Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
Records 1-30 (of 57 Records) |
Query Trace: Carr W[original query] |
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Risk-stratified treatment for drug-susceptible pulmonary tuberculosis
Chang VK , Imperial MZ , Phillips PPJ , Velásquez GE , Nahid P , Vernon A , Kurbatova EV , Swindells S , Chaisson RE , Dorman SE , Johnson JL , Weiner M , Sizemore EE , Whitworth W , Carr W , Bryant KE , Burton D , Dooley KE , Engle M , Nsubuga P , Diacon AH , Nhung NV , Dawson R , Savic RM . Nat Commun 2024 15 (1) 9400 The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment. |
Pyrazinamide safety, efficacy, and dosing for treating drug-susceptible pulmonary tuberculosis: A phase 3, randomized, controlled clinical trial
Xu AY , Velásquez GE , Zhang N , Chang VK , Phillips PP , Nahid P , Dorman SE , Kurbatova EV , Whitworth WC , Sizemore E , Bryant K , Carr W , Brown NE , Engle ML , Nhung NV , Nsubuga P , Diacon A , Dooley KE , Chaisson RE , Swindells S , Savic RM . Am J Respir Crit Care Med 2024 RATIONALE: Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/ACTG A5349 represents the largest Phase 3 randomized controlled therapeutic trial to date for such investigation. OBJECTIVES: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure with efficacy and safety outcomes. We aimed to determine pyrazinamide dosing strategies that optimize risks and benefits. METHODS: We analyzed pyrazinamide steady-state pharmacokinetic data using population nonlinear mixed-effects models. We evaluated the contribution of pyrazinamide exposure to long-term efficacy using parametric time-to-event models and safety outcomes using logistic regression. We evaluated optimal dosing with therapeutic windows targeting ≥95% durable cure and safety within the observed proportion of the primary safety outcome. MEASUREMENTS AND MAIN RESULTS: Among 2255 participants with 6978 plasma samples, pyrazinamide displayed 7-fold exposure variability (151-1053 mg·h/L). Body weight was not a clinically relevant predictor of drug clearance and thus did not justify the need for weight-banded dosing. Both clinical and safety outcomes were associated with pyrazinamide exposure, resulting in a therapeutic window of 231-355 mg·h/L for the control and 226-349 mg·h/L for the rifapentine-moxifloxacin regimen. Flat dosing of pyrazinamide at 1000 mg would have permitted an additional 13.1% (n=96) participants allocated to the control and 9.2% (n=70) to the rifapentine-moxifloxacin regimen dosed within the therapeutic window, compared to the current weight-banded dosing. CONCLUSIONS: Flat dosing of pyrazinamide at 1000 mg daily would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT02410772. |
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. |
Cryogenic air supply feasibility for a confined space: Underground refuge alternative case study
Yan L , Yantek DS , DeGennaro CR , Srednicki JR , Lambie B , Carr J . ASME J Heat Mass Transf 2024 146 (3) A breathable air source is required for a confined space such as an underground refuge alternative (RA) when it is occupied. To minimize the risk of suffocation, federal regulations require that mechanisms be provided and procedures be included so that, within the refuge alternative, the oxygen concentration is maintained at levels between 18.5% and 23% for 96 h. The regulation also requires that, during use of the RA, the concentration of carbon dioxide should not exceed 1%, and the concentration of carbon monoxide should not exceed 25 ppm. The National Institute for Occupational Safety and Health (NIOSH) evaluated the cryogenic air supply's ability to provide breathable air for a refuge alternative. A propane smoker was used to simulate human breathing by burning propane gas which will consume O(2) and generate CO(2) and H(2)O. The rate of propane burned at the smoker was controlled to represent the O(2) consumption rate for the breathing of a certain number of people. Two 96-h tests were conducted in a sealed shipping container, which was used as a surrogate for a refuge alternative. While burning propane gas to simulate human oxygen consumption, cryogenic air was provided to the shipping container to determine if the cryogenic air supply would keep the O(2) level above 18.5% and CO(2) level below 1% inside the shipping container as required by the federal regulations pertaining to refuge alternatives. Both of the 96-h tests simulated the breathing of 21 persons. The first test used the oxygen consumption rate (1.32 cu ft of pure oxygen per hour per person) specified in federal regulations, while the second test used the oxygen consumption rate specified by (Bernard et al. 2018, "Estimation of Metabolic Heat Input for Refuge Alternative Thermal Testing and Simulation," Min. Eng., 70(8), pp. 50-54) (0.67 cu ft of pure oxygen per hour per person). The test data shows that during both 96-h tests, the oxygen level was maintained within a 21-23% range, and the CO(2) level was maintained below 1% (0.2-0.45%). The information in this paper could be useful when applying a cryogenic air supply as a breathable air source for an underground refuge alternative or other confined space. [DOI: 10.1115/1.4064062]. |
Factors affecting medical residents' decisions to work after call
Carr MM , Foreman AM , Friedel JE , O'Brien DC , Wirth O . J Patient Saf 2024 20 (1) 16-21 BACKGROUND: Accreditation Council for Graduate Medical Education (ACGME) work-hour restrictions (WHRs) are intended to improve patient safety by reducing resident fatigue. Compliance with ACGME WHRs is not universal. PURPOSE: The purpose of this study was to identify factors that influence residents' decisions to take a postcall day (PCD) off according to ACGME WHRs. METHODS: Residents (N = 433) at one university were emailed a link to a survey in 2019. The survey included demographic details and a Discrete Choice Experiment examining influences on resident decisions to take a PCD off. RESULTS: One hundred seventy-five residents (40.4%) responded to the survey; 113 residents (26%) completed the survey. Positive feedback from attending physicians about taking PCDs off in the past had the greatest impact on respondents' decisions to take a PCD off, increasing the probability by 27.3%, followed by chief resident comments about the resident looking tired (16.6% increase), and having never heard their attendings comment about PCDs off as either positive or negative (13.9% increase). Factors that had the largest effect on decreasing the probability of taking a PCD were negative feedback about taking PCDs off (14.3% decrease), continuity of care concerns (10.8% decrease), and whether the resident was looking forward to an assignment (7.9% decrease). CONCLUSIONS: The most important influencer of residents' decisions to take a PCD off was related to feedback from their attending physicians, suggesting that compliance with WHRs can be improved by focusing on the residency program's safety culture. |
Estimated costs of 4-month pulmonary tuberculosis treatment regimen, United States
Winston CA , Marks SM , Carr W . Emerg Infect Dis 2023 29 (10) 2102-2104 We estimated direct costs of a 4-month or 6-month regimen for drug-susceptible pulmonary tuberculosis treatment in the United States. Costs were $23,000 per person treated. Actual treatment costs will vary depending on examination and medication charges, as well as expenses associated with directly observed therapy. |
Outcomes up to age 36 months after congenital Zika virus infection-U.S. states
Neelam V , Woodworth KR , Chang DJ , Roth NM , Reynolds MR , Akosa A , Carr CP , Anderson KN , Mulkey SB , DeBiasi RL , Biddle C , Lee EH , Elmore AL , Scotland SJ , Sowunmi S , Longcore ND , Ahmed M , Langlois PH , Khuwaja S , Browne SE , Lind L , Shim K , Gosciminski M , Blumenfeld R , Khuntia S , Halai UA , Locklear A , Chan M , Willabus T , Tonzel J , Marzec NS , Barreto NA , Sanchez C , Fornoff J , Hale S , Nance A , Iguchi L , Adibhatla SN , Potts E , Schiffman E , Raman D , McDonald MF , Stricklin B , Ludwig E , Denson L , Contreras D , Romitti PA , Ferrell E , Marx M , Signs K , Cook A , Leedom VO , Beauregard S , Orantes LC , Cronquist L , Roush L , Godfred-Cato S , Gilboa SM , Meaney-Delman D , Honein MA , Moore CA , Tong VT . Pediatr Res 2023 BACKGROUND: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure. METHODS: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively. RESULTS: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay. CONCLUSION: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families. IMPACT: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models. |
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. |
Automating case reporting of chlamydia and gonorrhea to public health authorities in Illinois clinics: Implementation and evaluation of findings
Mishra N , Grant R , Patel MT , Guntupalli S , Hamilton A , Carr J , McKnight E , Wise W , deRoode D , Jellison J , Collins NV , Pérez A , Karki S . JMIR Public Health Surveill 2023 9 e38868 BACKGROUND: Chlamydia and gonorrhea cases continue to rise in Illinois, increasing by 16.4% and 70.9% in 2019, respectively, compared with 2015. Providers are required to report both chlamydia and gonorrhea, as mandated by public health laws. Manual reporting remains a huge burden; 90%-93% of cases were reported to Illinois Department of Public Health (IDPH) via electronic laboratory reporting (ELR), and the remaining were reported through web-based data entry platforms, faxes, and phone calls. However, cases reported via ELRs only contain information available to a laboratory facility and do not contain additional data needed for public health. Such data are typically found in an electronic health record (EHR). Electronic case reports (eCRs) were developed and automated the generation of case reports from EHRs to be reported to public health agencies. OBJECTIVE: Prior studies consolidated trigger criteria for eCRs, and compared with manual reporting, found it to be more complete. The goal of this project is to pilot standards-based eCR for chlamydia and gonorrhea. We evaluated the throughput, completeness, and timeliness of eCR compared to ELR, as well as the implementation experience at a large health center-controlled network in Illinois. METHODS: For this study, we selected 8 clinics located on the north, west, and south sides of Chicago to implement the eCRs; these cases were reported to IDPH. The study period was 52 days. The centralized EHR used by these clinics leveraged 2 of the 3 case detection scenarios, which were previously defined as the trigger, to generate an eCR. These messages were successfully transmitted via Health Level 7 electronic initial case report standard. Upon receipt by IDPH, these eCRs were parsed and housed in a staging database. RESULTS: During the study period, 183 eCRs representing 135 unique patients were received by IDPH. eCR reported 95% (n=113 cases) of all the chlamydia cases and 97% (n=70 cases) of all the gonorrhea cases reported from the participating clinical sites. eCR found an additional 14 (19%) cases of gonorrhea that were not reported via ELR. However, ELR reported an additional 6 cases of chlamydia and 2 cases of gonorrhea, which were not reported via eCR. ELR reported 100% of chlamydia cases but only 81% of gonorrhea cases. While key elements such as patient and provider names were complete in both eCR and ELR, eCR was found to report additional clinical data, including history of present illness, reason for visit, symptoms, diagnosis, and medications. CONCLUSIONS: eCR successfully identified and created automated reports for chlamydia and gonorrhea cases in the implementing clinics in Illinois. eCR demonstrated a more complete case report and represents a promising future of reducing provider burden for reporting cases while achieving greater semantic interoperability between health care systems and public health. |
Perceptions of fatigue and safety climate pertaining to residency duty-hour restrictions
Carr MM , Friedel J , O'Brien D , Foreman AM , Wirth O . Cureus 2022 14 (9) e28929 INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME), which sets the standards for residency training, instituted work-hour restrictions in 2003. Our purpose was to assess residents' perceptions of fatigue and local safety climate specific to these duty-hour restrictions. METHODS: All residents (N=433) at one university were emailed a link to a survey in 2019. The survey included demographic details, on-call descriptors, an 18-point climate survey (CS), and the 33-point Chalder Fatigue Questionnaire (CFQ). The CS was adapted from a commonly used safety climate scale and intended to measure the respondent's perceptions of their program's attitudes and practices around resident duty-hour compliance. A Pearson correlational analysis was used to determine if there were associations between the variables. RESULTS: Mean CS score was 12.89 (95% confidence interval, CI 12.32-13.46, N=164, 48.5%). Respondents were most likely to disagree with "Residents are told when they are at risk of working beyond ACGME duty-hour restrictions," where 57 (34.7%) disagreed or strongly disagreed. Mean CFQ score was 16.02 (95% CI 14.87-17.17, N=113, 26.1%). As the CS score improved, CFQ scores decreased indicating an inverse relationship between duty-hour climate and fatigue (r=-0.328, p<0.05). Having a protected post-call day off, and having either the Program Director, Chief Resident, or Senior Resident decide that a resident takes a post-call day off were all associated with higher CS scores. Conclusion: We found that the CS had good internal consistency and evidence of construct validity. An inverse relationship between CS score and fatigue suggests that the level of fatigue is higher among residents in programs where residents perceived that ACGME duty-hour compliance was less important. |
A rapid review of collision avoidance and warning technologies for mining haul trucks
Hrica Jonathan K , Bellanca Jennica L , Benbourenane Iman , Carr Jacob L , Homer John , Stabryla Kathleen M . Min Metall Explor 2022 39 (4) 1357-1389 Given the recent focus on powered haulage incidents within the US mining sector, an appraisal of collision avoidance/warning systems (CXSs) through the lens of the available research literature is timely. This paper describes a rapid review that identifies, characterizes, and classifies the research literature to evaluate the maturity of CXS technology through the application of a Technology Readiness Assessment. Systematic search methods were applied to three electronic databases, and relevant articles were identified through the application of inclusion and exclusion criteria. Sixty-four articles from 2000 to 2020 met these criteria and were categorized into seven CXS technology categories. Review and assessment of the articles indicates that much of the literature-based evidence for CXS technology lies within lower levels of maturity (i.e., components and prototypes tested under laboratory conditions and in relevant environments). However, less evidence exists for CXS technology at higher levels of maturity (i.e., complete systems evaluated within operational environments) despite the existence of commercial products in the marketplace. This lack of evidence at higher maturity levels within the scientific literature highlights the need for systematic peer-reviewed research to evaluate the performance of CXS technologies and demonstrate the efficacy of prototypes or commercial products, which could be fostered by more collaboration between academia, research institutions, manufacturers, and mining companies. Additionally, results of the review reveal that most of the literature relevant to CXS technologies is focused on vehicle-to-vehicle interactions. However, this contrasts with haul truck fatal accident statistics that indicate that most haul truck fatal accidents are due to vehicle-to-environment interactions (e.g., traveling through a berm). Lastly, the relatively small amount of literature and segmented nature of the included studies suggests that there is a need for incremental progress or more stepwise research that would facilitate the improvement of CXS technologies over time. This progression over time could be achieved through continued long-term interest and support for CXS technology research. 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. |
Public health response and medical management of internal contamination in past radiological or nuclear incidents: A narrative review
Li C , Alves Dos Reis A , Ansari A , Bertelli L , Carr Z , Dainiak N , Degteva M , Efimov A , Kalinich J , Kryuchkov V , Kukhta B , Kurihara O , Antonia Lopez M , Port M , Riddell T , Rump A , Sun Q , Tuo F , Youngman M , Zhang J . Environ Int 2022 163 107222 Following a radiological or nuclear emergency, workers, responders and the public may be internally contaminated with radionuclides. Screening, monitoring and assessing any internal contamination and providing necessary medical treatment, especially when a large number of individuals are involved, is challenging. Experience gained and lessons learned from the management of previous incidents would help to identify gaps in knowledge and capabilities on preparedness for and response to radiation emergencies. In this paper, eight large-scale and five workplace radiological and nuclear incidents are reviewed cross 14 technical areas, under the broader topics of emergency preparedness, emergency response and recovery processes. The review findings suggest that 1) new strategies, algorithms and technologies are explored for rapid screening of large populations; 2) exposure assessment and dose estimation in emergency response and dose reconstruction in recovery process are supported by complementary sources of information, including 'citizen science'; 3) surge capacity for monitoring and dose assessment is coordinated through national and international laboratory networks; 4) evidence-based guidelines for medical management and follow-up of internal contamination are urgently needed; 5) mechanisms for international and regional access to medical countermeasures are investigated and implemented; 6) long-term health and medical follow up programs are designed and justified; and 7) capabilities and capacity developed for emergency response are sustained through adequate resource allocation, routine non-emergency use of technical skills in regular exercises, training, and continuous improvement. |
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. |
Interim guidance: 4-month rifapentine-moxifloxacin regimen for the treatment of drug-susceptible pulmonary tuberculosis - United States, 2022
Carr W , Kurbatova E , Starks A , Goswami N , Allen L , Winston C . MMWR Morb Mortal Wkly Rep 2022 71 (8) 285-289 On May 5, 2021, CDC's Tuberculosis Trials Consortium and the National Institutes of Health (NIH)-sponsored AIDS Clinical Trials Group (ACTG) published results from a randomized controlled trial indicating that a 4-month regimen containing rifapentine (RPT), moxifloxacin (MOX), isoniazid (INH), and pyrazinamide (PZA) was as effective as the standard 6-month regimen for tuberculosis (TB) treatment (1). On the basis of these findings, CDC recommends the 4-month regimen as a treatment option for U.S. patients aged ≥12 years with drug-susceptible pulmonary TB and provides implementation considerations for this treatment regimen. |
Lessons Learned From a Centers for Disease Control and Prevention Virtual Partner Services Technical Assistance Pilot Project to Respond to a Local Syphilis Outbreak.
Davis C , Wright SS , Babcock M , Kingdon E , Broussard D , Oyervides O , Carr D . Sex Transm Dis 2022 49 (2) 166-168 A virtual partner services technical assistance (TA) project was piloted with the Minnesota Department of Health to address an ongoing syphilis outbreak. The TA reduced the health department's disease intervention specialist workload, achieved partner services outcomes comparable with in-person methods, and identified lessons learned to replicate with other jurisdictions. |
Perceptions of Safety Climate and Fatigue Related to ACGME Residency Duty Hour Restrictions in Otolaryngology Residents
Carr MM , Friedel JE , Foreman AM , O'Brien DC , Wirth O . Otolaryngol Head Neck Surg 2021 166 (1) 1945998211010108 OBJECTIVE: To compare otolaryngology residents' perceptions of safety climate with respect to duty hour compliance and self-perceived fatigue. STUDY DESIGN: Cross-sectional study. SETTING: Forty-one otolaryngology residencies distributed across the United States. METHODS: A national sample of otolaryngology residents was surveyed electronically in 2019. The survey included demographic details, on-call descriptors, an 18-point Safety Climate Survey (SCS) modified to measure perceptions of program attitudes and practices around resident duty hour compliance, and the 33-point Chalder Fatigue Questionnaire (CFQ). RESULTS: Of 397 surveyed residents, 205 (51.6%) responded. The mean modified SCS score was 11.29 out of 18 (95% CI, 10.76-11.81). Respondents were most likely to disagree with "Residents are told when they are at risk of working beyond ACGME [Accreditation Council for Graduate Medical Education] duty hour restrictions," where 100 (48.8%) disagreed or strongly disagreed. The mean CFQ score was 15.99 of 33 (95% CI, 15.17-16.81). As the modified SCS score improved, CFQ scores decreased, indicating an inverse relationship between duty hour safety climate and fatigue. Having a protected postcall day off and having the program director, chief resident, or senior resident decide that a resident should take a postcall day off were all associated with higher modified SCS scores. CONCLUSION: Otolaryngology residents perceived a safety climate that is suboptimal with regard to duty hour restriction issues. Additionally, an inverse relationship between fatigue and modified SCS scores suggests that fatigue among residents may be lower in programs where residents perceive that ACGME duty hour compliance is more important. |
Simulation and measurement of the magnetic field coupling from a proximity detection system to trailing cables
Zhou C , Whisner B , Carr J . IEEE Trans Ind Appl 2020 56 (4) 4356-4364 Some of the common and serious hazards in underground mines are the dangers of being pinned, crushed, or struck by a large mining machine such as a scoop or a continuous mining machine (CMM). Proximity detection systems (PDSs) have been applied to protect miners from these hazards. The primary components of PDSs that are currently approved by the Mine Safety and Health Administration (MSHA) for use in underground coal mines are machine-mounted magnetic field generators and a miner-worn component (MWC), which measures the strength of the magnetic fields produced by the generators. Since these systems are magnetic field based, they can be adversely impacted by nearby cables due to parasitic coupling. Some mobile equipment in underground mines is electrically powered by long trailing cables that are pulled through the mine behind the equipment. Because the components of the PDS (generators and MWC) are frequently in close proximity to these cables, parasitic coupling can occur. Researchers from the National Institute for Occupational Safety and Health investigated the influence of trailing cables on the performance of PDSs. In particular, a three-phase model was proposed to describe the coupling process. The factors for controlling the magnetic field coupled from a field generator to a trailing cable were experimentally studied. The results show that the coupling is primarily controlled by two factors: The distance between the PDS components and the cable and the impedance between the cable and the ground. The coupling can be mitigated by either maintaining some minimum separation distance between the PDS components and the cable or increasing the impedance between the cable and the ground. The results presented in this article can help PDS manufacturers to design systems that are more immune to these effects. |
Surgical team exposure to cautery smoke and its mitigation during tonsillectomy
O'Brien DC , Lee EG , Soo JC , Friend S , Callaham S , Carr MM . Otolaryngol Head Neck Surg 2020 163 (3) 194599820917394 OBJECTIVES: To assess the exposure of surgical personnel to known carcinogens during pediatric tonsillectomy and adenoidectomy (T&A) and compare the efficacy of surgical smoke evacuation systems during T&A. STUDY DESIGN: Prospective, case series. SETTING: Tertiary children's hospital. SUBJECTS AND METHODS: The present study assessed operating room workers' exposure to chemical compounds and aerosolized particulates generated during T&A. We also investigated the effect of 3 different smoke-controlling methods: smoke-evacuator pencil cautery (SE), cautery with suction held by an assistant (SA), and cautery without suction (NS). RESULTS: Thirty cases were included: 12 in the SE group, 9 in SA, and 9 in NS. The chemical exposure levels were lower than or similar to baseline background concentrations, with the exception of methylene chloride and acetaldehyde. Within the surgical plume, none of the chemical compounds exceeded the corresponding occupational exposure limit (OEL). The mean particulate number concentration in the breathing zone during tonsillectomy was 508 particles/cm(3) for SE compared to 1661 particles/cm(3) for SA and 8208 particles/cm(3) for NS cases. NS was significantly different compared to the other two methods (P = .0009). CONCLUSIONS: Although the exposure levels to chemicals were considerably lower than the OELs, continuous exposures to these chemicals could cause adverse health effects to surgical personnel. These findings suggest that the use of a smoke-evacuator pencil cautery or an attentive assistant with handheld suction would reduce exposure levels to the aerosolized particles during routine T&A, compared to the use of cautery without suction. |
Effect of electrocautery settings on particulate concentrations in surgical plume during tonsillectomy
Carr MM , Patel VA , Soo JC , Friend S , Lee EG . Otolaryngol Head Neck Surg 2020 162 (6) 194599820914275 OBJECTIVES: To describe the effect of monopolar electrocautery (EC) settings on surgical plume particulate concentration during pediatric tonsillectomy. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary medical center. SUBJECTS AND METHODS: During total tonsillectomy exclusively performed with EC, air was sampled with a surgeon-worn portable particle counter. The airborne mean and maximum particle concentrations were compared for tonsillectomy performed with EC at 12 W vs 20 W, with smoke evacuation system (SES) and no smoke evacuation (NS). RESULTS: A total of 36 children were included in this analysis: 9 cases with EC at 12 W and SES (12SES), 9 cases with EC at 20 W and SES (20SES), 9 cases with EC at 12 W without SES (12NS), and 9 cases with EC at 20 W without SES (20NS). Mean particle number concentration in the breathing zone during tonsillectomy was 1661 particles/cm(3) for 12SES, 5515 particles/cm(3) for 20SES, 8208 particles/cm(3) for 12NS, and 78,506 particles/cm(3) for 20NS. There was a statistically significant difference in the particle number concentrations among the 4 groups. The correlation between the particle number concentration and EC time was either moderate (for 12SES) or negative (for remaining groups). CONCLUSION: Airborne particle concentrations during tonsillectomy are over 9.5 times higher when EC is set at 20 W vs 12 W with NS, which is mitigated to 3.3 times with SES. Applying lower EC settings with SES during pediatric tonsillectomy significantly reduces surgical plume exposure for patients, surgeons, and operating room personnel, which is a well-known occupational health hazard. |
Influence of steel mesh on magnetic proximity detection systems: An experimental study
Zhou C , Whisner BG , Carr JL , Srednicki J . Prog Electromagn Res M Pier M 2020 90 89-97 Proximity Detection Systems (PDSs) are used in the mining industry for protecting mine workers from striking, pinning, and crushing injuries when they work in close proximity to heavy machines such as continuous mining machines (CMMs). Currently all PDSs approved by the Mine Safety and Health Administration (MSHA) are magnetic field based systems which can be influenced by the presence of steel wire mesh that is commonly used for supporting roof and ribs in underground coal mines. In this paper, researchers at the National Institute for Occupational Safety and Health (NIOSH) characterized the influence of the mesh on the performance of magnetic PDSs by measuring the magnetic field difference around a CMM caused by the presence of the mesh. The results show that the magnetic fields are generally enhanced by the mesh which causes PDS detection zones to be increased correspondingly. It was discovered that the fields around the joints of two mesh sections have the greatest enhancement and thus deserve more attention. In addition, it was found that the presence of mesh can also cause a variation in the generator current. The experimental results show that the generator current variation and thus the magnetic field change caused by the mesh can be significant (on the order of ten) when the mesh is extremely close to the generator (e.g., less than 1 cm) and is negligible when mesh is relatively far (greater than 0.15 m). The findings in this paper can be used to develop guidelines and best practices to mitigate the influence of mesh on PDSs. |
Advancing diabetes-related equity through diabetes self-management education and training: Existing coverage requirements and considerations for increased participation
Carr D , Kappagoda M , Boseman L , Cloud LK , Croom B . J Public Health Manag Pract 2020 26 S37-s44 America is in the grips of a diabetes epidemic. Underserved communities disproportionately bear the burden of diabetes and associated harms. Diabetes self-management education and training (DSME/T) may help address the epidemic. By empowering patients to manage their diabetes, DSME/T improves health outcomes and reduces medical expenditures. However, participation in DSME/T remains low. Insurance coverage offers 1 approach for increasing participation in DSME/T. The impact of DSME/T insurance coverage on advancing diabetes-related health equity depends on which types of insurers must cover DSME/T and the characteristics of such coverage. We conducted a legal survey of DSME/T coverage requirements for private insurers, Medicaid programs, and Medicare, finding that substantial differences exist. Although 43 states require that private insurers cover DSME/T, only 30 states require such coverage for most or all Medicaid beneficiaries. Public health professionals and decision makers may find this analysis helpful in understanding and evaluating patterns and gaps in DSME/T coverage. |
Shielding material comparison for electromagnetic interference mitigation for the air pump motor of personal dust monitors
Li J , Carr J , DeGennaro C , Whisner B , McElhinney P . Min Metall Explor 2019 37 (1) 211-217 Since 2016, electromagnetic interference (EMI) of personal dust monitors (PDMs) with magnetic proximity detection systems (PDSs) has been observed in underground coal mines. The EMI causes the magnetic field measurements of a PDS to change, which, in turn, alters the calculated location of the miner relative to the machine. Any altered location calculation can potentially cause the PDS to fail to warn a worker who is at an unsafe distance from the machine, arousing a serious concern on safety hazard caused by EMI in underground mines. The search for EMI mitigation strategies led to the development and use of large shielding pouches and boxes to hold the entire PDM to reduce its magnetic emission. Research on these pouches and boxes found that although they were able to reduce the emitted radiation from the PDM, they also disturbed the magnetic field of the PDS, affecting its performance. Researchers from the National Institute for Occupational Safety and Health (NIOSH) have focused on shielding internal PDM components rather than shielding the entire PDM. The PDM air pump motor is one of the PDM components that has been identified as a major source of electromagnetic radiation and has been selected for further study and tests. The measurements show that a small copper or aluminum foil enclosure can effectively reduce the magnetic emission of the motor by between 50 and 85% at 73 kHz. This study compares the test results of the air pump motor with various cost-effective shielding materials. The data provided in this paper can serve as a reference for shielding enclosure design of the PDM air pump motor to reduce its electromagnetic emission as one form of EMI mitigation strategy. |
Influence of temperature on generator current and magnetic field of a proximity detection system
Li J , Smith A , Carr JB , Whisner B . Min Metall Explor 2019 36 (3) 541-545 Electromagnetic-based proximity detection systems (PDSs) are utilized on mining machinery to protect workers from being pinned or struck. These systems generate magnetic fields covering the space around a machine, and a miner-wearable component (MWC) detects the field. The PDS determines the distance of miners relative to the machine based on the detected magnetic flux density in the magnetic field. This information is used to establish warning and shutdown zones around the machine. Maintaining a stable magnetic field is essential for system accuracy. However, components used to generate magnetic fields can be influenced by temperature changes. Depending on ventilation conditions and seasonal alternation, a PDS can be subject to significant temperature fluctuation. To better understand and quantify this phenomenon, researchers from the National Institute for Occupational Safety and Health (NIOSH) developed an experimental apparatus to study the influence of temperature on magnetic field generator circuits used in PDSs. Results from the study show that the electric current through a generator can be influenced by both ambient and internal temperatures, modifying the magnetic field that is produced. These findings show that temperature can significantly influence the ability of PDSs, used in underground coal mines, to accurately determine a workers position in relation to mining machine. 2019, This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection. |
Updated baseline prevalence of birth defects potentially related to Zika virus infection
Olson SM , Delaney A , Jones AM , Carr CP , Liberman RF , Forestieri NE , Tong VT , Gilboa SM , Honein MA , Moore CA , Cragan JD . Birth Defects Res 2019 111 (13) 938-940 Zika virus (ZIKV) was first recognized as a human teratogen in 2016 (Rasmussen, Jamieson, Honein, & Petersen, 2016). During the ZIKV outbreak in the Americas, we launched rapid surveillance of pregnancies with laboratory evidence of ZIKV infection and targeted surveillance of birth defects. Because little was known about the birth defects associated with congenital ZIKV infection, a broad case definition was used for surveillance of birth defects potentially related to ZIKV based on early reports of congenital ZIKV infection in the literature and expert opinion. The initial case definition included microcephaly and/or brain abnormalities, neural tube defects (NTDs) and other early brain malformations (e.g., holoprosencephaly), eye abnormalities, and consequences of central nervous system (CNS) dysfunction such as arthrogryposis and hearing loss (Honein et al., 2017). The baseline prevalence of these defects in the United States prior to the ZIKV outbreak was estimated as 2.86 per 1,000 live births (95% CI: 2.65–3.07) using data from statewide birth defects surveillance programs in Massachusetts and North Carolina in 2013 and from three counties in metropolitan Atlanta, Georgia, during 2013–2014 (Cragan et al., 2017). |
The influence of a continuous mining machine and roof/rib mesh on magnetic proximity detection systems
Li J , Carr J , Zhou C . Min Metall Explor 2019 36 (4) [Epub ahead of print] Magnetic proximity detection systems (PDSs) are used with continuous mining machines (CMMs) to protect miners from striking and pinning accidents. Generators are used in a PDS to create magnetic fields covering the space around a CMM. The PDS determines the proximity of a miner relative to the CMM based on the magnetic flux density detected by a miner-wearable component (MWC) and simultaneously alerts the miner and stops the motion of the CMM if the miner is within a proximity that creates a striking hazard. A stable magnetic field is essential to the accuracy of the proximity calculations performed by the PDS. This paper presents the results of a systematic study of the magnetic influence of two types of steel structures found near a CMM - the body of the CMM itself and the wire mesh used for roof and rib control. The results show that the steel of the CMM body can change the magnetic field distribution and also alter electrical parameters of a PDS by changing its generator current. The study also shows that, depending on the distance between the wire mesh and a generator, the magnetic field can also be altered. |
Hepatitis C Virus Potentially Transmitted by Opioid Drug Diversion from a Nurse - Washington, August 2017-March 2018.
Njuguna HN , Stinson D , Montgomery P , Turner N , D'Angeli M , Carr J , Podczervinski S , Wasserman C , Ramachandran S , Lucas T , Bixler D , Perkins K , Benowitz I , Moorman A . MMWR Morb Mortal Wkly Rep 2019 68 (16) 374-376 During January 22-March 23, 2018, a local health department in Washington was notified of two patients who received a diagnosis of acute hepatitis C virus (HCV) infection. Neither patient had behavioral risk factors associated with HCV acquisition; however, both had received injectable narcotic (opioid) drugs from the same nurse during separate visits to an emergency department (ED) at a local hospital on December 6 and December 16, 2017. Investigation revealed that the nurse had accessed the automated drug dispensing system at a higher frequency than had other staff members, admitted diverting* patients' injectable narcotic and antihistamine drugs for personal use, and tested positive for HCV antibodies (anti-HCV) on March 19, 2018, but did not have quantifiable HCV RNA. Specimens from both patients were sent to CDC for genetic testing, and HCV viral variants analysis found a significant level of genetically similar HCV variants in both patients, indicating a common source of infection. Further investigation was conducted to confirm the infection source, identify other potentially exposed patients, and treat any new patients who received an HCV diagnosis. Monitoring frequency of access to drug dispensing systems can help identify staff members with abnormal dispensing patterns, including diversion activities (1). U.S. health care facilities are required to prevent, identify, and report any loss, diversion, or theft of controlled substances (2). |
Leveraging informatics to identify reportable cases: Pilot findings on electronic case reporting of chlamydia and gonorrhea
Mishra NK , Jellison JB , Hamilton A , Carr JB , Padilla RM , Viator NA . J Public Health Manag Pract 2019 25 (6) 595-597 Consensus-based technical guidance for electronic case reporting (eCR) of sexually transmitted infections was implemented within existing health information technologies to automatically detect chlamydia and gonorrhea cases based on diagnosis and laboratory observation codes and build a case report using industry standards. The process was evaluated using 12 420 ambulatory encounters among adolescents and adults 15 years and older seen at 8 Chicago-area community health centers between May 1 and June 30, 2017. We tabulated the frequency of matches between the case detection logic and patient data and compared the eCR identified cases with paper case reports. This study found that eCR increased provider reporting when compared with paper reporting alone. While additional work across stakeholder groups is needed, these early findings suggest that broadly adopted eCR will decrease both provider and public health burden while improving reporting timeliness and data completion to support case investigation. |
A method for estimating the low frequency coupling characteristics of a ferrite-cored rod antenna to a long conductor
Li J , Carr JL , Zhou CJ , Reyes MA , Noll JD . Prog Electromagn Res M Pier M 2018 75 193-203 Magnetic proximity detection systems (PDSs) used in underground mines occasionally generate false alarms when the miner-wearable component (MWC) is close to nearby conductors such as power cables. This is because the signals from the generators (antennas) of the PDS wirelessly couple to nearby cables, travel along these cables, and then couple back from the cable to a distant MWC to cause a false alarm. In order to manage such a false alarm, it is necessary to understand the basic near-field coupling characteristics from a generator to a long wire. Researchers from the National Institute for Occupational Safety and Health (NIOSH) have developed a method to measure such coupling characteristics for a ferrite-cored antenna to a straight wire. The method is introduced in this paper along with the test results. |
Updated framework for development of evidence-based recommendations by the Advisory Committee on Immunization Practices
Lee G , Carr W . MMWR Morb Mortal Wkly Rep 2018 67 (45) 1271-1272 The Advisory Committee on Immunization Practices (ACIP)* is a federal advisory committee that provides expert advice to the Director of CDC and the Secretary of the U.S. Department of Health and Human Services in the form of recommendations on the use of vaccines and related agents for control of vaccine-preventable diseases in the U.S. civilian population (1,2). Work groups that gather, analyze, and prepare scientific information assist in the recommendation formulation process and present options for recommendations based on the scientific evidence they have assessed. Recommendations that are approved by a majority of ACIP's voting members are then reviewed by the Director of CDC and published in MMWR if approved by the director. This report briefly summarizes an update to the ACIP process for developing evidence-based recommendations that ACIP adopted at its February 2018 meeting. |
Understanding barriers and predictors of maternal immunization: Identifying gaps through an exploratory literature review
Lutz CS , Carr W , Cohn A , Rodriguez L . Vaccine 2018 36 (49) 7445-7455 BACKGROUND: The Advisory Committee for Immunization Practices recommends that all pregnant women receive the seasonal influenza vaccine and the tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine during every pregnancy. However, vaccination coverage rates are suboptimal among pregnant women in the United States, leaving these women and their unborn children at risk of vaccine-preventable diseases and their complications. OBJECTIVES: We sought to understand the current landscape of published literature regarding maternal immunization, including barriers to and predictors of vaccine acceptance, and identify gaps in the research in order to inform strategies for future programmatic improvement. METHODS: We conducted a literature search using MEDLINE (OVID), PsychINFO, and CINAHL (Ebsco) databases. The search included published, English-language manuscripts that identified patient, provider, or system-level barriers to, predictors of, or interventions that improved uptake of maternal vaccines among pregnant women in the US. Studies were reviewed using an inductive thematic analysis approach. RESULTS: We included 75 studies in our review. Pregnant women identified 25 different barriers to accepting recommended maternal immunizations; barriers related to vaccine safety perceptions were the most common. Healthcare providers identified 24 different barriers to vaccinating their pregnant patients. The most commonly cited barriers among healthcare providers were financial concerns. Eighteen different predictors of vaccine acceptance were identified. Receipt of a healthcare provider's recommendation was the factor most frequently reported as a reason for vaccination among pregnant women. CONCLUSIONS: We were able to identify gaps in the literature regarding maternal immunization and make recommendations for future research. Efforts to address the challenges of maternal immunization in the United States should include increasing the focus on Tdap, implementing more high-level assessments of safety perceptions and associated concerns, and determining most effective interventions. |
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