Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-27 (of 27 Records) |
Query Trace: Dooley S[original query] |
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Pharmacokinetic-pharmacodynamic evidence from a phase 3 trial to support flat-dosing of rifampicin for tuberculosis
Ngo HX , Xu AY , Velásquez GE , Zhang N , Chang VK , Kurbatova EV , Whitworth WC , Sizemore E , Bryant K , Carr W , Weiner M , Dooley KE , Engle M , Dorman SE , Nahid P , Swindells S , Chaisson RE , Nsubuga P , Lourens M , Dawson R , Savic RM . Clin Infect Dis 2024 BACKGROUND: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the Phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes. METHODS: We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months, TB-related unfavorable outcomes at 9, 12, and 18 months using Cox proportional hazard models, and all trial-defined safety outcomes using logistic regression. RESULTS: Our model derived rifampicin exposure ranged from 4.57 mg·h/L to 140.0 mg·h/L with a median of 41.8 mg·h/L. Pharmacokinetic simulations demonstrated that flat-dosed rifampicin provided exposure coverage similar to weight-banded dose. Exposure-efficacy analysis (N=680) showed that participants with rifampicin exposure below the median experienced similar hazards of stable culture conversion and TB-related unfavorable outcomes compared to those with exposure above the median. Exposure-safety analysis (N=722) showed that increased rifampicin exposure was not associated with increased grade 3 or higher adverse events, or serious adverse events. CONCLUSIONS: Flat-dosing of rifampicin at 600 mg daily may be a reasonable alternative to the incumbent weight-banded dosing strategy for the standard of care 6-month regimen. Future research should assess the optimal dosing strategy for rifampicin, at doses higher than the current recommendation. |
Novel regimens of bedaquiline-pyrazinamide combined with moxifloxacin, rifabutin, delamanid and/or OPC-167832 in murine tuberculosis models (preprint)
Tasneen R , Garcia A , Converse PJ , Zimmerman MD , Dartois V , Kurbatova E , Vernon AA , Carr W , Stout JE , Dooley KE , Nuermberger EL . bioRxiv 2021 23 A recent landmark trial showed a 4-month regimen of rifapentine, pyrazinamide, moxifloxacin and isoniazid (PZMH) to be non-inferior to the 6-month standard of care. Here, two murine models of tuberculosis were used to test whether novel regimens replacing rifapentine and isoniazid with bedaquiline and another drug would maintain or increase the sterilizing activity of the regimen. In BALB/c mice, replacing rifapentine in the PZM backbone with bedaquiline (i.e., BZM) significantly reduced both lung CFU counts after 1 month and the proportion of mice relapsing within 3 months after completing 1.5 months of treatment. Addition of rifabutin to BZM (BZMRb) further increased the sterilizing activity. In the C3HeB/FeJ mouse model characterized by caseating lung lesions, treatment with BZMRb resulted in significantly fewer relapses than PZMH after 2 months of treatment. A regimen combining the new DprE1 inhibitor OPC-167832 and delamanid (BZOD) also had superior bactericidal and sterilizing activity compared to PZM in BALB/c mice and was similar in efficacy to PZMH in C3HeB/FeJ mice. Thus, BZM represents a promising backbone for treatment-shortening regimens. Given the prohibitive drug-drug interactions between bedaquiline and rifampin or rifapentine, the BZMRb regimen represents the best opportunity to combine, in one regimen, the treatment-shortening potential of the rifamycin class with that of BZM and deserves high priority for evaluation in clinical trials. Other 4-drug BZM-based regimens and BZOD represent promising opportunities for extending the spectrum of treatment-shortening regimens to rifamycin- and fluoroquinolone-resistant tuberculosis. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. |
Prospective association of daily steps with cardiovascular disease: A harmonized meta-analysis
Paluch AE , Bajpai S , Ballin M , Bassett DR , Buford TW , Carnethon MR , Chernofsky A , Dooley EE , Ekelund U , Evenson KR , Galuska DA , Jefferis BJ , Kong L , Kraus WE , Larson MG , Lee IM , Matthews CE , Newton RL Jr , Nordström A , Nordström P , Palta P , Patel AV , Pettee Gabriel K , Pieper CF , Pompeii L , Rees-Punia E , Spartano NL , Vasan RS , Whincup PH , Yang S , Fulton JE . Circulation 2022 147 (2) 122-131 BACKGROUND: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines. METHODS: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance-weighted random effects models. RESULTS: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults. CONCLUSIONS: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician-patient communication and population health to reduce the risk of CVD. |
Rifapentine with and without moxifloxacin for pulmonary tuberculosis in people with HIV (S31/A5349)
Pettit AC , Phillips PP , Kurbatova E , Vernon A , Nahid P , Dawson R , Dooley KE , Sanne I , Waja Z , Mohapi L , Podany AT , Samaneka W , Savic RM , Johnson JL , Muzanyi G , Lalloo UG , Bryant K , Sizemore E , Scott N , Dorman SE , Chaisson RE , Swindells S . Clin Infect Dis 2022 76 (3) e580-e589 BACKGROUND: Tuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 non-inferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had non-inferior efficacy and was safe for the treatment of drug-susceptible pulmonary TB (DS-PTB) compared with the standard 6-month regimen. We explored results among the pre-specified subgroup of people with HIV (PWH). METHODS: PWH and CD4 + counts ≥100 cells/μL were eligible if they were receiving or about to initiate efavirenz-based antiretroviral therapy (ART). Primary endpoints of TB disease-free survival 12 months post-randomization (efficacy) and ≥ grade 3 adverse events (AEs) on treatment (safety) were compared, using a 6.6% non-inferiority margin for efficacy. Randomization was stratified by site, pulmonary cavitation, and HIV-status. PWH were enrolled in a staged fashion, to support cautious evaluation of drug-drug interactions between rifapentine and efavirenz. RESULTS: 2,516 participants from 13 countries in sub-Saharan Africa, Asia, and the Americas were enrolled. Among 194 (8%) microbiologically eligible PWH, the median CD4 + count was 344 cells/μL (interquartile range: 223-455). The rifapentine-moxifloxacin regimen was non-inferior to control (absolute difference in unfavorable outcomes -7.4% [95% CI -20.8% to +6.0%]); the rifapentine regimen was not non-inferior to control (+7.5% [95% CI -7.3% to +22.4%]). Fewer AEs were reported in rifapentine-based regimens (15%) than the control regimen (21%). CONCLUSIONS: In people with HIV-associated DS-PTB with CD4 + counts ≥100 cells/μL on efavirenz-based ART, the 4-month daily rifapentine-moxifloxacin regimen was non-inferior to the 6-month control regimen and was safe. |
Novel regimens of bedaquiline-pyrazinamide combined with moxifloxacin, rifabutin, delamanid and/or OPC-167832 in murine tuberculosis models
Tasneen R , Garcia A , Converse PJ , Zimmerman MD , Dartois V , Kurbatova E , Vernon AA , Carr W , Stout JE , Dooley KE , Nuermberger EL . Antimicrob Agents Chemother 2022 66 (4) e0239821 A recent landmark trial showed a 4-month regimen of rifapentine, pyrazinamide, moxifloxacin, and isoniazid (PZMH) to be noninferior to the 6-month standard of care. Here, two murine models of tuberculosis were used to test whether novel regimens replacing rifapentine and isoniazid with bedaquiline and another drug would maintain or increase the sterilizing activity of the regimen. In BALB/c mice, replacing rifapentine in the PZM backbone with bedaquiline (i.e., BZM) significantly reduced both lung CFU counts after 1 month and the proportion of mice relapsing within 3 months after completing 1.5 months of treatment. The addition of rifabutin to BZM (BZMRb) further increased the sterilizing activity. In the C3HeB/FeJ mouse model characterized by caseating lung lesions, treatment with BZMRb resulted in significantly fewer relapses than PZMH after 2 months of treatment. A regimen combining the new DprE1 inhibitor OPC-167832 and delamanid (BZOD) also had superior bactericidal and sterilizing activity compared to PZM in BALB/c mice and was similar in efficacy to PZMH in C3HeB/FeJ mice. Thus, BZM represents a promising backbone for treatment-shortening regimens. Given the prohibitive drug-drug interactions between bedaquiline and rifampin or rifapentine, the BZMRb regimen represents the best opportunity to combine, in one regimen, the treatment-shortening potential of the rifamycin class with that of BZM and deserves high priority for evaluation in clinical trials. Other 4-drug BZM-based regimens and BZOD represent promising opportunities for extending the spectrum of treatment-shortening regimens to rifamycin- and fluoroquinolone-resistant tuberculosis. |
Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts
Paluch AE , Bajpai S , Bassett DR , Carnethon MR , Ekelund U , Evenson KR , Galuska DA , Jefferis BJ , Kraus WE , Lee IM , Matthews CE , Omura JD , Patel AV , Pieper CF , Rees-Punia E , Dallmeier D , Klenk J , Whincup PH , Dooley EE , PetteeGabriel K , Palta P , Pompeii LA , Chernofsky A , Larson MG , Vasan RS , Spartano N , Ballin M , Nordstrm P , Nordstrm A , Anderssen SA , Hansen BH , Cochrane JA , Dwyer T , Wang J , Ferrucci L , Liu F , Schrack J , Urbanek J , Saint-Maurice PF , Yamamoto N , Yoshitake Y , Newton RLJr , Yang S , Shiroma EJ , Fulton JE . Lancet Public Health 2022 7 (3) e219-e228 BACKGROUND: Although 10000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged 18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models. FINDINGS: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47471 adults, among whom there were 3013 deaths (101 per 1000 participant-years) over a median follow-up of 71 years ([IQR 43-99]; total sum of follow-up across studies was 297837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 060 (95% CI 051-071) for quartile 2, 055 (049-062) for quartile 3, and 047 (039-057) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 067 [95% CI 056-083]) and a peak of 60 min (067 [050-090]), but not significant for time (min per day) spent walking at 40 steps per min or faster (112 [096-132]) and 100 steps per min or faster (086 [058-128]). INTERPRETATION: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity. FUNDING: US Centers for Disease Control and Prevention. |
Future-proofing and maximizing the utility of metadata: The PHA4GE SARS-CoV-2 contextual data specification package.
Griffiths EJ , Timme RE , Mendes CI , Page AJ , Alikhan NF , Fornika D , Maguire F , Campos J , Park D , Olawoye IB , Oluniyi PE , Anderson D , Christoffels A , da Silva AG , Cameron R , Dooley D , Katz LS , Black A , Karsch-Mizrachi I , Barrett T , Johnston A , Connor TR , Nicholls SM , Witney AA , Tyson GH , Tausch SH , Raphenya AR , Alcock B , Aanensen DM , Hodcroft E , Hsiao WWL , Vasconcelos ATR , MacCannell DR . Gigascience 2022 11 BACKGROUND: The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools and resources, and advocate for greater openness, interoperability, accessibility, and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a need for a fit-for-purpose, open-source SARS-CoV-2 contextual data standard. RESULTS: As such, we have developed a SARS-CoV-2 contextual data specification package based on harmonizable, publicly available community standards. The specification can be implemented via a collection template, as well as an array of protocols and tools to support both the harmonization and submission of sequence data and contextual information to public biorepositories. CONCLUSIONS: Well-structured, rich contextual data add value, promote reuse, and enable aggregation and integration of disparate datasets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19. The package is now supported by the NCBI's BioSample database. |
Efavirenz pharmacokinetics and HIV-1 viral suppression among patients receiving TB treatment containing daily high-dose rifapentine
Podany AT , Pham M , Sizemore E , Martinson N , Samaneka W , Mohapi L , Badal-Faesen S , Dawson R , Johnson JL , Mayanja H , Lalloo U , Whitworth WC , Pettit A , Campbell K , Phillips P , Bryant K , Scott N , Vernon A , Kurbatova E , Chaisson RE , Dorman S , Nahid P , Swindells S , Dooley KE , Fletcher CV . Clin Infect Dis 2021 75 (4) 560-566 BACKGROUND: A four-month regimen containing rifapentine and moxifloxacin has non-inferior efficacy compared to the standard 6-month regimen for drug-sensitive tuberculosis. We evaluated the effect of regimens containing daily, high-dose rifapentine on efavirenz pharmacokinetics and viral suppression in patients with HIV-associated TB. METHODS: In the context of a Phase 3 randomized controlled trial, HIV-positive individuals already virally suppressed on efavirenz--containing ART (EFV1), or newly initiating efavirenz (EFV2) received TB treatment containing rifapentine (1200mg), isoniazid, pyrazinamide, and either ethambutol or moxifloxacin. Mid-interval efavirenz concentrations were measured (a) during ART and TB co-treatment (Weeks 4, 8, 12 and 17, different by EFV group) and (b) when ART was taken alone (pre- or post-TB treatment, Weeks 0 and 22). Apparent oral clearance (CL/F) was estimated and compared. Target mid-interval efavirenz concentrations were > 1 mg/L. Co-treatment was considered acceptable if >80% of participants had mid-interval efavirenz concentrations meeting this target. RESULTS: EFV1 and EFV2 included 70 and 41 evaluable participants, respectively. The geometric mean ratio comparing efavirenz CL/F with vs. without TB drugs was 0.79 [90% CI 0.72-0.85] in EFV1 and 0.84 [90% CI 0.69-0.97] in EFV2. The percent of participants with mid-interval efavirenz concentrations >1mg/L in EFV1 at Weeks 0, 4, 8, and 17 was 96%, 96%, 88%, and 89%, respectively. In EFV2, at approximately 4 and 8 weeks post efavirenz initiation, the value was 98%. CONCLUSIONS: TB treatment containing high-dose daily rifapentine modestly decreased (rather than increased) efavirenz clearance and therapeutic targets were met supporting the use of efavirenz with these regimens, without dose adjustment. |
Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis
Dorman SE , Nahid P , Kurbatova EV , Phillips PPJ , Bryant K , Dooley KE , Engle M , Goldberg SV , Phan HTT , Hakim J , Johnson JL , Lourens M , Martinson NA , Muzanyi G , Narunsky K , Nerette S , Nguyen NV , Pham TH , Pierre S , Purfield AE , Samaneka W , Savic RM , Sanne I , Scott NA , Shenje J , Sizemore E , Vernon A , Waja Z , Weiner M , Swindells S , Chaisson RE . N Engl J Med 2021 384 (18) 1705-1718 BACKGROUND: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. METHODS: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months. RESULTS: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group. CONCLUSIONS: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.). |
Optimising pyrazinamide for the treatment of tuberculosis
Zhang N , Savic RM , Boeree MJ , Peloquin C , Weiner M , Heinrich N , Bliven-Sizemore E , Phillips PP , Hoelscher M , Whitworth W , Morlock G , Posey J , Stout JE , Mac Kenzie W , Aarnoutse R , Dooley KE . Eur Respir J 2021 58 (1) Pyrazinamide is a potent sterilising agent that shortens the treatment duration needed to cure tuberculosis. It is synergistic with novel and existing drugs for tuberculosis. The dose of pyrazinamide that optimises efficacy while remaining safe is uncertain, as is its potential role in shortening treatment duration further.Pharmacokinetic data, sputum culture, and safety laboratory results were compiled from TBTC Studies 27 and 28 and PanACEA MAMS-TB, multi-center Phase 2 trials in which participants received rifampicin (range 10-35 mg·kg(-1)), pyrazinamide (range 20-30 mg·kg(-1)), plus two companion drugs. Pyrazinamide pharmacokinetic-pharmacodynamic (PK/PD) and PK-toxicity analyses were performed.In TBTC studies (n=77), higher pyrazinamide maximum concentration (Cmax) was associated with shorter time to culture conversion (TTCC) and higher probability of two-month culture conversion (p-value<0.001). Parametric survival analyses showed that relationships varied geographically, with steeper PK-PD relationships seen among non-African than African participants. In PanACEA MAMS-TB (n=363), TTCC decreased as pyrazinamide Cmax increased and varied by rifampicin Cmax (p-value<0.01). Modeling and simulation suggested that very high doses of pyrazinamide (>4500 mg) or increasing both pyrazinamide and rifampicin would be required to reach targets associated with treatment shortening. Combining all trials, liver toxicity was rare (3.9% with Grade 3 or higher liver function tests, LFT), and no relationship was seen between pyrazinamide Cmax and LFT levels.Pyrazinamide's microbiologic efficacy increases with increasing drug concentrations. Optimising pyrazinamide alone, though, is unlikely to be sufficient to allow tuberculosis treatment shortening; rather, rifampicin dose would need to be increased in parallel. |
High-dose rifapentine with or without moxifloxacin for shortening treatment of pulmonary tuberculosis: Study protocol for TBTC study 31/ACTG A5349 phase 3 clinical trial
Dorman SE , Nahid P , Kurbatova EV , Goldberg SV , Bozeman L , Burman WJ , Chang KC , Chen M , Cotton M , Dooley KE , Engle M , Feng PJ , Fletcher CV , Ha P , Heilig CM , Johnson JL , Lessem E , Metchock B , Miro JM , Nhung NV , Pettit AC , Phillips PPJ , Podany AT , Purfield AE , Robergeau K , Samaneka W , Scott NA , Sizemore E , Vernon A , Weiner M , Swindells S , Chaisson RE . Contemp Clin Trials 2020 90 105938 INTRODUCTION: Phase 2 clinical trials of tuberculosis treatment have shown that once-daily regimens in which rifampin is replaced by high dose rifapentine have potent antimicrobial activity that may be sufficient to shorten overall treatment duration. Herein we describe the design of an ongoing phase 3 clinical trial testing the hypothesis that once-daily regimens containing high dose rifapentine in combination with other anti-tuberculosis drugs administered for four months can achieve cure rates not worse than the conventional six-month treatment regimen. METHODS/DESIGN: S31/A5349 is a multicenter randomized controlled phase 3 non-inferiority trial that compares two four-month regimens with the standard six-month regimen for treating drug-susceptible pulmonary tuberculosis in HIV-negative and HIV-positive patients. Both of the four-month regimens contain high-dose rifapentine instead of rifampin, with ethambutol replaced by moxifloxacin in one regimen. All drugs are administered seven days per week, and under direct observation at least five days per week. The primary outcome is tuberculosis disease-free survival at twelve months after study treatment assignment. A total of 2500 participants will be randomized; this gives 90% power to show non-inferiority with a 6.6% margin of non-inferiority. DISCUSSION: This phase 3 trial formally tests the hypothesis that augmentation of rifamycin exposures can shorten tuberculosis treatment to four months. Trial design and standardized implementation optimize the likelihood of obtaining valid results. Results of this trial may have important implications for clinical management of tuberculosis at both individual and programmatic levels. TRIAL REGISTRATION: NCT02410772. Registered 8 April 2015,https://www.clinicaltrials.gov/ct2/show/NCT02410772?term=02410772&rank=1. |
Knowledge, attitudes, and practices among veterinarians during an outbreak of canine leptospirosis-Maricopa County, Arizona, 2017
LaFerla Jenni M , Woodward P , Yaglom H , Levy C , Iverson SA , Kretschmer M , Jarrett N , Dooley E , Narang J , Venkat H . Prev Vet Med 2019 172 104779 Leptospirosis, caused by Leptospira spp., is a zoonotic bacterial disease important to both human and animal health. Six pathogenic serovars are currently known to commonly infect and cause disease in dogs in the United States. While canine leptospirosis infection is historically rare in Arizona (</=5 cases reported annually) (ADHS unpublished data) several clusters were reported in Maricopa County (MC) during February 2016-January 2017. Public health initiated an outbreak response and developed a knowledge, attitudes, and practices survey for veterinarians. The goals were to determine awareness and general attitudes about canine leptospirosis and to identify gaps in veterinarians' knowledge in treatment and prevention. We distributed a 40-question self-administered online survey to 1058 Arizona Veterinary Medical Association members, made available during February 9-May 15, 2017. We analyzed the results using Pearson's Chi-squared or Fisher's exact test; a P-value <0.05 was considered statistically significant. We analyzed 202 complete responses. Veterinarians from 10 (66%) of 15 Arizona counties were represented. MC practices were more likely to stock leptospirosis vaccine (80%) than other counties combined (58%) (P=0.004). The average composite knowledge score was 24.4 out of 38 (range 12-37, median 24); 49% of respondents demonstrated higher knowledge as defined by authors, largely in identification of leptospirosis risk factors (86%) and routes of exposure (73%). Fewer than half (45%) of respondents correctly identified the length of time bacteria can be shed in dogs' urine. Eighty-one percent of respondents demonstrated lower knowledge about clinical signs associated with leptospirosis; only 47% of respondents identified eight clinical signs commonly associated with leptospirosis. Sixty-one percent of MC respondents agreed that leptospirosis is an important canine disease in their geographic area, while only 40% of other county respondents agreed (P=0.03). Seventy percent of respondents identified diagnostic testing options. The majority correctly selected infection-control practices in line with recommendations from 2 national clinical guidelines. More respondents would recommend leptospirosis vaccination if dogs traveled or lived in rural areas (87-96%) than if dogs attended day care or were boarded (63%). We identified opportunities for education, including the local epidemiology of leptospirosis, transmission prevention strategies, vaccine safety, testing, clinical identification, and emerging risk factors. Our findings will help guide the design of educational materials for small animal veterinarians in Arizona regarding recommendations for prevention of animal and human leptospirosis infections; these efforts could also shift the culture of reporting companion animal diseases to improve future One Health collaborations. |
HIV data to care-using public health data to improve HIV care and prevention
Sweeney P , DiNenno EA , Flores SA , Dooley S , Shouse RL , Muckleroy S , Margolis AD . J Acquir Immune Defic Syndr 2019 82 Suppl 1 S1-s5 BACKGROUND: "Data to Care" (D2C) is a public health strategy that uses surveillance and other data to improve continuity of HIV care for persons with HIV (PWH) by identifying those who are in need of medical care or other services and facilitating linkage to these services. The primary goal of D2C is to increase the number of PWH who are engaged in care and virally suppressed. METHODS: Data to Care can be implemented using several approaches. Surveillance-based D2C is usually initiated by health departments, using HIV surveillance and other data to identify those not in care. Health care providers may also initiate D2C by identifying patients who may have fallen out of care and working collaboratively with health departments to investigate, locate, and relink the patients to medical care or other needed services. RESULTS: Although D2C is a relatively new strategy, health department D2C programs have reported both promising results (eg, improved surveillance data quality and successful linkage to or re-engagement in care for PWH) and challenges (eg, incomplete or inaccurate data in surveillance systems, barriers to data sharing, and limitations of existing data systems). CONCLUSIONS: Data to Care is expected to enable health departments to move closer toward achieving national HIV prevention goals. However, additional information on appropriate implementation practices at each step of the D2C process is needed. This JAIDS Special Supplement explores how CDC funding to state health departments (eg, technical assistance and demonstration projects), and partnerships across federal agencies, are advancing our knowledge of D2C. |
Using 3 health surveys to compare multilevel models for small area estimation for chronic diseases and health behaviors
Wang Y , Holt JB , Xu F , Zhang X , Dooley DP , Lu H , Croft JB . Prev Chronic Dis 2018 15 E133 BACKGROUND: We used a multilevel regression and poststratification approach to generate estimates of health-related outcomes using Behavioral Risk Factor Surveillance System 2013 (BRFSS) data for the 500 US cities. We conducted an empirical study to investigate whether the approach is robust using different health surveys. METHODS: We constructed a multilevel logistic model with individual-level age, sex, and race/ethnicity as predictors (Model I), and sequentially added educational attainment (Model II) and area-level poverty (Model III) for 5 health-related outcomes using the nationwide BRFSS, the Massachusetts BRFSS 2013 (a state subset of nationwide BRFSS), and the Boston BRFSS 2010/2013 (an independent survey), respectively. We applied each model to the Boston population (2010 Census) to predict each outcome in Boston and compared each with corresponding Boston BRFSS direct estimates. RESULTS: Using Model I for the nationwide BRFSS, estimates of diabetes, high blood pressure, physical inactivity, and binge drinking fell within the 95% confidence interval of corresponding Boston BRFSS direct estimates. Adding educational attainment and county-level poverty (Models II and III) further improved their accuracy, particularly for current smoking (the model-based estimate was 15.2% by Model I and 18.1% by Model II). The estimates based on state BRFSS and Boston BRFSS models were similar to those based on the nationwide BRFSS, but area-level poverty did not improve the estimates significantly. CONCLUSION: The estimates of health-related outcomes were similar using different health surveys. Model specification could vary by surveys with different geographic coverage. |
Comparison of methods for estimating prevalence of chronic diseases and health behaviors for small geographic areas: Boston validation study, 2013
Wang Y , Holt JB , Zhang X , Lu H , Shah SN , Dooley DP , Matthews KA , Croft JB . Prev Chronic Dis 2017 14 E99 INTRODUCTION: Local health authorities need small-area estimates for prevalence of chronic diseases and health behaviors for multiple purposes. We generated city-level and census-tract-level prevalence estimates of 27 measures for the 500 largest US cities. METHODS: To validate the methodology, we constructed multilevel logistic regressions to predict 10 selected health indicators among adults aged 18 years or older by using 2013 Behavioral Risk Factor Surveillance System (BRFSS) data; we applied their predicted probabilities to census population data to generate city-level, neighborhood-level, and zip-code-level estimates for the city of Boston, Massachusetts. RESULTS: By comparing the predicted estimates with their corresponding direct estimates from a locally administered survey (Boston BRFSS 2010 and 2013), we found that our model-based estimates for most of the selected health indicators at the city level were close to the direct estimates from the local survey. We also found strong correlation between the model-based estimates and direct survey estimates at neighborhood and zip code levels for most indicators. CONCLUSION: Findings suggest that our model-based estimates are reliable and valid at the city level for certain health outcomes. Local health authorities can use the neighborhood-level estimates if high quality local health survey data are not otherwise available. |
Population pharmacokinetics of pyrazinamide in patients with tuberculosis
Alsultan A , Savic R , Dooley KE , Weiner M , Whitworth W , Mac Kenzie WR , Peloquin CA . Antimicrob Agents Chemother 2017 61 (6) The current treatment used for tuberculosis (TB) is lengthy and needs to be shortened and improved. Pyrazinamide (PZA) has potent sterilizing activity and has the potential to shorten TB treatment duration, if optimized. The goals of this study were (a) to develop a population pharmacokinetic (PK) model for PZA among patients enrolled in PK sub-studies of Tuberculosis Trial Consortium (TBTC) trials 27 and 28, and (b) to determine covariates that affect PZA PK. We also (c) performed simulations and target attainment analysis using the proposed targets of Cmax >35 mcg/ml or AUC >363 mcg*hr/ml to see if higher weight-based dosing could improve PZA efficacy. Seventy-two patients participated in the sub-studies. The mean (standard deviation, SD) maximum plasma concentration (Cmax) was 30.8 (7.4) mcg/ml, and the area under the concentration-versus-time curve (AUC0-24) was 307 mcg*hr/ml (83). A one-compartment open model best described PZA PK. Only body weight was a significant covariate for PZA clearance. Women had a lower V/F compared to men, and both Cl/F and V/F increased with body weight. Our simulations show that higher doses for PZA (>50mg/kg) are needed to achieve the therapeutic target of AUC/MIC >11.3 in >80% of patients, while doses >80mg/kg are needed for 90% target attainment, given specific assumptions about MIC determinations. For the therapeutic targets of Cmax >35 mcg/ml and/or AUC >363 mcg*hr/ml, doses in the range of 30-40 mg/kg are needed to achieve the therapeutic target in >90 % of the patients. Further clinical trials are needed to evaluate the safety and efficacy of higher doses for PZA.Reference in this manuscript to any specific commercial product, process, service, manufacturer, or company does not constitute endorsement or recommendation by the U.S. Government or CDC. The findings and conclusions are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. |
Defining the optimal dose of rifapentine for pulmonary tuberculosis: Exposure-response relations from two phase 2 clinical trials
Savic RM , Weiner M , Mac Kenzie WR , Engle M , Whitworth WC , Johnson JL , Nsubuga P , Nahid P , Nguyen NV , Peloquin CA , Dooley KE , Dorman SE . Clin Pharmacol Ther 2017 102 (2) 321-331 Rifapentine is a highly active antituberculosis antibiotic with treatment-shortening potential; however, exposure-response relations and the dose needed for maximal bactericidal activity have not been established. We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine (n = 405) with rifampin (n = 252) as part of intensive-phase therapy. Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed-effects modeling. Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy. Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus, black, male, or fasting when taking drug. Rifapentine exposure, large lung cavity size, and geographic region were independently associated with time to culture conversion in liquid media. Maximal treatment efficacy is likely achieved with rifapentine at 1200 mg daily. Patients with large lung cavities appear less responsive to treatment, even at high rifapentine doses. |
Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial
Dorman SE , Savic RM , Goldberg S , Stout JE , Schluger N , Muzanyi G , Johnson JL , Nahid P , Hecker EJ , Heilig CM , Bozeman L , Feng PJ , Moro RN , MacKenzie W , Dooley KE , Nuermberger EL , Vernon A , Weiner M . Am J Respir Crit Care Med 2015 191 (3) 333-43 RATIONALE: Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. OBJECTIVES: We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. METHODS: Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. MEASUREMENTS AND MAIN RESULTS: A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). CONCLUSIONS: Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629). |
Quantification of rifapentine, a potent anti-tuberculosis drug, from dried blood spot samples using liquid chromatographic-tandem mass spectrometric analysis
Parsons TL , Marzinke MA , Hoang T , Bliven-Sizemore E , Weiner M , Mac Kenzie W , Dorman SE , Dooley KE . Antimicrob Agents Chemother 2014 58 (11) 6747-57 Quantifying anti-tuberculosis drug concentrations in multinational trials currently requires collection of modest blood volumes, centrifugation, aliquoting of plasma, freezing, and keeping samples frozen during shipping. We prospectively enrolled healthy individuals into Tuberculosis Trials Consortium Study 29B, a Phase I dose escalation study of rifapentine, a rifamycin under evaluation in tuberculosis treatment trials. We developed a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for quantification of rifapentine in whole blood from dried blood spots (DBS) to facilitate pharmacokinetic/pharmacodynamic analyses in trials. Paired plasma and whole blood samples were collected by venipuncture; whole blood was spotted on Whatman 903(R) cards. Methods were optimized for plasma and then validated for DBS. The analytical measuring range was 50 to 80,000 ng/ml in whole blood DBS. Analytes were stable on cards for 11 weeks with desiccant at room temperature protected from light. Method concordance for paired plasma and whole blood DBS samples was determined after correcting for participant hematocrit or population-based estimates of bias from Bland-Altman plots. The application of either correction factor resulted in excellent correlation between plasma and whole blood DBS (Passing-Bablok regression corrected for hematocrit; y=0.98x+356). Concentrations of rifapentine may be determined from whole blood DBS collected via venipuncture after normalization to account for dilutional effects of red blood cells; additional studies are focused on the application of this methodology to capillary blood collected by finger stick. Simplicity of processing, storage, shipping and low blood volume makes whole blood DBS attractive for rifapentine pharmacokinetic evaluations, especially in international and pediatric trials. |
Population pharmacokinetics of rifapentine and desacetyl rifapentine in healthy volunteers: nonlinearities in clearance and bioavailability
Savic RM , Lu Y , Bliven-Sizemore E , Weiner M , Nuermberger E , Burman W , Dorman SE , Dooley KE . Antimicrob Agents Chemother 2014 58 (6) 3035-3042 Rifapentine is under active investigation as a potent drug that may help shorten the tuberculosis (TB) treatment duration. A previous rifapentine dose escalation study with daily dosing indicated a possible decrease in bioavailability as the dose increased and an increase in clearance over time for rifapentine and its active metabolite, desacetyl rifapentine. This study aimed to assess the effects of increasing doses on rifapentine absorption and bioavailability and to evaluate the clearance changes over 14 days. A population analysis was performed with nonlinear mixed-effects modeling. Absorption, time-varying clearance, bioavailability, and empirical and semimechanistic autoinduction models were investigated. A one-compartment model linked to a transit compartment absorption model best described the data. The bioavailability of rifapentine decreased linearly by 2.5% for each 100-mg increase in dose. The autoinduction model suggested a dose-independent linear increase in clearance of the parent drug and metabolite over time from 1.2 and 3.1 liters . h-1, respectively, after a single dose to 2.2 and 5.0 liters . h-1, respectively, after 14 once-daily doses, with no plateau being reached by day 14. In clinical trial simulations using the final model, rifapentine demonstrated less-than-dose-proportional pharmacokinetics, but there was no plateau in exposures over the dose range tested (450 to 1,800 mg), and divided dosing increased exposures significantly. Thus, the proposed compartmental model incorporating daily dosing of rifapentine over a wide range of doses and time-related changes in bioavailability and clearance provides a useful tool for estimation of drug exposure that can be used to optimize rifapentine dosing for TB treatment. |
Safety and pharmacokinetics of escalating daily doses of the antituberculosis drug rifapentine in healthy volunteers
Dooley KE , Bliven-Sizemore EE , Weiner M , Lu Y , Nuermberger EL , Hubbard WC , Fuchs EJ , Melia MT , Burman WJ , Dorman SE . Clin Pharmacol Ther 2012 91 (5) 881-8 Rifapentine (RPT) is an antituberculosis drug that may shorten treatment duration when substituted for rifampin (RIF). The maximal tolerated daily dose of RPT and its potential for cytochrome 3A4 induction and autoinduction at clinically relevant doses are unknown. In this phase I, dose-escalation study among healthy volunteers, daily doses as high as a prespecified maximum of 20 mg/kg/day were well tolerated. Steady-state RPT concentrations increased with dose from 5 to 15 mg/kg, but area under the plasma concentration-time curve (AUC(0-24)) and maximum concentration (C(max)) were similar in the 15- and 20-mg/kg cohorts. Although RPT pharmacokinetics (PK) appeared to be time-dependent, accumulation occurred with daily dosing. The mean AUC(0-12) of oral midazolam (MDZ), a cytochrome 3A (CYP3A) probe drug, was reduced by 93% with the coadministration of RPT and by 74% with the coadministration of RIF (P < 0.01). Changes in the oral clearance of MDZ did not vary by RPT dose. In conclusion, RPT was tolerated at doses as high as 20 mg/kg/day, its PK were less than dose-proportional, and its CYP3A induction was robust. |
"The anticipation alone could kill you": past and potential clients' perspectives on HIV testing in non-health care settings
Joseph HA , Fasula AM , Morgan RL , Stuckey A , Alvarez ME , Margolis A , Stratford D , Dooley SW . AIDS Educ Prev 2011 23 (6) 577-94 HIV testing in non-health care settings is an effective strategy for increasing the proportion of persons aware of their infection. We conducted 21 focus groups with 186 past and potential clients in five U.S. cities to explore attitudes and experiences related to HIV counseling and testing in non-health care settings. Qualitative analysis yielded several key themes. HIV-related stigma and fear emerged as a main theme throughout the discussions. Knowing one's HIV status quickly and accurately was of primary importance; HIV prevention counseling was secondary. Participants prioritized a supportive, nonjudgmental environment with adequate privacy and confidentiality. Provision of immediate emotional support, medical information, and linkage services to HIV-infected clients were considered essential. Staff with HIV-specific skills to address clients' emotional and informational needs was considered a strength of non-health care testing programs. Frequently, however, participants compared non-health care settings unfavorably to health care settings regarding privacy, competency, confidentiality, and test accuracy. Recommendations for enhancing counseling and testing services in non-health care settings are discussed. |
Return on public health investment: CDC's expanded HIV testing initiative
Hutchinson AB , Farnham PG , Duffy N , Wolitski RJ , Sansom SL , Dooley SW , Cleveland JC , Mermin JH . J Acquir Immune Defic Syndr 2011 59 (3) 281-6 BACKGROUND: Over a three-year period, CDC invested $102.3 million in a large-scale HIV testing program, the Expanded HIV Testing Initiative, for populations disproportionally affected by HIV. Policy makers, who must optimize public health given a set budget, are interested in the financial return on investment (ROI) of large-scale HIV testing. METHODS: We conducted an ROI analysis using expenditure and outcome data from the program. A health system perspective was used that included all program expenditures including medical costs of treating newly diagnosed patients. We incorporated benefits of HIV transmissions averted from persons diagnosed of their infection through the Initiative compared to when, on average, those persons would have been diagnosed without the Initiative (3 years later in the base case). HIV transmissions were derived from a published mathematical model of HIV transmission. In sensitivity analysis, we tested the effect of 1 -5 year alternate testing intervals and differences in the prevalence of undiagnosed HIV infection. RESULTS: Under the Initiative, 2.7 million persons were tested for HIV, there was a newly diagnosed HIV positivity rate of 0.7%, and an estimated 3,381 HIV infections were averted. It achieved a return of $1.95 for every dollar invested. ROI ranged from $1.46 - $2.01 for alternative testing intervals of one to five years and remained above $1 (positive return on investment) with a prevalence of undiagnosed HIV infection as low as 0.12%. CONCLUSION: The Expanded Testing Initiative yielded ROI values of >$1 under a broad range of sensitivity analyses and provides further support for large-scale HIV testing programs. |
Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: a report from the National Down Syndrome Project.
Bean LJH , Allen EG , Tinker SW , Hollis ND , Locke AE , Druschel C , Hobbs CA , O'Leary L , Romitti PA , Royle MH , Torfs CP , Dooley KJ , Freeman SB , Sherman SL . Birth Defects Res A Clin Mol Teratol 2011 91 (10) 885-93 BACKGROUND: Maternal folic acid supplementation has been associated with a reduced risk for neural tube defects and may be associated with a reduced risk for congenital heart defects and other birth defects. Individuals with Down syndrome are at high risk for congenital heart defects and have been shown to have abnormal folate metabolism. METHODS: As part of the population-based case-control National Down Syndrome Project, 1011 mothers of infants with Down syndrome reported their use of supplements containing folic acid. These data were used to determine whether a lack of periconceptional maternal folic acid supplementation is associated with congenital heart defects in Down syndrome. We used logistic regression to test the relationship between maternal folic acid supplementation and the frequency of specific heart defects correcting for maternal race or ethnicity, proband sex, maternal use of alcohol and cigarettes, and maternal age at conception. RESULTS: Lack of maternal folic acid supplementation was more frequent among infants with Down syndrome and atrioventricular septal defects (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.08-2.63; p = 0.011) or atrial septal defects (OR, 1.69; 95% CI, 1.11-2.58; p = 0.007) than among infants with Down syndrome and no heart defect. Preliminary evidence suggests that the patterns of association differ by race or ethnicity and sex of the proband. There was no statistically significant association with ventricular septal defects (OR, 1.26; 95% CI, 0.85-1.87; p = 0.124). CONCLUSIONS: Our results suggest that lack of maternal folic acid supplementation is associated with septal defects in infants with Down syndrome. (Birth Defects Research (Part A), 2011. (c) 2011 Wiley-Liss, Inc.) |
Total serum IgE levels in systemic lupus erythematosus and associations with childhood onset allergies
Parks C , Biagini R , Cooper G , Gilkeson G , Dooley M . Lupus 2010 19 (14) 1614-22 Elevated serum IgE has been described in systemic lupus erythematosus (SLE), but associations with disease risk and characteristics remain unresolved. We assessed total serum IgE levels and atopy (IgE > 100 IU/ml) in recently diagnosed SLE patients (n = 228) compared with population controls (n = 293) and in relation to disease activity, autoantibodies, clinical features, total immunoglobulins, C-reactive protein, and allergy history. Multivariate models estimated determinants of IgE and atopy in patients and controls, and associations of SLE with allergy and atopy. Total IgE levels were higher in patients than controls (median = 42 vs. 29 IU/ml); 32% of patients and 25% of controls were atopic (p = 0.06). IgE levels were significantly higher in non-Whites and patients reporting childhood onset (<18 years) asthma and hives, and in controls reporting childhood asthma, hay fever, eczema, and adult onset hives. After accounting for racial differences, atopy was not associated with SLE, nephritis, or other clinical and laboratory parameters. In sum, our findings provide limited evidence of a direct association between total serum IgE and SLE overall or with other disease characteristics after adjusting for demographic characteristics and allergy history. Future studies may want to explore potentially shared risk factors for development of allergy, atopy, and SLE. |
Increasing public health partner services for human immunodeficiency virus: results of a second national survey
Katz DA , Hogben M , Dooley Jr SW , Golden MR . Sex Transm Dis 2010 37 (8) 469-75 BACKGROUND: Recent US national efforts taken to prevent human immunodeficiency virus (HIV) infection have emphasized HIV case-finding, including partner services (PS). METHODS: We collected data on HIV PS procedures and outcomes in 2006 from health departments in US metropolitan areas with the highest number of cases of acquired immunodeficiency syndrome, gonorrhea, chlamydial infection, and primary and secondary syphilis, and compared our results with the data collected through a similar study carried out in 2001. RESULTS: Of the 71 eligible jurisdictions, 51 (72%) participated in this study. In 2006, health departments interviewed 11,270 (43%) of the 26,185 persons with newly reported HIV, which was an increase from the 32% reported in 2001 (P < 0.01). Among 10,498 potentially exposed partners, 2228 (21%) had been previously diagnosed with HIV, 803 (8%) were newly HIV-diagnosed, 3337 (32%) tested HIV-negative, and 4130 (39%) were not successfully notified, were notified but refused HIV testing and denied previous diagnosis, or did not have an outcome recorded. Combining data from all jurisdictions, public health staff needed to interview 13.6 persons with HIV to identify one new case of infection; this number was unchanged from 2001 (13.8; P = 0.75). CONCLUSION: In the United States, the proportion of persons diagnosed with HIV receiving PS has increased since 2001, whereas HIV case-finding yields have remained stable. Despite this, most people newly diagnosed with HIV still do not receive PS. |
An evaluation of the reliability of HIV partner notification disposition coding by disease intervention specialists in the United States
Katz DA , Hogben M , Dooley SW Jr , Golden MR . Sex Transm Dis 2009 36 (7) 459-62 BACKGROUND: The reliability of CDC HIV partner notification (PN) disposition codes has not been evaluated. METHODS: Disease Intervention Specialists (DIS) working for health departments in high HIV/STD-morbidity metropolitan areas completed a questionnaire that presented vignettes describing PN interviews. Questionnaires asked DIS to indicate whether they would record a disposition and what codes they would assign to each partner. RESULTS: A total of 136 DIS from 28 of 29 eligible states participated. Partner 1: The index case says he will inform his partner of his HIV diagnosis and, at follow-up, reports that the partner has tested negative. Seventeen percent of DIS indicated they would record a partner disposition. DIS used 7 different codes to define the PN outcomes. Partner 2: The index case says she will inform her partner, who attends the clinic, indicates no history of testing, and tests HIV-negative. 93% of DIS reported they would record a disposition, 90% of whom used code 6, "Not Previously Tested, New Negative." Partner 3: The index case with partner 2 (above) agrees to have DIS notify her second partner. When contacted, the partner tells DIS that he had previously tested negative and will arrange to be tested himself. He subsequently reports testing HIV-negative, but DIS do not confirm this. Seventy-three percent of DIS recorded a disposition for the partner, of whom 84% used code J, "Located, Refused Counseling and Testing." CONCLUSIONS: CDC HIV PN disposition codes are reliable for simple scenarios with verified outcomes, but less reliable when DIS elicit partner-reported outcomes. |
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