Precision Errors and Monitoring Time Interval in Pediatric Muscle Imaging and Neuromuscular Performance Assessment.

OBJECTIVES: To determine precision errors and monitoring time intervals in imaged muscle properties and neuromuscular performance, and to explore growth-related factors associated with precision errors in children. METHODS: We included 35 children (mean age 10.5yrs) in the precision study cohort and 40 children (10.7yrs) in the follow-up study cohort. We assessed forearm and lower leg muscle properties (area, density) with peripheral quantitative computed tomography. We measured neuromuscular performance via maximal pushup, grip force, countermovement and standing long jump force, power, and impulse along with long jump length. We calculated precision errors (root-mean-squared coefficient of variation) from the precision cohort and monitoring time intervals using annual changes from the follow-up cohort. We explored associations between precision errors (coefficient of variation) and maturity, time interval (between repeated measures), and anthropometric changes using Spearman's rank correlation (p<0.05). RESULTS: Muscle measures exhibited precision errors of 1.3-14%. Monitoring time intervals were 1-2.6yrs, except muscle density (>43yrs). We identified only one association between precision errors and maturity (maximal pushup force: rho=-0.349; p=0.046). CONCLUSIONS: Imaging muscle properties and neuromuscular performance measures had precision errors of 1-14% and appeared suitable for follow-up on ~2yr scales (except muscle density). Maximal pushup force appeared more repeatable in mature children.

Aligning US Agency Policies for Cardiovascular Devices Through the Breakthrough Devices Program.

Importance: The US Food and Drug Administration (FDA) and Centers for Medicare & Medicaid Services (CMS) have different statutory authorities; FDA evaluates safety and effectiveness for market authorization of medical devices while CMS determines whether coverage is "reasonable and necessary" for its beneficiaries. CMS has recently enacted policies automatically providing supplemental reimbursement for new, costly devices authorized after designation in FDA's Breakthrough Devices Program (BDP) and in June 2023 issued notice for a new Transitional Coverage for Emerging Technologies pathway, accelerating coverage for Breakthrough devices. Observations: Aiming to incentivize innovation, FDA awards Breakthrough designations early in device development to expedite market authorization and can accept greater uncertainty in benefit and risk, contingent on postmarket evidence generation. Since 2020, Breakthrough designation has effectively automatically qualified devices to receive supplemental Medicare reimbursement after CMS waived a long-standing requirement that devices demonstrate "substantial clinical improvement" for beneficiaries. Using publicly available information, 3 examples of cardiovascular devices illustrate that the BDP may allow for FDA authorization based on less rigorous evidence, such as single-arm trials focused on surrogate end points with short-term follow-up whose participants are often not representative of Medicare beneficiaries. In 1 case, Breakthrough designation allowed a 30% decrease in enrollment of a trial used to support approval. Initial positive findings for some devices have remained unverified, and in 1 case even partially nullified, by postmarket studies. Manufacturers have also used Breakthrough designations to set the price of devices to facilitate additional pass-through payments, leading to higher short-term and long-term costs to CMS and health care systems. Conclusions and Relevance: The BDP may qualify new, costly devices for higher and automatic Medicare reimbursement despite evidence not being representative of CMS beneficiaries and persistent uncertainty of benefit and risk. To ensure the best evidence is generated to inform clinical care, FDA could apply more selectivity to BDP eligibility, specify objective criteria for revoking Breakthrough designation when appropriate, and ensure timely postmarket evidence generation, whereas CMS could independently review clinical evidence, advise manufacturers about standards for coverage review, and make supplemental payments and long-term device reimbursement contingent on clinical outcome benefit and postmarket evidence generation.

Global Neurology: The Good, the Bad, and the Ugly.

Global health programs engaging in isolated or short-term medical missions can and do cause harm, reinforce health care disparities, and impede medical care in the regions where it is so desperately needed. Related ethical, medical, and legal concerns are reviewed in this article. The authors recommend abandoning these ill-considered missions and focusing attention and resources on advancing neurology through ethically congruent, multisectoral, collaborative partnerships to establish sustainable, self-sufficient training programs within low- and middle-income countries.

Racial differences in the care of pediatric sagittal craniosynostosis: a single-institution cohort study affecting state Medicaid policy.

OBJECTIVE: Although research has shown the cost-effectiveness of endoscopic versus open repair of sagittal synostosis, few studies have shown how race, insurance status, and area deprivation impact care for these patients. The authors analyzed data from children evaluated for sagittal synostosis at a single institution to assess how socioeconomic factors, race, and insurance status affect the surgical treatment of this population. They hypothesized that race and indicators of disadvantage negatively impact workup and surgical timing for craniosynostosis surgery. METHODS: Medical records of patients treated for sagittal synostosis between 2010 and 2019 were reviewed. Area deprivation index (ADI) and rural-urban commuting area codes, as well as median income by zip code, were used to measure neighborhood disadvantage. Black and White patients were compared as well as patients using Medicaid versus private insurance. RESULTS: Fifty patients were prospectively included in the study. Thirty-one underwent open repair; 19 had endoscopic repair. All 8 (100%) Black patients had open repair, compared to 54.8% of White patients (p = 0.018). Black patients were more likely to use Medicaid compared to White patients (75.0% vs 28.6%, p = 0.019). White patients were younger at surgery (5.5 vs 10.0 months, p = 0.001), and Black patients had longer surgeries (147.5 minutes vs 110.0 minutes, p = 0.021). The median household income by zip code was similar for the two groups. Black patients were generally from areas of greater disadvantage compared to White patients, based on both state and national ADI scores (state: 7.5 vs 4.0, p = 0.013; national: 83.5 vs 60.0, p = 0.013). All (94.7%) but 1 patient undergoing endoscopic repair used private insurance compared to 14 (45.2%) patients in the open repair group (p = 0.001). Patients using Medicaid were from areas of greater disadvantage compared to those using private insurance by both state and national ADI scores (state: 6.0 vs 3.0, p = 0.001; national: 75.0 vs 52.0, p = 0.001). CONCLUSIONS: Because Medicaid in the geographic region of this study did not cover helmeting after endoscopic repair of sagittal synostosis, these patients usually had open repair, resulting in significant racial and socioeconomic disparities in treatment of sagittal synostosis. This research has led to a change in Alabama Medicaid policy to now cover the cost of postoperative helmeting.

Elevated expression of interleukin 16 in chronic lymphocytic leukemia is associated with disease burden and abnormal immune microenvironment.

Interleukin-16 (IL-16) is a novel biomarker that has been implicated in many cancers as well as inflammatory diseases. In this study, we examined plasma levels of 30 cytokines and chemokines in chronic lymphocytic leukemia (CLL) and monoclonal B cell lymphocytosis (MBL) patients, and examined their association with disease stage, CLL biomarkers and T cell subsets. Interleukin 16 (IL-16) was identified as a relatively uncharacterized cytokine significantly elevated in CLL patients compared to healthy controls and MBL patients. Plasma levels of IL-16 were significantly elevated by Rai stage 0, increased by Rai stage 3-4, correlated strongly with lymphocyte count and were decreased after Ibrutinib treatment. CLL cells expressed IL-16 mRNA and spontaneously secreted IL-16 in vitro. CLL cells express IL-16 mRNA at significantly higher levels in lymphoid tissues than blood, and we observed that IL-16 release was increased in co-cultures of CLL and autologous CD4 + T cells. Elevated plasma IL-16 levels were associated with abnormalities in the immune microenvironment including multiple inflammatory cytokines and chemokines and expansion of type 1 follicular helper T cells. Taken together, our results identify IL-16 as a novel biomarker in CLL with potential functional roles in cellular interactions between CLL cells and T cells.

Costs of Tuberculosis at 3 Treatment Centers, Canada, 2010-2016.

We estimated costs of managing different forms of tuberculosis (TB) across Canada by conducting a retrospective chart review and cost assessment of patients treated for TB infection, drug-susceptible TB (DS TB), isoniazid-resistant TB, or multidrug-resistant TB (MDR TB) at 3 treatment centers. We included 90 patients each with TB infection and DS TB, 71 with isoniazid-resistant TB, and 62 with MDR TB. Median per-patient costs for TB infection (in 2020 Canadian dollars) were $804 (interquartile range [IQR] $587-$1,205), for DS TB $12,148 (IQR $4,388-$24,842), for isoniazid-resistant TB $19,319 (IQR $7,117-$41,318), and for MDR TB $119,014 (IQR $80,642-$164,015). Compared with costs for managing DS TB, costs were 11.1 (95% CI 9.1-14.3) times lower for TB infection, 1.7 (95% CI 1.3-2.1) times higher for isoniazid-resistant TB, and 8.1 (95% CI 6.1-10.6) times higher for MDR TB. Broadened TB infection treatment could avert high costs associated with managing TB disease.

Harnessing new mHealth technologies to Strengthen the Management of Multidrug-Resistant Tuberculosis in Vietnam (V-SMART trial): a protocol for a randomised controlled trial.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem globally. Long, complex treatment regimens coupled with frequent adverse events have resulted in poor treatment adherence and patient outcomes. Smartphone-based mobile health (mHealth) technologies offer national TB programmes an appealing platform to improve patient care and management; however, clinical trial evidence to support their use is lacking. This trial will test the hypothesis that an mHealth intervention can improve treatment success among patients with MDR-TB and is cost-effective compared with standard practice. METHODS AND ANALYSIS: A community-based, open-label, parallel-group randomised controlled trial will be conducted among patients treated for MDR-TB in seven provinces of Vietnam. Patients commencing therapy for microbiologically confirmed rifampicin-resistant or multidrug-resistant tuberculosis within the past 30 days will be recruited to the study. Participants will be individually randomised to an intervention arm, comprising use of an mHealth application for treatment support, or a 'standard care' arm. In both arms, patients will be managed by the national TB programme according to current national treatment guidelines. The primary outcome measure of effectiveness will be the proportion of patients with treatment success (defined as treatment completion and/or bacteriological cure) after 24 months. A marginal Poisson regression model estimated via a generalised estimating equation will be used to test the effect of the intervention on treatment success. A prospective microcosting of the intervention and within-trial cost-effectiveness analysis will also be undertaken from a societal perspective. Cost-effectiveness will be presented as an incremental cost per patient successfully treated and an incremental cost per quality-adjusted life-year gained. ETHICS: Ethical approval for the study was granted by The University of Sydney Human Research Ethics Committee (2019/676). DISSEMINATION: Study findings will be disseminated to participants and published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: ACTRN12620000681954.

Care for Chiari malformation type I: the role of socioeconomic disadvantage and race.

OBJECTIVE: There is little research on the effect of social determinants of health on Chiari malformation type I (CM-I). The authors analyzed data on all children evaluated for CM-I at a single institution to assess how socioeconomic factors and race affect the surgical treatment of this population. METHODS: Medical records of patients treated for CM-I at the authors' institution between 1992 and 2017 were reviewed. Area Deprivation Index (ADI) and Rural-Urban Commuting Area (RUCA) codes for each patient were used to measure neighborhood disadvantage. Non-Hispanic White patients were compared to non-White patients and Hispanic patients of any race (grouped together as non-White in this study) in terms of insurance status, ADI, and RUCA. Patients with initially benign CM-I, defined as not having undergone surgery within 9 months of their initial visit, were then stratified by having delayed symptom presentation or not, and compared on these same measures. RESULTS: The sample included 665 patients with CM-I: 82% non-Hispanic White and 18% non-White. The non-White patients were more likely to reside in disadvantaged (OR 3.4, p < 0.001) and urban (OR 4.66, p < 0.001) neighborhoods and to have public health insurance (OR 3.11, p < 0.001). More than one-quarter (29%) of patients underwent surgery. The non-White and non-Hispanic White patients had similar surgery rates (29.5% vs 28.9%, p = 0.895) at similar ages (8.8 vs 9.7 years, p = 0.406). There were no differences by race/ethnicity for symptoms at presentation. Surgical and nonsurgical patients had similar ADI scores (3.9 vs 4.2, p = 0.194), RUCA scores (2.1 vs 2.3, p = 0.252), and private health insurance rates (73.6% vs 74.2%, p = 0.878). A total of 153 patients underwent surgery within 9 months of their initial visit. The remaining 512 were deemed to have benign CM-I. Of these, 40 (7.8%) underwent decompression surgery for delayed symptom presentation. Patients with delayed symptom presentation were from less disadvantaged (ADI 3.2 vs 4.2; p = 0.025) and less rural (RUCA 1.8 vs 2.3; p = 0.023) areas than those who never underwent surgery. CONCLUSIONS: Although non-White patients were more likely to be socioeconomically disadvantaged, race and socioeconomic disadvantage were not associated with undergoing surgical treatment. However, among patients with benign CM-I, those undergoing decompression for delayed symptom presentation resided in more affluent and urban areas.

Effectiveness and cost-effectiveness of a health systems intervention for latent tuberculosis infection management (ACT4): a cluster-randomised trial.

BACKGROUND: Reaching the UN General Assembly High-Level Meeting on Tuberculosis target of providing tuberculosis preventive treatment to at least 30 million people by 2022, including 4 million children under the age of 5 years and 20 million other household contacts, will require major efforts to strengthen health systems. The aim of this study was to evaluate the effectiveness and cost-effectiveness of a health systems intervention to strengthen management for latent tuberculosis infection (LTBI) in household contacts of confirmed tuberculosis cases. METHODS: ACT4 was a cluster-randomised, open-label trial involving 24 health facilities in Benin, Canada, Ghana, Indonesia, and Vietnam randomly assigned to either a three-phase intervention (LTBI programme evaluation, local decision making, and strengthening activities) or control (standard LTBI care). Tuberculin and isoniazid were provided to control and intervention sites if not routinely available. Randomisation was stratified by country and restricted to ensure balance of index patients with tuberculosis by arm and country. The primary outcome was the number of household contacts who initiated tuberculosis preventive treatment at each health facility within 4 months of the diagnosis of the index case, recorded in the first or last 6 months of our 20-month study. To ease interpretation, this number was standardised per 100 newly diagnosed index patients with tuberculosis. Analysis was by intention to treat. Masking of staff at the coordinating centre and sites was not possible; however, those analysing data were masked to assignment of intervention or control. An economic analysis of the intervention was done in parallel with the trial. ACT4 is registered at ClinicalTrials.gov, NCT02810678. FINDINGS: The study was done between Aug 1, 2016, and March 31, 2019. During the first 6 months of the study the crude overall proportion of household contacts initiating tuberculosis preventive treatment out of those eligible at intervention sites was 0·21. After the implementation of programme strengthening activities, the proportion initiating tuberculosis preventive treatment increased to 0·35. Overall, the number of household contacts initiating tuberculosis preventive treatment per 100 index patients with tuberculosis increased between study phases in intervention sites (adjusted rate difference 60, 95% CI 4 to 116), while control sites showed no statistically significant change (-12, -33 to 10). There was a difference in rate differences of 72 (95% CI 10 to 134) contacts per 100 index patients with tuberculosis initiating preventive treatment associated with the intervention. The total cost for the intervention, plus LTBI clinical care per additional contact initiating treatment was estimated to be CA$1348 (range 724 to 9708). INTERPRETATION: A strategy of standardised evaluation, local decision making, and implementation of health systems strengthening activities can provide a mechanism for scale-up of tuberculosis prevention, particularly in low-income and middle-income countries. FUNDING: Canadian Institutes of Health Research.

Post-Traumatic Stress Symptoms in Caregivers and Children with Hydrocephalus.

OBJECTIVE: Hydrocephalus is a disorder of cerebrospinal fluid dynamics, traditionally treated by placement of a ventricular shunt. Shunts are effective but imperfect as they fail in an unpredictable pattern, and the patient's well-being is dependent on adequate shunt function. The omnipresent threat of shunt failure along with the potential need for invasive investigations can be stressful for patients and caregivers. Our objective was to measure post-traumatic stress symptoms (PTSS) in children with hydrocephalus and their caregivers. METHODS: A cross-sectional analysis of children with hydrocephalus and their caregivers was conducted. Caregivers completed a measure of their own PTSS (the Post-Traumatic Stress Disorders Checklist for the Diagnostic and Statistical Manual of Mental Disorders-V) and resilience (the Connor Davidson Resilience Scale). Pediatric patients rated their own PTSS and resilience using the Acute Stress Checklist for Kids and Connor Davidson Resilience Scale. RESULTS: Ninety-one caregivers completed the Post-Traumatic Stress Disorders Checklist for the Diagnostic and Statistical Manual of Mental Disorders-V. Mean score was 17.0 (standard deviation 15.7; median 13.0). Fourteen percent scored above 33, the threshold suggestive of a preliminary diagnosis of post-traumatic stress disorder. There was a statistically significant association between caregiver post-traumatic stress and marital status, child's race, and caregiver education. More than half (52%) of caregivers reported their child's hydrocephalus as the most significant source of their PTSS. Children did not have markedly elevated levels of PTSS. Forty-one percent of caregivers and 60% of children scored in the lowest resilience quartile compared with the general population. CONCLUSIONS: Results from this study suggest that post-traumatic stress affects caregivers with hydrocephalus, yet levels of resilience for caregivers and pediatric patients are low.

Daily Evaluation Cards Are Superior for Student Assessment Compared to Single Rater In-Training Evaluations.

INTRODUCTION: The University of Manitoba's ambulatory pediatric clerkship transitioned to daily encounter cards (DECs) from single in-training evaluation reports (ITERs). The impact of this change on quality of student assessment was unknown. Using the validated Completed Clinical Evaluation Report Rating (CCERR) scale, we compared the assessment quality of the single ITER to the DEC-based system. METHODS: Block randomization was used to select from a cohort of ITER- and DEC-based assessments during equivalent points in clerkship training. Data were transcribed and anonymized and scored by two blinded raters using the CCERR. RESULTS: Inter-rater reliability for total CCERR scores was substantive (> 0.6). Mean total CCERR score for the DEC cohort was significantly higher than for the ITER cohort (25.2 vs. 16.8, p < 0.001), as were the mean scores for each item (2.81 vs. 1.86, p < 0.05). Multivariate logistical regression supported the significant influence of assessment method on assessment quality. CONCLUSIONS: There is improvement in the average quality of student assessments associated with the transition from an ITER-based system to a DEC-based system. However, the improvement to only average CCERR scores for the DEC cohort suggests an unmet need for faculty development.

A novel in situ multiplex immunofluorescence panel for the assessment of tumor immunopathology and response to virotherapy in pediatric glioblastoma reveals a role for checkpoint protein inhibition.

Immunotherapy with oncolytic herpes simplex virus-1 therapy offers an innovative, targeted, less-toxic approach for treating brain tumors. However, a major obstacle in maximizing oncolytic virotherapy is a lack of comprehensive understanding of the underlying mechanisms that unfold in CNS tumors/associated microenvironments after infusion of virus. We demonstrate that our multiplex biomarker screening platform comprehensively informs changes in both topographical location and functional states of resident/infiltrating immune cells that play a role in neuropathology after treatment with HSV G207 in a pediatric Phase 1 patient. Using this approach, we identified robust infiltration of CD8+ T cells suggesting activation of the immune response following virotherapy; however there was a corresponding upregulation of checkpoint proteins PD-1, PD-L1, CTLA-4, and IDO revealing a potential role for checkpoint inhibitors. Such work may ultimately lead to an understanding of the governing pathobiology of tumors, thereby fostering development of novel therapeutics tailored to produce optimal responses.

Air-Quality Assessment of On-Site Brick-Kiln Worker Housing in Bhaktapur, Nepal: Chemical Speciation of Indoor and Outdoor PM2.5 Pollution.

Brick workers and their families in Nepal generally live in poorly ventilated on-site housing at the brick kiln, and may be at higher risk for non-occupational exposure to fine particulate matter air pollution and subsequent respiratory diseases due to indoor and outdoor sources. This study characterized non-occupational exposure to PM2.5 by comparing overall concentrations and specific chemical components of PM2.5 inside and outside of brick workers' on-site housing. For all samples, the geometric mean PM2.5 concentration was 184.65 µg/m3 (95% confidence interval: 134.70, 253.12 µg/m3). PM2.5 concentrations differed by kiln number (p = 0.009). Kiln number was significantly associated with 16 of 29 (55%) air pollutant, temperature, or relative humidity variables. There was not a significant interaction between kiln number and location of sample for PM2.5 (p = 0.16), but there was for relative humidity (p = 0.02) and temperature (p = 0.01). Results were qualitatively similar when we repeated analyses using indoor samples only. There was no difference in the chemical makeup of indoor and outdoor PM2.5 in this study, suggesting that outdoor PM2.5 air pollution easily infiltrates into on-site brick worker housing. Outdoor and indoor PM2.5 concentrations found in this study far exceed recommended levels. These findings warrant future interventions targeted to this vulnerable population.

Cost-effectiveness of Latent Tuberculosis Infection Screening before Immigration to Low-Incidence Countries.

Prospective migrants to countries where the incidence of tuberculosis (TB) is low (low-incidence countries) receive TB screening; however, screening for latent TB infection (LTBI) before immigration is rare. We evaluated the cost-effectiveness of mandated and sponsored preimmigration LTBI screening for migrants to low-incidence countries. We used discrete event simulation to model preimmigration LTBI screening coupled with postarrival follow-up and treatment for those who test positive. Preimmigration interferon-gamma release assay screening and postarrival rifampin treatment was preferred in deterministic analysis. We calculated cost per quality-adjusted life-year gained for migrants from countries with different TB incidences. Our analysis provides evidence of the cost-effectiveness of preimmigration LTBI screening for migrants to low-incidence countries. Coupled with research on sustainability, acceptability, and program implementation, these results can inform policy decisions.

Cortical porosity assessment in the distal radius: A comparison of HR-pQCT measures with Synchrotron-Radiation micro-CT-based measures.

OBJECTIVE: To determine the agreement between cortical porosity derived from high resolution peripheral quantitative computed tomography (HR-pQCT) (via standard threshold, mean density and density inhomogeneity methods) and synchrotron radiation micro-CT (SR-µCT) derived porosity at the distal radius. METHODS: We scanned 10 cadaveric radii (mean donor age: 79, SD 11 years) at the standard distal region using HR-pQCT and SR-µCT at voxel sizes of 82 µm and 17.7 µm, respectively. Common cortical regions were delineated for each specimen in both imaging modalities. HR-pQCT images were analyzed for cortical porosity using the following methods: Standard threshold, mean density, and density inhomogeneity (via recommended and optimized equations). We assessed agreement in porosity measures between HR-pQCT methods and SR-µCT by reporting predicted variance from linear regression and mean bias with limits of agreement (LOA). RESULTS: The standard threshold and mean density methods predicted 85% and 89% of variance and indicated underestimation (mean bias -9.1%, LOA -15.9% to -2.2%) and overestimation (10.4%, 4.6% to 16.2%) of porosity, respectively. The density inhomogeneity method with recommended equation predicted 89% of variance and mean bias of 14.9% (-4.3 to 34.2) with systematic over-estimation of porosity in more porous specimens. The density inhomogeneity method with optimized equation predicted 91% of variance without bias (0.0%, -5.3 to 5.2). CONCLUSION: HR-pQCT imaged porosity assessed with the density inhomogeneity method with optimized equation indicated the best agreement with SR-µCT derived porosity.

Screening for Latent Tuberculosis Infection in Migrants With CKD: A Cost-effectiveness Analysis.

RATIONALE & OBJECTIVE: In countries with a low tuberculosis (TB) incidence, TB disproportionately affects populations born abroad. TB persists in these populations through reactivation of latent TB infection (LTBI) acquired before immigration. Those with chronic kidney disease (CKD) are at increased risk for reactivation and may benefit from LTBI screening and treatment. STUDY DESIGN: Health administrative data from British Columbia, Canada, were used to inform a cost-effectiveness analysis evaluating LTBI screening in those diagnosed with stage 4 or 5 CKD not requiring dialysis (late-stage CKD) and those who began dialysis therapy. SETTING & POPULATION: Permanent residents establishing residency in British Columbia, Canada, between 1985 and 2012 who had late-stage CKD diagnosed or began dialysis therapy. INTERVENTIONS: Screening with the tuberculin skin test or interferon-gamma release assay (IGRA) compared to no LTBI screening at the time of late-stage CKD diagnosis and time of dialysis therapy initiation. Treatment for those who tested positive was isoniazid for 9 months. OUTCOMES: Costs (2016 Can $), TB cases, and quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio for QALYs gained was calculated. MODEL, PERSPECTIVE, & TIMEFRAME: Discrete event simulation model using a health care system perspective, 1.5% discount rate, and 5-year time horizon. RESULTS: Screening with IGRA was superior to the tuberculin skin test in all situations. Screening with IGRA was less expensive and resulted in better outcomes compared to no screening in those initiating dialysis therapy from countries with an elevated TB incidence. In individuals with late-stage CKD, screening with IGRA was only cost-effective in those 60 years or older (cost per QALY gained, <$48,000) from countries with an elevated TB incidence. LIMITATIONS: This study has limitations in generalizability to different epidemiologic settings and in modeling complicated clinical decisions. CONCLUSIONS: LTBI screening should be considered in non-Canadian-born residents initiating dialysis therapy and those with late stage CKD who are older.