Fractional Flow Reserve Cardio-Oncology Effects on Inpatient Mortality, Length of Stay, and Cost Based on Malignancy Type: Machine Learning Supported Nationally Representative Case-Control Study of 30 Million Hospitalizations.

Background and Objectives: There are no nationally representative studies of mortality and cost effectiveness for fractional flow reserve (FFR) guided percutaneous coronary interventions (PCI) in patients with cancer. Our study aims to show how this patient population may benefit from FFR-guided PCI. Materials and Methods: Propensity score matched analysis and backward propagation neural network machine learning supported multivariable regression was performed for inpatient mortality in this case-control study of the 2016 National Inpatient Sample (NIS). Regression results were adjusted for age, race, income, geographic region, metastases, mortality risk, and the likelihood of undergoing FFR versus non-FFR PCI. All analyses were adjusted for the complex survey design to produce nationally representative estimates. Results: Of the 30,195,722 hospitalized patients meeting criteria, 3.37% of the PCIs performed included FFR. In propensity score adjusted multivariable regression, FFR versus non-FFR PCI significantly reduced inpatient mortality (OR 0.47, 95%CI 0.35−0.63; p < 0.001) and length of stay (LOS) (in days; beta −0.23, 95%CI −0.37−−0.09; p = 0.001) while increasing cost (in USD; beta $5708.63, 95%CI, 3042.70−8374.57; p < 0.001), without significantly increasing complications overall. FFR versus non-FFR PCI did not specifically change cancer patients' inpatient mortality, LOS, or cost. However, FFR versus non-FFR PCI significantly increased inpatient mortality for Hodgkin's lymphoma (OR 52.48, 95%CI 7.16−384.53; p < 0.001) and rectal cancer (OR 24.38, 95%CI 2.24−265.73; p = 0.009). Conclusions: FFR-guided PCI may be safely utilized in patients with cancer as it does not significantly increase inpatient mortality, complications, and LOS. These findings support the need for an increased utilization of FFR-guided PCI and further studies to evaluate its long-term impact.

Artificial intelligence-augmented analysis of contemporary procedural, mortality, and cost trends in carcinoid heart disease in a large national cohort with a focus on the "forgotten pulmonic valve".

Background: Carcinoid heart disease is increasingly recognized and challenging to manage due to limited outcomes data. This is the largest known cohort study of valvular pathology, treatment (including pulmonary and tricuspid valve replacements [PVR and TVR]), dispairties, mortality, and cost in patients with malignant carcinoid tumor (MCT). Methods: Machine learning-augmented propensity score-adjusted multivariable regression was conducted for clincal outcomes in the 2016-2018 U.S. National Inpatient Sample (NIS). Regression models were weighted by the complex survey design and adjusted for known confounders and the likelihood of undergoing valvular procedures. Results: Among 101,521,656 hospitalizations, 55,910 (0.06%) had MCT. Patients with MCT vs. those without had significantly higher inpatient mortality (2.93 vs. 2.04%, p = 0.002), longer mean length of stay (12.20 vs. 4.62, p < 0.001), and increased mean total cost of stay ($70,252.18 vs. 51,092.01, p < 0.001). There was a step-wise increased rate of TVR and PVR with each subsequent year, with significantly more TV (0.16% vs. 0.01, p < 0.001) and PV (0.03 vs. 0.00, p = 0.040) diagnosed with vs. without MCT for 2016, with comparable trends in 2017 and 2018. There were no significant procedural disparities among patients with MCT for sex, race, income, urban density, or geographic region, except in 2017, when the highest prevalence of PV procedures were performed in the Western North at 50.00% (p = 0.034). In machine learning and propensity score augmented multivariable regression, MCT did not significantly increase the likelihood of TVR or PVR. In sub-group analysis restricted to MCT, neither TVR nor PVR significantly increased mortality, though it did increase cost (respectively, $141,082.30, p = 0.015; $355,356.40, p = 0.012). Conclusion: This analysis reflects a favorable trend in recognizing the need for TVR and PVR in patients with MCT, with associated increased cost but not mortality. Our study also suggests that pulmonic valve pathology is increasingly recognized in MCT as reflected by the upward trend in PVRs. Further research and updated societal guidelines may need to focus on the "forgotten pulmonic valve" to improve outcomes and disparities in this understudied patient population.

Stress cardiomyopathy in hospitalized patients with cancer: machine learning analysis by primary malignancy type.

AIMS: Previous studies have shown that patients with stress (Takotsubo) cardiomyopathy (SC) and cancer have higher in-hospital mortality than patients with SC alone. No studies have examined outcomes in patients with active cancer and SC compared to patients with active cancer without SC. We aimed to assess the potential association between primary malignancy type and SC and their shared interaction with inpatient mortality. METHODS AND RESULTS: We analysed SC by primary malignancy type with propensity score adjusted multivariable regression and machine learning analysis using the 2016 United States National Inpatient Sample. Of 30 195 722 adult hospitalized patients, 4 719 591 had active cancer, of whom 568 239 had SC. The mean age of patients with cancer and SC was 69.1, of which 74.7% were women. Among patients with cancer, those with SC were more likely to be female and have white race, Medicare insurance, hypertension, heart failure with reduced ejection fraction, obesity, cerebrovascular disease, anaemia, and chronic obstructive pulmonary disease (P < 0.003 for all). In machine learning-augmented, propensity score multivariable regression adjusted for age, race, and income, only lung cancer [OR 1.25; 95% CI: 1.08-1.46; P = 0.003] and breast cancer [OR 1.81; 95% CI: 1.62-2.02; P < 0.001] were associated with a significantly increased likelihood of SC. Neither SC alone nor having both SC and cancer was significantly associated with in-hospital mortality. The presence of concomitant SC and breast cancer was significantly associated with reduced mortality (OR 0.48; 95% CI: 0.25-0.94; P = 0.032). CONCLUSIONS: This analysis demonstrates that primary malignancy type influences the likelihood of developing SC. Further studies will be necessary to delineate characteristics in patients with lung cancer and breast cancer which contribute to development of SC. Additional investigation should confirm lower mortality in patients with SC and breast cancer and determine possible explanations and protective factors.

Characteristics of ambulatory spine care visits in the United States, 2009-2016.

BACKGROUND: Back pain is a leading reason for seeking care in the United States (US), and is a major cause of morbidity. OBJECTIVE: To analyze demographic, patient, and visit characteristics of adult ambulatory spine clinic visits in the United States from 2009-2016. METHODS: Data from the National Ambulatory Medical Care Survey from 2009-2016 were used and were sample weighted. RESULTS: Most patients presenting for ambulatory spine care were 45-64 years (45%), were most commonly female (56.8%), and private insurance (45%) and Medicare (26%) were most common payors. The percentage of visits for spine care done at a primary care setting was 50.1% in 2009-2010 and 48.3% in 2014-2015. Approximately 15.5% were seen in orthopedic surgery clinics in 2009-2010 and 7.3% in 2015-2016. MRI was utilized in 11.7% in 2009-2010 and 11.0% in 2015-2016. Physical therapy was prescribed in 13.2% and narcotic analgesic medications were prescribed in 36.2% of patients in 2015-2016. CONCLUSIONS: MRI was used more frequently than guidelines recommended, and physical therapy was less frequently utilized despite evidence. A relatively high use of opiates in treatment of back pain was reported and is concerning. Although back pain represents a substantial public health burden in the United States, the delivery of care is not evidence-based.

Percutaneous Coronary Intervention in Patients With Gynecological Cancer: Machine Learning-Augmented Propensity Score Mortality and Cost Analysis for 383,760 Patients.

BACKGROUND: Despite the growing number of patients with both coronary artery disease and gynecological cancer, there are no nationally representative studies of mortality and cost effectiveness for percutaneous coronary interventions (PCI) and this cancer type. METHODS: Backward propagation neural network machine learning supported and propensity score adjusted multivariable regression was conducted for the above outcomes in this case-control study of the 2016 National Inpatient Sample (NIS), the United States' largest all-payer hospitalized dataset. Regression models were fully adjusted for age, race, income, geographic region, cancer metastases, mortality risk, and the likelihood of undergoing PCI (and also with length of stay [LOS] for cost). Analyses were also adjusted for the complex survey design to produce nationally representative estimates. Centers for Disease Control and Prevention (CDC)-based cost effectiveness ratio (CER) analysis was performed. RESULTS: Of the 30,195,722 hospitalized patients meeting criteria, 1.27% had gynecological cancer of whom 0.02% underwent PCI including 0.04% with metastases. In propensity score adjusted regression among all patients, the interaction of PCI and gynecological cancer (vs. not having PCI) significantly reduced mortality (OR 0.53, 95%CI 0.36-0.77; p = 0.001) while increasing LOS (Beta 1.16 days, 95%CI 0.57-1.75; p < 0.001) and total cost (Beta $31,035.46, 95%CI 26758.86-35312.06; p < 0.001). Among gynecological cancer patients, mortality was significantly reduced by PCI (OR 0.58, 95%CI 0.39-0.85; p = 0.006) and being in East North Central, West North Central, South Atlantic, and Mountain regions (all p < 0.03) compared to New England. PCI reduced mortality but not significantly for metastatic patients (OR 0.74, 95%CI 0.32-1.71; p = 0.481). Eighteen extra gynecological cancer patients' lives were saved with PCI for a net national cost of $3.18 billion and a CER of $176.50 million per averted death. CONCLUSION: This large propensity score analysis suggests that PCI may cost inefficiently reduce mortality for gynecological cancer patients, amid income and geographic disparities in outcomes.

Assessment of Physician Sleep and Wellness, Burnout, and Clinically Significant Medical Errors.

Importance: Sleep-related impairment in physicians is an occupational hazard associated with long and sometimes unpredictable work hours and may contribute to burnout and self-reported clinically significant medical error. Objective: To assess the associations between sleep-related impairment and occupational wellness indicators in physicians practicing at academic-affiliated medical centers and the association of sleep-related impairment with self-reported clinically significant medical errors, before and after adjusting for burnout. Design, Setting, and Participants: This cross-sectional study used physician wellness survey data collected from 11 academic-affiliated medical centers between November 2016 and October 2018. Analysis was completed in January 2020. A total of 19 384 attending physicians and 7257 house staff physicians at participating institutions were invited to complete a wellness survey. The sample of responders was used for this study. Exposures: Sleep-related impairment. Main Outcomes and Measures: Association between sleep-related impairment and occupational wellness indicators (ie, work exhaustion, interpersonal disengagement, overall burnout, and professional fulfillment) was hypothesized before data collection. Assessment of the associations of sleep-related impairment and burnout with self-reported clinically significant medical errors (ie, error within the last year resulting in patient harm) was planned after data collection. Results: Of all physicians invited to participate in the survey, 7700 of 19 384 attending physicians (40%) and 3695 of 7257 house staff physicians (51%) completed sleep-related impairment items, including 5279 women (46%), 5187 men (46%), and 929 (8%) who self-identified as other gender or elected not to answer. Because of institutional variation in survey domain inclusion, self-reported medical error responses from 7538 physicians were available for analyses. Spearman correlations of sleep-related impairment with interpersonal disengagement (r = 0.51; P < .001), work exhaustion (r = 0.58; P < .001), and overall burnout (r = 0.59; P < .001) were large. Sleep-related impairment correlation with professional fulfillment (r = -0.40; P < .001) was moderate. In a multivariate model adjusted for gender, training status, medical specialty, and burnout level, compared with low sleep-related impairment levels, moderate, high, and very high levels were associated with increased odds of self-reported clinically significant medical error, by 53% (odds ratio, 1.53; 95% CI, 1.12-2.09), 96% (odds ratio, 1.96; 95% CI, 1.46-2.63), and 97% (odds ratio, 1.97; 95% CI, 1.45-2.69), respectively. Conclusions and Relevance: In this study, sleep-related impairment was associated with increased burnout, decreased professional fulfillment, and increased self-reported clinically significant medical error. Interventions to mitigate sleep-related impairment in physicians are warranted.

Burden of hereditary cancer susceptibility in unselected patients with pancreatic ductal adenocarcinoma referred for germline screening.

BACKGROUND: Recent guidelines recommend consideration of germline testing for all newly diagnosed pancreatic ductal adenocarcinoma (PDAC). The primary aim of this study was to determine the burden of hereditary cancer susceptibility in PDAC. A secondary aim was to compare genetic testing uptake rates across different modes of genetic counselling. PATIENTS AND METHODS: All patients diagnosed with PDAC in the province of British Columbia, Canada referred to a population-based hereditary cancer program were eligible for multi-gene panel testing, irrespective of cancer family history. Any healthcare provider or patients themselves could refer. RESULTS: A total of 305 patients with PDAC were referred between July 2016 and January 2019. Two hundred thirty-five patients attended a consultation and 177 completed index germline genetic testing. 25/177 (14.1%) of unrelated patients had a pathogenic variant (PV); 19/25 PV were in known PDAC susceptibility genes with cancer screening or risk-reduction implications. PDAC was significantly associated with PV in ATM (OR, 7.73; 95% CI, 3.10 to 19.33, P = 6.14E-05) when comparing age and gender and ethnicity-matched controls tested on the same platform. The overall uptake rate for index testing was 59.2% and was significantly higher with 1-on-1 consultations and group consultations compared to telehealth consultations (88.9% vs 82.9% vs 61.8%, P < .001). CONCLUSION: In a prospective clinic-based cohort of patients with PDAC referred for testing irrespective of family history, germline PV were detected in 14.1%. PV in ATM accounted for half of all PVs and were significantly associated with PDAC. These findings support recent guidelines and will guide future service planning in this population.

Use of Advance Care Planning Billing Codes in a Tertiary Care Center Setting.

INTRODUCTION: The Centers for Medicare and Medicaid Services released the final payment rules for reimbursement of advance care planning (ACP) effective January 2016. In its first year, 23,000 providers nationwide submitted 624,000 claims using the Current Procedural Terminology codes 99497 and 99498. The objectives of our study were to 1) assess the frequency of ACP codes used at a single academic tertiary care center in Iowa, 2) determine when and by whom the codes were used, and 3) summarize ACP clinical notes. METHODS: Using the electronic medical record data warehouse from a single tertiary teaching hospital and affiliated clinics, date of service, department where service was provided, provider name and type, patient medical record number, date of birth, and gender linked to the ACP codes 99497 and 99498 were collected. The content of ACP clinical notes were reviewed and summarized. Study period was from January 1, 2016 through September 19, 2018. RESULTS: During the 33 months, code 99497 was used 17 times and code 99498 was never used. Code 99497 was successfully reimbursed 4 times. DISCUSSION: Charges were not reimbursed if the ACP visits did not meet the minimum time requirement or were conducted by an individual not considered a qualified health care professional per Medicare rules. CONCLUSION: ACP codes 99497 and 99498 were very rarely used at this tertiary care center during the initial 33-months after the Medicare rules went into effect. Interventions are needed to promote the use of ACP codes, so the time spent in important ACP discussions are properly compensated.

Socialising Health Burden Through Different Network Topologies: A Simulation Study.

An aging population and the expectation of premium quality health services combined with the increasing economic burden of the healthcare system requires a paradigm shift toward patient oriented healthcare. The guardian angel theory described by Szolovits [1] explores the notion of enlisting patients as primary providers of information and motivation to patients with similar clinical history through social connections. In this study, an agent based model was developed to simulate to explore how individuals are affected through their levels of intrinsic positivity. Ring, point-to-point (paired buddy), and random networks were modelled, with individuals able to send messages to each other given their levels of variables positivity and motivation. Of the 3 modelled networks it is apparent that the ring network provides the most equal, collective improvement in positivity and motivation for all users. Further study into other network topologies should be undertaken in the future.

Raltegravir in second-line antiretroviral therapy in resource-limited settings (SELECT): a randomised, phase 3, non-inferiority study.

BACKGROUND: For second-line antiretroviral therapy, WHO recommends a boosted protease inhibitor plus nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs). However, concerns about toxicity and cross-resistance motivated a search for regimens that do not contain NRTIs. We aimed to assess whether boosted lopinavir plus raltegravir would be non-inferior to boosted lopinavir plus NRTIs for virological suppression in resource-limited settings. METHODS: A5273 was a randomised, open-label, phase 3, non-inferiority study at 15 AIDS Clinical Trials Group (ACTG) research sites in nine resource-limited countries (three sites each in India and South Africa, two each in Malawi and Peru, and one each in Brazil, Kenya, Tanzania, Thailand, and Zimbabwe). Adults with plasma HIV-1 RNA concentrations of at least 1000 copies per mL after at least 24 weeks on a regimen based on a non-NRTI inhibitor were randomly assigned (1:1) to receive oral ritonavir-boosted lopinavir (100 mg ritonavir, 400 mg lopinavir) plus 400 mg raltegravir twice a day (raltegravir group) or to ritonavir-boosted lopinavir plus two or three NRTIs selected from an algorithm (eg, zidovudine after failure with tenofovir and vice versa; NRTI group). Randomised group assignment was done with a computer algorithm concealed to site personnel, and stratified by HIV-1 RNA viral load, CD4 cell count, and intention to use zidovudine, with the groups balanced by each site. The primary endpoint was time to confirmed virological failure (two measurements of HIV-1 RNA viral load >400 copies per mL) at or after week 24 in the intention-to-treat population. Non-inferiority (10% margin) was assessed by comparing the cumulative probability of virological failure by 48 weeks. This trial was registered with ClinicalTrials.gov, NCT01352715. FINDINGS: Between March 13, 2012, and Oct 2, 2013, we randomly assigned 515 participants: 260 to the raltegravir group and 255 to the NRTI group; two participants in the raltegravir group and one in the NRTI group were excluded from analyses because of ineligibility. By the end of follow-up (October, 2014), 96 participants had virological failure (46 in the raltegravir group and 50 in the NRTI group). By 48 weeks, the cumulative probability of virological failure was 10·3% (95% CI 6·5-14·0) in the raltegravir group and 12·4% (8·3-16·5) in the NRTI group, with a weighted difference of -3·4% (-8·4 to 1·5), indicating that raltegravir was non-inferior, but not superior, to NRTIs. 62 (24%) participants in the raltegravir group and 81 (32%) in the NRTI group had grade 3 or higher adverse events; 19 (7%) and 29 (11%), respectively, had serious adverse events. Three participants in each group died, all from HIV-related causes. INTERPRETATION: In settings with extensive NRTI resistance but no available resistance testing, our data support WHO's recommendation for ritonavir-boosted lopinavir plus NRTI for second-line antiretroviral therapy. Ritonavir-boosted lopinavir plus raltegravir is an appropriate alternative, especially if NRTI use is limited by toxicity. FUNDING: National Institutes of Health.

Translating the Tuberculosis Research Agenda: Much Accomplished, but Much More to Be Done.

Despite the availability of effective diagnostics and curative treatment regimens for tuberculosis, millions of people die each year of this disease. The steady global increase in the number of tuberculosis cases caused by multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis are of major concern, especially in light of the thin tuberculosis drug pipeline. New tuberculosis drugs are undergoing clinical evaluation, and renewed hope comes from fresh approaches to improve treatment outcomes using a range of adjunct host-directed cellular and repurposed drug therapies. Current efforts in developing second-generation and new rapid point-of-care diagnostic assays take advantage of recent genetic and molecular advances. Slow progress in the development of prophylactic and therapeutic vaccines requires increased funding for basic as well as translational research. Although major challenges remain, these can be overcome by cementing our resolve, raising advocacy, bolstering global funder investments, and leveraging more effective collaborations through equitable public-private partnerships.

Grandmothering life histories and human pair bonding.

The evolution of distinctively human life history and social organization is generally attributed to paternal provisioning based on pair bonds. Here we develop an alternative argument that connects the evolution of human pair bonds to the male-biased mating sex ratios that accompanied the evolution of human life history. We simulate an agent-based model of the grandmother hypothesis, compare simulated sex ratios to data on great apes and human hunter-gatherers, and note associations between a preponderance of males and mate guarding across taxa. Then we explore a recent model that highlights the importance of mating sex ratios for differences between birds and mammals and conclude that lessons for human evolution cannot ignore mammalian reproductive constraints. In contradiction to our claim that male-biased sex ratios are characteristically human, female-biased ratios are reported in some populations. We consider the likelihood that fertile men are undercounted and conclude that the mate-guarding hypothesis for human pair bonds gains strength from explicit links with our grandmothering life history.

Justifying one's transgressions: how rationalizations based on equity, equality, and need affect trust after its violation.

We investigate how efforts to justify a transgression as an attempt to address matters of equity, equality, or need would affect the implications of an apology for trust after its violation, and how this would depend on the intended beneficiary. To do so, we conducted 2 studies, including a new research design that supplements the rigor of experiments with far greater realism. Although combining a justification with an apology tended to elicit higher trust relative to an apology alone when the violation benefited another party, doing so was ineffective or harmful when the violation benefited the violator. Finer-grained analyses comparing the 3 types of justifications, furthermore, revealed that the addition of equity-based justifications elicited higher trust than the addition of equality- or need-based justifications in general, and that the addition of need-based justifications was particularly harmful when the violation benefited the self. Perceived fairness mediated these effects.

Modelling the impact of marine reserves on a population with depensatory dynamics.

In this study, we use a spatially implicit, stage-structured model to evaluate marine reserve effectiveness for a fish population exhibiting depensatory (strong Allee) effects in its dynamics. We examine the stability and sensitivity of the equilibria of the modelled system with regards to key system parameters and find that for a reasonable set of parameters, populations can be protected from a collapse if a small percentage of the total area is set aside in reserves. Furthermore, the overall abundance of the population is predicted to achieve a maximum at a certain ratio A of reserve area to fished area, which depends heavily on the other system parameters such as the net export rate of fish from the marine reserves to the fished areas. This finding runs contrary to the contested "equivalence at best" result when comparing fishery management through traditional catch or effort control and management through marine reserves. Lastly, we analyse the problem from a bioeconomics perspective by computing the optimal harvesting policy using Pontryagin's Maximum Principle, which suggests that the value for A which maximizes the optimal equilibrium fishery yield also maximizes population abundance when the cost per unit harvest is constant, but can increase substantially when the cost per unit harvest increases with the area being harvested.

Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test.

Rapid progress has been made in the development of new diagnostic assays for tuberculosis in recent years. New technologies have been developed and assessed, and are now being implemented. The Xpert MTB/RIF assay, which enables simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance, was endorsed by WHO in December, 2010. This assay was specifically recommended for use as the initial diagnostic test for suspected drug-resistant or HIV-associated pulmonary tuberculosis. By June, 2012, two-thirds of countries with a high tuberculosis burden and half of countries with a high multidrug-resistant tuberculosis burden had incorporated the assay into their national tuberculosis programme guidelines. Although the development of the Xpert MTB/RIF assay is undoubtedly a landmark event, clinical and programmatic effects and cost-effectiveness remain to be defined. We review the rapidly growing body of scientific literature and discuss the advantages and challenges of using the Xpert MTB/RIF assay in areas where tuberculosis is endemic. We also review other prospects within the developmental pipeline. A rapid, accurate point-of-care diagnostic test that is affordable and can be readily implemented is urgently needed. Investment in the tuberculosis diagnostics pipeline should remain a major priority for funders and researchers.

Tuberculosis comorbidity with communicable and non-communicable diseases: integrating health services and control efforts.

Recent data for the global burden of disease reflect major demographic and lifestyle changes, leading to a rise in non-communicable diseases. Most countries with high levels of tuberculosis face a large comorbidity burden from both non-communicable and communicable diseases. Traditional disease-specific approaches typically fail to recognise common features and potential synergies in integration of care, management, and control of non-communicable and communicable diseases. In resource-limited countries, the need to tackle a broader range of overlapping comorbid diseases is growing. Tuberculosis and HIV/AIDS persist as global emergencies. The lethal interaction between tuberculosis and HIV coinfection in adults, children, and pregnant women in sub-Saharan Africa exemplifies the need for well integrated approaches to disease management and control. Furthermore, links between diabetes mellitus, smoking, alcoholism, chronic lung diseases, cancer, immunosuppressive treatment, malnutrition, and tuberculosis are well recognised. Here, we focus on interactions, synergies, and challenges of integration of tuberculosis care with management strategies for non-communicable and communicable diseases without eroding the functionality of existing national programmes for tuberculosis. The need for sustained and increased funding for these initiatives is greater than ever and requires increased political and funder commitment.

Clinical research and development of tuberculosis diagnostics: moving from silos to synergy.

The development, evaluation, and implementation of new and improved diagnostics have been identified as critical needs by human immunodeficiency virus (HIV) and tuberculosis researchers and clinicians alike. These needs exist in international and domestic settings and in adult and pediatric populations. Experts in tuberculosis and HIV care, researchers, healthcare providers, public health experts, and industry representatives, as well as representatives of pertinent US federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, National Institutes of Health, United States Agency for International Development) assembled at a workshop proposed by the Diagnostics Working Group of the Federal Tuberculosis Taskforce to review the state of tuberculosis diagnostics development in adult and pediatric populations.