get tested or would need to be paid $5 to get tested for TB, HIV, or syphilis. Among persons who received tuberculin skin testing, only 14/78 (18%) participants returned to have their skin tests read. Only 14/109 (13%) persons who underwent HIV testing returned to receive their HIV results. CONCLUSION: The relatively high-risk persons screened in this community outreach study placed low value on testing. Reported willingness to pay for such testing, while low, likely overestimated the true willingness to pay. Successful TB, HIV, and syphilis integrated testing programs in high risk populations will likely require one-visit diagnostic testing and incentives.Item Open Access Geographic analysis of latent tuberculosis screening: A health system approach.(PloS one, 2020-01) Bonnewell, John P; Farrow, Laura; Dicks, Kristen V; Cox, Gary M; Stout, Jason EBackground
Novel approaches are required to better focus latent tuberculosis infection (LTBI) efforts in low-prevalence regions. Geographic information systems, used within large health systems, may provide one such approach.Methods
A retrospective, cross-sectional design was used to integrate US Census and Duke Health System data between January 1, 2010 and October 31, 2017 and examine the relationships between LTBI screening and population tuberculosis risk (assessed using the surrogate measure of proportion of persons born in tuberculosis-endemic regions) by census tract.Results
The median proportion of Duke patients screened per census tract was 0.01 (range 0-0.1, interquartile range 0.01-0.03). The proportion of Duke patients screened within a census tract significantly but weakly correlated with the population risk. Furthermore, patients residing in census tracts with higher population tuberculosis risk were more likely to be screened with TST than with an IGRA (p<0.001).Conclusion
The weak correlation between patient proportion screened for LTBI and our surrogate marker of population tuberculosis risk suggests that LTBI screening efforts should be better targeted. This type of geography-based analysis may serve as an easily obtainable benchmark for LTBI screening in health systems with low tuberculosis prevalence.Item Open Access Geographic information system-based screening for TB, HIV, and syphilis (GIS-THIS): a cross-sectional study.(PLoS One, 2012) Goswami, Neela D; Hecker, Emily J; Vickery, Carter; Ahearn, Marshall A; Cox, Gary M; Holland, David P; Naggie, Susanna; Piedrahita, Carla; Mosher, Ann; Torres, Yvonne; Norton, Brianna L; Suchindran, Sujit; Park, Paul H; Turner, Debbie; Stout, Jason EOBJECTIVE: To determine the feasibility and case detection rate of a geographic information systems (GIS)-based integrated community screening strategy for tuberculosis, syphilis, and human immunodeficiency virus (HIV). DESIGN: Prospective cross-sectional study of all participants presenting to geographic hot spot screenings in Wake County, North Carolina. METHODS: The residences of tuberculosis, HIV, and syphilis cases incident between 1/1/05-12/31/07 were mapped. Areas with high densities of all 3 diseases were designated "hot spots." Combined screening for tuberculosis, HIV, and syphilis were conducted at the hot spots; participants with positive tests were referred to the health department. RESULTS AND CONCLUSIONS: Participants (N = 247) reported high-risk characteristics: 67% previously incarcerated, 40% had lived in a homeless shelter, and 29% had a history of crack cocaine use. However, 34% reported never having been tested for HIV, and 41% did not recall prior tuberculin skin testing. Screening identified 3% (8/240) of participants with HIV infection, 1% (3/239) with untreated syphilis, and 15% (36/234) with latent tuberculosis infection. Of the eight persons with HIV, one was newly diagnosed and co-infected with latent tuberculosis; he was treated for latent TB and linked to an HIV provider. Two other HIV-positive persons had fallen out of care, and as a result of the study were linked back into HIV clinics. Of 27 persons with latent tuberculosis offered therapy, nine initiated and three completed treatment. GIS-based screening can effectively penetrate populations with high disease burden and poor healthcare access. Linkage to care remains challenging and will require creative interventions to impact morbidity.Item Open Access Health Care Utilization Behaviors Predict Disengagement From HIV Care: A Latent Class Analysis.(Open forum infectious diseases, 2018-05) Okeke, Nwora Lance; Clement, Meredith E; McKellar, Mehri S; Stout, Jason EBackground
The traditional definition of engagement in HIV care in terms of only clinic attendance and viral suppression provides a limited understanding of how persons living with HIV (PLWH) interact with the health care system.Methods
We conducted a retrospective analysis of patients with ≥1 HIV clinic visits at the Duke Adult Infectious Diseases Clinic between 2008 and 2013. Health care utilization was characterized by 4 indicators: clinic attendance in each half of the year (yes/no), number of emergency department (ED) visits/year (0, 1, or 2+), inpatient admissions/year (0, 1, 2+), and viral suppression (never, intermittent, always). Health care engagement patterns were modeled using latent class/latent transition analysis.Results
A total of 2288 patients (median age, 46.4 years; 59% black, 71% male) were included in the analysis. Three care engagement classes were derived from the latent class model: "adherent" "nonadherent," and "sick." Patients age ≤40 years were more likely to be in the nonadherent class (odds ratio, 2.64; 95% confidence interval, 1.38-5.04) than other cohort members. Whites and males were more likely to transition from nonadherent to adherent the following year. Nonadherent patients were significantly more likely to disengage from care the subsequent year than adherent patients (23.6 vs 0.2%, P < .001).Conclusions
A broader definition of health care engagement revealed distinct and dynamic patterns among PLWH that would have been hidden had only previous HIV clinic attendance had been considered. These patterns may be useful for designing engagement-targeted interventions.Item Open Access Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis.(PloS one, 2022-01) Di Stefano, Leon; Ogburn, Elizabeth L; Ram, Malathi; Scharfstein, Daniel O; Li, Tianjing; Khanal, Preeti; Baksh, Sheriza N; McBee, Nichol; Gruber, Joshua; Gildea, Marianne R; Clark, Megan R; Goldenberg, Neil A; Bennani, Yussef; Brown, Samuel M; Buckel, Whitney R; Clement, Meredith E; Mulligan, Mark J; O'Halloran, Jane A; Rauseo, Adriana M; Self, Wesley H; Semler, Matthew W; Seto, Todd; Stout, Jason E; Ulrich, Robert J; Victory, Jennifer; Bierer, Barbara E; Hanley, Daniel F; Freilich, Daniel; Pandemic Response COVID-19 Research Collaboration Platform for HCQ/CQ Pooled AnalysesBackground
Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients.Methods
We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions.Results
Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively).Conclusions
The findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.Item Open Access Impact of the COVID-19 pandemic on adult mental health-related admissions at a large university health system in North Carolina - one year into the pandemic.(PloS one, 2023-01) Der, Tatyana; Helmke, Nicole; Stout, Jason E; Turner, Nicholas AObjective
Pandemic-associated stress may have exacerbated preexisting mental health and substance use disorders (MH/SUD) and caused new MH/SUD diagnoses which would be expected to lead to an increase in visits to emergency departments and hospital admissions for these conditions. This study assessed whether the proportion of hospital and emergency department encounters for MH/SUD diagnoses increased during the first year of the COVID-19 pandemic in the United States.Methods
We conducted a longitudinal (interrupted time series) analysis of 994,724 eligible encounters identified by electronic query between January 1, 2016 and March 31, 2021. Of these, 55,574 encounters involved MH/SUD diagnosis. The pre-pandemic period was defined as January 1, 2016 to March 31, 2020, and the pandemic period was defined as April 1, 2020 to March 31, 2021. All statistical analyses were performed with R.Results
No significant trend in MH/SUD encounters at baseline (rate ratio 1.00, 95% CI 0.99-1.01, p = 0.75) was observed. However, the onset of the pandemic was temporally associated with a significant level increase in the proportion of MH/SUD encounters relative to overall encounters (rate ratio 1.14, 95% CI 1.06-1.21, p<0.001) with no change in the overall trend (rate ratio 0.99, 95% CI 0.90-1.10, p = 0.89).Conclusions
The significant pandemic-associated increase in the proportion of MH/SUD encounters relative to overall encounters was driven largely by sustained numbers of MH/ SUD encounters despite a decrease in total encounters. Increased support for mental health care is needed for these vulnerable patients during pandemics.Item Open Access Incidence, Long-Term Outcomes, and Healthcare Utilization of Patients With Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome and Disseminated Mycobacterium avium Complex From 1992-2015.(Open Forum Infect Dis, 2017) Collins, Lauren F; Clement, Meredith E; Stout, Jason EBACKGROUND: Despite the advent of combination antiretroviral therapy (cART), patients with human immunodeficiency virus (HIV) continue to develop late-stage complications including acquired immune deficiency syndrome (AIDS), disseminated Mycobacterium avium complex (DMAC), and death. METHODS: We performed an observational retrospective cohort study of HIV-infected adults who developed DMAC in the Duke University Health System from 1992 to 2015 to determine the incidence, long-term outcomes, and healthcare utilization of this population at high risk for poor outcomes. Findings were stratified by the "pre-cART" era (before January 1, 1996) and "post-cART" thereafter. RESULTS: We identified 330 adult HIV-infected patients newly diagnosed with DMAC, the majority (75.2%) of whom were male and non-Hispanic black (69.1%), with median age of 37 years. Incidence of DMAC declined significantly from 65.3/1000 in 1992 to 2.0/1000 in 2015, and the proportion of females and non-Hispanic blacks was significantly higher in the post-cART era. The standardized mortality ratios for DMAC patients who received cART were 69, 58, 27, 5.9, and 6.8 at years 1-5, respectively, after DMAC diagnosis. For patients diagnosed with DMAC in 2000 or later (n = 135), 20% were newly diagnosed with HIV in the 3 months preceding presentation with DMAC. Those with established HIV had a median time from HIV diagnosis to DMAC diagnosis of 7 years and were more likely to be black, rehospitalized in the 6 months after DMAC diagnosis, and die in the long term. CONCLUSIONS: Disseminated Mycobacterium avium complex continues to be a lethal diagnosis in the cART era, disproportionately afflicts minority populations, and reflects both delayed entry into care and failure to consistently engage care.