Last data update: Oct 28, 2024. (Total: 48004 publications since 2009)
Records 1-30 (of 101 Records) |
Query Trace: Lam E[original query] |
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Building data triangulation capacity for routine immunization and vaccine preventable disease surveillance programs to identify immunization coverage inequities
Rachlin A , Adegoke OJ , Bohara R , Rwagasore E , Sibomana H , Kabeja A , Itanga I , Rwunganira S , Mafende Mario B , Rosette NM , Usman Obansa R , Abah AU , Adeoye OB , Sikare E , Lam E , Murrill CS , Montesanti Porter A . Vaccines (Basel) 2024 12 (6) The Expanded Programme on Immunization (EPI) and Vaccine Preventable Disease (VPD) Surveillance (VPDS) programs generate multiple data sources (e.g., routine administrative data, VPD case data, and coverage surveys). However, there are challenges with the use of these siloed data for programmatic decision-making, including poor data accessibility and lack of timely analysis, contributing to missed vaccinations, immunity gaps, and, consequently, VPD outbreaks in populations with limited access to immunization and basic healthcare services. Data triangulation, or the integration of multiple data sources, can be used to improve the availability of key indicators for identifying immunization coverage gaps, under-immunized (UI) and un-immunized (zero-dose (ZD)) children, and for assessing program performance at all levels of the healthcare system. Here, we describe the data triangulation processes, prioritization of indicators, and capacity building efforts in Bangladesh, Nigeria, and Rwanda. We also describe the analyses used to generate meaningful data, key indicators used to identify immunization coverage inequities and performance gaps, and key lessons learned. Triangulation processes and lessons learned may be leveraged by other countries, potentially leading to programmatic changes that promote improved access and utilization of vaccination services through the identification of UI and ZD children. |
Migration from Epi Info to District Health Information Software 2 for Vaccine-Preventable Disease Surveillance - World Health Organization African Region, 2019-2023
Adegoke OJ , Rachlin A , Porter AM , Katsande R , Kubenga S , Potter R , Titlestad OH , Noubi Tchoupopnou Royd L , Rosencrans L , Kinkade C , Crispino V , Shragai T , Kossi E , Chu HA , Murrill CS , Lam E , Wiysonge CS , Kazembe L , Pezzoli L , Alegana V , Benido I . MMWR Morb Mortal Wkly Rep 2024 73 (23) 529-533 High-quality vaccine-preventable disease (VPD) surveillance data are critical for timely outbreak detection and response. In 2019, the World Health Organization (WHO) African Regional Office (AFRO) began transitioning from Epi Info, a free, CDC-developed statistical software package with limited capability to integrate with other information systems, affecting reporting timeliness and data use, to District Health Information Software 2 (DHIS2). DHIS2 is a free and open-source software platform for electronic aggregate Integrated Disease Surveillance and Response (IDSR) and case-based surveillance reporting. A national-level reporting system, which provided countries with the option to adopt this new system, was introduced. Regionally, the Epi Info database will be replaced with a DHIS2 regional data platform. This report describes the phased implementation from 2019 to the present. Phase one (2019-2021) involved developing IDSR aggregate and case-based surveillance packages, including pilots in the countries of Mali, Rwanda, and Togo. Phase two (2022) expanded national-level implementation to 27 countries and established the WHO AFRO DHIS2 regional data platform. Phase three (from 2023 to the present) activities have been building local capacity and support for country reporting to the regional platform. By February 2024, eight of 47 AFRO countries had adopted both the aggregate IDSR and case-based surveillance packages, and two had successfully transferred VPD surveillance data to the AFRO regional platform. Challenges included limited human and financial resources, the need to establish data-sharing and governance agreements, technical support for data transfer, and building local capacity to report to the regional platform. Despite these challenges, the transition to DHIS2 will support efficient data transmission to strengthen VPD detection, response, and public health emergencies through improved system integration and interoperability. |
The potential use of artificial intelligence for venous thromboembolism prophylaxis and management: clinician and healthcare informatician perspectives
Lam BD , Dodge LE , Zerbey S , Robertson W , Rosovsky RP , Lake L , Datta S , Elavakanar P , Adamski A , Reyes N , Abe K , Vlachos IS , Zwicker JI , Patell R . Sci Rep 2024 14 (1) 12010 Venous thromboembolism (VTE) is the leading cause of preventable death in hospitalized patients. Artificial intelligence (AI) and machine learning (ML) can support guidelines recommending an individualized approach to risk assessment and prophylaxis. We conducted electronic surveys asking clinician and healthcare informaticians about their perspectives on AI/ML for VTE prevention and management. Of 101 respondents to the informatician survey, most were 40 years or older, male, clinicians and data scientists, and had performed research on AI/ML. Of the 607 US-based respondents to the clinician survey, most were 40 years or younger, female, physicians, and had never used AI to inform clinical practice. Most informaticians agreed that AI/ML can be used to manage VTE (56.0%). Over one-third were concerned that clinicians would not use the technology (38.9%), but the majority of clinicians believed that AI/ML probably or definitely can help with VTE prevention (70.1%). The most common concern in both groups was a perceived lack of transparency (informaticians 54.4%; clinicians 25.4%). These two surveys revealed that key stakeholders are interested in AI/ML for VTE prevention and management, and identified potential barriers to address prior to implementation. |
Implementation of a rapid diagnostic assay package for cryptococcosis, histoplasmosis and tuberculosis in people living with HIV in Paraguay
Aguilar G , Lopez G , Sued O , Medina N , Caceres DH , Pereira J , Jordan A , Lezcano V , Vicenti C , Benitez G , Samudio T , Perez F . BMC Infect Dis 2024 24 (1) 406 BACKGROUND: Opportunistic infections (OIs) are common causes of mortality among people living with HIV (PLHIV). We determined prevalence and 30-day mortality due to histoplasmosis, cryptococcosis, and TB in PLHIV with advanced HIV disease (AHD). METHODS: PLHIV 18 years and older, with a CD4 + T-cell count of less than 350 cells/mm3 newly diagnosed with HIV infection or re-engaged in care after being without ART for more than 90 days (Group A). The second group included symptomatic PLHIV regardless of ART status or CD4 + T-cell count (Group B); all followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was done by enzyme immunoassay (EIA), Cryptococcus antigen (CrAg) was detected in serum and cerebrospinal fluid (CSF) specimens by lateral flow assay (LFA), and lipoarabinomannan (LAM) detection in urine was by LFA (TB LAM) and in sputum by GeneXpert for diagnosis of Mycobacterium infections. RESULTS: From August 2021 to June 2022, 491 PLHIV were enrolled; 482 (98%) had a CD4 + T-cell result, and 381 patients (79%) were classified with AHD according to CD4 + T-cell count (< 200 CD4/mm(3)). Frequency of an OI was 38% (n = 145/381). Antigen test positivity rate was 16% (72/467) for TB-LAM, 9% (43/464) for HisAg, and 11% (51/484) for CrAg. Twenty-one of 34 (62%) patients receiving CSF CrAg tests were positive, confirming meningitis. Significant differences in 30-day mortality were observed in patients with an OI (16%) vs. no OI (7%) (p = 0.002). Mortality was highest in patients with histoplasmosis (25%), co-infection (22%), cryptococcosis (18% overall; 19% for cryptococcal meningitis), and TB (10%). CONCLUSIONS: TB and fungal OIs, including co-infection, were common in PLHIV in Paraguay and had high associated mortality. Laboratories and health facilities need access to CD4 + T-cell testing and rapid diagnostic assays. |
Machine learning natural language processing for identifying venous thromboembolism: Systematic review and meta-analysis
Lam BD , Chrysafi P , Chiasakul T , Khosla H , Karagkouni D , McNichol M , Adamski A , Reyes N , Abe K , Mantha S , Vlachos IS , Zwicker JI , Patell R . Blood Adv 2024 Venous thromboembolism (VTE) is a leading cause of preventable in-hospital mortality. Monitoring VTE cases is limited by the challenges of manual chart review and diagnosis code interpretation. Natural language processing (NLP) can automate the process. Rule-based NLP methods are effective but time consuming. Machine learning (ML)-NLP methods present a promising solution. We conducted a systematic review and meta-analysis of studies published before May 2023 that use ML-NLP to identify VTE diagnoses in the electronic health records. Four reviewers screened all manuscripts, excluding studies that only used a rule-based method. A meta-analysis evaluated the pooled performance of each study's best performing model that evaluated for pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with confidence interval (CI) were calculated by DerSimonian and Laird method using a random-effects model. Study quality was assessed using an adapted TRIPOD tool. Thirteen studies were included in the systematic review and 8 had data available for meta-analysis. Pooled sensitivity was 0.931 (95% CI 0.881-0.962), specificity 0.984 (95% CI 0.967-0.992), PPV 0.910 (95% CI 0.865-0.941) and NPV 0.985 (95% CI 0.977-0.990). All studies met at least 13 of the 21 NLP-modified TRIPOD items, demonstrating fair quality. The highest performing models used vectorization rather than bag-of-words, and deep learning techniques such as convolutional neural networks. There was significant heterogeneity in the studies and only four validated their model on an external dataset. Further standardization of ML studies can help progress this novel technology towards real-world implementation. |
Lessons learned from early implementation of the Growing Expertise in E-health Knowledge and Skills (GEEKS) program in Nigeria, 2019 - 2021
Rachlin A , Adegoke OJ , Sikare E , Adeoye OB , Dagoe E , Adeyelu A , Tolentino H , MacGregor J , Obasi S , Adah G , Garba AB , Abah AU , Friday J , Oyiri F , Porter AM , Olajide L , Wilson I , Usman R , Usifoh N , Fasogbon O , Franka R , Ghiselli M , Nguku P , Waziri N , Lam E , Bolu O . Pan Afr Med J 2023 46 81 INTRODUCTION: the Growing Expertise in E-health Knowledge and Skills (GEEKS) program is an applied apprenticeship program that aims to improve informatics capacity at various levels of the national health system and create a sustainable informatics workforce. Nigeria adapted the GEEKS model in 2019 as a mechanism to strengthen data quality and use of routine immunization (RI) and vaccine-preventable disease (VPD) surveillance data among Expanded Programme on Immunization (EPI) staff. Since the start of the GEEKS-EPI program, there has not been a formal assessment conducted to measure the extent to which GEEKS-EPI has been able to build local informatics workforce capacity and strengthen RI and VPD surveillance (VPDS) data quality and use in Nigeria. METHODS: we conducted a qualitative assessment to inform the extent to which GEEKS-EPI has been able to build informatics skillsets to enhance local workforce capacity, foster collaboration across government agencies, and create a sustainable informatics workforce in Nigeria. In-Depth Interviews (IDIs) and Focus Group Discussions (FGDs) were held with GEEKS-EPI supervisors, mentors, and mentees from previous GEEKS-EPI cohorts. RESULTS: while there were challenges reported during early implementation of the GEEKS-EPI program in Nigeria, particularly early on in the COVID-19 pandemic, participants and supervisors reported that the fellowship provided a framework for building a sustainable RI and VPDS informatics workforce through regular mentorship, peer-to-peer exchanges and Subject Matter Expert (SME)-led trainings. CONCLUSION: lessons learned from early implementation of GEEKS-EPI in Nigeria will help to inform its implementation in other countries, where strengthened national RI and VPDS informatics capacity is the primary objective. |
Strengthening the WHO Regional Office for Africa (WHO AFRO) COVID-19 vaccination information system
Shragai T , Bukhari A , Atagbaza AO , Oyaole DR , Shah R , Volkmann K , Kamau L , Sheillah N , Farham B , Wong MK , Lam E , Mboussou F , Impouma B . BMJ Glob Health 2024 9 (1) This manuscript describes the process and impact of strengthening the WHO Regional Office for Africa (WHO AFRO)'s COVID-19 vaccination information system. This system plays a critical role in tracking vaccination coverage, guiding resource allocation and supporting vaccination campaign roll-out for countries in the African region. Recognising existing data management issues, including complex reporting prone to human error, compromised data quality and underutilisation of collected data, WHO AFRO introduced significant system improvements during the COVID-19 pandemic. These improvements include shifting from an Excel-based to an online Azure-based data collection system, automating data processing and validation, and expansion of collected data. These changes have led to improvements in data quality and quantity including a decrease in data non-validity, missingness, and record duplication, and expansion of data collection forms to include a greater number of data fields, offering a more comprehensive understanding of vaccination efforts. Finally, the creation of accessible information products-including an interactive public dashboard, a weekly data pack and a public monthly bulletin-has improved data use and reach to relevant partners. These resources provide crucial insights into the region's vaccination progress at national and subnational levels, thereby enabling data-driven decision-making to improve programme performance. Overall, the strengthening of the WHO AFRO COVID-19 vaccination information system can serve as a model for similar efforts in other WHO regions and contexts. The impact of system strengthening on data quality demonstrated here underscores the vital role of robust data collection, capacity building and management systems in achieving high-quality data on vaccine distribution and coverage. Continued investment in information systems is essential for effective and equitable public health efforts. |
Outreach strategies to promote HIV testing and linkage-to-care focusing on a young sexual and gender-diverse population in Bangkok, Thailand
Chiaprasert P , Lolekha R , Rungmaitree S , Maleesatharn A , Sethaputra C , Durier Y , Srisoonthonthai P , Pumpradit W , Northbrook SC , Weerarak P , Chokephaibulkit K . PLoS One 2024 19 (1) e0296130 INTRODUCTION: Human Immunodeficiency Virus (HIV) prevalence among young gender-diverse (a wide range of gender identities for people whose gender identity is different from the sex that they were assigned at birth) individuals is high but testing coverage among this key population remains low. We aim to evaluate strategies for outreach, HIV testing, and linkage to proper management in young men-who-have-had-sex-with-men (MSM, homosexual male) and transgender women (TGW) in Bangkok, Thailand. METHODS: The "YM2M outreach program" consisted of two strategies: 1) online platforms (OP) and 2) physical outreach activities (POA). Participant questionnaires were completed on a voluntary basis during outreach activities during 2018-2021. Demographic and behavioral characteristics were assessed for association with HIV positivity. RESULTS: A total of 3,972 homosexual male and TGW participated in the YM2M program: 2,973 by OP and 999 by POA. Of 2,230 participants who reported gender identity, 603/1,392 (43.3%) of OP and 252/985 (25.6%) of POA were gender diverse. Of 631 (21.2%) participants in OP and 970 (97.1%) in POA who underwent testing, 286 (45.3%) in OP and 41 (4.2%) in POA were HIV-positive. The venue reporting highest HIV yield was the Mor-Lam (11.5%). Among those with an HIV-positive test, 175 (61.2%) from OP and 23 (51.1%) from POA were successfully linked to HIV care. The independent factors associated with HIV positive in OP were being youth (adjusted odd ratio (aOR), 0.37; 95%CI 0.16-0.81; P = 0.01) and suspected or confirmed STI (aOR 15.39; 95%CI 7.17-33.03, P<0.01); while those in in POA at Mor-Lam were being gender diverse (aOR, 8.43; 95%CI 1.94-36.62; P<0.01) and reactive syphilis test (aOR, 5.40;95%CI 2.45-11.88; P<0.01). Linkage to pre-exposure prophylaxis (PrEP) among HIV-negative participants was low, 4.9% and 2.6% in OP and POA participants, respectively. CONCLUSIONS: While uptake of HIV testing was higher in POA while OP was more effective in identifying undiagnosed people living with HIV/AIDS and linking them to care. Neither strategy was considered effective in linkage to PrEP. |
Notes from the field: Supply interruptions of first- and second-line oral drugs to treat tuberculosis during the previous 12 months - California, January-March, 2023
Nabity SA , Agraz-Lara R , Bravo A , Benjamin R , Fong V , Lam CK , Keh C , Mase S , Flood J . MMWR Morb Mortal Wkly Rep 2024 72 (5253) 1390-1391 Tuberculosis (TB) drug supply disruptions are a recurring concern in the United States (1). Contributors to these disruptions include loss of manufacturers to the U.S. market, inefficient supply chains, and lack of active ingredients available for import.* The last severe U.S. TB drug shortage occurred in 2012, when isoniazid (INH) was temporarily unavailable for several months (2). INH and rifampin (RIF) are the cornerstones for treatment of drug-susceptible TB, and rifapentine (RPT), a long acting rifamycin, has been incorporated into shorter first-line regimens† to treat both latent TB infection (LTBI) (3) and TB disease§ (4). In recent years, the U.S. supply of several TB drugs has again been disrupted. The Food and Drug Administration has declared shortages of RPT (on March 25, 2020), RIF (on December 22, 2021), and INH (on May 17, 2023).¶ Approximately one fifth of all U.S. TB cases are reported from California (5). TB drug procurement is decentralized among the state’s 61 local TB programs,** mirroring the decentralization among U.S. states and territories. The California Department of Public Health and the California TB Controllers Association assessed the impact of the shortage on California’s TB programs. |
Artificial intelligence for venous thromboembolism prophylaxis: Clinician perspectives
Lam BD , Zerbey S , Pinson A , Robertson W , Rosovsky RP , Lake L , Dodge LE , Adamski A , Reyes N , Abe K , Vlachos IS , Zwicker JI , Schonberg M , Patell R . Res Pract Thromb Haemost 2023 7 (8) 102272 Hospital-associated venous thromboembolism (VTE) is a major public health challenge, and while thromboprophylaxis is known to be effective, it remains misused [1]. Clinicians face enormous complexity when determining who should receive thromboprophylaxis. To better understand current practices around VTE prophylaxis in adult hospitalized patients, we previously surveyed 607 clinicians across the United States between 2021 and 2022 [2]. Overall, 48% of respondents reported patients at their institution are not on appropriate VTE prophylaxis almost all the time. The majority reported that technology such as artificial intelligence (AI) may help improve rates of appropriate prophylaxis. However, only 35% reported using existing risk assessment models (RAMs); 68% reported using their own clinical assessment instead. Therefore, we invited survey respondents to participate in focus groups to better understand how they approach VTE prophylaxis, with a focus on their perspectives regarding using AI decision support. |
Adverse events among persons with TB using in-person vs. electronic directly observed therapy
Salerno MM , Burzynski J , Mangan JM , Hill A , deCastro BR , Goswami ND , Lam CK , Macaraig M , Schluger NW , Vernon AA . Int J Tuberc Lung Dis 2023 27 (11) 833-840 BACKGROUND: We evaluated patient safety within a randomized crossover trial comparing electronic directly observed therapy (eDOT) to in-person DOT (ipDOT) in persons undergoing TB treatment in New York City, NY, USA.METHODS: Participant symptoms, symptom severity, and clinical management were documented. We assessed adverse event reports (AERs) by DOT method during the two-period crossover. Using Cox proportional-hazards mixed-effects models, we estimated the adjusted hazard ratio (aHR) of participants reporting an adverse event (AE) vs. not reporting an AE.RESULTS: Of 211 participants, 57 (27.0%) reported AEs during the two-period crossover; of these, 54.4% (31/57) were reported while using eDOT vs. 45.6% (26/57) while using ipDOT. Controlling for study group and period, the aHR for eDOT vs. ipDOT was 0.98 (95% CI 0.49-1.93). Although statistically not significant, the wide confidence intervals suggest that a significant association cannot be entirely ruled out. Gastrointestinal symptoms were most frequently reported (42.1%, 24/57). AER types and severity did not differ significantly by DOT method. Days from symptom onset to medical attention was similar across DOT methods (median: 1.0 day, IQR 0.0-2.0). No participants switched DOT methods due to AERs or monitoring concerns.CONCLUSION: Further evaluation to ascertain whether AERs differ when patients use eDOT vs. ipDOT is warranted. |
A review of pulmonary neutrophilia and insights into the key role of neutrophils in particle-induced pathogenesis in the lung from animal studies of lunar dusts and other poorly soluble dust particles
Lam CW , Castranova V , Driscoll K , Warheit D , Ryder V , Zhang Y , Zeidler-Erdely P , Hunter R , Scully R , Wallace W , James J , Crucian B , Nelman M , McCluskey R , Gardner D , Renne R , McClellan R . Crit Rev Toxicol 2023 53 (8) 1-39 The mechanisms of particle-induced pathogenesis in the lung remain poorly understood. Neutrophilic inflammation and oxidative stress in the lung are hallmarks of toxicity. Some investigators have postulated that oxidative stress from particle surface reactive oxygen species (psROS) on the dust produces the toxicopathology in the lungs of dust-exposed animals. This postulate was tested concurrently with the studies to elucidate the toxicity of lunar dust (LD), which is believed to contain psROS due to high-speed micrometeoroid bombardment that fractured and pulverized lunar surface regolith. Results from studies of rats intratracheally instilled (ITI) with three LDs (prepared from an Apollo-14 lunar regolith), which differed 14-fold in levels of psROS, and two toxicity reference dusts (TiO(2) and quartz) indicated that psROS had no significant contribution to the dusts' toxicity in the lung. Reported here are results of further investigations by the LD toxicity study team on the toxicological role of oxidants in alveolar neutrophils that were harvested from rats in the 5-dust ITI study and from rats that were exposed to airborne LD for 4 weeks. The oxidants per neutrophils and all neutrophils increased with dose, exposure time and dust's cytotoxicity. The results suggest that alveolar neutrophils play a critical role in particle-induced injury and toxicity in the lung of dust-exposed animals. Based on these results, we propose an adverse outcome pathway (AOP) for particle-associated lung disease that centers on the crucial role of alveolar neutrophil-derived oxidant species. A critical review of the toxicology literature on particle exposure and lung disease further supports a neutrophil-centric mechanism in the pathogenesis of lung disease and may explain previously reported animal species differences in responses to poorly soluble particles. Key findings from the toxicology literature indicate that (1) after exposures to the same dust at the same amount, rats have more alveolar neutrophils than hamsters; hamsters clear more particles from their lungs, consequently contributing to fewer neutrophils and less severe lung lesions; (2) rats exposed to nano-sized TiO(2) have more neutrophils and more severe lesions in their lungs than rats exposed to the same mass-concentration of micron-sized TiO(2); nano-sized dust has a greater number of particles and a larger total particle-cell contact surface area than the same mass of micron-sized dust, which triggers more alveolar epithelial cells (AECs) to synthesize and release more cytokines that recruit a greater number of neutrophils leading to more severe lesions. Thus, we postulate that, during chronic dust exposure, particle-inflicted AECs persistently release cytokines, which recruit neutrophils and activate them to produce oxidants resulting in a prolonged continuous source of endogenous oxidative stress that leads to lung toxicity. This neutrophil-driven lung pathogenesis explains why dust exposure induces more severe lesions in rats than hamsters; why, on a mass-dose basis, nano-sized dusts are more toxic than the micron-sized dusts; why lung lesions progress with time; and why dose-response curves of particle toxicity exhibit a hockey stick like shape with a threshold. The neutrophil centric AOP for particle-induced lung disease has implications for risk assessment of human exposures to dust particles and environmental particulate matter. |
Artificial intelligence in the prediction of venous thromboembolism: A systematic review and pooled analysis
Chiasakul T , Lam BD , McNichol M , Robertson W , Rosovsky RP , Lake L , Vlachos IS , Adamski A , Reyes N , Abe K , Zwicker JI , Patell R . Eur J Haematol 2023 111 (6) 951-962 BACKGROUND: Accurate diagnostic and prognostic predictions of venous thromboembolism (VTE) are crucial for VTE management. Artificial intelligence (AI) enables autonomous identification of the most predictive patterns from large complex data. Although evidence regarding its performance in VTE prediction is emerging, a comprehensive analysis of performance is lacking. AIMS: To systematically review the performance of AI in the diagnosis and prediction of VTE and compare it to clinical risk assessment models (RAMs) or logistic regression models. METHODS: A systematic literature search was performed using PubMed, MEDLINE, EMBASE, and Web of Science from inception to April 20, 2021. Search terms included "artificial intelligence" and "venous thromboembolism." Eligible criteria were original studies evaluating AI in the prediction of VTE in adults and reporting one of the following outcomes: sensitivity, specificity, positive predictive value, negative predictive value, or area under receiver operating curve (AUC). Risks of bias were assessed using the PROBAST tool. Unpaired t-test was performed to compare the mean AUC from AI versus conventional methods (RAMs or logistic regression models). RESULTS: A total of 20 studies were included. Number of participants ranged from 31 to 111 888. The AI-based models included artificial neural network (six studies), support vector machines (four studies), Bayesian methods (one study), super learner ensemble (one study), genetic programming (one study), unspecified machine learning models (two studies), and multiple machine learning models (five studies). Twelve studies (60%) had both training and testing cohorts. Among 14 studies (70%) where AUCs were reported, the mean AUC for AI versus conventional methods were 0.79 (95% CI: 0.74-0.85) versus 0.61 (95% CI: 0.54-0.68), respectively (p < .001). However, the good to excellent discriminative performance of AI methods is unlikely to be replicated when used in clinical practice, because most studies had high risk of bias due to missing data handling and outcome determination. CONCLUSION: The use of AI appears to improve the accuracy of diagnostic and prognostic prediction of VTE over conventional risk models; however, there was a high risk of bias observed across studies. Future studies should focus on transparent reporting, external validation, and clinical application of these models. |
Venous thromboembolism prophylaxis for hospitalized adult patients: a survey of US health care providers on attitudes and practices
Lam BD , Dodge LE , Datta S , Rosovsky RP , Robertson W , Lake L , Reyes N , Adamski A , Abe K , Panoff S , Pinson A , Elavalakanar P , Vlachos IS , Zwicker JI , Patell R . Res Pract Thromb Haemost 2023 7 (6) 102168 BACKGROUND: Venous thromboembolism (VTE) is a leading cause of preventable mortality among hospitalized patients, but appropriate risk assessment and thromboprophylaxis remain underutilized or misapplied. OBJECTIVES: We conducted an electronic survey of US health care providers to explore attitudes, practices, and barriers related to thromboprophylaxis in adult hospitalized patients and at discharge. RESULTS: A total of 607 US respondents completed the survey: 63.1% reported working in an academic hospital, 70.7% identified as physicians, and hospital medicine was the most frequent specialty (52.1%). The majority of respondents agreed that VTE prophylaxis is important (98.8%; 95% CI: 97.6%-99.5%) and that current measures are safe (92.6%; 95% CI: 90.2%-94.5%) and effective (93.8%; 95% CI: 91.6%-95.6%), but only half (52.0%; 95% CI: 47.9%-56.0%) believed that hospitalized patients at their institution are on appropriate VTE prophylaxis almost all the time. One-third (35.4%) reported using a risk assessment model (RAM) to determine VTE prophylaxis need; 44.9% reported unfamiliarity with RAMs. The most common recommendation for improving rates of appropriate thromboprophylaxis was to leverage technology. A majority of respondents (84.5%) do not reassess a patient's need for VTE prophylaxis at discharge, and a minority educates patients about the risk (16.2%) or symptoms (18.9%) of VTE at discharge. CONCLUSION: Despite guideline recommendations to use RAMs, the majority of providers in our survey do not use them. A majority of respondents believed that technology could help improve VTE prophylaxis rates. A majority of respondents do not reassess the risk of VTE at discharge or educate patients about this risk of VTE at discharge. |
Outbreak of multidrug-resistant tuberculosis - Kansas, 2021-2022
Groenweghe E , Swensson L , Winans KD , Griffin P , Haddad MB , Brostrom RJ , Tuckey D , Lam CK , Armitige LY , Seaworth BJ , Corriveau EA . MMWR Morb Mortal Wkly Rep 2023 72 (35) 957-960 An outbreak of multidrug-resistant (MDR) tuberculosis (TB) involved 13 persons in four households in a low-income, under-resourced urban Kansas community during November 2021-November 2022. A majority of the seven adults identified in the Kansas outbreak were born outside the United States in a country that had experienced an MDR TB outbreak with the same genotype during 2007-2009, whereas most of the six children in the Kansas outbreak were U.S.-born. Prompt identification, evaluation, and treatment of persons with MDR TB and their contacts is essential to limiting transmission. |
Health and economic outcomes of newborn screening for infantile-onset Pompe disease (preprint)
Richardson JS , Kemper AR , Grosse SD , Lam WKK , Rose AM , Ahmad A , Gebremariam A , Prosser LA . medRxiv 2020 2020.04.28.20080606 Purpose To estimate health and economic outcomes associated with NBS for infantile-onset Pompe disease in the United States.Methods A decision analytic microsimulation model simulated health and economic outcomes of a birth cohort of 4 million children in the United States. Universal NBS and treatment was compared to clinical identification and treatment of infantile-onset Pompe disease. Main outcomes were projected cases identified, costs, quality adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) over the life course.Results Universal NBS for Pompe disease and confirmatory testing was estimated to cost an additional $26 million annually. Additional medication costs associated with earlier treatment initiation were $181 million; however, $8 million in medical care costs for other services were averted due to delayed disease progression. Infants with screened and treated infantile-onset Pompe disease experienced an average lifetime increase of 11.66 QALYs compared to clinical detection. The ICER was $408,000/QALY from the health care perspective and $379,000/QALY from a societal perspective. Results were sensitive to the cost of enzyme replacement therapy.Conclusions Newborn screening for Pompe disease results in substantial health gains for individuals with infantile-onset Pompe disease, but with additional costs.Competing Interest StatementThe authors have declared no competing interest.Funding StatementFinancial support for this study was provided by a grant from the Agency for Health Care Research and Quality, R01 HS020644. The funding agreement ensured the authors independence in designing the study, interpreting the data, writing, and publishing the report.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Not regulatedAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe manuscript and supplementary materials are designed to provide sufficient information for an interested reader to replicate the analysis. The statistical code is available by request from Dr. Prosser lisapros{at}umich.edu. |
Evidence and recommendation for guanidinoacetate methyltransferase deficiency newborn screening
Ream MA , Lam WKK , Grosse SD , Ojodu J , Jones E , Prosser LA , Rose AM , Comeau AM , Tanksley S , Powell CM , Kemper AR . Pediatrics 2023 152 (2) Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine biosynthesis due to pathogenic variants in the GAMT gene that lead to cerebral creatine deficiency and neurotoxic levels of guanidinoacetate. Untreated, GAMT deficiency is associated with hypotonia, significant intellectual disability, limited speech development, recurrent seizures, behavior problems, and involuntary movements. The birth prevalence of GAMT deficiency is likely between 0.5 and 2 per million live births. On the basis of small case series and sibling data, presymptomatic treatment with oral supplements of creatine, ornithine, and sodium benzoate, and a protein-restricted diet to reduce arginine intake, appear to substantially improve health and developmental outcomes. Without newborn screening, diagnosis typically happens after the development of significant impairment, when treatment has limited utility. GAMT deficiency newborn screening can be incorporated into the tandem-mass spectrometry screening that is already routinely used for newborn screening, with about 1 per 100 000 newborns screening positive. After a positive screen, diagnosis is established by finding an elevated guanidinoacetate concentration and low creatine concentration in the blood. Although GAMT deficiency is significantly more rare than other conditions included in newborn screening, the feasibility of screening, the low number of positive results, the relative ease of diagnosis, and the expected benefit of presymptomatic dietary therapy led to a recommendation from the Advisory Committee on Heritable Disorders in Newborns and Children to the Secretary of Health and Human Services that GAMT deficiency be added to the Recommended Uniform Screening Panel. This recommendation was accepted in January 2023. |
Cost of Tuberculosis Therapy Directly Observed on Video for Health Departments and Patients in New York City; San Francisco, California; and Rhode Island (2017-2018)
Beeler Asay GR , Lam CK , Stewart B , Mangan JM , Romo L , Marks SM , Morris SB , Gummo CL , Keh CE , Hill AN , Thomas A , Macaraig M , St John K , JAmpie T , Chuck C , Burzynski J . Am J Public Health 2020 110 (11) 1696-1703 Objectives. To assess costs of video and traditional in-person directly observed therapy (DOT) for tuberculosis (TB) treatment to health departments and patients in New York City, Rhode Island, and San Francisco, California.Methods. We collected health department costs for video DOT (VDOT; live and recorded), and in-person DOT (field- and clinic-based). Time-motion surveys estimated provider time and cost. A separate survey collected patient costs. We used a regression model to estimate cost by DOT type.Results. Between August 2017 and June 2018, 343 DOT sessions were captured from 225 patients; 87 completed a survey. Patient costs were lowest for VDOT live ($1.01) and highest for clinic DOT ($34.53). The societal (health department + patient) costs of VDOT live and recorded ($6.65 and $12.64, respectively) were less than field and clinic DOT ($21.40 and $46.11, respectively). VDOT recorded health department cost was not statistically different from field DOT cost in Rhode Island.Conclusions. Among the 4 different modalities, both types of VDOT were associated with lower societal costs when compared with traditional forms of DOT.Public Health Implications. VDOT was associated with lower costs from the societal perspective and may reduce public health costs when TB incidence is high. |
Implementation of newborn screening for conditions in the United States first recommended during 2010-2018
Singh S , Ojodu J , Kemper AR , Lam WKK , Grosse SD . Int J Neonatal Screen 2023 9 (2) The Recommended Uniform Screening Panel (RUSP) is the list of conditions recommended by the US Secretary of Health and Human Services for inclusion in state newborn screening (NBS). During 2010-2022, seven conditions were added to the RUSP: severe combined immunodeficiency (SCID) (2010), critical congenital heart disease (CCHD) (2011), glycogen storage disease, type II (Pompe) (2015), mucopolysaccharidosis, type I (MPS I) (2016), X-linked adrenoleukodystrophy (X-ALD) (2016), spinal muscular atrophy (SMA) (2018), and mucopolysaccharidosis, type II (MPS II) (2022). The adoption of SCID and CCHD newborn screening by programs in all 50 states and three territories (Washington, D.C.; Guam; and Puerto Rico) took 8.6 and 6.8 years, respectively. As of December 2022, 37 programs screen for Pompe, 34 for MPS I, 32 for X-ALD, and 48 for SMA. The pace of implementation based on the average additional number of NBS programs per year was most rapid for SMA (11.3), followed by CCHD (7.8), SCID (6.2), MPS I (5.4), Pompe (4.9), and X-ALD (4.7). |
Challenges associated with electronic and in-person directly observed therapy during a randomized trial
Mangan JM , Burzynski J , deCastro BR , Salerno MM , Lam CK , Macaraig M , Reaves M , Kiskadden-Bechtel S , Bowers S , Sathi C , Dias MP , Goswami ND , Vernon A . Int J Tuberc Lung Dis 2023 27 (4) 298-307 BACKGROUND: Electronic directly observed therapy (eDOT) has been proposed as an alternative to traditional in-person DOT (ipDOT) for monitoring TB treatment adherence. Information about the comparative performance and implementation of eDOT is limited.METHODS: The frequency of challenges during DOT, challenge type, and effect on medication observation were documented by DOT method during a crossover, noninferiority randomized controlled trial. A logistic mixed-effects model that adjusted for the study design was used to estimate the percentage of successfully observed doses when challenges occurred.RESULTS: A total of 20,097 medication doses were scheduled for observation with either eDOT (15,405/20,097; 76.7%) or ipDOT (4,692/20,097; 23.3%) for 213 study participants. In total, one or more challenges occurred during 17.3% (2,672/15,405) of eDOT sessions and 15.6% (730/4,692) of ipDOT sessions. Among 4,374 documented challenges, 27.3% (n = 1,192) were characterized as technical, 65.9% (n = 2,881) were patient-related, and 6.9% (n = 301) were program-related. Estimated from the logistic model (n = 6,782 doses, 173 participants), the adjusted percentage of doses successfully observed during problematic sessions was 21.7% (95% CI 11.2-37.8) for eDOT and 4.2% (95% CI 1.1-14.7) for ipDOT.CONCLUSION: Compared to ipDOT, challenges were encountered in a slightly higher percentage of eDOT sessions but were more often resolved to enable successful dose observation during problematic sessions. |
Recommendations for use of video directly observed therapy during tuberculosis treatment - United States, 2023
Mangan JM , Woodruff RS , Winston CA , Nabity SA , Haddad MB , Dixon MG , Parvez FM , Sera-Josef C , Salmon-Trejo LAT , Lam CK . MMWR Morb Mortal Wkly Rep 2023 72 (12) 313-316 U.S. clinical practice guidelines recommend directly observed therapy (DOT) as the standard of care for tuberculosis (TB) treatment (1). DOT, during which a health care worker observes a patient ingesting the TB medications, has typically been conducted in person. Video DOT (vDOT) uses video-enabled devices to facilitate remote interactions between patients and health care workers to promote medication adherence and clinical monitoring. Published systematic reviews, a published meta-analysis, and a literature search through 2022 demonstrate that vDOT is associated with a higher proportion of medication doses being observed and similar proportions of cases with treatment completion and microbiologic resolution when compared with in-person DOT (2-5). Based on this evidence, CDC has updated the recommendation for DOT during TB treatment to include vDOT as an equivalent alternative to in-person DOT. vDOT can assist health department TB programs meet the U.S. standard of care for patients undergoing TB treatment, while using resources efficiently. |
CDC's COVID-19 international vaccine implementation and evaluation program and lessons from earlier vaccine introductions
Soeters HM , Doshi RH , Fleming M , Adegoke OJ , Ajene U , Aksnes BN , Bennett S , Blau EF , Carlton JG , Clements S , Conklin L , Dahlke M , Duca LM , Feldstein LR , Gidudu JF , Grant G , Hercules M , Igboh LS , Ishizumi A , Jacenko S , Kerr Y , Konne NM , Kulkarni S , Kumar A , Lafond KE , Lam E , Longley AT , McCarron M , Namageyo-Funa A , Ortiz N , Patel JC , Perry RT , Prybylski D , Reddi P , Salman O , Sciarratta CN , Shragai T , Siddula A , Sikare E , Tchoualeu DD , Traicoff D , Tuttle A , Victory KR , Wallace A , Ward K , Wong MKA , Zhou W , Schluter WW , Fitter DL , Mounts A , Bresee JS , Hyde TB . Emerg Infect Dis 2022 28 (13) S208-s216 The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions. |
Implementation of data triangulation and dashboard development for COVID-19 vaccine adverse event following immunisation (AEFI) data in Nigeria
Shragai T , Adegoke OJ , Ikwe H , Sorungbe T , Haruna A , Williams I , Okonkwo R , Onu K , Asekun A , Gberikon M , Iwara E , Abimiku A , Rufai A , Okposen B , Gidudu J , Lam E , Bolu O . BMJ Glob Health 2023 8 (1) Nigeria began administering COVID-19 vaccines on 5 March 2021 and is working towards the WHO's African regional goal to fully vaccinate 70% of their eligible population by December 2022. Nigeria's COVID-19 vaccination information system includes a surveillance system for COVID-19 adverse events following immunisation (AEFI), but as of April 2021, AEFI data were being collected and managed by multiple groups and lacked routine analysis and use for action. To fill this gap in COVID-19 vaccine safety monitoring, between April 2021 and June 2022, the US Centers for Disease Control and Prevention, in collaboration with other implementing partners led by the Institute of Human Virology Nigeria, supported the Government of Nigeria to triangulate existing COVID-19 AEFI data. This paper describes the process of implementing published draft guidelines for data triangulation for COVID-19 AEFI data in Nigeria. Here, we focus on the process of implementing data triangulation rather than analysing the results and impacts of triangulation. Work began by mapping the flow of COVID-19 AEFI data, engaging stakeholders and building a data management system to intake and store all shared data. These datasets were used to create an online dashboard with key indicators selected based on existing WHO guidelines and national guidance. The dashboard went through an iterative review before dissemination to stakeholders. This case study highlights a successful example of implementing data triangulation for rapid use of AEFI data for decision-making and emphasises the importance of stakeholder engagement and strong data governance structures to make data triangulation successful. |
Utility of the lateral flow urine lipoarabinomannan tuberculosis assay in patients with advanced HIV disease at antiretroviral therapy centres in Mumbai, India
Acharya S , Deshpande P , Asirvatham ES , Palkar A , Sarman CJ , Laxmeshwar C , Setia MS , Rathod D , Koli S , Dale J , Yeldandi V , Allam R , Agarwal R , Verma S , Upadhyaya S , Nyendak M . PLoS One 2022 17 (9) e0273970 BACKGROUND: People with Advanced HIV Disease (AHD) are at higher risk of TB coinfection and mortality. However, there are challenges in TB diagnosis with the currently recommended diagnostic tools. WHO recommends lateral flow urine lipoarabinomannan (LF-LAM) assay to assist TB diagnosis among AHD patients. We assessed the utility and acceptability of using urine LF-LAM assay for TB diagnosis among patients at public Antiretroviral Therapy (ART) Centres in Mumbai. METHODS: The cross-sectional study was conducted among adult AHD patients accessing care from 17 ART centres during November,2020-June, 2021. Urine LF-LAM was offered as routine care for eligible patients in combination with standard diagnostic tests. We calculated the proportion of positive LF-LAM results by CD4 categories and TB symptoms and performed multivariable logistic regression to determine the factors associated with LF-LAM positivity. RESULTS: Among 2,390 patients, the majority (74.5%) had CD4 between 101-200 cells/mm3. The mean age was 43.7 years (SD:10.6), 68.6% were male, 8.4% had TB symptoms and 88.0% were on ART. The overall proportion of patients with urine LF-LAM positive results was 6.4%. Among PLHIV with CD4≤100 cells/mm3, the positivity was 43.0% and 7.7% in symptomatic and asymptomatic patients, respectively. Among PLHIV with a CD4>100 cells/mm3, the positivity was 26.7% and 2.7% in symptomatic and asymptomatic patients respectively. Urine LF-LAM positivity was higher among inpatients, ART naïve, patients on treatment for <6 months, symptomatic and in WHO clinical stage III/IV of HIV disease as compared to the reference categories. We detected an additional 131 TB cases with urine LF-LAM in combination with the standard diagnostic tests. CONCLUSION: The study demonstrated the utility of urine LF-LAM for TB diagnosis among AHD patients and the simple, user-friendly test was acceptable as part of routine care. Inclusion of urine LF-LAM test in the current diagnostic algorithm may facilitate early TB diagnosis among AHD patients. |
Evidence and recommendation for mucopolysaccharidosis type II newborn screening in the United States
Ream MA , Lam WKK , Grosse SD , Ojodu J , Jones E , Prosser LA , Rosé AM , Comeau AM , Tanksley S , Powell CM , Kemper AR . Genet Med 2022 25 (2) 100330 Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is an X-linked condition caused by pathogenic variants in the iduronate-2-sulfatase gene. The resulting reduced activity of the enzyme iduronate-2-sulfatase leads to accumulation of glycosaminoglycans that can progressively affect multiple organ systems and impair neurologic development. In 2006, the US Food and Drug Administration approved idursulfase for intravenous enzyme replacement therapy for MPS II. After the data suggesting that early treatment is beneficial became available, 2 states, Illinois and Missouri, implemented MPS II newborn screening. Following a recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children in February 2022, in August 2022, the US Secretary of Health and Human Services added MPS II to the Recommended Uniform Screening Panel, a list of conditions recommended for newborn screening. MPS II was added to the Recommended Uniform Screening Panel after a systematic evidence review reported the accuracy of screening, the benefit of presymptomatic treatment compared with usual case detection, and the feasibility of implementing MPS II newborn screening. This manuscript summarizes the findings of the evidence review that informed the Advisory Committee's decision. |
Phylogenetic Structure and Comparative Genomics of Multi-National Invasive Haemophilus influenzae Serotype a Isolates.
Topaz N , Tsang R , Deghmane AE , Claus H , Lâm TT , Litt D , Bajanca-Lavado MP , Pérez-Vázquez M , Vestrheim D , Giufrè M , Van Der Ende A , Gaillot O , Kuch A , McElligott M , Taha MK , Wang X . Front Microbiol 2022 13 856884 Recent reports have indicated a rise of invasive disease caused by Haemophilus influenzae serotype a (Hia) in North America and some European countries. The whole-genome sequences for a total of 410 invasive Hia isolates were obtained from 12 countries spanning the years of 1998 to 2019 and underwent phylogenetic and comparative genomic analysis in order to characterize the major strains causing disease and the genetic variation present among factors contributing to virulence and antimicrobial resistance. Among 410 isolate sequences received, 408 passed our quality control and underwent genomic analysis. Phylogenetic analysis revealed that the Hia isolates formed four genetically distinct clades: clade 1 (n = 336), clade 2 (n = 13), clade 3 (n = 3) and clade 4 (n = 56). A low diversity subclade 1.1 was found in clade 1 and contained almost exclusively North American isolates. The predominant sequence types in the Hia collection were ST-56 (n = 125), ST-23 (n = 98) and ST-576 (n = 51), which belonged to clade 1, and ST-62 (n = 54), which belonged to clade 4. Clades 1 and 4 contained predominantly North American isolates, and clades 2 and 3 predominantly contained European isolates. Evidence of the presence of capsule duplication was detected in clade 1 and 2 isolates. Seven of the virulence genes involved in endotoxin biosynthesis were absent from all Hia isolates. In general, the presence of known factors contributing to β-lactam antibiotic resistance was low among Hia isolates. Further tests for virulence and antibiotic susceptibility would be required to determine the impact of these variations among the isolates. |
Comparative pulmonary toxicities of lunar dusts and terrestrial dusts (TiO(2) & SiO(2)) in rats and an assessment of the impact of particle-generated oxidants on the dusts' toxicities
Lam CW , Castranova V , Zeidler-Erdely PC , Renne R , Hunter R , McCluskey R , Scully RR , Wallace WT , Zhang Y , Ryder VE , Cooper B , McKay D , McClellan RO , Driscoll KE , Gardner DE , Barger M , Meighan T , James JT . Inhal Toxicol 2022 34 51-67 Humans will set foot on the Moon again soon. The lunar dust (LD) is potentially reactive and could pose an inhalation hazard to lunar explorers. We elucidated LD toxicity and investigated the toxicological impact of particle surface reactivity (SR) using three LDs, quartz, and TiO(2). We first isolated the respirable-size-fraction of an Apollo-14 regolith and ground two coarser samples to produce fine LDs with increased SR. SR measurements of these five respirable-sized dusts, determined by their in-vitro ability to generate hydroxyl radicals (OH), showed that ground LDs>unground LDTiO(2) quartz. Rats were each intratracheally instilled with 0, 1, 2.5, or 7.5mg of a test dust. Toxicity biomarkers and histopathology were assessed up to 13weeks after the bolus instillation. All dusts caused dose-dependent-increases in pulmonary lesions and toxicity biomarkers. The three LDs, which possessed mineral compositions/properties similar to Arizona volcanic ash, were moderately toxic. Despite a 14-fold OH difference among these three LDs, their toxicities were indistinguishable. Quartz produced the lowest OH amount but showed the greatest toxicity. Our results showed no correlation between the toxicity of mineral dusts and their ability to generate free radicals. We also showed that the amounts of oxidants per neutrophil increased with doses, time and the cytotoxicity of the dusts in the lung, which supports our postulation that dust-elicited neutrophilia is the major persistent source of oxidative stress. These results and the discussion of the crucial roles of the short-lived, continuously replenished neutrophils in dust-induced pathogenesis are presented. |
In-person vs electronic directly observed therapy for tuberculosis treatment adherence: A randomized noninferiority trial
Burzynski J , Mangan JM , Lam CK , Macaraig M , Salerno MM , deCastro BR , Goswami ND , Lin CY , Schluger NW , Vernon A . JAMA Netw Open 2022 5 (1) e2144210 IMPORTANCE: Electronic directly observed therapy (DOT) is used increasingly as an alternative to in-person DOT for monitoring tuberculosis treatment. Evidence supporting its efficacy is limited. OBJECTIVE: To determine whether electronic DOT can attain a level of treatment observation as favorable as in-person DOT. DESIGN, SETTING, AND PARTICIPANTS: This was a 2-period crossover, noninferiority trial with initial randomization to electronic or in-person DOT at the time outpatient tuberculosis treatment began. The trial enrolled 216 participants with physician-suspected or bacteriologically confirmed tuberculosis from July 2017 to October 2019 in 4 clinics operated by the New York City Health Department. Data analysis was conducted between March 2020 and April 2021. INTERVENTIONS: Participants were asked to complete 20 medication doses using 1 DOT method, then switched methods for another 20 doses. With in-person therapy, participants chose clinic or community-based DOT; with electronic DOT, participants chose live video-conferencing or recorded videos. MAIN OUTCOMES AND MEASURES: Difference between the percentage of medication doses participants were observed to completely ingest with in-person DOT and with electronic DOT. Noninferiority was demonstrated if the upper 95% confidence limit of the difference was 10% or less. We estimated the percentage of completed doses using a logistic mixed effects model, run in 4 modes: modified intention-to-treat, per-protocol, per-protocol with 85% or more of doses conforming to the randomization assignment, and empirical. Confidence intervals were estimated by bootstrapping (with 1000 replicates). RESULTS: There were 173 participants in each crossover period (median age, 40 years [range, 16-86 years]; 140 [66%] men; 80 [37%] Asian and Pacific Islander, 43 [20%] Black, and 71 [33%] Hispanic individuals) evaluated with the model in the modified intention-to-treat analytic mode. The percentage of completed doses with in-person DOT was 87.2% (95% CI, 84.6%-89.9%) vs 89.8% (95% CI, 87.5%-92.1%) with electronic DOT. The percentage difference was -2.6% (95% CI, -4.8% to -0.3%), consistent with a conclusion of noninferiority. The 3 other analytic modes yielded equivalent conclusions, with percentage differences ranging from -4.9% to -1.9%. CONCLUSIONS AND RELEVANCE: In this trial, the percentage of completed doses under electronic DOT was noninferior to that under in-person DOT. This trial provides evidence supporting the efficacy of this digital adherence technology, and for the inclusion of electronic DOT in the standard of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03266003. |
Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity.
Perelygina L , Faisthalab R , Abernathy E , Chen MH , Hao L , Bercovitch L , Bayer DK , Noroski LM , Lam MT , Cicalese MP , Al-Herz W , Nanda A , Hajjar J , Vanden Driessche K , Schroven S , Leysen J , Rosenbach M , Peters P , Raedler J , Albert MH , Abraham RS , Rangarjan HG , Buchbinder D , Kobrynski L , Pham-Huy A , Dhossche J , Cunningham Rundles C , Meyer AK , Theos A , Atkinson TP , Musiek A , Adeli M , Derichs U , Walz C , Krüger R , von Bernuth H , Klein C , Icenogle J , Hauck F , Sullivan KE . Front Immunol 2021 12 796065 Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions. |
Shotgun metagenome sequencing of a Sudanese toombak snuff tobacco: Genetic attributes of a high tobacco-specific nitrosamine (TSNA) containing smokeless tobacco product.
Tyx RE , Rivera AJ , Stanfill SB , Zaatari GS , Watson CH . Lett Appl Microbiol 2021 74 (3) 444-451 The most alarming aspect of the Sudanese toombak smokeless tobacco is that it contains high levels of highly toxic Tobacco-Specific Nitrosamines (TSNAs). Understanding the microbiology of toombak is of relevance because TSNAs are an indirect result of microbial-mediated nitrate reductions. We conducted shotgun metagenomic sequencing on a toombak product for which relevant features are presented here. The microbiota was composed of over 99% Bacteria. The most abundant taxa included Actinobacteria, specifically genera Enteractinococcus and Corynebacterium, while Firmicutes were represented by Family Bacillaceae and the genus Staphylococcus. Selected gene targets were nitrate reduction and transport, antimicrobial resistance, and other genetic transference mechanisms. Canonical nitrate reduction and transport genes (i.e., nar) were found for Enteractinococcus and Corynebacterium while various species of Staphylococcus exhibited a notable number of antimicrobial resistance and genetic transference genes. The nitrate reduction activity of the microbiota in toombak is suspected to be a contributing factor to its high levels of TSNAs. Additionally, the presence of antimicrobial resistance and transference genes could contribute to deleterious effects on oral and gastrointestinal health of the end user. Overall, the high toxicity and increased incidences of cancer and oral disease of toombak users warrants further investigation into the microbiology of toombak. |
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